ORCID Profile
0000-0002-6406-4076
Current Organisations
Queensland Skin and Cancer Foundation- QI Derm
,
Princess Alexandra Hospital
,
Prince Charles Hospital
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Medical Biotechnology | Biochemistry and Cell Biology | Regenerative medicine (incl. stem cells) | Gene expression (incl. microarray and other genome-wide approaches) | Epigenetics (incl. genome methylation and epigenomics) | Dermatology | Biomedical Engineering not elsewhere classified | Genetics | Biochemistry and Cell Biology not elsewhere classified | Regenerative Medicine (incl. Stem Cells and Tissue Engineering) | Cell Development, Proliferation and Death
ANZSRC Socio-Economic Objective (SEO)
Skin and Related Disorders | Expanding Knowledge in the Biological Sciences |
Related Links
Publications
Fetal stem cell microchimerism: natural-born healers or killers?
Publisher: Oxford University Press (OUP)
Date: 27-07-2010
Abstract: After four decades of study, the biological role of fetal microchimerism (FMC) remains elusive. Transfer of fetal cells to the mother begins soon after implantation, and increases with gestational age. FMC cells then decline after delivery, but remain detectable for years post-partum. These cells have been implicated in rheumatoid arthritis remission during pregnancy and the prevention of breast cancer by graft-versus-tumor-effects. However, any beneficial effects contrast with their suspected malevolence in triggering of systemic sclerosis after childrearing or their stromal support for tumor formation. Recent evidence that FMC cells participate in disease and tissue repair has stirred controversy on their origin. The detection of FMC cells during early embryogenesis together with the ersity of hematopoietic, mesenchymal and endothelial markers, and plasticity of morphology when integrated into various tissues, provides evidence for their stemness. However, proof of their phenotype in conventional stem cell differentiation assays has been beset with difficulty in isolating and expanding them in culture. Unraveling the function of FMC cells will provide insight into both their engagement in disease and their therapeutic potential.
Past stem cells and finally in transit: SLC1A3 instructs skin niche coupling
Publisher: EMBO
Date: 18-04-2018
HLA-G Expression in Atopic Dermatitis
Publisher: Elsevier BV
Date: 09-2001
Resident vascular endothelial progenitor definition and function: the age of reckoning
Publisher: Springer Science and Business Media LLC
Date: 09-09-2022
DOI: 10.1007/S10456-021-09817-2
Abstract: The cardiovascular system is composed around the central function of the endothelium that lines the inner surfaces of its vessels. In recent years, the existence of a progenitor population within the endothelium has been validated through the study of endothelial colony-forming cells (ECFCs) in human peripheral blood and certain vascular beds. However, our knowledge on endothelial populations in vivo that can give rise to ECFCs in culture has been limited. In this review we report and analyse recent attempts at describing progenitor populations in vivo from murine studies that reflect the self-renewal and stemness capacity observed in ECFCs. We pinpoint seminal discoveries within the field, which have phenotypically defined, and functionally scrutinised these endothelial progenitors. Furthermore, we review recent publications utilising single-cell sequencing technologies to better understand the endothelium in homeostasis and pathology.
Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells
Publisher: Proceedings of the National Academy of Sciences
Date: 06-02-2007
Abstract: Fetal progenitor cells enter the maternal circulation during pregnancy and can persist for decades. We aimed to determine the role of these cells in tissue inflammation during pregnancy. WT female mice were mated to males transgenic for the EGFP (ubiquitous) or the luciferase gene controlled by the VEGF receptor 2 (VEGFR2 V-Luc) promoter. A contact hypersensitivity reaction was triggered during such pregnancies. Fetal cells were tracked by using real-time quantitative lification of the transgene (real-time PCR), Y chromosome in situ hybridization (FISH), immunofluorescence or in vivo bioluminescence imaging. Real-time PCR disclosed fetal cells in the inflamed areas in all tested mice (17/17) with higher frequency and numbers in the inflamed compared with the control areas ( P = 0.01). Double labeling demonstrated CD31+ EGFP+ fetal cells organized as blood vessels. In WT pregnant mice bearing V-Luc fetuses, a specific luciferase activity signal could be detected at the hypersensitivity site only, demonstrating the elective presence of VEGFR2-expressing fetal cells. In conclusion, using various techniques, we found the presence of fetal endothelial cells lining blood vessels in maternal sites of inflammation. These results imply that fetal endothelial progenitor cells are acquired by the mother and participate in maternal angiogenesis during pregnancy.
Clinicopathological factors associated with death from thin (≤ 1·00 mm) melanoma
Publisher: Oxford University Press (OUP)
Date: 24-11-2019
DOI: 10.1111/BJD.18560
Abstract: Thin cutaneous melanomas (≤ 1·00 mm) are increasing worldwide, causing around a quarter of all melanoma deaths in the U.S.A. and Australia. Identification of predictive factors for potentially fatal thin melanomas could allow better use of resources for follow-up. To identify the clinicopathological factors associated with fatal thin melanomas. This large, nested case-case study extracted data from the population-based Queensland Cancer Registry, Australia. Our cohort consisted of Queensland residents aged 0-89 years who were diagnosed with a single, locally invasive thin melanoma (≤ 1·00 mm) between 1995 and 2014. Fatal cases (eligible patients who died from melanoma) were in idually matched to three nonfatal cases (eligible patients who were not known to have died from melanoma) according to sex, age, year of diagnosis and follow-up interval. Using conditional logistic regression, we calculated odds ratios (ORs) for melanoma-specific death, adjusting for all collected clinicopathological variables. In the cohort, 27 660 eligible patients were diagnosed with a single, thin melanoma. The final case-case series included 424 fatal cases and 1189 nonfatal cases. Fatal cases were sixfold as likely to arise on the scalp as on the back [OR 6·39, 95% confidence interval (CI) 2·57-15·92] and six times as likely to be of thickness 0·80-1·00 mm as of < 0·30 mm (OR 6·00, 95% CI 3·55-10·17). Scalp location is a strong prognostic factor of death from thin melanoma. Further, this study provides support that melanomas with a thickness of 0·80-1·00 mm are the more hazardous thin lesions. Patients with these tumour characteristics require specific attention during follow-up. What's already known about this topic? Thin invasive melanomas (≤ 1·00 mm) contribute a substantial proportion of melanoma fatalities, owing to the high volume of disease. There is a need to find prognostic factors that will better identify fatal thin melanomas at the time of diagnosis. What does this study add? In this large population-based study, fatal thin tumours were sixfold as likely to be located on the scalp as on the back. Thin melanomas of 0·80-1·00 mm thickness were six times as likely to be associated with death as tumours < 0·30 mm. Scalp location and increasing thickness are strong predictive factors of fatal thin melanomas, indicating that patients with these tumour characteristics require close follow-up.
Quality of Abstracts in 3 Clinical Dermatology Journals
Publisher: American Medical Association (AMA)
Date: 05-2003
Sneddon Syndrome revealing dysfibrinogenemia
Publisher: Wiley
Date: 07-2003
CD34+ cells in maternal placental blood are mainly fetal in origin and express endothelial markers
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1038/LABINVEST.2009.55
Abstract: Fetal CD34+ cells enter the maternal circulation during pregnancy and may persist for decades. These cells are usually depicted as hematopoietic stem rogenitor cells. Our objective was to further determine the phenotype of fetal chimeric CD34+ cells in placental maternal blood from the intervillous space (IVS). Human healthy term placentas were analyzed (n=9). All fetuses were male. CD34+ cells were identified in the IVS and further characterized as fetal or maternal using X and Y chromosome fluorescence in situ hybridization. The phenotype of fetal cells was further analyzed using anti-CD117 (c-kit), anti-CD133, anti-CD31, anti-von Willebrand factor (vWF), anti-vimentin, anti-CD45 and anti-cytokeratin (CK) antibodies. We used preecl tic placentas of male (n=3) and healthy placentas of female fetuses (n=3) as controls. As expected fetal cells were easily identified in the IVS and significantly increased in cases of preecl sia. Most CD34+ cells in the IVS were of fetal origin (90%) and were not surrounded by CK staining further showing that they were not in fetal trophoblastic villi. Similarly, about 40% of CD31+ and 6% of vimentin+ cells in the IVS were fetal in origin. No CD117+ or CD133+ fetal cells were found in the IVS of examined placentas. Besides, all the CD34+ cells identified in the IVS were co-labeled with vWF or CD31, suggesting their endothelial origin. These results suggest that most CD34+ cells in maternal placental blood at term are fetal in origin from endothelial and not hematopoietic lineages.
Increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy
Publisher: Wiley
Date: 03-2009
DOI: 10.1002/IJC.24036
Abstract: Pregnancy results in the transfer of stem cells from the fetus to the maternal circulation. These cells are able to migrate and differentiate within various damaged maternal tissues. We recently showed the presence of fetal-derived cells in human breast carcinomas during pregnancy. In this study, we aimed to reproduce these results in a murine model of "pregnancy-associated" breast carcinoma. We bred virgin MMTV-H-Ras transgenic female mice with male mice transgenic for luciferase under the control of the VEGFR2 promoter. Tumors that developed during or following gestation were analyzed and their nuclear grade classified. Fetal cells were detected by Y chromosome Fluorescence in situ hybridization FISH in 9/9 of breast carcinomas but only in 2 liver controls from the same animals. The number of fetal cells was 20 and 4.9 per million maternal cells in these tissues, respectively (p < 0.05). High grade tumors had significantly more fetal cells (p < 0.05). In vivo imaging of the luciferase signal under control of the VEGFR2 promoter as well as von Willebrand staining did not reveal an endothelial phenotype of fetal cells. Sixty two percent of the fetal cells expressed cytokeratins but were not tumoral. In conclusion, fetal cells-expressing cytokeratin-are always present in murine breast carcinomas associated with gestation. Interestingly, high-grade tumors contain more fetal cells.
PARP1 polymorphisms play opposing roles in melanoma occurrence and survival
Publisher: Wiley
Date: 06-11-2015
DOI: 10.1002/IJC.29280
Immunosuppression Agent Cyclosporine Reduces Self-Renewal and Vessel Regeneration Potentiation of Human Endothelial Colony Forming Cells.
Publisher: Oxford University Press (OUP)
Date: 13-10-2018
DOI: 10.1002/SCTM.18-0103
Abstract: Endothelial colony forming cells (ECFC) and mesenchymal stem cells (MSC) combined have great potential to be used for cell therapy of ischemic vascular diseases. However, to improve allogeneic stem cell engraftment the use of immunosuppression, such as cyclosporine has been suggested. Our aim was to assess the impact of cyclosporine on hind limb revascularisation upon MSC and ECFC combination therapy. Balb/c immunocompetent mice subjected to hind limb ischemia (right femoral artery ligation) were given both human ECFC and MSC (weekly intramuscular injections) with or without cyclosporine (daily injection). Surprisingly, mice receiving cyclosporine had a significant decrease in reperfusion based on laser Doppler imaging compared to vehicle controls and had poorer limb survival. In vitro, the downstream calcineurin target NFATC4 was highly expressed in the self-renewing fraction of ECFCs. ECFCs cultured with cyclosporine had reduced colony formation capacity and tube formation in Matrigel. Lastly, ECFC displayed increased proliferation and loss of capacity for long term culture when in the presence of cyclosporine clearly showing a loss of quiescence and progenitor function. Our findings demonstrate the deleterious impact of cyclosporine on ECFC function, with significant impact on ECFC-based allogeneic cellular therapy. Stem Cells Translational Medicine 2019 :162&
Specific maternal microchimeric T cells targeting fetal antigens in β cells predispose to auto-immune diabetes in the child
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.JAUT.2011.02.003
Abstract: During pregnancy there is an exchange of cells between the fetus and the mother including T lymphocytes that can persist after delivery. Previous studies have described an increased numbers of maternal cells in children with juvenile diabetes as compared to their unaffected siblings. Our objective was to assess the possibility for these chimeric T cells to trigger an anti-beta cell response. We mated OT2 transgenic female mice having T cells specifically targeting ovalbumin to RIP-OVA males expressing ovalbumin in pancreatic β cells. This allowed us to examine RIP-OVA progeny from OT2 mothers to assess the consequences of maternal T cells acquired during gestation or lactation. We quantitatively analyzed the pancreas of RIP-OVA mice from OT2 mothers for islet infiltration and compared them to RIP-OVA mice not exposed to OT2 mothers or to wild-type mice from OT2 mothers. RIP-OVA mice from OT2 mothers had significantly more peri-insulitis (p=0.0083) compared to wild-type littermates. Similarly RIP-OVA mice from OT2 mothers had more peri-insulitis as compared to RIP-OVA mice from RIP-OVA mothers (p=0.0073). Presence and specific anti-ovalbumin activity of maternal OT2 cells in the offsprings' peripheral lymphoid tissues was found in a separate group of mice. In animals presenting islet inflammation, CD3+ infiltrating cells in the pancreas were however derived from the offspring and not from OT2 mothers. In accordance, OT2 and RIP-OVA double transgenic mice with high levels of auto-reactive T cells had more peri-insulitis and sometimes intense insulitis when they were from OT2 mothers as compared to RIP-OVA mothers (p=0.046). In highly specific fetal/maternal combinations, maternal T cells with activity against the offspring pancreatic beta cells, presumably chimeric in fetal organs, initiate islet inflammation and may therefore predispose to auto-immune diabetes.
Distant Mesenchymal Progenitors Contribute to Skin Wound Healing and Produce Collagen: Evidence from a Murine Fetal Microchimerism Model
Publisher: Public Library of Science (PLoS)
Date: 05-2013
Accelerated Endothelial to Mesenchymal Transition Increased Fibrosis via Deleting Notch Signaling in Wound Vasculature.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.JID.2017.12.004
Abstract: Skin wound healing in adults is characterized by a peak of angiogenesis followed by regression of the excessive vasculature in parallel with collagen deposition and fibrosis in the wound. We hypothesized that regressing vessels in healing wounds were in fact entering an endothelial to mesenchymal transition contributing to scarring. Using vascular-specific fate tracking (Cdh5-cre
Management of organ transplant recipients attending a high-throughput skin cancer surgery and surveillance clinic in Queensland
Publisher: Oxford University Press (OUP)
Date: 27-09-2019
DOI: 10.1111/BJD.17001
Abstract: The incidence of skin cancer in organ transplant recipients (OTRs) is very high, due mainly to long-term immunosuppressive therapy. The problem is particularly severe for OTRs living in Queensland, Australia, and results in significant mortality. To describe the experience of the first dedicated outpatient high-throughput transplant skin clinic in Queensland. This prospective evaluation study was conducted at a newly established, outpatient transplant skin cancer surgery and surveillance clinic. Participants (89 OTRs and 12 non-OTRs) were referred to the Princess Alexandra Hospital Transplant Skin Clinic during December 2016 to May 2017, and were each followed for 3 months. Self-completed questionnaires were administered at baseline and the end of follow-up (n = 94), and details of any skin cancers occurring in that period were extracted from hospital records. In the 3-month follow-up of 101 participants, a total of 615 skin lesions were detected in the 3-month follow-up of 101 participants, of which 478 (78%) were treated in the clinic and 55 (9%) were referred to another specialist. Of the 478 treated lesions, 268 were histopathologically confirmed skin cancers, equivalent to 2·7 (95% confidence interval 2·5-2·8) skin cancers per participant per 3 months. The overall number needed to treat for any skin cancer was 1·4 (95% confidence interval 1·3-1·5). Three-quarters (374) of in-clinic treatments were surgical, and most (90%) were complete excisions. The median time from detection of skin cancer to excision was 7 days. This high-volume surgical outpatient transplant skin clinic enables efficient treatment of skin cancers in very-high-risk OTRs.
Germline variants are associated with increased primary melanoma tumor thickness at diagnosis
Publisher: Oxford University Press (OUP)
Date: 17-10-2020
DOI: 10.1093/HMG/DDAA222
Abstract: Germline genetic variants have been identified, which predispose in iduals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness. To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness. The analyses utilized 10 604 in iduals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated in iduals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 in iduals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry. We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P & 5 × 10−8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion.
Transgenic Flash Mice for In Vivo Quantitative Monitoring of Canonical Wnt Signaling to Track Hair Follicle Cycle Dynamics
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1038/JID.2014.92
Abstract: Hair follicles (HFs) upon development enter a lifelong cycle of growth, regression, and resting. These phases have been extensively studied at the cellular and molecular levels for in idual HFs. However, HFs group into domains with coordinated cycling strongly influenced by their environment. These macroscopic hair domains have been difficult to study and can be influenced by physiological or pathological conditions, such as pregnancy or skin wounds. To robustly address this issue, we generated a mouse model for quantitative monitoring of β-catenin activity reflecting HF cycle dynamics macroscopically by using live bioluminescence imaging. These mice allowed live tracking of HF cycles and development, and highlighted hair regenerative patterns known to occur through macro-environmental cues, including initiation events, propagating anagen and border stability, and allowed refinement of a mechanistic mathematical model that integrates epidermal cell population dynamics into an excitable reaction-diffusion model. HF cycling could be studied in situations of pregnancy, wound healing, hair plucking, as well as in response to cyclosporine or Wnt3a stimulation. In conclusion, we developed a model for analysis of HF cycling at the macroscopic level that will allow refined analysis of hair cycle kinetics as well as its propagation dynamics.
Prognostic importance of a second invasive primary melanoma according to tumour stage
Publisher: Oxford University Press (OUP)
Date: 14-11-2017
DOI: 10.1111/BJD.15863
Anti‐IL17A, Ixekizumab, for treatment‐resistant chronic venous leg ulcers: A phase II randomized, double‐blind, placebo‐controlled pilot trial
Publisher: Wiley
Date: 24-03-2023
DOI: 10.1111/JDV.19041
Fetal microchimerism in skin wound healing
Publisher: Informa UK Limited
Date: 04-2012
DOI: 10.4161/CHIM.20739
Increase lymphangiogenesis in melanoma during pregnancy: correlation with the prolactin signalling pathway
Publisher: Wiley
Date: 02-05-2012
Variations in supportive care needs of patients after diagnosis of localised cutaneous melanoma: a 2-year follow-up study
Publisher: Springer Science and Business Media LLC
Date: 25-08-2017
DOI: 10.1007/S00520-016-3378-9
Abstract: We aimed to describe variations in unmet supportive care needs of patients diagnosed with localised melanoma at high risk of recurrence and factors associated with initial and persisting moderate-to-high needs. We ascertained 386 patients diagnosed with clinical stage IB-II melanoma and administered surveys every 6 months for 2 years. The proportion experiencing at least one moderate-to-high need was assessed among salient subgroups: 306 patients with no previous melanoma and 80 with previous melanoma at enrolment, 30 who experienced disease recurrence during follow-up and 31 who developed another primary. Baseline factors associated with (a) needs at enrolment and (b) persistent needs over 2 years (or as long as disease-free) were identified by logistic regression analyses. The proportion of patients with needs substantially declined over the first 6 months (if no previous melanoma, from 48 to 22 %, p < 0.001 previous melanoma, 35 to 17 %, p = 0.007), and in those remaining disease-free, needs declined further by 24 months (to 14 and 6 % respectively). By contrast, 50 % of those experiencing recurrence, and 39 % of those who developed another primary, reported needs. Stressful life events and anxiety were associated with needs at enrolment. At least one need, mainly fear of recurrence, persisted in 22 % of disease-free participants. Persistent needs were predicted by age, depression, anxiety and other stressful life events. Melanoma patients' needs peak when first diagnosed and if disease recurs. Younger people or those experiencing additional stressful events, anxiety or depression are more likely to experience persistent needs and may benefit from tailored support.
Ectopic expression of SOX18 in Basal cell carcinoma negatively regulates tumour progression
Publisher: Elsevier BV
Date: 06-2020
Skin Carcinoma Arising From Donor Cells in a Kidney Transplant Recipient
Publisher: American Association for Cancer Research (AACR)
Date: 03-2005
DOI: 10.1158/0008-5472.CAN-04-2783
Abstract: The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the s les with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation.
Breast cancer stroma frequently recruits fetal derived cells during pregnancy
Publisher: Springer Science and Business Media LLC
Date: 02-2008
DOI: 10.1186/BCR1860
Ten-Year Survival after Multiple Invasive Melanomas Is Worse than after a Single Melanoma: a Population-Based Study
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JID.2016.03.014
Abstract: The prognosis of melanoma patients who are diagnosed with multiple primary lesions remains controversial. We used a large population-based cohort to re-examine this issue, applying a delayed entry methodology to avoid survival bias. Of 32,238 eligible patients diagnosed between 1995 and 2008, 29,908 (93%) had a single invasive melanoma, 2,075 (6%) had two, and 255 (1%) had three. Allowing for differences in entry time, 10-year cause-specific survival for these three groups was 89% (95% confidence interval [CI] = 88-90%), 83% (95% CI = 80-86%), and 67% (95% CI = 54-81%), respectively. After adjustment for key prognostic factors, the hazard ratio of death within 10 years from melanoma was two times higher for those with two melanomas (hazard ratio = 2.01, 95% CI = 1.57-2.59 P < 0.001) and nearly three times higher when three melanomas were diagnosed (hazard ratio = 2.91, 95% CI = 1.64-5.18 P < 0.001) compared with people with a single melanoma. Melanoma-specific mortality remained elevated after adjusting for maximum thickness or ulceration of any melanoma regardless of the index tumor. After appropriately accounting for the interval between diagnosis of the first and subsequent melanomas, patients with multiple invasive melanomas have significantly poorer survival than patients with a single invasive melanoma.
Whole-mount staining coupled to a UV-inducible basal cell carcinoma murine model
Publisher: Elsevier BV
Date: 03-2021
Life-Threatening Dermatoses Occurring During Gestation
Publisher: Springer Berlin Heidelberg
Date: 2009
Defining tissue resident vascular stem cells.
Publisher: Impact Journals, LLC
Date: 29-09-2017
Proper use and interpretation of diaphragmatic ultrasonography.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2017
The association between BRAF‐V600E mutations and death from thin (≤1.00 mm) melanomas: A nested case–case study from Queensland, Australia
Publisher: Wiley
Date: 16-05-2023
DOI: 10.1111/JDV.19173
Nomograms to predict recurrence and survival in stage IIIB and IIIC melanoma after therapeutic lymphadenectomy
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.EJCA.2014.02.010
Abstract: Current staging algorithms in melanoma patients undergoing therapeutic lymph node dissection (LND) fail to accurately distinguish long-term survivors from those at risk of rapid relapse. Our goal was to establish and validate nomograms for predicting both recurrence and survival after LND. A prospective cohort of stage IIIB and IIIC melanoma patients was ascertained from a tertiary hospital in Brisbane, Australia. Failure-time multivariate analysis identified key factors that, in adjusted combinations, generated nomograms to predict 2-year recurrence and 5-year melanoma-specific survival. The predictive value of these nomograms was further validated in a patient cohort from Rotterdam, The Netherlands. In 494 Australian patients, number of positive lymph nodes, extra-capsular extension and nodular histopathological subtype were the main independent predictors of 2-year recurrence while age, number of positive nodes and extra-capsular extension were the independent predictors of survival. Predictive value was confirmed in The Netherlands cohort of 331 patients. The nomograms were able to classify patients according to their 2-year recurrence and 5-year survival rates even within each stage III sub-class. Models that include extra-capsular extension predict outcomes in patients with clinically involved lymph nodes. This tool may help tailor treatment and monitoring of this group of patients.
Single-Cell Transcriptional Profiling of Aortic Endothelium Identifies a Hierarchy from Endovascular Progenitors to Differentiated Cells
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.CELREP.2019.04.102
Abstract: The cellular and molecular profiles that govern the endothelial heterogeneity of the circulatory system have yet to be elucidated. Using a data-driven approach to study the endothelial compartment via single-cell RNA sequencing, we characterized cell subpopulations within and assigned them to a defined endothelial hierarchy. We show that two transcriptionally distinct endothelial populations exist within the aorta and, using two independent trajectory analysis methods, confirm that they represent transitioning cells rather than discrete cell types. Gene co-expression analysis revealed crucial regulatory networks underlying each population, including significant metabolic gene networks in progenitor cells. Using mitochondrial activity assays and phenotyping, we confirm that endovascular progenitors display higher mitochondrial content compared to differentiated endothelial cells. The identities of these populations were further validated against bulk RNA sequencing (RNA-seq) data obtained from normal and tumor-derived vasculature. Our findings validate the heterogeneity of the aortic endothelium and previously suggested hierarchy between progenitor and differentiated cells.
Fetal cells participate over time in the response to specific types of murine maternal hepatic injury
Publisher: Oxford University Press (OUP)
Date: 03-2007
Abstract: In humans, fetal microchimeric cells transferred to maternal tissues during pregnancy can adopt a hepatocyte phenotype. Our objective was to determine whether fetal cells participate in the response to specific murine post-partum hepatic injuries. Wild-type female mice were bred to males transgenic for the enhanced green fluorescent protein (GFP) (n = 42). Following delivery, we created models of chemical or surgical injury with carbon tetrachloride (CCl(4)) injection or by performing partial hepatectomy. Liver injury was assessed histologically. Fetal cells in maternal liver were detected and measured by real-time PCR lification of the gfp transgene and by immunofluorescence using anti-GFP antibodies. PCR results showed that in chemical but not surgical injury, fetal GFP+ cells were detectable in maternal liver and spleen and that fetal cell presence was significantly increased over time following injury (4 versus 8 weeks, P = 0.006 for liver and P = 0.0006 for spleen). In some animals, following chemical injury, GFP+ cells were detected by immunofluorescence. The results of this preliminary study suggest that specific types of injury may elicit different fetal cell responses in maternal organs. There is a significant effect of time on fetal cell presence in liver and spleen. Furthermore, real-time PCR lification is more sensitive than immunofluorescence for the detection of microchimeric fetal cells.
Self-Renewal and High Proliferative Colony Forming Capacity of Late-Outgrowth Endothelial Progenitors is Regulated by Cyclin-Dependent Kinase Inhibitors Driven by Notch Signaling
Publisher: Oxford University Press (OUP)
Date: 06-01-2016
DOI: 10.1002/STEM.2262
Abstract: Since the discovery of endothelial colony forming cells (ECFC), there has been significant interest in their therapeutic potential to treat vascular injuries. ECFC cultures display significant heterogeneity and a hierarchy among cells able to give rise to high proliferative versus low proliferative colonies. Here we aimed to define molecularly this in vitro hierarchy. Based on flow cytometry, CD34 expression levels distinguished two populations. Only CD34 + ECFC had the capacity to reproduce high proliferative potential (HPP) colonies on replating, whereas CD34− ECFCs formed only small clusters. CD34 + ECFCs were the only ones to self-renew in stringent single-cell cultures and gave rise to both CD34 + and CD34− cells. Upon replating, CD34 + ECFCs were always found at the centre of HPP colonies and were more likely in G0/1 phase of cell cycling. Functionally, CD34 + ECFC were superior at restoring perfusion and better engrafted when injected into ischemic hind limbs. Transcriptomic analysis identified cyclin-dependent kinase (CDK) cell cycle inhibiting genes (p16, p21, and p57), the Notch signaling pathway (dll1, dll4, hes1, and hey1), and the endothelial cytokine il33 as highly expressed in CD34 + ECFC. Blocking the Notch pathway using a γ-secretase inhibitor (DAPT) led to reduced expression of cell cycle inhibitors, increased cell proliferation followed by a loss of self-renewal, and HPP colony formation capacity reflecting progenitor exhaustion. Similarly shRNA knockdown of p57 strongly affected self-renewal of ECFC colonies. ECFC hierarchy is defined by Notch signalling driving cell cycle regulators, progenitor quiescence and self-renewal potential.
Temporal regulation of natural killer T cell interferon gamma responses by β-catenin-dependent and-independent wnt signaling
Publisher: Frontiers Media SA
Date: 16-03-2018
R-propranolol is a small molecule inhibitor of the SOX18 transcription factor in a rare vascular syndrome and hemangioma
Publisher: eLife Sciences Publications, Ltd
Date: 30-07-2019
DOI: 10.7554/ELIFE.43026
Abstract: Propranolol is an approved non-selective β-adrenergic blocker that is first line therapy for infantile hemangioma. Despite the clinical benefit of propranolol therapy in hemangioma, the mechanistic understanding of what drives this outcome is limited. Here, we report successful treatment of pericardial edema with propranolol in a patient with Hypotrichosis-Lymphedema-Telangiectasia and Renal (HLTRS) syndrome, caused by a mutation in SOX18. Using a mouse pre-clinical model of HLTRS, we show that propranolol treatment rescues its corneal neo-vascularisation phenotype. Dissection of the molecular mechanism identified the R(+)-propranolol enantiomer as a small molecule inhibitor of the SOX18 transcription factor, independent of any anti-adrenergic effect. Lastly, in a patient-derived in vitro model of infantile hemangioma and pre-clinical model of HLTRS we demonstrate the therapeutic potential of the R(+) enantiomer. Our work emphasizes the importance of SOX18 etiological role in vascular neoplasms, and suggests R(+)-propranolol repurposing to numerous indications ranging from vascular diseases to metastatic cancer.
Long-term deaths from melanoma according to tumor thickness at diagnosis
Publisher: Wiley
Date: 28-02-2020
DOI: 10.1002/IJC.32930
Fetal-cell microchimerism, lymphopoiesis, and autoimmunity
Publisher: Springer Science and Business Media LLC
Date: 18-08-2009
DOI: 10.1007/S00005-009-0044-7
Abstract: During all human and murine pregnancies, fetal cells enter the maternal circulation and tissues and may persist there for decades. The immune consequences of this phenomenon have been explored for many years as a potential origin of autoimmunity or protection from cancer in women after pregnancy. The leading hypothesis, suggesting that semi-allogenic fetal T cells may trigger a graft-versus-host type of disease, has been supported by several studies showing an increased frequency of fetal-cell microchimerism (FMc) in women affected with systemic sclerosis. However, a large proportion of healthy women or women affected with non-immune disorders also display fetal T cells, challenging the direct pathogenic role of such cells. In addition, recent evidence showing the transfer of various fetal progenitor cells to the mother during gestation has shed new light on the interpretation of microchimerism in autoimmunity. This review discusses the functional capacity of fetal hematopoietic progenitors to form T and B cells in maternal hematopoietic tissues, where they undergo an educational process probably resulting in tolerance to maternal antigens. Therefore, hypotheses other than the transfer of fetal cells to the mother's circulation should be considered in explaining the observed association of FMc and autoimmune disorders.
Pathways from Diagnosis to Death from Keratinocyte Cancer in Kidney Transplant Recipients
Publisher: S. Karger AG
Date: 2022
DOI: 10.1159/000524120
Abstract: b i Background: /i /b Kidney transplant recipients are at increased risk of developing and dying from keratinocyte cancer. We aimed to describe the clinical course of keratinocyte cancer-related deaths in a cohort of kidney transplant recipients. b i Methods: /i /b In kidney transplant recipients transplanted between 1995 and 2014 in Queensland, Australia, we ascertained keratinocyte cancer deaths by searching national transplant and state death registries to March 2020. Deceased transplant recipients’ medical records were reviewed to assess features of the primary lesion of the fatal keratinocyte cancer, metastases, and clinical information before death. b i Results: /i /b Of 658 kidney transplant recipient deaths, 49 (7%) were due to keratinocyte cancer, and medical records were available for 36 (73%). One death was due to basal cell carcinoma, and 35 were from squamous cell carcinoma (SCC), primarily from the head and neck (24 69%). The most common site of metastasis was the lungs (21 58%). Median time (minimum, maximum) from the diagnosis of primary SCC to metastasis was 5 months (0, 29). After this, the median time to death was 9 months (1, 50). b i Conclusion: /i /b Fatal keratinocyte cancers overwhelmingly arise on the head and neck, with lungs the most common metastasis site. The short time from diagnosis of primary to death indicates the aggressive nature of these keratinocyte cancers.
Differential Effects of Ultraviolet Irradiation in Neonatal Versus Adult Mice are Not Explained By Defective Macrophage or Neutrophil Infiltration
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1038/JID.2014.78
Abstract: Epidemiological studies suggest that ultraviolet B exposure (UVR) during childhood is the most important environmental risk factor for melanoma. In accordance, neonatal, but not adult, UVR exacerbates melanoma incidence in mouse models. The inability of neonates, as opposed to adults, to mount a proper neutrophil inflammatory response in the skin upon UVR exposure has been one of the driving hypotheses explaining this observation for the past decade. However, this aspect remains controversial. Here, we evaluated the UVR-induced inflammatory response in neonatal versus adult mice. In neonates, a significant neutrophil infiltration could be identified and quantified using three different antibodies by flow cytometry or immunohistochemistry. On day 1 after UVR, neutrophils were increased by 84-fold and on day 4 macrophages increased by 37-fold compared with nonexposed age-matched skin. When compared with adults, neonatal skin harbored a higher proportion of neutrophils in the myeloid compartment without significant differences in absolute counts. This response was reproduced with different kinetics in C57Bl/6 and FVB mice with a more rapid attenuation of neutrophil counts in the latter. Overall, our results suggest that the greatly increased sensitivity to melanomagenesis in neonates does not result from their incompetence in terms of myeloid inflammatory response to UVR.
A molecular classification of human mesenchymal stromal cells
Publisher: PeerJ
Date: 24-03-2016
DOI: 10.7717/PEERJ.1845
Abstract: Mesenchymal stromal cells (MSC) are widely used for the study of mesenchymal tissue repair, and increasingly adopted for cell therapy, despite the lack of consensus on the identity of these cells. In part this is due to the lack of specificity of MSC markers. Distinguishing MSC from other stromal cells such as fibroblasts is particularly difficult using standard analysis of surface proteins, and there is an urgent need for improved classification approaches. Transcriptome profiling is commonly used to describe and compare different cell types however, efforts to identify specific markers of rare cellular subsets may be confounded by the small s le sizes of most studies. Consequently, it is difficult to derive reproducible, and therefore useful markers. We addressed the question of MSC classification with a large integrative analysis of many public MSC datasets. We derived a sparse classifier (The Rohart MSC test) that accurately distinguished MSC from non-MSC s les with % accuracy on an internal training set of 635 s les from 41 studies derived on 10 different microarray platforms. The classifier was validated on an external test set of 1,291 s les from 65 studies derived on 15 different platforms, with % accuracy. The genes that contribute to the MSC classifier formed a protein-interaction network that included known MSC markers. Further evidence of the relevance of this new MSC panel came from the high number of Mendelian disorders associated with mutations in more than 65% of the network. These result in mesenchymal defects, particularly impacting on skeletal growth and function. The Rohart MSC test is a simple in silico test that accurately discriminates MSC from fibroblasts, other adult stem rogenitor cell types or differentiated stromal cells. It has been implemented in the www.stemformatics.org resource, to assist researchers wishing to benchmark their own MSC datasets or data from the public domain. The code is available from the CRAN repository and all data used to generate the MSC test is available to download via the Gene Expression Omnibus or the Stemformatics resource.
Prospective study of patterns of surgical management in adults with primary cutaneous melanoma at high risk of spread, in Queensland, Australia
Publisher: Wiley
Date: 08-2015
DOI: 10.1002/JSO.24013
Abstract: Knowledge of variation in diagnosis and surgery in high-risk primary melanoma patients is limited. We assessed frequency and determinants of diagnostic procedures, wide local excision (WLE) and sentinel lymph node biopsy (SLNB). People in Queensland newly diagnosed with melanoma, clinical stage 1b or 2, were recruited prospectively. Patient information was collected from questionnaires and pathology records. Differences in surgical procedures in relation to host and tumor characteristics were assessed. In 787 participants, primary melanoma was diagnosed by surgical excision (74%), shave (14%), punch (12%) or incisional (1%) biopsy. General practitioners (GPs) diagnosed 80%. Diagnostic procedure differed by remoteness of residence, health sector, treating doctor's specialty and melanoma site and thickness. 766 patients had WLE, 86% by surgeons. Of 134 residual melanomas, 13 (10%) were ≤ 1 mm at diagnosis but > 1 mm at WLE, mostly after shave biopsy. SLNB was performed in 261 (33%) patients. SLNB was more common in those under 50, in remoter locations or treated by GP initially, and less common with head and neck melanoma. Diagnostic and surgical procedures for primary melanoma vary substantially and partial biopsy can influence initial tumor microstaging. Patient, tumor and doctor characteristics influence SLNB practice.
Does Pregnancy After a Diagnosis of Melanoma Affect Prognosis? Systematic Review and Meta-analysis
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2015
Potential Role of Cathepsin K in Regulation of Micro Tumor Environment, Onset and Progression of Cancers in Human- A Review
Publisher: MDPI AG
Date: 27-03-2020
DOI: 10.20944/PREPRINTS202003.0405.V1
Abstract: The effect of proteolytic enzymes including Cathepsin K, a cysteine cathepsin, in onset and progression of cancers in human has been research intensive. Cathepsin K involves in many aspects and stages of cancers including apoptosis, cell proliferation, cancer immunology, inflammatory cell recruitment to tumors and aiding in the process of mobilization of normal healthy cells from their tissue compartments assisting in metastasis and angiogenesis. The objective of this review is to collect together and summarize and analyze the biochemical and physiological pathways of how cathepsin K is involved in onset and progression of cancers with more emphasis on breast and prostate cancers and cathepsin K regulated mechanisms underlying metastasis of such cancers to bones. Information for the review was gathered through published literature from global databases such as Google Scholar, PUBMED and NCBI on different studies on physiological interactions between enzymatic activity of cathepsin K with cancers and metastasis to bones. Analysis of published studies reveal that immunohistochemical studies of breast cancer cells indicate that they overexpress cathepsin K resulting in induction of aberrant mechanisms of cell signaling in breast cancers, creating a higher tendency for their metastasis to bones. Immunohistochemical, immunoprecipitation and fluorgenic assays of several studies done on the association of the same enzymatic activity on prostate cancers shows elevated levels of cathepsin K. Lesions derived from prostate cancer cell masses were observed to undergo increased bone formation and resorption levels. Such resorption levels cause secretion of biological factors promoting tumor expansion. In addition, studies indicate that Cathepsin K was observed to be a key component promoting higher bone resorption levels in patients suffering from cancer. Authors suggest that, to completely understand the association of cathepsin K on cancerous cells and their mechanism in metastasis, distributary patterns of cathepsin K in healthy human tissues needs to be extensively studied initially. It is also suggested that metastasis of breast and prostate cancers to bone could be terminated and overcome by successful production of efficient and precise inhibitory therapeutics targeting the enzymatic activity of Cathepsin K with minimum unintended adverse health effects.
Keratinocyte Sonic Hedgehog Upregulation Drives the Development of Giant Congenital Nevi via Paracrine Endothelin-1 Secretion
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.JID.2017.10.032
Abstract: Giant congenital nevi are associated with clinical complications such as neurocutaneous melanosis and melanoma. Virtually nothing is known about why some in iduals develop these lesions. We previously identified the sonic hedgehog (Shh) pathway regulator Cdon as a candidate nevus modifier gene. Here we validate this by studying Cdon knockout mice, and go on to establishing the mechanism by which Shh exacerbates nevogenesis. Cdon knockout mice develop blue nevi without the need for somatic melanocyte oncogenic mutation. In a mouse model carrying melanocyte NRAS
Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma
Publisher: Wiley
Date: 04-04-2016
DOI: 10.1002/IJC.30085
Abstract: Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study s le was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study s le died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed.
Evolution of skin cancer numbers in solid organ transplant recipients: a pilot study
Publisher: Wiley
Date: 16-08-2021
DOI: 10.1111/AJD.13685
Subcutaneous neurofibromas are associated with mortality in neurofibromatosis 1: A cohort study of 703 patients
Publisher: Wiley
Date: 2005
DOI: 10.1002/AJMG.A.30394
Abstract: Neurofibromatosis 1 (NF1) is a common genetic disorder with an autosomal dominant mode of inheritance, an increased morbidity and mortality, and a shorter lifespan. Although the disease is fully penetrant by the age of 8, the variability in symptoms and complications is high, even among members of the same family. The aim of this study was to identify easily recognizable clinical features that may be associated with mortality in a cohort of patients affected with NF1. We used prospectively collected data from the Neurofibromatosis Institute Database (NFID) and included in our analysis 703 patients who fulfilled the NIH diagnostic criteria for NF1. Clinical, especially dermatological features were tested as potential factors associated with mortality. Among the patients, 405 (57.6%) were children and 298 (42.4%) were adults. The mean follow-up was 2.4 years (median = 0.98, range: 0-15.3 years). Forty patients died during follow-up, mostly due to tumor development such as sarcoma (n = 18). In the adult population, subcutaneous neurofibromas (odds ratio [OR] = 3.6, 95% confidence interval (CI): [1.2-11.3], P = 0.02) and male gender (OR = 5.6, [1.5-20.9], P = 0.004) were independent predictors of mortality after adjustment for age. Among children, the presence of facial plexiform neurofibromas and pruritus were significantly associated with mortality in univariate analysis. Our study describes independent risk factors of mortality in a large cohort of adult and pediatric patients. Close follow-up should be obtained for patients presenting with subcutaneous neurofibromas.
Manifestations cutanées associées aux maladies inflammatoires chroniques intestinales
Publisher: Elsevier BV
Date: 11-2009
Clustering of prevention behaviours in patients with high‐risk primary melanoma
Publisher: Wiley
Date: 07-11-2018
DOI: 10.1002/PON.4565
Abstract: Because melanoma patients are at high risk of further disease, we aimed to study their melanoma prevention behaviours. In a large cohort of patients newly diagnosed with high-risk melanoma in Queensland, Australia, we assessed clustering of preventive behaviours using latent class analysis. We assessed associated factors with prevalence proportion ratios (PPRs) and 95% confidence intervals (CIs) estimated by Poisson regression and also if preventive behaviour was associated with better tumour prognosis at diagnosis. Among 789 primary melanoma patients (57% male 21% with previous melanoma), we identified 4 different behaviour clusters: "no/ low prevention" (34% of cohort), "sun protection only" (25%), "skin checks only" (25%), and "sun protection and skin checks" (17%). Prevalence of clusters differed between males and females and also the component behaviours. Preventive behaviours were associated with having skin that burned and past cutaneous cancer, and for males, combined sun protective and skin checking behaviour was associated with higher education and non-smoking. In patients with no past history of cutaneous cancer, males in the "skin checks only" cluster had significantly reduced chances of a thick (poor prognosis) melanoma (PPR = 0.79, 95% CI 0.68, 0.91) and females in the "sun protection and skin checks" cluster were significantly less likely to have an ulcerated melanoma (PPR = 0.85, 95% CI 0.74, 0.98) compared with the "no/ low prevention" cluster. These findings allow tailoring of preventive advice to melanoma patients to reduce their risk of future primary and recurrent disease.
Limited functional capacity of microchimeric fetal hematopoietic progenitors acquired by mothers during pregnancy
Publisher: Elsevier BV
Date: 10-2010
Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types
Publisher: The Company of Biologists
Date: 15-05-2017
DOI: 10.1242/DEV.143917
Abstract: SOX family proteins SOX2 and SOX18 have been reported as being essential in determining hair follicle type however, the role they play during development remains unclear. Here, we demonstrate that Sox18 regulates the normal differentiation of the dermal papilla of all hair types. In guard (primary) hair dermal condensate (DC) cells, we identified transient Sox18 in addition to SOX2 expression at E14.5, which allowed fate tracing of primary DC cells until birth. Similarly, expression of Sox18 was detected in the DC cells of secondary hairs at E16.5 and in tertiary hair at E18.5. Dominant-negative Sox18 mutation (opposum) did not prevent DC formation in any hair type. However, it affected dermal papilla differentiation, restricting hair formation especially in secondary and tertiary hairs. This Sox18 mutation also prevented neonatal dermal cells or dermal papilla spheres from inducing hair in regeneration assays. Microarray expression studies identified WNT5A and TNC as potential downstream effectors of SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts as a mesenchymal molecular switch necessary for the formation and function of the dermal papilla in all hair types.
Concise Review: Functional Definition of Endothelial Progenitor Cells: A Molecular Perspective.
Publisher: Oxford University Press (OUP)
Date: 05-07-2016
Abstract: The development of a therapy using endothelial progenitor cells provides great hope for patients in treating cardiovascular diseases going forward. For continual development of this therapy toward the clinical, further understanding of the fundamental biology of these cells is required. This will enable a greater understanding of their stemness capacity and provide insight into their ability to differentiate and drive tissue regeneration when injected into a host.
Fetal progenitor cells naturally transferred through pregnancy participate in inflammation and angiogenesis during wound healing
Publisher: Wiley
Date: 05-10-2011
DOI: 10.1096/FJ.11-180695
Abstract: The phenotype and fate of fetal microchimeric cells transfered into the maternal circulation during pregnancy are not well described. Since progenitors from distal sites mobilize during wound healing, we analyzed the recruitment and plasticity of fetal progenitors into maternal wounds. Wounds were generated on normal and bleomycin-induced fibrotic skin of parous or pregnant wild-type females with fluorescent GFP(+) fetuses. Analyses were performed on skin and blood specimens through PCR, immunohistochemistry, and flow cytometry. Controls consisted of parous and pregnant females without wounds and virgin females with wounds. Fetal cells were detected in all skin specimens of parous mice as long as healing was not achieved. During early stages of wound healing, fetal cells expressed mainly leukocyte markers, while in later phases endothelial markers prevailed. Fetally derived vessels connected to maternal circulation were also found, demonstrating the transfer of fetal endothelial progenitor cells. Wounding mobilized fetal CD34(+)ckit(-) cells into the blood during pregnancy. Most of this population was CD11b(-)VEGFR2(-). Another part was CD11b(+) with a fraction expressing VEGFR2. VEGFa-spiked Matrigel plugs partially mimicked this fetal progenitor recruitment and mobilization into the blood. In summary, fetal cells that mobilize in response to wounding are mainly progenitor cells and participate in angiogenesis and inflammation.
Acute myelogenous leukemia in a patient receiving etanercept for psoriasis
Publisher: Elsevier BV
Date: 2007
Lichen plan buccal érosif associé à un syndrome de Good
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.REVMED.2009.12.010
Abstract: Good syndrome is characterized by thymoma, hypogammaglobulinemia, low number of peripheral B cells, and variably, peripheral CD4 T cell lymphopenia and inverted CD4/CD8 T cell ratio, associated with infections and autoimmune diseases. We report an 85-year-old woman who presented with oral erosive lichen planus and thymic tumor. Improvement of oral erosive lichen planus was observed after resection of a benign thymoma, but was ineffective on the immunodeficiency syndrome. Only 11 patients with Good syndrome and lichen planus have been previously reported and are reviewed. The association of oral erosive lichen planus with Good syndrome is rare, but does not seem to be fortuitous.
Clinical and biological determinants of melanoma progression: Should all be considered for clinical management?
Publisher: Wiley
Date: 25-05-2015
DOI: 10.1111/AJD.12348
Abstract: Cutaneous melanoma is a heterogeneous disease affecting the regulation of multiple genes and proteins that contribute to melanoma progression. Survival for patients with locally invasive disease varies greatly, even within tumour stages based on current prognostic criteria. This has prompted investigations into the value of additional clinical or biological parameters predicting survival. In particular, the improved knowledge of tumour biology has fed the hope that the outcome may be predicted at the molecular level. The prognostic value of numerous potential biomarkers has therefore been evaluated in protein and gene expression studies, and genomic associations with melanoma prognosis are beginning to emerge. These potential biomarkers interrogate key tumour and host processes important for tumour development and progression, such as proliferation, invasion and migration through epithelial mesenchymal transition or the host immune or vascular responses. This research may allow more in idualised information on prognosis if the challenges regarding the quality and validation of studies are overcome.
Perinatal Tissue-Derived Endothelial Progenitor Cells
Publisher: Springer International Publishing
Date: 2016
The utility of an erythroblast scoring system and gender-independent short tandem repeat (STR) analysis for the detection of aneuploid fetal cells in maternal blood
Publisher: Wiley
Date: 2005
DOI: 10.1002/PD.1199
Abstract: The aim of this study was to determine whether fetal nucleated red blood cells (NRBCs) could be distinguished from maternal cells in peripheral blood using an erythroblast scoring system based on the unique morphological and hemoglobin staining characteristics of this cell type. Presumptive fetal NRBCs were further analyzed for the presence of paternally inherited DNA polymorphisms to prove fetal origin. NRBCs were isolated by density gradient separation, CD15/45 depletion, and gamma hemoglobin positive selection from peripheral blood of nine women following termination of pregnancy for trisomy 21 (n=4), 18 (n=1), 13 (n=2), and other genetic abnormalities (n=2). Candidate fetal NRBCs, based on four discrete morphological and hemoglobin staining criteria, were then subjected to fluorescent PCR (polymerase chain reaction) lification of chromosome 21 (D21S1411, D21S11) and chromosome 18 (D18S535) short tandem repeat (STR) DNA polymorphisms. In all cases, candidate fetal NRBCs were accurately identified on the basis of morphologic and hemoglobin staining characteristics and confirmed to be fetal in origin based on the presence of shared and nonshared polymorphic DNA alleles when compared to DNA isolated from maternal cells. Using the erythroblast scoring system and subsequent analysis of inherited DNA polymorphisms, we were able to distinguish fetal NRBCs from maternal cells and prove fetal origin independent of gender. These results suggest that this novel combined approach to fetal cell isolation and genetic analysis is a promising method for noninvasive prenatal diagnostic applications.
Early phase of maternal skin carcinogenesis recruits long-term engrafted fetal cells
Publisher: Wiley
Date: 12-2008
DOI: 10.1002/IJC.23819
Abstract: During pregnancy, fetal cells enter the maternal circulation. These may be mesenchymal stem cells, haematopoietic or endothelial progenitors, which may persist for decades and be recruited to damaged maternal tissues. Recently, fetal cells were also identified in tumour tissues such as cervical cancer and breast carcinomas. However, the timing of malignant tumour infiltration was not demonstrated. In this study, we used two step carcinogenesis to assess the presence of fetal cells in early phases of skin tumour formation in previously pregnant mice. Wild-type female C57/BL6 mice were bred to transgenic mice for EGFP. After delivery, skin papillomas were induced by two-step carcinogenesis. The tumours were dissected 9 months after gestation. Fetal cells were identified in 75% of cutaneous papillomas (9/12 tumours), but never in normal skin from the same mice. Fetal cells expressed von-Willebrand factor, and less frequently CD45 or cytokeratin but did not express the tumoral epidermal keratins. Our study shows that long-term engrafted fetal cells home to early stage skin tumours where they participate in formation of the stroma.
Intrauterine Bone Marrow Transplantation in Osteogenesis Imperfecta Mice Yields Donor Osteoclasts and Osteomacs but Not Osteoblasts
Publisher: Elsevier BV
Date: 11-2015
Combination of human endothelial colony-forming cells and mesenchymal stromal cells exert neuroprotective effects in the growth-restricted newborn
Publisher: Springer Science and Business Media LLC
Date: 18-11-2021
DOI: 10.1038/S41536-021-00185-5
Abstract: The foetal brain is particularly vulnerable to the detrimental effects of foetal growth restriction (FGR) with subsequent abnormal neurodevelopment being common. There are no current treatments to protect the FGR newborn from lifelong neurological disorders. This study examines whether pure foetal mesenchymal stromal cells (MSC) and endothelial colony-forming cells (ECFC) from the human term placenta are neuroprotective through modulating neuroinflammation and supporting the brain vasculature. We determined that one dose of combined MSC-ECFCs (cECFC 10 6 ECFC 10 6 MSC) on the first day of life to the newborn FGR piglet improved damaged vasculature, restored the neurovascular unit, reduced brain inflammation and improved adverse neuronal and white matter changes present in the FGR newborn piglet brain. These findings could not be reproduced using MSCs alone. These results demonstrate cECFC treatment exerts beneficial effects on multiple cellular components in the FGR brain and may act as a neuroprotectant.
Two Observations Raising Questions about Risk Factors of Cutaneous Necrosis Induced by Terlipressin (Glypressin®)
Publisher: S. Karger AG
Date: 2009
DOI: 10.1159/000195676
Abstract: i Introduction: /i Triglycyl lysine vasopressin (terlipressin, Glypressin®) is a potent vasoconstrictive drug which became popular because of its prolonged duration of action, ease of administration and lower incidence of side effects. Ischemic complications are rare but may be life threatening. i Observations: /i Case 1, a 68-year-old man with alcoholic cirrhosis and hepatocellular carcinoma, was admitted due to acute functional renal failure. He was first treated for septic shock with intravenous catecholamines. He then developed hepatorenal syndrome and received terlipressin as intravenous bolus (4 mg/day). Three days later, he presented a diffuse purpuric and necrotic eruption with tongue ischemia. He died from i Staphylococcus aureus /i infection. Case 2, a 74-year-old man with metastatic carcinoma, presented severe renal insufficiency. He developed sepsis and pseudohepatorenal syndrome, which was treated with terlipressin (0.5 mg/h) using an infusion pump. Four days later, he developed an isolated large erythematous and purpuric macular plaque of the scalp near skin metastases. The patient died a few weeks later from tumor progression. In both cases, skin biopsies showed ischemic necrosis caused by thrombosis of superficial dermal capillaries. i Conclusion: /i These cases point to the risk of either widespread or localized necrosis. Although the precise incidence of these events as well as risk factors remain to be determined, hypovolemia, concomitant administration of vasoactive drugs and the mode of administration of terlipressin may influence the occurrence of these complications.
Interleukin‐23 regulates interleukin‐17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization
Publisher: Wiley
Date: 05-01-2018
Anxiety and depression after diagnosis of high-risk primary cutaneous melanoma: a 4-year longitudinal study
Publisher: Springer Science and Business Media LLC
Date: 09-06-2020
The influence of fetal loss on the presence of fetal cell microchimerism: A systematic review
Publisher: Wiley
Date: 11-2003
DOI: 10.1002/ART.11324
Abstract: Fetal cells enter the maternal circulation during most pregnancies. Their persistence for years occurs in only some women and has been associated with several autoimmune diseases such as systemic sclerosis. The objective of this study was to determine whether pregnancy history influences the persistence of fetal microchimeric cells. We reviewed all reports of studies on fetal cell microchimerism, defined as male DNA in maternal tissue, that describe in idual pregnancy histories, disease diagnoses, and microchimerism status. The total numbers of pregnancies, births, and sons, the history of fetal loss (spontaneous abortion and elective termination), and the presence of a maternal autoimmune disease were tested as factors potentially associated with persistent microchimerism. One hundred twenty-four subjects from 11 studies met the inclusion criteria. Only fetal loss was significantly associated with the presence of microchimerism (odds ratio 2.4, 95% confidence interval 1.2-6.0). These results suggest that fetomaternal cell trafficking following fetal loss may be important for the engraftment of microchimeric cells in maternal tissue. This may be due to an increased amount of fetomaternal transfusion or to transfer of a cell type that is more likely to engraft. We recommend that investigators in future studies on microchimerism report detailed pregnancy information, since these data are critical for the understanding of factors that influence the development of fetal cell microchimerism.
Risk of Melanoma Recurrence After Diagnosis of a High-Risk Primary Tumor
Publisher: American Medical Association (AMA)
Date: 06-2019
Sox9 and Rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors
Publisher: Springer Science and Business Media LLC
Date: 07-05-2021
DOI: 10.1038/S41467-021-22717-9
Abstract: Endothelial to mesenchymal transition (EndMT) is a leading cause of fibrosis and disease, however its mechanism has yet to be elucidated. The endothelium possesses a profound regenerative capacity to adapt and reorganize that is attributed to a population of vessel-resident endovascular progenitors (EVP) governing an endothelial hierarchy. Here, using fate analysis, we show that two transcription factors SOX9 and RBPJ specifically affect the murine EVP numbers and regulate lineage specification. Conditional knock-out of Sox9 from the vasculature ( Sox9 fl/fl /Cdh5-Cre ER RosaYFP ) depletes EVP while enhancing Rbpj expression and canonical Notch signalling. Additionally, skin wound analysis from Sox9 conditional knock-out mice demonstrates a significant reduction in pathological EndMT resulting in reduced scar area. The converse is observed with Rbpj conditionally knocked-out from the murine vasculature ( Rbpj fl/fl /Cdh5-CreER RosaYFP ) or inhibition of Notch signaling in human endothelial colony forming cells, resulting in enhanced Sox9 and EndMT related gene ( Snail, Slug, Twist1, Twist2, TGF-β ) expression. Similarly, increased endothelial hedgehog signaling ( Ptch1 fl/fl /Cdh5-CreER RosaYFP ), that upregulates the expression of Sox9 in cells undergoing pathological EndMT, also results in excess fibrosis. Endothelial cells transitioning to a mesenchymal fate express increased Sox9 , reduced Rbpj and enhanced EndMT. Importantly, using topical administration of siRNA against Sox9 on skin wounds can substantially reduce scar area by blocking pathological EndMT. Overall, here we report distinct fates of EVPs according to the relative expression of Rbpj or Notch signalling and Sox9 , highlighting their potential plasticity and opening exciting avenues for more effective therapies in fibrotic diseases.
Chemoprevention of cutaneous squamous cell carcinoma and its precursors in solid organ transplant recipients using topical sirolimus: A randomized, double-blind, placebo-controlled pilot trial
Publisher: Elsevier BV
Date: 11-2022
Early detection of melanoma: a consensus report from the Australian Skin and Skin Cancer Research Centre Melanoma Screening Summit
Publisher: Elsevier BV
Date: 04-2020
Epidermal mutation accumulation in photodamaged skin is associated with skin cancer burden and can be targeted through ablative therapy
Publisher: American Association for the Advancement of Science (AAAS)
Date: 10-05-2023
Abstract: The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine ( n = 23) and human ( n = 37) epidermal s les. Epidermal mutations accumulated in a UV dose–dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse ( n = 8) and human ( n = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by % ( n = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.
Painful cutaneous nodules in a 57-year-old woman with human immunodeficiency virus infection
Publisher: Oxford University Press (OUP)
Date: 04-2010
Survival in patients with multiple primary melanomas: Systematic review and meta-analysis
Publisher: Elsevier BV
Date: 11-2020
Training and Retaining Physician‒Scientists in Dermatology: Australia
Publisher: Elsevier BV
Date: 2022
Oncogenes and morphogens: intricacies of targeted therapy in cutaneous basal cell carcinoma
Publisher: Oxford University Press (OUP)
Date: 12-2017
DOI: 10.1111/BJD.15988
A Review on Molecular Functional and Structural Characterization of Human Cysteine Cathepsins in Bacterial Expression Systems
Publisher: MDPI AG
Date: 27-11-2019
DOI: 10.20944/PREPRINTS201911.0345.V1
Abstract: Cysteine cathepsins, a class of proteinaceous enzymes, regulate a wide variety of metabolic processes in human including protein breakdown and turnover and immune functions. Eleven cysteine cathepsins have been identified so far and a wide array of studies related to identifying their specific functions, regulation and distribution patterns in tissues have been conducted. However, in recent past, the association of cysteine cathepsins in occurrence and progression of cancers have been identified and this has caused unrest in scientists triggering them to investigate the physiology, biochemical pathways and interactions of these cathepsins in cancer metastasis and therefore has become a noteworthy topic of intensive research. This review focusses and collects together the published work on molecular functional and structural characterization studies that have been done so far on in vitro expression of genes encoding for cysteine cathepsins in the Escherichia coli bacterial expression system. Accordingly, it was found out that all cathepsins except for cathepsins K, C, H, X and W have been expressed this way and the majority of them were found to be expressed in E. coli BL21(DE3) pLysS expression host via pET3 expression vector. In addition, it was also noted that in most of the expression studies, the substrate that was used to validate the enzymatic activity of the recombinant enzyme that was produced was a cysteine residue along with a benzyloxy-carbonyl salt. Through this review, the authors suggest that there is a very high need that all cysteine cathepsins need to be characterized both structurally and functionally on a molecular platform to better understand their interactions including the biochemical pathways. It is also momentous that the mass production of the recombinant forms of these enzymes are facilitated via expression in such bacterial expression systems and in turn, would also provide a strong platform for the development and progression of studies related to human physiology including oncological studies such as cancer metastasis. Moreover, as per biochemical features of the enzymes that could be identified, the production of efficient inhibitors or inducers as per the necessity to improve health and promote wellbeing among the mankind could be facilitated.
Increase in preventive behaviour by organ transplant recipients after sun protection information in a skin cancer surveillance clinic
Publisher: Oxford University Press (OUP)
Date: 05-09-2018
DOI: 10.1111/BJD.16836
Meso-Endothelial Bipotent Progenitors from Human Placenta Display Distinct Molecular and Cellular Identity
Publisher: Elsevier BV
Date: 03-2018
A Murine Kitl Allele Regulates Skin Mast Cell Density across 58 Collaborative Mouse Cross Strains
Publisher: Elsevier BV
Date: 08-2022
Survival of patients with early invasive melanoma down-staged under the new eighth edition of the American Joint Committee on Cancer staging system
Publisher: Elsevier BV
Date: 2019
In vitro pre-vascularisation of tissue-engineered constructs A co-culture perspective
Publisher: Publiverse Online S.R.L
Date: 2014
Dermatological manifestations associated with pregnancy
Publisher: Informa UK Limited
Date: 08-2009
DOI: 10.1586/EDM.09.26
Natural history of fetal cell microchimerism during and following murine pregnancy
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.JRI.2005.02.001
Abstract: In humans, fetal cells enter the maternal circulation during all pregnancies and can persist for decades. Human studies, however, are often limited by the number of subjects and the availability of healthy and diseased tissues for analysis. We sought to develop a murine model to establish the natural history of fetal cell microchimerism in various maternal tissues during and after healthy pregnancies resulting from congenic and allogenic matings. We bred C57BL/6J and DBA/2J virgin female mice to C57BL/6J males transgenic for the enhanced green fluorescent protein (GFP), which shows autosomal dominant inheritance with complete penetrance and is under the control of a ubiquitous chicken beta-actin promoter and a cytomegalovirus enhancer. During pregnancy and at different times after delivery, female mice were sacrificed. Tissues were collected and the presence of the gfp transgene and GFP+ cells was assessed by real-time quantitative PCR and by immunofluorescence. During pregnancy, microchimerism was detected in all tissues from mice carrying GFP+ fetuses. Fetal cells were often mononuclear. The frequency of fetal cells in the lungs was significantly higher compared to other tissues. The level of microchimerism was also significantly higher in congenic compared to allogenic matings. After delivery, the frequency of fetal cells decreased and fetal cells were undetectable at 2 and 3 weeks after the first delivery. However, some mice that had three gestations had detectable fetal cells 3 weeks after their last delivery. Using sensitive methods of detection, we demonstrate that fetal cell microchimerism occurs during all murine pregnancies. We describe a useful model for the study of the consequences of this phenomenon.
Tell me about your stemness. I'll give your cancer risk!
Publisher: Springer Science and Business Media LLC
Date: 09-12-2017
DOI: 10.1038/CDD.2016.144
Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.JAUT.2013.10.005
Abstract: The origins of autoimmunity are not yet understood despite significant advances in immunology. The trafficking of maternal cells to the offspring represents the very first immunological event in foetal life and is reinforced during lactation. The persistence of maternal cells in offspring's tissues and circulation has been associated with several autoimmune disorders. However a direct causal effect has never been demonstrated. Maternal T cells specifically targeting foetal insulin producing cells have been shown to generate islet inflammation without directly participating in this process. Our objective was to evaluate if alloreactive maternal cells could directly trigger a graft-versus host like reaction or indirectly influence the development of the offspring's regulatory T cells favouring autoimmunity. We adopted a breeding strategy comparing genetically identical offspring from either strongly alloreactive transgenic mothers compared to immunodeficient mothers. We detected maternal alloreactive T cells in the offspring and early signs of inflammation in small intestine of 6 weeks old offspring. Interestingly, CD4(+) Foxp3(+) regulatory T cell frequency was diminished in mesenteric lymph nodes from eight months old offspring born of alloreactive mothers compared to offspring of immunodeficient mothers. Our study favours a hypothesis where highly alloreactive maternal cell microchimerism indirectly predisposes offspring to autoimmunity.
Functional Definition of Progenitors Versus Mature Endothelial Cells Reveals Key SoxF-Dependent Differentiation Process.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-02-2016
DOI: 10.1161/CIRCULATIONAHA.116.024754
Abstract: During adult life, blood vessel formation is thought to occur via angiogenic processes involving branching from existing vessels. An alternate proposal suggests that neovessels form from endothelial progenitors able to assemble the intimal layers. We here aimed to define vessel-resident endothelial progenitors in vivo in a variety of tissues in physiological and pathological situations such as normal aorta, lungs, and wound healing, tumors, and placenta, as well. Based on protein expression levels of common endothelial markers using flow cytometry, 3 subpopulations of endothelial cells could be identified among VE-Cadherin+ and CD45– cells. Lineage tracing by using Cdh5cre ERt2 /Rosa-YFP reporter strategy demonstrated that the CD31–/loVEGFR2lo/intracellular endothelial population was indeed an endovascular progenitor (EVP) of an intermediate CD31intVEGFR2lo/intracellular transit lifying (TA) and a definitive differentiated (D) CD31hiVEGFR2hi/extracellular population. EVP cells arose from vascular-resident beds that could not be transferred by bone marrow transplantation. Furthermore, EVP displayed progenitor-like status with a high proportion of cells in a quiescent cell cycle phase as assessed in wounds, tumors, and aorta. Only EVP cells and not TA and D cells had self-renewal capacity as demonstrated by colony-forming capacity in limiting dilution and by transplantation in Matrigel plugs in recipient mice. RNA sequencing revealed prominent gene expression differences between EVP and D cells. In particular, EVP cells highly expressed genes related to progenitor function including Sox9 , Il33 , Egfr , and Pdfgrα. Conversely, D cells highly expressed genes related to differentiated endothelium including Ets1& , Gata2 , Cd31 , Vwf , and Notch . The RNA sequencing also pointed to an essential role of the Sox18 transcription factor. The role of SOX18 in the differentiation process was validated by using lineage-tracing experiments based on S ox18Cre ERt2 /Rosa-YFP mice. Besides, in the absence of functional SOX18/SOXF, EVP progenitors were still present, but TA and D populations were significantly reduced. Our findings support an entirely novel endothelial hierarchy, from EVP to TA to D, as defined by self-renewal, differentiation, and molecular profiling of an endothelial progenitor. This paradigm shift in our understanding of vascular-resident endothelial progenitors in tissue regeneration opens new avenues for better understanding of cardiovascular biology.
Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors
Publisher: Elsevier BV
Date: 06-2020
Murine dorsal hair type is genetically determined by polymorphisms in candidate genes that influence BMP and WNT signalling
Publisher: Wiley
Date: 20-03-2020
DOI: 10.1111/EXD.14090
Genetic Variation in the MAPK/ERK Pathway Affects Contact Hypersensitivity Responses
Publisher: Elsevier BV
Date: 09-2018
5.11 Engineering the Haematopoietic Stem Cell Niche In Vitro
Publisher: Elsevier
Date: 2017
Novel isolation strategy to deliver pure fetal-origin and maternal-origin mesenchymal stem cell (MSC) populations from human term placenta
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.PLACENTA.2014.09.001
Abstract: The placenta is an abundant source of mesenchymal stem/stromal cells (MSC). Although presumed of translationally-advantageous fetal origin, the literature instead suggests a high incidence of either contaminating or pure maternal MSC. Despite definitional criteria that MSC are CD34-, increasing evidence suggests that fetal MSC may be CD34 positive in vivo. We flow sorted term placental digests based on CD34+ expression and exploited differential culture media to isolate separately pure fetal and maternal MSC populations. This method has considerable translational implications, in particular to clinical trials underway with "placental" MSC of uncertain or decidual origin.
Patterns and cost of care according to keratinocyte cancer risk stratification in a volunteer population screening clinic: Real‐world data from the TRoPICS study
Publisher: Wiley
Date: 24-04-2023
DOI: 10.1111/AJD.14054
Abstract: Risk prediction tools have been developed for keratinocyte cancers (KCs) to effectively categorize in iduals with different levels of skin cancer burden. Few have been clinically validated nor routinely used in clinical settings. To assess whether risk prediction tool categories associate with interventions including chemoprophylaxis for skin cancer, and health‐care costs in a dermatologist‐run screening clinic. Adult participants who presented to a walk‐in screening facility were invited to participate. A self‐completed KC risk prediction tool was used to classify participants into one of the five risk categories. Participants subsequently underwent full skin examination by a dermatologist. Dermatological interventions and skin cancer‐related medical prescriptions were documented. Total health‐care costs, both to the health‐care system and patients were evaluated. Of the 507 participants recruited, 5‐fluorouracil cream and nicotinamide were more frequently prescribed in the higher risk groups as chemoprophylaxis ( p 0.005). A significant association with high predicted risk was also observed in the use of cryotherapy and curettage and cautery ( p 0.05). The average health‐care costs associated with a skin check visit increased from $90 ± 37 (standard deviation) in the lowest risk group to $149 ± 97 in the highest risk group ( p 0.0001). We observed a positive association between higher predicted risk of skin cancer and the prescription of chemoprophylaxis and health‐care costs involved with opportunistic community skin cancer screening. A clinical use of risk stratification may be to provide an opportunity for clinicians to discuss skin cancer prevention and chemoprophylaxis with in idual patients.
Whole-Mount Immunofluorescent Staining Coupled to Multicolor Lineage Tracing Model for Analyzing the Spatiotemporal Organization of Epidermal Stem Cells
Publisher: Springer New York
Date: 2018
Abstract: An overall three-dimensional picture of the distribution of epidermal cells at a given time point is of importance to better characterize epidermal progenitors. We introduce a whole-mount immunofluorescent staining coupled to a multicolor lineage tracing model for analyzing the spatiotemporal organization of epidermal stem cells. Laser scanning confocal microscopy with multiple labelling allows for robust imaging of dorsal skin with excellent resolution.
Prospective surface marker-based isolation and expansion of fetal endothelial colony-forming cells from human term placenta
Publisher: Oxford University Press (OUP)
Date: 08-10-2013
Abstract: The term placenta is a highly vascularized tissue and is usually discarded upon birth. Our objective was to isolate clinically relevant quantities of fetal endothelial colony-forming cells (ECFCs) from human term placenta and to compare them to the well-established donor-matched umbilical cord blood (UCB)-derived ECFCs. A sorting strategy was devised to enrich for CD45−CD34+CD31Lo cells prior to primary plating to obtain pure placental ECFCs (PL-ECFCs) upon culture. UCB-ECFCs were derived using a well-described assay. PL-ECFCs were fetal in origin and expressed the same cell surface markers as UCB-ECFCs. Most importantly, a single term placenta could yield as many ECFCs as 27 UCB donors. PL-ECFCs and UCB-ECFCs had similar in vitro and in vivo vessel forming capacities and restored mouse hind limb ischemia in similar proportions. Gene expression profiles were only minimally ergent between PL-ECFCs and UCB-ECFCs, probably reflecting a vascular source versus a circulating source. Finally, PL-ECFCs and UCB-ECFCs displayed similar hierarchies between high and low proliferative colonies. We report a robust strategy to isolate ECFCs from human term placentas based on their cell surface expression. This yielded much larger quantities of ECFCs than UCB, but the cells were comparable in immunophenotype, gene expression, and in vivo functional ability. We conclude that PL-ECFCs have significant bio-banking and clinical translatability potential.
Human primed endothelial colony forming cells exert neuroprotective effects in the growth restricted newborn piglet
Publisher: Cold Spring Harbor Laboratory
Date: 17-02-2021
DOI: 10.1101/2021.02.15.431307
Abstract: The fetal brain is particularly vulnerable to the detrimental effects of fetal growth restriction (FGR) with subsequent abnormal neurodevelopment being common. There are no current treatments to protect the FGR newborn from lifelong neurological disorders. This study examines whether pure fetal mesenchymal stem cells and endothelial colony forming cells (ECFC) from the human term placenta are neuroprotective through modulating neuroinflammation and supporting the brain vasculature. We determined that one dose of these primed ECFCs (pECFC) on the first day of life to the newborn FGR piglet improved damaged vasculature, restored the neurovascular unit, reduced brain inflammation and improved adverse neuronal and white matter changes present in the FGR newborn piglet brain. These findings could not be reproduced using mesenchymal stromal cells alone. These results demonstrate pECFC treatment exerts beneficial effects on multiple cellular components in the FGR brain and act as a neuroprotectant. Stem cell treatment improves brain outcomes in the growth restricted newborn
Endovascular progenitors infiltrate melanomas and differentiate towards a variety of vascular beds promoting tumor metastasis
Publisher: Springer Science and Business Media LLC
Date: 03-01-2019
DOI: 10.1038/S41467-018-07961-W
Abstract: Tumor vascularization is a hallmark of cancer central to disease progression and metastasis. Current anti-angiogenic therapies have limited success prompting the need to better understand the cellular origin of tumor vessels. Using fate-mapping analysis of endothelial cell populations in melanoma, we report the very early infiltration of endovascular progenitors (EVP) in growing tumors. These cells harbored self-renewal and reactivated the expression of SOX18 transcription factor, initiating a vasculogenic process as single cells, progressing towards a transit lifying stage and ultimately differentiating into more mature endothelial phenotypes that comprised arterial, venous and lymphatic subtypes within the core of the tumor. Molecular profiling by RNA sequencing of purified endothelial fractions characterized EVPs as quiescent progenitors remodeling the extracellular matrix with significant paracrine activity promoting growth. Functionally, EVPs did not rely on VEGF-A signaling whereas endothelial-specific loss of Rbpj depleted the population and strongly inhibited metastasis. The understanding of endothelial heterogeneity opens new avenues for more effective anti-vascular therapies in cancer.
Solid Phase Excitation-Emission Matrix Spectroscopy for In-Situ Chemical Analysis of Combustion Aerosols
Publisher: American Chemical Society (ACS)
Date: 22-04-2020
DOI: 10.26434/CHEMRXIV.12167865
Abstract: Exposure to combustion generated aerosols such as PM from residential woodburning, forest fires, cigarette smoke, and traffic emission have been linked to adverse health outcomes. It is important to assess the chemical composition of PM to examine personal exposure. Excitation-emission matrix (EEM) spectroscopy has been shown as a sensitive and cost-effective technique for evaluation of combustion PM composition and as a source apportionment tool. However, EEM measurements are hindered by a solvent extraction step and a need for benchtop instrumentation. Here, we present a methodology that eliminates this labor-intensive s le preparation and allows to automate and miniaturize the detection platform. A miniature electrostatic collector deposits PM s le onto transparent polydimethylsiloxane (PDMS) coated substrate, where PAH components are extracted into solid-phase (SP) solvent and analyzed using EEM spectroscopy in-situ. We evaluated external and internal excitation schemes to optimized signal to noise ratio. Analysis of woodsmoke and cigarette smoke s les showed good agreement with liquid extraction EEM spectra. Internal excitation is hindered by fluorescent interference from PDMS at λ nm. The external excitation EEM spectra are dependent on the incident angle ranges of 30-40⁰ and 55-65⁰ showed the best results. The proposed SP-EEM technique can be used for development of miniaturized sensors for chemical analysis of combustion generated PM.
Understanding Miro GTPases: Implications in the Treatment of Neurodegenerative Disorders
Publisher: Springer Science and Business Media LLC
Date: 06-02-2018
Comparative performance of predictors of death from thin (≤ 1·0 mm) melanoma
Publisher: Oxford University Press (OUP)
Date: 22-07-2021
DOI: 10.1111/BJD.20480
Statins may reduce disease recurrence in patients with ulcerated primary melanoma
Publisher: Oxford University Press (OUP)
Date: 05-04-2020
DOI: 10.1111/BJD.19012
Concise Review: Understanding Clonal Dynamics in Homeostasis and Injury Through Multicolor Lineage Tracing
Publisher: Oxford University Press (OUP)
Date: 26-11-2014
DOI: 10.1002/STEM.1804
Abstract: Lineage tracing is an essential tool to study stem cell fate. Although traditional lineage tracing techniques have considerably advanced our understanding of stem cell behavior, they pose significant limitations for identification and longitudinal tracking of the progeny of in idual stem cells, to compare their behaviors. This is of importance given the well-established heterogeneity among stem cells both in terms of potentialities and proliferative capacities. The recent development of multicolor genetic reporters addressable to specific cell populations largely overcomes these issues. These new “rainbow” technologies provide increased resolution in clonal identification and offer the possibility to study the relative distribution, contacts, tiled arrangement, and competitive interactions among cells or groups of cells of the same type. Stem Cells 2014 :3046–3054
Microchimérisme postgestationnel en pathologie humaine
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.LPM.2008.05.020
Abstract: Microchimerism is defined as the persistence within an in idual of a low level of cells or DNA derived from another in idual. The most common source of microchimerism is pregnancy. Bidirectional transplacental materno-fetal cell trafficking occurs during most pregnancies and chimeric cells can persist in blood or tissues for decades after childbirth. It can leads to fetal (fetal-maternal transfer) or maternal (maternal-fetal transfer) microchimerism. Characterization of cells implied in microchimerism is incompletely known: it could be at least partly, fetal progenitors cells with ability of self renewal and specific differentiation according to the surrounding tissue. The transferred fetal cells can be recruited in various injured maternal tissues (auto-immune diseases, stroma of various tumours associated with pregnancy) but their precise biological role is uncertain. Microchimerism has been implicated in the pathogenesis of autoimmune diseases (especially systemic sclerosis) but current data suggest that fetal microchimeric cells may participate in maternal physiological response and injured tissue repair. Similar observations were made with maternal microchimerism (excepted with juvenile idiopathic inflammatory myopathies whose immunopathogenesis is probably related with transfer of maternal immune cells).
Diagnosis of an additional in situ melanoma does not influence survival for patients with a single invasive melanoma: A registry-based follow-up study
Publisher: Wiley
Date: 18-01-2016
DOI: 10.1111/AJD.12429
Abstract: Using a large (N= 25 493) population-based cohort from Queensland, Australia, we compared melanoma survival among cases with a single invasive melanoma only against those who also had a diagnosis of a single in situ melanoma. After adjustment for sex, age, body site, clinicopathological subtype, thickness and ulceration, it was found that there was no difference (P = 0.99) in 10-year melanoma-specific mortality following a diagnosis of an invasive lesion, whether or not an in situ melanoma was also present. We conclude that in situ melanomas do not alter the prognosis of an invasive melanoma.
Absence of fetal cell microchimerism in cutaneous lesions of lupus erythematosus
Publisher: BMJ
Date: 2005
New insights into naevoid melanomas: a clinicopathological reassessment
Publisher: Wiley
Date: 02-10-2017
DOI: 10.1111/HIS.13317
Abstract: Because the term ‘naevoid melanoma’ has variable clinical and pathological interpretations, we aimed to clarify the features of melanomas referred to as naevoid. A review was undertaken of 102 melanomas diagnosed histopathologically as naevoid melanomas and ascertained by European Organization for Research and Treatment of Cancer Melanoma Group Subcommittee pathologists from their records. We found these could be classified morphologically into three groups. Thirteen melanomas were overlying genuine naevi and were therefore excluded. Of the 89 melanomas considered to be naevoid, 11 presented clinically as exophytic papillomatous nodules with little junctional component and composed of small atypical cells showing numerous mitoses and no change with depth we termed these ‘papillomatous naevoid’ melanomas. The other 78 were flat or only slightly raised, and had a superficial spreading melanoma‐like component with maturation to a small cell, but still an atypical, dermal component we termed these ‘maturing naevoid’ melanomas. We showed that papillomatous and maturing naevoid melanomas also have differing immunochemical profiles. Preliminary clinical follow‐up suggested different outcomes for these two naevoid melanoma types. Melanomas that have been classified as naevoid melanomas comprise two types with distinct clinical, histopathological and immunohistochemical features that may also be prognostically significant.
Fetal cell-free DNA circulates in the plasma of pregnant mice: relevance for animal models of fetomaternal trafficking
Publisher: Oxford University Press (OUP)
Date: 11-2004
Risque de cancer du sein lié à la grossesse
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.JGYN.2007.10.004
Abstract: After a pregnancy, there is a transitory increase in the risk of breast cancer. During the pregnancy, the number of mammary epithelial cells increases massively. This increase seems partly due to the expansion of stem cells and proliferating intermediate cells. This proliferation of epithelial cells is accompanied by angiogenesis and by recruitment of stromal cells, as well as changes of the extracellular matrix. During any pregnancy, there is cell trafficking between mother and foetus. Hematopoietic or mesenchymal foetal stem cells are transferred in maternal circulation and could be used by the tumor as support cells and take part in the tumoral development. The study of the mechanisms of this specific oncogenesis may help to develop chemoprevention strategies.
Calpain Activity Is Essential in Skin Wound Healing and Contributes to Scar Formation
Publisher: Public Library of Science (PLoS)
Date: 16-05-2012
Subtype-Specific Analyses Reveal Infiltrative Basal Cell Carcinomas Are Highly Interactive with their Environment
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.JID.2021.02.760
Abstract: Little is known regarding the molecular differences between basal cell carcinoma (BCC) subtypes, despite clearly distinct phenotypes and clinical outcomes. In particular, infiltrative BCCs have poorer clinical outcomes in terms of response to therapy and propensity for dissemination. In this project, we aimed to use exome sequencing and RNA sequencing to identify somatic mutations and molecular pathways leading to infiltrative BCCs. Using whole-exome sequencing of 36 BCC s les (eight infiltrative) combined with previously reported exome data (58 s les), we determine that infiltrative BCCs do not contain a distinct somatic variant profile and carry classical UV-induced mutational signatures. RNA sequencing on both datasets revealed key differentially expressed genes, such as POSTN and WISP1, suggesting increased integrin and Wnt signaling. Immunostaining for periostin and WISP1 clearly distinguished infiltrative BCCs, and nuclear β-catenin staining patterns further validated the resulting increase in Wnt signaling in infiltrative BCCs. Of significant interest, in BCCs with mixed morphology, infiltrative areas expressed WISP1, whereas nodular areas did not, supporting a continuum between subtypes. In conclusion, infiltrative BCCs do not differ in their genomic alteration in terms of initiating mutations. They display a specific type of interaction with the extracellular matrix environment regulating Wnt signaling.
Protocol for establishing a child and adolescent twin register for mental health research and capacity building in Sri Lanka and other low and middle-income countries in South Asia
Publisher: BMJ
Date: 10-2019
DOI: 10.1136/BMJOPEN-2019-029332
Abstract: Worldwide, 10%–20% of children and adolescents experience mental health conditions. However, most such disorders remain undiagnosed until adolescence or adulthood. Little is known about the factors that influence mental health in children and adolescents, especially in low and middle-income countries (LMIC), where environmental threats, such as poverty and war, may affect optimal neurodevelopment. Cohort studies provide important information on risks and resilience across the life course by enabling tracking of the effects of early life environment on health during childhood and beyond. Large birth cohort studies, including twin cohorts that can be aetiologically informative, have been conducted within high-income countries but are not generalisable to LMIC. There are limited longitudinal birth cohort studies in LMIC. We sought to enhance the volume of impactful research in Sri Lanka by establishing a Centre of Excellence for cohort studies. The aim is to establish a register of infant, child and adolescent twins, including mothers pregnant with twins, starting in the districts of Colombo (Western Province) and Vavuniya (Northern Province). We will gain consent from twins or parents for future research projects. This register will provide the platform to investigate the aetiology of mental illness and the impact of challenges to early brain development on future mental health. Using this register, we will be able to conduct research that will (1) expand existing research capacity on child and adolescent mental health and twin methods (2) further consolidate existing partnerships and (3) establish new collaborations. The initiative is underpinned by three pillars: high-quality research, ethics, and patient and public involvement and engagement (PPIE). Ethical approval for this study was obtained from the Ethics Review Committee of Sri Lanka Medical Association and Keele University’s Ethical Review Panel. In addition to journal publications, a range of PPIE activities have been conducted.
Modifying Porous Silicon with Self-Assembled Monolayers for Biomedical Applications: The Influence of Surface Coverage on Stability and Biomolecule Coupling
Publisher: Wiley
Date: 08-12-2008
Healing of sickle cell ulcers during pregnancy: a favourable effect of foetal cell transfer?
Publisher: Wiley
Date: 10-2008
Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
Current Aspects of the Endocannabinoid System and Targeted THC and CBD Phytocannabinoids as Potential Therapeutics for Parkinson’s and Alzheimer’s Diseases: a Review
Publisher: Springer Science and Business Media LLC
Date: 19-08-2020
DOI: 10.1007/S12035-020-02054-6
Abstract: Neurodegeneration leading to Parkinson’s disease (PD) and Alzheimer’s disease (AD) has become a major health burden globally. Current treatments mainly target controlling symptoms and there are no therapeutics available in clinical practice to preventing the neurodegeneration or inducing neuronal repairing. Thus, the demand of novel research for the two disorders is imperative. This literature review aims to provide a collection of published work on PD and AD and current uses of endocannabinoid system (ECS) as a potential drug target for neurodegeneration. PD is frequently treated with l -DOPA and deep brain stimulation. Recent gene modification and remodelling techniques, such as CRISPR through human embryonic stem cells and induced pluripotent stem cells, have shown promising strategy for personalised medicine. AD characterised by extracellular deposits of amyloid β-senile plaques and neurofibrillary tangles of tau protein commonly uses choline acetyltransferase enhancers as therapeutics. The ECS is currently being studied as PD and AD drug targets where overexpression of ECS receptors exerted neuroprotection against PD and reduced neuroinflammation in AD. The delta-9-tetrahydrocannabinoid (Δ 9 -THC) and cannabidiol (CBD) cannabinoids of plant Cannabis sativa have shown neuroprotection upon PD and AD animal models yet triggered toxic effects on patients when administered directly. Therefore, understanding the precise molecular cascade following cannabinoid treatment is suggested, focusing especially on gene expression to identify drug targets for preventing and repairing neurodegeneration.
Secretome Components from Faecalibacterium prausnitzii Strains A2-165 and AHMP21 Modulate Cutaneous Wound Inflammation
Publisher: Elsevier BV
Date: 11-2020
Presence of Chimeric Maternally Derived Keratinocytes in Cutaneous Inflammatory Diseases of Children: The Example of Pityriasis Lichenoides
Publisher: Elsevier BV
Date: 02-2006
Abstract: During pregnancy, maternal cells may enter the fetal circulation and persist until adulthood. The fate of these cells remains unknown. As unexplained T-cell-mediated conditions such as pityriasis lichenoides (PL) may occur in children, we aimed at identifying maternal cells in lesional skin of PL and controls. Archived skin biopsy specimens from young males with PL, atopic dermatitis, or normal skin were scanned for the presence of female (presumably maternal) cells using fluorescence in situ hybridization (FISH) with X and Y chromosome-specific probes. Phenotyping of maternal cells relied on FISH combined with anti-CD45, anti-CD1a, or anti-cytokeratin labelling, identifying leukocytes, Langerhans cells, and keratinocytes, respectively. Maternal cells were found in PL (11/12) and controls (4/7), but their average frequency was higher in PL: 99 per million cells as compared to 5 per million cells in controls (P = 0.005). In the epidermis, the maternal microchimeric cells were labelled by anti-cytokeratin in all cases. We identified maternally derived keratinocytes in the skin of male children with inflammatory skin disorders. These cells may either help repair the damaged skin or home initially in the skin and trigger a host (child) versus graft (mother) disease.
Fetal cell microchimerism in cancer: a meaningful event?
Publisher: Future Medicine Ltd
Date: 11-2009
DOI: 10.2217/FON.09.111
Abstract: The influence of pregnancy on the occurrence and evolution of maternal tumors has been long debated. Breast carcinomas or melanomas have been suspected to be more severe during gestation. Recently, many investigators have described the transfer and persistence of fetal cells in maternal circulation and tissues during and after pregnancy. These fetal microchimeric cells have been described in a variety of maternal injured tissues where they displayed the host-tissue phenotype. Given the wide variety of injury and tissue types described, cancer has appeared as a potential situation that could be influenced by fetal microchimeric cells. This new unexplored effect of gestation on tumor course has been hypothesized as either protective against cancer, via the activity of allogenic fetal cells, or as promoting cancer, via a supportive role of fetal microchimeric cells in the tumor stroma. In this review, we will detail recent data supporting these hypotheses.
Erythema Nodosum–like Eruption as a Manifestation of Azathioprine Hypersensitivity in Patients With Inflammatory Bowel Disease
Publisher: American Medical Association (AMA)
Date: 06-2007
DOI: 10.1001/ARCHDERM.143.6.744
Abstract: Clinical manifestations of hypersensitivity to azathioprine may mimic symptoms of the initial disease. We report 5 cases of peculiar skin hypersensitivity reactions to azathioprine in patients with inflammatory bowel disease. In 5 patients with a recent azathioprine regimen, manifestations appeared between 8 and 18 days after drug introduction. All patients had a high fever. Three patients initially had erythema nodosum 2 patients had sterile pustules. All had elevated neutrophil counts and serum C-reactive protein levels, whereas eosinophil counts were normal, ruling out drug-induced rash with eosinophilia and systemic symptoms. In 3 patients who were rechallenged with azathioprine or with 6-mercaptopurine, dermatological lesions recurred within hours. Erythema nodosum and pustules are rarely reported manifestations of azathioprine hypersensitivity. Both skin lesions may be related to the clinical activity of inflammatory bowel disease. Relapse of such lesions shortly after thiopurine rechallenge should raise the hypothesis of hypersensitivity rather than pharmacological manifestations.
In Vivo Imaging Reveals a Pioneer Wave of Monocyte Recruitment into Mouse Skin Wounds
Publisher: Public Library of Science (PLoS)
Date: 10-2014
Fetal Cell Microchimerism, a Low‐Grade Naturally Occurring Celltherapy
Publisher: Wiley
Date: 15-07-2009
Hypothesised cutaneous sites of origin of stage III melanomas with unknown primary: A multicentre study
Publisher: Wiley
Date: 25-04-2022
DOI: 10.1002/IJC.34020
Abstract: Based on molecular evidence that melanomas with unknown primary (MUPs) arise from the skin, we hypothesised that sites of MUPs are disproportionately on trunk and lower limbs, sites that are not readily visible to patients and clinicians. We tested this hypothesis by inferring the anatomic site of origin of MUPs from the corresponding known cutaneous sites of melanoma patients with known primary tumours (MKPs). We analysed data from three separate cohorts of patients from Brisbane, Australia (n = 236) Manchester, UK (n = 51) and Padova, Italy (n = 33), respectively, who first presented with stage III melanoma with lymph node metastases. We matched two MKP patients to each MUP patient based on lymph node dissection (LND) site, age and sex, and imputed cutaneous sites of origin of MUPs from their two matched MKPs for study countries, giving two possible sites for each MUP per centre. Overall, results showed that MUP patients were predominantly male, and trunk was the most likely origin, comprising around a third to a half of MUPs across the three cohorts. The remaining MUP inferred sites varied by country. In the Australian cohort, the legs accounted for a third of imputed sites of MUPs, while in the UK and Italian cohorts, the most frequent site was the arms followed by the legs. Our findings suggest the need for regular and thorough skin examination on trunk and limbs, especially in males, to improve early detection of cutaneous melanoma and reduce the risk of metastatic disease at the time of presentation.
Differential roles of the pRb and Arf/p53 pathways in murine naevus and melanoma genesis
Publisher: Wiley
Date: 09-2010
Mesenchymal stem cell therapy in skin: why and what for?
Publisher: Wiley
Date: 25-04-2013
DOI: 10.1111/EXD.12141
Abstract: In recent years, few stem cells have gained as much clinical notoriety as mesenchymal stem cells. Indeed, MSCs are already in use for a range of systemic inflammatory and autoimmune conditions that also affect the skin, such as acute and chronic graft versus host disease or lupus erythematosus. Most interestingly, these cells are able to improve skin wound healing in multiple preclinical models and few patient series. An additional potential of these cells is the delivery of missing structural elements in skin inherited disorders. However, we here contend that MSCs are not appropriate for cell replacement therapies in the context of wound healing. Indeed, engraftment of cells in the dermis is poor in the absence of irradiation and the observed effects seem mainly due to paracrine factors. In this viewpoint, we favour the hypothesis of a replete niche and competition with resident mesenchymal populations in the dermis not allowing the engraftment of newly delivered MSCs. Consequently, we propose that the benefit of MSCs may be at least in part reproduced by the growth factors or immunomodulatory molecules that they produce. In any case, the rapid progress in this field has allowed the emergence of important questions in skin biology that need to be addressed in parallel with the predictable future use of MSCs in the clinic.
Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling
Publisher: Wiley
Date: 24-10-2017
DOI: 10.1096/FJ.201600937
Abstract: The prospect of using endothelial progenitors is currently h ered by their low engraftment upon transplantation. We report that mesenchymal stem/stromal cells (MSCs), independent of source and age, improve the engraftment of endothelial colony forming cells (ECFCs). MSC coculture altered ECFC appearance to an elongated mesenchymal morphology with reduced proliferation. ECFC primed via MSC contact had reduced self-renewal potential, but improved capacity to form tube structures in vitro and engraftment in vivo Primed ECFCs displayed major differences in transcriptome compared to ECFCs never exposed to MSCs, affecting genes involved in the cell cycle, up-regulating of genes influencing mesenchymal transition, adhesion, extracellular matrix. Inhibition of NOTCH signaling, a potential upstream regulator of mesenchymal transition, in large part modulated this gene expression pattern and functionally reversed the mesenchymal morphology of ECFCs. The collective results showed that primed ECFCs survive better and undergo a mesenchymal transition that is dependent on NOTCH signaling, resulting in significantly increased vasculogenic potential.-Shafiee, A., Patel, J., Wong, H. Y., Donovan, P., Hutmacher, D. W., Fisk, N. M., Khosrotehrani, K. Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling.
Elective pregnancy termination and microchimerism: Comment on the article by Khosrotehrani et al
Publisher: Wiley
Date: 2004
DOI: 10.1002/ART.20650
Fetal Endothelial Progenitors and Mesenchymal Stem Cells From the Human Term Placenta
Publisher: Elsevier
Date: 2018
Associations of Statins and Diabetes with Diagnosis of Ulcerated Cutaneous Melanoma
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.JID.2017.07.836
Abstract: Ulcerated primary melanomas are associated with an inflammatory tumor microenvironment. We hypothesized that systemic proinflammatory states and anti-inflammatory medications are also associated with a diagnosis of ulcerated melanoma. In a cross-sectional study of 787 patients with newly diagnosed clinical stage IB or II melanoma, we estimated odds ratios for the association of proinflammatory factors (high body mass index, diabetes, cardiovascular disease, hypertension, and smoking) or the use of anti-inflammatory medications (statins, aspirin, corticosteroids, and nonsteroidal anti-inflammatory drugs), with ulcerated primary melanoma using regression models and subgroup analyses to control for melanoma thickness and mitotic rate. On the basis of information from 194 patients with ulcerated and 593 patients with nonulcerated primary melanomas, regular statin users had lower likelihood of a diagnosis of ulcerated primary melanoma (odds ratio 0.67, 95% confidence interval 0.45-0.99), and this association remained after adjusting for age, sex, thickness, and mitosis. When analysis was limited to melanomas that were ≤2 mm thick and had ≤2 mitoses/mm
Multiplex melanoma families are enriched for polygenic risk
Publisher: Oxford University Press (OUP)
Date: 27-07-2020
DOI: 10.1093/HMG/DDAA156
Abstract: Cancers, including cutaneous melanoma, can cluster in families. In addition to environmental etiological factors such as ultraviolet radiation, cutaneous melanoma has a strong genetic component. Genetic risks for cutaneous melanoma range from rare, high-penetrance mutations to common, low-penetrance variants. Known high-penetrance mutations account for only about half of all densely affected cutaneous melanoma families, and the causes of familial clustering in the remainder are unknown. We hypothesize that some clustering is due to the cumulative effect of a large number of variants of in idually small effect. Common, low-penetrance genetic risk variants can be combined into polygenic risk scores. We used a polygenic risk score for cutaneous melanoma to compare families without known high-penetrance mutations with unrelated melanoma cases and melanoma-free controls. Family members had significantly higher mean polygenic load for cutaneous melanoma than unrelated cases or melanoma-free healthy controls (Bonferroni-corrected t-test P = 1.5 × 10−5 and 6.3 × 10−45, respectively). Whole genome sequencing of germline DNA from 51 members of 21 families with low polygenic risk for melanoma identified a CDKN2A p.G101W mutation in a single family but no other candidate high-penetrance melanoma susceptibility genes. This work provides further evidence that melanoma, like many other common complex disorders, can arise from the joint action of multiple predisposing factors, including rare high-penetrance mutations, as well as via a combination of large numbers of alleles of small effect.
Conditional survival in patients with stage IB‐IIIA melanoma undergoing sentinel node biopsy in Queensland: A longitudinal study
Publisher: Wiley
Date: 18-01-2023
DOI: 10.1111/AJD.13974
Abstract: Tumour characteristics such as thickness and ulceration, along with sentinel lymph node (SLN) status, have been essential in predicting survival in patients with locally invasive melanomas at the time of diagnosis. It is unclear if these prognostic factors are relevant 1, 2 or 5 years after diagnosis. The key aim of this project was to analyse conditional survival in a cohort of Queensland patients with stage IB to IIIA melanomas (American Joint Committee on Cancer's staging system, 8th version) and to test the relevance of clinicopathological prognostic factors for melanoma outcome after varying intervals of survival time. Patients with primary invasive cutaneous melanoma who were referred to a tertiary melanoma clinic and underwent SLN biopsy between 1994 and 2011 were ascertained. The effect of patient and tumour characteristics on melanoma survival were calculated using multivariate Cox proportional hazard models at diagnosis and at variable times after diagnosis. The final analysis included 651 patients (average age 49 years, 55.5% male) with stage IB to IIIA melanoma. At diagnosis, and after 1 and 2 years survived, SLN positivity, thickness and ulceration were predictive of 10‐year survival since diagnosis. However, once patients survived 5 years, only SLN status was predictive. Overall conditional melanoma survival improved with increasing time survived. Five years after diagnosis, 10‐year conditional melanoma survival (MSS) was 91% (95% CI 86%–95%) compared with 85% (82%–88%) predicted at diagnosis. The improvement in MSS was observed mainly for Stage II melanoma patients and not for those with a positive SLN biopsy. This study confirms the improvement of prognosis according to time survived since diagnosis suggesting that after 5 years survival the classic prognostic indicators may not have the same influence.
Fetal Microchimeric Cells Participate in Tumour Angiogenesis in Melanomas Occurring during Pregnancy
Publisher: Elsevier BV
Date: 02-2009
A state-of-the-art review on Ag/AgCl ion-selective electrode used for non-destructive chloride detection in concrete
Publisher: Elsevier BV
Date: 11-2020
Pregnancy-acquired fetal progenitor cells
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JRI.2012.08.004
Abstract: The transfer and persistence of fetal progenitor cells into the mother throughout pregnancy has sparked considerable interest as a trafficking stem cell and immunological phenomenon. Indeed, the intriguing longevity of semi-allogeneic fetal microchimeric cells (FMC) in parous women raises questions over their potential clinical implications. FMC have been associated with both immune-modulatory roles and participation in maternal tissue repair. Although their influence on maternal health is as yet unresolved, FMC selectively home to damaged maternal tissues and often integrate, adopting site-appropriate phenotypes. FMC features, such as plasticity and persistence in their maternal host, suggest that they likely include pluripotent, or various multipotent and committed stem and progenitor cells. Recent efforts to determine what cell types are involved have established that FMC include cells of ectodermal, endodermal, mesodermal, and perhaps trophectodermal lineages. This review details FMC phenotypes and discusses how FMC themselves may be considered a naturally occurring stem cell therapy.
ST2 receptor invalidation maintains wound inflammation, delays healing and increases fibrosis
Publisher: Wiley
Date: 06-10-2015
DOI: 10.1111/EXD.12833
Fetal endothelial and mesenchymal progenitors from the human term placenta: Potency and clinical potential
Publisher: Oxford University Press (OUP)
Date: 13-03-2015
Abstract: Over the last decade, fetal stem cells from a variety of sources have been reported and have shown potential clinical applications. This study briefly reviews recent findings in the fetal stem cell arena, and particularly human term placenta as a robust cell source that harbors large quantities of both fetal and maternal stem cells of various types. It also appraises prospective isolation of large quantities of fetal endothelial progenitor cells and pure preparations of fetal or maternal mesenchymal stromal cells from the same placenta.
Level of contact hypersensitivity response to diphencyprone and keratinocyte cancer
Publisher: Wiley
Date: 19-07-2019
DOI: 10.1111/JDV.15766
Abstract: Keratinocyte cancers (KC) are common and pose a significant financial burden globally. Ultraviolet radiation is a significant factor in their development, through mutagenesis promotion but also through local and systemic immunosuppression. Although systemic immunosuppression is well understood, cutaneous immunity has been more difficult to evaluate. This study used a contact sensitizer, diphencyprone (DPCP), which elicits a contact hypersensitivity reaction in skin, to compare the degree of reactivity to DPCP in patients with a high KC burden versus those with a low KC burden. A prospective study was performed in immunocompetent patients aged 70 ± 5 years of age, comparing patients with a high KC burden (>10 previous KC) with those with a low KC burden (<2 previous KC). All patients were sensitized with 2% DPCP and then patch tested two weeks later with eight different concentrations of DPCP with the threshold concentration and total degree of reaction recorded. Nine patients were recruited, 5 in the 'high cancer' group and 4 in the 'low cancer' group. All patients were Fitzpatrick skin type 1 or 2. All patients developed a reaction to DPCP. Patients in the low cancer group developed a reaction at a significantly lower threshold DPCP concentration than the high cancer group (P = 0.039). The cumulative intensity of reaction was higher in the low cancer group (P = 0.087). Patients with a high KC burden required a higher threshold concentration of DPCP to elicit a hypersensitivity reaction, supporting the concept of a lower skin immunity in these patients. DPCP reactivity threshold could be a useful tool in the evaluation of skin immunity and propensity to develop keratinocyte cancers.
Reply to Meta-analysis concerning mortality for pregnancy-associated melanoma
Publisher: Wiley
Date: 25-09-2015
DOI: 10.1111/JDV.13347
Clinical Risk Factors for Mortality in Patients With Neurofibromatosis 1
Publisher: American Medical Association (AMA)
Date: 02-2003
DOI: 10.1001/ARCHDERM.139.2.187
Abstract: To identify the main clinical features associated with mortality in patients with neurofibromatosis 1. Cohort study. Referral center for neurofibromatosis. Three hundred seventy-eight patients with neurofibromatosis 1 who had more than 1 year of follow-up in the center. Mortality. Clinical features, especially dermatological, were evaluated as potential factors associated with mortality. Factors associated independently with mortality were the presence of subcutaneous neurofibromas (odds ratio, 10.8 95% confidence interval, 2.1-56.7 P<.001), the absence of cutaneous neurofibromas (odds ratio, 5.3 95% confidence interval, 1.2-25.0 P =.03), and facial asymmetry (odds ratio, 11.4 95% confidence interval, 2.6-50.2 P<.01). Some features that can be found by a routine clinical examination are associated with mortality in patients with neurofibromatosis 1. Clinical follow-up should be focused on patients with subcutaneous neurofibromas and/or the absence of cutaneous neurofibromas and/or facial asymmetry.
Sun protection behavior after diagnosis of high-risk primary melanoma and risk of a subsequent primary
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JAAD.2018.06.068
Abstract: Melanoma survivors are at high risk of further primary melanomas. To assess sun behavior after melanoma diagnosis and in relation to further primary melanomas. We applied repeated measures latent class analysis to reported primary prevention behavior at time of diagnosis and every 6 months for 2 years after diagnosis in patients with clinical stage IB or II melanoma. Correlates of behavior trajectories and risk of subsequent primaries were determined by using multivariable logistic and Cox regression analyses, respectively. Among the 448 male and 341 female patients, sunscreen use fell into 3 trajectories: stable never-use (26% of males and 12% of females), stable sometimes-use (35% of males and 29% of females), and increased to often-use (39% of males and 59% of females). Most reduced their weekend sun exposure, but in 82% of males and 69% of females it remained increased. Males, smokers, the less educated, those who tanned, and those not self-checking their skin were more likely to have trajectories of inadequate protection. Patients with a history of melanoma before the study doubled their risk of another primary melanoma in the next 2 years if sunscreen use in that time was inadequate (hazard ratio, 2.45 95% confidence interval, 1.00-6.06). Patient-reported data are susceptible to recall bias. Our results may assist clinicians in identifying patients not using adequate sun protection and providing information for patient counseling.
Supportive care needs, anxiety, depression and quality of life amongst newly diagnosed patients with localised invasive cutaneous melanoma in Queensland, Australia
Publisher: Wiley
Date: 29-10-2015
DOI: 10.1002/PON.3718
Abstract: The aim of this paper is to determine levels of supportive care needs, anxiety, depression and symptoms amongst patients newly diagnosed with localised invasive primary melanoma and if these varied amongst patients who had a sentinel lymph node biopsy (SLNB). We also considered quality of life compared with general population norms. Patients newly diagnosed with clinical stage IB-II invasive melanoma were ascertained through Queensland hospitals, specialist clinics and pathology laboratories. Validated surveys measured 46 need items (Supportive Care Needs Survey-Short Form + melanoma subscale), anxiety and depression (Hospital Anxiety and Depression Scale) and quality of life and symptoms (Functional Assessment of Cancer Therapy-Melanoma). Regression models compared outcomes according to whether or not participants had a SLNB. We surveyed 386 patients, 155 before and 231 after wide local excision, of whom 46% reported ≥1 moderate-level or high-level unmet need. The three highest needs were for help with fears about cancer spreading (17%), information about risk of recurrence (17%) and outcomes when spread occurred (16%). Those who had a SLNB were more likely to report a moderate or high unmet need for help with uncertainty about the future or with lymphoedema (p < 0.05). Overall, 32% of participants had anxiety and 15% had depression regardless of performance of SLNB. Melanoma-specific symptoms were worse in SLNB patients (p = 0.03). Compared with the general population, emotional well-being was lower amongst melanoma patients. A substantial proportion of newly diagnosed patients with localised invasive melanoma need further melanoma-specific information and support with psychological concerns. Patients who have a SLNB clear of disease may need help with symptoms after surgery.
Spot Counting to Locate Fetal Cells in Maternal Blood and Tissue: A Comparison of Manual and Automated Microscopy
Publisher: Wiley
Date: 2007
DOI: 10.1002/JEMT.20439
Abstract: Fetal cell detection in maternal tissue requires an accurate, efficient, and reproducible microscopy method. Our objective was to compare manual scoring to a commercially available automated scanning system for the detection of chromosome signals by fluorescence in situ hybridization (FISH). X and Y chromosome FISH signals were detected on slides of calibrated mixtures of blood, paraffin-embedded liver sections, and post-termination blood. For manual scoring (400x magnification), the number of cells located and duration of scoring were recorded. For automated scanning using the Metasystems Metafer3/Metafer4 Scanning System (200x magnification), duration of scanning, number of gallery images generated, duration of manual review of gallery images, and number of confirmed fetal cells were recorded. From all slides the number of target fetal cells located by manual and automated microscopy was highly correlated (r = 0.90). However, automated scanning required on average 4-fold more time than manual scoring (P < 0.0001), with an average automated scanning time of 9.7 h per slide compared with 2.4 h per slide when scored manually. In general, the accuracy of automated and manual microscopy is comparable, although manual scoring is more efficient because of the level of magnification necessary for automated scanning of cells, and a large number of gallery images generated by automated scanning that must then be reviewed manually. This suggests that when rapid analysis is required (i.e., clinical situations), manual microscopy is preferable. In contrast, automated scanning may have advantages over manual microscopy when time constraints are less imposed (i.e., research situations).
An improved method for efficient recovery of high quality DNA from date palm (Phoenix dactylifera L; Arecaceae)
Publisher: Elsevier BV
Date: 2021
Fetal Microchimeric Cells in a Fetus-Treats-Its-Mother Paradigm Do Not Contribute to Dystrophin Production in Serially ParousmdxFemales
Publisher: Mary Ann Liebert Inc
Date: 10-10-2012
Increased melanoma recurrence in patients with multiple primary invasive melanomas
Publisher: Elsevier BV
Date: 06-2022
Pregnancy‐Acquired Fetal Progenitors as Natural Cell Therapy
Publisher: Wiley
Date: 19-02-2013
Fetal cell microchimerism: helpful or harmful to the parous woman?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2003
DOI: 10.1097/00001703-200304000-00014
Abstract: Fetal cells enter the maternal circulation during most pregnancies and can persist in maternal blood and tissues after delivery. Concerns with regard to the histocompatibility of these fetal cells have raised the question of the long-term consequences of an immune response on maternal health. In the past few years, many investigators have demonstrated an association between the persistence of fetal cells in maternal tissues and blood and maternal autoimmune disease, especially systemic sclerosis. In this review we will summarize more recent data that provide a new insight into bi-directional feto-maternal cell trafficking. Persisting fetal cells have been found in the tissue of women affected with endocrine or infectious disease as well as healthy parous women. These data suggest the possibility that fetal microchimeric cells may also participate in the maternal physiological response to tissue injury. The medical consequences of pregnancy, therefore, appear to extend well beyond delivery.
Lack of Evidence From a Transgenic Mouse Model that the Activation and Migration of Melanocytes to the Epidermis after Neonatal UVR Enhances Melanoma Development
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1038/JID.2015.203
Diet quality is associated with primary melanoma thickness
Publisher: Wiley
Date: 07-05-2022
DOI: 10.1111/JDV.18174
Abstract: Patients' diets can influence the outcome of several common cancers, but the effect on melanoma prognosis is unknown. To assess the association between quality of melanoma patients' prediagnosis diets and primary tumour thickness, the main prognostic indicator for melanoma. We used baseline data from patients newly diagnosed with tumour stage Ib to IV cutaneous melanoma, with completed questionnaires about food intake in the past year and other factors. Diet quality was measured by the Healthy Eating Index (HEI) and melanoma thickness was extracted from histopathology reports. We estimated prevalence ratios (PR adj ) and 95% confidence intervals (CIs) adjusted for confounding factors using Poisson regression models to assess associations between HEI scores and melanoma thickness. Of 634 study patients, 238 (38%) had melanomas mm thick at diagnosis. Patients with the highest HEI scores were significantly less likely to be diagnosed with thick melanoma than patients with lowest HEI scores (PR adj 0.93, 95% CI 0.86–0.99) (P trend = 0.03). There was no evidence of effect modification by age, sex, previous melanoma or comorbidities. Melanoma thickness at diagnosis is significantly associated with quality of patients' diets before diagnosis.
Idiopathic recurrent palmoplantar hidradenitis: a case with late onset and long-lasting course
Publisher: Oxford University Press (OUP)
Date: 03-2007
Endosteal-like extracellular matrix expression on melt electrospun written scaffolds
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.ACTBIO.2016.12.040
Abstract: Tissue engineering technology platforms constitute a unique opportunity to integrate cells and extracellular matrix (ECM) proteins into scaffolds and matrices that mimic the natural microenvironment in vitro. The development of tissue-engineered 3D models that mimic the endosteal microenvironment enables researchers to discover the causes and improve treatments for blood and immune-related diseases. The aim of this study was to establish a physiologically relevant in vitro model using 3D printed scaffolds to assess the contribution of human cells to the formation of a construct that mimics human endosteum. Melt electrospun written scaffolds were used to compare the suitability of primary human osteoblasts (hOBs) and placenta-derived mesenchymal stem cells (plMSCs) in (non-)osteogenic conditions and with different surface treatments. Using osteogenic conditions, hOBs secreted a dense ECM with enhanced deposition of endosteal proteins, such as fibronectin and vitronectin, and osteogenic markers, such as osteopontin and alkaline phosphatase, compared to plMSCs. The expression patterns of these proteins were reproducibly identified in hOBs derived from three in idual donors. Calcium phosphate-coated scaffolds induced the expression of osteocalcin by hOBs when maintained in osteogenic conditions. The tissue-engineered endosteal microenvironment supported the growth and migration of primary human haematopoietic stem cells (HSCs) when compared to HSCs maintained using tissue culture plastic. This 3D testing platform represents an endosteal bone-like tissue and warrants future investigation for the maintenance and expansion of human HSCs. This work is motivated by the recent interest in melt electrospinning writing, a 3D printing technique used to produce porous scaffolds for biomedical applications in regenerative medicine. Our team has been among the pioneers in building a new class of melt electrospinning devices for scaffold-based tissue engineering. These scaffolds allow structural support for various cell types to invade and deposit their own ECM, mimicking a characteristic 3D microenvironment for experimental studies. We used melt electrospun written polycaprolactone scaffolds to develop an endosteal bone-like tissue that promotes the growth of HSCs. We combine tissue engineering concepts with cell biology and stem cell research to design a physiologically relevant niche that is of prime interest to the scientific community.
The effects of a multidisciplinary high-throughput skin clinic on healthcare costs of organ transplant recipients
Publisher: Wiley
Date: 02-05-2019
DOI: 10.1111/JDV.15458
Abstract: A long-term complication among organ transplant recipients (OTRs) is skin malignancies which are associated with level and duration of immunosuppressive treatment, sun exposure and age. Dermatological surveillance is recommended for OTRs at high risk of skin malignancies, but evidence is lacking on the benefits of such services. To examine the economic impact on patients and on the hospital service of a multidisciplinary high-throughput skin cancer clinic in Brisbane, Australia, dedicated to dermatological and surgical care of high-risk OTRs. In a pre ostdesign, hospital admission and cost data were obtained for 101 consecutively enrolled study participants from 12 months prior to the introduction of the clinic (to February 2016), the 3-month 'run-in' period (March to May 2016) and 12 months subsequent (to June 2017). Differences between pre- and post-clinic hospital costs were tested using non-parametric bootstrapping and interrupted time series analysis. A survey of patient out-of-pocket costs and perceived financial burden was also undertaken during the clinic. Overall hospital costs were higher after the clinic but 3-monthly hospital costs for skin procedures trended downwards. Despite 3-monthly mean, hospital visits increasing from 85 to 314, mean 3-monthly costs reduced by AU$1491 (P < 0.001) indicating greater cost efficiency. Total patient out-of-pocket costs were AU$18 377 over 3 months. Clinical costing data revealed higher, more rapid throughput and significantly lower per patient costs pre- and postestablishment of a multidisciplinary skin cancer clinic for OTRs.
Patients undergoing lymphadenectomy for stage III melanomas of known or unknown primary site do not differ in outcome
Publisher: Wiley
Date: 08-2013
DOI: 10.1002/IJC.28318
Abstract: The outcome of patients with palpable melanoma metastases in lymph nodes in the presence (metastatic melanoma of known primary site, MKP) or absence (metastatic melanoma of unknown primary site, MUP) of an identifiable primary tumour remains controversial. Some of the previous studies contained large case series that included historical patients. We aimed to compare outcomes of those with MUPs versus MKPs with palpable lymph node invasion, after staging with modern imaging technology. Aprospective study of patients from a single tertiary institution who were undergoing lymph node dissection for palpable metastatic melanoma between 2000 and 2011 was conducted. All patients were ascertained by computerised tomography scanning and most diagnosed after 2004 had positron emission tomography scanning also. Clinicopathological details about the primary melanoma and lymph node dissections were gathered. Factors associated with recurrence and melanoma-specific mortality in those with MKP and with MUP were assessed using univariate and multivariate analyses. Out of 485 patients studied, 82 had MUP and 403 had MKP. Patients were followed up for a median of 17.4 and 19.0 months, for MKP and MUP, respectively. Five-year adjusted melanoma-specific survival was 58% for MUPs versus 49% for MKPs and was not significantly different between the two groups (adjusted Cox proportional Hazard ratio = 0.88 95% confidence interval [0.58, 1.33] p = 0.54). Previously established prognostic factors such as number of positive nodes and extracapsular extension were confirmed in both sets of patients. We conclude that among melanoma patients presenting with clinically detectable nodes, when accurately staged, those without an identifiable primary lesion have similar outcomes to patients with MKP.
Medical management of neurofibromatosis 1: a cross-sectional study of 383 patients
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1067/S0190-9622(03)01481-6
Abstract: The morbidity and mortality caused by neurofibromatosis 1 are a result of complications that may involve any of the body systems. Two models of management have been proposed for the detection of various complications in specialized neurofibromatosis clinics: investigation protocols (including extensive imaging and analysis of 24-hour urinary catecholamine levels) or clinical follow-up without imaging. Our purpose was to validate the strategy of clinical follow-up (without routine imaging and 24-hour urinary catecholamine levels). We retrospectively compared the number of treated complications during 2 successive periods from our database: screening investigations from November 1988 to June 1995 and clinical examination from July 1995 to June 2000. The number of treated complications during the 2 periods was not statistically different (27/166 vs 28/217 Fisher's exact test, P =.39). Screening investigations added little to clinical follow-up. Indeed, routine clinical examination can easily identify complications that require treatment in adult patients with neurofibromatosis 1.
Primary cutaneous follicular B-cell lymphoma arising at the site of radiotherapy for breast cancer
Publisher: Oxford University Press (OUP)
Date: 2007
Neurofibromatosis 1: Analysis of the demand for prenatal diagnosis in a French cohort of 361 patients
Publisher: Wiley
Date: 2007
DOI: 10.1002/AJMG.A.32066
Abstract: The severity of neurofibromatosis 1 and its variable expressivity make prenatal diagnosis appealing. We conducted our research to assess patient characteristics associated with the desire for prenatal diagnosis. Between 1995 and 2004, 361 neurofibromatosis 1 adult patients were interviewed about their desire for prenatal diagnosis. Answers were classified in three groups: (1) 'no ' (2) 'uncertain ' (3) 'yes.' Socio-demographical and clinical data were analyzed by logistic multinomial regression for their association with the desire for prenatal diagnosis. Male-to-female sex ratio was 0.93. Mean age at study +/- SD was 33.5 +/- 10. Seven four patients (20.5%) would consider prenatal diagnosis 240 (66.5%) did not and 47 (13.0%) were uncertain. In multivariate analysis, compared to the 'no' group, a longer follow-up (OR = 1.25 [1.11-1.41]), a younger age at study time (OR = 1.25 [1.11-1.41]), not having child (OR = 2.46 [1.03-5.97]) and a higher educational level (OR = 5.07 [1.05-24.47]) were independently associated with the 'yes' group. Compared to the 'no' group in iduals who were in the 'uncertain' groups were younger (0.95 [0.90-0.99]), less often married (0.11 [0.01-0.89]) and had a longer follow-up (1.26 [1.09-1.46]). There is a significant demand for prenatal diagnosis among neurofibromatosis 1 French patients. This demand is associated with in iduals who are younger, have no child, have a longer follow up, and higher level of education.
Epidermal YAP2-5SA-ΔC Drives β-Catenin Activation to Promote Keratinocyte Proliferation in the Mouse Skin in vivo.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JID.2016.10.029
Abstract: The epidermis is a highly regenerative tissue. YAP is a pivotal regulator of stem rogenitor cells in tissue regeneration, including in the epidermis. The molecular mechanisms downstream of YAP that activate epidermal cell proliferation remain largely unknown. We found that YAP and β-catenin co-localize in the nuclei of keratinocytes in the regenerating epidermis in vivo and in proliferating HaCaT keratinocytes in vitro. Inactivation of YAP in HaCaT keratinocytes resulted in reduced activated β-catenin and reduced keratinocyte numbers in vitro. In addition, we found that in the hyperplastic epidermis of YAP2-5SA-ΔC mice, the mutant YAP2-5SA-ΔC protein was predominantly localized in the keratinocyte nuclei and caused increased expression of activated nuclear β-catenin. Accordingly, β-catenin transcriptional activity was elevated in the skin of live YAP2-5SA-ΔC/TOPFLASH mice. Lastly, loss of β-catenin in basal keratinocytes of YAP2-5SA-ΔC/K14-creERT/CtnnB1
Reduced Il17a Expression Distinguishes a Ly6c lo MHCII hi Macrophage Population Promoting Wound Healing
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1038/JID.2012.368
Abstract: Macrophages are the main components of inflammation during skin wound healing. They are critical in wound closure and in excessive inflammation, resulting in defective healing observed in chronic wounds. Given the heterogeneity of macrophage phenotypes and functions, we here hypothesized that different subpopulations of macrophages would have different and sometimes opposing effects on wound healing. Using multimarker flow cytometry and RNA expression array analyses on macrophage subpopulations from wound granulation tissue, we identified a Ly6c(lo)MHCII(hi) "noninflammatory" subset that increased both in absolute number and proportion during normal wound healing and was missing in Ob/Ob and MYD88-/- models of delayed healing. We also identified IL17 as the main cytokine distinguishing this population from proinflammatory macrophages and demonstrated that inhibition of IL17 by blocking Ab or in IL17A-/- mice accelerated normal and delayed healing. These findings dissect the complexity of the role and activity of the macrophages during wound inflammation and may contribute to the development of therapeutic approaches to restore healing in chronic wounds.
The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice
Publisher: MDPI AG
Date: 23-10-2018
DOI: 10.3390/IJMS19113289
Abstract: The incidence of chronic wounds is escalating, and the associated healing process is especially problematic in an aging population with increased morbidity. Targeting increased inflammation in chronic wounds is a promising but challenging therapeutic strategy. Indeed, inflammation and especially macrophages are required for wound healing. As the NLRP3 inflammasome has been implicated with various other inflammatory diseases, in this study, we used MCC950—a selective NLRP3 small molecule inhibitor—on murine models of both acute and chronic wounds. This molecule, while tested for other inflammatory conditions, has never been investigated to reduce topical inflammation driving chronic wounds. We found that there were no significant differences when the treatment was applied either topically or orally in wild-type C57Bl/6 mice and that it even impaired wound healing in obese mice. The treatment was also unable to improve re-epithelialisation or angiogenesis, which are both required for the closure of wounds. We are inclined to believe that MCC950 may inhibit the closure of chronic wounds and that it does not alter wound-associated macrophage polarisation.
Significance of Erythema Nodosum and Pyoderma Gangrenosum in Inflammatory Bowel Diseases
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2008
Melanoma during pregnancy: Level of evidence and principles of precaution
Publisher: Elsevier BV
Date: 2017
Transfer of Fetal Cells With Multilineage Potential to Maternal Tissue
Publisher: American Medical Association (AMA)
Date: 07-07-2004
Bimodal behaviour of interfollicular epidermal progenitors regulated by hair follicle position and cycling.
Publisher: EMBO
Date: 21-10-2016
Abstract: Interfollicular epidermal ( IFE ) homeostasis is a major physiological process allowing maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track in idual keratinocyte clones. Two modes of clonal progression could be observed in the adult murine dorsal skin. Clones attached to hair follicles showed rapid increase in size during the growth phase of the hair cycle. On the other hand, clones distant from hair follicles were slow cycling, but could be mobilized by a proliferative stimulus. Reinforced by mathematical modelling, these data support a model where progenitor cycling characteristics are differentially regulated in areas surrounding or away from growing hair follicles. Thus, while IFE progenitors follow a non‐hierarchical mode of development, spatiotemporal control by their environment can change their potentialities, with far‐reaching implications for epidermal homeostasis, wound repair and cancer development.
Endothelial Progenitors: A Consensus Statement on Nomenclature
Publisher: Oxford University Press (OUP)
Date: 10-03-2017
DOI: 10.1002/SCTM.16-0360
Abstract: Endothelial progenitor cell (EPC) nomenclature remains ambiguous and there is a general lack of concordance in the stem cell field with many distinct cell subtypes continually grouped under the term “EPC.” It would be highly advantageous to agree on standards to confirm an endothelial progenitor phenotype and this should include detailed immunophenotyping, potency assays, and clear separation from hematopoietic angiogenic cells which are not endothelial progenitors. In this review, we seek to discourage the indiscriminate use of “EPCs,” and instead propose precise terminology based on defining cellular phenotype and function. Endothelial colony forming cells and myeloid angiogenic cells are ex les of two distinct and well-defined cell types that have been considered EPCs because they both promote vascular repair, albeit by completely different mechanisms of action. It is acknowledged that scientific nomenclature should be a dynamic process driven by technological and conceptual advances ergo the ongoing “EPC” nomenclature ought not to be permanent and should become more precise in the light of strong scientific evidence. This is especially important as these cells become recognized for their role in vascular repair in health and disease and, in some cases, progress toward use in cell therapy.
Pregnancy Promotes Melanoma Metastasis through Enhanced Lymphangiogenesis
Publisher: Elsevier BV
Date: 04-2011
Prognostic implications of biopsy with tumor transection for patients with high-risk primary melanoma
Publisher: Elsevier BV
Date: 06-2020
Correction: In Vivo Imaging Reveals a Pioneer Wave of Monocyte Recruitment into Mouse Skin Wounds
Publisher: Public Library of Science (PLoS)
Date: 08-12-2014
Use of support services in a sample of patients with high‐risk primary melanomas in urban, regional and rural Queensland
Publisher: Elsevier BV
Date: 06-2017
Abstract: To characterise use of support services in patients diagnosed with high-risk primary melanoma by their location of residence. In a cross-sectional study of 787 patients with histologically-confirmed clinical stage 1B-2 melanoma, we estimated odds ratios (ORs) using regression models to assess the association of support service use with residence in rural, regional or urban areas. We also evaluated demographic and clinical correlates of support service use. Among 113 rural patients, 33 (29%) used support services around time of diagnosis compared to 88 (39%) of 224 regional participants and 164 of 448 (37%) urban participants. Regional participants more commonly used support services compared to rural participants (OR 1.84 CI 1.09-3.10), but there was no association with urban versus rural residence (OR 1.32 CI 0.82-2.13). As well, females (OR 1.58 CI 1.15-2.18), those <65 years (OR 1.96 CI 1.42-2.71), or with higher education (OR 2.30 CI 1.53-3.44), or those with T-stage 4B (OR 2.69 CI 1.36-5.32) were more likely to use support services than other patients. Use of support services is lower among rural patients and other sub-groups of primary melanoma patients who have poorer prognoses than others. Implications for public health: Appropriate triage to support services is required for rural and other vulnerable patient groups to ensure optimal patient care.
Melanoma survival is superior in females across all tumour stages but is influenced by age
Publisher: Springer Science and Business Media LLC
Date: 24-06-2015
DOI: 10.1007/S00403-015-1585-8
Abstract: Among patients with invasive melanoma, females are known to have higher survival than males globally. However, this survival advantage has not been explored in thin melanomas, the most common form of the disease. In addition, it is unclear if this advantage is true across all age groups. We aimed to compare melanoma survival between males and females by clinical stage and within age groups. Melanomas from 1995 to 2008 were extracted from the Queensland Cancer Registry and the Surveillance, Epidemiology, and End Results (SEER) Program, and melanoma-specific deaths were ascertained up to 2011. Flexible parametric survival models compared survival between groups. The Queensland cohort of 28,979 patients experienced 1712 melanoma deaths and the SEER cohort of 57,402 patients included 6929 melanoma deaths. Survival rates were in favour of females across nearly all tumour stages, including thin invasive tumours in both cohorts after adjusting for demographic and clinical factors [odds ratio (OR) death female:male for stage I melanoma = 0.64 in Queensland and OR = 0.79 in the US, both P < 0.001]. The sex influence on survival interacted with age categories. In particular, the survival advantage was inconsistent in females with stage I melanoma aged under 60. Females with melanoma have a survival advantage over males including in stage I melanomas. However, this advantage is dependent on age at diagnosis, suggesting an underlying biological mechanism influenced by age that exists from the very early stages of the disease.
Determinants of Murine Skin Microbiota Composition in Homeostasis and Wound Healing
Publisher: Cold Spring Harbor Laboratory
Date: 21-06-2021
DOI: 10.1101/2021.06.20.449197
Abstract: Animal microbiota have complex interactions with hosts and environment that determines its composition. Yet the ability of hosts to determine their microbiota composition is less well studied. In this study, to investigate the role host genetics in determining skin microbiota, we used 30 different mouse strains from the recombinant inbred panel, the Collaborative Cross. Murine skin microbiota composition was strongly dependent on murine strain with 50% of the variation explained by murine strain. In particular, a quantitative trait locus on chromosome 4 associates both with Staphylococcus abundance and principal-component multi-trait analyses. Additionally, excisional wound associated changes in microbiota composition were not uniform across mouse strains and were host-specific, the genetic background accounting for about 40% of the variation in microbiota. Genetic background also had the highest effect on the healing speed of wounds accounting for over 50% of the variation while mouse age and microbiota composition change accounted only for 20% and 5% of the healing speed despite reaching statistical significance. In conclusion, host genetics has a significant impact on the skin microbiota composition during both homeostasis and wound healing. These findings have long reaching implications in our understanding of associations between microbiota dysbiosis and disease.
Neonatal cases of infantile myofibromatosis do not derive from maternal cells transferred during pregnancy
Publisher: Oxford University Press (OUP)
Date: 06-2009
Wound-associated macrophages control collagen 1α2 transcription during the early stages of skin wound healing
Publisher: Wiley
Date: 02-01-2013
DOI: 10.1111/EXD.12068
Abstract: Wound-associated fibrosis is important to provide tensile strength upon wound healing but at the same time is detrimental to proper tissue regeneration. To date, there is no clear evidence of the role of macrophages and their subpopulations in the control of the kinetics of collagen production during wound healing. To evaluate in vivo the contribution of macrophages in collagen transcription, we depleted macrophages after wounding luciferase reporter mice of the collagen 1 alpha 2 (Col 1α2) promoter activity. Our data reveal that Col 1α2 starts to be transcribed at D2 after wounding, reaching a plateau after 7 days. Sustained macrophage depletion significantly reduced collagen 1α2 transcription from D4, indicating that the control of fibrosis by macrophages occurs during the early stages of the wound healing process. In conclusion, our results demonstrate an important role of wound macrophages in the control of collagen production during wound healing.
A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning
Publisher: eLife Sciences Publications, Ltd
Date: 11-07-2017
DOI: 10.7554/ELIFE.22772
Abstract: The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.
Survival outcomes in patients with multiple primary melanomas
Publisher: Wiley
Date: 10-04-2015
DOI: 10.1111/JDV.13144
Abstract: A substantial number of melanoma patients will develop multiple primary melanomas (MPM). Currently, little is known about the impact of MPM on survival. We aimed to determine whether melanoma survival is worse for patients with MPM compared to those with a single invasive primary melanoma (SPM). A cohort study was conducted. Patients were sourced from an Australian population, with follow-up information collected retrospectively from registry data. Melanoma-specific survival analysis was performed to find associated variables after adjustment for known prognostic factors, using four different models, each selecting a different index melanoma lesion. 1068 stage I and II melanoma patients were followed up for a median of 24.4 years. MPM was found in 17.8% of the cohort (190 patients), more likely among males and older age groups. Other clinicopathological parameters were similar between the MPM and SPM (878 patients) cohorts. After adjustment for age, sex and Breslow thickness, MPM was a hazard for death from melanoma, across all models, reaching significance when considering the last invasive lesion as the index melanoma (HR = 2.76, P = 0.017). Patients with multiple invasive lesions seem more at risk of death from melanoma, independent of known prognostic factors.
Mesenchymal stem/stromal cells enhance engraftment, vasculogenic and pro-angiogenic activities of endothelial colony forming cells in immunocompetent hosts
Publisher: Springer Science and Business Media LLC
Date: 19-10-2017
DOI: 10.1038/S41598-017-13971-3
Abstract: The clinical use of endothelial colony forming cells (ECFC) is h ered by their restricted engraftment. We aimed to assess engraftment, vasculogenic and pro-angiogenic activities of ECFC in immunocompetent (C57BL/6: WT) or immunodeficient ( rag1 −/− C57BL/6: Rag1) mice. In addition, the impact of host immune system was investigated where ECFC were co-implanted with mesenchymal stem/stromal cells (MSC) from adult bone marrow (AdBM-MSC), fetal bone marrow (fBM-MSC), fetal placental (fPL-MSC), or maternal placental (MPL-MSC). Transplantation of ECFCs in Matrigel plugs resulted in less cell engraftment in WT mice compared to Rag1 mice. Co-implantation with different MSCs resulted in a significant increase in cell engraftment up to 9 fold in WT mice reaching levels of engraftment observed when using ECFCs alone in Rag1 mice but well below levels of engraftment with MSC-ECFC combination in Rag1 recipients. Furthermore, MSCs did not reduce murine splenic T cell proliferation in response to ECFCs in vitro . ECFCs enhanced the murine neo-vascularization through paracrine effect, but with no difference between Rag1 and WT mice. In conclusions, the host adaptive immune system affects the engraftment of ECFCs. MSC co-implantation improves ECFC engraftment and function even in immunocompetent hosts mostly through non-immune mechanisms.
Determination of testicular estrogen receptor alpha expression of male chickens (Gallus domesticus) with age
Publisher: Veterinary World
Date: 07-2019
DOI: 10.14202/VETWORLD.2019.994-997
Abstract: Background and Aim: Estrogen activity, a central component of reproductive growth, is regulated by the receptor proteins, estrogen receptor alpha (ERα), and ER beta (ERβ) in chickens as in many other species. ERα expresses predominantly in gonads. Although the expression of ERα in embryonic gonads has been studied in detail, the expression of ERα in post-hatching male gonads has not been studied adequately. Therefore, the current research was conducted to determine the post-hatching changes in the expression of ERα in the left gonads of male chickens with age. Materials and Methods: Shaver Brown male chickens were raised and cared for according to the management guide and sacrificed at the intervals of 1, 4, and 8 weeks of age. The total RNA was extracted from the left gonads using the Trizol method and reverse transcribed using a pair of gene-specific primers. Following polymerase chain reaction lification, the expression of ERα was quantified relative to the expression of the reference gene GAPDH. Results: The results showed that ERα expression significantly increases with age at p=0.0032. However, the increment of ERα expression from week 1 to week 4 was 2.04-fold and from week 4 to week 8 was 1.39-fold, with the later age reflecting a diminishing pattern in the increment. Conclusion: These results differentiate the post-hatching ERα expression of the left gonads of male chickens increase with age but with a diminishing gradient that may support their reproductive functions in later stages of life.
Solid Phase Excitation-Emission Matrix Spectroscopy for In-Situ Chemical Analysis of Combustion Aerosols
Publisher: American Chemical Society (ACS)
Date: 22-04-2020
DOI: 10.26434/CHEMRXIV.12167865.V1
Abstract: Exposure to combustion generated aerosols such as PM from residential woodburning, forest fires, cigarette smoke, and traffic emission have been linked to adverse health outcomes. It is important to assess the chemical composition of PM to examine personal exposure. Excitation-emission matrix (EEM) spectroscopy has been shown as a sensitive and cost-effective technique for evaluation of combustion PM composition and as a source apportionment tool. However, EEM measurements are hindered by a solvent extraction step and a need for benchtop instrumentation. Here, we present a methodology that eliminates this labor-intensive s le preparation and allows to automate and miniaturize the detection platform. A miniature electrostatic collector deposits PM s le onto transparent polydimethylsiloxane (PDMS) coated substrate, where PAH components are extracted into solid-phase (SP) solvent and analyzed using EEM spectroscopy in-situ. We evaluated external and internal excitation schemes to optimized signal to noise ratio. Analysis of woodsmoke and cigarette smoke s les showed good agreement with liquid extraction EEM spectra. Internal excitation is hindered by fluorescent interference from PDMS at λ nm. The external excitation EEM spectra are dependent on the incident angle ranges of 30-40⁰ and 55-65⁰ showed the best results. The proposed SP-EEM technique can be used for development of miniaturized sensors for chemical analysis of combustion generated PM.
Microchimerism: Fears and Hopes
Publisher: S. Karger AG
Date: 2005
DOI: 10.1159/000081473
Age at Diagnosis of Neurofibromatosis 1: An Audit of Practice
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000116622
Fetal Bone Marrow-Derived Mesenchymal Stem/Stromal Cells Enhance Humanization and Bone Formation of BMP7 Loaded Scaffolds
Publisher: Wiley
Date: 25-09-2017
Abstract: Tissue engineered constructs built with human cells capable of generating a bone-like organ within the mouse have attracted considerable interest over the past decade. Here, we aimed to compare the utility of human mesenchymal stem/stromal cells (MSC) isolated from fetal term placenta (fPL-MSC) and fetal first trimester bone marrow (fBM-MSC) in a polycaprolactone scaffold/BMP7-based model in nude mice. Furthermore, fPL-MSC were co-seeded with fetal placenta-derived endothelial colony forming cells (ECFC) to assess the impact of ECFC on fPL-MSC osteogenesis. X-ray radiography and micro computed tomography analyses showed enhanced bone formation in all BMP7 groups however there was no difference after 2 months in bone formation between scaffolds seeded with fPL-MSC alone or combination of ECFC and fPL-MSC. Of interest, fBM-MSC showed the highest level of bone formation. Additionally, endochondral ossification contributed in generation of bone in fBM-MSC. Histological analysis showed the primary role of BMP in generation of cortical and trabecular bone, and the recruitment of hematopoietic cells to the scaffolds. Current in vivo engineered bone organs can potentially be used for drug screening or as models to study bone tissue development in combination with haematopoiesis.
Clinical utility of skin cancer and melanoma risk scores for population screening: TRoPICS study
Publisher: Wiley
Date: 27-12-2021
DOI: 10.1111/JDV.17062
Abstract: Screening for skin cancer can be cost‐effective if focused on high‐risk groups. Risk prediction tools have been developed for keratinocyte cancers and melanoma to optimize advice and management. However, few have been validated in a clinical setting over the past few years. To assess the clinical utility of risk assessment tools to identify in iduals with prevalent skin cancers in a volunteer‐based screening clinic. Participants were adults presenting for a skin check at a volunteer‐based skin cancer screening facility. We used previously published tools, based on questionnaire responses, to predict melanoma and keratinocyte cancers [KCs basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] and classified each participant into one of five risk categories. Participants subsequently underwent a full skin examination by a dermatologist. All suspicious lesions were biopsied, and all cancers were histopathologically confirmed. Of 789 people who presented to the clinic, 507 (64%) consented to the study. Twenty‐two BCCs, 19 SCCs and eight melanomas were diagnosed. The proportion of keratinocyte cancers diagnosed increased according to risk category from % in the lowest to 24% in the highest risk category ( P 0.001). Subtype analysis revealed similar proportionate increases in BCC or SCC prevalence according to risk category. However, a similar proportion of melanoma cases were detected in the low‐risk and high‐risk groups. The risk prediction model for keratinocyte cancers can reliably identify in iduals with a significant skin cancer burden prior to a skin examination in the community setting. The prediction tool for melanoma needs to be tested in a larger s le exposed to a wider range of environmental risk factors.
Predictive Factors of Eczema-Like Eruptions among Patients without Cutaneous Psoriasis Receiving Infliximab: A Cohort Study of 92 Patients
Publisher: S. Karger AG
Date: 2009
DOI: 10.1159/000235582
Abstract: i Background: /i Anti-tumor-necrosis-factor-α agents are limited by their side effects. Eczema is one of the most frequent adverse reactions affecting quality of life. i Objective: /i To assess potential predictive risk factors for eczema in patients receiving infliximab. i Methods: /i We conducted a prospective cohort study including patients treated with infliximab for a variety of disorders with the exception of cutaneous psoriasis. Clinical features were compared among patients with and without eczema under therapy. i Results: /i 92 consecutive patients were included 15 developed eczema after the initiation of infliximab. In univariate analyses, a personal history of atopic symptoms was the only predictive factor for the occurrence of eczema (odds ratio = 3.6). Sex, age, principal diagnosis, dose and duration of infliximab and concomitant use of other immunosuppressors had no influence on the occurrence of eczema. i Conclusions: /i A personal history of atopic symptoms is predictive of eczema under infliximab. Specific information should be provided to atopic patients starting such a treatment.
Cellulitis due to Myroides odoratimimus in a patient with alcoholic cirrhosis
Publisher: Oxford University Press (OUP)
Date: 26-11-2007
Misleading pustular plaques of the lower limbs during Crohn's disease: two case reports
Publisher: Springer Science and Business Media LLC
Date: 03-10-2007
Abstract: Extraintestinal manifestations of Crohn's disease may involve the skin, the eyes, the genital mucosa, and the joints. Dermatoses associated with Crohn's disease include neutrophilic dermatoses, erythema nodosum, granulomatous dermatitis, blistering dermatoses, and non-specific skin manifestations. Cutaneous Crohn's disease is characterized by skin non-caseating epithelioid granulomatas with giant cells, remote from the gastrointestinal tract. We report herein two new cases. On both patients, differential diagnosis of neutrophilic dermatoses and infectious disease were evoked, and antimicrobial agents were introduced in one of them. Given the atypical presentation, the final diagnosis of cutaneous Crohn's disease could only be made with histological examination. In patient 1, the plaques decreased in size and infiltration by more than 75% after 3 weeks of treatment with bethametasone dipropionate 0.05% cream. In patient 2, the plaques decreased by more than 50% after 6 weeks of treatment with prednisolone (45 mg/day) and azathioprine (100 mg/day). Cutaneous Crohn's disease may present as dusky, erythematous, infiltrated, and ulcerated plaques and nodules. Female-to-male sex ratio is about 2, and the mean age at onset is 35. Recurrently, the hypothesis of a skin mycobacterial or fungal infection greatly delays proper treatment. Rarity of cutaneous Crohn's disease h ers therapeutic assessment in controlled trials. Thus, available literature is limited to case reports and sparse small series, with contradictory results. These reports are subject to publication bias, and no definite evidence-based recommendations can be made on the most adequate therapeutic strategy.
Increased mortality for pregnancy-associated melanoma: systematic review and meta-analysis
Publisher: Wiley
Date: 17-02-2015
DOI: 10.1111/JDV.12972
Abstract: Among women, pregnancy-associated melanomas may have a poorer prognosis than other melanomas, but evidence is inconsistent. We conducted a systematic review and meta-analysis to assess the effect on melanoma outcome of a coinciding pregnancy. The objective of the study was to conduct a systematic review and meta-analysis of risk of death from, or recurrence of, pregnancy-associated melanomas compared with other melanomas in women of reproductive age. Cochrane (1996-2013), MEDLINE (1950-2013), EMBASE (1966-2013), CINAHL (1982-2013), and PUBMED (1951-2013) databases were searched for studies assessing the risk of death and recurrence in pregnancy-associated melanomas. Eligible studies investigated melanoma outcomes in women with pregnancy-associated melanomas (diagnosed during pregnancy or in 12 months following pregnancy), included a comparison group and reported measures of risk of melanoma death or disease-free survival. Eligible study designs were cohort studies of women of childbearing age with confirmed diagnoses of cutaneous melanoma. In idual study effect estimates were pooled using the weighted average method. Studies that did not report a quantitative estimate were summarized narratively. Of 304 citations identified, 14 studies met the inclusion criteria, with assessed outcomes being melanoma death (7), recurrence (3), or both (4). Pooled estimates of mortality risk from four studies showed increased risk of melanoma death after adjustment for patient age and stage of melanoma (pHR 1.56, 95% CI 1.23-1.99) for pregnancy-associated melanoma compared with other melanomas. Based on limited quantitative evidence, pregnancy-associated melanomas appear to have poorer outcomes than other melanomas.
Manifestations cutanées associées aux maladies inflammatoires chroniques intestinales
Publisher: Elsevier BV
Date: 11-2009
Igf1rsignalling acts on the anagen-to-catagen transition in the hair cycle
Publisher: Wiley
Date: 27-04-2017
DOI: 10.1111/EXD.13287
Abstract: Insulin-like growth factor 1 (Igf1) is important for skin development and homoeostasis. However, overexpression and inactivation studies have produced variable findings regarding its role in hair follicle (HF) biology. Here, we studied a conditional and inducible knockout of the Igf1 receptor (Igf1r) in keratin 15-expressing bulge cells. Deletion of Igf1r after the development of the skin appendages in K15-Igf1r
STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.JID.2016.04.014
Abstract: Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen), and rest (telogen) regulated by their mesenchymal component, the dermal papilla (DP). On the basis of the reports of its specific expression in the DP, we investigated signal transducer and activator of transcription (STAT5) activation during hair development and cycling. STAT5 activation in the DP began in late catagen, reaching a peak in early anagen before disappearing for the rest of the cycle. This was confirmed by the expression profile of suppressor of cytokine signaling 2, a STAT5 target in the DP. This pattern of expression starts after the first postnatal hair cycle. Quantification of hair cycling using the Flash canonical Wnt signaling in vivo bioluminescence reporter found that conditional knockout of STAT5A/B in the DP targeted through Cre-recombinase under the control of the Sox18 promoter resulted in delayed anagen entry compared with control. Microarray analysis of STAT5 deletion versus control revealed key changes in tumor necrosis factor-α, Wnt, and fibroblast growth factor ligands, known for their role in inducing anagen entry. We conclude that STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling.
Manifestations cutanées associées aux maladies inflammatoires chroniques intestinales
Publisher: Elsevier BV
Date: 11-2009
Feto-Maternal Cell Trafficking: A Transfer of Pregnancy Associated Progenitor Cells
Publisher: Springer Science and Business Media LLC
Date: 2006
DOI: 10.1385/SCR:2:2:111
Multi-lineage potential of fetal cells in maternal tissue: a legacy in reverse
Publisher: The Company of Biologists
Date: 15-04-2005
DOI: 10.1242/JCS.02332
Abstract: Fetal cells circulate in pregnant women and persist in blood and tissue for decades post-partum. The mother thus becomes chimeric. Factors that may influence such fetal cell microchimerism include histocompatibility, fetal or placental abnormalities, or a reproductive history that includes miscarriage or elective termination. Fetal cell microchimerism is associated with some maternal autoimmune diseases, such as systemic sclerosis. Moreover, a novel population of fetal cells, the pregnancy-associated progenitor cells (PAPCs), appears to differentiate in diseased or injured maternal tissue. The cellular origin of these cells is at present unknown but could be a hematopoietic stem cell, a mesenchymal stem cell, or a novel cell type. Pregnancy therefore results in the acquisition of cells with stem-cell-like properties that may influence maternal health post-partum. Rather than triggering disease, these cells may instead combat it.
Patient age and risk of recurrence of primary melanoma at high risk of spread
Publisher: Oxford University Press (OUP)
Date: 29-11-2021
DOI: 10.1111/BJD.19601
Cervical cancer and microchimerism
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2003
DOI: 10.1016/S0029-7844(03)00615-X
Abstract: To determine whether microchimerism is involved in the pathogenesis or progression of cervical cancer. Cervical tissue was obtained from eight women who had at least one live-born son and who underwent radical hysterectomy after a diagnosis of cervical cancer. Control tissue was obtained from four women without cervical cancer who had at least one live-born son and from three women with cervical cancer and no male births. Tissue sections were analyzed with fluorescence in situ hybridization for the presence of fetal cells, defined by an X and Y chromosome. Immunolabeling was used to determine the phenotype of the presumed fetal cells. Male cells were found in cervical tissue from all four patients for whom large sections (approximately 1.5 x 2 cm) were analyzed. Only one male cell was found in two of the four patients for whom small biopsy specimens (approximately 0.1 x 0.5 cm) were analyzed. No male cells were found in tissue specimens from controls, whether they were small or large sections. In immunolabeling studies, eight of 18 male cells from one patient were CD45-positive and nine of 37 male cells from two patients were cytokeratin-positive. No cells were positive for both markers. Cervical cancer might be associated with microchimerism, possibly from fetomaternal cell trafficking. These results further expand the potential relationship between microchimerism and disease in women.
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