ORCID Profile
0000-0003-4206-8743
Current Organisation
Cabrini Institute
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Publisher: Elsevier BV
Date: 08-2020
Publisher: American Society of Clinical Oncology (ASCO)
Date: 09-2022
DOI: 10.1200/OP.22.00060
Abstract: Totally implantable ports require regular maintenance to prevent port-related complications. Manufacturers recommend monthly maintenance port flushes for patients for the life of the port. Previous studies show that extending intervals between maintenance port flushes up to 16 weeks does not increase incidence of port-related complications. To date, no prospective study has been conducted to evaluate the medical safety of extending flush intervals from monthly to every 12 weeks within a heterogeneous disease cohort. Research Question: Is it feasible and medically safe to extend intervals between maintenance port flushes to every 12 weeks in patients with cancer not on active treatment? This study enrolled oncology and hematology patients who had retained their port following completion of anticancer treatment. Clinical data were extracted for 1,059 participants. The primary end points of this study were the overall number of ports removed and incidence of port-related complications reported between cohorts 1 and 2 (flushes every 4-8 weeks), and cohort 3 (flushes every 12 weeks). Data were allocated into three study cohorts on the basis of year and duration between port flushes. No difference was observed in the overall percentage of ports removed because of physician-reported complications across all cohorts (25%-30%). No change in the incidence of port-related complications including suspected infection and malfunction was observed between cohorts 1 and 2 (8%), or cohort 3 (5%). Our findings show that extending maintenance port flush intervals to 12 weeks does not increase the incidence of port-related adverse events and is medically safe.
Publisher: Springer US
Date: 20-11-2019
DOI: 10.1007/978-1-4939-9936-1_4
Abstract: Macrophage migration inhibitory factor (MIF) is expressed and released ubiquitously by numerous cell types and tissues. MIF is detected and constitutively expressed at the protein level both intra- and extracellularly. This chapter outlines methods for cultivating, purifying, detecting, and quantifying concentrations of MIF from murine primary derived macrophages and dendritic cell culture supernatants.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Springer US
Date: 20-11-2019
DOI: 10.1007/978-1-4939-9936-1_5
Abstract: MIF is a key regulator of host immune responses and increased levels secreted from cells, or found circulating systemically, have been implicated in the pathogenesis of many inflammatory and autoimmune disorders. Here, we describe methods for detecting and quantifying extracellular concentrations of MIF in both human- and murine-derived biological s les.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.FERTNSTERT.2014.03.011
Abstract: To use a proteomic approach to evaluate possible postinflammatory alterations in the protein composition of motile sperm in patients 3 months after acute epididymitis. Prospective case-control study. University medical school research laboratory. Eight patients 3 months after acute unilateral epididymitis and 10 healthy controls. None. Proteome analysis of sperm s les collected by swim-up from control and acute epididymitis patients analyzed by two-dimensional gel electrophoresis and subsequent protein identification by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry immunofluorescence staining for mitochondrial ATP synthase subunit β (ATP5B), α-tubulin (TUBA1A), and tubulin-β2c (TUBB4B) for validation purposes. Proteome analysis identified 35 proteins in sperm from epididymitis patients that were down-regulated, irrespective of subcellular localization and biologic function. Furthermore, immunofluorescence microscopy confirmed ATP5B, TUBA1A, and TUBB4B were less abundantly expressed in epididymitis s les compared with controls. Despite normal semen parameters observed by conventional semen analysis in patients after epididymitis, significant changes to sperm protein composition were observed. These changes may be implicated as additional factors contributing to subfertility/infertility in men after episodes of epididymitis.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.JHEP.2010.12.042
Abstract: Viruses target innate immune pathways to evade host antiviral responses. Recent studies demonstrate a relationship between hepatitis B disease states and the host's innate immune response, although the mechanism of immunomodulation is unknown. In humans, the innate immune system recognizes pathogens via pattern recognition receptors such as the Toll-like receptors (TLR), initiating anti-inflammatory responses. TLR expression and pro-inflammatory cytokine production is reduced in hepatitis B e antigen (HBeAg)-positive patients following TLR stimulation. The aim of this study was to investigate interactions between TLR signaling pathways and the mature HBeAg protein localized in the cytosol. The ability of HBeAg to inhibit TLR signaling and association with TLR adapters was evaluated by immunoprecipitation, immunostaining, and reporter studies. Our findings show that HBeAg co-localizes with Toll/IL-1 receptor (TIR)-containing proteins TRAM, Mal, and TLR2 at the sub-cellular level, which was not observed for Hepatitis B core antigen. Co-immunoprecipitation analysis demonstrated HBeAg interacted with TIR proteins Mal and TRAM, while a mutated HBeAg ablated interaction between Mal and MyD88. Importantly, HBeAg also disrupted homotypic TIR:TIR interaction critical for TLR-mediated signaling. Finally, HBeAg suppressed TIR-mediated activation of the inflammatory transcription factors, NF-κB and Interferon-β promoter activity. Our study provides the first molecular mechanism describing HBeAg immunomodulation of innate immune signal transduction pathways via interaction and targeting of TLR-mediated signaling pathways. These finding suggest the mechanism as to how HBeAg evades innate immune responses contributing to the pathogenesis of chronic hepatitis B infection and the establishment of viral persistence.
Publisher: Frontiers Media SA
Date: 07-06-2018
Publisher: Springer Science and Business Media LLC
Date: 03-08-2021
DOI: 10.1186/S13058-021-01461-4
Abstract: Particular breast cancer subtypes pose a clinical challenge due to limited targeted therapeutic options and/or poor responses to the existing targeted therapies. While cell lines provide useful pre-clinical models, patient-derived xenografts (PDX) and organoids (PDO) provide significant advantages, including maintenance of genetic and phenotypic heterogeneity, 3D architecture and for PDX, tumor–stroma interactions. In this study, we applied an integrated multi-omic approach across panels of breast cancer PDXs and PDOs in order to identify candidate therapeutic targets, with a major focus on specific FGFRs. MS-based phosphoproteomics, RNAseq, WES and Western blotting were used to characterize aberrantly activated protein kinases and effects of specific FGFR inhibitors. PDX and PDO were treated with the selective tyrosine kinase inhibitors AZD4547 (FGFR1-3) and BLU9931 (FGFR4). FGFR4 expression in cancer tissue s les and PDOs was assessed by immunohistochemistry. METABRIC and TCGA datasets were interrogated to identify specific FGFR alterations and their association with breast cancer subtype and patient survival. Phosphoproteomic profiling across 18 triple-negative breast cancers (TNBC) and 1 luminal B PDX revealed considerable heterogeneity in kinase activation, but 1/3 of PDX exhibited enhanced phosphorylation of FGFR1, FGFR2 or FGFR4. One TNBC PDX with high FGFR2 activation was exquisitely sensitive to AZD4547. Integrated ‘omic analysis revealed a novel FGFR2-SKI fusion that comprised the majority of FGFR2 joined to the C-terminal region of SKI containing the coiled-coil domains. High FGFR4 phosphorylation characterized a luminal B PDX model and treatment with BLU9931 significantly decreased tumor growth. Phosphoproteomic and transcriptomic analyses confirmed on-target action of the two anti-FGFR drugs and also revealed novel effects on the spliceosome, metabolism and extracellular matrix (AZD4547) and RIG-I-like and NOD-like receptor signaling (BLU9931). Interrogation of public datasets revealed FGFR2 lification, fusion or mutation in TNBC and other breast cancer subtypes, while FGFR4 overexpression and lification occurred in all breast cancer subtypes and were associated with poor prognosis. Characterization of a PDO panel identified a luminal A PDO with high FGFR4 expression that was sensitive to BLU9931 treatment, further highlighting FGFR4 as a potential therapeutic target. This work highlights how patient-derived models of human breast cancer provide powerful platforms for therapeutic target identification and analysis of drug action, and also the potential of specific FGFRs, including FGFR4, as targets for precision treatment.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.MOLIMM.2017.02.013
Abstract: Autophagy is a ubiquitous cellular mechanism for the targeted lysosomal degradation of various cytosolic constituents, from proteins to organelles. As an essential homeostatic mechanism, autophagy is upregulated in response to numerous environmental and pharmacological stimuli, including starvation, where it facilitates the recycling of essential amino acids. In addition, autophagy plays specific roles within the immune system it serves as a source of peptides for antigen presentation, a mechanism for the engulfment and degradation of intracellular pathogens and as a key regulator of inflammatory cytokines. In particular, autophagy has been shown to play a number of roles in regulating inflammasome activation, from the removal of inflammasome-activating endogenous signals, to the sequestration and degradation of inflammasome components. Autophagy also plays a role in determining the fate of IL-1β, which is concentrated in autophagosomes. This review discusses a growing body of literature that suggests autophagy is a critical regulator of inflammasome activation and the subsequent release of IL-1 family cytokines.
Publisher: Elsevier
Date: 2017
Publisher: Wiley
Date: 10-07-2007
Abstract: Toll-like receptors (TLRs) are essential mediators of both innate and adaptive immunity by recognizing and eliciting responses upon invasion of pathogens. The response of TLRs must be stringently regulated as exaggerated expression of signalling components as well as pro-inflammatory cytokines can have devastating effects on the host, resulting in chronic inflammatory diseases, autoimmune disorders and aid in the pathogenesis of TLR-associated human diseases. Therefore, it is essential that negative regulators act at multiple levels within TLR signalling cascades, as well as through eliciting negative-feedback mechanisms in order to synchronize the positive activation and negative regulation of signal transduction to avert potentially harmful immunological consequences. This review explores the various mechanisms employed by negative regulators to ensure the appropriate modulation of both immune and inflammatory responses.
Publisher: Wiley
Date: 2018
DOI: 10.1002/CTI2.1042
Publisher: Informa UK Limited
Date: 10-05-2016
Publisher: American Society for Microbiology
Date: 03-2014
DOI: 10.1128/IAI.01373-13
Abstract: Infectious epididymitis in men, a frequent entity in urological outpatient settings, is commonly caused by bacteria originating from the anal region ascending the genitourinary tract. One of the most prevalent pathogens associated with epididymitis is Escherichia coli . In our previous study, we showed that semen quality is compromised in men following epididymitis associated with specific E. coli pathovars. Thus, our aim was to investigate possible differences in immune responses elicited during epididymitis following infection with the uropathogenic E. coli (UPEC) strain CFT073 and the nonpathogenic enteric E. coli (NPEC) strain 470. Employing an in vivo experimental epididymitis model, C57BL/6 mice were infected with UPEC CFT073, NPEC 470, or phosphate-buffered saline (PBS) as a sham control for up to 7 days. After infection with NPEC 470, the expression of proinflammatory cytokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha in the epididymis was significantly increased. Conversely, UPEC CFT073-challenged mice displayed inflammatory gene expression at levels comparable to sham PBS-treated animals. Moreover, by day 7 only NPEC-infected animals showed activation of adaptive immunity evident by a substantial influx of CD3 + and F4/80 + cells in the epididymal interstitium. This correlated with enhanced production of Th1-associated cytokines IL-2 and gamma interferon (IFN-γ). Furthermore, splenocytes isolated from UPEC-infected mice exhibited diminished T-cell responses with significantly reduced secretion of IL-2 and IFN-γ in contrast to NPEC-infected animals. Overall, these findings provide new insights into understanding pathogen-specific modulation of host immunity during acute phases of epididymitis, which may influence severity of disease and clinical outcomes.
Publisher: Wiley
Date: 2019
DOI: 10.1002/CTI2.1045
Publisher: Frontiers Media SA
Date: 11-11-2015
No related grants have been discovered for Tali Lang.