ORCID Profile
0000-0002-9441-6466
Current Organisations
Bond University Faculty of Health Sciences and Medicine
,
Bond University
,
University of Peradeniya
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Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.PRP.2022.153801
Abstract: CYP1A1 enzyme is integral to the biotransformation of polycyclic aromatic hydrocarbons to carcinogenic compounds. This study aimed to screen mutations in exon 7 (ex7) of CYP1A1 and investigate its clinicopathological correlations in fresh tissue s les from 85 patients (42 women 43 men) with colorectal carcinoma (CRC). Tumour tissues and matched non-neoplastic mucosa tissues were collected prospectively. Genomic DNA was extracted from all tissues, and subject to high-resolution melt curve analysis for CYP1A1-ex7. Sanger sequencing was employed to detect specific mutations. Three known single nucleotide polymorphisms (SNPs) were identified in both tumour and matched non-neoplastic tissue for the same in idual. Of the 85 patients, one third (n = 28) harboured either rs1048943, rs1799814, or rs41279188. Patients who had a SNP at ex7 of CYP1A1 were significantly more likely to be over 65 years of age (p = 0.015). Furthermore, in iduals harbouring a SNP at exon7 showed a low incidence of perineural cancer infiltration (p = 0.025) when compared to the wild-type population. Overall, polymorphisms at exon 7 of CYP1A1 are present in patients with CRC and associated with a few clinicopathological characteristics.
Publisher: Sri Lanka Journals Online (JOL)
Date: 20-05-2014
Publisher: MDPI AG
Date: 12-07-2023
Abstract: Faysal Bin Hamid was not included as an author in the original publication [...]
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.PRP.2021.153530
Abstract: Heme, a molecule abundant in red meat, is assumed to exert carcinogenic effects on normal colonic cells and tumour suppressive effects on cancer cells, though the hypothesis has not been explicitly proven yet. The present study aims to investigate hemin induced cytotoxic, genetic and biological alterations in both normal and cancerous colonic epithelial cells, which may imply its carcinogenic and anticarcinogenic properties. Normal colonic epithelial cells and colon carcinoma cells were treated with a 0-500 µM concentration of hemin for 1-4 days following which cytotoxicity and wound healing assays, western blot, rt-PCR and cell cycle analysis were performed. Interestingly, hemin was cytotoxic to normal colonic cells, but carcinoma cells were more resistant. Cell migration potential of both normal colonic cells and colon carcinoma cells was impeded by hemin. Hemin caused upregulation of both P53 and β-catenin gene and proteins expression in normal colonic cells with concomitant cell cycle arrest at G1(Gap 1) and G2/M (Gap 2/ Mitosis). G1 and G2 cell cycle arrests were also observed in colon carcinoma cells. In conclusion, the present study confirms that hemin, a main heme molecule present in red meat, facilitates behavioural, genetic and cell cycle kinetic alterations in both normal colonic epithelial and colon carcinoma cells.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.PRP.2022.153885
Abstract: Literature suggests Heme oxygenase (HO) system to be a double-edged sword which can promote both cytoprotection as well as carcinogenicity. The aim of this study was to investigate the role of heme in HO-1 and HO-2 induced colorectal carcinogenesis and the clinicopathological significance of their expressions in patients with colorectal carcinoma (CRC). HO-1 and HO-2 expression alterations in normal colonic epithelial (FHC) and colon cancer cells (SW480) were explored following treatment with 0 µM, 25 µM, 100 µM and 250 µM concentrations of hemin, using qPCR. Fifty paired CRC and adjacent non-neoplastic s les were subjected to qPCR to determine the HO-1 and HO-2 expression. Clinicopathological associations of HO-1 and HO-2 expression levels were determined. Low concentrations of hemin caused upregulation and high concentration caused downregulation of HO-1 expression, whereas HO-2 expression was significantly downregulated with all hemin concentrations in FHC. HO-1 expression in SW480 was increased with all hemin concentrations and HO-2 expression was downregulated at the highest hemin concentration. HO-1 and HO-2 expressions in adjacent non-neoplastic tissue was significantly higher than that of CRC. Expression of HO-1 was significantly higher than HO-2, in both CRC and adjacent non-neoplastic tissue. Sex, HFE expression and lymph-vascular invasion were significantly correlated with HO-1 expression. HO-2 expression showed significant associations with staging, local spread and recurrence of tumour. HO-1 and HO-2 expression is respectively induced and repressed by exogenous hemin in normal colon and colon cancer cells. HO-1 and HO-2 expression profiles in CRC are correlated with the assessed clinicopathological features of CRC, suggesting the possible implications of HO expression status in CRC pathogenesis.
Publisher: BENTHAM SCIENCE PUBLISHERS
Date: 2023
DOI: 10.2174/9789815079364123010010
Abstract: Circulating tumour cells (CTCs), as 'liquid biopsy”, has a major benefit over traditional tissue biopsy and has the potential to become a less invasive and more costeffective cancer biomarker. The presence of CTCs in the circulation indicates the presence of a tumour and the possibility of metastatic spread. Hence, the characterisation of CTCs is expected to provide crucial insights into the mechanisms of metastasis. It can also provide useful information about the future use of CTCs as a surrogate endpoint biomarker in diagnosis, prognosis, and treatment response prediction by minimizing the limitations of tissue biopsies. Also, it provides a new horizon for the development of novel targeted therapies. However, the lack of specific and effective methods is the key limitation in CTC detection and isolation in patients with cancer. Therefore, more responsive methods and approaches may be needed to improve the accuracy of CTC measurements. Herein, this book chapter will provide a current picture of CTCs as surrogate biomarkers for disease diagnosis, prognosis and predicting therapy response, along with the risk of relapse in cancers. br
Publisher: Korean Neurological Association
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 26-04-2016
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.HUMPATH.2022.02.001
Abstract: The relationship between red and processed meat and its risk toward colorectal carcinoma (CRC) is not fully explored in literature. Polycyclic aromatic hydrocarbons (PAHs) are procarcinogenic molecules that are ingested with meat cooked at high temperatures. The metabolic conversion of PAHs to carcinogenic diol epoxides is in part mediated by the aryl hydrocarbon receptor (AhR)-dependent induction of CYP1A1. This study aims to examine the expression profiles and polymorphisms of the AHR (aryl hydrocarbon receptor) gene which is involved in the metabolic conversion of PAHs in patients with CRC. Genetic analysis was done in matched cancer and non-neoplastic tissues from 79 patients diagnosed with CRCs. Low AHR mRNA expression was associated with mucinous colorectal adenocarcinoma. Exon 10 of AHR showed that 27% of patients had the rs2066853 single-nucleotide polymorphism resulting in an arginine-to-lysine change at codon 554. This variant was significantly associated with a lower likelihood of perineural invasion, presence of synchronous cancer, and multiple colorectal polyps. Furthermore, rs2066853 in iduals were significantly more likely to be of more advanced age and have a more favorable tumor grade and pathological stage. These results imply the pathogenic roles of AHR in PAH-associated colorectal carcinogenesis.
Publisher: MDPI AG
Date: 16-09-2023
Publisher: MDPI AG
Date: 06-03-2023
DOI: 10.3390/IJMS24055051
Abstract: Information regarding genetic alterations of driver cancer genes in circulating tumour cells (CTCs) and their surrounding immune microenvironment nowadays can be employed as a real-time monitoring platform for translational applications such as patient response to therapeutic targets, including immunotherapy. This study aimed to investigate the expression profiling of these genes along with immunotherapeutic target molecules in CTCs and peripheral blood mononuclear cells (PBMCs) in patients with colorectal carcinoma (CRC). Expression of p53, APC, KRAS, c-Myc, and immunotherapeutic target molecules PD-L1, CTLA-4, and CD47 in CTCs and PBMCs were analysed by qPCR. Their expression in high versus low CTC-positive patients with CRC was compared and clinicopathological correlations between these patient groups were analysed. CTCs were detected in 61% (38 of 62) of patients with CRC. The presence of higher numbers of CTCs was significantly correlated with advanced cancer stages (p = 0.045) and the subtypes of adenocarcinoma (conventional vs. mucinous, p = 0.019), while being weakly correlated with tumour size (p = 0.051). Patients with lower numbers of CTCs had higher expression of KRAS. Higher KRAS expression in CTCs was negatively correlated with tumour perforation (p = 0.029), lymph node status (p = 0.037), distant metastasis (p = 0.046) and overall staging (p = 0.004). CTLA-4 was highly expressed in both CTCs and PBMCs. In addition, CTLA-4 expression was positively correlated with KRAS (r = 0.6878, p = 0.002) in the enriched CTC fraction. Dysregulation of KRAS in CTCs might evade the immune system by altering the expression of CTLA-4, providing new insights into the selection of therapeutic targets at the onset of the disease. Monitoring CTCs counts, as well as gene expression profiling of PBMCs, can be helpful in predicting tumour progression, patient outcome and treatment.
Publisher: BENTHAM SCIENCE PUBLISHERS
Date: 2023
DOI: 10.2174/9789815079364123010007
Abstract: Chromosomal abnormalities induce genomic instability and are associated with cancer hallmarks. Chromosomal abnormalities can be categorised into structural and numerical aberrations and are seen under a light microscope. Given the ease of detecting and observing such changes using karyotyping, chromosomal aberrations may be a useful diagnostic tool. For ex le, the discovery of the Philadelphia chromosome was a cytogenetic hallmark of chronic myeloid leukaemia and acute lymphoblastic leukaemia. Thus, this chapter explores potential aberrations which have the potential to be used as cancer markers in a clinical setting. Recurrent structural aberrations with known genetic mutations are observed in cancers of the bones, lungs, salivary glands, soft tissue, stomach, thyroid, and uterus. The association of these genetic alterations with various cancers suggests a causative role of structural aberrations in carcinogenesis and is characteristic of some cancers. Additionally, mono- and tri-somies, known as aneuploidy, are common to all cancer types, however, their roles as a cause or consequence are difficult to establish due to the sheer loss or gain of genetic material, respectively. Cancers with the most frequent trisomies, include Ewing’s sarcoma of the bone, astrocytoma of the brain, and renal adenocarcinoma. Common cancer monosomies include meningioma of the brain and ovarian adenocarcinoma. These chromosomal aberrations forge the path to a better understanding of cancer genetics. Though there are potential chromosome markers in cancer, the heterogeneity of cancer genetics makes this a challenging tool to incorporate into current oncological diagnostic guidelines.& nbsp br
Publisher: BENTHAM SCIENCE PUBLISHERS
Date: 2023
DOI: 10.2174/9789815079364123010005
Abstract: Despite ever-growing experimental evidence for the utility of a wide range of tumour markers, only a handful are understood to be useful in clinical applications. Tumour markers are useful for screening and diagnosis of cancers, prognostication, guiding treatment pathways and post-treatment surveillance studies. The tumour makers play a significant role in cancer care and the markers included in the current treatment guidelines will be discussed in detail in this chapter. The utility of the tumour markers in the management of colorectal, breast, thyroid, hepatobiliary, pancreatic, ovarian, testicular, neuroendocrine and prostate cancer are detailed herein to provide an update on the current use of tumour markers in the clinical settings.& nbsp br
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.JFLM.2018.03.008
Abstract: Mothers of alleged infanticides might claim that umbilical cord broke during precipitate delivery causing injuries detected on baby at autopsy. There is paucity of evidence regarding this possibility. The objective of the study was to determine relationship between tensile strength and diameter or weight per unit length of cord. Diameters and weights per unit length of fresh umbilical cords were determined. Tensile strengths were measured by Hounsfield Testing Machine. Relationship between tensile strength versus cord diameter and weight per unit length were analyzed. Of 122 cords, average tensile strength, diameter and weight per centimeter were 50.4 N, 7.73 mm and 6.87 g respectively. The tensile strengths were directly proportional to diameter. There was no association between tensile strength and weight per centimeter. Measurement of the diameter of cord is important during autopsy to predict tensile strength and thereby to presume whether cord could have broken by the weight of the baby.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.HUMPATH.2021.07.013
Abstract: The study aimed to screen mutation of human homeostatic iron regulator (HFE) in colorectal carcinoma (CRC) and detect their associations with clinicopathological parameters. Expression of HFE was determined by quantitative polymerase chain reaction in matched CRC and non neoplastic colorectal mucosal tissue of 76 patients. Genomic DNA extracted were subjected to high high-resolution melt curve analysis and Sanger sequencing to detect mutations in HFE. The associations of the identified mutations with a variety of clinical features were determined. Approximately 60% of CRC showed low HFE expression. Of the ten 10 mutations identified in exons 2 and 4, c.187C>G (H63D), c845G>A (C282Y), c.193A>T (S65C), g.3828T>C, g.5795T>C, and g.5728G>A were known mutations. Four novel mutations were discovered : c.184G>A, c.220T>G, c.322A>C, and c.324T>C. Heterozygous H63D and C282Y mutations were seen in 71% and 49% of cancer tissue, respectively. Tumour site (p = 0.048) and gender (p = 0.039) were significantly associated with H63D and C282Y mutation status, respectively. Local spread of cancer was significantly associated with C282Y mutations in CRC cancer and adjacent non-neoplastic tissue (p = 0.029 & and p = 0.004, respectively). There was a statistically significant association between H63D and C282Y negativity in matched non-neoplastic colorectal mucosa tissue and pathological staging of cancer (p = 0.047 & and p = 0.001, respectively). Patients with H63D and C282Y mutations in cancer tissue tend to have higher survival rates. Hence HFE mutations are common in CRC and are associated with clinicopathological parameters, implying the potential clinical significance of HFE mutations in colorectal carcinogenesis.
Publisher: Hindawi Limited
Date: 2018
DOI: 10.1155/2018/5342936
Publisher: Springer Nature Singapore
Date: 2023
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.CRITREVONC.2018.03.025
Abstract: Emerging evidence that heme iron in red meat is a risk factor for colorectal carcinogenesis is a topic that has received recent scrutiny. This review aims to summarise the mechanism of colorectal carcinogenesis by heme contained in red and processed meat. Heme iron can induce cytotoxicity by 'cytotoxic heme factor' and promote surface epithelial cell apoptosis and compensatory epithelial hyperplasia. Heme, induces peroxidation of lipids, leading to free radical formation and generation of DNA adducts in colorectal epithelial cells. In addition, heme catalyses the formation of N-nitroso-compounds, which in turn results in the initiation of colorectal carcinogenesis. Emerging data suggest that intestinal dysbiosis can promote carcinogenic properties of heme. Heme induces multiple genetic alterations by regulating WNT signalling pathway and causing mutations in major colon cancer genes such as APC, TP53 and KRAS. However, a balanced diet containing green vegetables, olive oil and calcium may reduce the carcinogenic effects of heme.
Publisher: MDPI AG
Date: 11-10-2021
Abstract: Polycyclic aromatic hydrocarbons (PAHs) are commonly ingested via meat and are produced from high-temperature cooking of meat. Some of these PAHs have potential roles in carcinogenesis of colorectal cancer (CRC). We aimed to investigate PAH concentrations in eight types of commonly consumed ready-to-eat meat s les and their potential effects on gene expressions related to CRC. Extraction and clean-up of meat s les were performed using QuEChERS method, and PAHs were detected using GC-MS. Nine different PAHs were found in meat s les. Interestingly, roast turkey contained the highest total PAH content, followed by salami meat. Hams of varying levels of smokedness showed a proportional increase of phenanthrene (PHEN), anthracene (ANTH), and fluorene (FLU). Triple-smoked ham s les showed significantly higher levels of these PAHs compared to single-smoked ham. These three PAHs plus benzo[a]pyrene (B[a]P), being detected in three meat s les, were chosen as treatments to investigate in vitro gene expression changes in human colon cells. After PAH treatment, total RNA was extracted and rtPCR was performed, investigating gene expression related to CRC. B[a]P decreased mRNA expression of TP53. In addition, at high concentrations, B[a]P significantly increased KRAS expression. Treatments with 1 µM PHEN, 25 µM, and 10 µM FLU significantly increased KRAS mRNA expression in vitro, implying the potential basis for PAH-induced colorectal carcinogenesis. Opposingly, the ANTH treatment led to increased TP53 and APC expression and decreased KRAS expression, suggesting an anti-carcinogenic effect. To conclude, PAHs are common in ready-to-eat meat s les and are capable of significantly modifying the expression of key genes related to CRC.
Publisher: Sri Lanka Journals Online (JOL)
Date: 07-08-2014
Location: Australia
No related grants have been discovered for Sujani Kodagoda Gamage.