ASSESSMENT OF MOLECULAR BIOMARKERS FOR BLADDER CANCER DIAGNOSIS, GRADING AND PROGNOSIS

Worldwide, bladder cancer is a very significant public health problem, in terms of prevalence, mortality and management for individuals and their families. Bladder cancer is the fourth most commonly diagnosed cancer in men and one of the heaviest cancers in terms of cost. Although transurethral resection of the bladder followed by intravesical instillation of live attenuated Bacillus Calmette–Guérin (BCG) is considered as the gold standard for patients with intermediate and high risk, only a small portion of patient responds to the BCG-therapy. Bladder cancer management is faced by the therapy failure, great side effects and some difficulties in histological classification. Accordingly, growing interest is given to the use of genetic, epigenetic and immunologic biomarkers for molecular signature characterization and tumor stratification. In Morocco, great efforts have been made to contribute to the improvement of management of bladder cancer and many studies were made to evaluate some genetic and epigenetic biomarkers. Generated data is of a great interest for characterization of bladder cancer tumors in Morocco and could be used for better management of this disease

THE MOLECULAR BASIS OF VIRO-INDUCED CARCINOGENESIS

Cancer is the most emerging condition effecting millions of people globally and the leading cause of death. Worldwide, cancer is considered a great public health problem...

EVALUATION OF GPX1 PRO198LEU POLYMORPHISM, GSTP1 EXPRESSION AND GENE PROMOTER METHYLATION IN MOROCCAN PATIENTS WITH BLADDER CANCER

Bladder cancer (BC) is the third most common male malignancy in Morocco. The risk factors for developing BC are multiples including dietary conditions, environmental exposure and oxidative stress. Glutathione Peroxidase-1 (GPX1) and Glutathione S-Transferase Pi (GSTP1) are two key enzymes in cell detoxification process. GPX1 Pro198Leu polymorphism is associated with a decrease of enzyme activity and may contribute to BC susceptibility. Deregulated expression of GSTP1 enzyme was reported in various human tumors, also, epigenetic silencing of GSTP1 gene by aberrant promoter methylation has been shown to be involved in the molecular pathway for cancer development. In this study, we aimed to assess the presence of GPX1 Pro198Leu polymorphism and determine the expression status of GSTP1-in relation to its promoter methylation- in Moroccan population to evaluate their association with the risk of developing BC in Moroccan patients. Genotyping of GPX1 Pro198Leu polymorphism was carried out by Sanger sequencing. GSTP1 expression was assessed by immunohistochemistry, GSTP1 promoter methylation status was studied by Methylation Specifiq PCR method. No significant association between GPX1 Pro198Leu polymorphism and BC occurrence was found (Pro/Leu vs. Pro/Pro: p=0.425). For the analysis of Pro198Leu polymorphism and progression of BC, no association was observed neither for stages (Pro/Leu vs. Pro/Pro: p=0.500) nor grades (Pro/Leu vs. Pro/Pro: p=0.415). GSTP1 expression was strong in 23.33%, moderate in 60% and weak in 13.33% of BC cases. Variability of the expression does not correlate with high-grade cancer or invasive-stage (p˃0.05). No GSTP1 promoter methylation was detected in all cases. Our results showed that GPX1 Pro198Leu polymorphism and GSTP1 expression are not closely associated with the risk of BC in our population, suggesting that the effect of these biomarkers on BC development might be a result of a combination with other genetic and epigenetic alterations and/or non-genetic variables such as diet and lifestyle factors

Human papillomavirus detection in moroccan patients with nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma (NPC) is a malignant tumor which arises in surface epithelium of the posterior wall of the nasopharynx. There's is evidence that Epstein Barr virus (EBV) is associated to NPC development. However, many epidemiologic studies point to a connection between viral infections by the human papillomavirus (HPV) and NPC.</p> <p>Method</p> <p>Seventy Moroccan patients with NPC were screened for EBV and HPV. EBV detection was performed by PCR amplification of BZLF1 gene, encoding the ZEBRA (Z Epstein-Barr Virus Replication Activator) protein, and HPV infection was screened by PCR amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 35, 45 and 59.</p> <p>Results</p> <p>The age distribution of our patients revealed a bimodal pattern. Sixty two cases (88.9%) were classified as type 3 (undifferentiated carcinoma), 6 (8.6%) as type 2 (non keratinizing NPC) and only 2 (2.9%) cases were classified as type 1 (keratinizing NPC). EBV was detected in all NPC tumors, whereas HPV DNA was revealed in 34% of cases (24/70). Molecular analysis showed that 20.8% (5/24) were infected with HPV31, and the remaining were infected with other oncogenic types (i.e., HPV59, 16, 18, 33, 35 and 45). In addition, statistical analysis showed that there's no association between sex or age and HPV infection (P > 0.1).</p> <p>Conclusion</p> <p>Our data indicated that EBV is commonly associated with NPC in Moroccan patients and show for the first time that NPC tumours from Moroccan patients harbour high risk HPV genotypes.</p

A review of the infection-associated cancers in North African countries

Cancer is typically classified as a leading non-communicable disease; however, infectious agents, such as Helicobacter pylori (H. pylori), hepatitis B virus (HBV), hepatitis C virus (HCV) and human papilloma virus (HPV), contribute significantly to the pathogenesis of various cancers. Less developed countries, including countries of the North African (NA) region, endure the highest burden of infection-related cancers. The five most common infection-associated cancers in NA in order of incidence are bladder cancer, cervical cancer, liver cancer, stomach cancer, and nasopharyngeal carcinoma. This review aims to outline the epidemiologic pattern of infection-associated cancers in five NA countries (namely: Morocco, Algeria, Tunisia, Libya and Egypt) highlighting the similarities and differences across the region. The present study employed an initial literature review of peer-reviewed articles selected from PubMed, ScienceDirect and World Health Organization (WHO) databases based on key word searches without restriction on publication dates. Original research articles and reports written in French, as well as data from institutional reports and regional meeting abstracts were also included in this extensive review. Egypt, Libya, Tunisia, Algeria and Morocco were selected to be the focus of this review

Prevalence of mucosal and cutaneous human papillomavirus in Moroccan breast cancer

Background: Due to recent technical improvements and some encouraging new results, there has been a resurgence of interest in the possibility that a substantial proportion of breast cancers (BCs) may be caused by viral infections, including Human papillomavirus (HPV). The aim of this study was to determine the prevalence of mucosal and cutaneous HPV in tumours from Moroccan BC patients. Materials and methods: Frozen tumours from 76 BC cases and 12 controls were evaluated for the presence of 62 HPV-types using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. Results: HPV DNA was found in 25.0% of BC tumours and only 8.3% of controls. Beta and gamma HPV types were found in 10.5% and 6.6% of BC tumours, respectively. High-risk mucosal types HPV16 and 18 were not detected in the subjects, but other probable/possible high-risk or high-risk -HPV types (HPV51, 52, 58, 59, and 66) were found in 5.3% of BC tumours. Statistical analysis showed no significant difference between, controls, BC cases and the inflammatory status (p > 0.05). Conclusion: HPV DNA was found 3 times as frequently in the BC tumours as in the controls. However, this difference requires confirmation in a larger sample. Keywords: Breast cancer, Human papillomavirus, Inflammatory breast cancer, Type-specific multiplex genotyping, Morocc

Leaf Extracts of <em>Cistus ladanifer</em> Exhibit Potent Antioxidant and Antiproliferative Activities against Liver, Prostate and Breast Cancer Cells

Chemical composition, antioxidant, and antiproliferative properties of C. ladanifer crude extracts, including hexane (Hex), dichloromethane (DCM), ethyl acetate (E.A) and ethanol (EtOH) were investigated. The chemical composition of C. ladanifer crude extracts was determined by use of GC-MS, whereas DPPH and FRAP assays were employed to determine its antioxidant capacity. The obtained results showed that the ethanolic extract exhibited a significant antioxidant effect recording an IC50 value of 266.6 ± 0.828 μg/mL with DPPH assay, and a higher reducing power 0.494 ± 0.035 using the FRAP test. The extracts exhibited significant antiproliferative activity against three cancer cell lines. The DCM extract exhibited the highest total polyphenol content (76.066 ± 9.978 μg AGE/mg) and was revealed to be more effective against HepG2 (31.54 ± 0.242 μg/mL). The Hex extract that presented the highest flavonoid content (50.209 ± 3.805 μg CE/mg) exhibited the highest antiproliferative activity against 22Rv1 and MDA-MB-231 recording IC50 values 11.32 ± 2.126 μg/mL and 82.4 ± 1.124 μg/mL, respectively. All four extracts exhibited minimal toxicity against human skin-derived fibroblast cells indicating the specificity of their observed anticancer activity. GC-MS analysis identified interesting phytochemicals underlying the obtained antioxidant and cytotoxic activities. Taken together, results of the current study highlight the significance of C. ladanifer as a valuable source of antioxidant and anticancer bioactive compounds, thereby warranting further detailed investigation