Samar K. Kassim

Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAs

A new, sensitive, noninvasive method for the detection of urothelial carcinomas of the urinary bladder would open new possibilities in both the diagnosis and followup of patients.

Increased bcl-2 expression is associated with primary resistance to chemotherapy in human epithelial ovarian cancer

OBJECTIVE bcl-2, an anti-apoptotic factor, has a role in the pathogenesis of ovarian cancer as well as in resistance to chemotherapy. DESIGN AND METHODS 20 benign, and 26 malignant epithelial ovarian tissues were analyzed for bcl-2 protein and mutant p53 by enzyme-immunoassay (EIA). Flowcytometric analysis was also performed. Patients of malignant group were followed up to monitor overall survival and primary resistance to chemotherapy. RESULTS bcl-2 was significantly higher in malignant group than benign group (p < 0.001). A cutoff value was determined for bcl-2 (63.8 kU/g protein). At this cutoff, sensitivity is 80.7%, and specificity is 85%. Using chi square analysis, a significant correlation was found between bcl-2 and FIGO stage (p = 0.01), overall survival (p = 0.01), as well as primary resistance to chemotherapy (p = 0.03). By correlation coefficient analysis the relation between bcl-2 and synthetic phase fraction was highly significant (p = 0.002). Bcl-2, p53, and FIGO stage were significantly correlated to poor survival (p = 0.01) in univariate analysis. However, in multivariate analysis, only FIGO stage, and p53 were independent risk factors. CONCLUSION EIA could be a useful tool for investigating the prognostic value of bcl-2, and its possible prediction of platinum resistance in epithelial ovarian cancer. This might help in selecting patients for future anti-bcl-2 therapy.

H3ABioNet, a sustainable Pan-African Bioinformatics Network for Human Heredity and Health in Africa

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.

The value of CA 125 and CA72-4 in management of patients with epithelial ovarian cancer.

The role of the tumor markers CA125 and CA72-4 has been evaluated in the diagnosis and management of ovarian cancer. Both markers were measured in 30 patients with proven epithelial ovarian cancer, 30 patients with benign pelvic masses and 30 normal women. CA125 and CA72-4 were measured using the luminometric immunoassay and immuno-radiometric assay respectively. All patients with ovarian cancer were submitted to surgical staging and cytoreduction followed by adjuvant platinum based chemotherapy for 3–6 courses. Fixing the specificity at 95%, CA125 had a sensitivity of 76.7% at a cut-off 85u/ml while CA72-4 had a sensitivity of 70% at a cut-off 8.5 u/ml. The combination of CA72-4 with CA125 increased the sensitivity to 95% while fixing the specificity at 95%. Among seven cases with stage I and II ovarian cancer five cases had CA125 level below 85 U/ml, three patients out of them had CA72-4 above 8.5 U/ml. CA 72-4 could reflect the residual disease following cytoreduction and could improve the detection of relapse by CA125. Conclusion: CA72-4 could complement the standard tumor marker CA125 both in diagnosis and follow up of patients with epithelial ovarian cancer.

Lipopolysaccharide Repeated Challenge Followed by Chronic Mild Stress Protocol Introduces a Combined Model of Depression in Rats: Reversibility by Imipramine and Pentoxifylline

OBJECTIVES The present study examined the effect of combined exposure to repeated challenge using low doses of lipopolysaccharide (LPS) and chronic mild stress (CMS) together. This combined exposure is thought to expose the animals to more realistic challenges, testable on different levels (behavioral, neurochemical, immunohistochemical and gene expression). The role of glial cells was examined, as well. Additionally, the effects of chronic administration of the tricyclic antidepressant imipramine and the anti-TNF-α pentoxyphylline were investigated. METHODS Wistar rats were exposed to either repeated LPS (50μg/kg i.p.) over 2weeks, CMS protocol for 4weeks or LPS over 2weeks then 4weeks of CMS. Two groups of rats were exposed to LPS/CMS protocol and treated with either imipramine or pentoxifylline. Rats were examined for behavioral, neurochemical and gene expression changes. RESULTS Animals exposed to LPS/CMS elaborated depressive-like symptoms with significant increase in both serum corticosterone and TNF-α levels compared to those in the saline, LPS or CMS groups. Hippocampal kynurenine/tryptophan ratio and TNF-α gene expression showed significant increase in the LPS/CMS model compared to those in saline, LPS or CMS groups. The immunohistochemical findings scrutinized the topography of the examined effects. Chronic treatment with imipramine or pentoxifylline significantly ameliorated the behavioral, neurochemical, immunohistochemical and TNF-α gene expression changes induced by the LPS/CMS protocol. CONCLUSION This study gave a clue to the neurobiological processes underlying, at least, the subtypes of depressive disorders. It highlighted the possible interactions between stress and immune-inflammatory pathways in the pathogenesis of depression and suggested a new animal model of depression that addresses these pathways.

Evaluation of nitric oxide (NO) levels in hepatitis C virus (HCV) infection: Relationship to schistosomiasis and liver cirrhosis among Egyptian patients

Nitric oxide (NO), a recently discovered free radical, is overproduced in liver cirrhosis. Hepatitis C virus (HCV) might increase NO levels via increased inducible NO synthase (iNOS). This work was carried out to study the effect of HCV-induced liver cirrhosis on NO levels among Egyptian patients. The study included 46 patients with liver cirrhosis, and 30 healthy individuals of matched age and sex. NO levels determined as the stable endproduct nitrate, showed a statistically significant increase among patients compared to the control group (P < 0.001). Furthermore, NO levels increased proportionally with the severity of liver cirrhosis as assessed by Child’s classification (P < 0.05). Moreover, schistosomial infection enhanced NO levels in cirrhotic patients with HCV infection compared to non-bilharzial patients (P < 0.001). Polymerase chain reaction (PCR) and branched DNA assays were used for detection of HCV RNA positivity, and measurement of the virus load, respectively. Both showed a positive correlation with the NO levels (P < 0.001). At a nitrate cutoff value of 70 μmol/L, the sensitivity and specificity were 83.0% and 37.0% respectively. Chi square analysis showed a significant correlation between ALT levels and both HCV RNA positivity by polymerase chain reaction (PCR) (P < 0.02), and virus load (P < 0.05). Interestingly enough, there was a significant positive correlation between HCV RNA and schistosomal antibody titer as measured by hemaglutination inhibition assay (HAI) (P < 0.05). The data presented in this report indicated an association between NO levels and the development and progression of liver cirrhosis. Furthermore, the findings obtained from this study demonstrated that schistomiasis is an important risk factor involved in enhancement of NO levels and virus replication. The latter may aggravate liver cell injury and hence the development of cirrhosis.

Epstein-Barr Virus, Human Papillomavirus, and Flow Cytometric Cell Cycle Kinetics in Nasopharyngeal Carcinoma and Inverted Papilloma among Egyptian Patients

It is widely accepted that the Epstein-Barr virus is etiologically associated with the development of nasopharyngeal carcinoma. The human papillomavirus is also associated with inverted papilloma. We used the polymerase chain reaction technique to detect both viruses in both types of tumors. Flow cytometry was also used to study the DNA pattern and proliferative behavior of the tumors in relation to the viruses. EBV was detected in 13/20 (65%) of NPC specimens, and in none of IP (n = 10) or control specimens (n = 10). This indicates the contribution of EBV as an etiologic factor in NPC. Five cases of NPC (25%) were positive for HPV 16, two of them were EBV positive. Four HPV 16 positive cases were found among cases with inverted papilloma, but none among the control cases. Flow cytometry revealed that all NPC, IP, and control samples were diploid except one aneuploid NPC sample. Proliferative capacity (PC) of primary tumors was predictive of tumor recurrence in NPC. Using 13.6% as a cut-off point for PC, we were able to discriminate between high risk and low risk groups with 100% sensitivity and 86% specificity. PC can be used as a baseline prognostic parameter in NPC, making it possible to modify courses of treatment in an attempt to inhibit tumor recurrence.

Formal concept analysis for mining hypermethylated genes in breast cancer tumor subtypes

The main purpose of this paper is to show the use of formal concept analysis (FCA) as data mining approach for mining the common hypermethylated genes between breast cancer subtypes, by extracting formal concepts which representing sets of significant hypermethylated genes for each breast cancer subtypes, then the formal context is built which leading to construct a concept lattice which is composed of formal concepts. This lattice can be used as knowledge discovery and knowledge representation therefore, becoming more interesting for the biologists.

Using formal concept analysis for mining hyomethylated genes among breast cancer tumors subtypes

Hypomethylation of DNA have been associated with cancer in several investigations. Hypomethylated of CPG islands associated with promoters can affect the expression of genes to be more expressed. The Illumina GoldenGate Methylation Cancer Panel I can measure DNA methylation at 1505 CpG loci of 806 cancer related genes. A powerful tools to analysis the DNA methylation data are needed. In this paper, formal concept analysis (FCA) is used as data mining tool for mining the hypomethylated genes among breast cancer subtypes, by building formal concepts with significant hypomethylated genes for each breast cancer subtypes. The concept lattice is constructed based on a formal context which is composed of formal concepts. This lattice reflects the biological relationships among breast cancer subtypes.

Telomerase activity, and tissue polypeptide specific antigen (TPS) in Egyptian breast cancer patients

OBJECTIVES Breast cancer is the most common malignancy among Egyptian women. The aim of this study is to evaluate the role of both telomerase and TPS estimation in assessment of breast cancer. METHODS The study included 40 patients with breast cancer, and 20 patients with benign breast diseases. Telomerase activity in breast tissues was assessed using TRAP assay. TPS was measured in sera of the patients by ELISA. RESULTS Telomerase positivity was 15% in benign group vs. 60% in malignant group (p = 0.0009). It was significantly correlated to stage, and lymph node status (p < 0.02). Telomerase positivity showed significant correlation to tumor recurrence (p = 0.0076) in a follow-up period of 36 months. Mean rank of TPS was significantly higher in malignant than benign groups (p < 0.001), and in telomerase positive than telomerase negative patients (p < 0.001). In malignant group, mean rank of TPS was significantly higher in late stages (p < 0.002), in higher grade (p < 0.05), in larger tumor size (p < 0.01), and in lymph node positive patients (p < 0.001). ROC curve was utilized to choose the best cutoff for serum TPS (88 U/L). At this cutoff, the sensitivity was 95%, and the specificity was 75%. At a higher cutoff (109 U/L), TPS positivity was significantly correlated to stage, grade, lymph node status, and telomerase positivity (p < 0.05). CONCLUSION Telomerase positivity and serum TPS might be used as additional markers for assessment of breast cancer.