Significance of telomerase activity, C-erbB2, malondialdhyde and NO as biological markers in urine of bladder cancer patients

At the National Cancer Institute [NCI], Cairo, Egypt, bladder neoplasm constitutes 30% of all cancers. Evaluation of urinary markers may hold a promising method for detection of bladder neoplasms with higher sensitivity and specificity, for follow-up in order to regulate the interval of cystoscopic examination, reduce the burden and discomfort of patients amid enhance the opportunities to excise the tumor preceding muscular invasion. The present study aims to evaluate the possible diagnostic role of telomerase activity, C-erbB2, malondialdehyde and NO in the urine of bladder cancer patients. Eighty urine samples were taken from 3 groups of individuals; 1] Ten healthy age matched control subjects, 2] Twenty schistsoma haematobium infested patients and 3] Fifty pre-operative bladder cancer patients. Urine samples [50mL] were collected and subjected to the assay of telomerase activity in urine [TAU], it was measured by PCR-ELISA technique using the telomerase repeat amplification protocol [TRAP], malondialdehyde and nitric oxide were determined spectrophotometrically and C-erbB2 was measured by ELISA technique. TAU was increased in 72% of bladder cancer cases, it was normal in bilhazial non malignant group compared to controls. Its increase in bladder cancer patients with bilharzial infection was statistically insignificant compared to non bilharzial cancer group. TAU of bladder cancer patients were increased in ascending manner with grades of the tumor [GI = 62.5 +/- 16.7, GII = 66.64 +/- 9.37 and GIII = 163 +/- 51]. Malondialdehyde level was increased in bladder cancer patients with bilharzial infestation than those without bilharziasis, but the difference was statistically insignificant. C-erbB2 expression was increased in 27% of bladder cancer patients; while no single case of the bilharzial group showed positive C-erbB2 expression. As regard the stage of tumor NO level in bladder cancer patients showed statistical significant difference between stage I. II amid stage III [p = 0.04]. There was only a statistically significant positive correlation between telomerase and C-erbB2 in bladder cancer patients [r = 0.456 and p = 0.005]. The study of telomerase activity in the urine of bladder cancer cases may be used as an indicator for early detection of this disease. Further studies should be done to evaluate the possibility of using telomerase as one of the most important tumor markers

Hepatitis c virus and hepatocellular carcinoma

Different etiological factors such as hepatitis viral infection, alcohol, aflatoxin and chemical carcinogens were mentioned in relation to HCC. However, the global distribution of HCC is strongly linked to the prevalence of hepatitis virus infection. The exact pathogenic mechanisms involved in viral-associated HCC are unclear although direct and indirect mechanisms are possible. Direct carcinogenicity is less certain in HCV-Induced HCC since it is a typical RNA virus and therefore the integration of viral genome into host cell chromosomes has not been shown to occur. However, the presence of two conserved potential nuclear localization signals and a DNA binding motif in the HCV core protein suggest a possible functional role as a regulatory element. Moreover, some studies demonstrated that this protein interacts with certain cellular proto-oncogenes at the transcriptional level, resulting in the promotion of cell proliferation and thus affecting normal hepatocyte growth. Therefore the pathogenesis of HCC may be attributed at least in part to the upregulation of hepatocyte growth induced by HCV core protein and other viral proteins like NS3 and NS5. However, the process of malignant transformation represents a dynamic interplay between classes of genes; oncogenes, tumor suppressor genes, mismatch repair genes, genes controlling apoptosis and cell cycle regulatory genes. In conclusion, since the exact mechanism of action of HCV in the context of HCC is still poorly understood, clarification of the molecular basis of viral replication in hepatocytes, the possible genetic and cytogenetic abnormalities that may be induced by the virus were emphasized in this review. Moreover, early detection of hepatocellular changes by molecular biomarkers may help to detect individuals at high risk of development HCC, thus allowing more effective intervention for cure or prevention

Gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer: national cancer institute Cairo experience

The aim of the present study is to document the antitumor activity of the combination of gemcitabine and cisplatin for the treatment of advanced NSCLC, assess the nature and severity of the side effects and elicit the impact of the combination chemotherapy on progression free survival and overall survival. From August 1997 to August 2001 we conducted a phase II study of gemcitabine and cisplatin in 60 chemonaive patients [21 stage IIIB and 39 stage IV]. For the first 34 cases, gemcitabine was given at a dose of 1,000 mg/m[2] IV on days 1, 8 and 15 with cisplatin 100 mg/m[2] on day 15, every 28 days. In the following 26 patients, the regimen was modified to gemcitabine 1,250 mg/m[2] days 1 and 8 and cisplatin 80 mg/m[2] day 1, every 21 days. Patients included 53 males and 7 females [median age. 52 years [range, 28-69]]. Twenty-nine had adenocarcinoma, 18 large-cell carcinoma and 13 squamous-cell carcinoma. Thirty-one patients had a performance status [PS] of 2 and 22 presented with weight loss. All patients were evaluable for response. Three patients achieved a complete response [CR] and 22 had partial response [PR], giving an overall response of 41.7%, with a median duration of 10 months [range, 4-46 months]. The time to progression [TTP] was 8 months [range, 2-46 months], with a median overall survival of 9 months [range, 2-46 months]. The one-year survival rate was 30.3% for the entire study population, 44% for responders, and statistically improved in patients with a PS of 1 and those with no weight loss. A total of 255 cycles were administered [median, four cycles/patient]. Myelosuppresion was significant [but manageable] with grade 3/4 neutropenia in 32.6% of cases, anemia in 18.6% and thrombocytopenia in 20.4%, Nonhematologic toxicity was limited to grade 3/4 nausea and vomiting in 28.8% of cases and impaired liver enzymes in 13.6%. Inspite of the relatively poor prognostic characteristics in the study population, gemcitabine and cisplatin was an effective combination with tolerable, manageable toxicity in advanced NSCLC