Cancer Science & Therapy

Background: The status of DNA repair systems impacts the sensitivity of tumors to chemotherapeutics. The anti-neoplastic activity of temozolomide, an alkylating agent, is affected by the enzyme O6-Methylguanine-DNA methyltransferase (MGMT), and by the mismatch repair system (MMR). Lack of MGMT makes a tumor susceptible to temozolomide provided MMR is functional. A non-functional MMR renders the tumor resistant to alkylating agents. We assayed MGMT and MMR in order to estimate the proportion of patients affected by NSCLC who may derive benefit from temozolomide, an alkylating agent not currently used in lung cancer. Method: MGMT and MMR were assayed by promoter methylation testing and by microsatellite instability testing, respectively, on 96 paraffin-embedded NSCLC samples. Methylation testing, which detects gene silencing, was conducted by methylation-specific PCR of the MGMT promoter. MSI testing, which detects a non-functional MMR, was conducted by multiplex PCR of six microsatellite regions. Results: Ninety three samples yielded interpretable results. Eighty of those (83%) had no defects detected in either MGMT or MMR. Nine samples (10%) had methylation of the MGMT promoter and four samples (4%) had microsatellite instability. The defects were not overlapping. Conclusions: Our results indicate that approximately 10% of NSCLC may be susceptible to alkylating agents, and that in the remaining population, only 4% will be resistant to these agents. Our understanding of the molecular characteristics of NSCLC suggests that alkylating agents, such as temozolomide, alone or in combination with MGMT inhibitors, may be viable option to treat selected NSCLC patients.

Study background: Anticancer chemotherapy Anthracycline (ANT) antibiotics associated with cardiac and renal toxicity which represents serious complication. In this study, the protective effect of the 2 beta-blockers carvedilol and nebivolol were tested in a rat model of ANT induced cardio and renal-toxicity by repeated intraperitoneal doxorubicin (Dox) administration. Methods: Six groups of animals were used, each 8 rats divided as control group- received intraperitoneal saline every other day; control carvedilol: rats received carvedilol dose 30mg/kg/day orally; control nebivolol: rats received nebivolol 1mg/kg/day orally; doxorubicin alone: a dose of 3 mg/kg/day was administered intraperitoneal every other day; doxorubicin + carvedilol: carvedilol started at the same day with Dox; doxorubicin + nebivolol: nebivolol started at the same day with Dox. All substances were administered for 12 days. Detection & quantification of doxorubicin-induced heart and renal damage and therapeutic action of beta-blockers was done using Langendorff's technique, echo-cardiographic function examinations, serum creatinine, total proteins and histopathology. Results: The administration of doxorubicin in the dose of 3 mg/kg/day for 12 days produced pronounced heart impairment, as well as renal nephrotoxic changes. Significant reduction of Doxo-cardiotoxicity and nephrotoxicity in Nebivolol-treated animals more than Carvedilol treated animals. Conclusions: Coadministration of either carvedilol or nebivolol with doxorubicin was able to ameliorate up to almost contradict doxorubicin-induced myocardial injury, glomerular filtration disturbance and renal tubular damage with upper hand for nebivolol. So, they can be considered a feasible candidate to protect against nephrotoxicity & cardiotoxicity commonly encountered with doxorubicin treatment.

Breast cancers are usually treated with surgery and radiation excretes adverse effects. Azurin, a potent anticancer redox protein secreted by Pseudomonas aeruginosa (P. aeruginosa) species has been reported to have activity against breast cancer cell lines; this had prompted researchers to search for novel methods to enhance this protein's production. Researchers previously have reported on the synthesis of blue copper protein azurin from different microbial sources specifically from P. aeruginosa. Our investigation used customized methods to focus on synthesizing azurin from different strains of P. aeruginosa with apparent homogeneity. We screened the growth of different P. aeruginosa strains (1934, 741, 2453, and 1942) for the synthesis of azurin and for enhanced azurin production. We exposed azurin properties using matrix-assisted laser desorption/ionization, sodium dodecyl sulfate polyacrylamide gel electrophoresis and Fourier transform infrared spectroscopy. Additional studies of possible molecular mechanisms and reactive oxygen species (ROS) generation of P. aeruginosa 2453 secreted azurin are needed. We examined which strain among P. aeruginosa strains 1934, 741, 2453, and 1942 best enhanced azurin production. Our current study also revealed which strain of the four had the strongest antiproliferative effect of azurin. P. aeruginosa MTCC (Microbial Type culture collection) 2453 was the strain that secreted the most azurin and showed remarkable apoptosis in breast carcinoma cells like T- 47D and ZR-75-1. This study demonstrates customized methods to synthesize azurin from different strains of P. aeruginosa with apparent homogeneity and their apoptotic effects on breast carcinoma cells with possible molecular mechanisms and ROS.

Background and Aims: Phenotypic analysis of lymphomas is now considered compulsory for precise classification which is the starting point for best possible patient management. The aims of this study were to investigate the frequencies of T cell (using CD3) and Hodgkin's cell (using CD30) lymphomas in Sudan. Methods: In this retrospective study, paraffin embedded tissue blocks from 62 patients with lymphomas and three patients with benign lymph proliferative disorders were studied. Although, all of the 65 specimens were immunostained for CD3, only 30 specimens were immunostained for CD30 expression. Results: Out of the 62 cases of lymphomas, 13(21%) were cases of Hodgkin's lymphoma and the remaining 49 (79%) were Non-Hodgkin's lymphomas. Of the 62 cases immunostained for CD3 expression, 15(24%) were identified as CD3-positive. Of the 30 cases immunostained for CD30 expression, 12(40%) were demonstrated as CD30-positive, all of them from the cases of Hodgkin's lymphomas. Conclusion: There is high frequency of T-cell lymphomas among Sudanese lymphoma's patients. CD30 marker has a reasonable specificity and sensitivity measures as a marker for identifying Hodgkin's lymphomas. Studies for immunophenotyping of lymphoma with extra markers are highly recommended.