Cytotoxicity and antimicrobial activity of alkaloids extracted from Catharanthus roseus associated endophytic fungi

Aims@#The aim of this study was to isolate the endophytic fungi from Catharanthus roseus and screen the cytotoxicity and antimicrobial activity of alkaloids extracted from these fungi. @*Methodology and results@#A total of 56 endophytic fungal isolates were screened from C. roseus plant parts. Aspergillus fumigatus and Fusarium oxysporum were the most frequent species. Determinations of alkaloids extracted from the most dominant endophytic fungal species were done. The highest significant total alkaloids productions were by A. fumigatus and Aspergillus niger, while the least significant one was by Botrytis cinera. Antimicrobial assay of endophytic fungal extracts indicated that both A. niger and F. oxysporum exhibited significant antimicrobial activities, while A. fumigatus exerted the least activity. In vitro cytotoxicity assay of the endophytic fungal extracts was done against human breast cancer (MCF-7) and liver cancer (HEPG-2) cell lines using SRB assay method. A. niger extract showed potential cytotoxic effect on MCF-7 cell line with IC50 value of 42.1 μg/mL, while the least cytotoxic effect was exhibited by F. oxysporum on MCF-7 cell line with IC50 value of 66.9 μg/mL. Gas Chromatography Mass Spectroscopy (GC-MS) was used for analysis of alkaloids in mycelial and filtrate extracts of A. niger, where eleven compounds were detected. @*Conclusion, significance and impact of study@#Alkaloids extracted from Catharanthus roseus associated endophytic fungi had cytotoxic and antimicrobial activities.

Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study / 癌症

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.

Primary gastrointestinal non-Hodgkin's lymphoma [PGI NHL]: management and outcome

Sixty-four patients with PGI NHL were included in this study. The study outlined the clinicopathological features, modalities of diagnosis and treatment, outcome and variables affecting the overall survival. The stomach was involved in 36 cases and intestinal lymphoma was implicated in 28 cases. Stage IIE was the commonest stage. The predominant histological type was high-grade. The overall survival in all cases was 63% at 30 months according to the Kaplan Meier method. The stage of the disease, extension of resection, site of the lesion whether gastric or intestinal and achievement of complete remission [CR] were found to affect the overall survival

Clinical implications of BRCA1 gene mutations in patients with breast cancer

The aim of the present study was to outline BRCA 1 gene mutations and to highlight its clinical implications in patients with breast cancer. This study included 84 patients with breast cancer who were treated in the period from January 1997 to May 2001 in South Valley University Hospital and South Egypt Cancer Institute, Assiut University. Definitive treatment including surgery, chemotherapy, radiotherapy, and hormonal therapy, were adopted for patients according to the stage of the disease. Follow-up was performed to assess relapse and overall survival at 36 months, according to Kaplan-Meier method. Three genetic tests were carried out to outline and detect genetic polymorphism of BRCA 1 gene mutations. The first two assays were conducted with DNA [BRCA 1 and RAPDs assays]. The third test was serum protein profile. The results showed that BRCA 1 mutations were positive in 63% of breast cancer patients and were negative in the remaining 37%. All the patients had sporadic breast cancer. BRCA 1 mutations were positive in 2% of the control group. Genetic polymorphism revealed by RAPDs markers showed a strong correlation between BRCA l mutations and incidence of some polymorphic bands of OP6 [533 and 825] [88 and 76%, respectively]. There was a statistically significant correlation between BRCA 1 mutations and the commonest clinico-pathological features including premenopausal status, stages II and III, infiltrating ductal carcinoma, grade II and overall survival rate. In conclusion, BRCA 1 mutations may prove to be important etiological factors in sporadic breast cancer patients. BRCA l mutations correlate with the commonest clinico-pathological features and outcome. Other genetic polymorphisms like RAPDs fingerprint may affect the penetrance of RRCA 1 mutations

Premarital counseling: View of the target group

The aim of this study was to assess the knowledge and attitude of the secondary technical nursing school students towards premarital counseling in Alexandria. The study was conducted at four secondary technical nursing schools. 200 students from the chosen schools participated in this study. Questionnaire sheet was developed to assess students knowledge and a 3-point Likert-like scale was used to assess the students attitude. The results revealed that 46.5% of the studied sample had an average score in knowledge, while 65.5% of the students had a positive attitude towards premarital counseling