Ciência e terapia do câncer

Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for local control and their effect on overall survival (OAS).

Materials and methods: This is a retrospective study included 121 patients with primary locally advanced NSCLC diagnosed between 2001 and 2010 at the radiotherapy department, National Cancer Institute, Cairo University, Egypt.

Results: The study showed significant correlation between the tumor size ≤ 7 cm, old age >60, moderately differentiated tumors G2 and treatment outcomes; better locoregional control and better survival rates. On the opposite side poorly differentiated tumors G3, tumor size >7 cm had the worst locoregional control and survival rates. The study also showed significant statistical correlation between treatment modality, locoregional control and survival rates. Patients who were treated by either concomitant chemo-radiotherapy or sequential chemoradiotherapy had better local control compared to other patients who were treated by radical radiotherapy, and they also had the best survival rates among all the other treatment groups. The average 6 months OAS rates for all studied patients were 60.3% while 12 months survival rates were 38.8%. The median OAS was 7 months. The data was summarized by descriptive statistics [i.e., mean, standard deviation (SD), frequencies]. Mean values and standard deviation were compared using simple T-test (2 variables). Percentages were compared using Chi-square test or Fisher’s exact test. Kaplan-Meier test was used for predictive survival rates. Conclusions: From the present study, we concluded that concomitant chemradiotherapy is the treatment of choice for locally advanced non small cell lung cancer; also we concluded that better performance status and higher hemoglobin levels have better treatment outcome in these cases.

NF-κB is regulated by two distinct pathways namely the Classical NF-κB pathway and the recently discovered alternative NF-κB pathway. While the classical NF-κB pathway has been extensively studied for its role in cancer, our understanding of the regulation of the alternative NF-κB pathway and its role in cancer has been limiting. Nevertheless, significant progress has been made recently that revolves around the regulation of NF-κB inducing kinase and its role in cancer. These recent developments will be discussed in this editorial.

Plants are important sources of biologically active natural products which differ in terms of structure and biological properties. One of the biological activities of plant compounds that attracts great interest is the ability to exert anticancer activity in different cancer types. Boldine is a natural alkaloid that occurs abundantly in the leaves and bark of Peumus boldus. It has been demonstrated to present anticancer properties in bladder carcinoma and in glioma cancer cells in vitro. In the present study, we evaluated the effect of boldine in an in vivo experimental model of glioma and investigated some parameters of toxicity in healthy animals. Our results show that boldine did not cause any toxicity in the animals treated. In rats with implanted glioma and treated with boldine a significant reduction in tumor size was observed. Pathological analysis of implanted gliomas showed a reduction in the mitotic index as well as in other histological characteristics in boldine treated animals, indicating a less invasive and proliferative tumor. No change was observed in the VEGF expression in treated animals. Our results suggest that boldine could be a promise adjuvant therapy in the treatment of malignant gliomas

Background: Tri-modality bladder sparing therapy in selected bladder cancer patients may be an alternatives treatment option to immediate radical cystectomy as it may result in satisfactory Quality Of Life (QOL). The present study evaluated the effects of this conservative approach versus surgical approach, i.e. Radical Cystectomy (RC) and orthotopic neobladder, on QOL of patients.

Patients and methods: This is a prospective study of patients with bladder cancer in group I (using tri-modality bladder sparing therapy) and group II (using RC and orthotopic neobladder). Patients in both groups were subjected to interview NCCN-FACT FBlSI18 questionnaire, inquiring about physical and emotional disease related symptoms, treatment side effects and function and well being. SPSS version18 software was used for statistical analysis.

Results: Internal consistency of the 18 items in both groups was assessed by Cronbach’s α which was adequate at 0.89 at Group I and 0.84 at Group II. Univariate analysis showed that there were statistically significant difference (p<0.05) in favor of group I patients compared to those in group II, regarding bladder function, potency and bowel symptoms. Multivariate analysis revealed that only T stage significantly affected physical and emotional disease related symptoms, and treatment side effects subscales in favor of bladder preservation group.

Conclusions: Tri-modality bladder sparing therapy resulted in well-functioning bladders, mild bowel symptoms, and satisfactory sexual functioning in contrast to the surgical approach in bladder cancer patients and should be considered as a reasonable option for these patients.

Stress-Induced Premature Senescence (SIPS), a senescence-like state achieved as a result of a variety of stresses, is associated with relative inability to undergo apoptosis. Sirtuins are a family of histone deacetylases known primarily for their implication in the aging process; however their role in cancer, an aging associated disease, is still poorly understood. In the present study, we investigated whether alterations in sirtuins expression may be associated with aggressive tumor behavior. We have compared expression profiles of sirtuins between drug sensitive and resistant cancer cells MCF7, SaOS-2, A2780 and HL-60. Expression levels of Sirtuin 1-6 varied among cell lines; however Sirtuin-7 was significantly reduced in all chemoresistant cells tested. Knockdown of Sirt7 expression in human breast MCF7 cell line by RNAi induced senescence-associated β-galactosidase activity, reduced cell proliferation rate, induced drug resistance and increased cell migration, suggesting that this gene may play an active role in regulating cancer cell response to stress. Thus, Sirt7 may represent a compelling target for anti-cancer interventions

Purpose: Leptomycin B [LMB] is an anti fungal metabolite which was tested for anti cancer activity, but failed in clinical trials due to non specific killing at higher concentrations. Leptomycin B acts on CRM1, a nuclear export protein that exports p53 out of the nucleus. Leptomycin B blocks CRM1, hence leading to sequestration of p53 in the nucleus, which in turn leads to apoptosis. DR5 antibody is one of the most successful compounds being used in the market for cancer therapy. In this project, Leptomycin B is combined with DR5 [dual treatment] and tested on PC3, LNCAP and MCF7 cells to find out whether leptomycin B increases the percentage of apoptotic cells. This project aims at testing leptomycin B on PC3 cells which are p53 null mutants, and to find out the expression levels of p53 related genes using RT-PCR. Nutlin 3a, a MDM2 antagonist is also combined with dual treatment to check whether there is increased apoptosis.

Results: Leptomycin induced apoptosis in PC3 cells [p53 null mutants] even at lower concentrations. Dual treatment showed an increased percentage in apoptotic cells when compared to DR5 alone treatment. Nutlin was also found to induce apoptosis in PC3 cells.

Conclusion: Leptomycin B and Nutlin 3a induce p53 independent apoptosis. Dual treatment can be considered for further trials for better killing of cancer cells