SelSA-1, a novel HDAC inhibitor demonstrates enhanced chemotherapeutic potential by redox modulation.

Colorectal cancer (CRC) is a multistep disorder resulting from genetic and epigenetic genome changes. It is the third most common malignancy in developed nations accounting for roughly 600,000 deaths annually. Persistent gut inflammation, as observed in inflammatory bowel disease (IBD), is a key risk factor for CRC development. From an epigenetic viewpoint, the pharmacological inhibition of HDACs using HDAC inhibitors such as SAHA has emerged as a suitable anticancer strategy in the recent past. However, the clinical success of these strategies is limited and has risk factors associated with their uses. Thus, considering the critical involvement of epigenetic regulation of key molecular mechanisms in carcinogenesis as well as HDAC inhibitory and anti-tumorigenic properties of Selenium (Se), we aimed to explore the potentially safer and enhanced chemotherapeutic potential of a Se derivative of SAHA namely SelSA-1, in an experimental model of colitis-associated experimental cancer (CAC) model and mechanism involved therein. The in vitro study indicated improved efficiency, specificity, and better safety margin in terms of lower IC50 value of SelSA-1 than SAHA in both NIH3T3 (9.44 and 10.87 µM) and HCT 115 (5.70 and 7.49 µM) cell lines as well on primary colonocytes (5.61 and 6.30 µM) respectively. In an in vivo experimental model, SelSA-1 efficiently demonstrated amelioration of the multiple plaque lesions (MPLs), tumor burden/incidence, and modulation of various histological and morphological parameters. Further, redox-mediated alterations in apoptotic mediators suggested induction of cancer cell apoptosis by SelSA-1. These findings indicate the enhanced chemotherapeutic and pro-resolution effects of SelSA-1 in part mediated through redox modulation of multiple epigenetic and apoptotic pathways.

Comparison of iso-effective and cost-effective high-dose-rate brachytherapy treatment schedules in cervical cancer - regional cancer center experience.

PURPOSE: The study is to evaluate the difference between outcomes of two high-dose-rate fractionation schedules in the treatment of intracavitary brachytherapy (ICBT) of cervical cancer. MATERIAL AND METHODS: A retrospective analysis of 163 cervical cancer patients was completed. All patients received external beam radiotherapy (EBRT) to whole pelvis with concurrent weekly chemotherapy, followed by ICBT with either 7 Gy per fraction in three fractions (arm A) or 9 Gy per fraction in two fractions (arm B). Median follow-up was 19 months. The outcomes were compared in terms of 2-year actuarial local control, disease-free survival, overall survival, and late toxicity in the two treatment arms. RESULTS: The 2-year actuarial local control rates in arm A and arm B were 88.5% and 91.5%, respectively. The actuarial 2-year disease-free survival rates in arm A and arm B were 85.9% and 82.6%, respectively. The actuarial 2-year overall survival in arm A and arm B were 95.7% and 100%, respectively (p = 0.06). There were 12.7% and 15.2% local failures in arm A and arm B, respectively. Distant metastases were seen in 8.5% and 7.6% in arm A and arm B, respectively. The 2-year actuarial risk of developing late rectal toxicity in arm A and arm B were 5.6% and 5.4%, respectively. The 2-year actuarial risk of developing late bladder toxicity in arm A and arm B were 2.8% and 2.2%, respectively. CONCLUSIONS: ICBT treatment with 9 Gy in two fractions offers equivocal local control rates and survival rates in cancer cervix cases with many advantages of short overall treatment time, improved patient compliance, cost effectiveness, and reduced exposure to aesthetic agents. The toxicities observed were few, low grade, and easily manageable.