Evaluation of the Cytotoxic Effects of the Novel Antineoplastic Agent 1,4,5-Oxathiazinane-4,4-dioxide on Triple Negative Breast Cancer Cells.

BACKGROUND/AIM: Adjuvant therapeutic options are limited for triple negative breast cancer (TNBC). Thus, we evaluated the cytotoxic effects of the newly synthesized antineoplastic agent 1,4,5-Oxathiazinane-4,4-dioxide (OTD) on TNBC cells as a potential cancer therapeutic strategy. MATERIALS AND METHODS: TNBC primary BT-20 and metastatic MDA-MB-231 cell lines were treated with increasing concentrations of OTD for various time periods to assess cell viability. Cell necrosis, apoptosis, necroptosis, autophagy, and ROS generation were evaluated using assay kits or specific inhibitors. RESULTS: Treatment with OTD resulted in a dose- and time-dependent cell death of TNBC BT-20 and MDA-MB-231 cells. OTD also dose-dependently arrested TNBC cell proliferation. Notably, treatment with OTD induced both necrosis and apoptosis of TNBC cells, while the pan-caspase inhibitor Z-VAD-FMK partially attenuated OTD-induced cell death. Importantly, abrogated OTD-induced cell death was observed in the presence of the ROS scavenger N-acetylcysteine (NAC), whereas enhanced OTD-induced cell death was observed after the addition of the glutathione synthesis inhibitor BSO, indicating OTD-induced killing of TNBC cells via a reactive oxygen species-dependent mechanism. CONCLUSION: OTD is strongly cytotoxic to both primary and metastatic TNBC cells, possibly by inducing multiple cell death pathways.

RandomiSed clinical trial assessing Use of an anti-inflammatoRy aGent in attenUating peri-operatiVe inflAmmatioN in non-meTastatic colon cancer - the S.U.R.G.U.V.A.N.T. trial.

BACKGROUND: Peri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised. METHODS: We conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence. RESULTS: A total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo (p = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group (p = 0.27). Surgical site infection was reduced in the Taurolidine treated group (p = 0.09). CONCLUSION: Peri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer. TRIAL REGISTRATION: The trial was registered with EudraCT (year = 2008, registration number = 005570-12 ) and ISRCTN (year = 2008, registration number = 77,829,558 ).

Extended Adjuvant Endocrine Therapy in Breast Cancer: Evidence and Update - A Review.

The optimal duration and treatment strategies involving adjuvant endocrine therapy in early breast cancer remained largely undetermined. As data emerge on the various modalities of treatment in both pre- and postmenopausal groups, debates, and discussions continue. Most studies to date focused on the 5-year duration of treatment consisting of mainly tamoxifen. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) study demonstrated that anastrozole is superior to tamoxifen and has become the mainstream treatment in postmenopausal women with early breast cancer, although the duration was arbitrarily set for 5 years, analogous to tamoxifen treatment. Several clinical trials, however, have emerged to support extended endocrine therapy as it becomes clear that the recurrence risk of breast cancer does not decrease beyond the initial 5 years of treatment. The advent of molecular signatures also plays an important role in the breast cancer profiling, and where available should be incorporated in the overall decision-making. Furthermore, side effects and noncompliance pose another issue in achieving an optimal treatment benefit. The decision-making as regards to extended endocrine treatment should therefore focus not only on the cancer biology alone but also include treatment side effects, assessment of risk of recurrence and patients' preference. In this review, we present an overview of the published studies to date as well as ongoing studies on the topic to better refine the options for adjuvant hormonal therapy.

Focused Versus Bilateral Parathyroid Exploration for Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

BACKGROUND: Focused exploration (FE) and bilateral parathyroid exploration (BE) are the standard surgical options for patients with primary hyperparathyroidism. However, the relative risk of recurrence, persistence, overall failure, reoperation, and any complications associated with either surgical approach is unclear. This study compared the outcomes and complication rates after FE and BE for patients with primary hyperparathyroidism. METHODS: PubMed and Embase were searched for studies comparing these outcomes between FE and BE. A meta-analysis was performed using RevMan 5.3 software. Published data were pooled using the DerSimonian random-effect model, and results were presented as odds ratio (OR) or mean difference with 95% confidence interval (CI). RESULTS: A total of 12,743 patients from 19 studies were included in this meta-analysis. In comparison with BE, the FE arm had comparable rates of recurrence (OR 1.08; 95% CI 0.59-2.00; p = 0.80; n = 9 studies), persistence (OR 0.89; 95% CI 0.58-1.35; p = 0.58; n = 13), overall failure (OR 0.88; 95% CI 0.58-1.34; p = 0.56; n = 13), and reoperation (OR 1.05; 95% CI 0.25-4.32; p = 0.95, n = 4). The operative time was significantly shorter (mean difference = -39.86; 95% CI -53.05 to -26.84; p < 0.01, n = 9), with a lower overall complication rate in the FE arm (OR  0.35; 95% CI 0.15-0.84; p = 0.02; n = 12). The latter was attributed predominantly to a lower risk of transient hypocalcemia (OR  0.36; 95% CI 0.14-0.90; p = 0.03; n = 9). There was a significant heterogeneity among these studies for all outcomes except for disease recurrence. CONCLUSIONS: Compared with BE, FE has similar recurrence, persistence, and reoperation rates but significantly lower overall complication rates and shorter operative time.