A novel method for potentiation of chemotherapy in soft tissue sarcomas with BromAc.

Single-agent doxorubicin currently forms part of standard care for patients with sarcomas. However, efficacy is limited by the presence of dose-dependent cardiotoxicity and toxicity to renal, hepatic, and neurological systems. Therefore, there is a pressing need for novel drug regimens which can provide increased efficacy and safety. BromAc is a novel drug combination developed as a mucolytic agent which has demonstrated anticancer activity both in vitro and in vivo in several cancers. Here, we investigated the efficacy of BromAc in combination with doxorubicin for four subtypes of sarcoma. Cell proliferation, alongside western blot for a variety of cell cycle, apoptosis, and autophagy biomarkers assays was performed following treatment of cell lines in vitro at various concentrations of BromAc and doxorubicin. The impact of drug treatment on MUC1 and MUC4 levels was assessed through immune-cytological methods. Drug agent synergy was assessed through the Chou-Talalay framework. BromAc treatment in combination with doxorubicin was more efficacious than single-agent doxorubicin, with synergistic effects observed. The immuno-cytological analysis demonstrated significant mucin depletion following treatment with BromAc and doxorubicin used in combination, providing a potential mechanistic underpinning for the observed anticancer effects.

Evaluation of Micronutrient Status Post Laparoscopic Sleeve Gastrectomy: an Australian Perspective.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a type of bariatric technique that has comparable outcomes to Roux-en-Y gastric bypass, the current gold standard. However, it can be associated with nutritional deficiencies postoperatively. The aim of this study was to evaluate micronutrient status post LSG. METHODS: This is a retrospective study of 565 patients who underwent an LSG from January 2015 to September 2018. Patients lost to follow-up at 3, 6 and 12 months were 6.3%, 18.6% and 32.4%, respectively. Follow-up of the patients included regular dietetic input and micronutrient supplementation. Data that was collected included both anthropometry and nutritional markers. RESULTS: The mean preoperative weight and body mass index (BMI) were 118.13 ± 25.36 kg and 42.40 ± 7.66 kg/m2, respectively. Statistically, significant reductions in anthropometric parameters including weight, BMI (30.50 kg/m2), total weight loss (28.03%), excess weight loss (72.03%) and BMI loss (12.32 kg/m2) were observed at all timepoints up to 12 months follow-up. At 12 months, there were significant increases in 25-OH vitamin D with the incidence of deficiency decreasing from 45.7 to 15.0% compared to baseline. The incidence of hyperparathyroidism also decreased from 32.2 to 18.9% compared to baseline, and incidence of folate deficiency increased from 7.7 to 19.2%. Other nutritional parameters including calcium, iron, ferritin, vitamin B12, holotranscobalamin (active B12) and haemoglobin did not significantly change. CONCLUSIONS: Modest effects on micronutrient status were observed in the 12-month postoperative period. Of clinically significant, de novo folate deficiencies increased, and vitamin D deficiency and hyperparathyroidism decreased. Thus, optimizing postoperative micronutrient status is imperative following LSG.

Enhancing the potency of chemotherapeutic agents by combination with bromelain and N-acetylcysteine - an in vitro study with pancreatic and hepatic cancer cells.

Current systemic dosages of chemotherapeutic drugs such as gemcitabine, 5-FU, cisplatin, doxorubicin are administered every 7 days over 4 cycles due to systemic toxicity. An increase in potency of the drugs will result in dosage reduction with more frequent administration and efficacy increase. Hence, we investigated how the drugs potency can be increased by combining with bromelain and N-acetylcysteine. Tumour cells (5,000/well) were seeded into a 96 well plate and treated 24 hrs later with either single agents or in combinations at various concentrations. Cell survival was assessed by the sulforhodamine B assay after 72 hours of exposure. LD 50 was determined for each treatment and the Combination Index (CI) was assessed to determine synergy using Tallarida's method. CI indicated that synergy was dependent on the concentration of the agents used and was cell line specific. For bromelain and N-acetylcysteine, certain ratio of the two agents gave very good synergy that was prevalent in almost all cell lines. Gemcitabine and 5-FU and doxorubicin reacted favourably with most concentrations of bromelain and NAC investigated. Cisplatin and oxaliplatin were not very compatible with NAC. A value of CI <0.5 indicated that the current clinical chemotherapeutic dosage can be dramatically reduced. Bromelain with NAC showed synergy in all tumour cell lines and acting synergistically with chemotherapeutic drugs. Synergistic combinations resulting in considerable dosage reduction of chemotherapeutic agents may enable more frequent treatment with higher efficacy.