Safety Measures for Operating Team and Operation Theater During the Current Scenario of COVID-19

The COVID-19 has become a major threat to Pakistan and worldwide, and has become a significant issue for global health, economy and societies. This rapid spread was occurred from Wuhan, China to most of the part of the world. To elaborate the concept and recommendations regarding the safety precautions in operation theater (O.T) and inside associated team during the current scenario of COVID-19. Many research and review articles were studied to collect information about Covid-19 and strategies published in various journals using the search engine, PubMed and Medline. The COVID-19 has significantly changed all aspects of daily life around the world since very start of this year 2020. SARS-CoV-2 (COVID-19), a novel corona virus, has been infected many healthcare workers. In this perspective, hospitals need a strategy to manage their resources, staff and supplies so that patients receive optimal treatment. A decision tree algorithm was developed that defined the recommendations for safety measures in operation theater and operating procedures, these include identifying and developing an isolation room, administrative measures such as transformations in working flow and procedures, introducing personal protective equipment for the employees and formulating anesthetic clinical guidelines. These control actions are essential to enhance the excellence of care provided to COVID-19 patients and to minimize the risk of spread to other patients or staff. The operating room is a dynamic environment with numerous staff like anesthesiologists, physicians, nurses, O.T attendants and technicians; however, we agree that the containment steps are important in order to improve the standard of treatment provided to COVID-19 patients and to minimize the chance of viral spread to patients other than COVID-19 and hospital staff

Abstract 4639: Do cation-selective transporters help or hurt the antitumor efficacy of metformin in breast cancer

Abstract Introduction Metformin is effective against many cancers including breast cancer. Activation of intracellular adenosine monophosphate-activated protein kinase (AMPK) is implied in metformin anticancer efficacy. Due to its hydrophilicity and positive charge, metformin relies on cation-selective transporters for cellular uptake. Accordingly, metformin cellular uptake, AMPK activation and anti-proliferative effects increased when organic cation transporter 3 (OCT3) was expressed in BT20 cells (BT20-OCT3) that have very low levels of cation-selective transporters (Cai et al., AAPS Abstract W4368, 2013). Our previous studies showed that human breast cancer cell lines and tumors exhibit wide variability in expression of metformin transporters, e.g. OCT1-3, plasma monoamine transporter (PMAT), and multidrug and toxin extrusion (MATE) transporters 1-2 (Zhang et al., AACR Abstract 9800, 2012). This study aims to assess the pivotal role of transporters in metformin antitumor effects using xenograft mice with tumors from BT20 and OCT3-BT20 cells. Methods BT20 cells stably transfected with OCT3 were produced, and OCT3 activity verified by [14C]metformin (50µM) uptake in presence/absence of 50µM famotidine (OCT3 and MATE1 inhibitor) or 500 µM quinidine (pan transporter inhibitor). Optimum metformin dose for tumor study was assessed by a dose-range pharmacokinetic study in mice dosed intraperitoneally (IP) with 15, 30, 50, 100, and 150mg/kg [14C]metformin. Xenograft mice were produced using 2×106 BT20/OCT3-BT20 cells. Doxorubicin (DOX; 4mg/kg) or DOX + 100mg/kg metformin was given IP every 5 days, and tumor volumes measured over 25 days. Results Metformin plasma AUC0-24hr was linear up to 100 mg/kg (AUC0-24hr of 95, 160, 366, 770 and 510 µmol*hr/L at 15, 30, 50, 100 and 150 mg/kg, respectively); hence, this dose was used for antitumor efficacy study. Surprisingly, tumors were larger in DOX + metformin group compared to DOX (45.3 vs. 23.5 mm3) in mice with OCT3-BT20 tumors. In mice with BT20 tumors, tumors were smaller in DOX + metformin group compared to DOX (20.5 vs. 61.8 mm3). Since BT20 tumors grew slowly, tumor measurements were possible in only 2 mice/group. Hence, the more aggressive MCF-7 human breast cancer cell was used to develop an OCT3-expressing (OCT3-MCF7) clone in which metformin uptake was 4.5-fold higher than in MCF-7 cells (65.66 vs. 15.17 pmol/mg protein/min). Metformin antitumor effect in xenograft mice with MCF-7 and OCT3-MCF7 tumors is under evaluation. Conclusion In vitro data imply that OCT3 expression in human breast cancer cells enhances metformin cellular uptake and anti-proliferative effect. In vivo xenograft mice studies show that BT20 tumors over-expressing OCT3 are less responsive to metformin + DOX than native BT20 tumors; however, further studies are needed to show statistical significance. Citation Format: Hao Cai, Muhammad Wahajuddin, Ruth Everett, Dhiren R. Thakker. Do cation-selective transporters help or hurt the antitumor efficacy of metformin in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4639. doi:10.1158/1538-7445.AM2014-4639</jats:p

The Capacity of Drug-Metabolising Enzymes in Modulating the Therapeutic Efficacy of Drugs to Treat Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma (STS) that predominantly affects children and teenagers. It is the most common STS in children (40%) and accounts for 5&ndash;8% of total childhood malignancies. Apart from surgery and radiotherapy in eligible patients, standard chemotherapy is the only therapeutic option clinically available for RMS patients. While survival rates for this childhood cancer have considerably improved over the last few decades for low-risk and intermediate-risk cases, the mortality rate remains exceptionally high in high-risk RMS patients with recurrent and/or metastatic disease. The intensification of chemotherapeutic protocols in advanced-stage RMS has historically induced aggravated toxicity with only very modest therapeutic gain. In this review, we critically analyse what has been achieved so far in RMS therapy and provide insight into how a diverse group of drug-metabolising enzymes (DMEs) possess the capacity to modify the clinical efficacy of chemotherapy. We provide suggestions for new therapeutic strategies that exploit the presence of DMEs for prodrug activation, targeted chemotherapy that does not rely on DMEs, and RMS-molecular-subtype-targeted therapies that have the potential to enter clinical evaluation