Simultaneous siRNA Targeting of Src and Downstream Signaling Molecules Inhibit Tumor Formation and Metastasis of a Human Model Breast Cancer Cell Line

Src and signaling molecules downstream of Src, including signal transducer and activator of transcription 3 (Stat3) and cMyc, have been implicated in the development, maintenance and/or progression of several types of human cancers, including breast cancer. Here we report the ability of siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc to inhibit the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S, a widely used model for breast cancer research.Src and its downstream signaling partners were specifically targeted and knocked-down using siRNA. Changes in the growth properties of the cultured cancer cells/tumors were documented using assays that included anchorage-dependent and -independent (in soft agar) cell growth, apoptosis, and both primary and metastatic tumor growth in the mouse tumor model. siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc inhibited the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S. This knock-down resulted in reduced growth in monolayer and soft agar cultures, and a reduced ability to form primary tumors in NOD/SCID mice. In addition, direct intra-tumoral injection of siRNAs targeting these signaling molecules resulted in a substantial inhibition of tumor metastases as well as of primary tumor growth. Simultaneous knock-down of Src and Stat3, and/or Myc exhibited the greatest effects resulting in substantial inhibition of primary tumor growth and metastasis.These findings demonstrate the effectiveness of simultaneous targeting of Src and the downstream signaling partners Stat3 and/or cMyc to inhibit the growth and oncogenic properties of a human cancer cell line. This knowledge may be very useful in the development of future therapeutic approaches involving targeting of specific genes products involved in tumor growth and metastasis

Enhancing the management of deteriorating patients with Australian on line e-simulation software: Acceptability, transferability, and impact in Hong Kong

International concerns relating to healthcare professionals’ failure to rescue deteriorating patients exist. Web-based training programs have been developed and evaluated in Western settings but further testing is required before application in non-Western countries, as traditional modalities of learning may differ between cultures. We trialed an Australian English language online simulation program for the management of deteriorating patients, Feedback Incorporating Review and Simulation Techniques to Act on Clinical Trends (FIRST2ACTWeb), to test cultural acceptability, transferability, and educational impact. The study was designed as a quasi-experimental evaluation of the FIRST2ACTWeb program with final year nursing students from a Bachelor of Nursing program at the University of Hong Kong. Participants completed pre-course and post-course tests, three interactive scenarios, and program evaluations. The program was positively evaluated, with significant improvements in knowledge, skills, self-rating of performance, confidence, and competence. Outcomes were comparable to earlier evaluations with Australian students, demonstrating that an interactive simulation-based program of patient deterioration management has cultural and language acceptability and transferability across communities with significant educational impact. © 2016 John Wiley & Sons Australia, Ltd