Bosutinib Reduces the Efficacy of Dasatinib in Triple-negative Breast Cancer Cell Lines

Background—Triple-negative breast cancer (TNBC) is an aggressive sub-type of breast cancer. Dasatinib and bosutinib are FDA-approved Src/Abl kinase inhibitor drugs. Dasatinib potently inhibits the proliferation of many TNBC cell lines. Material and Methods—The cell viability/proliferation for a panel of 4 TNBC cell lines was measured by detection of cellular ATP levels and cell numbers directly determined by automated cell counting. Results—Bosutinib (≤1 μM) had little to no inhibitory activity on cell viability/proliferation, while dasatinib-alone generated potent IC50 values of <100 nM. Combination treatment of cells with both dasatinib and bosutinib resulted in reduced efficacy of dasatinib in all four cell lines, with two of them displaying a dramatic loss of efficacy. Direct cell counting confirmed that bosutinib enhanced cell proliferation in the presence of dasatinib. Conclusion—Bosutinib potently reduced the in vitro anti-proliferative efficacy of dasatinib in TNBC cell lines. We, thereby, report on a novel drug-induced loss in dasatinib sensitivity

Veterans Affairs general surgery service: the last bastion of integrated specialty care

BACKGROUND: In a time of increasing specialization, academic training institutions provide a compartmentalized learning environment that often does not reflect the broad clinical experience of general surgery practice. This study aimed to evaluate the contribution of the Veterans Affairs (VA) general surgery surgical experience to both index Accreditation Council for Graduate Medical Education (ACGME) requirements and as a unique integrated model in which residents provide concurrent care of multiple specialty patients. METHODS: Institutional review board approval was obtained for retrospective analysis of electronic medical records involving all surgical cases performed by the general surgery service from 2005 to 2009 at the Nashville VA. Over a 5-year span general surgery residents spent an average of 5 months on the VA general surgery service, which includes a postgraduate year (PGY)-5, PGY-3, and 2 PGY-1 residents. Surgeries involved the following specialties: surgical oncology, endocrine, colorectal, hepatobiliary, transplant, gastrointestinal laparoscopy, and elective and emergency general surgery. The surgeries were categorized according to ACGME index requirements. RESULTS: A total of 2,956 surgeries were performed during the 5-year period from 2005 through 2009. Residents participated in an average of 246 surgeries during their experience at the VA; approximately 50 cases are completed during the chief year. On the VA surgery service alone, 100% of the ACGME requirement was met for the following categories: endocrine (8 cases); skin, soft tissue, and breast (33 cases); alimentary tract (78 cases); and abdominal (88 cases). Approximately 50% of the ACGME requirement was met for liver, pancreas, and basic laparoscopic categories. CONCLUSIONS: The VA hospital provides an authentic, broad-based, general surgery training experience that integrates complex surgical patients simultaneously. Opportunities for this level of comprehensive care are decreasing or absent in many general surgery training programs. The increasing level of responsibility and simultaneous care of multiple specialty patients through the VA hospital systems offers a crucial experience for those pursuing a career in general surgery. Published by Elsevier Inc

7th Annual Lady Grace Revere Osler Lecture in Surgical Quality: Future Quality: The Training of the Surgeon-Revisited

At the conclusion of this presentation the participant should be able to: 1. Better understand the trajectory of the past 115 years of surgical education 2. Address: How and for How Long we should train a surgeon 3. Discuss surgical education, quality, and capacity in the US and Sub-Saharan Africa Presentation: 1 hou

Identifying knowledge needed to improve surgical care in Southern Africa using a theory of change approach

Surgical healthcare has been prioritised in the Southern African Development Community (SADC), a regional intergovernmental entity promoting equitable and sustainable economic growth and socioeconomic development. However, challenges remain in translating political prioritisation into effective and equitable surgical healthcare. The AfroSurg Collaborative (AfroSurg) includes clinicians, public health professionals and social scientists from six SADC countries; it was created to identify context-specific, critical areas where research is needed to inform evidence-grounded policy and implementation. In January 2020, 38 AfroSurg members participated in a theory of change (ToC) workshop to agree on a vision: ‘An African-led, regional network to enable evidence-based, context-specific, safe surgical care, which is accessible, timely, and affordable for all, capturing the spirit of Ubuntu[1]’ and to identify necessary policy and service-delivery knowledge needs to achieve this vision. A unified ToC map was created, and a Delphi survey was conducted to rank the top five priority knowledge needs. In total, 45 knowledge needs were identified; the top five priority areas included (1) mapping of available surgical services, resources and providers; (2) quantifying the burden of surgical disease; (3) identifying the appropriate number of trainees; (4) identifying the type of information that should be collected to inform service planning; and (5) identifying effective strategies that encourage geographical retention of practitioners. Of the top five knowledge needs, four were policy-related, suggesting a dearth of much-needed information to develop regional, evidenced-based surgical policies. The findings from this workshop provide a roadmap to drive locally led research and create a collaborative network for implementing research and interventions. This process could inform discussions in other low-resource settings and enable more evidenced-based surgical policy and service delivery across the SADC countries and beyond