Ami N. Shah

Aberrant activation of members of the Src family of nonreceptor protein tyrosine kinases is common in solid tumor malignancies and may contribute to the development and/or progression of these tumors. As a result, four Src inhibitors are now in more than 50 clinical trials for at least 14 different types of solid tumors. In this review, we briefly discuss the preclinical rationale for Src inhibitors, the development strategies most likely to be successful in the clinic, and the rationale for Src inhibitors in combination with other agents as part of a more comprehensive therapeutic strategy. As the use of Src family inhibitors in clinical trials on solid tumors is in its infancy, further studies on the roles of Src family kinases in tumor progression, chemoresistance, epidermal-to-mesenchymal transition, and other properties of tumor progression will be important in designing the most effective clinical trials using these inhibitors.

BACKGROUND: Operating rooms are major contributors to a hospital's carbon footprint due to the large volumes of resources consumed and waste produced. The objective of this study was to identify quality improvement initiatives that aimed to reduce the environmental impact of the operating room while decreasing costs. STUDY DESIGN: A literature search was performed using PubMed, Scopus, CINAHL, and Google Scholar and included broad terms for "operating room," "costs," and "environment" or "sustainability." The "triple bottom line" framework, which considers the environmental, financial, and social impacts of interventions to guide decision making, was used to inform data extraction. The studies were then categorized using the 5 "Rs" of sustainability-refuse, reduce, reuse, repurpose, and recycle-and the impacts were discussed using the triple bottom line framework. RESULTS: A total of 23 unique quality improvement initiatives describing 28 interventions were included. Interventions were categorized as "refuse" (n = 11; 39.3%), "reduce" (n = 8; 28.6%), "reuse" (n = 3; 10.7%), and "recycle" (n = 6; 21.4%). While methods of measuring environmental impact and cost savings varied greatly among studies, potential annual cost savings ranged from $873 (intervention: education on diverting recyclable materials from sharps containers; environmental impact: 11.4 kg sharps waste diverted per month) to $694,141 (intervention: education to reduce regulated medical waste; environmental impact: 30% reduction in regulated medical waste). CONCLUSIONS: Quality improvement initiatives that reduce both cost and environmental impact have been successfully implemented across a variety of centers both nationally and globally. Surgeons, healthcare practitioners, and administrators interested in environmental stewardship and working toward a culture of sustainability may consider similar interventions in their institutions.

Aberrant expression or activation of protein tyrosine kinases, including Src and related Src family kinases, is a common occurrence in many human cancers, resulting in deregulation of expression of numerous mediators of cellular functions, including pro-angiogenic molecules. In addition, Src activation regulates vascular permeability of endothelial cells. How these processes contribute to tumor progression and metastasis are the subjects of this review. As Src-selective inhibitors have entered clinical trials for a number of solid tumors, further understanding of the roles of Src kinases in mediating tumor angiogenesis as well as modulating tumor/microenvironment interactions will provide insights into the best use of these inhibitors in treating patients afflicted with tumors in which Src is activated.

The actin filament-associated protein AFAP-110 is an actin cross-linking protein first identified as a substrate of the viral oncogene v-Src. AFAP-110 regulates actin cytoskeleton integrity but also functions as an adaptor protein that affects crosstalk between Src and PKC. Here we investigated the roles of AFAP-110 in the tumorigenic process of prostate carcinoma. Using immunohistochemistry of human tissue arrays, we found that AFAP-110 was absent or expressed at very low levels in normal prostatic epithelium and benign prostatic hyperplasia but significantly increased in prostate carcinomas. The level of AFAP-110 in carcinomas correlated with the Gleason scores. Downregulation of AFAP-110 in PC3 prostate cancer cells inhibited cell proliferation in vitro and tumorigenicity and growth in orthotopic nude mouse models. Furthermore, downmodulation of AFAP-110 resulted in decreased cell-matrix adhesion and cell migration, defective focal adhesions, and reduced integrin beta1 expression. Reintroduction of avian AFAP-110 or a mutant disabling its interaction with Src restored these properties. However, expression of an AFAP-110 lacking the PKC-interacting domain failed to restore properties of parental cells. Thus, increased expression of AFAP-110 is associated with progressive stages of prostate cancer and is critical for tumorigenic growth, in part by regulating focal contacts in a PKC-dependent mechanism.