Can't kick that oncogene habit

One of the most exciting developments in recent cancer treatment has been the move away from crude cytotoxic agents toward drugs that inhibit specific targets in specific cellular pathways. One assumption of this strategy is that maintenance of human cancers is dependent upon a limited cadre of therapeutically tractable oncogenic lesions. In this issue of Cancer Cell, an intriguing paper from Sharma et al. endorses this approach by showing that evolution appears to be working for us. They show that an innate asymmetry in the dynamics of intracellular signaling biases pathway inhibition in favor of cell death. This bias may significantly potentiate targeted cancer therapies

Nursing some sense out of Myc

Data recently published in BMC Biology provide insights into the normal physiological function of c-myc in the development and regeneration of the mammary gland and indicate a key role in epithelial cell proliferation, elaboration of ductal alveoli, and the biosynthetic capacity and milk production of the mature organ

Pollution prevention opportunity assessment for electronics prototype laboratory.

This Pollution Prevention Opportunity Assessment (PPOA) was conducted for Sandia National Laboratories/California Electronics Prototype Laboratory (EPL) in May 2005. The primary purpose of this PPOA is to provide recommendations to assist Electronics Prototype Laboratory personnel in reducing the generation of waste and improving the efficiency of their processes. This report contains a summary of the information collected, analyses performed and recommended options for implementation. The Sandia National Laboratories Pollution Prevention staff will continue to work with the EPL to implement the recommendations

Pollution prevention opportunity assessment for MicroFab and SiFab facilities at Sandia National Laboratories.

This Pollution Prevention Opportunity Assessment (PPOA) was conducted for the MicroFab and SiFab facilities at Sandia National Laboratories/New Mexico in Fiscal Year 2011. The primary purpose of this PPOA is to provide recommendations to assist organizations in reducing the generation of waste and improving the efficiency of their processes and procedures. This report contains a summary of the information collected, the analyses performed, and recommended options for implementation. The Sandia National Laboratories Environmental Management System (EMS) and Pollution Prevention (P2) staff will continue to work with the organizations to implement the recommendations

Pollution prevention opportunity assessment for organization 1700.

This Pollution Prevention Opportunity Assessment (PPOA) was conducted for Sandia National Laboratories/New Mexico Organization 1700 in June, 2006. The primary purpose of this PPOA is to provide recommendations to assist Organization 1700 in reducing the generation of waste and improving the efficiency of their processes and procedures. This report contains a summary of the information collected, analyses performed and recommended options for implementation. The Sandia National Laboratories Pollution Prevention staff will continue to work with Organization 1700 to implement the recommendations

Participants’ Perspectives of a Worksite Wellness Program Using an Outcome-Based Contingency Approach

Worksite wellness programs in the U.S. are increasingly common. Social workers in healthcare and administration should familiarize themselves with the various wellness programs and the impact they have on workers and organizations. This study examined a worksite wellness outcome-based contingency approach (WWOCA). This approach bases individual employee health insurance discounts on each participant achieving biometric goals. A mixed-method explanatory approach was used. Quantitative health measures of participants (n = 397) and six focus group discussions (n = 45) were conducted using a convenience sample. Results indicate that over half of the participants met their work-based health goals (i.e., body measurements at the average or excellent rankings) with increases from 56% in year one to 87% in year two and 90% by year three. However, focus group participants expressed a high sense of failure in relation to health goal attainment, frustration with loss of the financial incentive, and stress and anxiety linked to negative feedback about their body measurements. These results suggest that many participants’ self-worth was negatively impacted when participants had difficulty conforming to worksite wellness standards. Social workers in healthcare and administration will need to advocate for worksite wellness programs that promote human dignity and avoid discriminating based on employee health status

Myc Cooperates with Ras by Programming Inflammation and Immune Suppression.

The two oncogenes KRas and Myc cooperate to drive tumorigenesis, but the mechanism underlying this remains unclear. In a mouse lung model of KRasG12D-driven adenomas, we find that co-activation of Myc drives the immediate transition to highly proliferative and invasive adenocarcinomas marked by highly inflammatory, angiogenic, and immune-suppressed stroma. We identify epithelial-derived signaling molecules CCL9 and IL-23 as the principal instructing signals for stromal reprogramming. CCL9 mediates recruitment of macrophages, angiogenesis, and PD-L1-dependent expulsion of T and B cells. IL-23 orchestrates exclusion of adaptive T and B cells and innate immune NK cells. Co-blockade of both CCL9 and IL-23 abrogates Myc-induced tumor progression. Subsequent deactivation of Myc in established adenocarcinomas triggers immediate reversal of all stromal changes and tumor regression, which are independent of CD4+CD8+ T cells but substantially dependent on returning NK cells. We show that Myc extensively programs an immune suppressive stroma that is obligatory for tumor progression

Bcl-xL gain of function and p19ARF loss of function cooperate oncogenically with Myc in vivo by distinct mechanisms

SummaryOverexpression of Bcl-xL, loss of p19ARF, and loss of p53 all accelerate Myc oncogenesis. All three lesions are implicated in suppressing Myc-induced apoptosis, suggesting that this is a common mechanism by which they synergize with Myc. However, using an acutely switchable model of Myc-induced tumorigenesis, we demonstrate that each lesion cooperates with Myc in vivo by a distinct mechanism. While Bcl-xL blocks Myc-induced apoptosis, inactivation of p19ARF enhances it. However, this increase in apoptosis is matched by increased Myc-induced proliferation. p53 inactivation shares features of both lesions, partially suppressing apoptosis while augmenting proliferation. Bcl-xL and p19ARF loss together synergize to further accelerate Myc oncogenesis. Thus, differing lesions cooperate oncogenically with Myc by discrete mechanisms that can themselves synergize with each other