In addition to mutations, copy number gain of oncogenes is also important for “oncogene addiction”. We previously reported that extensive chromosomal instabilityis a poor independent prognostic factor in endometrial carcinomas. Although extensive chromosomal instability is more common in type II endometrial carcinomas, the percentage of extensive chromosomal instability was 31% in our clinical endometrioid adenocarcinoma samples. We found that both group D cell linesharbor extensive CNAs, with copy number gain at the locus of K-Ras, although they do not possess any mutations in K-Ras, PTEN and PIK3CA. The antiproliferative HhAntag691 effect of combined inhibition of MAPK pathway and PI3K/mTOR pathway in group D cells suggests that this combination therapy might be an option to treat tumors with CNA in K-Ras. The dual inhibition of the PI3K and MAPK pathways might overcome the resistance to PI3K/mTOR inhibition alone in certain endometrial tumors with K-Ras alterations through its enhanced cytostatic effect. Cheung et al reported that endometrial cell lines with wild-type PI3K pathway members were resistant to an mTOR inhibitor, rapamycin, suggesting that other unexamined factors, including CNA in K-Ras, might be involved in the anti-tumor effect of rapalogs. Phosphorylation of 4E-BP1 is not only regulated by 
mTORC1, but also by ERK signaling, suggesting the crosstalk between PI3K/mTOR pathway and MAPK pathway. It would be necessary to evaluate the in vivo effect of the combined therapy in tumors with K-Ras alterations to address the activity of the MAPK pathway in endometrial cancer. Individuals with HIV infection are at increased risk for premature cardiovascular diseasedue to the higher prevalence of traditional risk factors, toxicity from antiretroviral therapy, as well as direct effects of HIV itself. Specifically, HIV-related inflammation persists despite effective viral suppression with ART treatment and this may further amplify CVD risk. CVD prevention strategies that encompass both antiinflammatory benefits as well as traditional risk factor modification may be uniquely beneficial in this context. Similar to the general population, high blood pressureand cholesterol account for a significant proportion of CVD risk among patients with HIV infection and remain a key component of prevention strategies. In the general population, epidemiologic data demonstrate a consistent graded relationship between BP and cholesterol with CVD, which persists through normal BP valuesand moderate total cholesterol levels. For a target population at higher absolute CVD risk, such as individuals with HIV infection, these data suggest risk factor reductions may be beneficial irrespective of whether individual BP or cholesterol levels exceed current thresholds for treatment. Angiotensin converting enzyme inhibitorsand HMGCoA reductase SB203580 distributor inhibitorshave been shown to reduce CVD risk through their BP and cholesterol lowering properties, respectively. However, both classes of medications appear to have additional anti-inflammatory pleotropic effects that may be uniquely beneficial for HIV positive patients. Prior to expanding the use of ACE-I and/or statins for HIV-infected persons to patients for whom these treatments are not currently indicated, safety and tolerability data are needed to inform largescale trials that more clearly define the net risk-benefit balance. The goal of this study was to determine if a strategy using lisinoprilat 10 mg daily and pravastatinat 20 mg daily as adjunctive treatment was feasible, well tolerated, and led to risk factor reductions when given alone or in combination to virologically suppressed patients receiving ART.