Transitions between different cell cycle states are regulated at checkpoints controlled by cyclin-dependent kinases (CDKs) 1 which are activated by cyclins and inhibited by CDK inhibitors (reviewed in Refs. 1-4). Many checkpoints are deregulated in oncogenesis, and, hence, negative controls on cell cycle progression may play an important role in preventing tumorigenesis. By inhibiting cyclin-dependent kinase activities, CDK inhibitors can act as negative regulators of cell growth and therefore can potentially function as tumor suppressors. Two major classes of CDK inhibitors have been identified: first, p21 WAF1/CIP1/SDI1 (p21), p27 KIP1, and p57 KIP2 belong to a family of related CDK inhibitors that inhibits a broad range of CDK-cyclin complexes, and second, p15 INK4B/MTS2, p16 INK4/MTS1

The cysteine protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (LLnL) inhibited the growth of the Calu-1 lung carcinoma cells and induced a prolonged cell cycle arrest in the S phase. c-Jun N-terminal kinases (JNKs) participate in cellular responses to mitogenic stimuli, environmental stresses, and apoptotic signals but its role in cell cycle checkpoint control has not been elucidated. In this report, we examined the role of JNK in LLnLinduced S phase checkpoint by overexpression of a dominant-negative mutant of JNK1 (JNK1 ± APF) in Calu-1 cells. Expression of high levels of JNK1 ± APF blocked the growth-inhibitory e ects of LLnL and abrogated S phase arrest induced by LLnL. These results support the role of JNK in the activation of cell cycle checkpoint induced by LLnL.

e16589 Background: The impact of PTSD on the health of veterans with prostate cancer is unknown. Methods: From September 2015 to October 2016, patients with prostate cancer at a Veterans Administration Hospital completed self-report surveys assessing their overall health status. Survey findings for patients with PTSD were compared to those without PTSD. Patients were considered PTSD+ if they had a diagnosis of PTSD in their Electronic Medical Record (EMR) or scored ≥50 on the PTSD Checklist—Civilian Version (PCL-C). Health outcomes included scores on the following measures: VR-36 (Physical Component Score [PCS] and Mental Component Score [MCS]), Beck Depression Index (BDI), Beck Anxiety Index (BAI), and Pain Visual Analogue Scale (VAS). Results: A total of 104 veterans (18 PTSD+) completed all surveys. The average age was 74.6 ±7.8. 82.7% of patients were Caucasian. PTSD+ Veterans were significantly younger (p<0.001). No PTSD-related differences were found for race/ethnicity, BMI, or VR-36 PCS scores. PTSD+ patients had lower overall VR-36 MCS scores (36.9±12.8 vs. 52.7±10.5; p<0.001), and higher Pain VAS scores (3.9±2.6 vs. 2.1±2.2; p<0.01). PTSD+ patients were more likely to meet criteria for depression (61.1% vs. 8.1%; p<0.01) and anxiety (55.6% vs. 4.7%; p<0.01), and to have a history of suicidality (18.75% vs. 0.00%; p<0.01). Conclusions: Compared to PTSD- veterans with prostate cancer, PTSD+ patients were more likely to self-report increased symptoms of depression, anxiety, and pain as well as overall poorer mental health status. Further research is warranted to identify opportunities to improve mental health care for PTSD+ veterans with prostate cancer. [Table: see text]