Translational research in oncology research & development and its impact on early development in China: report of the 5th Annual Meeting of the US Chinese Anti-Cancer Association (USCACA) at 2013 AACR Annual Meeting.

In April 2013, the US Chinese Anti-Cancer Association (USCACA) held its 5th annual meeting in conjunction with the American Association for Cancer Research (AACR) 2013 Annual Meeting in Washington DC. The USCACA executive committee reported activities and programs and highlighted the partnership and collaboration between USCACA and other major organizations. The key initiatives and programs of USCACA included 1) USCACA-TIGM Esophageal Cancer Program that funds translational research of esophageal cancer prevention and treatment at the Xinxiang Medical University in Henan province, China; 2) the USCACA-NFCR-AFCR Scholarship Program, which has supported 10 young outstanding Chinese cancer researchers and will award 4 fellowships at the Guangzhou International Symposium on Oncology in November this year; 3) USCACA-Hengrui Training Program for Early Phase Clinical Research, which has supported the training of a Chinese scholar at two major cancer centers in the US; and 4) USCACA has continued its partnership with the Chinese Journal of Cancer, which has reached significant international impact.

Bridging the US and China together to conquer cancer: report of the 4th annual meeting of the US Chinese Anti-Cancer Association (USCACA).

A global collaborative effort is pivotal to conquer cancer. Themed "Emerging role of China in global clinical development of novel anti-cancer drugs", the US Chinese Anti-Cancer Association (USCACA) held its 4th annual meeting in Chicago on June 2, 2012, in conjunction with the American Society of Clinical Oncology (ASCO) annual meeting to further bridge the US and China together to outsmart cancer. Although a young organization, USCACA has made significant contributions to this goal in the 3 years since its inception through extensive collaboration with academic organizations, the pharmaceutical industry, and governmental agencies. USCACA has engaged various stakeholders in developing translational and personalized medical strategies to facilitate new anti-cancer drug development and clinical trials in China. USCACA has initiated and implemented the USCACA-National Foundation for Cancer Research (NFCR) scholarship to encourage overseas returnees to continue cancer research in China. USCACA announced the Hengrui-USCACA scholarship to fund clinical trial staff from China to conduct the observation of early oncologic clinical trials in the US. During the annual meeting, distinguished panelists and the audience discussed the following critical topics:(1) oncologic translational research and early development capabilities in China;(2) novel chemical entity development and partnership with Chinese companies; and (3) Chinese participation in global anti-cancer drug development. USCACA will continue to promote collaborations among cancer researchers and clinicians in the US and China by engaging in more frequent communications and joint efforts across fields, disciplines, and countries, diligently working together toward curing and eliminating cancers.

Protein kinase C-mediated down-regulation of cyclin D1 involves activation of the translational repressor 4E-BP1 via a phosphoinositide 3-kinase/Akt-independent, protein phosphatase 2A-dependent mechanism in intestinal epithelial cells.

We reported previously that protein kinase Calpha (PKCalpha), a negative regulator of cell growth in the intestinal epithelium, inhibits cyclin D1 translation by inducing hypophosphorylation/activation of the translational repressor 4E-BP1. The current study explores the molecular mechanisms underlying PKC/PKCalpha-induced activation of 4E-BP1 in IEC-18 nontransformed rat ileal crypt cells. PKC signaling is shown to promote dephosphorylation of Thr(45) and Ser(64) on 4E-BP1, residues directly involved in its association with eIF4E. Consistent with the known role of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway in regulation of 4E-BP1, PKC signaling transiently inhibited PI3K activity and Akt phosphorylation in IEC-18 cells. However, PKC/PKCalpha-induced activation of 4E-BP1 was not prevented by constitutively active mutants of PI3K or Akt, indicating that blockade of PI3K/Akt signaling is not the primary effector of 4E-BP1 activation. This idea is supported by the fact that PKC activation did not alter S6 kinase activity in these cells. Further analysis indicated that PKC-mediated 4E-BP1 hypophosphorylation is dependent on the activity of protein phosphatase 2A (PP2A). PKC signaling induced an approximately 2-fold increase in PP2A activity, and phosphatase inhibition blocked the effects of PKC agonists on 4E-BP1 phosphorylation and cyclin D1 expression. H(2)O(2) and ceramide, two naturally occurring PKCalpha agonists that promote growth arrest in intestinal cells, activate 4E-BP1 in PKC/PKCalpha-dependent manner, supporting the physiological significance of the findings. Together, our studies indicate that activation of PP2A is an important mechanism underlying PKC/PKCalpha-induced inhibition of cap-dependent translation and growth suppression in intestinal epithelial cells.