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Xu Z.,Beijing Institute of Radiation Medicine | Xu Z.,Xinxiang Medical University | Zhu L.,Beijing Institute of Radiation Medicine | Yao M.,Medical Library of the Chinese PLA | And 3 more authors.
BioMed Research International

Thrombin and its membrane receptor, protease-activated receptor 1 (PAR1), have been reported to promote the development of lung cancer in vitro and in vivo. However, the intracellular molecular mechanism or signaling pathway that mediates the cytological effects after the thrombin-receptor interaction is poorly understood. Our previous study observed that the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was downregulated in thrombin-stimulated lung cancer. In this study, the role of PTEN in thrombin-mediated cell function and the corresponding cell signaling pathway were studied in lung cancer cell Glc-82. The results indicated that thrombin downregulates the PTEN expression level and that PTEN plays an important role in thrombin-mediated Glc-82 functions, including cell cycle progression, cell apoptosis, and cell migration. The PI3K/AKT signaling pathway and its related proteins, including p27 and S phase kinase associated protein 2 (Skp2), are involved in the effects induced by PTEN downregulation. PAR1 plays a role in thrombin-mediated reduction of PTEN expression. This study suggested that the PTEN/PI3K/AKT signaling pathway plays an important role in thrombin/PAR1-mediated lung cancer cell growth and migration. © 2015 Zhishan Xu et al. Source

Zhu Y.,Medical Library of the Chinese PLA | Long X.-M.,Medical Library of the Chinese PLA | Zhang J.-P.,Medical Library of the Chinese PLA | Du H.-Z.,Medical Library of the Chinese PLA
Chinese Journal of New Drugs

Vandetanib is an orally active antagonist of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), epidermal growth factor receptor (EGFR) and RET kinase. It was approved for the treatment of metastatic medullary thyroid cancer (MTC) by U. S. Food and Drug Administration (FDA) on June 4, 2011. The pharmacokinetics and pharmacodynamics of vandetanib were reviewed in this paper. Also, it is mainly introduced that the antitumor activity of vandetanib in some phase II to phase III clinical trials, such as its antitumor activity in the phase II ZACTHYF trial and the phase III ZETA trial for MTC, as well as the negative results or no overall survival advantages of the four randomized phase III clinical trials for non-small cell lung cancer (NSCLC). Meanwhile, the therapeutic or clinical benefits of vandetanib and the adverse events in the patients with MTC and NSCLC were evaluated and discussed. Additionally, some phase II clinical trials evaluating the efficacy of vandetanib in prostate cancer, advanced breast cancer, malignant glioma, and so on, have been completed. Some phase II clinical trials in recurrent high-grade gliomas, biliary tract cancer, locally advanced or metastatic urinary tract cancer, and so on, are currently recruiting participants. These clinical trials will better define the appropriate schedule, the optimal setting of evaluation, and the safety of long-term use of vandetanib. Source

Liu X.-T.,Medical Library of the Chinese PLA | Cheng J.,Medical Library of the Chinese PLA | Chen R.,Medical Library of the Chinese PLA | Du H.-Z.,Medical Library of the Chinese PLA
Chinese Journal of New Drugs

Objective: To understand the status of international development of new anticancer medicines for hematological malignancies. Methods: The development of 241 new medicines for leukemia, lymphoma, myeloma and other hematological cancers were induced, reviewed and outlined based on the Medicines in Development Database created by the Pharmaceutical Research and Manufacturers of America (PhRMA) and related reports. The new medicines for the treatment of hematological cancers in Phase III clinical trials, or submitted to NDA/BLA in 2013 were mainly analyzed and discussed. Results: The 241 new medicines were classified into 6 categories, including 24 medicines for hematological malignancies, 97 for leukemia, 98 for lymphoma, 52 for myeloma, and 15 for myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS), respectively. There were 356 clinical trials from Phase I to III, or submissions to NDA/BLA in total. There were 56 new medicines in Phase III clinical trials or submissions to NDA/BLA, but 6 clinical trials or submissions were stopped or rejected by FDA with varies reasons. Conclusion: Original medicines are the focus in the development of medicines treating hematological cancers by the international pharmaceutical companies and biopharmaceutical companies, but many existing drugs for other diseases are re-investigated for new therapeutic indications of hematological cancers. There are several kinds of biological medicines in the candidate medicines for treating hematological cancers, such as monoclonal antibodies (MAb), antibody-drug conjugates (ADC), PGG β-glucan, therapeutic vaccines and so on. Source

Du H.-Z.,Medical Library of the Chinese PLA | Yang C.-H.,Medical Library of the Chinese PLA | Liu G.-L.,Medical Library of the Chinese PLA | Liu N.,Medical Library of the Chinese PLA | Wang T.-J.,Medical Library of the Chinese PLA
Chinese Journal of New Drugs

The report, New Medicines in Development for Cancer and the Medicines in Development Database, was issued in 2009 by the Pharmaceutical Research and Manufacturers of America (PhRMA). Based on this report, 16 novel targeted therapies for non-small-cell lung cancer (NSCLC) currently at phase III clinical trials are analyzed. Referring to the classification of the targeted cancer therapies in the related Chinese papers and in the Fact Sheet of the US National Cancer Institute, the 16 targeted therapies are classified into 4 types, namely EGFR inhibitors, VEGF inhibitors, multitargeted agents and novel targeted agents. With further analysis and conclusion, the 16 targeted therapies show 3 features: (1) They present a trend of diversifying development. Multitargeted agents and novel targeted agents account for 87.5%. (2) Therapeutic vaccines begin to show a promising future. They might be a new member of the targeted cancer therapies for NSCLC in the near future. (3) Some targeted agents for NSCLC at phase III clinical trials are the approved targeted ones for other caners. It indicates that international pharmaceutical companies can take advantages of the resources available to develop more medicines for NSCLC. Source

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