Project description:Incidence of canine mammary carcinoma is two times higher than the rate of human breast cancer. Mammary tumors are the most common type of cancer in intact female dogs and account for about half of all neoplasms in these dogs. Well-established models of breast cancer have shown that neoplastic cells often have a loss of intercellular communication, particularly gap junction proteins. Thus, the objective of this study is to explore the aspect of gap junction intercellular communication in canine mammary carcinoma, non-cancerous (CMEC) and cancerous (CMT12, CMT27, and CF41.Mg) cells, and patient-derived tumors. Both non-cancerous and cancerous mammary cells express connexins 26 and 43 using immunofluorescence; however, the level of expression is significantly different in quantitative analysis using western blot in which connexin 43 in both CMT12 and CMT27 is significantly decreased compared to CMEC. Furthermore, a decrease of gap junction capacity in CMT12 and CMT27 was observed compared to CMEC. Immunostaining of CMT27-xenograft tumors revealed positive Cx26 and negative Cx43 expression. Similarly, immunostaining of spontaneous canine mammary tumors revealed that Cx26 is present in all tumors while Cx43 is present in 25% of tumors. Overall, the study provides for the first time that a differential pattern of connexin expression exists between non-cancerous and cancerous mammary cells in dogs. This study will pave the path for further in vitro work of connexins in comparative canine models and possibly allow for novel therapeutics to be developed.
Project description:Table of contents A1 Proceedings of 2016 China Cancer Immunotherapy Workshop, Beijing, China Bin Xue, Jiaqi Xu, Wenru Song, Zhimin Yang, Ke Liu, Zihai Li A2 Set the stage: fundamental immunology in forty minutes Zihai Li A3 What have we learnt from the anti-PD-1/PD-L1 therapy of advanced human cancer? Lieping Chen A4 Immune checkpoint inhibitors in lung cancer Edward B. Garon A5 Mechanisms of response and resistance to checkpoint inhibitors in melanoma Siwen Hu-Lieskovan A6 Checkpoint inhibitor immunotherapy in lymphoid malignancies Wei Ding A7 Translational research to improve the efficacy of immunotherapy in genitourinary malignancies Chong-Xian Pan A8 Immune checkpoint inhibitors in gastrointestinal malignancies Weijing Sun A9 What’s next beyond PD-1/PDL1? Yong-Jun Liu A10 Cancer vaccines: new insights into the oldest immunotherapy strategy Lei Zheng A11 Bispecific antibodies for cancer immunotherapy Delong Liu A12 Updates on CAR-T immunotherapy Michel Sadelain A13 Adoptive T cell therapy: personalizing cancer treatment Cassian Yee A14 Immune targets and neoantigens for cancer immunotherapy Rongfu Wang A15 Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with advanced and metastatic solid tumors Meixia Chen, Yao Wang, Zhiqiang Wu, Hanren Dai, Can Luo, Yang Liu, Chuan Tong, Yelei Guo, Qingming Yang, Weidong Han A16 Cancer immunotherapy biomarkers: progress and issues Lisa H. Butterfield A17 Shaping of immunotherapy response by cancer genomes Timothy A. Chan A18 Unique development consideration for cancer immunotherapy Wenru Song A19 Immunotherapy combination Ruirong Yuan A20 Immunotherapy combination with radiotherapy Bo Lu A21 Cancer immunotherapy: past, present and future Ke Liu A22 Breakthrough therapy designation drug development and approval Max Ning A23 Current European regulation of innovative oncology medicines: opportunities for immunotherapy Harald Enzmann, Heinz Zwierzina
Project description:Introduction and Objectives: The phase 2 TERRAIN trial compared the efficacy and safety of enzalutamide (ENZA) vs. bicalutamide (BIC) in patients (pts) with metastatic castration-resistant prostate cancer who had progressed on luteinizing hormone-releasing hormone agonist/antagonist therapy or after bilateral orchiectomy while maintaining castration therapy during the study. An age effect analysis was pre-specified to investigate the efficacy and safety of ENZA vs. BIC. Results are presented in younger (<75 years) and older (?75 years) pts in the TERRAIN population. Methods: In this double-blind study in North America and Europe, pts were randomized 1:1 to ENZA 160 mg/day or BIC 50 mg/day. The primary efficacy endpoint was centrally assessed progression-free survival (PFS) and a secondary efficacy endpoint was time to prostate-specific antigen (PSA) progression. Results: 184 pts were randomized to ENZA and 191 pts to BIC. 126 (68.5%) and 119 (62.3%) pts were <75, and 58 (31.5%) and 72 (37.7%) pts were ?75, in the ENZA and BIC arms, respectively. PFS was significantly improved with ENZA vs. BIC in pts <75 years (median 16.6 vs. 5.8 months; HR 0.38 (95% CI 0.27, 0.52) and pts ?75 years (median 13.8 vs. 6.4 months; HR 0.59 (95% CI 0.37, 0.92). Median time to PSA progression was similarly significantly improved with ENZA vs. BIC in younger (median 22.1 vs. 8.2 months; HR 0.27 (95% CI 0.18, 0.40) and older pts (median 16.6 vs. 5.8 months; HR 0.33 (95% CI 0.19, 0.57). Adverse events (AEs) with ENZA were more frequent in older pts (98.3%) vs. younger pts (92.8%), but a similar distribution of treatment-related AEs between treatment arms was observed in either age group. Conclusions: ENZA had greater efficacy than BIC regardless of age, with superior PFS and time to PSA progression. ENZA showed safety consistent with its known safety profile in both age subgroups.