3 results
Search Results
2. Anti-tumor effects of a recombinant anti-prostate specific membrane antigen immunotoxin against prostate cancer cells.
- Author
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Ping Meng, Qing-chuan Dong, Guang-guo Tan, Wei-hong Wen, He Wang, Geng Zhang, Yan-zhu Wang, Yu-ming Jing, Chen Wang, Wei-jun Qin, Jian-lin Yuan, Meng, Ping, Dong, Qing-Chuan, Tan, Guang-Guo, Wen, Wei-Hong, Wang, He, Zhang, Geng, Wang, Yan-Zhu, Jing, Yu-Ming, and Wang, Chen
- Subjects
TUMOR prevention ,PROSTATE-specific membrane antigen ,ANTIBODY-toxin conjugates ,PROSTATE cancer treatment ,CANCER cells ,REVERSE transcriptase polymerase chain reaction ,WESTERN immunoblotting ,CANCER treatment ,PROSTATE tumors treatment ,ADENOCARCINOMA ,ANIMALS ,ANTIGENS ,GENE therapy ,GENETIC techniques ,MICE ,PROSTATE tumors ,PROTEINS ,PROTEOLYTIC enzymes ,TOXINS ,CANCER cell culture - Abstract
Background: To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein.Methods: We established a novel fusion gene, immunocasp-3, composed of NH2-terminal leader sequence fused with an anti-prostate-specific membrane antigen (PSMA) antibody (J591), the furin cleavage sequences of diphtheria toxin (Fdt), and the reverse coding sequences of the large and small subunits of caspase-3 (revcaspase-3). The expressing level of the immunocasp-3 gene was evaluated by using the reverse transcription-PCR (RT-PCR) and western blot analysis. Cell viability assay and cytotoxicity assay were used to evaluate its anti-tumor effects in vitro. Apoptosis was confirmed by electron microscopy and Annexin V-FITC staining. The antitumor effects of immunocasp-3 were assessed in nude mice xenograft models containing PSMA-overexpressing LNCaP cells.Results: This study shows that the immunocasp-3 proteins selectively recognized and induced apoptotic death in PSMA-overexpressing LNCaP cells in vitro, where apoptotic cells were present in 15.3% of the cells transfected with the immunocasp-3 expression vector at 48 h after the transfection, in contrast to 5.5% in the control cells. Moreover, LNCaP cells were significantly killed under the condition of the co-culture of the immunocasp-3-secreting Jurkat cells and more than 50% of the LNCaP cells died when the two cell lines were co-cultured within 5 days. In addition, The expression of immunocasp-3 also significantly suppressed tumor growth and greatly prolonged the animal survival rate in vivo.Conclusion: A novel fusion gene, immunocasp-3, may represent a viable approach to treating PSMA-positive prostate cancer. [ABSTRACT FROM AUTHOR]- Published
- 2017
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3. PD-L1 expression in papillary renal cell carcinoma.
- Author
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Takanobu Motoshima, Yoshihiro Komohara, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda, Masatoshi Eto, Motoshima, Takanobu, Komohara, Yoshihiro, Ma, Chaoya, Dewi, Arni Kusuma, and Noguchi, Hirotsugu
- Subjects
GENE expression ,CANCER cells ,CANCER invasiveness ,T cells ,LIGANDS (Biochemistry) ,IMMUNOTHERAPY ,RENAL cell carcinoma ,PROGRESSION-free survival ,CANCER treatment ,ANTIGENS ,KIDNEY tumors ,RETROSPECTIVE studies ,DIAGNOSIS - Abstract
Background: The immune escape or tolerance of cancer cells is considered to be closely involved in cancer progression. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activating T cells, and several types of cancer cells were found to express PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2).Methods: In the present study, we investigated PD-L1/2 expression in papillary renal cell carcinoma (pRCC).Result: We found PD-L1 expression in 29 of 102 cases, but no PD-L2 expression was seen. PD-L1 expression was not significantly correlated with any clinicopathological factor, including progression-free survival and overall survival. The frequency of PD-L1-positive cases was higher in type 2 (36%) than in type 1 (22%) pRCC; however, there was no significant difference in the percentages of score 0 cases (p value = 0.084 in Chi-square test). The frequency of high PD-L1 expression cases was higher in type 2 (23%) than in type 1 (11%), and the frequency of high PD-L1 expression cases was higher in grade 3/4 (21%) than in grade 1/2 (13%). However, no significant association was found between PD-L1 expression and all clinicopathological factors in pRCC.Conclusion: High expression of PD-L1 in cancer cells was potentially associated to highly histological grade of malignancy in pRCC. The evaluation of the PD-L1 protein might still be useful for predicting the efficacy of anti-cancer immunotherapy using immuno-checkpoint inhibitors, however, not be useful for predicting the clinical prognosis. [ABSTRACT FROM AUTHOR]- Published
- 2017
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