Pathologic characteristics and cell cycle regulatory protein expression as a prognosis marker after curative resection in gall bladder cancer

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 15634-15634
Author(s):  
M. Lee ◽  
S. Hong ◽  
E. Chung ◽  
Y. Koh ◽  
J. Kang ◽  
...  
2020 ◽  
Vol 19 (16) ◽  
pp. 2019-2033 ◽  
Author(s):  
Pratibha Pandey ◽  
Mohammad H. Siddiqui ◽  
Anu Behari ◽  
Vinay K. Kapoor ◽  
Kumudesh Mishra ◽  
...  

Background: The aberrant alteration in Jab1 signalosome (COP9 Signalosome Complex Subunit 5) has been proven to be associated with the progression of several carcinomas. However the specific role and mechanism of action of Jab1 signalosome in carcinogenesis of gall bladder cancer (GBC) are poorly understood. Objective: The main objective of our study was to elucidate the role and mechanism of Jab1 signalosome in gall bladder cancer by employing siRNA. Methods: Jab1 overexpression was identified in gall bladder cancer tissue sample. The role of Jab1-siRNA approach in cell growth inhibition and apoptotic induction was then examined by RT-PCR, Western Blotting, MTT, ROS, Hoechst and FITC/Annexin-V staining. Results: In the current study, we have shown that overexpression of Jab1 stimulated the proliferation of GBC cells; whereas downregulation of Jab1 by using Jab1-siRNA approach resulted incell growth inhibition and apoptotic induction. Furthermore, we found that downregulation of Jab1 induces cell cycle arrest at G1 phase and upregulated the expression of p27, p53 and Bax gene. Moreover, Jab1-siRNA induces apoptosis by enhancing ROS generation and caspase-3 activation. In addition, combined treatment with Jab1-siRNA and gemicitabine demonstrated an enhanced decline in cell proliferation which further suggested increased efficacy of gemcitabine at a very lower dose (5μM) in combination with Jab1-siRNA. Conclusion: In conclusion, our study strongly suggests that targeting Jab1 signalosome could be a promising therapeutic target for the treatment of gall bladder cancer.


2019 ◽  
Vol 19 (6) ◽  
pp. 826-837 ◽  
Author(s):  
Pratibha Pandey ◽  
Preeti Bajpai ◽  
Mohammad H. Siddiqui ◽  
Uzma Sayyed ◽  
Rohit Tiwari ◽  
...  

Background:Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.Objective:In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.Methods:In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.Results:Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.Conclusion:Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.


Author(s):  
Pratibha Pandey ◽  
Uzma Sayyed ◽  
Rohit Tiwari ◽  
Neelam Pathak ◽  
Mohammad Haris Siddiqui ◽  
...  

Curcumin, the primary bioactive component isolated from turmeric, has been shown to possess variety of biologic functions including anti-cancer activity. However, meticulous mechanism of the curcumin in gall bladder cancer has not been explored yet. Therefore, in our study, we elucidated the mechanism of the anticancer action of curcumin against human gall bladder cancer cells. It was found that the curcumin treated GBC cells decreased cell viability in a dose and time-dependent manner. Nuclear condensation, Annexin V-FITC/PI positive cells, and caspase-3 activation confirmed the apoptotic induction due to anti-proliferative action of curcumin. Furthermore, curcumin induced disruption in the mitochondrial membrane potential and increased reactive oxygen species generation which has not yet been reported in earlier studies of curcumin with gall bladder cancer. Moreover, curcumin-induced apoptosis of gall bladder cancer cells was also accompanied by significant amount of growth arrest at the G0/G1 phase of the cell cycle which has also not been documented previously. To the best part of my knowledge, this study has established curcumin as one of the promising chemotherapeutic agent against gall bladder carcinoma. Thus the present study explored a novel mechanism explaining the anti cancerous effects of curcumin, and may provide an alternative therapeutic approach which can overcome the side effects of chemotherapy. Keywords: Gall bladder carcinoma Curcumin; Cell cycle analysis; Caspase-3; Apoptosis


2009 ◽  
Vol 27 (7) ◽  
pp. 764-773 ◽  
Author(s):  
T. Padma Priya ◽  
V. K. Kapoor ◽  
Narendra Krishnani ◽  
Vinita Agrawal ◽  
Suraksha Agarwal

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