In Vitro and in Vivo Metabolism of the Anti-Cancer Agent CI-1040, a MEK Inhibitor, in Rat, Monkey, and Human

2004 ◽  
Vol 21 (9) ◽  
pp. 1670-1679 ◽  
Author(s):  
Paul A. Wabnitz ◽  
David Mitchell ◽  
David A.M. Wabnitz
Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 33
Author(s):  
Hee Ra Jung ◽  
Seongman Jo ◽  
Min Jae Jeon ◽  
Hyelim Lee ◽  
Yeonjeong Chu ◽  
...  

In cancer immunotherapy, the cyclic GMP–AMP synthase–stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from ‘cold’ to ‘hot’ through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity. Furthermore, KAS-08 was validated as an effective STING pathway activator in vitro and in vivo. The synergistic effect of cGAMP-mediated immunity and efficient anti-cancer effects successfully demonstrated the therapeutic potential of KAS-08 for combination therapy in cancer treatment.


2021 ◽  
Author(s):  
Mengmeng Liu ◽  
Yue Pan ◽  
Xufeng Tao ◽  
Ning Li ◽  
Kun Li ◽  
...  

Abstract BackgroundPDAC is universally acknowledged to be one of the highest mortality rate of cancer-related deaths. PCSCs, regulated by EMT, could promote the proliferation of PDAC. Berberine with high medicinal value has usually been used as an anti-cancer agent. Hence the purpose of this study is to investigate the anti-cancer effect of berberine in PDAC. MethodsMTT assay was used to verify berberine inhibiting the proliferation of PDAC. Immunofluorescence staining, stem cell sphere, wound healing and transwell migration assay were demonstrated the anti-proliferation and anti-stemness of PCSCs in vitro . PANC-02 cells were injected in C57BL/6 mice to establish the orthotopic pancreatic-cancer model in vivo . H&E and Ki67 immunohistogical staining assay were used to evaluated the effect of berberine in PDAC in vivo. q-PCR and Western blot methods were applied to detect the expression of EMT procedure.ResultsIn this study, berberine has selective anti-cancer effect in PDAC in vitro . Moreover, berberine suppressed the proliferation and stemness of PCSCs in PDAC. In vivo , berberine reduced the tumor size and decreased the expression of Ki67 in orthotopic pancreatic-cancer pancreases. In addition, berberine inhibit the EMT signaling pathway both in vitro and in vivo . ConclusionsOur study indicates that berberine inhibit the proliferation of PDAC in vivo and vitro . The mechanism of anti-cancer effect on berberine may suppress the PCSCs through inhibiting EMT procedure. Therefore, berberine may be the novel antineoplastic drug with clinical effectiveness in PDAC. Keywords: Berberine, PDAC, PCSCs, EMT, berberine


2020 ◽  
Vol 21 (1) ◽  
pp. 11-24
Author(s):  
Chandrasai Potla Durthi ◽  
Madhuri Pola ◽  
Satish Babu Rajulapati ◽  
Anand Kishore Kola ◽  
Mohammad Amjad Kamal

L-glutaminase has versatile applications in pharma and food industries. In pharmaceutical industry, L-glutaminase can be used as anti-oxidant and anti-cancer agent to treat Acute Lymphocytic Leukaemia (ALL). Whereas, in the food industry, L-glutaminase is used for acrylamide degradation, theanine production, flavour enhancer, soy sauce and many. The other applications include nitrogen metabolism and its use as biosensor in hybridoma technology. Both intra-cellular and extra-cellular L-glutaminases from wide range of sources were identified. Because of its diverse applications, there is a need to improve the production of L-glutaminase by enzyme engineering technology. Effect of recombination on L-glutaminase production was also reported. Researchers also confirmed the antitumor properties of L-glutaminase by conducting in vitro, in vivo and in silico studies. Bacillus sps. and Aspergillus sps. are the commercial producers of L-glutaminase. In this review, the applications, different sources of Lglutaminase, anti-cancer properties were discussed.


2017 ◽  
Vol 126 ◽  
pp. 12-24 ◽  
Author(s):  
Baojian Guo ◽  
Shengquan Hu ◽  
Chengyou Zheng ◽  
Hongyu Wang ◽  
Fangcheng Luo ◽  
...  
Keyword(s):  
Mao B ◽  

2012 ◽  
Vol 47 ◽  
pp. 432-444 ◽  
Author(s):  
Bo Zhong ◽  
Xiaohan Cai ◽  
Snigdha Chennamaneni ◽  
Xin Yi ◽  
Lili Liu ◽  
...  

2018 ◽  
Vol 26 (16) ◽  
pp. 4687-4692 ◽  
Author(s):  
Mingxu Ma ◽  
Jianchun Zhao ◽  
Hejuan Cheng ◽  
Mengyan Deng ◽  
Zhongpeng Ding ◽  
...  

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