Hydroxychloroquine based chemical drug for combination therapy with 5-Fu for inhibiting the pathway of Akt/mTOR in autophagy process on colon cancer

Author(s):  
Zhi Liao ◽  
yan chen ◽  
lizhu han ◽  
dongke yu ◽  
tingting shi ◽  
...  

Abstract: In order to improve the effect of hydroxychloroquine (HCQ) on the selectivity in anti-tumour therapy, the α-linolenic acid conjugated hydroxychloroquine (AHQ) was designed, which was aiming to enhance anti-tumor...

2020 ◽  
Vol 2020 ◽  
pp. 1-4 ◽  
Author(s):  
Jeffrey Chi ◽  
Jennifer Park ◽  
Muhammad Wasif Saif

Combination therapy with ibrutinib and cetuximab is being studied in a phase 1b/2 trial in patients with advanced gastrointestinal and genitourinary malignancies. Rash is a common cutaneous adverse effect for both medications. Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor approved for the treatment of several hematologic malignancies. The rash can be asymptomatic, nonpalpable, mild skin eruption, or palpable purpuric rash. A rarer panniculitis form has also been reported. Cetuximab, an epidermal growth factor (EGFR) inhibitor, approved for treatment in head and neck and advanced gastrointestinal malignancies is also known to cause acneiform rash in majority of patients. The rash is due to inhibition of EGFR in the basal keratinocytes and hair follicles. In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash. The combination therapy with the BTK inhibitor and a direct EGFR inhibitor may potentiate the rash inducing effects of the drugs. Here, we describe a case of vasculitis in a patient with metastatic colon cancer who received both ibrutinib and cetuximab on a phase Ib/II clinical trial.


2010 ◽  
Vol 2 (4) ◽  
pp. 261-272 ◽  
Author(s):  
Diogo Assed Bastos ◽  
Suilane Coelho Ribeiro ◽  
Daniela de Freitas ◽  
Paulo M. Hoff

Author(s):  
Nobuyuki Ogawa ◽  
Toshiyoshi Fujiwara ◽  
Shunsuke Kagawa ◽  
Masahiko Nishizaki ◽  
Yoshinori Morimoto ◽  
...  

Author(s):  
Qing Ren ◽  
Bo Yang ◽  
Guangzhen Zhu ◽  
Shunyu Wang ◽  
Chengli Fu ◽  
...  

The probiotic bacterial strain Lactobacillus plantarum ZS2058 has been proved to manifest comprehensive functions, which were due to ability to synthesise conjugated fatty acids (CFAs). To investigate the specific functions of CFAs produced by this probiotic bacterium, α-linolenic acid was isomerized by Lactobacillus plantarum strain ZS2058, and two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated lipid peroxidation was related to the antiproliferation activity of CLNAs. Examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. And no sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first report showing the ability of CLNAs to activate antioxidant defenses resulting in pyroptosis.


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