scholarly journals MLH1 mediates cytoprotective nucleophagy to resist 5-Fluorouracil-induced cell death in colorectal carcinoma

Neoplasia ◽  
2022 ◽  
Vol 24 (2) ◽  
pp. 76-85
Author(s):  
Shaista Manzoor ◽  
Maha Saber-Ayad ◽  
Azzam A. Maghazachi ◽  
Qutayba Hamid ◽  
Jibran Sualeh Muhammad
Cancer ◽  
1996 ◽  
Vol 77 (8) ◽  
pp. 1711-1716 ◽  
Author(s):  
Shunichi Tsujitani ◽  
Hiroyuki Shirai ◽  
Shigeru Tatebe ◽  
Kenji Sugamura ◽  
Satoshi Ohfuji ◽  
...  

2020 ◽  
Vol 6 (4) ◽  
Author(s):  
Zainab Waleed Aziz ◽  
Asmaa Mohammadsheet Mahmood ◽  
Zahraa Osama Yahiya ◽  
Wahda Mohammed Taib Al –Nuaimy

Abstract     Objectives: Programmed Cell Death Ligand1 (PD-L1) tissue expression in CRC (colorectal cancer) displays conflicting results among various studies. We aimed to identify the rate of PD-L1 positivity in colorectal carcinoma, and it's immune infiltrating cells, their relationship with clinicopathologic parameters of patients, and to correlate the results with other studies.    Methods: PD-L1 antibody retrospectively analyzed immunohistochemically in tissue microarray blocks of 99 specimens with colonic and rectal carcinomas operated between January 2015 to December 2017. A comparison performed between PD-L1 expression  in tumor cells (TCs) as well as tumor-infiltrating immune cells (TIICs) for age, sex, histological differentiation, the primary tumor location, number of involved lymph nodes, angiolymphatic invasion, and TNM stage.   Results: Of the 99 patients, the median age was 54.5 (range: 18 to 83) years. Fourteen samples were PD-L1 positive in TCs, increased to 32%  in TIICs. A significant expression of PD-L1in TCs was correlated with medullary histology (p= 0.03), number of the involved lymph nodes (p= 0.02), distant metastasis (p= 0.001), and TNM stage (p= 0.0001). The PD-L1 status in TIICs was again connected with adverse clinical and pathological parameters.    Conclusions: The expression of PD-L1 in TCs and TIICs is associated significantly with advanced cancer or lymphatic invasion in patients who underwent surgery after a diagnosis of CRC. The research designates the significance of estimation of TCs and TIICs in correlation to clinicopathologic characteristics of patients a finding that could produce a piece of evidence for precise electing immunotherapy.       Keywords: Programmed cell death ligand1, colorectal carcinoma, Tissue microarray study, Immunohistochemistry.      


2018 ◽  
Vol 46 (sup3) ◽  
pp. S247-S253 ◽  
Author(s):  
Firdos Alam Khan ◽  
Sultan Akhtar ◽  
Dana Almohazey ◽  
Munthar Alomari ◽  
Sarah Ameen Almofty ◽  
...  

2020 ◽  
Vol 21 (22) ◽  
pp. 8522
Author(s):  
María Fuentes-Baile ◽  
Pilar García-Morales ◽  
Elizabeth Pérez-Valenciano ◽  
María P. Ventero ◽  
Jesús M. Sanz ◽  
...  

The combination of the choline binding domain of the amidase N-acetylmuramoyl-L-alanine (CLytA)-D-amino acid oxidase (DAAO) (CLytA-DAAO) and D-Alanine induces cell death in several pancreatic and colorectal carcinoma and glioblastoma cell lines. In glioblastoma cell lines, CLytA-DAAO-induced cell death was inhibited by a pan-caspase inhibitor, suggesting a classical apoptotic cell death. Meanwhile, the cell death induced in pancreatic and colon carcinoma cell lines is some type of programmed necrosis. In this article, we studied the mechanisms that trigger CLytA-DAAO-induced cell death in pancreatic and colorectal carcinoma and glioblastoma cell lines and we acquire a further insight into the necrotic cell death induced in pancreatic and colorectal carcinoma cell lines. We have analyzed the intracellular calcium mobilization, mitochondrial membrane potential, PARP-1 participation and AIF translocation. Although the mitochondrial membrane depolarization plays a crucial role, our results suggest that CLytA-DAAO-induced cell death is context dependent. We have previously detected pancreatic and colorectal carcinoma cell lines (Hs766T and HT-29, respectively) that were resistant to CLytA-DAAO-induced cell death. In this study, we have examined the putative mechanism underlying the resistance in these cell lines, evaluating both detoxification mechanisms and the inflammatory and survival responses. Overall, our results provide a better understanding on the cell death mechanism induced by CLytA-DAAO, a promising therapy against cancer.


2015 ◽  
Vol 2 ◽  
pp. 14056 ◽  
Author(s):  
Roberta Marchione ◽  
David Laurin ◽  
Lavinia Liguori ◽  
Marie P Leibovitch ◽  
Serge A Leibovitch ◽  
...  

1996 ◽  
Vol 16 (12) ◽  
pp. 6654-6660 ◽  
Author(s):  
M Gorospe ◽  
X Wang ◽  
K Z Guyton ◽  
N J Holbrook

Prostaglandin A2 (PGA2) suppresses tumor growth in vivo, is potently antiproliferative in vitro, and is a model drug for the study of the mammalian stress response. Our previous studies using breast carcinoma MCF-7 cells suggested that p21(Waf1/Cip1) induction enabled cells to survive PGA2 exposure. Indeed, the marked sensitivity of human colorectal carcinoma RKO cells to the cytotoxicity of PGA2 is known to be associated with a lack of a PGA2-mediated increase in p21(Waf1/Cip1) expression, inhibition of cyclin-dependent kinase activity, and growth arrest. To determine if cell death following exposure to PGA2 could be prevented by forcing the expression of p21(Waf1/Cip1) in RKO cells, we utilized an adenoviral vector-based expression system. We demonstrate that ectopic expression of p21(Waf1/Cip1) largely rescued RKO cells from PGA2-induced apoptotic cell death, directly implicating p21(Waf1/Cip1) as a determinant of the cellular outcome (survival versus death) following exposure to PGA2. To discern whether p21(Waf1/Cip1)-mediated protection operates through the implementation of cellular growth arrest, other growth-inhibitory treatments were studied for the ability to attenuate PGA2-induced cell death. Neither serum depletion nor suramin (a growth factor receptor antagonist) protected RKO cells against PGA2 cytotoxicity, and neither induced p21(Waf1/Cip1) expression. Mimosine, however, enhanced p21(Waf1/Cip1) expression, completely inhibited RKO cell proliferation, and exerted marked protection against a subsequent PGA2 challenge. Taken together, our results directly demonstrate a protective role for p21(Waf1/Cip1) during PGA2 cellular stress and provide strong evidence that the implementation of cellular growth arrest contributes to this protective influence.


Author(s):  
Rayane Ganassin ◽  
Giulia Rosa Tavares de Oliveira ◽  
Márcia Cristina Oliveira da Rocha ◽  
José Athayde Vasconcelos Morais ◽  
Mosar Corrêa Rodrigues ◽  
...  

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