Predicting 5-FU sensitivity using human colorectal cancer specimens: comparison of tumor dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activities with in vitro chemosensitivity to 5-FU

2002 ◽  
Vol 7 (6) ◽  
pp. 335-342 ◽  
Author(s):  
K. Isshi ◽  
T. Sakuyama ◽  
T. Gen ◽  
Y. Nakamura ◽  
T. Kuroda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dihydropyrimidine Dehydrogenase ◽  
Human Colorectal Cancer ◽  
Orotate Phosphoribosyl Transferase ◽  
Phosphoribosyl Transferase ◽  
In Vitro Chemosensitivity

Bioactive Peptides Sensitize Cells to Anticancer Effects of Oxaliplatin in Human Colorectal Cancer Xenografts in Nude Mice

2019 ◽  
Vol 26 (7) ◽  
pp. 512-522
Author(s):  
Xian Li ◽  
Long Xia ◽  
Xiaohui Ouyang ◽  
Qimuge Suyila ◽  
Liya Su ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Nude Mice ◽  
Low Dose ◽  
Bioactive Peptides ◽  
Human Colorectal Cancer ◽  
Short Term ◽  
Hct 116

<P>Background: Despite new agent development and short-term benefits in patients with Colorectal Cancer (CRC), metastatic CRC cure rates have not improved due to high rates of oxaliplatin resistance and toxicity. There is an urgent need for effective tools to prevent and treat CRC and reduce morbidity and mortality of CRC patients. Exploring the effects of bioactive peptides on the antitumor to CRC was of vital importance to the clinical application. </P><P> Objective: This study aimed to investigate the therapeutic impact of Anticancer Bioactive Peptides (ACBP) on anticancer effect of oxaliplatin (LOHP) in human colorectal cancer xenografts models in nude mice. </P><P> Methods: HCT-116 cells were cultured in vitro via CCK-8 assays and the absorbance was measured at 450 nm. Apoptosis and cell cycle were assessed by Flow Cytometry (FCM) in vitro. HCT-116 human colorectal cancer cells inoculated subcutaneously in nude mice of treatment with PBS (GG), ACBP, LOHP, ACBP+LOHP (A+L) in vivo. The quality of life was assessed by dietary amount of nude mice, the weight of nude mice, inhibition rates, tumor weight and tumor volume. Immunohistochemistry and RT-qPCR method was conducted to determine the levels of apoptosisregulating proteins/genes in transplanted tumors. </P><P> Results: ACBP induced substantial reductions in viable cell numbers and apoptosis of HCT116 cells in combined with LOHP in vitro. Compared with the control GG group, ACBP combined low dose oxaliplatin (U) group demonstrated significantly different tumor volume, the rate of apoptosis, the expression levels of Cyt-C, caspase-3,8,9 proteins and corresponding RNAs (P<0.05). The expression of pro-apoptotic proteins in the cytoplasm around the nucleus was significantly enhanced by ACBP. Short term intermittent use of ACBP alone indicted a certain inhibitory effect on tumor growth, and improve the quality of life of tumor bearing nude mice. </P><P> Conclusion: ACBP significantly increased the anti-cancer responses of low dose oxaliplatin (L-LOHP), thus, significantly improving the quality of life of tumor-bearing nude mice.</P>

scholarly journals Clarithromycin inhibits autophagy in colorectal cancer by regulating the hERG1 potassium channel interaction with PI3K

2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Giulia Petroni ◽  
Giacomo Bagni ◽  
Jessica Iorio ◽  
Claudia Duranti ◽  
Tiziano Lottini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Option ◽  
Autophagic Flux ◽  
Macromolecular Complex ◽  
Human Colorectal Cancer ◽  
Akt Phosphorylation ◽  
Channel Interaction ◽  
Dependent Cell ◽  
Resistance To Chemotherapy

AbstractWe have studied how the macrolide antibiotic Clarithromycin (Cla) regulates autophagy, which sustains cell survival and resistance to chemotherapy in cancer. We found Cla to inhibit the growth of human colorectal cancer (CRC) cells, by modulating the autophagic flux and triggering apoptosis. The accumulation of cytosolic autophagosomes accompanied by the modulation of autophagic markers LC3-II and p62/SQSTM1, points to autophagy exhaustion. Because Cla is known to bind human Ether-à-go-go Related Gene 1 (hERG1) K+ channels, we studied if its effects depended on hERG1 and its conformational states. By availing of hERG1 mutants with different gating properties, we found that fluorescently labelled Cla preferentially bound to the closed channels. Furthermore, by sequestering the channel in the closed conformation, Cla inhibited the formation of a macromolecular complex between hERG1 and the p85 subunit of PI3K. This strongly reduced Akt phosphorylation, and stimulated the p53-dependent cell apoptosis, as witnessed by late caspase activation. Finally, Cla enhanced the cytotoxic effect of 5-fluorouracil (5-FU), the main chemotherapeutic agent in CRC, in vitro and in a xenograft CRC model. We conclude that Cla affects the autophagic flux by impairing the signaling pathway linking hERG1 and PI3K. Combining Cla with 5-FU might be a novel therapeutic option in CRC.

scholarly journals Development of Preclinical Models to Understand and Treat Colorectal Cancer

2018 ◽  
Vol 31 (03) ◽  
pp. 199-204 ◽  
Author(s):  
Judith Sebolt-Leopold
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Tumors ◽  
Human Colorectal Cancer ◽  
Preclinical Models ◽  
In Vivo Models ◽  
Molecular Determinants ◽  
Experimental Therapies ◽  
Molecular Aberrations

AbstractThe establishment and validation of preclinical models that faithfully recapitulate the pathogenesis and treatment response of human colorectal cancer (CRC) is critical to expedient therapeutic advances in the clinical management of this disease. Integral to the application of precision medicine for patients diagnosed with metastatic CRC is the need to understand the molecular determinants of response for a given therapy. Preclinical models of CRC have proven invaluable in answering many of our basic questions relating to the molecular aberrations that drive colorectal tumor progression. This review will address the comparative merits and limitations of the broad spectrum of in vitro and in vivo models available for study of colorectal tumors and their response to experimental therapies.

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