scholarly journals Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiao Wu ◽  
Sai-Ching Jim Yeung ◽  
Sicheng Liu ◽  
Aiham Qdaisat ◽  
Dewei Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Weight Loss ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Colorectal Cancer Patient ◽  
Nutrition Support ◽  
Immunodeficient Mice ◽  
The Impact

AbstractWeight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

scholarly journals Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines

2012 ◽  
Vol 10 (1) ◽  
pp. 109 ◽  
Author(s):  
Sebastian Gnosa ◽  
Yang-Mei Shen ◽  
Chao-Jie Wang ◽  
Hong Zhang ◽  
Johannes Stratmann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Colon Cancer Cell Lines ◽  
Colorectal Cancer Patients

scholarly journals Serum DJ-1 Is a Biomarker of Colorectal Cancer and DJ-1 Activates Mitophagy to Promote Colorectal Cancer Progression

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4151
Author(s):  
William Tzu-Liang Chen ◽  
Han-Bin Yang ◽  
Tao-Wei Ke ◽  
Wen-Ling Liao ◽  
Shih-Ya Hung
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Colorectal Adenocarcinoma ◽  
Reactive Oxygen Species Generation ◽  
Cancer Drug ◽  
Adenocarcinoma Cells ◽  
Colorectal Cancer Progression ◽  
Colorectal Cancer Patients

Colorectal cancer is the second most common cancer and the third cancer-associated death in Taiwan. Currently used serum markers for detecting colorectal cancer lack excellent diagnostic accuracy, which results in colorectal cancer being often recognized too late for successful therapy. Mitophagy is the selective autophagic degradation of damaged or excessive mitochondria. DJ-1 is an antioxidant protein that attenuates oxidative stress and maintains mitochondrial quality through activating mitophagy. Mitophagy activation contributes to anti-cancer drug resistance. However, the role of DJ-1-induced mitophagy in colorectal cancer progression remains unclear. In the present study, we collected matched tumor and adjacent normal tissues and serum from patients and cancer cells to demonstrate the clinical value and physiological function of DJ-1 in colorectal cancer. We found that DJ-1 increased in tumor tissues and serum; it was positively correlated with TNM (tumor-node-metastasis) stages of colorectal cancer patients. Through stable knockdown DJ-1 expression in metastatic colorectal adenocarcinoma cells SW620, DJ-1 knockdown inhibited cancer cell survival, migration, and colony formation. In SW620 cells, DJ-1 knockdown induced an incomplete autophagic response that did not affect ATP production; DJ-1 knockdown enhanced intracellular reactive oxygen species generation and damaged mitochondrial accumulation and mitophagy inhibition. It suggests that DJ-1 knockdown inhibits mitophagy that causes metastatic colorectal adenocarcinoma cells to be unable to remove damaged mitochondria and further enhance cancer cell apoptosis. Our data indicate that DJ-1 might be clinically valuable as serum and tissue biomarkers for predicting the TNM stage in colorectal cancer patients. Since DJ-1-induced mitophagy promotes tumor progression, DJ-1 inhibition is a potential therapeutic strategy for colorectal cancer treatment.

scholarly journals Physical Activity after Colorectal Cancer Diagnosis and Mortality in a Nationwide Retrospective Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4804
Author(s):  
Meesun Lee ◽  
Yunseo Lee ◽  
Doeun Jang ◽  
Aesun Shin
Keyword(s):  
Physical Activity ◽  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Early Stage ◽  
Colorectal Cancer Patient ◽  
Prognostic Impact ◽  
Specific Mortality

Physical activity reduces the risk of colon cancer, but its prognostic impact after cancer diagnosis remains unclear. To evaluate the association between post-diagnosis activity and cause-specific mortality, we reconstructed a colorectal cancer patient cohort from the 2009–16 Korean National Health Insurance Service (NHIS) database. Subgroup analyses were performed by treatment group. In total, 27,143 colon cancer patients and 16,453 rectal cancer patients were included in the analysis (mean follow-up, 4.3 years; median 4.0 years). In the surgically treated group, a high level of activity (the weighted sum of the frequencies for walking, moderate, and vigorous activity greater than or equal to 3 times/week) was inversely associated with all-cause mortality (colon cancer: HR, 0.79; 95% CI, 0.72 to 0.88; rectal cancer: HR, 0.75; 95% CI, 0.66 to 0.86) and colorectal cancer-specific mortality (colon cancer: HR, 0.85; 95% CI, 0.76 to 0.97; rectal cancer: HR, 0.77; 95% CI, 0.66 to 0.90). No significant results were shown for cardiovascular disease-specific mortality. No association was shown in patients who received chemoradiotherapy without surgery. The present study may provide evidence for post-diagnosis physical activity as a prognostic factor in colorectal cancer, particularly in surgically treated early-stage patients.

scholarly journals Exploring the impact of gene mutation on the progression of multistage colorectal cancer

2021 ◽  
Author(s):  
Wentao Wang ◽  
Haiquan Qin ◽  
Zigao Huang ◽  
Jiankun Liao ◽  
Yongjie Qin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Mucinous Adenocarcinoma ◽  
Normal Tissue ◽  
Tumor Development ◽  
Gene Mutations ◽  
Growth Cycle ◽  
The Right ◽  
The Impact

Abstract OBJECTIVE: This article focused on the key role that the cumulative mutations of somatic genes play during the progression of colorectal cancer from benign adenoma to highly malignant mucinous adenocarcinoma. Moreover, the article explains the reasons for the differences in the prognosis of the left-sided and right-sided colon cancer by comparing the number of mutations in the cases. METHODS: In this study, tumor specimens from patients with different stages and different states of co-occurring colonic adenoma, colonic adenocarcinoma, and colonic mucinous adenocarcinoma were extracted and analyzed for gene mutations in different tumor development stages during the progressive evolution from normal tissue to mucinous adenocarcinoma by second-generation sequencing gene detection. Conclusion: The number of somatic gene mutations showed an increasing trend during the progression from normal tissue to the mucinous adenocarcinoma with the highest malignancy. No difference in the underlying genetic level between the right-sided and left-sided colon cancer was observed. However, the prognosis of the right-sided colon cancer patients was worse than that of the left-sided colon cancer patients, suggesting that the longer growth cycle of the right-sided colon cancer may be the main reason for the difference of prognosis.

Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Jeyalakshmi Kandhavelu ◽  
Kumar Subramanian ◽  
Amber Khan ◽  
Aadilah Omar ◽  
Paul Ruff ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Target Prediction ◽  
Computational Prediction ◽  
Initial Step ◽  
Kegg Pathways ◽  
Candidate Mirnas ◽  
Common Cancer ◽  
Colon Cancer Progression

Background:Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. </P><P> Methods: The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.Results:We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.

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