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Gastrointestinal Disorders
Special Issues
Colorectal Cancer: Biology and Therapy
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Colorectal Cancer: Biology and Therapy

A special issue of Gastrointestinal Disorders (ISSN 2624-5647).

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 17688

Special Issue Editors

Prof. Dr. Masahito Shimizu

E-Mail Website
Guest Editor
First Department of Internal Medicine, Gifu University Hospital, Gifu 501-1194, Japan
Interests: liver carcinogenesis; cancer chemoprevention; chronic hepatitis; metabolic syndrome; retinoid; phytochemicals; clinical trial
Special Issues, Collections and Topics in MDPI journals
Dr. Yohei Shirakami

E-Mail Website
Guest Editor
Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
Interests: cancer prevention; gastroenterological disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is a common malignant disease and its incidence in clinical practice has increased gradually. CRC is considered to be heterogeneous with multiple genetic mutations and epigenetic alterations in genes that control cellular growth and differentiation. A number of molecular genetic studies have identified several gene defects and mutations related to sporadic CRC. In addition, other factors, including chronic inflammation, such as inflammatory bowel diseases, and metabolic syndrome are also predisposing factors to CRC development. While significant advances have been made in research for molecular biology and characterization, as well as detecting, diagnosing, therapy of CRC over the past decade, this disease still has a high mortality rate. A better understanding of the biology of CRC will lead to reduction of incidence, development of novel therapies, and improved prognosis. In terms of the therapies of CRC, molecular-targeted agents for personalized therapies, and immune checkpoint inhibitors are recently paid much attention.

This Special Issue of Gastrointestinal Disorders will focus on the biology of CRC in relation to existing and newly developed therapies.

Prof. Dr. Masahito Shimizu
Prof. Dr. Yohei Shirakami
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Gastrointestinal Disorders is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Colorectal cancer
  • Bowel cancer
  • Colon cancer
  • Tumor biology
  • Tumor heterogeneity
  • Molecular pathology
  • Adenoma-carcinoma sequence
  • Genetic and epigenetic markers
  • Immunotherapy
  • Prognostic biomarkers
  • EGFR pathways
  • Early diagnosis
  • Clinical trials

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Published Papers (4 papers)

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Research

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11 pages, 972 KiB  
Article
Sarcopenia as a Risk Factor of Morbimortality in Colorectal Cancer Surgery
by Mariana Pereira, Ana Pereira, Patrícia Silva, Catarina Costa and Sandra F. Martins
Gastrointest. Disord. 2020, 2(2), 107-117; https://doi.org/10.3390/gidisord2020010 - 24 Apr 2020
Cited by 2 | Viewed by 2627
Abstract
Background: Colorectal cancer (CRC) surgery is associated with high rates of postoperative morbimortality. Sarcopenia has been identified as an independent predictor of these surgical outcomes. Methods: A sample of 272 patients who underwent CRC surgery between January 2005 and May 2010 at Braga [...] Read more.
Background: Colorectal cancer (CRC) surgery is associated with high rates of postoperative morbimortality. Sarcopenia has been identified as an independent predictor of these surgical outcomes. Methods: A sample of 272 patients who underwent CRC surgery between January 2005 and May 2010 at Braga Hospital, was selected. Sarcopenia was defined by the skeletal muscle mass index, measured by preoperative computed tomography (CT), at L3 level, using ImageJ® software. Associations between sarcopenia and qualitative variables were analyzed by Chi-Square Test (χ2) or Fisher’s Exact Test and, for quantitative variables, by Mann-Whitney Test. A multivariate logistic regression was performed to assess if sarcopenia was an independent predictor of major morbidity. The overall and recurrence-free survivals were analyzed by Kaplan-Meier method and multivariate Cox regression was performed for recurrence-free survival. Results: The prevalence of sarcopenia was 19.1%. Sarcopenia was associated with male gender, no CRC family history and colon tumour (p < 0.001, p = 0.029 and p = 0.017, respectively). The presence of sarcopenia was associated with postoperative morbidity Clavien–Dindo classification (p = 0.003), and sarcopenia was an independent predictor for major complications (grade ≥ III) (p = 0.003). Conclusions: The evaluation of sarcopenia in patients undergoing CRC surgical resection allows to predict a higher probability of major postoperative morbimortality. Full article
(This article belongs to the Special Issue Colorectal Cancer: Biology and Therapy)
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7 pages, 1127 KiB  
Article
Bifidobacteria and Mucosal-Associated Invariant T (MAIT) Cells: A New Approach to Colorectal Cancer Prevention?
by Hüseyin Sancar Bozkurt and Eamonn M. M. Quigley
Gastrointest. Disord. 2019, 1(2), 266-272; https://doi.org/10.3390/gidisord1020022 - 31 May 2019
Cited by 9 | Viewed by 5302
Abstract
Colorectal cancer is the most preventable form of cancer worldwide. The pathogenesis of colorectal cancer includes gut inflammation, genetic and microbial composition factors. İmpairment of the gut microbiota has been associated with development of colorectal cancer. The genus Bifidobacterium is an important component [...] Read more.
Colorectal cancer is the most preventable form of cancer worldwide. The pathogenesis of colorectal cancer includes gut inflammation, genetic and microbial composition factors. İmpairment of the gut microbiota has been associated with development of colorectal cancer. The genus Bifidobacterium is an important component of the commensal gut microbiota. Bifidobacteria are considered to have important roles in multiple homeostatic functions: immunologic, hormonal and metabolic. Mucosal-associated invariant T cells (MAIT) are components of the immune system involved in protection against infectious pathogens and regulate the pathogenesis of various inflammatory diseases and, potentially, colorectal cancer. Engagement between Bifidobacterium and MAIT cells could exert a beneficial effect on colorectal cancer prevention and treatment. Full article
(This article belongs to the Special Issue Colorectal Cancer: Biology and Therapy)
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10 pages, 2480 KiB  
Article
Inhibition of Stearoyl-CoA Desaturase-1 Activity Suppressed SREBP Signaling in Colon Cancer Cells and Their Spheroid Growth
by Xian-Yang Qin and Soichi Kojima
Gastrointest. Disord. 2019, 1(1), 191-200; https://doi.org/10.3390/gidisord1010014 - 26 Jan 2019
Cited by 9 | Viewed by 4583
Abstract
Unsaturated fatty acids are critical in promoting colon tumorigenesis and its stemness. Stearoyl-CoA desaturase-1 (SCD1) is a rate-limiting lipid desaturase associated with colon cancer cell proliferation and metastasis control. This study aims to evaluate the effects of SCD1 inhibition on colon cancer spheroid [...] Read more.
Unsaturated fatty acids are critical in promoting colon tumorigenesis and its stemness. Stearoyl-CoA desaturase-1 (SCD1) is a rate-limiting lipid desaturase associated with colon cancer cell proliferation and metastasis control. This study aims to evaluate the effects of SCD1 inhibition on colon cancer spheroid growth in a three-dimensional cell culture system. An analysis of clinical data showed that increased SCD1 gene expression in colon tumors was negatively correlated with the prognosis. A chemical inhibitor of SCD1, CAY10566, inhibited the growth of colon cancer cells in both monolayer and sphere cultures. In addition, oleic acid administration—a monounsaturated fatty acid generated by the action of SCD1—prevented the suppression of sphere formation by CAY10566. RNA-sequencing data from 382 colon tumor patient samples obtained from the Cancer Genome Atlas database showed that 806 genes were SCD1-associated genes in human colon cancer. Correlation analysis identified the master regulator of lipid homeostasis sterol regulatory element-binding protein 2 (SREBP2) as a prominent transcription factor, whose expression was positively correlated with SCD1 in human colon cancer. SCD1 knockdown using siRNA in colon cancer samples, suppressed SREBP2 gene expression, providing direct evidence that SREBP signaling is under the control of SCD1 in these cells. Pathway analysis in the Ingenuity Pathways Analysis platform showed that SCD1 expression positively correlated with genes involved in multiple pathways, including lipid synthesis and incorporation, cell proliferation, and tissue tumorigenesis. Further network analysis revealed a central role for Myc in the network hierarchy of the SCD1-correlated genes. These findings suggested that SCD1 inhibition would be an effective strategy for suppressing colon cancer spheroid growth, partly through downregulating SREBP-mediated lipid and cholesterol metabolism and Myc signaling. Full article
(This article belongs to the Special Issue Colorectal Cancer: Biology and Therapy)
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Review

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17 pages, 505 KiB  
Review
Diabetes Mellitus and Colon Carcinogenesis: Expectation for Inhibition of Colon Carcinogenesis by Oral Hypoglycemic Drugs
by Junichi Kato, Yohei Shirakami and Masahito Shimizu
Gastrointest. Disord. 2019, 1(2), 273-289; https://doi.org/10.3390/gidisord1020023 - 12 Jun 2019
Cited by 3 | Viewed by 4496
Abstract
The global deaths due to colorectal cancer and diabetes mellitus have increased by 57% and 90%, respectively. The relationship between various cancers and diabetes mellitus has been shown in multiple epidemiological studies. Hence, better management of diabetes mellitus is expected to reduce the [...] Read more.
The global deaths due to colorectal cancer and diabetes mellitus have increased by 57% and 90%, respectively. The relationship between various cancers and diabetes mellitus has been shown in multiple epidemiological studies. Hence, better management of diabetes mellitus is expected to reduce the risk of various cancers. This review focuses on colorectal cancer and aims to summarize recent findings on the antitumor effects of various oral hypoglycemic drugs on colorectal cancer and their estimated mechanisms. Of the seven classes of oral hypoglycemic agents, only metformin was found to have suppressive effects on colorectal cancer in both clinical and basic research. Clinical and basic researches on suppressing effects of glinides, dipeptidyl peptidase-4 inhibitors, thiazolidinedione, α-glucosidase inhibitors, and sodium glucose cotransporter-2 inhibitors against colon carcinogenesis have been insufficient and have not arrived at any conclusion. Therefore, further research regarding these agents is warranted. In addition, the suppressive effects of these agents in healthy subjects without diabetes should also be investigated. Full article
(This article belongs to the Special Issue Colorectal Cancer: Biology and Therapy)
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