Special Issue "Colorectal Cancers"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 30 April 2019

Special Issue Editor

Guest Editor
Prof. Dr. Jean-Francois Beaulieu

Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Website | E-Mail
Interests: colorectal cancer; integrins and cell-extracellular matrix interactions; oncogenes, transcription, biomarkers

Special Issue Information

Dear Colleagues,

Colorectal cancer is one of the most common cancers worldwide, and it is predicted that the number of cases will continue to rise over the next 20 years. Despite the recent progress in screening techniques and the improvements in treatments, bowel cancer remains a significant cause of cancer mortality. A better comprehension of the cellular and molecular bases underlying colorectal neoplasm initiation and progression, from adenoma to metastasis, is crucial to establishing non-invasive, efficient detection tests for the identification of lesions at early stages, as well as for refining the current therapeutic approaches and developing new ones useful in advanced stages of the disease.

In this Special Issue, we aim to cover all aspects of colorectal cancer research. To this end, we welcome articles on basic, preclinical, and clinical research on colorectal cancer.

Prof. Dr. Jean-Francois Beaulieu
Guest Editor

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 papers will be 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. Cancers is an international peer-reviewed open access monthly 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 1800 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

  • advances in early detection of colorectal lesions
  • biomarkers for assessing colorectal cancer
  • colorectal cancer stem cells
  • colorectal carcinogenesis and metastasis
  • colorectal tumor microenvironment
  • drug delivery to colorectal cancer cells
  • epigenetics of colorectal cancer
  • genetics and genomics of colorectal cancer
  • imaging of colorectal lesions
  • inflammatory bowel diseases and colorectal carcinogenesis
  • microbiome and colorectal cancer
  • molecular targeted therapies for colorectal cancer
  • mouse models of colorectal cancer
  • precision medicine for colorectal cancer
  • signaling pathways in colorectal cancer cells
  • subtyping/molecular profiling of colorectal lesions
  • therapeutic approaches to colorectal cancer

Published Papers (8 papers)

View options order results:
result details:
Displaying articles 1-8
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Dual Targeting of Y-Box Binding Protein-1 and Akt Inhibits Proliferation and Enhances the Chemosensitivity of Colorectal Cancer Cells
Cancers 2019, 11(4), 562; https://doi.org/10.3390/cancers11040562 (registering DOI)
Received: 15 March 2019 / Revised: 16 April 2019 / Accepted: 17 April 2019 / Published: 19 April 2019
PDF Full-text (2318 KB) | Supplementary Files
Abstract
KRAS-mutated colorectal cancers (CRCs) are resistant to cetuximab treatment. The multifunctional Y-box binding protein 1 (YB-1) is overexpressed in CRC and is associated with chemoresistance. In this study, the effects of oncogenic mutated KRAS(G12V) and KRAS(G13D) on YB-1 phosphorylation were investigated in CRC [...] Read more.
KRAS-mutated colorectal cancers (CRCs) are resistant to cetuximab treatment. The multifunctional Y-box binding protein 1 (YB-1) is overexpressed in CRC and is associated with chemoresistance. In this study, the effects of oncogenic mutated KRAS(G12V) and KRAS(G13D) on YB-1 phosphorylation were investigated in CRC cells. The effects of the inhibition of p90 ribosomal S6 kinase (RSK) on YB-1 phosphorylation, cell proliferation and survival were tested with and without treatment with 5-fluorouracil using pharmacological inhibitors and siRNA. YB-1 phosphorylation status and subcellular distribution in CRC patient tissues were determined by immunofluorescence staining and confocal microscopy. Endogenous expression of mutated KRAS(G13D) and conditional expression of KRAS(G12V) significantly stimulated YB-1 phosphorylation via RSK and were associated with cetuximab resistance. Inhibition of YB-1 by targeting RSK stimulated the Akt signaling pathway, and this stimulation occurred independently of KRAS mutational status. Akt activation interfered with the antiproliferative effect of the RSK inhibitor. Consequently, dual targeting of RSK and Akt efficiently inhibited cell proliferation in KRAS(G13D)-mutated HCT116 and KRAS wild-type SW48 cells. Treatment with 5-fluorouracil (5-FU) significantly enhanced YB-1 phosphorylation in KRAS(G13D)-mutated HCT116 cells but not in KRAS wild-type SW48 cells. Dual targeting of Akt and RSK sensitized HCT116 cells to 5-FU by stimulating 5-FU-induced apoptosis and inhibiting repair of 5-FU-induced DNA damage. YB-1 was highly phosphorylated in CRC patient tumor tissues and was mainly localized in the nucleus. Together, dual targeting of RSK and Akt may be an alternative molecular targeting approach to cetuximab for treating CRC in which YB-1 is highly phosphorylated. Full article
(This article belongs to the Special Issue Colorectal Cancers)
Open AccessArticle Expression Profiling of Calcium Channels and Calcium-Activated Potassium Channels in Colorectal Cancer
Cancers 2019, 11(4), 561; https://doi.org/10.3390/cancers11040561 (registering DOI)
Received: 1 April 2019 / Revised: 15 April 2019 / Accepted: 17 April 2019 / Published: 19 April 2019
PDF Full-text (1451 KB)
Abstract
Background: Colorectal cancer (CRC) is a highly devastating cancer. Ca2+-dependent channels are now considered key regulators of tumor progression. In this study, we aimed to investigate the association of non-voltage gated Ca2+ channels and Ca2+-dependent potassium channels [...] Read more.
Background: Colorectal cancer (CRC) is a highly devastating cancer. Ca2+-dependent channels are now considered key regulators of tumor progression. In this study, we aimed to investigate the association of non-voltage gated Ca2+ channels and Ca2+-dependent potassium channels (KCa) with CRC using the transcriptional profile of their genes. Methods: We selected a total of 35 genes covering KCa channels KCNN14, KCNMA1 and their subunits KCNMB14, endoplasmic reticulum (ER) calcium sensors STIM1 and STIM2, Ca2+ channels ORAI13 and the family of cation channels TRP (TRPC17, TRPA1, TRPV1/2,46 and TRPM18). We analyzed their expression in two public CRC datasets from The Cancer Genome Atlas (TCGA) and GSE39582. Results: KCNN4 and TRPM2 were induced while KCNMA1 and TRPM6 were downregulated in tumor tissues comparing to normal tissues. In proximal tumors, STIM2 and KCNN2 were upregulated while ORAI2 and TRPM6 were downregulated. ORAI1 decreased in lymph node metastatic tumors. TRPC1 and ORAI3 predicted poor prognosis in CRC patients. Moreover, we found that ORAI3/ORAI1 ratio is increased in CRC progression and predicted poor prognosis. Conclusions: KCa and Ca2+ channels could be important contributors to CRC initiation and progression. Our results provide new insights on KCa and Ca2+ channels remodeling in CRC. Full article
(This article belongs to the Special Issue Colorectal Cancers)
Open AccessArticle Improvement of Metastatic Colorectal Cancer Patient Survival: Single Institution Experience
Cancers 2019, 11(3), 369; https://doi.org/10.3390/cancers11030369
Received: 5 February 2019 / Revised: 7 March 2019 / Accepted: 9 March 2019 / Published: 15 March 2019
PDF Full-text (1596 KB) | HTML Full-text | XML Full-text
Abstract
The survival rates of patients with metastatic colorectal cancer (mCRC) have improved in recent years. We analysed the survival of mCRC patients followed at a single institution over the last 17 years. We retrospectively collected data from 899 mCRC patients treated from 2001 [...] Read more.
The survival rates of patients with metastatic colorectal cancer (mCRC) have improved in recent years. We analysed the survival of mCRC patients followed at a single institution over the last 17 years. We retrospectively collected data from 899 mCRC patients treated from 2001 to 2016. Patients were divided into two groups based on the year of diagnosis: Cohort A (2001–2006) and Cohort B (2007–2014). A total of 788 patients were analysed. The median survival of the whole population was 32.0 months with a significant difference between Cohort A and B (29.2 vs. 33.5 months; p = 0.041). Surgical procedures significantly increased in Cohort B, however, no significant changes in survival were observed in patients undergoing surgery (58.9 months Cohort A vs. 58.2 months Cohort B, p = 0.822). Similarly, we did not demonstrate survival improvement in patients treated with systemic therapy alone (18.9 months Cohort A vs. 20.7 months Cohort B; p = 0.948). At the multivariate analysis, right-sided primary and synchronous metastatic tumour were found to be independent unfavorable prognostic factors. Improvements of mCRC patient survival might relate to integrated approach, with more patients undergoing extra-hepatic surgery. The medical approach seems to have had a more favourable impact on subgroups characterized by a worse prognosis. Full article
(This article belongs to the Special Issue Colorectal Cancers)
Figures

Figure 1

Open AccessArticle Deciphering the Mechanism of Action Involved in Enhanced Suicide Gene Colon Cancer Cell Killer Effect Mediated by Gef and Apoptin
Cancers 2019, 11(2), 264; https://doi.org/10.3390/cancers11020264
Received: 6 December 2018 / Revised: 20 February 2019 / Accepted: 20 February 2019 / Published: 23 February 2019
PDF Full-text (2138 KB) | HTML Full-text | XML Full-text
Abstract
Despite the great advances in cancer treatment, colorectal cancer has emerged as the second highest cause of death from cancer worldwide. For this type of tumor, the use of suicide gene therapy could represent a novel therapy. We recently demonstrated that co-expression of [...] Read more.
Despite the great advances in cancer treatment, colorectal cancer has emerged as the second highest cause of death from cancer worldwide. For this type of tumor, the use of suicide gene therapy could represent a novel therapy. We recently demonstrated that co-expression of gef and apoptin dramatically inhibits proliferation of the DLD-1 colon cell line. In the present manuscript, we try to establish the mechanism underlying the enhanced induction of apoptosis by triggering both gef and apoptin expression in colon tumor cells. Scanning microscopy reveals that simultaneous expression of gef and apoptin induces the apparition of many “pores” in the cytoplasmic membrane not detected in control cell lines. The formation of pores induced by the gef gene and accentuated by apoptin results in cell death by necrosis. Moreover, we observed the presence of apoptotic cells. Performing protein expression analysis using western blot, we revealed an activation of mitochondrial apoptosis (increased expression of Pp53, cytochrome c, Bax, and caspase 9) and also the involvement of the extrinsic pathway through caspase 8activation. In conclusion, in this manuscript we demonstrate for the first time that the extrinsic pathway of apoptosis and pore formation is also involved in the cell death caused by the co-expression of the gef and apoptin genes. Our results suggest that co-expression of gef and apoptin genes induces an increase in post-apoptotic necrotic cell death and could be a valuable tool in the design of new antitumor strategies focused on the enhancement of the immune response against cancer cell death. Full article
(This article belongs to the Special Issue Colorectal Cancers)
Figures

Figure 1

Open AccessArticle Progressive Oncological Surgery Is Associated with Increased Curative Resection Rates and Improved Survival in Metastatic Colorectal Cancer
Cancers 2019, 11(2), 218; https://doi.org/10.3390/cancers11020218
Received: 10 January 2019 / Revised: 7 February 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
Cited by 1 | PDF Full-text (1131 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Secondary resection rates in first-line chemotherapy trials for metastatic colorectal cancer (mCRC) remain below 15%, representing a clear contrast to reports by specialised surgical centres, where progressive liver, peritoneal-surface, and pulmonary surgery increased access to curative-intent treatment. We present a long-term evaluation [...] Read more.
Background: Secondary resection rates in first-line chemotherapy trials for metastatic colorectal cancer (mCRC) remain below 15%, representing a clear contrast to reports by specialised surgical centres, where progressive liver, peritoneal-surface, and pulmonary surgery increased access to curative-intent treatment. We present a long-term evaluation of oncosurgical management in a single-centre, analysing the aggregate effect of gradual implementation of surgical subspecialties and systemic treatments on mCRC patients’ resection rates and prognosis. Methods: Patients with newly diagnosed mCRC from 2003 to 2014 were retrospectively categorised into palliative treatment (PAT) and curative intent surgery (CIS) and three time periods were analysed for treatment changes and factors associated with survival. Results: Four hundred-twenty patients were treated (PAT:250/CIS:170). Over time periods, the number of presenting patients remained consistent, whereas curative resection rates increased from 29% to 55%, facilitated by an increment of patients undergoing hepatectomy (21 to 35%), pulmonary surgery (6 to 17%), and peritonectomy/intraoperative chemotherapy (0 to 8%). Also, recently, significantly more multi-line systemic treatments were applied. The median survival markedly improved from 21.9 months (2003–2006; 95% confidence interval (CI) 17.3–26.5) to 36.5 months (2011–2014; 95% CI 26.6–46.4; p = 0.018). PAT was a significant factor of poor survival and diagnosis of mCRC in the latest time period was independently associated with a distinctly lower risk for palliative treatment (odds ratio 0.15). Conclusions: In modern eras of medical oncology, achieving appropriate resection rates through utilization of state-of-the-art oncological surgery by dedicated experts represents a cornerstone for long-term survival in mCRC. Full article
(This article belongs to the Special Issue Colorectal Cancers)
Figures

Figure 1

Review

Jump to: Research

Open AccessReview Oxaliplatin-Based Intra-arterial Chemotherapy in Colo-Rectal Cancer Liver Metastases: A Review from Pharmacology to Clinical Application
Cancers 2019, 11(2), 141; https://doi.org/10.3390/cancers11020141
Received: 17 December 2018 / Revised: 18 January 2019 / Accepted: 22 January 2019 / Published: 24 January 2019
PDF Full-text (859 KB) | HTML Full-text | XML Full-text
Abstract
Liver metastases (LM) are often consequences of colo-rectal cancer (CRC)and the majority of patients have unresectable LM. Oxaliplatin-based intravenous chemotherapy represents the gold standard treatment for CRC. Intravenous oxaliplatin has several side effects i.e., nephrologic, hematologic and neurological toxicity. Moreover, hepatic arterial infusion [...] Read more.
Liver metastases (LM) are often consequences of colo-rectal cancer (CRC)and the majority of patients have unresectable LM. Oxaliplatin-based intravenous chemotherapy represents the gold standard treatment for CRC. Intravenous oxaliplatin has several side effects i.e., nephrologic, hematologic and neurological toxicity. Moreover, hepatic arterial infusion (HAI) of antitumor drugs deeply modifies the treatment of LMCRC due to the knowledge that LM are perfused by the hepatic artery network, whereas healthy tissue is perfused by the portal vein. Therefore, oxaliplatin-based HAI becomes an interesting possibility to treat LMCRC. The aim of this review is to shed light on the important impact of the oxaliplatin-based chemotherapy from a non-conventional clinical point of view, considering that, being universally accepted its antitumor effect if administered intravenously, fragmentary information are known about its clinical applications and benefits deriving from intra-arterial administration in loco-regional chemotherapy. Full article
(This article belongs to the Special Issue Colorectal Cancers)
Figures

Figure 1

Open AccessReview Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: The Current Knowledge
Received: 19 November 2018 / Revised: 10 December 2018 / Accepted: 24 December 2018 / Published: 29 December 2018
PDF Full-text (2439 KB) | HTML Full-text | XML Full-text
Abstract
Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in [...] Read more.
Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumour-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review, we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC. Full article
(This article belongs to the Special Issue Colorectal Cancers)
Figures

Figure 1

Open AccessReview Epigenetic Regulation by lncRNAs: An Overview Focused on UCA1 in Colorectal Cancer
Cancers 2018, 10(11), 440; https://doi.org/10.3390/cancers10110440
Received: 19 October 2018 / Revised: 6 November 2018 / Accepted: 8 November 2018 / Published: 14 November 2018
Cited by 1 | PDF Full-text (2257 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancers have become the second leading cause of cancer-related deaths. In particular, acquired chemoresistance and metastatic lesions occurring in colorectal cancer are a major challenge for chemotherapy treatment. Accumulating evidence shows that long non-coding (lncRNAs) are involved in the initiation, progression, and [...] Read more.
Colorectal cancers have become the second leading cause of cancer-related deaths. In particular, acquired chemoresistance and metastatic lesions occurring in colorectal cancer are a major challenge for chemotherapy treatment. Accumulating evidence shows that long non-coding (lncRNAs) are involved in the initiation, progression, and metastasis of cancer. We here discuss the epigenetic mechanisms through which lncRNAs regulate gene expression in cancer cells. In the second part of this review, we focus on the role of lncRNA Urothelial Cancer Associated 1 (UCA1) to integrate research in different types of cancer in order to decipher its putative function and mechanism of regulation in colorectal cancer cells. UCA1 is highly expressed in cancer cells and mediates transcriptional regulation on an epigenetic level through the interaction with chromatin modifiers, by direct regulation via chromatin looping and/or by sponging the action of a diversity of miRNAs. Furthermore, we discuss the role of UCA1 in the regulation of cell cycle progression and its relation to chemoresistance in colorectal cancer cells. Full article
(This article belongs to the Special Issue Colorectal Cancers)
Figures

Figure 1

Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top