Publisher Correction: Deacetylation of serine hydroxymethyl-transferase 2 by SIRT3 promotes colorectal carcinogenesis

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

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4'-Geranyloxyferulic Acid-L-name prodrug inhibits inflammation-related colorectal carcinogenesis in mice

Planta Medica ◽

10.1055/s-0032-1320405 ◽

2012 ◽

Vol 78 (11) ◽

Author(s):

T Tanaka ◽

S Genovese ◽

T Kochi ◽

F Epifano ◽

L Scauri ◽

...

Keyword(s):

Colorectal Carcinogenesis

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Chemoprevention of Colorectal Carcinogenesis by Natural Anti-Inflammatory Agents

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/187152310791110661 ◽

2010 ◽

Vol 9 (2) ◽

pp. 150-157 ◽

Cited By ~ 1

Author(s):

Yumiko Yasui ◽

Takuji Tanaka

Keyword(s):

Colorectal Carcinogenesis ◽

Anti Inflammatory

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Regulation of microRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200917112802 ◽

2020 ◽

Vol 20 ◽

Author(s):

Sridhar Muthusami ◽

Ilangovan Ramachandran ◽

Sneha Krishnamoorthy ◽

Yuvaraj Sambandam ◽

Satish Ramalingam ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Mechanisms ◽

Colorectal Carcinogenesis ◽

Model Systems ◽

Necrosis Factor Alpha ◽

Multi Stage ◽

Mechanistic Approach ◽

Tnf Α ◽

Factor Alpha

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

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768 THE ORIGIN AND FUNCTION OF CANCER-ASSOCIATED FIBROBLASTS IN COLORECTAL CARCINOGENESIS

Gastroenterology ◽

10.1016/s0016-5085(20)31086-6 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-160

Author(s):

Hiroki Kobayashi ◽

Krystyna Gieniec ◽

Tamsin Lannagan ◽

Tongtong Wang ◽

Samuel Asfaha ◽

...

Keyword(s):

Colorectal Carcinogenesis ◽

Cancer Associated Fibroblasts ◽

And Function

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A Dinucleotide Deletion in the CD24 Gene Is a Potential Risk Factor for Colorectal Cancer

The American Surgeon ◽

10.1177/0003134820919737 ◽

2020 ◽

Vol 86 (5) ◽

pp. 480-485

Author(s):

Lior Segev ◽

Ilana Naboishchikov ◽

Diana Kazanov ◽

Ezra Bernstein ◽

Meital Shaked ◽

...

Keyword(s):

Colorectal Cancer ◽

Peripheral Blood ◽

Intracellular Signaling ◽

Genetic Variant ◽

Colorectal Carcinogenesis ◽

Polymorphism Analysis ◽

Peripheral Blood Leukocytes ◽

Clinical Value ◽

Blood Leukocytes ◽

Multistep Process

Background CD24 is a sialoglycoprotein anchored to the cell surface via glycosylphosphatidylinositol and is involved in intracellular signaling processes. It plays an important role in the early stages of the multistep process of colorectal carcinogenesis. Several single nucleotide polymorphisms in the CD24 gene are reported to exert a diverse effect on cancer risk. We aimed to elucidate whether CD24 TG/del genetic variants are associated with susceptibility to colorectal cancer (CRC). Methods The study included 179 subjects, 36 with CRC (prior to surgery) and 143 healthy control subjects. Deoxyribonucleic acid was purified from peripheral blood leukocytes, and by using restriction fragment length polymorphism analysis, the CD24 gene was genotyped for the specific genetic variant, TG deletion. Additionally, CD24 protein expression levels were determined by Western blotting analysis. Results The incidence of the TG/del was higher among the CRC patients compared with healthy controls, 14% and 10%, respectively ( P = .54). CD24 protein levels were significantly higher among CRC patients. There were no significant differences in CD24 expression between CRC patients at different stages of the disease or between patients who carry the mutation and those who did not. Conclusions CD24 genetic variant might be of clinical value for risk assessment as part of cancer prevention programs. Further study on larger populations is needed to validate the importance of this dinucleotide deletion in CRC development. Overexpression of CD24 protein occurs early along the multistep process of CRC carcinogenesis, and a simple blood sample based on CD24 expression on peripheral blood leukocytes can contribute to early diagnosis.

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The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models

Scientific Reports ◽

10.1038/s41598-021-84571-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rayko Evstatiev ◽

Adam Cervenka ◽

Tina Austerlitz ◽

Gunther Deim ◽

Maximilian Baumgartner ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Mouse Models ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Food Additives ◽

Colorectal Carcinogenesis ◽

Testing Procedures ◽

Inflammatory Models ◽

Inflammatory Bowel

AbstractInflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a considerable environmental exposure. Numerous safety studies in healthy animals have revealed no relevant toxicity by EDTA. Here we show that, in the presence of intestinal inflammation, EDTA is surprisingly capable of massively exacerbating inflammation and even inducing colorectal carcinogenesis at doses that are presumed to be safe. This toxicity is evident in two biologically different mouse models of inflammatory bowel disease, the AOM/DSS and the IL10−/− model. The mechanism of this effect may be attributed to disruption of intercellular contacts as demonstrated by in vivo confocal endomicroscopy, electron microscopy and cell culture studies. Our findings add EDTA to the list of food additives that might be detrimental in the presence of intestinal inflammation, but the toxicity of which may have been missed by regulatory safety testing procedures that utilize only healthy models. We conclude that the current use of EDTA especially in food and pharmaceuticals should be reconsidered. Moreover, we suggest that intestinal inflammatory models should be implemented in the testing of food additives to account for the exposure of this primary organ to environmental and dietary stress.

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Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon

Scientific Reports ◽

10.1038/s41598-020-79450-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jakob Weglage ◽

Friederike Wolters ◽

Laura Hehr ◽

Jakob Lichtenberger ◽

Celina Wulz ◽

...

Keyword(s):

Signaling Pathways ◽

Colorectal Carcinogenesis ◽

Sub Saharan Africa ◽

Interleukin 4 ◽

Health Burden ◽

Sub Saharan ◽

Considerable Morbidity ◽

First Time

AbstractSchistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

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Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer

Cancers ◽

10.3390/cancers13071493 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1493

Author(s):

Camila Meirelles S. Silva ◽

Mateus C. Barros-Filho ◽

Deysi Viviana T. Wong ◽

Julia Bette H. Mello ◽

Livia Maria S. Nobre ◽

...

Keyword(s):

Colorectal Cancer ◽

Unmet Need ◽

Area Under The Curve ◽

Discrimination Performance ◽

Colorectal Carcinogenesis ◽

The Cancer Genome Atlas ◽

Colon Perforation ◽

Data Series ◽

Predictive Tool ◽

Incidence And Mortality

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.

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