scholarly journals Recruitment of M1 Macrophages May Not Be Critical for Protection against Colitis-Associated Tumorigenesis

2021 ◽  
Vol 22 (20) ◽  
pp. 11204
Author(s):  
Itzel Medina-Andrade ◽  
Jonadab E. Olguín ◽  
Stephanie Guerrero-García ◽  
Jossael A. Espinosa ◽  
Elizabeth Garduño-Javier ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Development ◽  
Cell Types ◽  
Colon Tissue ◽  
M1 Macrophages ◽  
Colon Tumors ◽  
Colon Tumorigenesis ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Specific Deletion

A close connection between inflammation and the risk of developing colon cancer has been suggested in the last few years. It has been estimated that patients diagnosed with some types of inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease, have up to a 30% increased risk of developing colon cancer. However, there is also evidence showing that the activation of anti-inflammatory pathways, such as the IL-4 receptor-mediated pathway, may favor the development of colon tumors. Using an experimental model of colitis-associated colon cancer (CAC), we found that the decrease in tumor development in global IL4Rα knockout mice (IL4RαKO) was apparently associated with an inflammatory response mediated by the infiltration of M1 macrophages (F480+TLR2+STAT1+) and iNOS expression in colon tissue. However, when we developed mice with a specific deletion of IL4Rα in macrophages (LysMcreIL4Rα−/lox mice) and subjected them to CAC, it was found that despite presenting a large infiltration of M1 macrophages into the colon, these mice were as susceptible to colon-tumorigenesis as WT mice. These data suggest that in the tumor microenvironment the absence of IL4Rα expression on macrophages, as well as the recruitment of M1 macrophages, may not be directly associated with resistance to developing colon tumors. Therefore, it is possible that IL4Rα expression in other cell types, such as colonic epithelial cells, could have an important role in promoting the development of colitis-associated colon tumorigenesis.

scholarly journals Tussilagone Reduces Tumorigenesis by Diminishing Inflammation in Experimental Colitis-Associated Colon Cancer

Biomedicines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 86 ◽  
Author(s):  
Sang-Hyeon Nam ◽  
Jin-Kyung Kim
Keyword(s):  
Colon Cancer ◽  
Experimental Colitis ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Colon Tissue ◽  
Colon Tumorigenesis ◽  
Inflammatory Status ◽  
Tussilago Farfara ◽  
Preventive Activity ◽  
Induced Apoptosis

Background: Tussilagone, a major component of Tussilago farfara L., has anti-angiogenic and anti-inflammatory effects. However, the therapeutic and preventive activity of tussilagone in colitis-associated colon carcinogenesis is unknown. Methods: We intended to investigate the therapeutic effects and the potential mechanism of action underlying the pharmacological activity of tussilagone on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). We injected BALB/c mice with AOM and administered 2% DSS in drinking water. The mice were given tussilagone (2.5 and 5 mg/kg body weight) and colon tissues was collected at 72 days. We used Western blotting, immunohistochemistry and real-time RT-PCR analyses to examine the tumorigenesis and inflammatory status of the colon. Results: Tussilagone administration significantly reduced the formation of colonic tumors. In addition, tussilagone treatment markedly reduced the inflammatory mediators and increased heme oxygease-1 in protein and mRNA levels in colon tissues. Meanwhile, nuclear NF-κB-positive cells were elevated and nuclear Nrf2-positive cells were demised by tussilagone treatment in colon tissues. Tussilagone also reduced cell proliferation, induced apoptosis and decreased the β-catenin expression. Conclusions: Tussilagone administration decreases the inflammation and proliferation induced by AOM/DSS and induced apoptosis in colon tissue. Overall, this study indicates the potential value of tussilagone in suppressing colon tumorigenesis.

scholarly journals Hospitalization-Based Major Comorbidity of Inflammatory Bowel Disease in Canada

2007 ◽  
Vol 21 (8) ◽  
pp. 507-511 ◽  
Author(s):  
Charles N Bernstein ◽  
Alice Nabalamba
Keyword(s):  
Inflammatory Bowel Disease ◽  
Colon Cancer ◽  
Bowel Disease ◽  
International Classification Of Diseases ◽  
International Classification ◽  
Increased Risk ◽  
Classification Of Diseases ◽  
Inflammatory Bowel ◽  
Hodgkin's Lymphomas

OBJECTIVE: To define the patterns of hospitalization for known major comorbidities associated with inflammatory bowel disease (IBD) in Canada.METHODS: The data source was the Statistics Canada Health Person Oriented Information hospital database (1994/1995 to 2003/2004). The number of stays for a diagnosis of Crohn’s disease or ulcerative colitis by theInternational Classification of Diseases, ninth edition, codes 555 or 556, or theInternational Classification of Diseases, 10th edition, Canadian Enhancement, codes K50 or K51, was extracted. Age- and sex-specific and age-adjusted rates of hospitalization for selected IBD-related comorbidities were assessed.RESULTS: Rates of Hodgkin’s disease and non-Hodgkin’s lymphoma were low in the hospitalized IBD population. Rates for colon cancer, rectal cancer, pulmonary emboli and deep venous thromboembolism were generally higher among IBD patients younger than 50 years of age compared with the non-IBD hospitalized population.CONCLUSIONS: IBD was associated with life-threatening comorbidities such as venous thromboembolic disease and colon cancer among persons younger than 50 years of age to a greater extent than the general hospitalized population. Recent secular trends in rates of non-Hodgkin’s lymphomas will need to be followed to determine whether the whole population, including IBD patients who receive immunomodulating therapies, are at increased risk.

scholarly journals MicroRNAs in the Myelodysplastic Syndrome

Acta Naturae ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 4-15
Author(s):  
Yuliya A. Veryaskina ◽  
Sergei E. Titov ◽  
Igor B. Kovynev ◽  
S. S. Fedorova ◽  
Tatiana I. Pospelova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndrome ◽  
Tumor Development ◽  
Cell Types ◽  
Assessment System ◽  
Expression Levels ◽  
Hematological Disorders ◽  
Prognostic System ◽  
Increased Risk ◽  
New Biomarkers

The myelodysplastic syndrome (MDS) holds a special place among blood cancers, as it represents a whole spectrum of hematological disorders with impaired differentiation of hematopoietic precursors, bone marrow dysplasia, genetic instability and is noted for an increased risk of acute myeloid leukemia. Both genetic and epigenetic factors, including microRNAs (miRNAs), are involved in MDS development. MicroRNAs are short non-coding RNAs that are important regulators of normal hematopoiesis, and abnormal changes in their expression levels can contribute to hematological tumor development. To assess the prognosis of the disease, an international assessment system taking into account a karyotype, the number of blast cells, and the degree of deficiency of different blood cell types is used. However, the overall survival and effectiveness of the therapy offered are not always consistent with predictions. The search for new biomarkers, followed by their integration into the existing prognostic system, will allow for personalized treatment to be performed with more precision. Additionally, this paper explains how miRNA expression levels correlate with the prognosis of overall survival and response to the therapy offered.

BNIP3L (Nix) expression in colon cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15097-e15097
Author(s):  
J. E. Littlejohn ◽  
D. Jupiter ◽  
X. Cao ◽  
L. Zhang ◽  
M. Shabahang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
Mrna Levels ◽  
Normal Colon ◽  
Colon Tissue ◽  
Human Colon Cancer ◽  
Variable Expression ◽  
Colon Tumors ◽  
Normal Colon Tissue ◽  
Protein Levels

e15097 Background: Microenvironmental adaptation to hypoxic conditions is critical for a cell to survive in a growing solid tumor. BNIP3L (Nix) mediates apoptosis during hypoxia in cancer cell lines, and Nix knockdown promotes tumor growth in-vivo through decreased apoptosis and increased proliferation, suggesting a means by which cells can adapt. Little is known specifically about Nix expression and its importance in human colon cancer. To gain insight into expression of this gene in colon tumors, the present study analyzed mRNA microarray data from 227 colon tumors and 22 normal colon tissue samples and queried differential expression of Nix. These results were compared to the protein levels present in human colon tumors. Methods: mRNA expression of 227 human colon tumors (made available by the Expression Project for Oncology (expO)) and 22 normal colon samples (retrieved from the Gene Expression Omnibus (GEO)) was analyzed. These samples were hybridized to the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array, assaying 17,726 NCBI Entrez genes. Immunohistochemistry was performed on human tissue microarray CO701 (US Biomax, Inc.) containing 62 tumor samples. Results: Nix mRNA levels were shown to increase from normal to cancer (log-fold change of 0.961, Benjamini-Hochberg FDR adjusted p < 0.001). IHC demonstrated variable levels of Nix present in colon tumors: 38/62 (61.3%) of tumors stained positive for Nix while 24/62 (38.7%) were negative. Conclusions: We have shown that mRNA levels of Nix are upregulated in the transition from normal colon tissue to cancer but that protein levels in tumors demonstrate variable expression. This suggests that silencing of Nix occurs at various stages of tumorigenic progression and results in isolated populations of cells within a growing tumor that are uniquely resistant to apoptosis. Better understanding of Nix in the context of a growing colon tumor is needed and could lead to development of more successful therapeutics. No significant financial relationships to disclose.

P005 A SURVEY STUDY OF GASTROENTEROLOGISTS’ VIEWS ON DYSPLASIA SURVEILLANCE AND CHROMOENDOSCOPY IN IBD

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S47-S47
Author(s):  
Laurie Grossberg ◽  
Francis Farraye ◽  
Konstantinos Papamichail ◽  
Adam Cheifetz ◽  
Joseph Feuerstein
Keyword(s):  
Colon Cancer ◽  
White Light ◽  
Survey Study ◽  
White Light Endoscopy ◽  
Physician Characteristics ◽  
Increased Risk ◽  
History Of ◽  
Inflammatory Bowel ◽  
Surveillance Protocol ◽  
Ulcerative Proctosigmoiditis

Abstract Background Patients with inflammatory bowel disease (IBD) have an increased risk of colon cancer. Current guidelines are equivocal in their recommendations for chromoendoscopy. The objective of this study is to assess gastroenterologists’ current attitudes and barriers toward chromoendoscopy in IBD. Methods A 23 question survey was distributed to members of the Crohn’s & Colitis Foundation via email. We collected physician characteristics, practice demographics, and data regarding chromoendoscopy use and barriers to chromoendoscopy. Results A total of 57 gastroenterologists from 22 US states [male, n=42 (74%); practicing in an academic university n=44 (77%)] met inclusion criteria. All respondents agree that patients with IBD involving more than 1/3 of the colon have increased risk of colon cancer. Most gastroenterologists agree that patients with extensive UC (100%), left-sided UC (80%), or Crohn’s involving more than 1/3 of the colon (98%) should be in a surveillance protocol, however, 37%, 9%, and 2% also believe that patients with distal ulcerative proctosigmoiditis, ulcerative proctitis, and ileal Crohn’s disease should be in a surveillance protocol respectively. All gastroenterologists perform surveillance in patients without other risk factors within 3 years, however the interval varies: 28% every year, 47% every 2 years, and 25% every 3 years. 61% believe that chromoendoscopy is the preferred method for dysplasia surveillance, but 72% use white light endoscopy most often for surveillance in their clinical practice. Two-thirds (38/57) of gastroenterologists reported ever performing chromoendoscopy. The most common reasons to use chromoendoscopy were history of dysplasia found on random biopsy (89%), history of nonpolypoid dysplasia (76%), or history of primary sclerosing cholangitis (76%). Only 8 gastroenterologists reported using chromoendoscopy for all IBD surveillance. Physicians agree that the top barriers to chromoendoscopy use include longer procedure time (43), lack of standardized training in chromoendoscopy (42), and lack of reimbursement for chromoendoscopy (36); however, most would be likely or very likely to use chromoendoscopy if data showed which patients would benefit most from chromoendoscopy (95%) and if data showed benefits of chromoendoscopy compared to other techniques (93%). Conclusion Most gastroenterologists believe that chromoendoscopy is the ideal method for IBD surveillance, yet white light endoscopy is used most often. Physicians agree that longer procedure times and lack of reimbursement deter chromoendoscopy use, but the majority would be willing to use chromoendoscopy if data showed superiority of chromoendoscopy compared to other techniques and identified patients that would benefit the most.

scholarly journals High Expression of TTK As Colon Stem Cell Marker Correlated With M1 Macrophages Infiltration

2021 ◽  
Author(s):  
Hua Chen ◽  
Zhicong Wu ◽  
Nisha Wu ◽  
Zunya Ma ◽  
Yanling Liang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune Cells ◽  
Tumor Development ◽  
Colon Adenocarcinoma ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
Stem Cell Marker ◽  
M1 Macrophages ◽  
Normal Tissues

Abstract Background: Tumor stemness-related genes promote tumor progression and resistance to immunotherapy, but the relation between tumor-infiltrating immune cells and colon adenocarcinoma (COAD) stemness-related genes remains unclear. Methods: The mRNAsi scores, a stemness index derived from transcriptomic data of the TCGA COAD cohort were used for integrated bioinformatics analysis. The Weighted Gene Co-expression Network Analysis (WGCNA) was applied to classify the modules correlated with mRNAsi scores. The Gene Expression Omnibus (GEO) cohorts GSE76402 was used to verify the DEGs between colon cancer and normal tissues. Real-time PCR and Flow-cytometry were used to validate the expression of genes and cancer stem cells marker in the spheres of colon cancer cells. The Single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT algorithm were used to explore the correlation between significant genes and the immune cells in tumor microenvironment. Result: The mRNAsi score was associated with tumor development and progression. TTK were identified as COAD stemness-related genes based on WGCNA analysis. TTK were negatively correlated with immunity. Interestingly, M1 Macrophages had a higher infiltration in COAD with high TTK expression. Higher infiltration of M1 Macrophages would result in the worse survival rate of COAD patients. Conclusion: TTK may have the potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity and improve outcomes of COAD patients.

scholarly journals The Gut Microbiome Modulates Colon Tumorigenesis

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Joseph P. Zackular ◽  
Nielson T. Baxter ◽  
Kathryn D. Iverson ◽  
William D. Sadler ◽  
Joseph F. Petrosino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Gut Microbiome ◽  
Tumor Development ◽  
Tumor Formation ◽  
Normal Functioning ◽  
Operational Taxonomic Units ◽  
Tumor Bearing ◽  
Colon Tumorigenesis

ABSTRACT Recent studies have shown that individuals with colorectal cancer have an altered gut microbiome compared to healthy controls. It remains unclear whether these differences are a response to tumorigenesis or actively drive tumorigenesis. To determine the role of the gut microbiome in the development of colorectal cancer, we characterized the gut microbiome in a murine model of inflammation-associated colorectal cancer that mirrors what is seen in humans. We followed the development of an abnormal microbial community structure associated with inflammation and tumorigenesis in the colon. Tumor-bearing mice showed enrichment in operational taxonomic units (OTUs) affiliated with members of the Bacteroides, Odoribacter, and Akkermansia genera and decreases in OTUs affiliated with members of the Prevotellaceae and Porphyromonadaceae families. Conventionalization of germfree mice with microbiota from tumor-bearing mice significantly increased tumorigenesis in the colon compared to that for animals colonized with a healthy gut microbiome from untreated mice. Furthermore, at the end of the model, germfree mice colonized with microbiota from tumor-bearing mice harbored a higher relative abundance of populations associated with tumor formation in conventional animals. Manipulation of the gut microbiome with antibiotics resulted in a dramatic decrease in both the number and size of tumors. Our results demonstrate that changes in the gut microbiome associated with inflammation and tumorigenesis directly contribute to tumorigenesis and suggest that interventions affecting the composition of the microbiome may be a strategy to prevent the development of colon cancer. IMPORTANCE The trillions of bacteria that live in the gut, known collectively as the gut microbiome, are important for normal functioning of the intestine. There is now growing evidence that disruptive changes in the gut microbiome are strongly associated with the development colorectal cancer. However, how the gut microbiome changes with time during tumorigenesis and whether these changes directly contribute to disease have not been determined. We demonstrate using a mouse model of inflammation-driven colon cancer that there are dramatic, continual alterations in the microbiome during the development of tumors, which are directly responsible for tumor development. Our results suggest that interventions that target these changes in the microbiome may be an effective strategy for preventing the development of colorectal cancer.

scholarly journals Macrophages produce and functionally respond to interleukin-34 in colon cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Eleonora Franzè ◽  
Federica Laudisi ◽  
Antonio Di Grazia ◽  
Martin Marônek ◽  
Vittoria Bellato ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mononuclear Cells ◽  
Cell Types ◽  
Positive Role ◽  
Growth And Survival ◽  
Colon Tumorigenesis ◽  
Adjacent Mucosa ◽  
Lamina Propria Mononuclear Cells ◽  
Enhanced Expression ◽  
And Diffusion

Abstract In colorectal cancer (CRC), macrophages represent a major component of the tumor mass and exert mostly functions promoting tumor cell survival, proliferation, and dissemination. Interleukin-34 (IL-34) is a cytokine overproduced by colon cancer (CRC) cells and supposed to make a valid contribution to the growth and diffusion of CRC cells. The biological functions of IL-34 are mediated by the macrophage colony-stimulating factor receptor (M-CSFR-1), which controls monocyte/macrophage differentiation, growth, and survival. We here investigated whether, in CRC, tumor-associated macrophages (TAMs) express M-CSFR-1 and functionally respond to IL-34. By flow-cytometry analysis of tumor-infiltrating cells (TICs) and lamina propria mononuclear cells (LPMCs) isolated from normal, adjacent mucosa of CRC patients, we showed that CD68/HLA-DRII-expressing TICs and LPMCs expressed M-CSFR-1. Both these cell types produced IL-34 even though the expression of the cytokine was more pronounced in TICs as compared to normal LPMCs. Moreover, in CRC samples, there was a positive correlation between IL-34-producing cells and CD68-positive cells. Stimulation of LPMCs and TICs with IL-34 resulted in enhanced expression of CD163 and CD206, two markers of type II-polarized macrophages, and this was evident at both RNA and protein level. In the same cell cultures, IL-34 stimulated expression and production of IL-6, a cytokine known to promote CRC cell growth and diffusion. Finally, knockdown of IL-34 in TICs with specific antisense oligonucleotides with: a specific antisesne oligonucleotide decreased IL-6 production and the number of TAMs producing this cytokine. This is the first to show a positive role of IL-34 in the control of TAMs in CRC, further supporting the notion that IL-34 sustains colon tumorigenesis.

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