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International Journal of Molecular... Jan 2017Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries,... (Review)
Review
Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include spp, and enteropathogenic . CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%); inherited (5%) and familial (25%). The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53), and mutations; in particular, genes such as c-MYC, , , , , and can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined with monoclonal antibodies or proteins against vascular endothelial growth factor (VEGF) and epidermal growth receptor (EGFR). Besides traditional chemotherapy, alternative therapies (such as agarose tumour macrobeads, anti-inflammatory drugs, probiotics, and gold-based drugs) are currently being studied to increase treatment effectiveness and reduce side effects.
Topics: Colorectal Neoplasms; Genetic Predisposition to Disease; Humans; Neoplasm Staging; Risk Factors; Signal Transduction
PubMed: 28106826
DOI: 10.3390/ijms18010197 -
Frontiers in Immunology 2020Colorectal cancer is the third most common cancer in the world with increasing incidence and mortality rates globally. Standard treatments for colorectal cancer have... (Review)
Review
Colorectal cancer is the third most common cancer in the world with increasing incidence and mortality rates globally. Standard treatments for colorectal cancer have always been surgery, chemotherapy and radiotherapy which may be used in combination to treat patients. However, these treatments have many side effects due to their non-specificity and cytotoxicity toward any cells including normal cells that are growing and dividing. Furthermore, many patients succumb to relapse even after a series of treatments. Thus, it is crucial to have more alternative and effective treatments to treat CRC patients. Immunotherapy is one of the new alternatives in cancer treatment. The strategy is to utilize patients' own immune systems in combating the cancer cells. Cancer immunotherapy overcomes the issue of specificity which is the major problem in chemotherapy and radiotherapy. The normal cells with no cancer antigens are not affected. The outcomes of some cancer immunotherapy have been astonishing in some cases, but some which rely on the status of patients' own immune systems are not. Those patients who responded well to cancer immunotherapy have a better prognostic and better quality of life.
Topics: Animals; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Cancer Vaccines; Colorectal Neoplasms; Combined Modality Therapy; Disease Management; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Immunotherapy, Adoptive; Molecular Targeted Therapy
PubMed: 33042104
DOI: 10.3389/fimmu.2020.01624 -
EBioMedicine Oct 2019Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and leading cause of cancer-related deaths worldwide. In recent years, there has been a growing... (Review)
Review
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and leading cause of cancer-related deaths worldwide. In recent years, there has been a growing realisation that lifestyle plays a major role for CRC development and that intestinal microbiota, which are shaped by lifestyle and nutrition habits, may be critically involved in the pathogenesis of CRC. Although the precise mechanisms for how the microbiota contribute to CRC development and progression remain elusive, increasing evidence suggests a direct causative role for the intestinal microbiota in modulating signalling pathways, anti-tumour immune responses and cell proliferation. Recent advances in understanding host-microbe interactions have shed light onto the putative use of intestinal microbiota as a powerful tool in CRC diagnosis and therapy. Here, we will discuss the role of the intestinal microbiota in CRC pathogenesis, their potential utility as diagnostic markers, and consider how microbes could be used in therapeutic approaches for the treatment of CRC.
Topics: Animals; Biomarkers; Colorectal Neoplasms; Disease Management; Disease Susceptibility; Gastrointestinal Microbiome; Humans; Molecular Targeted Therapy; Prognosis
PubMed: 31631043
DOI: 10.1016/j.ebiom.2019.09.050 -
Cell Host & Microbe Aug 2013Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that symbiotic Fusobacterium spp. are associated with human colorectal...
Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that symbiotic Fusobacterium spp. are associated with human colorectal carcinoma, but whether this is an indirect or causal link remains unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas relative to surrounding tissues and in stool samples from colorectal adenoma and carcinoma patients compared to healthy subjects. Additionally, in the Apc(Min/+) mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from Apc(Min/+) mice exposed to F. nucleatum exhibit a proinflammatory expression signature that is shared with human fusobacteria-positive colorectal carcinomas. However, unlike other bacteria linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression.
Topics: Adenoma; Animals; Carcinogenesis; Colorectal Neoplasms; Cytokines; Disease Models, Animal; Fusobacterium nucleatum; Humans; Leukocytes; Mice
PubMed: 23954159
DOI: 10.1016/j.chom.2013.07.007 -
International Journal of Molecular... Jun 2021Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a... (Review)
Review
Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a hallmark of cancer, is closely related to the initiation and progression of carcinomas, including CRC. Accumulating evidence shows that activation of oncogenic pathways and loss of tumor suppressor genes regulate the metabolic reprogramming that is mainly involved in glycolysis, glutaminolysis, one-carbon metabolism and lipid metabolism. The abnormal metabolic program provides tumor cells with abundant energy, nutrients and redox requirements to support their malignant growth and metastasis, which is accompanied by impaired metabolic flexibility in the tumor microenvironment (TME) and dysbiosis of the gut microbiota. The metabolic crosstalk between the tumor cells, the components of the TME and the intestinal microbiota further facilitates CRC cell proliferation, invasion and metastasis and leads to therapy resistance. Hence, to target the dysregulated tumor metabolism, the TME and the gut microbiota, novel preventive and therapeutic applications are required. In this review, the dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed. Possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota, are discussed.
Topics: Animals; Cellular Reprogramming; Colorectal Neoplasms; Gastrointestinal Microbiome; Humans; Immunotherapy; Tumor Microenvironment
PubMed: 34200820
DOI: 10.3390/ijms22126262 -
Medicina (Kaunas, Lithuania) Apr 2023Colorectal cancer (CRC) is a disease of major public health and socioeconomic concern [...].
Colorectal cancer (CRC) is a disease of major public health and socioeconomic concern [...].
Topics: Humans; Colorectal Neoplasms; Public Health
PubMed: 37241053
DOI: 10.3390/medicina59050821 -
Archivos Argentinos de Pediatria Oct 2021Although colorectal carcinoma (CRC) is the third most common type of cancer in adults, only 1-4 % of cases are reported in individuals younger than 25-30 years. Its... (Review)
Review
Although colorectal carcinoma (CRC) is the third most common type of cancer in adults, only 1-4 % of cases are reported in individuals younger than 25-30 years. Its presentation is usually confused with other diseases, leading to significant delays in diagnosis. Given its low incidence, few pediatricians will see a case throughout their practice. However, multiple hereditary syndromes during childhood predispose to CRC. The objective of this review is to provide an update on syndromes predisposing to CRC. Screening indications will be reviewed because an early diagnosis during localized stages is the main prognostic factor. In addition, patient and family genetic counseling tools will be enhanced. In turn, the clinical and histological manifestations and prognostic factors typical of CRC in the pediatric population will be discussed. Although treatment guidelines are extrapolated from the adult experience, therapy guidelines will be summarized here.
Topics: Adolescent; Child; Colorectal Neoplasms; Humans; Incidence; Mass Screening
PubMed: 34569749
DOI: 10.5546/aap.2021.eng.e487 -
Journal of B.U.ON. : Official Journal... 2021Proviral integration of Moloney murine leukemia virus (PIM) family kinases can promote the survival and movement of carcinoma cells and the metastatic growth of various...
PURPOSE
Proviral integration of Moloney murine leukemia virus (PIM) family kinases can promote the survival and movement of carcinoma cells and the metastatic growth of various types of carcinoma. However, there are few studies on PIM1 in colorectal carcinoma (CRC), so we decided to investigate this issue.
METHODS
Data about PIM1 expression and clinical and mutation information were downloaded from The Carcinoma Genome Atlas (TCGA). Survival analysis was performed by Kaplan-Meier method and the cumulative incidence of survival events was calculated. The correlation of PIM1 mRNA expression and immune infiltration score with the mutation index (TMB; tumor mutational burden), MSI (microsatellite instability)) was tested by Spearman's method. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of PIM1 enrichment and carcinoma-related pathways in CRC were performed.
RESULTS
PIM1 was elevated in most carcinomas, especially CRC. In CRC, PIPM1 had a correlation with the overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). They indicated that PIPM1 acts in the progression of CRC. PIM1 was correlated with MSI, immune score and immune cell infiltration. Thereby it linked its expression with the evaluation of treatment response.
CONCLUSIONS
Bioinformatics analysis confirmed PIM1 as a good biomarker for the prognosis and treatment evaluation of CRC.
Topics: Animals; Biomarkers, Tumor; Colorectal Neoplasms; Humans; Immunomodulation; Mice; Prognosis; Proto-Oncogene Proteins c-pim-1; Survival Analysis
PubMed: 34077000
DOI: No ID Found -
World Journal of Gastroenterology Dec 2015Colorectal carcinoma (CRC), as the third most common new cancer diagnosis, poses a significant health risk to the population. Interval CRCs are those that appear after a... (Review)
Review
Colorectal carcinoma (CRC), as the third most common new cancer diagnosis, poses a significant health risk to the population. Interval CRCs are those that appear after a negative screening test or examination. The development of interval CRCs has been shown to be multifactorial: location of exam-academic institution versus community hospital, experience of the endoscopist, quality of the procedure, age of the patient, flat versus polypoid neoplasia, genetics, hereditary gastrointestinal neoplasia, and most significantly missed or incompletely excised lesions. The rate of interval CRCs has decreased in the last decade, which has been ascribed to an increased understanding of interval disease and technological advances in the screening of high risk individuals. In this article, we aim to review the literature with regard to the multifactorial nature of interval CRCs and provide the most recent developments regarding this important gastrointestinal entity.
Topics: Adenomatous Polyps; Carcinoma; Colonic Polyps; Colorectal Neoplasms; Humans; Incidence; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors
PubMed: 26668498
DOI: 10.3748/wjg.v21.i45.12735 -
Journal of Experimental & Clinical... Mar 2016Acting as inflammatory mediators, tumor oncogenes or suppressors, microRNAs are involved in cell survival, death, epithelial-mesenchymal transition and metastasis, etc.... (Review)
Review
BACKGROUND
Acting as inflammatory mediators, tumor oncogenes or suppressors, microRNAs are involved in cell survival, death, epithelial-mesenchymal transition and metastasis, etc. Investigating the communication between microRNAs and tumorigenesis is critical to our understanding of the pathogenesis of multiple disease states.
MAIN BODY
Currently, colorectal carcinoma (CRC), one of the most common malignancies worldwide, has a poor prognosis due to lack of an effective therapeutic option. Increasing evidence has identified altered profiles and regulatory potential of microRNAs in conditions related to environmentally-caused colorectal inflammation and colitis-associated cancer. Many studies have shed light on a more thorough understanding of the function and distribution of microRNAs in CRC initiation and emergence. However, the molecular mechanisms by which microRNAs modulate cellular processes still need to be further elucidated and may offer a foundation for evaluating microRNA-based therapeutic potential for CRC in both animal models and clinical trials.
CONCLUSION
In this review, the roles and mechanisms of microRNAs involved in CRC from pathogenesis to therapy are summarized and discussed, which may provide more useful hints for CRC prevention and therapy.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Molecular Targeted Therapy; Prognosis; Signal Transduction
PubMed: 26964533
DOI: 10.1186/s13046-016-0320-4