Risk Of Colon Cancer Research Articles

Clinical approaches to the ketogenic diet in the treatment of obesity and other chronic diseases: a systematic review

Introduction: The ketogenic diet, a restrictive diet, is mainly characterized by high fat content, low or absent carbohydrate content, and low or normal amounts of protein. Objective: It was to present the important role of the ketogenic diet in the treatment of obesity and other chronic diseases. Methods: The PRISMA Platform systematic review rules were followed. The research was carried out from September to October 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 111 articles were found, and 44 articles were evaluated, and 22 were included in this systematic review. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 19 studies with a high risk of bias and 32 studies that did not meet GRADE. Most studies showed homogeneity in their results, with X2=65.7%>50%. It was concluded that the therapeutic use of the ketogenic diet is relevant in the treatment of obesity and metabolic syndrome. Furthermore, this work also showed the benefits of the metabolism of ketone bodies in the adjuvant treatment of cancer, diabetes, and obesity, thus contributing to updating knowledge about the use of the ketogenic diet in the therapy of diseases of great clinical and epidemiological importance. When it comes to obese and diabetic people, it is important to highlight that due to the lower consumption of fiber, and an increased consumption of proteins (mainly of animal origin) and fat, the risk of heart disease, colon cancer, and intestinal constipation increases.

Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer.

Colon cancer affects people of all ages. However, its frequency, as well as the related morbidity and mortality, are high among older adults. The complex physiological changes in the aging gut substantially limit the development of cancer therapies. Here, we identify a potentially unique intestinal microenvironment that is linked with an increased risk of colon cancer in older adults. Our findings show that aging markedly influenced persistent fucosylation of the apical surfaces of intestinal epithelial cells, which resulted in a favorable environment for tumor growth. Furthermore, our findings shed light on the importance of the host-commensal interaction, which facilitates the dysregulation of fucosylation and promotes tumor growth as people get older. We analyzed colonic microbial populations at the species level to find changes associated with aging that could contribute to the development of colon cancer. Analysis of single-cell RNA-sequencing data from previous publications identified distinct epithelial cell subtypes involved in dysregulated fucosylation in older adults. Overall, our study provides compelling evidence that excessive fucosylation is associated with the development of colon cancer, that age-related changes increase vulnerability to colon cancer, and that a dysbiosis in microbial diversity and metabolic changes in the homeostasis of older mice dysregulate fucosylation levels with age.

Role of dietary intake of specific polyunsaturated fatty acids (PUFAs) on colorectal cancer risk in Iran.

High-fat diets have been associated with colorectal cancer (CRC) risk, and the role of polyunsaturated fatty acids (PUFAs) has been reported to vary based on the length of PUFAs. We explored the association between dietary omega-6 and omega-3 PUFAs intake and CRC. We analyzed 865 CRC patients and 3206 controls from a case-control study of Iran (IROPICAN study). We used multivariate logistic regression models to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association between PUFAs intake and CRC risk. Our results showed that gamma-linolenic acid (18:3 n-6, GLA), arachidonic acid (20:4n-6, ARA), a-linolenic acid (Cis-18:3n-3, ALA), eicosapentaenoic acid (20:5n-3, EPA), docosahexaenoic acid (22:6n-3, DHA) consumption was not associated with the risk of CRC. However, the OR of linoleic acid (18: 2n-6, LA) intake was 1.47 (95% CI 1.01-2.14, p = 0.04) for proximal colon and that of docosapentaenoic acid (22:5n-3, DPA) intake was 1.33 (95% CI 1.05-1.69, p = 0.01) for rectum. This study indicates a high level of LA is associated with an increased risk of proximal colon cancer, and DPA intake was positively associated with rectum cancer risk. Furthermore, our study noted a high intake of n-6 (from vegetable oils) compared to n-3 PUFAs (from fish and seafood) in this population. Public awareness and government support is needed to increase fish and seafood production and consumption in Iran.

Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk

We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC–MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80–1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61–0.96, p = 0.01) and was more pronounced in women (0.69, 0.49–0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

LOWER MORTALITY RISK WITH COMBINATION THERAPY WITH ANTI-TNF THERAPY AND THRIOPURINE COMPARED TO THIOPURINE ALONE IN ELDERLY PATIENTS WITH UC

Abstract INTRODUCTION Despite increasing incidence rates of ulcerative colitis (UC) in the elderly, efficacy and safety data for medical management in this cohort is lacking due to underrepresentation in clinical trials and registries. Selection of medical therapy is often complex, taking into consideration a multitude of factors, including real and perceived risks of infection and malignancy. In the past, immunomodulators, such as thiopurines, were commonly used as monotherapy for maintenance, offering the added advantages of affordability and oral administration. Indeed, there are elderly patients who have been maintained for decades on thiopurine monotherapy. Further, thiopurines can be used in combination with anti-TNF therapy for improved efficacy and reduced immunogenicity compared to monotherapy with either agent in ulcerative colitis (UC). Whether the use of combination therapy imposes an additive risk compared to thiopurine monotherapy is still unclear. This study aimed to investigate outcomes of thiopurine monotherapy versus combination therapy with anti-TNF agents in elderly patients (age ≥65 years) with UC. METHODS The TriNetX Research Network was accessed on October 15th, 2023, to compare outcomes in elderly patients 65 years or older with UC who are receiving thiopurine monotherapy and patients who are receiving combination therapy with an anti-TNF (adalimumab, certolizumab pegol, golimumab, or infliximab). The outcomes examined were 1-year rate of corticosteroid and colectomy as well as 10-year rate of mortality, colon cancer, skin cancer, and respiratory and urinary tract infections. Statistical risk analysis was performed using the TriNetX analytical platform. RESULTS A total of 2,597 patients (2,245 thiopurines monotherapy and 352 AZA plus anti-TNF combination therapy) were included in the study (Table 1). Among the monotherapy and combination therapy cohorts, mean age was 71 years old and approximately 56% male. Ten-year mortality was higher in the thiopurine monotherapy group (OR 1.67, p=0.002). The combination therapy cohort had higher rates of steroid use (32.4% vs. 24.3%, p=0.001) and colectomy at 1 year compared to the monotherapy cohort (4.5% vs. 1.2%, p<0.001). There was no significant difference in 10-year risk of colon cancer (OR 1.05, p=0.88), skin cancer (OR 1.51, p=0.06), incidence of respiratory (OR 1.48, p=0.07) and urinary tract infections (OR 1.18, p=0.23). CONCLUSION The study findings highlight the risks of thiopurine use in patients over the age of 65 given the significantly higher 10-year mortality risk in thiopurine monotherapy-treated patients. The results also suggest that combination therapy with thiopurine and anti-TNF therapies - despite utilization in patients with more active disease indicators - is not associated with an additive risk in terms of infection and mortality in elderly patients. Table 1 Characteristics and Outcomes of Elderly Patients with UC either on Thiopurine Monotherapy or Combination Therapy with anti-TNF agents

Alteration of metabolic syndrome and the risk of colorectal cancer in individuals younger than 50 years.

81 Background: Colorectal cancer (CRC) is a significant global health concern, with a rising incidence of early-onset cases in individuals under 50. This trend may be influenced by various factors, including metabolic syndrome (MetS), obesity, dietary habits, and lifestyle choices. However, the impact of changing MetS status on the risk of early-onset CRC remains understudied. Methods: A total of 3,340,635 Korean national insurance beneficiaries that received two consecutive biennial mandatory health exams (2009–2011) were followed-up until 2019. Participants were categorized into MetS-free, recovered, developed, or persistent groups. The study assessed CRC risk patterns associated with these MetS dynamics, considering factors like age, sex, smoking, alcohol consumption, exercise, and income status. Results: Among 20-39-year-olds, those with persistent MetS had a 16% higher risk of CRC (adjusted hazard ratio [aHR] 1.16; 95% CI, 1.00–1.33) compared to MetS-free individuals. Furthermore, persistent MetS was associated with a 29% higher risk of rectal cancer in this age group, while recovery from MetS also increased rectal cancer risk by 28%. Among 40-49-year-olds, the MetS-persistent group had a 22% higher risk of CRC (aHR 1.22; 95% CI, 1.14-1.30), with a 34% higher risk of distal colon cancer, while those who developed MetS showed a 26% higher risk of CRC compared to the MetS-free group. Conclusions: This study highlights that the persistence of MetS in young adults is associated with an increased risk of early-onset CRC. The findings suggest that managing MetS in young individuals through lifestyle modifications, such as weight reduction and regular exercise, could be beneficial in reducing the risk of early-onset CRC.

Uncovering the clinical relevance of unclassified variants in DNA repair genes: a focus on BRCA negative Tunisian cancer families.

Introduction: Recent advances in sequencing technologies have significantly increased our capability to acquire large amounts of genetic data. However, the clinical relevance of the generated data continues to be challenging particularly with the identification of Variants of Uncertain Significance (VUSs) whose pathogenicity remains unclear. In the current report, we aim to evaluate the clinical relevance and the pathogenicity of VUSs in DNA repair genes among Tunisian breast cancer families. Methods: A total of 67 unsolved breast cancer cases have been investigated. The pathogenicity of VUSs identified within 26 DNA repair genes was assessed using different in silico prediction tools including SIFT, PolyPhen2, Align-GVGD and VarSEAK. Effects on the 3D structure were evaluated using the stability predictor DynaMut and molecular dynamics simulation with NAMD. Family segregation analysis was also performed. Results: Among a total of 37 VUSs identified, 11 variants are likely deleterious affecting ATM, BLM, CHEK2, ERCC3, FANCC, FANCG, MSH2, PMS2 and RAD50 genes. The BLM variant, c.3254dupT, is novel and seems to be associated with increased risk of breast, endometrial and colon cancer. Moreover, c.6115G>A in ATM and c.592+3A>T in CHEK2 were of keen interest identified in families with multiple breast cancer cases and their familial cosegregation with disease has been also confirmed. In addition, functional in silico analyses revealed that the ATM variant may lead to protein immobilization and rigidification thus decreasing its activity. We have also shown that FANCC and FANCG variants may lead to protein destabilization and alteration of the structure compactness which may affect FANCC and FANCG protein activity. Conclusion: Our findings revealed that VUSs in DNA repair genes might be associated with increased cancer risk and highlight the need for variant reclassification for better disease management. This will help to improve the genetic diagnosis and therapeutic strategies of cancer patients not only in Tunisia but also in neighboring countries.

Dietary Folate and Cofactors Accelerate Age-dependent p16 Epimutation to Promote Intestinal Tumorigenesis.

Our study demonstrates that dietary folate and cofactors modulate tumor-suppressor gene methylation to increase intestinal tumorigenesis. Our findings highlight the need for monitoring the long-term safety of folate fortification in high-risk individuals.

Association of metformin and statin uses with the prognosis of colon cancer: a meta-analysis.

Metformin and statins are commonly used globally for the treatment of type 2 diabetes mellitus and dyslipidemia, respectively. Recently, multiple novel pathways have been discovered, which may contribute to the treatment of various types of cancer. Several meta-analysis studies have reported that the use of metformin or statins is associated with a lower risk of colon cancer compared to nonusers. In this study, our aim was to perform a meta-analysis and investigate the prognostic roles of these two medications in colon cancer. To identify relevant articles, literature searches were performed in the PubMed and Web of Science databases using a combination of keywords related to metformin, statins and colon cancer prognosis until August 2023. The study utilized STATA 12.0 software (Stata Corporation, College Station, Texas, USA) to compute all the hazard ratios (HRs) and 95% confidence intervals (CIs) regarding the association between metformin or statin uses and prognostic-related outcomes. Our analysis revealed that the use of metformin was associated with a significantly lower overall mortality of colon cancer (HR = 0.63; 95% CI = 0.51-0.77; I2 = 94.9%; P < 0.001), as well as lower cancer-specific mortality of colon cancer (HR = 0.68; 95% CI = 0.50-0.94; I2 = 91.9%; P < 0.001). Similarly, the use of statins was also associated with a lower overall mortality of colon cancer (HR = 0.68; 95% CI = 0.60-0.78; I2 = 93.8%; P < 0.001), as well as a lower cancer-specific mortality of colon cancer (HR = 0.74; 95% CI = 0.67-0.81; I2 = 82.2%; P < 0.001). Our meta-analysis study suggests that statins and metformin may have potential as adjuvant agents with significant benefits in the prognosis of colon cancer.

Dietary Cannabidiol Activates PKA/AMPK Signaling and Attenuates Chronic Inflammation and Leaky Gut in DSS-Induced Colitis Mice.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut, accompanied by impaired epithelial integrity, increased macrophage infiltration, and enhanced colon cancer risk. Cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is supplemented into mice diet, and its beneficial effects against dextran sulfate sodium (DSS)-induced experimental colitis is evaluated. Eight-week-old mice were fed a standard diet supplemented with or without CBD (200mg kg-1 ) for 5 weeks. In the 4th week of dietary treatment, mice were subjected to 2.5% DSS induction for 7 days, followed by 7 days of recovery, to induce colitis. CBD supplementation reduced body weight loss, gross bleeding, fecal consistency, and disease activity index. In addition, CBD supplementation protected the colonic structure, promoted tissue recovery, and ameliorated macrophage infiltration in the colonic tissue, which was associated with the activation of cyclic AMP-protein kinase A, extracellular signal-regulated kinase ½, and AMP-activated protein kinase signaling pathways. CBD supplementation also suppressed NLRP3 inflammasome activation and related pro-inflammatory marker secretion. Consistently, CBD feeding reduced tight junction protein claudin2 and myosin light chain kinase in DSS-treated mice. Dietary CBD protects against inflammation and colitis symptoms induced by DSS, providing an alternative approach to IBD management.

Study of Inulin Content and Extractions Methods in Several Types of Tubers: Review Paper

Inulin is a source of fiber that can be used as a functional food. Foods that contain inulin can help overcome health problems such as obesity, colon cancer risk, lower blood sugar levels and reduce insulin resistance. The purpose of this paper is to summarize some research results on inulin content in tubers and their extraction methods. The inulin content in dahlia, gembili, uwi, potato, sweet potato, jicama, onion and garlic tubers are 74%; 15%; 12%; 7%; 13%; 41% and 33%, respectively. Extraction methods used include ethanol:water precipitation, microwave-assisted extraction, hot water extraction and ultrasound. In the future, inulin is expected to contribute to the treatment of digestive-related diseases.

Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study.

Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation. For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments. Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland. Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

Relationship Between Aspirin Use and Site-Specific Colorectal Cancer Risk Among Individuals With Metabolic Comorbidity.

The relationship between aspirin usage and the risk of colorectal cancer (CRC) among individuals with both hypertension (HTN) and diabetes mellitus (DM) remains unclear. This study aims to explore the impact of aspirin use on the site-specific CRC risk in patients with metabolic comorbidity. A case-control study was conducted among 1,331 CRC patients and 2,771 controls recruited from the Nation Cancer Center in Korea. Multinomial logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between aspirin use, metabolic disease status, and site-specific CRC risk. Among the 4,102 participants, 1,191 individuals had neither HTN nor DM, 2,044 were diagnosed with HTN, 203 with DM, and 664 presented with HTN and DM comorbidity. An increasing number of HTN and DM was associated with an increased risk of overall CRC (HTN or DM: OR, 1.70; 95% CI, 1.39-2.07; HTN and DM: OR, 8.43; 95% CI, 6.37-11.16), while aspirin use was associated with a decreased risk of overall CRC (OR, 0.31; 95% CI, 0.21-0.46). These results remained consistent across anatomical sites. Among individuals with HTN and DM comorbidity, aspirin use notably associated with lower risk of overall CRC (OR, 0.39; 95% CI, 0.21-0.72), proximal colon (OR, 0.32; 95% CI, 0.13-0.71) and rectal cancer (OR, 0.27; 95% CI, 0.08-0.97), but not distal colon cancer (OR, 0.58; 95% CI, 0.27-1.24). This study showed that aspirin use is negatively associated with overall and site-specific CRC, even among individuals with HTN and DM comorbidity.

Awareness and knowledge of inflammatory bowel disease among the population of Qassim

Objective: This study aimed to assess awareness and knowledge about the symptoms, risk factors, complications, and management of inflammatory bowel disease (IBD), and the differences between IBD and irritable bowel syndrome (IBS), in Al-Qassim population. Results: In this cross-sectional study the data were collected from 648 individuals. The questionnaires were distributed through social media applications, and also online in public places in the Qassim region in the form of an electronic barcode that opened directly to the online questionnaire to reach the maximum diversity of participants. Results: A sizeable majority of participants had some awareness of IBD (42.9%). A significant portion (42%) had acquired information from the media. Most participants (62%) correctly reported abdominal pain or cramping diarrhea as symptoms of IBD. About the same number were aware that family history was a risk factor for IBD. Nearly three-quarters of the participants were aware that medical treatment exists for IBD depending on the case. However, the study identified significant knowledge gaps; only a minority correctly reported that IBD patients have high risks of anemia and colon cancer, and the distinctions among various bowel diseases (e.g., ulcerative colitis, Crohn&amp;apos;s disease, IBS, IBD) were generally poorly understood by participants. The results established statistically significant associations between awareness of IBD and age, medical specialty, employment status, education, and family history of IBD. Conclusion: The study highlighted the need for targeted education and awareness campaigns to increase public knowledge and reduce the prevalence of the disease in the community.

Causal effects of circulating glutamine on colitis, IBD, and digestive system cancers: a Mendelian randomisation study.

Backgrounds: There is growing evidence linking glutamine levels to the risk of gastrointestinal diseases, yet the presence of a causal relationship remains uncertain. In this study, we employed a Mendelian randomization (MR) approach to investigate potential causal associations between glutamine and colitis, inflammatory bowel disease (IBD), and digestive tumors. Methods: Genetic instrumental variables for glutamine exposure were identified from a genome-wide association study (GWAS) involving 114,751 participants. We pooled statistics from GWAS of gastrointestinal diseases in European populations, encompassing colitis (cases=1193, controls=461,740), IBD (cases=31,665, controls=33,977), Crohn's disease (cases=17,897, controls=33,977), ulcerative colitis (cases=1,239, controls=990), oesophageal cancer (cases=740, controls=372,016), gastric cancer (cases=6,563, controls=195,745), liver cell carcinoma (cases=168, controls=372,016), hepatic bile duct cancer (cases=418, controls=159,201), pancreatic cancer (cases=1,196, controls=475,049), and colon cancer (cases=1,494, controls=461,439). To ensure the validity of our findings, we utilized several analytical approaches including inverse variance weighted, weighted median, weighted mode, MR-Egger, and simple mode method. Results: Using the IVW method, we found that glutamine levels were inversely associated with colon cancer (OR = 0.998; 95% CI: 0.997-1.000; P = 0.027), colitis (OR = 0.998; 95% CI: 0.997-1.000; P = 0.020), and IBD (OR = 0.551; 95% CI: 0.343-0.886; P = 0.014). Subgroup analysis revealed a negative association between glutamine and Crohn's disease (OR = 0.375; 95% CI: 0.253-0.557; P = 1.11E-06), but not with ulcerative colitis (OR = 0.508; 95% CI: 0.163-1.586; P = 0.244). Glutamine levels showed no significant correlation with oesophageal cancer (OR = 1.000; 95% CI: 0.999-1.001; P = 0.566), gastric cancer (OR = 0.966; 95% CI: 0.832-1.121; P = 0.648), liver cell carcinoma (OR = 1.000; 95% CI: 0.999-1.000; P = 0.397), hepatic bile duct cancer (OR = 0.819; 95% CI: 0.499-1.344; P = 0.430), and pancreatic cancer (OR = 1.130; 95% CI: 0.897-1.423; P = 0.301). Sensitivity analyses also supports this finding, affirming the reliability and robustness of our study. Conclusions: This study suggests that blood glutamine levels in European populations may lower the risk of colon cancer, colitis, and IBD, particularly Crohn's disease. Nevertheless, additional research involving a diverse range of ancestries is imperative to corroborate this causal relationship.

Review article: do stimulant laxatives damage the gut? A critical analysis of current knowledge.

Stimulant laxatives are well established as first- or second-line treatments for constipation and although they have a reliable therapeutic effect, alleged safety concerns still exist, particularly with long-term use. The potential harmful effects on the gastrointestinal system (including carcinogenicity) of the long-term use of diphenylmethane [bisacodyl, sodium picosulfate (SPS)] and senna stimulant laxatives were assessed in a comprehensive review of the publications identified in literature searches performed in PubMed and Embase up to and including June 2023. We identified and reviewed 43 publications of interest. While stimulant laxatives at supratherapeutic doses have been shown to cause structural alterations to surface absorptive cells in animals and humans, these effects are reversible and not considered clinically relevant. No formal long-term studies have demonstrated morphological changes in enteric neural elements or intestinal smooth muscle with bisacodyl or SPS in humans. Furthermore, there is no convincing evidence that stimulant laxatives are associated with the development of colon cancer, and in fact, chronic constipation itself has been reported to potentially increase the risk of colon cancer, therefore, the use of stimulant laxatives might reduce this risk. Many studies suggesting a possible harmful effect from laxatives were limited by their failure to consider confounding factors such as concomitant neurological disease, metabolic disorders, and age. These findings highlight the lack of evidence for the harmful effects of laxatives on the colon, and thus, the benefits of treatment with stimulant laxatives, even in the long-term, should be reconsidered for the management of patients with constipation.

Emerging functions of lycopene in the management of digestive premalignant lesions.

Common digestive precancerous lesions, including oral potentially malignant disorders (OPMDs), gastric ulcers and colorectal adenoma, harbor high risk of cancerous transformation. Early intervention of these lesions is significant to prevent carcinogenesis and improve patients' prognosis. Lycopene, a carotenoid predominantly accumulated in tomatoes, is clinically recommended with its cis structure; as lycopene harbors the most potent antioxidative effects among carotenoids, its chemopreventive effects on the premalignant lesions is noted. Despite several reviews have assessed lycopene's efficacy for OPMDs, emerging studies have reported varying efficacy for digestive precancerous lesion with no comprehensive summary. Therefore, this review initially evaluates the efficacy and underlying mechanisms of lycopene for management of digestive precancerous lesions. According to the included studies, lycopene may show high promise in the management of digestive precancerous lesions, such as relieving mouth opening and burning sensation of oral submucous fibrosis (OSF), presenting potentially equivalent efficacy on managing oral lichen planus (OLP) as steroids and alleviating gastrointestinal precancers' symptoms, meanwhile lowering colon cancer risk. Moreover, its mechanisms for managing digestive precancerous lesions are concretely summarized, including anti-oxidative stress effects, anti-inflammatory response and regulation of cell proliferation and apoptosis, especially its modifications on TLR4/TRIF/NF-κB signaling pathway and p53-dependent cell cycle control and apoptosis. More studies are warranted to confirm its long-term efficacy and preventive role against malignant transformation of digestive precancerous lesions as evidence is insufficient.

Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention.

Self-antigens abnormally expressed on tumors, such as MUC1, have been targeted by therapeutic cancer vaccines. We recently assessed in two clinical trials in a preventative setting whether immunity induced with a MUC1 peptide vaccine could reduce high colon cancer risk in individuals with a history of premalignant colon adenomas. In both trials, there were immune responders and non-responders to the vaccine. Here we used PBMC pre-vaccination and 2 weeks after the first vaccine of responders and non-responders selected from both trials to identify early biomarkers of immune response involved in long-term memory generation and prevention of adenoma recurrence. We performed flow cytometry, phosflow, and differential gene expression analyses on PBMCs collected from MUC1 vaccine responders and non-responders pre-vaccination and two weeks after the first of three vaccine doses. MUC1 vaccine responders had higher frequencies of CD4 cells pre-vaccination, increased expression of CD40L on CD8 and CD4 T-cells, and a greater increase in ICOS expression on CD8 T-cells. Differential gene expression analysis revealed that iCOSL, PI3K AKT MTOR, and B-cell signaling pathways are activated early in response to the MUC1 vaccine. We identified six specific transcripts involved in elevated antigen presentation, B-cell activation, and NF-κB1 activation that were directly linked to finding antibody response at week 12. Finally, a model using these transcripts was able to predict non-responders with accuracy. These findings suggest that individuals who can be predicted to respond to the MUC1 vaccine, and potentially other vaccines, have greater readiness in all immune compartments to present and respond to antigens. Predictive biomarkers of MUC1 vaccine response may lead to more effective vaccines tailored to individuals with high risk for cancer but with varying immune fitness.

Study of Impact of Dietary Factors on Prevalence of Colon Cancer

The third most frequent cancer worldwide is colorectal cancer. Globally, 1.5 million new cases of colorectal cancer were reported in 2023, making up 10% of all new cancer cases. According to estimates, colorectal cancer is the fourth most prevalent cancer-related cause of death.be accountable for about 700,000 cancer-related deaths. Survival from colorectal cancer depends on the stage of the disease, with later-stage diagnoses having a worse prognosis. 90% of colorectal cancer patients who receive an early diagnosis survive five years. Western Africa has the lowest estimated rates, while Australia and New Zealand have the highest. Men and women worldwide experience colorectal cancer in similar ways. More than 2.2 million colorectal cancer cases are anticipated to be diagnosed during the next 15 years, a 60% rise. It is one of the malignancies whose incidence is rising globally. The diet has a direct connection with the colon cancer because inflammation in the bowels and gut is influenced by what we consume, and inflammation is a risk factor for the development of colorectal cancer. Researchers have identified sugar, animal fats, red and processed meats as the key food ingredients that produce inflammation in the body and may raise the risk of colon cancer.

Repurposing TAK875 as a novel STAT3 inhibitor for treating inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic immune-mediated disease associated with a high recurrence rate and an elevated risk of colon cancer. In this study, we screened a bioactive compound library using a luciferase reporter assay and identified the compound TAK875 as a novel inhibitor of signal transducer and activator of transcription 3 (STAT3). Surface plasmon resonance analysis, differential scanning fluorimetry, and isothermal titration calorimetry demonstrated that TAK875 directly bound to recombinant STAT3. TAK875 suppressed the lipopolysaccharide (LPS)-induced release of nitric oxide, inducible nitric oxide synthase, and inflammatory factors in RAW264.7 cells, likely by inhibiting STAT3 phosphorylation. In addition, TAK875 inhibited the differentiation of CD4+ T cells into T-helper 17 cells, which may partially account for its anti-inflammatory effect. TAK875 also alleviated the LPS-induced accumulation of intracellular reactive oxygen species, thus displaying its antioxidant effects. Finally, we demonstrated its satisfactory anti-inflammatory effect in a dextran sulfate sodium-induced mouse model of ulcerative colitis. In conclusion, this study presented TAK875 as a novel STAT3 inhibitor and demonstrated its anti-inflammatory and antioxidant effects both in vitro and in vivo.