Search Results (1,063)

The escalating incidence of colorectal cancer (CRC), particularly the alarming rise in early-onset cases, necessitates a paradigm shift from a purely genetic perspective to a broader investigation of promising pathways. This review explores the “nutri-epigenetic” interface, positioning liquid biopsy as a critical technology for translating dietary impacts into actionable clinical biomarkers. We contrast the molecular consequences of the Western dietary pattern, characterized by methyl-donor deficiency and pro-inflammatory metabolites, with the protective mechanisms of the Mediterranean diet. Mechanistically, we detail how Western-style diets drive a specific “epigenetic double-hit”: promoting global DNA hypomethylation (destabilizing LINE-1) while paradoxically inducing promoter hypermethylation of critical tumour suppressors (MLH1, APC, MGMT) and silencing tumour-suppressive microRNAs (miR-34b/c, miR-137) via methylation of their encoding genes. Conversely, we highlight the capacity of Mediterranean bioactive compounds (e.g., resveratrol, curcumin, butyrate) to inhibit DNA methyltransferases and restore epigenetic homeostasis. Bridging molecular biology and clinical utility, we demonstrate how these diet-sensitive signatures, specifically circulating methylated DNA and dysregulated microRNAs, can be captured via liquid biopsy. We propose that these circulating analytes serve as dynamic, accessible biomarkers for monitoring the molecular progression toward a carcinogenic state, thereby establishing a novel framework for personalized risk stratification and validating the efficacy of preventive nutritional strategies. Full article

Background/Objectives: Unhealthy lifestyles lead to chronic low-grade inflammation, increasing the risk of colorectal cancer. Few studies in East Asia have examined the association between the dietary inflammation potential and colorectal cancer incidence. Therefore, we aimed to investigate this association further in the Japanese population. Methods: This study included 38,807 men aged 45–74 years who participated in the Japan Public Health Center-based prospective study (JPHC Study). The energy-adjusted dietary inflammatory index (E-DII) was derived from a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. Differences in risk due to a combination of E-DII and lifestyle were examined using interaction term. Results: During 14 years of follow-up, 1415 colorectal cancer cases occurred. A tendency to increased colorectal cancer risk was observed with consumption of pro-inflammatory diets among Japanese men (adjusted HR [95% CI] for the highest quintile: 1.20 [0.99–1.46], p trend = 0.08), with a significantly increased risk of colon cancer (HR: 1.28 [1.01–1.63], p trend = 0.03). A possible interaction was observed with alcohol consumption (p = 0.07), which was statistically significant for proximal colon cancer (HR: 1.14 [1.05–1.25] in drinkers; p interaction = 0.01). No significant interactions with other lifestyle factors were found. Conclusions: Consumption of pro-inflammatory diets increases colorectal cancer risk among Japanese men; alcohol consumption further increases this risk for drinkers. These findings suggest that colorectal cancer may be prevented through dietary modification. Full article

Objective: To develop and validate a genetic diagnostic model for colorectal cancer (CRC). Methods: First, differential expression genes (DEGs) between colorectal cancer and normal groups were screened using the TCGA database. Subsequently, a two-sample Mendelian randomization analysis was performed using the eQTL genomic data from the IEU OpenGWAS database and colorectal cancer outcomes from the R12 Finnish database to identify associated genes. The intersecting genes from both methods were selected for the development and validation of the CRC genetic diagnostic model using nine machine learning algorithms: Lasso Regression, XGBoost, Gradient Boosting Machine (GBM), Generalized Linear Model (GLM), Neural Network (NN), Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Random Forest (RF), and Decision Tree (DT). Results: A total of 3716 DEGs were identified from the TCGA database, while 121 genes were associated with CRC based on the eQTL Mendelian randomization analysis. The intersection of these two methods yielded 27 genes. Among the nine machine learning methods, XGBoost achieved the highest AUC value of 0.990. The top five genes predicted by the XGBoost method—RIF1, GDPD5, DBNDD1, RCCD1, and CLDN5—along with the five most significantly differentially expressed genes (ASCL2, IFITM3, IFITM1, SMPDL3A, and SUCLG2) in the GSE87211 dataset, were selected for the construction of the final colorectal cancer (CRC) genetic diagnostic model. The ROC curve analysis revealed an AUC (95% CI) of 0.9875 (0.9737–0.9875) for the training set, and 0.9601 (0.9145–0.9601) for the validation set, indicating strong predictive performance of the model. SHAP model interpretation further identified IFITM1 and DBNDD1 as the most influential genes in the XGBoost model, with both making positive contributions to the model’s predictions. Conclusions: The gene expression profile in colorectal cancer is characterized by enhanced cell proliferation, elevated metabolic activity, and immune evasion. A genetic diagnostic model constructed based on ten genes (RIF1, GDPD5, DBNDD1, RCCD1, CLDN5, ASCL2, IFITM3, IFITM1, SMPDL3A, and SUCLG2) demonstrates strong predictive performance. This model holds significant potential for the early diagnosis and intervention of colorectal cancer, contributing to the implementation of third-tier prevention strategies. Full article

(E)-Flavokawain A (FKA), the primary chalcone constituent of Piper methysticum, exhibits diverse pharmacological properties and holds significant potential for therapeutic development. Objectives: This study aims to investigate the anti-colorectal cancer effects and mechanisms of FKA. Methods: Using AOM/DSS-induced colorectal cancer models in C57 mice, the research examines the impact of different FKA doses, employing 16S rRNA and metabolomics to explore the potential mechanism. Results: The findings indicated that FKA significantly inhibited the progression of colorectal cancer in C57 mice by modulating the composition of the gut microbiota. This modulation involved the suppression of endotoxin secretion by pathogenic bacteria and the concurrent augmentation of beneficial bacteria. Furthermore, in the context of metabolic pathways, FKA regulates lipid metabolism and arachidonic acid metabolism, thereby mitigating the inflammatory transformation associated with colorectal cancer. Conclusions: These findings provide valuable insights supporting the potential of FKA as a viable preventive strategy against CRC. Full article

Background and Objectives: Aggressive cancer development is characterized by rapid tumor growth and progressive immune dysfunction. Tumor-derived microRNAs (miRNAs) emerge as master regulators of both malignant transformation and immune evasion, making them promising therapeutic targets. Using the highly aggressive CT-26 peritoneal adenomatosis model, this study explored the potential of selective miRNA inhibition to simultaneously suppress tumor growth and overcome immunosuppression. Methods and Results: Our results revealed that inhibition of miR-155, miR-21, and miR-17 by methylsulfonyl phosphoramidate (mesyl) oligonucleotides exhibited markedly different therapeutic profiles. miR-155 inhibition demonstrated minimal efficacy. miR-21 suppression provided early tumor regression and prevented cancer-associated thymic atrophy, translating into extended survival. miR-17 inhibition displayed delayed but superior tumor growth inhibition, significantly reducing pathologically elevated polymorphonuclear myeloid-derived suppressor cell (MDSC) populations, and nearly doubled animal lifespan. Combination therapy targeting all three miRNAs integrated these complementary mechanisms, maintaining consistent anti-tumor efficacy across early and late stages while providing thymic protection and MDSC reduction. Importantly, therapeutic responses in vivo substantially exceeded predictions based on in vitro tumor cell proliferation and motility measurements, revealing critical contributions of systemic immunomodulation. Conclusions: These findings demonstrate that miRNA inhibition reshapes tumor–immune interactions, positioning anti-miRNA therapeutics as immunomodulatory agents for effective colorectal cancer treatment. Full article

Background: Vitamin E has been studied for its role in reducing the growth of colorectal cancer (CRC). CRC is a worldwide health concern. A meta-analysis reported that CRC patients have a lower concentration of serum vitamin E, suggesting it to be a risk factor. Although rodent models are widely used in disease research, their application in studying vitamin E as a preventive or therapeutic agent in CRC is not well characterized. To address this gap, we conducted a scoping review to examine the available evidence, adhering to the PRISMA-ScR checklist. Methods: We searched PubMed, Google Scholar, Scopus, and Web of Science (WoS) for full-text English original articles published before May 2024, using Medical Subject Headings (MeSH) terms and free text. The following search string strategy was applied: (Vitamin E OR tocopherol$ OR tocotrienol$) AND (Colo$ cancer OR colo$ carcinoma) AND (Rodentia OR mouse OR Rodent$ OR mice OR murine OR rats OR guinea OR rabbit OR hamsters OR Animal model OR Animal testing OR animals) AND (neoplasm$ OR “tumor mass” OR tumor volume OR tumor weight OR tumor burden). Data were charted into five categories using a standardized, pretested form. The charted data were synthesized using descriptive and narrative methods. Conclusions: This study highlights that γ- and δ-tocopherols, as well as δ-tocotrienol and its metabolites, were reported to reduce tumor volume and formation in various rodent models. While these results are promising, this scoping review identifies a need for further research to address translational barriers such as dosing, bioavailability, and long-term safety before clinical application. Full article

Carrots are exceptional sources of bioactive compounds with potential health benefits. This study investigated the relationship between the biodiversity of carrot cultivars (colour and size) and their potential chemopreventive properties. Four distinct carrot cultivars (orange, white, yellow, and purple) of normal and miniature sizes were comprehensively analysed for polyphenolic composition, bio-accessibility through in vitro simulated digestion, and in vitro antiproliferative activity against the HCT-116 colon cancer cell line. Our findings revealed that vegetable size influenced phytochemical composition more than vegetable colour, with mini purple carrots exhibiting exceptionally high polyphenolic concentrations and superior antiproliferative activity compared to orange, yellow, or white varieties. Notably, the bioaccessibility of bioactive compounds remained remarkably low across all samples, suggesting that these phytochemicals reach the colon in intact form, potentially enabling direct interaction with cancer cells. Interestingly, we found no direct correlation between total phenolic content and antiproliferative activity. In vitro cell cycle analysis revealed that mini purple carrot extracts induced S-phase arrest similar to the chemotherapeutic agent 5-FU, whereas other extracts caused G0/G1-phase arrest. The specific polyphenolic composition appears to be fundamentally important for bioactivity, with chlorogenic acid and diferulic acid-derivative isomer 2 potentially acting synergistically. These findings highlight the importance of carrot biodiversity in delivering functional foods with enhanced health-promoting properties, particularly for colorectal cancer prevention. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. Despite therapeutic advances, prevention through dietary bioactives remains a promising strategy. The Annurca apple (Malus pumila Miller cv. Annurca), a Mediterranean food rich in chlorogenic acid, exhibits antioxidant and anti-inflammatory effects. This study evaluated, via molecular docking, the multi-target interaction profile of chlorogenic acid against key CRC-related proteins. Methods: The optimized 3D structure of chlorogenic acid was docked to ten protein targets implicated in CRC pathogenesis, using the GOLD v.2022.3.0 software. Validation of the docking protocol was achieved by re-docking native ligands (RMSD ≤ 2.0 Å). Binding affinities were assessed by ChemPLP scoring, and interaction networks were visualized in Maestro Schrödinger. Results: Chlorogenic acid displayed consistent binding across all evaluated targets (ChemPLP 57.12–69.66), showing the highest affinity for nAChR (69.66), CXCR2 (65.13), ERβ (63.18) and TGFBR2 (62.94). The ligand formed multiple hydrogen bonds and π-π stacking interactions involving Asp1040 (VEGFR-1), Cys919 (VEGFR-2), Lys320 (CXCR2), and Tyr195 residues (nAChR), contributing to strong complex stabilization. Interaction patterns in CYP19A1, ERβ, and ERRγ suggested potential modulation of hormonal and metabolic signaling. The compound also demonstrated stable binding to mTOR (60.01), indicating a possible inhibitory role in proliferative pathways. Collectively, these findings reveal a broad, polypharmacological binding profile involving angiogenic, inflammatory, and hormonal regulators. Conclusions: Chlorogenic acid acts as a promising multi-target ligand in CRC prevention, with our in silico evidence supporting its ability to modulate diverse oncogenic pathways. Further experimental studies are warranted to confirm its efficacy and translational potential. Full article

Colonoscopy is central to colorectal cancer (CRC) prevention, and its effectiveness is determined by the quality of mucosal inspection and lesion detection. The adenoma detection rate (ADR) remains the most widely validated quality benchmark due to its strong inverse association with interval CRC. However, reliance on ADR alone is increasingly recognized as insufficient, particularly given the growing understanding of the serrated neoplasia pathway, which contributes up to one-third of sporadic CRCs. This has driven the emergence of complementary metrics, such as the sessile polyp detection rate (SPDR) and adenomas per colonoscopy (APC). Although SPDR offers important advantages for capturing serrated pathology, challenges persist, including interobserver variability, inconsistent pathology thresholds, limited endoscopist training, and the absence of standardized benchmarks. Alongside these evolving metrics, technological advancements such as image-enhanced endoscopy, computer-aided detection, high-definition optics, and distal attachment devices have demonstrated measurable improvements in detecting subtle lesions and reducing operator-dependent variability. Large real-world registries, including GIQuIC, now support the development and validation of composite models that integrate ADR, SPDR, and APC to better reflect the full spectrum of neoplasia detection. As the field advances, redefining colonoscopy quality will require reconciling established metrics with newer indicators that more comprehensively address both conventional adenomas and serrated lesions. Full article

Colorectal cancer is one of the leading causes of cancer-associated mortality, and multifactorial resistance remains one of the main challenges in its treatment. Essential oils and their main compounds show interesting anticancer properties, but their mechanism of action is yet to be defined. This study aims to assess the cytotoxic effects of eugenol (EU) and cinnamaldehyde (CN) on colorectal cancer (CRC) cells, highlighting possible mechanisms of action. These compounds were tested on normal immortalized colonocytes (NCM-460) and two CRC cell lines: Caco-2, a human colon epithelial adenocarcinoma cell line, and SW-620, colon cancer cells derived from a lymph node metastatic site. The efficacy of EU and CN was evaluated through CellTiter-Glo^® and clonogenic assays and by determining proinflammatory cytokine secretion. Transcriptome analysis was used to identify possible pathways affected by EU and CN treatments. The results confirmed that EU and CN were selectively cytotoxic and pro-apoptotic against CRC cells, with different putative mechanisms. While EU drove cytotoxicity through robust transcriptional remodeling, CN yielded a stronger anti-inflammatory action. We confirmed that EU and CN are promising natural candidates in CRC prevention and treatment, even in association with chemotherapeutic drugs. Full article

Cancer is one of the biggest health burdens for women in the Middle East and North Africa (MENA), with the incidence of breast, cervical and colorectal cancer on the rise. Although preventive measures such as the HPV vaccination and population-based screening are available, access to them remains very unequal. Women in rural, low-income and refugee communities face additional barriers, cultural stigmatisation, low health literacy, gender norms and fragile health systems, leading to delayed diagnoses and poorer outcomes. This review summarises the results of 724 peer-reviewed publications to assess the current situation of cancer screening in MENA and Mediterranean countries. The studies were classified into four dimensions: cancer type (breast, cervical, colorectal), behavioural constructs (awareness, uptake, education), vulnerability factors (e.g., migrants, refugees, low-literacy groups), and geography (indigenous MENA populations versus diaspora and Mediterranean immigrant communities). The results show large inequalities in access and participation due to fragmented policies, socio-cultural resistance and infrastructure gaps. Nevertheless, promising approaches are emerging: community-led outreach, mobile screening programmes, AI-assisted triage and culturally appropriate digital health interventions. Comparisons between the local and diaspora populations make it clear that systemic and cultural barriers persist even in well-equipped facilities. Closing the screening gap requires a culturally sensitive, digitally enabled and policy aligned approach. Key priorities include engaging religious and community leaders, promoting men’s engagement in women’s health and securing sustainable funding. With coordinated action across all sectors, MENA countries can build inclusive screening programmes that reach vulnerable women and reduce preventable cancer mortality. Full article

Cancer is the second leading cause of death in the U.S., with 612,000 deaths estimated in 2023. Cancer screening (CS) reduces mortality through early detection, but the impact of chronic conditions like adult asthma (AA) on screening is less understood. This study explores the association between AA and uptake of prostate, breast, cervical, and colorectal CS using BRFSS 2016, 2018, 2020 and 2022 data. Weighted and adjusted multivariable logistic regression assessed the association between AA and CS across sex and age-based subgroups with significant effect modification testing and subsequent subgroup analyses. Results showed significantly higher CS adherence among individuals with AA across all four CS sites compared to counterparts without asthma (CCWA). Males (55–69 years old (YO)) with AA had 15% significantly higher weighted and adjusted odds (WAO) of prostate CS (95% CI: 1.04–1.27). Women (50–74 YO) with AA had 16% significantly higher WAO of breast CS (95% CI: 1.01–1.32), with non-depressed, heavy-drinking women showing 300% significantly higher WAO (95% CI: 2.20–7.22) of breast CS. Women (21–65 YO) with AA had 9% significantly higher WAO of cervical CS (95% CI: 1.02–1.17), with education significantly modifying the association (WAOR for college-educated women = 1.23, 95% CI: 1.11–1.36). When CCWA, colorectal CS showed significantly higher odds of 36% for men aged 50–75 (95% CI: 1.24–1.49) and 24% for women aged 50–75 (95% CI: 1.15–1.33). This is the first national study to examine the association between AA and uptake of prostate, female breast, cervical, and colorectal CS over four years. Individuals with AA had significantly greater odds of CS adherence than CCWA. Effect modification by heavy drinking and education suggests the need for targeted outreach and low-literacy interventions. Full article

Background/Objectives: Modeling analyses for colorectal cancer (CRC) screening focusing solely on the costs of screening do not fully capture the value of screening programs. We evaluated the clinical and economic effects of CRC stool-based screening tests, including impacts on cancer-related outcomes. Methods: A cohort-based decision-analytic cost-estimator model estimated outcomes for a single round of screening with next-generation multi-target stool DNA (ng mt-sDNA) test or fecal immunochemical test (FIT) from a US payer perspective. Undiagnosed cancers were assumed to become symptomatic (and detected) within 10 years. Clinical assumptions, advanced precancerous lesion and CRC prevalence, and test performance inputs were from clinical trial data. Adherence rates for initial screening and follow-up colonoscopy after a positive result were from real-world data. Input costs included the screening tests, follow-up colonoscopy (with and without polypectomy), and CRC treatment. Results: Compared with FIT, more individuals completed ng mt-sDNA (321,000 vs. 713,000, respectively), leading to the detection of more CRC cases (436 with FIT vs. 2235 with ng mt-sDNA), more advanced precancerous lesions, and more CRC at earlier stages. The cost of screening per patient screened was USD 801 for ng mt-sDNA and USD 124 for FIT. Follow-up colonoscopy cost was USD 149 million with ng mt-sDNA versus USD 22 million with FIT, whereas CRC treatment costs were lower for ng mt-sDNA (USD 1423 million versus USD 1474 million, respectively). When accounting for both direct and CRC averted costs, the total cost of screening and treatment was USD 1383 million with ng mt-sDNA versus USD 1427 million with FIT. Conclusions: Higher screening costs with ng mt-sDNA versus FIT are counterbalanced by savings realized from enhanced CRC prevention and earlier detection due to the superior test performance and better adherence with ng mt-sDNA. Full article

Cancer stem cells (CSCs) remain challenging to isolate and characterize because of their plastic phenotype. To overcome this issue, we used a microfluidic lab-on-a-chip analysis approach based on ultra-high frequency dielectophoresis (UHF-DEP) to measure the dielectrophoretic signature of colorectal cancer cells. We demonstrated that CSCs exhibit a distinct and lower frequency signature than differentiated cancer cells. Extracellular vesicles (EVs) released by tumor cells are implicated in tumor progression and metastasis. As CSC-derived EVs carry a more aggressive cargo, we hypothesized that treating differentiated colorectal cancer cells with these vesicles might affect their phenotype which would be detected by our lab on a chip. Indeed, the dielectrophoretic signature of cells treated with those EVs was altered in comparison to untreated cells, even in cases where no detectable biological changes were observed. Compared to conventional approaches using biomarkers to characterize CSCs, this UHF-DEP lab on a chip is a label-free method providing rapid and relevant results. Such a method could be useful in the clinic for the early detection of CSCs in the tumor mass, as well as for monitoring CSC-derived EVs in the bloodstream in order to study responses to therapy and prevent relapses. Full article

Background: Anastomotic leakage (AL) following rectal cancer surgery is a significant cause of mortality and morbidity. Although transanal drainage tubes are expected to reduce the rate of AL, their preventive effect remains controversial. Aim: To evaluate whether transanal drainage tube (TAD) provides protection against AL in patients without other protective methods after low anterior resection (LAR). Methods: A retrospective cohort study was performed in patients undergoing LAR for rectal cancer between 2018 and 2023. Based on postoperative management, patients were divided into four distinct groups as follows: in TAD group, after colorectal anastomosis, a 32F silicone tube was inserted through the anus by more than 5 cm above the anastomosis. The tube was secured around the anus with a skin suture and a drainage bag was attached. The tube was removed after 3–5 days after surgery. In the non-TAD group, no transanal drainage tube and no diverting stomas, respectively, were used after the anastomosis. In the ileostomy and colostomy group a stoma was often performed as a primary measure in preventing anastomotic leakage. Clinical characteristics and postoperative complications were compared among the groups. Complications were categorized as general (eventration, seroma) or septic (fistula, abscess) and further classified as early (<7 days after surgery) or tardive (between 7 and 30 days after surgery). Statistical significance was defined as a p-value < 0.05. Results: A total of 171 patients were included: 47 (27.5%) in the TAD group, 54 (32.2%) in the non-TAD group, 25 (14.6%) in colostomy group, and 45 (26.3%) in ileostomy group. Overall, eight patients (4.7%) developed anastomotic leakage (AL). In the non-TAD group, 3 patients experienced AL (all early); in the ileostomy group, 2 patients (1 early, 1 tardive); and in the colostomy group, 2 patients (both tardive). The TAD group had one patient with AL as a tardive complication. The incidence of early general complications was significant lower in TAD group compared with the non-TAD group (OR 0.23, 95% CI [0.06–0.85]; p = 0.004), while there was no significant difference in early septic complications between TAD and ileostomy group (p = 0.71). The incidence of tardive general complications was significantly more frequent in the ileostomy group (OR 0.10, 95% CI [0.02–0.44]; p = 0.0008) compared with TAD group. Overall, total complications were significantly lower in TAD group compared to non-TAD (OR 0.15, 95% CI [0.05–0.44]; p < 0.001), ileostomy (OR 0.20, 95% CI [0.07–0.56]; p = 0.003), and colostomy ((OR 0.46 CI [0.21–0.99]; p = 0.049) groups. Furthermore, the TAD group showed a reduction rate of AL compared to the ileostomy, colostomy, and non-TAD groups (2.12% vs. 4.4%, 8%, and 5.5%) but the incidence of AL was almost similar (p = 0.65). Conclusions: The elective use of TAD is a simple and effective protective method for the prevention of overall postoperative complications, also helping to reduce the rate of AL in patients. Nevertheless, there is limited information in the literature regarding the optimal size and material of TAD, despite these factors playing an important role in the viability and effectiveness of the method. Full article