Search Results (7,471)

Background/Objectives: Colon capsule endoscopy (CCE) is a non-invasive method for visualising the colon, but its clinical adoption has been slow. Although the COVID-19 pandemic reignited interest in CCE, its role in conventional gastrointestinal investigations remains unclear, leading to varied practices across Europe. This highlights the need for a comprehensive understanding of diverse approaches to CCE in clinical practice. Method: A web-based survey was conducted from January to July 2024, targeting European gastroenterologists and colorectal surgeons interested in capsule endoscopy through the International Capsule Endoscopy Research (iCARE) Group. The survey aimed to understand CCE application across Europe and investigate factors influencing its uptake. Results: Thirty-eight (n = 38) valid responses were received from 19 European countries. While 88% reported access to CCE, only 45% had local services readily available, and just 7% included CCE in national guidelines. The most common indication for CCE was for patients who declined or could not tolerate colonoscopy (30%), with 77% of CE specialists preferring its use in fit patients. Ease of access was significantly associated with service availability (p = 0.0358). Barriers to uptake included lack of reimbursement, insufficient knowledge, and limited use in research settings. Only 27% of specialists viewed CCE positively, while 57% had a negative perception. Conclusions:This study reveals the wide variation in CCE practices and critical factors influencing its uptake. Understanding common indications and patient groups is the key to guiding its future development, particularly as AI and telemedicine enhance its potential for rapid full digestive tract visualisation. Full article

The intratumoral microbiome plays a significant role in many cancers, such as lung, pancreatic, and colorectal cancer. Pancreatic cancer (PC) is one of the most lethal malignancies and is often diagnosed at advanced stages. Fusobacterium nucleatum (Fn), an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in several extra-oral human diseases and, lately, in pancreatic cancer progression and prognosis. It is now recognized as oncobacterium. Fn engages in pancreatic tumorigenesis and metastasis through multifaceted mechanisms, including immune response modulation, virulence factors, control of cell proliferation, intestinal metabolite interactions, DNA damage, and epithelial–mesenchymal transition. Additionally, compelling research suggests that Fn may exert detrimental effects on cancer treatment outcomes. This paper extends the perspective to pancreatic cancer associated with Fn. The central focus is to unravel the oncogenomic changes driven by Fn in colonization, initiation, and promotion of pancreatic cancer development. The presence of Fusobacterium species can be considered a prognostic marker of PC, and it is also correlated to chemoresistance. Furthermore, this review underscores the clinical research significance of Fn as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment. It is thought that given the role of Fn in tumor formation and metastasis processes via its FadA, FapA, Fap2, and RadD, new therapies for tumor treatment targeting Fn will be developed. Full article

Royal jelly (RJ), a natural bee product known for its abundance of bioactive compounds, is often referred to as a “superfood” and has been utilized in alternative medicine for centuries. Numerous studies have highlighted its therapeutic properties, including anticancer activity. A major challenge in standard cancer therapy is the migration of cancer cells, which leads to metastasis and the formation of secondary tumors with often fatal outcomes. Cancer cell migration is facilitated by the epithelial-to-mesenchymal transition (EMT) and the aberrant activation of the Wnt/β-catenin signaling pathway. A key component of this pathway, the transcription factor β-catenin, regulates the expression of various cellular components that play critical roles in cell motility. This study investigated the antimigratory potential of RJ on the colorectal cancer cell line SW-480 and its effects on β-catenin protein expression. RJ significantly suppressed the motility of SW-480 cells and markedly reduced β-catenin protein levels 24 h after treatment. These findings underscore the potential of RJ as a functional food to regulate colorectal cancer cell motility through modulation of β-catenin, thereby reducing disease aggressiveness. Full article

Background and Objectives: Colorectal cancer is the second leading cause of cancer-related deaths in the U.S., and colonoscopy is a critical tool for colon cancer screening and diagnosis. Electrolyte disturbances and autonomic nervous system dysfunction that may occur due to bowel preparation and the colonoscopy procedure itself may play a role in the development of cardiac arrhythmia. This study aimed to assess the index of cardiac–electrophysiological balance (iCEB) to predict ventricular arrhythmia risk related to colonoscopy. Materials and Methods: Patients undergoing elective colonoscopy with a normal sinus rhythm were included. Electrocardiography (ECG) recordings both before bowel preparation and after the colonoscopy procedure were obtained. Values of the index of cardiac–electrophysiological balance (iCEB) were compared. Results: Among 36 patients, it was determined that the heart rate values of the patients before bowel preparation were higher than the heart rate values after colonoscopy [74.5 (60–108) bpm vs. 68.5 (53–108) bpm, p = 0.021]. The duration of QT interval increased (370.9 ± 27.8 ms vs. 398.7 ± 29.4 ms, p < 0.001) and the iCEB increased from 4.1 ± 0.5 to 4.5 ± 0.6 (p < 0.001), indicating a significant post-procedural risk of ventricular arrhythmias. Conclusions: These findings suggest that routine iCEB assessment post-colonoscopy could identify high-risk patients requiring closer monitoring. Full article

London rocket (Sisymbrium irio) is a wild green consumed globally, yet its phytochemical composition remains underexplored. In this study, we analyzed the leaves of wild S. irio plants and those grown in controlled environments (GCE) with varying electrical conductivities (EC) and light spectra. Plants were assessed for growth, phenolic content, vitamin C, antioxidant activity, glucosinolates, and antiproliferative effects against HT-29 human colorectal cancer cells. The optimal biomass yield occurred at the EC levels of 3.0–3.5 dS m⁻¹ under Valoya^® LED light. Wild plants showed higher antioxidant activity (DPPH and ABTS assays) than GCE samples, with values of 8.03–8.67 and 6.49–6.81 mmol TE per 100 g dry weight, respectively. The vitamin C range was 50.7–84.3 and 84.5–186.9 mg 100 g⁻¹ fresh weight for GCE and wild samples, respectively. Phenolic content was higher in wild plants than in the GCE ones, with apigetrin as the primary phenolic compound. The MTT assay showed that ethanol extracts from wild plants weakly inhibited HT-29 cell growth, with a GI₅₀ of 210–380 µg mL⁻¹ after 72 h of cells exposure to plant extracts. Principal Component Analysis suggested that EC and UV exposure increase the antioxidant activity, total phenolics, and glucosinolates in wild plants, offering insights into the bioactive profiles of S. irio leaves. Full article

Background: Gegen Qinlian Decoction (GQD), is used for intestinal disorders like ulcerative colitis, irritable bowel syndrome, and colorectal cancer. But the precise mechanisms underlying its anti-inflammatory and anti-tumor effects are not fully elucidated. Methods: Use network pharmacology to identify targets and pathways of GQD. In vivo (azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CAC) mouse model) and in vitro (lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages) experiments were conducted to explore GQD’s anti-inflammatory and anti-tumor effects. We monitored mouse body weight and disease activity index (DAI), and evaluated colon cancer tissues using hematoxylin and eosin staining. Expression of Ki67 and F4/80 was determined by immunohistochemistry analysis. The protein levels of TLR4 signaling pathway were assessed by western blotting analysis. Enzyme-linked immunosorbent assay measured IL-1β, IL-6, and TNF-α levels. Immunofluorescence (IF) staining visualized NF-κB and IRF3 translocation. Results: There were 18, 9, 24 and 77 active ingredients in the four herbs of GQD, respectively, targeting 435, 156, 485 and 691 genes. Through data platform analysis, it was concluded that there were 1104 target genes of GQD and 2022 target genes of CAC. Moreover, there were 99 intersecting genes between GQD and CAC. The core targets of GQD contained NFKB1, IL1B, IL6, TLR4, and TNF, and GQD reduced inflammation by inhibiting the TLR4 signaling pathway. In vivo experiment, GQD increased mouse body weight, lowered DAI scores, while also alleviating histopathological changes in the colon and decreasing the expressions of Ki67 and F4/80 in the AOM/DSS-induced mice. GQD reduced IL-1β, IL-6, and TNF-α levels in the serum and downregulated TLR4, MyD88, and phosphorylation of IκBα, P65, and IRF3 in the colon tissue from AOM/DSS-induced mice. In vitro, GQD suppressed pro-inflammatory cytokines and TLR4 signaling pathway in the LPS-induced RAW264.7 cells, and combined with TAK242, it further reduced the phosphorylation of IκBα, P65. Conclusions: GQD mitigated CAC by inhibiting the TLR4 signaling pathway, offering a potential therapeutic approach for CAC management. Full article

Background/Objectives: The primary method used to pharmacologically arrest cancer development and its metastasis is to disrupt the cell division process. There are a few approaches that may be used to meet this objective, mainly through inhibiting DNA replication or mitosis. Despite intensive studies on new chemotherapeutics, the biggest problem remains the side effects associated with the inhibition of cell division in non-tumoural host cells. Methods: The efficacy and selectivity of the kojic acid derivative (L1) was studied in vitro with the use of tumoural (Caco2, SW480, HT29, T98G) and non- tumoural (HEK293T, RAW) cell lines. Light and electron microscopy observations were supported by the next generation sequencing (NGS), cytoflow, and spectroscopy analysis of mRNA and biomolecules, respectively. Results: The light and electron microscopy observations showed that L1 treatment leads to significant morphological changes in Caco2 cells, which are characteristic of mitosis arrest. Moreover, the fluorescent tubulin staining revealed the formation of tubulin ring structure associated with the apoptotic stage. Mitotic exit into apoptosis was further conformed by the cytoflow of early/late apoptosis stages and caspase-3 analysis. NGS investigation showed differentiated expressions of genes involved in mitosis and apoptosis processes. The observed IC50 in tumoural cell lines were as follows: Caco2 (IC50 = 68.2 mM), SW480 (IC50 = 15.5 mM), and HT29 (IC50 = 4.7 mM). Conclusions: The findings presented here suggest that L1 could be a valid candidate for oral prevention and/or chemotherapy in colorectal cancer. Considering high selectivity of L1 versus tumoural cell lines, more in-depth mechanistic studies could reveal unknown stages in carcinogenesis. Full article

Background/Objectives: The relationship between lipid profiles, telomere length (TL), and cancer risk remains unclear. Methods: This study employed two-sample Mendelian randomization (MR) with mediation analysis to investigate their causal relationships, examining lipid profiles as exposure, TL as mediator, and nine cancer types as outcomes. We conducted our analysis using two-stage least squares (2SLS) regression integrated with inverse variance weighted (IVW) methods to address potential endogeneity and strengthen our causal inference. Results: we found that unfavorable lipid profiles were causally linked to increased TL (p < 0.05). TL showed positive causal associations with lung and hematologic cancers (OR > 1, p < 0.05). Direct associations were observed between total and low-density lipoprotein (LDL) cholesterol and gastric cancer (OR < 1, p < 0.05), and between remnant cholesterol and colorectal cancer (OR > 1, p < 0.05). Mediation analysis revealed TL as a significant mediator in the pathway from lipid profiles to cancer development (p < 0.05). No horizontal pleiotropy was detected. Conclusions: Our findings suggest that lipid metabolism disorders may influence cancer development through telomere regulation, particularly in lung and hematologic cancers. This emphasizes the importance of lipid management in cancer prevention and treatment, especially for these cancer types. Full article

Background: Antibiotics have recently been suggested to increase the risk of colorectal cancer. Here, we aimed to investigate the association of frequent antibiotic use and genetic susceptibility with the increased risk of the development of colorectal cancer. Therefore, a genome-wide association study was conducted in colorectal cancer patients with frequent antibiotic use and controls to identify potential chromosomal regions that could indicate an increased risk of colorectal cancer associated with antibiotic use. The results were replicated with a case-case analysis. Methods: A genome-wide case-control study involving 143 colorectal cancer cases with frequent exposure to antibiotics and 1642 healthy individuals with unknown antibiotic use was undertaken. A logistic regression model was used to identify associations between certain chromosomal regions (loci) and the risk of colorectal cancer in cases with frequent antibiotic use. The results were replicated in a follow-up association case-case study comparing the frequent users to those with a more modest use of antibiotics. Results: Six chromosomal regions were associated with colorectal cancer in patients exposed to frequent antibiotic use. Two of the six regions contained genes already suggested to be associated with colorectal cancer tumorigenesis, epithelial-mesenchymal transition and colorectal cancer recurrence. The results for the six chromosomal regions were further replicated in a case-case analysis where all the chromosomal regions were confirmed with high odds ratios (ORs) supporting the hypothesis that frequent antibiotic use is associated with an increased risk of colorectal cancer development. Conclusions: The study suggested that genetic modifiers could influence the risk of colorectal cancer associated with the frequent use of antibiotics. Full article

Colon cancer (CC) is the third most frequent neoplasm, with a considerably high mortality rate. Due to the side effects of conventional forms of CC treatment (surgery, chemotherapy, and radiotherapy), several studies have focused on the use of medicinal plant derivatives to provide a green therapy for CC; although phytochemicals have shown promising results against CC, translating the results obtained in vitro and in vivo to the clinical setting remains a challenge. Indeed, like other orally applied medicines, medicinal plant derivatives have to cross different physiological barriers to reach the CC microenvironment, which considerably limits their dose-dependent therapeutic efficacy. On the other hand, phytocompounds are not free from biopharmaceutical drawbacks, so novel strategies using nanoparticles (NPs) have been proposed to overcome the physiological barriers of the body and provide controlled release of actives of interest. Accordingly, the current review provides an overview and discussion on the predisposing factors to CC and conventional treatment, the use of medicinal plants in CC treatment, and the advantages provided by NPs in the treatment of CC. Full article

Colorectal cancer (CRC) is often associated with metastasis and recurrence and is the leading cause of cancer-related mortality. In the progression of CRC, recent studies have highlighted the critical role of neutrophils, particularly tumor-associated neutrophils (TANs). TANs have both tumor-promoting and tumor-suppressing activities, contributing to metastasis, immunosuppression, angiogenesis, and epithelial-to-mesenchymal transition. Tumor-promoting TANs promote tumor growth by releasing proteases, reactive oxygen species, and cytokines, whereas tumor-suppressing TANs enhance immune responses by activating T cells and natural killer cells. Understanding the mechanisms underlying TAN mobilization, plasticity, and their role in the tumor microenvironment has revealed potential therapeutic targets. This review provides a comprehensive overview of TAN biology in CRC and discusses both the tumor-promoting and tumor-suppressing functions of neutrophils. Novel therapeutic approaches targeting TANs, such as chemokine receptor antagonists, aim to modulate neutrophil reprogramming and offer promising avenues for improving treatment outcomes of CRC. Full article

Background: Whether colorectal cancer (CRC) screening with a fecal immunochemical test (FIT) reduces mortality remains unclear. In South Korea, CRC screening with a FIT for individuals aged ≥ 50 years has been part of the Korean National Cancer Screening Program (KNCSP) since 2004. The aim of this study was to evaluate the effectiveness of the KNCSP in reducing CRC-specific mortality. Methods: We conducted a nested case-control study using cohort-based data derived from the KNCSP database. The cohort included 5,944,540 colorectal cancer-free individuals aged ≥ 50 years as of 2004. Individuals who died after CRC diagnosis were defined as cases (n = 29,992) and their sociodemographic characteristics were matched to those of the selected controls. The effects of screening exposure, frequency, and time interval on CRC-specific mortality were analyzed according to age group. Conditional logistic regression analysis was performed. Results: Compared with individuals who had never been screened, those who had ever been screened showed an OR of 0.74 (95% CI, 0.71–0.76) for CRC-specific mortality. CRC-specific mortality decreased as the number of screenings increased. Similar results were observed for those aged 50–79 years; however, the results for those aged 75–79 years were not statistically significant. Moreover, those aged ≥ 80 years had the opposite results. Conclusions: CRC mass screening using FIT is effective for individuals aged 50–74 years; therefore, this study suggests that countries considering introducing national CRC screening implement FIT for those within this age range. Full article

Epidermal growth factor receptor (EGFR) inhibition is crucial in treating RAS wild-type metastatic colorectal cancer, yet current testing methods may miss rare RAS variants affecting treatment efficacy. We analyzed 4122 colorectal cancer patients receiving anti-EGFR antibodies from the Center for Cancer Genomics and Advanced Therapeutics database, identifying 54 patients (1.3%) with rare RAS variants undetectable by standard testing. These patients showed significantly lower response rates to anti-EGFR therapy (28.3%) compared to RAS wild-type cases (44.6%, p = 0.003). Disease control rates were also lower in rare variant cases (60.9%) versus wild-type cases (80.0%). Most common rare variants included KRAS Q22K, A59E, and A11_G12insGA. Comprehensive genomic profiling revealed additional alterations in TP53 (90.7%), APC (87.0%), and non-V600E BRAF mutations (25.9%). Our findings suggest that rare RAS variants predict poor anti-EGFR therapy response, highlighting the potential benefit of comprehensive genomic profiling before treatment initiation. This study provides real-world evidence supporting the clinical relevance of rare RAS variants in treatment decision-making for colorectal cancer. Future studies should focus on developing cost-effective comprehensive testing strategies and evaluating alternative treatment approaches for patients with rare RAS variants. Full article

Background: Recent advancements in understanding plasma extracellular vesicles (EVs) and their role in disease biology have provided additional unique insights into the study of Colorectal Cancer (CRC). Methods: This study aimed to gain biological insights into disease progression from plasma-derived extracellular vesicle proteomic profiles of 80 patients (20 from each CRC stage I–IV) against 20 healthy age- and sex-matched controls using a high-resolution SWATH-MS proteomics with a reproducible centrifugation method to isolate plasma EVs. Results: We applied the High-Stringency Human Proteome Project (HPP) guidelines for SWATH-MS analysis, which refined our initial EV protein identification from 1362 proteins (10,993 peptides) to a more reliable and confident subset of 853 proteins (6231 peptides). In early-stage CRC, we identified 11 plasma EV proteins with differential expression between patients and healthy controls (three up-regulated and eight down-regulated), many of which are involved in key cancer hallmarks. Additionally, within the same cohort, we analysed EV proteins associated with tumour recurrence to identify potential prognostic indicators for CRC. A subset of up-regulated proteins associated with extracellular vesicle formation (GDI1, NSF, and TMED9) and the down-regulation of TSG101 suggest that micro-metastasis may have occurred earlier than previously anticipated. Discussion: By employing stringent proteomic analysis and a robust SWATH-MS approach, we identified dysregulated EV proteins that potentially indicate early-stage CRC and predict recurrence risk, including proteins involved in metabolism, cytoskeletal remodelling, and immune response. While our findings underline discrepancies with other studies due to differing isolation and stringency parameters, they provide valuable insights into the complexity of the EV proteome, emphasising the need for standardised protocols and larger, well-controlled studies to validate potential biomarkers. Full article

Background: Although genetic testing has improved our ability to diagnose Lynch syndrome (LS), there is still limited information on the extent of variations in the clinical and genetic landscape among LS variant heterozygotes (LSVH) in Africa. We sought to investigate the cancer spectrum, cumulative risk, and survival outcomes of LSVH with pathogenic/likely pathogenic variants (P/LPVs) in the MLH1 and MSH2 genes using a LS registry in South Africa over the last 30 years. Methods: A retrospective study was conducted to retrieve demographic, clinical, and genetic data of all LSVH with P/LPVs in the MLH1 and MSH2 genes from our LS registry. Genetic data were analyzed according to cancer spectrum, cumulative risk, and crude survival. We used the Chi-squared and t-test to assess differences between groups, and Kaplan–Meier survival analyses were used to analyze the cumulative risk and crude survival outcomes. A p-value < 0.05 at a 95% confidence interval was considered statistically significant. Results: We analyzed a total of 577 LSVH from 109 families. About 450 (78%) and 127 (22%) LSVH harbored a disease-causing mutation in MLH1 and MSH2, respectively. A South African founder PV (MLH1:c.1528C>T) accounted for 74% (n = 426) of all LSVH. CRC was the most common diagnosed cancer in both MLH1 and MSH2 LSVH. MLH1 LSVH had a younger age at cancer diagnosis than MSH2 LSVH (43 vs. 47 years, respectively, p = 0.015). Extracolonic cancers were predominantly higher in female LSVH (n = 33, 35%) than in male LSVH (n = 8, 7%) with the MLH1:c.1528C>T founder PV. The cumulative risk of any cancer and CRC at any age was higher in MLH1 LSVH than in MSH2 LSVH (p = 0.020 and p = 0.036, respectively). LSVH with the MLH1:c.1528C>T PV had a better 10-year overall survival after the first cancer diagnosis, particularly for CRC. Conclusions: LSVH with P/LPVs in the MLH1 and MSH2 genes exhibited significant gene- and sex-specific differences in cancer spectrum, cumulative risk and survival outcomes. Cancer risk and survival estimates described in this study can be used to guide surveillance and genetic counselling for LSVH in our population. Full article