Search Results (10,636)

Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA in blood, has emerged across multiple cancers as a minimally invasive precision biomarker to detect minimal residual disease (MRD); predict recurrence; and monitor treatment response. This review’s objective was to summarize recent advances in ctDNA as a tool for therapeutic decision-making in MCC, contextualized by findings in other malignancies. Methods: A comprehensive literature review was performed, focusing on studies published between 2016 and 2026 that evaluate ctDNA in MCC and other cancers. Key prospective trials, observational studies, and case reports were identified through PubMed and relevant conference proceedings. Data on ctDNA assay methods (tumor-informed vs. tumor-agnostic), clinical sensitivity, lead time for recurrence detection, and predictive value for therapy response were extracted and synthesized. Results: Across cancers such as colorectal, lung, and melanoma, ctDNA positivity after curative treatment predicts relapse months in advance of imaging and can guide adjuvant therapy decisions. In MCC, recent studies demonstrate that ctDNA levels correlate with MCC tumor burden and exhibit high sensitivity and specificity for clinically evident disease. Stage I-III MCC patients who were ctDNA-positive within four months of treatment had a 7.4-fold higher recurrence risk within the subsequent 12–18 months of follow-up. Serial ctDNA monitoring may enable earlier intervention in otherwise asymptomatic ctDNA-positive MCC cases, helping distinguish responders from non-responders. Conclusions: ctDNA is an emerging precision biomarker that offers significant prognostic and surveillance utility in MCC. It enables earlier detection of recurrence, potentially allowing treatment to begin before clinical disease manifests. It also helps stratify patients by risk and treatment response, informing personalized surveillance intensity and therapeutic choices. Integrating ctDNA monitoring into MCC management could improve outcomes by guiding timely interventions, although prospective trials are needed to confirm that ctDNA-guided decisions translate to improved patient survival. Formal cost-effectiveness analyses have not yet been conducted and represent an important area for future investigation. Full article

Colorectal cancer is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths, while its resistance to treatment continues to represent a major therapeutic challenge. In the present study, a series of phenothiazine derivatives, including hybrids containing a 1,2,3-triazole linker and the zidovudine (AZT) fragment, were synthesized and evaluated for their anticancer activity against colorectal cancer cell lines HCT116 and HT-29 as well as non-cancerous BEAS-2B cells. Cytotoxic activity was determined using the Alamar Blue assay, while the mechanisms of action were investigated by flow cytometric analysis of apoptosis, cell cycle progression, and reactive oxygen species (ROS) generation. Additionally, changes in the expression of genes associated with apoptosis, oxidative stress, and DNA damage response were analyzed by RT-qPCR. The obtained results demonstrated that AZT-containing derivatives exhibited stronger anticancer activity than non-conjugated phenothiazine analogs. Compounds A9–A12 induced pronounced apoptosis and significant disturbances in cell cycle progression, particularly in HCT116 cells. Among the analyzed derivatives, compound A9 displayed the most favorable overall biological profile, combining strong proapoptotic and cytotoxic activity with relatively high selectivity toward cancer cells and moderate effects on non-cancerous cells. The results indicate that molecular hybridization of phenothiazine derivatives with the AZT scaffold represents a promising strategy for the development of novel anticancer agents targeting colorectal cancer. Full article

Background/Objectives: The stool DNA-based SDC2 methylation (meSDC2) test has emerged as a promising noninvasive tool for the early detection of colorectal cancer (CRC). This study aimed to validate the clinical performance of the meSDC2 test for CRC detection in a multicenter hospital setting. Materials and Methods: This prospective, retrospective, multicenter, single-blind, case–control study was conducted at three tertiary medical centers. The primary endpoints were sensitivity and specificity for CRC detection. Secondary endpoints included test performance by tumor stage and location, and positivity rates in non-CRC lesions. Results: Among 636 participants, 260 (40.9%) had CRC, 173 (27.2%) had colorectal polyps, and 182 (28.6%) had normal colonoscopy findings. The meSDC2 test demonstrated a sensitivity of 87.7% (95% CI: 83.7–91.7%) and a specificity of 86.2% (95% CI: 82.7–89.7%) for CRC detection, with an AUC of 0.869 (95% CI: 0.841–0.895). Specificity among participants with negative colonoscopy findings was 91.8%. Positivity rates were 28.3% (95% CI: 15.3–41.3%) for advanced adenomas and 13.8% (95% CI: 6.6–21.0%) for non-advanced adenomas. Compared with the fecal immunochemical test (FIT), the meSDC2 test showed significantly higher sensitivity, whereas FIT demonstrated higher specificity. Combined testing improved sensitivity to 95.6% and 82.4% specificity. The meSDC2 test also showed significantly greater sensitivity than FIT for early-stage CRC (p = 0.037), while combined testing further improved sensitivity for both early- and late-stage CRC(p = 0.037 and p = 0.006, respectively). Conclusions: The stool-based meSDC2 test demonstrated high sensitivity, specificity, and consistent diagnostic performance across subgroups, supporting its clinical utility as a reliable and noninvasive CRC screening tool. Full article

Lavandula dentata is a medicinal and aromatic plant rich in specialised secondary metabolites, but the biomedical potential of leaf-surface metabolites recovered from pruning biomass remains poorly investigated. In this study, a pruning-derived leaf-surface extract of L. dentata was obtained by brief acetone immersion followed by n-hexane partitioning. Its chemical profile was investigated by ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry analysis combined with feature-based molecular networking, which revealed an enrichment in methoxylated flavonoids and pentacyclic triterpenes, including oleanane- and ursane-like derivatives. The biological activity of the extract was evaluated in HCT116 colorectal cancer cells, MDA-MB-231 triple-negative breast cancer cells, and HaCaT keratinocytes. After 24 h treatment, the extract selectively reduced HCT116 cell viability in a concentration-dependent manner, with an IC₅₀ of 27.8 ± 1.049 μg/mL, whereas MDA-MB-231 and HaCaT cells were less sensitive. Mechanistic analyses in HCT116 cells showed increased early and late apoptotic populations, mitochondrial membrane depolarisation, and enhanced cleavage of caspase-9, caspase-3, and PARP. These findings indicate that a chemically profiled L. dentata leaf-surface extract selectively impairs colorectal cancer cell survival by activating mitochondria-mediated apoptosis. The study also supports the valorisation of pruning-derived aromatic plant biomass as a source of bioactive natural products with potential biomedical relevance. Full article

Background and Objectives: Sessile serrated lesions (SSLs) are increasingly recognized as relevant precursors in alternative pathways of colorectal carcinogenesis, yet their endoscopic recognition remains challenging. Materials and Methods: We conducted a systematic review of studies reporting endoscopic and patient-related features associated with SSLs. PubMed/MEDLINE was searched for studies published between 2003 and November 2025. Eleven studies including 13,453 participants were identified. Results: Frequently reported endoscopic hallmarks included proximal colon location, larger lesion size, flat or slightly elevated morphology, indistinct borders, mucous cap, cloud-like surface, and pit-pattern features consistent with Kudo/Fujii types III–IV. Considerable heterogeneity in definitions and analytical reporting was observed. Conclusions: Although several features may raise suspicion for SSLs, standardized evidence remains limited, supporting a cautious and comprehensive approach to polyp assessment. Full article

Colorectal cancer (CRC) has been increasingly associated with gut microbiota dysbiosis and the presence of specific bacterial pathogens. This study evaluated the in vitro growth-inhibitory activity of 18 biologically active compounds, including phytochemicals, synthetic analogs, and clinically used antibiotics, against CRC-associated bacterial strains. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method and analyzed in relation to chemical structure. Conventional antibiotics, particularly tetracycline and ciprofloxacin, exhibited the strongest antibacterial activity. Among non-antibiotic compounds, nitroxoline and carbadox showed moderate activity, whereas quaternary benzylisoquinoline-derived alkaloids and polyphenols were less effective. Structure–activity relationship analysis suggested that aromatic heterocyclic scaffolds, electron-withdrawing substituents, and metal-chelating groups contribute to antibacterial potency. We obtained novel MIC data for several compounds, including ferron and oxyquinoline, against underexplored CRC-associated bacterial strains. These findings expand current knowledge of the antibacterial activity of structurally diverse compounds against CRC-associated bacteria and provide a basis for future studies on microbiota-targeted antimicrobial strategies. Full article

Andean berry (Vaccinium meridionale Swartz) is an underutilized fruit that could serve as a source of bioactive compounds with biological properties associated with apoptosis and cytotoxicity in colorectal cancer cells. This study aimed to evaluate the cytotoxic and proapoptotic effects of Andean berry juice (ABJ) in human SW480 and SW620 colon cancer cell lines, which represent early-stage and metastatic colorectal cancer, respectively. The juice was prepared from freeze-dried fruits, and several concentrations were assayed in cells. Bioactive compounds in ABJ showed the strongest reductions in metabolic activity and proliferation observed in SW620 cells. ABJ treatments promoted early apoptosis while inducing cell cycle arrest in the S phase (SW480) and in the G2/M (SW620). Mild mitochondrial depolarization was observed, while increased reactive oxygen species (ROS) accumulation was detected in both cell lines. More proteins involved in the apoptotic process were modulated in SW620 cells, whereas SW480 displayed greater fold changes in regulatory and stress-response proteins. Proteomics and bioinformatics analyses suggested that extrinsic apoptosis predominated in SW480 cells, whereas intrinsic apoptosis was observed in SW620 cells. These results highlighted the cytotoxic and pro-apoptotic potential of the combined activity of polyphenolic compounds from ABJ, demonstrating distinct mechanisms in vitro. Full article

Background: Frailty is associated with adverse postoperative outcomes and functional decline in older adults undergoing colorectal cancer (CRC) surgery. The long-term course of frailty and functional outcomes among patients undergoing prehabilitation before CRC surgery remains insufficiently investigated. Methods: This prospective observational cohort study evaluated long-term functional and physiological outcomes in older adults with frailty syndrome undergoing colorectal cancer (CRC) surgery who participated in a structured prehabilitation program. Forty-one patients aged >70 years were assessed before prehabilitation and at one-year follow-up. Frailty (the Clinical Frailty Scale [CFS] and the 5-item Frailty Index [5-FI]), physical activity, postural function, respiratory parameters, and functional performance (the 6 min walk test [6MWT] and the Timed Up and Go [TUG] test) were evaluated. Results: Of the 93 eligible patients, 41 completed the one-year follow-up and were therefore included in the final analysis. A small but statistically significant increase in frailty was observed using 5-FI (mean difference = 0.029, p = 0.012), with no significant change in CFS. Postural function improved (p = 0.031), while physical activity and functional performance remained stable (6MWT: 392.71 vs. 384.36 m, p = 0.885; TUG: 12.36 vs. 10.42 s, p = 0.051). A significant reduction in pre- and post-exercise oxygen saturation was observed; however, the magnitude of change (before: −1.25%, p = 0.006; after: −0.91%, p < 0.001) was small and of uncertain relevance. Conclusions: Over a one-year follow-up of prehabilitated CRC patients with frailty, their functional performance remained stable despite a subtle progression of frailty. These findings suggest a dissociation between physiological vulnerability and functional status. Due to the observational design of the study and the lack of a control group, the results should be interpreted as descriptive rather than causal. Full article

Insulin resistance (IR) is traditionally viewed within the context of type 2 diabetes. However, it increasingly appears to represent a broader systemic metabolic risk state with potential relevance for carcinogenesis. Chronic hyperinsulinemia can activate insulin-like growth factor-1-dependent pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinase signaling, promoting cellular proliferation while limiting apoptosis. At the same time, IR is closely linked to oxidative stress, chronic low-grade inflammation, and epigenetic alterations, together shaping a tumor-promoting microenvironment. Epidemiological studies report consistent associations between IR and increased cancer risk, particularly for endometrial, liver, and colorectal cancers. Yet causality remains uncertain and likely varies by tumor type. Notably, metabolic dysfunction may also occur in individuals with normal body mass index (BMI), underscoring the limitations of BMI-based risk assessment. Unlike previous reviews that primarily focused on individual mechanisms or epidemiological associations, this review examines IR as a systemic metabolic risk state by integrating molecular, epidemiological, biomarker-based, and prevention-oriented perspectives. Particular emphasis is placed on strategies for earlier risk identification using integrated biomarker approaches, including fasting glucose, homeostatic model assessment of insulin resistance, triglyceride-to-high-density lipoprotein ratio, high-sensitivity C-reactive protein, and insulin-like growth factor-1. Emerging tools such as continuous glucose monitoring and hepatokine profiling may further refine risk detection. Sustained lifestyle modification—diet, physical activity, sleep, and stress regulation—remains central to prevention. Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and dual incretin agents, offer additional metabolic benefits, although their long-term impact on cancer risk is still unclear. Therefore, IR is best understood not as an isolated risk factor, but as a systemic metabolic risk state that may influence cancer development, with implications for prevention and early risk stratification. Full article

An undescribed seco-kaurane diterpenoid, benincaside A (BA), was isolated from the seeds of Benincasa hispida. The seeds of B. hispida have been traditionally used in folk medicine and previous studies have reported anti-tumor potential in B. hispida seed extracts. Accordingly, we investigated the cytotoxicity and underlying mechanisms of BA in colorectal cancer cells. BA inhibited growth in HT29, Colo205, HCT116, and CT26 colorectal cancer cells, as determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while showing no toxicity toward normal human umbilical vein endothelial cells (HUVEC) and human fibroblast WS-1 cells. In HCT116 cells, BA-induced deoxyribonucleic acid (DNA) damage and apoptosis, as evidenced by morphological changes, 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, and assays of caspase-8 and caspase-3 activities. BA triggered apoptotic cell death via the extrinsic pathway, as indicated by elevated caspase-8 and caspase-3 activities. Intracellular reactive oxygen species (ROS) generation was observed in BA-treated HCT116 cells. The growth-inhibitory effects were significantly attenuated by pretreatment with N-acetylcysteine (NAC, an antioxidant), caffeine (an ATM kinase inhibitor), z-VAD-fmk (pan-caspase inhibitor), or z-IETD-fmk (caspase-8-specific inhibitor). Colorimetric assays confirmed increased caspase-8 and caspase-3 activities in BA-treated cells. This study is the first to report ROS-dependent signaling as a key mechanism underlying BA-induced cell death in HCT116 human colorectal cancer cells. Full article

Background: Colorectal neuroendocrine carcinomas (NECs), including small cell (SCNEC) and large cell (LCNEC) subtypes, are rare but aggressive malignancies with limited population-level data. Moreover, prior studies have limited stratification by histologic subtype and anatomic location, despite evidence of disease heterogeneity in colorectal malignancies. This study aimed to characterize the clinical characteristics, treatment patterns, and outcomes of colorectal NEC by histologic subtype and tumor location, and to compare them with neuroendocrine tumors (NETs) and adenocarcinomas (ACs). Methods: A retrospective cohort review was conducted utilizing the SEER database from 2000 to 2022 to identify patients with colorectal SCNEC, LCNEC, NET, and AC. Demographic, clinical, therapeutic and survival data were analyzed and compared using Kaplan–Meier methods, log-rank tests, and Cox proportional hazards regression. Results: A total of 790 SCNEC, 498 LCNEC, 31,200 NET, and 638,898 AC cases were identified. SCNEC and LCNEC were associated with advanced stage at diagnosis (66% and 55% stage IV, respectively) and inferior survival outcomes compared to NET and AC (median OS (mOS) of 7 and 8 months for SCNEC and LCNEC, respectively, p = 0.0002). Stratified by location, colonic SCNEC had the poorest survival (mOS 5 months), worse than rectal SCNEC (mOS 9 months); this pattern was not observed in LCNEC. Surgical resection was associated with improved OS in both NEC subtypes (HR range 0.25–0.56, all p < 0.012). Radiation therapy was associated with improved survival in NEC overall (SCNEC HR 0.58; LCNEC HR 0.71, both p < 0.05), with the observed benefit appearing greatest in rectal NEC. Demographic factors were associated with survival in NET and AC but had no significant impact in NEC. Conclusions: Colorectal SCNEC and LCNEC are highly aggressive malignancies with poor outcomes, with SCNEC demonstrating modestly inferior outcomes compared to LCNEC. This study demonstrates that both histologic subtype and anatomic site of disease are important determinants of prognosis and treatment response. This supports the concept that colorectal NEC represents a biologically heterogeneous disease, with colonic SCNEC showing the worst outcomes and rectal NEC associated with a potential enhanced response to radiation. These findings support the need for further prospective and molecular studies to better define treatment approaches and targeted therapies for these rare malignancies. Full article

Modern computational biology is increasingly applied in preclinical studies, and mathematical models can provide valuable insights into biological system behavior. Numerical modeling tools can significantly and rapidly help in predicting the cellular response to different treatments, numerous newly synthesized compounds tested on different model systems. This study is devoted to the application of a biphasic numerical model to explain and predict the behavior of colorectal carcinoma cell lines in investigated co-treatments. The model was used to estimate parameters related to cell proliferation and death and to predict cellular behavior through the determination of treatment efficiency and effectiveness. This study showed that the experimental results can be mathematically confirmed, and the data for the most effective treatment can be obtained. The most efficient co-treatment concentration was identified by the model as the condition associated with the lowest proliferation-related parameter and the greatest reduction in cell viability. The model indicated that the most efficient concentration does not appear to induce a rapid adaptive cellular response and may therefore represent a suitable candidate for subsequent treatment cycles. The model suggests that the investigated treatments may have limited therapeutic potential in both cell lines due to the sustained viability of rapidly proliferating cells and evidence of continued de-differentiation. Full article

The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in metabolic, gastrointestinal, hepatic, cancer, and neuroimmune conditions, including MASLD/MASH, inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes, hypertension, colorectal cancer, Parkinson’s disease, and autism spectrum disorder. Across these conditions, microbiome findings are biologically plausible but heterogeneous. Many associations are shaped by diet, geography, medication exposure, host genetics, disease stage, sampling methods, and analytical pipelines. Microbial alterations should therefore be interpreted as context-dependent signals and candidate modifiers rather than universal causal markers. Conventional microbiota targeted strategies include diet, physical activity, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These approaches are clinically familiar, but their effects are often broad, host specific, strain dependent, and difficult to assign to one mechanism. Fecal microbiota transplantation has the clearest clinical role in recurrent Clostridioides difficile infection, while evidence for most other indications remains inconsistent. Engineered microbial therapeutics offer greater experimental precision through signal sensing, payload delivery, metabolic modulation, and genetic circuit design. However, most evidence remains preclinical or early translational. Progress requires stronger human trials, standardized methods, mechanistic validation, safety monitoring, ecological containment, transparent reporting, and proportionate regulation. Full article

Colorectal cancer (CRC) is intricately linked to gut microbiota dysbiosis and tryptophan (Trp) metabolic dysregulation. This study aimed to clarify the role and mechanisms of 20(S/R)-ginsenoside Rh1 in suppressing colorectal cancer through the regulation of gut microbiota and Trp metabolism. Azoxymethane/dextran sulfate sodium (AOM/DSS)was employed to induce a CRC mouse model, followed by treatment with 20(S/R)-ginsenoside Rh1 at 100 mg·kg⁻¹·day⁻¹ for 6 weeks. 20(S/R)-ginsenoside Rh1 significantly reduced the disease activity index (DAI) score, restored colon length, and decreased tumor count. 20(S/R)-Ginsenoside Rh1 ameliorated gut dysbiosis by increasing gut microbial diversity and elevating the prevalence of beneficial bacteria, including Lactobacillus, and stimulated the production of indole derivatives, including indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), and indole-3-lactic acid (ILA) by enriching Trp -metabolizing bacteria such as Lactobacillus reuteri. These changes further activated the AhR/CYP1A1/IL-22 and PXR/TLR4 pathways, upregulated the expression of intestinal tight junction proteins, suppressed the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IFN-γ, and elevated the levels of the anti-inflammatory cytokine IL-10. Furthermore, 20(S/R)-ginsenoside Rh1 reduces the serum kynurenine (Kyn)/Trp ratio, downregulates the expression of forkhead box P3 (FoxP3), a marker of regulatory T (Treg) cells, and increases the number of CD8⁺ T cells by inhibiting the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in colonic tissue. In conclusion, 20(S/R)-ginsenoside Rh1 showed potential anti-CRC activity, with our study observing links between its action and gut microbiota structure regulation, Trp metabolism modulation, AhR/PXR-mediated intestinal barrier activation, and IDO1-related immune suppression reversal. Full article

Adult intussusception is an uncommon condition that usually indicates an underlying pathological lead point. Ileal perineurioma is an exceptionally rare benign peripheral nerve sheath tumor with limited gastrointestinal reports. We describe a 59-year-old woman presenting with acute severe abdominal pain, vomiting, and distension. Contrast-enhanced computed tomography demonstrated ileal intussusception with small-bowel obstruction. Emergency laparotomy confirmed terminal ileal intussusception, and segmental resection was performed. Histopathological evaluation revealed a spindle-cell neoplasm with characteristic pseudo-onion bulb architecture. Immunohistochemistry showed strong positivity for epithelial membrane antigen (EMA) and Glucose Transporter-1 (GLUT-1), while other markers were negative, confirming perineurioma. The postoperative course was uneventful, with no recurrence on follow-up. This case highlights ileal perineurioma as a rare but important differential diagnosis in adult small-bowel intussusception, with definitive diagnosis reliant on histopathological and immunohistochemical evaluation. Full article