Search Results (5,294)

Colorectal cancer is the third most commonly diagnosed cancer worldwide, and early detection of polyps via colonoscopy is essential for improving patient survival. However, automatic polyp segmentation faces three key challenges: balancing global context with local detail, delineating ambiguous boundaries under low contrast, and handling large variations in polyp size and morphology. To address these challenges, we propose WMA-Net, a Wavelet-Guided Mamba-Attention Network that uses wavelet-domain semantic–boundary separation as the organizing design principle. Rather than introducing a new individual operator, the contribution lies in how existing components—wavelet decomposition, Mamba state space modeling, multi-directional pixel difference convolution, and uncertainty-aware reverse attention—are combined and coordinated within one boundary-aware framework. The architecture integrates pixel difference convolution for multi-directional edge detection, frequency-selective cross-scale fusion with dual-stream wavelet-domain processing, Mamba-based multi-scale aggregation with linear complexity, and uncertainty-aware progressive boundary refinement. Extensive experiments on five public polyp benchmarks demonstrate state-of-the-art performance on four out of five datasets. On the seen datasets, WMA-Net achieves mean Dice scores of 94.4% on CVC-ClinicDB and 93.6% on Kvasir-SEG. On the unseen datasets, WMA-Net attains 91.7% on CVC-300, 82.3% on CVC-ColonDB, and 83.8% on ETIS-LaribPolypDB, demonstrating robust cross-dataset generalization. Comprehensive ablation studies validate the effectiveness and synergy of each proposed module. Full article

Inflammatory bowel diseases, particularly ulcerative colitis (UC), are chronic relapsing inflammatory disorders with limited therapeutic options. The zinc-finger transcription factor ZBTB4 has been implicated in the initiation and progression of cancer, but its role in UC remains unknown. Here, we found that ZBTB4 deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in C57BL/6J male mice. Compared with the wild type, ZBTB4 deficiency increases weight loss, colon shortening and proinflammatory cytokine production. RNA-seq analysis revealed that ZBTB4 deficiency enhances Serpine1 expression and activates the NF-κB pathway. NF-κB inhibition by JSH-23 alleviated the effect of ZBTB4 deficiency on DSS-induced colitis. These results imply the protective role of ZBTB4 in UC. Through an integrated drug screening, we identified a natural sesquiterpene lactone, handelin, as a potential compound to enhance ZBTB4 expression in NCM460 cells. Handelin administration relieved colitis in wild-type mice but produced no effect in ZBTB4 knockout mice, demonstrating that its anti-colitic effect depends on ZBTB4 expression. Collectively, our results indicate the key role of ZBTB4 in UC and ZBTB4 agonists may serve as a novel approach for UC treatments. Full article

Background: Cannabinoids are studied as anticancer agents, but their effects vary across tumors, compounds, and experimental settings, underscoring the need to define consistent patterns. Our objective was to map cannabinoid efficacy across cancer preclinical models and identify tumor settings with the greatest translational promise. Methods: The protocol was registered on PROSPERO (CRD42025543744); PubMed, Embase, and CENTRAL were searched on 4 April 2024 for in vitro and in vivo studies assessing cannabinoid antitumor effects alone or with chemotherapy versus vehicle or chemotherapy only. Random-effects models yielded pooled mean differences (MD) with 95% confidence intervals (CI). MDs of viable cells were calculated for in vitro assays and tumor volume (mm³) for in vivo studies. Reports of various compounds, cannabidiol (CBD), tetrahydrocannabinol (THC) or synthetic cannabinoids, were pooled. Results: We included 189 studies in the final analysis. In vitro, cannabinoids reduced cell viability modestly overall, with significant effects in glioblastoma (MD −18.77 [CI: −27.15; −10.39]) and a nonsignificant trend in breast cancer (MD −6.75 [CI: −13.90; 0.40]). For in vivo, monotherapy showed the most consistent efficacy in glioblastoma, significantly reducing tumor volume by MD −980.58 mm³; [CI: −1270.2; −690.88]. Addition to temozolomide produced a favorable but nonsignificant decrease of MD −220.65 mm³; [CI: −579.34; 138.03, vs. temozolomide]. In breast cancer, cannabinoids achieved smaller yet significant tumor reductions (MD −402.64 mm³); [CI: −671.84; −133.45]. Synthetic agents had the largest effect (MD −1295.19 mm³); [CI: −1664.33; −928.05] -CBD plus doxorubicin vs. doxorubicin). Lung cancer (MD −562.17 mm³); [CI: −693.99; −430.35] and prostate cancer (MD −1136.59 mm³); [95% CI: −1320.97; −952.21] also had a significant response, whereas colon, pancreatic, and hepatocellular carcinoma models showed inconsistent or null responses. Conclusions: Cannabinoids show promise as adjuncts in oncotherapy, particularly in glioblastoma and breast cancer, to enhance chemotherapy efficacy. These findings should be interpreted with caution given the high inter-study heterogeneity typical of preclinical research and should be considered hypothesis-generating, warranting further validation in standardized and clinically relevant models. Full article

Background: Plants of the genus Nepeta are widely used in ethnomedicine for treating inflammatory disorders due to their rich content of bioactive compounds. This study investigated how extraction temperature specifically affects the bioactive potential of aqueous extracts from wild-grown Nepeta nuda L. Methods: The previously used maceration approach for this plant was applied at 30–60 °C to flowers, leaves, and stems. Phytochemical profiling included spectrophotometric assays, metabolite identification, and quantification. Biological activities reported for this plant were assessed, including antioxidant, anti-inflammatory, antiviral, antiproliferative, and antibacterial capacities. Results: Extraction yield was highest in flowers and leaves, where it increased significantly with rising temperature, while stems were less productive. All plant organs exhibited notable bioactivity falling into two groups: lower temperatures (30 and 40 °C) were optimal for antiviral and anti-inflammatory effects, whereas and higher temperatures (50 and 60 °C) enhanced antioxidant potential. The phytochemical composition, evaluated at representative extraction temperatures, revealed differential accumulation of p-coumaric acid and luteolin in all organs at 40 °C, while extraction at 60 °C corresponded to elevated levels of phenolic compounds. Flower extracts were confirmed to have the richest metabolic composition and were therefore subjected to further investigation. Extracts obtained at 40 °C influenced C1q binding, supporting their anti-inflammatory activity, whereas extraction at 60 °C resulted in stronger antiproliferative activity in colon cancer cell line. Antibacterial effects were similar at both temperatures. Conclusions: These findings highlight the importance of optimizing extraction conditions for future pharmacological applications of N. nuda. Full article

Background/Objectives: Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide and a leading cause of cancer-related mortality. Surgical resection remains the cornerstone of curative treatment. Over the past two decades, robotic-assisted surgery has emerged as an evolution of minimally invasive surgery, aiming to overcome several limitations of conventional laparoscopy. This narrative review summarizes the current state of the art of robotic surgery in CRC. Methods: A narrative review of the literature was conducted using PubMed/MEDLINE and Scopus databases, focusing on publications from 2015 to 2026. The review provides an overview of robotic platforms and summarizes the available clinical evidence. Priority was given to randomized controlled trials, meta-analyses, large observational studies, and clinical practice guidelines. The review focuses on major commercially available robotic systems, including the da Vinci^®, Hugo™ RAS, and Versius^® platforms, as well as emerging robotic technologies. Results: Robotic colorectal surgery showed potentially favorable perioperative and oncological outcomes compared with laparoscopy. In rectal cancer, robotic approaches were associated with improved total mesorectal excision quality, lower conversion rates, and improved postoperative functional outcomes. Emerging evidence also suggested potential improvements in disease-free survival and local disease control following robotic rectal surgery. In colon cancer, robotic colectomy were associated with lower conversion rates, reduced blood loss, and faster postoperative recovery, with comparable long-term oncological outcomes. However, robotic procedures showed longer operative times and higher procedural costs. Conclusions: Robotic colorectal surgery appears to be a safe and effective minimally invasive approach, particularly in rectal cancer surgery. The development of new robotic platforms and increasing market competition may improve cost sustainability and expand its future role in colorectal cancer management. Full article

The use of wheat bran (WB) to obtain functional meat products is a concept to be studied, due to sustainability issues and the nutritional advantages related to the decrease in caloric value, and the intake of phytonutrients, which can limit the incidence of diseases such as obesity, diabetes, or colon cancer. Beef meatballs with added wheat bran (5, 10, and 15%) were analyzed in terms of their physico-chemical parameters: pH, proximal composition, fiber content, caloric value and texture, antioxidant activity, fatty acids, amino acids, mineral content, and peroxide value. The fiber concentration in the meatballs increased proportionally with the WB addition. Although the antioxidant activity of the meatballs with WB was higher at the time of sample production, their stability proved to be weaker over time. The addition of wheat bran resulted in an overall decrease in amino acid concentrations and an increase in polyunsaturated fatty acid concentrations from 9.32 g/100 g to 14.36 g/100 g. For Mg, Ca, Mn, Cu, and Cr, there were significant increases between groups (p < 0.001), while Na and Zn decreased with the addition of wheat bran. The peroxide value (PV) and free acidity (FFA) decreased with the increase in the proportion of added fiber. The increase in the percentage of wheat bran also generated significant reductions (p < 0.001) for all textural parameters investigated. Including wheat bran in meatballs can present technical challenges related to composition cohesion and product shaping, as well as sensory acceptance. At the industrial scale, problems may arise related to the processing equipment, and the shaping of meatballs becoming difficult with the increased wheat bran addition. Full article

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), increase colorectal cancer (CRC) risk. Methods: Mouse IBD and CRC models with a combination of pharmacological, knockout and knock-in approaches was employed to analyze the involvement of TOP2s and NOS2 in CRC tumorigenesis. Key pathologies, such as inflammatory and neoplastic scores, were examined by immunohistochemical assays. Results: In colon tissues from acute, chronic colitis and CRC mouse models and from CD patients, the biomarkers γH2AX and 53BP1_pS25/S29 of DNA breaks (mainly representing DSBs) accumulated, alongside increases in topoisomerase II (TOP2) and nitric oxide synthase 2 (NOS2). Genetic ablation of NOS2 (Nos2^-/-) or TOP2β (Top2β^f/f) as well as pharmacological inhibition with ICRF-193 (a TOP2 inhibitor) or PTIO (a NO scavenger) reduced DSB formation and disease severity. Consistently, Nos2^-/-, or ICRF-treated, mice exhibited decreased tumor burden. DSBs and tumor accumulation were pronounced in the distal colon, mirroring human CRC distribution. While ICRF-193 suppressed tumor growth, Top2β^f/f deficiency (with a compensatory TOP2α upregulation) enhanced tumor development, indicating potential roles for TOP2 isozymes in tumor formation and progression. Conclusion: Collectively, these findings identify the cooperative action of TOP2 and NOS2 in driving DSBs, highlighting a potential therapeutic target in inflammation-associated CRC. Full article

CXCL14 is a highly conserved chemokine with potential roles in tumor progression and immune modulation. This study investigates the functional impact of CXCL14 on colon cancer by exploring its effects on tumor cell behavior and the immune microenvironment. We generated stable cell lines overexpressing CXCL14 in mouse MC38 and CT26 cells and human HCT15 colon cancer cells, and used these models to assess tumor growth, invasion, and immune cell infiltration. Our results demonstrate that CXCL14 suppresses colon cancer cell proliferation, migration, and metastasis. In vitro, CXCL14 inhibited the expression of matrix metalloproteinases (MMPs), key regulators of epithelial–mesenchymal transition (EMT), suggesting a role in promoting mesenchymal–epithelial transition (MET). Additionally, in vivo studies using a subcutaneous tumor model showed that CXCL14 not only suppressed tumor growth but also enhanced the infiltration of immune cells, including NK cells, dendritic cells (DCs), and T cells, converting the tumor microenvironment from a “cold” to a “hot” phenotype. RNA sequencing and pathway analyses revealed that CXCL14 regulates the expression of genes associated with angiogenesis, immune response, and cell signaling, particularly through the MAPK pathway. Furthermore, CXCL14’s influence on tumor progression was confirmed in a spleen-to-liver metastasis model, where its overexpression reduced metastatic spread. In conclusion, CXCL14 inhibits colon cancer progression by modulating both tumor cell behavior and the immune landscape, making it a promising candidate for targeted immunotherapy. Our findings highlight CXCL14’s potential to enhance anti-tumor immunity and provide new insights into its therapeutic applications in colon cancer. Full article

The maintenance of gastrointestinal homeostasis relies on a tightly coordinated interplay between the intestinal epithelium, the immune system, and the commensal microbiome. Disruption of this balance underlies inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, and is characterized by chronic, relapsing mucosal inflammation driven by genetic susceptibility, environmental factors, immune dysregulation, and microbial imbalance. Persistent inflammation promotes repeated cycles of epithelial injury and aberrant repair, creating a permissive environment for dysplasia and the development of colitis-associated cancer, most notably colorectal carcinoma. Recent evidence identifies the anti-apoptotic regulator myeloid cell leukemia-1 (Mcl1) as a critical determinant of epithelial integrity and cellular turnover during mucosal stress. Loss or destabilization of Mcl1 disrupts epithelial homeostasis, amplifies inflammatory signaling, and accelerates tumor initiation, whereas its adaptive upregulation in established malignancy promotes tumor cell survival, metabolic fitness, and therapeutic resistance. Thus, Mcl1 functions as a context-dependent molecular switch via restraining malignant transformation during chronic inflammation while supporting tumor progression once neoplasia is established. This functional duality positions Mcl1 as both a biomarker of disease progression and a therapeutically actionable vulnerability. In this review, we synthesize recent advances elucidating how Mcl1 integrates epithelial cell-fate decisions, immune signaling and tumor evolution across the IBD–cancer continuum. We further support these concepts through integrative analyses of multiple transcriptomic datasets comparing normal colonic mucosa with colorectal tumors, and we discuss emerging pharmacological strategies targeting Mcl1 in colitis-associated cancer. Full article

Background and Clinical Significance: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. Skeletal muscle metastases are extremely rare and typically occur in advanced or poorly differentiated tumors. In selected oligometastatic cases, surgical excision can provide symptom relief and requires a multidisciplinary approach. Case Presentation: We report a 73-year-old female patient with colonic adenocarcinoma treated with right hemicolectomy and side-to-side mechanical anastomosis, followed by adjuvant CAPOX chemotherapy. The tumor was characterized by MSI-H (microsatellite instability-high) status. During adjuvant treatment (less than 6 months after surgery), she developed progressive right thigh pain, later diagnosed as an intramuscular skeletal muscle metastasis measuring approximately 16 × 13 × 8 cm. The patient underwent en bloc resection of the tumor, followed by adjuvant chemotherapy after metastasectomy. Upon disease progression, first-line chemotherapy in combination with targeted therapy (bevacizumab) was administered. Conclusions: Skeletal muscle metastases from colorectal adenocarcinoma are rare. This case emphasizes the importance of recognizing atypical metastatic patterns and suggests that, in selected oligometastatic cases, surgical excision combined with a multidisciplinary approach may improve symptom control and clinical outcomes. Full article

Sulforaphane, a bioactive isothiocyanate found abundantly in cruciferous vegetables, has attracted significant attention for its chemopreventive and therapeutic potential, particularly in cancer. There is now an abundance of peer-reviewed research documenting true synergies between sulforaphane and (a) cancer treatment drugs, (b) pharmaceuticals in development but not yet on the market or in the regulatory pipeline, (c) other phytochemicals, and (d) proprietary mixtures such as leaf extracts and other botanicals, as well as evidence that some cell lines resistant to various cancer drugs become more susceptible when treated with sulforaphane. Most of the published studies demonstrate evidence for synergy in cancer, including cancers of the bladder, blood, brain, breast, colon, esophagus, liver, lung, ovaries, prostate, and skin, where reducing drug dosages could yield substantial patient benefits. Importantly, non-cancer indications have also been reported, such as mitigation of cardiac toxicity, inflammation, obesity, and pain (including antihyperalgesic and antinociceptive effects). Synergistic effects are most often demonstrated in cell line models, with many studies providing robust mechanistic evidence, and some employing the gold-standard Chou–Talalay method for quantifying synergy. Current evidence on the synergistic interactions of sulforaphane with both phytochemicals and pharmaceuticals highlights underlying mechanisms such as modulation of oxidative stress, inflammation, apoptosis, and epigenetic regulation, suggesting significant clinical and therapeutic implications. By providing a comprehensive overview of sulforaphane synergies in both cancer and non-cancer contexts, we aim to inform future research and support the development of integrated therapeutic strategies. Full article

Background: Splenic flexure cancers represent a small but anatomically complex subset of colorectal malignancies, characterised by variable vascular supply and lymphatic drainage. This has led to ongoing uncertainty regarding the optimal extent of resection and level of vascular ligation. With increasing adoption of robotic surgery, a range of operative approaches has been described, although these remain inconsistently reported and poorly synthesised. Aim: We aimed to map operative heterogeneity in robotic splenic flexure cancer surgery, focusing on resection extent, vascular ligation, reconstruction strategy, and technical configuration. Methods: A structured scoping review was performed in accordance with PRISMA-ScR guidelines. MEDLINE (PubMed) and Embase (Ovid) were searched from inception to January 2026. Studies reporting robotic resection for primary splenic flexure colon cancer with extractable operative detail were included. Data were synthesised descriptively and grouped into three tiers based on study design: comparative cohorts, case series, and technical reports. Results: Sixteen studies comprising 97 robotic resections were included. Three were comparative cohort studies; two were case series, and eleven were single-case technical reports. Comparative studies consistently described a flexure-directed segmental resection with preservation of the inferior mesenteric artery and division of the left colic artery. In contrast, there was greater variability in management of the middle colic branches and inferior mesenteric vein. Reconstruction strategy differed across tiers, with extracorporeal anastomosis more commonly reported in comparative cohorts, while intracorporeal techniques were frequently described in technical series. Anastomotic configuration, specimen extraction, and use of indocyanine green fluorescence varied widely. Terminology relating to complete mesocolic excision and D2/D3 lymphadenectomy was inconsistent and often poorly defined. Conclusions: Robotic splenic flexure surgery shows broad agreement in overall resection strategy but considerable variability in vascular control, reconstruction, and technical execution. This likely reflects differences in reporting rather than clear differences in oncological intent. A more consistent and structured operative description is needed to allow meaningful comparison and to support the development of evidence-based approaches in this technically demanding area. Full article

Bone metastasis remains a major cause of morbidity in advanced cancer, driven not only by tumor–bone crosstalk but also by profound immune remodeling within the marrow. Myeloid-derived suppressor cells (MDSCs), including polymorphonuclear (PMN-MDSC) and monocytic (M-MDSC) subsets, are increasingly recognized as central effectors of this process, integrating inflammatory signals with metabolic and stromal cues to enforce immune suppression and support skeletal colonization. In this review, we synthesize current evidence that bone metastases transform the bone marrow into an “MDSC amplifier,” where vascular and endosteal niches, CXCL12-rich stromal compartments, hypoxia, and adipocyte-derived lipids collectively promote MDSC recruitment, persistence, and functional maturation. We discuss the dominant suppressive programs deployed by MDSCs in bone (e.g., arginase-1 activity, reactive oxygen/nitrogen species, and checkpoint ligand expression), and how these mechanisms converge to impair cytotoxic T-cell and NK-cell responses while fostering regulatory T-cell dominance. Importantly, because the marrow is a hematopoietic organ, bone lesions can also generate systemic consequences through myeloid spillover, providing a mechanistic basis for reduced responsiveness to immune checkpoint blockade in bone-dominant disease. We then evaluate pharmacologic strategies to target MDSCs in the context of bone metastasis, including approaches that block trafficking (e.g., CCR2/CXCR2 axes), deplete or reprogram suppressive myeloid states (e.g., STAT3-directed strategies, differentiation therapy), and disrupt bone-resorptive feedback loops (e.g., receptor activator of NF-κB ligand (RANKL) inhibition and bisphosphonates), emphasizing rational combinations and sequencing to limit marrow toxicity. Finally, we highlight emerging single-cell and spatial profiling tools that can resolve bone-specific heterogeneity in MDSCs and guide biomarker-driven, mechanism-informed therapeutic development. Full article