Colorectal cancer (CRC) is the third most common and second most deadly cancer worldwide. Despite advances in screening and treatment, CRC is heterogeneous and the response to therapy varies significantly, limiting personalized treatment options. Certain molecular biomarkers, including microsatellite instability (MSI), are critical in planning personalized treatment, although only a subset of patients may benefit. Currently, the primary methods for assessing MSI status include immunohistochemistry (IHC) for DNA mismatch repair proteins (MMRs), polymerase chain reaction (PCR)-based molecular testing, or next-generation sequencing (NGS). However, these techniques have limitations, are expensive and time-consuming, and often result in inter-method inconsistencies. Deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) are critical predictive biomarkers of response to immune checkpoint inhibitor (ICI) therapy and MSI testing is recommended to identify patients who may benefit. There is a pressing need for a more robust, reliable, and cost-effective approach that accurately assesses MSI status. Recent advances in computational pathology, in particular the development of technologies that digitally scan whole slide images (WSI) at high resolution, as well as new approaches to artificial intelligence (AI) in medicine, are increasingly gaining ground. This review aims to provide an overview of the latest findings on WSI and advances in AI methods for predicting MSI status, summarize their applications in CRC, and discuss their strengths and limitations in daily clinical practice.

Colorectal cancer (CRC) is the second‑leading cause of cancer-related mortality worldwide. It is frequently characterized by chemotherapy resistance，which is a predominant factor contributing to unfavorable patient prognosis. B7-H3 is a novel tumor marker and a potential immunotherapy target. High B7-H3 expression in colorectal cancer is associated with adverse prognosis. In this study, we noted increased B7-H3 expression in colorectal cancer tumor tissues. Both in vivo and in vitro experiments demonstrated that increased B7-H3 expression promotes resistance to chemotherapy in CRC. Furthermore, our findings suggest that B7-H3 mediates CRC resistance by modulating CYP1B1 expression. Mechanistic investigations indicated that B7-H3 inhibited the ubiquitination of CYP1B1, stabilized its expression，and consequently enhanced chemotherapeutic resistance in CRC. In summary, our results underscore the significance of the B7-H3-CYP1B1 interaction as a crucial therapeutic target for overcoming chemotherapy resistance in CRC.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with both genetic and environmental risk factors. The PON1 rs854560 (L55M) polymorphism has been implicated in cancer susceptibility through its role in oxidative stress regulation, but its association with CRC remains unclear, particularly in Asian populations.

This study aimed to investigate the association between the PON1 rs854560 polymorphism and CRC susceptibility in a Chinese cohort, while assessing its impact on PON1 expression and enzymatic activity.

A case-control study was conducted on 1,003 CRC patients and 1,303 healthy controls. The impact of the Pon1-rs854560 SNP was assessed by comparing the genotypes of individuals diagnosed with CRC to those of controls without the disease.

Genotype distribution showed slight differences between the case and control groups. The frequency of the AA genotype was slightly lower in the case group (91.72%) than in the control group (93.71%). The AT genotype was observed at similar frequencies in both groups (8.28% in the case group and 6.14% in the control group). Notably, the TT genotype was absent in the case group but present in 0.15% of the control group. Genotype combination analysis suggested that individuals carrying the AT + TT genotype (8.28%) had a higher susceptibility to CRC compared to those with the AA + AT genotype (100%). Allele frequency analysis revealed a slightly higher frequency of allele T in the case group (8.28%) than in the control group (6.45%). Additionally, lower PON1 mRNA and protein expression were associated with CRC progression, including features such as poorer differentiation, deeper tumor invasion, and vascular, nerve, and lymphatic metastasis.

The PON1 rs854560 polymorphism influences CRC risk in Chinese individuals, likely through reduced PON1 expression and detoxification capacity. These findings highlight its potential as a genetic biomarker for CRC susceptibility and suggest PON1's role in tumor progression. Further studies should validate these associations in diverse populations and explore therapeutic strategies targeting PON1 activity.

Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating the repair process. While inflammation is a fundamental component of the body's defense and healing process, its dysregulation can lead to pathological consequences, contributing to various acute and chronic diseases, such as autoimmune disorders, cancer, metabolic syndromes, cardiovascular diseases, neurodegenerative conditions, and other systemic complications. Generally, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), antihistamines, biologics, and colchicine are used as pharmacological agents in the management of inflammatory diseases. However, these conventional treatments often have limitations, including adverse side effects, long-term toxicity, and drug resistance. In contrast, enzyme-based therapeutics have emerged as a promising alternative due to their high specificity, catalytic efficiency, and ability to modulate inflammatory pathways with reduced side effects. These enzymes function by scavenging reactive oxygen species (ROS), inhibiting cytokine transcription, degrading circulating cytokines, and blocking cytokine release by targeting exocytosis-related receptors. Additionally, their role in tissue repair and regeneration further enhances their therapeutic potential. Most natural anti-inflammatory enzymes belong to the oxidoreductase class, including catalase and superoxide dismutase, as well as hydrolases such as trypsin, chymotrypsin, nattokinase, bromelain, papain, serratiopeptidase, collagenase, hyaluronidase, and lysozyme. Engineered enzymes, such as Tobacco Etch Virus (TEV) protease and botulinum neurotoxin type A (BoNT/A), have also demonstrated significant potential in targeted anti-inflammatory therapies. Recent advancements in enzyme engineering, nanotechnology-based enzyme delivery, and biopharmaceutical formulations have further expanded their applicability in treating inflammatory diseases. This review provides a comprehensive overview of both natural and engineered enzymes, along with their formulations, used as anti-inflammatory therapeutics. It highlights improvements in stability, efficacy, and specificity, as well as minimized immunogenicity, while discussing their mechanisms of action and clinical applications and potential future developments in enzyme-based biomedical therapeutics.

Colorectal cancer (CRC) is among the most commonly diagnosed cancers in Switzerland. Supported by a solid evidence base for CRC screening, cantons have increasingly established organized screening programs. This report summarizes and discusses the state of this program landscape using findings from the Swiss Improving Organized Colorectal Cancer Screening: An Implementation Science Study.

Semi-structured interviews were conducted with clinical or administrative leads for Swiss CRC screening programs to understand key characteristics, including host organization, enrollment pathways, screening modalities, and program deliverers.

Eleven out of 13 existing or planned programs in 2021 participated, eight of which have been developed since 2020. All programs offer mail invitations to citizens 50-69 years old and fecal immunochemical testing, though positivity thresholds vary. Access to colonoscopy and the role of healthcare providers vary between programs.

Cantonal influences on designing and implementing preventive services allow programs to adapt to local conditions. However, they also challenge opportunities for cross-program learning, efficiencies, and equity. Strengthening the infrastructure connecting programs for shared knowledge building and program improvement will be vital for sustaining Swiss organized CRC screening.

The tumor-stroma ratio (TSR) has been regarded as an important factor associated with tumor metastasis, based on the 'seed and soil' theory, which may have guiding significance for the selection of chemotherapy regimens. Therefore, a high TSR may be a new risk factor for tumor recurrence in patients with stage II colorectal cancer (CRC). The present study aimed to evaluate the prognostic value of TSR in CRC, especially for the computer-calculated TSR. A comprehensive literature retrieval was performed using the PubMed, Web of Science, Embase and Cochrane Library databases to identify relevant studies published up to December 13, 2023. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the prognostic value of the TSR in CRC. A total of 21 studies published between 2007 and 2023 were included in the present meta-analysis. The combined analysis demonstrated that a high TSR was significantly associated with worse overall survival (OS; HR=1.84; 95% CI, 1.44-2.34; P<0.001), disease-free survival (DFS; HR=1.85; 95% CI, 1.27-2.68; P<0.001), cancer-specific survival (CSS; H=1.97; 95% CI, 1.46-2.65; P<0.001) and recurrence free survival (RFS; HR=1.55; 95% CI, 1.25-1.92; P<0.001) in patients with CRC. Moreover, an elevated computer-calculated TSR was also associated with poor OS (HR=1.89; 95% CI, 1.48-2.40; P<0.001) and DFS (HR=1.85; 95% CI, 1.27-2.68; P<0.001). However, a high TSR was not associated with poor OS in patients with stage I CRC (HR=1.01; 95% CI, 0.48-2.14; P=0.97). In conclusion, the results of the present meta-analysis indicate that a high TSR is associated with poor OS, DFS, CSS and RFS in patients with CRC, especially for those with stage II-III. In addition, TSR calculated by computer using whole-slide images may also be an effective prognostic marker for OS and DFS in patients with CRC.

Background/Objectives: Lung cancer is a leading cause of cancer-related mortalities, with early diagnosis crucial for survival. While biopsy is the gold standard, manual histopathological analysis is time-consuming. This research enhances lung cancer diagnosis through deep learning-based feature extraction, fusion, optimization, and classification for improved accuracy and efficiency. Methods: The study begins with image preprocessing using an adaptive fuzzy filter, followed by segmentation with a modified simple linear iterative clustering (SLIC) algorithm. The segmented images are input into deep learning architectures, specifically ResNet-50 (RN-50), ResNet-101 (RN-101), and ResNet-152 (RN-152), for feature extraction. The extracted features are fused using a deep-weighted averaging-based feature fusion (DWAFF) technique, producing ResNet-X (RN-X)-fused features. To further refine these features, particle swarm optimization (PSO) and red deer optimization (RDO) techniques are employed within the selective feature pooling layer. The optimized features are classified using various machine learning classifiers, including support vector machine (SVM), decision tree (DT), random forest (RF), K-nearest neighbor (KNN), SoftMax discriminant classifier (SDC), Bayesian linear discriminant analysis classifier (BLDC), and multilayer perceptron (MLP). A performance evaluation is performed using K-fold cross-validation with K values of 2, 4, 5, 8, and 10. Results: The proposed DWAFF technique, combined with feature selection using RDO and classification with MLP, achieved the highest classification accuracy of 98.68% when using K = 10 for cross-validation. The RN-X features demonstrated superior performance compared to individual ResNet variants, and the integration of segmentation and optimization significantly enhanced classification accuracy. Conclusions: The proposed methodology automates lung cancer classification using deep learning, feature fusion, optimization, and advanced classification techniques. Segmentation and feature selection enhance performance, improving diagnostic accuracy. Future work may explore further optimizations and hybrid models.

This study aims to provide updated estimate on the global burden of Gallbladder cancer (GBC) in 2022 and to predict the trends through the year 2042.

Data were extracted from GLOBOCAN 2022 database. Incidence and mortality rates were calculated by sex, country, world region and Human Development Index (HDI). Trends up to the year 2042 were predicted based on global demographic projections by HDI.

Worldwide, there were 122,469 new GBC cases and 89,045 deaths identified in 2022. While the highest absolute number was observed in South Central Asia and Eastern Asia, particularly India and China, countries in South America, particularly Bolivia, showed the highest age-standardised rate. Medium HDI countries showed more than double the incidence and mortality rates compared to low HDI countries. Over half of GBC cases and deaths occurred in individuals aged 50-74 years. Predictions indicate a 65.3 % increase in new cases and a 67.6 % increase in deaths by 2042, with High HDI countries and Low HDI countries experiencing the largest absolute and percentage increases, respectively.

The global burden of GBC is substantial, especially concentrated in South Central Asia, Eastern Asia and South America. With significant increase of burden over the next 20 years, there is an urgent need for effective cancer control strategies in regions exhibiting great GBC burden.

Desmoplastic reaction is recognized as a prognostic factor in colorectal cancer. However, its significance in locally advanced rectal cancer after neoadjuvant chemoradiotherapy remains underexplored.

To assess the prognostic value of desmoplastic reaction in specimens from patients with advanced rectal cancer after chemoradiotherapy.

This was a retrospective study.

This study was conducted at a single comprehensive cancer center.

The study included 255 patients with advanced rectal cancer who underwent fluoropyrimidine-based chemoradiotherapy followed by total mesorectal excision from 2005 to 2014. Desmoplastic reaction was classified into mature, intermediate, and immature categories based on histological analysis.

The primary outcomes were recurrence-free survival and overall survival.

Desmoplastic reaction was classified as mature (69.0%), intermediate (5.5%), or immature (25.5%). The mature group had a higher percentage of good responders (34.1%) compared with the intermediate (0%) and immature (4.6%) groups ( p < 0.0001). The mature group correlated with better outcomes, with a higher 5-year recurrence-free survival (85.4%) and overall survival (93.0%) as compared with intermediate (45.1% and 76.2%, respectively) and immature (65.8% and 88.8%, respectively) groups. In the multivariable analysis, intermediate/immature desmoplastic reaction was significantly associated with poorer recurrence-free survival ( p = 0.03). Among poor responders, intermediate/immature desmoplastic reaction was associated with poorer recurrence-free survival ( p = 0.03). Adjuvant chemotherapy did not significantly improve the 5-year recurrence-free survival rate for the mature group (adjuvant chemotherapy vs no chemotherapy, 86.4% vs 84.8%; p = 0.64), with worse trends observed in the intermediate/immature combined group (55.9% vs 69.4%, respectively, p = 0.27).

The limitations include the subjective nature of the desmoplastic reaction assessment and the retrospective design of the study.

Desmoplastic reaction in surgical specimens after chemoradiotherapy is associated with responses to chemoradiotherapy and serves as a significant prognostic factor in advanced rectal cancer, particularly for those responding poorly to chemoradiotherapy. See Video Abstract .

ANTECEDENTES:La reacción desmoplásica se reconoce como un factor pronóstico en el cáncer colorrectal. Sin embargo, su importancia en el cáncer rectal localmente avanzado después de la quimiorradioterapia neoadyuvante sigue sin explorarse.OBJETIVO:Evaluar el valor pronóstico de la reacción desmoplásica en muestras de pacientes con cáncer rectal avanzado después de la quimiorradioterapia.DISEÑO:Este es un estudio retrospectivo.ESCENARIO:Este estudio se llevó a cabo en un solo centro oncológico integral.PACIENTES:El estudio incluyó a 255 pacientes con cáncer rectal avanzado que se sometieron a quimiorradioterapia basada en fluoropirimidina seguida de una escisión mesorrectal total entre 2005 y 2014. La reacción desmoplásica se clasificó en categorías madura, intermedia e inmadura según el análisis histológico.RESULTADOS PRINCIPALES:Los resultados primarios fueron la supervivencia sin recurrencia y la supervivencia general. RESULTADOS: La reacción desmoplásica se clasificó como madura (69,0%), intermedia (5,5%) o inmadura (25,5%). El grupo maduro tuvo un mayor porcentaje de buenos respondedores (34,1%) en comparación con los grupos intermedio (0%) e inmaduro (4,6%) (p < 0,0001). El grupo maduro se correlacionó con mejores resultados, con una mayor supervivencia libre de recurrencia a 5 años (85,4%) y supervivencia general (93,0%) en comparación con los grupos intermedio (45,1% y 76,2%, respectivamente) e inmaduro (65,8% y 88,8%, respectivamente). En el análisis multivariable, la reacción desmoplásica intermedia/inmadura se asoció significativamente con una peor supervivencia libre de recurrencia ( p = 0,03). Entre los malos respondedores, la reacción desmoplásica intermedia/inmadura se asoció con una peor supervivencia libre de recurrencia (p = 0,03). La quimioterapia adyuvante no mejoró significativamente la tasa de supervivencia sin recurrencia a 5 años para el grupo maduro (quimioterapia adyuvante vs. ninguna quimioterapia, 86,4% vs. 84,8%; p = 0,64), observándose tendencias peores en el grupo combinado intermedio/inmaduro (55,9% vs. 69,4%, respectivamente, p = 0,27).LIMITACIONES:Las limitaciones incluyen la naturaleza subjetiva de la evaluación de la reacción desmoplásica y el diseño retrospectivo del estudio.CONCLUSIONES:La reacción desmoplásica en muestras quirúrgicas después de la quimiorradioterapia se asocia con respuestas a la quimiorradioterapia y sirve como un factor pronóstico significativo en el cáncer rectal avanzado, particularmente para aquellos que responden mal a la quimiorradioterapia. (Traducción-Yesenia Rojas-Khalil ).

The adoption of a watch and wait (W&W) approach in patients with rectal cancer, and a complete clinical response (cCR) following neoadjuvant therapy, is increasing worldwide. Despite this, pragmatic unbiased outcome data is limited. This study aimed to investigate national outcomes associated with W&W in Aotearoa New Zealand (AoNZ).

A national retrospective study of patients with adenocarcinoma of the rectum managed with a W&W approach between January 2015 and December 2022 in AoNZ was performed by STRATA, a student and trainee led collaborative network. The Cancer Registry and the New Zealand Ministry of Health National Minimum Data Set were linked to identify patients who had rectal cancer and who were treated with neoadjuvant therapy but not rectal resection. Research teams across 17 AoNZ hospitals then screened these patients for inclusion and data collection.

One thousand five hundred and eighteen patients were screened across 17 hospitals, 133 met inclusion criteria. Median age was 71 years. Median follow-up was 2.2 years. The 2-year cumulative incidence of local regrowth was 18.2% (95% CI 10.7%-25.1%), of which 92% was present in the bowel wall, and 68% underwent surgery, all with curative intent. The 2-year cumulative distant metastasis rate was 8.8% (95% CI 3.0%-14.2%) and the 2-year overall survival was 94.8% (95% CI 90.4%-99.4%).

This nationwide study of a W&W approach has clinical outcomes similar to the international literature. This data will help guide further implementation of a W&W approach in the management of patients with rectal cancer and inform both clinicians and patients.

Increasing morbidity and mortality in CRC is a potential threat to human health. The major challenges for better treatment outcomes are the heterogeneity of CRC cases, complicated molecular pathway cross-talks, the influence of gut dysbiosis in CRC, and the lack of multimodal target-specific drug delivery. The overexpression of many receptors in CRC cells may pave the path for targeting them with multiple ligands. The design of a more target-specific drug-delivery device with multiple ligand-functionalized, green-synthesized silver nanoparticles is highly promising and may also deliver other approved chemotherapeutic agents. This review presents the various aspects of colorectal cancer and over-expressed receptors that can be targeted with appropriate ligands to enhance the specific drug delivery potency of green synthesised silver nanoparticles. This review aims to broaden further research into this multi-ligand functionalised, safer and effective silver nano drug delivery system.

Although immune checkpoint inhibitor (ICI) therapy is currently the standard of care in microsatellite-unstable (MSI) metastatic colorectal cancer (CRC), ICI therapy, alone or in combination with other therapies, is not a treatment approach in microsatellite-stable (MSS) CRC, which is present in 95% of patients. In this review, we focus on metabolic singularities-at the transcriptomic (either bulk or single cell), proteomic, and post-translational modification levels-that induce immunosuppression in cancer and specifically in MSS CRC. First, we evaluate the current efficacy of ICIs in limited and metastatic disease in MSS CRC. Second, we discuss the latest findings on the potential biomarkers for evaluating ICI efficacy in MSS CRC using strict REMARK criteria. Third, we review the current evidence on metabolic patterns in CRC tumors and immune cell metabolism to advance our understanding of metabolic crosstalk and to pave the way for the development of combination strategies to enhance ICI efficacy.

Maternal embryonic leucine zipper kinase (MELK), a pivotal signaling protein, plays a crucial role in various physiological processes, such as cell growth, survival, and differentiation. There is currently a growing interest in MELK as a promising therapeutic target for multiple cancers, including triple-negative breast cancer (TNBC). Exploring MELK as a target offers a prospective strategy to impede cancer progression and enhance the efficacy of conventional anticancer therapies. In this study, we employed a multistep docking procedure to evaluate the anticancer potential of phyto-compounds from the NPACT and PhytoHub databases targeting the MELK protein. A collection of 23 740 compounds underwent hierarchical multistep docking, accompanied by an analysis of binding interactions. The extensive analysis identified five compounds (PHUB000697, PHUB002010, NPACT00373, PHUB002005, and PHUB001739) as potent inhibitors of the MELK protein, exhibiting docking scores lower than -11 Kcal/mol, that is, -12.90, -12.00, -11.23, -11.19, and -11.09 Kcal/mol, respectively. PHUB000697 exhibited very crucial interactions with Gly20, Lys40, Cys89, and Glu93 (2.74 Å). To evaluate the stability of protein-ligand interactions in dynamic states, 100 ns molecular dynamics (MD) simulations were conducted using the entire trajectory, revealing a substantial binding affinity for all identified compounds toward the MELK protein. Consequently, these five compounds emerge as promising candidates for future drug development targeting the MELK protein in treating TNBC. However, experimental assessment is essential to understand the molecular interaction mechanisms better. We are aiming to report a few in vitro and in vivo studies on these compounds to validate the computational results.

Integrating network pharmacological analysis and bioinformatic techniques, this study systematically investigated the molecular mechanisms of six medicinal food homologous plants (Astragalus membranaceus, Ganoderma lucidum, Dioscorea opposite, Curcuma longa, Glycyrrhiza uralensis, and Pueraria lobata) against colorectal cancer. Through screening the TCMSP database, 303 active compounds and 453 drug targets were identified. By integrating differential expression gene analysis with WGCNA on the GSE41258 dataset from the GEO database, 49 potential therapeutic targets were identified. GO and KEGG enrichment analyses demonstrated that these targets are primarily involved in drug response, fatty acid metabolism, and key cancer-related pathways. Cross-validation using three machine learning algorithms-LASSO regression, SVM-RFE, and Random Forest-pinpointed four critical target genes: CA1, CCND1, CXCL2, and EIF6. Further, CIBERSORT immune infiltration analysis revealed strong associations between these core genes and the tumor immune microenvironment in colorectal cancer patients, notably in modulating M0 macrophage infiltration and mast cell activity. Molecular docking analyses confirmed robust binding interactions between active compounds and core target proteins. This study systematically elucidated the molecular mechanisms of six medicinal food homologous plants against colorectal cancer, providing scientific evidence for their rational clinical application.

Fusobacterium nucleatum, a gram-negative anaerobic bacterium, has emerged as a significant player in colorectal cancer (CRC) pathogenesis. The bacterium causes a persistent inflammatory reaction in the colorectal mucosa by stimulating the release of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α, creating an environment conducive to cancer progression. F. nucleatum binds to and penetrates epithelial cells through adhesins such as FadA, impairing cell junctions and encouraging epithelial-to-mesenchymal transition (EMT), which is associated with cancer advancement. Additionally, the bacterium modulates the host immune system, suppressing immune cell activity and creating conditions favorable for tumor growth. Its interactions with the gut microbiome contribute to dysbiosis, further influencing carcinogenic pathways. Evidence indicates that F. nucleatum can inflict DNA damage either directly via reactive oxygen species or indirectly by creating a pro-inflammatory environment. Additionally, it triggers oncogenic pathways, especially the Wnt/β-catenin signaling pathway, which promotes tumor cell growth and longevity. Moreover, F. nucleatum alters the tumor microenvironment, impacting cancer cell behavior, metastasis, and therapeutic responses. The purpose of this review is to elucidate the molecular mechanisms by which F. nucleatum contributes to CRC. Understanding these mechanisms is crucial for the development of targeted therapies and diagnostic strategies for CRC associated with F. nucleatum.

To elucidate the metabolic mechanisms by which acteoside (ACT) isolated from Cistanche tubulosa alleviates cancer-related fatigue (CRF) in a murine model of colon cancer with cachexia.

BALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and ACT (100 mg/kg) alone or in combination for 21 days. Fatigue-associated behaviors, tumor inhibition rate, and skeletal muscle morphology assessed by hematoxylin-eosin (H&E) staining and electron microscopy were evaluated. Finally, liquid chromatography-mass spectrometry (LC/MS) was employed to investigate alterations in the plasma metabolic profile of tumor-bearing mice with CRF in response to ACT treatment, and the affinity between metabolite-associated proteins and ACT was verified by Surface plasmon resonance (SPR) assay.

Our study demonstrated the presence of CRF in the colon cancer mouse model, with the severity of fatigue increasing alongside tumor growth. Administration of ACT ameliorated both tumor burden and PTX-induced muscle fatigue-like behavior. LC/MS analysis identified a panel of differentially regulated metabolites, including trans-aconitine, citric acid, 3-coumaric acid, ephedrine, thymine, cytosine, indole-3-acetic acid, and pantothenol-9. These metabolites were primarily enriched in pathways associated with valine biosynthesis, tyrosine metabolism, tryptophan metabolism, and biosynthesis of pyridine alkaloids. Furthermore, several key enzymes, including CYP3A4, CYP19A1, CYP2E1, TNF, BCL-2, RYR2, and ATP2A1, were identified as potential targets underlying the anti-CRF effects of ACT.

This study suggests that ACT derived from C. tubulosa harbors protective properties against cancer-related fatigue mediated by tumor cells.

Previous studies have shown that colorectal cancer incidence is increasing among younger adults (aged <50 years) in multiple high-income western countries in contrast with stabilising or decreasing trends in incidence in older adults (aged ≥50 years). This study aimed to investigate contemporary colorectal cancer incidence trends in younger adults versus older adults.

Colorectal cancer incidence data, including year of diagnosis, sex, and 5-year age group for 50 countries and territories, were extracted from the WHO-International Agency for Research on Cancer Cancer Incidence in Five Continents Plus database. The Human Development Index 2022 was retrieved from the United Nations Development Programme and grouped into very high (>0·80), high (0·70-0·79), medium (0·55-0·69), and low (<0·55) categories. Age-standardised incidence rates (ASR) per 100 000 person-years of early-onset (diagnosed between ages 25 to 49 years) and late-onset (diagnosed between ages 50 to 74 years) colorectal cancer (ICD 10th revision, C18-20), diagnosed between 1943-2003 and 2015-17, were calculated using the direct method and Segi-Doll world standard population). The primary study objective was to examine contemporary colorectal cancer incidence trends in younger adults versus older adults using data until 2017 from 50 countries and territories. Temporal trends were visualised and quantified with joinpoint regression, stratified by age at diagnosis (25-49 years or 50-74 years). Average annual percentage changes (AAPC) were estimated.

In the most recent 5 years (2013-17 for all countries analysed, except for Japan [2011-15], Spain [2012-16], and Costa Rica [2012-16]), the incidence rate of early-onset colorectal cancer was highest in Australia (ASR 16·5 [95% CI 16·1-16·9]), the USA (Puerto Rico; 15·2 [14·2-16·2]), New Zealand (14·8 [14·0-15·6]), the USA (14·8 [14·7-14·9]), and South Korea (14·3 [14·0-14·5]) and lowest in Uganda (4·4 [3·6-5·2]) and India (3·5 [3·3-3·7]). The highest incidence rates among older adults were found in the Netherlands (168·4 [166·9-170·0]) and Denmark (158·3 [155·8-160·9]) and the lowest were in Uganda (45·9 [38·5-51·4]) and India (23·5 [22·8-24·3]). In terms of AAPC, in the most recent 10 years, incidence rates of early-onset colorectal cancer were stable in 23 countries, but increased in 27 countries with the greatest annual increases in New Zealand (AAPC 3·97% [95% CI 2·44-5·52]), Chile (3·96% [1·26-6·74]), Puerto Rico (3·81% [2·68-4·96]), and England (3·59% [3·12-4·06]). 14 of the 27 countries and territories showed either stable (Argentina, France, Ireland, Norway, and Puerto Rico) or decreasing (Australia, Canada, Germany, Israel, New Zealand, Slovenia, England, Scotland, and the USA) trends in older adults. For the 13 countries with increasing trends in both age groups, the average annual percentage increase in younger compared to older adults was higher in Chile, Japan, Sweden, the Netherlands, Croatia, and Finland; lower in Thailand, France (Martinique), Denmark, and Costa Rica; and similar in Türkiye, Ecuador, and Belarus. The rise in early-onset colorectal cancer was faster among men than women in Chile, Puerto Rico, Argentina, Ecuador, Thailand, Sweden, Israel, and Croatia, whereas faster increase among women compared to men was in England, Norway, Australia, Türkiye, Costa Rica, and Scotland.

Early-onset colorectal cancer incidence rates are rising in 27 of 50 countries and territories examined, with the rise either exclusive to early-onset disease or faster than the increase in older adults in 20 of the 27 countries. The findings underscore the need for intensified efforts to identify factors driving these trends and increase awareness to help facilitate early detection.

Intramural Research Program of the American Cancer Society, Cancer Grand Challenges, and National Institutes of Health.

Cancer is a major cause of mortality. Timely information about cancer mortality trends is essential for prioritizing health programs.

This study aims to use a Joint point regression model to predict the mortality rates of the top 10 common cancers in Babol City.

This cross-sectional study considered all registered cancer-related deaths from 2013 to 2021 in the Babol University of Medical Sciences' death registration and classification system. Crude and age-standardized rates and cancer trends were calculated and predicted for the next 5 years, overall and by type of cancer and gender.

Over these 9years, 2417 deaths from the 10 common cancers were recorded. We observed an increase in mortality rates with a slope of 12.05% from 2013 to 2016, and a gentler slope of 3.2% from 2016 to 2021. Cancer mortality rates are predicted to increase by 6.43% in the next 5 years without intervention. Detailed analysis indicates that breast cancer will have the highest mortality rate during 2022-2026, rising by 13.6% annually. Predictions based on gender indicate that, breast cancer mortality will increase by 13.6% annually for women. Also, stomach cancer mortality rates will increase by 0.15% in men annually.

Cancer mortality in Babol remains a significant public health issue with an increasing trend. Nevertheless, these rising mortality rates require urgent interventions, including cancer prevention programs, increased access to medical services, and improved quality of life.

The optimal approach to the treatment of colorectal carcinoma and synchronous liver metastases remains controversial. The objective of this review was to analyze the outcomes of adopting the liver-first approach for the treatment of patients with colorectal cancer with synchronous hepatic metastases who initially underwent systemic chemotherapy and/or resection of the metastatic lesions and primary colorectal carcinoma.

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The MEDLINE, EMBASE, LILACS, and Cochrane Central Register of Controlled Trials databases were searched for the identification and retrieval of eligible studies. Studies that included details of using the liver-first approach for the treatment of synchronous liver metastases of colorectal cancer and its outcomes, including the patients' survival data, were included. Proportional meta-analysis was performed using the random-effects restricted maximum likelihood method to summarize the three- and five-year overall survival and recurrence rates of the patients.

Eight hundred and fifty-five articles describing the results of studies on the liver-first approach were identified. Three independent reviewers screened the titles and abstracts of the articles and excluded 750 articles. Thereafter, 29 retrospective and comparative studies that met the inclusion criteria were included. No randomized controlled trials were identified in the database search.

Neoadjuvant treatment with systemic chemotherapy for hepatic metastasis can prepare a patient for resection of liver metastases, offering the opportunity for potentially curative treatment of synchronous hepatic metastases initially considered unresectable. The decision regarding the resection of primary colorectal carcinoma and liver metastases should be based on individualized patient response. Prospero database registration ID: CRD42022337047 (www.crd.york.ac.uk/prospero).

To systematically evaluate the efficacy and safety of PD-1 inhibitors in neoadjuvant therapy for locally advanced colorectal cancer (LACRC).

Retrieved from PubMed, Embase, and the Cochrane Library, all relevant studies about PD-1 inhibitors for neoadjuvant treatment of LACRC were collected from inception to 31 December 2023. The efficacy was assessed by the rate of pathological complete response (PCR), clinical complete response (CCR), and major pathological response (MPR), and the safety was evaluated by the incidence of all adverse effects (TRAEs). Subgroup analysis was conducted by experimental design, types of PD-1 inhibitors, and disease types.

A total of 803 patients were included in 21 studies. The results of the meta-analysis showed that the PCR rate of PD-1 inhibitors in the treatment of LACRC was 54% (95% CI: 43%-65%, P<0.05); the CCR of anti-PD-1 was 40% (95% CI: 26%-54%, P<0.05); the MPR was 66% (95% CI: 56%-76%, P<0.05); and the irAEs was 27% (95% CI: 17%-37%, P<0.05). Subgroup analysis showed that the PCRs in prospective studies and retrospective studies were 49% (95% CI: 32%-66%, P<0.05) and 57% (95% CI: 42%-73%, P<0.05), respectively. Among the 803 patients, 619 (77%) were diagnosed with rectal cancer (RC), and the PCR and MPR were 49% and 65%, respectively; 184 (23%) were diagnosed with colorectal cancer (CRC), and the PCR and MPR were both 67%. In our meta-analysis, types of PD-1 inhibitors, including sintilimab, toripalimab, camrelizumab, avelumab, pembrolizumab, and tislelizumab, and patients who received PD-1 inhibitors alone or in combination achieved good PCR rates.

Neoadjuvant therapy combined with a PD-1 inhibitor has a favorable PCR and relatively low incidences of irAEs for patients with LACRC, suggesting that this regimen including a PD-1 inhibitor is significantly effective and sufficiently safe.

Current tools for predicting survival outcomes in colon cancer patients predominantly rely on clinical and pathologic characteristics. However, accumulating evidence demonstrates a significant correlation between nutritional status and patient outcomes. This study aimed to establish a new dynamic nomogram for individualized prediction of postoperative overall survival (OS). The clinicopathological and nutritional data of colon cancer patients undergoing radical resection were retrospectively collected and randomly divided into the primary and validation cohorts. Risk factors on OS rates were investigated by Cox analyses and, the nomogram was constructed using significant predictors. Among 1,024 patients, 341 deaths were observed after median follow-up of 54 months. Five independent prognostic factors, including nutritional status assessments, were incorporated into the nomogram. The C-index regarding 1-, 3-, and 5-year OS were 0.830, 0.859, and 0.757 in the primary cohort and 0.843, 0.870, and 0.773 in the validation cohort, respectively. Calibration curves for the probability of OS exhibited an optimal agreement. Decision curve analyses revealed the greater application value of the nomogram than the TNM staging system. Based on the nomogram, patients could be stratified into three scenarios with significant prognostic classification (P < 0.0001). In conclusion, we developed and validated an easy-to-use dynamic nomogram for predicting postoperative OS in colon cancer patients.

To explore the postsurgery lived experiences of patients with colorectal cancer with a permanent ostomy for informing initiatives to improve patient care and future quantitative research.

A descriptive qualitative phenomenological study.

We conducted this study in the Colorectal Cancer Division at the Cancer Center of West China Hospital, Sichuan University, a premier institution renowned for its comprehensive cancer care and research.

12 patients who had undergone surgeries for colorectal cancer with a permanent ostomy.

Our interviews revealed profound adjustments in the lives of colorectal cancer survivors living with permanent ostomies. Participants articulated a transition to a 'new normal', characterised by extensive daily life adjustments, psychological adaptation and ongoing management challenges. Key themes identified included the adaptation to a reshaped daily routine and altered perceptions of quality of life. Many faced substantial challenges in stoma care, requiring significant learning and adaptation. Psychological adaptations were marked by a redefinition of body autonomy and personal identity, alongside a recalibration of social interactions and privacy. The need for robust professional guidance and a comprehensive social support system was universally emphasised.

Patients with colorectal cancer with permanent ostomies navigate significant changes in their lives postsurgery, undertaking a complex process of reconstructing and adapting to a new normalcy. They recalibrate their physical, psychological and social well-being, demonstrating resilience and adaptability in the face of these challenges. Their pervasive expression of needs for information and support may reflect gaps in the existing patient education and support measures and communication strategies. Healthcare professionals and policy-makers should adopt a patient-centred approach acknowledging the multifaceted nature of postsurgery recovery and adaptation by fostering open communication, tailoring personalised education and facilitating supportive community networks.

Endoplasmic reticulum stress may affect the occurrence and development of cancer. However, its effect on the prognosis of colon cancer (CC) patients is not clear yet. Herein, based on TCGA database, we screened 15 endoplasmic reticulum stress responsive genes (ERSRGs) associated with the prognosis of CC patients by Cox regression. By LASSO and multivariate Cox regression analyses, a prognostic risk assessment model involving 12 genes (DNAJB2, EIF4A1, YPEL4, COQ10A, IRX3, ASPHD1, NTRK2, TRIM39, XBP1, GRIN2B, LRRC59, and RORC) was built. The survival curves indicated that patients in the low-risk group had good prognosis. ROC curves demonstrated a good performance of this 12-gene prognostic model, and the Riskscore could be considered as an independent prognostic factor. Patients in low-risk group benefit more from immune checkpoint inhibitor and immune checkpoint blockade (ICB) treatment. Besides, the enrichment analysis suggested a remarkable difference in Ca2+ signaling in both groups. Finally, based on the cMAP database, we identified several potential drugs that could target high-risk groups, such as Dasatinib, GNF-2, Saracatinib, and WZ-1-84. To sum up, our research constructed an ERSRGs-characteristic prognostic model. The model is a promising biomarker for prediction of clinical outcomes and immune therapy response of CC patients. SIGNIFICANCE: Based on the transcriptomic data of colon cancer in the TCGA database, this study screens 12 endoplasmic reticulum stress-related genes (ERSRGs), including DNAJB2, EIF4A1, YPEL4, COQ10A, IRX3, ASPHD1, NTRK2, TRIM39, XBP1, asphD1, NTRK2. GRIN2B, LRRC59, and RORC, and a prognostic model was constructed. This model can be used as a predictor of prognosis and immunotherapy response in colon cancer patients. At the same time, model-based prediction of drugs can also be a potential option for colon cancer treatment in the future.

Metastatic colorectal cancer continues to have a high fatality rate, with approximately only 14% of patients surviving more than 5 years. To improve the survival rate of these patients, the development of new therapeutic drugs is a priority. In this study, we investigated the effects of Oroxylin A on the metastasis of human colorectal cancer cells and its potential molecular mechanism. This study utilised CCK8 assay, transwell assay, flow cytometry, western blot analysis, molecular docking, HE staining, immunofluorescence staining, and xenograft models. The proliferation, migration, and invasion of colon cancer cells were effectively suppressed by Oroxylin A in a dose-dependent manner. Oroxylin A has the potential to inhibit the process of epithelial‒mesenchymal transition (EMT) by upregulating the expression of E-cadherin, a marker associated with epithelial cells, while downregulating the levels of N-cadherin, Snail, vimentin, and slug, which are markers associated with mesenchymal cells. In addition, 200 mg/kg of Oroxylin A inhibited the growth of colorectal tumours. Molecular docking technology revealed that Oroxylin A can bind to TGFβ and inhibit the activation of the TGFβ-smad signalling pathway. The overexpression of TGFβ weakened the inhibitory effect of Oroxylin A on the proliferation, migration, and invasion of human colorectal cancer cells, as well as the promoting effect on apoptosis. Oroxylin A inhibited the activation of the TGF-smad signalling pathway and the EMT process, thereby suppressing the migration and invasion of human colorectal cancer cells.

Colorectal cancer is one of the most common cancers worldwide. DNA methylation sites may serve as a new gene signature for colorectal cancer diagnosis. The search for representative DNA methylation sites is urgently needed. This study aimed to systematically identify a methylation gene panel for colorectal cancer diagnosis via tissue and fecal samples.

A total of 181 fecal and 50 tumor tissue samples were collected. They were obtained from 83 colorectal cancer patients and 98 healthy subjects. These samples were evaluated for DNA methylation of 9 target genes via quantitative bisulfite next-generation sequencing. We employed the rank-sum test to screen the colorectal cancer-specific methylation sites in the tissue and fecal cohorts. A data model was subsequently constructed and validated via the dedicated validation dataset.

Compared with the fecal and negative control samples, the colorectal cancer tissue samples presented significantly higher methylation rates for all the selected gene sites. The methylation rates of the tissue and preoperative fecal samples showed the same high and low rates at the same sites. After screening, a panel of 29 loci in the SDC2, SEPT9, and VIM genes proved to be reliable biomarkers for colorectal cancer diagnosis in fecal samples. Logistic regression models were then constructed and validated using this panel. The sensitivity of the model was 91.43% (95% CI = [89.69, 93.17]), the specificity was 100% (95% CI = [100,100]), and the AUC value is 99.31% (95% CI = [99,99.62]). The diagnostic accuracy of the model for stage I and stage II colorectal cancer was 100% (11/11) and 91.3% (21/23), respectively. Overall, this study confirms that the gene locus panel and the model can be used to diagnose colorectal cancer effectively through feces.

Our study identified a set of key methylation sites for colorectal cancer diagnosis from fecal samples, highlighting the importance of using tissue and fecal samples to accurately assess DNA methylation levels to screen for methylation sites, and developing an effective diagnostic model for colorectal cancer.

Colorectal cancer remains one of the most common causes of cancer-related mortality worldwide, and lymph node staging is crucial in the diagnostic and therapeutic process. Sentinel lymph nodes are the first involved in this process, but their validity in colorectal surgery has not yet been established. Following the emergence of new imaging instrumentation, some authors have attempted to propose different techniques for lymph node identification. However, a clear pattern of mesorectal lymph node distribution relative to the primary lesion site has yet to be defined.

Our analysis retrospectively reviewed suspicious mesorectal pathological lymph nodes on pre-operative magnetic resonance imaging (MRI) of rectal cancer patients, in order to assess the distribution patterns of possible tumour-related rectal lymph nodes. Mesorectal space was subdivided into quadrants and levels, and morphological features and distances from the lymph node to the primary rectal tumour were recorded.

Two hundred and fifty-five mesorectal lymph nodes distributed among 60 patients were collected. Results show that in 92.1% of cases, nodes were distributed in the same mesorectal quadrant as the rectal primary tumour, and in 88.5% of cases, they were found at the same level as the rectal primary tumour.

Although a clear node distribution pattern was not established, these results may suggest at least a lymphatic drainage preference lane, worthy of further investigation.

Liposomes, made up of phospholipid bilayers, are efficient nanocarriers for drug delivery because they can encapsulate both hydrophilic and lipophilic drugs. Conventional cancer treatments sometimes involve considerable toxicities and adverse drug reactions (ADRs), which limits their clinical value. Despite liposomes' promise in addressing these concerns, clinical trials have revealed significant limitations, including stability, targeted distribution, and scaling challenges. Recent clinical trials have focused on enhancing liposome formulations to increase therapeutic efficacy while minimizing negative effects. Notably, the approval of liposomal medications like Doxil demonstrates their potential in cancer treatment. However, the intricacy of liposome preparation and the requirement for comprehensive regulatory approval remain substantial impediments. Current clinical trial updates show continued efforts to improve liposome stability, targeting mechanisms, and payload capacity in order to address these issues. The future of liposomal drug delivery in cancer therapy depends on addressing these challenges in order to provide patients with more effective and safer treatment alternatives.

The aim of this study is to investigate the impact of arginine on immune function and postoperative complications in colorectal cancer (CRC) patients.

We conducted a comprehensive search to identify eligible RCTs in various databases, such as PubMed, Cochrane Library, EMBASE, Web of Science, MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP Medicine Information System (VIP), and Chinese Biomedical Database (CBM). This study aimed to examine IgA, IgG, and IgM levels as well as CD4+ and CD8+ counts as well as the CD4+/CD8+ ratio. Anastomotic leaking, length of stay (LOS), and surgical site infection (SSI) were included as secondary outcomes. Stata (StataCorp, version 14.0) was utilized for data analysis. To ensure the results were reliable, we used meta-regression, sensitivity analysis, and publication bias analysis.

A total of 24 publications (including 1883 patients) out of 681 that were retrieved fulfilled the inclusion criteria. The arginine group showed notable improvements in humoral immunity, with gains in IgA (SMD=0.45, 95% CI: 0.30-0.60), IgG (SMD=0.80, 95% CI: 0.64-0.96), and IgM (SMD=0.66, 95% CI: 0.39-0.93). With regards to cellular immunity, the arginine group exhibited a substantial increase in the CD4+ T cell count (SMD = 1.03, 95% CI: 0.67-1.38) compared to the control group. However, the CD4+/CD8+ ratio decreased significantly (SMD=1.37, 95% CI: 0.88-1.86) in the same arginine group, indicating a change in the balance between these two cell types. Additionally, the CD8+ T cell count showed a notable decrease (SMD=-0.70, 95% CI: -1.09 to -0.32) in the arginine group when compared to the control group. Anastomotic leakage was also considerably lower in the arginine group (SMD=-0.05, 95% CI: -0.08 to -0.02), the rate of SSIs was lower (RR = -0.02, 95% CI: -0.05-0), and the length of time patients spent in the hospital was shorter (SMD=-0.15, 95% CI: -0.38 to -0.08).

After radiation treatment for CRC, arginine improves immune function and decreases the risk of infection problems.

Registration with PROSPERO for this meta-analysis is number CRD42024520509.

The aim of this retrospective observational study was to investigate the geographical or sex differences in patients with synchronous colorectal liver metastases (sCRLM) in terms of assessment by a multidisciplinary team conference (MDT), curative treatment, and overall survival.

All sCRLM patients in the South-East Health Care Region of Sweden from 2009 to 2015 were included (n = 615). Data were derived from the Swedish Colorectal Cancer Registry, Swedish Registry of Liver and Bile Surgery and medical records.

Patients who had a hepatobiliary unit (HBU) at the nearest hospital were more likely to undergo liver surgery (HBU+, 37% (n = 106), compared to HBU-, 22% (n = 60); p = 0.001) and had a better median survival (p < 0.001). No sex differences were observed. In multivariate Cox regression analyses of overall survival, assessment by an MDT that included a liver surgeon was independently linked to better survival (HR 0.574, 0.433-0.760).

There were no sex differences in access to liver surgery or overall survival, however, there were geographical inequalities, where residency near a hospital with HBU was associated with increased overall survival and the possibility to receive liver surgery. Assessment at MDT with liver surgeon present was associated with greater survival, indicating its important role for treatment.

Colorectal cancer (CRC) incidence has been increasing. Colonoscopy is still a gold standard method for its early diagnosis but using colonoscopy alone as a mass screening method is unrealistic. This study is to investigate whether combining fecal immunochemical test (FIT) and high-risk-factors questionnaire (HRFQ) with colonoscopy improve the cost-effectiveness of a mass CRC screening.

CRC screening protocol combining FITs and HRFQ in the first stage and colonoscopy in the second stage was used in 50 villages/towns in 2007-2015. Residents aged 40-74 years were eligible for this free screening. A total of 160 210 (76.12%) participants completed first-stage screening, and 28 679 (17.90%) participants were defined as positive, among which 21 715 (75.72%) participants completed colonoscopy and were included in the final analysis. Outcomes were followed up until 2020.

The compliance was 76.12% and 75.72% in the first and second screening stage, respectively. A total of 252 CRC, 4033 adenoma, 1234 advanced neoplasm, and 5534 total neoplasm cases were detected in the screening. The positive predictive values of CRC, adenoma, advanced neoplasm, and total neoplasm were higher in FITs+ than those in the HRFQ+ population, respectively. A total of 64.60% and 43.42% total neoplasm cases were found in FITs+ and HRFQ+ (8.02% for both), respectively. The total colorectal neoplasm and CRC cases detected by combining HRFQ and FITs increased by 55.08% and 40.00%, respectively, and their increases were higher compared to HRFQ. The detection cost per any neoplasm by combining HRFQ and FITs was <$5331, while that by FITs and HRFQ alone was <$4570 and $5380, respectively.

Combining FITs and HRFQ with colonoscopy improve the cost-effectiveness of a mass CRC screening program. This protocol can be recommended for most populations, especially those in the countries and areas with high population density and low physician/population ratio.

Major innovation into how we pursue diagnosis and therapies for gastrointestinal (GI) diseases is urgently needed to seek better, less invasive, and less costly innovations in diagnostic and therapeutic interventions in the GI tract. Learning from prior paradigm shifts in cardiac and vascular we present here several initial steps we have undertaken to follow the endoluminal path, using advanced imaging methods, including endoscopy, and data management with avoidance of entry into a body cavity when possible. We will review the benefit and ease of incorporating routine fluoroscopy with endoscopy to improve safety and efficiency. We describe the development of "hybrid" procedure rooms for GI interventions and rationale for their use. We also emphasize the importance of collaborating with interventional radiologists, software engineers, and data specialists. We predict major improvement in outcomes in both diagnosis and treatment will follow.

Colon cancer (CC) is a significant cause of death worldwide, particularly in Saudi Arabia. To increase the accuracy of diagnosis and treatment, it is important to discover new specific biomarkers for CC. The main objectives of this research are to identify potential specific biomarkers for the early diagnosis of CC by analyzing the expressions of eight cancer testis (CT) genes, as well as to analyze how epigenetic mechanisms control the expression of these genes in CC cell lines. Tissue samples were collected from 15 male patients with CC tissues and matched NC tissues for gene expression analysis. The expression levels of specific CT genes, including ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12, were assessed using quantitative techniques. To validate the gene expression patterns, we used publicly available CC statistics. To investigate the effect of inhibition of DNA methylation and histone deacetylation on CT gene expression, in vitro experiments were performed using HCT116 and Caco-2 cell lines. There was no detected expression of the genes neither in the patient samples nor in NC tissues, except for TEX48, which exhibited upregulation in CC samples compared to NC tissues in online datasets. Notably, CT genes showed expression in testis samples. In vitro, experiments demonstrated significant enhancement in mRNA expression levels of ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12 following treatment with 5-aza-2'-deoxycytidine and trichostatin A in HCT116 and Caco-2 cell lines. Epigenetic treatments modify the expression of CT genes, indicating that these genes can potentially be used as biomarkers for CC. The importance of conducting further research to understand and target epigenetic mechanisms to improve CC treatment cannot be overemphasized.

The prognosis of colorectal cancer has continuously improved in recent years thanks to continuous progress in both the therapeutic and diagnostic fields. The specific objective of this study is to contribute to the diagnostic field through the evaluation of the correlation between superior hemorrhoidal vein (SHV) ectasia detected on computed tomography (CT) and Tumor (T), Node (N), and distant metastasis (M) examination and mesorectal fascia (MRF) invasion in the preoperative staging of rectal cancer.

Between January 2018 and April 2022, 46 patients with histopathological diagnosis of rectal cancer were retrospectively enrolled, and the diameter of the SHV was evaluated by CT examination. The cutoff value for SHV diameter used is 3.7 mm. The diameter was measured at the level of S2 during portal venous phase after 4× image zoom to reduce the interobserver variability. The parameters evaluated were tumor location, detection of MRF infiltration (defined as the distance < 1 mm between the tumor margins and the fascia), SHV diameter, detection of mesorectal perilesional lymph nodes, and detection of metastasis.

A total of 67.39% (31/46) of patients had SHV ectasia. All patients with MRF infiltration (4/46, 7.14%) presented SHV ectasia (average diameter of 4.4 mm), and SHV was significantly related with the development of liver metastases at the moment of primary staging and during follow-up.

SHV ectasia may be related to metastasis and MRF involvement; therefore, it could become a tool for preoperative staging of rectal cancer.

There are nearly 1.15 million new cases of colon cancer, as well as 586,858 deaths from colon cancer worldwide in 2020. The aim of this study is to reveal whether ZMIZ1 can control the fate of colon cancer cells and the mechanism by which it functions. Specific shRNA transfection was used to knock down the expression of ZMIZ1 in colon cancer cell lines (HCT116 and HT29), and cell proliferation was detected using EdU and CCK-8 reagents, apoptosis by flow cytometry, and autophagy by western blot. The interaction of ZMIZ1 and SIRT1 was analyzed. Knockdown of ZMIZ1 significantly inhibited autophagy and proliferation, and induced apoptosis of HCT116 and HT29 cells. The mRNA level of SIRT1 was not affected by ZMIZ1 knockdown, but the protein level of SIRT1 was significantly decreased and the protein level of the SIRT1-specific substrate, acetylated FOXO3a, was reduced. Immunoprecipitation assays identified the interaction between SIRT1 and ZMIZ1 in HCT116 and HT29 cells. ZMIZ1 increased intracellular ubiquitination of SIRT1. Knockdown or pharmacological inhibition of SIRT1 neutralized the effects of ZMIZ knockdown on proliferation, autophagy and apoptosis in HCT116 and HT29 cells. ZMIZ1 may control the fate of colon cancer cells through the SIRT1/FOXO3a axis. Targeting ZMIZ1 would be beneficial for the treatment of colon cancer.

Colorectal cancer is one of the most common cancers in the world. While colonoscopy is an effective screening technique, navigating an endoscope through the colon to detect polyps is challenging. A 3D map of the observed surfaces could enhance the identification of unscreened colon tissue and serve as a training platform. However, reconstructing the colon from video footage remains difficult. Learning-based approaches hold promise as robust alternatives, but necessitate extensive datasets. Establishing a benchmark dataset, the 2022 EndoVis sub-challenge SimCol3D aimed to facilitate data-driven depth and pose prediction during colonoscopy. The challenge was hosted as part of MICCAI 2022 in Singapore. Six teams from around the world and representatives from academia and industry participated in the three sub-challenges: synthetic depth prediction, synthetic pose prediction, and real pose prediction. This paper describes the challenge, the submitted methods, and their results. We show that depth prediction from synthetic colonoscopy images is robustly solvable, while pose estimation remains an open research question.

To identify factors associated with post-recurrence survival (PRS), we examined our institutional recurrence patterns following definitive resection for rectal cancer. We reviewed all patients with rectal cancer diagnosed at three hospitals in the east of Iran from 2011 to 2020. The optimal cut-off value was determined by receiver operating characteristic (ROC) analysis to determine early recurrence. The effect of recurrence time was evaluated on PRS. 326 eligible patients with a mean ± SD age of 56 ± 12.8 years were included in this study. In a median (IQR: Inter-quartile range) follow-up time of 76 (62.2) months, 106 (32.5%) patients experienced at least any recurrence (locoregional or distant metastasis) following primary resection. The median (IQR) time from initial surgery to recurrence was 29.5 (31.2) months. Based on ROC analysis, early recurrence was specified at ≤ 29 months. However, for the patients who experienced only locoregional recurrence, 33 months was the cut-off to define early recurrence. Recurrence time and recurrence management were both significant variables on PRS. Moreover, TNM staging was significantly associated with early recurrence (P = 0.003). In this research, recurrence time, recurrence management and TNM staging were found to be correlated with PRS.

Colorectal cancer is a leading cause of cancer-related deaths worldwide, with approximately 1.9 million new cases and over 935,000 deaths in 2020. Right-sided colon cancer, a subset of colorectal cancer, represents a significant health burden. Laparoscopic colon surgery has significantly improved postoperative recovery. The superiority of one approach or landmark over another is still argued about due to the lack of large-scale prospective studies. However, deep understanding both of the anatomical variation and characteristics of each approach is of extreme importance to minimizing adverse effects and maximizing patient benefit after laparoscopic right hemicolectomy. Among these, the cranial-to-caudal approach offers advantages such as reduced intraoperative blood loss, shorter operation time, and decreased risk of vascular injury. The purpose of this study is to compare the efficacy and safety of two cranial-to-caudal approaches for laparoscopic right hemicolectomy (LRH). Specifically, the study aims to evaluate the differences between the conventional cranial-to-caudal approach with medial ligation of the middle colic vein (MCV), and the cranial-to-caudal approach with cranial MCV ligation and surgical trunk sheath opening (CC-plus). The goal is to determine which method offers superior outcomes in terms of intraoperative blood loss, operation time, and overall patient recovery.

This single-center retrospective study compared two cranial-to-caudal approaches for LRH. The study included 51 patients who underwent LRH between January 2021 and November 2023 at the Second Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups: Group A (26 patients) used the cranial-to-caudal approach with medial ligation of the middle colic vein (MCV), and Group B (25 patients) used the cranial-to-caudal approach with cranial MCV ligation and surgical trunk sheath opening (CC-plus). General characteristics, intraoperative parameters, and postoperative outcomes were compared. Statistical analysis was performed using SPSS version 20.0, with significance set at p < 0.05.

There were no significant differences between the groups regarding age, gender, tumor location, or clinical staging. All patients achieved R0 resection with no perioperative deaths. The CC-plus group had significantly reduced intraoperative blood loss and shorter operation time compared to the CC group (p < 0.05). No significant differences were found in first postoperative exhausting time, first postoperative defecation time, and postoperative hospital stay between the two groups. Furthermore, no significant differences were evaluated in postoperative complications (surgical site infection (SSI), ileus or bowel obstruction, refractory diarrhea, anastomotic leakage, deep vein thrombosis (DVT), hemorrhage) between the two groups on a median follow up of 12.6 months. Pathological examination showed no significant differences in total lymph nodes dissected and tumor stage.

The cranial-to-caudal approach with MCV ligation via the cranial approach (CC-plus) is a safe and effective method for LRH, offering advantages in terms of reduced operation time and intraoperative blood loss. This study's findings suggest that the CC-plus approach may be superior to the conventional cranial-to-caudal approach.

RNA binding motif 5 (RBM5) has emerged as crucial regulators in many cancers.

To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer (CRC) dictates that is essential.

Through Gene Expression Profiling Interactive Analysis, we analyzed RBM5 expression in colon adenocarcinoma and rectum adenocarcinoma tissues. For detecting the mRNA expression of RBM5, quantitative real time-polymerase chain reaction was performed. Protein expression levels of RBM5, hexokinase 2, lactate dehydrogenase A, phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated-protein kinase B (p-AKT), and AKT were determined via Western blot. Functionally, cell counting kit-8 and 5-ethynyl-2'-deoxyuridine (EDU) assay were performed to evaluate proliferation of CRC cells. Invasiveness and migration of CRC cells were evaluated through conducting transwell assays. Glucose consumption, lactate production and adenosine-triphosphate (ATP) production were measured through a glucose assay kit, a lactate assay kit and an ATP production assay kit, respectively. Besides, RNA immunoprecipitation assay, half-life RT-PCR and dual-luciferase reporter assay were applied to detect interaction between RBM5 and PTEN. To establish a xenotypic tumor mice, CRC cells were subcutaneously injected into the right flank of each mouse. Protein expression of RBM5, Ki67, and PTEN in tumor tissues was examined using immunohistochemistry staining. Haematoxylin and eosin staining was used to evaluate tumor liver metastasis in mice.

We discovered down-regulation of RBM5 expression in CRC tissues and cells. RBM5 overexpression repressed proliferation, migration and invasion of CRC cells. Meantime, RBM5 impaired glycolysis in CRC cells, presenting as decreased glucose consumption, decreased lactate production and decreased ATP production. Besides, RBM5 bound to PTEN mRNA to stabilize its expression. PTEN expression was positively regulated by RBM5 in CRC cells. The protein levels of PI3K and p-AKT were significantly decreased after RBM5 overexpression. The suppressive influences of RBM5 on glycolysis, proliferation and metastasis of CRC cells were partially counteracted by PTEN knockdown. RBM5 suppressed tumor growth and liver metastasis in vivo.

This investigation provided new evidence that RBM5 was involved in CRC by binding to PTEN, expanding the importance of RBM5 in the treatment of CRC.

Structural modification based on existing drugs, which ensures the safety of marketed drugs, is an essential approach in developing new drugs. In this study, we modified the structure of cabotegravir by introducing the front alkyne on the core structure through chemical reaction, resulting in the synthesis of 9 compounds resembling 1,2,3-triazoles. The potential of these new cabotegravir derivatives as tumor suppressors in gastrointestinal tumors was investigated. Based on the MTT experiment, most compounds showed a reduction in the viability of KYSE30 and HCT116 cells. Notably, derivatives 5b and 5h exhibited the most significant inhibitory effects. To further explore the effects of derivatives 5b and 5h on gastrointestinal tumors, KYSE30 cells were chosen as a representative cell line. Both derivatives can effectively curtail the migration and invasion capabilities of KYSE30 cells and induce apoptosis in a dose-dependent manner. We further demonstrated these derivatives induce cell apoptosis in KYSE30 cells by inhibiting the expression of Stat3 protein and Smad2/3 protein. Based on the above results, we suggest they show promise in developing drugs for esophageal squamous cell carcinoma.