Nanotechnology has revolutionized cancer treatment by providing innovative solutions through nanocancer therapies, nanovaccines, and nanoparticles. This review focuses on the application of these technologies in colorectal cancer (CRC), highlighting their progression from preclinical studies to clinical trials. Nanoparticles, including liposomes, silica, gold, and lipid nanoparticles, possess unique properties that enhance drug delivery, improve therapeutic efficacy, and minimize systemic toxicity. Additionally, nanovaccines are being developed to elicit robust immune responses against CRC cells. This paper offers a comprehensive overview of the current state of nanotechnology-based treatments for CRC, emphasizing key preclinical studies and clinical trials that demonstrate their potential. Furthermore, the review discusses the challenges faced in this field. It outlines future directions for research, underscoring the need for ongoing efforts to translate these promising technologies into practical clinical applications.

MicroRNA (miRNA) is involved in the genesis in viand development of colorectal cancer. The in vivo imaging of miRNA at the tumor sites is essential for understanding its role in colorectal cancer pathology and therapeutic target identification. However, achieving accurate imaging of miRNA at the tumor sites is hindered by the low abundance of miRNAs in tumor cells and nonspecific signal leakage in normal tissues. Here, we report a multivariate-gated catalytic hairpin assembly (CHA) nanosensor for the specific amplified imaging of microRNA-21 (miR-21) in human colorectal cancer tissues to reveal the underlying miR-21-associated molecular mechanism. The endogenous glutathione and exogenous near-infrared multivariate-gated design in combination with CHA probes improves the signal strength of target miR-21 and reduces the background interference. The nanosensor enables specific amplified imaging of miR-21 in vivo, and the signal-to-background ratios are 1.6-fold compared with traditional CHA methods. With the assistance of the designed nanosensor, we achieve the preliminary identification of tumor tissues and normal tissues from human clinical surgical resection samples. The overexpressed miR-21 is found to suppress the core mismatch repair recognition protein human mutS homologue 2 involved in DNA damage recognition and repair to inhibit the therapeutic efficacy of colorectal cancer. The strategy of probe design, which combines multivariate-gated activation methods with a signal amplification system, is applicable for accurate miRNA imaging and disease-relevant molecular mechanism research.

An initial analysis of population-based cancer survival data from Georgia revealed lower CRC survival rates compared to high-income countries. We conducted the study to address this issue and propose strategies for enhancing CRC care.

We analyzed CRC statistics, reviewed screening programs, and examined published CRC research in Georgia. Finally, we surveyed 16 oncologists from major institutions all over the country to assess molecular testing, treatment standards, and access to modern medications.

Despite CRC screening being available in Georgia, late diagnoses persist, with over a 1/3 of cases presenting with acute intestinal obstruction. As a result, 65 % of CRC patients are diagnosed at locally advanced or metastatic stages. All 16 oncologists reported limited molecular testing due to costs, with 13 not routinely performing MSI/MMR and NRAS/KRAS/BRAF testing. Consequently, only 15 % of patients receive anti-EGFR therapy. Oxaliplatin-based therapy is almost universally used for metastatic CRC as the first-line treatment. No CRC clinical trials have been conducted in Georgia over the past three years. Treatment for locally advanced rectalcancer typically includes chemoradiotherapy followed by surgery, with notable variation in multidisciplinary team meeting practices.

Study provides several practical recommendations: it is crucial to promote CRC screening programs, enhance access to modern treatment options, and standardize national diagnostic/treatment protocols. There is an urgent need for more clinical trials to increase access to modern therapeutics, as well as to strengthen MDT meetings. These measures are expected to improve CRC care with a further reduction in CRC mortality rates.

Colorectal cancer is a significant cause of mortality globally, with several factors impacting patient outcomes, including access to healthcare, early detection, and treatment. Despite this, the specific factors affecting incidence of death among colorectal cancer patients in the Amhara region have not been thoroughly investigated. Thus, this study seeks to assess incidence and determinants of mortality among colorectal cancer patients in Amhara Region oncology centers.

The mean age of the participants was 48.6 years (SD ± 15). Median survival time was 23.8 months. The overall incidence rate or incidence density of a colorectal cancer mortality rate was 2.9 per 100 person-months (95% CI: 2.5-3.4). Survival rates of colorectal cancer patients 1and 5 year was 69.78% and 16.1%, respectively. The result of the multivariable analysis showed that colorectal cancer patients who had presenting symptoms [AHR = 2.67 (95% CI: 1.95, 3.67)], Base line HGB level < 12.5 mg/dl [AHR = 1.63 (95% CI: 1.12, 2.37)], WHO or ECOG poor performance status [AHR = 2.99 (95% CI: 2.17, 4.12), late stage of cancer [AHR = 2.32 (95% CI: 1.42, 3.79)] and location of tumor on colorectal [AHR = 1.76 (95% CI: 1.20, 2.55)] were significantly associated with mortality of colorectal cancer.

The study highlights significant findings on the survival and mortality of colorectal cancer patients. The overall mortality rate was 2.9 per 100 person-months. Multivariable analysis identified presenting symptoms, low baseline hemoglobin levels, poor performance status, late-stage cancer, and tumor location as significant predictors of mortality. Highlighting the need for early detection and targeted care strategies.

CRC has the third-highest cancer incidence and death. Many human cancers, including colorectal cancer, are connected to abnormal signaling pathway gene expression. Many human malignancies include Hippo and Rap1 signaling. This research examined curcumin's therapeutic effects on colorectal cancer cell lines' Hippo and Rap1 signaling pathway genes. The role of the above signaling pathways is considered in colorectal cancer development. No research has examined curcumin's influence on key genes in these pathways; thus, this work is meant to uncover its more precise mechanism. First, the gene expression omnibus database is queried to discover GSE8671, a dataset that contains differentially expressed genes associated in CRC formation. DAVID was used to discover the corporation of these genes and signaling pathways (Hippo and Rap1), and the cancer genome atlas (TCGA) database was utilized to select genes and assess their expression and biomarker potential. MTT, apoptosis, and quantitative PCR were used to assess whether curcumin is therapeutic for colorectal cancer cell lines. An in-silico analysis identified the dysregulation of several critical genes AXIN2, MYC, TEAD4, MET, LPAR1, and ADCY9 in colorectal cancer, highlighting their involvement in the Hippo and Rap1 signaling pathways. Experimental assessments, including MTT assays, apoptosis assays, and quantitative PCR (qPCR) analysis, demonstrated that the targeted modulation of these genes effectively inhibits cancer cell proliferation. Specifically, treatment with curcumin resulted in a significant reduction in cell viability in HT-29 and HCT-116 colorectal cancer cell lines, thereby facilitating apoptotic cell death. Furthermore, curcumin administration was associated with the upregulation of LPAR1 and ADCY9 gene expression, while concurrently downregulating AXIN2, MYC, TEAD4, and MET in both cell lines. This study reveals compelling evidence of curcumin's potent anticancer properties, highlighting its transformative influence on the Hippo and Rap1 signaling pathways within colorectal cancer cells. These findings not only underscore curcumin's potential as a therapeutic agent but also pave the way for innovative strategies in the fight against colorectal cancer.

This study developed a prognostic model for patients with colon adenocarcinoma (COAD) based on glycosylation-associated genes. By analyzing TCGA-COAD data, 110 key genes were identified, and a prognostic model incorporating five glycosylation-related genes was constructed. The model exhibits good predictive performance and is significantly associated with clinical features such as age, N stage, M stage, and lymph node count. The prognostic genes are involved in various biological processes and pathways, influence T cell differentiation, and may contribute to CRC development. High-risk patients show a higher degree of immune cell infiltration. This model aids in the early diagnosis, prognosis assessment, and treatment planning for CRC, and offers a direction for further research.

This study addresses the complex multifactorial causes of Alzheimer's disease (AD) and colorectal cancer (CRC), two significant public health issues. Despite previous research, the precise relationship between AD and CRC remains unclear. This study aimed to explore the potential causal relationship between AD and CRC using Mendelian randomization (MR) and to identify risk genes through colocalization and transcriptomic analyses.

The study used a two-sample Mendelian randomization (MR) approach to investigate the causal effect of AD on CRC. Genome-wide association study (GWAS) summary statistics for AD and CRC were utilized. Colocalization analysis was conducted to identify risk genes associated with AD, which were then validated through transcriptomic analysis in CRC samples. The study used GWAS data from a cohort of European patients and applied several MR methods, including MR Egger, weighted median, and inverse-variance weighted approaches, to ensure robust findings.

The MR analysis revealed a significant positive causal relationship between AD and CRC, indicating that an increased genetic predisposition to AD is associated with a elevated risk of developing CRC. The colocalization analysis identified COLEC11 as a significant risk gene for AD, which also showed a strong positive correlation with clinical features and survival outcomes in CRC. Elevated COLEC11 expression was linked to advanced clinical stages, increased tumor mutational burden, microsatellite instability, and poorer overall survival in CRC patients.

This study provides evidence of a causal relationship between AD and CRC, suggesting that shared genetic and inflammatory pathways may underlie both conditions. The identification of COLEC11 as a potential link between AD and CRC offers new avenues for research and therapeutic interventions. These findings contribute to a deeper understanding of the interplay between neurodegenerative and oncologic diseases, highlighting the importance of exploring common pathogenic mechanisms.

Colorectal cancer (CRC) is considered a widespread cancer, ranking second in mortality and incidence among cancer patients worldwide. CRC develops from adenoma to carcinoma through the dynamic interplay of genetic and environmental factors. The conventional modes of treatment, including operation, chemotherapy, and irradiation, are associated with significant challenges, such as drug resistance and toxicity, necessitating the exploration of new treatment modalities. These difficulties reveal the necessity of the emergence of new therapeutic approaches. This review mainly emphasizes the bacterial-based therapies that have recently developed like the engineered bacteriophage therapy and bacterial immunotherapy that pale the existing chemotherapy in terms of toxicity but are effective in killing tumor cells. Also, it also investigates various molecular genetic engineering strategies such as CRISPR-Cas9, CRISPR prime editing and gene silencing to achieve better targeting of CRC. Implementing these new approaches into the forefront of CRC treatment may bring better, more effective therapy with fewer side effects on patients' quality of life.

Colon cancer (CC) is a leading cause of cancer-related mortality worldwide. Accurate prognostic markers are essential for patient risk stratification and personalized treatment. Copper-induced cell-death-related genes (CRG) have emerged as potential players in cancer prognosis, yet their role in CC remains unclear.

This study aimed to comprehensively evaluate the expression of CRG and their roles in CC using gene expression and clinical data from TCGA and GEO databases. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses identified prognostic genes, leading to the construction of a CRG prognostic signature. The signature's predictive accuracy was validated using Kaplan-Meier survival curves, Receiver Operating Characteristic (ROC) curves, and a nomogram model. Additionally, we conducted experiments including immunofluorescence staining and cellular assays to validate the key genes' biological functions.

A 12-gene CRG signature was significantly associated with overall survival in CC patients. The high-risk group, as classified by median risk score, exhibited significantly shorter survival times compared to the low-risk group. The signature's predictive accuracy was further confirmed with Area Under the Curve (AUC) scores exceeding 0.75 in TCGA and GSE17536 cohorts. Notably, the risk score was significantly correlated with immune checkpoints, chemotherapy sensitivity, and tumor microenvironment. Furthermore, the risk score showed a strong association with immunotherapy response in patients from GSE78220 and GSE39688 cohorts. Bioinformatics analysis of KIF7, a key gene within the signature, revealed its upregulation in CC and significant associations with tumor mutation burden, microsatellite instability, and immune cell infiltration across various cancers. Experiments confirmed that KIF7 was upregulated in CC and its knockdown reduced cell proliferation, migration, and invasion.

The CRG prognostic signature can effectively predict overall survival, immune microenvironment and chemotherapy response in CC. KIF7, as a potential prognostic marker, has significant potential for the prediction and treatment of CC.

Macrophages play a crucial role in tumor initiation and progression, while macrophage-associated gene signature in colorectal cancer (CRC) patients has not been investigated. Our study aimed to identify macrophage-related molecular subgroups and develop a macrophage-related risk model to predict CRC prognosis. The mRNA expression profile and clinical information of CRC patients were obtained from TCGA and GEO databases. CRC patients from TCGA were divided into high and low macrophage subgroups based on the median macrophage score. The ESTIMATE and CIBERSORT algorithms were used to assess immune cell infiltration between subgroups. GSVA and GSEA analyses were performed to investigate differences in enriched pathways between subgroups. Univariate and LASSO Cox regression were used to build a prognostic risk model, which was further validated in the GSE39582 dataset. A high macrophage score subgroup was associated with poor prognosis, highly activated immune-related pathways and an immune-active microenvironment. A total of 547 differentially expressed macrophage-related genes (DEMRGs) were identified, among which seven genes (including RIMKLB, UST, PCOLCE2, ZNF829, TMEM59L, CILP2, DTNA) were identified by COX regression analyses and used to build a risk score model. The risk model shows good predictive and diagnostic values for CRC patients in both TCGA and GSE39852 datasets. Furthermore, multivariate Cox regression analysis showed that the risk score was an independent risk factor for overall survival in CRC patients. Our findings provided a novel insight into macrophage heterogeneity and its immunological role in CRC. This risk score model may serve as an effective prognostic tool and contribute to personalised clinical management of CRC patients.

Hydrogen sulfide (H2S) is a critical molecule that participates in various molecular, physiological, and pathophysiological processes in biological systems. Emerging evidence has revealed that H2S is implicated in the progression of colon cancer and immune escape. Against this backdrop, the present study aimed to construct a prognostic risk feature for colon adenocarcinoma (COAD) by leveraging hydrogen sulfide-related genes (HSRG). Transcriptomic data and corresponding clinical-pathological information of colon cancer were obtained from The Cancer Genome Atlas and gene expression omnibus databases. Univariate Cox regression analysis was employed to assess the prognostic relevance of HSRG. Consensus clustering was utilized to perform molecular subtyping of COAD, followed by comparison of immune cell infiltration, drug sensitivity, and immune therapy response between subtypes. Differential expression gene and gene set enrichment analyses were conducted between subtypes. Univariate, lasso, and multivariate Cox regression analyses were applied to construct a prognostic model derived from HSRG. A nomogram model for predicting COAD prognosis was constructed and evaluated. In this study, we identified 12 HSRGs that were associated with COAD prognosis. Consensus clustering analysis revealed 3 COAD molecular subtypes that exhibited significant differences in terms of prognosis, tumor immune cell infiltration, drug sensitivity, and immune therapy response. Gene set enrichment analysis demonstrated that immunoregulatory processes were significantly suppressed in the poor-prognosis subtype while Wnt-related pathways and processes were significantly upregulated. Based on the differentially expressed genes between subtypes, we constructed a risk model comprising 11 genes that effectively distinguished high-risk patients from low-risk patients with significant associations with patient survival outcomes, drug treatment, pathological staging, and T staging. The HSRG-derived risk feature was an independent prognostic factor for COAD in drug treatment and pathological staging and could be integrated into a nomogram for prognosis prediction. Calibration curve, receiver operating characteristic curve, and decision curve analysis demonstrated excellent performance of the nomogram in evaluating COAD prognosis. Our study systematically assessed the prognostic significance of HSRG in COAD, identified HSRG-based molecular subtypes and risk features, and highlighted their potential utility in predicting prognosis and treatment response.

Oral metastasis from the colon is quite rare with limited reporting and scientific evidence. The most common metastasis from colorectal cancer is to the liver followed by lungs, bones, and other organs. However rare occurrences like metastasis to the oral cavity might worsen the prognosis and treatment outcome. Oral metastatic tumors account only 1% of all the malignant neoplasms of the jaw. In most of the cases metastasis has been reported in the jaw bones compared to soft tissues. Persistent pain and delayed, prolonged healing should raise the question of an underlying lesion. An unusual case of secondary oral metastasis presenting as an ulcero-proliferative growth in left mandibular alveolus from the primary colon adeno carcinoma has been reported.

Over the past years, insights in the cancer neuroscience field increased rapidly, and a potential role for neurons in colorectal carcinogenesis has been recognized. However, knowledge on the neuronal distribution, subtypes, origin, and associations with clinicopathological characteristics in human studies is sparse. In this study, colorectal tumor tissues from the Netherlands Cohort Study on diet and cancer (n = 490) and an in-cohort validation population (n = 529) were immunohistochemically stained for the pan-neuronal markers neurofilament (NF) and protein gene product 9.5 (PGP9.5) to study the association between neuronal marker expression and clinicopathological characteristics. In addition, tumor and healthy colon tissues were stained for neuronal subtype markers, and their immunoreactivity in colorectal cancer (CRC) stroma was analyzed. NF-positive and PGP9.5-positive nerve fibers were found within the tumor stroma and mostly characterized by the neuronal subtype markers vasoactive intestinal peptide and neuronal nitric oxide synthase, suggesting that inhibitory neurons are the most prominent neuronal subtype in CRC. NF and PGP9.5 protein expression were not consistently associated with tumor stage, sublocation, differentiation grade, and median survival. NF immunoreactivity was associated with a worse CRC-specific survival in the study cohort (P = .025) independent of other prognostic factors (hazard ratio, 2.31; 95% CI, 1.33-4.03; P = .003), but these results were not observed in the in-cohort validation group. PGP9.5, in contrast, was associated with a worse CRC-specific survival in the in-cohort validation (P = .046) but not in the study population. This effect disappeared in multivariate analyses (hazard ratio, 0.81; 95% CI, 0.50-1.32; P = .393), indicating that this effect was dependent on other prognostic factors. This study demonstrates that the tumor stroma of CRC patients mainly harbors inhibitory neurons and that NF as a single marker is significantly associated with a poorer CRC-specific survival in the study cohort but necessitates future validation.

Increasing studies have revealed the critical roles of human microbiome in a wide variety of disorders. Identification of disease-associated microbes might improve our knowledge and understanding of disease pathogenesis and treatment. Computational prediction of microbe-disease associations would provide helpful guidance for further biomedical screening, which has received lots of research interest in bioinformatics. In this study, a deep learning-based computational approach entitled SGJMDA is presented for predicting microbe-disease associations. Specifically, SGJMDA first fuses multiple similarities of microbes and diseases using a nonlinear strategy, and extracts feature information from homogeneous networks composed of the fused similarities via a graph convolution network. Second, a heterogeneous microbe-disease network is built to further capture the structural information of microbes and diseases by employing multi-neighborhood graph convolution network and jumping knowledge network. Finally, potential microbe-disease associations are inferred through computing the linear correlation coefficients of their embeddings. Results from cross-validation experiments show that SGJMDA outperforms 6 state-of-the-art computational methods. Furthermore, we carry out case studies on three important diseases using SGJMDA, in which 19, 20, and 11 predictions out of their top 20 results are successfully checked by the latest databases, respectively. The excellent performance of SGJMDA suggests that it could be a valuable and promising tool for inferring disease-associated microbes.

The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be established.

This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency.

This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and guidelines.

The 46 recommendations in this CPG are formed with consideration for stakeholders' values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.

To construct chimeric antigen receptor (CAR)-T cells targeting epithelial cell adhesion molecule (EpCAM) antigen (anti-EpCAM-CAR-T).

A third-generation CAR-T cell construct used a single-chain variable fragment derived from monoclonal antibody against human EpCAM. Peripheral blood mononuclear cells were extracted from volunteers. The proportion of cluster of differentiation 8 positive (CD8+) and CD4 + T cells was measured using flow cytometry. Western blot was used to detect the expression of EpCAM-CAR. The killing efficiency was detected using the MTT assay and transwell assay, and the secretion of killer cytokines tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was detected using the ELISA. The inhibitory effect of EpCAM-CAR-T on colorectal cancer in vivo was detected using xenografts.

It was found that T cells expanded greatly, and the proportion of CD3+, CD8 + and CD4 + T cells was more than 60%. Furthermore, EpCAM-CAR-T cells had a higher tumour inhibition rate in the EpCAM expression positive group than in the negative group (P < 0.05). The secretion of killer cytokines TNF-α and IFN-γ in the EpCAM expression positive cell group was higher than that in the negative group (P < 0.05). In the experimental group treated with EpCAM-CAR-T cells, the survival rate of nude mice was higher (P < 0.05), and the tumour was smaller than that in the blank and control groups (P < 0.05). The secretion of serum killer cytokines TNF-α and IFN-γ in tumour-bearing nude mice in the experimental group treated with EpCAM-CAR-T cells was higher than that in the blank and control groups (P < 0.05).

This study successfully constructed EpCAM-CAR cells and found that they can target and recognise EpCAM-positive tumour cells, secrete killer cytokines TNF-α and IFN-γ and better inhibit the growth and metastasis of colorectal cancer in vitro and in vivo than unmodified T cells.

The purpose of this study was to investigate the causal association between unhealthy lifestyle style factors and the risk of colorectal cancer, with the aim of preventing the occurrence of colorectal cancer by modifying unhealthy lifestyles. A two-sample Mendelian randomization (MR) approach was employed in this study, utilizing the inverse-variance weighted method as the primary research method. This MR analysis analyzed data of 3022 colorectal cancer cases and 174,006 controls from the FinnGen database. Single nucleotide polymorphisms (SNPs) associated with unhealthy lifestyle factors were selected as instrumental variables (IVs), including two obesity-related indicators, BMI (body mass index) and WHR (waist-to-hip ratio). Four phenotypes of smoking (smoking initiation, ever smoked, smoking per day, smoking cessation) and one phenotype of alcohol consumption (drinks per week). Four phenotypes of physical activity (accelerometer-based physical activity, moderate-to-vigorous physical activity, vigorous physical activity, strenuous sports or other exercises). All SNPs were obtained from published genome-wide association studies. The study found that the obesity-related indicator, higher WHR (OR = 1.38, 95% CI 1.12-1.70; P = 0.002) were associated with an increased risk of colorectal cancer, and two smoking phenotypes, cigarettes per day(OR = 1.30, 95% CI 1.01-1.68; P = 0.042)and smoking initiation (OR = 3.48, 95% CI 1.15-10.55; P = 0.028), were potentially associated with an increased risk of colorectal cancer. However, there was no evidence to suggest that physical activities and alcohol consumption were associated with colorectal cancer (all p > 0.05). In addition, the study detected no pleiotropy (all p > 0.05). This MR analysis indicates a causal association between a higher waist-to-hip ratio and the risk of colorectal cancer and a suggestive association between smoking and the risk of colorectal cancer among Europeans. These findings contribute to the understanding of the etiology of colorectal cancer and have potential implications for its prevention.

Colon cancer (CC) is one of the most frequent cancers worldwide being responsible for over 500 thousand deaths in 2022. Its financial and human burden is expected to increase in the next decades accompanying the growing and aging of the global population. Much of this burden could be alleviated considering that the lethality of CC is mostly due to its late diagnosis and failure in the individualized management of patients. Coordinated government actions and implementation of better diagnostic tools capable of detecting CC earlier and of tracking tumoral evolution are mandatory to achieve a reduction in CC's social impact. CtDNA-based liquid biopsy (LB) has great potential to contribute to patients' screening adhesion, CC earlier detection, and to longitudinal tumor follow-up. In this review, we will discuss the latest epidemiological data on CC disease, diagnostic, subtypes, genetics, and treatment management focusing on the advantages and limitations of ctDNA-based LB, including important bottlenecks and solutions necessary for its clinical translation. The latest ctDNA-directed CC clinical trials will also be examined.

Despite that colorectal and liver cancer are among the most prevalent tumours in the world, the identification of non-invasive biomarkers to aid on their diagnose and subsequent prognosis is a current unmet need that would diminish both their incidence and mortality rates. In this context, conventional flow cytometry has been widely used in the screening of biomarkers with clinical utility in other malignant processes like leukaemia or lymphoma. Therefore, in this review, we will focus on how advanced cytometry panels covering over 40 parameters can be applied on the study of the immune system from patients with colorectal and hepatocellular carcinoma and how that can be used on the search of novel biomarkers to aid or diagnose, prognosis, and even predict clinical response to different treatments. In addition, these multiparametric and unbiased approaches can also provide novel insights into the specific immunopathogenic mechanisms governing these malignant diseases, hence potentially unravelling novel targets to perform immunotherapy or identify novel mechanisms, rendering the development of novel treatments. As a consequence, computational cytometry approaches are an emerging methodology for the early detection and predicting therapies for gastrointestinal cancers.

Complete remission of colorectal cancer (CRC) is still unachievable in the majority of patients by common fractionated radiotherapy, leaving risks of tumor metastasis and recurrence. Herein, clinical CRC samples demonstrated a difference in the phosphorylation of translation initiation factor eIF2α (p-eIF2α) and the activating transcription factor 4 (ATF4), whose increased expression by initial X-ray irradiation led to the resistance to subsequent radiotherapy. The underlying mechanism is studied in radio-resistant CT26 cells, revealing that the incomplete mitochondrial outer membrane permeabilization (iMOMP) triggered by X-ray irradiation is key for the elevated expression of p-eIF2α and ATF4, and therefore radio-resistance. This finding guided to discover that metformin and 2-DG are synergistic in reversing radio resistance by inhibiting p-eIF2α and ATF4. Liposomes loaded with metformin and 2-DG (M/D-Lipo) are thus prepared for enhancing fractionated radiotherapy of CRC, which achieved satisfactory therapeutic efficacy in both local and metastatic CRC tumors by reversing radio-resistance and preventing T lymphocyte exhaustion.

The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC.

We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC.

The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC.

These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy.

Despite the recognized benefits of structured cancer screening, tests outside organized screening programs are common. Comprehensive reports on outside program screening in Europe are lacking, but the Flemish breast cancer (BC) and colorectal cancer (CRC) screening programs monitor data on non-organized tests prescribed by GPs and specialists.

Using data at aggregated level, logistic regression was used to examine the relationship between health care utilization and screening coverage in 308 Flemish municipalities during 2015-18.

With regards to BC, municipalities with higher rates of gynecologists' visits had lower odds of coverage inside (-8%) and higher odds of coverage outside (+17%) the program. By contrast, municipalities with higher rates of GP visits, had higher odds of coverage inside (+6%) and lower odds of coverage outside (-7%) the program. As for CRC, municipalities with higher rates of visits gastroenterologists' visits had lower odds of coverage inside (-3%). Instead, municipalities with higher rates of GP visits, had higher odds of coverage both inside (+2%) and outside (+5%) the program. Municipalities with higher percentages of people with chronic conditions had higher odds of coverage within both the BC and CRC programs (+5% and +3%), and lower odds of outside screening (-7% and -6%). Municipalities with higher percentages of people 65+ with dementia and with mood disorders had, respectively, higher odds (+13% and +5%) and lower odds (-3% and -4%) of coverage inside both the BC and CRC programs.

Our findings underscore the impact of healthcare utilization on cancer screening coverage at the municipal level in Flanders.

Background The incidence of colorectal cancer (CRC) is increasing in developing countries. The factors contributing to the risk of CRC are not known in developing countries. Therefore, this study aimed to explore the role of a healthy lifestyle on CRC in the adult population in the Kurdistan Region of Iraq. Methodology In this case-control investigation, patients previously diagnosed with CRC were included as cases (n = 84) and the healthy adult population as healthy controls (n = 87). The patients were selected from the Gastroenterology Unit of Azadi Teaching Hospital and Emergency Teaching Hospital. The healthy controls were selected from the caregivers of patients who met the eligibility criteria. Results Individuals with a history of chronic disease (63.08% vs. 40.52%; p = 0.0043), a history of hypertension (71.74% vs. 40.80%; p = 0.0003), and a history of inflammatory bowel disease (IBD) (59.42% vs. 42.16%; p = 0.0267) had a significantly higher prevalence of CRC compared to healthy controls. CRC patients had significantly lower diet quality scores than healthy controls (36.27 vs. 37.83; p = 0.0002). The study showed that CRC patients had a significantly lower lifestyle index score compared to healthy controls (10.20 vs. 11.69; p = 0.0002). In addition, CRC patients had lower scores for diet (0.42 vs. 1.00; p < 0.0001), smoking (2.92 vs. 4.0; p < 0.0001), and physical activity (1.02 vs. 1.70; p < 0.0001) compared to healthy controls. However, CRC patients and healthy controls had similar alcohol index scores (5.0 vs. 530; p = 1.000) and body mass index (1.04 vs. 1.01; p = 0.8982). Conclusions This study showed that CRC was associated with having a history of bad diet quality and unhealthy lifestyles. In addition, a history of chronic diseases, hypertension, and IBD was associated with the risk of CRC.

Intra-tumoural heterogeneity and cancer cell plasticity in colorectal cancer (CRC) have been key challenges to effective treatment for patients. It has been suggested that a subpopulation of LGR5-expressing cancer stem cells (CSCs) is responsible for driving tumour relapse and therapy resistance in CRC. However, studies have revealed that the LGR5+ve CSC population is highly sensitive to chemotherapy. It has been hypothesised that another subset of tumour cells can phenotypically revert to a stem-like state in response to chemotherapy treatment which replenishes the LGR5+ve CSC population and maintains tumour growth. Recently, a unique stem cell population marked by enriched clusterin (CLU) expression and termed the revival stem cell (RevSC) was identified in the regenerating murine intestine. This CLU-expressing cell population is quiescent during homeostasis but has the ability to survive and regenerate other stem cells upon injury. More recently, the CLU+ve signature has been implicated in several adverse outcomes in CRC, including chemotherapy resistance and poor patient survival; however, the mechanism behind this remains undetermined. In this review, we discuss recent insights on CLU in CRC and its roles in enhancing the plasticity of cells and further consider the implications of CLU as a prospective target for therapeutic intervention.

Colorectal cancer (CRC) is globally recognized as a prevalent malignancy known for its significant mortality rate. Recent years have witnessed a rising incidence trend in colorectal cancer, emphasizing the necessity for early diagnosis. Our study focused on examining the impact of the SMAD7 gene variant rs4939827 on the risk of colorectal cancer occurrence. The composition of our study group included 340 individuals, comprising 170 CRC diagnosed patients and 170 healthy controls. We performed genotyping of all biological samples using the TaqMan assay on the ABI 7500 Real-Time PCR System (Applied Biosystems, Waltham, MA, USA). This investigation focused on the rs4939827 gene variant, assessing its association with CRC risk and clinicopathological characteristics. Genotyping results for the SMAD7 gene variant rs4939827 revealed a 42.6% prevalence of the C allele in CRC patients (p = 0.245) and a 22.8% prevalence of the T allele in control subjects (p = 0.109). This study concluded that there was an elevated risk of CRC in the dominant model for CC/CT+TT, with a p-value of 0.113 and an odds ratio (OR) of 2.781, within a 95% confidence interval (CI) of 0.998 to 3.456. The findings of our research indicate a correlation between variants of the SMAD7 gene and the likelihood of developing colorectal cancer in our study population. Consequently, these results could be instrumental in facilitating early diagnosis of colorectal cancer utilizing information on single-nucleotide polymorphism (SNP) and genetic susceptibility to the disease.

Colon cancer is a common and malignant cancer featuring high morbidity and poor prognosis.

This study was performed to explore the regulatory role of MT1G in colon cancer as well as its unconcealed molecular mechanism.

The expressions of MT1G, c-MYC, and p53 were assessed with the application of RT-qPCR and western blot. The impacts of MT1G overexpression on the proliferative ability of HCT116 and LoVo cells were measured by CCK-8 and BrdU incorporation assays. Additionally, transwell wound healing, and flow cytometry assays were employed to evaluate the invasive and migrative capacities as well as the apoptosis level of HCT116 and LoVo cells. Moreover, the activity of the P53 promoter region was assessed with the help of a luciferase reporter assay.

It was found that the expressions of MT1G at both mRNA and protein levels were greatly decreased in human colon cancer cell lines, particularly in HCT116 and LoVo cell lines. After transfection, it was discovered that the MT1G overexpression suppressed the proliferation, migration and invasion but promoted the apoptosis of HCT116 and LoVo cells, which were then partially reversed after overexpressing c-MYC. Additionally, MT1G overexpression reduced c-MYC expression but enhanced the p53 expression, revealing that the MT1G overexpression could regulate c-MYC/P53 signal. Elsewhere, it was also shown that c-MYC overexpression suppressed the regulatory effects of MT1G on P53.

To conclude, MT1G was verified to regulate c-MYC/P53 signal to repress the proliferation, migration and invasion but promote the apoptosis of colon cancer cells, which might offer a novel targeted-therapy for the improvement of colon cancer.

Colorectal cancer (CRC) is a common and deadly form of cancer, leading to the need for new therapeutic targets and strategies for treatment. Recent studies have shown the cGAS-STING pathway to be a promising target for cancer therapy. The cGAS-STING pathway is a part of the innate immune system and serves to identify DNA damage and viral infection, promoting an immune response. Activation of this pathway leads to the production of immune mediators, such as type I interferons, that activate immune cells to attack cancer cells. Research has identified the cGAS-STING pathway as a frequently dysregulated component in CRC, promoting tumor growth and metastasis, or leading to chronic inflammation and tissue damage. The modulation of this pathway presents a potential therapeutic approach, either activating or inhibiting the pathway to enhance the immune response and prevent inflammation, respectively. Developing drugs that can modulate the cGAS-STING pathway offers promise for improving treatment outcomes for CRC patients. The present review explores recent research on the role of cGAS-STING in CRC and highlights the potential therapeutic benefits of targeting this pathway.

Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence of CRC is rising in low- and middle-income countries but decreasing in high-income countries due to the widespread use of surveillance colonoscopy. In Africa, the implementation of screening programs remains a challenge, even in countries, such as Ghana that have established CRC screening guidelines.

The purpose of this review was to identify the barriers and recommend strategies for implementing CRC screening in African countries.

A literature search using PubMed was conducted with the following search terms: colorectal neoplasm, early detection of cancer, mass screening, colonoscopy, faecal occult blood test, faecal immunochemical test (FIT) and Africa. After inclusion and exclusion criteria were applied, a total of 13 articles were reviewed.

The most common barriers reported were limited endoscopic capacity, poor knowledge of CRC and CRC screening, health care factors, cultural factors and sociodemographic factors. Recommendations to increase the availability of CRC screening tests were to include the use of FITs, to provide more training for health care providers, and to expand educational programs for patients, physicians, and religious/community leaders.

The primary barrier to screening for CRC in Africa is the limited endoscopic capacity, specifically the lack of infrastructure and trained personnel, which requires systematic changes by governing bodies. In addition, health care professionals should be involved in educating patients about CRC and CRC screening. Further research is needed to clarify the factors related to subtypes of CRC and to explore the feasibility of using FITs in Africa.

Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, accounting for the second most common cause of gastrointestinal tumors. As one of the intestinal barriers, gut bacteria form biofilm, participate in intestinal work, and form the living environment of intestinal cells. Metagenomic next-generation sequencing (mNGS) of the gut bacteria in a large number of CRC patients has been established, enabling specific microbial signatures to be associated with colorectal adenomato-carcinoma. Gut bacteria are involved in both benign precursor lesions (polyps), in situ growth and metastasis of CRC. Therefore, the term tumorigenic bacteria was proposed in 2018, such as Escherichia coli, Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, etc. Meanwhile, bacteria toxins (such as cytolethal distending toxin (CDT), Colibactin (Clb), B. fragilis toxin) affect the tumor microenvironment and promote cancer occurrence and tumor immune escape. It is important to note that there are differences in the bacteria of different types of CRC. In this paper, the role of tumorigenic bacteria in the polyp-cancer transformation and the effects of their secreted toxins on the tumor microenvironment will be discussed, thereby further exploring new ideas for the prevention and treatment of CRC.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment. In addition, recent studies have shown that radiotherapy and ICBs act synergistically, with radiotherapy stimulating the immune system that is activated by ICBs. However, both treatments are also associated with severe toxicity and efficacy issues, which can lead to temporary or permanent discontinuation of these treatment programs. There's growing evidence pointing to the gut microbiome playing a role in these issues. Some microorganisms seem to contribute to radiotherapy-associated toxicity and hinder ICB efficacy, while others seem to reduce radiotherapy-associated toxicity or enhance ICB efficacy. Consequently, fecal microbiota transplantation (FMT) has been applied to reduce radio- and immunotherapy-related toxicity and enhance their efficacies. Here, we have reviewed the currently available preclinical and clinical data in CRC treatment, with a focus on how the gut microbiome influences radio- and immunotherapy toxicity and efficacy and if these treatments could benefit from FMT.

Colorectal cancer, is one of most prevalent the cancer in the world. 5-Fluorouracil is a standard chemotherapeutic drug while the acquisition of resistance to 5-Fluorouracil is one of the problems during treatment. In this study, we aimed to find the miRNAs that modulate the expression of Tyms and Abcg2 as resistance-inducing genes in the resistant cell lines to 5-Fluorouracil.

5-Fluorouracil-resistant HCT116 and SW480 cell lines were generated by consecutive treatment of cells with 5-Fluorouracil. This resistance induction was validated by MTT assays. The expression of the Tyms and Abcg2 gene and miR-548c-3p were studied by quantitative real-time PCR in the cell lines.

We hypothesized that miR-548c-3p is targeting Tyms and Abcg2 simultaneously. Increased expression Tyms gene in the two most resistant cell lines derived from HCT116 and all resistant cell lines derived from SW480 except one were seen. Increased expression of Abcg2 was observed in the most resistant HCT116-derived cell line and all resistant cell lines, derived from SW480. In all resistant cell lines, the expression of miR-548c-3p was decreased.

It can be concluded downregulation of miR548c-3p is in line with Tyms and Abcg2 overexpression in resistant cell lines to 5-Fluorouracil.

colonoscopy is the best method for detecting polyps, with a reduction in colorectal cancer mortality of 29% and reaching 47% for distal tumors. However, it fails to demonstrate a significant reduction in proximal colon cancer mortality, and is the most common segment with interval neoplasm. The present study aimed to evaluate the impact on detection of polyps of a second sequential evaluation of cecum and ascending colon, with or without the use of indigo carmine chromoendoscopy.

prospective, non-randomized clinical trial. Patients were divided into two groups. The first (G1) underwent a routine colonoscopy, followed by a second endoscopy assessment of ascending colon and cecum. The second group (G2) underwent a routine colonoscopy, followed by a second assessment of the ascending colon and cecum with indigo carmine chromoendoscopy.

In total, 203 patients were analyzed, 101 in the G1 and 102 in the G2. Newer polyps were identified in both groups after the second assessment with a significantly higher number of polyps detected in the patients in the G2 (p=0.0001). The number of patients who had at least one polyp in the two endoscopic assessments was significantly higher in the G2 (53 or 52% vs 27 or 26.7%, p=0.0002). In the second endoscopic assessment, the number of polyps found was also significantly higher in the G2 (50 or 76.9%) compared to the G1 (15 or 23.1%), p<0.0001.

the second assessment with dye-based chromoendoscopy increases the detection of polyps in the ascending colon and cecum.

The development of deep learning systems in artificial intelligence (AI) has enabled advances in endoscopy, and AI-aided colonoscopy has recently been ushered into clinical practice as a clinical decision-support tool. This has enabled real-time AI-aided detection of polyps with a higher sensitivity than the average endoscopist, and evidence to support its use has been promising thus far. This review article provides a summary of currently published data relating to AI-aided colonoscopy, discusses current clinical applications, and introduces ongoing research directions. We also explore endoscopists' perceptions and attitudes toward the use of this technology, and discuss factors influencing its uptake in clinical practice.

Synchronous carcinoma is defined as multiple malignant lesions presented in a single patient at initial diagnosis. Synchronous colorectal adenocarcinoma is a rare entity that has been increasingly recognized, likely due to the significant improvement in imaging and diagnostic tools. Making the appropriate diagnosis of synchronous colorectal cancer has a major role in the management's determination and treatment plans. Herein, we are reporting a case of a 73-year-old gentleman who was diagnosed with synchronous colorectal adenocarcinoma with two masses in the left colon and was treated initially surgically followed by chemotherapy.

The incidence of small intestinal cancer (SIC) is increasing, however, its aetiology remains unclear due to a lack of data from large-scale prospective cohorts. We examined modifiable risk factors in relation to SIC overall and by histological subtype.

We analysed 450,107 participants enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. Cox proportional hazards models were used to estimate univariable and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).

During an average of 14.1 years of follow-up, 160 incident SICs (62 carcinoids, 51 adenocarcinomas) were identified. Whilst univariable models revealed a positive association for current versus never smokers and SIC (HR, 95% CI: 1.77, 1.21-2.60), this association attenuated in multivariable models. In energy-adjusted models, there was an inverse association across vegetable intake tertiles for SIC overall (HRT3vsT1, 95% CI: 0.48, 0.32-0.71, p-trend: < 0.001) and for carcinoids (HRT3vsT1, 95% CI: 0.44, 0.24-0.82, p-trend: 0.01); however, these attenuated in multivariable models. Total fat was also inversely associated with total SIC and both subtypes but only in the second tertile (SIC univariable HRT2vsT1, 95% CI: 0.57, 0.38-0.84; SIC multivariable HRT2vsT1, 95% CI: 0.55, 0.37-0.81). Physical activity, intake of alcohol, red or processed meat, dairy products, or fibre were not associated with SIC.

These exploratory analyses found limited evidence for a role of modifiable risk factors in SIC aetiology. However, sample size was limited, particularly for histologic subtypes; therefore, larger studies are needed to delineate these associations and robustly identify risk factors for SIC.

H2.0-like homeobox (HLX) is highly expressed in several hematopoietic malignancies. However, the role of HLX in the carcinogenesis and progression of colorectal cancer (CRC) patients has rarely been reported.

In this study, the data were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. The diagnostic value of HLX was analyzed by the R package "pROC." The overall survival was estimated using the "survival" and "survminer" packages. A nomogram was established to predict 1-, 3-, and 5-year overall survival of CRC patients. The CIBERSORT software was employed to calculate the relative proportions of 22 immune cells.

HLX expression was downregulated in CRC patients. Remarkably, HLX expression was increased with stage (stage I-stage III) of CRC, and the CRC patients with high HLX expression exhibited a poor prognosis. The promoter methylation level of HLX was prominently increased in CRC samples compared to paracancerous samples. We also found that the six miRNAs target HLX genes, leading to its downregulation, and HLX expression had a negative correlation with its downstream target gene BRI3BP in both CRC and normal samples. Finally, we found that the 12 immune infiltrating cells were observably different between high and low HLX expression groups. The HLX had a significant positive correlation with 8 immune checkpoints (PD-1 (PDCD1), CTLA4, PDL-1 (CD274), PDL-2 (PDCD1LG2), CD80, CD86, LAG3, and TIGIT) expressions.

HLX probably played a carcinostasis role in the early stages of CRC but exhibited a cancer-promoting effect in the advanced stages. Meanwhile, HLX could serve as a reliable prognostic indicator for CRC.

Colon cancer remains a leading cause of cancer-related deaths, and there has been a rise in the incidence of early-onset colon cancer or colon cancer diagnosed before the age of 50 years old. Early-onset colon cancer has several differences in clinical presentation, as well as histopathology, genetic alteration, and molecular profiling. Early-onset colon cancer can be differentiated into familial type that includes hereditary familial syndrome and sporadic type. Demographic variance also exists in both developing and developed countries. Due to the rising incidence of colon cancer diagnosed in younger age, it is imperative to examine the available evidence regarding the mortality rate of early-onset colon cancer. Colon cancer is affected by numerous modifiable and non-modifiable risk factors. Increasing obesity and lifestyle disorders in the younger population, such as smoking, may influence this increasing trend. There are existing guidelines for colon cancer screening in both average-risk and high-risk individuals. This narrative review aims to highlight the pathogenesis of early-onset CRC; its clinical presentation, treatment, prognosis; and how it differs from late-onset CRC.

There is increasing evidence for a close correlation between risk stratification, prognosis and the immune environment in colon adenocarcinoma (COAD). However, the efficacy of immunotherapy is different among different patients with COAD. Therefore, the current work tends to use immune-related gene to develop a gene-pair model to evaluate the COAD prognosis, and to develop a new method for risk stratification of COAD, which is conducive to better predict the immunotherapy effect of patients.

Specifically, from the TCGA and GEO (GSE14333 and GSE39582) databases, we first collected gene expression profiles, associated survival follow-up information of COAD patients. Through systematic bioinformatics analysis, we established a prognosis-related model of colon cancer with three pairs of "immune gene pairs", with uni- and multivariate and lasso cox regression analyses verifying the model stability. Most immune cells showed markedly different levels of infiltration between the two risk subgroups calculated by the model. More, single-cell RNA-seq analyses were also performed to validate the selected genes in the immune gene-pair model.

A prognosis-related model of colon cancer with three pairs of "immune gene pairs" were built and validated by several datasets. The analysis of immune landscape of COAD revealed that low-risk subgroup obtained by the prognosis-related model for COAD can be further divided into three subclusters with different prognosis. Then, we applied the Tumor online Prognostic analyses Platform (ToPP) to construct a prognostic model using these five genes. Results show that APOD, ISG20 and STC2 are risk factors, while CXCL9 and IL7R are protection factors. We also found that only the five-gene model could also predict the prognosis of COAD patients, indicating the robustness of the gene-pair model. Among the five genes, including CXCL9, APOD, STC2, ISG20, and IL7R, in the gene-pair model, single-cell RNA sequencing reveals the high expression of CXCL9 and IL7R in inflammatory macrophages. Using cell-cell interaction and trajectory analysis, data indicate that CXCL9+/IL7R+ pro-inflammatory macrophages were capable of secreting and activating more anti-tumor pathways than CXCL9-/IL7R- pro-inflammatory macrophages.

In short, we have successfully developed an "immune gene pair" related model that can judge the prognostic status of patients with COAD and may contribute to risk stratification and evaluate potential beneficiaries of immunotherapy, providing new ideas for the anti-COAD management and therapy.

Most prior studies have reported cancer mortality trends across countries for specific cancer types. Herein, we examine recent patterns and trends in cancer mortality rates for the eight common forms of cancer in 47 countries across five continents (except Africa) based on the World Health Organization mortality database.

Rates were age-standardized to the 1966 Segi-Doll world population, and trends in the age-standardized rates for the most recent 10 years of data were examined using Joinpoint regression.

Cancer-specific mortality rates vary substantially across countries, with rates of infection-related (cervix and stomach) and tobacco-related cancers (lung and esophagus) varying by 10-fold. Recent mortality rates for all major cancers decreased in most of the studied countries except lung cancer in females and liver cancer in males, where increasing rates were observed in most countries. Rates decreased or stabilized in all countries for lung cancer in men and stomach cancer in both sexes.

The findings reinforce the importance of implementing and strengthening resource-stratified and targeted cancer prevention and control programs in all parts of the world to further reduce or halt the rising cancer burden.

The results may inform cancer prevention and treatment strategies and in so doing, reduce the marked global cancer disparities observed today.

Cases of digestive cancers diagnosed during pregnancy are rare. The increasing prevalence of pregnancy in women aged 30-39 years (and not exceptionally 40-49 years) could explain the frequent co-occurrence of cancers and pregnancy. The diagnosis of digestive cancers in pregnancy is difficult due to the overlap between neoplasm symptomatology and the clinical picture of pregnancy. A paraclinical evaluation may also be difficult depending on the trimester of the pregnancy. Diagnosis is also delayed by practitioners' hesitation to use invasive investigations (imaging, endoscopy, etc.) due to fetal safety concerns. Therefore, digestive cancers are often diagnosed during pregnancy in advanced stages, where complications such as occlusions, perforations, and cachexia have already arisen. In this review, we highlight the epidemiology, clinical aspects, paraclinical evaluation, and particularities of the diagnosis and treatment of gastric cancer during pregnancy.

Despite extensive research on sex differences in primary thyroid cancer, there is a lack of data on the role of sex in the risk of developing second primary thyroid cancer (SPTC). We aimed to investigate the risk of SPTC development according to patient sex, with an emphasis concerning previous malignancy location as well as age.

Cancer survivors diagnosed with SPTC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The SEER*Stat software package obtained standardized incidence ratios (SIR) and absolute excess risks of subsequent thyroid cancer development.

Data for 9,730 (62.3%) females and 5,890 (37.7%) males were extracted for a total of 15,620 SPTC individuals. Asian/Pacific Islanders had the highest incidence of SPTC [SIR =2.67, 95% confidence interval (CI): 2.49-2.86]. The risk of SPTC was higher in males (SIR =2.01, 95% CI: 1.94-2.08) than when compared to females (SIR =1.83, 95% CI: 1.79-1.88; P<0.001). Head and neck tumors had significantly higher SIRs for SPTC development in males when compared to females.

Survivors of primary malignancies have an increased risk SPTC, especially males. Our work suggests that oncologists and endocrinologists may consider the need for increased surveillance of both male and female patients given their increased risk of SPTC.

In spite of the increasing number of biologics license applications, the development of covalent inhibitors is still a growing field within drug discovery. The successful approval of some covalent protein kinase inhibitors, such as ibrutinib (BTK covalent inhibitor) and dacomitinib (EGFR covalent inhibitor), and the very recent discovery of covalent inhibitors for viral proteases, such as boceprevir, narlaprevir, and nirmatrelvir, represent a new milestone in covalent drug development. Generally, the formation of covalent bonds that target proteins can offer drugs diverse advantages in terms of target selectivity, drug resistance, and administration concentration. The most important factor for covalent inhibitors is the electrophile (warhead), which dictates selectivity, reactivity, and the type of protein binding (i.e., reversible or irreversible) and can be modified/optimized through rational designs. Furthermore, covalent inhibitors are becoming more and more common in proteolysis, targeting chimeras (PROTACs) for degrading proteins, including those that are currently considered to be 'undruggable'. The aim of this review is to highlight the current state of covalent inhibitor development, including a short historical overview and some examples of applications of PROTAC technologies and treatment of the SARS-CoV-2 virus.

Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation.

In this study, we statistically analyzed the relationship between VDR expression and CRC development in patients and detected invasion and apoptosis in CRC cells with VDR overexpression and interference. We also detected the expression of key genes involved in Wnt/β-catenin signalling (β-catenin, lymphoid enhancer factor (LEF)-1 and cyclin D1) in SW480 cells and nude mice injected with VDR-overexpressing SW480 cells and observed tumour development. Additionally, we performed Co-immunoprecipitation (Co-IP) and glutathione-S-transferase (GST) pull-down assays to identify the protein interactions of VDR with β-catenin, dual luciferase (LUC) and chromatin immunoprecipitation (ChIP) to detect the activation of LEF-1 by VDR.

The VDR level was closely related to the development and prognosis of CRC patients. VDR overexpression inhibited invasion but promoted apoptosis in cancer cells. β-catenin shRNA contributed oppositely to cancer cell activity with VDR shRNA. Additionally, VDR interacted with β-catenin at the protein level and blocked its nuclear accumulation. VDR regulated the expression of β-catenin, cyclin D1 and LEF-1 and directly activated LEF-1 transcription in vitro. Furthermore, nude mice injected with VDR-overexpressing SW480 cells revealed suppression of tumour growth and decreased expression of β-catenin, cyclin D1 and LEF-1.

This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/β-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment.