Prevention Of Colorectal Cancer Research Articles

Berberine: Potential preventive and therapeutic strategies for human colorectal cancer.

Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and the financial burden cannot be ignored. CRC is a multi-step process and can be caused by the disturbance of gut microbiome and chronic inflammation's stimulation. Additionally, the presence of precancerous lesions is also a risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi-target, safe, and economical herbal medicine and natural products. This paper summarizes berberine's (BBR) regulatory mechanisms in the occurrence and development of CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. Therefore, using BBR as an adjunct to CRC prevention and treatment could become a future trend in oncology.

Third-generation PacBio sequencing to explore gut bacteria and gender in colorectal cancer

BackgroundGut bacteria have an important influence on colorectal cancer (CRC). The differences of gut bacteria between genders have been the hot spots. ObjectiveTo analyze the relationship between gut bacteria and gender differences in patients with CRC. MethodsA total of 212 patients with CRC and 212 healthy volunteers were recruited. The subjects' fecal samples were obtained, and the fecal microorganisms were analyzed by the third-generation sequencing PacBio. The composition of gut bacteria was analyzed. Linear discriminant analysis Effect Size (LEfSe) was used to analyze the differences in gut bacteria. Pearson coefficient was used to calculate the correlation between differential bacteria. CRC risk prediction models were used to rank the importance of effective differential bacteria. ResultsEscherichia flexneri and Phocaeicola vulgatus were the most frequent bacteria in both male and female CRC patients. Bacteroides, Verrucomicrobia and Akkermansiaceae were highly enriched in male CRC group, while Bacteroidetes, Phocaeicola and Tissierellales were highly enriched in female CRC group. Peptostreptococcus anaerobius and Phocaeicola vulgatus were important CRC related bacteria in males and females, respectively. Peptostreptococcus anaerobius was the most important characteristic bacterium of males (AUC = 0.951), and the sensitivity and specificity of the discovery set were 78.74 % and 93.98 %, respectively. Blautia stercoris was the most important characteristic bacterium of females (AUC = 0.966), and the sensitivity and specificity of the discovery set were 90.63 % and 90.63 %, respectively. ConclusionGut bacteria varied in different genders. Therefore, gender should be considered when gut bacteria are applied in the diagnose and prevention of CRC.

Inhibitory Effects of Soluble Dietary Fiber from Foxtail Millet on Colorectal Cancer by the Restoration of Gut Microbiota.

Colorectal cancer (CRC) is a common malignant tumor that occurs in the colon. Gut microbiota is a complex ecosystem that plays an important role in the pathogenesis of CRC. Our previous studies showed that the soluble dietary fiber of foxtail millet (FMB-SDF) exhibited significant antitumor activity in vitro. The present study evaluated the anticancer potential of FMB-SDF in the azoxymethane (AOM)- and dextran sodium sulfate (DSS)-induced mouse CRC models. The results showed that FMB-SDF could significantly alleviate colon cancer symptoms in mice. Further, we found that FMB-SDF consumption significantly altered gut microbiota diversity and the overall structure and regulated the abundance of some microorganisms in CRC mice. Meanwhile, KEGG pathway enrichment showed that FMB-SDF can also alleviate the occurrence of colon cancer in mice by regulating certain cancer-related signaling pathways. In conclusion, our findings may provide a novel approach for the prevention and biotherapy of CRC.

The association of cancer-preventive lifestyle with colonoscopy screening use in border Hispanic adults along the Texas-Mexico border.

The relationship between engaging in two domains of cancer-preventive behaviors, lifestyle behaviors and colonoscopy screening, is unknown in Hispanic adults. Accordingly, the study examined the association between lifestyle and colonoscopy screening in Hispanic adults along the Texas-Mexico border, where there is suboptimal colorectal cancer prevention. Lifestyle behavior adherence and compliance with colonoscopy screening schedules were assessed using 2013-2023 data from the Cameron County Hispanic Cohorta population-based sample of Hispanic adults living along the Texas-Mexico border. The 2018 World Cancer Research Fund scoring system characterized healthy lifestyle engagement. Multivariable logistic regression quantified the association between lifestyle behaviors and colonoscopy screening. Among 914 Hispanic adults, there was a mean adherence score of 2.5 out of 7 for recommended behaviors. Only 33.0% (95% CI 25.64-41.39%) were up-to-date with colonoscopy. Complete adherence to fruit and vegetable (AOR [adjusted odds ratio] 5.2, 95% CI 1.68-16.30; p = 0.004), fiber (AOR 2.2, 95% CI 1.06-4.37; p = 0.04), and ultra-processed foods (AOR 2.8, 95% CI 1.30-6.21; p = 0.01) consumption recommendations were associated with up-to-date colonoscopy screening. Having insurance versus being uninsured (AOR 10.8, 95% CI 3.83-30.62; p < 0.001) and having local medical care versus in Mexico (AOR 7.0, 95% CI 2.26-21.43; p < 0.001) were associated with up-to-date colonoscopy. Adherence to dietary lifestyle recommendations was associated with being up-to-date with colonoscopy screenings. Those with poor dietary behavior are at risk for low-colonoscopy use. Improving lifestyle behaviors may complement colonoscopy promotion interventions. Healthcare accessibility influences up-to-date colonoscopy prevalence. Our findings can inform cancer prevention strategies for the Hispanic population.

Establishment and validation of an artificial intelligence-based model for real-time detection and classification of colorectal adenoma

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.

A Contemporary Review on the Critical Role of Nonsteroidal Anti-inflammatory Agents in Colorectal Cancer Therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-KB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.

Bridging current knowledge gap: better primary colorectal cancer prevention in people living with metabolic dysfunction-associated steatotic liver.

Bridging current knowledge gap: better primary colorectal cancer prevention in people living with metabolic dysfunction-associated steatotic liver.

Blood-Based Epigenetic Age Acceleration and Incident Colorectal Cancer Risk: Findings from a Population-Based Case-Control Study.

This study investigates the association between epigenetic age acceleration (EAA) derived from DNA methylation and the risk of incident colorectal cancer (CRC). We utilized data from a random population sample of 9,360 individuals (men and women, aged 45-69) from the HAPIEE Study who had been followed up for 16 years. A nested case-control design yielded 35 incident CRC cases and 354 matched controls. Six baseline epigenetic age (EA) measures (Horvath, Hannum, PhenoAge, Skin and Blood (SB), BLUP, and Elastic Net (EN)) were calculated along with their respective EAAs. After adjustment, the odds ratios (ORs) for CRC risk per decile increase in EAA ranged from 1.20 (95% CI: 1.04-1.39) to 1.44 (95% CI: 1.21-1.76) for the Horvath, Hannum, PhenoAge, and BLUP measures. Conversely, the SB and EN EAA measures showed borderline inverse associations with ORs of 0.86-0.87 (95% CI: 0.76-0.99). Tertile analysis reinforced a positive association between CRC risk and four EAA measures (Horvath, Hannum, PhenoAge, and BLUP) and a modest inverse relationship with EN EAA. Our findings from a prospective population-based-case-control study indicate a direct association between incident CRC and four markers of accelerated baseline epigenetic age. In contrast, two markers showed a negative association or no association. These results warrant further exploration in larger cohorts and may have implications for CRC risk assessment and prevention.

MEGANET: Improved framework with nature inspired approach for colorectal cancer polyp classification

BACKGROUND: Polyps are tumorous growths in the colon or rectal area which can turn into cancer at later stages, thus detection of polyps is very important for timely prevention of colorectal cancer. The aim of the study is to develop a framework to accurately detect polyp images in colonoscopy images. OBJECTIVE: Development of an intelligent framework for classification of colorectal cancer from colon and rectal images. The standard machine learning, convolutional neural networks and ensemble models with nature inspired approach were implemented for this study. Model optimization was performed by varying hyper parameters. The main objective was to find an optimal model with high accuracy, optimized weights and less parameters. METHODS: The deep learning Convolutional Neural Network (CNN) models such as VGG19, ResNet50, EfficientNet, Ensemble Model (EM), and Modified Ensemble CNN with Genetic Algorithm (MEGANET) were implemented for the classification of colon images. RESULTS: Ensemble model was also created with two best performing deep learning models to further achieve higher accuracy of 96%. The ensemble model outperformed the other models in terms of accuracy, precision, recall, and F1 score. But this model has more complexity. The MEGANET, nature inspired evolutionary ensemble CNN model was implemented with transfer learning and genetic algorithms for weights optimization and parameter reduction. It achieved accuracy of 95%, on training data. CONCLUSION: The MEGANET performed similar to EM with less number of parameters on training, validation and test dataset. In future different methods will be implemented to further reduce the parameters and attain reasonable accuracy using MEGANET.

Multilevel analysis of social determinants of advanced stage colorectal cancer diagnosis

The advanced stage at diagnosis of colorectal cancer (CRC) may be related to individual factors, socioeconomic conditions, and healthcare service availability. The objective of the study was to analyze the prevalence of advanced stage CRC at the time of diagnosis and its association with individual, contextual, socioeconomic, and healthcare service indicators. An observational, cross-sectional study was conducted, analyzing cases of malignant neoplasms of the colon and rectum in individuals of both sexes, aged between 18 and 99 years, diagnosed between 2010 and 2019 in Brazil (n = 69,047). Data were collected from the Hospital Cancer Registry (HCR), Atlas of Human Development in Brazil, and from the National Registry of Health Institutions (NRHI). A Multilevel Poisson Regression model with random intercept was used. The prevalence of advanced stage CRC at diagnosis was 65.6%. Advanced stage was associated with older age groups prevalence ratio (PR) 4.40 and younger age groups (PR 1.84), low Human Development Index (HDI) (PR 1.22), and low density of family health strategy teams (PR 1.10). The study highlights the unequal distribution of social determinants of health in the diagnosis CRC in Brazil, revealing the need to evaluate and redirect public policies aimed at improving early detection and prevention of CRC in the country.

UViT-Seg: An Efficient ViT and U-Net-Based Framework for Accurate Colorectal Polyp Segmentation in Colonoscopy and WCE Images.

Colorectal cancer (CRC) stands out as one of the most prevalent global cancers. The accurate localization of colorectal polyps in endoscopy images is pivotal for timely detection and removal, contributing significantly to CRC prevention. The manual analysis of images generated by gastrointestinal screening technologies poses a tedious task for doctors. Therefore, computer vision-assisted cancer detection could serve as an efficient tool for polyp segmentation. Numerous efforts have been dedicated to automating polyp localization, with the majority of studies relying on convolutional neural networks (CNNs) to learn features from polyp images. Despite their success in polyp segmentation tasks, CNNs exhibit significant limitations in precisely determining polyp location and shape due to their sole reliance on learning local features from images. While gastrointestinal images manifest significant variation in their features, encompassing both high- and low-level ones, a framework that combines the ability to learn both features of polyps is desired. This paper introduces UViT-Seg, a framework designed for polyp segmentation in gastrointestinal images. Operating on an encoder-decoder architecture, UViT-Seg employs two distinct feature extraction methods. A vision transformer in the encoder section captures long-range semantic information, while a CNN module, integrating squeeze-excitation and dual attention mechanisms, captures low-level features, focusing on critical image regions. Experimental evaluations conducted on five public datasets, including CVC clinic, ColonDB, Kvasir-SEG, ETIS LaribDB, and Kvasir Capsule-SEG, demonstrate UViT-Seg's effectiveness in polyp localization. To confirm its generalization performance, the model is tested on datasets not used in training. Benchmarking against common segmentation methods and state-of-the-art polyp segmentation approaches, the proposed model yields promising results. For instance, it achieves a mean Dice coefficient of 0.915 and a mean intersection over union of 0.902 on the CVC Colon dataset. Furthermore, UViT-Seg has the advantage of being efficient, requiring fewer computational resources for both training and testing. This feature positions it as an optimal choice for real-world deployment scenarios.

Fasting hyperglycaemia and fatty liver drive colorectal cancer: a retrospective analysis in 1145 patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of increased adiposopathy, whose pathogenetic features have been proposed as tumourigenic triggers for colorectal cancer (CRC). We aim to identify specific metabolic signatures involved in CRC development that may be used as non-invasive biomarkers, paving the way for specific and personalized strategies of CRC prevention and early detection. We retrospectively assessed CRC onset during a time frame of 8 years in a cohort of 1145 out-patients individuals who had previously been evaluated for Metabolic Syndrome. 28 patients developed CRC. No association between CRC development and visceral and general obesity was detected, while baseline fasting plasma glucose (FPG) and non-invasive liver fibrosis scores were significantly higher in patients with CRC, compared to those who did not develop cancer. Liver steatosis and MASLD were more frequently diagnosed in patients who developed CRC compared to no cancer developers. Canonical correlations among metabolic biomarkers were not present in CRC developers, differently from no cancer group. In ROC analysis, FPG and non-invasive scores also showed good sensitivity and specificity in predicting colon cancer. We then calculated ORs for metabolic biomarkers, finding that higher FPG and non-invasive scores were associated with an increased risk of developing CRC. MASLD and increased FPG may play a role in the clinical background of CRC, bringing to light the fascinating possibility of a reversed gut-liver axis communication in the pathogenesis of CRC. Thus, the use of non-invasive scores of fatty liver may be helpful to predict the risk of CRC and serve as novel prognostic factors for prevention and therapeutic strategies.

Evaluating the Efficacy of Resect-and-Discard and Resect-and-Retrieve Strategies for Diminutive Colonic Polyps.

Diminutive polyps present a unique challenge in colorectal cancer (CRC) prevention strategies. This study aims to assess the characteristics and variables of diminutive polyps in a Romanian cohort, intending to develop a combined resect-and-retrieve or resect-and-discard strategy that reduces the need for an optical diagnosis. A prospective cohort study was conducted at two endoscopy centers in Romania from July to December 2021. Adult patients undergoing colonoscopies where polyps were identified and resected were included. Endoscopic procedures employed advanced diagnostic features, including blue-light imaging (BLI) and narrow-band imaging (NBI). Logistic regression analysis was utilized to determine factors impacting the probability of adenomatous polyps with high-grade dysplasia (HGD). A total of 427 patients were included, with a mean age of 59.42 years (±11.19), predominantly male (60.2%). The most common indication for a colonoscopy was lower gastrointestinal symptoms (42.6%), followed by screening (28.8%). Adequate bowel preparation was achieved in 87.8% of cases. The logistic regression analysis revealed significant predictors of HGD in adenomatous polyps: age (OR = 1.05, 95% CI: 1.01-1.08, p = 0.01) and polyp size (>5 mm vs. ≤5 mm, OR = 4.4, 95% CI: 1.94-10.06, p < 0.001). Polyps classified as Paris IIa, Ip, and Isp were significantly more likely to harbor HGD compared to the reference group (Is), with odds ratios of 6.05, 3.68, and 2.7, respectively. The study elucidates significant associations between the presence of HGD in adenomatous polyps and factors such as age, polyp size, and Paris classification. These findings support the feasibility of a tailored approach in the resect-and-discard and resect-and-retrieve strategies for diminutive polyps, potentially optimizing CRC prevention and intervention practices. Further research is warranted to validate these strategies in broader clinical settings.

Nativity Disparities in Colorectal Cancer Screening Among Hispanics in the United States.

Hispanics in the United States (U.S.) have previously exhibited lower guideline-concordant colorectal cancer (CRC) screening uptake than non-Hispanic (NH) Whites, with disparities accentuated in foreign-born Hispanics, however it is unclear whether nativity-related CRC screening disparities have changed in the last two decades and whether these disparities are attenuated after adjusting for socioeconomic and demographic characteristics. We evaluated CRC screening adherence in foreign- and U.S.-born Hispanics compared to U.S.-born NH Whites. We used 2019 National Health Interview Survey data to compare the prevalence of up-to-date CRC screening per the 2019 U.S. Preventive Services Task Force recommendations among Hispanic nativity subgroups (i.e., foreign- and U.S.-born) and U.S.-born NH Whites using unadjusted and adjusted weighted log-linked binomial regression. Foreign- and U.S.-born Hispanics had a significantly lower unadjusted prevalence of up-to-date screening than U.S.-born NH Whites (47.18% and 64.18% versus 70.70%; p < 0.0001 and p = 0.0109, respectively). After adjusting for socioeconomic and demographic differences, the prevalence of up-to-date screening was lower in foreign-born Hispanics compared to U.S.-born NH Whites [adjusted prevalence ratio 0.80 (95% confidence interval 0.70-0.91)]; however, no statistically significant difference was observed between U.S.-born Hispanics and NH Whites. Our results suggest a low screening uptake in foreign-born Hispanics independent of socioeconomic and demographic differences. Future interventions should target foreign-born Hispanics to address disparities and promote early detection and prevention of CRC regardless of socioeconomic factors.

Colorectal Cancer: Epidemiology, Risk Factors, and Prevention.

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related to CRC. Prevention is the most effective method for controlling CRC. Primary prevention includes determining and avoiding modifiable risk factors (e.g., alcohol consumption, smoking, and dietary factors) as well as increasing protective factors (e.g., physical activity, aspirin). Further studies, especially randomized, controlled trials, are needed to clarify the association between CRC incidence and exposure to different risk factors or protective factors. Detection and removal of precancerous colorectal lesions is also an effective strategy for controlling CRC. Multiple factors, both at the individual and community levels (e.g., patient preferences, availability of screening modalities, costs, benefits, and adverse events), should be taken into account in designing and implementing CRC screening programs. Health policymakers should consider the best decision in identifying the starting age and selection of the most effective screening strategies for the target population. This review aims to present updated evidence on the epidemiology, risk factors, and prevention of CRC.

Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention.

Colorectal cancer stands as the third most prevalent form of cancer worldwide, with a notable increase in incidence in Western countries, mainly attributable to unhealthy dietary habits and other factors, such as smoking or reduced physical activity. Greater consumption of vegetables and fruits has been associated with a lower incidence of colorectal cancer, which is attributed to their high content of fiber and bioactive compounds, such as flavonoids. In this study, we have tested the flavonoids quercetin, luteolin, and xanthohumol as potential antitumor agents in an animal model of colorectal cancer induced by azoxymethane and dodecyl sodium sulphate. Forty rats were divided into four cohorts: Cohort 1 (control cohort), Cohort 2 (quercetin cohort), Cohort 3 (luteolin cohort), and Cohort 4 (xanthohumol cohort). These flavonoids were administered intraperitoneally to evaluate their antitumor potential as pharmaceutical agents. At the end of the experiment, after euthanasia, different physical parameters and the intestinal microbiota populations were analyzed. Luteolin was effective in significantly reducing the number of tumors compared to the control cohort. Furthermore, the main significant differences at the microbiota level were observed between the control cohort and the cohort treated with luteolin, which experienced a significant reduction in the abundance of genera associated with disease or inflammatory conditions, such as Clostridia UCG-014 or Turicibacter. On the other hand, genera associated with a healthy state, such as Muribaculum, showed a significant increase in the luteolin cohort. These results underline the anti-colorectal cancer potential of luteolin, manifested through a modulation of the intestinal microbiota and a reduction in the number of tumors.

Abstract LB375: Multimodality dietary intervention for colorectal cancer prevention: The MyBestGI randomized trial

Abstract Colorectal cancer (CRC) is one of the cancers most highly affected by diet. Recommendations for reducing risk of CRC include weight management, eating plentiful plant-based high fiber foods, and limiting intakes of red meats and ultra-processed foods. In addition, an increased proportion of monounsaturated and omega-3 fats in the diet is beneficial for promoting weight management and reducing inflammation. Despite the evidence supporting the importance of diet and the demonstrated success for eliciting dietary changes in research settings, simple methods that can be easily implemented in medical settings are lacking. We developed a bespoke mHealth app (MyBestGI), incorporating an autonomy-supporting, self-regulatory approach to behavior change. The program promotes identification of the benefits of healthy eating on well-being. Two versions of the program are being tested in a 12-month, 3-arm randomized trial that seeks to recruit 240 people at increased risk for CRC. Participants are randomized to either 1) a control group that receives written information on cancer preventive diets, 2) a treatment group that receives a MyBestGI app version for logging 4 food groups associated with increased risks of CRC (red meats, processed meats, added sugars and refined grains), or 3) a treatment group that receives a MyBestGI app version for logging the same 4 food groups to limit plus 7 food groups to encourage in personalized quantities. The two treatment groups also receive a user manual, behavior-oriented, biweekly text messages, and supportive coaching calls. Logging food groups is requested at least 3 per week for 3 months, and 3 per week every other week for the next 9 months. The app displays logging results relative to individualized targets and has features that prompt reflecting on the user’s own results and planning for future eating. The primary endpoints are weight loss and improvement in a dietary cancer prevention score. Recruitment began in June 2023, and the study is enrolling 8-10 participants per month. The drop-out rate is lower than expected. Compliance with study procedures and app use is high. Responses to the end-of-day reflection questions within the app show that 92% of users are neutral, happy, or very happy with their dietary behavior for the day. For the 15 participants who had 12 weeks of logging data available, foods were logged for an average of 38 days (range 20-75) which is slightly higher than the requested logging of 36 days over 12 weeks. Review of the support calls for protocol fidelity indicates participants are enthusiastic about the MyBestGI program, making changes in their eating, and are internalizing the autonomy-supporting beliefs promoted in the program. These early results suggest users are engaging with the MyBestGI app at a very high level, making use of the provided app features, and enjoying the program. The MyBestGI approach therefore has excellent potential to support dietary change towards a cancer preventive diet in a format that is facile to implement in high-risk populations. Citation Format: Zora Djuric, Michelle Segar, Ananda Sen, Reema Kadri, Rob Adwere-Boamah, Juno Orr, Katherine Poore, Samara Rifkin, Lorraine Buis. Multimodality dietary intervention for colorectal cancer prevention: The MyBestGI randomized trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB375.

Anticolorectal Cancer Activity of Bilobalide in Patient-Derived Colorectal Cancer Organoids and AOM/DSS Mouse Model

Bilobalide has shown strong anti-inflammatory activity. Colorectal cancer (CRC) is closely associated with inflammation. However, no studies have reported on the use of bilobalide for treating CRC. This study aims to evaluate the effect of bilobalide on CRC prevention. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunofluorescence showed that bilobalide significantly inhibits the M2 polarization of macrophages dependent on phorbol 12-myristate 13-acetate (PMA) and interleukin-4 (IL-4). Analysis of signaling pathways showed that the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT3) was regulated. In particular, human CRC organoids were established. Western blotting, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), and analysis of cell viability and morphology further supported the hypothesis that the anti-CRC effects of bilobalide could be explained by its ability to suppress M2 macrophage polarization and promote M1 transformation. C57BL/6 mice treated with azoxymethane (AOM)/dextran sodium sulfate (DSS) were divided into three groups, i.e., control, AOM/DSS, low (2.5 mg/kg), and high (5 mg/kg). High-dose bilobalide markedly inhibited the progression of CRC, as evidenced by the increased body weight, decrease in disease activity index (DAI) death rate, and alleviation of colon length reduction and tumorigenesis. According to the in vivo results, reduced levels of inflammatory cytokines in the serum included tumor necrosis factor (TNF-α), IL-6, IL-1β, and IL-10. Bilobalide reduced oxidative stress indices, lipid peroxide (LPO), and malondialdehyde (MDA) and increased reduced glutathione (GSH). In addition, the expression of proliferating cell nuclear antigen (PCNA), Ki67, cellular Myc (c-Myc), and CD206 was downregulated in the drug-treated groups, as confirmed by the immunohistochemical staining. Collectively, these results indicated that bilobalide administration improve experimental CRC by inhibiting M2 macrophage polarization and oxidative stress. Thus, bilobalide may prevent CRC and serve as a potential therapeutic target for CRC.

Linking Pathways from Perceived Absolute and Comparative Risk to Colorectal Cancer Screening Intention: Towards an Extended Cognitive Mediation Model

ABSTRACT Digital media platforms are crucial in providing health information to the public, including learning about cancer prevention strategies. Although the Cognitive Mediation Model (CMM) is a sound theoretical framework for explaining the underpinning process of health knowledge acquisition, one important remaining gap is how individuals are motivated to process health information through different discussion-generated elaboration strategies. To better understand the knowledge acquisition process, this paper extends the CMM in the context of colorectal cancer prevention. We introduced perceived absolute risk and perceived comparative risk as two distinct risk assessments as the antecedents facilitating individuals’ attention to cancer information on digital media, two types of interpersonal communication as discussion-generated elaboration strategies, and two dimensions of knowledge assessment in our extended CMM. Based on a nationally representative online survey among 965 Chinese public, we found that two types of risk perception were positively associated with paying attention to colorectal cancer information on digital media, which in turn facilitated both types of interpersonal communication. However, information processing strategies differed in leading to cancer knowledge and screening intention. Only subjective knowledge was positively associated with colorectal screening intention. Our findings offered implications for the literature and health promotion practices.

Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p < 0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2 = 0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. artificial intelligence-enhanced csPWS improved diagnostic performance with AUC = 0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.