Search

Treatment of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is still evolving. Conducting a randomized trial is challenging due to the high heterogeneity in the presentation of peritoneal disease and various surgical approaches. Biological research may facilitate more rapid translation of information into clinical practice. There is an emerging need for a preclinical model to improve HIPEC treatment protocols in terms of drug doses and treatment durations. The aim of the study is to design a tool that serves as an in vitro three-dimensional (3D) microfluidic peritoneal metastatic colorectal cancer model to test the efficacy of different HIPEC treatments.

Purpose: This study was planned to determine the problems and affecting factors that children encounter Purpose: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Accurate survival prediction is crucial for advanced-stage patients to optimize treatment strategies and improve clinical outcomes. This study aimed to develop an artificial intelligence-assisted clinical decision support system (CDSS) for survival prediction in CRC patients using clinical and genomic data from the Cancer Genome Atlas Colon Adenocarcinoma Collection (TCGA-COAD) dataset. Methods: Machine learning algorithms, including C4.5 Decision Tree, Support Vector Machines (SVM), Random Forest, and Naive Bayes, were employed to create survival prediction models. Clinical parameters and genomic data from key pathways, such as glycolysis/gluconeogenesis and mTORCI, were integrated into the models. The models were evaluated based on accuracy and performance. Results: The Random Forest algorithm achieved the highest accuracy (82.3%) when only clinical parameters were used. When clinical data were combined with gene expression data, the model's accuracy increased further. The resulting models were incorporated into a user-friendly web interface, SurvCOCA, for clinical use. Conclusions: This study demonstrates the potential of Al-based tools to improve prognosis predictions in CRC patients. Further research is needed, with larger datasets and additional machine learning algorithms, to enhance clinical decision-making and optimize treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is one of the most common cancer types globally, with a high mortality rate. The FAK-Rho-ROCK successive signaling cascade promotes growth, migration and invasion of cancer cells. Focal adhesions are major sites of interactions between extracellular mechanical environments and intracellular biochemical signaling molecules/cytoskeleton and therefore focal adhesion proteins have been proposed to play important roles in mechanotransduction. This study aims to evaluate the effects of combination treatments with Focal Adhesion Kinase (FAK), Rho-ROCK, and YAP/TAZ inhibitors on the proliferative and epithelial-mesenchymal transition (EMT)-related metastatic characteristics of colorectal cancer cells. Material and Methods: In vitro experiments were performed using the HCT-116 colon cancer cell line. The effects of Y-15 (FAK inhibitor), ROCK inhibitor-2, and YAP/TAZ inhibitor-2, either applied alone or in combination, on cell proliferation were analyzed using the WST-1 cell viability assay. Epithelial-mesenchymal transition (EMT) markers, E-cadherin and N-cadherin, were evaluated via immunofluorescence staining, and fluorescent intensity was analyzed using ImageJ software. Results: Y-15, when applied alone or in combination with other inhibitors, significantly reduced cell proliferation (p<0.005). Moreover, the combination of Y-15 and ROCK inhibitor-2 increased E-cadherin levels while decreasing N-cadherin levels (p<0.0159, p<0.0286). While the effect of YAP/TAZ inhibitor-2 alone was limited, specific effects were observed in combination treatments. Conclusion: This study demonstrates the potential of FAK-Rho-ROCK pathway inhibitors in the treatment of colorectal cancer. The ability of Y-15, in particular, to inhibit cell viability/proliferation and metastatic processes suggests that combination strategies targeting these pathways could contribute to the development of new therapeutic approaches for CRC. [ABSTRACT FROM AUTHOR]

The editorial in "Frontiers in Genetics" focuses on biomarkers and mechanisms of gastrointestinal diseases, emphasizing the importance of early diagnosis and personalized treatments in precision medicine. Various studies highlighted in the editorial explore genetic, epigenetic, and multi-omics perspectives of gastrointestinal diseases, offering insights into disease initiation, progression, and treatment. Key findings include the identification of DDX59-AS1 as a predictor of oral squamous cell carcinoma, a prognostic model for liver hepatocellular carcinoma metastasis, and the impact of dietary factors on colorectal cancer and inflammatory bowel disease. The research underscores the significance of biomarker discovery and molecular mechanisms in enhancing the diagnosis, prognosis, and treatment of gastrointestinal diseases, with a call for further exploration into these areas to improve patient outcomes through precision medicine. [Extracted from the article]

OBJECTIVES: Recently, the development of technologies to culture intestinal epithelial cells in vitro as different forms of intestinal organoids causes drawing attention in this area. The isolation and culture of colorectal crypts were first demonstrated in the very recent decade with the identification of stem cell marker Lgr5. The growth of crypts into organoids provides an in vitro model for studying the mucosal physiology, colorectal cancer tumorigenesis, and regeneration. In the current study, cancer stem cell isolation, tissue decontamination, organoid freezing and thawing processes, and organoid culture media ingredients have been evaluated. The aim of this investigation is optimization and production of human colorectal cancer organoids. MATERIAL & METHODS: The colorectal cancerous tissues are collected from Dokuz Eylul University Hospital. Isolation method of cancer cell is performed by EDTA solution and agitation is provided by shaker. Matrigel is used to create optimal 3D structure to grow cancer stem cells up to colorectal tissue. L-WRN cell line has been used to produce secreted factors which are WNT-3A, Rspondin and Noggin in purpose of supporting the development of organoids. RESULTS: Different parameters have been evaluated to obtain more efficient organoids. The experiment is performed in our laboratory presented that, human colorectal cancer organoids have been generated and manipulated in our laboratory. CONCLUSIONS: The currency protocol explains how the generation of 3D organoid cultures from cancerous human colorectal tissue is manipulated. The in vitro 3D organoid model is a promising and novel approach which present us more real-like working material. [ABSTRACT FROM AUTHOR]

The importance of microfluidics has already been revealed regarding the study of tumor biology. Mostly, its ability to study fundamental mechanisms associated with invasion, proliferation, metastasis, angiogenesis and microenvironment have been shown. These microfluidics-based models of cancer are designed to include both cancer cells and neighbour cells such as endothelial cells, immune cells. Microfluidic platforms have different progress in mimicking organs based on the spread of cancer cells to distant organs or predict the toxicity and pharmacokinetics of oncologic agents. Accurate recapitulation of the full metastatic processes or metabolism of an oncologic agent, different organ-on-a-chip' platforms can be combined to create more advance 'human-on-a-chip' platforms. These platforms have accepted as useful models for the prediction of the efficacy and toxicity of chemotherapeutic agents and improving animal models for the aim of preclinical use. Above all, primary tumor cells isolated from patients can be cultured on microfluidic culture based systems and tested for different agents with high specificity. In future, more complex and physiologically relevant 'human-on-achip' platforms will be developed to focus on the mechanistic features of tumor biology, and these systems will be candidate to test individualized cancer therapies before traditional in vivo models. [ABSTRACT FROM AUTHOR]

The organoid term is commonly used to describe ex vivo multicellular structures, which include the specific cell types of an organ and harbor its in vivo organization. These multicellular structures derive from stem cells such as adult stem cells, which have differentiation ability to generate any cell type. Early work of stem cell derived organoids performed for intestinal tissue and cortical tissue, and they showed promising capacity to organize into complex in vivo like structures. But today, organoids have been presented for various tissues such as intestine, stomach, lung, liver, prostate and brain. Therefore, they can be used to mimic developmental processes and disease states, as well as improve cell-based therapies. During the development process of organoid based studies, researchers started to work on organoids from primary tumors to understand tumor biology and solve problems on in vitro drug testing. Organoid models offer various experimental advantages for modelling cancer and understanding tumor biology, such as long term culturing, differrent tissue compartments and gene manipulation. Additionally, while organoids are very promising models to study of cancer, disadvantages arise from the lack of essential systems such as the vascular, lymphatic and immune systems; and their architecture cannot always present the organ structure as same as in vivo. Overall, organoids are important to model cancer and use them for understanding tumor biology and testing drugs. [ABSTRACT FROM AUTHOR]

Fluoropyrimidine-based chemotherapy is extensively used for the treatment of solid cancers, including colorectal cancer. However, fluoropyrimidine-driven toxicities are a major problem in the management of the disease. The grade and type of the toxicities depend on demographic factors, but substantial inter-individual variation in fluoropyrimidine-related toxicity is partly explained by genetic factors. The aim of this study was to investigate the effect of dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) polymorphisms in colorectal cancer patients. Eighty-five patients who were administered fluoropyrimidine-based treatment were included in the study. The DPYD, TYMS and MTHFR polymorphisms were scanned by a next generation Sequenom MassARRAY. Fluoropyrimidine toxicities were observed in 92% of all patients. The following polymorphisms were detected: DPYD 85T>C (29.4% heterozygote mutants, 7.1% homozygote mutants), DPYD IVS 14+1G>A (1.2% heterozygote mutants), TYMS 1494del TTAAAG (38.4% heterozygote mutants, 24.7% homozygote mutants), MTHFR 677C>T (43.5% heterozygote mutants, 9.4% homozygote mutants) and MTHFR 1298A>C (8.2% heterozygote mutants, 2.4% homozygote mutants). A statistically significant association was demonstrated between MTHFR 677C>T and fluoropyrimidine-related toxicity (p value = 0.007). Furthermore, MTHFR 1298A>C was associated with hematopoietic toxicity (p value = 0.008). MTHFR polymorphisms may be considered as related factors of fluoropyrimidine toxicity and may be useful as predictive biomarkers for the determination of the colorectal cancer patients who can receive the greatest benefit from fluoropyrimidine-based treatments. [ABSTRACT FROM AUTHOR]

Purpose: Curcumin is a natural phytopolyphenol compound isolated from the root of turmeric (Curcuma longa) and possesses a wide range of biological properties. The purpose of this study was to evaluate the antiproliferative, wound healing, anti-invasive and anti-migrative effects of curcumin on HCT-116 and LoVo colorectal cancer cell lines., Methods: The antiproliferative activity of 2.5-75 µM curcumin was tested on HCT-116 and LoVo colorectal cell lines and the viability of the cells was tested with WST-1 reagent by using ELISA plate reader at 450 nm. xCELLigence RTCA DP system was used for the detection of anti-invasive and anti-migrative effects of curcumin., Results: The IC50 of curcumin was 10±0.03 for HCT-116 and 20±0.05 µM for LoVo cell lines. The IC50 of curcumin (10µM for HCT-116 and 20 µM for LoVo) showed anti-metastatic activity on these cell lines., Conclusion: This study showed that curcumin could be evaluated as a promising anti-cancer agent for human colorectal cancer.