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Plant-derived polyphenols are naturally occurring compounds widely distributed in plants. They have received greater attention in the food and pharmaceutical industries due to their potential health benefits, reducing the risk of some chronic diseases due to their antioxidant, anti-inflammatory, anticancer, cardioprotective, and neuro-action properties. Polyphenolic compounds orally administered can be used as adjuvants in several treatments but with restricted uses due to chemical instability. The review discusses the different structural compositions of polyphenols and their influence on chemical stability. Despite the potential and wide applications, there is a need to improve the delivery of polyphenolics to target the human intestine without massive chemical modifications. Oral administration of polyphenols is unfeasible due to instability, low bioaccessibility, and limited bioavailability. Nano-delivery systems based on polysaccharides (starch, pectin, chitosan, and cellulose) have been identified as a viable option for oral ingestion, potentiate biological effects, and direct-controlled delivery in specific tissues. The time and dose can be individualized for specific diseases, such as intestinal cancer. This review will address the mechanisms by which polysaccharides-based nanostructured systems can protect against degradation and enhance intestinal permeation, oral bioavailability, and the potential application of polysaccharides as nanocarriers for the controlled and targeted delivery of polyphenolic compounds. [ABSTRACT FROM AUTHOR]

Cancer involves abnormal cell growth, with types like intestinal and oesophageal cancer often diagnosed in advanced stages, making them hard to cure. Symptoms are like burning sensations in the stomach and swallowing difficulties are specified as colorectal cancer. Deep learning significantly impacts the medical image processing and diagnosis, offering potential improvements in accuracy and efficiency. The Kruskal Szekeres Generative Adversarial Network Augmented Deep Autoencoder (KSGANA-DA) is introduced for early colorectal cancer detection and it comprises two stages; Initial stage, data augmentation uses Affine Transform via Random Horizontal Rotation and Geometric Transform via Kruskal–Szekeres that coordinates to improve the training dataset diversity, boosting detection performance. The second stage, a Deep Autoencoder Anatomical Landmark-based Image Segmentation preserves edge pixel spatial locations, improving precision and recall for early boundary detection. Experiments validate KSGANA-DA performance and different existing methods are implemented into Python. The results of KSGANA-DA are to provide higher precision by 41%, recall by 7%, and lesser training time by 46% than compared to conventional methods. [ABSTRACT FROM AUTHOR]

Background: In 2017, the Food and Drug Administration approved pembrolizumab for treatment of any mismatch repair–deficient (dMMR) tumor making MMR immunohistochemistry (IHC) testing beneficial for all tumor types. For the first time, MMR IHC was not performed exclusively to screen for Lynch syndrome (LS). Methods: In this study, all MMR IHC reports issued between 2017 and 2021 at an academic hospital were reviewed and completion of genetic testing was determined through chart review. Colorectal cancers (CRCs), endometrial cancers (ECs), and noncancerous lesions were excluded. Results: Between 2017 and 2021, MMR IHC was completed in 1939 patients with a malignancy other than CRC or EC. Absent or weak staining for at least one MMR protein was detected in 115 (5.9%) patients and 59 (51%) of those completed germline genetic testing. Overall, the identification rate of LS in this cohort was 0.72%, which is similar to the rate in our previously reported CRC and EC universal screening cohort. A diagnosis of LS was most commonly made in patients with dMMR brain (18.75%) and small intestinal cancers (10.20%). Five additional patients were found to carry a pathogenic variant in a non‐LS gene. Conclusions: Pan‐cancer MMR testing for pembrolizumab consideration can identify LS cases at a rate similar to universal CRC and EC screening programs. A persistent challenge is subsequent uptake of genetic testing. MMR testing should be prioritized in brain and small intestinal tumors, and multigene panel testing is recommended in patients with dMMR, as unexpected pathogenic variants in non‐LS genes were found as frequently as LS gene variants. The use of mismatch repair immunohistochemistry testing across tumor types has increased significantly in the age of immune checkpoint inhibitors. Pan‐cancer mismatch repair–deficient immunohistochemistry testing has identified Lynch syndrome cases at a rate similar to the colorectal and endometrial cohorts. [ABSTRACT FROM AUTHOR]

Appropriate host‐microbiota interactions are essential for maintaining intestinal homeostasis; hence, an imbalance in these interactions leads to inflammation‐associated intestinal diseases. Toll‐like receptors (TLRs) recognize microbial ligands and play a key role in host–microbe interactions in health and disease. TLR13 has a well‐established function in enhancing host defenses against pathogenic bacteria. However, its role in maintaining intestinal homeostasis and controlling colitis‐associated colon cancer (CAC) is largely unknown. This study aimed to investigate the involvement of TLR13‐mediated signaling in intestinal homeostasis and colonic tumorigenesis using ex vivo cell and in vivo CAC animal model. Tlr13‐deficient mice were prone to dextran sodium sulfate (DSS)‐induced colitis. During the early stages of the CAC regimen (AOM/DSS‐treated), Tlr13 deficiency led to severe ulcerative colitis. Moreover, Tlr13‐deficient mice exhibited increased intestinal permeability, as evidenced by elevated levels of fluorescein isothiocyanate (FITC)‐dextran, endotoxins, and bacterial translocation. Enhanced cell survival and proliferation of colonic intestinal cells were observed in Tlr13‐deficient mice. A transcriptome analysis revealed that Tlr13 deficiency is associated with substantial changes in gene expression profile of colonic tumor tissue. Tlr13‐deficient mice were more susceptible to CAC, with increased production of interleukin (IL)‐6, IL‐12, and TNF‐α cytokines and enhanced STAT3, NF‐κB, and MAPK signaling in colon tissues. These findings suggest that TLR13 plays a protective role in maintaining intestinal homeostasis and controlling CAC. Our study provides a novel perspective on intestinal health via TLR13‐mediated signaling, which is crucial for deciphering the role of host‐microbiota interactions in health and disease. [ABSTRACT FROM AUTHOR]

Background: The Aryl Hydrocarbon Receptor (AHR) is a transcription factor that regulates several biological processes. Its potential in anti-tumor immunotherapy is becoming clearer, yet no bibliometric studies on this topic exist. This study aims to understand the current research landscape and identify future directions through a bibliometric analysis of AHR's anti-tumor immunological effects. Methods : We conducted a comprehensive bibliometric analysis of AHR antitumor immunotherapy papers in the Web of Science Core Collection. Various aspects of the publications were analyzed, and research hotspots and future trends were identified using scientific bibliometric tools and statistical methods. Results: We collected 592 English papers published between 2010 and 2023, with an almost annual increase. Most publications were from the USA, followed by China, Germany, and Italy. The journal "Frontiers in Immunology" had the most papers, and the most cited paper was Christiane A. Opitz's "An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor." The research is centered around AHR gene expression, with a growing focus on intestinal disease and the development of Programmed cell death ligand 1 (PD-L1) drugs. Conclusion: This bibliometric study highlights the significance of AHR in immunomodulatory research, outlining the research trends and key contributors. It suggests AHR's immune effects may mediate the process of colitis cancer transformation, providing valuable insights for future anti-tumor immunotherapy strategies based on AHR. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that cancer stemness plays a crucial role in tumor progression, metastasis, and chemoresistance. Upon exposure to internal or external stress, ribosomes stand sentinel and facilitate diverse biological processes, including oncological responses. In the present study, ribosome-inactivating stress (RIS) was evaluated for its modulation of cancer cell stemness as a pivotal factor of tumor cell reprogramming. Based on the concept of stress-responsive cancer cell stemness, we addressed human intestinal cancer cell line-based off-the-shelf spheroid cultures. Intestinal cancer cell line-based spheroids exhibited heightened levels of CD44+CD133+ cancer stemness, which was improved by chemical-induced RIS. Further evaluations revealed the potential of these stress-imprinted spheroids as a platform for chemoresistance screening. Compared to adherent cells, stemness-improved spheroid cultures displayed reduced apoptosis in response to 5-fluorouracil (5-FU), a frontline chemotherapeutic agent against colorectal cancer. Moreover, serial subcultures with repeated RIS exposure maintained and even enhanced cancer stemness and chemoresistance patterns. In particular, isolated CD44+CD133+ cancer stem cells exhibited higher chemoresistance compared to unsorted cells. To elucidate the mechanisms underlying RIS-induced stemness, RNA-seq analysis identified Wnt signaling pathways and stemness-associated signals as notable features in spheroids exposed to RIS. Loss-of-function studies targeting connective tissue growth factor (CTGF), a negative regulator of Wnt signaling, revealed that CTGF-deficient spheroids exhibited improved cancer stemness and resistance to 5-FU, with RIS further enhancing these effects. In conclusion, this proof-of-concept study demonstrates the feasibility of leveraging stress-responsive cancer stemness for the development of spheroid-based platforms for chemoresistance evaluation and elucidation of pathophysiological processes of colorectal tumorigenesis under environmental stress. [ABSTRACT FROM AUTHOR]

Background: Obesity and type 2 diabetes (T2D) promote inflammation, increasing the risk of colorectal cancer (CRC). High-fat diet (HFD)-induced obesity is key to these diseases through biological mechanisms. This study examined the impact of genetic background on the multimorbidity of intestinal cancer, T2D, and inflammation due to HFD-induced obesity. Methods: A cohort of 357 Collaborative Cross (CC) mice from 15 lines was fed either a control chow diet (CHD) or HFD for 12 weeks. Body weight was tracked biweekly, and blood glucose was assessed at weeks 6 and 12 via intraperitoneal glucose tolerance tests (IPGTT). At the study's endpoint, intestinal polyps were counted, and cytokine profiles were analyzed to evaluate the inflammatory response. Results: HFD significantly increased blood glucose levels and body weight, with males showing higher susceptibility to T2D and obesity. Genetic variation across CC lines influenced glucose metabolism, body weight, and polyp development. Mice on HFD developed more intestinal polyps, with males showing higher counts than females. Cytokine analysis revealed diet-induced variations in pro-inflammatory markers like IL-6, IL-17A, and TNF-α, differing by genetic background and sex. Conclusions: Host genetics plays a crucial role in susceptibility to HFD-induced obesity, T2D, CRC, and inflammation. Genetic differences across CC lines contributed to variability in disease outcomes, providing insight into the genetic underpinnings of multimorbidity. This study supports gene-mapping efforts to develop personalized prevention and treatment strategies for these diseases. [ABSTRACT FROM AUTHOR]

The soluble epoxide hydrolase (sEH; encoded by the EPHX2 gene) is an α/β hydrolase fold protein that is, widely distributed throughout the body. Recent studies have highlighted that sEH, in the metabolism of polyunsaturated fatty acids, plays a part in the pathogenesis of various diseases, including cardiovascular disease, Alzheimer's disease and intestine‐associated disease. This review discusses the current findings on the role of sEH in the development of intestine‐ and intestine‐associated diseases, including colitis, colorectal cancer, and other intestinal diseases, as well as the potential underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

Background: Pimitespib (TAS‐116), a first‐in‐class, oral, selective heat‐shock protein 90 inhibitor, is approved as fourth‐line treatment for gastrointestinal stromal tumors in Japan. This phase 1 study evaluated the cardiac safety of pimitespib. Methods: In this open‐label, nonrandomized, multicenter study, Japanese patients (aged ≥20 years) with refractory, advanced solid tumors received placebo on day −1, then pimitespib 160 mg daily on days 1–5 of the cardiac safety evaluation period. Electrocardiograms were conducted at baseline, and on days −2, −1, 1, and 5; and blood samples were collected on days 1 and 5. Patients then received once‐daily pimitespib for 5 days every 3 weeks. The primary end point was the time‐matched difference in QT interval corrected for heart rate using the Fridericia correction (QTcF) between pimitespib and placebo. Pharmacokinetics, safety, and preliminary efficacy were also assessed. Results: Of the 22 patients in the cardiac safety‐evaluable population, no clinically relevant QTc prolongation was observed; the upper bound of the one‐sided 95% confidence interval for the time‐matched difference in change from baseline in QTcF was <20 msec at all time points on days 1 and 5. Pimitespib pharmacokinetic parameters were consistent with previous data, and the time‐matched difference in change from baseline in QTcF showed no marked increase as plasma concentrations increased. The safety profile was acceptable; 40% of patients experienced grade 3 or greater adverse drug reactions, mostly diarrhea (20%). The median progression‐free survival was 3.1 months. Conclusions: In Japanese patients with refractory, advanced solid tumors, pimitespib was not associated with clinically relevant QTc prolongation, and there were no cardiovascular safety concerns. Plain Language Summary: Pimitespib is a new anticancer drug that is being used to treat cancer in the stomach or intestines (gastrointestinal stromal tumors).This study demonstrated that pimitespib had no marked effect on heart rhythm or negative effects on the heart or blood vessels and had promising anticancer effects in Japanese patients with advanced solid tumors who were unable to tolerate or benefit from standard treatment. [ABSTRACT FROM AUTHOR]

Long-standing chronic inflammation of the digestive tract leads to Inflammatory Bowel Diseases (IBD), comprising Crohn's Disease (CD) and Ulcerative colitis (UC). The persistent prevalence of these conditions in the gut is a predisposing factor for Colitis-Associated Cancer (CAC), one of the most common sub-types of Colorectal Cancer (CRC), emphasizing the role of inflammation in tumorigenesis. Therefore, targeted intervention of chronic intestinal inflammation is a potential strategy for preclusion and treatment of inflammation-driven malignancies. The association between bile acids (BA) and gut immune homeostasis has been explored in the recent past. However, the exact downstream mechanism by which secondary BA successfully regulating intestinal inflammation and inflammation-dependent CAC is unclear. Our study demonstrated that Ursodeoxycholic acid (UDCA), a secondary bile acid of host gut microbial origin, finetunes the dialogue between activated macrophages and intestinal epithelial cells, modulating inflammation-driven epithelial-mesenchymal transition (EMT), a hallmark of cancer. UDCA treatment and dependency on the TGR5/GPBAR1 receptor significantly upregulated the Suppressor of Cytokine Signaling 1 (SOCS1) expression, contributing to the regulation of pro-inflammatory cytokines in activated macrophages. In this study, we also noticed heightened expression of SOCS1 in UDCA-mitigated CAC in the AOM-DSS mouse model with reduced inflammatory gene expression. Overall, our observations highlight the possible utility of UDCA for inflammation-driven intestinal cancer. [ABSTRACT FROM AUTHOR]

Managing colon cancer with intestinal nonrotation, a type of congenital intestinal malrotation, is challenging due to the presence of anatomical abnormalities and severe adhesions. When patients have nonrotation, it is markedly more difficult to determine which vessels correspond to the colic vessels and ileal vessels until all vascular branching patterns become evident. The optimal approach for right‐sided colon cancer with intestinal nonrotation has yet to be established. In the present case of ascending colon cancer with intestinal nonrotation, we performed laparoscopic right hemicolectomy with D3 dissection using a modified cranial approach. This approach involves tracing, without resecting, branches from the superior mesenteric vein and superior mesenteric artery in a cranial‐to‐caudal manner until the ileocolic artery and ileocolic vein, which course toward the cecum, are identified, followed by the dissection of the colic vessels and lymph nodes in a caudal‐to‐cranial fashion. [ABSTRACT FROM AUTHOR]

Intestinal cancer (IC) poses a significant global health challenge that drives continuous efforts to explore effective treatment modalities. Conventional treatments for IC are effective, but are associated with several limitations and drawbacks. Chinese herbal medicine (CHM) plays an important role in the overall cancer prevention and therapeutic strategies. Recent years have seen a growing body of research focus on the potential of CHM in IC treatment, showing promising results in managing IC and mitigating the adverse effects of radiotherapy and chemotherapy. This review provides updated information from preclinical research and clinical observation on CHM's role in treatment of IC, offering insights into its comprehensive management and guiding future prevention strategies and clinical practice. [ABSTRACT FROM AUTHOR]

The malignant transformation of mature cystic teratomas during pregnancy is a rare occurrence in medical literature. In this case report, we present a remarkable instance of mucinous intestinal adenocarcinoma arising from a mature ovarian cystic teratoma diagnosed during pregnancy. This is among the few reports detailing the effective use of the FOLFOX 6 chemotherapy regimen for treating this type of intestinal cancer. Furthermore, we emphasize the immunohistochemical results that confirm the colorectal histological origin. [ABSTRACT FROM AUTHOR]

Abstract Intestinal cancer (IC) poses a significant global health challenge that drives continuous efforts to explore effective treatment modalities. Conventional treatments for IC are effective, but are associated with several limitations and drawbacks. Chinese herbal medicine (CHM) plays an important role in the overall cancer prevention and therapeutic strategies. Recent years have seen a growing body of research focus on the potential of CHM in IC treatment, showing promising results in managing IC and mitigating the adverse effects of radiotherapy and chemotherapy. This review provides updated information from preclinical research and clinical observation on CHM’s role in treatment of IC, offering insights into its comprehensive management and guiding future prevention strategies and clinical practice.

Background and Aim: Intestinal metaplasia (IM) of the gastric mucosa is strongly associated with the risk of gastric cancer (GC). This study was performed to investigate the usefulness of endoscopic and histological risk stratification for GC using IM. Methods: This was a post‐hoc analysis of a multicenter prospective study involving 10 Japanese facilities (UMINCTR000027023). The ridge/tubulovillous pattern, light blue crest (LBC), white opaque substance (WOS), endoscopic grading of gastric IM (EGGIM) score using non‐magnifying image‐enhanced endoscopy, and operative link on gastric IM assessment (OLGIM) were evaluated for their associations with GC risk in all patients. Results: In total, 380 patients (115 with GC and 265 without GC) were analyzed. The presence of an LBC (limited to antrum: odds ratio [OR] 2.4 [95% confidence interval 1.1–5.0], extended to corpus: OR 3.6 [2.1–6.3]), the presence of WOS (limited to antrum: OR 3.0 [1.7–5.3], extended to corpus: OR 4.2 [2.1–8.2]), and histological IM (limited to antrum: OR 3.2 [1.4–7.4], extended to corpus: OR 8.5 [4.5–16.0]) were significantly associated with GC risk. Additionally, the EGGIM score (5–8 points: OR 8.8 [4.4–16.0]) and OLGIM (stage III/IV: OR 12.5 [6.1–25.8]) were useful for stratification of GC risk. The area under the receiver operating characteristic curve value for GC risk was 0.740 for OLGIM and 0.706 for EGGIM. Conclusions: The LBC, WOS, EGGIM, and OLGIM were strongly associated with GC risk in Japanese patients. This finding can be useful for GC risk assessment in daily clinical practice. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fifth most common cause of cancer-related death worldwide. Early detection is crucial for improving survival rates and treatment outcomes. However, accurate GC-specific biomarkers remain unknown. This study aimed to identify the metabolic differences between intestinal metaplasia (IM) and GC to determine the pathways involved in GC. A metabolic analysis of IM and tissue samples from 37 patients with GC was conducted using ultra-performance liquid chromatography with tandem mass spectrometry. Overall, 665 and 278 significant features were identified in the aqueous and 278 organic phases, respectively, using false discovery rate analysis, which controls the expected proportion of false positives among the significant results. sPLS-DA revealed a clear separation between IM and GC samples. Steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and arginine and proline metabolism were the most significantly altered pathways. The intensity of 11 metabolites, including N1, N2-diacetylspermine, creatine riboside, and N-formylkynurenine, showed significant elevation in more advanced GC. Based on pathway enrichment analysis and cancer stage-specific alterations, we identified six potential candidates as diagnostic biomarkers: aldosterone, N-formylkynurenine, guanosine triphosphate, arginine, S-adenosylmethioninamine, and creatine riboside. These metabolic differences between IM and GC provide valuable insights into gastric carcinogenesis. Further validation is needed to develop noninvasive diagnostic tools and targeted therapies to improve the outcomes of patients with GC. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is the most important subtype of lung cancer. It is well known that the gut microbiome plays an important role in the pathophysiology of various diseases, including cancer, but little research has been done on the intestinal microbiome associated with LUAD. Utilizing bioinformatics tools and data analysis, we identified novel potential prognostic biomarkers for LUAD. To integrate differentially expressed genes and clinical significance modules, we used a weighted correlation network analysis system. According to the Peryton database and the gutMGene database, the composition and structure of gut microbiota in LUAD patients differed from those in healthy individuals. LUAD was associated with 150 gut microbiota and 767 gut microbiota targets, with Krüppel-like factor 5 (KLF5) being the most closely related. KLF5 was associated with immune status and correlated well with the prognosis of LUAD patients. The identification of KLF5 as a potential prognostic biomarker suggests its utility in improving risk stratification and guiding personalized treatment strategies for LUAD patients. Altogether, KLF5 could be a potential prognostic biomarker in LUAD. [ABSTRACT FROM AUTHOR]

Intestinal dysbiosis is a major contributor to colorectal cancer (CRC) development, leading to bacterial translocation into the bloodstream. This study aimed to evaluate the presence of circulated bacterial DNA (cbDNA) in CRC patients (n = 75) and healthy individuals (n = 25). DNA extracted from peripheral blood was analyzed using PCR, with specific primers targeting 16S rRNA, Escherichia coli (E. coli), and Fusobacterium nucleatum (F. nucleatum). High 16S rRNA and E. coli detections were observed in all patients and controls. Only the detection of F. nucleatum was significantly higher in metastatic non-excised CRC, compared to controls (p < 0.001), non-metastatic excised CRC (p = 0.023), and metastatic excised CRC (p = 0.023). This effect was mainly attributed to the presence of the primary tumor (p = 0.006) but not the presence of distant metastases (p = 0.217). The association of cbDNA with other clinical parameters or co-morbidities was also evaluated, revealing a higher detection of E. coli in CRC patients with diabetes (p = 0.004). These results highlighted the importance of bacterial translocation in CRC patients and the potential role of F. nucleatum as an intratumoral oncomicrobe in CRC. [ABSTRACT FROM AUTHOR]

Uterine metastases from extragenital sites are rare. We present a case of a woman who had undergone surgery for small intestinal cancer and subsequently developed metastases in her left ovary and uterus. A nulliparous woman in her 50s underwent laparoscopic partial small bowel resection with lymph node dissection for small intestinal cancer. Five months later, computed tomography (CT) revealed a left ovarian tumor and ascites. She underwent bilateral adnexectomy and adjuvant chemotherapy, and the ovarian tumor was diagnosed as a small intestinal cancer metastasis. Two years after the small intestinal cancer surgery, a positron emission tomography (PET)‐CT scan revealed a uterine accumulation. Cervical cytology was negative for intraepithelial lesion or malignancy. Endometrial histology showed an adenocarcinoma of the uterus. The patient underwent total abdominal hysterectomy followed by adjuvant chemotherapy. Histopathology and immunohistochemistry of the uterine tumor revealed that it was a metastasis of small intestinal cancer (Cytokeratin 7 [CK7] [−], Cytokeratin 20 [CK20] [+], Special AT‐Rich Sequence‐Binding Protein 2 [SATB2] [+], Paired Box Gene 2 [PAX2] [−], and estrogen receptor [ER] [−]). In patients with cancer, histopathology and immunohistochemistry are important for distinguishing between primary and metastatic tumors and for guiding the choice of treatment. [ABSTRACT FROM AUTHOR]

The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided into five groups: Helicobacter pylori (H. pylori)-associated gastritis with gastric intestinal metaplasia (GIM) (n = 12), chronic atrophic gastritis (CAG) with GIM (n = 13), H. pylori-associated gastritis without GIM (n = 19), GC (n = 6) and controls (n = 5). TRPV1 expression was determined with immunohistochemistry and was significantly higher in patients with H. pylori-associated gastritis compared with controls (p = 0.002). TRPV1 expression was even higher in the presence of GIM compared with patients without GIM and controls (p < 0.001). There was a complete loss of TRPV1 expression in patients with GC. TRPV1 expression seems to contribute to gastric-mucosal inflammation and precursors of GC, which significantly increases in cancer precursor lesions but is completely lost in GC. These findings suggest TRPV1 expression to be a potential marker for precancerous conditions and a target for individualized treatment. Longitudinal studies are necessary to further address the role of TRPV1 in gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is among the most common malignant tumors affecting the gastrointestinal tract. Liver metastases, a complication present in approximately 50% of colorectal cancer patients, are a considerable concern. Recently, studies have revealed the crucial role of miR-455 in tumor pathogenesis. However, the effect of miR-455 on the progression of liver metastases in colorectal cancer remains controversial. As an antagonist of bone morphogenetic protein(BMP), Gremlin 1 (GREM1) may impact organogenesis, body patterning, and tissue differentiation. Nevertheless, the role of miR-455 in regulating GREM1 in colorectal cancer liver metastases and how miR-455/GREM1 axis influences tumour immune microenvironment is unclear. Methods: Bioinformatics analysis shows that miR-455/GREM1 axis plays crucial role in liver metastasis of intestinal cancer and predicts its possible mechanism. To investigate the impact of miR-455/GREM1 axis on the proliferation, invasion, and migration of colorectal cancer cells, colony formation assay, wound healing and transwell assay were examined in vitro. The Dual-Luciferase reporter gene assay and RNA pull-down assay confirmed a possible regulatory effect between miR-455 and GREM1. In vivo, colorectal cancer liver metastasis(CRLM) model mice was established to inquiry the effect of miR-455/GREM1 axis on tumor growth and macrophage polarization. The marker of macrophage polarization was tested using immunofluorescence(IF) and quantitative real-time polymerase chain reaction(qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), cytokines were detected in culture medium supernatants. Results: We found that miR-455 and BMP6 expression was increased and GREM1 expression was decreased in liver metastase compared with primary tumor. miR-455/GREM1 axis promotes colorectal cancer cells proliferation, migration, invasion via affected PI3K/AKT pathway. Moreover, downregulating GREM1 augmented BMP6 expression in MC38 cell lines, inducing M2 polarization of macrophages, and promoting liver metastasis growth in CRLM model mice. Conclusion: These data suggest that miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization. These results offer valuable insights and direction for future research and treatment of CRLM. [ABSTRACT FROM AUTHOR]

Background and aims: Crohn's disease (CD)‐associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating evidence revealed that younger‐onset sporadic colorectal cancer may exhibit unique biological features. To the best of our knowledge, few previous articles reported clinicopathological features in patients with CD‐associated anorectal cancer (CDAAC). Therefore, we aimed to clarify the relationship between the younger onset of cancer and clinicopathological characteristics and prognosis, and the efficacy of cancer surveillance in patients with CDAAC. Methods: CD patients who had been diagnosed with intestinal cancers from 1983 to 2020 were collected from 39 Japanese institutions in this study. Of 316 patients with CD‐associated intestinal cancers, we analyzed 211 patients with CDAAC. We divided the patients into two groups according to the median age at cancer diagnosis (45 years old). Results: Younger‐onset CDAAC (YO‐CDAAC) patients were significantly more likely to have a poor outcome than those with older‐onset CDAAC (OO‐CDAAC) in terms of both disease‐free survival (DFS) (p = 0.0014) and overall survival (OS) (p = 0.023). Multivariate analysis showed that age under 45 years old at diagnosis of cancer was one of the independent factors for poor DFS and OS (hazard ratios: 2.15, 95% confidence interval: 1.09–4.26, p = 0.028, hazard ratios: 1.95, 95% confidence interval: 1.05–3.60, p = 0.033, respectively). Patients detected via surveillance showed significantly better DFS and OS rates than symptomatic patients in YO‐CDAAC (p = 0.012 and 0.0031, respectively). Conclusions: YO‐CDAAC may have a poorer prognosis compared with OO‐CDAAC. Surveillance could be important to improve cancer prognosis, especially in young CD patients with anorectal disease. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer worldwide. The role of intestinal microbiota in carcinogenesis has also become an important research topic, and CRC is closely related to the intestinal microbiota. Selenium-containing compounds have attracted more attention as anticancer drugs as they can have minimal side effects. The purpose of this study was to determine and compare the effect of sodium selenite and selenomethionine on the microbial communities of nude mice with CRC. A CRC ectopic tumorigenesis model was established by subcutaneously injecting HCT116 cells into nude mice. The mice were then intraperitoneally injected with sodium selenite and selenomethionine for 24 days to regulate their intestinal microbiota. Compared with sodium selenite, selenomethionine resulted in a greater reduction in the richness and diversity of intestinal microbiota in nude mice with CRC, and the richness and diversity were closer to healthy levels. Selenomethionine also regulated a wider variety of flora. Additionally, sodium selenite and selenomethionine produced different microorganisms, changed function and metabolic pathways in the intestinal microbiota. Both sodium selenite and selenomethionine have certain effects on restoring the intestinal microbial diversity in nude mice with CRC, and the effect of selenomethionine is better than that of sodium selenite. [ABSTRACT FROM AUTHOR]

The long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) maintains the integrity of the intestinal epithelial barrier and regulates local inflammation. However, its influences on intestinal microbial communities and tissue susceptibility to cancer development remain unexplored. Here, we report that MALAT1 regulates host anti-microbial response gene expression and the composition of mucosal-associated microbial communities in a region-specific manner. In the APC mutant mouse model of intestine tumorigenesis, knocking out MALAT1 results in higher polyp counts in the small intestine and colon. Interestingly, intestine polyps that developed in the absence of MALAT1 were smaller in size. These findings highlight the unexpected bivalent role of MALAT1 in restricting and promoting cancer progression at different disease stages. Among the 30 MALAT1-targets shared by both the small intestine and colon, ZNF638 and SENP8 levels are predictive of colon adenoma patient overall survival and disease-free survival. Genomic assays further revealed that MALAT1 modulates intestinal target expression and splicing through both direct and indirect mechanisms. This study expands the role of lncRNAs in regulating intestine homeostasis, microbial communities, and cancer pathogenesis.

Background: Development of sequential changes of mucous leading to gastric cancer and familial cases of gastric cancer of intestinal type is widely connected with Helicobacter pylori infections. In this study we analysed variants of genes involved in cancerogenesis and inflammatory processes of intestines in patients infected with H.pylori. Our goal was to test whether mutations in these genes predestinate to development of gastric cancer, and whether there is a genetic factor that makes it more likely for infections with H.pylori to cause gastric cancer. As infections with H. pylori are relatively common, discovering such genetic predispositions could be used for establishing risk-groups and for planning treatments. Methods: Our studies cover analysis of variants in genes involved in cancerogenesis: TP53 (rs11540652, rs587782329, COSM10771), MSH2 (rs193922376), MLH1 (rs63750217), and inflammatory processes of intestine: NOD2 (rs2066847, rs2066842), IL1A (rs1800587) and IL1B (rs1143634) from H.pylori-infected patients. Results: Mutations were more common in the group of patients with gastric cancer of intestinal type and familial cases of gastric cancer in comparison with patients with chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer (p-value = 0.00824), with the prevalence of p53 mutations in patients with familial gastric cancer vs. patients with other changes of mucosa (p-value = 0.000049). Additionally, gastric cancer patients have mainly genotype TT or CT of the rs2066842 variant of the NOD2 gene. Conclusions: The lack of statistically significant changes of other interleukin genes involved in inflammatory processes may suggest the presence of H.pylori infection as a potential trigger for the development of the inflammatory process of the mucosa, leading through microbiota dysbiosis to the development of enteric gastric cancer. Mutations in analysed genes correlated with more severe mucosal changes, with a much more frequent presence of TP53 gene mutations, with a limited presence of other mutations in the familial history of gastric cancer. [ABSTRACT FROM AUTHOR]

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as Smad4 and BMPR1A. This study explores the impact of Smad4 knock-out on the development of intestinal polyps using collaborative cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in Smad4 knock-out mice across the entire population, emphasizing the broad influence of Smad4 on polyposis. Sex-specific analyses demonstrate higher polyp counts in knock-out males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to Smad4 knock-out, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-nearest neighbors and linear regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides new information on understanding the intricate genetic interplay in the context of Smad4 knock-out, offering valuable insights that could inform the identification of potential therapeutic targets for juvenile polyposis and related diseases. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a type of intestinal cancer that causes more than 600,000 deaths every year. Overcoming the problems of metastasis requires detailed studies to reveal the potential molecular mechanisms. This study aims to reveal the molecular mechanism of CRC metastasis involving non-coding RNA regulation. The expression profile of FTH1P3 was analyzed based on the data of TCGA-COAD patient cohorts. Q-PCR analysis was performed to validate the expression of FTH1P3 in colorectal cancer cells. JASPR was used to screen transcription factors of FTH1P3. q-ChIP analysis was used to validate the target between FTH1P3 and transcription factor. Scratch assay and transwell assay were used to evaluate the migration and invasion ability of colorectal cancer cells. FTH1P3 is highly expressed in CRC patient cohort. FTH1P3 induced migration and invasion of SW480 cell through regulating epithelial-mesenchymal transition (EMT). In addition, FTH1P3 is a direct target of SNAI2. SNAI2 promotes the expression of FTH1P3. Both FTH1P3 and SNAI2 were directly targeted and repressed by miR-218-5p. Interestingly, ectopic FTH1P3 caused a decreased miR-218-5p level and an elevated nucleic SNAI2 protein expression level. Of note, only ectopic SNAI2 protein resulted in a repressed miR-218-5p and an increased FTH1P3, whereas SNAI2 3'UTR failed to affect the expression of miR-218-5p and FTH1P3. SNAI2 transcriptionally activates FTH1P3 expression. Both SNAI2 and FTH1P3 are targets of miR-218-5p. SNAI2/FTH1P3/miR-218-5p form a positive feedback loop in the regulation of CRC metastasis. [ABSTRACT FROM AUTHOR]

Copper, a trace element and vital cofactor, plays a crucial role in the maintenance of biological functions. Recent evidence has established significant correlations between copper levels, cancer development and metastasis. The strong redox‐active properties of copper offer both benefits and disadvantages to cancer cells. The intestinal tract, which is primarily responsible for copper uptake and regulation, may suffer from an imbalance in copper homeostasis. Colorectal cancer (CRC) is the most prevalent primary cancer of the intestinal tract and is an aggressive malignant disease with limited therapeutic options. Current research is primarily focused on the relationship between copper and CRC. Innovative concepts, such as cuproplasia and cuproptosis, are being explored to understand copper‐related cellular proliferation and death. Cuproplasia is the regulation of cell proliferation that is mediated by both enzymatic and nonenzymatic copper‐modulated activities. Whereas, cuproptosis refers to cell death induced by excess copper via promoting the abnormal oligomerisation of lipoylated proteins within the tricarboxylic acid cycle, as well as by diminishing the levels of iron‐sulphur cluster proteins. A comprehensive understanding of copper‐related cellular proliferation and death mechanisms offers new avenues for CRC treatment. In this review, we summarise the evolving molecular mechanisms, ranging from abnormal intracellular copper concentrations to the copper‐related proteins that are being discovered, and discuss the role of copper in the pathogenesis, progression and potential therapies for CRC. Understanding the relationship between copper and CRC will help provide a comprehensive theoretical foundation for innovative treatment strategies in CRC management. [ABSTRACT FROM AUTHOR]

Background: Neonatal necrotizing enterocolitis (NEC) is a common gastrointestinal emergency in neonates. MiRNA-192-5p was found associated with ulcerative colitis (UC) progression, also with aberrant expression in intestinal cancer tissue. However, the effects of miRNA-192-5p on NEC have not been reported. Methods: Based on the bioinformatics analysis of the GEO dataset, miR-192-5p was identified as the differentially expressed miRNA in NEC, and activated leukocyte cell adhesion molecule (ALCAM) was predicted as its target. After that, in vitro, rat intestinal epithelial cell-6 (IEC-6) were stimulated with LPS to construct a cell model of NEC. IEC-6 cells were transfected with miRNA-192-5p mimics, miRNA-192-5p inhibitors, or miRNA-192-5p inhibitors + sh-ALCAM, and relevant negative control. In vivo, SD rats were treated with artificial feeding, hypoxic reoxygenation, cold stimulation, and LPS gavage to induce NEC, followed by injection of agomiR-NC or agomiRNA-192-5p. Then effects of miRNA-192-5p on NEC model IEC-6 cell viability, apoptosis, ALCAM expression, Interleukin (IL)-1β and IL-6 levels, intestinal injury, intestinal permeability were detected. Results: MiRNA-192-5p expression was downregulated in NEC IEC-6 cells, whose overexpression increased IEC-6 cell viability. MiRNA-192-5p inhibitors increased IL-1β, IL-6 levels and promoted IEC-6 cell apoptosis. MiRNA-192-5p targeting of ALCAM decreased ALCAM expression, IL-1β, and IL-6 levels. AgomiRNA-192-5p decreased ALCAM, IL-1β, and IL-6 levels in intestinal tissue and pathological damage and increased miRNA-192-5p levels. Conclusion: MiR-192-5p protects against intestinal injury by inhibiting ALCAM-mediated inflammation and intestinal epithelial cells, which would provide a new idea for NEC treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: Colitis‐associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. Methods: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score‐matched data. Results: A total of 1077 patients with UC‐CAC, 297 with CD‐CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score‐matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). Conclusion: CAC, including early‐stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression. [ABSTRACT FROM AUTHOR]

Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1β, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms. [ABSTRACT FROM AUTHOR]

Iron supplements are widely consumed. However, excess iron may accelerate intestinal tumorigenesis. To determine the effect of excess iron on intestinal tumor burden and protein expression changes between tumor and normal tissues, ApcMin/+ mice were fed control (adequate) and excess iron (45 and 450 mg iron/kg diet, respectively; n = 9/group) for 10 wk. Tumor burden was measured, and two-dimensional fluorescence difference gel electrophoresis was used to identify differentially expressed proteins in tumor and normal intestinal tissues. There was a significant increase (78.3%; p ≤ 0.05) in intestinal tumor burden (mm2/cm) with excess iron at wk 10. Of 980 analyzed protein spots, 69 differentially expressed (p ≤ 0.05) protein isoforms were identified, representing 55 genes. Of the isoforms, 56 differed (p ≤ 0.05) between tumor vs. normal tissues from the adequate iron group and 23 differed (p ≤ 0.05) between tumors from the adequate vs. excess iron. Differentially expressed proteins include those involved in cell integrity and adaptive response to reactive oxygen species (including, by gene ID: ANPEP, DPP7, ITGB1, PSMA1 HSPA5). Biochemical pathway analysis found that iron supplementation modulated four highly significant (p ≤ 0.05) functional networks. These findings enhance our understanding of interplay between dietary iron and intestinal tumorigenesis and may help develop more specific dietary guidelines regarding trace element intake. [ABSTRACT FROM AUTHOR]

Background/Aim: Intestinal malrotation (IM) often remains undetected until adulthood, being discovered during testing or surgery for other comorbidities. Preoperative understanding of this anatomical abnormality is crucial. Case Report: An 80-year-old woman presented with cecal cancer. Three-dimensional computed tomography (CT) revealed that the cecum was located at the midline of the abdominal cavity, the duodenum did not cross the midline, and the ileocolic vein ran to the left. Clinically diagnosed with stage IVc cecal cancer complicated by IM, the patient underwent laparoscopic surgery. The ascending colon and cecum were not fixed to the retroperitoneum. The duodenum lacked the second, third, and fourth portions and the small bowel was distributed on the left and right sides of the abdominal cavity. Adhesions had shortened the mesentery, which were released close to their normal positions. Conclusion: Although laparoscopic surgery is superior to open surgery in terms of securing the field of view in a narrow space, providing a magnifying effect, and minimal invasiveness, it has a limited field of view and is inferior in terms of grasping the overall anatomy, which may be disadvantageous in cases of anatomical abnormalities. Colorectal cancer with IM is rare; however, the rate of preoperative diagnosis seems to be increasing thanks to improvements in diagnostic imaging, such as three-dimensional CT scans. In this study, we also reviewed 49 cases of colorectal cancer associated with IM. [ABSTRACT FROM AUTHOR]

Common bean landraces, besides contributing to the preservation of the social and cultural identity of the local communities of the production area, typically display adaptability to adverse agro-climatic conditions. This adapted germplasm is a repository of the gene pool and also shows typical phytochemical profiles, representing an essential source of bioactive components. However, genetic erosion is progressively affecting this genetic material, creating serious threats to its cultivation in marginal rural areas and use as a source of biodiversity and bioproducts. In the present work, a comprehensive approach was used to characterize the seed morpho-colorimetric traits, genetic diversity, and NMR metabolomic profiles of three Italian common bean landraces. Specific physiological and biochemical features (antioxidant molecules, osmolytes, structural reorganization of photosynthetic pigment, etc.), together with the accumulation of distinctive metabolites, contribute to the description of the observed diversity among the landraces in terms of the salt stress response and antiproliferative abilities on intestinal human cancer cells. This information could be useful in establishing their value in terms of environmental and/or human health "service", both essential to translating landraces into competitive products, a prerequisite for envisioning appropriate strategies for their conservation and a driving force for the revitalization of marginal rural areas. [ABSTRACT FROM AUTHOR]

Background: Cancer rates continue to climb, owing largely to the world population's aging and growth, as well as economically developing countries, a surge in cancer-causing behavior, particularly smoking. The third or fourth most prevalent type of cancer is colon cancer. Cancer of the large intestine (colon) is one of the primary causes of death from cancer. Colorectal cancer prevention is mostly based on adenomatous disease screening approaches. The cytotoxic and pharmacological properties of Phoenix pusilla are widely documented. As a result, there is little recorded evidence of its cytotoxic activity against colon cancer cells. Therefore, we planned to study the efficacy of a methanolic leaf extract of Phoenix pusilla against in vitro colon cancer cells. Aim: To evaluate the anti-cancer effects of the methanolic leaf extract of Phoenix pusilla on colon cancer cell lines. Materials and Methods: In vitro screening and anti-cancer effects of the methanolic effect of Phoenix pusilla on colon cancer cell lines were assessed by cell viability assays and cell and nuclear morphological studies. For the in vitro cell culture study, different concentrations of Phoenix pusilla leaf extract (0, 25, 50, 75, 100, 150 µg/ml) were used, and IC50 doses were calculated. Results: The results of the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay revealed that the fraction of viability cells significantly decreased in treated cells when compared to untreated control groups, was expressed as 100%, and an inhibitory concentration of µg/ml was identified. A phase-contrast microscope was used to observe cell shrinkage and cytoplasmic membrane blebbing. A fluorescent microscope was used to examine the apoptotic nuclei (internally dyed nuclei, shattered nuclei, and condensed chromatin). Conclusion: In conclusion, the present study results showed that the leaf extracts of Phoenix pusilla had a strong cytotoxic effect and induced significant apoptosis in the colon cancer cell lines at a concentration of 75 µg/ml in the 24 h incubation period. More research is needed to investigate the extract's active components as well as the molecular mechanisms underlying its anti-cancer properties. [ABSTRACT FROM AUTHOR]

Pyroptosis is an innate immune response triggered by the activation of inflammasomes by various influencing factors, characterized by cell destruction. It impacts the immune system and cancer immunotherapy. In recent years, the roles of pyroptosis and inflammasomes in intestinal inflammation and cancer have been continuously confirmed. This article reviews the latest progress in pyroptosis mechanisms, new discoveries of inflammasomes, mutual regulation between inflammasomes, and their applications in intestinal diseases. Additionally, potential synergistic treatment mechanisms of intestinal diseases with pyroptosis are summarized, and challenges and future directions are discussed, providing new ideas for pyroptosis therapy. [ABSTRACT FROM AUTHOR]

Backgrounds: Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC. Materials and methods: We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 − 8) was also assessed in tumor specimens from 64 patients. Results: The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels. Conclusion: These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs. [ABSTRACT FROM AUTHOR]

Background: Inhalation exposure to carcinogenic metals such as cadmium (Cd) is a significant global health concern linked to various cancers. However, the precise carcinogenic mechanism underlying inhalation exposure remains elusive. Methods: In this study, CT26 mouse colon cancer (CC) cells were implanted into BALB/c mice to establish CC mouse models. Some of the CC mice were implanted with intestinal stents. The mice were exposed to atomized oxygen and nitrogen (O2/N2) gas containing Cd. Results: Atmospheric Cd intensified inflammation in CC cells and heightened Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase 1 (NOX1) activity, which is an indirect measurement of increased reactive oxygen species (ROS) production. This escalated ROS production triggered abnormal Wnt protein secretion, activated the Wnt/β-catenin signaling pathway, and stimulated CC cell proliferation. No discernible body weight effect was seen in the CC mice, possibly due to the later-stage tumor weight gain, which masked the changes in body weight. Cd facilitated colon tumor restructuring and cell migration at the later stage. The implantation of intestinal stents inhibited the expression of Superoxide Dismutase 1 (SOD1) in the colon tumors of the CC mice, with no evident effects on the expression levels of NOX1, SOD2, and Catalase (CAT) enzymes. Elevated ROS levels, indirectly reflected by enzyme activity, did not substantially impact the Wnt/β-catenin signaling pathway and even contributed to slowing its imbalance. Stent implantation eased the inflammation occurring in colon tumors by reducing CC cell proliferation but it induced discomfort in the mice, leading to a reduction in food intake and weight. Conclusions: Cd partially fosters CC tumorigenesis via the ROS-mediated Wnt/β-catenin signaling pathway. The effect of Cd on the invasive effect of intestinal stents in the cancerous colon is not significant. [ABSTRACT FROM AUTHOR]

Numerous studies have suggested a robust association between amylase and ovarian cancer. however, few amylase-producing ovarian cancers have been reported because amylase is a rare product of ovarian cancer. A case of an elderly female patient with an upper abdominal unfitness, intestinal wall along with uterine adnexal invasion, and high serum and urinary amylase is summarized in this article. The patient was initially suspected of having a gastrointestinal tumor. Initial laboratory findings showed markedly significantly raised serum and urinary amylase levels. Imaging showed invasion of the intestinal wall and uterine adnexa, and histology of the specimen taken through the abdominal wall lump and electron colonoscopy showed ovarian cancer. The patient's blood amylase levels decreased to normal after 4 cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin. Following this, she underwent interval debulking surgery, which included total hysterectomy, bilateral adnexectomy, great omentectomy, appendectomy, resection of pelvic and abdominal lesions, and partial rectal resection. Postoperative pathology and immunohistochemistry staining confirmed a diagnosis of high-grade serous ovarian cancer. This case suggests that in female patients, hyperamylasemia may indicate the presence of ovarian cancer. It is necessary to perform a multisite, multipoint histologic examination to identify the tumor's origin in patients with multiple sites of invasion. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is an important cancer-related death worldwide. Among its histological subtypes, intestinal gastric cancer (IGC) is the most common. A previous work showed that increased expression of the THY1 gene was associated with poor overall survival in IGC. Furthermore, it was shown that IGC tumor cells with high expression of THY1 have a greater capacity for tumorigenesis and metastasis in vitro. This study aimed to identify molecular differences between IGC with high and low expression of THY1. Using a feature selection method, a group of 35 genes were found to be the most informative gene set for THY1high IGC tumors. Through a classification model, these genes differentiate THY1high from THY1low tumors with 100% of accuracy both in the test subset and the independent test set. Additionally, this group of 35 genes correctly clustered 100% of the samples. An extensive validation of this potential molecular signature in multiple cohorts successfully segregated between THY1high and THY1low IGC tumors (>95%), proving to be independent of the gene expression quantification methodology. These genes are involved in central processes to tumor biology, such as the epithelial–mesenchymal transition (EMT) and remodeling of the tumor tissue composition. Moreover, patients with THY1high IGC demonstrated poor survival and a more advanced clinicopathological staging. Our findings revealed a molecular signature for IGC with high THY1 expression. This signature showed EMT and remodeling of the tumor tissue composition potentially related to the biology of IGC. Altogether, our results indicate that THY1high IGC tumors are a particular subset of tumors with a specific molecular and prognosis profile. [ABSTRACT FROM AUTHOR]

Background: Limited evidence suggests a possible connection between natural or occupational exposure to chromium and an increased risk of gastrointestinal cancer. The main objective of this study is to investigate the literature regarding chromium exposure and gastrointestinal health issues (i.e., cancer). Methods: A systematic literature search was performed using PubMed, Google Scholar and ScienceDirect. Included observational studies were assessed for their risk of bias. Results: 16 observational studies and 7 reviews and meta-analyses met the inclusion criteria. Most of the studies investigated gastric and hepatocellular cancer, followed by colorectal, oral, esophageal and pancreatic cancer. There is a limited amount of evidence regarding non-malignant gastrointestinal diseases. Chromium exposure is suspected to increase gastric and colorectal cancer risks. We did not find any convincing indications for increases in oral, esophageal and hepatocellular cancer. Pancreatic, gallbladder and extrahepatic bile ducts carcinogenesis is likely not associated with chromium exposure. Conclusion: We found weak evidence that chromium exposure is associated with gastric and colorectal cancer. Our review also highlights the existing controversial evidence regarding oral, esophageal and hepatocellular cancer, as well as the gap in studies investigating small intestinal cancer and non-malignant gastrointestinal health issues. [ABSTRACT FROM AUTHOR]

While clinical practice guidelines for hereditary diffuse gastric cancer are well established, there is no consensus on the approach for familial intestinal gastric cancer (FIGC). In low‐incidence gastric cancer (GC) areas such as the United States or most European countries, there are no evidence‐based recommendations on endoscopic assessment in FIGC families. We aim to describe the yield of GC surveillance in these families, and to identify epidemiological risk factors for the development of GC and its precursor lesions. This is a multicenter observational study involving nine tertiary Spanish hospitals, in which all individuals fulfilling FIGC criteria who underwent endoscopic surveillance were included between 1991 and 2020. Forty‐one healthy individuals of 31 families were recruited. The median number of upper gastrointestinal endoscopies per individual was 3 (interquartile range, IQR, 1‐4). The median interval time between tests was 2 years (IQR 1.5‐2.5), and the median follow‐up was 9 years (IQR 3‐14.5). In 18 (43.9%) subjects, a precursor lesion of GC was found during follow‐up, and in 2 (4.9%), an early GC was identified, in which curative treatment was offered. Helicobacter pylori (Hp) infection proved to be independently associated with an increased risk of developing precursor lesions or GC, adjusted by age, gender and follow‐up, with an Odds Ratio of 6.443 (1.36‐30.6, P value.019). We present the first outcomes that support endoscopic surveillance with biopsies and detection of Hp in FIGC families, although the periodicity has yet to be defined. [ABSTRACT FROM AUTHOR]

To assess the impact of short-term postoperative complications on oncologic outcomes for patients with epithelial ovarian cancer undergoing primary cytoreductive surgery (PCS) or interval cytoreductive surgery (ICS) with intestinal resection. A retrospective chart review was performed for patients with ovarian cancer who underwent PCS or ICS with at least one intestinal resection at our institution from 1/1/2015 to 12/31/2020. Progression-free survival (PFS) and overall survival (OS) were analyzed for the PCS and ICS cohorts separately. Short-term complications within 30 days of surgery (surgical secondary events [SSEs]) were graded by a validated institutional SSE system. Among 437 patients who underwent intestinal resections during PCS (n = 289) or ICS (n = 148), 183 (42%) had one, 180 (41%) had two, and 74 (17%) had three intestinal resections. Six (1.4%) of 437 patients experienced an anastomotic leak postoperatively. There were no perioperative deaths. There was no difference in PFS and OS for patients who underwent PCS with any SSE vs. no SSE within 30 days of surgery (HR, 1.05; 95% CI: 0.76–1.47; p = 0.75 and HR, 0.79; 95% CI: 0.49–1.26; p = 0.32, respectively). There was no difference in PFS and OS for patients who underwent ICS with any SSE vs. no SSE within 30 days of surgery (HR, 1.43; 95% CI: 0.99–2.07; p = 0.055 and HR. 1.18; 95% CI: 0.72–1.93; p = 0.52, respectively. Short-term postoperative morbidity for patients who underwent intestinal surgery during primary surgical management for advanced ovarian cancer did not impact oncologic outcomes. • Grade ≥3 adverse events occurred in 12% of patients within 30 days of primary (PCS) or interval cytoreductive surgery (ICS). • In the entire cohort, 6 patients (1.4%) experienced an anastomotic leak postoperatively. • Postoperative morbidity after PCS and ICS led to a 3- and 5-day delay to chemotherapy initiation, respectively. • Patients initiating postoperative chemotherapy < or > 42 days after PCS and ICS had no difference in PFS and OS. • Postoperative morbidity after PCS or ICS with intestinal surgery did not impact oncologic outcomes. [ABSTRACT FROM AUTHOR]

Compelling evidence has mounted surrounding the relationship between the gut microbiome and many intestinal and extraintestinal cancers. Few studies exist investigating the relationship between the gut microbiome and sarcoma. We hypothesize that the presence of distant osteosarcoma induces change to the profile of flora within the mouse. Twelve mice were used for this experiment: six were sedated and received an injection of human osteosarcoma cells into the flank, while six served as controls. Baseline stool and weight were collected. Tumor size and mouse weight were recorded weekly, and stool samples were collected and stored. Fecal microbiomes of the mice were profiled by 16S rRNA gene sequencing and analyzed for alpha diversity, relative abundances of microbial taxa, and abundance of specific bacteria at different time points. Alpha diversity was increased in the osteosarcoma group compared with the control group. The family Lachnospiraceae had the second strongest negative net average change in relative abundance over time in the osteosarcoma group whereas it had a positive net average change in the control group. An increased Firmicutes/Bacteroidota (F/B) ratio was observed in the osteosarcoma group relative to the control mice. These differences suggest that there may be an interplay between the gut microbiome and osteosarcoma. Clinical significance: Due to the paucity of literature available, our work can support novel research on this relationship and the development of new, personalized treatments for osteosarcoma. [ABSTRACT FROM AUTHOR]

The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma. We analyzed 474 cases of primary gastric lymphoma, mainly DLBCL and MALT, from three clinical centres retrospectively, and compared the clinicopathological parameters of primary gastric lymphoma patients complicated with gastric cancer, precancerous conditions, or with no complications. A total of 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer, including metachronous gastric adenocarcinoma (3.2%) and synchronous gastric adenocarcinoma (1.9%). Of the patients with gastric lymphoma, 14.6% had precancerous conditions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients with an ulcerative type (p = 0.009) and Lugano classification stage IIE + IV (p < 0.001) lymphoma had a higher risk of complicating with gastric cancers or precancerous conditions. The rate of infection of Helicobacter pylori (Hp) was 68.4% in patients with primary gastric lymphoma, which was higher in patients with MALT lymphoma (p < 0.001), Lugano classification stage I + II (p < 0.001), and patients complicated with precancerous conditions and gastric cancer (p < 0.001), especially gastric cancer of the intestinal type (p = 0.04). Gastric cancer (95.8%) and precancerous conditions (91.3%) occurred mostly in Hp-infected primary gastric lymphoma patients, with a minor subset of Hp-eradicated patients. Primary gastric lymphoma patients had a higher detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population. Patients with primary gastric lymphoma have a high risk of developing gastric cancer and precancerous conditions, and this risk may be related to Helicobacter pylori infection. Follow-up of primary gastric lymphoma provides an opportunity for the detection of early gastric cancer. 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer. 14.6% of the patients with gastric lymphoma had premalignant lesions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients complicating with gastric cancer had a higher infection rate of Helicobacter pylori (100.0%), a detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population. [ABSTRACT FROM AUTHOR]

Background: There are some concerns about the higher risk of certain gastrointestinal (GI) cancers in patients with a history of bariatric metabolic surgery (BMS). The current study aimed to investigate the association of BMS with GI cancer hospital admission including esophageal, gastric, colorectal, small intestinal, liver, gallbladder, bile duct, and pancreatic cancers. Methods: The analysis utilized the US national inpatient sample (NIS) data from 2016 to 2020, employing ICD-10 codes. A propensity score matching in a 3:1 ratio was done to match the BMS and non-BMS groups. Results: A total of 328,369 patients with a history of BMS and 4,989,154 with obesity and without a history of BMS were included in this study. BMS was independently associated with a higher risk of gastric and pancreatic cancers hospital admission (OR: 1.69 (CI 95%: 1.42–2.01) and OR: 1.46 (CI 95%: 1.27–1.68)), respectively. In addition, BMS was independently associated with a lower risk of colorectal and liver cancer hospital admission (OR: 0.57 (CI 95%: 0.52–0.62) and OR: 0.72 (CI 95%: 0.52–0.98)), respectively. Besides, esophageal, gallbladder, bile duct, and small intestinal cancer were not significantly different between the two groups. In patients with GI cancer, although the BMS group had significantly lower total charges and length of hospital stay compared to the non-BMS group, the rate of in-hospital mortality was not significantly different. Conclusion: The current study showed that bariatric surgery may be associated with a higher risk of gastric and pancreatic cancer and a lower risk of colorectal and liver cancer hospital admission. Further research is needed to explore this association. [ABSTRACT FROM AUTHOR]

Diagnosis of adenocarcinoma in the liver is a frequent scenario in routine pathology and has a critical impact on clinical decision making. However, rendering a correct diagnosis can be challenging, and often requires the integration of clinical, radiologic, and immunohistochemical information. We present a deep learning model (HEPNET) to distinguish intrahepatic cholangiocarcinoma from colorectal liver metastasis, as the most frequent primary and secondary forms of liver adenocarcinoma, with clinical grade accuracy using H&E-stained whole-slide images. HEPNET was trained on 714,589 image tiles from 456 patients who were randomly selected in a stratified manner from a pool of 571 patients who underwent surgical resection or biopsy at Heidelberg University Hospital. Model performance was evaluated on a hold-out internal test set comprising 115 patients and externally validated on 159 patients recruited at Mainz University Hospital. On the hold-out internal test set, HEPNET achieved an area under the receiver operating characteristic curve of 0.994 (95% CI, 0.989–1.000) and an accuracy of 96.522% (95% CI, 94.521%–98.694%) at the patient level. Validation on the external test set yielded an area under the receiver operating characteristic curve of 0.997 (95% CI, 0.995–1.000), corresponding to an accuracy of 98.113% (95% CI, 96.907%–100.000%). HEPNET surpassed the performance of 6 pathology experts with different levels of experience in a reader study of 50 patients (P =.0005), boosted the performance of resident pathologists to the level of senior pathologists, and reduced potential downstream analyses. We provided a ready-to-use tool with clinical grade performance that may facilitate routine pathology by rendering a definitive diagnosis and guiding ancillary testing. The incorporation of HEPNET into pathology laboratories may optimize the diagnostic workflow, complemented by test-related labor and cost savings. [Display omitted] An innovative artificial intelligence algorithm predicts major forms of hepatic adenocarcinoma using conventional histopathologic slides with clinical grade performance, supporting pathologists in diagnosis making with explainable model decision. [ABSTRACT FROM AUTHOR]

Background. TMUB1 is a transmembrane protein involved in biological signaling and plays an important role in the stability and transcription of P53. However, its role in tumor remains unknown. Methods. Using R language, the expression level of 33 cancer spectrum TMUB1 was analyzed by the public database TCGA, GEO and HPA, the differential expressed gene (DEG) screening and protein interaction (PPI) network was constructed, and the differential genes of TMUB1 in colon cancer were identified. The relevant signaling pathways were identified by gene functional annotation and enrichment analysis. The ssGSEA algorithm in GSVA were used for immune infiltration analysis. The Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, nomogram and calibration map analysis were constructed to evaluate the correlation between TMUB1 expression and clinical prognosis. The expression levels of TMUB1 in intestinal cancer cell lines as well as in 10 intestinal cancer tissues were verified by qPCR experiments. Results. Through the bioinformatics analysis of multiple databases and preliminary experimental studies, we found that the expression of TMUB1 was significantly increased in colon cancer tumors, and was correlated with the clinical N stage, pathological grade, lymphatic metastasis and BMI of colon cancer. TMUB1 may be involved in the regulation of the malignant progression of colon cancer. Meanwhile, patients with high expression of TMUB1 mRNA had worse OS and DSS, and TMUB1 expression was an independent prognostic factor for OS and DSS. It was further found that highly expressed TMUB1 tissues showed low levels of immune infiltration and stromal infiltration. Conclusion. We reported the expression level of TMUB1 in colon cancer and analyzed its potential prognostic value in colon cancer through the bioinformatics analysis and preliminary experimental studies. The high expression of TMUB1 is a negative prognostic factor for colon cancer patients. TMUB1 may be a potential target for colon cancer. [ABSTRACT FROM AUTHOR]