Search Results (2,917)

Background: Intraductal papillary mucinous neoplasms (IPMNs) display four histological subtypes: gastric foveolar, pancreaticobiliary, intestinal, and oncocytic. All of these subtypes harbor a different risk of cancer development. The clinical impact of these subtypes concerning the occurrence of high-grade dysplasia (HGD)/cancer (C) in specific morphological types, such as branch-duct (BD), main-duct (MD), and mixed-type (MT) IPMNs, has been less investigated. Hence, our aim was to investigate the prevalence of histological subtypes and their possible association with HGD/C concerning morphologically different IPMNs. Methods: This was a retrospective review of demographics, risk factors, and histological features in a surgical cohort of patients having undergone resection for suspect malignant IPMNs at a high-volume tertiary center from 2007 to 2017. Results: A total of 273 patients were resected for IPMNs from during the study period, of which 188 were included in the final analysis. With sex- and age-adjusted multivariable logistic regression analysis across the entire cohort, gastric foveolar subtypes were associated with a reduced prevalence of HGD/C (OR = 0.30; 0.11–0.81, 95% CI, 95%CI; p = 0.01). With univariable logistic regression analysis, in the BD-IPMN subgroup, the pancreaticobiliary subtype was associated with an increased prevalence of HGD/C (OR = 18.50, 1.03–329.65, 95% CI; p = 0.04). In MD- and MT-IPMNs, the gastric foveolar subtype was associated with a decreased prevalence of HGD/cancer (OR = 0.30, 0.13–0.69, 95% CI; p = 0.004). Conclusions: In MD and MT-IPMNs, the gastric-foveolar subtype is associated with a lower prevalence of HGD/C, possibly identifying in such a high-risk group, a subgroup with more indolent behavior. In BD-IPMNs, the pancreaticobiliary subtype is associated with a higher prevalence of HGD/C, conversely identifying among those patients, a subgroup deserving special attention. Full article

Background: The natural history and prognosis of mesenteric panniculitis (MP) are not well-described. Despite referral for colonoscopy being common for this indication, colonoscopy findings in MP patients have not been reported. Therefore, we aimed to describe upper and lower gastrointestinal (GI) endoscopy findings in patients with mesenteric panniculitis, compared to matched controls, to investigate their clinical outcomes including incidence of malignancy and mortality. Methods: Retrospective case–control study was conducted, and included patients who were diagnosed with mesenteric panniculitis according to Coulier radiologic criteria on abdominal computerized tomography between 1/2005 and 12/2019, and followed to 12/2021. The case group was compared to a matched control group without MP on abdominal CT. Clinical data and the upper and lower endoscopies’ reports were reviewed in both groups. We excluded patients who, beyond diagnosis of MP, were also diagnosed with current malignancy, significant intra-abdominal morbidity or inflammatory bowel disease. Results: The initial set of 376 patients with MP, after exclusion, included 187 patients. A total of 56.1% were male, with a mean age 60 ± 15 years. Of them, 74 (39%) patients underwent follow-up CT scans, which demonstrated, in 66 (89.2%) patients, a stable MP without any aggravation. Colonoscopy was performed in 89 MP patients, and 98/187 controls. No significant difference in the colonoscopies’ findings was found between the two groups. Gastroscopy was performed in 84 MP and 79 controls. No case of gastric cancer was found. No statistically significant difference was found in the rate of gastroscopy findings. By the end of the follow-up period, malignancy was diagnosed in four patients of the MP group. None were colon cancer. The mortality rate in the MP group was 3.2%, without a significant difference compared to the controls. None were MP related. Conclusions: MP identified on abdominal CT is not associated with pathologic endoscopy findings or future diagnosis of colon cancer, and also has no impact on mortality rate. Since repeating abdominal CT did not reveal any disease progression, the necessity of follow-up imaging for MP should be carefully reconsidered. Full article

The search for bioactive compounds for the treatment of several diseases has led to the study of endophytic fungi. Neoplastic diseases are among the most significant health concerns due to their high mortality rate, and there is a dearth of efficacious pharmaceutical agents for the treatment of cancer. Gastric cancer is one of the most aggressive forms of cancer and is among those with the highest mortality rates in Brazil. Accordingly, the objective of this study was to identify compounds with cytotoxic activity from the mangrove-derived endophytic fungus Trichoderma sp. Isolation of the chemical compounds was conducted using chromatographic methods, while structural elucidation was achieved through the application of spectroscopic (NMR and UV) and spectrometric (MS) techniques. The fungus Trichoderma sp. was found to produce five distinct koninginins (A, B, C, E, and J). The organic phases of the extracts and isolated compounds were evaluated for their antimicrobial and cytotoxic potentials, respectively, through microdilution testing and the MTT method. In the cytotoxicity assay, both the AF extract and koninginin A demonstrated favorable outcomes, indicating their potential as promising anticancer therapeutic agents. Full article

Background: Gastric cancer (GC) is a leading cause of cancer-related mortality, particularly in East Asia. Despite treatment advances, the prognosis remains poor owing to late diagnosis and high metastatic potential. Phosphorylated AXL (pAXL), a receptor tyrosine kinase, promotes cancer progression, including epithelial–mesenchymal transition (EMT), tumor growth, and metastasis. In this study, we aimed to investigate the relationship between pAXL expression and prognosis in patients with GC, focusing on survival outcomes and other biomarkers such as fibronectin and phosphorylated AKT (pAkt). Methods: Immunohistochemistry was performed to assess the expression of pAXL, fibronectin, and pAkt in 188 GC specimens collected between 2000 and 2013. H-scores were calculated based on staining intensity and percentage. The association between pAXL expression and patient outcomes was assessed using Kaplan–Meier survival analysis and multivariate logistic regression. Results: Higher pAXL expression was significantly associated with improved survival, particularly in male patients. pAXL expression positively correlated with fibronectin and pAkt upregulation, suggesting its role in promoting tumor invasion and EMT. Multivariate analysis identified pAXL, fibronectin, and pAkt as significant prognostic indicators, whereas other factors such as age, tumor grade, and tumor size were not statistically significant. Conclusions: This study identified pAXL as a valuable prognostic marker in GC, with higher expression levels associated with better survival outcomes, particularly in male patients. pAXL enhanced the invasive potential of GC cells through fibronectin and pAkt regulation, making it a promising therapeutic target. Further research is needed to explore the potential of pAXL-targeted therapies and better understand their role in cancer progression and treatment response. Full article

Plant biotechnology creates opportunities for the cultivation of plants regardless of their natural habitats, which are often protected or difficult to access. Maintaining suspension cell cultures in bioreactors is an advanced part of biotechnological research that provides possibilities for obtaining plant tissue on a large scale. In this study, the suspension culture cultivation of a Chinese endemic plant, Schisandra henryi, in a stirred tank bioreactor was elaborated for the first time. The phytochemical profile of the tissue extracts was determined with UHPLC-MS/MS for the lignans (fifteen dibenzocyclooctadiene lignans, one aryltetralin lignan, and two neolignans) and UHPLC-DAD-ESI-MS³ for the phenolic compounds (procyanidins and their derivatives and catechin). The maximum total lignan content of 1289 µg/100 g DW was detected for the extracts from suspensions cultured in a bioreactor for over 10 days. For the phenolic compounds, catechin was the dominant compound (390.44 mg/100 g DW). The biological activity of the extracts was tested too. To determine antioxidant potential we used DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), Molybdenum reduction, and β-carotene bleaching tests. The inhibition activity of the S. henryi extract on the enzymes responsible for skin aging, hyaluronidase and tyrosinase, was assessed with spectrophotometry. The cytotoxic activity of the extracts was estimated on human ovarian SKOV-3, cervical HeLa, and gastric AGS cancer cells and non-cancer, normal fibroblasts by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The results showed the great potential of the obtained cell biomass extracts. The results of the antioxidant tests indicated their strong ability to reduce the level of free radicals, similarly to that of ascorbic acid, as well as the weak capacity to protect lipids from oxidation. Moreover, anticancer potential, particularly on the cervical and gastric cancer cells, was confirmed too. Full article

Background/Objectives: Chemerin, which is a multifunctional cytokine and adipokine, has been implicated in inflammatory and metabolic processes and might play a role in upper gastrointestinal (GI) malignancies, particularly gastric and esophageal cancer. The aim of this review is to explore the role of chemerin in the pathophysiology of upper GI cancers, as well as its potential as a biomarker for early detection and as a therapeutic target. Methods: A comprehensive review of recent studies about chemerin’s biochemical properties and interaction with its receptors, as well as its effects on inflammatory responses, immune regulation, and metabolic processes, was conducted. The clinical implications of chemerin for gastric and esophageal cancer were analyzed, whereas the potential therapeutic strategies targeting chemerin were discussed. Results: Elevated chemerin levels are associated with poor prognosis in gastric cancer and promote invasiveness and metastasis in esophageal cancer. Chemerin receptor antagonists show promising results in inhibiting cancer cell migration, invasion, and progression. Conclusions: Chemerin could represent a valuable prognostic biomarker and therapeutic target for upper GI cancers. Future observational studies should validate its clinical applications and investigate the efficacy of chemerin inhibitors as potential therapeutic targets. Full article

Background/Objectives: Metabolic and bariatric surgery (MBS) is known to reduce cancer risk. However, the association between specific bariatric procedures and cancer incidence is not well-studied. This study examined the association between four different MBS procedures and cancer incidence. Methods: Bariatric surgery registry data were linked with statewide cancer registry data from 1979 to 2018. The study included 27,092 adult subjects (aged ≥ 18 years old at surgery) who underwent MBS (BMI ≥ 30 kg/m² at surgery) from 1979 to 2017. Cancer records were linked to MBS patient records, resulting in 1547 cancer cases. Cox proportional hazards regression was used to examine the association between MBS procedure types and cancer incidence. Results: Of all patients, 75% underwent Roux-en-Y gastric bypass (RYGB), 9% adjustable gastric banding (AGB), 10% sleeve gastrectomy (SG), and 6% duodenal switch (BPD-DS). The overall cancer incidence during the follow-up period was 6.4% for RYGB, 4.6% for AGB, 1.6% for SG, and 5.9% for BPD-DS. The mean follow-up duration from surgery to cancer incidence or censoring was 167 months (standard deviation = 121 months). Compared to RYGB, patients who underwent AGB (Hazard Ratio [HR] = 1.26, p = 0.03) and BPD-DS (HR = 1.91, p < 0.01) had a significantly higher hazard of developing cancer, while SG (HR = 1.17, p = 0.33) showed no significant difference. Conclusions: These findings suggest that AGB and BPD-DS may be associated with higher cancer risks compared to RYGB. Additional large population studies are needed to better understand the long-term cancer risks and mechanisms associated with different MBS types. Full article

Background and Objective: Serum markers such as gastrin and pepsinogen are useful for stratifying gastric cancer risk. However, their utility in predicting metachronous gastric cancer after endoscopic submucosal dissection (ESD) in patients with gastric cancer after Helicobacter pylori eradication (GCAE) is unclear. This study aimed to clarify predictive factors for metachronous gastric cancer after ESD with a focus on serum markers. Methods: A retrospective analysis was conducted on 197 patients with 224 GCAE lesions who underwent ESD at Hiroshima University Hospital between April 2010 and December 2019. In total, 63 patients with 74 differentiated-type lesions were classified into metachronous gastric cancer (MG) and non-metachronous gastric cancer (NMG) groups, excluding proton pump inhibitor (PPI) users, female patients, and undifferentiated-type cases. The predictive value of serum markers was assessed using ROC curve analysis, and their association with carcinogenesis was evaluated using multiple logistic regression. Furthermore, the incidence of MG was compared between long-term PPI users and non-users. Results: ROC analysis revealed that serum gastrin had the highest discriminative ability for MG (AUC 0.77, cut-off 99 pg/mL, sensitivity 61.6%, and specificity 80.0%). Severe mucosal atrophy and high gastrin levels were significantly more common in the MG group and were independent predictors (p < 0.01). Although serum gastrin levels were significantly elevated in PPI users, no increased risk of MG was observed. Conclusions: In addition to severe mucosal atrophy, PPI-independent elevated serum gastrin levels may be associated with an increased risk of MG after ESD. Serum gastrin may serve as a valuable marker for post-ESD cancer surveillance in GCAE patients. Full article

Background/Objectives: Adenocarcinomas of the esophagogastric junction and stomach present clinical entities with significant cancer-related morbidity and mortality, often requiring multimodal treatments. Preoperative chemotherapy, mainly the FLOT regimen, is increasingly being utilized in the neoadjuvant setting for the treatment of these malignancies, with varying degrees of tumor response. Methods: We conducted a retrospective, single-institution review on 75 patients operated on for adenocarcinoma of the esophagogastric junction and stomach after neoadjuvant FLOT. We investigated whether tumor response correlates with disease response in lymph nodes examined on surgical specimens. We also investigated the role of tumor-infiltrating lymphocytes (TILs) in correlation with primary tumor response and disease response in lymph nodes on pathological specimens. Results: Our results suggest that TILs correlate in a differential manner with regards to primary tumors versus lymph nodes, thus suggesting that there are different biologic processes in place. Conclusions: Our results provide unique evidence on tumor-infiltrating lymphocytes in the adenocarcinoma histology of the esophagogastric junction and stomach and might be important for further studies. Full article

Gastric cancer (GC) is one of the most common cancers worldwide. Most patients are diagnosed at the progressive stage of GC, and progress in the development of effective anti-GC drugs has been insufficient. The tumor microenvironment (TME) regulates various functions of tumor cells, and interactions between the cellular and molecular components of the TME—e.g., inflammatory cells, fibroblasts, vasculature cells, and innate and adaptive immune cells—promote the aggressiveness of cancer cells and dissemination to distant organs. This review summarizes the roles of various TME cells and molecules in regulating the malignant progression and metastasis of GC. We also address the important roles of signaling pathways in mediating the interaction between cancer cells and the different components of the GC TME. Finally, we discuss the implications of these molecular mechanisms for developing novel and effective therapies targeting molecular and cellular components of the GC TME to control the malignant progression of GC. Full article

Kinin receptors B1 and B2 are involved in migration and invasion in gastric, glioma, and cervical cancer cells, among others. However, the role of kinin receptors in breast cancer cells has been poorly studied. We aimed to reveal the impact of B1 and B2 receptors on migration and invasion in breast cancer cells and demonstrate their capacity to modulate in vivo tumor growth. MDA-MB-231, MCF-7, and T47D cells treated with Lys-des[Arg⁹]bradykinin (LDBK) or bradykinin (BK) were used to evaluate migration and invasion. Des-[Arg⁹]-Leu⁸-BK and HOE-140 were used as antagonists for the B1 and B2 receptors. MDA-MB-231 cells incubated or not with antagonists were subcutaneously inoculated in BALBc NOD/SCID mice to evaluate tumor growth. LDBK and BK treatment significantly increased migration and invasion in breast cancer cells, effects that were negated when antagonists were used. The use of antagonists in vivo inhibited tumor growth. Moreover, the migration and invasion induced by kinins in breast cancer cells were inhibited when focal adhesion kinase (FAK) and Src inhibitors were used. The novelty revealed in our work is that B1 and B2 receptors activated by LDBK and BK induce migration and invasion in breast cancer cells via a mechanism that involves the FAK–Src signaling pathway, and the antagonism of both receptors in vivo impairs breast tumor growth. Full article

Gastric cancer (GC) presents a significant health challenge and ranks as the fifth most common cancer in the world. Unfortunately, most patients with GC exhaust standard care treatment options due to late diagnosis and tumour heterogeneity that leads to drug resistance, resulting in poor survival outcomes. Potentially, this situation can be improved by personalising treatment choice. Organoids are an emerging cell model system that recapitulates tumour heterogeneity and drug responses. Coupled with genomic analysis, organoid culture can be used to guide personalised medicine. The GC organoid field, however, lacks standardised methodologies for assessing organoid drug sensitivities. Comparing results across different GC organoid studies and correlating organoid drug responses with patient outcomes is challenging. Hence, we aim to summarise the methodologies used in GC organoid drug testing and correlation with clinical outcomes and discuss design considerations and limitations to enhance the robustness of such studies in the future. Full article