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Journal For Immunotherapy of Cancer Jul 2024Tertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric...
BACKGROUND
Tertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric cancers (GCs), however, TLSs are predominantly found in GC with poor prognosis and limited treatment response. We, therefore, hypothesize that immune cell composition and function of TLS depends on tumor location and the tumor immune environment.
METHODS
Spatial transcriptomics and immunohistochemistry were used to characterize the phenotype of CD45 immune cells inside and outside of TLS using archival resection specimens from GC primary tumors and peritoneal metastases.
RESULTS
We identified significant intrapatient and interpatient diversity of the cellular composition and maturation status of TLS in GC. Tumor location (primary vs metastatic site) accounted for the majority of differences in TLS maturity, as TLS in peritoneal metastases were predominantly immature. This was associated with higher levels of tumor-infiltrating macrophages and Tregs and less plasma cells compared with tumors with mature TLS. Furthermore, mature TLSs were characterized by overexpression of antitumor immune pathways such as B cell-related pathways, MHC class II antigen presentation while immature TLS were associated with protumor pathways, including T cell exhaustion and enhancement of DNA repair pathways in the corresponding cancer.
CONCLUSION
The observation that GC-derived peritoneal metastases often contain immature TLS which are associated with immune suppressive regulatory tumor-infiltrating leucocytes, is in keeping with the lack of response to immune checkpoint blockade and the poor prognostic features of peritoneal metastatic GC, which needs to be taken into account when optimizing immunomodulatory strategies for metastatic GC.
Topics: Humans; Stomach Neoplasms; Tertiary Lymphoid Structures; Peritoneal Neoplasms; Male; Female; Tumor Microenvironment
PubMed: 38955417
DOI: 10.1136/jitc-2024-009243 -
Open Biology Jul 2024The enzymatic breakdown and regulation of food passage through the vertebrate antral stomach and pyloric sphincter (antropyloric region) is a trait conserved over 450...
The enzymatic breakdown and regulation of food passage through the vertebrate antral stomach and pyloric sphincter (antropyloric region) is a trait conserved over 450 million years. Development of the structures involved is underpinned by a highly conserved signalling pathway involving the hedgehog, bone morphogenetic protein and Wingless/Int-1 (Wnt) protein families. Monotremes are one of the few vertebrate lineages where acid-based digestion has been lost, and this is consistent with the lack of genes for hydrochloric acid secretion and gastric enzymes in the genomes of the platypus () and short-beaked echidna () . Furthermore, these species feature unique gastric phenotypes, both with truncated and aglandular antral stomachs and the platypus with no pylorus. Here, we explore the genetic underpinning of monotreme gastric phenotypes, investigating genes important in antropyloric development using the newest monotreme genomes (mOrnAna1.pri.v4 and mTacAcu1) together with RNA-seq data. We found that the pathway constituents are generally conserved, but surprisingly, NK3 homeobox 2 () was pseudogenized in both platypus and echidna. We speculate that the unique sequence evolution of and sequences in the echidna lineage may correlate with their pyloric-like restriction and that the convergent loss of gastric acid and stomach size genotypes and phenotypes in teleost and monotreme lineages may be a result of eco-evolutionary dynamics. These findings reflect the effects of gene loss on phenotypic evolution and further elucidate the genetic control of monotreme stomach anatomy and physiology.
Topics: Animals; Stomach; Homeodomain Proteins; Transcription Factors; Platypus; Phylogeny; Evolution, Molecular
PubMed: 38955222
DOI: 10.1098/rsob.240071 -
CEN Case Reports Jul 2024Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy,...
Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy, hyperpigmentation, and diarrhea. While the relationship between CCS and nephritis remains unclear, seven cases of nephritis complicated by CCS have been reported to date, all of which were membranous nephropathy (MN). A 57-year-old man presented with taste disturbance, hair loss, nail plate atrophy, skin pigmentation, and frequent diarrhea. Endoscopic findings showed multiple polyposis of the stomach and large intestine. Given the above, he was diagnosed with CCS. The symptoms gradually improved with prednisolone treatment, although urinary protein and hypoproteinemia appeared during the tapering of prednisolone. He was diagnosed with MN using a renal biopsy, and immunofluorescence microscopy with IgG subclass staining showed predominantly diffuse granular capillary wall staining of IgG4. The cause of secondary MN was not found, including malignant tumors. Nephrotic-range proteinuria persisted despite treatment with prednisolone and cyclosporine. Additional treatment with mizoribine resulted in incomplete remission type 1 of nephrotic syndrome, suggesting that mizoribine may be a treatment option for patients with CCS with steroid-resistant MN. Considering a high prevalence of hypoproteinemia due to chronic diarrhea and protein-losing enteropathy in patients with CCS, proteinuria might be overlooked; thus, follow-up urinalysis would be recommended in patients with CCS.
PubMed: 38954395
DOI: 10.1007/s13730-024-00908-9 -
Frontiers in Pharmacology 2024Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and...
BACKGROUND
Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.
METHODS
We fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.
RESULTS
In OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe's mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.
CONCLUSION
This study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.
PubMed: 38953111
DOI: 10.3389/fphar.2024.1406493 -
Frontiers in Immunology 2024The predominant characteristic of autoimmune gastritis (AIG) is corpus-dominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are...
The predominant characteristic of autoimmune gastritis (AIG) is corpus-dominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are needed on the endoscopic features of the early stage. In this report, we present two cases of early-stage AIG in which endoscopic examinations showed no atrophy of the gastric mucosa but displayed a transition of collecting venules from a regular to an irregular arrangement. In addition, yellowish-white cobblestone-like elevations were observed in the fundic gland region. Histologically, the observed manifestations included pseudohypertrophy and protrusion of parietal cells into the lumen, possibly along with hyperplasia of G cells, lymphocytic infiltration and potentially pseudopyloric gland metaplasia. Serologically, the anti-parietal cell antibody returned positive results, whereas the anti-intrinsic factor antibody yielded negative results. In this study, we summarized some endoscopic features of two patients, aiming to provide clues for endoscopists to detect early-stage AIG.
Topics: Humans; Autoimmune Diseases; Male; Gastritis; Female; Middle Aged; Autoantibodies; Gastric Mucosa; Parietal Cells, Gastric; Gastroscopy; Biopsy; Aged; Adult
PubMed: 38953024
DOI: 10.3389/fimmu.2024.1416292 -
PeerJ 2024Peritoneal metastasis (PM) is the most prevalent type of metastasis in patients with gastric cancer (GC) and has an extremely poor prognosis. The detection of free...
BACKGROUND
Peritoneal metastasis (PM) is the most prevalent type of metastasis in patients with gastric cancer (GC) and has an extremely poor prognosis. The detection of free cancer cells (FCCs) in the peritoneal cavity has been demonstrated to be one of the worst prognostic factors for GC. However, there is a lack of sensitive detection methods for FCCs in the peritoneal cavity. This study aimed to use a new peritoneal lavage fluid cytology examination to detect FCCs in patients with GC, and to explore its clinical significance on diagnosing of occult peritoneal metastasis (OPM) and prognosis.
METHODS
Peritoneal lavage fluid from 50 patients with GC was obtained and processed the isolation by size of epithelial tumor cells (ISET) method. Immunofluorescence and fluorescence hybridization (FISH) were used to identify FCCs expressing chromosome 8 (CEP8), chromosome 17 (CEP17), and epithelial cell adhesion molecule (EpCAM).
RESULTS
Using a combination of the ISET platform and immunofluorescence-FISH, the detection of FCCs was higher than that by light microscopy (24.0% . 2.0%). Samples were categorized into positive and negative groups, based on the expressions of CEP8, CEP17, and EpCAM. Statistically significant relationships were demonstrated between age ( = 0.029), sex ( = 0.002), lymphatic invasion ( = 0.001), pTNM stage ( = 0.001), and positivity for FCCs. After adjusting for covariates, patients with positive FCCs had lower progression-free survival than patients with negative FCCs.
CONCLUSION
The ISET platform highly enriched nucleated cells from peritoneal lavage fluid, and indicators comprising EpCAM, CEP8, and CEP17 confirmed the diagnosis of FCCs. As a potential detection method, it offers an opportunity for early intervention of OPM and an extension of patient survival.
Topics: Humans; Peritoneal Neoplasms; Male; Female; Middle Aged; Stomach Neoplasms; Peritoneal Lavage; In Situ Hybridization, Fluorescence; Aged; Ascitic Fluid; Prognosis; Epithelial Cell Adhesion Molecule; Adult; Cytodiagnosis; Neoplastic Cells, Circulating; Cytology
PubMed: 38952968
DOI: 10.7717/peerj.17602 -
Communications Biology Jun 2024Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to...
Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.
Topics: Animals; Mice, Inbred C57BL; Rickettsia; Mice; Click Chemistry; Stomach; Disease Models, Animal; Spotted Fever Group Rickettsiosis; Female; Rickettsia Infections; Azides
PubMed: 38951577
DOI: 10.1038/s42003-024-06468-z -
Molecular Imaging and Radionuclide... Jun 2024Meckel scintigraphy is used to diagnose Meckel's diverticulum. Previously, premedication with ranitidine was the most frequently used method to increase the accuracy of...
OBJECTIVES
Meckel scintigraphy is used to diagnose Meckel's diverticulum. Previously, premedication with ranitidine was the most frequently used method to increase the accuracy of scintigraphy. However, ranitidine can no longer be used because it is banned by the Food and Drug Administration. The aim of this study was to investigate the usability of pantoprazole as a premedication instead of ranitidine in Meckel scintigraphy.
METHODS
Twelve New Zealand rabbits were used in this experimental study. Rabbits were divided into two groups: pantoprazole and control. Six rabbits were premedicated with pantoprazole for three days. Meckel scintigraphy was performed on all rabbits. Counts were made and compared by drawing regions of interest from the stomach walls.
RESULTS
According to the findings of this experimental study, pantoprazole significantly increased Tc-99m-pertechnetate uptake in the stomach of rabbits on both visual and quantitative evaluation.
CONCLUSION
Pantoprazole increases the gastric wall uptake of Tc-99m-pertechnetate in rabbits and is a potential drug for premedication in Meckel scintigraphy.
PubMed: 38949418
DOI: 10.4274/mirt.galenos.2024.48254 -
PeerJ 2024Gastric cancer (GC), one of the highest venous thromboembolism (VTE) incidence rates in cancer, contributes to considerable morbidity, mortality, and, prominently, extra...
OBJECTIVE
Gastric cancer (GC), one of the highest venous thromboembolism (VTE) incidence rates in cancer, contributes to considerable morbidity, mortality, and, prominently, extra cost. However, up to now, there is not a high-quality VTE model to steadily predict the risk for VTE in China. Consequently, setting up a prediction model to predict the VTE risk is imperative.
METHODS
Data from 3,092 patients from December 15, 2017, to December 31, 2022, were retrospectively analyzed. Multiple logistic regression analysis was performed to assess risk factors for GC, and a nomogram was constructed based on screened risk factors. A receiver operating curve (ROC) and calibration plot was created to evaluate the accuracy of the nomogram.
RESULTS
The risk factors of suffering from VTE were older age (OR = 1.02, 95% CI [1.00-1.04]), Karnofsky Performance Status (KPS) ≥ 70 (OR = 0.45, 95% CI [0.25-0.83]), Blood transfusion (OR = 2.37, 95% CI [1.47-3.84]), advanced clinical stage (OR = 3.98, 95% CI [1.59-9.99]), central venous catheterization (CVC) (OR = 4.27, 95% CI [2.03-8.99]), operation (OR = 2.72, 95% CI [1.55-4.77]), fibrinogen degradation product (FDP) >5 µg/mL (OR = 1.92, 95% CI [1.13-3.25]), and D-dimer > 0.5 mg/L (OR = 2.50, 95% CI [1.19-5.28]). The area under the ROC curve (AUC) was 0.82 in the training set and 0.85 in the validation set.
CONCLUSION
Our prediction model can accurately predict the risk of the appearance of VTE in gastric cancer patients and can be used as a robust and efficient tool for evaluating the possibility of VTE.
Topics: Humans; Nomograms; Venous Thromboembolism; Stomach Neoplasms; Retrospective Studies; Male; Female; Middle Aged; Risk Factors; Aged; China; Risk Assessment; ROC Curve; Fibrin Fibrinogen Degradation Products; Adult
PubMed: 38948205
DOI: 10.7717/peerj.17527 -
Trauma Case Reports Aug 2024A 6-year-old male child was admitted to the hospital because of abdominal trauma and acute stomach pain. Computed tomography scan revealed a jejunal mesenteric hematoma...
A 6-year-old male child was admitted to the hospital because of abdominal trauma and acute stomach pain. Computed tomography scan revealed a jejunal mesenteric hematoma and an enhanced intestinal wall compressed by the hematoma. The patient presented with vomiting 10 days after the injury. He underwent upper endoscopy under tracheal intubation and general anesthesia 12 days after the injury. A double elementary diet tube was inserted endoscopically with the tip placed in the jejunum beyond the stenosis and the decompressed portion of the stomach. Stenosis was improving, and the patient was discharged on the 27th day after the injury. In conclusion, a double elementary diet tube can be effective for treating posttraumatic duodenal stenosis in pediatric patients.
PubMed: 38948103
DOI: 10.1016/j.tcr.2024.101060