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1.
Cancer Sci ; 114(12): 4596-4606, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37798255

RESUMO

Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.


Assuntos
Polipose Adenomatosa do Colo , Fibromatose Agressiva , Neoplasias Gástricas , Humanos , Genes APC , Fibromatose Agressiva/genética , Genótipo , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Fenótipo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Estudos de Associação Genética , Mutação
2.
Acta Med Okayama ; 77(5): 545-552, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37899266

RESUMO

To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant.


Assuntos
Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Gastropatias , Masculino , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Estudos Retrospectivos , Amiloidose/diagnóstico , Amiloidose/patologia , Gastropatias/diagnóstico , Gastropatias/patologia
3.
BMC Complement Altern Med ; 19(1): 205, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391093

RESUMO

BACKGROUND: Gastric ulcer is one of the most prevalent diseases worldwide. In Iranian folk medicine, Achillea wilhelmsii (AW) is used as a treatment for gastric ulcer. Previous reports also mentioned Antiulcerogenic properties for this herbal plant. This study investigated the therapeutic effects of Achillea wilhelmsii C. Koch extract on indomethacin-induced gastric lesion in rats, from both proteomic and metabolomic perspectives. METHODS: The rats were divided into 4 groups. Gastric ulceration was induced by a single dose of indomethacin (45 mg/kg) by oral gavage. An amount of 800 mg/kg of AW extract was administered orally. Serum and tissue samples were collected for further investigations. The metabolomic study was performed by 1H-NMR CPMG spectrometry. Proteomic analysis was also executed by using two dimensional gel electrophoresis (2DE) followed by liquid chromatography coupled to tandem mass spectrometry (LC-ESI/MS/MS). Real time PCR was used to confirm some of the genes. RESULTS: The macroscopic and microscopic investigations confirmed the effectiveness of the AW extract. There was a panel of metabolites which showed alteration during gastric lesion development. The levels of some of these metabolite reversed nearly to their control values after the administration of AW extract. There were also changes in the levels of some proteins including Alb, Fabp5, Hspb1, Tagln, Lgals7, Csta and Myl9 which were reversed after AW administration. CONCLUSIONS: Our findings suggested that Achillea wilhelmsii C. Koch extract could be a potential therapy to be used for indomethacin-induced gastric lesion treatment in the future. However, further investigations are needed to confirm the results.


Assuntos
Achillea/química , Antiulcerosos/administração & dosagem , Extratos Vegetais/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/isolamento & purificação , Humanos , Indometacina/efeitos adversos , Masculino , Metabolômica , Extratos Vegetais/isolamento & purificação , Proteômica , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo
4.
Molecules ; 23(1)2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29315228

RESUMO

Ximenia americana L. (Olacaceae) is used in ethnomedicine as cicatrizant and for the treatment of gastric disorders. This study identified the chemical constituents of the aqueous extract of X. americana (XaAE) and evaluated its antiulcerogenic activity. After lyophilization, XaAE was analyzed by liquid chromatography-mass spectrometry (LC-MS) and its antiulcerogenic effect was evaluated in acute gastric lesions induced by ethanol, acidified ethanol, and indomethacin. Antisecretory action, mucus production and the participation of sulfhydryl groups (-SH) and nitric oxide (NO) were also investigated. The chromatographic analysis identified procyanidins B and C and catechin/epicatechin as major compounds. Oral administration of XaAE (100, 200 and 400 mg/kg) inhibited the gastric lesions induced by ethanol (76.1%, 77.5% and 100%, respectively), acidified ethanol (44.9%, 80.6% and 94.9%, respectively) and indomethacin (56.4%, 52.7% and 64.9%, respectively). XaAE reduced gastric contents and acidity (51.4% and 67.7%, respectively) but did not alter the production of gastric mucus. The reduction of the -SH and NO groups promoted by N-ethylmaleimide (NEM) and Nω-nitro-l-arginine-methyl-ester (L-NAME) respectively, reduced the gastroprotective effect of XaAE. In conclusion, XaAE has gastroprotective activity mediated in part by -SH, NO and antisecretory activity. This antiulcer action was initially correlated to its major constituents, procyanidins B and C and catechin/epicatechin.


Assuntos
Gastroenteropatias/prevenção & controle , Olacaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Metabolismo Secundário , Animais , Arginina/análogos & derivados , Arginina/química , Catequina/química , Catequina/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Etanol/química , Gastroenteropatias/induzido quimicamente , Indometacina/química , Espectrometria de Massas/métodos , Camundongos , Fitoterapia/métodos , Extratos Vegetais/isolamento & purificação , Proantocianidinas/química , Proantocianidinas/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Água
5.
Clin Gastroenterol Hepatol ; 14(10): 1420-5, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27317852

RESUMO

BACKGROUND & AIMS: Gastric intestinal metaplasia (GIM) is a common finding from routine endoscopies. Although GIM is an early step in gastric carcinogenesis, there is controversy regarding routine surveillance of patients with GIM in regions with a low prevalence of gastric cancer. We aimed to determine the incidence of gastric cancer among patients with GIM and risk factors for gastric cancer. METHODS: We performed a retrospective cohort study of patients from the Kaiser Permanente Southern California region diagnosed with GIM from 2000 through 2011. GIM was identified by a keyword search of pathology reports; gastric cancer cases were identified by cross-reference with an internal cancer registry. The incidence of gastric cancer in patients with GIM (n = 923; median age at diagnosis, 68 y) was compared with that of an age- and sex-matched reference population (controls). Risk factors such as ethnicity, smoking status, history of Helicobacter pylori infection, and family history of gastric cancer were evaluated by individual Cox proportional hazards regression. We then performed a second case-cohort study to evaluate the risk of gastric cancer based on the location and extent of GIM. The median duration of follow-up evaluation was 4.6 years (interquartile range, 3.0-6.7 y). RESULTS: We identified 25 patients with GIM who developed gastric cancers. Seventeen cases of cancer were diagnosed at the same time as the diagnosis of GIM. Eight cases of cancer were identified within a median time period of 4.6 years after a diagnosis of GIM (interquartile range, 2-5.7 y). The overall incidence rate for the cohort was 1.72 (95% confidence interval, 0.74-3.39). Among the risk factors evaluated, only family history (hazard ratio, 3.8; 95% confidence interval, 1.5-9.7; P = .012) and extent of GIM (odds ratio, 9.4; 95% confidence interval, 1.8-50.4) increased the risk for gastric cancer. The incidence rate for gastric cancer in patients with a positive family history was 8.12 (95% confidence interval, 1.67-23.73). CONCLUSIONS: In an analysis of patients with GIM listed in the Kaiser Permanente Southern California database, 2.7% were diagnosed with gastric cancer; almost 70% of cases of gastric cancer were detected at the time of GIM diagnosis. Family history and extensive metaplasia were associated with an increased risk of subsequent gastric cancer. Targeted surveillance of patients with these criteria could increase early detection of gastric cancer.


Assuntos
Neoplasias Gástricas/epidemiologia , Estômago/patologia , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Prestação Integrada de Cuidados de Saúde , Feminino , Helicobacter pylori , Humanos , Incidência , Estudos Longitudinais , Masculino , Metaplasia/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
6.
Cir Esp ; 94(3): 175-8, 2016 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26711539

RESUMO

Gastric mucosal and submucosal lesions can be resected by endoscopy, laparoscopy or open surgery. Operative methods have varied depending on the location, endophytic growth and size of the lesion. Interest in minimally invasive surgery has increased and many surgeons are attempting laparoscopic approaches, especially in lesions of the stomach near the esophagogastric junction not amendable to endoscopic removal, because conventional surgery can produce stenosis and distort the postoperative anatomy, and increase morbimortality. We report our experience with laparoscopic intragastric surgery in 3 consecutive patients, with no complications. Laparoscopic intragastric surgery extends the surgeons' armamentarium to resect complex gastric lesions, while offering patients the benefits of minimal access surgery.


Assuntos
Laparoscopia , Junção Esofagogástrica , Mucosa Gástrica , Gastroscopia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Gástricas
7.
Pharm Biol ; 52(12): 1591-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25026358

RESUMO

CONTEXT: Many scientific reports have shown the involvement of oxidative stress and inflammation as well as diminished gastroprotective substances in the pathogenesis of gastric lesions using various models. Therefore, treatment with antioxidants like tocopherol and tocotrienol may afford beneficial effects in attentuating the formation of the gastric lesions. OBJECTIVE: The aim of this work was to summarize documented reports on the effects of vitamin E on various models of gastric lesion. METHODS: A literature search was performed from databases in Medline (PubMed), Web of Science, ScienceDirect, and Googlescholar from June to December 2013. RESULTS AND CONCLUSION: The potential roles of tocopherol and tocotrienol in modifying the effects of ulcerogenic agents are discussed in this review. The protective effects of the vitamin E might involve ameliorating oxidative stress and inflammation as well as restoration of endogenous gastroprotective substances. This vitamin has the potential to be used as a therapy for gastric mucosal injury.


Assuntos
Mucosa Gástrica/efeitos dos fármacos , Tocoferóis/farmacologia , Tocotrienóis/farmacologia , Animais , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Mucosa Gástrica/patologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Estresse Oxidativo/efeitos dos fármacos , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle
8.
Am J Physiol Gastrointest Liver Physiol ; 304(9): G814-22, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23494120

RESUMO

Gastric mucosal health is maintained in response to potentially damaging luminal factors. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt protective mechanisms leading to bleeding and ulceration. The plasminogen activator system has been implicated in fibrinolysis following gastric ulceration, and an inhibitor of this system, plasminogen activator inhibitor (PAI)-1, is expressed in gastric epithelial cells. In Helicobacter pylori-negative patients with normal gastric histology taking aspirin or NSAIDs, we found elevated gastric PAI-1 mRNA abundance compared with controls; the increase in patients on aspirin was independent of whether they were also taking proton pump inhibitors. In the same patients, aspirin tended to lower urokinase plasminogen activator mRNA. Immunohistochemistry indicated PAI-1 localization to epithelial cells. In a model system using MKN45 or AGS-GR cells transfected with a PAI-1 promoter-luciferase reporter construct, we found no evidence for upregulation of PAI-1 expression by indomethacin, and, in fact, cyclooxygenase products such as PGE2 and PGI2 weakly stimulated expression. Increased gastric PAI-1 mRNA was also found in mice following gavage with ethanol or indomethacin, but plasma PAI-1 was unaffected. In PAI-1(-/-) mice, gastric hemorrhagic lesions in response to ethanol or indomethacin were increased compared with C57BL/6 mice. In contrast, in PAI-1-H/Kß mice in which PAI-1 is overexpressed in parietal cells, there were decreased lesions in response to ethanol and indomethacin. Thus, PAI-1 expression is increased in gastric epithelial cells in response to mucosal irritants such as aspirin and NSAIDs probably via an indirect mechanism, and PAI-1 acts as a local autoregulator to minimize mucosal damage.


Assuntos
Mucosa Gástrica/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/fisiologia , Animais , Aspirina/farmacologia , Dinoprostona , Etanol/toxicidade , Feminino , Humanos , Indometacina/toxicidade , Masculino , Camundongos , Inibidor 1 de Ativador de Plasminogênio/biossíntese , RNA Mensageiro/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/biossíntese
9.
J Ethnopharmacol ; 305: 116057, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36574790

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia coriaria (Jacq.) Willd is widely used as a traditional medinal plant in Mexico for protective and healing purposes and the treatment of gastrointestinal diseases. AIM OF THE STUDY: To investigate the gastroprotective effect of extract of Caesalpinia coriaria pods against ethanol-induced and indomethacin-induced gastric lesion models, its anti-inflammatory and antioxidative activities, and its main compounds through LC-MS analysis. MATERIALS AND METHODS: Male Wistar rats were orally administered a methanol extract obtained from the pods of C. coriaria at doses of 10, 30, 100, and 300 mg/kg prior to inducing gastric lesions with ethanol or indomethacin. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations. Determination of prostaglandin E2 (PGE2), alpha tumor necrosis factor (TNF-α), leukotriene B4 (LTB4), nitrites/nitrates, superoxide dismutase (SOD), and H2S gastric levels were investigated. Its main compounds of the active extract through LC-MS analysis. RESULTS: Phenolic compounds were identified as major components of methanol extract. LC-MS analysis identified 15 constituents, and the significant compounds were gallic acid, 3-O-galloylquinic acid, digalloylglucose, tetragalloylglucose, valoneic acid dilactone, pentagalloylglucose, digalloylshikimic acid, and ellagic acid. Pretreatment with the extract at doses of 100 and 300 mg/kg significantly reduced gastric ulcer lesions in both models. Compared with the reference drugs (omeprazole or ranitidine, respectively), no significant difference was found (p < 0.05). The extract's gastroprotective effect was accompanied by significant decreases in leukocyte recruitment, and gastric levels of TNF-α and LTB4 by two to fourfold (p < 0.05). Also, gastric levels of PGE2 gastric levels were maintained and the antioxidant enzyme activities of SOD and nitrate/nitrite in the gastric tissue were improved (p < 0.05). The LC-MS analysis indicated the presence of hydrolyzable tannins (mainly gallic acid derivatives). CONCLUSION: The results suggest that the gastroprotective effect of the methanol extract of C. coriaria pods occurs through anti-inflammatory, antioxidant, and NO modulation properties, and gallic acid derivatives may be the main possible compounds responsible for its actions.


Assuntos
Antiulcerosos , Caesalpinia , Magnoliopsida , Úlcera Gástrica , Ratos , Animais , Indometacina , Metanol/uso terapêutico , Ratos Wistar , Etanol/uso terapêutico , Antioxidantes/uso terapêutico , Extratos Vegetais/efeitos adversos , Fitoterapia , Fator de Necrose Tumoral alfa , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Ácido Gálico/uso terapêutico , Superóxido Dismutase , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico
10.
J Clin Med ; 12(17)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37685504

RESUMO

OBJECTIVES: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. METHODS: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. RESULTS: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and an irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogen+ously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HPs and PPI-Ls were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). CONCLUSION: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

11.
EBioMedicine ; 86: 104340, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36356476

RESUMO

BACKGROUND: Early detection of gastric cancer (GC) remains challenging. We aimed to examine urine proteomic signatures and identify protein biomarkers that predict the progression of gastric lesions and risk of GC. METHODS: A case-control study was initially designed, covering subjects with GC and gastric lesions of different stages. Subjects were aged 40-69 years, without prior diagnosis of renal or urological diseases. We enrolled a total of 255 subjects, with 123 in the discovery stage from Linqu, China, a high-risk area for GC and 132 in the validation stage from Linqu and Beijing. A prospective study was further designed for a subset of 60 subjects with gastric lesions, which were followed for 297-857 days. FINDINGS: We identified 43 differentially expressed urine proteins in subjects with GC vs. mild or advanced gastric lesions. Baseline urinary levels of ANXA11, CDC42, NAPA and SLC25A4 were further positively associated with risk of gastric lesion progression. Three of them, except for SLC25A4, also had higher expression in GC than non-GC tissues. Integrating these four proteins showed outstanding performance in predicting the progression of gastric lesions (AUC (95% CI): 0.92 (0.83-1.00)) and risk of GC (AUC (95% CI): 0.81 (0.73-0.89) and 0.84 (0.77-0.92) for GC vs. mild or advanced gastric lesions respectively). INTERPRETATION: This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of GC. These biomarkers in a non-invasive approach may have translational significance for defining high-risk populations of GC and its early detection. FUNDING: Funders are listed in the Acknowledgement.


Assuntos
Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Proteômica , Estudos de Casos e Controles , Estudos Prospectivos , Detecção Precoce de Câncer , Biomarcadores , Biomarcadores Tumorais
12.
Pharmaceutics ; 14(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35335941

RESUMO

Peptic ulcers are lesions that affect the gastrointestinal tract and that can be triggered by external factors such as alcohol use. This study investigated the gastroprotective role of two anthocyanidins, malvidin and cyanidin chloride, in an ethanol-induced gastric ulcer model in male and female mice (ovariectomized and supplemented with 17ß-estradiol or not) and aimed to evaluate the effectiveness of anthocyanidins in preventing the formation of lesions and to identify the underlying mechanisms, while considering hormonal differences. Moreover, in silico comparative analysis was performed to predict the properties and biological behaviors of the molecules. We observed that the hormonal status did not interfere with the gastroprotective action of malvidin, although antioxidant mechanisms were modulated differently depending on sex. On the other hand, cyanidin showed gastroprotective activity at different doses, demonstrating that, for the same experimental model, there is a need to adjust the effective dose depending on sex. In silico analysis showed that, despite being structurally similar, the interaction with receptors and target proteins in this study (myeloperoxidase, superoxide dismutase, catalase, and reduced glutathione) differed between the two molecules, which explains the difference observed in in vivo treatments.

13.
Theranostics ; 12(10): 4671-4683, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832080

RESUMO

Rationale: Gastric cancer (GC) is preceded by a stepwise progression of precancerous gastric lesions. Distinguishing individuals with precancerous gastric lesions that have progression potential to GC is an important need. Perturbated lipid metabolism, particularly the dysregulation of de novo lipogenesis, is involved in gastric carcinogenesis. We conducted the first prospective lipidomics study exploring lipidomic signatures for the risk of gastric lesion progression and early GC. Methods: Our two-stage study of targeted lipidomics enrolled 400 subjects from the National Upper Gastrointestinal Cancer Early Detection Program in China, including 200 subjects of GC and different gastric lesions in the discovery and validation stages. Of validation stage, 152 cases with gastric lesions were prospectively followed for the progression of gastric lesions for a median follow-up of 580 days (interquartile range 390-806 days). We examined the lipidomic signatures associated with the risk of advanced gastric lesions and their progression to GC. Our published tissue proteomic data were referred to further investigate highlighted lipids with their biologically related protein expression in gastric mucosa. Results: We identified 11 plasma lipids significantly inversely associated with the risk of gastric lesion progression and GC occurrence. These lipids were integrated as latent profiles to identify 5 clusters of lipid expression that had distinct risk of gastric lesion progression. The latent profiles significantly improved the ability to predict the progression potential of gastric lesions (AUC: 0.82 vs 0.68, Delong's P = 4.6×10-4) and risk of early GC (AUC: 0.81 vs 0.55, P = 6.3×10-5). Significant associations were found between highlighted lipids, their biologically correlated proteins and the risk of GC, supporting the role of the pathways involving monocarboxylic acid metabolism and lipid transport and catabolic process in GC. Conclusions: Our study revealed the lipidomic signatures associated with the risk of gastric lesion progression and GC occurrence, exhibiting translational implications for GC prevention.


Assuntos
Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Lipidômica , Lipídeos , Estudos Prospectivos , Proteômica , Neoplasias Gástricas/patologia
14.
Clin J Gastroenterol ; 15(3): 560-567, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35294725

RESUMO

Gastric duplication cysts are rare congenital malformation with a potential neoplastic progression and they may represent a challenge in differential diagnosis with exophytic pancreatic cyst neoplasm. We describe a case of a 38-year old man, complaining of recurrent epigastric pain due to a large abdominal mass, referred to our Hospital for EUS evaluation. Differential diagnosis was between gastric duplication cyst and exophytic pancreatic cyst because of FNA pointed out amylase 1280 UI/L and CEA 593.33 ng/mL. Despite antibiotic prophylaxis, an overinfection of the lesion occurred after the FNA, likely due to the technical failure to drain the cyst completely. Afterwards, the patient was referred to surgery and the pathologist confirmed the diagnosis of gastric duplication cyst. In this setting, EUS procedure has gained a leading play, complementary to traditional imaging tests, although its role has been not yet standardized in the reported literature. Here, we describe and discuss our demanding case, and we propose an algorithm to simplify and standardize the diagnostic workup.


Assuntos
Cisto Pancreático , Neoplasias Pancreáticas , Gastropatias , Adulto , Diagnóstico Diferencial , Endossonografia , Humanos , Masculino , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Gastropatias/diagnóstico por imagem
15.
Arch Iran Med ; 25(6): 394-398, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35943019

RESUMO

BACKGROUND: The Sydney system offers a standard biopsy protocol for detection and follow-up of gastric preneoplastic lesions such as intestinal metaplasia (IM). The highest frequency of cardia-type gastric adenocarcinoma (GA) in Iran has been documented in the north-western part of the country. This study aims to investigate the effect of the addition of mucosal biopsies of gastric cardia to the standard Sydney protocol on the rate of detection of IM in the asymptomatic residents of this high-risk region for proximal gastric cancer. METHODS: A retrospective new analysis was performed on the previous data obtained in cross-sectional endoscopic screening in 2000 as well as a biopsy study of 508 asymptomatic volunteer residents in Meshkinshahr district, Ardabil province. The screening study was conducted in a group of residents aged 40 years and older who did not have any previous GI or hemodynamic problems. RESULTS: Intestinal metaplasia at the Sydney protocol sampling sites was detected in 107 samples belonging to 76 of the 508 (14.99%) volunteers. Twenty-one patients had IM at the cardia. Of these, five patients had IM-cardia (IM only at the cardia). Therefore, adding a cardia biopsy to the set of biopsies diagnosed five more IM cases which were not diagnosed on the standard Sydney protocol (P=0.062). CONCLUSION: The addition of a biopsy from the cardia to the Sydney protocol biopsy set does not seem to improve the frequency of detection of IM in the residents of this high-risk geographic area for proximal gastric carcinoma.


Assuntos
Adenocarcinoma , Lesões Pré-Cancerosas , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Biópsia , Cárdia/patologia , Estudos Transversais , Humanos , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
16.
Pharmaceuticals (Basel) ; 15(7)2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35890153

RESUMO

The aim of this study was to improve the solubility and prevent the ulcerogenic effect of flurbiprofen. Initially, binary and ternary solid dispersions (BSDs and TSDs) of flurbiprofen were prepared by using non-ordered mesoporous silica and gelucire. After preformulation testing (solubility, flow properties, % yield, and entrapment efficiency), four formulations were selected for further detailed studies. Solid-state characterization of optimized formulations (S1, S6, S7, and S12) showed successful drug incorporation in the solid dispersion at the molecular state without any noticeable interactions. The in vitro solubility and release study showed an increase in solubility and 98-100% of drug release in 30-45 min. The in vivo gastro-protective effect of the optimized formulations containing flurbiprofen and silica (1:1) with 25% w/w gelucire (S6 and S12) showed a reduction in the gastric lesion index (GLI) after four days of treatment. Moreover, histological images of the stomach lining (S6 and S12) illustrated normal epithelial cells and a partially protected mucosal membrane. Thus, TSD exhibited a significant increase in solubility and the dissolution rate and reduced the gastric ulceration. Therefore, TSDs are dubbed as efficacious carriers to enhance the bioavailability of flurbiprofen while simultaneously reducing its side effects.

17.
Physiol Rep ; 9(7): e14822, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33818003

RESUMO

The present study investigated the effects of Shilajit extract on aspirin-induced gastric lesions in rats. We evaluated macroscopic and histopathological lesions in the stomach, measured the activity of oxidative stress enzymes in gastric tissue homogenates, and assessed serum electrolytes and parameters of kidney and liver function. Forty-five male rats were allocated to five groups: Normal control, positive control, omeprazole treatment, Shilajit treatment, and Shilajit control. The treatment period lasted for four consecutive days. The size and number of gastric lesions were significantly reduced in the Shilajit and omeprazole groups compared to the positive control group, indicating a reduction in mucosal damage and the severity of edema and leukocyte infiltration in tissue sections. A significant increase was observed in the levels of all oxidative stress parameters, except malondialdehyde, in rats treated with Shilajit and omeprazole compared to those in the positive control group. The effect of the aqueous extract of Shilajit was comparable to that of omeprazole. These results indicated the protective effects of Shilajit against aspirin-induced gastric lesions.


Assuntos
Antioxidantes/uso terapêutico , Minerais/uso terapêutico , Úlcera Péptica/tratamento farmacológico , Resinas Vegetais/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Aspirina/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Minerais/administração & dosagem , Minerais/farmacologia , Omeprazol/administração & dosagem , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Estresse Oxidativo , Úlcera Péptica/etiologia , Ratos , Ratos Wistar , Resinas Vegetais/administração & dosagem , Resinas Vegetais/farmacologia
18.
Ann Med ; 53(1): 1696-1708, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34555996

RESUMO

BACKGROUND AND AIM: The fruit of Garcinia is a rich and valuable source of bioactive compounds and is traditionally used for treating wounds and ulcers. The present study was carried out to investigate the protective effect of chromatographically standardized fruit extract of Garcinia cowa (GCE) on ethanol-induced gastric lesions in rats and its possible mechanisms. METHODS: The effect of GCE (200 and 400 mg/kg body weight) was evaluated by determining various gastric ulcer parameters like gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant enzyme, and gastric histopathological study. RESULTS AND CONCLUSIONS: Oral administration of GCE at doses of 200 and 400 mg/kg exhibited significant (p < .01) dose-dependent inhibition of ulcer index by 18.94-44.02%, respectively. Pre-treatment of rats with GCE (400 mg/kg) significantly restored the depleted gastric wall mucus level by 34.09% and NP-SH content by 33.35% induced by ethanol administration. In addition, GCE (400 mg/kg) showed a significant decrease in microvascular permeability of Evans Blue by 47.43%, rationalizing its protective effect. Furthermore, a significant increase in oxidative enzyme levels with reduction in malondialdehyde level and elevation of superoxide dismutase (SOD) activity was observed in the GCE treated group as compared to the ulcer control group. The histopathological assessment also confirmed the protective nature of GCE. HPTLC analysis showed the presence of 0.27%, 0.11% w/w gallic acid, and amentoflavone, respectively in GCE. The content of α-mangostin and xanthochymol in the G. cowa extract sample quantified by HPLC-PDA method was 0.72 and 8.46%, respectively. The results obtained indicate that the protective effect of GCE against gastric ulcers in rats through multiple actions confirmed by the reduction of oxidative stress and restoration of adhered gastric mucus, NP-SH content, and histological architecture.KEY MESSAGESEthanol is the most typical ulcerogenic agent and has been shown to extend the risk of ulcer in humans.Natural products are promising alternative medication for the development of new drugs to regulate gastrointestinal diseases.Garcinia cowa protects the gastric mucosa through multiple actions that include restoration of adhered gastric mucus and inhibition of lipid peroxidation.


Assuntos
Antiulcerosos/farmacologia , Garcinia/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/uso terapêutico , Etanol/química , Frutas , Humanos , Malondialdeído/sangue , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo
19.
J Dig Dis ; 22(11): 656-662, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34693636

RESUMO

OBJECTIVE: We aimed to establish a standardized procedure for white light gastroscopy (WLG) to screen gastric lesions including early gastric cancer (EGC) in China and to verify its efficacy and feasibility in clinical practice. METHODS: A standardized WLG procedure for outpatients at nine tertiary hospitals in Beijing was established. Clinical information of the participants and details of the endoscopic procedures were recorded. RESULTS: A total of 1051 participants were enrolled in a baseline conventional endoscopic survey between March 2014 and December 2015, while 2156 patients were enrolled in the standardized WLG operation from January 2016 to June 2017. The procedure time of the standardized procedure was significantly longer than that of the baseline conventional procedure (P = 0.003). More images were obtained during the standardized procedure compared with the baseline conventional procedure (P < 0.001). The overall detection rate of gastric lesions in the standardized procedure group was significantly higher than that in the baseline procedure group (52.5% vs 38.4%, P < 0.01). The satisfaction scores of both participants and endoscopists in the standardized procedure group were significantly higher than in the baseline procedure group. CONCLUSIONS: Compared with the conventional procedure, standardized WLG procedure significantly improves the detection rate of gastric lesions as well as the satisfaction score of participants and endoscopists despite its longer procedure time. It is effective and feasible in clinical practice in China for the use of currently available endoscopic equipment.


Assuntos
Gastroscopia , Neoplasias Gástricas , China , Detecção Precoce de Câncer , Estudos de Viabilidade , Humanos , Neoplasias Gástricas/diagnóstico
20.
NanoImpact ; 24: 100355, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-35559814

RESUMO

The use of bisphosphonates constitutes the gold-standard therapy for the control and treatment of bone diseases. However, its long-term use may lead to gastric problems, which limits the treatment. Thus, this study aimed to formulate a nanostructured system with biodegradable polymers for the controlled release of alendronate sodium. The nanoparticles were characterized, and its gastric toxicity was investigated in rats. The synthesis process proved to be effective for encapsulating alendronate sodium, exhibiting nanoparticles with an average size of 51.02 nm and 98.5% of alendronate sodium incorporation. The release tests demonstrated a controlled release of the drug in 420 min, while the morphological analyzes showed spherical shapes and no apparent roughness. The biological tests demonstrated that the alendronate sodium nanoformulation reversed the gastric lesions, maintaining the normal levels of malondialdehyde and myeloperoxidase. Also, the encapsulated alendronate sodium showed no toxicity in murine osteoblastic cells, even at high concentrations.


Assuntos
Alendronato , Nanopartículas , Alendronato/toxicidade , Animais , Preparações de Ação Retardada/farmacologia , Mucosa Gástrica , Camundongos , Nanopartículas/toxicidade , Polímeros/farmacologia , Ratos
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