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2.
Anticancer Res ; 41(7): 3349-3361, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230131

RESUMO

BACKGROUND/AIM: The present study investigated the oncogenic functions of TACC3 in the progression of gastric cancer (GC). MATERIALS AND METHODS: We analysed TACC3 in relation to cell growth, invasion capability, expression of epithelial-mesenchymal transition (EMT)-related markers, and ERK/Akt/cyclin D1 signaling factors. The correlation between the immunohistochemically confirmed expression of TACC3 and clinical factors was also analyzed. RESULTS: The increased proliferation and invasion of TACC3-over-expressing GC cells was accompanied by altered regulation of EMT-associated markers and activation of ERK/Akt/cyclin D1 signaling. Immunohistochemical analysis of TACC3 in human GC tissues revealed that its expression is correlated with aggressive characteristics and poor prognosis of intestinal-type GC. CONCLUSION: TACC3 contributes to gastric tumorigenesis by promoting EMT via the ERK/Akt/cyclin D1 signaling pathway. The correlation between TACC3 expression and multiple clinicopathological variables implies that its effective therapeutic targeting in GC will depend on the tumor subtype.


Assuntos
Carcinogênese/genética , Ciclina D1/genética , Transição Epitelial-Mesenquimal/genética , Sistema de Sinalização das MAP Quinases/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Transdução de Sinais/genética , Estômago/patologia , Neoplasias Gástricas/patologia
3.
Anticancer Res ; 41(7): 3523-3534, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230148

RESUMO

BACKGROUND: The aim of this study was the analysis of the influence of prognostic factors on short- and long-term outcomes of gastric cancer resection. PATIENTS AND METHODS: A database of 709 patients who had gastric cancer resection between 2007 and 2015 was compiled. RESULTS: Total gastrectomy (TG) and subtotal proximal gastrectomy (SPG) significantly increased the risk of overall complications (p=0.0015 and 0.0173, respectively) and surgical complications (p=0.0141 and 0.0035, respectively). Moreover the resection of an additional organ was an independent prognostic factor of overall complications (p<0.0001), systemic complications (p=0.0503), surgical complications (p<0.0001) and relaparotomy (p=0.0259). T stage (p<0.0001), N stage (p<0.0001), M stage (p<0.0001) and radical resection (p<0.0001) significantly affected 5-year survival rates. CONCLUSION: Early diagnosis and radical resection was crucial in 5-year survival rates. However, the type of gastrectomy and the resection of an additional organ were the most important factors in short-term outcomes of treatment for such patients.


Assuntos
Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Idoso , Feminino , Gastrectomia/métodos , Humanos , Masculino , Estadiamento de Neoplasias/métodos , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/patologia , Prognóstico , Estudos Retrospectivos , Estômago/patologia , Taxa de Sobrevida , Resultado do Tratamento
4.
Anticancer Res ; 41(7): 3583-3588, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230154

RESUMO

BACKGROUND/AIM: This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated. RESULTS: No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049). CONCLUSION: PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.


Assuntos
Fosfolipases A2 do Grupo II/metabolismo , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Tegafur/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante/métodos , Combinação de Medicamentos , Feminino , Gastrectomia/métodos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Masculino , Estadiamento de Neoplasias/métodos , Prognóstico , RNA Mensageiro/metabolismo , Estômago/efeitos dos fármacos , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
5.
Lancet Digit Health ; 3(6): e371-e382, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34045003

RESUMO

BACKGROUND: The tumour stroma microenvironment plays an important part in disease progression and its composition can influence treatment response and outcomes. Histological evaluation of tumour stroma is limited by access to tissue, spatial heterogeneity, and temporal evolution. We aimed to develop a radiological signature for non-invasive assessment of tumour stroma and treatment outcomes. METHODS: In this multicentre, retrospective study, we analysed CT images and outcome data of 2209 patients with resected gastric cancer from five independent cohorts recruited from two centres (Nanfang Hospital of Southern Medical University [Guangzhou, China] and Sun Yat-sen University Cancer Center [Guangzhou, China]). Patients with histologically confirmed gastric cancer, at least 15 lymph nodes harvested, preoperative abdominal CT available, and complete clinicopathological and follow-up data were eligible for inclusion. Tumour tissue was collected for patients in the training cohort (321 patients), internal validation cohort one (246 patients), and external validation cohort one (128 patients). Four stroma classes were defined according to the protein expression of α-smooth muscle actin and periostin assessed by immunohistochemistry. The primary objective was to predict the histologically based stroma classes by using preoperative CT images. We trained a deep convolutional neural network model using the training cohort and tested the model in the internal and external validation cohort one. We evaluated the model's association with prognosis in the training cohort, two internal, and two external validation cohorts and compared outcomes of patients who received or did not receive adjuvant chemotherapy. FINDINGS: The deep-learning model achieved a high diagnostic accuracy for assessing tumour stroma in both internal validation cohort one (area under the receiver operating characteristic curve [AUC] 0·96-0·98]) and external validation cohort one (AUC 0·89-0·94). The stromal imaging signature was significantly associated with disease-free survival and overall survival in all cohorts (p<0·0001). The predicted stroma classes remained an independent prognostic factor adjusting for clinicopathological variables including tumour size, stage, differentiation, and Lauren histology. In patients with stage II or III disease in predicted stroma classes one and two subgroups, patients who received adjuvant chemotherapy had improved survival compared with those who did not (in those with stage II disease hazard ratio [HR] 0·48 [95% CI 0·29-0·77], p=0·0021; and in those with stage III disease HR 0·70 [0·57-0·85], p=0·00042). However, in the other two subgroups adjuvant chemotherapy was not associated with survival and might even be detrimental in the predicted stroma class 4 subgroup (HR 1·48 [1·08-2·03], p=0·013). INTERPRETATION: The deep-learning model could allow for accurate and non-invasive evaluation of tumour stroma from CT images in gastric cancer. The radiographical model predicted chemotherapy outcomes and could be used in combination with clinicopathological criteria to refine prognosis and inform treatment decisions of patients with gastric cancer. FUNDING: None.


Assuntos
Aprendizado Profundo , Neoplasias Gástricas/diagnóstico , Estômago/patologia , Tomografia Computadorizada por Raios X/métodos , Área Sob a Curva , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , China , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Curva ROC , Radiografia , Estudos Retrospectivos , Neoplasias Gástricas/classificação , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia
7.
Cell Death Dis ; 12(4): 368, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824303

RESUMO

Autophagy defection contributes to inflammation dysregulation, which plays an important role in gastric cancer (GC) progression. Various studies have demonstrated that long noncoding RNA could function as novel regulators of autophagy. Previously, long noncoding RNA MALAT1 was reported upregulated in GC cells and could positively regulate autophagy in various cancers. Here, we for the first time found that MALAT1 could promote interleukin-6 (IL-6) secretion in GC cells by blocking autophagic flux. Moreover, IL-6 induced by MALAT1 could activate normal to cancer-associated fibroblast conversion. The interaction between GC cells and cancer-associated fibroblasts in the tumour microenvironment could facilitate cancer progression. Mechanistically, MALAT1 overexpression destabilized the PTEN mRNA in GC cells by competitively interacting with the RNA-binding protein ELAVL1 to activate the AKT/mTOR pathway for impairing autophagic flux. As a consequence of autophagy inhibition, SQSTM1 accumulation promotes NF-κB translocation to elevate IL-6 expression. Overall, these results demonstrated that intercellular interaction between GC cells and fibroblasts was mediated by autophagy inhibition caused by increased MALAT1 that promotes GC progression, providing novel prevention and therapeutic strategies for GC.


Assuntos
Autofagia/genética , Proliferação de Células/genética , Fibroblastos/metabolismo , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , Transdução de Sinais/genética , Estômago/patologia , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/genética , Microambiente Tumoral/genética
8.
Aging (Albany NY) ; 13(8): 12224-12238, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882457

RESUMO

Unmasking the complex regulatory pathways that mediate the malignant phenotypes of cancer cells can provide novel targets for therapies that could limit the recurrence and metastasis of gastric cancer (GC). Herein, we intended to clarify the role of embryonic ectoderm development protein (EED), microRNA-228-5p (miR-338-5p), methyltransferase like 3 (METTL3) and CUB domain containing protein 1 (CDCP1) in GC. Differentially expressed miRNAs and their target genes were extracted by in silico analysis. The studies revealed high expression of EED in GC tissues and cell lines and it high expression in GC patients was shown to be associated with poor prognosis. The chromatin immunoprecipitation assay identified that EED methylated miR-338-5p to inhibit its expression. EED knockdown could restrain the proliferative and invasive abilities of GC cells by inducing miR-338-5p. Furthermore, miR-338-5p targeted m6A methylase METTL3, while METTL3 amplified the translation of CDCP1 via m6A activity which led to accelerated proliferation and invasion of GC cells. Moreover, in vivo experiments validated that EED promoted the progression of GC through mediating the miR-338-5p/METTL3/CDCP1 axis. Collectively, EED downregulated miR-338-5p through histone methylation, which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Complexo Repressor Polycomb 2/metabolismo , Neoplasias Gástricas/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Idoso , Animais , Antígenos de Neoplasias/biossíntese , Moléculas de Adesão Celular/biossíntese , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Gastrectomia , Técnicas de Silenciamento de Genes , Humanos , Masculino , Metilação , Metiltransferases/metabolismo , Camundongos , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Complexo Repressor Polycomb 2/genética , Prognóstico , Biossíntese de Proteínas/genética , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Aging (Albany NY) ; 13(8): 12007-12015, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888645

RESUMO

Long noncoding RNAs (LncRNAs) participate in tumor development and tumorigenesis. However, the mechanism, function and expression of LINC00514 in GC remain unknown. We showed that LINC00514 was upregulated in GC specimens compared with nontumor specimens. Overexpression of LINC00514 induced cell growth and EMT progression in GC cells. By using bioinformatics prediction, we found that miR-204-3p contained binding sequences for LINC00514. Luciferase reporter analysis noted that miR-204-3p overexpression decreased the luciferase expression under LINC00514-wild-type and KRAS-wild-type reporters but not that under mutant reporter. Ectopic LINC00514 expression decreased miR-204-3p expression. miR-204-3p expression was decreased in GC specimens compared with nontumor specimens and that LINC00514 was negatively correlated with miR-204-3p in GC specimens. Furthermore, KRAS was identified as a target gene for miR-204-3p according to TargetScan. Elevated miR-204-3p expression inhibited KRAS expression in HGC-27 cells, and ectopic expression of LINC00514 enhanced KRAS expression. Elevated LINC00514 expression enhanced cell growth and EMT progression by sponging KRAS. Our data indicated that LINC00514 may act as an oncogene and therapeutic target for GC.


Assuntos
MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Biologia Computacional , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Oncogenes , RNA Longo não Codificante/genética , Estômago/patologia , Neoplasias Gástricas/patologia , Regulação para Cima
10.
Molecules ; 26(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917379

RESUMO

Polyphenols are classified as an organic chemical with phenolic units that display an array of biological functions. However, polyphenols have very low bioavailability and stability, which make polyphenols a less bioactive compound. Many researchers have indicated that several factors might affect the efficiency and the metabolism (biotransformation) of various polyphenols, which include the gut microbiota, structure, and physical properties as well as its interactions with other dietary nutrients (macromolecules). Hence, this mini-review covers the two-way interaction between polyphenols and gut microbiota (interplay) and how polyphenols are metabolized (biotransformation) to produce various polyphenolic metabolites. Moreover, the protective effects of numerous polyphenols and their metabolites against various gastrointestinal disorders/diseases including gastritis, gastric cancer, colorectal cancer, inflammatory bowel disease (IBD) like ulcerative colitis (UC), Crohn's disease (CD), and irritable bowel syndrome (IBS) like celiac disease (CED) are discussed. For this review, the authors chose only a few popular polyphenols (green tea polyphenol, curcumin, resveratrol, quercetin), and a discussion of their proposed mechanism underpinning the gastroprotection was elaborated with a special focus on clinical evidence. Overall, this contribution would help the general population and science community to identify a potent polyphenol with strong antioxidant, anti-inflammatory, anti-cancer, prebiotic, and immunomodulatory properties to combat various gut-related diseases or disorders (complementary therapy) along with modified lifestyle pattern and standard gastroprotective drugs. However, the data from clinical trials are much limited and hence many large-scale clinical trials should be performed (with different form/metabolites and dose) to confirm the gastroprotective activity of the above-mentioned polyphenols and their metabolites before recommendation.


Assuntos
Gastroenteropatias/tratamento farmacológico , Polifenóis/uso terapêutico , Substâncias Protetoras/uso terapêutico , Estômago/patologia , Animais , Gastroenteropatias/microbiologia , Gastroenteropatias/fisiopatologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Metaboloma/efeitos dos fármacos , Polifenóis/química , Polifenóis/farmacologia , Estômago/efeitos dos fármacos
11.
Life Sci ; 277: 119497, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33864820

RESUMO

AIMS: Gastric cancer is a malignant tumor with a poor prognosis, and the interaction between tumor cells and cancer-associated fibroblasts (CAFs) further contributes to progression and treatment failure. Recent studies have revealed the potential value of melatonin in cancer therapy, but its role in gastric cancer and CAFs requires further exploration. MAIN METHODS: CAFs were isolated using the tissue block method. Cell Counting Kit-8 and cell cycle assays were used to determine the cell proliferation ability, while the cell metastatic capacity was detected by a wound healing assay and Transwell migration/invasion assay. Furthermore, the expression levels of proteins involved were examined using quantitative real-time PCR (qRT-PCR) and western blotting. KEY FINDINGS: Melatonin not only inhibits cell proliferation and metastasis by reducing the production of reactive oxygen species (ROS) in gastric cancer cells but also inhibits CAFs-induced gastric cancer cell progression by reducing the production of metalloproteinase 2 (MMP2) and metalloproteinase 2 (MMP9) in CAFs. The direct and indirect inhibitory effects of melatonin on gastric cancer cells are involved in the NF-kB signaling pathways. SIGNIFICANCE: This study provides insights into the role of melatonin in the tumor microenvironment, further deepens available knowledge regarding the mechanism of action of melatonin in gastric cancer and suggests the potential value of melatonin in gastric cancer treatment.


Assuntos
Fibroblastos Associados a Câncer/patologia , Melatonina/farmacologia , Neoplasias Gástricas/metabolismo , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , China , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Melatonina/metabolismo , Invasividade Neoplásica/patologia , Transdução de Sinais/efeitos dos fármacos , Estômago/patologia , Neoplasias Gástricas/tratamento farmacológico , Microambiente Tumoral
12.
Pan Afr Med J ; 38: 71, 2021.
Artigo em Francês | MEDLINE | ID: mdl-33889237

RESUMO

Gastrointestinal (GI) bezoars are aggregates of undigested material found in the GI tract. Trichobezoar is the most common type of bezoars and consists of ingested hair, carpet fibers or fitted carpet fibers. They are mainly located in the gastric region, rare forms extend to the duodenum or small intestine and are described as Rapunzel syndrome. Typical CT imaging features play a diagnostic and prognostic role. We report the case of a 13-year-old girl hospitalized for occlusive syndrome due to trichobezoar.


Assuntos
Bezoares/diagnóstico por imagem , Estômago/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Bezoares/patologia , Feminino , Hospitalização , Humanos , Estômago/patologia
13.
Biomed Res Int ; 2021: 6616059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860041

RESUMO

Background: Helicobacter pylori pathogenicity and disease severity are determined by the tyrosine phosphorylation motifs of CagA protein. This study is aimed at detecting the presence of H. pylori and identifying the CagA tyrosine phosphorylation motifs in Ghanaian patients. Material and Methods. A total of 94 archival genomic DNA samples from gastric biopsies were used for the study, and H. pylori was detected by amplifying the 16S rRNA gene. The 3'-end variable region of the cagA gene was amplified, and the entire 3'-end was sequenced and translated into amino acids. Results: H. pylori was detected in 53.2% (50/94) of the samples, and all the detected bacteria harboured the cagA gene. Two variants of the bacteria were identified based on the size of the amplified cagA gene: 207 bp and 285 bp. The 207 bp and 285 bp variants accounted for 74% and 22%, respectively, and 4% showed both fragments. Translated amino acid sequence of the cagA gene showed EPIYA-A, EPIYA-B, and EPIYA-C (ABC type) motifs, indicating the Western variant. The CagA protein C-terminal showed insertion of amino acids in the sequence flanking the EPIYA-A motif at the N-terminal and a complete deletion of the EPIYA-CC and EPIYA-CCC motifs together with the flanking sequences. Conclusions: H. pylori identified were Western variant (ABC type) with unique amino acid insertions, suggesting unique variants in Ghanaian patients. Further investigation is however required to understand the role of the molecular diversity of the variant in gastric disease outcome.


Assuntos
Antígenos de Bactérias/química , Proteínas de Bactérias/química , Helicobacter pylori/fisiologia , Estômago/microbiologia , Estômago/patologia , Tirosina/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Biópsia , Gana , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Fosforilação , RNA Ribossômico 16S/genética , Relação Estrutura-Atividade
14.
J Forensic Sci ; 66(4): 1564-1569, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33729557

RESUMO

Acute iron toxicity in adults is rare, usually occurring due to intentional ingestion in suicide attempts. Few cases of the clinical and autopsy findings in acute iron toxicity have previously been reported in the literature. Ingestion of large amounts of iron salts can lead to hemorrhagic shock, multi-system organ failure, coagulopathy, and death. We present the case of a 25-year-old man who reportedly ingested a large quantity of iron tablets along with ethanol in a suicide attempt and subsequently died approximately 65.5 h later. His clinical course and laboratory findings demonstrated hepatic and renal compromise with markedly elevated serum iron levels. At autopsy, iron encrustations were present over the gastric rugae. Superficial deposits of stainable iron were present overlying areas of mucosal necrosis with underlying submucosal fibrin thrombi. No significant stainable iron was present in the liver. Literature review revealed that the clinical course and laboratory testing of severe acute iron overdose is fairly non-specific. The length and type of treatment may alter the clinical course and laboratory results. Peak serum iron levels may be helpful in differentiating acute toxicity from chronic iron overload states. Gross findings of gastric iron encrustation are specific for acute ingestion when present.


Assuntos
Ferro/envenenamento , Suicídio Consumado , Oligoelementos/envenenamento , Adulto , Overdose de Drogas , Esôfago/patologia , Mucosa Gástrica/patologia , Humanos , Mucosa Intestinal/patologia , Ferro/sangue , Masculino , Estômago/patologia , Oligoelementos/sangue
15.
BMC Vet Res ; 17(1): 98, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653341

RESUMO

BACKGROUND: Ménétrier-like disease is a rare hypertrophic canine gastropathy, reported in only seven dogs. Clinical signs are vomiting, anorexia and weight loss. Macroscopically, giant cerebriform gastric mucosal folds are typically seen in the corpus and fundus of the stomach. Histopathologically, fundic mucous cell hyperplasia and loss of parietal and chief cells are typical. CASE PRESENTATION: A nine-year-old spayed female Pointer had a history of intermittent vomiting, marked weight loss and hypoalbuminaemia. A gastroduodenoscopy was performed three times within three months with macroscopic changes remaining the same. The gastric mucosa of the corpus, fundus and proximal antrum was markedly irregular, with cerebriform mucosal folds. In the first gastric biopsies, histopathology revealed a moderate granulomatous gastritis, with a severe manifestation of Helicobacter-like organisms. Treatment for Helicobacter spp. decreased the vomiting slightly. The dog was diagnosed with concurrent leishmaniosis; the conventional anti-Leishmania treatment decreased the vomiting moderately, the hypoalbuminaemia resolved and the dog gained weight back to a normal body condition. Granulomatous gastritis was not present in the gastric biopsies after these treatments. The dog increased vomiting when palliative treatment (maropitant citrate, ondansetron and esomeprazole) was discontinued, and thus, full-thickness biopsies of the stomach were taken and Ménétrier-like disease was diagnosed. The affected area was too large to be surgically removed; thus, palliative treatment was reinstated. The dog remained clinically well 39 months after the first clinical presentation. CONCLUSIONS: This is the first report of Ménétrier-like disease in a dog with a simultaneous manifestation of granulomatous gastritis, helicobacteriosis and leishmaniosis. The clinical signs decreased after treatment of helicobacteriosis and leishmaniosis, but vomiting remained probably as a sign of Ménétrier-like disease. Treatment options for dogs are surgical removal of the abnormal area or palliative treatment. In humans, promising results for a cure have been shown with cetuximab treatment, a human monoclonal antibody, but no canine antibody is commercially available yet. The dog here was doing well 39 months after first presentation, which is the longest reported survival time for Ménétrier-like disease with only palliative treatment in dogs. Full-thickness biopsies are preferred in macroscopic hypertrophic lesions of the stomach for better assessment of Ménétrier-like disease.


Assuntos
Doenças do Cão/patologia , Gastrite Hipertrófica/veterinária , Infecções por Helicobacter/veterinária , Leishmaniose/veterinária , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/microbiologia , Doenças do Cão/parasitologia , Cães , Feminino , Gastrite Hipertrófica/diagnóstico , Gastrite Hipertrófica/tratamento farmacológico , Helicobacter , Infecções por Helicobacter/tratamento farmacológico , Hipoalbuminemia/veterinária , Leishmania/imunologia , Leishmaniose/tratamento farmacológico , Estômago/patologia , Estômago/cirurgia , Vômito/tratamento farmacológico , Vômito/veterinária
16.
Aging (Albany NY) ; 13(7): 9766-9779, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33744848

RESUMO

As biomolecules of great clinical value, lncRNAs play a crucial role as regulators in the processes of tumor origin, metastasis, and recurrence. Thus, lncRNAs are urgently needed for research in gastric cancer. We elucidated the specific function of OGFRP1, both in vitro and in vivo. OGFRP1 was expressed at abnormally high levels in gastric cancer samples (n = 408) compared to normal samples (n = 211). Similar results were obtained in 30 clinical case samples. Interference of OGFRP1 markedly blocked cell proliferation and migration, and it induced cell cycle arrest and the apoptosis of gastric cancer cells in vitro. Phosphorylation of AKT was inhibited in cells transfected with OGFRP1 siRNA, as compared to their control cells. The in vivo results further confirmed the antitumor effects of OGFRP1 knockdown on gastric cancer. Decreases in tumor volume (104.23±62.27 mm3) and weight (0.1006±0.0488 g) in nude mice were observed during the OGFRP1 interference, as compared with the control group (418.96±211.96 mm3 and 0.2741±0.0769 g). OGFRP1 promotes tumor progression through activating the AKT/mTOR pathway. Our findings provide a new potential target for the clinical treatment of human gastric cancer.


Assuntos
Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Mucosa Gástrica/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Fosforilação , RNA Longo não Codificante/genética , Transdução de Sinais/fisiologia , Estômago/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
17.
Genet Test Mol Biomarkers ; 25(3): 236-246, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33734892

RESUMO

Aims: To assess the expression and epigenetic regulation of Syncoilin, intermediate filament protein (SYNC) in gastric cancer tissues, and to determine its associations with clinicopathological features; immune infiltration of macrophages in tumors; and patient survival. Materials and Methods: Clinicopathological features, expression profiles, and methylation data of the SYNC gene were obtained from multi-institutional real-world public datasets. A total of 1601 samples from patients with gastric cancer were examined. The associations between clinicopathological features and SYNC expression levels were assessed by the chi-square test; survival was assessed using the Kaplan-Meier analysis. The infiltration levels of M1, 2-polarized tumor-associated macrophages (TAMs) in a gastric tumor immune microenvironment were quantified using deconvolution, and the correlation between SYNC expression level and M1, 2-polarized macrophages' infiltration was examined using the Pearson correlation test. SYNC gene methylation data were analyzed to investigate epigenetic control of its expression. Results: SYNC expression was elevated in gastric cancer tissues (p < 0.01), and was associated with a poorer overall survival (p < 0.01) and poorer postprogression survival (p = 0.01). Higher SYNC levels were significantly associated with more aggressive clinicopathological features in gastric cancer patients (p < 0.05). SYNC was also associated with the infiltration of M2-polarized TAMs in the gastric tumor immune microenvironment (p < 0.001). Hypomethylation was shown to be associated with SYNC's upregulation (p < 0.05). Conclusion: SYNC is highly expressed in gastric cancer tissues and has the potential to be a therapeutic target and to serve as a prognostic marker.


Assuntos
Proteínas de Filamentos Intermediários/genética , Linfócitos do Interstício Tumoral/imunologia , Proteínas Musculares/genética , Neoplasias Gástricas/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/imunologia , China , Metilação de DNA , Bases de Dados Genéticas , Epigênese Genética/genética , Epigenômica/métodos , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas de Filamentos Intermediários/metabolismo , Estimativa de Kaplan-Meier , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/metabolismo , Prognóstico , Estômago/patologia , Neoplasias Gástricas/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
18.
Ann Afr Med ; 20(1): 1-8, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33727504

RESUMO

Helicobacter pylori (H. pylori) is a Gram-negative, helically shaped flagellated bacterium. Major diseases associated with H. pylori infection include peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The incidence of H. pylori in the anatomotopographic regions of the stomach, such as antrum, corpus, fundus, and incisura angularis, has been investigated. Do the rates of H. pylori in the settlements change over time according to the age ranges of the hosts? Does this change affect the diseases caused by or related to H. pylori? It is estimated that the outcomes, which have been obtained, may provide a new perspective in terms of understanding the etiopathogenesis of H. pylori-induced diseases. A comprehensive literature search of PubMed/MEDLINE databases had been conducted using a combination of terms, "Helicobacter pylori," "Sydney System," "stomach," "pyloric antrum," "gastric corpus," "stomach cancer," and "Helicobacter pylori and age." There are very few articles examining the relationship between the topographic locations of H. pylori and host age range in the English language literature. Therefore, it is also purposed to emphasize the outcomes of our current research about the mentioned topic. In our opinion, similar studies should reveal the settlement and age range in the different geographic locations and societies as in our study. We believe that these findings will contribute to the efforts for understanding overtly of H. pylori-induced disease of the stomach.


Assuntos
Adenocarcinoma/microbiologia , Fatores Etários , Úlcera Duodenal/microbiologia , Infecções por Helicobacter/complicações , Neoplasias Gástricas/microbiologia , Úlcera Gástrica/microbiologia , Estômago/microbiologia , Adolescente , Adulto , Idoso , Biópsia , Endoscopia , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estômago/patologia , Adulto Jovem
19.
Oxid Med Cell Longev ; 2021: 1298657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728017

RESUMO

Background: Gastric electrical pacing (GEP) could restore interstitial cells of Cajal in diabetic rats. M2 macrophages contribute to the repair of interstitial cells of Cajal injury though secreting heme oxygenase-1 (HO-1). The aim of the study is to investigate the effects and mechanisms of gastric electrical pacing on M2 macrophages in diabetic models. Methods: Sixty male Sprague-Dawley rats were randomized into control, diabetic (DM), diabetic with the sham GEP (DM+SGEP), diabetic with GEP1 (5.5 cpm, 100 ms, 4 mA) (DM+GEP1), diabetic with GEP2 (5.5 cpm, 300 ms, 4 mA) (DM+GEP2), and diabetic with GEP3 (5.5 cpm, 550 ms, 4 mA) (DM+GEP3) groups. The apoptosis of interstitial cells of Cajal and the expression of macrophages were detected by immunofluorescence technique. The expression levels of the Nrf2/HO-1 and NF-κB pathway were evaluated using western blot analysis or immunohistochemical method. Malonaldehyde, superoxide dismutase, and reactive oxygen species were tested to reflect the level of oxidative stress. Results: Apoptosis of interstitial cells of Cajal was increased in the DM group but significantly decreased in the DM+GEP groups. The total number of macrophages was almost the same in each group. In the DM group, M1 macrophages were increased and M2 macrophages were decreased. However, M2 macrophages were dramatically increased and M1 macrophages were reduced in the DM+GEP groups. Gastric electrical pacing improved the Nrf2/HO-1 pathway and downregulated the phosphorylation of NF-κB. In the DM group, the levels of malonaldehyde and reactive oxygen species were elevated and superoxide dismutase was lowered, while gastric electrical pacing reduced the levels of malonaldehyde and reactive oxygen species and improved superoxide dismutase. Conclusion: Gastric electrical pacing reduces apoptosis of interstitial cells of Cajal though promoting M2 macrophages polarization to play an antioxidative stress effect in diabetic rats, which associates with the activated Nrf2/HO-1 pathway and the phosphorylation of NF-κB pathway.


Assuntos
Apoptose , Polaridade Celular , Diabetes Mellitus Experimental/fisiopatologia , Fenômenos Eletrofisiológicos , Células Intersticiais de Cajal/patologia , Macrófagos/patologia , Estresse Oxidativo , Estômago/fisiopatologia , Animais , Diabetes Mellitus Experimental/patologia , Eletroacupuntura , Heme Oxigenase-1/metabolismo , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fator de Células-Tronco/metabolismo , Estômago/patologia , Superóxido Dismutase/metabolismo
20.
Carbohydr Polym ; 261: 117829, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766334

RESUMO

In this study, a polysaccharide from marine alga Acanthophora spicifera (PAs) was isolated and structurally characterized. Its protective potential against chemically-induced gastric mucosa injury was evaluated. The gel permeation chromatography experiments and spectroscopy spectrum showed that PAs is a sulfated polysaccharide with a high molecular mass (6.98 × 105g/mol) and degree of sulfation of 1.23, exhibiting structural characteristic typical of an agar-type polysaccharide. Experimental results demonstrated that PAs reduced the hemorrhagic gastric injury, in a dose-dependent manner. Additionally, PAs reduced the intense gastric oxidative stress, measured by glutathione (GSH) and malondialdehyde (MDA) levels. PAs also prevented the reduction of mucus levels adhered to the gastric mucosa, promoted by the aggressive effect of ethanol. In summary, the sulfated polysaccharide from A. spicifera protected the gastric mucosa through the prevention of lipid peroxidation and enhanced the defense mechanisms of the gastric mucosa, suggesting as a promising functional food as gastroprotective agent.


Assuntos
Citoproteção/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Polissacarídeos/farmacologia , Rodófitas/química , Ágar/isolamento & purificação , Ágar/farmacologia , Animais , Mucosa Gástrica/patologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Rodófitas/metabolismo , Estômago/efeitos dos fármacos , Estômago/lesões , Estômago/patologia , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle , Sulfatos/química , Sulfatos/farmacologia
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