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1.
APMIS ; 128(1): 25-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31628820

RESUMO

Eradication failure of Helicobacter pylori infection could play a causal role in progression of gastric disorders. In this study, infection with H. pylori was followed in gastric biopsies of symptomatic adult patients at two phases during 1-year period. Analyses were done to show association of therapeutic regimens with the refractory infection, changes in sequence types (STs) and minimum inhibitory concentration (MIC) values, and progression of histopathological changes. Infection with H. pylori was confirmed in 32.3% (57/170) of the patients. Persistent infection with H. pylori was confirmed in 14 out of the 25 patients (56%) who participated at the second phase of the study. A difference between primary and secondary resistance rates to clarithromycin (49% vs 64.3%), metronidazole (76.36% vs 100%), and ciprofloxacin (45% vs 57.1%) was detected. Although the re-emerged strains in patients with refractory infection did not show alteration in STs, their MIC50 values showed twofold increases for clarithromycin and ciprofloxacin. While ciprofloxacin containing regimens were more successful, failure of metronidazole containing regimens was detected in 77% of the patients. Consequently, inappropriate medication has an impact on refractory H. pylori infection, which could cause to a rise in resistance levels to antibiotics and progression of pathological disorders.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Biópsia , Ciprofloxacino/farmacologia , Claritromicina/farmacologia , Feminino , Seguimentos , Técnicas Histológicas , Humanos , Concentração Inibidora 50 , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Estômago/microbiologia , Estômago/patologia
3.
Int J Nanomedicine ; 14: 7191-7213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564873

RESUMO

Background: Diosmin showed poor water solubility and low bioavailability. Poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles were successfully used to improve the drugs solubility and bioavailability. Coating of PLGA nanoparticles with chitosan can ameliorate their gastric retention and cellular uptake. Methodology: PLGA nanoparticles of diosmin were prepared using different drug and polymer amounts. Nanoparticles were selected based on entrapment efficiency% (EE%) and particle size measurements to be coated with chitosan. The selected nanoparticles either uncoated or coated were evaluated regarding morphology, ζ-potential, solid-state characterization, in vitro release, storage stability, and mucoadhesion. The anti-ulcer activity (AA) against ethanol-induced ulcer in rats was assessed through macroscopical evaluation, histopathological examination, immunohistochemical localization of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transmission electron microscopic examination of gastric tissues compared to free diosmin (100 mg/kg) and positive control. Results: Based on EE% and particle size measurements, the selected nanoparticles, either uncoated or coated with 0.1% w/v chitosan, were based on 1:15 drug-PLGA weight ratio and 20 mg diosmin employing methylene chloride as an organic phase. Examination by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed nanoscopic spherical particles. Drug encapsulation within the selected nanoparticles was suggested by Fourier transform-infrared, differential scanning calorimetry (DSC) and X-ray diffractometry results. Chitosan-coated nanoparticles were more stable against size enlargement probably due to the higher ζ-potential. Only coated nanoparticles showed gastric retention as revealed by SEM examination of stomach and duodenum. The superior AA of coated nanoparticles was confirmed by significant reduction in average mucosal damage, the majority of histopathological changes and NF-κB expression in gastric tissue when compared to positive control, diosmin and uncoated nanoparticles as well as insignificant difference relative to normal control. Coated nanoparticles preserved the normal ultrastructure of the gastric mucosa as revealed by TEM examination. Conclusion: The optimized chitosan-coated PLGA nanoparticles can be represented as a potential oral drug delivery system of diosmin.


Assuntos
Antiulcerosos/uso terapêutico , Quitosana/química , Diosmina/uso terapêutico , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Estômago/patologia , Úlcera/tratamento farmacológico , Adesividade , Animais , Antiulcerosos/farmacologia , Varredura Diferencial de Calorimetria , Diosmina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Duodeno/efeitos dos fármacos , Duodeno/patologia , Duodeno/ultraestrutura , Mucosa Gástrica/patologia , Mucosa Gástrica/ultraestrutura , Cinética , Masculino , Muco/química , NF-kappa B/metabolismo , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Estômago/efeitos dos fármacos , Estômago/ultraestrutura , Úlcera/patologia , Difração de Raios X
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 572-574, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484624

RESUMO

Bronchogenic cysts are rare congenital cysts caused by anomalism of foregut in the embryonic stage.They locate most frequently in the mediastinum and are rarely seen in stomach.Here we report a case of gastric bronchogenic cysts that was diagnosed and treated in Peking Union Medical College Hospital from April 2 to 9,2018.


Assuntos
Cisto Broncogênico/diagnóstico , Estômago/patologia , Humanos
5.
Internist (Berl) ; 60(11): 1201-1208, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31511906

RESUMO

This article reports about a 73-year-old woman of Bosnian descent who presented with acute renal failure. A renal biopsy was diagnostic for a postinfect necrotizing and extracapillary proliferative glomerulonephritis. The patient reported a febrile infection fever 2 weeks previously. The diagnostics did not reveal any indications of an ongoing infection. The glomerulonephritis responded to treatment with systemic steroids. The patient was readmitted to hospital 6 weeeks later in a severely ill condition. A gastric biopsy revealed a Strongyloides stercoralis infestation. Due to the systemic steroid therapy the patient had developed a so-called hyperinfection syndrome and died despite treatment on the intensive care unit. This case illustrates the need for awareness of this rare parasitosis, particularly in patients from endemic areas. A likely causal relationship with the glomerulonephritis is discussed and an overview of the diagnostics, course of the disease and treatment of this parasitosis is given.


Assuntos
Lesão Renal Aguda/etiologia , Glomerulonefrite/tratamento farmacológico , Prednisolona/efeitos adversos , Esteroides/efeitos adversos , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/diagnóstico , Idoso , Animais , Antiparasitários/uso terapêutico , Evolução Fatal , Feminino , Glomerulonefrite/diagnóstico , Humanos , Ivermectina/uso terapêutico , Prednisolona/uso terapêutico , Esteroides/uso terapêutico , Estômago/microbiologia , Estômago/patologia , Estrongiloidíase/complicações , Estrongiloidíase/tratamento farmacológico
6.
Int J Nanomedicine ; 14: 4911-4929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456637

RESUMO

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.


Assuntos
Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Quitosana/química , Mucosa Gástrica/efeitos dos fármacos , Nanopartículas/química , Oligossacarídeos/química , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacologia , Acetofenonas/uso terapêutico , Administração através da Mucosa , Animais , Biomarcadores/metabolismo , Varredura Diferencial de Calorimetria , Ciclo-Oxigenase 2/metabolismo , Liberação Controlada de Fármacos , Cinética , Masculino , Nanopartículas/ultraestrutura , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Suínos , Difração de Raios X
7.
Int J Nanomedicine ; 14: 6001-6018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447554

RESUMO

Background: The gastroretentive drug delivery system is an effective administration route, which can improve the bioavailability of the drug and the therapeutic effect by prolonging the release time of the drug and controlling the release rate in the stomach. Methods: Inspired by the excellent adhesion properties of mussel protein, we prepared novel catechol-grafted chitosan alginate/barium sulfate microcapsules (Cat-CA/BS MCs) with mucoadhesive properties and computed tomography (CT) imaging function for gastric drug delivery. First, barium sulfate nanoclusters used as CT contrast agent were synthesized in situ in the Cat-CA/BS MCs through a one-step electronic spinning method. Next, catechol-grafted chitosan as the mucoadhesive moiety was coated on the surface of Cat-CA/BS MCs by polyelectrolyte molecule self-assembly. Results: The prepared Cat-CA/BS MCs could effectively retained in the stomach for 48 hours and successively released ranitidine hydrochloride, which could be used for the treatment of gastric ulcer. Cat-CA/BS MCs exhibited superior CT contrast imaging properties for real-time tracking in vivo after oral administration. Conclusion: These findings demonstrate that Cat-CA/BS MCs serving as multifunctional oral drug carriers possess huge potential in gastroretentive drug delivery and non-invasive visualization.


Assuntos
Sulfato de Bário/química , Cápsulas/química , Catecóis/farmacologia , Quitosana/química , Sistemas de Liberação de Medicamentos , Estômago/efeitos dos fármacos , Estômago/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adesividade , Administração Oral , Animais , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos , Feminino , Camundongos Endogâmicos C57BL , Muco/química , Nanopartículas/química , Nanopartículas/ultraestrutura , Ranitidina/farmacologia , Espectroscopia de Luz Próxima ao Infravermelho , Estômago/patologia
8.
Medicine (Baltimore) ; 98(35): e16729, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464902

RESUMO

Caustic ingestion in adults is a rare but potentially life-threatening problem. It remains controversial whether endoscopic findings and mortality differ between acid and alkali ingestion. We compared ingestion of these agents and evaluated prediction parameters for survival and complications.Adult patients who presented with caustic ingestion were analyzed from 2005 to 2016. Mucosal injury was graded endoscopically by Zargar's score. Age, gender, intent of ingestion, caustic agents, comorbidities, management, complications, and mortality were examined.Thirty-one patients met inclusion criteria and were divided into acid (n = 10) and alkali group (n = 21). Ingestion of alkali resulted in higher grades (≥III) of esophageal (56% vs 24%, P = .01) and stomach injuries (43% vs 13%, P = .05) and was mostly done with suicidal intent (76% vs 30%, P = .003). Patients in the alkali group received more often surgical interventions, mechanical ventilation and tracheotomy. Overall complications including Zargar's-score ≥ grade III, mediastinitis, and aspiration pneumonia were higher in alkali group but all showed no statistical significance (P = .73). Mortality (acid: 1 (10%), alkali: 4 (19%), P = .52), age, gender, comorbidities, and intensive care management did not differ significantly between the groups. Chronic renal failure and mediastinitis were promising prediction parameters for mortality but did not reach statistical significance. No independent risk factors for the development of esophageal stenosis were identified.Alkaline agents caused a higher mucosal injury severity and were more often used in suicidal intent. Mediastinitis and chronic renal failure might be potential prediction parameters for survival but need to be evaluated in larger studies.


Assuntos
Queimaduras Químicas/complicações , Cáusticos/toxicidade , Estenose Esofágica/diagnóstico , Falência Renal Crônica/diagnóstico , Mediastinite/diagnóstico , Estômago/lesões , Ácidos/toxicidade , Adulto , Idoso , Álcalis/toxicidade , Queimaduras Químicas/diagnóstico , Endoscopia do Sistema Digestório , Estenose Esofágica/induzido quimicamente , Feminino , Humanos , Falência Renal Crônica/induzido quimicamente , Masculino , Mediastinite/induzido quimicamente , Pessoa de Meia-Idade , Estudos Retrospectivos , Estômago/patologia , Tentativa de Suicídio/estatística & dados numéricos , Análise de Sobrevida
9.
Anticancer Res ; 39(8): 4019-4022, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366483

RESUMO

Historically, analysis of intragastric exfoliative cytology (IEC) of gastric cancer (GC) was used with a diagnostic intent only. With the successful advent of endoscopic biopsy, the rate of detection of GC has improved worldwide and, as a consequence, IEC has been progressively abandoned. Today, however, there is a renewed interest in this field of research, as witnessed by several pertinent publications. As discussed in this review, in fact, currently the importance of analyzing IEC in patients with early and advanced GC seems to reside in its clinicopathological and prognostic significance. In fact, compared to non-sloughing tumors, GC exhibiting intragastric exfoliation was recently associated with an aggressive tumor phenotype (characterized by deeper infiltration of the gastric wall, lymph nodal or distant metastases, angiolymphatic and perineural invasion) and poorer prognosis. Adoption of IEC examination in routine practice might help identify patients at higher risk of developing local recurrence and peritoneal metastasis from early and advanced GC, optimizing their treatment and improving quality of life and life expectancy.


Assuntos
Citodiagnóstico/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Estômago/diagnóstico por imagem , Endoscopia , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Peritônio/diagnóstico por imagem , Peritônio/patologia , Prognóstico , Estômago/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
10.
Anticancer Res ; 39(8): 4243-4248, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366512

RESUMO

BACKGROUND/AIM: This study aimed to clarify the benefits and disadvantages of percutaneous endoscopic gastrostomy (PEG) for patients with esophageal cancer (EC) during preoperative therapy. MATERIALS AND METHODS: We retrospectively reviewed 92 patients who underwent esophagectomy for EC after preoperative therapy. Patients were divided into the PEG group (n=14) and the control group (n=78) and compared regarding patient characteristics, nutritional status, operative variables, and postoperative complications. RESULTS: In the PEG group first nutritional status and tumor stage were significantly worse, but changes of nutritional status from first visit to operation were significantly better. According to the intraoperative thermal imaging, there was no patient with blood flow disturbance in the gastric conduit due to PEG. Short-term surgical outcomes did not significantly differ. CONCLUSION: PEG has less adverse effects on gastric tube production in esophagectomy and may be considered in highly selective patients during preoperative therapy.


Assuntos
Endoscopia/métodos , Neoplasias Esofágicas/cirurgia , Gastrostomia/métodos , Estômago/cirurgia , Adulto , Idoso , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/patologia , Período Pré-Operatório , Estudos Retrospectivos , Estômago/patologia , Resultado do Tratamento
11.
Life Sci ; 231: 116688, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31348950

RESUMO

The extended infection with Helicobacter pylori (H. pylori), one of the most frequent infectious agents in humans, may cause gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. During H. pylori infection, different kinds of inflammatory cells such as dendritic cells, macrophages, neutrophils, mast cells, eosinophils, T cells and B cells are accumulated into the stomach. The interactions between chemokines and their respective receptors recruit particular types of the leukocytes that ultimately determine the nature of immune response and therefore, have a main influence on the consequence of infection. The suitable production of chemokines especially in the early stages of H. pylori infection shapes appropriate immune responses that contribute to the H. pylori elimination. The unbalanced expression of the chemokines can contribute in the induction of inappropriate responses that result in the tissue damage or malignancy. Thus, chemokines and their receptors may be promising potential targets for designing the therapeutic strategies against various types H. pylori-related gastrointestinal disorders. In this review, a comprehensive explanation regarding the roles played by chemokines in H. pylori-mediated peptic ulcer, gastritis and gastric malignancies was provided while presenting the potential utilization of these chemoattractants as therapeutic elements.


Assuntos
Quimiocinas/metabolismo , Quimiocinas/farmacologia , Infecções por Helicobacter/terapia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Quimiocinas CXC/imunologia , Quimiocinas CXC/metabolismo , Mucosa Gástrica/metabolismo , Gastrite , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Helicobacter pylori/metabolismo , Helicobacter pylori/patogenicidade , Humanos , Receptores CXCR/imunologia , Receptores CXCR/metabolismo , Receptores de Quimiocinas/imunologia , Receptores de Quimiocinas/metabolismo , Estômago/patologia , Neoplasias Gástricas/patologia , Linfócitos T/imunologia , Linfócitos T/metabolismo
12.
Gene ; 712: 143956, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31271843

RESUMO

Gastric cancer represents a common malignancy of digestive tract with high incidence and mortality. Increasing evidence suggests that the growth of gastric tumor cells relies largely on aerobic glycolysis. Currently, many potential anti-cancer candidates are derived from natural products. Here, we evaluated the effects of oleanolic acid (OA), a triterpenoid component widely found in the plants of Oleaceae family, on aerobic glycolysis and proliferation in human MKN-45 and SGC-7901 gastric cancer cells. Our results demonstrated that OA reduced the viability and proliferation of gastric cancer cells and inhibited the expression of cyclin A and cyclin-dependent kinase 2. OA blocked glycolysis in these cells evidenced by decreases in the uptake and consumption of glucose, intracellular lactate levels and extracellular acidification rate. Glycolysis inhibitor 2-deoxy-d-glucose, similar to OA, suppressed gastric cancer cell proliferation. OA also decreased the expression and intracellular activities of glycolysis rate-limiting enzymes hexokinase 2 (HK2) and phosphofructokinase 1 (PFK1). Moreover, OA downregulated the expression of hypoxia inducible factor-1α (HIF-1α) and decreased its nuclear abundance. Upregulation of HIF-1α by deferoxamine rescued OA-inhibited HK2 and PFK1. Furthermore, OA reduced the nuclear abundance of yes-associated protein (YAP) in gastric tumor cells. YAP inhibitor verteporfin, similar to OA, downregulated the expression of HIF-1α and glycolytic enzymes in gastric cancer cells; whereas overexpression of YAP abrogated all these effects of OA. Collectively, inhibition of YAP was responsible for OA blockade of HIF-1α-mediated aerobic glycolysis and proliferation in human gastric tumor cells. OA could be developed as a promising candidate for gastric cancer treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ácido Oleanólico/farmacologia , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/metabolismo , Neoplasias Gástricas/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Ciclo do Ácido Cítrico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicólise , Humanos , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Estômago/patologia , Neoplasias Gástricas/tratamento farmacológico , Fatores de Transcrição
13.
BMC Infect Dis ; 19(1): 546, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226948

RESUMO

BACKGROUND: The effectiveness of Helicobacter pylori first-line treatment has decreased drastically with the rise of strains resistant to clarithromycin. Therapy failure has also been described in patients with infections by strains with dissimilar antimicrobial susceptibilities. The present study aims to estimate the prevalence of resistance and heteroresistance to clarithromycin in H. pylori isolates from antrum and corpus of Colombian patients. METHODS: The study material included 126 isolates from antrum and corpus biopsies from 63 symptomatic patients over 18 years old who had a gastric endoscopy performed on them between June 2014 to August 2016. PCR amplification and sequencing of the H. pylori 23S rDNA gene was performed to determine the presence of mutations associated with clarithromycin resistance. Random amplified polymorphic DNA analysis was implemented in cases of resistance and heteroresistance. RESULTS: The overall frequency of resistance to clarithromycin was 38.1% (24/63 patients), of which 19 patients had resistant isolates in both stomach segments (14 with A2143G mutation and 5 with A2142G mutation), and 5 patients had a heteroresistant status. The remaining 61.9% (39/63 patients) presented only susceptible isolates. DNA fingerprinting analysis showed different patterns in 4/22 paired isolates. CONCLUSIONS: The high prevalence of H. pylori clarithromycin-resistance obtained (> 15%) constitutes an alert for gastroenterologists and suggests the need for reconsideration of the current eradication regimen for H. pylori in the studied population. The data show that heteroresistance status is an additional factor to be considered in the assessment of resistance. In consequence, it is advisable to examine at least two biopsies from different gastric segments.


Assuntos
Técnicas de Tipagem Bacteriana , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Colômbia/epidemiologia , Feminino , Genótipo , Técnicas de Genotipagem , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase/métodos , Prevalência , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Estômago/microbiologia , Estômago/patologia , Adulto Jovem
14.
Plant Foods Hum Nutr ; 74(3): 322-327, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31154569

RESUMO

Annona cherimola is a tree belonging to the family Annonacea, whose fruit (cherimoya) is very desirable, but its seeds are considered waste. Present in these seeds are compounds that have been described as selective antiproliferative agents for cancer cells. The aim of this study was to evaluate the antiproliferative activity of ethanol macerate extract (EMCHS) obtained from A. cherimola seeds against the human stomach gastric adenocarcinoma (AGS) cell line and the normal human gastric epithelial cell line (GES-1). The EMCHS extract presented an IC50 of 80.43 µg/mL in AGS cells, and a selectivity index (SI) of 3.5-fold higher than that of cisplatin. In addition, the EMCHS extract showed apoptotic activity in AGS cells since 50 µg/mL. Overxpression of PUMA gene in both cells demonstrate that EMCHS activate the apoptotic route. Future studies should be carried out to elucidate anticancer activity of EMCHS in vivo. This work represents the first showing antiproliferative effects of crude extracts obtained from seeds of A. cherimola in AGS cells.


Assuntos
Adenocarcinoma/tratamento farmacológico , Annona/química , Apoptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sementes/química , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Etanol , Expressão Gênica , Humanos , Proteínas Proto-Oncogênicas/genética , Estômago/patologia
15.
Mol Carcinog ; 58(8): 1427-1437, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31162747

RESUMO

The Helicobacter pylori (H. pylori) cytotoxin-associated gene A (CagA) and Krüppel-like transcription factor (KLF4) were both closely associated with the development and progression of gastric cancer (GC). However, the nature of the interactions between CagA and KLF4 in GC development has not been elucidated. Therefore, we focused on the CagA-mediated promotion of the malignant transformation of gastric epithelial cells. Herein, we first examined the expression of KLF4 in both human cancer and paracarcinoma tissues with or without H. pylori infection and found that KLF4 expression was significantly decreased in H. pylori-positive GC cells compared with the H. pylori-negative GC cells. Further functional studies revealed that the increased expression of CagA could suppress KLF4 expression and promote the malignant transformation of normal epithelial cells. Subsequently, we found that CagA could upregulate miR-155 and further restrict the expression of downstream KLF4. More importantly, the overexpression of miR-155 in GES-1 promoted epithelial-mesenchymal transition and eventually facilitated tumor growth in vivo. Overall, the identification of the CagA/miR-155/KLF4 signaling pathway provided a new insight into the development and treatment of GC.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Transformação Celular Neoplásica/patologia , Mucosa Gástrica/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Gástricas/patologia , Adulto , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/genética , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Mucosa Gástrica/citologia , Células HEK293 , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , MicroRNAs/metabolismo , Transplante de Neoplasias , Transdução de Sinais , Estômago/patologia , Neoplasias Gástricas/genética , Transplante Heterólogo
16.
Cancer Sci ; 110(8): 2643-2651, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222839

RESUMO

Scirrhous-type gastric cancer (SGC) is one of the most intractable cancer subtypes in humans, and its therapeutic targets have been rarely identified to date. Exploration of somatic mutations in the SGC genome with the next-generation sequencers has been hampered by markedly increased fibrous tissues. Thus, SGC cell lines may be useful resources for searching for novel oncogenes. Here we have conducted whole exome sequencing and RNA sequencing on 2 SGC cell lines, OCUM-8 and OCUM-9. Interestingly, most of the mutations thus identified have not been reported. In OCUM-8 cells, a novel CD44-IGF1R fusion gene is discovered, the protein product of which ligates the amino-terminus of CD44 to the transmembrane and tyrosine-kinase domains of IGF1R. Furthermore, both CD44 and IGF1R are markedly amplified in the OCUM-8 genome and abundantly expressed. CD44-IGF1R has a transforming ability, and the suppression of its kinase activity leads to rapid cell death of OCUM-8. To the best of our knowledge, this is the first report describing the transforming activity of IGF1R fusion genes. However, OCUM-9 seems to possess multiple oncogenic events in its genome. In particular, a novel BORCS5-ETV6 fusion gene is identified in the OCUM-9 genome. BORCS5-ETV6 possesses oncogenic activity, and suppression of its message partially inhibits cell growth. Prevalence of these novel fusion genes among SGC awaits further investigation, but we validate the significance of cell lines as appropriate reagents for detailed genomic analyses of SGC.


Assuntos
Adenocarcinoma Esquirroso/genética , Oncogenes/genética , Neoplasias Gástricas/genética , Células 3T3 , Adenocarcinoma Esquirroso/patologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Células HEK293 , Humanos , Receptores de Hialuronatos/genética , Proteínas de Membrana/genética , Camundongos , Mutação/genética , Receptor IGF Tipo 1/genética , Estômago/patologia , Neoplasias Gástricas/patologia
17.
Jpn J Radiol ; 37(8): 597-604, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177473

RESUMO

PURPOSE: Wall-carving technique (WC) is a special volume rendering technique of three-dimensional CT gastrography that can illustrate the enhancement of gastric wall at an arbitrary depth. We conducted the present study to evaluate the impact of contrast enhancement based on layer depth on WC of gastric cancer and to correlate them with pathological findings. METHODS: The subjects of this retrospective study consisted of 36 patients with advanced gastric cancer (22 men, 14 women; age range, 39-90 years; median, 67 years) who underwent contrast-enhanced CT before surgery. WC images of arterial phase were divided into first and second layer. Two radiologists in consensus evaluated the contrast enhancement of WC images for each layer and correlated with pathologic factors. RESULTS: Twenty-six (72%) of the gastric cancers showed a well-enhanced lesion in the first layer at the arterial phase on WC images, and 18 (50%) showed a well-enhanced lesion in the second layer. The study of second layers showed that the well-enhanced group had significantly more cases of differentiated type histology and intermediate stroma than the normally to poorly enhanced group (p = 0.008 and 0.0026). CONCLUSION: The contrast enhancement on WC of gastric cancer showed a significant relationship with pathological factors based on layer depth.


Assuntos
Meios de Contraste , Interpretação de Imagem Assistida por Computador/métodos , Intensificação de Imagem Radiográfica/métodos , Neoplasias Gástricas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estômago/diagnóstico por imagem , Estômago/patologia , Neoplasias Gástricas/patologia
18.
Diagn Pathol ; 14(1): 38, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077220

RESUMO

BACKGROUND: Gastric mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are infrequently encountered in routine practice. Some gastric neuroendocrine carcinomas (NECs) have a variety of differentiation patterns; however, pancreatic acinar differentiation in gastric NECs is rare. The molecular abnormalities of NECs with pancreatic acinar differentiation are not well understood. CASE PRESENTATION: A 67-year-old male with a gastric MiNEN with pancreatic acinar differentiation without any symptoms. The tumor consisted of two components, including both glandular and solid histological features. Although the former component was a common type of adenocarcinoma, the latter showed endocrine differentiation and expressed pancreatic acinar enzymes immunohistochemically. A positive signal with the anti-BCL10 antibody, which detects one of the pancreatic acinar enzymes, was also present specifically in the latter component. We also examined TP53 genomic mutations, DNA methylation status, and allelic imbalance (AI), which is an indicator of tumor aggressiveness. Although both components of this tumor showed no genomic mutation and a low methylation epigenotype, the frequency of AI was higher in the acinar-endocrine component than in the adenocarcinomatous component. The finding of AI indicated the progression of the conventional adenocarcinoma to an acinar-endocrine component and identified the aggressive potential of the acinar-endocrine component. CONCLUSIONS: We report a rare case of gastric MiNEN with pancreatic acinar differentiation. AI analysis revealed tumor progression and aggressiveness. In addition, the usefulness of the anti-BCL10 antibody for detecting the acinar-endocrine component was suggested.


Assuntos
Proteína 10 de Linfoma CCL de Células B/imunologia , Biomarcadores Tumorais/genética , Carcinoma de Células Acinares/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Gástricas/diagnóstico , Idoso , Anticorpos , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/patologia , Diferenciação Celular , Humanos , Imuno-Histoquímica , Masculino , Mutação , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Estômago/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
19.
Medicine (Baltimore) ; 98(20): e15696, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096513

RESUMO

Oxaliplatin plus S-1 (SOX) was a first-line regimen for advanced gastric cancer. The continuous administration of S-1 for 3 weeks can result in unacceptable gastrointestinal and hematological toxicities. Therefore, an alternative regimen (administration of S-1 for 1-week followed by 1-week rest) is warrant for improved tolerability and noninferiority efficacy. We conducted a study to evaluate the efficacy and safety of biweekly SOX as the first-line chemotherapy in patients with metastatic or advanced gastric cancer in China.Patients with metastatic or previously untreated advanced gastric cancer were enrolled. Oxaliplatin was administered intravenously at a dose of 85 mg/m on day 1, while S-1 was administered orally in doses of 80, 100, or 120 mg/day depending on different body surface areas of <1.25 m, 1.25-1.5 m, or >1.5 m respectively; the total dose of S-1 was administered twice daily on days 1-7 followed by a 7-day rest. This schedule was repeated every 2 weeks until disease progressed or intolerable toxicity occurred.Forty-six patients (M/F = 33/13) received biweekly oxaliplatin and S-1 as first-line chemotherapy. A total of 257 treatment cycles were administered and the median number of cycles administered was 6. Thirty-six patients (78.3%) received second-line chemotherapy. The median progression free survival and median overall survival was 4.4 months (95% CI, 3.37-5.36 months) and 10.3 months (95% CI, 8.88-11.3 months), respectively. The 1-year and 2-year survival rate was 41% and 13%. The objective response rate was 30.43%, and the disease control rate was 76.08%. The observed adverse events of Grade 3/4 included were leukocytopenia (13.04%); anemia (13.04%); neutropenia (15.22%); neurological toxicity (2.17%); diarrhea (2.17%).The biweekly SOX regimen as first-line treatment was active and well tolerated in Chinese patients with metastatic or advanced gastric cancer.


Assuntos
Oxaliplatina/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologia , Intervalo Livre de Doença , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Estômago/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/secundário , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Resultado do Tratamento
20.
Med Sci Monit ; 25: 3537-3541, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31080234

RESUMO

d_abstr_R Gastric cancer is a common malignancy with a poor prognosis, and surgical treatment remains the first-line approach to treatment to provide a cure. Despite advances in surgical techniques, radiotherapy, chemotherapy, and neoadjuvant therapy, gastric cancer remains the second leading cause of cancer death worldwide. Although the 5-year survival rate of early gastric cancer can reach >90%, due to the low early diagnosis rate, most patients present with advanced-stage gastric cancer. Therefore, there has been increasing interest in improving surgical treatment of advanced gastric cancer. Lymph node dissection is an important part of the surgical treatment of advanced gastric cancer due to the high incidence of lymph node metastasis. Although prospective studies have confirmed the safety and feasibility of laparoscopic surgery for early gastric cancer, the relevant treatment models of advanced gastric cancer still need to be further explored and validated. This review aims to provide an update on the recent advances in the surgical treatment of advanced gastric cancer.


Assuntos
Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia , Detecção Precoce de Câncer , Gastrectomia , Humanos , Laparoscopia , Excisão de Linfonodo/métodos , Metástase Linfática , Terapia Neoadjuvante , Estômago/patologia , Neoplasias Gástricas/patologia , Taxa de Sobrevida
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