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1.
Eur Rev Med Pharmacol Sci ; 24(1): 428-433, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31957857

RESUMO

OBJECTIVE: To explore the influences of propofol on the proliferation and apoptosis of cardia cancer cells via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. PATIENTS AND METHODS: A total of 65 surgical resection specimens of cardia cancer were selected as research objects and divided into control group and with low (12.5 µmol/L), medium (25 µmol/L), and high (50 µmol/L) propofol concentration groups. The apoptosis of cancer cells, ERK1/2 phosphorylation level, expressions of Caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) in each group were detected. RESULTS: Propofol in different concentrations could all effectively inhibit the proliferation of cardia cancer cells in a dose-dependent manner. Different concentrations of propofol promoted the apoptosis of cardia cancer cells, and the apoptosis rate constantly increased with the rising concentration of propofol (p<0.05). Propofol could repress the expression of Bcl-2 and up-regulate the expression levels of Caspase-3, Bax, and phosphorylated ERK1/2. CONCLUSIONS: Propofol can inhibit the proliferation and induce the apoptosis of cardia cancer cells, and the action mechanism may be correlated with the inhibition on the MAPK/ERK signaling pathway.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cárdia/efeitos dos fármacos , Propofol/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Cárdia/metabolismo , Cárdia/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
2.
J Gastrointest Cancer ; 50(4): 907-912, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30402826

RESUMO

PURPOSE: The optimal treatment for locally advanced GEJ and cardia adenocarcinoma is controversial. Several studies have shown that treating these patients with neoadjuvant chemoradiotherapy followed by surgery leads to survival benefits, and there are also studies that have declared conflicting results. It seems that there is still room for discussion. We calculated the survival rates and pathologic responses in our patients with characteristics which we mentioned above. METHODS: Patients with locally advanced, non-metastatic GEJ and cardia adenocarcinomas (only patients with Siewert's type I and II), who were referred to Imam Khomeini hospital (Institute of cancer) between 2005 and 2014 and received neoadjuvant chemoradiation and underwent surgery were enrolled in this retrospective cohort study. Evaluations were done every 3 months. RESULTS: Thirty-two patients enrolled in this study. Median follow up time was 23 months (Reverse Kaplan-Meier method). The rates of 1-year survival, 2-year survival, 3-year survival, 4-year survival, and 5-year survival were 75%, 52%, 52%, 37%, and 37%, respectively. No local recurrences occurred among patients; however, four patients experienced distal recurrence in the following locations: two cases (6.3%) in the liver, one case (3.1%) in the lung, and one case (3.1%) in the peritoneum. The rate of complete pathologic response (T0N0) was 21.9%. CONCLUSIONS: Neoadjuvant chemoradiation in patients with locally advanced GEJ and cardia adenocarcinoma will lead to a survival benefit.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cárdia/efeitos dos fármacos , Cárdia/patologia , Cárdia/efeitos da radiação , Cárdia/cirurgia , Intervalo Livre de Doença , Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/patologia , Mucosa Esofágica/efeitos da radiação , Mucosa Esofágica/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia , Junção Esofagogástrica/efeitos dos fármacos , Junção Esofagogástrica/patologia , Junção Esofagogástrica/efeitos da radiação , Junção Esofagogástrica/cirurgia , Feminino , Seguimentos , Gastrectomia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/efeitos da radiação , Mucosa Gástrica/cirurgia , Humanos , Irã (Geográfico)/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida
3.
Med Oncol ; 31(3): 858, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24477652

RESUMO

The relationship between the development of gastric cardia cancer (GCA) and alcohol consumption remains unclear. Alcohol flushing response reflects an accumulation of the carcinogenic acetaldehyde and has been proved to be a risk factor for many cancers. The main objective of the present study was to assess the impact of alcohol flushing response on GCA risk in a Chinese population in conjunction with lifetime alcohol consumption. The study subjects consist of 281 male patients [130 with GCA and 151 with esophageal squamous cell carcinoma (ESCC)] and 160 non-cancer male controls, matched with respect to age. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CI). There is no significant association between GCA risk and alcohol consumption. However, the adjusted ORs for flushing response of GCA and ESCC was 2.03 (95% CI 1.15-3.56, p=0.014) and 2.32 (95% CI 1.34-4.03, p=0.003), respectively, compared with those reporting no flushing response. Furthermore, compared with non-drinkers, the heavy drinkers and moderate drinkers with current/former flushing response experienced significant GCA risk (heavy drinkers: OR 2.59, 95% CI 1.06-6.31, p=0.037; moderate drinkers: OR 3.11, 95% CI 1.17-8.26, p=0.023), while drinkers without flushing response did not have increased risk. The drinkers with flushing response also had a higher ESCC risk than those without flushing response. In conclusion, alcohol flushing response is a clinically useful biomarker of susceptibility to GCA and ESCC risk from alcohol.


Assuntos
Consumo de Bebidas Alcoólicas , Cárdia/efeitos dos fármacos , Neoplasias Esofágicas/induzido quimicamente , Rubor/complicações , Rubor/fisiopatologia , Neoplasias Gástricas/induzido quimicamente , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/patologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Fatores de Risco , Neoplasias Gástricas/patologia
4.
Intern Med ; 49(20): 2195-202, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20962437

RESUMO

BACKGROUND: Rikkunshito, a traditional Japanese (Kampo) medicine, is widely prescribed as an oral preparation for the treatment of functional dyspepsia (FD). In our previous study, we reported that extracorporeal ultrasonography (US) is a useful technique for the assessment of the gastric accommodation reflex (AR) and duodenogastric motility. In this study, we examined the effects of Rikkunshito on the gastroduodenal function in patients with FD. METHODS: Sixteen FD patients (median age, 45 y) underwent US, before and after 14 days of treatment with Rikkunshito (7.5 g b.d.). For assessment of the AR, a cross-sectional area of the proximal stomach was measured after incremental ingestion of a liquid meal up to 400-mL. The expansion rate was used as the parameter to determine the AR. Then, the gastric emptying rate (GER), motility index (MI), and reflux index (RI) were evaluated using previously reported methods. RESULTS: Although no significant changes were observed in the total score of the Gastrointestinal Symptom Rating Scale (GSRS), the scores of 3 of the 15 symptoms of GSRS decreased significantly after treatment with Rikkunshito. The expansion rate of the proximal stomach was significantly greater after treatment with Rikkunshito than before the treatment. Although the GER and MI increased significantly, no significant differences in the RI were observed after treatment with Rikkunshito. CONCLUSION: These observations suggested that Rikkunshito may be beneficial for the treatment of FD patients with impaired AR and gastric motility. These results also suggested that Rikkunshito has a therapeutic potential for FD and GERD.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dispepsia/tratamento farmacológico , Gastroparesia/tratamento farmacológico , Medicina Kampo , Fitoterapia , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Adulto , Idoso , Cárdia/diagnóstico por imagem , Cárdia/efeitos dos fármacos , Cárdia/fisiopatologia , Dispepsia/diagnóstico por imagem , Dispepsia/fisiopatologia , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Refluxo Gastroesofágico/diagnóstico por imagem , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/fisiopatologia , Motilidade Gastrointestinal/efeitos dos fármacos , Gastroparesia/diagnóstico por imagem , Gastroparesia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/efeitos dos fármacos , Período Pós-Prandial , Reflexo Anormal/efeitos dos fármacos , Índice de Gravidade de Doença , Ultrassonografia Doppler em Cores
5.
Ann Surg Oncol ; 17(2): 470-5, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19859771

RESUMO

BACKGROUND: Placement of self-expanding stents is an effective palliation for dysphagia in non-resectable oesophageal or proximal gastric cancer. The aim of this analysis was to assess the efficacy of temporary stent placement for dysphagia relief during neo-adjuvant treatment for locally advanced disease. METHODS: A total of 38 patients scheduled for neo-adjuvant chemo(radio)therapy for locally advanced oesophageal cancer (n = 29), cardia cancer (n = 8) or subcardial gastric cancer (n = 1) underwent placement of self-expanding plastic stents (n = 13) or covered metal stents (n = 25) due to severe dysphagia and weight loss. RESULTS: Instant dysphagia relief was achieved in 37 (97.4%) of 38 patients. Dysphagia scores declined from mean 3.0 +/- 0.7 before stent placement to 0.6 +/- 0.9 at restaging. After completion of the neo-adjuvant therapy 20 (52.6%) of the 38 patients underwent resection of the tumour, 5 patients (13.2%) underwent primary resection without receiving chemotherapy while 12 patients (31.6%) did not undergo surgery. Stent-related complications were observed as perforation (n = 1), mediastinitis (n = 1), tracheo-oesophageal fistula (n = 2), bleeding (n = 1) and jejunal perforation caused by a migrated stent (n = 1). Serum albumin significantly decreased in patients with progressive disease despite successful stenting (40.0 +/- 4.9 mg/dl versus 29.7 +/- 6.4 mg/dl, p < 0.05) while stable albumin levels were found in patients who underwent surgery (39.9 +/- 4.3 mg/dl versus 39.1 +/- 3.8 mg/dl, p = 0.484). CONCLUSION: Placement of self-expanding stents is highly effective for instant dysphagia relief, enabling adequate oral nutrition during neo-adjuvant therapy, but is limited by a high re-intervention rate.


Assuntos
Adenocarcinoma/terapia , Transtornos de Deglutição/cirurgia , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante , Neoplasias de Células Escamosas/terapia , Cuidados Paliativos , Stents , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cárdia/efeitos dos fármacos , Cárdia/efeitos da radiação , Cárdia/cirurgia , Terapia Combinada , Transtornos de Deglutição/etiologia , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/patologia , Dosagem Radioterapêutica , Taxa de Sobrevida , Resultado do Tratamento
6.
J Environ Pathol Toxicol Oncol ; 27(3): 219-32, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18652569

RESUMO

The present study reports aqueous Azadirachta indica leaf extract (AAILE)-mediated induction of apoptosis in a murine forestomach tumorigenesis model. Histochemistry-based quantification of apoptosis revealed enhanced apoptotic index in the forestomach tumors of mice receiving AAILE along with benzo(a)pyrene (B(a)P). Transmission electron microscopy confirmed the presence of classical morphological features of apoptosis including chromatin condensation/marginalization, nuclear fragmentation, and formation of apoptotic bodies. Scanning electron microscopy showed surface modifications on the transformed squamous epithelial cells and certain mitotic cells among them over the forestomach tumors of mice receiving only B(a)P. In tumors of the mice receiving AAILE along with B (a)P, such mitotic cells were found to be absent; however, certain cells showing shrinkage and blebbings (characteristics of apoptosis) were observed. DNA fragmentation was observed to increase exclusively in the tumors of mice that received AAILE along with B(a)P. Lipid peroxidation (LPO) levels decreased in forestomach tissues of mice in all the groups studied when compared to control counterparts. However, levels of LPO were found to increase in the tumorous tissue of mice that received AAILE along with B(a)P when compared to mice receiving only B(a)P. Taken together, observations of the present study suggest that A. indica induces apoptosis in B(a)P-induced murine forestomach tumors.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Azadirachta/química , Cárdia/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias Gástricas/patologia , Animais , Benzo(a)pireno/toxicidade , Carcinógenos/toxicidade , Cárdia/metabolismo , Cárdia/patologia , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/ultraestrutura , Imuno-Histoquímica , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Folhas de Planta/química , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/tratamento farmacológico
8.
Cancer Epidemiol Biomarkers Prev ; 17(1): 126-34, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18187391

RESUMO

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use has been associated with a reduced risk of colon cancer; further epidemiologic data appear consistent for stomach and esophageal adenocarcinomas. Yet, data on potential confounding effects by upper gastrointestinal tract (UGI) disorders on adenocarcinomas of the UGI are limited. METHODS: This study recruited newly diagnosed patients with esophageal adenocarcinoma (n = 220), gastric cardia adenocarcinoma (n = 277), or distal gastric adenocarcinoma (n = 441) as well as 1,356 control subjects in Los Angeles County. Unconditional multivariable logistic regression analyses were done to evaluate the association between regular NSAID use, at least two pills per week for 1 month, and these cancers. RESULTS: Duration of regular use of aspirin and non-aspirin NSAIDs was associated with reduced relative odds of distal gastric adenocarcinoma [>5 years use versus no regular use: odds ratio (OR), 0.61; 95% confidence interval, 0.40-0.92; P(trend) = 0.009] and esophageal adenocarcinoma (OR, 0.60; 95% confidence interval, 0.38-0.95; P(trend) = 0.04) in multivariable models that included history of UGI disorders and other potential confounding factors. Daily regular use was also associated with statistically significant reduced ORs of these two tumor types. No significant heterogeneity in risk estimates was noted after stratification by history of UGI disorders for any of the sites studied. However, irregular users of NSAIDs also had reduced risk of these cancers when compared with nonusers. CONCLUSIONS: Results from this study support an inverse association between regular NSAID use and risk of esophageal and distal gastric adenocarcinomas in individuals with and without a history of UGI disorders with long duration and daily use, providing the greatest risk reduction. Reduced risk in irregular users suggests that factors other than an effect on cyclooxygenase may also be important.


Assuntos
Adenocarcinoma/epidemiologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Neoplasias Esofágicas/epidemiologia , Neoplasias Gástricas/epidemiologia , Adenocarcinoma/etiologia , Adulto , Idoso , Cárdia/efeitos dos fármacos , Cárdia/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/etiologia , Feminino , Humanos , Los Angeles/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Gástricas/etiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-17500043

RESUMO

Potential humoral factors controlling an intestinal brake mechanism in Chinook salmon were characterised in terms of their effect on frequency and amplitude of spontaneous contractions in gastrointestinal (GI) rings. Concentration-response curves of gut contractility were produced for cholecystokinin-8 (CCK-8), gastrin-1, glucagon-like peptide-1 (GLP-1) and 5-hydroxytryptamine (5-HT) using gut rings from cardiac stomach (CS), pyloric stomach (PY), pyloric sphincter (Psp) and intestine (Int). Calculated log10 molar (M) EC50 values for CCK-8 (n=7) were: CS -8.15+/-0.90, PY -7.88+/-0.48, Psp -8.98+/-0.68, Int -8.93+/-0.64. Log10 M EC50 values calculated for gastrin 1 (n=7) were: CS -12.45+/-0.66, PY -12.55+/-0.63, Psp -9.35+/-0.78, Int -12.69+/-1.12. Log10 M EC50 values calculated for 5-HT (n=6) were: CS -4.78+/-1.05 and Psp -6.18+/-1.14. GLP -1 (n=4) produced no response in any of the tissues examined. Spontaneous contractions, measured as spikes per minute and the peak force generated were also measured for each hormone-tissue combination. The Psp generated the greatest mass-specific force, with stomach rings generating the least force. Dilutions of serum from fish diagnosed with gastric dilation air sacculitis (GDAS +ve) increased gut contractility compared to controls (GDAS -ve).


Assuntos
Fármacos Gastrointestinais/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Serotonina/farmacologia , Sincalida/farmacologia , Animais , Cárdia/efeitos dos fármacos , Cárdia/fisiologia , Relação Dose-Resposta a Droga , Motilidade Gastrointestinal/fisiologia , Técnicas In Vitro , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Piloro/efeitos dos fármacos , Piloro/fisiologia , Salmão
10.
Dig Dis Sci ; 52(9): 2178-82, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17436103

RESUMO

The etiology of inflammation of the gastric cardia (carditis) is controversial, and gastroesophageal reflux disease (GERD) and H. pylori infection have been proposed as etiological factors. This study aimed to investigate the effect of acid suppression on histological changes in the gastric cardia. Gastric cardia biopsies of reflux patients were evaluated at baseline and after proton pump inhibitor (PPI) therapy. The updated Sydney classification was used to score the biopsies, and carditis scores (pre- and post-PPI therapy) were compared. A total of 31 patients were included, of which 5 patients were excluded, as cardiac mucosa was not documented in either pre- or post-PPI biopsies. The mean duration of PPI therapy was 30 months (SE, 3.04 months). There was no significant change in carditis scores post-PPI therapy. The mean mononuclear and neutrophil scores were 1.23 and 0.35 pre-PPI therapy and 1.73 and 0.62 post-PPI therapy, respectively. No change in mean intestinal metaplasia and atrophy scores was identified. In conclusion, acid suppressive therapy with PPI did not lead to a significant reduction in carditis scores. These results suggest that GERD probably does not play a major role in the pathogenesis of inflammation in the gastric cardia.


Assuntos
Cárdia/patologia , Inibidores Enzimáticos/uso terapêutico , Gastrite/tratamento farmacológico , Inibidores da Bomba de Prótons , Idoso , Idoso de 80 Anos ou mais , Biópsia , Cárdia/efeitos dos fármacos , Endoscopia Gastrointestinal , Feminino , Seguimentos , Gastrite/patologia , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Estudos Retrospectivos , Resultado do Tratamento
11.
Ann Oncol ; 17(1): 29-34, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16303863

RESUMO

PURPOSE: The synergic combination of oxaliplatin and capecitabine has demonstrated activity against various gastrointestinal cancers, including colon cancer. We therefore undertook this phase II study to test this first-line combination in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia. PATIENTS AND METHODS: Forty-three patients with histologic or cytologic confirmation of the above malignancy were recruited. The cohort had Eastern Cooperative Oncology Group performance statuses of 0, 1 and 2 in 47%, 51%, and 2%, respectively. Median age was 61 years (range 32-80). All had adequate organ function. Initially, patients were prescribed 130 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice a day, on days 1-14 of a 21-day cycle. Four treatment-related deaths in the first 24 patients led to a reduction in capecitabine to 850 mg/m2 orally twice a day, days 1-14, for the remainder of the cohort. RESULTS: The tumor response rate was 35% [95% confidence intervals (CI) 23% to 50%]. All responses were partial; seven of 24 occurred before the capecitabine dose reduction, and eight of 19 after. Median time to tumor progression was 4 months (95% CI 3.1-4.6), and median survival 6.4 months (95% CI 4.6-10). To date, there have been 36 deaths. Four were treatment-related (one infection, two myocardial infarctions, one respiratory failure), and all occurred before the capecitabine dose reduction. Notable grade 4 events from the entire cohort included diarrhea (two patients), vomiting (three), dyspnea (one), thrombosis (two) and anorexia (two). Grade 3 events included nausea (12 patients), diarrhea (12), fatigue (10), abdominal pain (seven), vomiting (six), dyspnea (six), hypokalemia (six), dehydration (five), hypokalemia (five) and infection (four). CONCLUSIONS: Oxaliplatin and capecitabine in combination demonstrates activity in metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia. The lower dose (capecitabine 850 mg/m2 orally twice a day, days 1-14, and oxaliplatin 130 mg/m2 intravenously on day 1) yielded an acceptable toxicity profile and merits further study.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cárdia/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina , Cárdia/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Relação Dose-Resposta a Droga , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Feminino , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Resultado do Tratamento
13.
Naunyn Schmiedebergs Arch Pharmacol ; 370(1): 35-45, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15235762

RESUMO

Two tachykinin peptides, bufokinin and Xenopus neurokinin A (X-NKA) were recently isolated from Xenopus laevis. In this study we investigated the tachykinin receptors in the Xenopus gastrointestinal tract. In functional studies using stomach circular muscle strips, all peptides had similar potencies (EC50 values 1-7 nM). The rank order of potency to contract the intestine was physalaemin (EC50 1 nM)> or =bufokinin (EC50 3 nM)>substance P (SP)> or =cod SP>NKA>>X-NKA (EC50 1,900 nM). No maximum response could be obtained for [Sar9,Met(O2)11]SP, eledoisin and kassinin. In stomach strips, the mammalian tachykinin receptor antagonists RP 67580 (NK1) and MEN 10376 (NK2) had agonistic effects but did not antagonize bufokinin or X-NKA. In intestinal strips, RP 67580 (1 microM) reduced the maximal response to X-NKA but not bufokinin, while MEN 10376 was ineffective. [125I]BH-bufokinin bound with high affinity to a single class of sites, of KD 213+/-35 (stomach) and 172+/-9.3 pM (intestine). Specific binding of [125I]BH-bufokinin was displaced by bufokinin> or =SP>NKA> or =eledoisin approximately kassinin>X-NKA, indicating binding to a tachykinin NK1-like receptor. Selective tachykinin receptor antagonists were weak or ineffective. Other iodinated tachykinins ([125I]NKA and [125I]BH-eledoisin) displayed biphasic competition profiles, with the majority of sites preferring bufokinin rather than X-NKA. In conclusion, there is evidence for two different tachykinin receptors in Xenopus gastrointestinal tract. Both receptors may exist in stomach, whereas the bufokinin-preferring NK1-like receptor predominates in longitudinal muscle of the small intestine. Antagonists appear to interact differently with amphibian receptors, compared with mammalian receptors.


Assuntos
Neurocinina A/análogos & derivados , Fisalemina/análogos & derivados , Receptores de Taquicininas/química , Receptores de Taquicininas/efeitos dos fármacos , Especificidade da Espécie , Substância P/análogos & derivados , Xenopus/metabolismo , Animais , Sítios de Ligação/efeitos dos fármacos , Cárdia/citologia , Cárdia/efeitos dos fármacos , Cárdia/metabolismo , Relação Dose-Resposta a Droga , Eledoisina/farmacologia , Feminino , Indóis/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Intestino Delgado/citologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Radioisótopos do Iodo , Isoindóis , Cassinina/farmacologia , Masculino , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Neurocinina A/antagonistas & inibidores , Neurocinina A/química , Neurocinina A/farmacologia , Fragmentos de Peptídeos/farmacologia , Fisalemina/farmacologia , Receptores de Taquicininas/fisiologia , Substância P/farmacologia
14.
Zhonghua Zhong Liu Za Zhi ; 25(3): 289-91, 2003 May.
Artigo em Chinês | MEDLINE | ID: mdl-12839698

RESUMO

OBJECTIVE: To evaluate the therapeutic effects of hydroxycamptothecin (H) combined with leucovorin (L), fluorouracil (F) and cisplatin (P) on advanced cancer of gastric cardia and colorectal cancer. METHODS: Sixty-five patients with advanced cancer of gastric cardia or colorectal cancer were treated by LFH or LFPH regimen. All patients completed four cycles of treatment, in 21 days per cycle. RESULTS: The overall response rate (RR) was 26.2% (17/65) with partial response (PR) in 17 patients, stable disease (SD) in 31 and progressive disease (PD) in 17. The clinical benefit response rate (CR + PR + SD) was 73.8% (48/65). The RR were 32.3% (10/31) for untreated patients and 20.6% (7/34) for retreated patients. The stable rate was 47.7% (31/65). The RR of patients with cancer of gastric cardia were 33.3% (5/15) for untreated treatment and 29.4% (5/17) for retreated ones. Median survival time (MST) was 10 months. Median time to progression (MTTP) was 8 months. Grade 3 - 4 toxicities were stomatitis (10.8%), nausea and vomiting (12.3%) and leukopenia (6.2%). Most patients (> 80%) developed Grade 1 - 2 alopecia. CONCLUSION: The regimen of HCPT combined with LV, 5-Fu and DDP appears to be an effective and tolerable therapeutic option for advanced cancer of gastric cardia and colorectal cancer, especially for the former and retreated patients, giving a satisfactory stable rate though not very high.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cárdia/efeitos dos fármacos , Cisplatino/administração & dosagem , Neoplasias Colorretais/mortalidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade
15.
Microbiol Res ; 158(1): 69-75, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12608582

RESUMO

This study was designed to determine whether magnesium ion in water would influence the colonization of Helicobacter pylori in 2-week-old miniature pigs. Groups A (2 pigs) and B (1 pig) were both fed a milk diet dissolved in drinking water, Group C (2 pigs) was fed a milk diet dissolved in deionized distilled water (DDW), and Group D (1 pig) was fed a milk diet dissolved in DDW supplemented with MgCl2. Groups B, C, and D were all challenged with H. pylori, and Group A was not. Necropsy was performed on the pigs on postinfection Day 5, and biopsy specimens were taken from 16 sites of the stomach. H. pylori were recovered from 11 of 16 sites in Group B, 1 of 32 sites in Group C, and 13 of 16 sites in Group D. On the other hand, the degree of lymphocyte infiltration increased in the order of Group A < Group B < Group C < Group D. These observations suggest that magnesium ion in drinking water is essential for the colonization of H. pylori in the pig stomach. Possible mechanisms for the lymphocyte infiltration are discussed.


Assuntos
Mucosa Gástrica/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Magnésio/farmacologia , Porco Miniatura/microbiologia , Abastecimento de Água/análise , Animais , Cárdia/efeitos dos fármacos , Cárdia/microbiologia , Cárdia/patologia , Contagem de Colônia Microbiana/métodos , Fundo Gástrico/efeitos dos fármacos , Fundo Gástrico/microbiologia , Fundo Gástrico/patologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Helicobacter pylori/efeitos dos fármacos , Linfócitos/patologia , Masculino , Antro Pilórico/efeitos dos fármacos , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Suínos
16.
Scand J Gastroenterol ; 37(3): 253-61, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11916186

RESUMO

BACKGROUND: Dietary nitrate increases saliva nitrite levels and swallowed saliva is the main source of nitrite entering the acidic stomach. In acidic gastric juice, this nitrite can generate potentially carcinogenic N-nitrosocompounds. However, ascorbic acid secreted by the gastric mucosa can prevent nitrosation by converting the nitrite to nitric oxide. METHODS: To study the potential for N-nitrosocompound formation in a model simulating salivary nitrite entering the acidic stomach and the ability of ascorbic acid to inhibit the process. Concentrations of ascorbic acid, total vitamin C, nitrite, nitrosomorpholine, oxygen and nitric oxide were monitored during the experiments. RESULTS: The delivery of nitrite into HCl containing thiocyanate resulted in nitrosation of morpholine, with the rate of nitrosation being greatest at pH 2.5. Under anaerobic conditions, ascorbic acid converted the nitrite to nitric oxide and prevented nitrosation. However, in the presence of dissolved air, the ascorbic acid was ineffective at preventing nitrosation. This was due to the nitric oxide combining with oxygen to reform nitrite and this recycling of nitrite depleting the available ascorbic acid. Further studies indicated that the rate of consumption of ascorbic acid by nitrite added to natural human gastric juice (pH 1.5) was extremely rapid with 200 micromol/l nitrite consumed 500 micromol/l ascorbic acid within 10 s. CONCLUSIONS: The rapid consumption of ascorbic acid in acidic gastric juice by nitrite in swallowed saliva indicates that the potential for acid nitrosation will be maximal at the GO junction and cardia where nitrite first encounters acidic gastric juice. The high incidence of mutagenesis and neoplasia at this anatomical location may be due to acid nitrosation arising from dietary nitrate.


Assuntos
Junção Esofagogástrica/efeitos dos fármacos , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Ácido Ascórbico/farmacologia , Cárdia/efeitos dos fármacos , Cárdia/fisiopatologia , Suplementos Nutricionais , Interações Medicamentosas , Junção Esofagogástrica/metabolismo , Ácido Gástrico/metabolismo , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Modelos Anatômicos , Nitratos/farmacologia , Nitritos/farmacologia , Compostos Nitrosos/metabolismo , Saliva/química , Sensibilidade e Especificidade , Relação Estrutura-Atividade
17.
Int J Cancer ; 87(5): 750-4, 2000 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10925371

RESUMO

Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.


Assuntos
Adenocarcinoma/prevenção & controle , Antioxidantes/administração & dosagem , Carcinoma de Células Escamosas/prevenção & controle , Cárdia/efeitos dos fármacos , Neoplasias Esofágicas/prevenção & controle , Neoplasias Gástricas/prevenção & controle , Adenocarcinoma/epidemiologia , Idoso , Ácido Ascórbico/administração & dosagem , Carcinoma de Células Escamosas/epidemiologia , Cárdia/patologia , Estudos de Casos e Controles , Dieta , Suplementos Nutricionais , Sinergismo Farmacológico , Neoplasias Esofágicas/epidemiologia , Feminino , Refluxo Gastroesofágico/epidemiologia , Humanos , Masculino , Análise Multivariada , Estresse Oxidativo/efeitos dos fármacos , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Neoplasias Gástricas/epidemiologia , Suécia/epidemiologia , Vitamina E/administração & dosagem , beta Caroteno/administração & dosagem
18.
Hepatogastroenterology ; 41(6): 546-8, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7721241

RESUMO

This study examines the effect of different H.p. strains (A-D) on dbc-AMP stimulated acid secretion by human parietal cells in vitro. H.p. strains A and D reduced acid secretion dose-dependently between 20 and 80%. In contrast, H.p. strains B and C had little or no effect. We conclude that H.p. strains vary in their ability to suppress acid secretion, and that the site of inhibition lies beyond the c-AMP level, possibly involving the K+H(+)-ATPase of the parietal cell. Interference with acid secretion may facilitate H.p. colonization of the stomach and may prove to be an important pathogenetic factor.


Assuntos
Cárdia/metabolismo , AMP Cíclico/metabolismo , Ácido Gástrico/metabolismo , Helicobacter pylori , Células Parietais Gástricas/metabolismo , Aminopirina/farmacologia , Biópsia , Campylobacter jejuni/crescimento & desenvolvimento , Radioisótopos de Carbono/farmacocinética , Cárdia/efeitos dos fármacos , Cárdia/microbiologia , Cárdia/patologia , Contagem de Colônia Microbiana , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Omeprazol/farmacologia , Células Parietais Gástricas/efeitos dos fármacos , Células Parietais Gástricas/microbiologia
19.
Am J Vet Res ; 50(5): 751-3, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2729720

RESUMO

Gas eructation function of the gastroesophageal sphincter (GES) was investigated in 6 conscious dogs before and after a sleeve was placed around the GES and gastric cardia and during IV infusion of a beta-adrenergic amine (epinephrine). To induce eructation, nitrogen gas was insufflated (351.4 +/- 2 ml/min; mean +/- SEM) into the stomach through 1 channel of a 4-lumen catheter. After baseline studies and epinephrine infusion studies were completed in each dog, surgery was done to limit partially gastric distension by intraluminal contents by placing a silicone rubber sleeve around the GES and the first few centimeters of the cardia. Gastroesophageal sphincter pressure was 31.8 +/- 2.2 mm of Hg in baseline studies, 17.3 +/- 1.3 mm of Hg during epinephrine infusion (P. less than 0.003), and 30.3 +/- 2.2 mm of Hg after the sleeve was placed around the GES and cardia. During insufflation, gastric pressures before eructation increased to 5.74 +/- 0.41 mm of Hg before and to 15.15 +/- 1.63 mm of Hg after cardia sleeve placement (P less than 0.001). Eructation occurred at intervals of 1.83 +/- 0.41 minutes before cardia sleeve placement, and eructations were not observed with the sleeve in place. Before the sleeve was placed, administration of epinephrine resulted in an eructation interval of 0.84 +/- 0.09 minutes, which was significantly different from that in the same dogs given no drugs (P less than 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Cárdia/fisiopatologia , Doenças do Cão/fisiopatologia , Epinefrina/farmacologia , Eructação/veterinária , Junção Esofagogástrica/fisiopatologia , Animais , Cárdia/efeitos dos fármacos , Cães , Junção Esofagogástrica/efeitos dos fármacos , Feminino , Masculino
20.
Vopr Onkol ; 32(2): 56-61, 1986.
Artigo em Russo | MEDLINE | ID: mdl-3962244

RESUMO

Painting with heavy catalytic gas oil was followed by skin tumor development in 97 (84.3%) mice: benign lesions--21 and carcinoma--76 cases. Pathologic changes in the upper part of the digestive tract were found in 55 out of 106 mice (51.9%): precancerous lesions (leukoplakia, dysplasia and papilloma) in 54 cases and cancer in one animal. Frequency of development of papilloma in the cardia was 27 times that in the esophagus. Multicentric growth was typical of precancerous lesions. Papilloma of the cardia was found in one control animal. Resorptive as well as direct action of gas oil seem to have been the causative factors of the development of precancerous and neoplastic lesions of the upper part of the gastrointestinal tract. The agent found its way into the digestive tract as animals licked each other in the course of the experiments.


Assuntos
Neoplasias Esofágicas/induzido quimicamente , Petróleo/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , Absorção Cutânea/efeitos dos fármacos , Neoplasias Gástricas/induzido quimicamente , Administração Tópica , Animais , Cárdia/efeitos dos fármacos , Cárdia/patologia , Neoplasias Esofágicas/patologia , Esôfago/efeitos dos fármacos , Esôfago/patologia , Feminino , Leucoplasia/induzido quimicamente , Leucoplasia/patologia , Camundongos , Papiloma/induzido quimicamente , Papiloma/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Fatores de Tempo
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