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1.
Oncol Rep ; 40(4): 1843-1854, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30066899

RESUMO

Lung cancer is the most common cause of cancer­associated mortality. MicroRNAs (miRNAs), as oncogenes or tumor suppressor genes, serve crucial roles not only in tumorigenesis, but also in tumor invasion and metastasis. Although miRNA­let­7a (let­7a) has been reported to suppress cell growth in multiple cancer types, the biological mechanisms of let­7a in lung adenocarcinoma are yet to be fully elucidated. In the present study, the molecular roles of let­7a in lung adenocarcinoma were investigated by detecting its expression in lung adenocarcinoma tissues and exploring its roles in the regulation of lung cancer cell proliferation. Let­7a expression was identified to be downregulated in lung adenocarcinoma tissues compared with normal tissues. Overexpression of let­7a effectively suppressed cancer cell proliferation, migration and invasion in H1299 and A549 cells. Let­7a also induced cell apoptosis and cell cycle arrest. Furthermore, let­7a significantly inhibited cell growth by directly regulating cyclin D1 signals. This novel regulatory mechanism of let­7a in lung adenocarcinoma provides possible avenues for future targeted therapies of lung cancer.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Pontos de Checagem do Ciclo Celular , Movimento Celular , Ciclina D1/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Transdução de Sinais , Taxa de Sobrevida , Células Tumorais Cultivadas
2.
Oncotarget ; 7(18): 25576-84, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27014909

RESUMO

The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.


Assuntos
Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Quimiorradioterapia Adjuvante/métodos , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Adulto Jovem
3.
Oncol Lett ; 10(2): 810-814, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26622575

RESUMO

Zinc finger protein X-linked (ZFX) is a zinc finger transcription factor and plays a significant role in the self-renewal ability of embryonic stem cells and various cancers. However, its expression and function in colorectal cancer (CRC) remain unclear. In the present study, we evaluated the expression of ZFX in CRC using quantitative polymerase chain reaction (qPCR), western blot analysis and immunohistochemistry (IHC), and further explored its potential functions in CRC cell lines using cell counting kit-8 and Transwell invasion assays. qPCR and western blot analysis revealed that ZFX was significantly upregulated in CRC tissues; IHC further confirmed this finding, revealing that higher expression of ZFX was significantly associated with larger tumor size (P=0.01), higher pathological stage (P=0.02), depth of invasion (P=0.047), lymph node invasion (P=0.02) and higher American Joint Committee on Cancer (AJCC) stage (P=0.04). CRC patients with higher ZFX expression also exhibited significantly shorter survival times (P=0.019). Moreover, knockdown of ZFX significantly suppressed proliferation and invasion in CRC cell lines HCT116 and LoVo. These results suggest that ZFX plays a notable role in CRC tumorigenicity and may serve as a novel marker and therapeutic target for CRC.

4.
Int J Colorectal Dis ; 30(3): 337-45, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25564344

RESUMO

PURPOSE: The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS: Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate. RESULTS: Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %. CONCLUSION: These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia Adjuvante , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Neoplasias Retais/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Estudos Prospectivos , Dosagem Radioterapêutica , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia
5.
Asian Pac J Cancer Prev ; 15(16): 6559-64, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25169487

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of bevacizumab in the treatment of patients with metastatic colorectal cancer (mCRC). METHODS: In a single-center, observational study of 91 Chinese patients with mCRC who received bevacizumab in combination with chemotherapy was conducted. OBJECTIVE response rates (ORRs), progression-free survival (PFS), overall survival (OS) and adverse events were recorded, and the relationships between various clinical factors and PFS or OS were evaluated by Cox proportional hazards models. RESULTS: Treatment with bevacizumab and chemotherapy was effective and tolerable. Univariate analysis showed that PFS and OS were significantly associated with the Eastern Cooperative Oncology Group performance status (ECOG- PS) score, duration of bevacizumab exposure, and whether chemotherapy was continued after discontinuation of bevacizumab treatment. A multivariate analysis showed that the duration of bevacizumab exposure and whether chemotherapy was continued after discontinuation of bevacizumab were independent prognostic factors for PFS and OS. CONCLUSION: In Chinese mCRC population, the shorter the duration of exposure to bevacizumab and chemotherapy, the worse the prognosis is.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , China , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Resultado do Tratamento , Adulto Jovem
6.
Hepatogastroenterology ; 59(113): 159-63, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22260830

RESUMO

BACKGROUND/AIMS: The aim of this study was to determine the efficacy and acute toxicity of our early experience with treating postoperatively non-metastatic gastric cancer with intensity-modulated radiotherapy (IMRT). METHODOLOGY: A retrospective review was performed on 47 consecutive patients with gastric cancer and treated with postoperatively adjuvant IMRT at Department of radiation oncology, Zhejiang cancer hospital, China, between January 2007 and August 2009. One patient who did not complete his radiation course was excluded, leaving 46 patients for analyses. The median radiation dose delivered was 4500cGy using 180cGy fractions. Concurrent chemotherapy administered were 5-fluorouracil (n=36), capecitabine (n=9) and none (n=1). RESULTS: The median follow-up time was fifteen months (range 6-28 months). 1-year OS and 2-year OS were 98.0% and 80.0%, assessed by Kaplan-Meier methods. Of the six patients who died, five (83.3%) developed a distant metastases. The overall survival time by tumor size was significantly different (>6cm vs. =6cm, p<0.05). There was no significant survival difference between 5-fluorouracil group and capecitabine group (p=0.80). CONCLUSIONS: The data support the use of IMRT in the adjuvant treatment in high risk gastric cancer postoperatively. Acute toxicity is tolerable. Capecitabine with concurrent IMRT was as effective and tolerable as 5-FU/IMRT. Distant metastasis was the main reason of treatment failure that must be addressed in future trials.


Assuntos
Gastrectomia , Radioterapia de Intensidade Modulada , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina , Quimioterapia Adjuvante , China , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/secundário , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
7.
World J Gastroenterol ; 16(14): 1788-94, 2010 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-20380014

RESUMO

AIM: To investigate the effects of interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF) gene polymorphisms, Helicobacter pylori (H. pylori) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progression group (no histological progression from normal or superficial gastritis, n = 137), group I (progressed from normal or superficial gastritis to SCAG, n = 134) and group II (progressed from normal or superficial gastritis to IM, n = 101). IL-8, MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.


Assuntos
Citocinas/genética , Gastrite Atrófica/etiologia , Intestinos/patologia , Adulto , Idoso , Estudos de Coortes , Feminino , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Interleucina-8/genética , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Masculino , Metaplasia/etiologia , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Neoplasias Gástricas/etiologia , Adulto Jovem
8.
J Hazard Mater ; 172(2-3): 880-7, 2009 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-19695772

RESUMO

Forest landscapes represent the major land-cover type for the watersheds of the East River, which is the source of water for 40 million people in South China. Forest soils with high levels of organic carbon are a potential terrestrial source of dissolved organic carbon (DOC) into the East River. DOC is of great concern, since it can form carcinogenic disinfection byproducts (DBPs) during drinking water treatment. In this study, soils from three altitudes (200, 450 and 900 m) in the Xiangtou Mountain Nature Reserve in South China, representing soils from evergreen moon forest, transitional evergreen broadleaf forest, and evergreen broadleaf forest, respectively, were evaluated for their potential contributions of DBP precursors into the East River. The water extractable organic carbon (WEOC) in three forest soils was physically and chemically fractionated into particulate organic carbon (1.2-0.45 microm), colloidal organic carbon (0.45-0.22 microm), and dissolved organic carbon (DOC) (<0.22 microm), hydrophobic acid (HPOA), transphilic acid and hydrophilic acid and were analysed for the formation potentials of trihalomethanes (THMs), haloacetonitriles (HANs), and chloral hydrate (CHD). Also, soils were incubated at 15, 25 and 35 degrees C for 14d in darkness to examine the impact of temperature effects on the availability and characteristics of WEOC. The extraction study showed that the amount of WEOC was proportional to soil organic carbon content, of which about 1% was water extractable. Regardless of soil type, DOC and HPOA were the most reactive fractions in forming THMs, CHD, and HANs. Production of DOC and HPOA in WEOC increased over 14 d incubation as incubation temperature increased, but the temperature did not alter the distribution of physical and chemical fractions and their reactivity in DBP formation. Results suggest higher inputs of DOC and DBP precursors from forest watersheds into source water may result in a warmer environment.


Assuntos
Acetonitrilos/análise , Carbono/química , Hidrato de Cloral/análise , Poluentes do Solo/análise , Trialometanos/análise , Fracionamento Químico , Clima , Hipnóticos e Sedativos , Solo , Árvores
9.
Ai Zheng ; 28(7): 762-7, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19624906

RESUMO

BACKGROUND AND OBJECTIVE: The roles of vascular endothelial growth factor (VEGF) in tumor angiogenesis is related with Ets family. Elf-1, a member of Ets family, has seldom been studied. This study aimed to investigate the expression of Elf-1 and VEGF in non-small cell lung cancer (NSCLC), and explore their correlations to clinicopathologic features of NSCLC. METHODS: Tissue microarray containing 69 specimens of NSCLC and six specimens of normal lung tissues was constructed. The expression of Elf-1 and VEGF was detected by PowerVision-9000 immunohistochemistry. RESULTS: Elf-1 and VEGF were not detected in all normal tissues; the positive rates of Elf-1 and VEGF were 72.46% and 63.77% in NSCLC, respectively. The expression levels of both Elf-1 and VEGF were significantly related with tumor differentiation, lymphatic metastasis, clinical stage, and postoperative survival time (all P < 0.01). Overexpression of them was related with poor prognosis: the survival rates were significantly lower in positive patients than in negative patients (both P < 0.01). Elf-1 expression was positively correlated to VEGF expression (r = 0.702, P < 0.01). CONCLUSIONS: The expression of Elf-1 and VEGF in NSCLC is related to differentiation, lymphatic metastasis, clinical stage and prognosis. Detecting their expression in combination can help to predict the malignant behavior of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida
10.
Zhonghua Wei Chang Wai Ke Za Zhi ; 11(3): 238-40, 2008 May.
Artigo em Chinês | MEDLINE | ID: mdl-18478467

RESUMO

OBJECTIVE: To evaluate the efficacy of preoperative radiochemotherapy and investigate the influencing factors in rectal cancer. METHODS: Fifty-three patients with locally advanced rectal cancer were treated with radiochemotherapy before surgery. Three-field technique of radiation therapy was administered with 46 Gy, 2 Gy per fraction, five times a week. Two cycles of chemotherapy were carried out at day 1, 2 and day 21, 22 during the radiation course. Surgery was performed 4-6 weeks after the radiochemotherapy. Response of preoperative radiochemotherapy was evaluated in all the patients by endoscopic ultrasonography (EUS), spiral computed tomography (SCT) and pathology. Influencing factors of the efficacy of radiochemotherapy were evaluated by univariate and Logistic analysis. RESULTS: Univariate analysis revealed that tumor size and histological grading were associated with the efficacy of preoperative radiochemotherapy. Logistic regression analysis showed that only tumor size was the significant predictive factor for response to preoperative radiochemotherapy. All patients underwent surgical resection after preoperative radiochemotherapy. The tumor was reduced by an average of 32.1%. T-level down-staging was 64.2%. Nodal negativity was 58.1%. Complete pathologic remission occurred in 11 patients. CONCLUSIONS: Preoperative radiochemotherapy can shrink the primary tumor and decrease lymph node metastasis rate. Patient with small tumor may have better response to preoperative radiochemotherapy.


Assuntos
Quimioterapia Adjuvante , Terapia Neoadjuvante , Radioterapia Adjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/terapia , Resultado do Tratamento , Adulto Jovem
11.
World J Gastroenterol ; 14(13): 2110-4, 2008 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-18395916

RESUMO

AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC. METHODS: One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method. RESULTS: Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression (P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging I + II + III (35.7% vs 65.2%, P = 0.0027). CONCLUSION: GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging I + II + III. Over-expression of CTGF in human GC cells results in an increased aggressive ability.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas Imediatamente Precoces/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fator de Crescimento do Tecido Conjuntivo , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/mortalidade , Fatores de Tempo , Resultado do Tratamento
12.
Mol Pharmacol ; 73(4): 1195-202, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18162605

RESUMO

In the mammalian cortex, alpha2 subunit-containing glycine receptors (GlyRs) mediate tonic inhibition, but the precise functional role of this type of GlyRs is difficult to establish because of the lack of subtype-selective antagonist. In this study, we found that cyclothiazide (CTZ), an epileptogenic agent, potently inhibited GlyR-mediated current (I(Gly)) in cultured rat hippocampal neurons. The inhibition was glycine concentration-dependent, suggesting a competitive mechanism. Note that GlyRs containing the alpha2 but not alpha1 or alpha3 subunits, when being heterologously expressed in human embryonic kidney 293T cells, were inhibited by CTZ, indicating subunit specificity of CTZ action. In addition, the degree of CTZ inhibition on I(Gly) in rat spinal neurons declined with time in culture, in parallel with a decline of alpha2 subunit expression, which is known to occur during spinal cord development. Furthermore, site-directed mutagenesis indicates that a single-amino acid threonine at position 59 near the N terminus of the alpha2 subunit confers the specificity of CTZ action. Thus, CTZ is a potent and selective inhibitor of alpha2-GlyRs, and threonine at position 59 plays a critical role in the susceptibility of GlyR to CTZ inhibition.


Assuntos
Anti-Hipertensivos/farmacologia , Benzotiadiazinas/farmacologia , Receptores da Glicina/antagonistas & inibidores , Animais , Linhagem Celular , Células Cultivadas , Hipocampo/efeitos dos fármacos , Hipocampo/embriologia , Hipocampo/metabolismo , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Proteínas Mutantes/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Picrotoxina/farmacologia , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores da Glicina/metabolismo , Especificidade por Substrato/efeitos dos fármacos , Taurina/farmacologia , Treonina
13.
Zhonghua Wai Ke Za Zhi ; 45(7): 455-8, 2007 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-17686300

RESUMO

OBJECTIVE: To investigate the effect of enterostomy in treatment of locally advanced rectal carcinoma patients with combined chemoradiotherapy and operation. METHODS: Clinical data from 51 cases of locally advanced rectal cancer patients treated with preoperative chemoradiotherapy and operation were analyzed. RESULTS: Thirty-three patients (64.9%) got staging down of their cancer after preoperative chemoradiotherapy, and 21.6% of patients (11 cases) had complete pathologic response. Thirty-seven patients received enterostomy, including extraperitoneal sigmoidostomy (29 cases), defunctioning ileostomy (8 cases) and double colostomy (3 cases with colon obstruction during preoperative therapy). One case experienced parastomal hernia and one stomal stenosis and 2 cases parastomal infection after enterostomy. No death of enterostomy occurred. CONCLUSION: Colostomy can reduce the pressure of obstructed intestinal tract and contribute much to the preoperative chemoradiotherapy, ileostomy can protect the distal stoma from leakage in sphincter saving operation. Enterostomy could be selected when needed in the favor of locally advanced rectal cancer patients.


Assuntos
Enterostomia/métodos , Neoplasias Retais/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Enterostomia/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Reto/efeitos dos fármacos , Reto/efeitos da radiação , Reto/cirurgia , Resultado do Tratamento
14.
Neurosci Lett ; 416(3): 211-6, 2007 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-17368719

RESUMO

In the present study, we used both histidine decarboxylase-deficient (HDC-KO) mice and wild-type (WT) mice to elucidate the possible role of carnosine in pentylenetetrazol (PTZ)-induced seizures. In the acute PTZ challenge study, PTZ (75 mg/kg) was injected intraperitoneally (i.p.) to induce seizures. Carnosine (200, 500 or 1000 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latency for myoclonic jerks in WT mice in a dose-dependent manner. The effects of carnosine (500 mg/kg) were time-dependent and reached a peak at 1h. However, it had no significant effect on HDC-KO mice. Carnosine (500 mg/kg) also significantly elevated the thresholds in WT mice but not HDC-KO mice following intravenous (tail vein) administration of PTZ. We also found that alpha-fluoromethylhistidine substantially reversed the protective effects of carnosine in WT mice. In addition, carnosine pretreatment reduced the cortical EEG activity induced by PTZ (75 mg/kg, i.p.). These results indicate that carnosine can protect against PTZ-induced seizures and its action is mainly through the carnosine-histidine-histamine metabolic pathway. This suggests that carnosine may be an endogenous anticonvulsant factor in the brain and may be used as a new antiepileptic drug in the future.


Assuntos
Anticonvulsivantes/uso terapêutico , Carnosina/uso terapêutico , Histamina/fisiologia , Histidina Descarboxilase/deficiência , Convulsões/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Interações de Medicamentos , Eletroencefalografia/métodos , Inibidores Enzimáticos/farmacologia , Masculino , Metilistidinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pentilenotetrazol , Tempo de Reação/efeitos dos fármacos , Convulsões/induzido quimicamente , Fatores de Tempo
15.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 35(4): 411-8, 2006 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16924706

RESUMO

OBJECTIVE: To evaluate protective effect of minocycline,a semisynthetic tetracycline derivative on different traumatic brain injuries in rats and mice. METHODS: The opened brain trauma was induced in rats and the closed head injury and cold brain injury were induced in mice. In 3 brain trauma models, minocycline (45 mg/kg, ip) was administered twice daily for 2 d before the operation, at 30 min before and 1 h after the operation, and once daily for 2 d following the operation (totally 8 doses in 5 d). After the operation, the behavioral alteration was observed daily, lesion area and survival neuron density were measured at the end of the experiments (14 d after the injuries). RESULT: For rat opened traumatic injury, minocycline promoted the recovery of hindlimb motor activity (inclined board angle), but did not alter other indexes. For mouse closed head traumatic injury, minocycline reduced the neuron loss, but did not improve behavioral dysfunction. For mouse cold injury-induced trauma, minocycline reduced death rate and lesion area, but did not remarkably improve behavior and neuron loss. CONCLUSION: Minocycline only has an incomplete neuroprotective effect on different brain traumatic injuries in rats and mice.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Minociclina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-Dawley
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 35(4): 419-23, 2006 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16924707

RESUMO

OBJECTIVE: To investigate effect of chronic transauricular kindled seizures on passive-avoidance test memory retention in rats. METHODS: Chronic transauricular kindled seizures was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. A passive avoidance test was used to measure memory retention ability. Morphological changes in neurons of hippocampal CA1 region was examined after HE staining. Histamine, gamma-aminobutyric acid (GABA) and glutamate levels in the hippocampus were measured by high performance liquid chromatography (HPLC). RESULT: Chronic transauricular kindled seizures impaired passive-avoidance test memory retention in rats. The damaged CA1 neurons were observed and histamine content in the hippocampus markedly decreased 24 h after the end of kindling in the chronic transauricular kindled rats. CONCLUSION: Chronic transauricular kindled seizure impaired passive-avoidance test memory retention, and it might be due to the damaged CA1 neurons and a decrease of histamine in the hippocampus induced by epilepsy.


Assuntos
Aprendizagem da Esquiva , Hipocampo/patologia , Excitação Neurológica , Transtornos da Memória/etiologia , Convulsões/fisiopatologia , Animais , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Histamina/metabolismo , Masculino , Transtornos da Memória/fisiopatologia , Ratos , Ratos Sprague-Dawley , Convulsões/metabolismo , Convulsões/patologia , Ácido gama-Aminobutírico/metabolismo
17.
Yao Xue Xue Bao ; 41(4): 333-7, 2006 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-16856478

RESUMO

AIM: To determine the effect of histamine on ischemia-induced cellular edema and viability reduction in rat hippocampal slices, and the involved subtypes of histamine receptor in this effect. METHODS: In vitro ischemic injury of hippocampal slices was induced by oxygen-glucose deprivation (OGD). The slice injury was determined by real-timely measuring the changes of light transmittance (LT) for the cellular edema in CA1 region of the hippocampal slice, and by detecting the product of 2, 3, 5-triphenyltetrazolium chloride (TTC), formazan, for the slice viability. The effect of histamine at various concentrations on the slice injury was observed, and the blockage by antagonists of histamine receptors was also investigated. RESULTS: Histamine (0.01-10 micromol x L(-1)) inhibited the peak value of LT during OGD in hippocampal slices and improved the reduced viability after OGD. Diphenhydramine (0.1-10 micromol x L(-1)), an H1 receptor antagonist, did not affect the effect of histamine, while cimetidine (0.1-10 micromol x L(-1)), an H2 receptor antagonist, partly abolished the protective effect of histamine. CONCLUSION: Histamine protects hippocampal slices against ischemia-induced cellular edema and viability reduction; this effect might be mediated via, at least partly, H2 receptor.


Assuntos
Hipocampo/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H2/farmacologia , Histamina/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Cimetidina/farmacologia , Difenidramina/farmacologia , Formazans/metabolismo , Glucose/deficiência , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Ratos , Ratos Sprague-Dawley
18.
Acta Pharmacol Sin ; 26(12): 1448-53, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16297342

RESUMO

AIM: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. METHODS: An 8-arm radial maze (4 arms baited) was used to assess spatial memory. RESULTS: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 microg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 microg/site, ih) and the H2 antagonist cimetidine (2.5 microg/site, ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. CONCLUSION: The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.


Assuntos
Hipocampo/fisiopatologia , Histamina/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/fisiopatologia , Animais , Cimetidina/farmacologia , Maleato de Dizocilpina , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Histamina/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H2/farmacologia , Histidina/administração & dosagem , Histidina/farmacologia , Injeções Intraventriculares , Masculino , Transtornos da Memória/induzido quimicamente , Pirilamina/farmacologia , Ratos , Ratos Sprague-Dawley
19.
Acta Pharmacol Sin ; 26(11): 1297-302, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16225750

RESUMO

AIM: To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. METHODS: Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and gamma-amino-butyric acid levels were measured by high performance liquid chromatography (HPLC). RESULTS: Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no ameliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures. CONCLUSION: Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.


Assuntos
Encéfalo/metabolismo , Carbamazepina/farmacologia , Histidina/farmacologia , Transtornos da Memória , Convulsões , Animais , Anticonvulsivantes/farmacologia , Tronco Encefálico/metabolismo , Sinergismo Farmacológico , Hipocampo/metabolismo , Histamina/metabolismo , Hipotálamo/metabolismo , Excitação Neurológica , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Ratos , Ratos Sprague-Dawley , Convulsões/etiologia , Convulsões/metabolismo , Convulsões/fisiopatologia
20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 8(2): 125-8, 2005 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16155821

RESUMO

OBJECTIVE: To explore the effect of combined preoperative chemotherapy with radiotherapy on locally advanced lower rectal carcinoma. METHODS: Thirty- five patients with locally advanced lower rectal carcinoma were received a new regimen of combined preoperative chemotherapy with radiotherapy. Routine fr action of radiation was given with total dose of 46 Gy,2 Gy per fraction,five ti mes a week. Patients received oxaliplatin 130 mg/m(2) (infusion) on day 1, plus leu novorin 200 mg/m(2) and 5- FU 500 mg/m(2)(intravenous bolus) from day 1 to day 3 eve ry 3 weeks for total two cycles before irradiation. Operation was performed 4 to 6 weeks later after neoadjuvant therapy. RESULTS: After neoadjuvant therapy,all patients underwent surgical resection with complete pathologic response in 7 patients,average tumor size decrease of in 34.4%, tumor stage decrease in 65.7% o f patients and nodal- negative change rate of 55.6%. Radical resection was per formed in 34 patients,in whom 18 patients received abdominoperineal resection(AP R) and 16 patients received sphincter- preserving surgery with 45.7% of anal preservation rate. One patient received palliative resection. No local recurrence occurred in all patients who received radical resection,but two cases had liver metastasis. CONCLUSION: Combined preoperative chemotherapy with radiotherapy is a better neoadjuvant therapy for lower advanced rectal cancer,which can decrease tumor stage,improve resectability and anal sphincter preservation rate,therefore ,this new neoadjuvant therapy with tolerable toxicity will has a promising application in the clinical setting.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Resultado do Tratamento
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