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1.
Surg Endosc ; 36(9): 6601-6608, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35118532

RESUMO

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) has been used to remove subepithelial lesions (SELs) in recent years; however, duodenal ESD is associated with high rates of immediate or delayed bleeding and perforation. Whether ESD can be recommended for the treatment of duodenal SELs remains controversial. Therefore, we evaluated the efficacy and safety of ESD for duodenal SELs. METHODS: We conducted a retrospective cohort study in 62 patients (62 lesions) who underwent ESD for duodenal SELs between January 2012 and December 2020. The therapeutic outcomes from ESD for duodenal SELs and procedure-related complications were analyzed. RESULTS: En bloc resection and complete resection rates associated with duodenal ESD were 90.3% and 100%, respectively; four patients had a positive microscopic margin on pathologic examination. The median procedure time was 45 min (range 20-106 min). During the procedure, two patients received emergency surgery for uncontrolled bleeding and perforation, respectively. After the procedure, delayed bleeding occurred in three patients (4.8%), which was successfully managed by clipping, and delayed perforation occurred in two patients (3.2%) and needed emergency surgery. Risk factors related to complications were analyzed. Lesion size was found to be significantly associated with the complications (P = 0.028). No recurrences were detected, and no distant metastasis was observed in any patient during a median follow-up period of 45.5 months (range, 6-103 months). CONCLUSION: Duodenal ESD is relatively safe and feasible for duodenal SELs, especially for lesions no more than 2 cm in size.


Assuntos
Ressecção Endoscópica de Mucosa , Dissecação/métodos , Duodeno/cirurgia , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
2.
Pancreas ; 46(3): 323-334, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28099248

RESUMO

OBJECTIVES: The aim of this study was to determine the prognostic value of YKL-40 expression in patients undergoing curative resection of pancreatic cancer. METHODS: This cohort study included 234 consecutive patients with pancreatic ductal adenocarcinoma who underwent curative resection. Surgical specimens were immunohistochemically assessed for YKL-40 expression. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of YKL-40 expression. A multivariate logistic regression model was performed to examine the correlation between YKL-40 expression and tumor stage. RESULTS: Of the 234 patients, YKL-40 overexpression was detected in 149 (63.7%) patients. Survival curves showed that patients with YKL-40 overexpression had significantly shorter survival time than those with low YKL-40 expression (P < 0.001). Cox regression analysis indicated that YKL-40 expression was an independent prognostic factor for both overall survival (hazard ratio, 3.82; 95% confidence interval [CI], 2.38-6.13) and progression-free survival (hazard ratio, 3.73; 95% CI, 2.33-5.99). Multivariate logistic regression analysis demonstrated that YKL-40 overexpression was an independent predictor for advanced tumor stage (odds ratio 4.15; 95% CI, 1.35-12.71). CONCLUSIONS: YKL-40 overexpression predicts poor prognosis and advanced tumor stage in patients undergoing curative resection of pancreatic cancer. Application of adjuvant treatment targeting the YKL-40 pathway may improve prognosis.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Ductal Pancreático/metabolismo , Proteína 1 Semelhante à Quitinase-3/biossíntese , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Prognóstico
3.
Fitoterapia ; 83(8): 1540-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22981504

RESUMO

Six new acylphloroglucinol derivatives, sampsonols A-F (1-6), were isolated from the petroleum ether extract of the aerial parts of Hypericum sampsonii. The structures and relative configurations of sampsonols A-F were elucidated by extensive spectroscopic analyses. All these compounds were tested for their in vitro cytotoxic and anti-inflammatory activities. Sampsonols A and B (1 and 2) showed significant cytotoxicity against four human tumor cell lines with IC(50) values in the range of 13-28µM, whereas sampsonols C and F (3 and 6) showed potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with IC(50) values of 27.3 and 29.3µM, respectively.


Assuntos
Hypericum/química , Floroglucinol/análogos & derivados , Floroglucinol/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Macrófagos/efeitos dos fármacos , Modelos Moleculares , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/química
4.
Chin Med J (Engl) ; 125(16): 2878-84, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22932084

RESUMO

BACKGROUND: The role of gastro-protecting agents on symptomatic chronic gastritis is unclear. This multicenter, open, randomized trial was designed to compare the comprehensive effects of gefarnate with sucralfate on erosive gastritis with dyspeptic symptoms. METHODS: Totally 253 dyspepsia patients confirmed with erosive gastritis were enrolled from six centers in China. They randomly received either daily 300 mg gefarnate or 3 g sucralfate for six weeks. The primary endpoint was the effective rate of both treatments on endoscopic erosion at week six. RESULTS: Gefarnate showed an effective rate of 72% and 67% on endoscopic score and dyspeptic symptom release, which is statistically higher than sucralfate (40.1% and 39.3%, P < 0.001, intension-to-treat). For histological improvement, gefarnate showed both effective in decreasing mucosal chronic inflammation (57.7% vs. 24.8%, P < 0.001, intension-to-treat) and active inflammation (36.4% vs. 23.1%, P < 0.05, intension-to-treat) than the control. A significant increase of prostaglandins and decrease of myeloperoxidase in mucosa were observed in gefarnate group. Severity of erosion is non-relevant to symptoms but Helicobacter pylori (H. pylori) status does affect the outcome of therapy. CONCLUSIONS: Gefarnate demonstrates an effective outcome on the mucosal inflammation in patients with chronic erosive gastritis. Endoscopic and inflammation score should be the major indexes used in gastritis-related trials.


Assuntos
Antiulcerosos/uso terapêutico , Dispepsia/tratamento farmacológico , Gastrite/tratamento farmacológico , Gefarnato/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sucralfato/uso terapêutico , Resultado do Tratamento , Adulto Jovem
5.
Ann Surg Oncol ; 19 Suppl 3: S464-74, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21822553

RESUMO

BACKGROUND: Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor angiogenesis, but its prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Our aim was to determine whether high DLL4 expression is correlated with poor prognosis after curative resection for PDAC. METHODS: Surgical specimens obtained from 89 patients with PDAC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Prognostic significance of DLL4 expression was evaluated by Kaplan-Meier method and Cox regression. The correlations of DLL4 expression with VEGFR-2 expression, tumor stage, and lymph node metastasis were examined by chi-square test and multivariate logistic regression. RESULTS: There were 38 (42.7%) and 51 patients who showed high and low DLL4 expression, respectively. Survival curves showed that patients with low DLL4 expression had a significantly better survival than those with high DLL4 expression (P < .001). Multivariate survival analysis demonstrated that high DLL4 expression was independently associated with both reduced overall survival (hazard ratio [HR] 2.24; 95% confidence interval [95% CI] 1.14-4.38) and reduced progression-free survival (HR 2.37; 95% CI 1.22-4.60). Multivariate logistic regression analyses showed that high DLL4 expression was independently associated with both advanced tumor stage (odds ratio [OR] 6.84; 95% CI 2.42-9.36) and lymph node metastasis (OR 3.27; 95% CI 1.04-10.34). We also found a positive correlation between DLL4 and VEGFR-2 expression (P < .001). CONCLUSIONS: High DLL4 expression is significantly associated with poor prognosis for surgically resected PDAC, advanced tumor stage, and lymph node metastasis. Application of adjuvant therapy targeting DLL4-Notch signaling may improve prognosis.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Área Sob a Curva , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/cirurgia , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Neutrófilos , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Contagem de Plaquetas , Modelos de Riscos Proporcionais , Curva ROC , Carga Tumoral , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
6.
Pancreas ; 40(7): 1091-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21926544

RESUMO

OBJECTIVES: The α-tocopherol and tocotrienol-rich fraction (TRF) are considered effective antioxidants. This study aimed to compare the antioxidative and antifibrotic effects of α-tocopherol and TFR in dibutylin dichloride (DBTC)-induced chronic pancreatitis (CP) rats. METHODS: Oral administration of α-tocopherol and TFR (both 800 mg/kg per day) started the next day after DBTC (8 mg/kg) infusion into the tail vein for 4 weeks. Histological examination, Sirius red staining, and measurement of the contents of hydroxyproline and malondialdehyde of the pancreas were performed to evaluate pancreatic damage and fibrosis. Immunohistochemical analysis of α-smooth muscle actin and real-time reverse transcription polymerase chain reaction for transforming growth factor-ß1 (TGF-ß1) and collagen-α1(I) were performed to evaluate the activation of pancreatic stellate cells and the mRNA levels of fibrosis-related genes, respectively. RESULTS: Both α-tocopherol and TRF reduced oxidative stress, ameliorated inflammation and fibrosis, and down-regulated the mRNA expression of TGF-ß1 and collagen-α1(I) in DBTC-induced CP. The TRF was superior to α-tocopherol in alleviating inflammation and fibrosis and down-regulating TGF-ß1 mRNA expression. CONCLUSIONS: Oral administration of α-tocopherol and TRF improves pancreatic inflammation and fibrosis in DBTC-induced CP rats, with TRF being more effective than α-tocopherol. Therefore, TRF may be a novel option for alleviating inflammation and, particularly, the fibrotic process in CP.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Pâncreas/efeitos dos fármacos , Pancreatite Crônica/tratamento farmacológico , Tocotrienóis/farmacologia , alfa-Tocoferol/farmacologia , Actinas/metabolismo , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Modelos Animais de Doenças , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Hidroxiprolina/metabolismo , Masculino , Malondialdeído/metabolismo , Compostos Orgânicos de Estanho , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/genética , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo , Tocotrienóis/administração & dosagem , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , alfa-Tocoferol/administração & dosagem
7.
World J Gastroenterol ; 16(36): 4599-604, 2010 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-20857533

RESUMO

AIM: To study the potential value and specificity of plasma miR-216a as a marker for pancreatic injury. METHODS: Two rat models were applied in this article: L-arginine-induced acute pancreatitis was used as one model to explore the potential value of plasma miR-216a for detection of pancreatic injury; nonlethal sepsis induced in rats by single puncture cecal ligation and puncture (CLP) was used as the other model to evaluate the specificity of plasma miR-216a compared with two commonly used markers (amylase and lipase) for acute pancreatitis. Plasmas were sampled from rats at indicated time points and total RNA was isolated. Real-Time Quantitative reverse transcriptase-polymerase chain reaction was used to quantify miR-216a in plasmas. RESULTS: In the acute pancreatitis model, among five time points at which plasmas were sampled, miR-216a concentrations were significantly elevated 24 h after arginine administration and remained significantly increased until 48 h after operation (compared with 0 h time point, P < 0.01, Kruskal-Wallis Test). In the CLP model, plasma amylase and lipase, two commonly used biomarkers for acute pancreatitis, were significantly elevated 24 h after operation (compared with 0 h time point, P < 0.01 and 0.05 respectively, Pairwise Bonferroni corrected t-tests), while miR-216a remained undetectable among four tested time points. CONCLUSION: Our article showed for the first time that plasma miR-216a might serve as a candidate marker of pancreatic injury with novel specificity.


Assuntos
Biomarcadores/sangue , MicroRNAs/sangue , Pâncreas/lesões , Pancreatite/sangue , Pancreatite/genética , Amilases/sangue , Animais , Arginina/farmacologia , Modelos Animais de Doenças , Humanos , Lipase/sangue , Masculino , Pâncreas/efeitos dos fármacos , Pancreatite/induzido quimicamente , Ratos , Ratos Sprague-Dawley
8.
Pancreas ; 39(7): 994-1001, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20467347

RESUMO

OBJECTIVES: So far, there are no investigations about the role of histone deacetylase 1 (HDAC1) in tumorigenesis of pancreatic ductal adenocarcinoma. This study was designed to elucidate the roles and mechanisms of HDAC1 in tumorigenesis of pancreatic ductal adenocarcinoma. METHODS: Real-time reverse transcription-polymerase chain reaction and immunohistochemistry techniques were adopted to detect the expression of HDAC1 in human pancreatic ductal adenocarcinoma tissues and paired paracancerous tissues. The roles of HDAC1 in human pancreatic cell line PaTu8988 were investigated using siRNA. RESULTS: Histone deacetylase 1 mRNA in pancreatic cancer tissues were significantly higher than in paracancerous tissues (P < 0.05). Immunohistochemistry showed that the indices of HDAC1 in pancreatic cancer tissues and paracancerous tissues were 56.4% (SD, 23.1%) and 6.7% (SD, 5.0%), respectively (P < 0.001). Knockdown of HDAC1 can generate a remarkable defect in proliferation and also can significantly induce apoptosis and S-phase arrest in PaTu8988 cells (P < 0.05). The Bcl-2 mRNA expression was significantly downregulated, whereas the p21 and Bax mRNA expression were significantly upregulated. CONCLUSIONS: The HDAC1 overexpression might play an important role in tumorigenesis of pancreatic cancer. Our data support the development of selective inhibitors targeting HDAC1 for the treatment of pancreatic ductal adenocarcinoma. Histone deacetylase 1 could be a new gene therapy target in pancreatic ductal adenocarcinoma.


Assuntos
Adenocarcinoma/enzimologia , Carcinoma Ductal Pancreático/enzimologia , Histona Desacetilase 1/genética , Neoplasias Pancreáticas/enzimologia , RNA Interferente Pequeno/genética , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Histona Desacetilase 1/análise , Histona Desacetilase 1/antagonistas & inibidores , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , RNA Mensageiro/análise , Regulação para Cima
10.
Zhonghua Bing Li Xue Za Zhi ; 38(3): 189-93, 2009 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-19575856

RESUMO

OBJECTIVE: To study the cytologic features of pancreatobiliary tumors in endoscopic retrograde cholangiopancreatography (ERCP)-guided brushing preparations and to evaluate the usefulness of cytology in the diagnosis of pancreatobiliary malignancy. METHODS: A retrospective analysis of 212 cases of ERCP-guided brush cytology smears performed during the period from January, 2004 to December, 2006. The cytologic diagnosis was confirmed either by the histologic diagnosis or the strict clinical criteria. RESULTS: Two of the cases studied were unsatisfactory for diagnosis, with no epithelial cells identified. One hundred and thirty-seven smears were diagnosed as "negative", 45 of which subsequently confirmed to be malignant (negative predictive value = 60.2%). Six of the 11 cases with "low-grade atypia" were proven to be malignant (positive predictive value = 54.5%), as compared to 19 of 23 cases of "high-grade atypia" (positive predictive value = 86.4%). All of the 41 cases with cytologic diagnosis of "malignancy" were confirmed to be malignant (positive predictive value = 100%). The cytologic features of malignancy in ERCP-guided brushing preparations included overlapping nuclei, anisonucleosis, coarse chromatin pattern, poor cellular cohesion, tumor diathesis, prominent nucleoli and atypical mitotic figures. CONCLUSIONS: The accuracy of ERCP-guided brush cytology relies on good specimen preparation and application of morphologic criteria. Grading of cytologic atypia is of clinical significance. A "negative" or "low-grade atypia" cytologic diagnosis requires further diagnostic workup to rule out the possibility of underlying malignancy, while a "high-grade atypia" or "malignant" diagnosis is relatively specific in guiding subsequent management of suspected pancreatobiliary malignancy.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias do Sistema Biliar/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/cirurgia , Biópsia , Colangiopancreatografia Retrógrada Endoscópica , Técnicas Citológicas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Manejo de Espécimes , Adulto Jovem
11.
Cancer Lett ; 285(1): 89-98, 2009 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-19481338

RESUMO

Conditionally-replicating adenovirus (CRAd) therapy is currently being tested against pancreatic cancer and has shown some promise. To improve the efficacy, a novel virus CRAd-Cans was designed by deletion of E1B-55kDa gene for selective replication in tumor cells, as well as carrying a new angiogenesis inhibitor gene, canstatin. CRAd-Cans mediated higher expression of canstatin in BxPC-3 pancreatic cancer cell line compared to the replication-deficient adenovirus Ad5-Cans. The modified CRAd-Cans manifested the same selective replication and cytocidal effects in pancreatic cancer cells as ONYX-015 in vitro, yet showed greater reduction of tumor growth in nude mice with markedly prolonged survival rate in vivo (P<0.05), compared to that of either ONYX-015 or Ad5-Cans. Pathological examination revealed viral replication, decreased microvessel density and increased cancer cell apoptosis in CRAd-Cans-treated xenografts. The results suggest that the novel oncolytic virus CRAd-Cans, showing synergistic effects of oncolytic therapy and anti-angiogenesis therapy, is a new promising therapeutics for pancreatic cancer.


Assuntos
Adenoviridae/genética , Proteínas E1B de Adenovirus/genética , Colágeno Tipo IV/genética , Deleção de Genes , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Neoplasias Pancreáticas/terapia , Fragmentos de Peptídeos/genética , Adenoviridae/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Colágeno Tipo IV/biossíntese , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Vírus Oncolíticos/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/virologia , Fragmentos de Peptídeos/biossíntese , Fatores de Tempo , Vacinas Virais , Replicação Viral , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Oncol Rep ; 21(6): 1439-47, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19424621

RESUMO

Epigenetic modifications play an important role during carcinogenesis. The main goal of this study was to examine expression levels of two critical enzymes, DNA methyltransferase-1 (DNMT1) and histone deacetylase-1 (HDAC1), by immunohistochemistry (IHC) in human pancreatic cancer and precancerous lesions: 20 foci containing normal ductal epithelial cells without an inflammatory back-ground (DE), 30 containing ductal epithelial cells with an inflammatory background (DEI), 48 of pancreatic intraepithelial neoplasia-1A (PanIN-1A), 103 of PanIN-1B, 99 of PanIN-2, 30 of PanIN-3, 18 of intraductal papillary mucinous neoplasm A (IPMA), 10 of IPMB, 20 of IPMC, and 54 of pancreatic ductal adenocarcinoma (PDAC). The expression levels of both DNMT1 and HDAC1 increased from normal to precancerous lesions to pancreatic cancer, in a malignancy-dependent manner. Correlations between expression levels and clinicopathological features of the 54 PDAC patients were also analyzed. The expression of DNMT1 significantly correlated with nerve infiltration, degree of tumor differentiation and TNM staging (p<0.05), while that of HDAC1 correlated with proliferative activity, degree of tumor differentiation and TNM staging (p<0.05). Patients with higher expression of DNMT1 and/or HDAC1 had an overall lower survival than those with lower expression (p<0.05). Higher expression of DNMT1 and HDAC1 correlated with advanced stages of the disease and reflect the malignancy of pancreatic carcinoma. They may become new prognostic markers and potential therapeutic targets for pancreatic cancer.


Assuntos
Adenocarcinoma Mucinoso/enzimologia , Adenocarcinoma/enzimologia , Carcinoma in Situ/enzimologia , Carcinoma Ductal Pancreático/enzimologia , Carcinoma Papilar/enzimologia , DNA (Citosina-5-)-Metiltransferases/análise , Histona Desacetilases/análise , Neoplasias Pancreáticas/enzimologia , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/patologia , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Carcinoma Papilar/patologia , Diferenciação Celular , Proliferação de Células , DNA (Citosina-5-)-Metiltransferase 1 , Feminino , Histona Desacetilase 1 , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
13.
Gastrointest Endosc ; 69(3 Pt 1): 517-24, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19231492

RESUMO

BACKGROUND: Patients diagnosed with extrahepatic bile duct carcinoma (EBDC) have a poor prognosis. OBJECTIVE: The purpose of these studies was to design radioactive stents for EBDC and to evaluate the feasibility and safety of the stents in healthy pigs. DESIGN: Plastic stents with inserted iodine-125 seeds were designed and tested in 11 healthy pigs. The pigs were divided into 4 groups on the basis of radiation doses. INTERVENTIONS: The stents with estimated radiation dose at a 5-mm radial distance from the axis of the seeds of 30 Gy, 60 Gy, and 90 Gy were implanted in the common bile duct (CBD) in groups A, B, and C (n = 3 in each group), with the control group (n = 2) being implanted with the stents containing nonradioactive seeds. MAIN OUTCOME MEASUREMENTS: Histologic evaluation was performed under a light microscope. RESULTS: The procedures were successfully performed on all pigs. Severe hyperplasia of the mucosa was seen in the control group. In the experimental groups, obvious mucosal necrosis near the radioactive seeds was observed but without perforation of the CBD wall. In lower-dose groups (30 Gy), mild hyperplasia of mucosal glands with fibrosis under the necrosis layer was seen. However, after the increase of the dose, mucosal glands were disappearing without a visible mucosal layer. CONCLUSIONS: The radioactive stents are safe at each dose in healthy pigs. Moreover, our observations indicate the feasibility to design specific radioactive stents according to the size, shape, and position of EBDC in future clinical applications.


Assuntos
Neoplasias dos Ductos Biliares/radioterapia , Ductos Biliares Extra-Hepáticos , Braquiterapia/instrumentação , Stents , Animais , Ductos Biliares Extra-Hepáticos/patologia , Desenho de Prótese , Suínos , Fatores de Tempo
14.
Zhonghua Nei Ke Za Zhi ; 47(4): 300-3, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18843954

RESUMO

OBJECTIVE: To evaluate the feasibility and safety of radioactive pancreatic duct stents implanted in the pancreatic ducts of pigs by endoscopy. METHODS: Different doses of 125I radioactive pancreatic duct stents were implanted in the pancreatic ducts of pigs by endoscopy. Blood tests were conducted before and after implantation. 14, 30 and 60 days after implantation of the radioactive stents, the pigs were euthanized in batch. All animals underwent post mortem examination to exclude intra-abdominal hemorrhage, pancreatic fistula or peritonitis. During autopsy, the liver, bile ducts, head of the pancreas, stomach and duodenum were examined for perforation, stricture or dilation and damage of the surrounding structures. RESULTS: Fourteen pigs were implanted with pancreatic duct stents by endoscopic procedures. There was no effusion, hemorrhage or necrosis in the adjacent duodenum, stomach, liver or right kidney. The normal morphological structures of the duct of Wirsung disappeared in all the treated pigs. Histopathological examination revealed that the stents were surrounded by necrotic tissue and outside fibrous tissue. During the follow-up period, the width of outside fibrous tissue gradually increased. There were no serious abnormalities noted in the blood tests after implantation. CONCLUSION: It is indicated that the radioactive stents are safe in all the different dose groups. For future clinical application, it is feasible to design a special radioactive stent for each patient according to the size, shape and position of the pancreatic tumor.


Assuntos
Braquiterapia/métodos , Ductos Pancreáticos/efeitos da radiação , Próteses e Implantes , Animais , Cateteres de Demora , Endoscopia , Estudos de Viabilidade , Radioisótopos do Iodo , Neoplasias Pancreáticas/radioterapia , Stents , Suínos
15.
Zhonghua Yi Xue Za Zhi ; 87(12): 826-8, 2007 Mar 27.
Artigo em Chinês | MEDLINE | ID: mdl-17565866

RESUMO

OBJECTIVE: To investigate the mRNA expression of GLI1, a transcription regulator of Hedgehog signaling pathway, in human pancreatic carcinoma and to explore its clinical significance. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GLI1 in the tumor tissues, tissues near tumor, and normal tissues obtained during operation from 25 pancreatic carcinoma patients. RESULTS: The GLI1 mRNA expression rate of the tumor tissues was 68.0% (17/25), significantly higher than those of the tissues near tumor, and normal tissues [24.0% (6/25) and 0 (0/25) respectively, both P < 0.01]. The GLI1 mRNA expression rate was significantly associated with the differentiation degree of tumor tissue (P = 0.014), and not significantly associated with the tumor size, invasion, and metastasis (all P > 0.05). CONCLUSION: GLI1 mRNA expression is strong in pancreatic carcinoma tissues and is significantly associated with the differentiation degree of tumor tissue. With diagnostic implication, GLI1 mRNA expression may be regarded as a parameter of determining the degree of malignancy and prognosis of pancreatic carcinoma.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/patologia , Fatores de Transcrição/genética , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína GLI1 em Dedos de Zinco
16.
Clin Cancer Res ; 13(11): 3326-32, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17545539

RESUMO

PURPOSE: Patients diagnosed with pancreatic cancer typically have a poor prognosis. The aims of these studies were to design radioactive stents and to evaluate the feasibility and safety of the stents in animals. EXPERIMENTAL DESIGN: To combine the effects of stents and brachytherapy, plastic stents with inserted iodine-125 seeds were designed and tested in 18 normal pigs. The pigs were divided into five groups on the basis of radiation dose. The estimated radiation dose at a 5-mm radial distance from the axis of the seeds was 50 Gy in group A, 100 Gy in group B, 150 Gy in group C, and 200 Gy in group D, with four pigs in each group. In the control group (n = 2), the same plastic stents with non-radioactive seeds were implanted in the pancreatic duct. RESULTS: The procedures were successfully done on 14 of 18 (78%) pigs, whereas pancreatic duct perforation occurred in four pigs (22%). The thickened wall of the dilated pancreatic duct was clearly observed in the control group. However, the normal morphologic structure of the pancreatic duct wall disappeared in the experimental groups. Histopathologic examination revealed that the stents were surrounded with necrotic tissues and lateral fibrous tissues. During the follow-up period, the width of outside fibrous tissues gradually increased. CONCLUSIONS: These results indicate that the radioactive stents are safe in all dose groups, and it is feasible to design a special radioactive stent for each patient according to the size, shape, and position of the pancreatic tumor.


Assuntos
Braquiterapia/instrumentação , Terapia Combinada/métodos , Radioisótopos do Iodo/uso terapêutico , Ductos Pancreáticos/cirurgia , Neoplasias Pancreáticas/terapia , Stents , Animais , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Humanos , Plásticos , Prognóstico , Radiometria , Projetos de Pesquisa , Stents/efeitos adversos , Suínos , Fatores de Tempo , Resultado do Tratamento
17.
World J Gastroenterol ; 12(41): 6652-7, 2006 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-17075979

RESUMO

AIM: To examine the effect of canstatin, a newly discovered endogenous inhibitor of angiogenesis, in the treatment of pancreatic cancer in vivo. METHODS: The canstatin cDNA fragment was synthesized and amplified from the total RNA extracted from human placenta tissues by RT-PCR. The resulting product was firstly cloned into pUCm-T vector, then into plasmid pET-22b (+) and transformed into E. coli BL21. Isopropyl-1-thio-b-Dgalactopyran-oside (IPTG) was used to induce the expression of canstatin protein and affinity chromatography was used to purify the protein. To determine the activity of purified recombinant human canstatin (rhCanstatin), orthotopic xenograft human pancreatic cancer models were established. Human pancreatic cancer cells (SW1990) were injected into the pancreas of BALB/c nude mice. Twenty-four nude mice with orthotopic xenograft tumor were randomly divided into 3 groups 10 d after the inoculation, and were treated with PBS 0.3 mL, or canstatin 5 mg/kg, or 10 mg/kg per day for 3 wk intraperitoneally. When the experiment was over, all tumors were resected and the effects of rhCanstatin on tumor growth, microvessel density (MVD) were analyzed. RESULTS: After IPTG induction, SDS-PAGE showed a new monomeric 24 kDa protein band. This protein was purified through affinity chromatography and refolded through dialysis with a final concentration of 60 mg/L. In orthotopic pancreatic cancer models, the final tumor volume in groups treated with PBS, canstatin 5 mg/kg, 10 mg/kg were 355.21+/-39.54 mm3, 112.73+/-10.47 mm3, and 61.75+/-6.99 mm3 respectively. The immunohistochemical examination showed that the MVD in tumors treated with canstatin was significantly less than that in other group. CONCLUSION: These findings demonstrate that the rhCanstatin effectively retards the growth of pancreatic cancer in a dose-dependent manner through inhibiting angiogenesis and may be a promising therapeutic agent for pancreatic cancer treatment in the clinic.


Assuntos
Colágeno Tipo IV/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Colágeno Tipo IV/genética , DNA Complementar/genética , Relação Dose-Resposta a Droga , Escherichia coli/genética , Humanos , Neovascularização Patológica/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Fragmentos de Peptídeos/genética , Plasmídeos/genética , RNA/genética , Proteínas Recombinantes/genética , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Chin J Dig Dis ; 5(3): 103-9, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15612244

RESUMO

OBJECTIVE: Visceral hypersensitivity is highly prevalent in most functional bowel disorders, such as irritable bowel syndrome (IBS), and activation of intestinal mast cells (MC) may play a role because they have been found in close proximity to gastrointestinal mucosal sensory nerve terminals containing neuropeptides and a bi-directional pathway connecting the central nervous system, gut, and MC has been demonstrated. The current study appraised the status of rectal visceral perception, as well as the changes in the MC and substance P (SP) in the intestinal mucosa of patients with IBS. METHODS: The study group comprised 42 patients with IBS and 19 healthy subjects who underwent anorectal manometry and rectal perception thresholds to balloon distension. The MC and the SP-ergic terminals in the mucosa were stained for respective histochemical and immunohistochemical investigations. The results were presented both qualitatively and quantitatively by color image analyzer, based on analysis of the intensity and area of stained fibrils. The structural relationship between the MC and nerve terminals was studied by electron microscopy, using an in situ embedding technique. RESULTS: The anorectal resting pressure, squeezing pressure and relaxation pressure were normal in both groups. The sensation threshold, defecation threshold and pain threshold in diarrhea-predominant IBS and the pain thresholds in constipation-predominant IBS were much lower than in the controls. Rectal compliance decreased in IBS. The number of MC in the terminal ileum, the ileocecal junction and the ascending colon was significantly elevated in IBS (P < 0.01), and the MC showed great variation. A significantly increased concentration of SP was found in the colon of the IBS patients compared with the controls. There was a positive correlation between the profiles of mucosal MC and the SP-ergic terminals, and MC were closely adjacent to SP-ergic terminals in the lamina propria. CONCLUSION: As altered rectal perception is present in almost all patients with IBS, it might be a reliable biological characteristic of the disease. Alterations in the MC and SP of the intestinal mucosa may be important factors in visceral hypersensitivity.


Assuntos
Síndrome do Intestino Irritável/fisiopatologia , Percepção , Reto/fisiologia , Adulto , Estudos de Casos e Controles , Defecação , Feminino , Humanos , Mucosa Intestinal/fisiologia , Masculino , Mastócitos/fisiologia , Pessoa de Meia-Idade , Limiar da Dor , Pressão , Reto/inervação , Substância P/análise
19.
World J Gastroenterol ; 9(10): 2258-60, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14562388

RESUMO

AIM: To determine the distribution of cagG gene of Helicobacter pylori (H pylori) isolates cultured from patients with various digestive diseases and its relationship with gastroduodenal diseases. METHODS: cagG was amplified by polymerase chain reaction in 145 H pylori isolates cultured from patients with chronic gastritis (n=72), duodenal ulcer (n=48), gastric ulcer (n=17), or gastric and duodenal ulcer (n=8), and the relationship between cagG status and the grade of gastric mucosal inflammation was determined. RESULTS: cagG was present in 91.7% of the 145 H pylori isolates, with the rates were 90.3%, 93.8%, 88.2% and 100.0%, respectively, in those from patients with chronic gastritis, duodenal ulcer, gastric ulcer, and gastric and duodenal ulcer. There was no significant difference among the four groups (P>0.05). The average grade of gastric mucosal inflammation in the antrum and corpus was 1.819+/-0.325 and 1.768+/-0.312, respectively in cagG positive patients, whereas the average inflammation grade was 1.649+/-0.297, 1.598+/-0.278 respectively in cagG negative cases (P>0.05). CONCLUSION: cagG gene of H pylori was quite conservative, and most H pylori strains in Chinese patients were cagG positive. cagG status was not related to clinical outcome or the degree of gastric mucosal inflammation. Therefore, cagG can not be used as a single marker for discrimination of H pylori strains with respect to a specific digestive disease.


Assuntos
Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Povo Asiático , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/microbiologia , Úlcera Péptica/patologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
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