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1.
Cancer Lett ; 324(1): 66-74, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22579806

RESUMO

Human hepatocellular carcinoma Hep G2 cells and Hep G2-bearing mice were used as in vitro and in vivo models to assess the efficacy and safety of MAP30, a natural component from Momordica charantia, as an anticancer agent against liver cancer. Molecular studies disclosed the contribution of both caspase-8 regulated extrinsic and caspase-9 regulated intrinsic caspase cascades in MAP30-induced cell apoptosis. The antitumor potential was also effective in Hep G2-bearing nude mice. Since bitter gourd is a staple in many Asian countries, MAP30 would serve as a novel and relatively safe agent for prophylaxis and treatment of liver cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Proteínas Inativadoras de Ribossomos Tipo 2/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Caspase 8/metabolismo , Caspase 9/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Momordica charantia/química , Necrose , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sementes/química , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
2.
World J Gastroenterol ; 18(47): 7087-92, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23323012

RESUMO

AIM: To improve the outcome of orthotopic transplantation in a mouse model, we used an absorbable gelatin sponge (AGS) in nude mice to establish an orthotopic implantation tumor model. METHODS: MHCC-97L hepatocellular carcinoma (HCC) cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice. One week later, the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice. The AGS was used to establish the nude mouse orthotopic implantation tumor model. The tumor suppressor gene, paired box gene 5 (PAX5), which is a tumor suppressor in HCC, was transfected into HCC cells to validate the model. Tumor growth was measured by bioluminescence imaging technology. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line. RESULTS: We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS. The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS. The detection of fluorescent signals showed that tumors grew in all live nude mice. The mice were divided into 3 groups: AGS-, AGS+/PAX5- and AGS+/PAX5+. Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice (P < 0.0001). These fluorescent signal results were consistent with observations made during surgery. Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC. Results from RT-PCR proved that the HCC originated from MHCC-97L cells. CONCLUSION: Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.


Assuntos
Carcinoma Hepatocelular/terapia , Modelos Animais de Doenças , Neoplasias Hepáticas/terapia , Transplante de Neoplasias , Animais , Linhagem Celular Tumoral , Gelatina/química , Humanos , Luminescência , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
3.
Cancer ; 110(4): 745-51, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17614104

RESUMO

BACKGROUND: The incidence of lymph node metastasis is high in patients who have pT3 gastric cancer. However, the impact of total retrieved lymph nodes (tLNs) on staging and survival of these patients is not clear. METHODS: For this study, the authors examined 1895 patients with pT3 gastric cancer who underwent surgery at Yonsei University Medical College from January 1987 to June 2000. RESULTS: Four hundred sixty of 1895 patients (24.3%) were diagnosed with pT3N0 gastric cancer. Patients who had < 31 tLNs (25th percentile) had less advanced lymph node (N) stage than the other patients (P < .001). Lymph node metastasis had a positive association with the number of tLNs in a logistic regression analysis (P < .001; hazards ratio, 1.014; 95% confidence interval, 1.006-1.021). With a median follow-up of 61.1 months, the overall 10-year survival rate (10-YSR) was 42.8%. Patients with pT3N0 disease who had < 31 tLNs had a 10-YSR of only 55.4%. Although this 10-YSR did not differ significantly from the rate for patients with N0 disease who had > or =31 tLNs (65.8%; P = .108), it approached the rate for the N1 group (53.3%; P = .207). In multivariable analyses, the number of tLNs emerged as an independent prognostic predictor in patients with pT3N2 and pT3N3 disease, but not in patients with pT3N0 or pT3N1 disease. CONCLUSIONS: Increasing numbers of tLNs may improve the accuracy of staging in patients who have pT3 gastric cancer. Because preoperative lymph node staging is difficult, a thorough lymph node dissection is mandatory in all serosa-positive patients.


Assuntos
Linfonodos/patologia , Neoplasias Gástricas/patologia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
4.
Ann Surg Oncol ; 14(1): 61-8, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17058123

RESUMO

BACKGROUND: The survival of patients with stage IV gastric cancer is poor due to frequent peritoneal failure. The aim of this study was to investigate the impact of early postoperative intraperitoneal chemotherapy (EPIC) after cytoreductive surgery on the long-term survival of these patients, as determined by residual disease status. METHODS: A total of 154 patients with stage IV gastric cancer were enrolled in our study. All patients underwent potentially curative or palliative resections. After surgery, the residual disease states of the patients were recorded. All patients received EPIC. RESULTS: Of all 154 patients, R0 resection was achieved in 37, R1 in 56, and R2 in 61. All patients received a mean of 4.3 EPIC perfusions. After a mean followup period of 29 months, 14 patients remained alive. The median survival of all 154 patients was 11.4 months. Survival times were analyzed according to the type of residual tumor; the median survival time was 25.5 months in the R0 group, 15.6 months in the R1 group, and 7.2 months in the R2 group (p < .001). Upon multivariate analysis, the residual tumor states and the cycle of EPIC perfusion were found to be independent prognostic predictors (p < .001 and p = .018, respectively). CONCLUSIONS: The residual tumor status is the most important predictor for the survival of very advanced gastric cancer patients who received cytoreductive surgery and EPIC. Therefore, complete cytoreductive surgery yielding R0 resection is mandatory for achieving the beneficial effects of EPIC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/cirurgia , Neoplasias Gástricas/cirurgia , Adolescente , Adulto , Idoso , Carcinoma/tratamento farmacológico , Carcinoma/mortalidade , Carcinoma/patologia , Quimioterapia Adjuvante , Feminino , Gastrectomia , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida
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