RESUMO
We conducted study to determine whether and how the expression of the hypoxia-inducible factor 1alpha (HIF-1alpha) gene relates to outcome in patients with epithelial ovarian cancer. A total of 66 patients with epithelial ovarian cancer, who underwent primary surgery followed by platinum-based chemotherapy, were entered into this study. We confirmed the expression of HIF-1alpha and the vascular endothelial growth factor (VEGF) by immunohistochemistry. To determine the quantity of HIF-1alpha and VEGF expression, messenger RNA of each gene was measured by real-time reverse transcription-polymerase chain reaction. The cutoff values were determined by the receiver-operating characteristic curve according to survival. The protein expressions of HIF-1alpha and VEGF were strongly observed in the cancer cells. The cutoff value of HIF-1alpha and VEGF gene expression was 6.0 and 3.0, respectively. The expression of HIF-1alpha did not relate to clinical stage, but tumor with low VEGF expression was observed more frequently in stage I patients. The response rate to chemotherapy did not differ between high and low expression of both genes. The overall survival for patients with high expression of HIF-1alpha was significantly lower, but disease-free survival did not differ between high and low expression of HIF-1alpha, whereas both overall and disease-free survival for patients with high expression of VEGF were significantly lower. Multivariate analysis revealed that FIGO stage and HIF-1alpha expression were independent prognostic factors but that VEGF was not. The present study suggested that the expression level of HIF-1alpha could be an independent prognostic factor in epithelial ovarian cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , Terapia Combinada , Intervalos de Confiança , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Ovariectomia/métodos , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
The raw material of triamcinolone was examined for preparation of the "Triamcinolone Reference Standard (Control 981)". The analytical data obtained were: melting point, 246 degrees C (decomposition); UV spectrum, lambda max of 239 nm and specific absorbance in methanol at 289 nm of 394; IR spectrum, specific absorptions at 3462, 1716, 1659, 1615, 1604, 1132 and 1061 cm-1; optical rotation, [alpha]D20 = +69.7 degrees; high-performance liquid chromatography, five impurities detected and amount of each impurity estimated to be less than 0.6% and total amount of impurities less than 1.4%; loss on drying, 0.24%. Based on the above results, the raw material was authorized as the Triamcinolone Reference Standard (Control 981) of the National Institute of Health Sciences.
Assuntos
Órgãos Governamentais , Triancinolona/normas , Japão , Farmacopeias como Assunto/normas , Padrões de ReferênciaRESUMO
The raw material of digoxin was examined to prepare a "Digoxin Reference Standard". The analytical data obtained were: optical rotation, [alpha](20)D = + 11.7 degree; loss on drying, 0.008%, infrared spectrum, the same as that of the Digoxin Reference Standard (Control 807); high-performance liquid chromatography, several impurities detected and the total amount estimated to be about 0.31%, assay by spectrophotometry, 100.1%. Based on the above results, the candidate material was authorized as the Digoxin Reference Standard (Control 991) of the National Institute of Health Sciences.
Assuntos
Digoxina/normas , Órgãos Governamentais , Japão , Farmacopeias como Assunto/normas , Padrões de ReferênciaRESUMO
The raw material of lanatoside C was examined for preparation of the "Lanatoside C Reference Standard". The analytical data obtained were: melting point, 247.4 degree C; optical rotation, [alpha]20(D) = + 34.0 degree, loss on drying, 6.93%; infrared spectrum, the same as that of the Lanatoside C Reference Standard (Control 784); thin-layer chromatography, two impurities detected; high-performance liquid chromatography, several impurities detected and the total amount estimated to be about 1.26%; assay by spectrophotometry, 103.0%. Based on the above results, the candidate material was authorized as the Lanatoside C Reference Standard (Control 981) of the National Institute of Health Sciences.
Assuntos
Órgãos Governamentais , Lanatosídeos/normas , Japão , Farmacopeias como Assunto/normas , Padrões de ReferênciaRESUMO
The raw material of glycyrrhizic acid examined for preparation of the "Glycyrrhizic Acid Reference Standard". The analytical data obtained were: UV spectrum: Lambda max, 251 nm; specific absorbance (E (1%) 1cm) in ethanol at 251 nm, 146; IR spectrum, specific absorptions at 1716,1656, 1215, and 1170 cm-1; and the spectrum of raw material was consistent with that of Standard (Control 941). Also, thin-layer chromatography, no impurities detected; high-performance liquid chromatography, three impurities detected. The amount of each impurity was estimated at less than 0.1%, and the total amount of impurities was less than 0.2%. Based on the above results, the candidate material was authorized as the Glycyrrhizic Acid Reference Standard (Control 991) of the National Institute of Health Sciences.
Assuntos
Ácido Glicirrízico/normas , Órgãos Governamentais , Japão , Farmacopeias como Assunto/normas , Padrões de ReferênciaRESUMO
We conducted the present study to investigate whether and how chemosensitivity can be determined by means of genetic diagnosis using drug-resistance genes in patients with epithelial ovarian cancer. A total of 75 patients who had epithelial ovarian cancer with measurable lesions were entered into this study. Thirty-three patients received first-line chemotherapy, consisting of paclitaxel and carboplatin (TJ). Forty-two patients received second-line chemotherapy, 22 received EP therapy consisting of etoposide and cisplatin (CDDP), and 20 received irinotecan (CPT-11) and CDDP (CPT-11/CDDP) therapy. Tumor samples were obtained before chemotherapy. MessengerRNA expressions of the multidrug-resistance (MDR)-1 gene, MDR-associated protein-1 (MRP-1), topoisomerase (topo) I, and topo IIalpha were measured by real-time reverse transcription-polymerase chain reaction. The cutoff values of each gene were determined by the receiver operating characteristic curve. MDR-1 expression was significantly higher in patients who did not respond to TJ therapy. The expression of topo IIalpha was significantly higher in patients who did respond to EP therapy. The expression of topo I was significantly higher in patients who did respond to CPT-11/CDDP. MRP-1 expression did not differ between responders and nonresponders in all regimens. The cutoff value was 80 for MDR-1, 90 for topo IIalpha, and 200 for topo I. Next, to evaluate genetic diagnosis, 31 patients were newly added. The accuracy of this genetic diagnosis for chemosensitivity was 85.7% for TJ, 77.8% for EP, and 100.0% for CPT-11/CDDP therapy. The present study suggests that genetic diagnosis may be useful to determine chemosensitivity in patients with epithelial ovarian cancer.
Assuntos
Antígenos de Neoplasias/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo I/genética , Proteínas de Ligação a DNA/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Adulto , Idoso , Antígenos de Neoplasias/biossíntese , Antígenos de Neoplasias/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , DNA Topoisomerases Tipo I/biossíntese , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/biossíntese , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/metabolismo , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Células Epiteliais/patologia , Feminino , Genes MDR , Humanos , Irinotecano , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/biossíntese , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , RNA Mensageiro/biossíntese , RNA Mensageiro/genéticaRESUMO
Our previous findings suggested that lower cell proliferation of clear cell carcinoma (CCC) of the ovary may contribute to its resistance to chemotherapy. We conducted the present study to find the gene that regulates cell proliferation of CCC and to elucidate whether it contributes to cisplatin (CDDP) resistance. Complementary DNA microarray analysis revealed that the gene expression level of galectin-3 of CCC cell lines (KK, RMG-I, HAC-2) was over threefold higher than that of ovarian serous adenocarcinoma (SAC) cell lines (HRA, KF). S-phase fraction increased after knocking down galectin-3 using small interfering RNA in RMG-I, KK, and HAC-2 cells. The protein expression of p27 decreased after knocking down galectin-3. CDDP-induced apoptosis was increased after knocking down galectin-3, and this cytotoxic effect was canceled by roscovitine. Immunohistochemical staining showed that galectin-3 expression in tumors of 20 CCC was significantly more frequent than that of 20 SAC (70.0% vs 15.0%, P = 0.0004). The present study showed that the expression of galectin-3 in CCC might contribute to its lower cell proliferation and lead to CDDP resistance.