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1.
BMC Cancer ; 9: 430, 2009 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-20003244

RESUMO

BACKGROUND: The inhibitor of DNA-binding (ID) has been involved in cell cycle regulation, apoptosis and angiogenesis. This prompted us to study ID functions in tumor advancement of ovarian cancers. METHODS: Sixty patients underwent surgery for ovarian cancers. In ovarian cancers, the levels of ID-1, ID-2 and ID-3 mRNAs were determined by real-time reverse transcription-polymerase chain reaction. The histoscore with the localization of ID-1 was determined by immunohistochemistry. Patient prognosis was analyzed with a 36-month survival rate. Microvessel counts were determined by immunohistochemistry for CD34 and factor VIII-related antigen. RESULTS: ID-1 histoscores and mRNA levels both significantly (p < 0.001) increased in ovarian cancers according to clinical stage, regardless of histopathological type. Furthermore, 30 patients with high ID-1 expression had a lower survival rate (53%) compared to patients with low ID-1 expression (80%). ID-1 histoscores and mRNA levels significantly (p < 0.0001) correlated with microvessel counts in ovarian cancers. CONCLUSION: ID-1 increased in ovarian cancer cells during tumor progression. Moreover, ID-1 expression levels correlated with microvessel counts. Therefore, ID-1 might work on tumor advancement via angiogenesis and is considered to be a candidate for a prognostic indicator in ovarian cancers.


Assuntos
Biomarcadores Tumorais/análise , Proteína 1 Inibidora de Diferenciação/biossíntese , Neovascularização Patológica/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Proteína 2 Inibidora de Diferenciação/biossíntese , Proteínas Inibidoras de Diferenciação/biossíntese , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Estadiamento de Neoplasias , Neovascularização Patológica/patologia , Neoplasias Ovarianas/mortalidade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
2.
Gynecol Oncol ; 114(1): 84-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19356789

RESUMO

OBJECTIVE: Receptor EphB4 and the corresponding ligand ephrinB2 contribute to tumor growth in various human tumors. This prompted us to study the expression and localization of EphB4 and ephrinB2 in uterine cervical cancers to analyze the EphB4/ephrinB2 functions against clinical backgrounds. METHODS: Immunohistochemistry and real-time RT-PCR have been done to determine the histoscores and mRNA levels of EphB4 and ephrinB2, respectively, in sixty-two uterine cervical cancer tissue samples. Patient prognoses were analyzed with a 36-month survival rate. RESULTS: The localization of EphB4 and ephrinB2 was dominantly in the cancer cells of uterine cervical cancers of all cases given. Both the histoscores and mRNA levels of EphB4 and ephrinB2 significantly increased with clinical stages (I

Assuntos
Efrina-B2/genética , Receptor EphB4/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Primers do DNA , Efrina-B2/metabolismo , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Metástase Linfática/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Receptor EphB4/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias do Colo do Útero/patologia
3.
BMC Cancer ; 8: 301, 2008 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-18937843

RESUMO

BACKGROUND: Protease activated receptor-2 (PAR-2) has been implicated in cellular proliferation, invasion and metastasis in various tumors. Lymph node metastasis is an important patient prognostic factor for uterine cervical cancers. This prompted us to study the role of PAR-2 in lymph node metastasis of uterine cervical cancers. METHODS: Thirty patients underwent surgery for uterine cervical cancers. PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. Patient prognosis was analyzed with a 48-month survival rate. RESULTS: PAR-2 histoscores and mRNA levels significantly (P < 0.05) increased in 12 of 30 metastatic lymph node lesions from the corresponding primary tumor. The 48-month survival rate of the 12 patients with increased PAR-2 levels in metastatic lymph nodes was 42%, while the rate of the other 18 patients with no change in PAR-2 levels was 82%, regardless of histopathological type. CONCLUSION: PAR-2 might work on lymph node metastasis of uterine cervical cancers, and is considered to be a novel prognostic indicator for uterine cervical cancers.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Receptor PAR-2/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/análise , Receptor PAR-2/genética , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade
4.
Cancer Lett ; 247(1): 98-102, 2007 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-16675104

RESUMO

Osteopontin (OPN) is a glycophosphoprotein that has variety of physiological functions. OPN is expressed in various human cancers and associated with tumor progression, invasion and metastasis in many manners. The purpose of this study is to investigate the clinical significance of OPN expression in metastatic lymph node of uterine cervical cancers, since the prognosis of the patients with lymph node metastasis is extremely poor. Immunohistochemical staining revealed OPN was distributed in the cytoplasm and nuclear compartments of the cancer and stromal cells within and around the tumor. In 25 of the 40 cases, stronger staining for OPN was found in the cancer cells or stromal cells of the metastatic lymph node lesion than in those of the primary tumor. The OPN level was significantly (P<0.05) increased in 25 of 40 metastatic lymph node lesions of uterine cervical cancers. The OPN increased cases identified by immunohistochemical staining were consistent with those identified by the sandwich immunoassay. The prognosis of the 25 patients with significant increase of OPN in uterine cervical cancers was extremely poor, whereas the 24-month survival rate of the 15 patients with no increase of OPN was 67%. This indicates that OPN may contribute to lymph node metastasis and its advancement, and that the OPN level in metastatic lesion may be a prognostic indicator in uterine cervical cancers.


Assuntos
Osteopontina/metabolismo , Neoplasias do Colo do Útero/metabolismo , Adulto , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Prognóstico , Análise de Sobrevida , Neoplasias do Colo do Útero/patologia
5.
Oncology ; 73(3-4): 246-51, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18424889

RESUMO

OBJECTIVE: Angiogenesis is essential for the development, growth and advancement of solid tumors. Interferon-gamma-inducible protein 10 (IP-10) regulates lymphocyte chemotaxis, mediates vascular pericyte proliferation and acts as an angiostatic agent, thus inhibiting tumor growth. This prompted us to study the clinical implications of IP-10 expression related to angiogenesis in uterine endometrial cancers. METHOD: Sixty patients underwent curative resection for uterine endometrial cancers. In the tissue of these cancers, the levels of IP-10, vascular endothelial growth factor, interleukin-8 and basic fibroblast growth factor (bFGF) were determined by enzyme immunoassay, and the localization of IP-10 and counts of microvessels were determined by immunohistochemistry. RESULT: IP-10 is diffusely localized in the cancer cells, but not in the stromal cells. There was a significant, reverse correlation between microvessel counts and IP-10 levels in uterine endometrial cancers. The IP-10 levels significantly decreased with more advanced disease and significantly reverse-correlated with bFGF levels in uterine endometrial cancers. CONCLUSIONS: IP-10 might affect the suppression of angiogenesis associated with bFGF in advanced cancer. Furthermore, IP-10 activation might be effective in the suppression of regrowth or recurrence after intensive treatment for advanced endometrial cancers.


Assuntos
Adenocarcinoma/irrigação sanguínea , Biomarcadores Tumorais/metabolismo , Quimiocina CXCL10/metabolismo , Neoplasias do Endométrio/irrigação sanguínea , Neovascularização Patológica/metabolismo , Adenocarcinoma/secundário , Adulto , Idoso , Progressão da Doença , Neoplasias do Endométrio/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Interleucina-8/metabolismo , Microcirculação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
J Steroid Biochem Mol Biol ; 104(3-5): 237-40, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17532621

RESUMO

Estrogen is recognized as a significant modifier in the development, growth and invasion of uterine endometrial cancer. Steroid receptor coactivator-3 (SRC-3; AIB1, ACTR, RAC3, TRAM-1, and pCIP) is a member of the p160 family of coactivator for nuclear hormone receptors including estrogen receptor (ER). It is reported that SRC-3 is overexpressed in various cancers. However, SRC-3 expression manner in uterine endometrial cancer is not fully understood. In this study, we showed SRC-3 mRNA expression correlates with clinical stage, depth of myometrial invasion and dedifferentiation. The prognosis of the 25 patients with higher expression of SRC-3 mRNA in uterine endometrial cancers was extremely poor (36%), whereas the 24-month survival rate of the 15 patients with lower expression of SRC-3 mRNA was 96%. These data indicate that SRC-3 might be an important indicator of uterine endometrial cancer advancement and survival.


Assuntos
Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Histona Acetiltransferases/genética , Transativadores/genética , Adulto , Idoso , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Progressão da Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Coativador 3 de Receptor Nuclear , Prognóstico , Taxa de Sobrevida
7.
J Steroid Biochem Mol Biol ; 104(3-5): 301-4, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17509876

RESUMO

The expression of estrogen receptor (ER)alpha and ERbeta mRNAs did not show any specific manner according to clinical backgrounds in ovarian cancers. On the other hand, the levels of estrogen-related receptor (ERR)alpha mRNA increased with clinical stages regardless of histopathological types in ovarian cancers. However, ERRbeta and ERRgamma mRNA levels were extremely low to determine reliably. ERRalpha can bind to the steroid receptor coactivator family without any ligands, and drive transcription activity of the target genes. The manner of ERR and ER gene expressions might show an independent usage of common cofactors. It is speculated that the up regulation of ERRalpha might be related to advancement of ovarian cancers regardless of plausible interaction via cofactors regulated by ERs. Although ERRalpha is not directly related to growth of ovarian cancer, ERRalpha is a candidate for prognostic factors for ovarian cancer.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Receptores de Estrogênio/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Análise de Sobrevida , Receptor ERRalfa Relacionado ao Estrogênio
8.
Oncol Rep ; 17(3): 617-22, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17273742

RESUMO

We have previously reported on the inhibitory effect of Glycyrrhizae radix (Gl radix) on mouse endometrial carcinogenesis. The present study was performed to clarify the effects of Gl radix and glycyrrhizin (GL), the main part of Gl radix, on estradiol (E2)-related endometrial carcinogenesis. Both Gl radix and GL exerted a significant decrease in the COX-2, IL-1alpha and TNF-alpha mRNA expressions. GL generated a significant decrease in the incidence of endometrial adenocarcinoma. Accordingly, the preventive effects of Gl radix may be attributable to GL, thus being related with the suppression of COX-2, IL-1alpha and TNF-alpha. Gl radix and GL could therefore be a promising formula for the chemoprevention of human endometrial cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Endométrio/prevenção & controle , Glycyrrhiza/química , Ácido Glicirrízico/uso terapêutico , Neoplasias Hormônio-Dependentes/prevenção & controle , Extratos Vegetais/uso terapêutico , Animais , Ciclo-Oxigenase 1/efeitos dos fármacos , Ciclo-Oxigenase 2/efeitos dos fármacos , Neoplasias do Endométrio/metabolismo , Estrogênios/metabolismo , Feminino , Imuno-Histoquímica , Interleucina-1alfa/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Ovariectomia , RNA Mensageiro/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/efeitos dos fármacos
9.
Oncol Rep ; 17(2): 345-50, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17203172

RESUMO

Protease activated receptor-2 (PAR-2) is the second member of a novel family of G-protein coupled seven-transmembrane domain receptors. PAR-2 has been reported to be expressed in various tumors and play a vital role in the regulation of cancer cell growth. The purpose of this study was to clarify the roles of PAR-2 in the angiogenic pathway in uterine endometrial cancers. PAR-2 expression was analyzed in 61 uterine endometrial cancer and 15 normal endometrium tissue specimens. PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time RT-PCR, respectively. Microvessel counts were determined by immunohistochemistry for CD31 and factor VIII-related antigen. The localization of PAR-2 was dominant in the cancer cells of endometrial cancer tissues of all cases studied. PAR-2 histoscores highly correlated with PAR-2 mRNA levels in the same tissues (r=0.87, p<0.001). PAR-2 histoscores and mRNA levels both significantly increased in uterine endometrial cancers with clinical stages (I

Assuntos
Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Regulação Neoplásica da Expressão Gênica , Neovascularização Patológica , Receptor PAR-2/biossíntese , Adulto , Idoso , Progressão da Doença , Endométrio/metabolismo , Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , RNA Mensageiro/metabolismo
10.
Jpn J Antibiot ; 60(4): 200-5, 2007 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-18018417

RESUMO

The usefulness of switch therapy, from injection to oral medicine, for the treatment of peritonitis was evaluated. Thirty-five patients, who agreed to enroll the study, were randomly assigned to four treatment groups; one group treated with carbapenem antibacterial agent alone and three groups treated with switch therapy, in which injectable quinolone was switched to oral quinolone. For the intravenous administration group, if the patient showed the tendency of improvement by the third day, the intravenous injection was continued. However, if the patient did not show any improvement, the medication was changed to other medicine. For the switch therapy group, if the body temperature dropped to 37.5 degrees C or lower for at least 8 hours and if blood findings and clinical findings showed the tendency of improvement by the fourth day, the medication was switched to oral medicine. There was no difference in therapeutic effects among treatment groups. However, both duration of hospitalization and total medical costs were significantly reduced in the switch therapy groups comparing to those in the intravenous administration group. The results of this study showed that the switch therapy, from injection to oral medicine, was one of useful treatments in treating peritonitis.


Assuntos
Antibacterianos/administração & dosagem , Ciprofloxacina/administração & dosagem , Clindamicina/administração & dosagem , Fluoroquinolonas/administração & dosagem , Naftiridinas/administração & dosagem , Ofloxacino/administração & dosagem , Oxazinas/administração & dosagem , Peritonite/tratamento farmacológico , Tienamicinas/administração & dosagem , Administração Oral , Adulto , Idoso , Esquema de Medicação , Quimioterapia Combinada , Feminino , Custos de Cuidados de Saúde , Humanos , Injeções Intravenosas , Meropeném , Pessoa de Meia-Idade
11.
Oncol Rep ; 16(6): 1343-8, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17089059

RESUMO

An evaluation of the effects of a traditional Chinese herbal medicine, Hochu-ekki-to (Bu-zong-yi-qi-tang) on endometrial carcinogenesis was performed in experiments with female mice. In the short-term experiment, dietary exposure of Hochu-ekki-to (0.2% for 2 weeks) decreased the estradiol-17beta (E2)-stimulated expression levels of c-jun (P<0.001), tumor necrosis factor (TNF)-alpha (P<0.005), estrogen receptors (ER)-alpha (P<0.001) and ER-beta (P<0.005), as determined by reverse transcription-polymerase chain reaction and a Southern blot analysis in the uteri of the ovarectomized mice. In the long-term experiment, the mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and then were divided into four groups. Group 1 (25 mice) was given a diet with Hochu-ekki-to and 5 ppm E2. Group 2 (25 mice) was given a diet with E2 alone. Group 3 (25 mice) was given a diet with Hochu-ekki-to alone. Group 4 (25 mice) was kept on the basal diet alone and treated as a control. The incidence of uterine endometrial cancer in the group with Hochu-ekki-to treatment was substantially lower than of the control group. The inhibitory effect of Hochu-ekki-to on endometrial carcinogenesis is thus suggested to decrease the expressions of c-jun, TNF-alpha, ER-alpha and -beta.


Assuntos
Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias do Endométrio/prevenção & controle , Animais , Southern Blotting , Carcinógenos/toxicidade , Neoplasias do Endométrio/induzido quimicamente , Estradiol/toxicidade , Feminino , Metilnitrosoureia/toxicidade , Camundongos , Camundongos Endogâmicos ICR , Proteínas Proto-Oncogênicas c-jun/efeitos dos fármacos , Receptores de Estrogênio/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/efeitos dos fármacos
12.
Oncol Rep ; 15(5): 1133-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16596174

RESUMO

This study was performed to examine the relationship between the anti-tumor effects of herbal medicine and endometrial carcinoma with ER-related mechanisms. An endometrial cancer cell line (Ishikawa) was used for this study. The cell viability and expression of estrogen receptors (ER) were determined by MTT and RT-PCR. A dose-dependent decrease of viability and apoptosis of the cancer cells was generated by exposure to the herbal medicines, Juzen-taiho-to or Shimotsu-to. The expression of ER-alpha mRNA, but not ER-beta mRNA was suppressed by Juzen-taiho-to or Shimotsu-to in an endometrial cancer cell line. The anti-tumor effect of these herbal medicines against endometrial carcinoma might be correlated to the ER-alpha related mechanism.


Assuntos
Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Receptor alfa de Estrogênio/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Medicina Herbária , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
13.
Oncol Rep ; 15(1): 21-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16328030

RESUMO

Angiogenesis is essential for the development, growth and advancement of solid tumors. Cyclooxygenase (cox)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of cox-2 expression and angiogenesis in ovarian cancer. There was a significant correlation between microvessel counts and cox-2 levels. Cox-2 localized in the cancer cells, but not in the stromal cells of ovarian cancer tissue. Cox-2 levels increased with the advancement, and the prognosis of the 30 patients with high cox-2 expression was extremely poor (33%), while the 24-month survival rate of the other 30 patients, those with low cox-2 expression, was 67%. Furthermore, cox-2 levels significantly correlated with VEGF levels. VEGF associated with cox-2 might work on angiogenesis with advancement. Therefore, long-term administration of cox-2 inhibitors might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced ovarian cancer.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Neovascularização Patológica , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclo-Oxigenase 2/análise , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Prognóstico , Fator A de Crescimento do Endotélio Vascular/análise
14.
Oncol Rep ; 15(4): 855-9, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16525671

RESUMO

The fact that the genetic alterations of PTEN are frequently found in hormone-dependent cancers, such as endometrial, breast, and prostate cancers, might suggest the involvement of PTEN in the hormone-dependent cell growth of such tumors. Estrogen promotes the cell growth of the tumors by inducing peptide growth factors in part. We analyzed the possible involvement of PTEN in peptide-growth factor-dependent cell growth in endometrial carcinoma cells. PTEN-null Ishikawa cells were efficiently infected with recombinant adenovirus at 20 MOI (multiplicity of infection) to express PTEN protein. In PTEN-IK cells, phospho-Akt/PKB was down-regulated regardless of the consistent expression of Akt/PKB. The cell growth of parental IK cells was significantly stimulated by EGF and IGF-I, and PTEN-IK cells were further sensitized to the EGF-or IGF-I-growth stimulation. EGFR antibody could completely compromise the stimulatory effects of EGF in both cell lines. Wortmannin, a PI3K inhibitor, or UO126, a MAPK inhibitor, partly suppressed EGF-mediated cell growth stimulation in both cell lines. EGF augmented the level of phospho-Akt/PKB of PTEN-IK cells more effectively than that of parental IK cells. These results imply that the dysfunction of PTEN leads cells into a less-sensitive phenotype to peptide growth factors by constitutive activation of the PI3K/Akt/PKB signaling pathway in endometrial carcinoma.


Assuntos
Proliferação de Células , Fator de Crescimento Epidérmico/fisiologia , PTEN Fosfo-Hidrolase/fisiologia , Adenoviridae/genética , Androstadienos/farmacologia , Anticorpos/farmacologia , Western Blotting , Butadienos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA Recombinante/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Inibidores Enzimáticos/farmacologia , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/genética , Receptores ErbB/imunologia , Feminino , Fator 2 de Crescimento de Fibroblastos/farmacologia , Expressão Gênica , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Nitrilas/farmacologia , PTEN Fosfo-Hidrolase/genética , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor ErbB-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Wortmanina
15.
Jpn J Antibiot ; 59(1): 35-40, 2006 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-16673581

RESUMO

In recent years, the number of the patients with pharyngeal infection caused by Chlamydia trachomatis is believed to be on the rise due to diversification in sexual behaviors. In addition, pharyngeal infection by C. trachomatis is often asymptomatic, and this is also believed to be a major factor for the increase of the disease. In this study, we conducted a survey among general females and commercial sex workers (CSWs) to study their sexual behavior and prevalence of chlamydial infections (in uterine cervix and pharynx). The results showed that orogenital contact has become a common act, even for general females. Chlamydial infections of uterine cervix were found in 33.3% and 7.9% of CSWs and general females, respectively. Chlamydial infections of pharynx were found in 22.5% and 5.2% of CSWs and general females, respectively. The evaluation of treatments of these infections with clarithromycin, levofloxacin, and azithromycin showed that 7, 10, and 14 days administrations of 400 mg clarithromycin, 7, 10, and 14 days administrations of 300 mg levofloxacin, and a single dose of 1000 mg of azithromycin, would eradicate 100% of C. trachomatis for infections of uterine cervix. For pharyngeal infections, 10 and 14 days administrations of clarithromycin and levofloxacin were shown to eradicate 100% of C. trachomatis. However, the eradication rates for 7 days administrations of clarithromycin and levofloxacin were 83.9% and 86.2%, respectively, and the rate for a single dose of azithromycin was 85.0%. From these results, it was thought that more than 10 days of administrations of clarithromycin or fluoroquinolone antibacterial agents such as levofloxacin are necessary to treat pharyngeal chlamydial infection. Clinical significance of pharyngeal chlamydial infection is still not clear; however, this study have shown the need for more detailed investigations using culture assay, in corporation with doctors in otolaryngology and internal medicine.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Faringite/tratamento farmacológico , Faringite/epidemiologia , Adulto , Azitromicina/uso terapêutico , Claritromicina/uso terapêutico , Feminino , Humanos , Japão/epidemiologia , Levofloxacino , Ofloxacino/uso terapêutico , Prevalência , Trabalho Sexual , Comportamento Sexual , Doenças Uterinas/tratamento farmacológico , Doenças Uterinas/epidemiologia
16.
Jpn J Antibiot ; 59(5): 364-72, 2006 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-17180805

RESUMO

There have not been sufficient clinical studies based on pharmacokinetics/pharmacodynamics (PK/PD) theory, on which many clinical doctors have recently focused. To consider the optimized administration method based on PK/PD theory for gatifloxacin (GFLX), which was one of the oral fluoroquinolone antibacterial, we influenzae investigated clinical efficacies and adverse events for pelvic inflammatory disease (PID) in giving GFLX daily 400 mg divided twice a day or four times a day. The number of leukocyte and the value of CRP were significantly reduced by chemotherapy in twice a day group, compared with four times a day group. We were able to measure the blood level in 4 cases. The AUC/MIC values for presumption causative bacteria (causative bacteria in both cases: Escherichia coli) in cured patients were 142.28 and 280.16, however, in therapy-failed patients, the AUC/MIC value to presumption causative bacterium were 4.10 (causative bacteria: Prevotella bivia) and 4.35 (causative bacteria: Pseudomonas aeruginosa). These results suggested the importance of the therapeutic method based on PK/PD theory.


Assuntos
Anti-Infecciosos/administração & dosagem , Fluoroquinolonas/administração & dosagem , Doença Inflamatória Pélvica/tratamento farmacológico , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Escherichia coli/efeitos dos fármacos , Feminino , Gatifloxacina , Humanos , Doença Inflamatória Pélvica/microbiologia
17.
Int J Oncol ; 26(3): 737-44, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15703831

RESUMO

The extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway plays a critical role in the anticancer action in vitro. ERK1/2 activation or phosphorylation is responsible for increased cyclooxygenase-2 (COX-2) protein expression in some cancer cells treated with selective COX-2 inhibitor NS398. We determined the effect of NS398 on ERK signaling and the synergistic effect of combined treatment with NS398 and a specific MEK inhibitor U0126 on three human endometrial cancer cell lines: Ishikawa, HEC-1A and AN3CA cells. Results showed that NS398 and U0126 individually, and especially the combination of both exhibited profound anti-proliferation of all three cell lines in a time- and concentration-dependent manner by [3-(4, 5)-dimethylthiazol-z-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay. The phosphorylated ERK1/2 was up-regulated in HEC-1A and AN3CA cells, but the COX-2 protein expression was unchanged in the three cancer cell lines treated with NS398 alone. However, both phosphorylated ERK1/2 and COX-2 protein expression were concentration-dependently decreased in all three cell types by combined treatment with NS398 and U0126 assessed by western blot analysis. Simultaneously, the combination of NS398 and U0126 resulted in 2-fold increase in apoptosis of all three lines over that by the individual alone, and enhanced G0/G1 phase arrest of Ishikawa and HEC-1A cells induced by U0126 treatment determined by flow cytometry. The synergistic and complementary effects of combining NS398 and U0126 were found to be associated with activation of caspase-3, alterations of Bcl-2 family proteins and cell cycle regulatory proteins detected by western blot analysis. Taken together, these findings correlate with blocking MEK-ERK signaling cascade and down-regulating COX-2 protein expression in endometrial cancer cells with combination treatment of NS398 and U0126, suggesting that the combinatory use of NS398 and specific MEK inhibitors may be valuable for chemotherapy or chemoprevention of human endometrial cancer.


Assuntos
Butadienos/farmacologia , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Neoplasias do Endométrio/patologia , Inibidores Enzimáticos/farmacologia , Nitrilas/farmacologia , Nitrobenzenos/farmacologia , Sulfonamidas/farmacologia , Western Blotting , MAP Quinases Reguladas por Sinal Extracelular/farmacologia , Feminino , Humanos , MAP Quinase Quinase Quinases/farmacologia , Transdução de Sinais , Células Tumorais Cultivadas
18.
J Steroid Biochem Mol Biol ; 94(1-3): 83-91, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15862953

RESUMO

The mRNAs of estrogen receptor beta (ERbeta), and its splice variant, ERbeta2, are abundant in granulosa cells in the ovary. With the use of antibodies, ERbeta protein has also been shown to be abundantly expressed, but to date no ERbeta2 protein has been demonstrated in the ovary. ERbeta2 has a peptide, 18 amino acids in length, inserted into its ligand-binding domain, resulting in a reported 35-fold reduction in its affinity for estrogen (E2). ERalpha, ERbeta1 and ERbeta2 were quantified by Western blotting and by RT-PCR and their cellular localization in the ovary was examined by immunohistochemistry. In 3- and 5-week-old virgin, pregnant, lactating and post-lactating rats, the level of ERalpha protein ranged between 1.6 and 3.8 fmol/microg total protein. That of ERbeta was 8.8-11.2 and of ERbeta2, in the same samples, 4.1-5.9 fmol/microg total protein. ERbeta2 and ERbeta1 proteins were, therefore, present in approximately equal amounts in the ovary throughout the various reproductive stages. The major ERbeta proteins in rat ovary, detected by their molecular weights on Western blots, were ERbeta1-530 and ERbeta2-548 (530+18 amino acids (aa)). Immunohistochemical staining revealed that ERbeta and ERbeta2 were expressed predominantly in granulosa cells of growing follicles, while ERalpha was found only in theca cells. In some theca cells, both ERalpha, ERbeta2 were expressed. The data suggests that in theca cells, where it is co expressed with ERalpha, ERbeta2 could function as a repressor of ERalpha. However, in granulosa cells where no ERalpha is detectable, and where E2 levels are high, ERbeta2, with its low affinity for E2, could be an important sensor through which E2 exerts regulatory control.


Assuntos
Receptor beta de Estrogênio/genética , Ovário/fisiologia , Processamento Alternativo , Animais , Sequência de Bases , Primers do DNA , Feminino , Células da Granulosa/fisiologia , Lactação/fisiologia , Mutagênese Insercional , Gravidez , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica
19.
J Steroid Biochem Mol Biol ; 93(2-5): 161-5, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15860258

RESUMO

In general, tumors induce angiogenic factors specific to them, which leads to angiogenesis with advancement. However, angiogenesis in uterine endometrial cancers is complicated because hormone dependency in growth also modifies the angiogenic potential. Therefore, anti-angiogenic therapy for tumor dormancy in uterine endometrial cancers must be thoroughly considered. The upstream of vascular endothelial growth factor (VEGF) gene conserves estrogen-responsive elements. Progesterone primed with estrogen induces thymidine phosphorylase (TP) in uterine endometrium. Sex steroid-dependent VEGF and TP are highly expressed in cases of early stage and well-differentiated uterine endometrial cancers, and basic fibroblast growth factor (bFGF) in cases of advanced and poorly differentiated uterine endometrial cancers. A transcriptional factor for angiogenesis, ETS-1, is linked to VEGF in well-differentiated uterine endometrial cancers, and to bFGF in poorly differentiated uterine endometrial cancers. Therefore, even if dedifferentiation and angiogenic switching occur due to advancement and long-term hormone therapy, the inhibition of ETS-1 along with main angiogenic factors might be an effective strategy to suppress uterine endometrial cancers as a novel anti-angiogenic therapy.


Assuntos
Neoplasias do Endométrio/irrigação sanguínea , Hormônios Esteroides Gonadais/metabolismo , Neoplasias Hormônio-Dependentes/irrigação sanguínea , Neovascularização Patológica/etiologia , Inibidores da Angiogênese/uso terapêutico , Linhagem Celular Tumoral , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Expressão Gênica , Humanos , Modelos Biológicos , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Proteína Proto-Oncogênica c-ets-1 , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-ets , Timidina Fosforilase/biossíntese , Timidina Fosforilase/genética , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
20.
J Steroid Biochem Mol Biol ; 94(1-3): 67-9, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15862951

RESUMO

Estrogen receptor (ER) alpha and beta mRNA levels increased from the first to the second trimester and then decreased until normal term delivery. Estrogen-related receptor (ERR) alpha, beta and gamma mRNA levels gradually increased up to the second trimester and then comparatively rapidly increased until normal term delivery. ERRs can bind to the steroid receptor coactivator family without any ligands and drive transcription activity of the target genes. The manner of ERR and ER gene expressions might show a competitive interaction associated with the use of common cofactors. It is speculated that the up-regulation of ERRs is related to placental growth after the down-regulation of ERs because of the remarkably high concentration of estrogens for ERs from the second trimester until delivery.


Assuntos
Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Placenta/fisiologia , Receptores de Estrogênio/genética , Sequência de Bases , Primers do DNA , Feminino , Idade Gestacional , Humanos , Gravidez
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