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1.
Cancer Cell ; 9(3): 189-98, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16530703

RESUMO

MicroRNA (miRNA) expression profiles for lung cancers were examined to investigate miRNA's involvement in lung carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate lung cancers from noncancerous lung tissues as well as molecular signatures that differ in tumor histology. miRNA expression profiles correlated with survival of lung adenocarcinomas, including those classified as disease stage I. High hsa-mir-155 and low hsa-let-7a-2 expression correlated with poor survival by univariate analysis as well as multivariate analysis for hsa-mir-155. The miRNA expression signature on outcome was confirmed by real-time RT-PCR analysis of precursor miRNAs and cross-validated with an independent set of adenocarcinomas. These results indicate that miRNA expression profiles are diagnostic and prognostic markers of lung cancer.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genética , MicroRNAs/análise , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida
2.
J Obstet Gynaecol Res ; 39(1): 311-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22639962

RESUMO

AIM: The optimal chemotherapy regimen for patients with endometrial cancer has not been established. We assessed the feasibility of paclitaxel plus carboplatin (TC) for postoperative chemotherapy in patients with endometrial cancer. MATERIAL AND METHODS: Patients with newly diagnosed endometrial cancer received TC (paclitaxel 180 mg/m(2) , carboplatin AUC6 mg/mL/min) every three weeks. Treatment was continued until disease progression or completion of six cycles. Toxicities were evaluated every cycle according to NCI-CTCAE version 3.0. RESULTS: Sixty patients were registered from December 2005 through November 2006. Forty-four of 60 (73.3%) cases completed all of the planned six cycles. Grades 3 and 4 hematologic toxicities were observed as follows: leukopenia (61.7%), neutropenia (95.0%), anemia (21.7%), and thrombocytopenia (5.0%). There were six patients who dropped out from the protocol by neutropenia. Grade 3 non-hematologic toxicities were observed as follows: nausea (3.3%), vomiting (1.7%), neuropathy (5.0%), myalgia (6.7%) and constipation (1.7%). No grade 4 non-hematologic toxicity was observed. CONCLUSION: This TC regimen is feasible for endometrial cancer patients.


Assuntos
Adenocarcinoma/tratamento farmacológico , Carboplatina/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Resultado do Tratamento
3.
J Med Ultrason (2001) ; 40(2): 157-62, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27277106

RESUMO

A pregnant Japanese female was referred to our hospital due to intrauterine fetal growth restriction. A prenatal diagnosis of right pulmonary agenesis could be made using ultrasonography and fetal magnetic resonance imaging, and a Caesarian section was performed at 34 weeks of gestation. The infant developed a respiratory disorder immediately, received systemic management in the neonatal intensive care unit (NICU), and was discharged at age of 103 days without any severe sequelae.

4.
Int J Gynecol Pathol ; 31(4): 364-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22653351

RESUMO

Choriocarcinoma is a highly malignant tumor of trophoblastic origin. Most cases occur in association with preceding gestational events. However, on very rare occasions, nongestational choriocarcinoma arises from germ cell or trophoblastic differentiation in different types of carcinoma. This article reports the case of a 58-year-old woman with primary nongestational choriocarcinoma of the uterus that developed 19 years after her final pregnancy and 4 years after menopause. A total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological examination showed choriocarcinoma of the uterus without components of other germ cell tumors. Karyotype analysis of the tumor cells demonstrated XX. We confirmed its nongestational origin by DNA polymorphism analysis at 15 short tandem repeat loci. After surgery, the patient was given four courses of combination chemotherapy. She is still alive and there has been no evidence of recurrence 3 years after surgery.


Assuntos
Coriocarcinoma não Gestacional/genética , Neoplasias Ovarianas/genética , Coriocarcinoma não Gestacional/patologia , Coriocarcinoma não Gestacional/cirurgia , DNA de Neoplasias/química , DNA de Neoplasias/genética , Feminino , Histocitoquímica , Humanos , Cariotipagem , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Pós-Menopausa/genética
5.
J Obstet Gynaecol Res ; 38(4): 639-44, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22413833

RESUMO

AIM: Adenomyosis patients treated with dienogest are considered to be at higher risk of uterine bleeding; however, the mechanisms which cause severe uterine bleeding in those patients are unknown. This study aims to investigate the risk factors of uterine bleeding among adenomyosis patients treated with dienogest. MATERIAL AND METHODS: Clinical data of 51 adenomyosis patients treated with dienogest were retrospectively collected from their medical records. The impact of potential risk factors (age, sagittal square area of the uterus before treatment, and estradiol at the third month of treatment) and confounders (hemoglobin before treatment and prior medical treatments) on the time to treatment discontinuation due to uterine bleeding was assessed using log-rank tests and a Cox proportional hazard model. RESULTS: Age (< 38 years, P = 0.004), hemoglobin before treatment (<12 g/dL, P = 0.047), and estradiol at the third month of treatment (≥ 60 pg/mL, P = 0.027) had statistically significant effects on the time to treatment discontinuation due to uterine bleeding. Age was still statistically significant after controlling for hemoglobin (P = 0.023). CONCLUSION: Adenomyosis patients treated with dienogest are at higher risk of treatment discontinuation due to uterine bleeding, especially when they are of younger age, have anemia before treatment, and/or have mildly suppressed or unsuppressed estradiol after they started dienogest treatment. Clinicians should pay special attention when they prescribe dienogest for such patients.


Assuntos
Endometriose/tratamento farmacológico , Nandrolona/análogos & derivados , Hemorragia Uterina/etiologia , Adulto , Feminino , Hemoglobinas/análise , Humanos , Pessoa de Meia-Idade , Nandrolona/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
6.
J Obstet Gynaecol Res ; 38(12): 1367-75, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22639843

RESUMO

AIM: Several previous reports showed that irinotecan hydrochloride plus cisplatin (CPT-P) was a candidate first-line chemotherapy regimen for clear cell adenocarcinoma of the ovary (CCC). However, long-term survival in CCC patients treated with CPT-P as first-line chemotherapy remains to be determined. The aim of the present study was to evaluate the long-term results of CPT-P as first-line chemotherapy for CCC. MATERIAL AND METHODS: We performed a retrospective review of 31 patients with CCC who were treated with CPT-P between 1996 and 2004. RESULTS: The median follow-up period was 91 months. The estimated 8-year overall survival (OS) rate in all patients was 64.5%, while the rate in 18 stage I, 21 stage I/II, and 10 stage III/IV patients was 88.9%, 85.7%, and 20.0%, respectively. The estimated 8-year OS rate in patients with pT1/pT2 disease was 87.0%, while the 3-year OS rate in patients with pT3 disease was 0%. Univariate analysis using the log-rank test revealed that Eastern Cooperative Oncology Group performance-status 1, pT3 stage, and presence of residual disease (stage II-IV) were significantly correlated with shortened patient survival. Multiple regression analysis revealed that pT3 predicted worse OS in patients with CCC than pT1 (P<0.001) or pT2 disease (P < 0.005). CONCLUSION: The long-term results suggest CPT-P as a candidate in first-line chemotherapy for CCC in not only stage I, but also in optimally debulked stage II-IV patients with pT1/pT2 disease.


Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/análogos & derivados , Cisplatino/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/cirurgia , Adulto , Idoso , Camptotecina/uso terapêutico , Feminino , Humanos , Irinotecano , Japão/epidemiologia , Laparotomia , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Cirurgia de Second-Look
7.
J Obstet Gynaecol Res ; 38(9): 1211-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22563698

RESUMO

AIM: CD147 is a membrane glycoprotein that is expressed in various cancer cells and is involved in tumor invasion and metastasis by inducing stromal fibroblastic cells to produce matrix metalloproteinases. This study was carried out to evaluate the correlation between CD147 expression and various clinicopathologic parameters, including histological grade and prognosis in a small sample set of human ovarian cancer patients. MATERIAL AND METHODS: Paraffin-embedded surgical tissue samples from 25 patients with ovarian serous and endometrioid adenocarcinoma were stained with anti-CD147 antibody (monoclonal antibody 12C3: MoAb 12C3) for immunohistochemical analysis. RESULTS: CD147 protein was expressed in 84.0% (21 of 25 cases) of cancerous lesions, but not in normal lesions. CD147 expression by ovarian cancer cells was inversely correlated with overall survival. There was no correlation between CD147 expression and histological grade. CONCLUSIONS: These results suggest that measurement of CD147 expression may enhance the understanding of the pathophysiology of epithelial ovarian cancer.


Assuntos
Anticorpos Monoclonais , Basigina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/metabolismo , Neoplasias Ovarianas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Feminino , Humanos , Imuno-Histoquímica , Japão/epidemiologia , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/patologia , Projetos Piloto
8.
Hinyokika Kiyo ; 58(6): 283-6, 2012 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-22874507

RESUMO

A 33-year-old British woman who had undergone caesarean section at 31 years of age was admitted to our hospital at 28 weeks of gestation due to a large amount of genital hemorrhage induced by total placenta previa. Magnetic resonance imaging showed placenta percreta with bladder invasion. To control the sudden hemorrhage at 31 weeks of gestation, we performed an operation emergently. An occlusion ballon was inserted into the bilateral internal iliac arteries by radiologists, caesarian section followed by simple hysterectomy was performed by gynecologists, and then the bladder wall with placenta percreta was removed by urologists. Although the operation was carefully undertaken with multi-department cooperation, 11,550 ml of blood was lost during the 6.5-hour operation. There are few reports of placenta percreta with bladder invasion, about 30 cases including 3 cases in our country have been reported around the world until now.


Assuntos
Placenta Acreta/patologia , Bexiga Urinária/patologia , Adulto , Feminino , Humanos , Histerectomia , Recém-Nascido , Imageamento por Ressonância Magnética , Placenta Acreta/cirurgia , Gravidez , Complicações Cardiovasculares na Gravidez/etiologia , Hemorragia Uterina/etiologia
9.
Int J Gynecol Cancer ; 21(9): 1547-54, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22080896

RESUMO

BACKGROUND: Based on the evidences showing that serum deprivation provokes apoptosis in a variety of cells, we have investigated the effect of serum deprivation on drug sensitivity. METHODS: After human ovarian cancer cells were preincubated in 0.5 % serum containing medium for 12 hours, cellular drug sensitivities were determined by colony-forming assay. RESULTS: Serum deprivation treatment resulted in significant increase in paclitaxel sensitivity by factors of mean ± SD, 148.6 ± 28.1 and 10.1 ± 1.0 (n = 3; P < 0.001) fold in platinum-resistant C13 and CP70 cells, respectively. Similarly, serum deprivation induced significant docetaxel sensitivity in these cell lines. However, no enhancement effect of serum deprivation was observed in platinum-sensitive 2008 and A2780 cells. Serum deprivation did not have any effect on the sensitivities to cisplatin, vincristin, and doxorubicin in all of these cells. More than 7-fold increase of apoptotic cells were observed in C13 or CP70 cells when they were treated by serum deprivation followed by paclitaxel compared with the treatment of either serum deprivation or paclitaxel alone. Confocal laser microscopy using rhodamine 123 and flow cytometric analysis with 3,3'-dihexyloxacarbocyanine iodide revealed that serum deprivation decreased mitochondrial membrane potential in C13 or CP70 cells, whereas no change was observed in 2008 and A2780 cells. This indicates that serum deprivation induced depolarization specifically in platinum-resistant cells. Electron microscopy revealed that serum deprivation caused regeneration of mitochondrial matrix structure in C13 or CP70 cells where mitochondria were usually destructed and disappeared. DISCUSSIONS: These results indicate that serum deprivation confers taxane hypersensitivity specifically in platinum-resistant cells by recovering their impaired mitochondrial functions. The evidence might be clinically beneficial for the development of new chemotherapeutic technology, particularly for the patients with platinum-resistant ovarian cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Meios de Cultura Livres de Soro/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Taxoides/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Meios de Cultura Livres de Soro/metabolismo , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Confocal , Microscopia Eletrônica , Neoplasias Ovarianas/patologia
10.
Reprod Med Biol ; 10(3): 179-184, 2011 09.
Artigo em Inglês | MEDLINE | ID: mdl-29662356

RESUMO

Purpose: To investigate potential indicators of in vitro fertilization (IVF) treatment outcome for female infertility patients aged ≥ 40 years based on the clinical course. Methods: We retrospectively examined results of 111 female infertility patients aged ≥ 40 years undergoing IVF treatment. We investigated the relationship between treatment cycle cancellation and the final outcome of IVF treatment in female infertility patients aged ≥ 40 years. Results: A total of 44 pregnancies were achieved. Overall pregnancy rate per initiated treatment cycle was 12.1%, and 24 spontaneous abortions occurred (54.5%). No woman aged ≥ 45 years achieved pregnancy. No patients conceived after 10 treatment cycles while 42 (11.5%) oocyte pick-up cycles and 120 (33.0%) embryo transfer cycles were canceled. Investigation of correlation with treatment cycle cancellation revealed that patients who experienced embryo transfer cancellation had a high spontaneous abortion rate while only a few patients who experienced oocyte pick-up cancellation achieved pregnancy and even fewer achieved a successful outcome. Conclusions: Our study suggests that, in addition to patient age and number of treatment cycles, cancellation of treatment cycle also provides another useful indicator for pregnancy outcome.

11.
Curr Oncol ; 28(6): 4709-4720, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34898550

RESUMO

This study aimed to assess the accuracy of predicting pelvic lymph node status using sentinel lymph node (SLN) biopsy with indocyanine green (ICG) and to examine the outcomes of SLN biopsy-guided abdominal radical trachelectomy (ART). Patients with stage IA2-IB2 cervical cancer from January 2009 to January 2021 were included. ICG was injected before ART and SLNs were identified, excised, and assessed intraoperatively using fast-frozen sections. Systemic pelvic lymphadenectomy was subsequently performed. The SLN detection rate, sensitivity, and false-negative rate were determined. Thirty patients desiring fertility preservation were enrolled, of whom 26 successfully completed ART and four underwent radical hysterectomies because of metastatic primary SLNs. Bilateral SLNs were identified in all patients. The sensitivity, false-negative rate, and negative predictive value were 100%, 7.7%, and 92.3%, respectively. Three (12%) patients were lost to follow-up: two relapsed and one died of tumor progression. Of the nine patients who tried to conceive after surgery, four achieved pregnancy and three delivered healthy live infants. In women with early-stage cervical cancer who desired to conserve fertility, SLN mapping with ICG had a very high detection rate, sensitivity, and low false-negative rate. SLN biopsy-guided ART is a feasible and accurate method for assessing pelvic node status.


Assuntos
Linfonodo Sentinela , Traquelectomia , Feminino , Humanos , Metástase Linfática/patologia , Estadiamento de Neoplasias , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/métodos
12.
Int J Clin Oncol ; 15(2): 117-24, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20333431

RESUMO

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.


Assuntos
Algoritmos , Medicina Baseada em Evidências , Seleção de Pacientes , Neoplasias do Colo do Útero/terapia , Árvores de Decisões , Feminino , Humanos , Japão , Estadiamento de Neoplasias , Sociedades Médicas , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
13.
Hypertens Pregnancy ; 39(1): 33-42, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31718385

RESUMO

Introduction: We performed an immunohistochemical investigation of the localization of Heme oxygenase(HO-1) and bilirubin(BR)/biopyrrin(BPn) to elucidate whether a response to oxidative stress is generated in the human placenta.Methods: Placentas from nine patients with preeclampsia(PE) and seven controls were investigated.Results: For HO-1 and BR/BPn expressions, a higher number of positive cells were observed in the PE group than in the control group.Conclusions: The degree of these expressions tended to relate to the onset of PE. This suggests that the heme catabolic pathway induced by oxidative stress plays an important role in the pathophysiology of PE.


Assuntos
Antioxidantes/metabolismo , Bilirrubina/metabolismo , Heme Oxigenase-1/metabolismo , Estresse Oxidativo/fisiologia , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Pré-Eclâmpsia/fisiopatologia , Gravidez
14.
Oncol Rep ; 21(5): 1209-14, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19360296

RESUMO

Most ovarian cancers arise from the mesothelial surface lining of the ovaries or from invaginations of this lining into the superficial ovarian cortex that form cortical inclusion cysts. Thus, these cysts are thought to be precursor lesions of ovarian carcinoma. Epithelial-mesenchymal transition, which is a transcriptional program for inducing maintenance of the mesenchymal phenotype, acts in tumor progression and metastasis. Little is known about the mechanisms involved in mesenchymal-epithelial transition (MET). We aimed to characterize the human ovarian surface epithelium (OSE) and inclusion cysts by immunohistochemical analysis to examine whether MET occurs during inclusion cyst formation in the OSE. We used specimens from 9 endometrial cancer patients who had undergone hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemical analysis was performed in 10 normal ovaries containing 92 inclusion cysts and in 4 normal tubes to examine the expression of antigen markers including calretinin, podoplanin, D2-40, thrombomodulin, HBME-1, vimentin, EMA, WT1, CA125, MOC31, TAG-72, Ber-EP4 and E-cadherin. The positive staining rates for mesothelial markers in normal OSE were 100% (10/10) for calretinin, 80% (8/10) for podoplanin, 80% (8/10) for D2-40, 70% (7/10) for thrombomodulin, 100% (10/10) for HBME-1, 100% (10/10) for vimentin. The positive staining rates for epithelial markers in tubal epithelium were 100% (4/4) for HBME-1, 100% (4/4) for vimentin, 100% (4/4) for EMA, 75% (3/4) for TAG-72, 100% (4/4) for Ber-EP4. Inclusion cysts showed positive staining for both markers with an incidence of 51% (47/92) for HBME-1, 44% (41/92) for vimentin, 65% (60/92) for TAG-72, 88% (81/92) for Ber-EP4. The OSE showed the characteristics of both mesenchymal and epithelium cells. In contrast, inclusion cysts gained epithelial characteristics, but lost mesenchymal characteristics. These findings support that MET occurs during the inclusion cyst formation from OSE.


Assuntos
Transformação Celular Neoplásica/patologia , Cistos Ovarianos/patologia , Neoplasias Ovarianas/patologia , Lesões Pré-Cancerosas/patologia , Diferenciação Celular/fisiologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Transformada , Transformação Celular Neoplásica/metabolismo , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Mesoderma/patologia , Cistos Ovarianos/metabolismo , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Ovário/patologia , Lesões Pré-Cancerosas/metabolismo
15.
Int J Mol Med ; 23(2): 229-36, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19148547

RESUMO

Investigation into the function of human trophoblasts has been largely restricted by a lack of suitable cell models. We aimed to produce normal human trophoblast cell lines with a long lifespan and to provide an ideal in vitro cell model. Primary human trophoblast cells were derived from a placenta that had undergone elective abortion at the 7th week of gestation. The cells were immortalized by infection with retroviral expression vectors containing the type 16 human papillomaviruses E6 and E7 in combination with human telomerase reverse transcriptase (hTERT). Characterization of the cell line was performed by immunocytochemistry using a panel of antibodies, Western blotting, real-time RT-PCR, an invasion assay, gelatin zymography, karyotype analysis and a nude mouse assay. Gene expression profiles under hypoxia (1% O2, 1 h) and subsequent reoxygenation (20% O2, 6 h) were analyzed using cDNA microarray. Immunocytochemistry revealed an extravillous trophoblastic phenotype by positive staining for hCGbeta, cytokeratin 7, HLA-G and CD9. A transwell insert invasion assay showed the invasiveness of this cell line and gelatin zymography detected the secretion of MMP-2 and MMP-9. Karyotype analysis exhibited an almost normal chromosomal number which ranged from 46 to 48 and the cells showed no tumorigenecity in a nude mouse assay. Forty-three genes showing reversible up- or down-regulation during hypoxia were detected using an oligonucleotide array. This newly immortalized cell line, HChEpC1b, is a useful model for the study of extravillous trophoblast function.


Assuntos
Linhagem Celular Transformada , Perfilação da Expressão Gênica , Proteínas Oncogênicas Virais/genética , Proteínas Repressoras/genética , Telomerase/genética , Trofoblastos/citologia , Animais , Hipóxia Celular , Linhagem Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus , Fenótipo , Placenta/citologia , Gravidez , Proteínas Repressoras/metabolismo , Telomerase/metabolismo , Trofoblastos/metabolismo
16.
J Reprod Immunol ; 77(2): 117-25, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17942160

RESUMO

Prolactin (PRL) was originally identified by its ability to stimulate mammary development and lactation, and its essential roles other than lactation have recently been implicated in female reproduction. However, little is known about PRL-mediated events in pregnancy. The tryptophan catabolism enzyme indoleamine 2,3-dioxygenase (IDO) is interferon-gamma (IFN-gamma)-inducible and has recently become a focus for maternal-fetal tolerance for successful pregnancy. Based on recognition that PRL is one of the up-regulated hormones in pregnancy, in a previous study we have shown that PRL induces IDO expression in monocytes in cooperation with a suboptimal concentration of IFN-gamma. Here, we demonstrate that PRL sensitizes monocytes to induce IDO expression in response to low doses of IFN-gamma without affecting the typical IFN-gamma signaling events, such as STAT1 phosphorylation and IRF-1 induction. In addition, IDO induction in these cell cultures was observed only after 24 h pre-exposure to PRL. These results indicate a priming effect of PRL on monocytes that occurs before IFN-gamma signaling and increases their sensitivity to IFN-gamma for IDO induction, rather than a synergistic effect of PRL and IFN-gamma on IDO induction. These results offer new insights into the roles of PRL in female reproduction, as well as provide a better understanding as to how IDO expression is regulated and achieved in pregnancy.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Interferon gama/imunologia , Monócitos/enzimologia , Prolactina/imunologia , Transdução de Sinais/imunologia , Adulto , Células Cultivadas , Indução Enzimática , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Glândulas Mamárias Humanas/enzimologia , Monócitos/imunologia , Adeno-Hipófise/metabolismo , Gravidez , Receptores de Interferon/imunologia , Receptores de Interferon/metabolismo , Receptores da Prolactina/imunologia , Receptores da Prolactina/metabolismo , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Receptor de Interferon gama
17.
Sci Total Environ ; 402(2-3): 171-5, 2008 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18558423

RESUMO

Cadmium may act like an estrogen and be a potential risk factor for estrogen-related diseases such as breast cancer and endometriosis. Here, we tested the hypothesis that higher cadmium exposure is associated with endometriosis among infertile Japanese women in a hospital-based case-control study. We recruited consecutive female patients aged 20-45 years who had complained of infertility and presented to a university hospital in Tokyo. The subjects were interviewed and provided a urine sample prior to a laparoscopic diagnosis of endometriosis between January 2000 and December 2001. The severity of endometriosis was then dichotomized into controls (stage 0 and I) and cases (stage II-IV). We finally measured urinary total cadmium concentration in 54 cases and 74 controls as a biomarker of long-term cumulative exposure. Odds ratios were adjusted for average menstrual cycle length, body-mass index and smoking status using unconditional logistic regression. Results showed no association between endometriosis and urinary cadmium concentration. Medians (interquartile ranges) of urinary cadmium concentration in cases and controls were 0.53 (0.40-0.73) and 0.54 (0.34-0.76) microg/g creatinine, respectively (P for difference=0.88). Adjusted odds ratio (95% confidence interval) for the highest versus lowest tertile of urinary creatinine-adjusted cadmium concentration was 0.86 (0.30 to 2.49, P for trend=0.79). Our results do not support the hypothesis that higher urinary cadmium concentration is associated with the risk of endometriosis.


Assuntos
Cádmio/urina , Endometriose/induzido quimicamente , Infertilidade Feminina/complicações , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Endometriose/complicações , Feminino , Humanos , Japão , Menstruação , Pessoa de Meia-Idade , Fatores de Risco , Sensibilidade e Especificidade , Fumar
18.
Obstet Gynecol ; 109(2 Pt2): 537-40, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17267887

RESUMO

BACKGROUND: The administration of chemotherapeutic drugs during pregnancy is rare. We describe a case of malignant ovarian tumor complicating pregnancy. CASE: After laparotomy at 18 weeks of gestation, the patient received three courses of cisplatin, vinblastine, and bleomycin. Elective cesarean delivery was performed at 31 weeks of gestation. A normal infant was delivered, and no evidence of tumor recurrence was observed. Metastasis to the liver was detected in the fifth month after delivery. However, this was treated successfully with three courses of cisplatin, etoposide, and bleomycin. There was no evidence of recurrence observed at 65 months after the initial treatment. CONCLUSION: Although the risk of chemotherapy to the fetus cannot be assessed based on a single case, this experience is encouraging.


Assuntos
Tumor do Seio Endodérmico/diagnóstico , Neoplasias Ovarianas/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Diagnóstico Pré-Natal , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Cesárea , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Diagnóstico Diferencial , Tumor do Seio Endodérmico/tratamento farmacológico , Tumor do Seio Endodérmico/patologia , Tumor do Seio Endodérmico/cirurgia , Feminino , Humanos , Recém-Nascido , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/cirurgia , Terceiro Trimestre da Gravidez , Cuidado Pré-Natal , Vimblastina/administração & dosagem
19.
Oncol Rep ; 18(1): 195-201, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17549368

RESUMO

Paclitaxel (PX) binds to and stabilizes tubulin, preventing depolymerization, and resulting in cell death. Based on a previous report showing the activity of phosphatidylinositol kinase (PIK) on tubulin, we investigated the effect of the PI4K inhibitor orobol and the PI3K activator platelet derived growth factor (PDGF) on PX sensitivity. Drug sensitivity was examined by classical colony forming assay. Tubulin isotype expression was determined by semi-quantitative RT-PCR. Microtubule texture was observed by laser confocal microscope using anti-beta-tubulin antibody. Apoptotic activity was estimated by frequency of condensed nuclear chromatin with Hoechst 33342 stain. Orobol enhanced PX sensitivity of human ovarian carcinoma 2008 cells by 18.9+/-1.2-fold (N=3; P<0.01). In contrast, pretreatment with PDGF rendered cells resistant to PX by 2.3+/-0.4-fold (N=3; P<0.01). Neither orobol nor PDGF showed any effect on cell growth. Orobol produced a 2.5-fold sensitization in cisplatin-resistant 2008/C13*5.25 (C13) cells, and PDGF rendered the cells 2.3-fold resistant to PX. Orobol suppressed the beta 4a-tubulin isotype expression by 85% and other isotypes by 20%. In contrast, PDGF induced beta 4a-tubulin isotype expression by 1.3-fold, while it supressed all the other isotypes by 20-40%. Orobol produced thick microtubules and PDGF generated ring condensed microtubules. Orobol promoted PX-induced apoptosis, while PDGF caused 50% reduction of apoptosis. These results indicate that orobol and PDGF regulate PX sensitivity by reciprocally altering the proportion of tubulin isotype expression and PX-induced apoptotic signaling.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Cistadenocarcinoma Seroso/tratamento farmacológico , Flavonoides/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Caspase 3/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Microscopia Confocal , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Células Tumorais Cultivadas
20.
Oncol Rep ; 17(4): 731-5, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17342307

RESUMO

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMPs). We evaluated whether EMMPRIN expression is related to tumor progression and patient outcome in human endometrial carcinoma. Paraffin-embedded surgical tissue samples from 112 patients with endometrial carcinoma were stained with anti-EMMPRIN antibody (monoclonal antibody 12C3:MoAb 12C3) for immunohistochemical analysis. EMMPRIN protein was expressed in cancerous lesions with the incidence of 97.3% (109 of 112 cases), but not in normal lesions. The scores determined by the combination of intensity and pattern of EMMPRIN staining in cancer cells correlated significantly with various histopathological risk factors: advanced stage, P=0.001; poorly differentiated carcinoma, P<0.001; lymph node metastasis, P=0.002; and lymphatic vessel infiltration, P=0.027. More importantly, recurrence-free survival was shortened in patients with higher EMMPRIN scores (HR, 3.08; 95% CI, 1.32-7.19; P=0.01). These results suggest that measurement of EMMPRIN expression with simple immunohistochemical staining may enhance the understanding of the pathophysiology of endometrial carcinoma.


Assuntos
Anticorpos Monoclonais/imunologia , Basigina/análise , Neoplasias do Endométrio/diagnóstico , Imuno-Histoquímica/métodos , Adulto , Idoso , Anticorpos Monoclonais Murinos , Basigina/imunologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
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