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This study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate-risk stage I and II or high-risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel-epirubicin-carboplatin (TEC), paclitaxel-anthracycline (doxorubicin)-carboplatin (TAC), or dose-dense paclitaxel-carboplatin (ddTC). The primary end-point was the completion rate (CRate) of six cycles of treatment. The secondary end-points were progression-free survival (PFS) and overall survival (OS). One hundred and one patients were treated as follows: 33 received TEC, 33 TAC, and 35 ddTC. The CRates for TEC, TAC, and ddTC were 94%, 64%, and 69%, respectively (P = .005). The TEC CRate was significantly higher than for the other two groups. However, the PFS and OS outcomes were not statistically different between the three groups. The 2-year survival rates were 94%, 97%, and 97% for TEC, TAC, and ddTC, respectively. When compared to the current standard treatments for endometrial cancer, TEC is a promising candidate for a phase III trial based on its significantly superior CRate and equivalent PFS and OS. This study is registered with UMIN Clinical Trials Registry (UMIN000008911).
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Endometriales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/efectos adversos , Quimioterapia Adyuvante , Neoplasias Endometriales/tratamiento farmacológico , Femenino , Humanos , Estadificación de Neoplasias , Paclitaxel/uso terapéuticoRESUMEN
OBJECTIVE: Turner syndrome (TS) is a congenital disease characterized by delayed puberty, ovarian dysgenesis and short stature. Although most patients are diagnosed with primary amenorrhea, approximately 15-20% of patients with TS are reported to have spontaneous menarche. However, little is known about their menstruation status after spontaneous menarche. In the current study, we investigated the menstrual abnormalities after spontaneous menarche in TS patients. DESIGN: Retrospective study. PATIENTS: This study included TS patients with spontaneous menarche at Osaka Police Hospital or Komura Women's Clinic between April 2015 and December 2019. MEASUREMENTS: Data regarding the age of menarche, menstruation status and chromosomal karyotype were collected and retrospectively analyzed. RESULTS: Of 172 TS patients, 32 with spontaneous menarche were identified. The median age of menarche was 12 years old. Premature ovarian insufficiency (POI) after menarche was observed in 12 patients (37.5%) and the median age at menopause was 20 years old. The average period from spontaneous menarche to menopause in these patients was 5.1 years. Five patients (15.6%) had irregular menstruation and 15 (46.9%) had regular menstruation. When examined according to the structural abnormality of the X chromosome, all patients with structural abnormality of the X chromosome were diagnosed with POI after spontaneous menarche, and none with mosaic without structural abnormality were diagnosed with POI. CONCLUSION: Approximately one-third of TS patients with spontaneous menarche were diagnosed with POI after menarche for an average of 5.1 years. Counseling is required for TS patients and their parents, including information about menstrual abnormalities or fertility preservation.
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Insuficiencia Ovárica Primaria , Síndrome de Turner , Adulto , Niño , Femenino , Humanos , Menarquia , Trastornos de la Menstruación/etiología , Insuficiencia Ovárica Primaria/genética , Estudios Retrospectivos , Síndrome de Turner/genética , Adulto JovenRESUMEN
INTRODUCTION: Ventriculoperitoneal (VP shunts) and lumboperitoneal shunts (LP shunts) are used to treat hydrocephalus. The effectiveness of LP shunts has recently been demonstrated. Due to population aging, the number of patients with LP shunts is expected to increase. PRESENTATION OF CASE: A 51-year-old female, in whom an LP shunt had been inserted to treat hydrocephalus after a subarachnoid hemorrhage, underwent laparoscopic right salpingo-oophorectomy for a right endometriotic cyst. We consulted a neurosurgeon and confirmed the route of the shunt. We started a normal laparoscopic procedure. The head of the shunt tube was located in Douglas' pouch and was an obstacle to the procedure. We moved the head of the shunt tube to the vesicouterine pouch and successfully conducted the standard operation. We report the case together with a literature review. DISCUSSION: There have been several reports about gynecological laparoscopic surgery being performed in patients with VP shunts. On the other hand, we did not find any English literature about gynecological laparoscopic surgery being conducted in patients with LP shunts during a PubMed search. CONCLUSION: This is the first report about gynecological laparoscopic surgery being performed in a patient with an LP shunt.
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PURPOSE: Development of new treatment strategies for endometrial cancer that has become refractory or resistant to taxane/platinum is a critical need. The present study was a phase I/II study of gemcitabine, levofolinate, irinotecan, and 5-fluorouracil (5-FU) (GLIF) combination chemotherapy to determine optimal dosages, safety, and efficacy. METHODS: Taxane/platinum-resistant or -refractory endometrial disease was defined as tumor progression within 6 months after a taxane/platinum-based regimen. Maximum tolerated dose was investigated by a 3 + 3-designed phase I study. The phase II study was conducted using the recommended doses determined in the phase I study. RESULTS: The dosages recommended for the phase II trial were determined, in the phase I trial, to be: gemcitabine 800 mg/m2, levofolinate 100 mg/m2, irinotecan 80 mg/m2, and 5-FU 1000 mg/m2. Thirty patients were enrolled, including the three patients who received GLIF therapy at the same dose as the recommended phase II dose in the phase I study. Two patients were excluded at this point due to study protocol violations, and the remaining 28 patients were included for analysis. Phase II revealed that the response and disease control rates were 7.1% (2/28) and 39.3% (11/28), respectively, and that the median PFS and OS were 3 months [95% confidence interval (CI) 3-7] and 12 months (95% CI 9-17), respectively. Febrile or grade 4 neutropenia was observed in 14% (4/28) of the cases. Grade 3 or 4 thrombocytopenia was not observed. CONCLUSION: We found that GLIF combination chemotherapy is potentially a useful treatment option for endometrial cancers refractory or resistant to taxane/platinum-based chemotherapy.
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Desoxicitidina/análogos & derivados , Neoplasias Endometriales/tratamiento farmacológico , Fluorouracilo , Glutamatos , Irinotecán , Administración Intravenosa , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Resistencia a Antineoplásicos , Neoplasias Endometriales/patología , Endometrio/patología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Glutamatos/administración & dosificación , Glutamatos/efectos adversos , Humanos , Irinotecán/administración & dosificación , Irinotecán/efectos adversos , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del Tratamiento , GemcitabinaRESUMEN
Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC50â¯<â¯5.0â¯nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative structures used in known conjugated drugs. These novel analogs showed excellent potency in a tumor cell proliferation assay, and thus this series of dolastatin 10 analogs is suitable as versatile payloads in conjugated drugs. Insights into the structure-activity relationships of the analogs are also discussed.
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Antineoplásicos/farmacología , Depsipéptidos/farmacología , Tiazoles/farmacología , Alcoholes/química , Aminas/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Depsipéptidos/síntesis química , Depsipéptidos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Estructura Molecular , Relación Estructura-Actividad , Compuestos de Sulfhidrilo/química , Tiazoles/síntesis química , Tiazoles/química , Tubulina (Proteína)/metabolismoRESUMEN
OBJECTIVE: Removal of the ovaries is common during surgery for endometrial cancer. However, because loss of the ovaries can cause several health problems in patients, strategies for the prevention of such problems need to be established. Hence, we decided to conduct a multicenter randomized clinical trial to assess the effect of raloxifene on bone mineral density (BMD), bone metabolism, and the lipid profile of patients who had undergone surgery for patients with endometrial cancer. MATERIALS AND METHODS: Patients with endometrial cancer were enrolled after treatment. The participants were randomized into 2 groups: group 1 included 39 women who received alfacalcidol (1 µg/d) alone and group 2 included 37 women who received alfacalcidol and the test drug, raloxifene hydrochloride, at a dose of 60 mg/d. The BMD of lumbar spine and femoral neck, serum bone markers, as well as lipid profile parameters were evaluated at enrollment as well as 6, 12, and 24 months after the enrollment. The primary efficacy end point was the percentage change from baseline to 24 months in lumbar spine (L2-L4) and femoral neck BMD. RESULTS: Sixty-four women completed the 24-month study. At 24 months, the lumbar and femoral neck BMDs were significantly increased in group 2 compared with group 1 (3.5% vs -0.8% and 2.3% vs -2.8%, respectively). In group 2, low-density lipoprotein-cholesterol levels were significantly reduced by 13.6% and serum N-terminal telopeptide of type I collagen as well as bone-specific alkaline phosphatase values were significantly reduced by 16.7% and 25.7%, respectively. The patients who received adjuvant therapy for endometrial cancer showed a significantly higher response to raloxifene (5.8% vs 1.9%). Recurrence was detected in 2 (2.6%) patients in group 1. No severe adverse events were noted in any patient during the study period. CONCLUSIONS: Raloxifene exerts positive effects on BMD, bone metabolism, and lipid profile parameters and could provide an improved therapeutic option for patients with endometrial cancer.
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Carcinoma Endometrioide/cirugía , Neoplasias Endometriales/cirugía , Histerectomía/efectos adversos , Complicaciones Posoperatorias/prevención & control , Clorhidrato de Raloxifeno/uso terapéutico , Adulto , Anciano , Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/fisiología , Carcinoma Endometrioide/epidemiología , Neoplasias Endometriales/epidemiología , Femenino , Humanos , Hidroxicolecalciferoles/administración & dosificación , Histerectomía/estadística & datos numéricos , Lípidos/sangre , Persona de Mediana Edad , Posmenopausia/efectos de los fármacos , Complicaciones Posoperatorias/epidemiología , Resultado del TratamientoRESUMEN
This case involved a 69-year-old woman who had been taking tamoxifen for 5 years after breast cancer surgery. She was referred to our clinic for endometrial cancer screening when tamoxifen was first prescribed. Subsequently, transvaginal ultrasonography and endometrial cytology were performed every 6 months. Despite these regular examinations, stage IVb papillary serous carcinoma was detected 8 months after the end of tamoxifen administration. Total abdominal hysterectomy was performed, but only a small polyp was seen upon macroscopic examination of the uterus. However, papillary serous carcinoma was found microscopically in almost all lymphovascular spaces in the uterus from the endometrium to the serosa. On the surface of the polyp, only endometrial intraepithelial carcinoma with positive immunostaining for p53 was detected. Chemotherapy, including a platinum compound, was administrated, but unfortunately it was ineffective and the patient died of her disease 14 months after the operation.
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Cistadenocarcinoma Papilar/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Antagonistas de Estrógenos/efectos adversos , Tamoxifeno/efectos adversos , Neoplasias Uterinas/diagnóstico , Anciano , Cistadenocarcinoma Papilar/etiología , Cistadenocarcinoma Seroso/etiología , Femenino , Humanos , Neoplasias Uterinas/etiologíaRESUMEN
PAX 8 is a paired-box gene that plays an important role in the embryogenesis of the thyroid gland, Müllerian ducts, and renal/upper urinary tract. PAX 8 expression is observed in carcinomas from each of these sites. Accordingly, PAX 8 immunostaining has been reported to be useful for the diagnosis of these carcinomas. Here, we report a case in which PAX 8 was useful for the diagnosis of a patient with cervical adenocarcinoma and multiple metastases. A 55-year-old female patient complained of cough and genital bleeding. Examination revealed a uterine cervical mass, masses in both breasts, and enlargement of the lymph nodes and subcutaneous nodules. Histology of the uterine cervical mass biopsy revealed a poorly differentiated adenocarcinoma. Cytology of the aspiration biopsy specimens of the breast masses indicated scirrhous cancer. PAX 8 immunostaining of the uterine cervical mass and breast mass biopsies was positive. We determined that the breast masses were metastases of the cervical adenocarcinoma and decided to treat the patient with chemotherapy consisting of paclitaxel and carboplatin. A partial response was observed. A hysterectomy was performed 5 months after chemotherapy because corpus cancer was newly diagnosed. The cervical adenocarcinoma was undetectable in the surgical specimen. Fifteen months have passed since the completion of chemotherapy and the metastases has been under control.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adenocarcinoma/química , Carboplatino/administración & dosificación , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Factor de Transcripción PAX8 , Paclitaxel/administración & dosificación , Factores de Transcripción Paired Box/análisis , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: To analyze the efficacy and safety of combination chemotherapy of docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or -resistant ovarian carcinomas and for first treatment of primary clear cell and mucinous ovarian carcinomas. STUDY DESIGN: Between 2002 and 2009, we conducted a prospective Phase II study of the efficacy and safety of combination chemotherapy using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan was determined during our previous Phase I study. RESULTS: A docetaxel plus irinotecan regimen provided a 53% response rate, 6 months progression-free survival (PFS), and 12 months overall survival (OS) for primary clear cell and mucinous ovarian carcinomas (similar to TC therapy). The differences of anti-tumor and survival effects between refractory and resistant cases were not statistically significant. The regimen also provided a 15% response rate, 5 months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used as a second-line chemotherapy. These data are similar to previous reports, however, our study provides the first data exclusively for the cases refractory or resistant to a gold standard TC therapy as a second-line chemotherapy. The regimen was demonstrated to be well tolerable. CONCLUSION: Combination chemotherapy of docetaxel and irinotecan may be a useful option to treat TC-refractory/resistant cases and primary clear cell and mucinous adenocarcinoma cases of ovarian carcinoma.
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Adenocarcinoma de Células Claras/tratamiento farmacológico , Adenocarcinoma Mucinoso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Resistencia a Antineoplásicos , Neoplasias Ováricas/tratamiento farmacológico , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma Mucinoso/mortalidad , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Carboplatino , Supervivencia sin Enfermedad , Docetaxel , Femenino , Humanos , Irinotecán , Japón/epidemiología , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Paclitaxel , Estudios Prospectivos , Taxoides/administración & dosificación , Taxoides/efectos adversosRESUMEN
Patients with Turner syndrome (TS) almost develop osteoporosis, resulting from chromosomal deficiency and estrogen deficiency by gonadal dysgenesis. The aim of this study was to assess bone mineral density (BMD) during continuous estrogen therapy in young TS patients by measuring lumbar spine BMD of 67 TS patients using dual-energy X-ray absorptiometry. Twenty-seven patients who were treated with adult-doses of estrogen prior to the first evaluation, exhibited a significantly higher initial BMD than 30 patients treated with low-dose estrogen therapy and 10 patients without estrogen therapy (0.808 g/cm², 0.714 g/cm², and 0.664 g/cm², respectively). During continuous adult-dose estrogen therapy, BMD significantly increased in each group (maximum BMD during the study, 0.842 g/cm², 0.790 g/cm², and 0.724 g/cm², respectively). Initial and maximum BMD showed significant negative correlation with the age at which adult-dose estrogen therapy was initiated (r = -0.57 and -0.45, respectively). Among the patients not treated with adult-dose estrogen therapy prior to the first evaluation, the annual increase in the rate and amount of BMD was significantly higher when adult-dose estrogen therapy was initiated before age 18 (rate, 4.4 % before age 18 vs. 3.1 % after age 18; amount, 0.03 g/cm² before age 18 vs. 0.02 g/cm² after age 18). In summary, estrogen therapy increased BMD in young TS patients and might be more effective if initiated by age 18.
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Densidad Ósea/efectos de los fármacos , Terapia de Reemplazo de Estrógeno , Estrógenos/uso terapéutico , Osteoporosis/prevención & control , Síndrome de Turner/tratamiento farmacológico , Absorciometría de Fotón , Adolescente , Adulto , Factores de Edad , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Didrogesterona/administración & dosificación , Didrogesterona/uso terapéutico , Estrógenos/administración & dosificación , Estrógenos Conjugados (USP)/administración & dosificación , Estrógenos Conjugados (USP)/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Vértebras Lumbares , Osteoporosis/etiología , Estudios Retrospectivos , Síndrome de Turner/fisiopatología , Adulto JovenRESUMEN
We report on the identification of 2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5H-pyrrolo[3,2-d]pyrimidine-5-yl}methyl)-4-fluorobenzonitrile (DSR-12727) (7a) as a potent and orally active DPP-4 inhibitor without mechanism-based inactivation of CYP3A. Compound 7a showed good DPP-4 inhibitory activity (IC(50)=1.1 nM), excellent selectivity against related peptidases and other off-targets, good pharmacokinetic and pharmacodynamic profile, great in vivo efficacy in Zucker-fatty rat, and no safety concerns both in vitro and in vivo.
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Inhibidores del Citocromo P-450 CYP3A , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Animales , Glucemia/metabolismo , Citocromo P-450 CYP3A/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/síntesis química , Inhibidores de la Dipeptidil-Peptidasa IV/química , Perros , Relación Dosis-Respuesta a Droga , Prueba de Tolerancia a la Glucosa , Haplorrinos , Humanos , Masculino , Conformación Molecular , Pirazoles/síntesis química , Pirazoles/química , Pirimidinas/síntesis química , Pirimidinas/química , Ratas , Ratas Zucker , Estereoisomerismo , Relación Estructura-Actividad , Factores de TiempoRESUMEN
BACKGROUND: TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determined. PATIENTS AND METHODS: Phase I/II prospective study for TEC therapy was performed. A retrospective comparison of the prognosis between adjuvant TEC therapy and radiation for completely resected cases with risk factors was also performed. RESULTS: The recommended dose of TEC therapy was determined to be paclitaxel 150 mg/m(2), epirubicin 50 mg/m(2), and carboplatin AUC 4. A TEC regimen at this dose level was shown to be tolerable. The response rate and median overall survival were 74% and 37 months for those with advanced primary disease (Group B) and 50% and 26 months for recurrent tumors (Group C), respectively. A retrospective comparison showed that adjuvant TEC therapy for completely resected stage III cases improved their prognosis when compared to an adjuvant radiation therapy. CONCLUSION: TEC therapy was demonstrated to be a tolerable and effective treatment, not only as a remission-induction therapy for advanced and recurrent endometrial carcinomas but also as the adjuvant therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Adulto , Anciano , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Neoplasias Endometriales/mortalidad , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Inducción de Remisión , Estudios RetrospectivosRESUMEN
Structures containing the (R)-3-amino-3-methyl piperidine unit as a new pharmacophore moiety have been shown to possess moderate inhibitory activity for DPP-4 with good pharmacokinetics profile. One of these compounds was found to have good oral bioavailability and PK/PD profile in ZF-rat.
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Dipeptidil Peptidasa 4/química , Inhibidores de la Dipeptidil-Peptidasa IV/química , Piperidinas/química , Pirimidinonas/química , Animales , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/síntesis química , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Evaluación Preclínica de Medicamentos , Humanos , Microsomas Hepáticos/metabolismo , Piperidinas/síntesis química , Piperidinas/farmacocinética , Pirimidinonas/síntesis química , Pirimidinonas/farmacocinética , Ratas , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
This study examines the role of vascular endothelial growth factor (VEGF) as a therapeutic target in clear cell carcinoma (CCC) of the ovary, which has been regarded as a chemoresistant histologic subtype. Immunohistochemical analysis using tissue microarrays of 98 primary ovarian cancers revealed that VEGF was strongly expressed both in early-stage and advanced-stage CCC of the ovary. In early-stage CCCs, patients who had tumors with high levels of VEGF had significantly shorter survival than those with low levels of VEGF. In vitro experiments revealed that VEGF expression was significantly higher in cisplatin-refractory human CCC cells (RMG1-CR and KOC7C-CR), compared with the respective parental cells (RMG1 and KOC7C) in the presence of cisplatin. In vivo treatment with bevacizumab markedly inhibited the growth of both parental CCC cell-derived (RMG1 and KOC7C) and cisplatin-refractory CCC cell-derived (RMG1-CR and KOC7C-CR) tumors as a result of inhibition of tumor angiogenesis. The results of the current study indicate that VEGF is frequently expressed and can be a promising therapeutic target in the management of CCC. Bevacizumab may be efficacious not only as a first-line treatment but also as a second-line treatment of recurrent disease in patients previously treated with cisplatin.
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Adenocarcinoma de Células Claras/terapia , Neoplasias Ováricas/terapia , Factores de Crecimiento Endotelial Vascular/metabolismo , Adenocarcinoma de Células Claras/patología , Inhibidores de la Angiogénesis/farmacología , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Bevacizumab , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/terapia , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Ratones , Ratones Desnudos , Neoplasias Ováricas/patología , Factores de Crecimiento Endotelial Vascular/biosíntesis , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
SUMMARY: A rare case of a clear cell adenocarcinoma and an adenosarcoma coexisting with a heterologous rhabdomyosarcoma in an endometriotic cyst of the ovary is reported. The tumor was composed of a cystic area and a solid area arising from the cyst wall. In the cystic lesion, a detached polypoid mass was also identified. The cyst wall was lined with a single layer of endometrial-type cells, whereas the solid area was composed of a clear cell adenocarcinoma. In the detached polypoid mass, an exophytic leaf-like pattern containing benign endometrial-type cells and squamous epithelial and rhabdomyosarcoma components, which were positive for desmin and myoglobin, was observed. Using X-chromosomal clonality assay, these clear cell adenocarcinoma and adenosarcoma components showed patterns of polyclonality. To the authors' knowledge, this is the first reported case of a clear cell adenocarcinoma and an adenosarcoma coexisting with heterologous rhabdomyosarcoma in an endometriotic cyst of the ovary.
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Adenocarcinoma de Células Claras/patología , Adenosarcoma/patología , Neoplasias Primarias Múltiples/patología , Quistes Ováricos/patología , Neoplasias Ováricas/patología , Rabdomiosarcoma/patología , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Adenosarcoma/genética , Adenosarcoma/metabolismo , Endometriosis/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/metabolismo , Quistes Ováricos/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Reacción en Cadena de la Polimerasa , Receptores Androgénicos/genética , Rabdomiosarcoma/genética , Rabdomiosarcoma/metabolismoRESUMEN
Three cases of cesarean scar pregnancy successfully treated with methotrexate are described. The diagnosis was confirmed by transvaginal sonographic examinations showing a well-formed gestational sac in the myometrium of the lower uterine segment. Initial treatment with a systemic injection of 50 mg of methotrexate was not sufficient, and multiple doses were required to obtain a complete remission in two cases. In a case with a beta-hCG level of more than 20,000 mIU/mL with a viable embryo in a gestational sac, a combination of systemic and local treatment with methotrexate was required. It took 7-11 weeks for the beta-hCG level to become undetectable and 12-17 weeks for the cesarean scar pregnancy mass to disappear completely.
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Abortivos no Esteroideos/uso terapéutico , Cesárea/efectos adversos , Metotrexato/uso terapéutico , Embarazo Ectópico/tratamiento farmacológico , Aborto Inducido/métodos , Adulto , Cicatriz/complicaciones , Femenino , Humanos , Embarazo , Embarazo Ectópico/diagnóstico por imagen , UltrasonografíaRESUMEN
A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and may suggest underlying skeletal fragility. Therefore, establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for patients who suffer from osteoporosis. The objective of this study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to monitor the response to alendronate therapy at the distal radius in early postmenopausal Japanese women. Thirty-two early postmenopausal women who were diagnosed with osteoporosis or osteopenia were randomized to either alendronate or control treatment. We analyzed the BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turnover (deoxypyridinoline) at baseline, 3, 6 and 12 months. The control group showed a significant decrease from baseline in the trabecular BMD of the radius at 12 months (3.5 +/- 3.7%; p < 0.01), whereas the alendronate group showed a significant increase (4.3 +/- 8.1%). The changes in the trabecular BMD of the radius between the alendronate and control groups were statistically different at 6 and 12 months (p < 0.01). However, in the total BMD at the diaphysis of the radius, no significant differences were seen in the changes in bone densities between the alendronate and control groups after 1 year of treatment. pQCT detected significant differences in BMD of the radius in early postmenopausal women after 1 year of treatment with alendronate. Collectively, our preliminary clinical trial showed that pQCT might be useful to monitor response to alendronate therapy, especially at the radius, and it might explain why alendronate prevents Colles' fracture.
Asunto(s)
Alendronato/farmacología , Conservadores de la Densidad Ósea/farmacología , Posmenopausia/efectos de los fármacos , Tomografía Computarizada por Rayos X , Absorciometría de Fotón , Adulto , Anciano , Aminoácidos/orina , Biomarcadores/metabolismo , Densidad Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/efectos de los fármacos , Persona de Mediana Edad , Radio (Anatomía)/diagnóstico por imagenRESUMEN
A rare case of mixed carcinoma of the ovary is reported, composed of a large cell neuroendocrine carcinoma and a mucinous borderline endocervical tumor. The large cell neuroendocrine carcinoma was composed of solid nests, sheets, and trabeculae of medium to large-sized cells, and was positive for synaptophysin. The mucinous epithelial tumor varied in appearance from a borderline to an intraepithelial carcinoma, and showed sparsely scattered immunoreactivity for chromogranin-A. Using an X-chromosome clonality assay, these 2 components showed patterns of monoclonality. These results suggest that the large cell neuroendocrine carcinoma may have arisen from the mucinous epithelial tumor.
Asunto(s)
Adenocarcinoma Mucinoso/patología , Carcinoma de Células Grandes/patología , Carcinoma Neuroendocrino/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Adenocarcinoma Mucinoso/genética , Adulto , Carcinoma de Células Grandes/genética , Carcinoma Neuroendocrino/genética , Células Clonales , Femenino , Humanos , Inmunohistoquímica , Neoplasias Primarias Múltiples/genética , Neoplasias Ováricas/genética , Reacción en Cadena de la Polimerasa , Receptores Androgénicos/genéticaRESUMEN
OBJECTIVE: A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and should alert the patient and physician to the possibility of underlying skeletal fragility. Therefore, the establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for the patients who suffer from osteoporosis. The objective of the present study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to assess the change of BMD at the distal radius in early postmenopausal women who receive hormone replacement therapy (HRT). METHODS: Twenty healthy early postmenopausal women who were diagnosed as osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin, deoxypyridinoline) every 6 months. RESULTS: The placebo group showed a significant decrease from the baseline in the trabecular BMD of the radius at 12 months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and placebo groups were statistically different at 12 months (p<0.05). On the other hand, in the cortical BMD of the radius, no significant differences were seen between the changes of bone densities in the HRT and control groups after 1 year of treatment. pQCT could detect a significant loss of BMD of the radius in early postmenopausal women after 1 year and HRT prevented its loss. CONCLUSION: Our preliminary clinical trial showed that pQCT might be useful for the early detection of bone loss in early postmenopausal women and for the monitoring BMD of the patients who receive HRT.
Asunto(s)
Densidad Ósea , Terapia de Reemplazo de Estrógeno , Osteoporosis Posmenopáusica/diagnóstico , Osteoporosis Posmenopáusica/prevención & control , Absorciometría de Fotón/métodos , Adulto , Anciano , Calcio/administración & dosificación , Estrógenos/administración & dosificación , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Medroxiprogesterona/administración & dosificación , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico por imagen , Valor Predictivo de las Pruebas , Radio (Anatomía)/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effects of estradiol (E2) and raloxifene on the migration of human monocytic THP-1 cells to endothelium. DESIGN: A prospective comparative study. THP-1 cells, a human acute monocytic leukemia cell line, were used for the study. Migration assays were performed using transwell inserts. THP-1 cells were exposed to E2 or raloxifene in the presence of monocytic chemoattractant protein-1 (MCP-1), a major chemoattractant for monocytes. The cells were transfected with small interfering RNA (siRNA) against estrogen receptor (ER) alpha and ERbeta for gene silencing. ER expression was evaluated by Western blot analysis. RESULTS: MCP-1 induced the migration of the cells for 90 minutes. The addition of E2 or raloxifene significantly inhibited the MCP-1-induced migration for 90 minutes. Preincubation of THP-1 cells with an ER antagonist, ICI 182780, significantly attenuated the inhibitory effects of E2 and raloxifene. Whereas transfection with siRNA of ERalpha significantly attenuated the inhibition by E2 of MCP-1-induced monocyte migration, transfection with control siRNA or siRNA of ERbeta had no effect on the rapid inhibitory action of E2. Moreover, preincubation of THP-1 cells with a transcriptional inhibitor, actinomycin D, had no effect on the rapid inhibitory action of E2. CONCLUSIONS: Our findings suggest that both E2 and raloxifene inhibited the MCP-1-induced monocyte migration through nongenomic ERalpha. This result may explain one of the antiatherosclerotic effects of E2 and raloxifene on vasculature.