Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Eur J Gynaecol Oncol ; 36(4): 397-401, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26390690

RESUMEN

PURPOSE OF INVESTIGATION: This study aimed to assess the role of omentectomy in the surgical therapy of endometrial cancer. MATERI- ALS AND METHODS: A retrospective study was performed in 98 patients who were pathologically diagnosed with endometrial cancer and had initially undergone surgical therapy at the present institution. This study analyzed the relationship between omental metastasis and clinicopathological factors. RESULTS: Omental metastasis was detected in nine patients (9%). On univariate analysis, significant number of omental metastatic lesions were detected in few cases by positive peritoneal cytology, adnexal metastasis, gross dissemination, and lymphovascular space involvement. On multivariate analysis, adnexal metastasis were a significant risk factor. The sensitivity of the spe- cial histological type and the specificity of the macroscopic peritoneal dissemination and adnexal metastasis were all high. CONCLUSION: Omentectomy plays a significant role in determining the exact surgical staging in cases with non-endometrioid cancer, adnexal metas- tasis, and macroscopic peritoneal dissemination.


Asunto(s)
Neoplasias Endometriales/patología , Epiplón/patología , Neoplasias Peritoneales/cirugía , Adulto , Anciano , Neoplasias Endometriales/cirugía , Femenino , Humanos , Persona de Mediana Edad , Epiplón/cirugía , Estudios Retrospectivos
2.
Eur J Gynaecol Oncol ; 36(4): 424-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26390696

RESUMEN

OBJECTIVE: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of third- line chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of third-line chemotherapy. MATERIALS AND METHODS: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. RESULTS: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0-3 months, 3-6 months, and 6-12 months and ≥ 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI ≥ 3 months than for TFI 0-3 months (795 days vs. 281 days, p < 0.001). Finally, according to univariate (HR = 0.256; p < 0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. CONCLUSIONS: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.


Asunto(s)
Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Ováricas/mortalidad , Pronóstico
3.
Br J Cancer ; 110(12): 2965-74, 2014 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-24867687

RESUMEN

BACKGROUND: Although T-cell immunity is thought to be involved in the prognosis of epithelial ovarian cancer (EOC) patients, immunosuppressive conditions hamper antitumour immune responses. Thus, their mechanisms and overcoming strategies need to be investigated. METHODS: The role of NF-κB in human EOC cells and macrophages was evaluated by in vitro production of immunosuppressive IL-6 and IL-8 by EOC cells and in vivo analysis of immune responses in nude mice implanted with human EOC cells using an NF-κB inhibitor DHMEQ. RESULTS: In EOC patients, increased plasma IL-6, IL-8, and arginase were observed. The NF-κB inhibitor DHMEQ inhibited the production of IL-6 and IL-8 by EOC cell lines. Immunosuppression of human DCs and macrophages by culture supernatant of EOC cells was reversed with the pretreatment of DHMEQ. Administration of DHMEQ to nude mice implanted with human EOC resulted in the restoration of T-cell stimulatory activity of murine DCs along with the reduction of tumour accumulation and arginase expression of MDSCs. Nuclear factor-κB inhibition in tumour-bearing mice also enhanced antitumour effects of transferred murine naive T cells. CONCLUSIONS: NF-κB is involved in the immunosuppression induced by human EOC, and its inhibitor may restore antitumour immune responses, indicating that NF-κB is an attractive target for EOC treatment.


Asunto(s)
Tolerancia Inmunológica , Interleucina-6/inmunología , Interleucina-8/inmunología , Neoplasias Glandulares y Epiteliales/inmunología , Neoplasias Ováricas/inmunología , Factor de Transcripción ReIA/inmunología , Traslado Adoptivo , Animales , Arginasa/sangre , Benzamidas/farmacología , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Medios de Cultivo Condicionados/farmacología , Ciclohexanonas/farmacología , Células Dendríticas/inmunología , Femenino , Humanos , Interleucina-6/biosíntesis , Interleucina-6/sangre , Interleucina-8/biosíntesis , Interleucina-8/sangre , Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Transducción de Señal/inmunología , Factor de Transcripción ReIA/antagonistas & inhibidores , Factor de Transcripción ReIA/genética , Trasplante Heterólogo
4.
Br J Cancer ; 108(3): 613-20, 2013 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-23299542

RESUMEN

BACKGROUND: Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied. METHODS: In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology. RESULTS: Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression. CONCLUSION: Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Anhidrasas Carbónicas/metabolismo , Hiperplasia/patología , Neoplasias Glandulares y Epiteliales/patología , Infecciones por Papillomavirus/patología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma Mucinoso/enzimología , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/virología , Adulto , Anciano , Anciano de 80 o más Años , Anhidrasa Carbónica IX , Carcinoma Lobular/enzimología , Carcinoma Lobular/patología , Carcinoma Lobular/virología , ADN Viral/genética , Femenino , Humanos , Hiperplasia/enzimología , Hiperplasia/virología , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/enzimología , Neoplasias Glandulares y Epiteliales/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/enzimología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Pronóstico , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/patología , Neoplasias Gástricas/virología , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/virología
6.
Eur J Gynaecol Oncol ; 33(1): 86-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22439412

RESUMEN

PURPOSE: The standard regimen for platinum-resistant/refractory recurrent epithelial ovarian cancer (EOC) remains to be determined. In this study, we retrospectively compared the effect of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in the treatment of platinum-resistant recurrent EOC. METHODS: Thirty patients who received salvage chemotherapy with CPT-11 or PLD were included in the study. CPT-11 (100 mg/m2) was administered intravenously on days 1, 8 and 15 every four weeks. PLD (50 mg/m2) was administered on day 1 every four weeks. Treatment was repeated, provided that no disease progression or intolerable toxicity occurred. RESULTS: Response rate in the CPT-11 group and PLD group showed no difference at 26.7% (p = 0.66) in both, while non-PD rate was 73.3% vs. 33.3% (p < 0.05), respectively. Progression-free survival after CPT-11 treatment and PLD treatment was 28.4 weeks and 16.8 weeks (p = 0.07), respectively. Hand-foot syndrome and mucositis were more common in the PLD group than in the CPT-11 group (p < 0.05). CONCLUSIONS: The results indicate that CPT-11 is a promising drug for the treatment of platinum-resistant recurrent EOC.


Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Camptotecina/análogos & derivados , Doxorrubicina/análogos & derivados , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Adulto , Anciano , Antibióticos Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Síndrome Mano-Pie/etiología , Humanos , Irinotecán , Estimación de Kaplan-Meier , Persona de Mediana Edad , Mucositis/etiología , Platino (Metal)/uso terapéutico , Polietilenglicoles/efectos adversos , Estudios Retrospectivos , Terapia Recuperativa
7.
Eur J Gynaecol Oncol ; 32(2): 146-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21614900

RESUMEN

For both cervical cancer (UCC) and endometrial cancer (EMC) there are no effective prognostic markers. In this study, we evaluated HIG2 protein expression in 332 uterine cancers (186 UCCs and 146 EMCs) and examined the relationship between HIG2 protein expression and clinical factors, including prognosis. Totally, HIG2 expression was detected in 58% of UCC and 66% of EMC. However, there was no significant relationship between HIG2 expression and age, clinical stage and histology in either UCC or EMC. In addition, HIG2 protein expression was not related to prognosis of UCC or EMC. The positivity rate of HIG2 protein was 56% and 61% in early-stage UCC and EMC, respectively and 67% in non-squamous cell carcinoma of UCC. The positivity rate of HIG2 protein was high even in early-stage UCC and EMC


Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Endometriales/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Neoplasias Endometriales/patología , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/patología
8.
Eur J Gynaecol Oncol ; 32(2): 160-3, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21614904

RESUMEN

PURPOSE: In this study, we compared second-line chemotherapy effects of nodal metastases with other metastases sites. METHODS: The medical records of 44 women with recurrent ovarian cancer who received second-line chemotherapy were retrospectively reviewed. RESULTS: Median age at the time of second-line chemotherapy was 55 years (range: 31-74). Recurrent sites were as follows: 29 patients had a solitary site (abdominal cavity: 8; lymph node: 3; pelvic cavity: 10; liver: 4; lung: 4) and 15 patients had multiple sites In total, the response rate was 30% (CR: 8, PR: 5). The response rate in sensitive cases was higher than in refractory/resistant cases (50% vs 5% p = 0.002). However, age, chemotherapy regimen, histologic type and number of diseases were not related with chemotherapy effect. In all diseases, response rate tended to be higher in lymph node disease than in the others (44% vs 27%). In both sensitive and refractory/resistant cases, response rate tended to be higher in lymph node disease. CONCLUSION: The response rate for lymph node diseases tended to be relatively high. Further study analyzing survival will be required to conclude the chemotherapy effect.


Asunto(s)
Metástasis Linfática/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Estudios Retrospectivos , Resultado del Tratamiento
9.
Br J Cancer ; 104(2): 353-60, 2011 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-21157448

RESUMEN

BACKGROUND: High-risk human papillomavirus (H-HPV) infection is linked to cervical neoplasia but its role in detecting cervical glandular lesions (GLs) is unclear. Carbonic anhydrase IX (CA-IX) is a hypoxic biomarker that is highly expressed in neoplastic cervical GLs. The diagnostic utility of these biomarkers was evaluated by the Gynecologic Oncology Group in Japanese women with a cytological diagnosis of atypical glandular cells. METHODS: Immunostaining was used to detect CA-IX in a conventional Pap smear. Immunoreactivity of CA-IX was interpreted by a panel of pathologists blinded to the histological diagnosis. Polymerase chain reaction was used to detect H-HPV in a liquid-based cytology specimen. RESULTS: Significant cervical lesions (SCLs), defined as cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ or invasive carcinoma, were observed in 37/88 (42%) of women. CA-IX testing alone (n=88) had a sensitivity of 89, 100 or 73% for SCLs, GLs or significant squamous lesions (SLs), respectively, with a false negative rate (FNR) of 14%. Testing for H-HPV (n=84) had a sensitivity of 65, 53 or 80% for SCLs, GLs or SLs, respectively, with a FNR of 22%. The combination of CA-IX and H-HPV testing had a sensitivity of 97, 100 or 93% for SCLs, GLs or SLs, respectively, with a FNR of 5%. Among eight H-HPV-negative GLs, six (75%) had a diagnosis of lobular endocervical glandular hyperplasia (LEGH). CONCLUSION: The combination of CA-IX and HPV testing improved the diagnostic accuracy. The low rate of H-HPV positivity in the GLs was associated with coexisting LEGH independent of H-HPV.


Asunto(s)
Alphapapillomavirus/patogenicidad , Anhidrasas Carbónicas/metabolismo , Displasia del Cuello del Útero/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Alphapapillomavirus/genética , Femenino , Genotipo , Humanos , Japón , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Displasia del Cuello del Útero/enzimología , Displasia del Cuello del Útero/virología
10.
Eur J Gynaecol Oncol ; 31(4): 364-8, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20882873

RESUMEN

PURPOSE: At present, it remains unclear whether the third-line chemotherapy has clinical benefit. In this study, we retrospectively evaluated the effect of third-line chemotherapy. METHODS: We reviewed the medical records of 40 women with recurrent epithelial ovarian cancer (EOC) who received third-line chemotherapy after platinum/taxan regimens as first line chemotherapy. RESULTS: In the first recurrence, 23 cases were platinum-sensitive and 17 cases were platinum-resistant. The cases for which the treatment-free interval from second-line chemotherapy (TFI) was a 3 months had a higher non-PD rate than those with TFI < 3 months (86% vs 33%, p = 0.002). In addition, the median overall survival (OS) was longer for TFI > or = 3 months than for TFI < 3 months (1195 days vs 235 days, p = 0.004). Finally, TFI was an independent significant prognostic factor by univariate (HR 3.28, p = 0.006) and multivariate (HR 3.21, p = 0.018) proportional hazard tests. CONCLUSION: TFI from second-line chemotherapy may predict a survival benefit of third-line chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Cisplatino/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Estudios Retrospectivos , Taxoides/administración & dosificación
11.
Br J Cancer ; 99(10): 1651-5, 2008 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-19002184

RESUMEN

Uterine cervical and endometrial cancers are common malignant solid neoplasms for which there are no useful prognostic markers. In this study, we evaluate the relationship between ATP-binding cassette superfamily F2 (ABCF2) expression and clinical factors including clinical stage, histologic type, grade and prognosis in uterine cervical and endometrial cancer. Two hundred and sixty seven cervical and 103 endometrial cancers were studied. ATP-binding cassette superfamily F2 cytoplasmic expression was detected by immunohistochemical staining and scored as positive or negative. Among cervical cancer cases, 149 (55.8%) expressed ABCF2. The overall survival was longer in ABCF2-negative than ABCF2-positive cases (P=0.0069). Statistically significant prognostic factors for survival were ABCF2 positivity (risk ratio (rr)=1.437), old age (rr=1.550) and advanced stage (rr=2.577). ATP-binding cassette superfamily F2 positivity was an independent prognostic factor by multivariate proportional hazard test (P=0.0002). Among endometrial cancer cases, 72 (69.9%) were cytoplasmic ABCF2 positive. However, there was no significant relationship between ABCF2 expression and age, clinical stage, histologic type, histologic grade, oestrogen receptor status or prognosis. ATP-binding cassette superfamily F2 expression may be a useful prognostic marker in cervical but not endometrial cancer. The role of ABCF2 protein may differ depending on the type of cancer.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/biosíntesis , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapia , Adulto Joven
12.
Int J Gynecol Cancer ; 18(5): 996-1006, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18028379

RESUMEN

In recent years, antibody therapy employing monoclonal antibodies has become a new approach for treating cancer. This study was performed to establish a human monoclonal antibody recognizing an epitope related to CA125 using KM mice and to assess its reactivity with ovarian cancer cells. A human ovarian clear cell adenocarcinoma cell line (RMG-I) was used to immunize KM mice, and hybridoma supernatant was obtained by a standard method employing enzyme-linked immunosorbent assay screening. Next, selection of hybridomas was performed with two antibodies (MA602-1 and MA602-6) and a sandwich immunoassay for CA125-like antigen, and then the limiting dilution was used to obtain a human monoclonal antibody. Immunohistochemical reactivity of this antibody (human monoclonal antibody for ovarian clear cell carcinoma-2 [HMOCC-2]) with ovarian cancer was assessed, while its specificity was analyzed by Western blotting. Various antibodies were used to identify the epitope targeted by HMOCC-2. Finally, the antitumor effect of HMOCC-2 was assessed by intraperitoneal administration to SCID (severe combined immunodeficiency) mice with heterografts of RMG-I tumors. HMOCC-2 showed a positive reaction with 60% (63/105) of ovarian cancer specimens. Western blotting of the membrane fraction of RMG-I revealed several bands at 120-250 kd. HMOCC-2 recognized the CA125-like antigens identified by several antibodies. HMOCC-2 also exhibited significant antitumor activity (P < 0.01) against ovarian cancer heterografts. HMOCC-2 reacts specifically with ovarian cancer cells via a target epitope analogous to that of CA125 and also exhibits activity against ovarian tumors. These findings suggest that it may have the potential to be employed clinically for molecular-targeting therapy.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Antígeno Ca-125/inmunología , Inmunoterapia , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/inmunología , Animales , Línea Celular Tumoral , Femenino , Humanos , Inmunohistoquímica , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Int J Gynecol Cancer ; 16(2): 799-804, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16681764

RESUMEN

The purposes of this study were to compare the relationships between para-aortic lymph node metastasis and various clinicopathologic factors to evaluate whether para-aortic lymph node dissection is necessary when treating endometrial cancer. A retrospective study was performed on 841 patients with endometrial cancer, who underwent the initial surgery at the Keio University Hospital. Clinicopathologic factors related to para-aortic lymph node metastasis significant on a univariate analysis were analyzed in a multivariate fashion using a logistic model. According to the multivariate analysis, the clinicopathologic factor most strongly related to the existence of para-aortic lymph node metastasis was positive pelvic lymph node metastasis (P < 0.01). Among the 155 patients who underwent pelvic and para-aortic lymph node dissection, the difference of 5-year overall survival by the presence of retroperitoneal lymph node metastasis was examined by Kaplan-Meier method. The prognosis was poor even if para-aortic lymph node dissection was performed in cases of positive para-aortic lymph node metastasis. In conclusion, when deciding whether to perform para-aortic lymph node dissection in patients with endometrial cancer, it is necessary to consider the pelvic lymph nodal status. If there is no pelvic lymph node metastasis, it could not be necessary to perform para-aortic lymph node dissection.


Asunto(s)
Adenocarcinoma/secundario , Neoplasias Endometriales/patología , Ganglios Linfáticos/patología , Vasos Linfáticos/patología , Adenocarcinoma/cirugía , Neoplasias Endometriales/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática/patología , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
14.
Int J Gynecol Cancer ; 16(1): 409-15, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16445667

RESUMEN

This study investigated the value of the in vitro histoculture drug response assay (HDRA) for predicting the efficacy of chemotherapy in patients with endometrial cancer. Specimens were obtained from 115 patients with endometrial cancer treated at Keio University Hospital between 1994 and 2002. Tumor fragments were cultured on collagen sponge gel with cisplatin for 7 days, and cell viability was assessed. The cutoff value of the 50% inhibitory concentration of cisplatin was set at 23 microg/mL. Sensitivity of stage III or IV disease to chemotherapy was investigated, and differences of 5-year progression-free survival between patients with sensitive and resistant tumors were evaluated by the Kaplan-Meier method. Tumors were evaluable in 93.0% of patients (107/115). Among 38 patients in stages III or IV, 23 received chemotherapy containing cisplatin. Seven sensitive tumors did not recur, while recurrence/progression occurred within 6 months in 8/16 patients with tumors showing low sensitivity. Among stages III and IV patients, there was a significant difference of 5-year progression-free survival (P < 0.05) between those with tumors showing high or low sensitivity. Accordingly, the HDRA may predict the efficacy of chemotherapy for endometrial cancer.


Asunto(s)
Cisplatino/farmacología , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Cisplatino/administración & dosificación , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Probabilidad , Pronóstico , Estudios Retrospectivos , Muestreo , Sensibilidad y Especificidad , Técnicas de Cultivo de Tejidos , Resultado del Tratamiento
15.
Placenta ; 27(2-3): 333-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16338478

RESUMEN

The incidence of choriocarcinoma has decreased over time and therapeutic results have improved about 90% complete remission in patients without extensive metastasis. However, some choriocarcinomas metastasize to other organs and show resistance to chemotherapy, having a poor prognosis despite multidisciplinary treatment. Better methods of early diagnosis for recurrence or micrometastasis, and treatment against cases with intractable gestational trophoblastic neoplasia (GTN) are needed to improve the prognosis. Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of two dissimilar subunits and a tumor marker to make a diagnosis and monitor therapeutic effect in GTN. Even when hCG levels in the serum become too low to measure with the hCG beta-CTP system which is the most sensitive assay, there are estimated to be approximately 10,000 trophoblastic cells in the body. Residual trophoblast cells may cause symptoms such as bleeding or undergo malignant transformation to choriocarcinoma. Since most monoclonal antibodies developed so far are murine, administration creates human anti-mouse antibodies, resulting in clinical failure. More recent mouse/human chimeric antibodies or humanized antibodies still possess substantial immunogenicity that makes repeated administration difficult. In the present study, KM mice that can produce completely human monoclonal antibodies were used to prepare hCG-specific human monoclonal antibody. This yielded 8-1A, a human monoclonal antibody capable of reacting with intact hCG. In the future, new diagnostic techniques and treatments for chorionic diseases may be developed using this kind of human monoclonal antibody.


Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/inmunología , Gonadotropina Coriónica/inmunología , Animales , Anticuerpos Monoclonales Humanizados , Western Blotting , Humanos , Inmunoquímica , Inmunoprecipitación , Ratones , Ratones Transgénicos
16.
Br J Cancer ; 93(9): 999-1004, 2005 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-16234823
17.
Int J Gynecol Cancer ; 15(3): 445-52, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15882168

RESUMEN

Despite cytoreductive surgery and chemotherapy, the prognosis of advanced ovarian cancer is still poor. Predicting the chemosensitivity of tumors might improve the outcome. Therefore, we investigated the clinical value of the histoculture drug response assay for ovarian cancer. Tumor specimens were cultured for 7 days on collagen gel sponge in medium containing cisplatin, and the 50% inhibitory concentration was determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay. Then the in vitro sensitivity to cisplatin was compared with the clinical response and survival. Apoptosis of tumor cells was also investigated. Among 173 ovarian cancer patients, 164 were evaluable by the assay, and 29 patients had measurable lesions for which the clinical response could be determined. The 5-year survival rate was significantly higher in patients with chemosensitive tumors than in those with chemoresistant tumors when the cutoff value was set at a 50% inhibitory concentration of 25 microg/mL and the accuracy of the assay was 82.8% (24/29). As chemosensitivity to cisplatin became greater, the number of apoptotic cells also increased. This chemosensitivity assay may help predict the clinical response to cisplatin-based chemotherapy, thus improving the survival of ovarian cancer patients.


Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Adulto , Anciano , Apoptosis , Supervivencia Celular , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Sensibilidad y Especificidad , Análisis de Supervivencia , Células Tumorales Cultivadas
18.
Int J Gynecol Cancer ; 15(1): 37-44, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15670295

RESUMEN

A new efficient screening for ovarian cancer based on a combination of two tumor markers, CA602 and CA546, is reported. These two tumor markers can be detected by a combination immunoenzymometric assay of these two antigens. This combination assay was initially performed in 1189 patients with clinically detected ovarian tumors (final pathological diagnosis: 645 cases of benign disease and 544 cases of malignant disease), and benign disease included 122 patients with endometriosis and 523 normal healthy women. The combination of CA602 and CA546 increased the detection rate of ovarian cancer from 77.8 to 85.8% compared with CA602 alone, demonstrating that the combination assay was effective at detecting ovarian cancers. The combination assay of CA602 and CA546 was then applied to 21,374 random subjects to screen for asymptomatic ovarian cancer. Ovarian cancer was detected in nine patients (detection rate: 0.04%), of which four cases were stage I disease. A retrospective analysis of these four patients revealed that a screening based on only a single assay would have been negative and further reiterates the effectiveness of this combination assay in detecting potential disease.


Asunto(s)
Adenocarcinoma/diagnóstico , Antígenos de Carbohidratos Asociados a Tumores/sangre , Biomarcadores de Tumor/sangre , Neoplasias Ováricas/diagnóstico , Adenocarcinoma/sangre , Adulto , Endometriosis/diagnóstico , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/sangre , Proyectos Piloto , Estudios Retrospectivos
19.
Int J Gynecol Cancer ; 15(1): 70-80, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15670300

RESUMEN

We performed two-color fluorescence in situ hybridization (FISH) on direct touch smears and liquid-based thin-layer (ThinPrep) cytological preparations of endometrial tumors to detect alterations of chromosome 1 and 17 that present with high incidence in endometrial cancers. The DNA probes used for two-color FISH analysis were a combination of the probes designed for 17cen (cCI 17-321) and 17p13.3 (D17S34), and a combination of the probes designed for 1q12 (D1Z1) and 1p36 (cCI1-5335). Numerical or structural alterations of chromosome 1 and/or 17 were detected in 95% (19 of 20 cases) of the direct touch smears obtained from endometrial cancer, while these alterations were also detected in 93% (12 of 13 cases) of samples obtained from grade 1 endometrioid adenocarcinoma cases, including three cases that could not be diagnosed as positive by conventional Papanicolaou cytopathologic staining. Using ThinPrep cytopathologic preparations, numerical or structural abnormalities were found in 26 (90%) and five (100%) cases, respectively, of samples obtained transcervically from 29 endometrial cancer and five atypical endometrial hyperplasia cases. Therefore, two-color FISH may be a useful diagnostic method for endometrial adenocarcinoma and premalignant lesions that demonstrate only slight cellular atypia in conventional cytopathologic preparations.


Asunto(s)
Adenocarcinoma/patología , Aberraciones Cromosómicas , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 1/genética , Neoplasias Endometriales/patología , Hibridación Fluorescente in Situ/métodos , Adenocarcinoma/genética , Adenocarcinoma/cirugía , Citodiagnóstico/métodos , Sondas de ADN , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/patología , Hiperplasia Endometrial/cirugía , Neoplasias Endometriales/genética , Neoplasias Endometriales/cirugía , Femenino , Procedimientos Quirúrgicos Ginecológicos , Humanos , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Lesiones Precancerosas/cirugía
20.
Jpn J Cancer Res ; 92(11): 1242-50, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11714450

RESUMEN

Cisplatin (DDP) is one of the key drugs used to treat patients with ovarian cancer, although resistance to DDP can occur. Paclitaxel and SN-38 (an active metabolite of irinotecan (CPT-11)) are two drugs that are effective in patients with DDP-resistant ovarian cancer. To study how these drugs may overcome the intrinsic and / or acquired resistance of cancer cells to DDP, we investigated the effect of a combination of DDP with paclitaxel and a combination of DDP with SN-38 on three ovarian cancer cell lines, RTSG (intrinsically resistant cell line), KF (DDP-sensitive cell line), and KFra (acquired resistant cell line obtained from KF). We found that these combinations showed additive to synergistic antitumor activity. A time-dependent platinum (Pt) accumulation was observed in the DDP-sensitive KF cell line, while a decrease occurred in the KFra cell line. Little accumulation was observed in RTSG. Intracellular Pt accumulation was increased in all three cell lines by exposure to paclitaxel or SN-38. Ouabain, a Na(+),K(+)-ATPase inhibitor, decreased Pt accumulation in KF and KFra cell lines and inhibited the paclitaxel- and SN-38-induced increases in Pt accumulation in these cell lines. When we assessed the mRNA levels of the multidrug resistance-associated protein (MRP), which may be an efflux pump for DDP, the combination of paclitaxel or SN-38 with DDP down-regulated these levels, which are up-regulated by DDP alone. These results suggest that paclitaxel and SN-38 overcome DDP resistance of ovarian cell lines by controlling intracellular accumulation of DDP via both the influx and efflux systems.


Asunto(s)
Camptotecina/farmacología , Cisplatino/metabolismo , Cisplatino/farmacología , Resistencia a Antineoplásicos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Neoplasias Ováricas/metabolismo , Paclitaxel/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Transporte Biológico/efectos de los fármacos , Camptotecina/análogos & derivados , División Celular/efectos de los fármacos , Cisplatino/farmacocinética , Proteínas de Unión al ADN/genética , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Humanos , Irinotecán , Proteína 3 Homóloga de MutS , Ouabaína/farmacología , Neoplasias Ováricas/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Células Tumorales Cultivadas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA