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1.
Gene ; 811: 146083, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34856363

RESUMO

Nearly three hundred thousand female patients are diagnosed with ovarian cancer in the world annually, and this number shows an increasing trend. However, characteristic symptoms caused by ovarian cancer are so few that early diagnosis remains challenging, and an effective screening method has not yet been established. Here, we conducted a case-control study in Japan to analyze the association between cervicovaginal microbiome and ovarian cancer, using 16S rRNA amplicon sequencing. Analysis of DNA extracted from cervical smear samples revealed Lactobacillus-dominant and Lactobacillus-deficient, highly-diversified bacterial communities in premenopausal and postmenopausal healthy controls, respectively, as reported for vaginal microbiota previously. We found that cervicovaginal microbiota in ovarian cancer patients, regardless of their menopausal status, were frequently a diversified community and similar to those in healthy subjects at postmenopausal ages. The diverse microbiota was associated with the major histotypes of epithelial ovarian cancer, including serous ovarian cancer and ovarian clear cell cancer. The present study implies the potential of a cervicovaginal microbiome biomarker in screening ovarian cancer in premenopausal women.


Assuntos
Carcinoma Epitelial do Ovário/microbiologia , Colo do Útero/microbiologia , Microbiota , Neoplasias Ovarianas/microbiologia , Vagina/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Tipagem Bacteriana/métodos , Biomarcadores , Estudos de Casos e Controles , DNA Bacteriano , Feminino , Humanos , Japão , Lactobacillus/classificação , Lactobacillus/genética , Metagenoma , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , RNA Ribossômico 16S , Adulto Jovem
2.
Oncol Rep ; 40(1): 309-318, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29749539

RESUMO

Ovarian clear cell carcinoma (OCCC) is a chemotherapy­resistant epithelial ovarian cancer with poor prognosis. To identify genomic alterations involved in the development of OCCC, we analyzed somatic copy number alterations in OCCC using comparative genomic hybridization (CGH). Here we showed that the chromosomal regions 8p11.21, 8p11.22, 12p13.31 and 20q13.2 were amplified in OCCC. We also demonstrated that small segments in the chromosomal regions 3q26.1, 4q13.2 and 22q11.23 were deleted. Kaplan­Meier survival analyses revealed that patients with amplification within 8p11.21 or a deletion within 3q26.1 had a shorter progression­free survival (PFS) time than those without such alterations. In addition, patients with amplification in three of the four chromosomal regions 8p11.21, 8p11.22, 12p13.31 and 20q13.2 had shorter overall survival (OS). We also demonstrated that amplification of 12p13.3 or three of the four chromosomal regions 8p11.21, 8p11.22, 12p13.31 and 20q13.2, or a deletion in the chromosomal region 3q26.1 was associated with chemotherapy resistance. Our findings suggest that copy number alterations in 8p11.21­22, 12p13.31, 20q13.2, 3q26.1, 4q13.2 and 22q11.23 are critical for the development and survival of OCCC.


Assuntos
Adenocarcinoma de Células Claras/genética , Variações do Número de Cópias de DNA/genética , Neoplasias Ovarianas/genética , Prognóstico , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Hibridização Genômica Comparativa , Intervalo Livre de Doença , Feminino , Amplificação de Genes/genética , Dosagem de Genes , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Ovário/patologia
3.
Oncotarget ; 9(20): 15266-15274, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29632642

RESUMO

Ovarian clear cell carcinoma (OCCC) exhibits distinct phenotypes, such as resistance to chemotherapy, poor prognosis and an association with endometriosis. Biomarkers and imaging techniques currently in use are not sufficient for reliable diagnosis of this tumor or prediction of therapeutic response. It has recently been reported that analysis of somatic mutations in cell-free circulating DNA (cfDNA) released from tumor tissues can be useful for tumor diagnosis. In the present study, we attempted to detect mutations in PIK3CA and KRAS in cfDNA from OCCC patients using droplet digital PCR (ddPCR). Here we show that we were able to specifically detect PIK3CA-H1047R and KRAS-G12D in cfDNA from OCCC patients and monitor their response to therapy. Furthermore, we found that by cleaving wild-type PIK3CA using the CRISPR/Cas9 system, we were able to improve the sensitivity of the ddPCR method and detect cfDNA harboring PIK3CA-H1047R. Our results suggest that detection of mutations in cfDNA by ddPCR would be useful for the diagnosis of OCCC, and for predicting its recurrence.

4.
PLoS One ; 10(2): e0116977, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25658832

RESUMO

When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC) include 1) a higher incidence among Japanese, 2) an association with endometriosis, 3) poor prognosis in advanced stages, and 4) a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH) to identify somatic copy number alterations (SCNAs) associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC. The entire 8q chromosome (minimum corrected p-value: q = 0.0001) and chromosome 20q13.2 including the ZNF217 locus (q = 0.0078) were amplified significantly more in Japanese than in Korean or German samples. This copy number amplification of the ZNF217 gene was confirmed by quantitative real-time polymerase chain reaction (Q-PCR). ZNF217 RNA levels were also higher in Japanese tumor samples than in non-Japanese samples (P = 0.027). Moreover, endometriosis was associated with amplification of EGFR gene (q = 0.047), which was again confirmed by Q-PCR and correlated with EGFR RNA expression. However, no SCNAs were significantly associated with prognosis or thrombosis. These results indicated that there may be an association between CCC and ZNF217 amplification among Japanese patients as well as between endometriosis and EGFR gene amplifications.


Assuntos
Adenocarcinoma de Células Claras/genética , Cromossomos Humanos Par 20 , Cromossomos Humanos Par 8 , Endometriose/genética , Neoplasias Ovarianas/genética , Adenocarcinoma de Células Claras/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Aberrações Cromossômicas , Hibridização Genômica Comparativa , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia , Reação em Cadeia da Polimerase em Tempo Real , Transativadores/genética
5.
Int J Gynecol Cancer ; 24(7): 1181-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25010038

RESUMO

AIM: The aim of this study was to evaluate the impact of surgical staging in stage I clear cell adenocarcinoma of the ovary (CCC). METHODS: We performed a retrospective review of 165 patients with stage I CCC treated with optimal or nonoptimal staging surgery. RESULTS: The median follow-up period in this study was 67 months. No significant difference was detected in recurrence-free survival (RFS) or overall survival (OS) between patients optimally and nonoptimally staged (RFS: P = 0.434; OS: P = 0.759). The estimated 5-year RFS and OS rates were 92.1% and 95.3% in patients with stages IA/IC1 and 81.0% and 83.7% in stages IC2/IC3, respectively. The multivariate analysis indicated that stages IC2/IC3 predicted worse RFS and OS than stages IA/IC1 in stage I CCC patients (RFS: P = 0.011; OS: P = 0.011). Subsequently, we investigated the impact of surgical staging, respectively, in stages IA/IC1 and stages IC2/IC3. Significant differences were observed in PFS and OS between patients optimally and nonoptimally staged with stages IA/IC1 (RFS: P = 0.021; OS: P = 0.024), but no significant difference was found in those with stages IC2/IC3. The multivariate analysis indicated that nonoptimal staging surgery predicted worse RFS than the optimal staging surgery in stages IA/IC1 CCC patients (P = 0.033). In addition, we investigated the impact of surgical staging for stages IA/IC1 in the adjuvant chemotherapy group. The 5-year RFS and OS rates in patients optimally and nonoptimally staged with stages IA/IC1 in the adjuvant chemotherapy group were 97.8% and 100%, and 85.2% and 89.4%, respectively. The multivariate analysis indicated that nonoptimal staging surgery predicted worse RFS than the optimal staging surgery for stages IA/IC1 patients in the adjuvant chemotherapy group (P = 0.019). CONCLUSIONS: The prognosis for women with stage 1A/IC1 is very good. Surgical staging category was the only independent prognostic factor for RFS in stages IA/IC1 CCC.


Assuntos
Adenocarcinoma de Células Claras/patologia , Técnicas de Diagnóstico por Cirurgia , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Paclitaxel , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/uso terapêutico , Topotecan/uso terapêutico
6.
Int J Clin Oncol ; 19(6): 1074-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24534911

RESUMO

BACKGROUND: The aim of this study was to investigate the impact of the histological findings on the treatment of malignant ovarian tumors in pregnant women. METHODS: This is a retrospective study of 41 patients diagnosed and treated for ovarian malignancy during pregnancy between 1985 and 2010. RESULTS: The median age of the study group was 30 years old, ranging from 20 to 41. Thirty-eight (92 %) patients were diagnosed with stage I, and one (2 %) with each of stages II, III, and IV. Twenty-five (61 %) patients had borderline malignancy, 8 (20 %) were diagnosed with epithelial ovarian cancer, 7 (17 %) with germ cell tumor, and one with sex cord stromal tumor. All patients received primary surgery; 7 (17 %) patients had cystectomy, 32 (78 %) had unilateral salpingo-oophorectomy, and 3 (7 %) underwent hysterectomy with bilateral salpingo-oophorectomy. Thirty-one (76 %) patients delivered live newborns; 21 had borderline tumor (84 %), 2 had ovarian cancers (25 %), and 8 had non-epithelial tumor (100 %). Six cases were terminated in order to perform the standard treatment for ovarian malignancy and 2 cases aborted spontaneously. CONCLUSION: In pregnant women, ovarian cancer is exceptionally less frequent compared with non-pregnant women, i.e. age-matched, statistically-corrected controls based on the Japanese annual report [8/33 (24 %) vs. control (60 %); ovarian cancer/(ovarian cancer + borderline tumor), P = 0.001]. The pregnant women with ovarian cancer chose to prioritize treatment of ovarian cancer at the sacrifice of their babies while those with borderline tumor or non-epithelial tumor were able to successfully deliver live newborns.


Assuntos
Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Adulto , Cistectomia/métodos , Feminino , Humanos , Histerectomia/métodos , Japão , Estadiamento de Neoplasias/métodos , Ovariectomia/métodos , Gravidez , Estudos Retrospectivos , Adulto Jovem
8.
Oncol Lett ; 3(3): 577-580, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22740955

RESUMO

The objective of this study was to ascertain the evidence on ovarian cancer during pregnancy and compile recommendations derived from this information. This was a retrospective study, based on clinical histories from patients diagnosed and treated at 4 independent hospitals for ovarian cancer during pregnancy, between 1992 and 2009. The median age at diagnosis was 30 years (range, 24-41). Out of 10 cases of ovarian cancer, 2 patients showed either bleeding or abdominal pain, while 8 patients were asymptomatic. All 10 cases were diagnosed via ultrasound, and the masses were detected in the first trimester in 7 patients and in the second trimester in 2 patients. Of the diagnosed tumors, 8 cases were epithelial tumors including 6 adenocarcinomas and 2 borderline tumors, and 2 germ cell tumors. The primary ovarian malignancies were at stage I of the disease. Unilateral salpingo-oophorectomy was performed in 9 patients and cystectomy was performed in one patient. Chemotherapy was administered to 4 patients, in 1 case during pregnancy. Neonatal outcome analysis showed a full- or pre-term delivery in 6 cases, abortion in 1 case and therapeutic termination in 3 cases. The majority of cases of ovarian cancer in pregnancy were incidentally detected by ultrasound at an early stage, resulting in good prognosis for the mother and the neonate.

9.
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
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