Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 497
Filtrar
1.
Am J Obstet Gynecol ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626553

RESUMO

BACKGROUND: Antenatal corticosteroid (ACS) therapy is standard of care for women at imminent risk of preterm labour. Despite this, much remains to be understood regarding an optimal (maximum benefit, minimal risk of side effects) ACS dosing strategy. Although conveying overall benefit when given to the right patient at the right time, ACS treatment efficacy is highly variable, and is not risk-free. Building on earlier findings, we hypothesized that when administered in combination with slow-release betamethasone acetate, betamethasone phosphate and the high materno-fetal betamethasone concentrations it generates are redundant for fetal lung maturation. OBJECTIVE: Using an established sheep model of prematurity and post-natal ventilation of the preterm lamb, we aimed to compare the pharmacodynamic effects of a low-dose treatment with betamethasone acetate only against a standard dose of betamethasone phosphate and betamethasone acetate as recommended by the American College of Obstetricians and Gynaecologists for women at risk of imminent preterm delivery between 24 and 35+6 weeks' gestation. METHODS: Ewes carrying a single fetus at 122±1 d gestational age (term=150d) were randomized to receive either: i) maternal intramuscular injections of sterile saline (the Saline Negative Control Group, n=12), ii) two maternal intramuscular injections of 0.25 mg/kg betamethasone phosphate + acetate spaced by 24h (the Beta-P+Ac Group, n=12); or iii) two maternal intramuscular injections of 0.125 mg/kg betamethasone acetate spaced by 24h (the Beta-Ac Group, n=11). Fetuses were surgically delivered 48h after treatment initiation and ventilated for 30 minutes to determine functional lung maturation. Fetuses were euthanized after ventilation and lung were collected for analysis using quantitative polymerase chain reaction and western blot assays. Fetal plasma ACTH levels were measured in the cord blood samples taken at delivery. RESULTS: Preterm lambs were defined as either ACS treatment responders or non-responders using an arbitrary cut-off, being a PaCO2 level at 30 minutes of ventilation being more extreme than two standard deviations from the mean value of the normally-distributed Saline Control Group values. Relative to Saline Control Group animals, both ACS treatment group animals showed significantly improved lung physiological responses (blood gas and ventilation data) and had a biochemical signature (mRNA and surfactant protein assays) consistent with functional maturation. However, the Beta-Ac Group had a significantly higher treatment response rate than the Beta-P+Ac Group. These physiological results were strongly correlated to the amount of surfactant protein A. Birth weight was lower in Beta-P+Ac Group and the fetal HPA axis was supressed to a greater extent in the Beta-P+Ac Group. CONCLUSION: Low dose ACS therapy solely employing Beta-Ac was sufficient for fetal lung maturation. The elevated materno-fetal betamethasone concentrations associated with the co-administration of betamethasone phosphate did not additionally improve lung maturation, but were associated with greater HPA axis suppression, a lower ACS treatment response rate, and lower birth weight - outcomes not desirable in a clinical setting. These data warrant a clinical investigation of sustained, low-dose ACS treatments that avoid high materno-fetal betamethasone exposures.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34628689

RESUMO

PURPOSE: To evaluate the risk of major congenital malformations (MCMs) associated with first-trimester exposure to propulsives with a special focus on domperidone using a large administrative database in Japan. METHODS: A large claims database was used from January 2005 to August 2016. The dates of pregnancy onset and delivery were estimated using the developed algorithms. Major congenital malformations were defined according to the International Classification of Diseases, 10th revision codes. We compared the infants' risk of overall MCMs between women with or without first-trimester prescriptions of propulsives and estimated the odds ratios (ORs) with unadjusted and adjusted analyses. We also compared the risk of overall MCMs between women with domperidone prescriptions and those with other propulsive prescriptions during the first trimester. RESULTS: Among 38 270 women, propulsives were prescribed to 3197 women (8.4%) in the first trimester, including domperidone to 371 women (1.0%). Propulsive prescriptions in the first trimester were not significantly associated with an increased risk of overall MCMs (adjusted OR [aOR] 1.030, 95% confidence interval [CI] 0.843-1.257). Compared to the prescription of other propulsives in the first trimester, the prescription of domperidone in the first trimester was not associated with an increased risk of overall MCMs (aOR 0.724, 95% CI 0.363-1.447). CONCLUSIONS: The first-trimester prescription of propulsives, including domperidone, was not associated with an increased risk of overall MCMs. This article is protected by copyright. All rights reserved.

4.
PLoS One ; 16(9): e0257847, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34559862

RESUMO

BACKGROUND: Intraamniotic inflammation is associated with up to 40% of preterm births, most notably in deliveries occurring prior to 32 weeks' gestation. Despite this, there are few treatment options allowing the prevention of preterm birth and associated fetal injury. Recent studies have shown that the small, non-competitive allosteric interleukin (IL)-1 receptor inhibitor, rytvela, may be of use in resolving inflammation associated with preterm birth (PTB) and fetal injury. We aimed to use an extremely preterm sheep model of chorioamnionitis to investigate the anti-inflammatory efficacy of rytvela in response to established intra-amniotic (IA) lipopolysaccharide (LPS) exposure. We hypothesized that rytvela would reduce LPS-induced IA inflammation in amniotic fluid (AF) and fetal tissues. METHODS: Sheep with a single fetus at 95 days gestation (estimated fetal weight 1.0 kg) had surgery to place fetal jugular and IA catheters. Animals were recovered for 48 hours before being randomized to either: i) IA administration of 2 ml saline 24 hours before 2 ml IA and 2 ml fetal intravenous (IV) administration of saline (Saline Group, n = 7); ii) IA administration of 10 mg LPS in 2 ml saline 24 hours before 2 ml IA and 2 ml fetal IV saline (LPS Group, n = 10); 3) IA administration of 10 mg LPS in 2 ml saline 24 hours before 0.3 mg/fetal kg IA and 1 mg/fetal kg fetal IV rytvela in 2 ml saline, respectively (LPS + rytvela Group, n = 7). Serial AF samples were collected for 120 h. Inflammatory responses were characterized by quantitative polymerase chain reaction (qPCR), histology, fluorescent immunohistochemistry, enzyme-linked inmmunosorbent assay (ELISA), fluorescent western blotting and blood chemistry analysis. RESULTS: LPS-treated animals had endotoxin and AF monocyte chemoattractant protein (MCP)-1 concentrations that were significantly higher at 24 hours (immediately prior to rytvela administration) relative to values from Saline Group animals. Following rytvela administration, the average MCP-1 concentrations in the AF were significantly lower in the LPS + rytvela Group relative to in the LPS Group. In delivery samples, the expression of IL-1ß in fetal skin was significantly lower in the LPS + rytvela Group compared to the LPS Group. CONCLUSION: A single dose of rytvela was associated with partial, modest inhibition in the expression of a panel of cytokines/chemokines in fetal tissues undergoing an active inflammatory response.

5.
Curr Issues Mol Biol ; 43(2): 1188-1202, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34563053

RESUMO

Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma is the most common uterine tumor. The leiomyoma subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, the oncological properties of this intravenous leiomyomatosis resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. CD44-positive mesenchymal tumor stem-like cells were detected in both patients with intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological properties of intravenous leiomyomatosis were found to be similar to those of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, cyclin E and Ki-67-positive cells were rare and no pathological findings suspecting malignancy were observed. It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

6.
Sci Rep ; 11(1): 17777, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493809

RESUMO

The elucidation of dynamic metabolomic changes during gestation is particularly important for the development of methods to evaluate pregnancy status or achieve earlier detection of pregnancy-related complications. Some studies have constructed models to evaluate pregnancy status and predict gestational age using omics data from blood biospecimens; however, less invasive methods are desired. Here we propose a model to predict gestational age, using urinary metabolite information. In our prospective cohort study, we collected 2741 urine samples from 187 healthy pregnant women, 23 patients with hypertensive disorders of pregnancy, and 14 patients with spontaneous preterm birth. Using gas chromatography-tandem mass spectrometry, we identified 184 urinary metabolites that showed dynamic systematic changes in healthy pregnant women according to gestational age. A model to predict gestational age during normal pregnancy progression was constructed; the correlation coefficient between actual and predicted weeks of gestation was 0.86. The predicted gestational ages of cases with hypertensive disorders of pregnancy exhibited significant progression, compared with actual gestational ages. This is the first study to predict gestational age in normal and complicated pregnancies by using urinary metabolite information. Minimally invasive urinary metabolomics might facilitate changes in the prediction of gestational age in various clinical settings.

8.
J Affect Disord ; 295: 632-638, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509778

RESUMO

BACKGROUND: Trajectories of postpartum depressive symptoms up to 1 year after childbirth and the related risk factors remain unclear. Accordingly, this study aimed to examine the 1-year trajectories of postpartum depressive symptoms and their associated risk factors. METHODS: A total of 22,493 pregnant women were recruited between July 2013 and September 2016 in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan. Among them, 11,668 women with no missing data were included in the analyses. Depressive symptoms were assessed at 1 month and 1 year postpartum using the Edinburgh Postnatal Depression Scale. Multinominal logistic regression analysis was conducted after adjusting for covariates. RESULTS: The prevalence of depression was 13.9% at 1 month and 12.9% at 1 year postpartum. We identified four depression trajectories, i.e., "persistent (depressed throughout the 1 year postpartum)" (6.0%), "recovered (depressed at 1 month postpartum and recovered within a year)" (7.9%), "late-onset (became depressed after 1 month postpartum)" (6.8%), and "resilient (not depressed throughout 1 year postpartum)" (79.2%). Psychological distress during pregnancy was significantly associated with all trajectories (persistent: odds ratio [OR]=10.24, 95% confidence interval (CI)=8.40-12.48; recovered: OR=3.78, 95%CI=3.28-4.36; and late-onset: OR=3.96, 95%CI=3.40-4.62). LIMITATIONS: Postpartum depression was evaluated only by a self-administered questionnaire and the dropout rate was not neglectable. CONCLUSIONS: This study highlighted the high prevalence of depressive symptoms at 1 year postpartum and found that half of the depressive symptoms at 1 year were late-onset. The findings suggest the necessity of long-term follow-up (up to 1 year) for perinatal mental health.

9.
Prev Med Rep ; 24: 101525, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34471594

RESUMO

This study examines the association between abnormal cervical cytology and subjective health in pregnant women, as an adjunct to the Japan Environment and Children's Study, which cross-sectionally analyzed a subset of the prospective cohort. A total of 3024 pregnant women at a childbirth facility whose medical records of cervical cytology in the first trimester of pregnancy were transcribed and who responded to the subjective health questionnaire were included herein. They were classified into excellent, good, fair, and poor groups based on their subjective health. Cervical cytology results obtained from perinatal medical records were classified into normal and abnormal cytology based on the Bethesda classification. Logistic regression analysis adjusted for baseline characteristics, including age, pre-pregnancy body mass index, parity, and other possible confounding factors, was used. Of 3024 pregnant women, 106 (3.5%) had abnormal cytology, with the prevalence being 1.3%, 3.7%, 3.9%, and 4.0%, respectively (p = 0.055) in the poor, fair, good, and excellent groups. The baseline characteristics, namely age, history of gynecological diseases, Kessler 6-item psychological distress scale score, and history of mental illness, were significantly different between groups. Compared to the poor group, the other three groups had a significantly higher abnormal cytology risk after adjusting for confounding factors (Fair: adjusted OR [aOR] = 3.6, 95% CI [1.0-12.1]; Good: aOR = 4.6 [1.3-15.5]; Excellent: aOR = 4.6 [1.2-17.8]). This study encourages young women to undergo cervical cancer screening because they are at risk for cervical cancer even if they think that they are healthy, and preventive activities like regular screening are essential.

10.
Gynecol Oncol Rep ; 38: 100847, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34557579

RESUMO

Objective: Ovarian cancer (OC) is an intractable gynecological tumor, and frequent recurrence is experienced within a few years even after the complete eradication of tumor tissues by radical resection and neo-adjuvant chemotherapies. The conventional recurrence marker, CA125, is widely used for follow-up after resection of OC, but CA125 has a long half-life in blood and lacks dynamic responses to tumor recurrence. Recent developments in liquid biopsy procedures are expected to overcome the difficulties in early diagnosis of OC recurrence after surgery. Methods: We applied droplet digital PCR (ddPCR) technology to detect circulating tumor-derived DNA in OC patients' plasma during follow-up. Exome sequencing of 11 tumor-normal pairs of genomic DNA from consecutive OC patients identified tumor-specific mutations, and ddPCR probes were selected for each sample. Results: Six of 11 cases showed apparent recurrence during follow-up (mean progression-free survival was 348.3 days) and all six cases were positive in ddPCR analyses. In addition, ddPCR became positive before increased plasma CA125 in five out of six cases. Increased allele frequency of circulating tumor DNA (ctDNA) is associated with increased tumor volume after recurrence. ddPCR detected ctDNA signals significantly earlier than increased CA125 in the detection of OC recurrence by imaging (49 days and 7 days before, respectively: p < 0.05). No ctDNA was detected in the plasma of recurrence-free cases. Conclusions: Our results demonstrate the potential of identifying ctDNA by ddPCR as an early detection tool for OC recurrence.

12.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445470

RESUMO

In regular IVF, a portion of oocytes exhibit abnormal numbers of pronuclei (PN) that is considered as abnormal fertilization, and they are routinely discarded. However, it is known that abnormal ploidy still does not completely abandon embryo development and implantation. To explore the potential of cytoplasm from those abnormally fertilized oocytes, we developed a novel technique for the transfer of large cytoplasm between pronuclear-stage mouse embryos, and assessed its impact. A large volume of cytoplast could be efficiently transferred in the PN stage using a novel two-step method of pronuclear-stage cytoplasmic transfer (PNCT). PNCT revealed the difference in the cytoplasmic function among abnormally fertilized embryos where the cytoplasm of 3PN was developmentally more competent than 1PN, and the supplementing of fresh 3PN cytoplasm restored the impaired developmental potential of postovulatory "aged" oocytes. PNCT-derived embryos harbored significantly higher mitochondrial DNA copies, ATP content, oxygen consumption rate, and total cells. The difference in cytoplasmic function between 3PN and 1PN mouse oocytes probably attributed to the proper activation via sperm and may impact subsequent epigenetic events. These results imply that PNCT may serve as a potential alternative treatment to whole egg donation for patients with age-related recurrent IVF failure.


Assuntos
Núcleo Celular/patologia , Citoplasma/patologia , Embrião de Mamíferos/patologia , Desenvolvimento Embrionário , Fertilização In Vitro/métodos , Zigoto/patologia , Animais , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Embrião de Mamíferos/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Endogâmicos ICR , Zigoto/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-34416000

RESUMO

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in mid-pregnancy are associated with small- (SGA) or large- (LGA) for-gestational-age independent of pre-pregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: To prospectively investigate the association between maternal TC in mid-pregnancy and SGA or LGA. DESIGN AND SETTING: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. PARTICIPANTS: A total of 37,449 non-diabetic, non-hypertensive mothers with singleton birth at term without congenital abnormalities. OUTCOME MEASURES: Birth weight for the gestational age <10 percentile and ≥90 percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7±4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, pre-pregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and Study Areas, one standard deviation decrement of maternal TC was linearly associated with SGA [odds ratio (OR): 95% confidence intervals (CI) = 1.20: 1.15-1.25]. In contrast, one standard deviation increment of maternal TC was linearly associated with LGA [OR: 95% CI = 1.13: 1.09-1.16]. Associations did not differ according to pre-pregnancy BMI and gestational weight gain (p for interaction>0.20). CONCLUSION: Maternal TC levels in mid-pregnancy were associated with SGA or LGA in Japanese. Maternal TC in mid-pregnancy may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

14.
Int J Clin Oncol ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34435284

RESUMO

OBJECTIVE: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. METHODS: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. RESULTS: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. CONCLUSION: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

15.
Int J Clin Oncol ; 26(11): 2123-2129, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34308512

RESUMO

BACKGROUND: Despite being widely used, to date (June 2021), the regimen of bevacizumab 10 mg/kg every 2 weeks (Q2W) combined with chemotherapy is not approved in Japan for patients with platinum-resistant recurrent ovarian cancer. In this retrospective analysis, we evaluated the usage patterns of bevacizumab administered for platinum-resistant recurrent ovarian cancer. METHODS: We obtained clinical data from 155 Japanese medical facilities between November 2013 and December 2018 via a survey. Items included the number of cases of platinum-resistant recurrent ovarian cancer treated with bevacizumab according to dosage. For regimens including bevacizumab 10 mg/kg Q2W, additional information was requested relating to concomitantly administered agents, and the efficacy and safety of the regimen. RESULTS: Of 1739 bevacizumab-containing regimens reported in 1633 patients with recurrent ovarian cancer, 264 used 10 mg/kg Q2W. The overall response rate (ORR) with this regimen was 26.1%. Response rates varied according to regimen and were particularly favorable when bevacizumab 10 mg/kg Q2W was administered with paclitaxel (ORR, 53.0%) versus liposomal doxorubicin (15.0%; P < 0.0001) and irinotecan (7.7%; P < 0.028). The most frequent Grade ≥ 3 adverse events associated with bevacizumab 10 mg/kg Q2W were neutropenia (11.7%) and hypertension (11.7%). The most frequent bevacizumab-associated Grade ≥ 3 adverse events with bevacizumab plus paclitaxel versus bevacizumab plus liposomal doxorubicin were hypertension (9.0% versus 13.9%) and proteinuria (3.0% versus 8.4%). CONCLUSIONS: Bevacizumab 10 mg/kg Q2W appears efficacious for patients with recurrent ovarian cancer, with a manageable toxicity profile. Approval of this regimen is clinically desirable for Japanese patients with ovarian cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ovarianas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Estudos Retrospectivos
16.
Sci Total Environ ; 794: 148643, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34198080

RESUMO

In recent years, there has been an increase in the number of problems associated with neurodevelopmental disorders in children, and there has been a growing interest in the relationship between environmental chemicals and children's health. The objective of this study was to examine whether an association exists between occupational or environmental prenatal maternal exposure to volatile organic compounds and the risk of neurodevelopmental disorders in children using Japanese translations of the Ages & Stages Questionnaires, Third Edition (J-ASQ-3). An increase in the risk of neurodevelopmental delay in 12-month-old children associated with maternal exposure to formalin or formaldehyde was identified in terms of problem-solving (odds ratio (OR): 1.76, 95% confidence interval (CI): 0.99-3.12) and personal-social skills (OR: 3.32, 95% CI: 1.46-7.55). It is not clear whether or not this tendency is reversible, and whether it is observed past 12 months of age. Further research and a preventive approach are needed.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Compostos Orgânicos Voláteis , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Japão , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Compostos Orgânicos Voláteis/toxicidade
17.
Tohoku J Exp Med ; 254(3): 145-153, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34219103

RESUMO

Although the addition of bevacizumab to platinum-based combination chemotherapy has been recommended as a standard regimen for patients with advanced or recurrent cervical cancer, there is no clear evidence regarding the effectiveness of bevacizumab monotherapy as salvage chemotherapy. This study prospectively examined the efficacy and safety of switching from platinum-based chemotherapy combined with bevacizumab to single maintenance therapy in patients with advanced or recurrent cervical cancer. Patients were first treated with standard combination chemotherapy. However, if chemotherapy was discontinued because of an adverse event, bevacizumab monotherapy was continued for patients who agreed to participate in this study and provided written informed consent. The study protocol was approved by the Independent Review Board of Tohoku University School of Medicine (reception number 2017-1-540). A total of 15 patients (median age of 55 years, range 33-69 years) participated in this study. The median number of cycles of bevacizumab single maintenance administration was 8, and the main reasons for discontinuation were disease progression and adverse events. Bevacizumab single maintenance therapy had a disease control rate of 53.3% (CR 40%, PR 6.7%, SD 6.7%). The most frequent grade 3/4 clinical adverse events were proteinuria (5/15) and hypertension (4/15). No treatment-related deaths occurred. Bevacizumab single maintenance therapy was effective as salvage chemotherapy in patients with advanced or recurrent cervical cancer, and the safety profile was generally consistent with those reported in previous studies of bevacizumab monotherapy.

18.
Toxins (Basel) ; 13(7)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209281

RESUMO

Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis is mainly due to delayed diagnosis. Therefore, biomarker identification and prognosis prediction are crucial in EOC. Altered cell metabolism is a characteristic feature of cancers, and metabolomics reflects an individual's current phenotype. In particular, plasma metabolome analyses can be useful for biomarker identification. In this study, we analyzed 624 metabolites, including uremic toxins (UTx) in plasma derived from 80 patients with EOC using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Compared with the healthy control, we detected 77 significantly increased metabolites and 114 significantly decreased metabolites in EOC patients. Especially, decreased concentrations of lysophosphatidylcholines and phosphatidylcholines and increased concentrations of triglycerides were observed, indicating a metabolic profile characteristic of EOC patients. After calculating the parameters of each metabolic index, we found that higher ratios of kynurenine to tryptophan correlates with worse prognosis in EOC patients. Kynurenine, one of the UTx, can affect the prognosis of EOC. Our results demonstrated that plasma metabolome analysis is useful not only for the diagnosis of EOC, but also for predicting prognosis with the variation of UTx and evaluating response to chemotherapy.

19.
PLoS One ; 16(6): e0251079, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161330

RESUMO

Platinum sensitivity is an important prognostic factor in patients with ovarian cancer. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core member of the nucleosome remodeling and deacetylase complex, which functions as a chromatin remodeler. Emerging evidence indicates that CHD4 could be a potential therapeutic target for cancer therapy. The purpose of this study was to clarify the role of CHD4 in ovarian cancer and investigate its therapeutic potential focusing on platinum sensitivity. In an analysis of the Cancer Genome Atlas ovarian cancer dataset, CHD4 gene amplification was associated with worse overall survival. CHD4 mRNA expression was significantly higher in platinum-resistant samples in a subsequent clinical sample analysis, suggesting that CHD4 overexpression conferred platinum resistance to ovarian cancer cells, resulting in poor patient survival. In concordance with these findings, CHD4 knockdown enhanced the induction of apoptosis mediated by cisplatin in ovarian cancer cells TOV21G and increased cisplatin sensitivity in multiple ovarian cancer cells derived from different subtypes. However, CHD4 knockdown did not affect the expression of RAD51 or p21, the known targets of CHD4 in other cancer types that can modulate platinum sensitivity. Knockdown and overexpression assays revealed that CHD4 positively regulated the expression of multi-drug transporter MDR1 and its coding protein p-glycoprotein. In addition, a first-in-class CHD4/SMARCA5 inhibitor ED2-AD101 showed synergistic interactions with cisplatin. Our findings suggest that CHD4 mediates platinum sensitivity by modulating MDR1 expression in ovarian cancer. Further, CHD4 suppression has a potential to be a novel therapeutic strategy in combination with platinum agents.

20.
J Obstet Gynaecol Res ; 47(9): 3352-3361, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34155729

RESUMO

AIM: Recent advances in cancer treatment have improved the prognosis of child, adolescent, and young adult (CAYA) cancer survivors. This study aimed to examine the current status of pregnancy outcomes among female cancer survivors in Japan. METHODS: The first questionnaire was sent to 633 major tertiary institutions certified by the Japan Society of Obstetrics and Gynecology to identify institutions managing cases of pregnant cancer survivors between January 2011 and December 2015. The second questionnaire was sent only to institutions with pregnant cancer survivors during the study period. RESULTS: We analyzed 2242 singleton deliveries of cancer survivors based on the responses received in the second questionnaire (199/255 responses; 78.0%). The three most frequent types of malignant tumors were uterine cervical (23.4%), breast (17.6%), and thyroid cancers (17.5%). Conception was aided by the use of assisted reproductive technology in 17.0% of the patients. The proportions of mothers aged 35-39.9 and ≥ 40 years were 36.5% and 11.8%, respectively. The prevalence of preterm birth (PTB) at <37, <34, and < 32 weeks' gestation were 16.7%, 6.8%, and 4.3%, respectively. The proportion of infants with low birth weight (LBW) was 18.9%. CONCLUSION: The present study findings suggest that advanced maternal age was common among pregnant cancer survivors and these survivors often gave birth to PTB and LBW infants in Japan. The likelihood of adverse pregnancy outcomes should be considered by healthcare providers when planning counseling and perinatal care for cancer survivors.


Assuntos
Neoplasias , Nascimento Prematuro , Adolescente , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Neoplasias/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Inquéritos e Questionários , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...