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1.
Am J Pathol ; 194(7): 1272-1284, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38537936

RESUMO

Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with epithelial ovarian cancer. However, TIL evaluation has not been used in routine clinical practice because of reproducibility issues. The current study developed two convolutional neural network models to detect TILs and to determine their spatial location in whole slide images, and established a spatial assessment pipeline to objectively quantify intraepithelial and stromal TILs in patients with high-grade serous ovarian carcinoma. The predictions of the established models showed a significant positive correlation with the number of CD8+ T cells and immune gene expressions. Patients with a higher density of intraepithelial TILs had a significantly prolonged overall survival and progression-free survival in multiple cohorts. On the basis of the density of intraepithelial and stromal TILs, patients were classified into three immunophenotypes: immune inflamed, excluded, and desert. The immune-desert subgroup showed the worst prognosis. Gene expression analysis showed that the immune-desert subgroup had lower immune cytolytic activity and T-cell-inflamed gene-expression profile scores, whereas the immune-excluded subgroup had higher expression of interferon-γ and programmed death 1 receptor signaling pathway. The established evaluation method provided detailed and comprehensive quantification of intraepithelial and stromal TILs throughout hematoxylin and eosin-stained slides. It has potential for clinical application for personalized treatment of patients with ovarian cancer.


Assuntos
Cistadenocarcinoma Seroso , Aprendizado Profundo , Linfócitos do Interstício Tumoral , Neoplasias Ovarianas , Humanos , Feminino , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/genética , Pessoa de Meia-Idade , Idoso , Prognóstico , Células Estromais/patologia , Células Estromais/imunologia , Células Estromais/metabolismo , Linfócitos Intraepiteliais/imunologia , Linfócitos Intraepiteliais/metabolismo
2.
J Obstet Gynaecol Res ; 49(9): 2245-2251, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37415252

RESUMO

Immunotherapy for ovarian cancer has been studied for many years and programmed cell death protein 1 ligand/programmed cell death protein 1 (PD-L1/PD-1) blockade has been attempted in several clinical trials; however, the expected therapeutic effect has not been achieved. In contrast, the PD-L1/PD-1 blockade has been clinically applied to endometrial and cervical cancers, and a certain therapeutic effect has been observed. In endometrial cancer, promising outcomes have been achieved with a combination of an anti-PD-1 antibody and lenvatinib, regardless of the number of regimens, even in cases of recurrence after platinum administration. Therefore, immunotherapy is expected to have a therapeutic effect on ovarian cancer regardless of platinum resistance. In this review, considering immunotherapy for ovarian cancer, we discuss the immune mechanisms that exist in ovarian cancer and the immunotherapeutic strategies that should be developed.


Assuntos
Antígeno B7-H1 , Neoplasias Ovarianas , Humanos , Feminino , Receptor de Morte Celular Programada 1/metabolismo , Platina , Neoplasias Ovarianas/tratamento farmacológico , Imunoterapia
3.
J Obstet Gynaecol Res ; 49(11): 2649-2655, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37534531

RESUMO

AIM: Chronic abruption-oligohydramnios sequence (CAOS), which is characterized by vaginal bleeding and oligohydramnios, adversely affects the lungs of fetuses due to bloody amniotic fluid and oligohydramnios. The criteria for termination of pregnancy remain controversial. This study aimed to examine respiratory function in infants within 3 years after birth and risk factors for respiratory prognosis, and to clarify the management of CAOS. METHODS: This study is a case series of patients with CAOS managed at our institution between 2010 and 2020. The clinical data of the patients and their infants within 3 years after birth were reviewed. The amniotic fluid volume was measured using the maximum vertical pocket (MVP). RESULTS: Six of 17 neonates (35.3%) used inhaled nitric oxide (iNO) to improve oxygenation. Women with longer periods of MVP <1 cm delivered more neonates using iNO; however, periods of MVP <2 cm were not associated with iNO use. Almost half of the infants required home oxygen therapy when discharged, regardless of amniotic fluid volume. At 18 months corrected age, only one child needed respiratory support, and the others discontinued. Two neonates, both born at 23 weeks of gestational age, died within 1 month after birth because of extremely preterm birth. CONCLUSIONS: The amniotic fluid volume could predict the use of iNO in neonates, but it did not affect the child's respiratory function after the newborn period. Almost all children born to women with CAOS can improve their respiratory function as they grow up.


Assuntos
Oligo-Hidrâmnio , Nascimento Prematuro , Gravidez , Lactente , Criança , Recém-Nascido , Humanos , Feminino , Oligo-Hidrâmnio/etiologia , Líquido Amniótico , Prognóstico , Pulmão , Síndrome
4.
J Obstet Gynaecol Res ; 49(9): 2361-2369, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37354106

RESUMO

AIM: We investigated the frequency of early recurrence of vaginal intraepithelial neoplasia grade 2/3 (VaIN 2/3) (within 2 years) after hysterectomy for cervical intraepithelial neoplasia grade 3 (CIN3). The characteristics of the clinicopathological factors common to them were explored including different surgical methods. METHODS: As a retrospective observational study, a total of 647 CIN3 patients were divided into a conization and hysterectomy group (C group, n = 492; H group, n = 155), and HSIL (CIN2/3 or VaIN2/3) recurrence within 2 years after surgery was evaluated. A stratified analyses was performed. Surgical methods were divided into trans-abdominal, trans-vaginal, and laparoscopic. RESULTS: The recurrence of VaIN3 was detected in four cases (2.6%) in the H group, which was similar to that of CIN2/3 in the C group, 12 out of 491 patients (2.4%). The patients who developed VaIN3 were significantly older than those who did not (median, VaIN3: 71.0; VaIN1 and less: 48.0; p < 0.0001). All VaIN3 cases were detected within 5 months, although majority of cases were negative in the margin (3/4 cases; margin negative). The method of hysterectomy was not related to the VaIN3 recurrence. CONCLUSION: For CIN3 patients for whom hysterectomy is the main treatment, VaIN3 can develop in 2.6% within very shortly after operation even if surgical margin was negative. The elder the age, the higher the risk of early recurrence could be. Laparoscopic surgery is considered to be acceptable methods of hysterectomy.


Assuntos
Carcinoma in Situ , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Neoplasias Vaginais , Feminino , Humanos , Conização , Neoplasias Vaginais/terapia , Displasia do Colo do Útero/patologia , Carcinoma in Situ/patologia , Estudos Retrospectivos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia
5.
Carcinogenesis ; 43(7): 647-658, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35353883

RESUMO

Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC. A multivariate analysis of 62 human USC cases revealed that the tumor-infiltrating cell status, few CD8+ cells and abundant myeloid-derived suppressor cells (MDSCs), was an independent prognostic factor (P < 0.005). A murine endometrial cancer cell (mECC) was obtained from C57BL/6 mice via endometrium-specific deletion of Pten and Tp53, and another high-grade cell (HPmECC) was established by further overexpressing Myc in mECCs. HPmECCs exhibited higher capacities of migration and anchorage-independent proliferation than mECCs (P < 0.01, P < 0.0001), and when both types of cells were inoculated into the uterus of C57BL/6 mice, the prognosis of mice bearing HPmECC-derived tumors was significantly poorer (P < 0.001). Histopathological analysis of HPmECC orthotopic tumors showed serous carcinoma-like features with prominent tumor infiltration of MDSCs (P < 0.05), and anti-Gr-1 antibody treatment significantly prolonged the prognosis of HPmECC-derived tumor-bearing mice (P < 0.05). High CCL7 expression was observed in human USC and HPmECC, and MDSCs migration was promoted in a CCL7 concentration-dependent manner. These results indicate that antitumor immunity is suppressed in USC due to increased number of tumor-infiltrating MDSCs via CCL signal.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Células Supressoras Mieloides , Animais , Linhagem Celular Tumoral , Quimiocina CCL7 , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microambiente Tumoral
6.
Support Care Cancer ; 30(9): 7569-7574, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35674795

RESUMO

PURPOSE: Healthy lifestyle is related to quality of life (QOL) after cancer diagnosis and prognosis. However, there are few reports on patients conscious of healthy lifestyle and patients requiring medical providers' attention regarding healthy lifestyle. We aimed to develop a healthy lifestyle consciousness index (HLCI) for cancer patients and evaluated its validity in gynecological cancer patients. METHODS: The HLCI was designed to assess degree of healthy lifestyle consciousness, including items regarding "diet," "exercise," "body weight," and "sleep." Exploratory factor analysis was performed for dimensionality of the scale; Cronbach's alpha was calculated to assess internal-consistency reliability. For criterion-based validity, we calculated proportions of stage III/IV gynecological malignancies in those with categorized HLCI scores based on tertiles. Concurrent validity was evaluated between HLCI and other quality of life (QOL) scales including European Organization for Research and Treatment of Cancer QLQ-C30 in limited patients. RESULTS: HLCI comprised five 10-point items (0-45); higher values implied improved healthy lifestyle consciousness. Data from 108 gynecological malignancy patients at Kyoto University Hospital were analyzed. The mean age of subjects was 55.8 years; 36.1% of them had uterine corpus cancer; 34.3% were at stage III/IV of gynecological malignancy. The factor analysis revealed HLCI was unidimensional; the reliability based on Cronbach's alpha was satisfactory (0.88). The proportions of stage III/IV gynecological malignancies were 25.7%, 33.3%, and 44.4% in those with first (7-24 points), second (25-30 points), and third (31-46 points) tertiles of HLCI score, respectively. For patients with other QOL scales (n = 25), the mean scores of global health status of QLQ-C30 were 33.3, 50.0, and 83.3 for first, second, and third tertiles of HLCI score, respectively. CONCLUSION: HLCI was successfully validated; thus, patients with advanced stages or higher QOL might have strong consciousness regarding healthy lifestyle. HLCI may be useful in precision care for improved lifestyles and QOL.


Assuntos
Qualidade de Vida , Neoplasias Uterinas , Estado de Consciência , Feminino , Estilo de Vida Saudável , Humanos , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
7.
Br J Cancer ; 122(6): 778-788, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31932754

RESUMO

BACKGROUND: The mechanism of resistance development to anti-VEGF therapy in ovarian cancer is unclear. We focused on the changes in tumour immunity post anti-VEGF therapy. METHODS: The frequencies of immune cell populations and hypoxic conditions in the resistant murine tumours and clinical samples were examined. The expression profiles of both the proteins and genes in the resistant tumours were analysed. The impact of granulocyte-monocyte colony-stimulating factor (GM-CSF) expression on myeloid-derived suppressor cell (MDSC) function in the resistant tumours was evaluated. RESULTS: We found a marked increase and reduction in the number of Gr-1 + MDSCs and CD8 + lymphocytes in the resistant tumour, and the MDSCs preferentially infiltrated the hypoxic region. Protein array analysis showed upregulation of GM-CSF post anti-VEGF therapy. GM-CSF promoted migration and differentiation of MDSCs, which inhibited the CD8 + lymphocyte proliferation. Anti-GM-CSF therapy improved the anti-VEGF therapy efficacy, which reduced the infiltrating MDSCs and increased CD8 + lymphocytes. In immunohistochemical analysis of clinical samples, GM-CSF expression and MDSC infiltration was enhanced in the bevacizumab-resistant case. CONCLUSIONS: The anti-VEGF therapy induces tumour hypoxia and GM-CSF expression, which recruits MDSCs and inhibits tumour immunity. Targeting the GM-CSF could help overcome the anti-VEGF therapy resistance in ovarian cancers.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Células Supressoras Mieloides/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Neoplasias Ovarianas/patologia
8.
Int J Cancer ; 145(6): 1635-1647, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31228268

RESUMO

Uterine serous carcinoma (USC) is a highly aggressive histological subtype of endometrial cancers harboring highly metastatic and chemoresistant features. Our previous study showed that STAT1 is highly expressed in USC and acts as a key molecule that is positively correlated with tumor progression, but it remains unclear whether STAT1 is relevant to the malicious chemorefractory nature of USC. In the present study, we investigated the regulatory role of STAT1 toward platinum-cytotoxicity in USC. STAT1 suppression sensitized USC cells to increase cisplatin-mediated apoptosis (p < 0.001). Furthermore, phosphorylation of STAT1 was prominently observed on serine-727 (pSTAT1-Ser727), but not on tyrosine-701, in the nucleus of USC cells treated with cisplatin. Mechanistically, the inhibition of pSTAT1-Ser727 by dominant-negative plasmid elevated cisplatin-mediated apoptosis by increasing intracellular accumulation of cisplatin through upregulation of CTR1 expression. TBB has an inhibitory effect on casein kinase 2 (CK2), which phosphorylate STAT1 at serine residues. Sequential treatment with TBB and cisplatin on USC cells greatly reduced nuclear pSTAT1-Ser727, enhanced intracellular accumulation of cisplatin, and subsequently increased apoptosis. Tumor load was significantly reduced by combination therapy of TBB and cisplatin in in vivo xenograft models (p < 0.001). Our results collectively suggest that pSTAT1-Ser727 may play a key role in platinum resistance as well as tumor progression in USC. Thus, targeting the STAT1 pathway via CK2 inhibitor can be a novel method for attenuating the chemorefractory nature of USC.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Fator de Transcrição STAT1/metabolismo , Serina/metabolismo , Neoplasias Uterinas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Xenoenxertos , Humanos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Fosforilação , Fator de Transcrição STAT1/química , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
9.
Br J Cancer ; 120(1): 115-127, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30382166

RESUMO

BACKGROUND: V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune-checkpoint protein. VISTA expression on tumour cells and the associated regulatory mechanisms remain unclear. We investigated VISTA expression and function in tumour cells, and evaluated its mechanism and activity. METHODS: VISTA in tumour cells was assessed by tissue microarray analysis, immunohistochemical staining and western blot. A series of in vitro assays were used to determine the function of tumour-expressed VISTA. In vivo efficacy was evaluated in syngeneic models. RESULTS: VISTA was highly expressed in human ovarian and endometrial cancers. Upregulation of VISTA in endometrial cancer was related to the methylation status of the VISTA promoter. VISTA in tumour cells suppressed T cell proliferation and cytokine production in vitro, and decreased the tumour-infiltrating CD8+ T cells in vivo. Anti-VISTA antibody prolonged the survival of tumour-bearing mice. CONCLUSIONS: This is the first demonstration that VISTA is highly expressed in human ovarian and endometrial cancer cells, and that anti-VISTA antibody treatment significantly prolongs the survival of mice bearing tumours expressing high levels of VISTA. The data suggest that VISTA is a novel immunosuppressive factor within the tumour microenvironment, as well as a new target for cancer immunotherapy.


Assuntos
Antígenos B7/genética , Neoplasias do Endométrio/genética , Neoplasias Ovarianas/genética , Linfócitos T/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imunoterapia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
10.
Anticancer Res ; 44(5): 2009-2019, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677756

RESUMO

BACKGROUND/AIM: Although serum squamous cell carcinoma (SCC) antigen values are known to be useful in predicting the prognosis of cervical SCC, they have only been examined in a cursory manner. This study aimed to meticulously investigate the clinical significance of serum SCC antigen levels in patients with locally advanced cervical squamous cell carcinoma (LACSC). PATIENTS AND METHODS: The study included patients who were diagnosed with local stage (T-stage) 1b3/2/3 LACSC and underwent initial treatment at our institute between January 2006 and December 2016 (T-1b3: n=30; T-2: n=75; T-3: n=34). The patients were divided into three groups based on pre-treatment SCC values, and differences in clinical background, laboratory and pathology findings, and prognosis were examined. RESULTS: No significant difference in the SCC distribution was observed among the T-1b3/2/3 cases with elevated SCC levels. In stages T-1b3, T-2, and T-3, most recurrences in the SCC-High group were distant (T-1b3: three out of five recurrences; T-2: six out of seven recurrences; T-3: four out of eight recurrences), while most recurrences in the SCC-Low group were pelvic (T-1b3: two out of three recurrences; T-2: eight out of eight recurrences; T-3: three out of three recurrences). CONCLUSION: In LACSC, serum SCC antigen levels before treatment correlate strongly with the recurrence site. Patients with low levels should be closely monitored for local recurrence, whereas those with high levels warrant vigilance for distant recurrence.


Assuntos
Antígenos de Neoplasias , Carcinoma de Células Escamosas , Recidiva Local de Neoplasia , Serpinas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Pessoa de Meia-Idade , Serpinas/sangue , Antígenos de Neoplasias/sangue , Prognóstico , Idoso , Adulto , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Biomarcadores Tumorais/sangue , Relevância Clínica
11.
Turk J Obstet Gynecol ; 21(1): 28-36, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38440965

RESUMO

Objective: Endometriosis is associated with various symptoms, but their severity varies from case to case. In this study, we investigated the reality of symptoms presented by patients with clinically early-stage endometriosis-associated ovarian cancer (EAOC) and explored the relationship between symptoms and laboratory/imaging findings, pathological findings, and prognosis. Materials and Methods: This was a retrospective case-control study of patients who received initial surgical treatment and were diagnosed with clinically early-stage EAOC, including ovarian endometrioid carcinoma (OEC), ovarian clear cell carcinoma (OCCC), and seromucinous borderline tumor (SMBT). Patients with OEC/OCCC diagnosed between 2006 and 2016 and those with SMBT diagnosed between 2006 and 2020 were included. Chi-square and Kaplan-Meier estimates were used for statistical analyses. Results: One hundred-seven patients (OEC, n=31; OCCC, n=39; SMBT, n=37) were included. Fifty-nine (55.1%) patients presented with symptoms, and the proportion of patients with OEC who presented with symptoms was significantly higher than that of others (OEC, 77.4%; OCCC, 43.6%; SMBT, 48.6%). The details of symptoms differed significantly among the pathological types (lower abdominal pain/abdominal discomfort/abnormal bleeding, OEC: 11/8/9; OCCC: 6/12/1; SMBT: 15/5/3). Only in the OEC group did symptomatic patients show significantly higher white blood cell (WBC) count and neutrophil/lymphocyte (N/L) ratio (symptomatic vs. asymptomatic, median: WBC count: 7250 vs. 5000, p=0.008; N/L ratio: 4.6 vs. 1.7, p=0.013). None of the asymptomatic patients showed recurrence during follow-up. Conclusion: Patients with EAOC show varying symptoms depending on the histological type of the tumor. Laboratory findings underlying symptoms also vary by histopathological type, which may reflect differences in the carcinogenesis process.

12.
Case Rep Womens Health ; 42: e00598, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577171

RESUMO

The transverse vaginal septum, a rare Müllerian duct anomaly, presents diagnostic and therapeutic challenges owing to its variable location, thickness, and potential association with uterine malformations. Therefore, an accurate diagnosis and selection of an appropriate treatment are important. Herein, the case of a 28-year-old nonpregnant woman with sexual dysfunction attributable to a transverse vaginal septum is presented. The septum, approximately 5 mm thick, was situated low on the vaginal wall near the urethral opening, with a small central aperture. Employing Y-V plasty, full extension of the posterior and lateral vaginal walls was achieved while minimizing the manipulation of the anterior wall to avoid urethral injury. Postoperatively, the patient achieved sexual function without vaginal stenosis. Y-V plasty is a minimally invasive and effective approach for preventing postoperative stenosis in the treatment of a thin transverse vaginal septum located low on the vaginal wall.

13.
Mol Cancer Ther ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958503

RESUMO

Ovarian clear cell carcinoma (OCCC), which has unique clinical characteristics, arises from benign endometriotic cysts, forming an oxidative stress environment due to excess iron accumulation, and exhibits poor prognosis, particularly in advanced stages owing to resistance to conventional therapeutics. Ferroptosis is an iron-dependent form of programmed cell death induced by lipid peroxidation and controlled by Hippo signaling. We hypothesized that overcoming ferroptosis resistance is an attractive strategy because OCCC acquires oxidative stress resistance during its development and exhibits chemoresistant features indicative of ferroptosis resistance. This study aimed to determine whether OCCC is resistant to ferroptosis and clarify the mechanism underlying resistance. Unlike ovarian high-grade serous carcinoma cells, OCCC cells were exposed to oxidative stress. However, OCCC cells remained unaffected by lipid peroxidation. Cell viability assays revealed that OCCC cells exhibited resistance to the ferroptosis inducer erastin. Moreover, Samroc analysis showed that the Hippo signaling pathway was enriched in OCCC cell lines and clinical samples. Furthermore, patients with low expression of nuclear Yes-associated protein 1(YAP1) exhibited a significantly poor prognosis of OCCC. Moreover, YAP1 activation enhanced ferroptosis in OCCC cell lines. Furthermore, suppression of zinc finger DHHC-type palmitoyltransferase 7 (ZDHHC7) enhanced ferroptosis by activating YAP1 in OCCC cell lines. Mouse xenograft models demonstrated that ZDHHC7 inhibition suppressed tumor growth via YAP1 activation by erastin treatment. In conclusion, YAP1 activation regulated by ZDHHC7 enhanced ferroptosis in OCCC. Thus, overcoming ferroptosis resistance is a potential therapeutic strategy for OCCC.

14.
Taiwan J Obstet Gynecol ; 62(5): 655-660, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37678991

RESUMO

OBJECTIVE: Diabetes in pregnancy is a major risk factor for adverse perinatal outcomes such as congenital anomalies, hypertensive disorders of pregnancy (HDP), and macrosomia. For the mechanism of onset of type 1 and type 2 diabetes are different, we focused on the difference in perinatal outcomes between the type 1 and type 2 diabetes groups. MATERIALS AND METHODS: We retrospectively reviewed 22 pregnancies with type 1 diabetes and 15 pregnancies with type 2 diabetes, who were managed in our single center, with regard to maternal diabetes conditions during pregnancy and neonatal birthweight and blood glucose level. Furthermore, we checked the effect of continuous glucose monitoring and continuous subcutaneous insulin injection in pregnancies with type 1 diabetes. RESULTS: Type 1 diabetes in pregnancy was less controllable and increased neonatal birth weight and neonatal hypoglycemia within 2 h after birth after neonatal care unit admission. Continuous glucose monitoring and continuous subcutaneous insulin injection that are convenient to use, had a similar effect in the management of type 1 diabetes during pregnancy, compared with conventional diabetes treatment. In contrast, maternal BMI and HDP were increased in women with type 2 diabetes. CONCLUSION: In the management of pregnancy with diabetes, we should pay attention to the difference in pregnancy prognosis between type 1 and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Insulinas , Recém-Nascido , Gravidez , Feminino , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Automonitorização da Glicemia , Estudos Retrospectivos , Glicemia
15.
Int Cancer Conf J ; 12(2): 120-125, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36896195

RESUMO

Uterine adenosarcoma is a rare gynecologic malignancy, and 10-25% of the cases exhibit clinically aggressive behaviors. Although TP53 mutations are frequently identified in high-grade adenosarcomas of the uterus, definitive gene alterations have not been identified in uterine adenosarcomas. Specifically, no reports have described mutations in homologous recombination deficiency-related genes in uterine adenosarcomas. This study presents a case of uterine adenosarcoma without sarcomatous overgrowth but with TP53 mutation that exhibited clinically aggressive behaviors. The patient had an ATM mutation, which is a gene associated with homologous recombination deficiency, and exhibited a good response against platinum-based chemotherapy and possible therapeutic target by poly(ADP-ribose) polymerase inhibitors.

16.
Obstet Gynecol ; 142(2): 307-318, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37411024

RESUMO

OBJECTIVE: To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN), compared with placebo or no intervention. DATA SOURCES: We searched Cochrane, PubMed, ISRCTN registry, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform up to November 23, 2022. METHODS OF STUDY SELECTION: We included randomized controlled trials and prospective nonrandomized studies with control arms that investigated the efficacy of imiquimod for histologically confirmed CIN or VAIN. The primary outcomes were histologic regression of the disease (primary efficacy outcome) and treatment discontinuation due to side effects (primary safety outcome). We estimated pooled odds ratios (ORs) of imiquimod, compared with placebo or no intervention. We also conducted a meta-analysis of the proportions of patients with adverse events in the imiquimod arms. TABULATION, INTEGRATION, AND RESULTS: Four studies contributed to the pooled OR for the primary efficacy outcome. An additional four studies were available for meta-analyses of proportions in the imiquimod arm. Imiquimod was associated with increased probability of regression (pooled OR 4.05, 95% CI 2.08-7.89). Pooled OR for CIN in the three studies was 4.27 (95% CI 2.11-8.66); results of one study were available for VAIN (OR, 2.67, 95% CI 0.36-19.71). Pooled probability for primary safety outcome in the imiquimod arm was 0.07 (95% CI 0.03-0.14). The pooled probabilities (95% CI) of secondary outcomes were 0.51 (0.20-0.81) for fever, 0.53 (0.31-0.73) for arthralgia or myalgia, 0.31 (0.18-0.47) for abdominal pain, 0.28 (0.09-0.61) for abnormal vaginal discharge or genital bleeding, 0.48 (0.16-0.82) for vulvovaginal pain, and 0.02 (0.01-0.06) for vaginal ulceration. CONCLUSION: Imiquimod was found to be effective for CIN, whereas data on VAIN were limited. Although local and systemic complications are common, treatment discontinuation is infrequent. Thus, imiquimod is potentially an alternative therapy to surgery for CIN. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022377982.


Assuntos
Antineoplásicos , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Imiquimode/efeitos adversos , Antineoplásicos/efeitos adversos , Estudos Prospectivos , Aminoquinolinas/uso terapêutico , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia
17.
Int Cancer Conf J ; 12(2): 126-130, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36896204

RESUMO

Para-ovarian cysts are occasionally encountered in clinical practice; however, malignant tumors derived from them are rare. Due to its rarity, the characteristic imaging findings of para-ovarian tumors with borderline malignancy (PTBM) are largely unknown. Herein, we report a case of PTBM, along with imaging findings. A 37-year-old woman came to our department with a suspected malignant adnexal tumor. Pelvic contrast-enhanced magnetic resonance imaging (MRI) revealed a solid part within the cystic tumor with a decrease in the apparent diffusion coefficient (ADC) value (1.16 × 10-3 mm2/s). We also performed Positron Emission Tomography-MRI and showed a strong accumulation of 18F-fluorodeoxyglucose (FDG) in the solid part (SUVmax = 14.8). In addition, the tumor appeared to develop independently of the ovary. Because tumor was derived from para-ovarian cyst, we suspected PTBM preoperatively and planned fertility sparing treatment. Pathological examination revealed a serous borderline tumor and PTBM was confirmed. PTBM can have unique imaging characteristics, including a low ADC value and high FDG accumulation. When a tumor appears to develop from para-ovarian cysts, borderline malignancy can be suspected, even if imaging findings suggest malignant potential.

18.
Int Cancer Conf J ; 12(3): 168-172, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37251011

RESUMO

There is no consensus on the use of hormone replacement therapy (HRT) after treatment of advanced corpus cancer. We report a case of advanced corpus cancer at a young age, in which HRT was initiated 7 years after surgery, and regional lymph node recurrence was later detected. The patient was 35 years old at the time of initial treatment in X year, when she was diagnosed with stageIIIC2 corpus cancer and underwent a hysterectomy with bilateral salpingo-oophorectomy and a retroperitoneal lymphadenectomy. HRT was started at X + 7 years, and at X + 9 years, a 25 × 12-mm-sized mass was found in the hilum of the right kidney. A laparoscopic resection revealed regional lymph node recurrence of the corpus cancer. A retrospective study further revealed that a tumor measuring 12 × 3 mm was found at X + 3 years and grew to 18 × 7 mm in X + 6 years, just before the start of the HRT. We hypothesize that HRT did not induce tumor recurrence; instead, it allowed for long-term follow-up and early diagnosis.

19.
iScience ; 26(2): 106020, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36824283

RESUMO

Despite modest clinical improvement with anti-vascular endothelial growth factor antibody (AVA) therapy in ovarian cancer, adaptive resistance is ubiquitous and additional options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance and we aimed to investigate the utility of a GLS inhibitor (GLSi). Our in vitro findings demonstrated increased glutamine abundance and a significant cytotoxic effect in AVA-resistant tumors when GLSi was administered in combination with bevacizumab. In vivo, GLSi led to a reduction in tumor growth as monotherapy and when combined with AVA. Furthermore, GLSi initiated after the emergence of resistance to AVA therapy resulted in a decreased metabolic conversion of pyruvate to lactate as assessed by hyperpolarized magnetic resonance spectroscopy and demonstrated robust antitumor effects with a survival advantage. Given the increasing population of patients receiving AVA therapy, these findings justify further development of GLSi in AVA resistance.

20.
J Obstet Gynaecol Res ; 38(5): 884-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22449361

RESUMO

Solitary fibrous tumor (SFT), which was first described as a pleural lesion by Klemperer and Rabin in 1931, is a rare, slow-growing neoplasm characterized by the proliferation of fibroblast-like spindle cells arranged in a patternless manner with few nuclear atypia. Extrathoracic SFT have increasingly been recognized, but those in the genital tract are extremely rare. Gynecological SFT behave as tumors with low malignant potential to recur, metastasize, or affect nearby organs resulting in infertility. We report a case of vulvar SFT slowly growing for 10 years, and propose a strategy for the diagnosis and treatment of gynecological SFT.


Assuntos
Tumores Fibrosos Solitários/patologia , Neoplasias Vulvares/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Tumores Fibrosos Solitários/cirurgia , Resultado do Tratamento , Neoplasias Vulvares/cirurgia
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