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1.
Anticancer Res ; 42(4): 2017-2022, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35347023

RESUMO

BACKGROUND/AIM: To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi. PATIENTS AND METHODS: This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum-based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum-free interval (PFI). RESULTS: Of the 28 patients with PFI <6 months, 23 received chemotherapy (non-platinum single agent, 20; trabectedin + pegylated liposomal doxorubicin (PLD), 3). Forty-two of the 43 patients with PFI 6-12 months underwent chemotherapy (platinum-based chemotherapy,11; trabectedin + PLD, 10; non platinum-single agent, 21). Thirty-one of the 32 patients with PFI >12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum - single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI <6 months, 6-12 months, and >12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively. CONCLUSION: Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.


Assuntos
Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/etiologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Estudos Retrospectivos
2.
J Cancer Res Ther ; 18(2): 488-495, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35645119

RESUMO

Background: Golgi phosphoprotein-3 (GOLPH 3) is involved in the development of several human cancers. However, the clinical significance and biological role of GOLPH 3 in ovarian cancer (OC) remains unknown. Methods: The expression of GOLPH 3 in OC cell lines was quantified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The role of GOLPH 3 in tumorigenicity, migration, and invasion of OC cell lines by small interference RNA, scratch wound-healing assays, and transwell assays was detected. In addition, western blotting was used to determine whether GOLPH 3 is associated with the PI3K/AKT/mTOR signaling pathway. Furthermore, RT-qPCR verified whether GOLPH 3 is associated with drug resistance. Results: GOLPH 3-positive expression rate was higher in OC. Downregulation of GOLPH 3 markedly inhibited the migration and invasion and may be related to the PI3K/AKT/mTOR signal pathway. Moreover, the result of the experiment proved that GOLPH 3 enhances the sensitivity of OC to cisplatin by regulating ATP7A/B. GOLPH 3 promoted the invasion and migration of OC, and the mechanism may be related to the PI3K/Akt/mTOR pathway. In addition, inhibition of GOLPH 3 increased the sensitivity of OC cells to cisplatin, which may be associated with ATP7A/B. Conclusion: This study found that GOLPH3 may promote the migration and invasion of OC cells through PI3K/Akt/mTOR pathway. At the same time, low expression of GOLPH3 increased the sensitivity of OC cells to cisplatin.


Assuntos
Cisplatino , Proteínas de Membrana , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Movimento Celular/genética , Proliferação de Células , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Proteínas de Membrana/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética
3.
Int J Clin Pract ; 2022: 9592969, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685604

RESUMO

Background: Previous observational studies and meta-analysis suggested a possible association between metformin use and reduced mortality in women with ovarian cancer (OC). However, clinical factors that may influence the relationship remain poorly evaluated. We performed an updated meta-analysis to systematically evaluate the above association and to observe the potential influences of study characteristics on the association. Methods: Relevant studies reporting the association between metformin use and mortality in women with OC in the multivariate adjusted model were identified by search of electronic databases that included PubMed, Embase, and Web of Science. The random-effects model was adopted to combine the results. Results: Nine studies including 10030 women with OC were included. Overall, metformin use was independently associated with reduced overall mortality (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55-0.93, P=0.01; I 2 = 62%). Consistent results were observed for studies comparing metformin users with nondiabetic women and studies comparing metformin users with diabetic women who did not use metformin (P for subgroup analysis = 0.70). Further subgroup analyses showed consistent results in studies with metformin use before or after the diagnosis of OC, with or without adjustment of body mass index (BMI) and with or without adjustment of concurrent medications (P for subgroup analyses all >0.10). Conclusion: Metformin use is associated with reduced mortality in women with OC, which may be independent of the diabetic status of the controls, timing of metformin use, or adjustment of BMI and concurrent medications. Clinical trials are needed to validate the potential benefits of metformin on survival of OC.


Assuntos
Diabetes Mellitus , Metformina , Neoplasias Ovarianas , Índice de Massa Corporal , Feminino , Humanos , Metformina/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Modelos de Riscos Proporcionais
4.
JAMA Netw Open ; 5(6): e2216370, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35679042

RESUMO

Importance: The American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound (US) risk scoring system has been studied in a selected population of women referred for suspected or known adnexal lesions. This population has a higher frequency of malignant neoplasms than women presenting to radiology departments for pelvic ultrasonography for a variety of indications, potentially impacting the diagnostic performance of the risk scoring system. Objective: To evaluate the risk of malignant neoplasm and diagnostic performance of O-RADS US risk scoring system in a multi-institutional, nonselected cohort. Design, Setting, and Participants: This multi-institutional cohort study included a population of nonselected women in the United States who presented to radiology departments for routine pelvic ultrasonography between 2011 and 2014, with pathology confirmation imaging follow up or 2 years of clinical follow up. Exposure: Analysis of 1014 adnexal lesions using the O-RADS US risk stratification system. Main Outcomes and Measures: Frequency of ovarian cancer and diagnostic performance of the O-RADS US risk stratification system. Results: This study included 913 women with 1014 adnexal lesions. The mean (SD) age of the patients was 42.4 (13.9 years), and 674 of 913 (73.8%) were premenopausal. The overall frequency of malignant neoplasm was 8.4% (85 of 1014 adnexal lesions). The frequency of malignant neoplasm for O-RADS US 2 was 0.5% (3 of 657 lesions; <1% expected); O-RADS US 3, 4.5% (5 of 112 lesions; <10% expected); O-RADS US 4, 11.6% (18 of 155; 10%-50% expected); and O-RADS 5, 65.6% (59 of 90 lesions; >50% expected). O-RADS US 4 was the optimum cutoff for diagnosing cancer with sensitivity of 90.6% (95% CI, 82.3%-95.9%), specificity of 81.9% (95% CI, 79.3%-84.3%), positive predictive value of 31.4% (95% CI, 25.7%-37.7%) and negative predictive value of 99.0% (95% CI, 98.0%-99.6%). Conclusions and Relevance: In this cohort study of a nonselected patient population, the O-RADS US risk stratification system performed within the expected range as published by the ACR O-RADS US committee. The frequency of malignant neoplasm was at the lower end of the published range, partially because of the lower prevalence of cancer in a nonselected population. However, a high negative predictive value was maintained, and when a lesion can be classified as an O-RADS US 2, the risk of cancer is low, which is reassuring for both clinician and patient.


Assuntos
Neoplasias Ovarianas , Adulto , Estudos de Coortes , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Fatores de Risco , Ultrassonografia/métodos , Estados Unidos/epidemiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-35682288

RESUMO

BACKGROUND: Previous studies showed that cancer significantly reduces the quality of life of patients. The purpose of this study was to analyze changes in the quality of life of women diagnosed with ovarian and breast cancer after surgical treatment followed by adjuvant cancer therapy. METHODS: The study covered 220 women diagnosed with ovarian (n = 89) or breast cancer (n = 131) after surgical treatment followed by adjuvant cancer therapy (chemotherapy, radiotherapy, hormone therapy). The tools used to measure the patients' quality of life were the standardized EORTC QLQ-C30 questionnaire, the QLQ-BR23 module for breast cancer and the QLQ-OV28 module for ovarian cancer. RESULTS: The subjective assessment of the health and quality of life of the women was carried out using the EORTC QLQ-C30 questionnaire and the QLQ-OV28 and QLQ-BR23 modules. Women with breast cancer rated their health higher than women with ovarian cancer. The health assessment performed by the patients was not related to the type of cancer (p > 0.05). They experienced pain, dyspnea and weakness regardless of the cancer location. Moreover, women's health status had a clinically significant impact on their family and social life, although no statistically significant differences were found between the two groups (p > 0.05). Whilst the patients with breast cancer rated their quality of life and health higher than the patients with ovarian cancer, the differences were not statistically significant (p > 0.05). CONCLUSIONS: Changes in the quality of life of women with breast and ovarian cancer concern the physical sphere, hobbies, fatigue/rest, pain, family and social spheres, and material conditions. It is necessary to support specialists at every stage of treatment of these patients, which may improve the results of the treatment and patients' perception of health and quality of life.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Neoplasias da Mama/tratamento farmacológico , Carcinoma Epitelial do Ovário , Feminino , Humanos , Neoplasias Ovarianas/terapia , Dor , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
6.
Int J Mol Sci ; 23(11)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35682890

RESUMO

Ovarian cancer (OC) is one of the most common gynecological cancers, with the worst prognosis and the highest mortality rate. Peritoneal dissemination (or carcinomatosis) accompanied by ascites formation is the most unfavorable factor in the progression and recurrence of OC. Tumor cells in ascites are present as either separate cells or, more often, as cell aggregates, i.e., spheroids which promote implantation on the surface of nearby organs and, at later stages, metastases to distant organs. Malignant ascites comprises a unique tumor microenvironment; this fact may be of relevance in the search for new prognostic and predictive factors that would make it possible to personalize the treatment of patients with OC. However, the precise mechanisms of spheroid formation and carcinomatosis are still under investigation. Here, we summarize data on ascites composition as well as the activity of fibroblasts and macrophages, the key stromal and immune components, in OC ascites. We describe current knowledge about the role of fibroblasts and macrophages in tumor spheroid formation, and discuss the specific functions of fibroblasts, macrophages and T cells in tumor peritoneal dissemination and implantation.


Assuntos
Carcinoma , Neoplasias Ovarianas , Neoplasias Peritoneais , Ascite/patologia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Microambiente Tumoral
7.
Int J Mol Sci ; 23(11)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35682896

RESUMO

Background: Recently, new paradigms for the etiology and origin of ovarian high-grade serous carcinoma (HGSC) have emerged. The carcinogens released during ovulation transform fallopian tube epithelial cells, exfoliating and metastasizing to the peritoneal organs, including the ovaries. Solid in vivo evidence of the paradigms in a mouse model is urgently needed but is hampered by the differing tubo-ovarian structures. In mice, there is a bursa structure surrounding the distal oviduct and ovary. This, on one hand, prevents the direct influence of ovulatory follicular fluid (FF) on the exfoliated tumor cells. On the other hand, it hinders the seeding of exfoliated tumor cells into the ovary. Methods: In this study, we created a bursa-free mouse xenograft model to examine the effect of superovulation on peritoneal and ovarian metastases of transformed human tubal epithelial cells after intraperitoneal injection in NSG mice. Results: The bursa-free mouse model showed a better effect of ovulation on peritoneal metastasis. In this model, superovulation increased the number of transformed human tubal epithelial cell seedlings after intraperitoneal injection. Compared to the bursa-intact state, bursa-free ovaries were more vulnerable to external tumor seeding in either normal ovulation or superovulation state. Conclusions: This study provides the first in vivo evidence that intraperitoneal spreading of tubal HGSC cells is enhanced by ovulation. This study also demonstrated a mouse model for studying ovary-peritoneum interaction in cancer development.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Animais , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Modelos Animais de Doenças , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/patologia , Feminino , Xenoenxertos , Humanos , Camundongos , Neoplasias Ovarianas/patologia , Ovulação
8.
PLoS One ; 17(6): e0269680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35687576

RESUMO

OBJECTIVE: At present, maintenance therapy with the antiangiogenic agent bevacizumab or with PARP-inhibitors represent two options for BRCA-wildtype ovarian cancer patients, after platinum-based first line chemotherapy. The identification of molecular markers to predict patient response to different maintenance therapies remains a major challenge. In the present study we analyzed the predictive potential of vascular endothelial growth factor C (VEGF-C) to identify ovarian cancer patients that might benefit from an antiangiogenic therapy. METHODS: 101 patients with primary epithelial ovarian cancer were analyzed for serum levels of VEGF-A,-C and CA-125 by ELISA. Serum levels were compared between patients with low pT-stage (pT1a-pT2c n = 11), healthy individuals (n = 27) and patients with higher pT-stage (> = pT3 n = 90). Adjusted ROC curves and an adjusted logistic regression model were carried out to evaluate the potential impact of VEGF-A and -C, as well as CA-125 serum level concentration on bevacizumab-therapy response, under consideration of covariates such as FIGO, pM, pN and residual tumor after surgery. RESULTS: A patient which has in comparison twice the VEGF-C concentration in serum, has a significant increased chance of response to bevacizumab by a factor of 2.79. Further, only VEGF-C serum levels were significantly higher in the group of patients with lower pT-stage compared to healthy individuals, whereas VEGF-A or CA-125 serum levels could not discriminate between healthy individuals and patients with ovarian cancer at low pT-stages. CONCLUSION: VEGF-C serum level might serve as as a biomarker to evaluate treatment response under bevacizumab.


Assuntos
Neoplasias Ovarianas , Fator C de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Antígeno Ca-125 , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Neoplasias Ovarianas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
BMJ Case Rep ; 15(6)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688572

RESUMO

Solid masses of the ovaries raise the suspicion of malignancy or metastasis and require histological diagnosis. Extramedullary haematopoesis (EMH) is a rare histological finding of a mass of the adnexa. The sonographic pattern of EMH has rarely been described in the literature. Transvaginal biopsy of EMH has not been reported in the literature. We present a case of adnexal EMH in a patient affected with ß-thalassaemia, and we performed a narrative review. Only in our case, the sonographic pattern was described, and a transvaginal ultrasound-guided core biopsy was used. Assessing patients' medical history and correlating it to the findings of diagnostic imaging is of paramount importance when evaluating patients with adnexal masses. The correct interpretation of sonographic images can avoid unnecessarily invasive procedures. A transvaginal biopsy could be a safe, easy and well-tolerated method to gain definite histological diagnosis in cases where a primary ovarian malignancy is not suspected.


Assuntos
Doenças dos Anexos , Doenças Hematológicas , Hematopoese Extramedular , Neoplasias Ovarianas , Talassemia beta , Anexos Uterinos/patologia , Doenças dos Anexos/diagnóstico , Feminino , Doenças Hematológicas/patologia , Humanos , Neoplasias Ovarianas/patologia , Talassemia beta/complicações
10.
J Surg Oncol ; 126(1): 10-19, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35689574

RESUMO

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.


Assuntos
Neoplasias da Mama , Ginecologia , Neoplasias Ovarianas , Oncologia Cirúrgica , Brasil/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Neoplasias Ovarianas/cirurgia
11.
BMC Womens Health ; 22(1): 224, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690772

RESUMO

OBJECTIVE: This study aimed to compare the efficacy of albumin-bound paclitaxel combined with carboplatin (Nab-TC) with that of traditional solvent-based paclitaxel combined with carboplatin (TC) as neoadjuvant chemotherapy (NAC) regimens for primary epithelial ovarian cancer. METHODS: Eighty patients with advanced primary epithelial ovarian cancer admitted for treatment at the Harbin Medical University Cancer Hospital from January 2015 to January 2020 were retrospectively selected. All patients underwent surgery after 1-4 courses of NAC with Nab-TC or TC regimen. Among the patients included for study, 40 patients in each group. RESULTS: The ORR in Nab-TC group was better compared to TC group (45% vs 40%), but the difference was not significant (P = 0.651). While the reduction rate of CA-125 value in the Nab-TC group was significantly better (P < 0.05). The postoperative complication rate such as postoperative blood transfusion (5% vs 35%) and postoperative infusion of human albumin (25% vs 55%) were significantly lower relative to the TC group. The median progression-free survival of the Nab-TC group was significantly longer relative to the TC group (20 months vs 13 months, P = 0.012), and the patient's quality of life was also better in the Nab-TC group (P < 0.05). Our study demonstrated that Nab-TC regimen and R0 represented the independent prognostic factors. CONCLUSION: The efficacy of the Nab-TC regimen as NAC for advanced primary epithelial ovarian cancer was non-inferior to that of the TC regimen along with a lower incidence of adverse reactions, a longer PFS and a higher quality of life, supporting its therapeutic value in the clinic.


Assuntos
Paclitaxel Ligado a Albumina , Neoplasias Ovarianas , Paclitaxel Ligado a Albumina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/etiologia , Paclitaxel/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos
12.
J Obstet Gynaecol Can ; 44(6): 700-702, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35691682

RESUMO

BACKGROUND: Paraneoplastic dermatomyositis following a diagnosis of ovarian cancer is rare. There are very few cases reported on the management of severe forms. CASE: We report the case of a 50-year-old woman diagnosed with stage IIIC high-grade serous ovarian cancer and a severe form of paraneoplastic dermatomyositis requiring mechanical ventilation. She had significant comorbidities further adding to the complexity of the chemotherapy regimen. Intravenous immunoglobulin and corticosteroids were also administered. The dermatomyositis remained poorly controlled, and the patient was ultimately referred to palliative care. CONCLUSION: The necessity to treat the underlying neoplasia creates a fine balance between the aggressive treatments required and the clinical state of the patient. Multidisciplinary collaboration is warranted to offer best management.


Assuntos
Dermatomiosite , Neoplasias Ovarianas , Síndromes Paraneoplásicas , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/tratamento farmacológico , Síndromes Paraneoplásicas/etiologia
13.
Einstein (Sao Paulo) ; 20: eAO6851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35649059

RESUMO

OBJECTIVE: To evaluate whether the presence of a hypointense signal at T2-weighted imaging in a solid ovarian lesion on magnetic resonance imaging is a predictor of stability and benignity. METHODS: This is a single center study, prospectively read with retrospective acquired data. The database was searched for patients who underwent magnetic resonance imaging between January 2008 and October 2019 and whose reports mentioned solid ovarian lesions with low signal on T2-weighted imaging. A total of 47 nodules were included. A radiologist who was blinded to the clinical indication for magnetic resonance imaging and original reports evaluated the cases. Objective and subjective criteria of ovarian lesions in magnetic resonance imaging were evaluated. RESULTS: Thirty-five nodules were considered benign/stable and 12 were considered non-stable. The analysis showed that the non-stable lesions showed statistically more hyperintensity at T1-weighted imaging compared to the stable lesions. CONCLUSION: T2-weighted imaging hypointensity can be considered a predictor of stability in solid ovarian lesions when associated with iso/hypointensity in T1-weighted imaging.


Assuntos
Cistos Ovarianos , Neoplasias Ovarianas , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Estudos Retrospectivos
14.
Comput Math Methods Med ; 2022: 9339325, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664644

RESUMO

Objective: To evaluate the value of combined detection of serum CA125, CA199, and HE4 in the diagnosis of ovarian cancer. Methods: Relevant articles retrieved from PubMed, Elsevier Science, Springer, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were screened strictly according to inclusion and exclusion criteria. Included literature published from January 2005 to December 2021. (2) Serum HE4, CA125, CA199, and their combination for ovarian cancer diagnostic tests were studied, and healthy subjects or patients with the benign disease were taken as a control group. (3) Pathological tissue diagnosis as the gold standard. (4) Complete original data can be obtained. (5) The sample size was ≥20. (6) Language is limited to Chinese and English. Data features and QUADAS table were extracted from the included literature, and QUADAS evaluation tool detail table was used for the included study. Conduct quality evaluation. Statistical analysis was carried out using meta-disc software version 1.4. Appropriate effect model was selected to merge the effect size, and the forest maps of merge sensitivity, merge specificity, and merge likelihood ratio were obtained. Results: The results of meta-analysis showed that there was a statistical difference in diagnostic specificity analysis of CA125 (OR = 1.91, 95% CI (1.58, 2.32), P < 0.00001, I 2 = 67%, Z = 6.58); diagnostic sensitivity analysis of CA125 (OR = 2.50, 95% CI (1.73, 3.62), P < 0.00001, I 2 = 0%, Z = 4.90); diagnostic specificity analysis of CA199 (OR = 1.98, 95% CI (1.60, 2.44), P < 0.00001, I 2 = 89%, Z = 6.35); diagnostic sensitivity analysis of CA199 (OR = 1.92, 95% CI (1.46, 2.52), P < 0.00001, I 2 = 73%, Z = 4.70); diagnostic specificity analysis of HE4 (OR = 2.08, 95% CI (1.65, 2.63), P < 0.00001, I 2 = 73%, Z = 6.19); diagnostic sensitivity analysis of HE4 (OR = 2.37, 95% CI (1.87, 3.00), P < 0.00001, I 2 = 83%, Z = 7.19). Conclusion: In the clinical assisted diagnosis of ovarian cancer, combined detection of CA125, CA199, and HE4 has the stronger discriminant ability and higher accuracy than single detection of CA125, which can improve the diagnostic efficiency.


Assuntos
Biomarcadores Tumorais , Neoplasias Ovarianas , Antígeno Ca-125 , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos
15.
J Egypt Natl Canc Inst ; 34(1): 24, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35665865

RESUMO

BACKGROUND: Ovarian cancer has the highest mortality amongst all gynaecological malignancies, with around two-thirds of patients diagnosed with advanced disease due to late presentation. Furthermore, around 90% of patients develop recurrence and eventually become chemoresistant. Therefore, there is a high demand to identify biomarkers specific to this disease for screening for early detection, as well as new therapeutic targets. Tight junctions (TJs) regulate paracellular permeability and are vital in establishing epithelial cell polarity. One hallmark of tumorigenesis is the loss of TJs, with loss of cell-to-cell adhesion. Claudins are integral TJ membrane proteins, which have been found to play a critical role in maintaining the TJ's barrier function. Furthermore, claudin-3 (CLDN3) and claudin-4 (CLDN4) are overexpressed in ovarian cancer. This article aims to explore the biological role of CLDN3 and CLDN4 and their potential in different aspects of the management of ovarian cancer. MAIN BODY: CLDN3 and CLDN4 have been shown to be effective markers for the early detection of ovarian cancer. Whilst there is difficulty in screening for both claudins in serum, their assessment by gene expression analysis and immunohistochemical methods shows promising potential as diagnostic and prognostic biomarkers for ovarian cancer. The localisation and overexpression of claudins, such as CLDN3, have been shown to correlate with poorer survival outcomes. The added value of combining claudins with other markers such as CA125 for diagnosis has also been highlighted. Therapeutically, CLDN3 and more so CLDN4 have been shown to be effective targets of Clostridium perfringens enterotoxin (CPE). Interestingly, CPE has also been shown to resensitise chemoresistant tumours to therapy. CONCLUSIONS: This review presents the diagnostic and prognostic potential of CLDN3 and CLDN4 and their emerging role as therapeutic targets in ovarian cancer. Clinical trials are required to validate the promising results of the in vitro and in vivo studies for CLDN3 and CLDN4, possibly adding onto current ovarian cancer management.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Claudina-3/genética , Claudina-3/metabolismo , Claudina-4/genética , Claudina-4/metabolismo , Claudinas/genética , Claudinas/metabolismo , Claudinas/uso terapêutico , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia
16.
Med Oncol ; 39(8): 112, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35666342

RESUMO

Snake venom L-Amino-acid oxidase (svLAAO) has become a critical research target in molecular biology and medical science since its widespread presence and diverse biological roles, including antitumor application. Our research confirmed that Crotalus adamanteus (C. adamanteus) venom LAAO exhibited potential anti-ovarian cancer activity both in vivo and in vitro. C. adamanteus venom LAAO significantly reduced viability of ovarian cancer cells and caused morphological changes that preceded cell death. The results of molecular biology experiments showed that C. adamanteus venom LAAO caused expression changes of genes related to apoptotic pathways either intrinsically or extrinsically in ovarian cancer cells. Animal experiments and histological analysis also proved that C. adamanteus venom LAAO could effectively inhibit the tissue damage caused by ovarian cancer, and animals treated with C. adamanteus venom LAAO showed higher survival time. Catalase blocked the major apoptosis induction of C. adamanteus venom LAAO on ovarian cancer cells, suggesting that the cytotoxicity of C. adamanteus venom LAAO on ovarian cancer cells was mainly mediated by H2O2. These results infer that C. adamanteus venom LAAO will have some advantages in new drug research and antitumor drug development in future.


Assuntos
Venenos de Crotalídeos , Neoplasias Ovarianas , Animais , Venenos de Crotalídeos/farmacologia , Crotalus/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio , L-Aminoácido Oxidase/química , L-Aminoácido Oxidase/metabolismo , L-Aminoácido Oxidase/farmacologia , Neoplasias Ovarianas/tratamento farmacológico
18.
J Ovarian Res ; 15(1): 70, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35668443

RESUMO

BACKGROUND: Mitochondrial dynamics (e.g. fission/fusion) play an important role in controlling chemoresistance in representative gynecologic malignancies, ovarian and cervical cancer. Processing the long form of Optic atrophy (L-Opa)1 is a distinctive character of mitochondrial fragmentation, associated with chemosensitivity. Here, we examined the role of prohibitin (Phb)1 in increasing L-Opa1 processing via the regulating mitochondrial protease, Oma1 and its direct interaction with p-p53 (ser15) and pro-apoptotic Bcl-2 antagonist/killer (Bak) 1 in the signaling axis and if this phenomenon is associated with prognosis of patients. METHODS: We compared Cisplatin (CDDP)-induced response of mitochondrial dynamics, molecular interaction among p-p53 (ser15)-Phb1-Bak, and chemoresponsiveness in paired chemosensitive and chemoresistant gynecologic cancer cells (ovarian and cervical cancer cell lines) using western blot, immunoprecipitation, sea horse, and immunofluorescence. Translational strategy with proximity ligation assessment in phb1-p-p53 (ser15) in human ovarian tumor sections further confirmed in vitro finding, associated with clinical outcome. RESULTS: We report that: (1) Knock-down of Phb1 prevents Cisplatin (cis-diamine-dichloroplatinum; CDDP) -induced changes in mitochondrial fragmentation and Oma1 mediated cleavage, and Opa1 processing; (2) In response to CDDP, Phb1 facilitates the p-p53 (ser15)-Phb1-Bak interaction in mitochondria in chemosensitive gynecologic cancer cells but not in chemoresistant cells; (3) Akt overexpression results in suppressed p-p53(Ser15)-Phb1 interaction and dysregulated mitochondrial dynamics, and (4) Consistent with in vitro findings, proximity ligation assessment (PLA) in human ovarian tumor sections demonstrated that p-p53(ser15)-Phb1-Bak interaction in mitochondria is associated with better chemoresponsiveness and clinical outcome of patients. Determining the molecular mechanisms by which Phb1 facilitates mitochondrial fragmentation and interacts with p53 may advance the current understanding of chemoresistance and pathogenesis of gynecologic cancer. CONCLUSION: Determining the key molecular mechanisms by which Phb1 facilitates the formation of p-p53 (ser15)-Bak-Phb1 and its involvement in the regulation of mitochondrial dynamics and apoptosis may ultimately contribute to the current understanding of molecular and cellular basis of chemoresistance in this gynecologic cancer.


Assuntos
Antineoplásicos , Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Dinâmica Mitocondrial , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proteína Supressora de Tumor p53/metabolismo
19.
J Ovarian Res ; 15(1): 69, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35668504

RESUMO

BACKGROUND: Dysregulation of Ectonucleoside Triphospahate Diphosphohydrolase 5 (ENTPD5) in tumors might be associated with tumor progression, while the role of ENTPD5 in the growth and metastasis of serous ovarian cancer (SOC) is still unclear. METHODS: ENTPD5 expression patterns in ovarian cancer tissues were analyzed by qRT-PCR and immunohistochemistry assay (IHC). Two SOC cell lines, SKOV3 and OVCAR8, were stably transfected with lentivirus to build knockdown and overexpression cell lines. Clone formation assay, collagen gel droplet culture technology, wound healing assay and flow cytometry were used to assess the migration and growth traits of SOC cells. Expression levels of ENTPD5, glucose regulated protein 78 (GRP78), eukaryotic translation initiation factor 2 alpha (eIF-2α), phosphorylated -eIF-2α and, C/EBP homologous protein (CHOP) in SOC cells were detected by Western blot. RESULTS: Compared to fallopian tube tissues, the expression of ENTPD5 was significantly higher in tumor tissues obtained from SOC patients, and positively correlated with clinical stage and metastasis. ENTPD5 knockdown robustly inhibited cell proliferation, migration, whereas ENTPD5 overexpression elicited the opposite effect on SOC cells. ENTPD5 knockdown arrested cell cycle in G0/G1 phase and increased apoptosis. Importantly, ENTPD5 knockdown was associated with significantly decreased protein levels for GRP78, CHOP, and p-eIF-2α, suggesting possible involvement of ENTPD5 in endoplasmic reticulum stress (ERS). CONCLUSIONS: Our study demonstrates that ENTPD5 knockdown inhibited SOC cell proliferation, migration and restrained the activation of the GRP78/p-eIF-2α/CHOP pathway, which provides a potentially effective therapeutic target for the treatment of SOC.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Apoptose , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Cistadenocarcinoma Seroso/patologia , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 2 em Eucariotos/farmacologia , Feminino , Glucose , Humanos , Proteínas Oncogênicas , Neoplasias Ovarianas/patologia , Proteína C/farmacologia , Pirofosfatases/farmacologia
20.
Obstet Gynecol ; 139(6): 1123-1129, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35675609

RESUMO

OBJECTIVE: The Affordable Care Act's (ACA) 2014 Medicaid expansion is associated with gains in insurance and early-stage diagnosis among patients with gynecologic cancer, but its association with mortality remains unknown. This study aims to assess whether the ACA's Medicaid expansion was associated with improved survival among patients with ovarian cancer. METHODS: In this retrospective cohort study of patients with newly diagnosed ovarian cancer, we compared 1-year survival before and after 2014 Medicaid expansion in patients aged 40-64 years in Medicaid expansion states (intervention group) to patients aged 40-64 years in non-Medicaid expansion states using a difference-in-difference analysis. Results were adjusted for age, comorbidities, treatment at an academic center, and variables associated with Medicaid insurance status (race, income, high-school education, distance traveled for care, and living in a rural area). RESULTS: Our sample included 19,558 patients with ovarian cancer: 9,013 in Medicaid expansion states and 10,545 in nonexpansion states. The ACA's Medicaid expansion was associated with increased 1-year survival among patients in expansion states compared with nonexpansion states (adjusted difference-in-difference 2.2%, 95% CI 0.4-4.1). After adding stage at diagnosis, the mortality difference between expansion and nonexpansion states was no longer evident. Medicaid expansion was associated with a significant improvement in 1-year survival for White patients (2.4%, 95% CI 0.4-4.4), but the difference was not significant for Black patients (1.3%, 95% CI -5.7 to 8.2) or rural patients (9.5%, 95% CI -8.0 to 26.9). CONCLUSION: The ACA's Medicaid expansion was associated with improvements in 1-year survival among patients with ovarian cancer, which was mediated by an earlier stage at diagnosis. Continued insurance expansion to nonexpansion states may improve survival and reduce disparities for patients with ovarian cancer.


Assuntos
Neoplasias Ovarianas , Patient Protection and Affordable Care Act , Feminino , Humanos , Cobertura do Seguro , Medicaid , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , Estados Unidos
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