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1.
Trials ; 25(1): 301, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38702828

RESUMO

BACKGROUND: Maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, has been shown to extend progression-free survival in patients with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy, regardless of biomarker status. However, there are limited data on niraparib's efficacy and safety in the neoadjuvant setting. The objective of Cohort C of the OPAL trial (OPAL-C) is to evaluate the efficacy, safety, and tolerability of neoadjuvant niraparib treatment compared with neoadjuvant platinum-taxane doublet chemotherapy in patients with newly diagnosed stage III/IV ovarian cancer with confirmed homologous recombination-deficient tumors. METHODS: OPAL is an ongoing global, multicenter, randomized, open-label, phase 2 trial. In OPAL-C, patients will be randomized 1:1 to receive three 21-day cycles of either neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) will then undergo interval debulking surgery; patients with stable disease may proceed to interval debulking surgery or alternative therapy at the investigator's discretion. Patients with disease progression will exit the study treatment and proceed to alternative therapy at the investigator's discretion. After interval debulking surgery, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy followed by niraparib maintenance therapy for up to 36 months. Adult patients with newly diagnosed stage III/IV ovarian cancer eligible to receive neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery may be enrolled. Patients must have tumors that are homologous recombination-deficient. The primary endpoint is the pre-interval debulking surgery unconfirmed overall response rate, defined as the investigator-assessed percentage of patients with unconfirmed complete or partial response on study treatment before interval debulking surgery per RECIST v1.1. DISCUSSION: OPAL-C explores the use of niraparib in the neoadjuvant setting as an alternative to neoadjuvant platinum-taxane doublet chemotherapy to improve postsurgical residual disease outcomes for patients with ovarian cancer with homologous recombination-deficient tumors. Positive findings from this approach could significantly impact preoperative ovarian cancer therapy, particularly for patients who are ineligible for primary debulking surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03574779. Registered on February 28, 2022.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Indazóis , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas , Piperidinas , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Terapia Neoadjuvante/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Piperidinas/efeitos adversos , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Indazóis/efeitos adversos , Indazóis/uso terapêutico , Indazóis/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervalo Livre de Progressão , Ensaios Clínicos Fase II como Assunto , Recombinação Homóloga , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Piperazinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Fatores de Tempo
2.
BMC Womens Health ; 24(1): 274, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704534

RESUMO

BACKGROUND: Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases. CASE PRESENTATION: In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml. CONCLUSIONS: GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias Ovarianas , Humanos , Feminino , Adulto , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/diagnóstico , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/diagnóstico , Assistência Perioperatória/métodos , Cistos Ovarianos/cirurgia , Cistos Ovarianos/complicações , Cistos Ovarianos/diagnóstico , Estadiamento de Neoplasias
3.
J Med Case Rep ; 18(1): 232, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704586

RESUMO

BACKGROUND: Mature cystic teratoma co-existing with a mucinous cystadenocarcinoma is a rare tumor that few cases have been reported until now. In these cases, either a benign teratoma is malignantly transformed into adenocarcinoma or a collision tumor is formed between a mature cystic teratoma and a mucinous tumor, which is either primarily originated from epithelial-stromal surface of the ovary, or secondary to a primary gastrointestinal tract tumor. The significance of individualizing the two tumors has a remarkable effect on further therapeutic management. CASE PRESENTATION: In this case, a mature cystic teratoma is co-existed with a mucinous cystadenocarcinoma in the same ovary in a 33-year-old Iranian female. Computed Tomography (CT) Scan with additional contrast of the left ovarian mass suggested a teratoma, whereas examination of resected ovarian mass reported an adenocarcinoma with a cystic teratoma. A dermoid cyst with another multi-septate cystic lesion including mucoid material was revealed in the gross examination of the surgical specimen. Histopathological examination revealed a mature cystic teratoma in association with a well-differentiated mucinous cystadenocarcinoma. The latter showed a CK7-/CK20 + immune profile. Due to the lack of clinical, radiological, and biochemical discoveries attributed to a primary lower gastrointestinal tract tumor, the immune profile proposed the chance of adenocarcinomatous transformation of a benign teratoma. CONCLUSIONS: This case shows the significance of large sampling, precise recording of the gross aspects, histopathological examination, immunohistochemical analysis, and the help of radiological and clinical results to correctly diagnose uncommon tumors.


Assuntos
Cistadenocarcinoma Mucinoso , Neoplasias Ovarianas , Teratoma , Tomografia Computadorizada por Raios X , Humanos , Feminino , Teratoma/patologia , Teratoma/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/complicações , Teratoma/diagnóstico , Adulto , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Cistadenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Mucinoso/cirurgia , Cistadenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Mucinoso/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/cirurgia
4.
BMJ Case Rep ; 17(5)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724214

RESUMO

This abstract describes a case of the growth of a serous borderline tumour recurrence and cyst to papillary projection ratio with associated ultrasound images. The aetiology, presentation and management of such cases are explored and compared to the literature.


Assuntos
Recidiva Local de Neoplasia , Humanos , Recidiva Local de Neoplasia/patologia , Feminino , Ultrassonografia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico , Pessoa de Meia-Idade
5.
Technol Cancer Res Treat ; 23: 15330338241252423, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38752261

RESUMO

OBJECTIVES: Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear. METHODS: Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1. RESULTS: Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells. CONCLUSIONS: In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC.


Assuntos
Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Neoplasias Ovarianas , RNA Circular , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Humanos , Feminino , MicroRNAs/genética , RNA Circular/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Prognóstico , Camundongos , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética
6.
Cancer Control ; 31: 10732748241256819, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38755968

RESUMO

Ovarian cancer (OC) is the most lethal gynecological tumor, characterized by its insidious and frequently recurring metastatic progression. Owing to limited early screening methods, over 70% of OC cases are diagnosed at advanced stages, typically stage III or IV. Recently, N6-methyladenosine (m6A) modification has emerged as a hotspot of epigenetic research, representing a significant endogenous RNA modification in higher eukaryotes. Numerous studies have reported that m6A-related regulatory factors play pivotal roles in tumor development through diverse mechanisms. Moreover, recent studies have indicated the aberrant expression of multiple regulatory factors in OC. Therefore, this paper comprehensively reviews research advancements concerning m6A in OC, aiming to elucidate the regulatory mechanism of m6A-associated regulators on pivotal aspects, such as proliferation, invasion, metastasis, and drug resistance, in OC. Furthermore, it discusses the potential of m6A-associated regulators as early diagnostic markers and therapeutic targets, thus contributing to the diagnosis and treatment of OC.


Ovarian cancer (OC) presents a formidable challenge in the medical field, often detected at advanced stages, necessitating urgent exploration of diagnostic and therapeutic avenues. This review delves into the intricate role of N6-methyladenosine (m6A) RNA modification in OC, a dynamic epigenetic process increasingly recognized for its regulatory role in cancer biology. Highlighting recent advancements, the review sheds light on how m6A-related factors influence crucial aspects of OC progression, including tumor growth, metastasis, and resistance to treatment. Specifically, m6A methyltransferases, binding proteins, and demethylases exert multifaceted effects on OC progression, influencing the expression of pivotal oncogenes and tumor suppressors. While promising, translating these insights into effective therapies requires further investigation. By comprehensively understanding the influence of m6A on OC, there lies hope for developing improved diagnostic techniques and novel treatment strategies to combat this complex disease.


Assuntos
Adenosina , Neoplasias Ovarianas , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética
7.
Int J Oncol ; 64(6)2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38757340

RESUMO

Ovarian cancer (OC) represents the most prevalent malignancy of the female reproductive system. Its distinguishing features include a high aggressiveness, substantial morbidity and mortality, and a lack of apparent symptoms, which collectively pose significant challenges for early detection. Given that aberrant DNA methylation events leading to altered gene expression are characteristic of numerous tumor types, there has been extensive research into epigenetic mechanisms, particularly DNA methylation, in human cancers. In the context of OC, DNA methylation is often associated with the regulation of critical genes, such as BRCA1/2 and Ras­association domain family 1A. Methylation modifications within the promoter regions of these genes not only contribute to the pathogenesis of OC, but also induce medication resistance and influence the prognosis of patients with OC. As such, a more in­depth understanding of DNA methylation underpinning carcinogenesis could potentially facilitate the development of more effective therapeutic approaches for this intricate disease. The present review focuses on classical tumor suppressor genes, oncogenes, signaling pathways and associated microRNAs in an aim to elucidate the influence of DNA methylation on the development and progression of OC. The advantages and limitations of employing DNA methylation in the diagnosis, treatment and prevention of OC are also discussed. On the whole, the present literature review indicates that the DNA methylation of specific genes could potentially serve as a prognostic biomarker for OC and a therapeutic target for personalized treatment strategies. Further investigations in this field may yield more efficacious diagnostic and therapeutic alternatives for patients with OC.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Epigênese Genética , Prognóstico , MicroRNAs/genética , Transdução de Sinais/genética , Regiões Promotoras Genéticas
8.
Nat Commun ; 15(1): 4253, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762636

RESUMO

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.


Assuntos
Cistadenocarcinoma Seroso , Aprendizado Profundo , Neoplasias Ovarianas , Platina , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/genética , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/genética , Platina/uso terapêutico , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Resultado do Tratamento , Gradação de Tumores , Estudos de Coortes , Adulto , Reprodutibilidade dos Testes
9.
Ter Arkh ; 96(3): 266-272, 2024 Apr 16.
Artigo em Russo | MEDLINE | ID: mdl-38713042

RESUMO

AIM: To investigate the antitumor effects of human placenta hydrolysate (HPH) peptides on three hormone-dependent human cell lines: prostate adenocarcinoma, breast carcinoma, and ovarian cancer by metabolic analysis of cell cultures. MATERIALS AND METHODS: The effect of HPH on tumor and control tumor cell lines was evaluated. Study stages: (A) de novo peptide sequencing by collision-induced dissociation mass spectrometry; (B) detection of peptides with anti-tumor properties; (C) expert analysis of the obtained lists of peptides. RESULTS: Dose-dependent cytotoxic effects of HPH on three tumor cell lines are shown: PC-3 (human prostate adenocarcinomas), OAW-42 (human ovarian cancer), BT-474 (human breast carcinomas), and IC50 constants (1.3-2.8 mg/ml) were obtained. The analysis of the HPH peptide fraction showed more than 70 peptides with antitumor properties in the composition of this HPH, including kinase inhibitors: mitogen-activated protein kinases, kappa-bi nuclear factor inhibitor kinase, AKT serine/threonine kinase 1, protein kinase C zeta, interleukin-1 receptor-associated kinase 4 and cyclin-dependent kinase 1. CONCLUSION: The results of the study indicate not only the oncological safety of the HPH used in therapy but also the mild antitumor effects of this HPH at high concentrations.


Assuntos
Neoplasias da Mama , Placenta , Neoplasias da Próstata , Humanos , Feminino , Placenta/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Gravidez , Neoplasias da Próstata/tratamento farmacológico , Masculino , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Células PC-3 , Hidrolisados de Proteína/farmacologia , Relação Dose-Resposta a Droga
10.
BMC Cancer ; 24(1): 565, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711015

RESUMO

BACKGROUND: Recent studies showed heterogeneity in stage IVB patients. However, few studies focused on the prognosis of supraclavicular metastatic ovarian cancer. This study aimed to explore the prognostic factors and the role of primary debulking in IVB ovarian cancer patients with supraclavicular lymph node metastasis. METHODS: We retrospectively analyzed patients newly diagnosed as primary epithelial ovarian cancer with supraclavicular lymph node metastasis from January 2015 to July 2020. Supraclavicular lymph node metastasis was defined as either the pathological diagnosis by supraclavicular lymph node biopsy, or the radiological diagnosis by positron emission tomography-computed tomography (PET-CT). RESULTS: In 51 patients, 37 was diagnosed with metastatic supraclavicular lymph nodes by histology, 46 by PET-CT, and 32 by both methods. Forty-four (86.3%) with simultaneous metastatic paraaortic lymph nodes (PALNs) by imaging before surgery or neoadjuvant chemotherapy were defined as "continuous-metastasis type", while the other 7 (13.7%) defined as "skip-metastasis type". Nineteen patients were confirmed with metastatic PALNs by histology. Thirty-four patients were investigated for BRCA mutation, 17 had germline or somatic BRCA1/2 mutations (g/sBRCAm). With a median follow-up of 30.0 months (6.3-63.4 m), 16 patients (31.4%) died. The median PFS and OS of the cohort were 17.3 and 48.9 months. Survival analysis showed that "continuous-metastasis type" had longer OS and PFS than "skip-metastasis type" (OS: 50.0/26.6 months, PFS: 18.5/7.2months, p=0.005/0.002). BRCA mutation carriers also had longer OS and PFS than noncarriers (OS: 57.4 /38.5 m, p=0.031; PFS: 23.6/15.2m, p=0.005). Multivariate analysis revealed only metastatic PALNs was independent prognostic factor for OS (p=0.040). Among "continuous-metastasis type" patients, 22 (50.0%) achieved R0 abdominopelvic debulking, who had significantly longer OS (55.3/42.3 months, p =0.034) than those with residual abdominopelvic tumors. CONCLUSIONS: In stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as "continuous-metastasis type" with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/mortalidade , Procedimentos Cirúrgicos de Citorredução/métodos , Adulto , Idoso , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/mortalidade , Linfonodos/patologia , Linfonodos/cirurgia , China/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Proteína BRCA1/genética , População do Leste Asiático
12.
J Ovarian Res ; 17(1): 96, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720349

RESUMO

OBJECTIVE: To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients. METHODS: Patients with BOTs younger than 20 years who underwent FSS were included in this study. RESULTS: A total of 34 patients were included, with a median patient age of 17 (range, 3-19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8-40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10-148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%. CONCLUSIONS: Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.


Assuntos
Preservação da Fertilidade , Neoplasias Ovarianas , Humanos , Feminino , Adolescente , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Preservação da Fertilidade/métodos , Criança , Estudos Retrospectivos , Adulto Jovem , Pré-Escolar , Resultado do Tratamento , Tratamentos com Preservação do Órgão/métodos , Recidiva Local de Neoplasia
13.
Sci Rep ; 14(1): 10427, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714753

RESUMO

This study aimed to synchronously determine epitranscriptome-wide RNA N6-methyladenosine (m6A) modifications and mRNA expression profile in high grade serous ovarian cancer (HGSOC). The methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to comprehensively examine the m6A modification profile and the RNA-sequencing (RNA-seq) was performed to analyze the mRNA expression profile in HGSOC and normal fallopian tube (FT) tissues. Go and KEGG analyses were carried out in the enrichment of those differentially methylated and expressed genes. MeRIP-seq data showed 53,794 m6A methylated peaks related to 19,938 genes in the HGSOC group and 51,818 m6A peaks representing 19,681 genes in the FT group. RNA-seq results revealed 2321 upregulated and 2486 downregulated genes in HGSOC. Conjoint analysis of MeRIP-seq and RNA-seq data identified differentially expressed genes in which 659 were hypermethylated (330 up- and 329 down-regulated) and 897 were hypomethylated (475 up- and 422 down-regulated). Functional enrichment analysis indicated that these differentially modulated genes are involved in pathways related to cancer development. Among methylation regulators, the m6A eraser (FTO) expression was significantly lower, but the m6A readers (IGF2BP2 and IGF2BP3) were higher in HGSOC, which was validated by the subsequent real-time PCR assay. Exploration through public databases further corroborated their possible clinical application of certain methylation regulators and differentially expressed genes. For the first time, our study screens the epitranscriptome-wide m6A modification and expression profiles of their modulated genes and signaling pathways in HGSOC. Our findings provide an alternative direction in exploring the molecular mechanisms of ovarian pathogenesis and potential biomarkers in the diagnosis and predicting the prognosis of the disease.


Assuntos
Adenosina , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , RNA Mensageiro , Humanos , Feminino , Adenosina/análogos & derivados , Adenosina/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Projetos Piloto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/metabolismo , Gradação de Tumores , Pessoa de Meia-Idade , Transcriptoma , Metilação de DNA
14.
South Med J ; 117(5): 266-271, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701848

RESUMO

OBJECTIVES: The aims of this study were to describe the baseline estimated blood loss (EBL) in surgery and transfusion rate in patients undergoing cytoreductive surgeries for ovarian malignancy, and identify perioperative variables associated with blood loss and transfusion. METHODS: A retrospective cohort study at a single institution was performed that included patients with known or suspected ovarian malignancy undergoing cytoreductive surgery between 2016 and 2021. t tests, χ2 tests, and multiple logistic regression analyses were used. RESULTS: Among 44 patients meeting inclusion criteria, 61% received perioperative blood transfusion. There were significant differences in EBL and preoperative hemoglobin levels between patients who did and did not receive transfusion (EBL 442.6 vs 236.8 mL, P = 0.0008; preoperative hemoglobin 10.2 vs 11.2 g/dL, P = 0.049). After adjusting for preoperative hemoglobin, the risk of transfusion increased for each additional 200 mL of EBL (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.5-9.5). Stratified by race, the association between EBL and transfusion risk remained statistically significant only for non-Latinx White patients (OR 6.1, 95% CI 1.7-21.9), who made up 77% of the study population, but not for patients of other races and ethnicities (OR 1.0, 95% CI 0.16-6.42). CONCLUSIONS: Perioperative blood transfusion is common in patients undergoing cytoreductive surgery. In this study, EBL and preoperative hemoglobin levels were significantly associated with transfusion receipt. Clinicians should optimize hemoglobin levels and intraoperative blood conservation strategies to reduce the need for transfusion. The results also highlight the importance of considering racial and ethnic differences when developing strategies to reduce transfusion risk.


Assuntos
Perda Sanguínea Cirúrgica , Transfusão de Sangue , Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Humanos , Feminino , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Estudos Retrospectivos , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/sangue , Transfusão de Sangue/estatística & dados numéricos , Pessoa de Meia-Idade , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Perda Sanguínea Cirúrgica/prevenção & controle , Idoso , Adulto , Hemoglobinas/análise , Fatores de Risco
15.
Technol Cancer Res Treat ; 23: 15330338241249692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706262

RESUMO

PURPOSE: PIWI-interacting RNAs (piRNAs) are a type of noncoding small RNA that can interact with PIWI-like RNA-mediated gene silencing (PIWIL) proteins to affect biological processes such as transposon silencing through epigenetic effects. Recent studies have found that piRNAs are widely dysregulated in tumors and associated with tumor progression and a poor prognosis. Therefore, this study aimed to investigate the effect of piR-1919609 on the proliferation, apoptosis, and drug resistance of ovarian cancer cells. METHODS: In this study, we used small RNA sequencing to screen and identify differentially expressed piRNAs in primary ovarian cancer, recurrent ovarian cancer, and normal ovaries. A large-scale verification study was performed to verify the expression of piR-1919609 in different types of ovarian tissue, including ovarian cancer tissue and normal ovaries, by RT-PCR and to analyze its association with the clinical prognosis of ovarian cancer. The expression of PIWILs in ovarian cancer was verified by RT-PCR, Western blotting and immunofluorescence. The effects of piR-1919609 on ovarian cancer cell proliferation, apoptosis and drug resistance were studied through in vitro and in vivo models. RESULTS: (1) piR-1919609 was highly expressed in platinum-resistant ovarian cancer tissues (p < 0.05), and this upregulation was significantly associated with a poor prognosis and a shorter recurrence time in ovarian cancer patients (p < 0.05). (2) PIWIL2 was strongly expressed in ovarian cancer tissues (p < 0.05). It was expressed both in the cytoplasm and nucleus of ovarian cancer cells. (3) Overexpression of piR-1919609 promoted ovarian cancer cell proliferation, inhibited apoptosis, and promoted tumor growth in nude mice. (4) Inhibition of piR-1919609 effectively reversed ovarian cancer drug resistance. CONCLUSION: In summary, we showed that piR-1919609 is involved in the regulation of drug resistance in ovarian cancer cells and might be an ideal potential target for reversing platinum resistance in ovarian cancer.


Assuntos
Apoptose , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , RNA Interferente Pequeno , Ensaios Antitumorais Modelo de Xenoenxerto , Feminino , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , RNA Interferente Pequeno/genética , Prognóstico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Modelos Animais de Doenças , Platina/uso terapêutico , Platina/farmacologia
16.
BMC Cancer ; 24(1): 551, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693472

RESUMO

OBJECTIVE: We aimed to screen novel gene signatures for ovarian cancer (OC) and explore the role of biomarkers in OC via regulating pyroptosis using bioinformatics analysis. METHODS: Differentially expressed genes (DEGs) of OC were screened from GSE12470 and GSE16709 datasets. Hub genes were determined from protein-protein interaction networks after bioinformatics analysis. The role of Centromeric protein M (CENPM) in OC was assessed by subcutaneous tumor experiment using hematoxylin-eosin and immunohistochemical staining. Tumor metastasis was evaluated by detecting epithelial-mesenchymal transition-related proteins. The proliferation, migration, and invasion were determined using cell counting kit and transwell assay. Enzyme-linked immunosorbent assay was applied to measure inflammatory factors. The mRNA and protein expression were detected using real-time quantitative PCR and western blot. RESULTS: We determined 9 hub genes (KIFC1, PCLAF, CDCA5, KNTC1, MCM3, OIP5, CENPM, KIF15, and ASF1B) with high prediction value for OC. In SKOV3 and A2780 cells, the expression levels of hub genes were significantly up-regulated, compared with normal ovarian cells. CENPM was selected as a key gene. Knockdown of CENPM suppressed proliferation, migration, and invasion of OC cells. Subcutaneous tumor experiment revealed that CENPM knockdown significantly suppressed tumor growth and metastasis. Additionally, pyroptosis was promoted in OC cells and xenograft tumors after CENPM knockdown. Furthermore, CENPM knockdown activated cGAS-STING pathway and the pathway inhibitor reversed the inhibitory effect of CENPM knockdown on viability, migration, and invasion of OC cells. CONCLUSION: CENPM was a novel biomarker of OC, and knockdown of CENPM inhibited OC progression by promoting pyroptosis and activating cGAS-STING pathway.


Assuntos
Proteínas de Membrana , Nucleotidiltransferases , Neoplasias Ovarianas , Piroptose , Transdução de Sinais , Humanos , Feminino , Piroptose/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Animais , Camundongos , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Movimento Celular/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus
17.
Cell Death Dis ; 15(5): 314, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702325

RESUMO

Ovarian cancer is one of the common tumors of the female reproductive organs. It has a high mortality rate, is highly heterogeneous, and early detection and primary prevention are very complex. Autophagy is a cellular process in which cytoplasmic substrates are targeted for degradation in lysosomes through membrane structures called autophagosomes. The periodic elimination of damaged, aged, and redundant cellular molecules or organelles through the sequential translation between amino acids and proteins by two biological processes, protein synthesis, and autophagic protein degradation, helps maintain cellular homeostasis. A growing number of studies have found that autophagy plays a key regulatory role in ovarian cancer. Interestingly, microRNAs regulate gene expression at the posttranscriptional level and thus can regulate the development and progression of ovarian cancer through the regulation of autophagy in ovarian cancer. Certain miRNAs have recently emerged as important regulators of autophagy-related gene expression in cancer cells. Moreover, miRNA analysis studies have now identified a sea of aberrantly expressed miRNAs in ovarian cancer tissues that can affect autophagy in ovarian cancer cells. In addition, miRNAs in plasma and stromal cells in tumor patients can affect the expression of autophagy-related genes and can be used as biomarkers of ovarian cancer progression. This review focuses on the potential significance of miRNA-regulated autophagy in the diagnosis and treatment of ovarian cancer.


Assuntos
Autofagia , MicroRNAs , Neoplasias Ovarianas , Humanos , Autofagia/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Regulação Neoplásica da Expressão Gênica , Animais , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética
18.
Int J Biol Sci ; 20(7): 2454-2475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725854

RESUMO

The emergence of Poly (ADP-ribose) polymerase inhibitors (PARPi) has marked the beginning of a precise targeted therapy era for ovarian cancer. However, an increasing number of patients are experiencing primary or acquired resistance to PARPi, severely limiting its clinical application. Deciphering the underlying mechanisms of PARPi resistance and discovering new therapeutic targets is an urgent and critical issue to address. In this study, we observed a close correlation between glycolysis, tumor angiogenesis, and PARPi resistance in ovarian cancer. Furthermore, we discovered that the natural compound Paris saponin VII (PS VII) partially reversed PARPi resistance in ovarian cancer and demonstrated synergistic therapeutic effects when combined with PARPi. Additionally, we found that PS VII potentially hindered glycolysis and angiogenesis in PARPi-resistant ovarian cancer cells by binding and stabilizing the expression of RORα, thus further inhibiting ECM1 and interfering with the VEGFR2/FAK/AKT/GSK3ß signaling pathway. Our research provides new targeted treatment for clinical ovarian cancer therapy and brings new hope to patients with PARPi-resistant ovarian cancer, effectively expanding the application of PARPi in clinical treatment.


Assuntos
Diosgenina/análogos & derivados , Glicólise , Neovascularização Patológica , Neoplasias Ovarianas , Saponinas , Transdução de Sinais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Linhagem Celular Tumoral , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Animais , Camundongos Nus , Camundongos , Angiogênese
19.
Int J Mol Sci ; 25(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732044

RESUMO

High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and hub-gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that PRKDC gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of PRKDC, has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of PRKDC in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. PRKDC and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC.


Assuntos
Aneuploidia , Cromossomos Humanos Par 8 , Variações do Número de Cópias de DNA , Progressão da Doença , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Cromossomos Humanos Par 8/genética , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Regulação Neoplásica da Expressão Gênica , Hibridização in Situ Fluorescente
20.
Sci Rep ; 14(1): 11048, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745057

RESUMO

Information about cell composition in tissue samples is crucial for biomarker discovery and prognosis. Specifically, cancer tissue samples present challenges in deconvolution studies due to mutations and genetic rearrangements. Here, we optimized a robust, DNA methylation-based protocol, to be used for deconvolution of ovarian cancer samples. We compared several state-of-the-art methods (HEpiDISH, MethylCIBERSORT and ARIC) and validated the proposed protocol in an in-silico mixture and in an external dataset containing samples from ovarian cancer patients and controls. The deconvolution protocol we eventually implemented is based on MethylCIBERSORT. Comparing deconvolution methods, we paid close attention to the role of a reference panel. We postulate that a possibly high number of samples (in our case: 247) should be used when building a reference panel to ensure robustness and to compensate for biological and technical variation between samples. Subsequently, we tested the performance of the validated protocol in our own study cohort, consisting of 72 patients with malignant and benign ovarian disease as well as in five external cohorts. In conclusion, we refined and validated a reference-based algorithm to determine cell type composition of ovarian cancer tissue samples to be used in cancer biology studies in larger cohorts.


Assuntos
Algoritmos , Metilação de DNA , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Biomarcadores Tumorais/genética
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