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1.
Anticancer Res ; 41(9): 4483-4488, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475073

RESUMO

BACKGROUND: Perivascular epithelioid cell tumors (PEComa)s are mesenchymal neoplasms located at various anatomic sites, which usually express both melanocytic and myogenic markers. CASE REPORT: A 60-year-old woman underwent laparotomy for a huge, heterogeneous, right ovarian mass. The histological examination of the surgical specimen revealed a neoplasm consisting of both cells with clear or eosinophilic cytoplasm and spindle cells in a myxoid stroma. Immunostaining was positive for human melanoma black-45, h-caldesmon, desmin, actin, and transcription factor 3. Cell atypias were moderate, mitoses were 4/10 high power fields (HPF) and margins were focally infiltrative. These findings pointed to a diagnosis of ovarian PEComa. Twenty-five months later, two subcutaneous lesions were surgically removed on the left trapezius muscle and the median subumbilical area, respectively. The former was a desmoid fibromatosis, whereas the latter was a recurrence of PEComa with greater nuclear pleomorphism and higher number of mitoses (26/50 HPF) compared to the primary tumor. The patient was free of disease 11 months later. CONCLUSION: A long-term follow-up of gynecological PEComas is strongly recommended.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias de Células Epitelioides Perivasculares/metabolismo , Neoplasias de Células Epitelioides Perivasculares/patologia , Resultado do Tratamento
2.
Anticancer Res ; 41(9): 4587-4601, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475087

RESUMO

BACKGROUND/AIM: Ovarian endometrioid carcinoma (EC) and high-grade serous carcinoma (HGSC) may exhibit various growth patterns and mimic mesonephric-like adenocarcinoma (MLA). We investigated the clinicopathological and molecular features of ovarian carcinomas with mesonephric-like differentiation (MLD). PATIENTS AND METHODS: We analyzed the electronic medical records and pathology slides of two EC-MLD and three HGSC-MLD patients, and conducted immunostaining and targeted sequencing of their samples. RESULTS: All cases showed architectural diversity, compactly aggregated small tubules and ducts, and eosinophilic intraluminal secretions, indicating the possibility of an ovarian MLA. However, the following histological and immunophenotypical features confirmed the diagnoses of EC-MLD and HGSC-MLD: squamous, tubal, and sertoliform differentiation; serous tubal intraepithelial carcinoma; solid, endometrioid, transitional (SET) feature; solid, transitional, endometrioid, mucinous-like (STEM) feature; diffuse expression of hormone receptors and Wilms tumor 1; mutant p53 immunostaining pattern; and wild-type v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene. CONCLUSION: A subset of ovarian ECs and HGSCs can display MLD and mimic an MLA. A thorough histological examination combined with ancillary tests is crucial to differentiate between these ovarian neoplastic entities.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/patologia , Ductos Mesonéfricos/patologia , Adulto , Carcinoma Endometrioide/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Diagnóstico Diferencial , Registros Eletrônicos de Saúde , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Estudos Retrospectivos , Proteína Supressora de Tumor p53/metabolismo , Proteínas WT1/metabolismo , Ductos Mesonéfricos/metabolismo
3.
Medicina (B Aires) ; 81(4): 565-573, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34453798

RESUMO

Ovarian cancer represents the third gynecological cancer in frequency in Argentina. There is a lack of information on this pathology in our country regarding the treatment and evolution of patients who suffer it. The aim of this study was to evaluate the perioperative and oncological results in patients with advanced epithelial ovarian tumor. We present a retrospective cohort in which we evaluated disease-free survival and overall survival in patients with epithelial ovarian tumor treated at the Hospital Italiano de Buenos Aires between June 2009 and June 2017. Of 170 patients included in the study, 72 (42.4%) received primary debulking surgery (CCP), while 98 (57.6%) received neoadjuvant therapy and interval surgery (CI). The optimal cyto-reduction rate was 75% and 79% respectively. No differences were found in perioperative outcomes, or in severe complications between the two groups. The median disease-free survival in the CCP group was 2.5 years (95% CI 1.6-3.1) while in the CI group it was 1.4 (95% CI 1.2-1.7) p < 0.001. The median overall survival was 5.8 years in CPP, and 3.5 years in CI. Faced with a meticulous selection by a group of experts, patients with advanced ovarian cancer treated with CCP present better oncological results than those who received neoadjuvant therapy and CI.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Feminino , Hospitais , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , Resultado do Tratamento
4.
Medicine (Baltimore) ; 100(32): e26849, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397893

RESUMO

ABSTRACT: This study aimed to investigate the effect of molecular targeted agents (MTAs) in chemo on platinum-resistant recurrent ovarian cancer (ROC). We performed this meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements. Randomized controlled trials reporting data about platinum-resistant ovarian cancer treated by MTAs were included. The endpoints for the present study included overall survival and progression-free survival. We analyzed 9 randomized controlled trials including 3631 patients with ROC. The pooled analysis indicated that a combination of MTAs with chemo could markedly increase objective response rate in those patients (P = .012). Nevertheless, the survival rate of those patients was not markedly changed (P = .19). Besides, the combination of MTAs with chemo dramatically aggravated the occurrence of adverse events (P < .05). Moreover, it resulted in the termination of treatment (P = .044) in those patients, but it had no effect on fatal adverse events (P = .16). Our results indicated that the combination of MTAs with chemo notably improved objective response rate in patients with platinum-resistant ROC, but its benefit did not translate into survival benefits.


Assuntos
Antineoplásicos , Terapia de Alvo Molecular/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas , Antineoplásicos/classificação , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Análise de Sobrevida
5.
Medicine (Baltimore) ; 100(32): e26895, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397915

RESUMO

ABSTRACT: There is a similarity of histological features and survival between ovarian mucinous carcinoma (MC) with expansile invasion and ovarian mucinous borderline tumor (MBT). The aim of this study was to compare the clinical outcomes of MC with expansile invasion with those of MBT based on the 2020 World Health Organization (WHO) criteria.A pathological review was performed on patients with MC, ovarian MBT, and seromucinous borderline tumors that underwent surgery at our hospital between 1984 and 2019. Clinicopathological features were compared retrospectively between MC with expansile invasion and MBT.Among 83 cases of MC, 85 cases of MBT, and 12 cases of seromucinous borderline tumor, 25 MC cases with expansile invasion and 98 MBT cases were included through review. MC cases with expansile invasion were diagnosed with advanced International Federation of Gynecology and Obstetrics (FIGO) stages more frequently (P = .02) than that of MBT cases. In addition, patients with MC with expansile invasion received adjuvant chemotherapy more often (P < .01) than that of patients with MBT. There were no statistically significant differences in recurrence rate (P = .10) between MC with expansile invasion and MBT. Progression-free survival (PFS) was worse in MC cases with expansile invasion than that in MBT cases (P = .01). However, a multivariate analysis for PFS showed that histological subtype, FIGO stage, and adjuvant chemotherapy were not an independent prognostic factor.The prognostic outcome of MC with expansile invasion might mimic those of MBT. These results showed ovarian borderline tumor treatment could be applied to MC treatment.


Assuntos
Adenocarcinoma Mucinoso/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Biópsia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
6.
Molecules ; 26(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361832

RESUMO

In recent times, researchers have aimed for new strategies to combat cancer by the implementation of nanotechnologies in biomedical applications. This work focuses on developing protein-based nanoparticles loaded with a newly synthesized NIR emitting and absorbing phthalocyanine dye, with photodynamic and photothermal properties. More precisely, we synthesized highly reproducible bovine serum albumin-based nanoparticles (75% particle yield) through a two-step protocol and successfully encapsulated the NIR active photosensitizer agent, achieving a good loading efficiency of 91%. Making use of molecular docking simulations, we confirm that the NIR photosensitizer is well protected within the nanoparticles, docked in site I of the albumin molecule. Encouraging results were obtained for our nanoparticles towards biomedical use, thanks to their negatively charged surface (-13.6 ± 0.5 mV) and hydrodynamic diameter (25.06 ± 0.62 nm), favorable for benefitting from the enhanced permeability and retention effect; moreover, the MTT viability assay upholds the good biocompatibility of our NIR active nanoparticles. Finally, upon irradiation with an NIR 785 nm laser, the dual phototherapeutic effect of our NIR fluorescent nanoparticles was highlighted by their excellent light-to-heat conversion performance (photothermal conversion efficiency 20%) and good photothermal and size stability, supporting their further implementation as fluorescent therapeutic agents in biomedical applications.


Assuntos
Indóis/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Soroalbumina Bovina/química , Proliferação de Células , Feminino , Humanos , Indóis/química , Luz , Simulação de Acoplamento Molecular , Nanopartículas/química , Neoplasias Ovarianas/patologia , Fármacos Fotossensibilizantes/química , Espectroscopia de Luz Próxima ao Infravermelho , Células Tumorais Cultivadas
7.
Medicine (Baltimore) ; 100(28): e26574, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260536

RESUMO

BACKGROUND: Ovarian cancer is one of the lethal gynecological diseases in women. However, using tumor microenvironment related genes to identify prognostic signature of ovarian cancer has not been discussed in detail. METHODS: The mRNA profiles of 386 ovarian cancer patients were retrieved from The Cancer Genome Atlas. Univariate Cox regression and LASSO Cox regression analyses were performed and 14 optimized prognostic genes related to tumor microenvironment were identified. RESULTS: The multivariate Cox hazards regression showed risk score was an independent prognostic signature for ovarian cancer. Nomogram model could reliably predict the patients' survival. Furthermore, M1 macrophages, M2 macrophages, and follicular helper T cells, differentially expressed between the high- and low-risk groups, were found to be associated with the risk score. CONCLUSION: CTL-associated antigen 4 (CTLA4) and indoleamine 2,3-Dioxygenase 1 (IDO1), which were previously shown to be important immune checkpoints, probably contribute to the immunosuppressive microenvironment aberration. This study may shed light on the prognosis of ovarian cancer.


Assuntos
Neoplasias Ovarianas/genética , Microambiente Tumoral/fisiologia , Fatores Etários , Idoso , Biomarcadores Tumorais , Antígeno CTLA-4/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nomogramas , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Células T Auxiliares Foliculares/metabolismo , Macrófagos Associados a Tumor/metabolismo
8.
Int J Mol Sci ; 22(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207568

RESUMO

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins' presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.


Assuntos
Proteína Tirosina Quinase CSK/biossíntese , Proteínas Correpressoras/biossíntese , Receptor alfa de Estrogênio/biossíntese , Receptor beta de Estrogênio/biossíntese , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Neoplasias Ovarianas/metabolismo , Fatores de Transcrição/biossíntese , Adulto , Idoso , Proteína Tirosina Quinase CSK/genética , Proteínas Correpressoras/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fatores de Transcrição/genética
9.
J Fam Pract ; 70(3): 147-149, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34314340
10.
Nat Commun ; 12(1): 4230, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244494

RESUMO

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXß2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXß2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXß2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXß2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.


Assuntos
Processamento Alternativo , Carcinoma Epitelial do Ovário/genética , Proteínas da Matriz Extracelular/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas da Matriz Extracelular/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Integrina alfaXbeta2/genética , Integrina alfaXbeta2/metabolismo , Estimativa de Kaplan-Meier , Camundongos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Ovário/patologia , Ovário/cirurgia , Fosforilação/genética , Prognóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA-Seq , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Molecules ; 26(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199287

RESUMO

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Peptídeos Cíclicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Peptídeos Cíclicos/administração & dosagem
12.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199929

RESUMO

BMI-1 is a key component of stem cells, which are essential for normal organ development and cell phenotype maintenance. BMI-1 expression is deregulated in cancer, resulting in the alteration of chromatin and gene transcription repression. The cellular signaling pathway that governs BMI-1 action in the ovarian carcinogenesis sequences is incompletely deciphered. In this study, we set out to analyze the immunohistochemical (IHC) BMI-1 expression in two different groups: endometriosis-related ovarian carcinoma (EOC) and non-endometriotic ovarian carcinoma (NEOC), aiming to identify the differences in its tissue profile. METHODS: BMI-1 IHC expression has been individually quantified in epithelial and in stromal components by using adapted scores systems. Statistical analysis was performed to analyze the relationship between BMI-1 epithelial and stromal profile in each group and between groups and its correlation with classical clinicopathological characteristics. RESULTS: BMI-1 expression in epithelial tumor cells was mostly low or negative in the EOC group, and predominantly positive in the NEOC group. Moreover, the stromal BMI-1 expression was variable in the EOC group, whereas in the NEOC group, stromal BMI-1 expression was mainly strong. We noted statistically significant differences between the epithelial and stromal BMI-1 profiles in each group and between the two ovarian carcinoma (OC) groups. CONCLUSIONS: Our study provides solid evidence for a different BMI-1 expression in EOC and NEOC, corresponding to the differences in their etiopathogeny. The reported differences in the BMI-1 expression of EOC and NEOC need to be further validated in a larger and homogenous cohort of study.


Assuntos
Endometriose/fisiopatologia , Endométrio/fisiopatologia , Células Epiteliais/patologia , Neoplasias Ovarianas/patologia , Complexo Repressor Polycomb 1/metabolismo , Células Estromais/patologia , Índice de Massa Corporal , Estudos de Casos e Controles , Células Epiteliais/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/metabolismo , Células Estromais/metabolismo
13.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199930

RESUMO

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.


Assuntos
Neoplasias do Endométrio/epidemiologia , Endometriose/epidemiologia , Endométrio/patologia , Predisposição Genética para Doença , Neoplasias Hormônio-Dependentes/epidemiologia , Neoplasias Ovarianas/epidemiologia , Polimorfismo de Nucleotídeo Único , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Endometriose/genética , Endometriose/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fatores de Risco , Espanha/epidemiologia
14.
Br J Radiol ; 94(1125): 20210091, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34289310

RESUMO

Ovarian cancer (OC) is the leading cause of gynecological cancer death, and most cases are diagnosed at advanced stages due to a nonspecific and insidious clinical presentation. Radiologists play a critical role in the decision of which patients are candidates for primary debulking surgery and who may benefit from neoadjuvant chemotherapy. This pictorial review summarizes the dissemination patterns of OC, main imaging findings of metastatic disease, and which findings may alter the treatment plan or predict suboptimal tumor resection.


Assuntos
Diagnóstico por Imagem/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Ovário/diagnóstico por imagem , Ovário/patologia , Cirurgiões
15.
Cochrane Database Syst Rev ; 7: CD005343, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34328210

RESUMO

BACKGROUND: Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require a combination of surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery. OBJECTIVES: To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before debulking surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows debulking surgery (primary debulking surgery (PDS)). SEARCH METHODS: We searched the following databases up to 9 October 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information. SELECTION CRITERIA: Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in each included trial. We extracted data of overall (OS) and progression-free survival (PFS), adverse events, surgically-related mortality and morbidity and quality of life outcomes.  We used GRADE methods to determine the certainty of evidence. MAIN RESULTS: We identified 2227 titles and abstracts through our searches, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1774 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the four studies where data were available and found little or no difference with regard to overall survival (OS) (Hazard Ratio (HR) 0.96, 95% CI 0.86 to 1.08; participants = 1692; studies = 4; high-certainty evidence) or progression-free survival in four trials where we were able to pool data (Hazard Ratio 0.98, 95% CI 0.88 to 1.08; participants = 1692; studies = 4; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were variably and incompletely reported across studies. There are probably clinically meaningful differences in favour of NACT compared to PDS with regard to overall postoperative serious adverse effects (SAE grade 3+): 6% in NACT group, versus 29% in PDS group, (risk ratio (RR) 0.22, 95% CI 0.13 to 0.38; participants = 435; studies = 2; heterogeneity index (I2) = 0%; moderate-certainty evidence). NACT probably results in a large reduction in the need for stoma formation: 5.9% in NACT group, versus 20.4% in PDS group, (RR 0.29, 95% CI 0.12 to 0.74; participants = 632; studies = 2; I2 = 70%; moderate-certainty evidence), and probably reduces the risk of needing bowel resection at the time of surgery: 13.0% in NACT group versus 26.6% in PDS group (RR 0.49, 95% CI 0.30 to 0.79; participants = 1565; studies = 4; I2 = 79%; moderate-certainty evidence). NACT reduces postoperative mortality: 0.6% in NACT group, versus 3.6% in PDS group, (RR 0.16, 95% CI 0.06 to 0.46; participants = 1623; studies = 5; I2 = 0%; high-certainty evidence). QoL on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scale produced inconsistent and imprecise results in three studies (MD -0.29, 95% CI -2.77 to 2.20; participants = 524; studies = 3; I2 = 81%; very low-certainty evidence) but the evidence is very uncertain and should be interpreted with caution. AUTHORS' CONCLUSIONS: The available high to moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT probably reduces the risk of serious adverse events, especially those around the time of surgery, and reduces the risk of postoperative mortality and the need for stoma formation. These data will inform women and clinicians (involving specialist gynaecological multidisciplinary teams) and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos de Citorredução/métodos , Terapia Neoadjuvante/métodos , Neoplasias Ovarianas , Viés , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/mortalidade , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/mortalidade , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
16.
Am J Cardiol ; 154: 120-122, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261592

RESUMO

Described herein is a 48-year-old woman with metastatic ovarian cancer who developed aortic regurgitation considered clinically to be the result of infective endocarditis but operative resection of the three aortic valve cusps disclosed the valve lesions to be typical of non-bacterial thrombotic endocarditis (NBTE). Aortic regurgitation as a consequence of NBTE is rare but at least 9 cases have been reported previously.


Assuntos
Insuficiência da Valva Aórtica/diagnóstico por imagem , Endocardite não Infecciosa/diagnóstico por imagem , Neoplasias Ovarianas/complicações , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/cirurgia , Diagnóstico Diferencial , Endocardite/diagnóstico , Endocardite não Infecciosa/complicações , Endocardite não Infecciosa/patologia , Endocardite não Infecciosa/cirurgia , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Ovarianas/patologia
17.
Molecules ; 26(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34279417

RESUMO

Ovarian cancer often has a poor clinical prognosis because of late detection, frequently after metastatic progression, as well as acquired resistance to taxane-based therapy. Herein, we evaluate a novel class of covalent microtubule stabilizers, the C-22,23-epoxytaccalonolides, for their efficacy against taxane-resistant ovarian cancer models in vitro and in vivo. Taccalonolide AF, which covalently binds ß-tubulin through its C-22,23-epoxide moiety, demonstrates efficacy against taxane-resistant models and shows superior persistence in clonogenic assays after drug washout due to irreversible target engagement. In vivo, intraperitoneal administration of taccalonolide AF demonstrated efficacy against the taxane-resistant NCI/ADR-RES ovarian cancer model both as a flank xenograft, as well as in a disseminated orthotopic disease model representing localized metastasis. Taccalonolide-treated animals had a significant decrease in micrometastasis of NCI/ADR-RES cells to the spleen, as detected by quantitative RT-PCR, without any evidence of systemic toxicity. Together, these findings demonstrate that taccalonolide AF retains efficacy in taxane-resistant ovarian cancer models in vitro and in vivo and that its irreversible mechanism of microtubule stabilization has the unique potential for intraperitoneal treatment of locally disseminated taxane-resistant disease, which represents a significant unmet clinical need in the treatment of ovarian cancer patients.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Esteroides/farmacologia , Taxoides/farmacologia , Moduladores de Tubulina/farmacologia , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Micrometástase de Neoplasia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
AJR Am J Roentgenol ; 217(3): 664-675, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34259544

RESUMO

OBJECTIVE. The purpose of our study was to develop a radiomics model based on preoperative MRI and clinical information for predicting recurrence-free survival (RFS) in patients with advanced high-grade serous ovarian carcinoma (HGSOC). MATERIALS AND METHODS. This retrospective study enrolled 117 patients with HGSOC, including 90 patients with recurrence and 27 without recurrence; 1046 radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images using a manual segmentation method. L1 regularization-based least absolute shrinkage and selection operator (LASSO) regression was performed to select features, and the synthetic minority oversampling technique (SMOTE) was used to balance our dataset. A support vector machine (SVM) classifier was used to build the classification model. To validate the performance of the proposed models, we applied a leave-one-out cross-validation method to train and test the classifier. Cox proportional hazards regression, Harrell concordance index (C-index), and Kaplan-Meier plots analysis were used to evaluate the associations between radiomics signatures and RFS. RESULTS. The fusion radiomics-based model yielded a significantly higher AUC value of 0.85 in evaluating RFS than the model using contrast-enhanced T1-weighted imaging features alone or T2-weighted imaging features alone (AUC = 0.79 and 0.74 and p = .02 and .01, respectively). Kaplan-Meier survival curves showed significant differences between high and low recurrence risk in patients with HGSOC by different models. The fusion model combining radiomics features and clinical information showed higher performance than the clinical model (C-index = 0.62 and 0.60, respectively). CONCLUSION. The proposed MRI-based radiomics signatures may provide a potential way to develop a prediction model and can help identify patients with advanced HGSOC who have a high risk of recurrence.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Máquina de Vetores de Suporte , Feminino , Humanos , Pessoa de Meia-Idade , Ovário/diagnóstico por imagem , Ovário/patologia , Estudos Retrospectivos , Análise de Sobrevida
19.
Molecules ; 26(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34279378

RESUMO

The aim of the study is to evaluate oxidant-antioxidant balance as well as lysosomal and anti-protease activities in ovarian cancer since it has been emphasized that the crucial inducing factor of carcinogenesis may be reactive oxygen/nitrogen species or, more precisely, oxidative stress-induced inflammation. The study involved 15 women with ovarian cancer, aged 59.9 ± 7.8 years, and 9 healthy women aged 56.3 ± 4.3 years (controls). The study material was venous blood collected from fasting subjects. In erythrocytes, the activities of superoxide dismutase, glutathione peroxidase, and catalase, as well as concentrations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARS), were investigated. CD, TBARS, and vitamins A and E plasma concentrations were also determined. Moreover, total antioxidant capacity and concentrations of 4-hydroxynonenal adducts and 8-iso-prostaglandin F2α, as well as activities of acid phosphatase, arylsulfatase, cathepsin D, and α1-antitrypsin, were studied in serum. The vitamin E and 8-iso-prostaglandin F2α concentrations as well as arylsulfatase activity were lower in the women with cancer compared to the controls (p = 0.006, p = 0.03, p = 0.001, respectively). In contrast, cathepsin D activity was lower in the controls (p = 0.04). In the peripheral blood of the women with cancer, oxidant-antioxidant and lysosomal disturbances were observed.


Assuntos
Lisossomos/metabolismo , Recidiva Local de Neoplasia/sangue , Neoplasias Ovarianas/sangue , Estresse Oxidativo , Idoso , Catalase/sangue , Catepsina D/sangue , Dinoprosta/sangue , Feminino , Glutationa Peroxidase/sangue , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitamina A/sangue , Vitamina E/sangue
20.
Eur J Nucl Med Mol Imaging ; 48(10): 3286-3302, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34215923

RESUMO

In most patients with ovarian carcinoma, the diagnosis is reached when the disease is long past the initial stages, presenting already an advanced stage, and they usually have a very bad prognosis. Cytoreductive or debulking surgical procedures, platinum-based chemotherapy and targeted agents are key therapeutic elements. However, around 7 out of 10 patients present recurrent disease within 36 months from the initial diagnosis. The metastatic spread in ovarian cancer follows three pathways: contiguous dissemination across the peritoneum, dissemination through the lymphatic drainage and, although less importantly in this case, through the bloodstream. Radiological imaging, including ultrasound, CT and MRI, are the main imaging techniques in which management decisions are supported, CT being considered the best available technique for presurgical evaluation and staging purposes. Regarding 2-[18F]FDG PET/CT, the evidence available in the literature demonstrates efficacy in primary detection, disease staging and establishing the prognosis and especially for relapse detection. There is limited evidence when considering the evaluation of therapeutic response. This guideline summarizes the level of evidence and grade of recommendation for the clinical indications of 2-[18F]FDG PET/CT in each disease stage of ovarian carcinoma.


Assuntos
Energia Nuclear , Medicina Nuclear , Neoplasias Ovarianas , Feminino , Fluordesoxiglucose F18 , Humanos , Imagem Molecular , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Compostos Radiofarmacêuticos , Estados Unidos
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