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1.
Int J Nanomedicine ; 16: 683-700, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33536754

RESUMO

Purpose: To develop an externally triggered rapid-release targeted system for treating ovarian cancer, gemcitabine (GMC) was entrapped into sonosensitive (SoS) folate (Fo)-modified liposomes (LPs). Methods: GMC-loaded LPs (GMC LPs), GMC-loaded Fo-targeted LPs (GMC-Fo LPs), and GMC-loaded Fo-targeted SoS LPs (GMC-SoS Fo LPs) were prepared utilizing a film-hydration technique and evaluated based on particle size, ζ-potential, and percentage entrapped drug. Cellular uptake of the fluorescent delivery systems in Fo-expressing ovarian cancer cells was quantified using flow cytometry. Finally, tumor-targeting ability, in vivo evaluation, and pharmacokinetic studies were performed. Results: GMC LPs, GMC-Fo LPs, and GMC-SoS Fo LPs were successfully prepared, with sizes of <120.3±2.4 nm, 39.7 mV ζ-potential, and 86.3%±1.84% entrapped drug. Cellular uptake of GMC-SoS Fo LPs improved 6.51-fold over GMC LPs (under ultrasonic irradiation - p<0.05). However, cellular uptake of GMC-Fo LPs improved just 1.24-fold over GMC LPs (p>0.05). Biodistribution study showed that of GMC concentration in tumors treated with GMC-SoS-Fo LPs (with ultrasound) improved 2.89-fold that of free GMC (p<0.05). In vivo, GMC-SoS Fo LPs showed the highest antiproliferative and antitumor action on ovarian cancer. Conclusion: These findings showed that externally triggered rapid-release SoS Fo-modified LPs are a promising system for delivering rapid-release drugs into tumors.


Assuntos
Desoxicitidina/análogos & derivados , Ácido Fólico/química , Ultrassom , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Desoxicitidina/administração & dosagem , Desoxicitidina/sangue , Desoxicitidina/farmacocinética , Desoxicitidina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Lipossomos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Tamanho da Partícula , Ratos Sprague-Dawley , Distribuição Tecidual/efeitos dos fármacos
2.
BMC Surg ; 21(1): 49, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478468

RESUMO

BACKGROUND: To evaluate the use of a human fibrin glue (Tisseel) for minor bleeding control and approximation of ovarian defect during transvaginal natural orifice ovarian cystectomy (TNOOC) of benign and non-endometriotic ovarian tumors. METHODS: A total of 125 women with benign and non-endometriotic ovarian tumors who underwent TNOOC between May 2011 and January 2020: 54 with the aid of Tisseel and 71 with traditional suture for hemostasis and approximation of ovarian defect. Surgical outcomes such as length of surgery, operative blood loss, postoperative pain score, and postoperative hospital stay were recorded. Before and immediately (10 days) and at 6 months after the procedure, serum anti-Müllerian hormone (AMH) levels were also determined. RESULTS: Complete hemostasis and approximation of ovarian defect were achieved in all cases. No significant difference was noted in the operating time, operative blood loss, postoperative pain scores after 12, 24 and 48 h, length of postoperative stay, and baseline AMH levels between the two groups. The operation did not have a negative effect on the immediate and 6-month postoperative AMH levels in the suture group. However, the decline in the AMH levels was significant immediately after surgery in the Tisseel group, nevertheless, no significant difference was noted in the AMH levels at 6 months (3.3 vs. 1.7 mg/mL; p = 0.042, adjusted p = 0.210). CONCLUSION: The use of Tisseel in TNOOC of benign and non-endometriotic ovarian tumors without suturing the ovarian tissue is clinically safe and feasible.


Assuntos
Adesivo Tecidual de Fibrina , Laparoscopia , Neoplasias Ovarianas , Suturas , Adolescente , Adulto , Hormônio Antimülleriano/sangue , Cistos/sangue , Cistos/cirurgia , Endometriose/cirurgia , Estudos de Viabilidade , Feminino , Adesivo Tecidual de Fibrina/administração & dosagem , Humanos , Cirurgia Endoscópica por Orifício Natural , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Técnicas de Sutura , Vagina/cirurgia , Adulto Jovem
3.
Medicine (Baltimore) ; 100(1): e24134, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429787

RESUMO

ABSTRACT: Ovarian cancer (OC), a common malignant heterogeneous gynecological tumor, is the primary cause of cancer-related death in women worldwide. Adenylate kinase (AK) 7 belongs to the adenylate kinase (AK) family and is a cytosolic isoform of AK. Recent studies have demonstrated that AK7 is expressed in several human diseases, including cancer. However, there is a scarcity of reports on the relationship between AK7 and OC. Here, we compared the expression of AK7 in normal and cancerous ovarian tissues from The Cancer Genome Atlas database and used the c2 test to assess the correlation between AK7 levels and the clinical symptoms of OC. Finally, the prognostic significance of AK7 in OC was determined using the Kaplan-Meier analyses and Cox regression and performed gene set enrichment analysis to detect any relevant signaling pathways. We found that AK7 levels were substantially downregulated in OC than that in normal ovarian tissues (P < .001). Low AK7 levels were related to the patients' age (P = .0093) in OC. The median overall survival (OS) of patients with low AK7-expressing OC was shorter than patients with high AK7-expressing OC (P = .019). The Cox regression analysis (multivariate) identified low AK7 levels were independently related to the prognosis of OC (HR 1.34; P = .048). Our study demonstrated that the downregulated levels of AK7 could serve as an independent prognostic indicator for the OS in OC. Additionally, gene set enrichment analysis revealed that EMT, apical junction, TGF-b signaling, UV response, and myogenesis were associated in the low AK7 expression phenotype (NOM P < .05).


Assuntos
Adenilato Quinase/análise , Neoplasias Ovarianas/complicações , Prognóstico , Adenilato Quinase/sangue , Adenilato Quinase/genética , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Regulação para Baixo , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/classificação
4.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370966

RESUMO

A 64-year-old postmenopausal female patient presented with approximately 5 years of intermittent spotting, progressive hirsutism and significantly increased libido and clitoral hypersensitivity with spontaneous orgasms multiple times a day beginning a few months prior. Initial hormone work-up revealed elevated total serum testosterone, androstenedione and 17-hydroxyprogesterone. Luteinising hormone, follicle stimulating hormone, estradiol, dehydroepiandrosterone-sulfate, thyroid stimulating hormone and prolactin were all within normal limits. Initial suspicions suggested an androgen-secreting tumour, likely in the ovary. The lesion was undetectable on transvaginal ultrasound and abdominal-pelvic CT scan. Laparoscopic bilateral salpingo-oophorectomy was performed to remove the likely source of excess androgens. Visible gross lesions were not observed intraoperatively; however, bilateral Leydig (hilus cell) tumours were confirmed by histopathology. Serum testosterone, androstenedione and 17-hydroxyprogesterone levels were normalised postoperatively within 2 weeks and 1 month, respectively.


Assuntos
Hirsutismo/etiologia , Tumor de Células de Leydig/diagnóstico , Neoplasias Ovarianas/diagnóstico , Ovário/patologia , 17-alfa-Hidroxiprogesterona/sangue , Androstenodiona/sangue , Feminino , Humanos , Tumor de Células de Leydig/sangue , Tumor de Células de Leydig/complicações , Tumor de Células de Leydig/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Ovário/cirurgia , Pós-Menopausa , Salpingo-Ooforectomia , Testosterona/sangue , Resultado do Tratamento
5.
Niger J Clin Pract ; 23(8): 1141-1147, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788493

RESUMO

Aims: This study was aimed at investigating the prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer (EOC) patients in Lagos, Nigeria. Methods: This was a retrospective cohort study involving the review of the clinical record of 72 patients with histologically confirmed EOC who were managed at the Lagos University Teaching Hospital, Lagos, Nigeria over a 7-year period from January 2010 to December 2016. Information on the sociodemographic data and platelet counts at diagnosis of EOC were retrieved from the patients' medical records. Descriptive statistics were then computed for all baseline patients' characteristics. Survival analyses were carried out using the Kaplan-Meier estimates. Multivariate analysis of these data was performed with the Cox proportional hazards model. Results: This study revealed that the prevalence of pretreatment thrombocytosis was 41.7% among the women with EOC. Fifty-three (73.6%) of the women had the advanced-stage disease (FIGO stage III-IV) while 52 (72.2%) had high-grade disease (II-III). The majority (66.7%) of the women had a serous histological type of EOC while 76.4% had documented recurrence. Pretreatment thrombocytosis was significantly associated with the women's parity (P = 0.009), serum carbohydrate antigen 125 levels (P = 0.018), median progression-free survival (PFS) (P < 0.001), 3-year median overall survival (OS) (P < 0.001), type of primary treatment (P = 0.002), extent of cytoreduction (P < 0.001), presence of ascites (P = 0.002), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.008), and histological type (P = 0.011). Pretreatment thrombocytosis was negatively associated with PFS (hazard ratio [HR] = 0.25; 95% CI 0.83, 0.75; P = 0.014) and 3-year OS (HR = 0.03; 95% CI 0.03, 0.27; P = 0.002). Conclusions: The study suggests that pretreatment thrombocytosis may be a useful predictor of survivals in EOC patients.


Assuntos
Transtornos Plaquetários/etiologia , Carcinoma Epitelial do Ovário/mortalidade , Neoplasias Ovarianas/mortalidade , Trombocitose/epidemiologia , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Nigéria/epidemiologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Contagem de Plaquetas , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Trombocitose/sangue
6.
Nat Commun ; 11(1): 3546, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669559

RESUMO

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.


Assuntos
Carcinoma Epitelial do Ovário/secundário , Citocinas/metabolismo , Lectinas/metabolismo , Omento/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Animais , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral/transplante , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Citocinas/administração & dosagem , Citocinas/sangue , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Proteínas Ligadas por GPI/administração & dosagem , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Lactoferrina/metabolismo , Lectinas/administração & dosagem , Lectinas/sangue , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Invasividade Neoplásica/patologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Ovário , Proteínas Recombinantes/administração & dosagem , Taxa de Sobrevida , Microambiente Tumoral
7.
Cancer Immunol Immunother ; 69(10): 2001-2007, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32393999

RESUMO

Cancer immunotherapy including vaccine therapy is a promising modality for cancer treatment, but few patients show its clinical benefits currently. The identification of biomarkers that can identify patients who will benefit from cancer immunotherapy is thus important. Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity-a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene-as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or recurrent ovarian cancer enrolled in clinical trials for personalized peptide vaccinations. We observed that (1) the cfDNA integrity was decreased after the first cycle of vaccination, and (2) the decreased levels of cfDNA integrity were correlated with vaccine-induced immune responses; i.e., decreased cfDNA integrity was observed in 91.7% and 59.3% of the IgG-positive and negative patients, respectively (p = 0.0445). Similarly, decreased cfDNA integrity was observed in 92.9% and 56.0% of CTL response-positive and negative patients, respectively (p = 0.0283). These results suggest that the circulating cfDNA integrity is a possible biomarker for cancer vaccine therapy.


Assuntos
Biomarcadores Tumorais/imunologia , Vacinas Anticâncer/imunologia , Carcinoma Epitelial do Ovário/imunologia , DNA Tumoral Circulante/sangue , Recidiva Local de Neoplasia/imunologia , Neoplasias Ovarianas/imunologia , Vacinas de Subunidades/imunologia , Vacinas Anticâncer/administração & dosagem , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/genética , DNA Tumoral Circulante/genética , Feminino , Seguimentos , Humanos , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Prognóstico , Vacinas de Subunidades/administração & dosagem
8.
Cancer Genomics Proteomics ; 17(3): 301-307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32345671

RESUMO

BACKGROUND: Environmental factors may influence the lifetime risk of cancer (penetrance) in women with a BRCA mutation. MATERIALS AND METHODS: In 89 BRCA-mutant women, affected or unaffected by breast/ovarian cancer, we explored serum levels of adipokines and their relation with the polymorphism SNP276G>T as modulators of BRCA penetrance. RESULTS: Affected women had significantly lower adiponectin than healthy women. Affected women with rs1501299 TT had significantly lower adiponectin and higher leptin than GT and GG genotypes. GT genotype was significantly associated with the disease status [odds ratio (OR)=3.24, 95% confidence interval (95% CI)=1.03-10.17]. Women in the lower tertile of serum adiponectin had a RR of BRCA-associated cancer of 2.80, 95% CI=1.1-7.1 (p for trend=0.03) compared with women in the higher tertile. CONCLUSION: In the SNP rs1501299 the T allele was significantly associated with lower serum levels of adiponectin in affected women, suggesting that the T allele might be related to cancer.


Assuntos
Adiponectina/sangue , Adiponectina/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Mutação , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Estudos Retrospectivos
9.
Minerva Med ; 111(2): 133-140, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338842

RESUMO

BACKGROUND: The serum marker CA 125 is still the most widely used biomarker for ovarian cancer (OC) diagnosis in gynecological and oncological setting, but its predictive role in early-stage OC is still debated. The aim of this study was to explore the value of CA 125 in distinguishing between early-stage OC and borderline ovarian tumor (BOT) and to evaluate the accuracy of CA 125 in the detection of early stage OC. METHODS: A retrospective cohort study was performed at the University Hospital of Bologna (Italy) on 1296 consecutive women suffering from OC or BOT (diagnosed at histology) between 1988-2017. Patients for whom CA 125 level was determined preoperatively were included. The positive cut-off level used was >35 U/mL. RESULTS: Of 910 patients, 192 (21.1%) were diagnosed with BOT and 718 (78.9%) with OC. The sensitivity of CA 125 for stage I OC was 54.4 (95% CI: 45.3-63.3) (51.5 for IA, 54.6 for IB, 58.3 for IC), but it increased to 78.0 (95% CI: 63.7-88.0) for stage II. Interestingly, in stage I OC, CA 125 presented a significantly higher sensitivity for the endometrioid histotype [72.4 (95% CI: 52.5-86.5) vs. 49.0 (95% CI: 38.6-59.4), P=0.026]. The positive likelihood ratio of CA 125 for early-stage OC compared to BOT was 1.29 (95% CI: 1.06-1.58). CONCLUSIONS: Despite its limited sensitivity for early-stage OCs, CA 125 still represents a useful serum marker to early differentiate between OCs and BOTs. Its sensitivity for stage I OC increases in endometrioid histotype.


Assuntos
Antígeno Ca-125/sangue , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/patologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
10.
Medicine (Baltimore) ; 99(14): e19638, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243392

RESUMO

BACKGROUND: This study aimed to systematically assess the prognostic value of lymphocyte monocyte ratio (LMR) in patients with ovarian cancer through performing a meta-analysis. METHODS: Web of Science, PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases were searched for potentially eligible studies. The baseline characteristics and relevant data were extracted. Hazard ratios with 95% confidence intervals (CIs) were combined to assess the prognostic value of LMR in patients with ovarian cancer. RESULTS: Nine studies enrolling 2809 patients were included. The pooled hazard ratios of lower LMR for overall survival and progression free survival in patients with ovarian cancer were 1.71 (95% CI, 1.40-2.09) and 1.68 (95% CI, 1.49-1.88), respectively. Subgroup analysis and sensitivity analysis were also performed. No significant publication bias was found. CONCLUSION: Our results suggested that lower LMR was associated with poorer overall survival and progression free survival in patients with ovarian cancer. The findings may assist prognosis evaluation and future research on therapies based on modulating host immune response in ovarian cancer.


Assuntos
Linfócitos/metabolismo , Monócitos/metabolismo , Neoplasias Ovarianas/mortalidade , Feminino , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Taxa de Sobrevida
11.
Cancer Chemother Pharmacol ; 85(5): 941-947, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32279102

RESUMO

PURPOSE: The aim of this study was to investigate the association between changes in the levels of vascular endothelial growth factors (VEGFs) after treatment with bevacizumab and gemcitabine (Bev-Gem) and the clinical outcome. METHODS: Platinum-resistant ovarian cancer patients treated with Bev-Gem therapy at our hospital between 2014 and 2018 were identified. Serum VEGF levels at the first and second treatment cycle were measured by ELISA. All patients were categorized into two groups-patients with > 50% decrease in serum VEGF-A levels (Group A) and patients with < 50% decrease serum VEGF-A levels (Group B). The association between clinical outcome and serum VEGF levels was investigated between the two groups. RESULTS: Among 18 patients, 10 were in Group A and 8 in Group B. Group A exhibited a lower response rate (0% vs.75% p < 0.01) and clinical benefit rate (60% vs.100% p = 0.02) than Group B. The median serum VEGF-A level of Group A before the first cycle of Bev-Gem therapy was higher than that in Group B (61.2 vs. 3.7 pg/mL, p < 0.01). Group A exhibited worse PFS (7 vs., 10 months, p < 0.01) and OS (17 vs. 26 months, p = 0.04) than Group B. There were more patients with > 10% increase in serum VEGF-B levels in Group A than in Group B (p < 0.01). CONCLUSION: The rapid decrease in VEGF-A levels and the resultant increase in serum VEGF-B levels might be associated with an unfavorable clinical outcome. Large-scale studies are needed to further examine these results.


Assuntos
Bevacizumab , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Recidiva Local de Neoplasia , Neoplasias Ovarianas , Fator A de Crescimento do Endotélio Vascular/sangue , Fator B de Crescimento do Endotélio Vascular/sangue , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Bevacizumab/farmacocinética , Biomarcadores Farmacológicos/sangue , Biomarcadores Tumorais/sangue , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacocinética , Progressão da Doença , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Prognóstico
12.
Artigo em Inglês | MEDLINE | ID: mdl-32273169

RESUMO

Ovarian cancer is the third most common gynaecological malignancy and the most lethal worldwide. Most patients are diagnosed with advanced disease which carries significant mortality. Improvements in treatment have only resulted in modest increases in survival. This has driven efforts to reduce mortality through screening. Multimodal ovarian cancer screening using a longitudinal CA125 algorithm has resulted in diagnosis at an earlier stage, both in average and high risk women in two large UK trials. However, no randomised controlled trial has demonstrated a definitive mortality benefit. Extended follow up is underway in the largest trial to date, UKCTOCS, to explore the delayed reduction in mortality that was noted. Meanwhile, screening is not currently recommended in the general population Some countries offer surveillance of high risk women. Novel screening modalities and longitudinal biomarker algorithms offer potential improvements to future screening strategies as does the development of better risk stratification tools.


Assuntos
Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Neoplasias Ovarianas/diagnóstico , Ovariectomia/métodos , Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/sangue , Feminino , Humanos , Programas de Rastreamento/tendências , Neoplasias Ovarianas/sangue , Prognóstico , Fatores de Risco , Sensibilidade e Especificidade
13.
Arch Gynecol Obstet ; 301(5): 1219-1225, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32266526

RESUMO

OBJECTIVE: To determine the diagnostic value and clinical significance of serum HE4 levels in differentiating between benign and malignant ovarian disease in patients with elevated CA125 levels. METHODS: The levels and positive expression rate of HE4 were compared between 371 patients with elevated CA125 levels and benign ovarian disease, and 132 patients with epithelial ovarian cancer to determine the diagnostic value of HE4. RESULTS: The level and positive expression rate of HE4 differed significantly between the benign and malignant groups, in that, there was no significant difference in HE4 expression between CA125 low- and high-level groups within the benign ovarian disease group, with levels of HE4 being in the normal range in both groups. However, the positive expression rates and levels of HE4 in the malignant group were significantly different between the serum CA125 low- and high-level groups. ROC curve analysis showed that optimal HE4 cutoff values for increased accuracy in diagnosis were 78.03 pmol/L and 119.70 pmol/L before and after menopause, respectively. CONCLUSIONS: Serum HE4 levels can potentially be used as a marker to differentiate between benign and malignant ovarian disease with elevated serum CA125 levels. The high specificity of HE4 was superior in identifying benign ovarian disease. We recommend increasing the cutoff values of HE4 in premenopausal patients and decreasing the cutoff values in postmenopausal patients for increased accuracy in the differential diagnosis of patients with elevated CA125 levels.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Neoplasias Ovarianas/diagnóstico , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Adulto , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário/sangue , Diagnóstico Diferencial , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Pré-Menopausa , Proteínas/análise , Proteínas/metabolismo , Curva ROC , Sensibilidade e Especificidade , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise
14.
Gynecol Oncol ; 157(2): 521-528, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32145911

RESUMO

OBJECTIVE: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. METHODS: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. RESULTS: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). CONCLUSIONS: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.


Assuntos
Antígeno Ca-125/sangue , Proteínas de Membrana/sangue , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico por imagem , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Adulto , Algoritmos , Biomarcadores Tumorais/sangue , Estudos de Viabilidade , Feminino , Humanos , Cooperação do Paciente , Projetos Piloto , Risco , Ultrassonografia , Conduta Expectante/métodos
15.
Rev Assoc Med Bras (1992) ; 66(1): 61-66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130383

RESUMO

OBJECTIVE: To relate disease-free survival and overall survival with type I and type II ovarian cancer and preoperative laboratory parameters biomarkers. METHODS: A retrospective study was carried out based on the collection of data from medical records of patients with ovarian tumors. Kaplan-Mayer curves were drawn based on the statistical analysis of the data and were compared using the Log-rank test. RESULTS: Disease-free survival in type I ovarian cancer was significantly higher than in type II (p=0.0013), as well as in those with normal levels of CA-125 (p=0.0243) and with a platelet-lymphocyte ratio (PLR) lower than 200 (p=0.0038). The overall survival of patients with type I ovarian cancer was significantly higher than in patients with type II, as well as in patients with normal CA-125 serum levels (p=0.0039) and those with a preoperative fasting glucose of less than 100 mg/dL. CONCLUSION: CA-125 levels may predict greater overall and disease-free survival. PLR < 200 may suggest greater disease-free survival, whereas normal fasting glucose may suggest greater overall survival.


Assuntos
Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Pessoa de Meia-Idade , Neutrófilos , Neoplasias Ovarianas/patologia , Contagem de Plaquetas , Valor Preditivo dos Testes , Período Pré-Operatório , Valores de Referência , Estudos Retrospectivos , Adulto Jovem
16.
Gynecol Oncol ; 157(1): 55-61, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32139151

RESUMO

OBJECTIVE: Endometrioid ovarian carcinoma (EOVC) is an uncommon subtype of epithelial ovarian carcinoma and its molecular characteristics have been incompletely described. Prior sequencing investigations have been limited to targeted gene panels. We performed whole-exome sequencing to build an unbiased genetic profile of molecular alterations in endometrioid ovarian tumors with a goal to better understand this disease in the context of epithelial ovarian cancer and endometrioid uterine cancers. METHODS: Whole-exome sequencing was performed on EOVC samples (n = 26) and matched normals (n = 15). Gene mutations, mutational signatures and copy number variations (CNVs) informed a multi-dimensional regression classifier allowing for comparison to endometrial carcinoma (UCEC) and high grade serous ovarian carcinoma (HGSC). RESULTS: EOVC has a distinct and heterogeneous genomic profile. Identified significantly mutated genes in EOVC (PTEN, CTNNB1, PIK3CA, KMT2D, KMT2B, PIK3R1, ARID1A and TP53) occurred at similar frequencies in UCEC. Hypermutation, resulting from both mismatch repair deficiency (MMRd) and POLE mutation, was observed in EOVC at a frequency similar to UCEC. Like UCEC, a subset of EOVC cases closely resembled HGSC, harboring TP53 mutations, homologous recombination deficiency (HRd) mutation signatures and widespread CNVs. A machine-learning classifier confirmed the heterogeneous composition of EOVC. Potential therapeutic targets were identified in 62% of EOVC cases. We validated our findings in an orthogonal clinical sequencing registry of EOVC cases. CONCLUSIONS: We identified that EOVC are a molecularly heterogeneous group of epithelial ovarian cancers with distinct mutational signatures. In an age of precision oncology, there is a pressing need to understand the unique molecular drivers in uncommon histologic subtypes to facilitate genomically driven oncologic treatments.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/patologia , Análise Mutacional de DNA , Feminino , Dosagem de Genes , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Sequenciamento Completo do Exoma
17.
BMC Cancer ; 20(1): 200, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164586

RESUMO

BACKGROUND: Existing data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT. METHODS: Electronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed using I2 statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias. RESULTS: Twelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis and I2 statistics ranged between 97 and 99%. Mean circulating TC (- 16.60 [- 32.43, - 0.77]mg/dL; P = 0.04) and HDL (- 0.25[- 0.43, - 0.08]mmol/L; P = 0.005) were significantly lower among OT cases compared to non-OT cases. CONCLUSION: Decreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.


Assuntos
Lipoproteínas HDL/sangue , Neoplasias Ovarianas/sangue , Triglicerídeos/sangue , Colesterol/sangue , Feminino , Humanos , Lipoproteínas LDL/sangue , Masculino , Fatores de Risco
18.
Gynecol Oncol ; 157(2): 398-404, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32063274

RESUMO

OBJECTIVE: To compare the efficacy of ascitic fluid cell block (ACB) with that of core needle biopsy (CNB) or the CA125/CEA ratio in diagnosing primary tubo-ovarian cancer in female patients with peritoneal carcinomatosis (PC) with ascites. METHODS: This retrospective study examined female patients with PC with ascites who had available results for ACB, peritoneal tumor CNB, and the CA125/CEA ratio. Several measures of the accuracy of ACB and the CA125/CEA ratio were calculated and compared, with CNB as the reference standard. RESULTS: Of 81 patients with available results, 57 were clinically diagnosed with primary tubo-ovarian cancer. Overall, 52, 47, and 64 patients were diagnosed via CNB, ACB, and CA125/CEA ratio > 25, respectively. CNB and ACB identified the cancer origin in 91.4% and 82.7% cases, respectively. The concordance ratio of the immunohistochemical findings between ACB and CNB was 93.6%. Two patients with inconclusive CNB results were diagnosed with primary tubo-ovarian cancer via ACB. The sensitivity, specificity, positive predictive value, negative predictive value, and positive likelihood ratio were 86.5%, 93.1%, 95.7%, 79.4%, and 12.5, respectively, for ACB and 94.2%, 48.3%, 76.6%, 82.4%, and 1.82, respectively, for CA125/CEA ratio > 25. CONCLUSIONS: ACB is not inferior to CNB in diagnosing primary tubo-ovarian cancer; the two methods complement each other. ACB can substitute CNB in diagnosing primary tubo-ovarian cancer in selected PC patients. ACB is superior to a CA125/CEA ratio of >25 in diagnosing primary tubo-ovarian cancer. ACB is effective, reliable, and convenient for diagnosing primary tubo-ovarian cancer in PC patients with ascites.


Assuntos
Adenocarcinoma/patologia , Líquido Ascítico/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Antígeno Ca-125/sangue , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/diagnóstico , Estudos Retrospectivos
19.
Cancer Biomark ; 27(3): 407-421, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32083570

RESUMO

BACKGROUND: The majority of ovarian cancer cases are diagnosed at an advanced stage with poor prognosis. This study evaluates autoantibodies against tumor antigens to identify candidate biomarkers for early detection of ovarian cancer in women at increased risk. OBJECTIVE: To assess the immunoreactivity of paraneoplastic antigens and tumor associated antigens with high-grade serous ovarian cancer (HGSOC) samples. METHODS: Five paraneoplastic antigens along with three tumor-associated antigens were evaluated with HGSOC patient serum samples. Validation screening was performed with n= 164 serum samples consisting of: 50 late stage HGSOC, 14 early stage HGSOC, 50 benign ovarian cyst, and 50 healthy control samples on ELISA and western blot. The four markers TRIM21, NY-ESO-1, TP53, and PAX8 were evaluated on a second validation serum set, n= 150. RESULTS: TRIM21 achieved the highest sensitivity in the first validation screening of 33% with 100% specificity. Combining TRIM21 with NY-ESO-1, TP53, and PAX8 provided 67% sensitivity with 94% specificity, and 56% sensitivity at 98% specificity. These four markers resulted in 46% sensitivity with 98% specificity in the second validation cohort; TRIM21 achieved the highest individual sensitivity of 36%. CONCLUSIONS: Autoantibodies to TRIM21, NY-ESO-1, and TP53 may complement CA125 in screening of women at genetic risk for ovarian cancer.


Assuntos
Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Detecção Precoce de Câncer/métodos , Proteínas de Membrana/imunologia , Neoplasias Ovarianas/imunologia , Ribonucleoproteínas/imunologia , Proteína Supressora de Tumor p53/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Feminino , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia
20.
Cancer Biomark ; 27(2): 225-242, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32083575

RESUMO

BACKGROUND: Deregulated microRNAs (miRNAs) in breast and gynecological cancer might contribute to improve early detection of female malignancies. OBJECTIVE: Specification of miRNA types in serum and urine as minimally-invasive biomarkers for breast (BC), endometrial (EC) and ovarian cancer (OC). METHODS: In a discovery phase, serum and urine samples from 17 BC, five EC and five OC patients vs. ten healthy controls (CTRL) were analyzed with Agilent human miRNA microarray chip. Selected miRNA types were further investigated by RT-qPCR in serum (31 BC, 13 EC, 15 OC patients, 32 CTRL) and urine (25 BC, 10 EC, 10 OC patients, 30 CTRL) applying two-sample t-tests. RESULTS: Several miRNA biomarker candidates exhibited diagnostic features due to distinctive expression levels (serum: 26; urine: 22). Among these, miR-518b, -4719 and -6757-3p were found specifically deregulated in BC serum. Four, non-entity-specific, novel biomarker candidates with unknown functional roles were identified in urine (miR-3973; -4426; -5089-5p and -6841). RT-qPCR identified miR-484/-23a (all p⩽ 0.001) in serum as potential diagnostic markers for EC and OC while miR-23a may also serve as an endogenous control in BC diagnosis. CONCLUSIONS: Promising miRNAs as liquid biopsy-based tools in the detection of BC, EC and OC qualified for external validation in larger cohorts.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias do Endométrio/genética , Neoplasias Ovarianas/genética , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/urina , Estudos de Casos e Controles , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/urina , Feminino , Humanos , Biópsia Líquida/métodos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/urina , Prognóstico
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