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[PMID]: 28453702 [Au] Autor: Monk BJ; Brady MF; Aghajanian C; Lankes HA; Rizack T; Leach J; Fowler JM; Higgins R; Hanjani P; Morgan M; Edwards R; Bradley W; Kolevska T; Foukas P; Swisher EM; Anderson KS; Gottardo R; Bryan JK; Newkirk M; Manjarrez KL; Mannel RS; Hershberg RM; Coukos G [Ad] Endereço: Arizona Oncology (US Oncology Network), University of Arizona, College of Medicine, Creighton University School of Medicine at St. Joseph's Hospital, Phoenix. [Ti] Título: A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study. [So] Source: Ann Oncol;28(5):996-1004, 2017 May 01. [Is] ISSN: 1569-8041 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6-12 months) and Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. Results: The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. Conclusions: The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. Trial registration: Clinicaltrials.gov, NCT 01666444. [Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Recidiva Local de Neoplasia/tratamento farmacológico Neoplasias Epiteliais e Glandulares/tratamento farmacológico Neoplasias Ovarianas/tratamento farmacológico [Mh] Termos MeSH secundário: Adjuvantes Imunológicos/administração & dosagem Adulto Idoso Idoso de 80 Anos ou mais Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia Benzazepinas/administração & dosagem Intervalo Livre de Doença Método Duplo-Cego Doxorrubicina/administração & dosagem Doxorrubicina/análogos & derivados Seres Humanos Imunidade Inata/efeitos dos fármacos Estimativa de Kaplan-Meier Meia-Idade Recidiva Local de Neoplasia/mortalidade Neoplasias Epiteliais e Glandulares/mortalidade Neoplasias Ovarianas/mortalidade Polietilenoglicóis/administração & dosagem Modelos de Riscos Proporcionais Resultado do Tratamento [Pt] Tipo de publicação: CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Adjuvants, Immunologic); 0 (Benzazepines); 0 (VTX-2337); 0 (liposomal doxorubicin); 30IQX730WE (Polyethylene Glycols); 80168379AG (Doxorubicin) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170429 [Cl] Clinical Trial: ClinicalTrial [St] Status: MEDLINE [do] DOI: 10.1093/annonc/mdx049

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[PMID]: 29325268 [Au] Autor: Li MJ; Li HR; Cheng X; Bi R; Tu XY; Liu F; Chen LH [Ad] Endereço: Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. [Ti] Título: [Clinical significance of targeting drug-based molecular biomarkers expression in ovarian clear cell carcinoma]. [So] Source: Zhonghua Fu Chan Ke Za Zhi;52(12):835-843, 2017 Dec 25. [Is] ISSN: 0529-567X [Cp] País de publicação: China [La] Idioma: chi [Ab] Resumo: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues. The positive rates of EGFR, HER2, AURKA,BRCA1, BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20% (8/40) vs 30% (7/23) , 22% (9/40) vs 35% (8/23) , 38% (15/40) vs 35% (8/23) , 42% (17/40) vs 39% (9/23) , 20% (8/40) vs 22% (5/23) , 25% (10/40) vs 17% (4/23) , and there were no significant differences between primary and recurrent OCCC (all 0.05). χ(2)-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance ( 0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all 0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC (4 months vs 10 months, log-rank test, 0.05 for HER2; and 4 months vs 10 months, 0.05 for AURKA); and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, 0.05 for HER2; and 13 months vs 43 months, 0.05 for AURKA). However, multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC ( 0.05). HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma. [Mh] Termos MeSH primário: Adenocarcinoma de Células Claras/tratamento farmacológico Adenocarcinoma de Células Claras/metabolismo Biomarcadores Tumorais/metabolismo Neoplasias Epiteliais e Glandulares/tratamento farmacológico Neoplasias Epiteliais e Glandulares/metabolismo Neoplasias Ovarianas/tratamento farmacológico Neoplasias Ovarianas/metabolismo Medicina de Precisão [Mh] Termos MeSH secundário: Adenocarcinoma de Células Claras/diagnóstico Adenocarcinoma de Células Claras/mortalidade Proteína BRCA2 China Intervalo Livre de Doença Feminino Seres Humanos Imuno-Histoquímica Estimativa de Kaplan-Meier Terapia de Alvo Molecular Recidiva Local de Neoplasia Neoplasias Epiteliais e Glandulares/diagnóstico Neoplasias Epiteliais e Glandulares/mortalidade Neoplasias Ovarianas/diagnóstico Neoplasias Ovarianas/mortalidade Receptor do Fator de Crescimento Epidérmico Receptor ErbB-2 Análise de Sobrevida Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (BRCA2 Protein); 0 (BRCA2 protein, human); 0 (Biomarkers, Tumor); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.1 (Receptor, ErbB-2) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180306 [Lr] Data última revisão: 180306 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180112 [St] Status: MEDLINE [do] DOI: 10.3760/cma.j.issn.0529-567x.2017.12.008

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[PMID]: 28743369 [Au] Autor: Phippen NT; Secord AA; Wolf S; Samsa G; Davidson B; Abernethy AP; Cella D; Havrilesky LJ; Burger RA; Monk BJ; Leath CA [Ad] Endereço: Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA. [Ti] Título: Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study. [So] Source: Gynecol Oncol;147(1):98-103, 2017 10. [Is] ISSN: 1095-6859 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC). METHODS: Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis. RESULTS: Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001). CONCLUSIONS: Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC. [Mh] Termos MeSH primário: Neoplasias Epiteliais e Glandulares/psicologia Neoplasias Ovarianas/psicologia Qualidade de Vida [Mh] Termos MeSH secundário: Adulto Fatores Etários Idoso Feminino Seres Humanos Meia-Idade Neoplasias Epiteliais e Glandulares/mortalidade Neoplasias Epiteliais e Glandulares/patologia Neoplasias Ovarianas/mortalidade Neoplasias Ovarianas/patologia Valor Preditivo dos Testes Prognóstico Análise de Regressão Análise de Sobrevida [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 180307 [Lr] Data última revisão: 180307 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170727 [St] Status: MEDLINE

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[PMID]: 29421517 [Au] Autor: Xue J; Li R; Zhao X; Ma C; Lv X; Liu L; Liu P [Ad] Endereço: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, Shandong Province, People's Republic of China. Electronic address: 201620468@mail.sdu.edu.cn. [Ti] Título: Morusin induces paraptosis-like cell death through mitochondrial calcium overload and dysfunction in epithelial ovarian cancer. [So] Source: Chem Biol Interact;283:59-74, 2018 Mar 01. [Is] ISSN: 1872-7786 [Cp] País de publicação: Ireland [La] Idioma: eng [Ab] Resumo: Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological cancers. Morusin, a prenylated flavonoid extracted from the root bark of Morus australis, has been reported to exhibit anti-tumor activity against various human cancers except EOC. In the present study, we explored the potential anti-cancer activity of morusin against EOC in vitro and in vivo and possible underlying mechanisms for the first time. We first found that morusin effectively inhibited EOC cell proliferation and survival in vitro and suppressed tumor growth in vivo. Then we observed that treatment of EOC cells with morusin resulted in paraptosis-like cell death, a novel mode of non-apoptotic programmed cell death that is characterized by extensive cytoplasmic vacuolation due to dilation of the endoplasmic reticulum (ER) and mitochondria and lack of apoptotic hallmarks. In addition, we discovered that morusin induced obvious increase in mitochondrial Ca levels, accumulation of ER stress markers, generation of reactive oxygen species (ROS), and loss of mitochondrial membrane potential (Δψm) in EOC cells. Furthermore, pretreatment with 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS), a chemical inhibitor of voltage-dependent anion channel (VDAC) on the outer mitochondrial membrane, effectively inhibited mitochondrial Ca influx, cytoplasmic vacuolation and cell death induced by morusin in EOC cells. Moreover, DIDS pretreatment also suppressed morusin-induced accumulation of ER stress markers, ROS production and depletion of Δψm. Consistently, tumor xenograft assays showed that co-treatment with DIDS partially reversed the inhibitory effects of morusin on tumor growth in vivo and inhibited the increased levels of ER stress markers induced by morusin in tumor tissues. Collectively, our results suggest that VDAC-mediated Ca influx into mitochondria and subsequent mitochondrial Ca overload contribute to mitochondrial swelling and dysfunction, leading to morusin-induced paraptosis-like cell death in EOC. This study may provide alternative therapeutic strategies for EOC exhibiting resistance to apoptosis. [Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos Cálcio/metabolismo Flavonoides/farmacologia Mitocôndrias/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Antineoplásicos/química Antineoplásicos/farmacologia Antineoplásicos/uso terapêutico Autofagia/efeitos dos fármacos Linhagem Celular Tumoral Estresse do Retículo Endoplasmático/efeitos dos fármacos Feminino Flavonoides/química Flavonoides/uso terapêutico Seres Humanos Potencial da Membrana Mitocondrial/efeitos dos fármacos Camundongos Camundongos Endogâmicos BALB C Camundongos Nus Mitocôndrias/metabolismo Morus/química Morus/metabolismo Neoplasias Epiteliais e Glandulares/tratamento farmacológico Neoplasias Epiteliais e Glandulares/metabolismo Neoplasias Epiteliais e Glandulares/patologia Neoplasias Ovarianas/tratamento farmacológico Neoplasias Ovarianas/metabolismo Neoplasias Ovarianas/patologia Estresse Oxidativo/efeitos dos fármacos Espécies Reativas de Oxigênio/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (Flavonoids); 0 (Reactive Oxygen Species); 62596-29-6 (morusin); SY7Q814VUP (Calcium) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180305 [Lr] Data última revisão: 180305 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180209 [St] Status: MEDLINE

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[PMID]: 28464843 [Au] Autor: Levan K; Mehryar M; Mateoiu C; Albertsson P; Bäck T; Sundfeldt K [Ad] Endereço: Sahlgrenska Cancer Center, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, University of Gothenburg, SE-405 30, Gothenburg, Sweden. kristina.levan@gu.se. [Ti] Título: Immunohistochemical evaluation of epithelial ovarian carcinomas identifies three different expression patterns of the MX35 antigen, NaPi2b. [So] Source: BMC Cancer;17(1):303, 2017 May 02. [Is] ISSN: 1471-2407 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: To characterize the expression of the membrane transporter NaPi2b and antigen targeted by the MX35 antibody in ovarian tumor samples. The current interest to develop monoclonal antibody based therapy of ovarian cancer by targeting NaPi2b emphasizes the need for detailed knowledge and characterization of the expression pattern of this protein. For the majority of patients with ovarian carcinoma the risk of being diagnosed in late stages with extensive loco-regional spread disease is substantial, which stresses the need to develop improved therapeutic agents. METHODS: The gene and protein expression of SLC34A2/NaPi2b were analyzed in ovarian carcinoma tissues by QPCR (n = 73) and immunohistochemistry (n = 136). The expression levels and antigen localization were established and compared to the tumor characteristics and clinical data. RESULTS: Positive staining for the target protein, NaPi2b was detected for 93% of the malignant samples, and we identified three separate distribution patterns of the antigen within the tumors, based on the localization of NaPi2b. There were differences in the staining intensity as well as the distribution pattern when comparing the tumor grade and histology, the mucinous tumors presented a significantly lower expression of both the targeted protein and its related gene. CONCLUSION: Our study identified differences regarding the level of the antigen expression between tumor grade and histology. We have identified differences in the antigen localization between borderline tumors, type 1 and type 2 tumors, and suggest that a pathological evaluation of NaPi2b in the tumors would be helpful in order to know which patients that would benefit from this targeted therapy. [Mh] Termos MeSH primário: Anticorpos Monoclonais/metabolismo Imuno-Histoquímica/métodos Neoplasias Epiteliais e Glandulares/química Neoplasias Ovarianas/química Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/análise [Mh] Termos MeSH secundário: Feminino Seres Humanos Neoplasias Epiteliais e Glandulares/metabolismo Neoplasias Epiteliais e Glandulares/patologia Neoplasias Ovarianas/metabolismo Neoplasias Ovarianas/patologia Ovário/química Ovário/metabolismo Ovário/patologia Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/genética Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Monoclonal); 0 (MX 35 monoclonal antibody); 0 (SLC34A2 protein, human); 0 (Sodium-Phosphate Cotransporter Proteins, Type IIb) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180305 [Lr] Data última revisão: 180305 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170504 [St] Status: MEDLINE [do] DOI: 10.1186/s12885-017-3289-2

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[PMID]: 29298771 [Au] Autor: Melamed A; Fink G; Wright AA; Keating NL; Gockley AA; Del Carmen MG; Schorge JO; Rauh-Hain JA [Ad] Endereço: Division of Gynecologic Oncology, Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA alexander.melamed@mgh.harvard.edu. [Ti] Título: Effect of adoption of neoadjuvant chemotherapy for advanced ovarian cancer on all cause mortality: quasi-experimental study. [So] Source: BMJ;360:j5463, 2018 01 03. [Is] ISSN: 1756-1833 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To estimate the causal effect of increased use of neoadjuvant chemotherapy (NACT) on all cause mortality in advanced epithelial ovarian cancer. DESIGN: Quasi-experimental fuzzy regression discontinuity design and cross sectional analysis. SETTING: Cancer programs throughout the United States accredited by the Commission on Cancer. PARTICIPANTS: 6034 women with a diagnosis of stage 3C or 4 epithelial ovarian cancer from regions that rapidly adopted use of NACT from 2011 to 2012 (27% increase in the New England and east south central regions) or remained unchanged (control regions, south Atlantic, west north central, and east north central regions). MAIN OUTCOME MEASURE: All cause mortality within three years of diagnosis. Kaplan-Meier curves and proportional hazard models were estimated to compare mortality differences between rapidly adopting regions and controls. RESULTS: 1156 women were treated for advanced epithelial ovarian cancer during 2011 and 2012 in the two rapidly adopting regions and 4878 women in the three control regions. In the rapidly adopting regions, patients treated in 2012 compared with 2011 had a mortality hazard ratio of 0.81 (95% confidence interval 0.71 to 0.94) after adjusting for mortality time trends, whereas no difference was observed in control regions (1.02, 0.93 to 1.12). Compared with control regions, larger declines in 90 day surgical mortality (7.0% to 4.0% 5.0% to 4.3%, P=0.01) and in the proportion of women not receiving surgery and chemotherapy (20.0% to 17.4% 19.0 to 19.5%, P=0.04) were observed in rapidly adopting regions. Cross sectional analysis confirmed that treatment in regions with greater use of NACT was associated was lower mortality (P=0.001). CONCLUSIONS: Adoption of NACT for advanced epithelial ovarian cancer in New England and east south central regions led to a sizable reduction in mortality within three years after diagnosis. [Mh] Termos MeSH primário: Quimioterapia Adjuvante Terapia Neoadjuvante Neoplasias Epiteliais e Glandulares/mortalidade Neoplasias Epiteliais e Glandulares/terapia Neoplasias Ovarianas/mortalidade Neoplasias Ovarianas/terapia [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Estudos Transversais Feminino Seres Humanos Estimativa de Kaplan-Meier Modelos Logísticos Meia-Idade Neoplasias Epiteliais e Glandulares/patologia Neoplasias Ovarianas/patologia Modelos de Riscos Proporcionais Taxa de Sobrevida Estados Unidos [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180301 [Lr] Data última revisão: 180301 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 180105 [St] Status: MEDLINE [do] DOI: 10.1136/bmj.j5463

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[PMID]: 29182373 [Au] Autor: Nakajo M; Jinguji M; Shinaji T; Nakajo M; Aoki M; Tani A; Sato M; Yoshiura T [Ad] Endereço: 1 Department of Radiology, Kagoshima University, Graduate School of Medical and Dental Sciences , Kagoshima , Japan. [Ti] Título: Texture analysis of F-FDG PET/CT for grading thymic epithelial tumours: usefulness of combining SUV and texture parameters. [So] Source: Br J Radiol;91(1083):20170546, 2018 Feb. [Is] ISSN: 1748-880X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To retrospectively investigate the standardized uptake value (SUV)-related and heterogeneous texture parameters individually and in combination for differentiating between low- and high-risk Fluorone-fludeoxyglucose ( F-FDG)-avid thymic epithelial tumours (TETs) with positron emission tomography (PET)/CT. METHODS: SUV-related and 6 texture parameters (entropy, homogeneity, dissimilarity, intensity variability, size-zone variability and zone percentage) were compared between 11 low-risk and 23 high-risk TETs (metabolic tumour volume >10.0 cm and SUV ≥2.5). Diagnostic performance was evaluated by receiver operating characteristic analysis. The diagnostic value of combining SUV and texture parameters was examined by a scoring system. RESULTS: High-risk TETs were significantly higher in SUVmax (p = 0.022), entropy (p = 0.038), intensity variability (p = 0.041) and size-zone variability (p = 0.045) than low-risk TETs. Diagnostic accuracies of these 4 parameters, dissimilarity and zone percentage which also showed significance in receiver operating characteristic analysis ranged between 64.7 and 73.5% without significant differences in AUC (range; 0.71 to 0.75) (p ≥ 0.05 each). Each parameter was scored as 0 (negative for high-risk) or 1 (positive for high-risk) according to each threshold criterion, then scores were summed [0 or 1 for low-risk TETs (median; 1); ≥2 for high-risk TETs (median; 4)]. The sensitivity, specificity and accuracy of detecting high-risk TETs were 100, 81.8 and 94.1%, respectively, with an AUC of 0.99. CONCLUSION: The diagnostic performances of individual SUVmax and texture parameters were relatively low. However, combining these parameters can significantly increase diagnostic performance when differentiating between relatively large low- and high-risk F-FDG-avid TETs. Advances in knowledge: Combined use of SUVmax and texture parameters can significantly increase the diagnostic performance when differentiating between low- and high-risk TETs. [Mh] Termos MeSH primário: Neoplasias Epiteliais e Glandulares/diagnóstico por imagem Neoplasias Epiteliais e Glandulares/patologia Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos Neoplasias do Timo/diagnóstico por imagem Neoplasias do Timo/patologia [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Feminino Fluordesoxiglucose F18 Seres Humanos Masculino Meia-Idade Gradação de Tumores Estadiamento de Neoplasias Compostos Radiofarmacêuticos Estudos Retrospectivos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Radiopharmaceuticals); 0Z5B2CJX4D (Fluorodeoxyglucose F18) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180226 [Lr] Data última revisão: 180226 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171129 [St] Status: MEDLINE [do] DOI: 10.1259/bjr.20170546

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[PMID]: 28468520 [Au] Autor: Yang WL; Lu Z; Bast RC [Ad] Endereço: a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA. [Ti] Título: The role of biomarkers in the management of epithelial ovarian cancer. [So] Source: Expert Rev Mol Diagn;17(6):577-591, 2017 Jun. [Is] ISSN: 1744-8352 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Despite advances in surgery and chemotherapy for ovarian cancer, 70% of women still succumb to the disease. Biomarkers have contributed to the management of ovarian cancer by monitoring response to treatment, detecting recurrence, distinguishing benign from malignant pelvic masses and attempting to detect disease at an earlier stage. Areas covered: This review focuses on recent advances in biomarkers and imaging for management of ovarian cancer with particular emphasis on early detection. Relevant literature has been reviewed and analyzed. Expert commentary: Rising or persistent CA125 blood levels provide a highly specific biomarker for epithelial ovarian cancer, but not an optimally sensitive biomarker. Addition of HE4, CA 72.4, anti-TP53 autoantibodies and other biomarkers can increase sensitivity for detecting early stage or recurrent disease. Detecting disease recurrence will become more important as more effective therapy is developed. Early detection will require the development not only of biomarker panels, but also of more sensitive and specific imaging strategies. Effective biomarker strategies are already available for distinguishing benign from malignant pelvic masses, but their use in identifying and referring patients with probable ovarian cancer to gynecologic oncologists for cytoreductive operations must be encouraged. [Mh] Termos MeSH primário: Biomarcadores Tumorais/normas Neoplasias Epiteliais e Glandulares/sangue Neoplasias Ovarianas/sangue [Mh] Termos MeSH secundário: Biomarcadores Tumorais/sangue Diagnóstico Diferencial Diagnóstico Precoce Feminino Seres Humanos Neoplasias Epiteliais e Glandulares/epidemiologia Neoplasias Epiteliais e Glandulares/patologia Neoplasias Ovarianas/epidemiologia Neoplasias Ovarianas/patologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Biomarkers, Tumor) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180225 [Lr] Data última revisão: 180225 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170505 [St] Status: MEDLINE [do] DOI: 10.1080/14737159.2017.1326820

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[PMID]: 29307835 [Au] Autor: Dou YD; Huang T; Wang Q; Shu X; Zhao SG; Li L; Liu T; Lu G; Chan WY; Liu HB [Ad] Endereço: Center for Reproductive Medicine, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, PR China; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, PR China. [Ti] Título: Integrated microRNA and mRNA signatures in peripheral blood lymphocytes of familial epithelial ovarian cancer. [So] Source: Biochem Biophys Res Commun;496(1):191-198, 2018 01 29. [Is] ISSN: 1090-2104 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: PURPOSE: Characterization of the genetic landscapes of familial ovarian cancer through integrated analysis of microRNA and mRNA by partial least squares (PLS) and Monte Carlo technique based on genome-wide association studies (GWAS). METHODS: The miRNA and mRNA transcriptional data in familial ovarian cancer were characterized from the Gene Expression Omnibus (GEO) database. The miRNA and mRNA expression profiles in peripheral blood lymphocytes (PBLs) of 74 familial ovarian cancer patients and 47 control subjects were analyzed with the integration of partial least squares (PLS) and Monte Carlo techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also performed. RESULTS: Total of 16 miRNA-mRNA pairs were identified with the target gene prediction results of miRNAs and mRNAs. An innovated miRNA-mRNA integrated network was constructed in which 6 downregulated miRNAs and 1 upregulated miRNAs were included. KEGG and GO pathway enrichment analysis revealed over-representation of dysregulated miRNAs in various biological processes especially in cancer pathology. Hsa-miR-34b played a pivotal role in this network and interacted with other miRNAs. Hsa-miR-136 and hsa-miR-335 were associated with p53 and Erk1/2 pathways and tumor suppressors, such as PTEN. CONCLUSIONS: The results from this research provide insights on miRNA-mRNA networks and offer new tools for studying transcriptional variants in familial ovarian cancer. [Mh] Termos MeSH primário: Biomarcadores Tumorais/genética Linfócitos/metabolismo MicroRNAs/genética Neoplasias Epiteliais e Glandulares/epidemiologia Neoplasias Epiteliais e Glandulares/genética Neoplasias Ovarianas/epidemiologia Neoplasias Ovarianas/genética RNA Mensageiro/genética [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Biomarcadores Tumorais/sangue China/epidemiologia Feminino Estudos de Associação Genética Marcadores Genéticos/genética Predisposição Genética para Doença/epidemiologia Predisposição Genética para Doença/genética Seres Humanos MicroRNAs/sangue Meia-Idade Neoplasias Epiteliais e Glandulares/diagnóstico Neoplasias Ovarianas/diagnóstico Prevalência RNA Mensageiro/sangue Reprodutibilidade dos Testes Fatores de Risco Sensibilidade e Especificidade Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Biomarkers, Tumor); 0 (Genetic Markers); 0 (MicroRNAs); 0 (RNA, Messenger) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180215 [Lr] Data última revisão: 180215 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180109 [St] Status: MEDLINE

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[PMID]: 29229394 [Au] Autor: Li M; Qian Z; Ma X; Lin X; You Y; Li Y; Chen T; Jiang H [Ad] Endereço: Department of Gynecology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, China. [Ti] Título: MiR-628-5p decreases the tumorigenicity of epithelial ovarian cancer cells by targeting at FGFR2. [So] Source: Biochem Biophys Res Commun;495(2):2085-2091, 2018 01 08. [Is] ISSN: 1090-2104 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Micro RNAs (miRNAs) are small non-coding RNAs which are 19-24 nucleotides in length. MiRNAs play a vital role in the whole process of tumour development, but how they influence the tumourigenecity of epithelial ovarian cancer (EOC)cells is rarely researched. In our study, it was verified that miR-628-5p decreased the stem like cell percentage of EOC cells by inducing their apoptosis. The animal experiments showed that miR-628-5p decreased the tumourigenecity of EOC cells. Besides, we found miR-628-5p targeted at and down-regulated the expression of fibroblast growth factor receptor 2 (FGFR2). FGFR2 expressed higher in ovarian cancer tissues and was correlated with worse prognosis. Our findings indicated that miR-628-5pplays an important role in ovarian cancer stem cell driven tumorigenesis. [Mh] Termos MeSH primário: Carcinogênese/metabolismo MicroRNAs/metabolismo Neoplasias Epiteliais e Glandulares/metabolismo Neoplasias Epiteliais e Glandulares/patologia Células-Tronco Neoplásicas/metabolismo Células-Tronco Neoplásicas/patologia Neoplasias Ovarianas/metabolismo Neoplasias Ovarianas/patologia Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo [Mh] Termos MeSH secundário: Apoptose Linhagem Celular Tumoral Seres Humanos [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (MIRN628 microRNA, human); 0 (MicroRNAs); EC 2.7.10.1 (FGFR2 protein, human); EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180214 [Lr] Data última revisão: 180214 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171213 [St] Status: MEDLINE

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