RESUMO
PURPOSE: The significance of the Risk of Ovarian Malignancy Algorithm (ROMA) in differentiating benign and malignant ovarian lesions has been evidenced. In our clinical work, we found that advanced ovarian cancer were accompanied commonly with high ROMA scores. Thus, this study aimed to clarify the performance of ROMA in different disease stage of epithelial ovarian cancer (EOC) prior to surgery. METHODS: Carbohydrate antigen (CA125) and human epididymis protein 4 (HE4) levels and ROMA scores in 221 patients with FIGO stage I, II or III/IV stage EOC were analyzed. The positive rates of CA125, HE4 and ROMA at each disease stage were calculated. Their cutoff values, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for distinguishing patients with FIGO stage I/II from those with FIGO stage III/IV were estimated via ROC curves. RESULTS: Serum CA125 and HE4 levels and ROMA scores rose significantly with advancing stage. ROMA and CA125 were significantly elevated more frequently in comparing with HE4 in EOC patients at with the same stage. Based on ROC curves, the cutoff values for FIGO stage III/IV EOC were 110 IU/mL, 126 pmol/L, 78 and 68% for CA125, HE4, premenopausal and postmenopausal ROMA, respectively. ROMA was the strongest predictor of FIGO stage, with the highest specificity, accuracy, and PPV, which were 84.4, 82.5, and 87.0% for postmenopausal patients, 89.3, 85.6, and 74.3% for premenopausal patients. CONCLUSIONS: Our data suggest high ROMA scores correlated with advanced ovarian cancer prior to surgery. These observations suggest potential utility of ROMA in the comprehensively preoperative evaluation of EOC patients.
Assuntos
Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/sangue , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Algoritmos , Antígeno Ca-125/sangue , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Cuidados Pré-Operatórios , Proteínas/análise , Curva ROC , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos , Adulto JovemRESUMO
PURPOSE: Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide. Although therapeutic strategies for GC have improved, the prognosis for advanced GC remains poor. Herein, the present study sought to design a personalized cancer therapy specific to a stage III GC patient. METHODS: The tumor was surgically removed and was used to establish a patient-derived tumor xenograft (PDTX) model utilizing nude mice. Various molecular-targeted anticancer treatments were tested in the study, including control (no treatment), bevacizumab, cetuximab, bevacizumab + cetuximab, trastuzumab, and trastuzumab + cetuximab. RESULTS: Trastuzumab + cetuximab treatment exhibited the best antitumor growth effect, followed by trastuzumab, bevacizumab + cetuximab, cetuximab, and bevacizumab. Similarly, trastuzumab + cetuximab was also the most effective treatment at inducing apoptosis and cell cycle arrest in primary cultures of the patient's gastric cancer cells. Among all treatments tested in the study, trastuzumab + cetuximab showed the most profound effect in reducing the protein expression of proliferation and metastatic markers (VEGF, MMP-7, EGFT, Ki-67 and, PCNA) in tumors obtained from PDTX models, which may be the mechanism underlying the profound antitumor growth effect exerted by trastuzumab + cetuximab. CONCLUSIONS: The data indicate that trastuzumab + cetuximab combinational therapy should be the most effective antitumor growth therapy for the GC patient whom we took the cancer cells from.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Neoplasias Gástricas/prevenção & controle , Idoso , Animais , Western Blotting , Cetuximab/administração & dosagem , Citometria de Fluxo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/patologia , Trastuzumab/administração & dosagem , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Gastric cancer (GC) is a prevalent disease with a high mortality rate, especially in developing countries. Accumulating evidence suggests that single nucleotide polymorphisms in microRNA (miRNA) genes might influence the susceptibility to GC; such sequence variation might contribute to the development of disease by altering crucial cellular pathways. In this study, we assessed the correlation between the miR-146a G>C, miR-196a-2 C>T, miR-499 T>C, miRNA-27a A>G, and miRNA-149 T>C polymorphisms and the susceptibility to GC. A comprehensive literature search for relevant studies published prior to August 2014 was conducted using PubMed/Medline, Embase, Web of Science, the Cochrane Library, and CNKI databases along with Google Scholar. Meta-analysis was performed using odds ratios (ORs) and 95% confidence intervals (CIs) as effect measures, incorporating 19 studies encompassing 8285 patients and 10,716 controls. Allelic, dominant, recessive, homozygous, and heterozygous genetic models were examined. Pooled results showed that none of the five polymorphisms studied were statistically related to GC. Stratified analyses by ethnicity and source of controls were conducted for miR- 146a G>C and miR-196a-2 C>T. Subgroup analysis suggested that the miR-146a G allele might increase the risk of GC in hospital-based case-control (HCC) but not in population-based case-control studies (HCC: recessive model: OR = 1.23, 95%CI = 1.10-1.37, P < 0.001; heterozygous model: OR = 1.19, 95%CI = 1.06-1.34, P = 0.004). Overall, this meta-analysis failed to detect an association between five common miR-146a gene polymorphisms and GC susceptibility. However, this does not necessarily completely rule out a correlation between miRNA polymorphisms and GC susceptibility.