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Aging (Albany NY) ; 11(19): 8474-8483, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584009


INTRODUCTION: We aimed to characterize the expression of major facilitator superfamily domain-containing protein 2A (MFSD2A) in hepatocellular carcinoma (HCC) patients and analyze its prognostic value. RESULTS: Immunohistochemistry revealed that low expression of MFSD2A was present in 37 of 79 cases (46.84%), which was significantly correlated with poor histological differentiation (P = 0.012). The plasma MFSD2A level in HCC patients was significantly lower than in healthy controls (P = 0.0079) and controls with chronic hepatitis B virus (HBV) infection (P = 0.0430). Moreover, patients with lower MFSD2A expression had shorter survival than higher expression (P = 0.021). Multivariate analysis revealed that MFSD2A was an independent prognostic predictor for HCC patients (P = 0.027). CONCLUSION: The current study indicate MFSD2A may be an optimal diagnostic and prognostic biomarker for HCC. METHODS: First, we examined MFSD2A expression in 24 paired HCC and nontumorous tissues by real-time quantitative PCR (RT-qPCR). Second, the protein levels of MFSD2A in 11 paired HCC and nontumorous tissues were investigated by western blotting (WB). Moreover, MFSD2A protein expression was evaluated by immunohistochemistry in 79 HCC patients. In addition, we detected the plasma level of MFSD2A in HCC patients and healthy individuals and investigated the relationship between MFSD2A expression and clinicopathological parameters or prognosis of HCC patients.

N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573


BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; number, NCT01872962.).

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem
Transl Oncol ; 11(4): 1007-1011, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29966863


The maximum tolerated dose (MTD) of lobaplatin as a single agent chemotherapy concurrent with intensity-modulated radiotherapy (IMRT) in Asian population with nasopharyngeal carcinoma (NPC) remains unclear. From June 2016 to December 2017, 17 patients diagnosed with stage III-IVb NPC from an Asian population were prospectively enrolled. Patients were administered lobaplatin with 25-50 mg/m2 escalation of dosage on day 1. Every 21 days (days 1, 22, and 43) during radiotherapy, cycles were repeated. We administered radiotherapy as 2.12-2.27 Gy per fraction with five daily fractions each week for 6 to 7 weeks. The evaluation of lobaplatin-related toxic effects was based on the Common Terminology Criteria for Adverse Events version 4.0. During the weekly treatment period, complete blood counts and biochemistry were performed. Dose-limiting toxicities (DLTs) were determined by the following events during any cycle in which lobaplatin was administered. Each dose group consisted of at least three cases. We proceeded to the subsequent dose group in the absence of DLT with a dose increment of 5 mg/m2 until DLT occurred. Periods from 1 week prior to the chemotherapy initiation to 3 weeks after the last chemotherapy were defined as DLT observation periods. MTD was determined by the dose that was immediately below the dose that produced DLT. After analysis, DLT occurred in three patients, including a group with two of three patients in 45 mg/m2 lobaplatin and another group with one of five patients in 40 mg/m2 lobaplatin. No grade 3-4 toxicity was observed in patients treated with lobaplatin <40 mg/m2. The tumor response rate at 12 weeks after treatment was 100%. In summary, lobaplatin concurrent with IMRT was active in stage III-IVb NPC, and the MTD for the lobaplatin as single-agent chemotherapy was 40 mg/m2 when combined with IMRT in an Asian population. This trial is registered with, number NCT03188497.

Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(2): 510-516, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28446303


OBJECTIVE: To investigate the survival status and prognosis of patients with essential thrombocythemia(ET) and analyze the prognostic factors for the patients' survival, so as to provide a evidence for clinical treatment and prognosis evaluation. METHODS: A retrospective analysis of 118 patients with ET was conducted in the Fifth Affiliated Hospital of Sun Yat-Sen University and Zhongshan Municipale People's Hospital from December 2002 to December 2013. The clinical characteristics were summarized, such as the survival curve and multi-factor analysis, therefore looking for the disease characteristics and risk factors affecting the survival and prognosis. RESULTS: Among 118 ET patients enrolled in this study, the survival rate of ET patients for 1, 3, 5 and 10 years were 95.5%,92.6%,89% and 81.6%, respectively. Kaplan-Meier survival curve showed that the age ≥60 years old at diagnosis, cardiovascular risk factors, anamnesis of thrombosis or hemorrhage, anemia(hemoglobin<120 g/L), thrombocythemia (≥1 000×109/L), risk stratification and hydroxyurea or HHT(hemoharringtonine) use in high-risk group were factors affecting the suvival rate, 7 out of those factors influencing survival rate were statistically significant (P<0.05). COX regression analysis showed that independent risk factors affecting survival have not yet been found. CONCLUSION: ET patients display a high survival rate and long survival time, and their conversion risk into the marrow fibrosis or leukemia has been found to be low. The age≥60 years old at diagnosis, cardiovascular risk factors, anamnesis of thrombosis or hemorrhage, anemia and therombocythemia are the risk factors affecting prognosis. The use of hydroxyurea or HHT in high-risk group can improve the prognosis.

Trombocitemia Essencial/patologia , Trombocitose , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
J Cell Biochem ; 113(7): 2268-78, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22334501


Early diagnosis and treatment is known to improve prognosis for nasopharyngeal carcinoma (NPC). The study determined the specific peptide profiles by comparing the serum differences between NPC patients and healthy controls, and provided the basis for the diagnostic model and identification of specific biomarkers of NPC. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can be used to detect the molecular mass of peptides. Mass spectra of peptides were generated after extracting and purification of 40 NPC samples in the training set, 21 in the single center validation set and 99 in the multicenter validation set using weak cationic-exchanger magnetic beads. The spectra were analyzed statistically using FlexAnalysis™ and ClinProt™ bioinformatics software. The four most significant peaks were selected out to train a genetic algorithm model to diagnose NPC. The diagnostic sensitivity and specificity were 100% and 100% in the training set, 90.5% and 88.9% in the single center validation set, 91.9% and 83.3% in the multicenter validation set, and the false positive rate (FPR) and false negative rate (FNR) were obviously lower in the NPC group (FPR, 16.7%; FNR, 8.1%) than in the other cancer group (FPR, 39%; FNR, 61%), respectively. So, the diagnostic model including four peptides can be suitable for NPC but not for other cancers. FGA peptide fragments identified may serve as tumor-associated biomarkers for NPC.

Biomarcadores Tumorais/sangue , Fibrinogênio/análise , Neoplasias Nasofaríngeas/diagnóstico , Peptídeos/sangue , Adulto , Sequência de Aminoácidos , Carcinoma , Feminino , Humanos , Fenômenos Magnéticos , Nanopartículas de Magnetita , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos