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Chronobiol Int ; 36(12): 1723-1732, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31609143


We investigated the relationship between head and neck squamous cell carcinoma (HNSCC) and the mRNA and protein expression levels of the circadian genes of the Period (Per) family, Per1, Per2 and Per3. Tissue sections of HNSCC and normal head and neck tissues from two patient cohorts from two different hospitals were collected to assess the mRNA and protein expressions of the three Per family genes using real-time quantitative PCR (RT-PCR) and immunohistochemistry (IHC). The clinicopathological features and disease prognosis for the latter cohort were analyzed through IHC and statistical methods. Protein positive expression levels of the three Per family genes in HNSCC tissues was found to be approximately two times lower than that in normal tissues (p < .01). Moreover, patients with locally advanced HNSCC showed significantly greater downregulation of Per1, Per2 and Per3 mRNA expression levels as compared to patients with early-stage cancer (p < .05). Immunohistochemical examination of HNSCC patient tissues revealed a positive correlation between the Per family protein expression and the clinical tumor staging (p < .05). In addition, the Per protein-positive expression group showed higher 3-year survival rates [overall survival (OS) and progression-free survival (PFS)] as assessed by Kaplan-Meier plots and statistical analysis (p < .05). Our findings confirm the positive correlation between Per family gene expression and survival outcomes and support their role as prognostic markers for HNSCC.

Int J Biol Sci ; 15(7): 1396-1403, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337970


Dendritic cells (DCs) are the most potent specialized antigen-presenting cells as now known, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. Immunologically, the motilities and T cell activation capabilities of DCs are closely related to the resulting immune responses. However, due to the complexity of the immune system, the dynamic changes in the number of cells during the peripheral tissue (e.g. skin and mucosa) immune response induced by DCs are still poorly understood. Therefore, this study simulated dynamic number changes of DCs and T cells in this process by constructing several ordinary differential equations and setting the initial conditions of the functions and parameters. The results showed that these equations could simulate dynamic numerical changes of DCs and T cells in peripheral tissue and lymph node, which was in accordance with the physiological conditions such as the duration of immune response, the proliferation rates and the motilities of DCs and T cells. This model provided a theoretical reference for studying the immunologic functions of DCs and practical guidance for the clinical DCs-based therapy against immune-related diseases.

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
J Cancer Res Ther ; 14(7): 1613-1619, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30589048


Purpose: The aim of this study was to evaluate the efficacy and toxicities of induction chronomodulated chemotherapy in comparison with conventional induction chemotherapy for nasopharyngeal carcinoma (NPC). Patients and Methods: Between 2003 and 2004, 60 patients with pathologically confirmed NPC were included and randomly assigned to two groups. Patients in the chronomodulated chemotherapy group (n = 30, CC group) received cisplatin at 80 mg/m2 through intravenous infusion from 10:00 to 22:00 and 5-fluorouracil (5-FU) at 1000 mg/m2 plus citrovorum factor at 200 mg/m2 from 22:00 to 10:00 each day for 3 days. Patients in the routine chemotherapy group (n = 30, RC group) received cisplatin infusion within 1 h and 5-FU infusion for about 24 h. The dose in the RC group was the same as that in the CC group. The total irradiation dose in each group was 70 Gy for the whole nasopharynx. Results: One month after induction chemotherapy, the overall response rate was 96.7% in the CC group versus 73.3% in the RC group (P = 0.011). By the end of the 10-year follow-up, 11 patients (36.7%) in the CC group had experienced local recurrence versus 11 patients (36.7%) in the RC group (P > 0.999). The overall survival rates at 1, 5, and 10 years were 96.7%, 53.3%, and 43.3%, respectively, in the CC group, and 96.7%, 43.3%, and 33.3%, respectively, in the RC group (P = 0.346). During induction chemotherapy, the incidence rates of leukocytopenia (43.3% vs. 80%, P = 0.003), thrombocytopenia (26.7% vs. 56.7%, P = 0.018), and nausea/vomiting (40% vs. 66.7%, P = 0.038) were significantly lower in the CC group than in the RC group. The incidence of radiation-induced complications was similar in these two groups. Conclusion: Compared with conventional chemotherapy, induction chrono-chemotherapy seemed to reduce chemotherapy-related toxicities and improve average local relapse time in patients treated with combined chemoradiotherapy for NPC.

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/terapia , Radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/mortalidade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Radioterapia/efeitos adversos , Radioterapia/métodos , Recidiva , Resultado do Tratamento
Int J Mol Sci ; 17(11)2016 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-27809226


Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation and functional maturation of DCs. To elucidate the potential mechanisms of DC dysfunction induced by VEGF, the effects of VEGF on the biophysical characteristics and motility of human mature DCs (mDCs) were investigated. The results showed that VEGF had a negative influence on the biophysical properties, including electrophoretic mobility, osmotic fragility, viscoelasticity, and transmigration. Further cytoskeleton structure analysis by confocal microscope and gene expression profile analyses by gene microarray and real-time PCR indicated that the abnormal remodeling of F-actin cytoskeleton may be the main reason for the deterioration of biophysical properties, motility, and stimulatory capability of VEGF-treated mDCs. This is significant for understanding the biological behavior of DCs and the immune escape mechanism of tumors. Simultaneously, the therapeutic efficacies may be improved by blocking the signaling pathway of VEGF in an appropriate manner before the deployment of DC-based vaccinations against tumors.

Fenômenos Biofísicos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Citoesqueleto/metabolismo , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Actinas/metabolismo , Apoptose/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Elasticidade , Eletroforese , Perfilação da Expressão Gênica , Ontologia Genética , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fragilidade Osmótica/efeitos dos fármacos , Pseudópodes/efeitos dos fármacos , Pseudópodes/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Migração Transendotelial e Transepitelial/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Viscosidade