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1.
Cancer Med ; 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31851786

RESUMO

BACKGROUND: Definitive chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients have demonstrated great variations in their responses to dCRT and inevitably progressed following treatment. METHODS: To identify prognostic biomarkers, we performed targeted next-generation sequencing of 416 cancer-related genes on primary tumors from 47 nonsurgical ESCC patients prior to dCRT treatment. The association between genetic alterations and patients' local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) was analyzed. RESULTS: TP53 (78% of patients), NOTCH1 (32%), ARID1A (13%), FAT1 (13%), and CDKN2A (13%) were commonly mutated in ESCC patients, while gene amplifications frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%), and YAP1 (11%). Univariate and multivariate analyses of clinical factors and genetic alterations indicated that sex is an independent prognostic factor, with males tending to have better LRFS (hazard ratio [HR], 0.25; 95%CI, 0.08-0.77, P = .015) and progression-free survival (PFS) (HR, 0.35; 95%CI, 0.13-0.93, P = .030) following dCRT. Meanwhile, YAP1 amplification (n = 7) was an adverse prognostic factor, and patients with this alteration demonstrated a tendency toward worse outcomes with shorter LRFS (HR, 4.06; 95%CI, 1.26-13.14, P = .019) and OS (HR, 2.78; 95%CI, 0.95-8.17, P = .062). In a subgroup analysis, while sex and M-stage were controlled, a much stronger negative effect of YAP1 amplification vs wild-type in LRFS was observed (log-rank P = .0067). CONCLUSION: The results suggested that YAP1 amplification is a potentially useful biomarker for predicting treatment outcomes and identifying patients with a high risk of relapse who should be closely monitored.

2.
Gigascience ; 6(7): 1-7, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28637269

RESUMO

Bamboo and rattan are widely grown for manufacturing, horticulture, and agroforestry. Bamboo and rattan production might help reduce poverty, boost economic growth, mitigate climate change, and protect the natural environment. Despite progress in research, sufficient molecular and genomic resources to study these species are lacking. We launched the Genome Atlas of Bamboo and Rattan (GABR) project, a comprehensive, coordinated international effort to accelerate understanding of bamboo and rattan genetics through genome analysis. GABR includes 2 core subprojects: Bamboo-T1K (Transcriptomes of 1000 Bamboos) and Rattan-G5 (Genomes of 5 Rattans), and several other subprojects. Here we describe the organization, directions, and status of GABR.


Assuntos
Calamus/genética , Bases de Dados Genéticas , Genoma de Planta , Melhoramento Vegetal , Sasa/genética , Evolução Molecular , Anotação de Sequência Molecular
3.
Onco Targets Ther ; 9: 4561-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27524911

RESUMO

OBJECTIVE: To make an informed choice of chemotherapy drugs according to the oncogene mRNA expression and to explore whether it could increase the survival rate of patients. PATIENTS AND METHODS: The study retrospectively analyzed 36 cases of nonsurgical esophageal squamous cell carcinoma patients treated at the Center for Oncology of Shandong Provincial Hospital from December 1, 2010, to November 1, 2013. Intensity-modulated radiation therapy was used for the treatment with a conventional radiotherapy dose of 60-66 Gy. Chemotherapy started 1-5 weeks after radiation therapy. The selection of the chemotherapy drug was based on the mRNA expression levels of excision repair cross-complementation 1, thymidylate synthetase, ribonucleotide reductase M1, and ß-tubulin isotype III. The objective response rate, progression-free survival, and overall survival were observed. RESULTS: The reason for poor prognosis of patients with high expression of excision repair cross-complementation 1 was unknown. No correlation was observed between patient survival and expression of thymidylate synthetase, ribonucleotide reductase M1, and ß-tubulin isotype III. Complete response, partial response, stable disease, and progressive disease were observed in 25, five, three, and three patients, respectively. The objective response rate was 83.3%. The 1-year, 2-year, and 3-year progression-free survival rates were 79.8%, 58.9%, and 54.4%, respectively. The 1-year, 2-year, and 3-year overall survival rates were 83.3%, 68.1%, and 58.4%, respectively. CONCLUSION: Selecting the chemotherapy drug according to the oncogene expression, combined with radiation therapy, could increase the 3-year survival rate in nonsurgical esophageal squamous cell carcinoma patients. Such conclusion needs to be further confirmed using a larger sample size.

4.
J Thorac Oncol ; 11(9): 1565-73, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27223457

RESUMO

INTRODUCTION: The current pathologic nodal classification (pN) based on anatomic location of involved lymph nodes (LNs) is unsatisfactory in distinguishing heterogeneous pN1 or pN2 non-small cell lung cancer (NSCLC). For the first time we comprehensively compared the prognostic significance of the number of positive LNs (nN), the ratio of the number of positive to removed LNs (LN ratio [LNR]), the combination of pN and nN (pN-nN), the combination of pN and LNR (pN-LNR), and pN to identify a superior classification. METHODS: We identified 700 patients with pN1 (n = 203) or pN2 (n = 497) NSCLC. We classified the patients into four nN categories (nN1, nN2, nN3-6, and nN≥7), four pN-nN categories (pN1-nN1-2, pN1-nN≥3, pN2-nN1-6, and pN2-nN≥7); four LNR categories (LNR≤0.05, 0.1≥LNR>0.05, 0.4≥LNR>0.1, and LNR>0.4), and four pN-LNR categories (pN1-LNR<0.1, pN1-LNR≥0.1, pN2-LNR<0.4, and pN2-LNR≥0.4). The log-rank test was used to analyze differences among groups, and Cox regression was used to evaluate relationships between each classification and survival. RESULTS: In adjusted analyses, pN-LNR was an independent prognostic factor for patients with pN1 or pN2 NSCLC, as were pN-nN, LNR, nN, and pN. pN-LNR was prognostically superior to the other four classifications. Postoperative radiotherapy (PORT) was an independent prognostic factor for pN2 NSCLC. Analyses stratified by LNR showed that PORT did not improve survival in patients with pN2-LNR<0.14 NSCLC, whereas significantly improved survival times in pN2-LNR≥0.14 NSCLC. CONCLUSIONS: We propose a potential revised nodal classification, pN-LNR, to further stratify patients with pN1 or pN2 NSCLC into subgroups so as to more precisely predict survival and help tailor individualized postoperative treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
5.
Thorac Cancer ; 6(3): 346-53, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26273382

RESUMO

BACKGROUND: To establish a prediction model in selecting fit patients with resected pIIIA-N2 non-small cell lung cancer (NSCLC) for postoperative radiotherapy (PORT), and evaluate the model in clinical practice. METHODS: Between January 2003 and December 2005, 221 patients with resected pIIIA-N2 NSCLC were retrospectively analyzed. The effect of PORT on overall survival (OS) of patients with different clinicopathological factors was evaluated and the results were used to establish a prediction model to select patients fit for PORT. RESULTS: Compared with the control, PORT significantly improved the OS of patients with a smoking index ≤400 (P = 0.033), cN2 (P = 0.003), pT3 (P = 0.014), squamous cell carcinoma (SCC) (P = 0.013), or ≥4 positive nodes (P = 0.025). Patients were divided from zero to all five factors into low, middle, and high PORT index (PORT-I) groups (scored 0-1, 2, and 3-5, respectively). PORT did not improve OS (3-year, P = 0.531), disease free survival (DFS) (P = 0.358), or loco-regional recurrence free survival (LRFS) (P = 0.412) in the low PORT-I group. PORT significantly improved OS (P = 0.033), and tended to improve DFS (P = 0.064), but not LRFS (P = 0.287) in the middle PORT-I group. PORT could significantly improve OS (P = 0.000), DFS (P = 0.000), and LRFS (P = 0.006) in the high PORT-I group. CONCLUSION: The prediction model is valuable in selecting patients with resected pIIIA-N2 NSCLC fit for PORT. PORT is strongly recommended for patients with three or more of the five factors of smoking index ≤400, cN2, pT3, SCC, and ≥4 positive nodes.

6.
Lung Cancer ; 85(3): 339-45, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25043903

RESUMO

BACKGROUND: This meta-analysis was performed to assess whether epidermal growth factor receptor (EGFR) mutation status was associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy. METHOD: We systematically identified eligible articles investigating the effects of chemotherapy in patients with NSCLC stratified by EGFR mutation status. The summary risk ratio (RR) for ORR and hazard ratios (HRs) for both PFS and OS were calculated using the inverse variance formula of meta-analysis. RESULTS: Identification for the current meta-analysis: 5 prospective studies (n=875) and 18 retrospective studies (n=1934) for ORR; 2 prospective studies (n=434) and 10 retrospective studies (n=947) for PFS; 2 prospective studies (n=438) and 7 retrospective studies (n=711) for OS. The ORR was significantly higher in patients with EGFR mutations in prospective studies (RR=1.42; 95% confidence interval [CI], 1.16-1.74; P=0.001), but not in retrospective studies (RR=1.12; 95% CI, 0.96-1.32; P=0.146). There was no obvious association between EGFR mutations and PFS both in prospective (HR=0.84; 95% CI: 0.65-1.09; P=0.197) and retrospective (HR=1.02; 95% CI: 0.87-1.18; P=0.838) studies. Association between EGFR mutations and OS was also not seen in prospective studies (HR=0.74; 95% CI: 0.27-2.05; P=0.566), but was seen in retrospective studies (HR=0.48; 95% CI: 0.33-0.72; P<0.001; I(2)=75.9%; P<0.001) with significant heterogeneity. CONCLUSION: EGFR mutations in advanced NSCLC may be associated with higher ORRs to chemotherapy, but may have nothing to do with PFS and OS. Further prospective studies are required to identify the influence of EGFR mutations on chemotherapy effects in advanced NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Razão de Chances , Viés de Publicação , Resultado do Tratamento
7.
Radiat Oncol ; 7: 119, 2012 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-22846375

RESUMO

BACKGROUND: Brain metastases (BM) is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC) after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI) has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2) NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. METHODS: Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan-Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. RESULTS: Fifty-three (24.4 %) patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86-9.19; P = 0.001) and the ratio of metastatic to examined nodes or lymph node ratio (LNR) ≥ 30 % (RR: 3.33, 95 % CI: 1.79-6.18; P = 0.000) were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. CONCLUSIONS: In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores de Risco
8.
Oncologist ; 16(5): 641-50, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21482587

RESUMO

BACKGROUND: For patients with resected pathological stage IIIA-N2 non-small cell lung cancer (NSCLC), the role of postoperative radiotherapy (PORT) is not well defined. In this single-institutional study, we re-evaluated the effect of PORT on overall survival (OS) as well as tumor control in this subgroup of patients. METHODS: In 2003-2005, 221 consecutive patients with resected pathological stage IIIA-N2 NSCLC at our institution were retrospectively analyzed in an institutional review board-approved study. The effect of PORT on OS, cancer-specific survival (CSS), and disease-free survival (DFS) was evaluated using the Kaplan-Meier method and log-rank tests. The impact of PORT on locoregional control and distant metastasis was also analyzed. Results. Compared with the control, patients treated with PORT had a significantly longer OS time (χ2, 3.966; p = .046) and DFS interval (χ2, 6.891; p = .009), as well as a trend toward a longer CSS duration (χ2, 3.486; p = .062). Patients treated with PORT also had a significantly higher locoregional recurrence-free survival rate (χ2, 5.048; p = .025) as well as distant metastasis-free survival rate (χ2, 11.248; p = .001). Multivariate analyses showed that PORT was significantly associated with a longer OS duration (p = .000). CONCLUSIONS: PORT can significantly improve the survival of patients with resected pathological stage IIIA-N2 NSCLC. A prospective randomized multicenter clinical trial is ongoing.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Análise de Sobrevida
9.
Eur J Haematol ; 86(1): 67-74, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21039888

RESUMO

OBJECTIVES: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which anti-platelet antibodies induce platelet destruction owing to an imbalanced immune response. Several studies have established that B cells play an important role in the production of anti-platelet antibodies and that dendritic cells (DC) are professional antigen-presenting cells of the immune system that may lead to the development of autoantibody through B cells. We aimed at investigating the role of B cells and DC in the pathogenesis of ITP through B-lymphocyte stimulator (BlyS) and toll-like receptor 7 (TLR7) signals. METHODS: Twenty-two patients with ITP and 20 healthy controls were enrolled in this study. Serum BlyS, its mRNA and TLR7 mRNA were measured using ELISA kits or RT-PCR, and CD14(+) or CD19(+) monocytes were investigated for the pathogenesis of ITP with in vitro culture systems. RESULTS: We demonstrated that serum BlyS levels in patients with ITP were significantly higher than those in healthy controls and that there was a positive correlation between serum BlyS levels and glycoprotein-specific antibody levels in patients with ITP. We found that TLR7 regulates dendritic cell-dependent B-cell responses through BlyS in patients with ITP. Dendritic cells stimulated with R848 (TLR7 ligand) are able to produce vast amounts of BlyS, which is crucial for B-cell survival, proliferation and differentiation, and increase anti-platelet antibodies production in in vitro coculture systems. CONCLUSIONS: These findings provide new insights into the pathogenesis of ITP by which TLR7 regulates DC-dependent B-cell responses through BlyS.


Assuntos
Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Células Dendríticas/imunologia , Púrpura Trombocitopênica Idiopática/etiologia , Receptor 7 Toll-Like/imunologia , Células Apresentadoras de Antígenos/patologia , Autoanticorpos/sangue , Fator Ativador de Células B/sangue , Fator Ativador de Células B/genética , Linfócitos B/patologia , Estudos de Casos e Controles , Células Cultivadas , Glicoproteínas/imunologia , Monócitos/patologia , Púrpura Trombocitopênica Idiopática/imunologia , RNA Mensageiro/análise , Receptor 7 Toll-Like/genética
10.
Chin Med J (Engl) ; 120(2): 125-31, 2007 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-17335654

RESUMO

BACKGROUND: The outcome of surgical treatment of non-small-cell lung cancer (NSCLC) remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. (18)F-fluoro-2-deoxy-glucose ((18)F-FDG) uptake on positron-emission tomography (PET) is associated with the aggressiveness of NSCLC. The present study focused on the role of (18)F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC. METHODS: A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value (SUV(max)), in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients' recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUV(max) and other factors was also analyzed. RESULTS: Patients with SUV(max) more than 11 had a disease-free survival and overall survival shorter than patients with SUV(max) less than 11 in univariate analyses (P < 0.001, P = 0.002). In the multivariate analysis, SUV(max) (dichotomized by 11) was the only significant predictor for tumor recurrence. TNM stage and SUV(max) (dichotomized by 11) were independent predictors for the overall survival. Associations of SUV(max) with p53 overexpression, proliferating cell nuclear antigen (PCNA) labeling index and microvascular density of the tumor were significant in the entire group. CONCLUSIONS: (18)F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Cintilografia
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