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1.
Front Oncol ; 9: 1319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828041

RESUMO

Background: ALK and ROS1 rearrangement accounts for 3-6% and 1-3% of non-small cell lung cancers, respectively, while coexistence of them in the same patient is extremely rare. Only three cases have ever been reported with concurrent ALK/ROS1 fusions in the same tumor indicating tumor heterogeneity. Therefore, comprehensive genetic profiling via next-generation sequencing (NGS) is needed to provide fully molecular diagnosis. Case Presentation: A 50-year old Chinese female with resectable stage IB bilateral lung adenocarcinomas (ADCs) harbored EML4 exon 6-ALK exon 19 and TPM3 exon 8-ROS1 exon 35 fusions in the right lower and the left upper tumors, respectively, identified by clinical NGS test targeting 425 cancer-relevant genes. The results were further confirmed at RNA level using RNA-seq. Genomic evolution analysis reveals that these bilateral tumors are synchronous multiple primary lung cancers with no shared somatic alterations for both genes and arm-level copy number variations (CNVs). No recurrence was observed during 12 months of post-surgery follow-up. Conclusions: Our case is the first report of concurrent ALK/ROS1 fusions as distinct driver events of synchronous multiple primary lung cancers, and highlights the importance of individual genetic testing for each of the multiple primary tumors for fully molecular diagnosis and precise treatment decision-making.

2.
Acta Otolaryngol ; 139(2): 172-177, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30734627

RESUMO

BACKGROUND: Studies have shown mixed results on the role of postoperative adjuvant radiotherapy (PORT) in surgically managed locally advanced laryngeal cancer. OBJECTIVES: The aim of this study is to review and investigate the role of PORT in patients with locally advanced laryngeal cancer using meta-analysis. MATERIALS AND METHODS: Relevant studies were searched using PubMed and eligible information has been extracted. Then, meta-analysis of hazard ratio (HR) was performed to evaluate the role of PORT in locally advanced laryngeal cancer. RESULTS: This meta-analysis included 7 published studies containing 2007 patients. For overall survival (OS), patients of locally advanced laryngeal cancer who were treated with PORT have a combined hazard ratio (HR) of 0.67 with 95%CI (0.56, 0.79), compared to those who were not treated with PORT, which was significantly associated with better survival. PORT was also associated with a better disease-free survival (DFS) and local control rate (LCR) in patients with locally advanced laryngeal cancer. The pooled HR and 95%CI for DFS and LCR were 0.72 (0.53, 0.99) and 0.29 (0.09, 0.99), respectively. CONCLUSIONS AND SIGNIFICANCE: This study suggested that PORT could improve the survival of patients with surgically managed locally advanced laryngeal cancer.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/radioterapia , Idoso , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Papel (figurativo) , Análise de Sobrevida , Resultado do Tratamento
3.
Asian Pac J Cancer Prev ; 16(14): 6123-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26320506

RESUMO

BACKGROUND: The aim of this study was to analyze the prognostic implications of pretreatment circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs) for the survival of patients with lung cancer. MATERIALS AND METHODS: Relevant literature was identified using Medline and EMBASE. Patient clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CEC and CEPC positive rates before treatment were extracted. STATA 12.0 was used for our analysis and assessment of publication bias. RESULTS: A total of 13 articles (8 for CEC and 5 for CEPC, n=595 and n=244) were pooled for the global meta-analysis. The odds ratio (OR) for OS predicted by pretreatment CECs was 1.641 [0.967, 2.786], while the OR for PFS was 1.168 [0.649, 2.100]. The OR for OS predicted by pretreatment CEPCs was 12.673 [5.274, 30.450], while the OR for PFS was 4.930 [0.931, 26.096]. Subgroup analyses were conducted according to clinical staging. Odds ratio (OR) showed the high level of pretreatment CECs only correlated with the OS of patients with advanced lung cancer (stage III-IV). CONCLUSIONS: High counts of CECs seem to be associated only with worse 1-year OS in patients with lung cancer, while high level of pretreatment CEPCs correlate with both worse PFS and OS.


Assuntos
Biomarcadores Tumorais/sangue , Células Progenitoras Endoteliais/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Células Neoplásicas Circulantes/patologia , Terapia Combinada , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Prognóstico , Taxa de Sobrevida
4.
Eur J Cancer ; 49(7): 1752-60, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23313143

RESUMO

BACKGROUND: Acquired resistance to 5-fluorouracil (5-FU) is one of the important reasons for failure in 5-FU-based chemotherapy. The upregulation of dihydropyrimidine dehydrogenase (DPD) in tumours was reported as an important factor for acquired 5-FU resistance. The aim of this study is to examine whether intra-hepatic DPD was involved in acquired 5-FU resistance. METHODS: HT-29 human colorectal xenograft tumours were established in nude mice. After long-term exposure to 5-FU, some of the tumour became "resistant" and the others remained "sensitive" to 5-FU. DPD expression levels in the livers and tumours of "resistant", "sensitive" or untreated mice were examined, and pharmacokinetics of 5-FU in rats' plasma were investigated. Gimeracil, a DPD inhibitor, was checked whether it could reverse the reduced bioavailability of 5-FU. RESULTS: DPD expression was upregulated obviously in tumours of "resistant" mice as reported previously. Importantly, DPD expression was also upregulated significantly in livers of "resistant" mice, compared with those of "sensitive" or untreated mice. Furthermore, the upregulation of DPD expression in livers led to accelerated metabolism of 5-FU. Gimeracil was found to reverse the reduced serum 5-FU concentration. The cultured tumour cells from 5-FU treated mice showed relative sensitivity to higher concentration of 5-FU, even the "resistant" tumour cells. CONCLUSION: Our study suggested that the upregulation of DPD in liver may be involved in acquired resistance to 5-FU, and DPD inhibitors or increasing 5-FU dosage may have potential application in overcoming 5-FU acquired resistance.


Assuntos
Di-Hidrouracila Desidrogenase (NADP)/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Fígado/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Animais , Antimetabólitos Antineoplásicos/sangue , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/farmacologia , Western Blotting , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Feminino , Fluoruracila/sangue , Fluoruracila/farmacocinética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Piridinas/farmacologia , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Cancer Chemother Pharmacol ; 69(1): 239-46, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21706279

RESUMO

PURPOSE: Antiangiogenic drugs inhibit tumor growth by decreasing blood supply and causing transient "normalization" of the tumor vasculature, thereby improving the delivery of systemic chemotherapy. A higher dose of antiangiogenic drugs may lead to a more marked decrease in intratumoral blood flow but may concomitantly cause a decrease in delivery of chemotherapeutic agents. The purpose of this study was to define an optimal schedule for the combination of gemcitabine with a recombinant endostatin, endostar. METHODS: We evaluated the antitumor effects with different schedules of gemcitabine combined with or without endostar. The changes of vascular endothelial growth factor (VEGF) levels in tumor extracts and sera after gemcitabine treatment were examined. Endostar was also assessed for its abilities to inhibit the increase in VEGF levels. Apoptotic cells and microvessel density within tumor tissue were also examined. RESULTS: Endostar administered simultaneously with or following gemcitabine improved the inhibition of tumor growth, compared with gemcitabine alone. VEGF levels decreased immediately after gemcitabine treatment, but increased in the following several days. Endostar administered simultaneously with or following gemcitabine could inhibit the increase in VEGF levels, thereby cause a decreased vessel density and an increased apoptosis in tumor tissue. CONCLUSIONS: Our finding suggested that endostar given simultaneously with or following gemcitabine might be optimal to enhance the antitumor effect.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Lewis/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Esquema de Medicação , Endostatinas/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Microvasos/efeitos dos fármacos , Proteínas Recombinantes
6.
Anticancer Drugs ; 22(6): 500-6, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21637159

RESUMO

In this study, we used two-dimensional gel electrophoresis and MALDI-Q-TOF-MS/MS analysis to examine the global protein expression of a pair of colorectal carcinoma cell lines, SW620 and irinotecan-resistant SW620. Of the 30 spots identified as differentially expressed proteins (±over twofold, P<0.05) between the two cell lines, 26 spots (corresponding to 26 unique proteins) were positively identified by MALDI-Q-TOF-MS/MS analysis. These proteins could be grouped into main classes including metabolism (15.38%), cell SSproliferation/differentiation (11.53%), molecular chaperone (11.53%), mRNA splicing (11.53%), and so on. The proteins, which might be involved in the development of tumor drug resistance, such as α-enolase, cofilin, and thioredoxin-dependent peroxide 1, have been validated by western blot analysis and have been discussed. The proteins identified in this study may be useful in showing the mechanisms underlying irinotecan resistance.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Proteômica , Fatores de Despolimerização de Actina/metabolismo , Sequência de Aminoácidos , Western Blotting , Camptotecina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Eletroforese em Gel Bidimensional , Humanos , Processamento de Imagem Assistida por Computador , Irinotecano , Dados de Sequência Molecular , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/genética , Fosfopiruvato Hidratase/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
7.
Clin Transl Oncol ; 13(4): 275-80, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21493189

RESUMO

INTRODUCTION: Cytokines play important roles in regulating immune responses. Interleukin-2 (IL-2) has usually been used as an adjuvant to enhance antitumour immune responses. However, its crucial role in activation-induced cell death, inhibition of homeostatic proliferation of CD8+ memory T cells and its notable biological side effects impair its prospect of application. IL-15 has several similar functions to IL-2 and shows potential advantages over IL-2, and is being investigated to enhance antitumour dendritic cell (DC) vaccine strategies in our ongoing studies. OBJECTIVE: In this preliminary study, we evaluated the ability of IL-15, compared with IL-2, to act as an adjuvant to enhance T-cell responses activated by DCs in vitro. MATERIALS AND METHODS: Bone marrow-derived DCs (BMDCs) were pulsed with tumour antigens and used to stimulate lymphocyte responses in the presence of IL-15 or IL-2. The activated T lymphocytes were examined by flow cytometric analysis, and interferon-γ (IFN-γ) enzyme-linked immunospot and cytotoxicity assays. RESULTS: IL-15 was observed to activate lymphocytes with comparable phenotype characteristics of activated/memory CD8+ lymphocytes, compared with IL-2. Both in primary and secondary stimulation with DCs, when using IL-15 as an adjuvant, activated lymphocytes showed higher proportions of IFN-γ-secreting subsets. In secondary stimulation with BMDCs in the presence of IL-15, the activated lymphocytes showed a stronger cytotoxicity to antigen-specific tumour target cells. CONCLUSIONS: Our study suggested that IL-15 might be a prospective adjuvant for a DC vaccine strategy against cancers. The further observation that IL-15 acts as an adjuvant for an antitumour DC vaccine strategy is worth investigating.


Assuntos
Células Dendríticas/imunologia , Interleucina-15/imunologia , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Animais , Células da Medula Óssea/imunologia , Separação Celular , Células Cultivadas , Citotoxicidade Imunológica , Células Dendríticas/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Interleucina-15/farmacologia , Interleucina-2/imunologia , Interleucina-2/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/efeitos dos fármacos
8.
Cancer ; 117(22): 5103-11, 2011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-21523768

RESUMO

BACKGROUND: It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first-line chemotherapy. METHODS: Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety-nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated. RESULTS: Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression-free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C). CONCLUSIONS: The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Neoplasias Pulmonares/complicações , Metformina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
9.
J Mol Med (Berl) ; 89(6): 595-602, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21331509

RESUMO

Sunitinib, a novel oral multi-targeted tyrosine kinase inhibitor for patients with metastatic renal cell carcinoma (mRCC) and advanced gastrointestinal stromal tumor, has a good prospect for clinical application and is being investigated for the potential therapy of other tumors. We observed the phenomenon that drinking tea interfered with symptom control in an mRCC patient treated with sunitinib and speculated that green tea or its components might interact with sunitinib. This study was performed to investigate whether epigallocatechin-3-gallate (EGCG), the major constituent of green tea, interacted with sunitinib. The interaction between EGCG and sunitinib was examined in vitro and in vivo. (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy and mass spectrometry (MS) were used to analyze the interaction between these two molecules and whether a new compound was formed. Solutions of sunitinib and EGCG were intragastrically administered to rats to investigate whether the plasma concentrations of sunitinib were affected by EGCG. In this study, we noticed that a precipitate was formed when the solutions of sunitinib and EGCG were mixed under both neutral and acidic conditions. (1)H-NMR spectra indicated an interaction between EGCG and sunitinib, but no new compound was observed by MS. Sticky semisolid contents were found in the stomachs of sunitinib and EGCG co-administrated mice. The AUC(0-∞) and C (max) of plasma sunitinib were markedly reduced by co-administration of EGCG to rats. Our study firstly showed that EGCG interacted with sunitinib and reduced the bioavailability of sunitinib. This finding has significant practical implications for tea-drinking habit during sunitinib administration.


Assuntos
Catequina/análogos & derivados , Interações Ervas-Drogas , Indóis/metabolismo , Indóis/farmacocinética , Pirróis/metabolismo , Pirróis/farmacocinética , Animais , Disponibilidade Biológica , Catequina/sangue , Catequina/metabolismo , Precipitação Química , Humanos , Indóis/sangue , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/metabolismo , Pirróis/sangue , Ratos , Ratos Sprague-Dawley , Sunitinibe , Chá/química
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