Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
BMC Cancer ; 21(1): 188, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622258

RESUMO

BACKGROUND: Gastric outlet obstruction (GOO) is a late complication of advanced gastric cancer, and it is controversial how to select the therapeutic strategies: gastrojejunostomy and palliative gastrectomy? Therefore, this study was to compare the surgical and survival outcomes of gastrojejunostomy and palliative gastrectomy. METHODS: In total, 199 gastric cancer patients with outlet obstruction treated by surgery between January 2000 and December 2015 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Patients were divided into gastrojejunostomy group and palliative gastrectomy group. Propensity score matching (PSM) was performed to balance the selection bias. RESULTS: After 1:1 PSM, a total of 104 patients were included for final analysis. The median overall survival (OS) times in the gastrojejunostomy group and palliative gastrectomy group were 8.50 and 11.87 months, respectively (P = 0.243). The postoperative complication rates in the gastrojejunostomy group and palliative gastrectomy group were 19.23% (10/52) and 17.31% (9/52), respectively (P = 0.800), and no treatment-related death was observed. Multivariate analysis showed that periton0eal seeding (P = 0.014) and chemotherapy (P < 0.001) were independent prognostic factors. Among them, peritoneal seeding was a risk factor and postoperative chemotherapy was a protective factor. CONCLUSIONS: Our results indicated that although the surgical complications of palliative gastrectomy were manageable, it showed no survival benefit. Therefore, relieving obstruction symptom, improving patients' quality of life and creating better conditions for chemotherapy appear to be the main therapeutic strategies for advanced gastric cancer with GOO.

2.
Signal Transduct Target Ther ; 5(1): 294, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33361761

RESUMO

Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for improving treatment. Here, we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples from 18 patients with coronavirus disease 2019 (COVID-19) during their treatment, convalescence, and rehabilitation. After analyzing the regulatory networks of differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) between the different clinical stages, we found that humoral immunity and type I interferon response were significantly downregulated, while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19. The formation of this T cell immune response might be driven by the activation of activating protein-1 (AP-1) related signaling pathway and was weakly affected by other clinical features. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.


Assuntos
/genética , Imunidade Humoral/genética , Linfócitos T/metabolismo , Transcriptoma/genética , /epidemiologia , Feminino , Humanos , Imunidade Humoral/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , MicroRNAs , RNA Longo não Codificante/genética , RNA-Seq , /patogenicidade , Linfócitos T/imunologia , Linfócitos T/patologia , Fator de Transcrição AP-1/genética
3.
Eur J Pharmacol ; 889: 173571, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33031798

RESUMO

Chemotherapy drugs exerts beneficial antitumor activity before and after cancer surgery. Post-injury complications are a potential hazard after surgical tumor resection. Inflammation caused by surgical stress is known to promote the progression of post-injury complications. Recent studies have found that chemotherapy drugs can promote post-injury inflammatory response, leading to increased post-injury complications. Imidazole derivatives have effective anticancer activity. However, the impact of post-operative inflammation caused by imidazole derivatives is unclear. In this study, two novel phenanthroimidazole derivatives (L082 and L142) were synthesized and characterized. These compounds showed significant inhibitory effects on different tumor cells. The compound L082 also inhibited liver cancer in vivo. In addition, L082 played a significant role in inhibiting the accumulation of inflammatory cells and promoting the elimination of inflammatory cells at the incision, which may be related to inhibiting the production of ROS and NO in oxidative and nitric stress. These results suggest that L082 can be used as a bifunctional drug to suppress tumors and reduce post-injury inflammation complications.

5.
J Cancer ; 10(14): 3214-3223, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31289592

RESUMO

Background: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. Methods: Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. Results: A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. Conclusions: Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.

6.
N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573

RESUMO

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; ClinicalTrials.gov number, NCT01872962.).


Assuntos
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
7.
Bioorg Chem ; 88: 102940, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028991

RESUMO

A series of imidazo[4,5f][1,10]phenanthroline derivatives (1-6) have been synthesized in this study, and their inhibitory activity was evaluated by MTT assay. Results showed that all of these compounds demonstrate a promising inhibitory activity against a panel of human cancer cell lines. The 6, the most effective compound with IC50 of approximately 2.3 ±â€¯0.1 µM, was against the growth and could induce autophagy of HepG2 cells. This condition was confirmed by abundant autophagic vacuoles appearing in cells and evident ultrastructural changes observed under transmission electron microscopy. The autophage induced by 6 has also been demonstrated by up-regulating LC3-II and Beclin1. The apoptosis and G2/M phase cell cycle arrest through DSB damage have also been confirmed after the HepG2 cells were treated by 6. These multiple effects, especially induction apoptosis and autophagy, indicate the potential of 6 for development as a novel anticancer drug.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , DNA de Neoplasias/efeitos dos fármacos , Imidazóis/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Fenantrolinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imidazóis/síntese química , Imidazóis/química , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Fenantrolinas/síntese química , Fenantrolinas/química , Células Tumorais Cultivadas , Peixe-Zebra
8.
Biotechnol Lett ; 41(6-7): 701-709, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30953310

RESUMO

OBJECTIVES: To investigate the effect of full-length fragment of DNA topoisomerase I gene (TOP1) matrix attachment regions (MARs) originating from the human genome on transgene expression in Chinese hamster ovary (CHO) cells and explore the underlying mechanisms. RESULTS: Results showed that TOP1 MAR cannot only enhance the transient and stable transgenic expression of enhanced green fluorescence protein (EGFP) but also increase long-term stability and ratio of positive colonies in transfected CHO cells with TOP1 MAR at the 5' or 3' ends of the EGFP expression cassette. Interestingly, the CHO cells were transfected with the 5',3' TOP1 MAR-containing vector featured the highest transient and stable expression, whereas those with the 3' TOP1 MAR-containing vector exhibited the most effective stability and ratio of positive colonies. We also observed that transgene copy numbers and mRNA of egfp gene were correlated with the expression levels of EGFP protein in polyclonal CHO cells. However, the heterogeneity of expression in monoclonal CHO cells was unaffected by transgene copy number. CONCLUSIONS: The findings may aid in the potential application of TOP1 MAR in expression enhancement of recombinant proteins in mammalian cells.


Assuntos
Células CHO , Engenharia Celular/métodos , DNA Topoisomerases Tipo I/genética , Expressão Gênica , Proteínas de Fluorescência Verde/biossíntese , Regiões de Interação com a Matriz , Proteínas Recombinantes/biossíntese , Animais , Cricetulus , Proteínas de Fluorescência Verde/genética , Humanos , Proteínas Recombinantes/genética
9.
J Cell Physiol ; 234(3): 2618-2630, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30191969

RESUMO

Paris polyphylla var. yunnanensis, named Chong Lou, is considered an antitumor substance. In this study, we investigated the effect of PP-22, a monomer purified from P. polyphylla var. yunnanensis, on the nasopharyngeal carcinoma cell line CNE-2 in vitro. The results showed that PP-22 could inhibit the proliferation of CNE-2 cells via the induction of apoptosis, with evidence of the characteristic morphological changes in the apoptosis in the nucleus and an increase in Annexin V-positive cells. In addition, we found that PP-22 could activate the p38 mitogen-activated protein kinase (MAPK) pathway and that this activation was reversed by SB203580, a specific inhibitor of the p38 MAPK pathway. In contrast, PP-22 promoted apoptosis via an intrinsic pathway, including the endoplasmic reticulum stress pathway, in a caspase-dependent manner. A further study showed that PP-22 also induced apoptosis by downregulating the signal transducers and activators of transcription 3 (STAT3) pathway, and the inhibitory effect was also confirmed by STAT3 small interfering RNA. In addition, PP-22 could promote autophagy by inhibiting the extracellular regulated protein kinases (ERK) pathway. And autophagy plays a protective role against apoptosis. Together, these data show that PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma CNE-2 cell line.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Saponinas/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Eur J Pharmacol ; 843: 285-291, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30445021

RESUMO

Combining radiosensitizers with ionizing radiation (IR) is an effective strategy to increase the radiation therapeutic effect for hepatocellular carcinoma (HCC) patients. A phenanthroline derivative, 2-phenyl-imidazo [4, 5 f] [1, 10] phenanthroline (L02), had been synthesized. This study investigated the radiosensitization and mechanisms of L02 combined with IR against HCC. The radiosensitization of L02 combined with IR was evaluated by the sensitivity enhancement ratio (SER) and the isobolographic analysis. The toxicity of L02 and cisplatin were compared by the zebrafish model. The cell cycle and apoptosis were examined by flow cytometry. DNA damage was measured by comet assay and the expressions of apoptosis related proteins were analyzed by western blotting. L02 was effective in sensitizing HCC to IR. The SERs in HepG2 and BEL7402 were 1.41 and 1.28, respectively. The sensitization of L02 was comparable with cisplatin. L02 treatment with IR had synergistic anti-tumor effect. L02 enhanced the percentage of IR induced apoptosis cells. L02 increased comet tail in comet assay when combined with IR. L02 sensitized HCC to IR by the activation of P53 signaling, the decrease in Bcl-2, up-regulation of cytochrome c and the subsequent activation of caspase-3. L02 sensitizes HCC to IR, mostly likely by inhibiting cell proliferation, inducing DNA damage and mitochondria-dependent apoptosis. L02 may be a novel radiosensitizer for HCC.


Assuntos
Mitocôndrias/efeitos dos fármacos , Fenantrolinas/farmacologia , Radiossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Mitocôndrias/efeitos da radiação , Tolerância a Radiação/efeitos dos fármacos , Raios X
11.
Oncotarget ; 8(32): 52708-52723, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28881764

RESUMO

Nasopharyngeal carcinoma (NPC) is a head and neck cancer with high incidence in South China and East Asia. To provide a theoretical basis for NPC risk screening and early prevention, we conducted a meta-analysis of relevant literature on the association of single nucleotide polymorphisms (SNP)s with NPC susceptibility. Further, expression of 15 candidate SNPs identified in the meta-analysis was evaluated in a cohort of NPC patients and healthy volunteers using next-generation sequencing technology. Among the 15 SNPs detected in the meta-analysis, miR-146a (rs2910164, C>G), HCG9 (rs3869062, A>G), HCG9 (rs16896923, T>C), MMP2 (rs243865, C>T), GABBR1 (rs2076483, T>C), and TP53 (rs1042522, C>G) were associated with decreased susceptibility to NPC, while GSTM1 (+/DEL), IL-10 (rs1800896, A>G), MDM2 (rs2279744, T>G), MDS1-EVI1 (rs6774494, G>A), XPC (rs2228000, C>T), HLA-F (rs3129055, T>C), SPLUNC1 (rs2752903, T>C; and rs750064, A>G), and GABBR1 (rs29232, G>A) were associated with increased susceptibility to NPC. In our case-control study, an association with increased risk for NPC was found for the AG vs AA genotype in HCG9 (rs3869062, A>G). In addition, heterozygous deletion of the GSTM1 allele was associated with increased susceptibility to NPC, while an SNP in GABBR1 (rs29232, G>A) was associated with decreased risk, and might thus have a protective role on NPC carcinogenesis. This work provides the first comprehensive assessment of SNP expression and its relationship to NPC risk. It suggests the need for well-designed, larger confirmatory studies to validate its findings.

12.
Oncotarget ; 8(36): 60504-60513, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28947989

RESUMO

We compared the treatment outcomes, toxicities and prognoses of patients with stage IE-IIE extranodal natural killer/T-cell lymphoma (ENKTL) treated with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT). Newly diagnosed early-stage ENKTL patients (N = 173) were enrolled and received extended involved-field radiotherapy following induction chemotherapy. Patients were treated with 3DCRT (n = 98) or IMRT (n = 75). One-to-one matching of the IMRT and 3DCRT groups was performed through propensity score matching, which yielded 23 pairs of patients. The two groups achieved similar complete remission rates before and after radiotherapy (P > 0.05). All patients were followed up for a median of 41 months. The rates of local recurrence-free survival (LRFS, P < 0.001), progression-free survival (PFS, P = 0.003) and overall survival (OS, P = 0.003) were longer in the IMRT than 3DCRT group. In the matched patients, IMRT was still associated with superior LRFS (P = 0.024), but not with improved PFS (P = 0.113) or OS (P = 0.115). Multivariate analysis also suggested IMRT was a favorable independent factor for LRFS (HR = 2.230, P = 0.043), but not for PFS (P = 0.195) or OS (P = 0.116). Equivalent acute toxicities were observed for 3DCRT and IMRT; however, among stage II patients who had received cervical irradiation, the rate of late xerostomia was lower in the IMRT than 3DCRT group (38.5% vs. 66.7%, P = 0.046). Overall, IMRT yielded a better treatment response and local control than 3DCRT, and tended to reduce late xerostomia in patients with cervical irradiation, but failed to enhance OS. Thus, IMRT is recommended for the treatment of stage IE-IIE ENKTL patients.

13.
Molecules ; 22(5)2017 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-28531122

RESUMO

Herein, a series of imidazo[4,5-f][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-f][1,10] phenanthroline, R = NO2, 1; CF3, 2; Cl, 3; OH, 4) have been synthesized in yields of 82.3-94.7% at 100 °C under the irradiation of microwave. MTT assay has been utilized to evaluate the inhibitory activity (IC50) of these compounds against the growth of various tumor cells, and the results revealed that these compounds, especially 1, exhibited excellent inhibitory activity against the growth of A549 cells with IC50 of 15.03 µM. Moreover, it's also confirmed that 1 can penetrate into the membrane of tumor cells and distribute in mitochondria when observed under microscopy, resulting apoptosis of tumor cells. The further studies showed that 1 can bind to bcl-2 G-quadruplex DNA, which demonstrated by the increase of melting point of bcl-2 G4 DNA in the presence of 1, as well as electronic titration and emission spectra. In a word, this kind of compound may develop as a potential apoptosis inducer in cancer chemotherapy via binding and stabilizing to the bcl-2 G-quadruplex DNA.


Assuntos
Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Quadruplex G/efeitos dos fármacos , Imidazóis/síntese química , Mitocôndrias/efeitos dos fármacos , Fenantrolinas/síntese química , Proteínas Proto-Oncogênicas c-bcl-2/agonistas , Células A549 , Antineoplásicos/farmacologia , Transporte Biológico , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica , Humanos , Imidazóis/farmacologia , Micro-Ondas , Mitocôndrias/metabolismo , Desnaturação de Ácido Nucleico , Fenantrolinas/farmacologia , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
14.
Front Immunol ; 8: 1786, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29312314

RESUMO

Background: CXCR5+CD8+ T cells have been demonstrated to play an important role in the control of chronic viral replication; however, the relationship between CXCR5+CD8+ T cells, HIV disease progression, and programmed cell death 1 (PD-1) expression profile on CXCR5+CD8+ T cells during HIV infection remain poorly understood. Methods: We enrolled a total of 101 HIV patients, including 62 typical progressors, 26 complete responders (CRs), and 13 immune non-responders (INRs). Flow cytometric analysis, immunohistochemical staining, and relative function (i.e., cytokine secretion and PD-1 blockade) assays were performed to analyze the properties of CXCR5+CD8+ T cells. Results: HIV-specific CXCR5+CD8+ T cells in the peripheral blood and distribution of CXCR5+CD8+ T cells in the lymph node (LN) were negatively correlated with disease progression during chronic HIV infection. PD-1 was highly expressed on CXCR5+CD8+ T cells and positively associated with peripheral CD4+ T cell counts. Functionally, IFN-γ and TNF-α production of CXCR5+CD8+ T cells were reduced by PD-1 pathway blockade, but the production of IFN-γ and TNF-α from CXCR5-CD8+ T cells increased in response to TCR stimulation. Interestingly, PD-1 expression was constantly retained on CXCR5+CD8+ T cells while significantly decreased on CXCR5-CD8+ T cells after successful antiretroviral treatment in chronic HIV-infected patients. Conclusion: PD-1+CXCR5+CD8+ T cells are functional cytotoxic T cells during chronic HIV infection. PD-1+CXCR5+CD8+ T cells may represent a novel therapeutic strategy for the disease.

15.
Oncotarget ; 8(7): 11480-11488, 2017 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-28002792

RESUMO

This study retrospectively investigated asparaginase-based chemotherapy treatment outcomes with or without radiotherapy in 143 patients with stage IE-IIE extranodal natural killer/T cell lymphoma (ENKTCL). All patients received a median of three cycles of asparaginase-based chemotherapy, while 121 patients received radiotherapy following the chemotherapy. The complete remission (CR) rate for all patients post-chemotherapy was 58.7%, and rose to 73.4% by the end of treatment. Patients who received radiotherapy achieved better survival outcomes than those who did not (89.7% vs. 49.0% for 2-year overall survival (OS), P<0.001; 86.8% vs. 37.4% for 2-year progression-free survival (PFS), P<0.001). Additionally, even patients who achieved CR post-chemotherapy exhibited differential survival rates with or without radiotherapy (90.8% vs. 60% for 2-year OS, P=0.006; 86.1% vs. 60% for 2-year PFS, P=0.044). Multivariate analysis revealed that radiotherapy was an independent factor favoring OS (HR=0.098, 95%CI=0.031-0.314, P=0.001) and PFS (HR=0.156, 95%CI=0.062-0.396, P=0.001). Thus, radiotherapy is recommended for stage IE-IIE ENKTCL patients treated with asparaginase-based chemotherapy, even in cases of CR following chemotherapy.


Assuntos
Quimiorradioterapia/métodos , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
16.
Transl Oncol ; 9(4): 329-35, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27567956

RESUMO

PURPOSE: It deserves investigation whether induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) is inferior to the current standard of IMRT plus concurrent chemotherapy (CC) in locoregionally advanced nasopharyngeal carcinoma. METHODS: Patients who received IC (94 patients) or CC (302 patients) plus IMRT at our center between March 2003 and November 2012 were retrospectively analyzed. Propensity-score matching method was used to match patients in both arms at equal ratio. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: In the original cohort of 396 patients, IC plus IMRT resulted in similar FFS (P = .565), OS (P = .334), DMFS (P = .854), and LRFS (P = .999) to IMRT plus CC. In the propensity-matched cohort of 188 patients, no significant survival differences were observed between the two treatment approaches (3-year FFS 80.3% vs 81.0%, P = .590; OS 93.4% vs 92.1%, P = .808; DMFS 85.9% vs 87.7%, P = .275; and LRFS 93.1% vs 92.0%, P = .763). Adjusting for the known prognostic factors in multivariate analysis, IC plus IMRT did not cause higher risk of treatment failure, death, distant metastasis, or locoregional relapse. CONCLUSIONS: IC plus IMRT appeared to achieve comparable survival to IMRT plus CC in locoregionally advanced nasopharyngeal carcinoma. Further investigations were warranted.

17.
Genet Mol Biol ; 39(2): 239-47, 2016 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-27192131

RESUMO

Dunaliella salina, a single-celled marine alga with extreme salt tolerance, is an important model organism for studying fundamental extremophile survival mechanisms and their potential practical applications. In this study, two-dimensional differential in-gel electrophoresis (2D-DIGE) was used to investigate the expression of halotolerant proteins under high (3 M NaCl) and low (0.75 M NaCl) salt concentrations. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and bioinformatics were used to identify and characterize the differences among proteins. 2D-DIGE analysis revealed 141 protein spots that were significantly differentially expressed between the two salinities. Twenty-four differentially expressed protein spots were successfully identified by MALDI-TOF/TOF MS, including proteins in the following important categories: molecular chaperones, proteins involved in photosynthesis, proteins involved in respiration and proteins involved in amino acid synthesis. Expression levels of these proteins changed in response to the stress conditions, which suggests that they may be involved in the maintenance of intracellular osmotic pressure, cellular stress responses, physiological changes in metabolism, continuation of photosynthetic activity and other aspects of salt stress. The findings of this study enhance our understanding of the function and mechanisms of various proteins in salt stress.

18.
Chin Med J (Engl) ; 129(3): 304-8, 2016 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-26831232

RESUMO

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV. METHODS: One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed. RESULTS: Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2). CONCLUSION: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.


Assuntos
Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Adulto , Alanina Transaminase/metabolismo , Alquinos , Fármacos Anti-HIV/uso terapêutico , Aspartato Aminotransferases/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Coinfecção/tratamento farmacológico , Ciclopropanos , Feminino , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Humanos , Masculino
19.
Yi Chuan ; 37(7): 720-30, 2015 07.
Artigo em Chinês | MEDLINE | ID: mdl-26351172

RESUMO

The auxin response gene family adjusts the auxin balance and the growth hormone signaling pathways in plants. Using bioinformatics methods, the auxin-response genes from the grape genome database are identified and their chromosomal location, gene collinearity and phylogenetic analysis are performed. Probable genes include 25 AUX_IAA, 19 ARF, 9 GH3 and 42 LBD genes, which are unevenly distributed on all 19 chromosomes and some of them formed distinct tandem duplicate gene clusters. The available grape microarray databases show that all of the auxin-response genes are expressed in fruit and leaf buds, and significant overexpressed during fruit color-changing, bud break and bud dormancy periods. This paper provides a resource for functional studies of auxin-response genes in grape leaf and fruit development.


Assuntos
Genoma de Planta , Ácidos Indolacéticos/farmacologia , Reguladores de Crescimento de Planta/farmacologia , Vitis/genética , Sequência de Aminoácidos , Mapeamento Cromossômico , Biologia Computacional , Dados de Sequência Molecular , Família Multigênica , Análise de Sequência com Séries de Oligonucleotídeos , Filogenia
20.
Asian Pac J Cancer Prev ; 15(15): 6047-52, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25124572

RESUMO

BACKGROUND: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy: >5% weight loss group and≤5% weight loss group. RESULTS: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss>5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) CONCLUSIONS: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Perda de Peso , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...