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1.
J Cell Biochem ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31930562

RESUMO

MicroRNA-125a (miR-125a) is related to the occurrence, development, and prognosis of various cancers according to relevant reports. However, its function role and mechanism in non-small cell lung cancer (NSCLC) is yet to be explored. Herein, we investigated the role and preliminary mechanism of miR-125a in NSCLC. First, miR-125a was noticeably downregulated in NSCLC tissues in contrast to adjacent normal tissues through the real-time quantitative polymerase chain reaction (RT-qPCR) assay. The inverted result was observed on the STAT3 and HAS1 expressions. Moreover, miR-125a was expressed at highest level in A549 among four human NSCLC cell lines. Second, functional studies indicated miR-125a restrained proliferation, invasion, migration, metastasis, and advocated apoptosis of NSCLC cells, but had no obvious effect on cell cycle. Next, results indicated that a target of miR-125a was STAT3 on the basis of prediction and confirmation by the dual-luciferase reporter assay. RT-qPCR and Western blot assays displayed that miR-125a overexpression conspicuously constrained STAT3 expression at messenger RNA and protein levels. Finally, the binding between HAS1 promoter region and STAT3 was predicted by PROMO database analysis and verified by chromatin immunoprecipitation assay, suggesting that STAT3 was bound with the HAS1 promoter regions. STAT3 overexpression exerted positive effects on HAS1 expression at protein and mRNA levels. Additionally, HAS1-related functional studies illustrated HAS1 pronouncedly suppressed the proliferative, invasive, and migratory potential of NSCLC cells in vitro. Collectively, our findings demonstrated that miR-125a prohibited the proliferation, invasion, and migration of NSCLC cells by HAS1 expression reduction as a result of inhibiting STAT3 expression in NSCLC. This study indicated that miR-125a might be of potential or value for NSCLC treatment.

2.
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.

3.
Anal Chem ; 91(24): 16002-16009, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31746200

RESUMO

Multiblock DNA probe attracted a large amount of scientific attention, for the development of multitarget biosensor and improved specificity/sensitivity. However, the development of multiblock DNA probes highly relied on the chemical synthesis of organic linkers or nanomaterials, which limited their practicability and biological compatibility. In this work, we developed a label-free assembling strategy using a triblock DNA capture probe, which connects two DNA probes with its intrinsic polyA fragment (probe-PolyA-probe, PAP). The middle polyA segment has a high affinity to the gold electrode surface, leading to excellent reproducibility, stability, and regeneration of our biosensor. Two flanking capture probes were tandemly co-assembled on the electrode surface with consistent spatial relationship and exactly the same amount. When combined with the target DNA, the hybridization stability was improved, because of the strong base stacking effect of two capture probes. The sensitivity of our biosensor was proved to be 10 fM, with a wide analysis range between 10 fM to 1 nM. Our PAP-based biosensor showed excellent specificity when facing mismatched DNA sequences. Even single nucleotide polymorphisms can be distinguished by each probe. The excellent practicability of our biosensor was demonstrated by analyzing genomic DNA both with and without PCR amplification.

4.
Clin Cancer Res ; 25(23): 6967-6975, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31413010

RESUMO

PURPOSE: Preclinical and retrospective studies suggested a role for metformin in sensitizing patients who have diabetes with non-small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors (TKIs). We therefore examined its effects in combination with gefitinib in patients without diabetes harboring EGFR mutations (EGFRm). PATIENTS AND METHODS: A total of 224 patients without diabetes with treatment-naïve stage IIIB-IV EGFRm NSCLC were randomly assigned in a 1:1 ratio to receive gefitinib plus either metformin or placebo. The primary endpoint was progression-free survival (PFS) rate at 1 year and secondary endpoints included overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of IL6 were also examined in an exploratory analysis. RESULTS: The median duration of follow-up was 19.15 months. The estimated 1-year PFS rates were 41.2% [95% confidence interval (CI), 30.0-52.2] with gefitinib plus metformin and 42.9% (95% CI, 32.6-52.7) with gefitinib plus placebo (P = 0.6268). Median PFS (10.3 months vs. 11.4 months) and median OS (22.0 months vs. 27.5 months) were numerically lower in the metformin group, while ORRs were similar between the two arms (66% vs. 66.7%). No significant treatment group differences were detected across all subgroups with respect to PFS, including those with elevated levels of IL6. Metformin combined with gefitinib resulted in a remarkably higher incidence of diarrhea compared with the control arm (78.38% vs. 43.24%). CONCLUSIONS: Our study showed that addition of metformin resulted in nonsignificantly worse outcomes and increased toxicity and hence does not support its concurrent use with first-line EGFR-TKI therapy in patients without diabetes with EGFRm NSCLC.

5.
Bioinformatics ; 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350562

RESUMO

MOTIVATION: The growth and survival of myeloma cells are greatly affected by their surrounding microenvironment. To understand the molecular mechanism and the impact of stiffness on the fate of myeloma initiating cells (MICs), we develop a systems biological model to reveal the dynamic regulations by integrating reverse phase protein array data and the stiffness associated pathway. RESULTS: We not only develop a stiffness associated signaling pathway to describe the dynamic regulations of the MICs, but also clearly identify three critical proteins governing the MIC proliferation and death, including FAK, mTORC1 and NFκB, which are validated to be related with multiple myeloma by our immunohistochemistry experiment, computation and manually reviewed evidences. Moreover, we demonstrate that the systematic model performs better than widely used parameter estimation algorithms for the complicated signaling pathway. AVAILABILITY: We can not only use the systems biological model to infer the stiffness associated genetic signaling pathway and locate the critical proteins, but also investigate the important pathways, proteins or genes for other type of the cancer. Thus, it holds universal scientific significance. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

6.
Cancer Med ; 8(5): 2599-2611, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30897289

RESUMO

BACKGROUND: Surfactant protein D (SP-D) is an innate immunity molecule in the alveoli. However, the associations between genetic variants of SP-D and radiation pneumonitis (RP) have never been investigated. METHODS: The Linkage disequilibrium of SP-D and tagSNPs were analyzed by using Haploview 4.1. Eight tagSNPs were genotyped among 396 lung cancer patients who received thoracic radiation therapy with follow-up time (median [P25, P75]: 11[6, 18]) using improved multiplex ligation detection reaction (iMLDR). The associations between clinical characteristics, tagSNP alleles, genotypes, haplotypes and onset time of grade ≥2 or ≥3 RP were evaluated by using univariate and multivariate Cox proportional hazard regression model. RESULTS: Three tagSNPs of SP-D (rs1998374, rs911887 and rs2255326) were significantly associated with grade ≥2 RP in multivariate analysis with multiple testing (Q test). The rs199874 had a protective effect for grade ≥2 RP in the dominant model (Hazard ratio (HR), 0.575; 95% confidence interval (CI), 0.378-0.875). The homozygous mutant genotype for rs911887 had risk effect for grade ≥2 RP (HR, 2.209; 95% CI, 1.251-3.902). The A mutant allele of rs2255326 also showed an elevated risk for grade ≥2 RP (HR, 1.777; 95% CI, 1.283-2.461) and this risk effect was still significant in the recessive genetic model (HR, 3.320; 95% CI, 1.659-6.644) and dominant genetic model (HR, 1.773; 95% CI, 1.166-2.696). Compared to the lung cancer patients bearing the most common haplotype C-G-T, the patients bearing the haplotype T-A-C (rs1998374-rs2255326-rs911887) showed a significant risk of both grade ≥2 RP (HR, 1.885; 95% CI, 1.284-2.765) and grade ≥3 RP (HR, 2.256; 95% CI, 1.248-4.080). CONCLUSIONS: Genetic variants of SP-D were associated with risk of RP development in lung cancer patients receiving thoracic radiotherapy.

7.
Free Radic Biol Med ; 129: 310-322, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30266681

RESUMO

Lonicera japonica (LJ) is widely used as the local medicine to improve body and prevent ills in China, but mechanisms of its healthy beneficial effects remain largely unclear. Here, we evaluated the anti-aging and healthspan promoting activities of 75% ethanol extract of LJ (LJ-E) in the animal model Caenorhabditis elegans. Our results showed that LJ-E (500 µg/mL) treatment enhanced the mean lifespan of worms by over 21.87% and significantly improved age-associated physiological functions in C. elegans. The 500 µg/mL concentration of LJ-E enhanced the survival rates under oxidative and thermal stresses, and decreased reactive oxygen species (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies showed that LJ-E-mediated lifespan extension was dependent on mev-1, daf-2, daf-16, and hsf-1, but not eat-2 genes. LJ-E could upregulate stress-inducible genes, viz., hsp-16.2, sod-3 and mtl-1. Moreover, we found that the D1086.10 protein interacted with superoxide dismutase (SOD)-3 by functional protein association networks analysis according to RNA-sequencing results. It was confirmed that D1086.10 was needed to promote longevity, and positively regulated expression of sod-3 by using D1086.10 mutants. Furthermore, LJ-E significantly delayed amyloid ß-protein induced paralysis in CL4176 strain. Given the important role of autophagy in aging and protein homeostasis, we observed that LJ-E could remarkably increase the mRNA expression of autophagy gene bec-1 in CL4176 strain, and decrease expression of autophagy substrate p62 protein by more than 40.0% in BC12921 strain. Finally, we found that combination composed of three major compounds (54 µg/mL chlorogenic acid, 15 µg/mL 1,5-dicaffeoylquinic acid and 7.5 µg/mL 1,3-dicaffeoylquinic acid) of 500 µg/mL LJ-E could significantly delay paralysis in CL4176 worms caused by Aß toxicity, comparable to that of LJ-E. Overall, our study may have important implications in using Lonicera japonica to promote healthy aging and have a potency to design therapeutics for age-related diseases.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Lonicera/química , Espécies Reativas de Oxigênio/antagonistas & inibidores , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/crescimento & desenvolvimento , Tecido Adiposo/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Ácido Clorogênico/farmacologia , Cinamatos/farmacologia , Citocromos b/genética , Citocromos b/metabolismo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Longevidade/genética , Metalotioneína/genética , Metalotioneína/metabolismo , Paralisia/prevenção & controle , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Estresse Fisiológico , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
8.
Chemosphere ; 210: 247-256, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30005346

RESUMO

The Chinese government is encouraging domestic cement producers to move from traditional coal power sources to the co-processing of waste as the primary energy source for the industry. In this study, 32 samples collected from the soil surrounding a cement plant in Beijing were analyzed for the presence of 16 U.S. EPA priority polycyclic aromatic hydrocarbons (PAHs) and 12 heavy metals. Ten samples were selected for polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) analysis. The pollution distribution patterns, sources, and potential risks to human health and the environment were investigated and evaluated. The highest concentrations of PCDD/Fs occurred 1200 m downwind from the cement plant. The levels of ∑16 PAHs ranged from 130.6 to 1134.3 µg kg-1 in the sampled soils. Source identification analysis suggested that the cement plant was the most likely source of PAH contamination. The concentrations of most of the heavy metals detected in the sampled soils were close to background levels, except for the levels of cadmium (Cd) and mercury (Hg), which were, on average, two times and six times higher than background values, respectively. The co-incineration of sludge, coal, and hazardous waste in the cement plant is a major contributing cause for the high levels of Hg in the surrounding soil. Risk assessment models, both the incremental lifetime cancer risks (ILCRs) for PAHs and the potential ecological risk index (RI) for heavy metals, indicate potential risks to the population and the environment surrounding the cement plant.


Assuntos
Materiais de Construção/análise , Monitoramento Ambiental/métodos , Resíduos Perigosos/análise , Metais Pesados/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Pequim , Humanos , Incineração
9.
Nucleic Acids Res ; 46(11): 5664-5677, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29750271

RESUMO

Base excision repair (BER) handles many forms of endogenous DNA damage, and apurinic/apyrimidinic endonuclease 1 (APE1) is central to this process. Deletion of both alleles of APE1 (a.k.a. Apex1) in mice leads to embryonic lethality, and deficiency in cells can promote cell death. Unlike most other BER proteins, APE1 expression is inversely correlated with cellular senescence in primary human fibroblasts. Depletion of APE1 via shRNA induced senescence in normal human BJ fibroblasts, a phenotype that was not seen in counterpart cells expressing telomerase. APE1 knock-down in primary fibroblasts resulted in global DNA damage accumulation, and the induction of p16INK4a and p21WAF1 stress response pathways; the DNA damage response, as assessed by γ-H2AX, was particularly pronounced at telomeres. Conditional knock-out of Apex1 in mice at post-natal day 7/12 resulted in impaired growth, reduced organ size, and increased cellular senescence. The effect of Apex1 deletion at post-natal week 6 was less obvious, other than cellular senescence, until ∼8-months of age, when premature aging characteristics, such as hair loss and impaired wound healing, were seen. Low APE1 expression in patient cancer tissue also correlated with increased senescence. Our results point to a key role for APE1 in regulating cellular senescence and aging features, with telomere status apparently affecting the outcome.


Assuntos
Senescência Celular , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Senilidade Prematura/genética , Animais , Células Cultivadas , Dano ao DNA , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/deficiência , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Fibroblastos/metabolismo , Camundongos Knockout , Telomerase/metabolismo , Telômero/metabolismo
11.
Biochem Biophys Res Commun ; 498(4): 751-757, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29526752

RESUMO

Immunotherapy targeting the programmed cell death-1/programmed death ligand 1(PD-L1) pathway has shown promising antitumor activity in brain metastases (BMs) of non-small cell lung cancer (NSCLC) patients with an acceptable safety profile; however, the response rates often differ between primary lesions and intracranial lesions. Studies are necessary to identify detailed characterizations of the response biomarkers. In this study, we aimed to compare the differences of PD-L1 expression and CD8+ tumor-infiltrating lymphocyte (TIL) density, two major response biomarkers of PD-1/PD-L1 blockade, between paired primary and brain metastatic lesions in advanced NSCLC. We observed that among primary lesions or BMs, only a small number of patients harbored common PD-L1 expression on both tumor cells and tumor-infiltrating immune cells. Additionally, we found that the numbers of CD8+ TILs were significantly fewer in BMs than in primary lung cancers. Low stromal CD8+ TIL numbers in BMs were associated with significantly shorter overall survival compared to high stromal CD8+ TIL counts. Notably, we demonstrated a discrepancy in PD-L1 expression and CD8+ TIL density between primary lung cancers and their corresponding BMs. Such heterogeneities are significantly associated with the time at which BMs occurred. Our study emphasizes the spatial and temporal heterogeneity of biomarkers for anti-PD-1/PD-L1 therapy, which should be concerned in clinical practice.


Assuntos
Antígeno B7-H1/análise , Neoplasias Encefálicas/secundário , Antígenos CD8/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/patologia , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Linfócitos T CD8-Positivos/patologia , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
12.
Environ Sci Pollut Res Int ; 25(12): 12127-12138, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29455349

RESUMO

In the present study, long-term environmental impacts of compact and ground cement composites, in which 30 wt.% of cement was replaced by washed municipal solid wastes incineration (MSWI) fly ash, were investigated for use in building industry. Consecutive leaching tests over a time span of 180 days were performed in acid water, deionized water, and saline water, respectively, with the accumulative concentration of different elements determined in the leachate. Different leaching behaviors are observed among different potential toxic elements (PTEs). For instance, higher concentrations of V in the leachate were observed from the compact cement composites than those from the ground ones. The concentration of Ba in the leachate increased with the decrease of particle size of the cement composites, and an initial increase in the leaching efficiency of Sn was followed by a clear decline with the leaching time. In addition, kinetic study revealed that the leaching behaviors of potential toxic elements follow a second-order model. The results demonstrated that the addition of washed MSWI fly ash into cement can contribute to the attrition resistance, indicating that the washed MSWI fly ash could be a promising alternative for cement as supplementary building materials.


Assuntos
Cinza de Carvão/análise , Materiais de Construção/análise , Poluentes Ambientais/análise , Incineração/métodos , Resíduos Sólidos/análise , China , Solubilidade , Propriedades de Superfície
13.
Sci Rep ; 8(1): 328, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321496

RESUMO

Genistein (GEN) has been previously reported to enhance the radiosensitivity of cancer cells; however, the detailed mechanisms remain unclear. Here, we report that GEN treatment inhibits the cytoplasmic distribution of Bcl-xL and increases nuclear Bcl-xL in non-small cell lung cancer (NSCLC). Interestingly, our in vitro data show that ionizing radiation IR treatment significantly increases IR-induced DNA damage and apoptosis in a low cytoplasmic Bcl-xL NSCLC cell line compared to that of high cytoplasmic Bcl-xL cell lines. In addition, clinical data also show that the level of cytoplasmic Bcl-xL was negatively associated with radiosensitivity in NSCLC. Furthermore, we demonstrated that GEN treatment enhanced the radiosensitivity of NSCLC cells partially due to increases in Beclin-1-mediated autophagy by promoting the dissociation of Bcl-xL and Beclin-1. Taken together, these findings suggest that GEN can significantly enhance radiosensitivity by increasing apoptosis and autophagy due to inhibition of cytoplasmic Bcl-xL distribution and the interaction of Bcl-xL and Beclin-1 in NSCLC cells, respectively.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Genisteína/farmacologia , Neoplasias Pulmonares/metabolismo , Radiação Ionizante , Radiossensibilizantes/farmacologia , Proteína bcl-X/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/genética , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Citoplasma/metabolismo , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Proteína bcl-X/genética
14.
Int J Radiat Oncol Biol Phys ; 100(2): 418-426, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29353657

RESUMO

PURPOSE: Oral mucositis is a common unpreventable complication associated with chemoradiation therapy. Shuanghua Baihe tablets have been approved by the Chinese Food and Drug Administration for treating recurrent oral mucosa ulceration. This study assessed whether Shuanghua Baihe tablets could prevent oral mucositis during chemoradiation therapy for locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: This multicenter, randomized, double-blind, placebo-controlled trial was conducted at 11 hospitals in China between January 22, 2014, and September 21, 2015. Eligible patients (N=240, 18-70 years old) with pathologically diagnosed locally advanced nasopharyngeal carcinoma were randomly assigned (computer-block randomization; 1:1) to receive Shuanghua Baihe tablets or a placebo (4 tablets, 3 times a day, for 7 weeks) at the initiation of chemoradiation therapy. Administration of Shuanghua Baihe tablets could be ended if grade 3 or higher oral mucositis developed and patients were unwilling to continue taking the drug. The primary endpoints were oral mucositis incidence and latency. RESULTS: The incidence of oral mucositis during this study was significantly lower in the Shuanghua Baihe group (85.0%; 95% confidence interval [CI], 78.6%-91.4%) than in the placebo group (96.6%; 95% CI, 93.4%-99.9%; P=.0028). The median latency period was 28 days in the Shuanghua Baihe group and 14 days in the placebo group (hazard ratio, 0.17; 95% CI, 0.12-0.23; P<.0001). Compared with placebo, Shuanghua Baihe tablets significantly reduced the oral mucositis severity scores recorded by the investigators (Oral Mucositis Score, 24.0 [range, 0.0-67.8] vs 57.5 [range, 0.0-98.0]; P<.0001), full-time nurses (Oral Assessment Guide score, 462.0 [range, 392.0-664.7] vs 520.4 [range, 392.0-714.0]; P<.0001), and patients (score for soreness of mouth and throat, 4.0 [range, 0-10] vs 6.0 [range, 0-10]; P<.0001). No serious adverse events were observed, and the incidence of mild or moderate gastrointestinal adverse events associated with Shuanghua Baihe tablets was 3.3%. The short-term response rate was similar in patients receiving Shuanghua Baihe tablets and those receiving placebo during chemoradiation therapy during this study. CONCLUSIONS: Shuanghua Baihe tablets reduced the occurrence, latency, and severity of oral mucositis in patients with nasopharyngeal cancer during chemoradiation therapy treatment.


Assuntos
Quimiorradioterapia/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Nasofaríngeas/terapia , Estomatite/prevenção & controle , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estomatite/etiologia , Comprimidos
15.
Acta Trop ; 178: 86-92, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29102457

RESUMO

Malaria infection poses a great threaten to public health even nowadays. The conventional diagnosis tools of malaria parasites and vectors require systematic training for the observers accompanied by the low throughput. In this study, a new detection system, i.e., multiplex microfluidic loop-mediated isothermal amplification (mµLAMP) array, was developed to provide a convenient, rapid and economical detection system for malaria diagnosis. A microfluidic-based detection chip was designed and developed, targeting the conserved gene of four Anopheles and two Plasmodium species responsible for most of the malaria cases occurred in China. The DNA preparation of Anopheles and Plasmodium samples was realized by using a newly-developed DNA extraction method. For this mµLAMP array system, the detection limit was determined to be 1pg of targeting DNA with high sensitivity (>95%) and specificity (100%). Further, the accuracy of such mµLAMP analysis was evaluated by the analysis of 48 Anopheles mosquito samples, of which 30 were termed to be target Anopheles, displaying high consistency with that by morphological analysis. In conclusion, the mµLAMP detection system was proved to be a visible, sensitive, specific and high-throughput diagnostic tool. Considering the portable manipulation of such detection system, our studies shed light on its potential application of malaria surveillance on the spot.


Assuntos
Anopheles/parasitologia , Malária/diagnóstico , Mosquitos Vetores/parasitologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Plasmodium/isolamento & purificação , Animais , China , Humanos , Microfluídica , Sensibilidade e Especificidade
16.
Biogerontology ; 19(1): 47-65, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29185166

RESUMO

Cistanche deserticola has been found to exert protection against aging and age-related diseases, but mechanisms underlying its longevity effects remain largely unclear. Here, the multicellular model organism Caenorhabditis elegans was employed to identify lifespan extending and protective effects against ß-amyloid (Aß) induced toxicity by echinacoside (ECH), a phenylethanoid glycoside isolated from C. deserticola. Our results showed that ECH extends the mean lifespan of worms and increases their survival under oxidative stress. Levels of intracellular reactive oxygen species and fat accumulation were also significantly suppressed by ECH. Moreover, ECH-mediated lifespan extension was found to be dependent on mev-1, eat-2, daf-2, and daf-16, but not sir-2.1 or hsf-1 genes. Furthermore, ECH triggered DAF-16 nuclear localization and upregulated two of its downstream targets, sod-3 and hsp-16.2. In addition, ECH significantly improved the survival of CL4176 worms in response to proteotoxic stress induced by Aß protein aggregation. Collectively, these findings suggested that reactive oxygen species scavenging, dietary restriction, and insulin/insulin-like growth factor signaling pathways could be partly involved in ECH-mediated lifespan extension. Thus, ECH may target multiple longevity mechanisms to extend lifespan and have a potency to prevent Alzheimer's disease progression.


Assuntos
Envelhecimento , Peptídeos beta-Amiloides/toxicidade , Cistanche , Glicosídeos/metabolismo , Longevidade , Estresse Oxidativo , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Antioxidantes/metabolismo , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Longevidade/efeitos dos fármacos , Longevidade/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Substâncias Protetoras/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
17.
Mol Ther Nucleic Acids ; 8: 111-122, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28918013

RESUMO

Cancer stem cells (CSCs) play an important role in osteosarcoma (OS) metastasis and recurrence, and both Wnt/ß-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/ß-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/ß-catenin and Notch signaling. The overexpression of miR-135b simultaneously targets multiple negative regulators of the Wnt/ß-catenin and Notch signaling pathways, including glycogen synthase kinase-3 beta (GSK3ß), casein kinase 1a (CK1α), and ten-eleven translocation 3 (TET3). Therefore, upregulated miR-135b promotes CSC traits, lung metastasis, and tumor recurrence in OS. Notably, antagonizing miR-135b potently inhibits OS lung metastasis, cancer cell stemness, CSC-induced tumor formation, and recurrence in xenograft animal models. These findings suggest that miR-135b mediates the constitutive activation of Wnt/ß-catenin and Notch signaling, and that the inhibition of miR-135b is a novel strategy to inhibit tumor metastasis and prevent CSC-induced recurrence in OS.

18.
Waste Manag ; 68: 221-231, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28655464

RESUMO

The present study systemically investigated the effect of a water-washing process on the removal of harmful chlorides, sulfates, and heavy metals in the air pollution control (APC) residue from municipal solid wastes incineration (MSWI), for sake of a better reuse and disposal of this kind of waste. In addition, the kinetic study was conducted to reveal the releasing mechanism of relevant element in the residue. The results show that, over 70wt.% of chlorides and nearly 25wt.% of sulfates in the residue could be removed by water washing. Based on an economical consideration, the optimal operation conditions for water washing of APC residue was at liquid/solid (L/S) ratio of 3mL:1g and extracting time of 5min. As expected, the concentrations of Co, Cr, Fe, Ni, V and Cu in the washing effluent increased with time during the washing process. However, the extracting regime differs among different heavy metals. The concentrations of Ba and Mn increased firstly but declined afterwards, and concentrations of Pb and Zn gradually declined while Cd and As kept constant with the increase of extracting time. It is worth mentioning that the bubbling of CO2 into the washing effluent is promisingly effective for a further removal of Pb, Cu and Zn. Furthermore, kinetic study of the water washing process reveals that the extracting of heavy metals during water washing follows a second-order model.


Assuntos
Cloro , Incineração , Metais Pesados , Eliminação de Resíduos , Poluição do Ar , Água
19.
Mol Ther ; 25(9): 2140-2149, 2017 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-28648665

RESUMO

Dysregulated microRNAs (miRNAs) play an important role in osteosarcoma (OS) progression. In the present study, we investigate the clinical significance of serum miR-491 level and the potential role of miR-491 in OS lung metastasis and chemoresistance. Clinical data show that the level of miR-491 was decreased in serum from OS patients compared with healthy control subjects, and that a decreased serum miR-491 level is correlated with increased metastasis, poor chemoresponse, and lower survival rate in OS patients. In vitro and in vivo experiments show that overexpression of miR-491 suppresses OS cell lung metastasis, whereas it enhances cisplatin (CDDP)-induced tumor growth inhibition and apoptosis. In contrast, inhibition of miR-491 stimulates OS cell lung metastasis and suppresses CDDP-induced tumor growth inhibition and apoptosis. Furthermore, we demonstrate that miR-491 exerts its role by directly targeting αB-crystallin (CRYAB) in OS. Our findings suggest that serum level of miR-491 has potential as a biomarker for predicting OS progression and prognosis of OS patients. Additionally, restoration of miR-491 may be a novel strategy for inhibiting OS lung metastasis and overcoming OS cell resistance to chemotherapy.


Assuntos
Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/secundário , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Cadeia B de alfa-Cristalina/genética , Apoptose , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , MicroRNA Circulante , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/sangue , Metástase Neoplásica , Estadiamento de Neoplasias , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Prognóstico , Interferência de RNA
20.
BMC Cancer ; 17(1): 245, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28376735

RESUMO

BACKGROUND: Central nervous system (CNS) brain metastasis of advanced non-small cell lung cancer (NSCLC) patients confers a worse quality of life and prognosis. The efficacy comparison of two first-generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib as first-line treatment for CNS metastasis NSCLC patients with EGFR-sensitizing mutations is yet to be elucidated. METHODS: A retrospective analysis was done on cerebral metastasis rate after erlotinib or gefitinib as first-line treatment for advanced NSCLC patients with EGFR-sensitizing mutations. Time to neurological progression (nTTP) and median progression-free survival (mPFS) were calculated. RESULTS: The study involved 279 patients (erlotinib group: 108, gefitinib group: 171). After a median follow-up of 22 months, 27 patients (25%) in the erlotinib group and 60 patients (35.1%) in the gefitinib group showed CNS progression. The HR of CNS progression for erlotinib versus gefitinib was 0.695 [95% confidence interval (CI), 0.406-1.190], suggesting a risk reduction of 30.5% although not achieving statistical significance. The 6-, 12- and 18-month cumulative CNS progression rates were 0.9, 3.7 and 12% for erlotinib compared with corresponding rates of 5.8, 9.4 and 17% for gefitinib (P = 0.181). However, for those patients with preexisting brain metastases prior to EGFR-TKI treatment, erlotinib as first line treatment significantly extended the median nTTP in comparison to gefitinib (30 months vs 15.8 months, p = 0.024). CONCLUSIONS: Our data show that nTTP can be effectively extended in preexisting brain metastases patients with EGFR-sensitizing mutations initially treated with erlotinib compared with gefitinib. If confirmed, our results indicate that erlotinib may play an important role in controlling CNS progression from EGFR mutation-positive NSCLC.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Receptores ErbB/genética , Adulto , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/secundário , Progressão da Doença , Intervalo Livre de Doença , Cloridrato de Erlotinib/administração & dosagem , Feminino , Gefitinibe , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Qualidade de Vida , Quinazolinas/administração & dosagem
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