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1.
Rev Med Suisse ; 15(666): 1790-1794, 2019 Oct 09.
Artigo em Francês | MEDLINE | ID: mdl-31599519

RESUMO

Actinomycosis is a chronic bacterial infection, caused by the genus Actinomyces, commensal of the digestive and genital tract. The most common presentation of the disease affects the cervicofacial region, but other anatomical sites in the abdomen, thorax and central nervous system may be involved. Differential diagnosis includes neoplasia. Prolonged culture of deep samples in an anaerobic environment is the gold standard of the diagnosis. The treatment of choice is intravenous penicillin G followed by oral amoxicillin for a total duration of 6 to 12 months. However, depending on the location and response to antibiotics, shorter therapy may be considered.


Assuntos
Actinomicose/diagnóstico , Actinomicose/tratamento farmacológico , Actinomyces/patogenicidade , Actinomicose/microbiologia , Actinomicose/patologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Humanos , Neoplasias/diagnóstico , Especificidade de Órgãos
2.
Anticancer Res ; 39(9): 4729-4736, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519572

RESUMO

BACKGROUND/AIM: Amphiregulin (AREG) and epiregulin (EREG) mRNA expression levels are predictors of response to anti-EGFR antibody therapy. Left-sided colon cancer is more sensitive to anti-EGFR antibodies than right-sided, although the mechanism is unclear. The aim of this study was to determine the relationship between AREG, EREG mRNA expression levels and tumor location as well as the efficacy of anti-EGFR antibody agents. MATERIALS AND METHODS: Real-time PCR was used to assess AREG and EREG mRNA expression in metastatic colorectal cancer (CRC) samples from 153 patients. RESULTS: Among KRASwt samples, high AREG expression (AREGHigh) was significantly more common in left-sided tumors than in right-sided. Among patients who received anti-EGFR antibody, response rates were significantly higher in AREGHigh than in AREGLow In the left-sided tumor group, overall survival was significantly longer in patients with high EREG levels than with low levels, whereas the right-sided tumor group showed no survival difference between them. CONCLUSION: AREG and EREG mRNA expression levels in left-sided CRC were higher than in right-sided tumors. This may help explain why left-sided CRC is more responsive to anti-EGFR antibodies.


Assuntos
Anfirregulina/genética , Neoplasias Colorretais/genética , Epirregulina/genética , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Especificidade de Órgãos/genética , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
3.
Anticancer Res ; 39(9): 4743-4748, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519574

RESUMO

BACKGROUND/AIM: Overexpression of human telomerase reverse transcriptase (hTERT) allows disordered proliferation and immortality of malignant cells, which has been of interest for the development of targeted therapies. The present study aimed to characterize hTERT gene expression in a series of cancer cell lines. MATERIALS AND METHODS: Leukemia cell lines K-562, its vincristine-resistant derivative K-562-Lucena1 and daunorubicin-resistant derivative FEPS; gastric adenocarcinoma lines AGP01, ACP02 and ACP03; melanoma SK-Mel-103 cells; and MN01 and MRC5, two non-neoplastic cell lines were analyzed by real-time polymerase chain reaction in order to evaluate hTERT gene expression. RESULTS: In leukemia cells, hTERT gene expression was significantly increased only in K-562 (p<0.05) and K-562-Lucena1 (p<0.001) when compared to the calibrator MRC5. For solid tumor types, only ACP03 presented a significant hTERT gene expression when compared to ACP02 (p<0.05). hTERT gene expression in K-562 and K-562-L ucena was significantly increased (p<0.05 to p<0.001) compared to all other cell lines except ACP03. CONCLUSION: In leukemia cell lines, hTERT gene overexpression was shown to be a potential target for pharmacological assays for drugs aiming to inhibit telomerase activity and control cell proliferation in oncohematological diseases.


Assuntos
Regulação Neoplásica da Expressão Gênica , Telomerase/genética , Biomarcadores Tumorais , Linhagem Celular Tumoral , Neoplasias Hematológicas/genética , Humanos , Neoplasias/genética , Especificidade de Órgãos/genética
4.
J Cancer Res Clin Oncol ; 145(10): 2413-2422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492983

RESUMO

PURPOSE: Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase that regulates centriole duplication. PLK4 deregulation causes centrosome number abnormalities, mitotic defects, chromosomal instability and, consequently, tumorigenesis. Therefore, PLK4 has emerged as a therapeutic target for the treatment of multiple cancers. In this review, we summarize the critical role of centrosome amplification and PLK4 in cancer. We also highlight recent advances in the development of PLK4 inhibitors and discuss potential combination therapies for cancer. METHODS: The relevant literature from PubMed is reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS: PLK4 is aberrantly expressed in multiple cancers and has prognostic value. Targeting PLK4 with inhibitors suppresses tumor growth in vitro and in vivo. CONCLUSIONS: PLK4 plays an important role in centrosome amplification and tumor progression. PLK4 inhibitors used alone or in combination with other drugs have shown significant anticancer efficacy, suggesting a potential therapeutic strategy for cancer. The results of relevant clinical trials await evaluation.


Assuntos
Biomarcadores Tumorais , Neoplasias/etiologia , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Centrossomo/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Especificidade de Órgãos/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Relação Estrutura-Atividade , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
Cancer Radiother ; 23(6-7): 666-673, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31451357

RESUMO

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the target volume. Tumor sensitivity to radiotherapy may be particularly inconstant depending on location, histology, somatic genetic parameters and the capacity of the immune system to infiltrate the tumor. In addition, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In a same population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists, namely in terms of late side effects that are in principle non-reversible. This review details the different radiobiological approaches that have been developed to better predict the tumor response but also the radiation-induced late effects.


Assuntos
Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Tolerância a Radiação , Biomarcadores Tumorais , Células Sanguíneas/efeitos da radiação , Reparo do DNA/genética , Humanos , Neoplasias/genética , Especificidade de Órgãos , Prognóstico , Proteômica , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Sensibilidade e Especificidade , Resultado do Tratamento
7.
Gene ; 715: 144028, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31374326

RESUMO

BACKGROUND: Type 2 diabetes (T2D) is a complex polygenic disease with unclear mechanism. In an attempt to identify novel genes involved in ß-cell function, we harness a bioinformatics method called Loss-of-function tool (LoFtool) gene score. METHODS: RNA-sequencing data from human islets were used to cross-reference genes within the 1st quartile of most intolerant LoFtool score with the 100th most expressed genes in human islets. Out of these genes, GNAS and EEF1A1 genes were selected for further investigation in diabetic islets, metabolic tissues along with their correlation with diabetic phenotypes. The influence of GNAS and EEF1A1 on insulin secretion and ß-cell function were validated in INS-1 cells. RESULTS: A comparatively higher expression level of GNAS and EEF1A1 was observed in human islets than fat, liver and muscle tissues. Furthermore, diabetic islets displayed a reduced expression of GNAS, but not of EEF1A, compared to non-diabetic islets. The expression of GNAS was positively correlated with insulin secretory index, GLP1R, GIPR and inversely correlated with HbA1c. Diabetic human islets displayed a reduced cAMP generation and insulin secretory capacity in response to glucose. Moreover, siRNA silencing of GNAS in INS-1 cells reduced insulin secretion, insulin content, and cAMP production. In addition, the expression of Insulin, PDX1, and MAFA was significantly down-regulated in GNAS-silenced cells. However, cell viability and apoptosis rate were unaffected. CONCLUSION: LoFtool is a powerful tool to identify genes associated with pancreatic islets dysfunction. GNAS is a crucial gene for the ß-cell insulin secretory capacity.


Assuntos
Cromograninas/biossíntese , Subunidades alfa Gs de Proteínas de Ligação ao GTP/biossíntese , Regulação da Expressão Gênica , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Idoso , Animais , Linhagem Celular , Cromograninas/genética , AMP Cíclico/genética , AMP Cíclico/metabolismo , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Células Secretoras de Insulina/citologia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Fator 1 de Elongação de Peptídeos/genética , Fator 1 de Elongação de Peptídeos/metabolismo , Ratos
8.
Food Chem ; 301: 125262, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377625

RESUMO

Differences in the expression of functional genes between beef Longissimus Lumborum (LL) and Psoas Major (PM) are not well understood. The aim of present study is to reveal transcriptome changes of beef LL and PM during early postmortem by high-throughput Illumina Hiseq4000 Sequencing. Hierarchical clustering analysis indicated significant differences in transcriptome profiles between LL and PM as well as 1 h and 12 h postmortem. A total of 65 genes differentially expressed between LL and PM (fold change ≥3, and p < 0.05; 34 were up-regulated in LL and 31 in PM), and the majority of them (53 genes) occurred at 12 h postmortem. These differentially expressed genes mainly involved in energy production and conversion, nucleotide metabolic, posttranslational modification, and transcription. KEGG analysis revealed that oxidative phosphorylation was one of the important pathways. This study gave new perspectives to understand the underlying mechanisms associated with muscle-specific beef quality.


Assuntos
Perfilação da Expressão Gênica , Músculos/metabolismo , Animais , Bovinos , Análise por Conglomerados , Cor , Especificidade de Órgãos , Carne Vermelha/análise
9.
Int J Nanomedicine ; 14: 5397-5413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409995

RESUMO

Background: Hyperlipidemia is the elevation of low density lipoprotein levels resulting in fat deposites in arteries and their hardening and blockage.  It is the leading cause of several life threatening pathological conditions like hypertension, cardiovascular diseases, diabetes etc. Purpose: The objective of this study was to prepare and optimize nontoxic, biocompatible ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels with varying content of polymer, monomer and montmorillonite. Moreover, lipid lowering potentials were determined and compared with other approaches. Methods: ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels (BM-1 to BM9) were prepared through free radical polymerization by using  ß-CD  as polymer, MAA as monomer, MBA as crosslinker and montmorillonite as clay. Developed networks were evaluated for FTIR, DSC, TGA, PXRD, SEM, sol-gel fraction (%), swelling studies, antihyperlipidemic studies and toxicity studies. Results: Optimum swelling (94.24%) and release (93.16%) were obtained at higher pH values. Based on R2 and "n" value LVT release followed zero order kinetics with Super Case II transport release mechanism, respectively. Tensile strength and elongation at break were found to be 0.0283MPa and 94.68%, respectively. Gel fraction was between 80.55 - 98.16%. Antihyperlipidemic studies revealed that LDL levels were markedly reduced from 522.24 ± 21.88mg/dl to 147.63 ± 31.5mg/dl. Toxicity studies assured the safety of developed network. Conclusion: A novel pH responsive crosslinked network containing ß-CD - g - poly (methacrylic acid) polymer and MMT was developed and optimized with excellent mechanical, swelling and release properties and lipid lowering potentials.


Assuntos
Bentonita/química , Hidrogéis/química , Lovastatina/administração & dosagem , Metacrilatos/química , Nanocompostos/química , beta-Ciclodextrinas/química , Acrilamidas/química , Administração Oral , Animais , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Cinética , Lipídeos/sangue , Nanocompostos/ultraestrutura , Especificidade de Órgãos , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Resistência à Tração , Termogravimetria , Testes de Toxicidade Aguda , Difração de Raios X
10.
Int J Nanomedicine ; 14: 5611-5622, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413566

RESUMO

Background: Multimodal imaging probes have become a powerful tool for improving detection sensitivity and accuracy, which are important in disease diagnosis and treatment. Methods: In this study, novel bifunctional magnetic resonance imaging (MRI)/fluorescence probes were prepared by loading gadodiamide into fluorescent silica nanoparticles (NPs) (Gd@Cy5.5@SiO2-PEG-Ab NPs) for targeting of prostate cancer (PCa). The physicochemical characteristics, biosafety and PCa cell targeting ability of the Gd@Cy5.5@SiO2-PEG-Ab NPs were studied in vitro and in vivo. Results: The Gd@Cy5.5@SiO2-PEG-Ab NPs had a spherical morphology with a relatively uniform size distribution and demonstrated high efficiency for Gd loading. In vitro and in vivo cell-targeting experiments demonstrated a high potential for the synthesized NPs to target prostate-specific membrane antigen (PSMA) receptor-positive PCa cells, enabling MRI and fluorescence imaging. In vitro cytotoxicity assays and in vivo hematological and pathological assays showed that the prepared NPs exhibited good biological safety. Conclusion: Our study demonstrates that the synthesized Gd@Cy5.5@SiO2-PEG-Ab NPs have great potential as MRI/fluorescence contrast agents for specific identification of PSMA receptor-positive PCa cells.


Assuntos
Gadolínio DTPA/química , Imagem por Ressonância Magnética , Nanopartículas/química , Polietilenoglicóis/química , Neoplasias da Próstata/diagnóstico por imagem , Dióxido de Silício/química , Animais , Anticorpos/metabolismo , Linhagem Celular Tumoral , Meios de Contraste , Endocitose , Fluorescência , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Especificidade de Órgãos , Polietilenoglicóis/síntese química , Padrões de Referência
11.
Presse Med ; 48(7-8 Pt 2): e219-e231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447333

RESUMO

Image-guided ablation is performed by percutaneously introducing ablation probes to deliver energy into a tumor to destroy it in a controlled and localized fashion. Ablation modalities can be broadly classified as thermal or non-thermal based on the mechanism of tumor destruction and are performed using different types of image guidance for planning, delivering and follow-up of the treatment. Ablation is performed in a minimally invasive fashion, providing greater residual organ preservation with minimal morbidity to the patient. Image-guided ablation is being used in the clinic for the treatment of primary and metastatic tumors, and this article reviews state of the art for the treatment of malignancies in the liver, lung, kidney and musculoskeletal tissue.


Assuntos
Ablação por Cateter/métodos , Neoplasias/cirurgia , Cirurgia Assistida por Computador/métodos , Ablação por Cateter/efeitos adversos , Tecido Conjuntivo/patologia , Tecido Conjuntivo/cirurgia , Humanos , Rim/patologia , Rim/cirurgia , Fígado/patologia , Fígado/cirurgia , Pulmão/patologia , Pulmão/cirurgia , Sistema Musculoesquelético/patologia , Sistema Musculoesquelético/cirurgia , Neoplasias/diagnóstico , Neoplasias/patologia , Especificidade de Órgãos , Complicações Pós-Operatórias/etiologia , Cirurgia Assistida por Computador/efeitos adversos , Resultado do Tratamento
12.
BMC Bioinformatics ; 20(1): 385, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288758

RESUMO

BACKGROUND: In cancer research, robustness of a complex biochemical network is one of the most relevant properties to investigate for the development of novel targeted therapies. In cancer systems biology, biological networks are typically modeled through Ordinary Differential Equation (ODE) models. Hence, robustness analysis consists in quantifying how much the temporal behavior of a specific node is influenced by the perturbation of model parameters. The Conditional Robustness Algorithm (CRA) is a valuable methodology to perform robustness analysis on a selected output variable, representative of the proliferation activity of cancer disease. RESULTS: Here we introduce our new freely downloadable software, the CRA Toolbox. The CRA Toolbox is an Object-Oriented MATLAB package which implements the features of CRA for ODE models. It offers the users the ability to import a mathematical model in Systems Biology Markup Language (SBML), to perturb the model parameter space and to choose the reference node for the robustness analysis. The CRA Toolbox allows the users to visualize and save all the generated results through a user-friendly Graphical User Interface (GUI). The CRA Toolbox has a modular and flexible architecture since it is designed according to some engineering design patterns. This tool has been successfully applied in three nonlinear ODE models: the Prostate-specific Pten-/- mouse model, the Pulse Generator Network and the EGFR-IGF1R pathway. CONCLUSIONS: The CRA Toolbox for MATLAB is an open-source tool implementing the CRA to perform conditional robustness analysis. With its unique set of functions, the CRA Toolbox is a remarkable software for the topological study of biological networks. The source and example code and the corresponding documentation are freely available at the web site: http://gitlab.ict4life.com/SysBiOThe/CRA-Matlab .


Assuntos
Algoritmos , Modelos Biológicos , Neoplasias/metabolismo , Software , Biologia de Sistemas/métodos , Animais , Simulação por Computador , Modelos Animais de Doenças , Receptores ErbB/metabolismo , Humanos , Cinética , Masculino , Camundongos , Especificidade de Órgãos , PTEN Fosfo-Hidrolase/deficiência , PTEN Fosfo-Hidrolase/metabolismo , Próstata/metabolismo , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais
13.
BMC Bioinformatics ; 20(1): 408, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357929

RESUMO

BACKGROUND: Understanding the phenotypic drug response on cancer cell lines plays a vital role in anti-cancer drug discovery and re-purposing. The Genomics of Drug Sensitivity in Cancer (GDSC) database provides open data for researchers in phenotypic screening to build and test their models. Previously, most research in these areas starts from the molecular fingerprints or physiochemical features of drugs, instead of their structures. RESULTS: In this paper, a model called twin Convolutional Neural Network for drugs in SMILES format (tCNNS) is introduced for phenotypic screening. tCNNS uses a convolutional network to extract features for drugs from their simplified molecular input line entry specification (SMILES) format and uses another convolutional network to extract features for cancer cell lines from the genetic feature vectors respectively. After that, a fully connected network is used to predict the interaction between the drugs and the cancer cell lines. When the training set and the testing set are divided based on the interaction pairs between drugs and cell lines, tCNNS achieves 0.826, 0.831 for the mean and top quartile of the coefficient of determinant (R2) respectively and 0.909, 0.912 for the mean and top quartile of the Pearson correlation (Rp) respectively, which are significantly better than those of the previous works (Ammad-Ud-Din et al., J Chem Inf Model 54:2347-9, 2014), (Haider et al., PLoS ONE 10:0144490, 2015), (Menden et al., PLoS ONE 8:61318, 2013). However, when the training set and the testing set are divided exclusively based on drugs or cell lines, the performance of tCNNS decreases significantly and Rp and R2 drop to barely above 0. CONCLUSIONS: Our approach is able to predict the drug effects on cancer cell lines with high accuracy, and its performance remains stable with less but high-quality data, and with fewer features for the cancer cell lines. tCNNS can also solve the problem of outliers in other feature space. Besides achieving high scores in these statistical metrics, tCNNS also provides some insights into the phenotypic screening. However, the performance of tCNNS drops in the blind test.


Assuntos
Antineoplásicos/uso terapêutico , Aprendizado Profundo , Neoplasias/tratamento farmacológico , Redes Neurais (Computação) , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Bases de Dados Factuais , Genômica , Humanos , Concentração Inibidora 50 , Especificidade de Órgãos/efeitos dos fármacos , Fenótipo , Análise de Regressão
14.
Int J Nanomedicine ; 14: 4309-4317, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354262

RESUMO

Background: The intraoperative visualization of tumor cells is a powerful modality for surgical treatment of solid tumors. Since the completeness of tumor excision is closely correlated with the survival of patients, probes that can assist in distinguishing tumor cells are highly demanded. Purpose: In the present study, a fluorescent probe JF1 was synthesized for imaging of tumor cells by conjugating a substrate of cathepsin B (quenching moiety) to Oregon Green derivative JF2 using a self-immolative linker. Methods: JF1 was then loaded into the folate-PEG modified CaCO3 nanoparticles. The folate receptor-targeted, pH-dependent, and cathepsin B activable CaCO3 nanoprobe was test in vitro and in vivo for tumor imaging. Results: CaCO3 nanoprobe demonstrated good stability and fast lighting ability in tumors under low pH conditions. It also showed lower fluorescence background than the single cathepsin B dependent fluorescent probe. The pH-dependent and cathepsin B controlled "turn-on" property enables precise and fast indication of tumor in vitro and in vivo. Conclusion: This strategy of controlled drug delivery enables in vivo imaging of tumor nodules with a high signal-to-noise ratio, which has great potential in surgical tumor treatment.


Assuntos
Carbonato de Cálcio/química , Catepsina B/metabolismo , Diagnóstico por Imagem , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Animais , Corantes Fluorescentes/química , Ácido Fólico/análogos & derivados , Ácido Fólico/química , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Nanopartículas/ultraestrutura , Neoplasias/patologia , Especificidade de Órgãos , Polietilenoglicóis/química
15.
Int J Nanomedicine ; 14: 4367-4381, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354266

RESUMO

Purpose: Polyethylenimine (PEI) has been widely used as a versatile template to develop multifunctional nanosystems for disease diagnosis and treatment. In this study, we manufactured iodine-131 (131I)-labeled PEI-entrapped gold nanoparticles (Au PENPs) as a novel nanoprobe for single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and radionuclide therapy. Materials and methods: PEI was PEGylated and sequentially conjugated with Buthus martensii Karsch chlorotoxin (BmK CT, a tumor-specific ligand which can selectively bind to MMP2), 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), and fluorescein isothiocyanate to form the multifunctional PEI template for entrapment of Au NPs. Then, the PEI surface was radiolabeled with 131I via HPAO to produce the novel nanoprobe (BmK CT-Au PENPs-131I). Results: The synthesized multifunctional Au PENPs before and after 131I radiolabeling were well-characterized as follows: structure, X-ray attenuation coefficient, colloid stability, cytocompatibility, and radiochemical stability in vitro. Furthermore, BmK CT-Au PENPs-131I were suitable for targeted SPECT/CT imaging and radionuclide therapy of tumor cells in vitro and in a xenograft tumor model in vivo. Conclusion: The developed multifunctional Au PENPs are a promising theranostic platform for targeted imaging and treatment of different MMP2-overexpressing tumors.


Assuntos
Ouro/química , Radioisótopos do Iodo/química , Nanopartículas Metálicas/química , Polietilenoimina/química , Compostos Radiofarmacêuticos/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Coloides/química , Glioma/patologia , Glioma/radioterapia , Humanos , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos BALB C , Camundongos Nus , Especificidade de Órgãos , Tamanho da Partícula , Propionatos/química , Venenos de Escorpião/toxicidade
16.
Plant Foods Hum Nutr ; 74(3): 436-442, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321622

RESUMO

In this work, the profiles of phenolics, fiber, pectins, sugars, organic acids and carotenoids, vitamin C, ash, protein and fat contents, as well as antioxidant capacity were compared in fruits, flowers, and bark of Viburnum opulus (VO). Antioxidant capacity was evaluated against ABTS, hydroxyl, peroxyl and superoxide free radicals, and as a reducing power by using in vitro test. The results showed great quantitative differences in the composition of the VO morphological parts tested. Fruits contained the highest concentrations of fat, organic acids, sugars, soluble dietary fiber (10.57 ± 0.54; 7.34 ± 0.06; 32.27 ± 1.25; 6.82 ± 0.38 g/100 g DW, respectively) and carotenoids (2.70 ± 0.07 mg/100 g DW). Whereas, the bark exceeded the remaining parts of the VO in terms of antioxidant capacity, ash (9.32 ± 0.17 g/100 g DW), total (59.34 ± 0.75 g/100 g DW) and insoluble dietary fiber (58.20 ± 0.73 g/100 g DW) contents as well as phenolic compounds (3.98 ± 0.04 g/100 g DW). Among the phenolic compounds quantified in this study, chlorogenic acid and (+)-catechin had the highest concentrations (> 1 g/100 g DW) in the flowers and bark, respectively.


Assuntos
Antioxidantes/análise , Carotenoides/análise , Nutrientes/análise , Fenóis/análise , Viburnum/química , Ácidos Carboxílicos/análise , Catequina/análise , Ácido Clorogênico/análise , Fibras na Dieta/análise , Flores/química , Frutas/química , Especificidade de Órgãos , Pectinas/análise , Casca de Planta/química , Açúcares/análise
17.
J Cancer Res Clin Oncol ; 145(8): 1949-1976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31292714

RESUMO

PURPOSE: Efflux transporters of the adenosine triphosphate-binding cassette (ABC)-superfamily play an important role in the development of multidrug resistance (multidrug resistant; MDR) in cancer. The overexpression of these transporters can directly contribute to the failure of chemotherapeutic drugs. Several in vitro and in vivo models exist to screen for the efficacy of chemotherapeutic drugs against MDR cancer, specifically facilitated by efflux transporters. RESULTS: This article reviews a range of efflux transporter-based MDR models used to test the efficacy of compounds to overcome MDR in cancer. These models are classified as either in vitro or in vivo and are further categorised as the most basic, conventional models or more complex and advanced systems. Each model's origin, advantages and limitations, as well as specific efflux transporter-based MDR applications are discussed. Accordingly, future modifications to existing models or new research approaches are suggested to develop prototypes that closely resemble the true nature of multidrug resistant cancer in the human body. CONCLUSIONS: It is evident from this review that a combination of both in vitro and in vivo preclinical models can provide a better understanding of cancer itself, than using a single model only. However, there is still a clear lack of progression of these models from basic research to high-throughput clinical practice.


Assuntos
Transportadores de Cassetes de Ligação de ATP/fisiologia , Antineoplásicos/isolamento & purificação , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Modelos Biológicos , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/genética , Técnicas de Cultura/métodos , Técnicas de Apoio para a Decisão , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Especificidade de Órgãos , Seleção de Pacientes
18.
Artigo em Inglês | MEDLINE | ID: mdl-31255700

RESUMO

Myogenic regulatory factor 4 (MRF4) is a basic helix-loop-helix (bHLH) transcription factor that plays crucial roles in myoblast differentiation and maturation. Here, we report the isolation of the olive flounder (Paralichthys olivaceus) mrf4 gene and the spatiotemporal analysis of its expression patterns. Sequence analysis indicated that flounder mrf4 shared a similar structure with other vertebrate MRF4, including the conserved bHLH domain. Flounder mrf4 contains 3 exons and 2 introns. Sequence alignment and phylogenetic analysis showed that it was highly homologous with Salmo salar, Danio rerio, Takifugu rubripes, and Tetraodon nigroviridis mrf4. Flounder mrf4 was first expressed in the medial region of somites that give rise to slow muscles, and later spread to the lateral region of somites that give rise to fast muscles. Mrf4 transcript levels decreased significantly in mature somites in the trunk region, and expression could only be detected in the caudal somites, consistent with the timing of somite maturation. Transient expression analysis showed that the 506 bp flounder mrf4 promoter was sufficient to direct muscle-specific GFP expression in zebrafish embryos.


Assuntos
Proteínas de Peixes/genética , Linguado/genética , Músculos/metabolismo , Fatores de Regulação Miogênica/genética , Regiões Promotoras Genéticas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Desenvolvimento Embrionário , Proteínas de Peixes/química , Linguado/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Fatores de Regulação Miogênica/química , Especificidade de Órgãos
19.
Nature ; 571(7765): 349-354, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292549

RESUMO

Ascidian embryos highlight the importance of cell lineages in animal development. As simple proto-vertebrates, they also provide insights into the evolutionary origins of cell types such as cranial placodes and neural crest cells. Here we have determined single-cell transcriptomes for more than 90,000 cells that span the entirety of development-from the onset of gastrulation to swimming tadpoles-in Ciona intestinalis. Owing to the small numbers of cells in ascidian embryos, this represents an average of over 12-fold coverage for every cell at every stage of development. We used single-cell transcriptome trajectories to construct virtual cell-lineage maps and provisional gene networks for 41 neural subtypes that comprise the larval nervous system. We summarize several applications of these datasets, including annotating the synaptome of swimming tadpoles and tracing the evolutionary origin of cell types such as the vertebrate telencephalon.


Assuntos
Linhagem da Célula/genética , Ciona intestinalis/citologia , Ciona intestinalis/genética , Análise de Célula Única , Transcriptoma , Animais , Sequência de Bases , Evolução Biológica , Ciona intestinalis/classificação , Ciona intestinalis/crescimento & desenvolvimento , Gastrulação , Redes Reguladoras de Genes , Larva/citologia , Larva/genética , Sistema Nervoso/citologia , Sistema Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Notocorda/citologia , Notocorda/embriologia , Especificidade de Órgãos , Sinapses/genética , Sinapses/metabolismo
20.
Anim Genet ; 50(5): 417-422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31268171

RESUMO

IPW (imprinted gene in the Prader-Willi syndrome region), a long non-coding RNA, is a paternally expressed gene in the PWS/AS imprinted domain on human chromosome 15 and mouse chromosome 7. Disruption of the PWS/AS region is associated with three neurogenic disorders in humans. In this study, we identified the bovine homolog of the IPW gene; multiple transcripts obtained by RT-PCR and RACE showed a complex and tissue-specific expression pattern of IPW in the brain, heart, kidney, liver, lung, spleen and skeletal muscle. An informative single nucleotide polymorphism (rs133341090) in the long exon H was identified by sequencing the genomic DNA, and mono-allelic expression of IPW was confirmed by sequencing the cDNAs of heterozygous individuals, indicating that IPW may be imprinted in cattle. The protein-coding potential of IPW transcripts was assessed using coding potential calculator (cpc) software, which showed a negative score. In addition, sequencing analysis also indicated multiple small open reading frames in the bovine IPW transcript, but none of the ATGs was consistent with Kozak consensus. Taken together, the IPW transcripts are most likely long non-coding RNAs.


Assuntos
Bovinos/genética , Cromossomos de Mamíferos , RNA Longo não Codificante/genética , Animais , Clonagem Molecular , Feminino , Expressão Gênica , Impressão Genômica , Masculino , Estrutura Molecular , Especificidade de Órgãos , Síndrome de Prader-Willi/genética , Homologia de Sequência do Ácido Nucleico
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