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1.
Front Bioeng Biotechnol ; 12: 1382071, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745843

RESUMO

Bicarbonate ion-containing solutions such as seawater, natural brines, bovine serum and other mineralizing fluids have been found to contain hyperalkaline droplets of a separate, liquid condensed phase (LCP), that have higher concentrations of bicarbonate ion (HCO3 -) relative to the bulk solution in which they reside. The existence and unique composition of the LCP droplets have been characterized by nanoparticle tracking analysis, nuclear magnetic resonance spectroscopy, fourier transform infrared spectroscopy, dissolved inorganic carbon analysis and refractive index measurements. Carbon dioxide can be brought into solution through an aqueous reaction to form LCP droplets that can then be separated by established industrial membrane processes as a means of concentrating HCO3 -. Reaction of calcium with the LCP droplets results in calcium carbonate precipitation and mineral formation. The LCP phenomenon may bear on native mineralization reactions and has the potential to change fundamental approaches to carbon capture, sequestration and utilization.

2.
Phys Med ; 93: 38-45, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34920381

RESUMO

PURPOSE: This study aimed to determine the optimal initial electron beam parameters of a Linac for radiotherapy with a multivariate approach using statistical and machine-learning tools. METHODS: For MC beam commissioning, a 6 MV Varian Clinac was simulated using the Geant4 toolkit. The authors investigated the relations between simulated dose distribution and initial electron beam parameters, namely, mean energy (E), energy spread (ES), and radial beam size (RS). The goodness of simulation was evaluated by the slope of differences between the simulated and the golden beam data. The best-fit combination of the electron beam parameters that minimized the slope of dose difference was searched through multivariate methods using conventional statistical methods and machine-learning tools of the scikit-learn library. RESULTS: Simulation results with 87 combinations of the electron beam parameters were analyzed. Regardless of being univariate or multivariate, traditional statistical models did not recommend a single parameter set simultaneously minimizing slope of dose differences for percent depth dose (PDD) and lateral dose profile (LDP). Two machine learning classification modules, RandomForestClassifier and BaggingClassifier, agreed in recommending (E = 6.3 MeV, ES = ±5.0%, RS = 1.0 mm) for predicting simultaneous acceptance of PDD and LDP. CONCLUSIONS: The machine learning with random-forest and bagging classifier modules recommended a consistent result. It was possible to draw an optimal electron beam parameter set using multivariate methods for MC simulation of a radiotherapy 6 MV Linac.


Assuntos
Elétrons , Aceleradores de Partículas , Simulação por Computador , Aprendizado de Máquina , Método de Monte Carlo
3.
Front Public Health ; 9: 658220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869134

RESUMO

Introduction: The patient-doctor relationship has evolved from early paternalism to a consumerism and partnership model that emphasizes cooperation. Patient-doctor relationships might vary with the socio-cultural environment, because the medical environment affects such relationships. Method: We investigated the patient-doctor relationship among medical students through concept mapping analysis. Twenty-six fourth-grade Korean medical students wrote a reflection journal and participated in the concept classification and the importance evaluation of the derived concept. ALSCAL multidimensional scaling and Ward hierarchical cluster analysis were performed. Also, the 5-point Likert scale was used to evaluate the importance of the concept. Results: Sixty-six statements about the patient-doctor relationship were extracted and grouped into six clusters. The x-axis is the dimension of "Information-Respect," and the y-axis is "Changeability-Persistence." Six patient-doctor concepts were derived and students evaluated "Patient-centered" as the most important. Conclusions: Medical students express various concepts of the patient-doctor relationship. Considering that they may encounter various medical conditions and patients, it is necessary that they understand deeply the complex patient-doctor relationship.


Assuntos
Relações Médico-Paciente , Estudantes de Medicina , Humanos , República da Coreia
4.
R Soc Open Sci ; 8(4): 201752, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33996119

RESUMO

In this study, in vitro preimplantation embryo culture media especially for outbred stock mice (Institute of Cancer Research (ICR)) were optimized with different concentrations of ethylenediaminetetraacetic acid (EDTA). A plot with embryo development rates against EDTA concentrations ranging from 0 to 500 µM showed a unique pattern with two characteristic peaks. Two hundred micromolar was adopted as an optimal concentration of EDTA. The optimized media were also evaluated with two culture systems: conventional large volume culture system (1 ml) and micro-droplet culture system. In the conventional large volume culture system, the blastocyst development rates were compared among three different media (F-10, KSOM and KSOM with the optimized 200 µM EDTA). The rates were 0.4%, 16.7% and 57.6%, respectively. The development rates for the micro-droplet (10 µl) culture system were 73.9%. In conclusion, 200 µM EDTA concentration in 10 µl droplets in the KSOM medium was found as the most suitable culture conditions for ICR mouse embryos, as the blastocyst development rate was higher in the micro-droplet culture system than in the traditional conventional large volume culture system.

5.
Int J Mol Sci ; 20(24)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817673

RESUMO

MicroRNAs (miRNAs) can be used to target a variety of human malignancy by targeting their oncogenes or tumor suppressor genes. The developmental endothelial locus-1 (Del-1) might be under miRNA regulation. This study investigated microRNA-137 (miR-137) function and Del-1 expression in triple-negative breast cancer (TNBC) cells and tissues. Del-1 mRNA and miRNA-137 levels were determined via qRT-PCR in breast cancer cells (MDA-MB-231, MCF7, SK-BR3, and T-47D) and tissues from 30 patients with TNBC. The effects of miR-137 on cell proliferation, migration, and invasion were determined using MTT assays, wound healing, and Matrigel transwell assays. The luciferase reporter assay revealed direct binding of miR-137 to the 3'-UTR of Del-1. miR-137 inhibited cell proliferation, migration, and invasion of MDA-MB-231 cells. Among the 30 TNBC specimens, miR-137 was downregulated and Del-1 level in plasma was significantly elevated relative to normal controls. It is concluded that miR-137 regulates Del-1 expression in TNBC by directly binding to the Del-1 gene and cancer progression. The results implicate miR-137 as a new therapeutic biomarker for patients with TNBC.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Moléculas de Adesão Celular/metabolismo , Proliferação de Células/fisiologia , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas de Ligação ao Cálcio/genética , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Ensaio de Imunoadsorção Enzimática , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , MicroRNAs/genética , Plasmídeos/genética , Neoplasias de Mama Triplo Negativas/genética
6.
Oncology ; 97(3): 180-188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31330520

RESUMO

BACKGROUND: Hormone receptor-positive breast cancer accounts for nearly two-thirds of breast cancer cases; it ultimately acquires resistance during endocrine treatment and becomes more aggressive. This study evaluated the role of developmental endothelial locus (Del)-1 in tamoxifen-resistant (TAM-R) breast cancer. METHODS: Del-1 expression in recurrent TAM-R breast cancer tissue was evaluated and compared to that in the original tumor tissue from the same patients. Del-1 expression was also evaluated in TAM-R cells by quantitative real-time PCR, western blotting, and enzyme-linked immunosorbent assay. The effects of Del-1 knockdown on the proliferation, migration, and invasion of TAM-R cells was assessed with wound-healing and Matrigel transwell assays. RESULTS: Del-1 was more highly expressed in recurrent breast cancer as compared to the original tumor tissues before initiation of endocrine treatment. Del-1 mRNA was upregulated in TAM-R and small interfering RNA-mediated knockdown of Del-1 suppressed the migration and proliferation of TAM-R cells while partly restoring TAM sensitivity. And the TAM resistance was recovered by knockdown of Del-1. CONCLUSIONS: TAM-R breast cancer is characterized by Del-1 overexpression and tumor progression can be inhibited by Del-1 depletion, which restores TAM sensitivity. Thus, therapeutic strategies that target Del-1 may be effective for the treatment of hormone-resistant breast cancer.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/genética , Proteínas de Transporte/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Tamoxifeno/farmacologia , Neoplasias da Mama/metabolismo , Proteínas de Ligação ao Cálcio , Proteínas de Transporte/metabolismo , Moléculas de Adesão Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Técnicas de Silenciamento de Genes , Humanos , Interferência de RNA , RNA Interferente Pequeno
7.
Lung Cancer ; 132: 99-106, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31097102

RESUMO

OBJECTIVES: MicroRNAs have critical roles in cancer development by regulating the expression of oncogenes or tumor suppressor genes. We identified and characterized a novel miRNA, miR-CHA1, in human lung cancer cells. The aim of this study was to investigate its novel function in human lung cancer by targeting XIAP. MATERIAL AND METHODS: Novel miRNA cloning, Real-time qRT-PCR, western blotting, dual luciferase assay, miRNA transfection, proliferation and apoptosis assay were carried on human lung cancer cell line A549. Fifteen paired NSCLC tissues and noncancerous lung tissues were collected. In vivo xenograft assay was performed. RESULTS: Expression of miR-CHA1 was downregulated in human lung cancer cell lines and tissues compared with normal cells and tissues. We identified a putative target gene, XIAP, whose expression was regulated by miR-CHA1 overexpression. XIAP is an inhibitor of apoptosis that represses the activation of caspase 3 and 9. XIAP mRNA and protein levels were directly suppressed by miR-CHA1. XIAP has an important role in carcinogenesis, and previous studies suggest that it may regulate cell survival and proliferation by its anti-apoptotic ability. CONCLUSION: Taken together, miR-CHA1 inhibited cell proliferation and induced apoptosis in vitro and in vivo by targeting XIAP. These data can be applied to identify novel therapeutic targets for lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Células A549 , Animais , Apoptose , Carcinogênese/genética , Caspase 3/metabolismo , Caspase 9/metabolismo , Proliferação de Células , Clonagem Molecular , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Nus , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Support Care Cancer ; 26(1): 297-303, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28791486

RESUMO

INTRODUCTION: To give informed consent, a patient needs to sufficiently understand the information provided by a physician to decide among treatment options. Although shared decision-making is becoming an important aspect of patient-centered care, little is known about decision-making by cancer patients in Korea. OBJECTIVES: This study assessed Korean cancer patients' understanding of treatment goals and the need to obtain further information after a physician obtained informed consent for radiotherapy. METHODS: In this prospective study, doctors and patients completed questionnaires independently after informed consent for radiotherapy had been obtained. The questionnaires for the doctors and patients were comprised of matched items regarding treatment aims and the need for further information. RESULTS: The study enrolled 103 cancer patients scheduled for radiotherapy. The proportion of respondents who stated that the intent of treatment was to bring about a cure was 80.6% among the patients (83 of 103 patients) and 53.4% (55 of 103 patients) among the doctors (p = 0.000). The proportion of respondents who believed that the aim was prolongation of life was 16.5 and 1.9%, respectively (p = 0.000). Regarding the need for further information, 42.7% (44/103) of the patients did not want further information because they had faith in the physicians' medical expertise. CONCLUSION: Many Korean cancer patients misunderstand the aims of treatment and half of participants do not want further information. Physicians should address whether specific interventions can solve these barriers so that Korean cancer patients can make truly autonomous treatment decisions.


Assuntos
Tomada de Decisões/ética , Consentimento Livre e Esclarecido/ética , Neoplasias/radioterapia , Relações Médico-Paciente/ética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Inquéritos e Questionários , Adulto Jovem
11.
Tumour Biol ; 39(6): 1010428317707374, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28653903

RESUMO

PURPOSE: Long noncoding RNA, snaR (small NF90-associated RNA), has been reported to be upregulated in various cancer cell lines. We evaluated the additional role of snaR in HER2-positive breast cancer cell lines. METHODS: We explored changes of expression of snaR among the selected long noncoding RNAs which have a potential in cancer proliferation or progression. The proliferation, migration, and invasion of HER2-positive breast cancer cells (SK-BR3) were evaluated by snaR with RNA interruption in 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, wound-healing assay, and Transwell assay. RESULTS: The expression of snaR was remarkably upregulated in SK-BR3 cell lines together with ANRIL, while the SFMBT2 was downregulated in SK-BR3 cell lines. Although Nespas, 7SK, PSF inhibiting RNA, mascRNA, Hoxa11as, NRON, AK023948, MER11C, p53 mRNA, CAR Intergenic 10, HUC 1 and 2, ZFAS1, SCA8, and SNHG5 were also upregulated and UCA1 was downregulated, the differences were not dominent. Based on the expression result, we explored the functional role of snaR in HER2-positive breast cancer. Downregulation of snaR with small interfering RNA was identified to significanlty inhibit migration as well as proliferation of SK-BR3 cells. CONCLUSION: In this study, snaR was identified as upregulated and to play a role in cancer progression of HER2-positive breast cancer cells. These results suggest snaR as a potential biomarker for HER2-positive breast cancer.


Assuntos
Neoplasias da Mama/genética , Proteínas de Neoplasias/biossíntese , RNA Longo não Codificante/biossíntese , Receptor ErbB-2/genética , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , RNA Mensageiro/biossíntese , Ativação Transcricional/genética
12.
BMC Cancer ; 17(1): 297, 2017 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-28454573

RESUMO

BACKGROUND: The aim of the present study was to investigate the long-term survival outcomes and toxicities associated with our experienced early administration of adjuvant concurrent chemoradiotherapy (CCRT). METHODS: Ninety-eight patients with pelvic lymph node metastasis, positive resection margin, and/or parametrial invasion who received adjuvant CCRT between 1995 and 2011 were analyzed retrospectively. The first cycle of platinum-based adjuvant chemotherapy was initiated within 2-3 weeks after surgery (median, 12 days) and continued every 4 weeks for a total of 4 cycles. Adjuvant radiotherapy was performed during the second and third cycles of chemotherapy. RESULTS: After a median follow-up period of 119 months for survivors, 13 patients (13.3%) experienced recurrence and 11 patients died of cancer during the follow-up period. The 5-year recurrence-free survival and cancer specific survival rates were 87.6% and 90.6%, respectively. Ninety-four patients (95.9%) received ≥3 cycles of chemotherapy. Total radiation dose of ≥45 Gy was delivered in 91 patients (92.9%). Grade 3-4 hematologic and gastrointestinal toxicities developed in 37 (37.8%) and 14 (14.3%) patients during CCRT, respectively. CONCLUSION: The present study confirmed the long-term safety and encouraging survival outcomes of early administration of adjuvant CCRT, suggesting the benefits of early time to initiation of adjuvant treatments.


Assuntos
Histerectomia/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Diarreia/etiologia , Feminino , Humanos , Histerectomia/efeitos adversos , Estimativa de Kaplan-Meier , Leucopenia/etiologia , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
13.
Cancer Res Treat ; 49(2): 484-493, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27554479

RESUMO

PURPOSE: The effects of biological subtypes within breast cancer on prognosis are influenced by age at diagnosis. We investigated the association of young age with locoregional recurrence (LRR) between patients with luminal subtypes versus those with nonluminal subtypes. MATERIALS AND METHODS: Medical records of 524 breast cancer patients with positive lymph nodes between 1999 and 2010 were reviewed retrospectively. All patients received curative surgery and adjuvant chemotherapy based on contemporary guidelines. Radiation was delivered for patients who underwent breast conserving surgery or those who had four or more positive lymph nodes after mastectomy. Adjuvant hormone therapy was administered to 413 patients with positive hormone receptors according to their menstrual status. RESULTS: During median follow-up of 84 months, the 10-year locoregional recurrence-free survival rate (LRRFS) was 84.3% for all patients. Patients < 40 years showed significantly worse 10-year LRRFS than those ≥ 40 years (73.2% vs. 89.0%, respectively; p=0.01). The negative effect of young age on LRRFS was only observed in luminal subtypes (69.7% for < 40 years vs. 90.8% for ≥ 40 years; p < 0.01). Multivariate analysis using luminal subtypes ≥ 40 years as a reference revealed luminal subtypes < 40 years were significantly associated with increased risk of LRR (hazard ratio, 2.33; p < 0.01). CONCLUSION: Young breast cancer patients with positive lymph nodes had a higher risk of LRR than those aged ≥ 40 years. This detrimental effect of young age on LRR was confined in luminal subtypes.


Assuntos
Neoplasias da Mama/diagnóstico , Linfonodos/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
14.
Anticancer Res ; 36(12): 6289-6295, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27919948

RESUMO

AIM: We evaluated the role of long noncoding ribonucleic acid (lncRNA) in breast cancer cell lines by quantitative reverse transcription-polymerase change reaction. MATERIALS AND METHODS: The effects of small NF90-associated RNA (snaR) with RNA interference on proliferation, migration and invasion of MDA-MB-231 cells were observed by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, wound healing and transwell assay. RESULTS: Among 90 lncRNAs, E2F transcription factor 4, p107/p130-binding (E2F4) antisense, insulin-like growth factor 2 antisense (IGF2AS), snaR, and small nucleolar RNA host gene 5 (SNHG5) were up-regulated in MDA-MB-231 and 7SK, antisense noncoding RNA in the INK4 locus (ANRIL), IGF2AS, Nespas, p53 mRNA, and snaR were up-regulated in MCF-7 cells. Down-regulation of snaR inhibited the proliferation, migration, and invasion of MDA-MD-231 breast cancer cells. CONCLUSION: LncRNA snaR was found to be up-regulated in breast cancer cells, and the cancer progression of MDA-MB-231 cells was significantly suppressed by down-regulation of snaR. Therefore, snaR knockdown has potential as a treatment modality for triple-negative breast cancer.


Assuntos
Proliferação de Células/genética , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , RNA Longo não Codificante/fisiologia , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias de Mama Triplo Negativas/genética
15.
Ann Coloproctol ; 30(5): 237-40, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25360432

RESUMO

Intramedullary spinal cord metastasis (ISCM) is an uncommon condition of the central nervous system (CNS) cause by systemic malignant tumors. Most ISCM cases are known to occur in patients with lung cancer and breast cancer; however, ISCM also very rarely occurs in patients with colorectal cancer. For the first time in Korea, we experienced a case of ISCM arising from rectal cancer, where a 75-year-old man presented with an abruptly-developed left-foot drop and numbness in both legs. The patient had lung metastases from rectal cancer that had been treated with chemotherapy. Magnetic resonance imaging revealed an intramedullary nodular lesion at the T12 level. ISCM was diagnosed and treated with steroids and radiotherapy. The patient's neurological symptoms were relieved for a while after treatment, but his condition deteriorated progressively. He died 4 months after ISCM had been diagnosed.

16.
J Nanosci Nanotechnol ; 14(11): 8296-304, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25958517

RESUMO

Thermodynamic modeling of the Gd(3+)-Eu(3+)-O(2-)-CO3(2-)-Cl- system has been adopted as a rational approach to establish routes to the better synthesis conditions for pure phase Eu(3+)-doped Gd2O3 nanoparticles. Quantitative analyses of the different reaction equilibria involved in the coprecipitation of Gd2(CO3)3 and Eu2(CO3)3 x 3H2O from aqueous solutions have been used to determine the optimum synthesis conditions. The characterization and photoluminescence spectra of Gd2O3 nanoparticles doped with Eu3+ activator ions at the concentrations of 1, 2, 3, 4 and 5 mol% synthesized by urea-based homogeneous coprecipitation are presented. The surface of the as-prepared mixture of Gd2(CO3)3 and Eu2(CO3)3 x 3H2O particles are coated with silica to avoid the agglomeration followed by annealing the carbonate precursors at 800 degrees C for 3 hours. Subsequently, the silica shell is removed with an alkali solution resulting in well-crystallized Eu(3+)-doped Gd2O3 nanoparticles. X-ray diffraction (XRD) results show that all the diffraction peaks are well indexed to the cubic Gd2O3 with high crystallinity. The photoluminescence spectra exhibit a characteristic f-f transition band that corresponds to Eu3+. The sharp red emission at 616 nm corresponds to the transition identified as 5D0 __7F2. Both the emission intensity at 616 nm and asymmetry factor of [I(5D0 --> 7F2)/I(5D0 --> 7F1)] exhibit clearly Eu(3+)-doping concentration-dependent luminescence behaviors. The rather fast decay time is closely correlated to the proper occupation of the Eu3+ activator ions in the C2 sites of the Gd2O3 cage, resulting in strong dependence on small changes of the total electric density and defect density. Thus, the best concentration of Eu3+ activator ions for the maximum brightness are the 3 mol% Eu(3+)-doped Gd2O3 at 5D0 --> 7F2 because it shows the longest decay time and more luminescent intensity than the other doping concentrations.


Assuntos
Európio/química , Gadolínio/química , Substâncias Luminescentes/química , Nanopartículas/química , Precipitação Química , Nanotecnologia , Dióxido de Silício/química , Termodinâmica
17.
J Nanosci Nanotechnol ; 14(11): 8365-71, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25958529

RESUMO

The final aim of this study was to confirm the neuroprotective effects of recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles stabilized by sodium cholate (rhEPO-Ch-NP) and compare their effects with those of rhEPO using an in vitro model of cerebral ischemia. Glutamate-induced excitotoxic damage on SH-SY5Y cells, a human neuroblastoma cell line, with or without rhEPO-Ch-NPs was quantitatively evaluated. The rhEPO-Ch-NPs were carefully prepared using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique with PLGA, sodium cholate hydrate, and ethyl acetate. The rhEPO-Ch-NPs were fully characterized by both transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). In addition, significant intracellular uptake of these particles was monitored by confocal microscopy. Notably, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and nuclear changes observed by 4',6-diamidino-2-phenylindole (DAPI) staining in SH-SY5Y cells demonstrated that rhEPO-Ch-NPs were safer at any concentration investigated and rescued more neuronal cells, while preserving normocytic features against glutamate-induced excitotoxic damages compared to rhEPO.


Assuntos
Eritropoetina/farmacologia , Ácido Glutâmico/toxicidade , Nanopartículas/química , Fármacos Neuroprotetores/farmacologia , Colato de Sódio/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Eritropoetina/química , Humanos , Ácido Láctico/química , Neuroblastoma , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia
18.
Case Rep Oncol Med ; 2013: 492329, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24324902

RESUMO

Neurolymphomatosis (NL) is a rare clinical disease where neoplastic cells invade the cranial nerves and peripheral nerve roots, plexus, or other nerves in patients with hematologic malignancy. Most NL cases are caused by B-cell non-Hodgkin's lymphoma (NHL). Diagnosis can be made by imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI). We experienced two cases of NL involving the brachial plexus in patients with NHL. One patient, who had NHL with central nervous system (CNS) involvement, experienced complete remission after 8 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy but relapsed into NL of the brachial plexus 5 months later. The other patient, who suffered from primary central nervous system lymphoma (PCNSL), had been undergoing chemoradiotherapy but progressed to NL of the brachial plexus.

19.
J Korean Med Sci ; 27(11): 1411-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23166426

RESUMO

Dexmedetomidine, which is a selective α2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 µg/kg) were injected to rats developed allodynia 14 days after vincristine injection, respectively. We evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline treatment did not show any differences for all the allodynia. Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 ± 0.4, 9.1 ± 1.9, 13.0 ± 3.6, 16.6 ± 2.4, and 24.4 ± 1.6 g at saline, 12.5, 25, 50, and 100 µg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 ± 4.2, 57.1 ± 6.8, 34.3 ± 5.7, 20.0 ± 6.2, and 14.3 ± 9.5 g at saline, 12.5, 25, 50, and 100 µg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).


Assuntos
Analgésicos/uso terapêutico , Dexmedetomidina/uso terapêutico , Hiperalgesia/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Hiperalgesia/induzido quimicamente , Injeções Intraperitoneais , Masculino , Limiar da Dor , Ratos , Ratos Sprague-Dawley , Vincristina/toxicidade
20.
Pharm Res ; 28(12): 3069-78, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21879387

RESUMO

PURPOSE: To test whether co-delivery of anticancer small interfering RNA (siRNA) and a chemical MEK inhibitor using cationic liposomes enhances anticancer activity in vitro and in vivo. METHOD: MEK inhibitor PD0325901 was encapsulated in lipid layers of N',N''-dioleylglutamide-based cationic liposomes (DGL). Mcl1-specific siRNA (siMcl1) was complexed to DGL or PD0325901-loaded liposomes (PDGL). Efficiency of cellular siRNA delivery was tested using fluorescent double-stranded RNA. Silencing of target proteins was evaluated using Western blotting and real-time quantitative polymerase chain reactions. In vivo anticancer activity was tested using xenografted mice. RESULTS: Size and zeta potential of PDGL were similar to DGL. PDGL could deliver double-stranded RNA into cells with efficiencies comparable to DGL. Cellular co-delivery of siMcl1 and PD0325901 reduced expression of Mcl1 and pERK1/2 proteins and more effectively reduced tumor cell survival than other treatments. In mice, siMcl1 and PD0325901 co-delivered by PDGL inhibited growth of tumors 79%. Substantial apoptosis of tumor cells was observed following PDGL-mediated co-delivery of siMcl1, but not in other groups. CONCLUSIONS: PDGL-mediated co-delivery of siMcl1 and MEK inhibitor, PD0325901, could serve as a potential strategy for combination chemogene anticancer therapy.


Assuntos
Benzamidas/administração & dosagem , Benzamidas/uso terapêutico , Difenilamina/análogos & derivados , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Neoplasias/terapia , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/uso terapêutico , Animais , Benzamidas/farmacologia , Cátions/metabolismo , Linhagem Celular Tumoral , Difenilamina/administração & dosagem , Difenilamina/farmacologia , Difenilamina/uso terapêutico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Inativação Gênica , Terapia Genética , Humanos , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Proteína de Sequência 1 de Leucemia de Células Mieloides , Neoplasias/genética , Neoplasias/patologia , RNA Interferente Pequeno/farmacologia
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