Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 71
Filtrar
1.
Medicina (Kaunas) ; 58(8)2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36013597

RESUMO

Background and Objectives: Infections and capsular contractures remain unresolved issues in implant-based breast reconstruction. Capsular contractures are thought to be caused by the endogenous flora of the nipple duct. However, little is known about the antibiotic susceptibility of the microorganisms involved. This study aimed to evaluate the composition of endogenous breast flora and its antimicrobial susceptibility in patients with breast cancer. This study will aid in selecting a prophylactic antibiotic regimen for breast reconstruction surgery. Materials and Methods: We obtained bacteriologic swabs from the nipple intraoperatively in patients who underwent implant-based breast reconstruction following nipple-sparing mastectomy between January 2019 and August 2021. Antibiotic susceptibility tests were performed according to the isolated bacteriology. Statistical analysis was performed based on several patient variables to identify which factors influence the antibiotic resistance rate of endogenous flora. Results: A total of 125 of 220 patients had positive results, of which 106 had positive culture results for coagulase-negative Staphylococcus species (CoNS). Among these 106 patients, 50 (47%) were found to have methicillin-resistant staphylococci, and 56 (53%) were found to have methicillin-susceptible staphylococci. The methicillin resistance rate in the neoadjuvant chemotherapy group (56.3%) was significantly higher (OR, 2.3; p = 0.039) than that in the non-neoadjuvant chemotherapy group (35.5%). Conclusions: Based on the results, demonstrating high and rising incidence of methicillin-resistant staphylococci of nipple endogenous flora in patients with breast cancer compared to the past, it is necessary to consider the selection of prophylactic antibiotics to reduce infections and capsular contracture after implant-based breast reconstruction.


Assuntos
Neoplasias da Mama , Contratura , Mamoplastia , Antibacterianos/uso terapêutico , Neoplasias da Mama/cirurgia , Contratura/cirurgia , Feminino , Humanos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Mastectomia/efeitos adversos , Mamilos/cirurgia , Estudos Retrospectivos , Staphylococcus
2.
Int J Mol Sci ; 21(21)2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114661

RESUMO

Cisplatin (cis-diamminedichloroplatinum (II), CDDP) is a chemotherapeutic drug widely used against many solid tumors. A pharmacokinetics study found that CDDP can bind to human serum albumin (HSA), which is the most abundant plasma protein in serum. HSA has the advantage of being a nanocarrier and can accumulate in tumors by passive targeting and active targeting mediated by the secreted protein acidic and rich in cysteine (SPARC). In this study, we investigated the possibility of using a CDDP-HSA complex (HSA-CDDP) as a SPARC-mediated therapeutic agent. To investigate the HSA-dependent therapeutic effect of HSA-CDDP, we used two types of U87MG glioma cells that express SPARC differently. HSA-CDDP was highly taken up in SPARC expressing cells and this uptake was enhanced with exogenous SPARC treatment in cells with low expression of SPARC. The cytotoxicity of HSA-CDDP was also higher in SPARC-expressing cells. In the tumor model, HSA-CDDP showed a similar tumor growth and survival rate to CDDP only in SPARC-expressing tumor models. The biosafety test indicated that HSA-CDDP was less nephrotoxic than CDDP, based on blood markers and histopathology examination. Our findings show that HSA-CDDP has the potential to be a novel therapeutic agent for SPARC-expressing tumors, enhancing the tumor targeting effect by HSA and reducing the nephrotoxicity of CDDP.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Glioma/tratamento farmacológico , Nefropatias/prevenção & controle , Albumina Sérica Humana/química , Administração Intravenosa , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/efeitos adversos , Cisplatino/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/metabolismo , Humanos , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Masculino , Camundongos , Osteonectina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Bioorg Chem ; 87: 803-809, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30978605

RESUMO

Eight anthocyanidin derivatives (1-8) were evaluated as potential inhibitors of the catalysis of α-glucosidase. Among them, compounds 4 and 8 had the highest levels of inhibitory activity at 100 µM (IC50 values of 14.4 ±â€¯0.1 and 29.7 ±â€¯1.2 µM) and acted in a dose-dependent manner. Enzyme kinetic analysis further revealed that these inhibitors interacted with α-glucosidase in a mixed noncompetitive mode. Moreover, fluorescence quenching studies provided parameters for calculating the binding mechanism between receptor and ligand. On the basis of these studies, and in silico simulations, we determined that the ligand was likely docked in the receptor. Thus, compounds 4 and 8 are excellent potential targets for in vitro cell-based and in vivo assays related to treatment of diabetes.


Assuntos
Antocianinas/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , alfa-Glucosidases/metabolismo , Antocianinas/síntese química , Antocianinas/química , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Espectrometria de Fluorescência , Relação Estrutura-Atividade
4.
Molecules ; 24(7)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934890

RESUMO

Catalpa ovata (Bignoniaceae) is widely distributed throughout Korea, China, and Japan. This study investigated the anti-inflammatory effects of catalpalactone isolated from C. ovata in lipopolysaccharide (LPS)-induced RAW264.7 cells. Catalpalactone significantly inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) expression in LPS-induced RAW264.7 cells. The levels of cytokines such as interleukin-6 and tumor necrosis factor-α were reduced under catalpalactone exposure in LPS-induced RAW264.7 cells. Additionally, catalpalactone suppressed signal transducer and activator of transcription 1 (STAT-1) protein expression and interferon-ß (IFN-ß) production. Treatment with catalpalactone prevented interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB) activation. Taken together, these results suggest that the anti-inflammatory effects of catalpalactone are associated with the suppression of NO production and iNOS expression through the inhibition of IRF3, NF-κB, and IFN-ß/STAT-1 activation.


Assuntos
Anti-Inflamatórios/farmacologia , Bignoniaceae/química , Lactonas/farmacologia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Lactonas/química , Lactonas/isolamento & purificação , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7
5.
Ther Drug Monit ; 40(3): 330-336, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29746433

RESUMO

BACKGROUND: Teicoplanin is a glycopeptide antibiotic that has become increasingly popular with the spread of methicillin-resistant Staphylococcus aureus. The aim of the study was to develop and validate an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for teicoplanin, and analyze trough teicoplanin concentrations achieved in patients with hematological diseases. METHODS: The UHPLC-MS/MS method for teicoplanin was developed, validated, and applied in a retrospective analysis of trough plasma teicoplanin concentrations from 305 patients receiving standard dose, and 17 patients receiving therapeutic drug monitoring (TDM)-guided individualized dose. RESULTS: The linear range was 3.9-52.9 mg/L. The imprecision was less than 12%, the limits of detection and quantification were less than 0.13 and 0.72 mg/L, respectively. The sample carry-over and ion suppression were insignificant. In the standard dose group, the median teicoplanin concentrations were 7.5 mg/L (days 3-5) and 8.9 mg/L (on days 6-8); and the proportion of trough levels achieving ≥10 mg/L was 20% (days 3-5) and 38% (days 6-8), respectively. In the TDM-guided individualized dose group, median teicoplanin concentration was higher (16.9 mg/L), and the proportion of trough levels ≥10 mg/L was also higher (77%) when compared with the standard dose group. CONCLUSIONS: Based on these results, the present UHPLC-MS/MS method can be considered suitable for routine TDM of teicoplanin. Also, based on the insufficient trough teicoplanin concentrations achieved with standard dose regimen, and the higher trough teicoplanin concentrations achieved with TDM-guided individualized dose regimen, this study highlights the importance of TDM of teicoplanin, especially in high-risk patient groups.


Assuntos
Antibacterianos/sangue , Monitoramento de Medicamentos/métodos , Doenças Hematológicas/sangue , Doenças Hematológicas/tratamento farmacológico , Espectrometria de Massas em Tandem/métodos , Teicoplanina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Cromatografia Líquida/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Teicoplanina/uso terapêutico , Adulto Jovem
6.
J Craniofac Surg ; 29(8): 2206-2210, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30320687

RESUMO

OBJECTIVE: The use of different expressions between physicians frequently results in confusion in the process of diagnosis and treatment of patients with headaches due to problems in the nose and nasal cavity. The aim of this study was to assess the terminologies that have been used most frequently to standardize these terminologies. METHODS: Terminologies that are most frequently used in general, including rhinogenic migraine, sinus headache, rhinogenic contact point headache, middle turbinate headache syndrome, and rhinogenic headache, were found by searching PubMed, Web of Science, and Google Scholar. These terminologies were objectively assessed on the basis of existing research and definitions and the range of diagnoses by organizations with public credibility. RESULTS: There were many terminologies in use for headache related to nose; however, these were not logical expressions and only partly explained the phenomenon. Among the terms, "rhinogenic headache" was most appropriate in expressing and describing the related symptoms. CONCLUSION: The results indicated that the term "rhinogenic headache" is most appropriate for describing pain in the nose and eyes in patients with deformation within the nose or the nasal cavity due to external injuries or underlying diseases related to nose as observed on computed tomography.


Assuntos
Dor Facial/etiologia , Cefaleia/etiologia , Transtornos de Enxaqueca/etiologia , Doenças Nasais/complicações , Terminologia como Assunto , Adulto , Feminino , Humanos , Masculino , Cavidade Nasal , Doenças Nasais/diagnóstico por imagem , Doenças dos Seios Paranasais/complicações , Doenças dos Seios Paranasais/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Conchas Nasais , Adulto Jovem
7.
Molecules ; 23(3)2018 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-29509670

RESUMO

Apios americana, a leguminous plant, is used as food in some countries. Although the biological activities of Apios extract have been reported, there have been no reports about the anti-inflammatory mechanism of lupinalbin A on the RAW264.7 cells. In this study, we investigated the anti-inflammatory effect of A. americana lupinalbin A on lipopolysaccharide (LPS)-treated RAW264.7 cells. Lupinalbin A significantly inhibited nitric oxide production and inducible nitric oxide synthase expression in LPS-treated RAW264.7 cells. The expression of cytokines, including interleukin-6, tumor necrosis factor-α, and chemokine of monocyte chemoattractant protein, was reduced under lupinalbin A exposure in LPS-treated RAW264.7 cells. In addition, lupinalbin A significantly decreased LPS-induced interferon (IFN)-ß production and STAT1 protein levels in RAW264.7 cells. Taken together, these results suggest that A. americana lupinalbin A exerts anti-inflammatory effects via the inhibition of pro-inflammatory cytokines and blocking of IFN-ß/STAT1 pathway activation.


Assuntos
Anti-Inflamatórios/farmacologia , Benzofuranos/farmacologia , Benzopiranos/farmacologia , Fabaceae/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Benzofuranos/química , Benzofuranos/isolamento & purificação , Benzofuranos/toxicidade , Benzopiranos/química , Benzopiranos/isolamento & purificação , Benzopiranos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Citocinas/biossíntese , Citocinas/genética , Interferon beta/biossíntese , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/biossíntese , Células RAW 264.7 , RNA Mensageiro/metabolismo , Fator de Transcrição STAT1/metabolismo
8.
Molecules ; 23(8)2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-30103438

RESUMO

Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2 diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide. DPP-IV inhibitors shorten the inactivation of GLP-1, permitting the incretin to stimulate insulin release, thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors from medicinal plants and foods, three flavonol glycosides (1⁻3) were isolated from the seeds of Lens culinaris Medikus (Fabaceae) and tested for their DPP-IV⁻inhibitory activity. We demonstrated for the first time, that compounds 1⁻3 inhibited DPP-IV activity in a concentration-dependent manner in our in vitro bioassay system. In addition, molecular docking experiments of compounds 1⁻3 within the binding pocket of DPP-IV were conducted. All investigated compounds readily fit within the active sites of DPP-IV, in low-energy conformations characterized by the flavone core structure having optimal electrostatic attractive interactions with the catalytic triad residues of DPP-IV.


Assuntos
Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Flavonóis/química , Flavonóis/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Lens (Planta)/química , Sementes/química , Sítios de Ligação , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Ligantes , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Relação Estrutura-Atividade
9.
Molecules ; 23(1)2018 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-29361770

RESUMO

The goal of this study was to identify phytochemicals with inhibitory activity against tyrosinase. Nine compounds 1-9 were isolated from the tubers of Apios americana. This is the first report of aromadendrin 5-methyl ether (1) being isolated from the Apios species. Among them, compounds 2 and 8 showed inhibitory activity toward tyrosinase. Based on a Dixon plot, the potential Ki values of competitive inhibitors 2 and 8 were calculated as 10.3 ± 0.8 µM and 44.2 ± 1.7 µM, respectively. An IC50 value of 13.2 ± 1.0 µM was calculated for the slow-binding inhibitor 2 after preincubation with tyrosinase. Additionally, the predicted binding sites between the receptor and ligand, as well as secondary structure changes, in the presence of 2 were examined by molecular simulation.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fabaceae/química , Monofenol Mono-Oxigenase/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/isolamento & purificação , Cinética , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Compostos Fitoquímicos/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
10.
Environ Monit Assess ; 190(7): 438, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29956012

RESUMO

Prediction of residual concentrations of applied pesticides during the pre-harvest period may be required to ensure the safety of agricultural products. In this study, time-dependent dissipation trends of carbaryl (CB), kresoxim-methyl (KM), flubendiamide (FB), flufenoxuron (FN), bitertanol (BT), and chlorantraniliprole (CN) applied to apples at recommended and threefold greater doses were modeled to estimate pre-harvest residue limit concentrations (CPHRL) indicating permissible pesticide concentrations during the pre-harvest period. Double-exponential (DE) model results best fit the dissipation trends of all tested pesticides (correlation coefficients of 0.91-0.99) compared to zero-, first-, and second-order models. Among the pesticides examined, CB half-lives in apples of 2.9 and 6.6 days were the shortest, while those of FN (21.1-32.7 days) were the longest. The CPHRL values for each pesticide in apples were estimated with DE model parameter values and could be used to determine harvest dates for safe apples with pesticide concentrations below their maximum residue limits. Application of the DE model for CPHRL calculation provides more accurate information for farmers to produce agricultural products safe from pesticide residues.


Assuntos
Monitoramento Ambiental , Malus/química , Modelos Químicos , Resíduos de Praguicidas/análise , Praguicidas/análise , Agricultura , Compostos de Bifenilo , Contaminação de Alimentos/análise , Cinética , Triazóis , ortoaminobenzoatos
11.
Ann Surg Oncol ; 24(5): 1336-1342, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28000075

RESUMO

BACKGROUND: Debate on the value of lymphadenectomy continues in endometrial cancer. The aim of this study was to investigate patient and clinician preferences for routine lymphadenectomy versus no lymphadenectomy in the surgical management of endometrial cancer. METHODS: A discrete choice experiment and trade-off question were designed and distributed to 103 endometrial cancer patients and 90 gynecologic oncologists. Participant preferences were quantified with regression analysis using scenarios based on three attributes: 5-year progression-free survival and the rates of acute and chronic complication. A trade-off technique varying the risk of recurrence for no lymphadenectomy was used to quantify any additional risk of recurrence that these participants would accept to receive no lymphadenectomy instead of routine lymphadenectomy. RESULTS: On the basis of discrete choice experiment, the recurrence rate and lymphedema risk had a statistically significant impact on respondents' preference. The trade-off question showed that the median additional accepted risk of having no lymphadenectomy was 2.8% for gynecologic oncologists (0.5-14%) and 3.0% for patients (0.5-10%), but this difference was not significant (p = 0.620). Patients who were younger or had a higher education level or no history of delivery or shorter duration since diagnosis were prepared to accept higher additional risks of having no lymphadenectomy. CONCLUSIONS: Our results show that the majority of endometrial cancer patients and clinicians will accept a small amount of recurrence risk to reduce the incidence of lymphedema. Regarding preference heterogeneity among patients, our results show that it is important for surgeons to take a patient-tailored approach when discussing surgical management.


Assuntos
Atitude do Pessoal de Saúde , Neoplasias do Endométrio/cirurgia , Excisão de Linfonodo , Preferência do Paciente/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Comportamento de Escolha , Intervalo Livre de Doença , Escolaridade , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Pessoa de Meia-Idade , Paridade , Medição de Risco , Inquéritos e Questionários
12.
Molecules ; 22(9)2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28867792

RESUMO

A new compound 1, 5-methoxy-2,5,7,4'-tetrahydroxy-coumaronochromone, along with seven known compounds (2-8), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these, two compounds 1 and 2 showed inhibitory activity on soluble epoxide hydrolase (sEH) at a concentration below 50 µM. The respective competitive (1) and mixed (2) inhibitors were revealed to have Ki values of 21.0 ± 0.8 and 14.5 ± 1.5 µM, based on the Dixon plot. The potential inhibitor (2) was visually presented in a predicted binding pose in the receptor by molecular docking. Additionally, molecular dynamics were performed for a detailed understanding of their complex by Gromacs 4.6.5 package.


Assuntos
Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/antagonistas & inibidores , Fabaceae/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Inibidores Enzimáticos/química , Cinética , Ligantes , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Compostos Fitoquímicos/química , Solubilidade
13.
Molecules ; 22(9)2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-28869556

RESUMO

The leaves of Perilla frutescens var. crispa (Lamiaceae)-known as 'Jureum-soyeop' or 'Cha-jo-ki' in Korean, 'ZI SU YE' in Chinese, and 'Shiso' in Japan-has been used as a medicinal herb. Recent gamma irradiated mutation breeding on P. frutescens var. crispa in our research group resulted in the development of a new perilla cultivar, P. frutescens var. crispa (cv. Antisperill; PFCA), which has a higher content of isoegomaketone. The leaves of PFCA were extracted by supercritical carbon dioxide (SC-CO2) extraction, and phytochemical investigation on this extract led to the isolation and identification of a new compound, 9-hydroxy-isoegomaketone [(2E)-1-(3-furanyl)-4-hydroxy-4-methyl-2-penten-1-one; 1]. Compound 1 exhibited inhibitory activity on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with an IC50 value of 14.4 µM. The compounds in the SC-CO2 extracts of the radiation mutant cultivar and the original plant were quantified by high-performance liquid chromatography with diode array detection.


Assuntos
Monoterpenos/química , Óxido Nítrico/biossíntese , Perilla frutescens/química , Folhas de Planta/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Furanos/química , Furanos/farmacologia , Raios gama , Cetonas/química , Cetonas/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Monoterpenos/farmacologia , Mutação , Perilla frutescens/genética , Perilla frutescens/efeitos da radiação , Extratos Vegetais/química , Extratos Vegetais/farmacologia
14.
Gynecol Oncol ; 143(3): 622-627, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27771167

RESUMO

BACKGROUND: The GOG-218 and ICON-7 studies recently showed that adding bevacizumab to first-line therapy for patients with advanced ovarian cancer increased progression-free survival. However, the high cost and long treatment duration prevents the incorporation of bevacizumab in practice. The aim of this study was to explore and quantify patients' preferences for adding bevacizumab to first-line therapy. METHODS: A discrete choice experiment (DCE) and trade-off question were designed and distributed to 102 ovarian cancer patients. Participants were asked to choose between two hypothetical first-line therapies that differed in terms of effectiveness, safety, and the financial burden. A trade-off technique varying the cost of bevacizumab was used to quantify a willingness-to-pay threshold for selecting bevacizumab. RESULTS: All attributes of the DCE had a statistically significant impact on respondents' preferences and the financial burden was the most important attribute. The results of the trade-off question showed that more than half of patients would prefer to add bevacizumab to standard chemotherapy when the cost of the drug was reduced to 17% (1/6) of the baseline cost. CONCLUSION: Patients' preferences for bevacizumab in the adjuvant treatment of ovarian cancer depend primarily on drug costs. Our results suggest that the current cost of bevacizumab is sufficiently high that the majority of ovarian cancer patients are not willing to pay to accept a small increase in progression-free survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Comportamento de Escolha , Procedimentos Cirúrgicos de Citorredução , Neoplasias Císticas, Mucinosas e Serosas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Preferência do Paciente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Bevacizumab/administração & dosagem , Bevacizumab/economia , Quimioterapia Adjuvante/economia , Análise Custo-Benefício , Intervalo Livre de Doença , Custos de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/psicologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/psicologia
15.
Mol Pharm ; 12(1): 194-203, 2015 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-25423047

RESUMO

We reported previously that human translationally controlled tumor protein (TCTP) contains, at its NH2-terminus, a protein transduction domain (PTD), which we called TCTP-PTD, with the amino acid sequence MIIYRDLISH. In this report we describe how TCTP-PTD penetrates A549 human lung cancer cell membranes and promotes protein internalization. Cellular uptake of fluorescent TCTP-PTD and a recombinant fusion protein consisting of TCTP-PTD and GFP (green fluorescent protein) was analyzed by confocal fluorescence microscopy and flow cytometry. Inhibitor assays using several agents that perturb the internalization process revealed that TCTP-PTD transduces the cells partly via lipid-raft/caveola-dependent endocytosis and partly by macropinocytosis in a dynamin/actin/microtubule-dependent pathway. To trace the pathway followed by the penetration of TCTP-PTD, the localization of PTDs was investigated in the lipid-raft, subcellular, and ER fractions. We found that, after entry, TCTP-PTD is localized in the cytoplasm and cytoskeleton, but not in the nucleus, and is transported into endoplasmic reticulum (ER). Expression levels of caveolin-1 in A549 and HeLa cells are different, and these differences appear to contribute to the sensitivity of TCTP-PTD uptake inhibition, against lipid-raft depleter, nystatin. This elucidation of the underlying mechanism of TCTP-PTD translocation may help the design of approaches that employ TCTP-PTD in the cellular delivery of bioactive molecules.


Assuntos
Biomarcadores Tumorais/química , Biomarcadores Tumorais/farmacocinética , Carcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Citoplasma/metabolismo , Endocitose , Proteínas de Fluorescência Verde/química , Células HeLa , Humanos , Microdomínios da Membrana/química , Microscopia Confocal , Peptídeos/química , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/química , Proteína Tumoral 1 Controlada por Tradução
16.
BMC Cancer ; 14: 165, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24606760

RESUMO

BACKGROUND: Translationally controlled tumor protein (TCTP), alternatively called fortilin, is believed to be involved in the development of the chemoresistance of tumor cells against anticancer drugs such as etoposide, taxol, and oxaliplatin, the underlying mechanisms of which still remain elusive. METHODS: Cell death analysis of TCTP-overexpressing HeLa cells was performed following etoposide treatment to assess the mitochondria-dependent apoptosis. Apoptotic pathway was analyzed through measuring the cleavage of epidermal growth factor receptor (EGFR) and phospholipase C-γ (PLC-γ), caspase activation, mitochondrial membrane perturbation, and cytochrome c release by flow cytometry and western blotting. To clarify the role of TCTP in the inhibition of apoptosome, in vitro apoptosome reconstitution and immunoprecipitation was used. Pull-down assay and silver staining using the variants of Apaf-1 protein was applied to identify the domain that is responsible for its interaction with TCTP. RESULTS: In the present study, we confirmed that adenoviral overexpression of TCTP protects HeLa cells from cell death induced by cytotoxic drugs such as taxol and etoposide. TCTP antagonized the mitochondria-dependent apoptotic pathway following etoposide treatment, including mitochondrial membrane damage and resultant cytochrome c release, activation of caspase-9, and -3, and eventually, the cleavage of EGFR and PLC-γ. More importantly, TCTP interacts with the caspase recruitment domain (CARD) of Apaf-1 and is incorporated into the heptameric Apaf-1 complex, and that C-terminal cleaved TCTP specifically associates with Apaf-1 of apoptosome in apoptosome-forming condition thereby inhibiting the amplification of caspase cascade. CONCLUSIONS: TCTP protects the cancer cells from etoposide-induced cell death by inhibiting the mitochondria-mediated apoptotic pathway. Interaction of TCTP with Apaf-1 in apoptosome is involved in the molecular mechanism of TCTP-induced chemoresistance. These findings suggest that TCTP may serve as a therapeutic target for chemoresistance in cancer treatment.


Assuntos
Fator Apoptótico 1 Ativador de Proteases/genética , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Epistasia Genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Fator Apoptótico 1 Ativador de Proteases/química , Caspase 3/metabolismo , Caspase 9/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Citocromos c/metabolismo , Fragmentação do DNA , Receptores ErbB/genética , Etoposídeo/farmacologia , Expressão Gênica , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosfolipase C gama/genética , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Inibidores da Topoisomerase II/farmacologia , Proteína Tumoral 1 Controlada por Tradução
17.
Biomed Chromatogr ; 28(7): 919-22, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24458571

RESUMO

A simple, fast and reliable high-performance liquid chromatography-triple quadrupole mass spectrometry method (HPLC-MS/MS method) was developed, validated and used for the simultaneous quantification of irinotecan and 7-ethyl-10-hydroxycamptothecin (SN38) in heparinized mouse plasma. Camptothecin was used as the internal standard. A single-step protein precipitation without evaporation and reconstitution steps was adopted as sample processing method. Our bioanalytical method was validated in compliance with the guidelines from the European Medicines Agency. The lower limit of quantification for both irinotecan and SN38 was 5 ng/mL. The calibration curves for both analytes fitted to a 1/x(2) weighted linear regression model and ranged from 5 to 1000 ng/mL. The intra-run and inter-run precisions were within 8.6%, and the intra-run and inter-run accuracies were within 96.4-103.9%. Our validated bioanalytical method was successfully applied to the pharmacokinetic study in mice, in which 4 mg/kg irinotecan was intraperitoneally injected.


Assuntos
Camptotecina/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Camptotecina/sangue , Camptotecina/química , Camptotecina/farmacocinética , Feminino , Irinotecano , Modelos Lineares , Masculino , Camundongos , Camundongos Endogâmicos ICR , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Anal Biochem ; 435(1): 47-53, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23256924

RESUMO

Protein transduction domains (PTDs), which are cell-penetrating peptides, have been employed for delivery of various cargos. We previously showed that the N-terminal fragment of translationally controlled tumor protein functions as a PTD (TCTP-PTD) by as yet poorly understood mechanisms. In this study, we generated several green fluorescent protein (GFP)-tagged TCTP fusion proteins by conjugating a single PTD or tandem PTDs at the N-terminus, the C-terminus, and both termini and compared their transduction efficiencies in human lung adenocarcinoma A549 cells to determine whether the protein transducing function of TCTP depends on the location or the number of PTD moieties in the TCTP molecule. Fluorimetric analysis and Western blotting assays revealed that TCTP-GFP fusion protein containing one or two TCTP-PTDs at its N-terminus showed more efficient cellular entry than either the C-terminal TCTP-PTD or TCTP-PTD with PTDs located at both the N- and C-terminals. This study demonstrates the feasibility of transduction of TCTP target cells employing its TCTP-PTD by simple co-incubation with purified proteins.


Assuntos
Biomarcadores Tumorais/genética , Transdução Genética/métodos , Adenocarcinoma/genética , Biomarcadores Tumorais/química , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/genética , Peptídeos Penetradores de Células/metabolismo , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Neoplasias Pulmonares/genética , Estrutura Terciária de Proteína , Transporte Proteico , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteína Tumoral 1 Controlada por Tradução
19.
Anal Bioanal Chem ; 405(30): 9817-24, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24126840

RESUMO

There is an increasing need for more sensitive analytical methods in pharmacokinetic studies, for example, for phase 0 clinical trials. A novel HPLC Chip-triple quadrupole mass spectrometer method (HPLC Chip-MS/MS method) for the quantification of 7-ethyl-10-hydroxycamptothecin (SN38) was developed, validated, and employed to the pharmacokinetic analysis of SN38 in ICR mice. Protein precipitation with a ratio of plasma/acetonitrile of 1:10 was chosen as the sample processing method. The nano-electrospray inserted in the microfluidic chip operated in positive mode, and selected reaction monitoring was used for quantification. Our bioanalytical method met all essential validation parameters-selectivity, accuracy, precision, dilution integrity, calibration curve, matrix effect, recovery, and different stability tests (benchtop, freeze-thaw, autosampler stability). The calibration curves (weight 1/x (2)) were linear for the range 50-10,000 pg/mL. Clogging was not observed until the end of the lifetime of the microfluidic chip (350-400 injections), and carryover was practically eliminated through the introduction of a step gradient elution program. After intraperitoneal injection of 0.1 mg/kg irinotecan, SN38 concentration could be measured up to 6 h with accuracy and precision. Thus, we developed a new, very sensitive HPLC Chip-MS/MS method for the determination of plasma SN38 that has been validated in compliance with guidelines from different regulation authorities.


Assuntos
Camptotecina/análogos & derivados , Cromatografia Líquida/métodos , Microfluídica/métodos , Nanotecnologia/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Camptotecina/análise , Irinotecano , Masculino , Camundongos , Camundongos Endogâmicos ICR
20.
Ultrasonography ; 42(4): 589-599, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37691417

RESUMO

Shear wave dispersion (SWD) imaging is a newly developed ultrasound technology designed to evaluate the dispersion slope of shear waves, which is related to tissue viscosity. This advanced imaging technique holds potential for distinguishing malignant lesions from benign lesions and normal breast tissue. The SWD slope, as determined by shear wave elastography (SWE), could offer crucial insights into the characterization of breast lesions. This article presents SWE and SWD images of both malignant and benign breast lesions, in addition to normal breast tissue.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa