Base de dados : MEDLINE
Pesquisa : D27.505.954.248.106 [Categoria DeCS]
Referências encontradas : 23872 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 2388 ir para página                         

  1 / 23872 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29442004
[Au] Autor:Wang Y; Li X; He Z; Chen W; Lu J
[Ti] Título:Rapamycin attenuates palmitate-induced lipid aggregation by up-regulating sirt-1 signaling in AML12 hepatocytes.
[So] Source:Pharmazie;71(12):733-737, 2016 12 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Rapamycin (Rap), a specific inhibitor of the mTOR signaling, has been shown to affect lipid metabolism in vitro and in vivo. Sirt-1, an NAD+ dependent deacetylase, regulates a variety of cellular processes, including aging, lifespan extension and glucose and lipid metabolism. Herein, we applied a cellular steatosis model to investigate whether rapamycin's role in lipid metabolism is sirt 1-associated. Cells were exposed to palmitate stimulation for 48 h with or without rapamycin treatment. Lipid droplets in AML12 cells were observed by oil red O staining, and the intracellular lipid content was measured. We found that rapamycin treatment, at a relatively low concentration, significantly attenuated lipid aggregation, whereas knockdown of sirt-1 by siRNA abrogated rapamycin's effect on ameliorating lipid accumulation. Moreover, rapamycin exposure increased the expression levels of sirt-1 and AMPK, and enhanced sirt-1 deacetylase activity in steatotic AML12 hepatocytes. This is the first report demonstrating that rapamycin ameliorates lipid accumulation through upregulating sirt-1 signaling supporting the hypothesis that rapamycin may positively influence sirt-1 signaling in maintaining metabolic homeostasis.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/farmacologia
Hepatócitos/efeitos dos fármacos
Hepatócitos/metabolismo
Metabolismo dos Lipídeos/efeitos dos fármacos
Palmitatos/antagonistas & inibidores
Sirolimo/farmacologia
Sirtuína 1/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Camundongos
Proteínas Quinases Ativadas por Mitógeno/biossíntese
Palmitatos/farmacologia
RNA Interferente Pequeno/farmacologia
Transdução de Sinais/efeitos dos fármacos
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Palmitates); 0 (RNA, Small Interfering); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.5.1.- (Sirt1 protein, mouse); EC 3.5.1.- (Sirtuin 1); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6695


  2 / 23872 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29344722
[Au] Autor:Generali D; Corona SP; Pusztai L; Rouzier R; Allevi G; Aguggini S; Milani M; Strina C; Frati A
[Ad] Endereço:Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, Trieste, 34129, Italy.
[Ti] Título:Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR.
[So] Source:J Cancer Res Clin Oncol;144(3):601-606, 2018 Mar.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Neoadjuvant hormonal therapy is generally considered a valid option for hormone receptor positive breast cancer (BC) patients who are unfit for chemotherapy or surgery. AIMS: Whilst numerous studies analyzed efficacy of neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor positive patients, there is a lack of research looking at the usefulness of a preoperative combinatorial approach of CT and HT in this patient subgroup. METHODS: Using a predictive model previously described in the literature, developed to analyze the probability of benefit from preoperative chemotherapy, we were able to compare pathological complete response (pCR) rates expected with the use of CT alone with the pCR rates reported in a population of 192 patients treated with the combination of tamoxifen plus anthracycline-based CT at Cremona Hospital between 2003 and 2006. RESULTS: Even with a relatively small patient population, this approach provided insightful information for the selection of hormone receptor positive BC patients most likely to benefit from the use of preoperative HT and CT in combination. Whilst no statistically significant benefit was obtained with the addition of tamoxifen to neoadjuvant chemotherapy in the entire population, or in any of the molecular stratification subgroups, the analysis of the calibration curve showed that a combinatorial approach may improve pCR in patients with luminal B tumors. More specific trials should be designed to confirm our initial results. CONCLUSION: To the best of our knowledge, this is the first report investigating the efficacy of the combination of CT and HT in the neoadjuvant treatment of hormone receptor positive BC.
[Mh] Termos MeSH primário: Antraciclinas/administração & dosagem
Antibióticos Antineoplásicos/administração & dosagem
Antineoplásicos Hormonais/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Tamoxifeno/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Neoplasias da Mama/cirurgia
Quimioterapia Adjuvante
Terapia Combinada
Feminino
Seres Humanos
Meia-Idade
Terapia Neoadjuvante
Período Pré-Operatório
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthracyclines); 0 (Antibiotics, Antineoplastic); 0 (Antineoplastic Agents, Hormonal); 094ZI81Y45 (Tamoxifen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180119
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2574-4


  3 / 23872 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29208258
[Au] Autor:Martirossian A; Shah S; Carrete L; Valle J; Valentine V
[Ad] Endereço:Department of Internal Medicine (AM, LC), University of Texas Medical Branch, Galveston, Texas; Department of Internal Medicine, Division of Pulmonary Critical Care & Sleep Medicine (SS, JV), University of Texas Medical Branch, Galveston, Texas; Department of Internal Medicine, Division of Pulmo
[Ti] Título:Durability of Sirolimus for Lymphangioleiomyomatosis.
[So] Source:Am J Med Sci;354(6):603-607, 2017 12.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lymphangioleiomyomatosis (LAM), a rare, multisystem disorder primarily affecting women of reproductive age, is characterized by cystic-appearing lung lesions, progressive loss of lung function, chylous effusions and renal angiomyolipomas. Sirolimus, an mammalian target of rapamycin inhibitor, has been shown to stabilize lung function, reduce symptoms and resolve chylous effusions in the short term for patients with LAM. Herein, we report a premenopausal female with LAM who experienced complete and durable resolution of her chylothoraces with significant and sustained improvement in lung function on sirolimus.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/uso terapêutico
Neoplasias Pulmonares/tratamento farmacológico
Linfangioleiomiomatose/tratamento farmacológico
Sirolimo/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Neoplasias Pulmonares/complicações
Neoplasias Pulmonares/diagnóstico por imagem
Linfangioleiomiomatose/complicações
Linfangioleiomiomatose/diagnóstico por imagem
Imagem por Ressonância Magnética
Derrame Pleural/etiologia
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE


  4 / 23872 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28744122
[Au] Autor:Zou D; Wang W; Lei D; Yin Y; Ren P; Chen J; Yin T; Wang B; Wang G; Wang Y
[Ad] Endereço:Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China.
[Ti] Título:Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system.
[So] Source:Int J Nanomedicine;12:4879-4889, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/efeitos dos fármacos
Neoplasias Encefálicas/tratamento farmacológico
Doxorrubicina/farmacologia
Gangliosídeo G(M1)/química
Glioma/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Antibióticos Antineoplásicos/administração & dosagem
Antibióticos Antineoplásicos/farmacologia
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacocinética
Sistemas de Liberação de Medicamentos/métodos
Gangliosídeos/química
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Masculino
Micelas
Regeneração Nervosa/efeitos dos fármacos
Ratos Wistar
Distribuição Tecidual
Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Gangliosides); 0 (Micelles); 0 (sialogangliosides); 37758-47-7 (G(M1) Ganglioside); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S138257


  5 / 23872 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29443777
[Au] Autor:Nomura H; Sakamoto K; Sugihara T; Okamoto S; Aoki Y; Tanigawa T; Matoda M; Omatsu K; Kanao H; Kato K; Utsugi K; Sugiyama Y; Takeshima N
[Ad] Endereço:Department of Gynecology, Cancer Institute Hospital.
[Ti] Título:Oral leukoplakia, a precancerous lesion of squamous cell carcinoma, in patients with long-term pegylated liposomal doxorubicin treatment.
[So] Source:Medicine (Baltimore);97(7):e9932, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pegylated liposomal doxorubicin (PLD) has a good safety profile, but long-term use has been associated with development of squamous cell carcinoma of the tongue and oral cavity (SCCTO) in some patients. The study objective was to estimate the prevalence of oral leukoplakia, a known precursor of SCCTO, in patients with ovarian cancer and long-term PLD use.After approval of the institutional review board, medical record of 114 patients who were treated with PLD at our institution between January 2010 and December 2016 were retrospectively reviewed. All those patients have been referred for routine monitoring of oral mucositis every time before administration by a dentist. The patient characteristics included in the evaluation were age, smoking and drinking habits, the PLD dose and schedule, and presence or absence of oral leukoplakia and SCCTO at each oral examination. The relationships of the incidence of oral leukoplakia and patient characteristics were analyzed.The median total PLD dose was 160 (range 40-1550) mg/m. Oral leukoplakia was seen in 6 (5.3%) patients. The median PLD dose, at the time of oral leukoplakia diagnosis, was 685 (range 400-800) mg/m. SCCTO was not found. Univariate analysis revealed that age, Brinkman index, and habitual drinking were not considered as risk factors for oral leukoplakia, and only total PLD dose (OR, 1.470; 95% CI, 1.19-1.91; P < .001) remained as a significant independent risk factor for oral leukoplakia. The ROC curve analysis indicated that the optimal cutoff value of the total PLD dose to predict development of oral leukoplakia was 400 mg/m. The sensitivity was 100% and the specificity was 88.8%. No patient discontinued PLD because of oral leukoplakia or SCCTO.The 2 most important clinical observations were the occurrence of oral leukoplakia in patients with long-term PLD use and that the development of oral leukoplakia was related to a total cumulative dose ≥400 mg/m. Routine oral surveillance is recommended, particularly when the cumulative total dose exceeds 400 mg/m.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/efeitos adversos
Doxorrubicina/análogos & derivados
Leucoplasia Bucal/induzido quimicamente
Neoplasias Ovarianas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Doxorrubicina/efeitos adversos
Esquema de Medicação
Feminino
Seres Humanos
Meia-Idade
Polietilenoglicóis/efeitos adversos
Estudos Retrospectivos
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (liposomal doxorubicin); 30IQX730WE (Polyethylene Glycols); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009932


  6 / 23872 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29307829
[Au] Autor:Li Z; Qu M; Sun Y; Wan H; Chai F; Liu L; Zhang P
[Ad] Endereço:Department of Oncology, Sanya People's Hospital, Sanya 572000, China.
[Ti] Título:Blockage of cytosolic phospholipase A2 alpha sensitizes aggressive breast cancer to doxorubicin through suppressing ERK and mTOR kinases.
[So] Source:Biochem Biophys Res Commun;496(1):153-158, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Advanced breast cancer is resistant to chemotherapy and its underlying mechanisms are not fully explored. In this work, we identified cytosolic phospholipase A2 alpha (cPLA2α) as a novel target to overcome chemoresistance in breast cancer. We demonstrated the increased transcriptional and translational expression of cPLA2α in breast cancer cells to acute and chronic exposure to doxorubicin. cPLA2α upregulation is also observed in breast cancer patients in response to chemotherapy. Inhibition of cPLA2α using two pharmacological inhibitors significantly enhances doxorubicin's effects to almost complete suppression in breast cancer cell growth, survival and migration. Similarly, depletion of cPLA2α significantly sensitizes breast cancer cells to doxorubicin treatment. We further found that cPLA2α inhibition led to decreased phosphorylation of ERK, mTOR, S6 and 4EBP1, suggesting the suppression of ERK and mTOR signaling pathways. These findings indicate the positive roles of cPLA2α in breast cancer cell growth, survival, migration and response to chemotherapy. Our work also highlights the therapeutic value of blocking cPLA2α to overcome chemoresistance in breast cancer.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Neoplasias da Mama/tratamento farmacológico
Doxorrubicina/administração & dosagem
MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores
Fosfolipases A2 do Grupo IV/metabolismo
Inibidores de Fosfolipase A2/administração & dosagem
Serina-Treonina Quinases TOR/antagonistas & inibidores
[Mh] Termos MeSH secundário: Antibióticos Antineoplásicos/administração & dosagem
Antibióticos Antineoplásicos/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Apoptose/efeitos dos fármacos
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Doxorrubicina/farmacologia
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Sinergismo Farmacológico
Ativação Enzimática/efeitos dos fármacos
Seres Humanos
Invasividade Neoplásica
Inibidores de Fosfolipase A2/farmacologia
Resultado do Tratamento
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Phospholipase A2 Inhibitors); 80168379AG (Doxorubicin); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 3.1.1.4 (Group IV Phospholipases A2); EC 3.1.1.4 (PLA2G4A protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  7 / 23872 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29390423
[Au] Autor:Amodeo I; Colnaghi M; Raffaeli G; Cavallaro G; Ciralli F; Gangi S; Leva E; Pignataro L; Borzani I; Pugni L; Mosca F
[Ad] Endereço:Neonatal Intensive Care Unit.
[Ti] Título:The use of sirolimus in the treatment of giant cystic lymphangioma: Four case reports and update of medical therapy.
[So] Source:Medicine (Baltimore);96(51):e8871, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Lymphatic malformations (LMs) are rare and benign anomalies resulting from the defective embryological development of the primordial lymphatic structures. Due to their permeative growth throughout all tissue layers, treatment is often challenging. Small asymptomatic lesions can be conservatively managed, while symptomatic lesions require active management. Surgery has been historically considered the treatment of choice, but today less invasive therapeutic options are preferred (sclerotherapy, laser therapy, oral medications). However, there are not uniform therapeutic protocols. Sirolimus is an oral medication that has been reported to be effective in the recent literature. Here we present the case of 4 newborns with giant multicystic lymphangioma treated with oral sirolimus after surgical resection had failed. PATIENT CONCERNS: At birth the LMs were clinically appreciated as giant masses involving different organs and structures. DIAGNOSES: All patients had a prenatal diagnosis of giant multicystic lymphangioma confirmed at histological and cytological analysis. INTERVENTIONS: Patients were treated with oral sirolimus after unsuccessful surgical resection. OUTCOMES: In all patients, sirolimus determined an overall reduction of the mass and a global involution from the macro- to the microcystic composition. Sirolimus was safe and poor disadvantages had been observed. The main and isolated adverse effect at laboratory analysis was progressive dyslipidemia, with increasing levels of total cholesterol and triglycerides. LESSONS: To date, our experience with sirolimus in the management of LMs is favorable. We recommend the use of sirolimus after unsuccessful surgical excision have been tried or when the surgical approach is not feasible. A multidisciplinary follow-up is needed to monitor disease evolution.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/uso terapêutico
Linfangioma Cístico/diagnóstico
Sirolimo/uso terapêutico
[Mh] Termos MeSH secundário: Administração Oral
Antibióticos Antineoplásicos/administração & dosagem
Diagnóstico Diferencial
Feminino
Seres Humanos
Recém-Nascido
Linfangioma Cístico/diagnóstico por imagem
Linfangioma Cístico/tratamento farmacológico
Imagem por Ressonância Magnética
Masculino
Sirolimo/administração & dosagem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008871


  8 / 23872 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29320562
[Au] Autor:Jarosz-Biej M; Kaminska N; Matuszczak S; Cichon T; Pamula-Pilat J; Czapla J; Smolarczyk R; Skwarzynska D; Kulik K; Szala S
[Ad] Endereço:Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
[Ti] Título:M1-like macrophages change tumor blood vessels and microenvironment in murine melanoma.
[So] Source:PLoS One;13(1):e0191012, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tumor-associated macrophages (TAMs) play a significant role in at least two key processes underlying neoplastic progression: angiogenesis and immune surveillance. TAMs phenotypic changes play important role in tumor vessel abnormalization/ normalization. M2-like TAMs stimulate immunosuppression and formation of defective tumor blood vessels leading to tumor progression. In contrast M1-like TAMs trigger immune response and normalize irregular tumor vascular network which should sensitize cancer cells to chemo- and radiotherapy and lead to tumor growth regression. Here, we demonstrated that combination of endoglin-based DNA vaccine with interleukin 12 repolarizes TAMs from tumor growth-promoting M2-like phenotype to tumor growth-inhibiting M1-like phenotype. Combined therapy enhances tumor infiltration by CD4+, CD8+ lymphocytes and NK cells. Depletion of TAMs as well as CD8+ lymphocytes and NK cells, but not CD4+ lymphocytes, reduces the effect of combined therapy. Furthermore, combined therapy improves tumor vessel maturation, perfusion and reduces hypoxia. It caused that suboptimal doses of doxorubicin reduced the growth of tumors in mice treated with combined therapy. To summarize, combination of antiangiogenic drug and immunostimulatory agent repolarizes TAMs phenotype from M2-like (pro-tumor) into M1-like (anti-tumor) which affects the structure of tumor blood vessels, improves the effect of chemotherapy and leads to tumor growth regression.
[Mh] Termos MeSH primário: Interleucina-12/administração & dosagem
Macrófagos/fisiologia
Melanoma Experimental/irrigação sanguínea
Melanoma Experimental/imunologia
Neovascularização Patológica/patologia
Microambiente Tumoral/imunologia
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/administração & dosagem
Animais
Antibióticos Antineoplásicos/farmacologia
Linfócitos T CD4-Positivos/efeitos dos fármacos
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/efeitos dos fármacos
Linfócitos T CD8-Positivos/imunologia
Proliferação Celular/efeitos dos fármacos
Doxorrubicina/farmacologia
Feminino
Células Matadoras Naturais/efeitos dos fármacos
Células Matadoras Naturais/imunologia
Macrófagos/efeitos dos fármacos
Melanoma Experimental/tratamento farmacológico
Melanoma Experimental/patologia
Camundongos
Camundongos Endogâmicos C57BL
Neovascularização Patológica/tratamento farmacológico
Neovascularização Patológica/imunologia
Células Tumorais Cultivadas
Vacinas de DNA/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Antibiotics, Antineoplastic); 0 (Vaccines, DNA); 187348-17-0 (Interleukin-12); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191012


  9 / 23872 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29025653
[Au] Autor:Yang S; Wang Y; Ren Z; Chen M; Chen W; Zhang X
[Ad] Endereço:Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
[Ti] Título:Stepwise pH/reduction-responsive polymeric conjugates for enhanced drug delivery to tumor.
[So] Source:Mater Sci Eng C Mater Biol Appl;82:234-243, 2018 Jan 01.
[Is] ISSN:1873-0191
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In this research, a charge-conversional polymer, poly-l-lysine-lipoic acid (PLL-LA), was prepared by dimethylmaleic anhydride (DA) modification and applied as a carrier with enhanced cell internalization and intracellular pH- and reduction-triggered doxorubicin (Dox) release. The surface charge of dimethylmaleic anhydride-poly-l-lysine-lipoic acid micelles (DA-PLL-LA) was negative at physiological pH and reversed to positive at the extracellular and intracellular pH of cancer cells. At tumor extracellular pH of 6.8, the conjugates underwent a rapid charge-reversible process with almost 80% DA cleavage within 2h, and then endocytosed into the endo/lysosomes more rapidly than at physiological pH of 7.4. The Dox/DA-PLL-LA micelles (Dox-micelles) demonstrated a sustained drug release in vitro under physiological condition, and rapid Dox release was triggered by both extracellular pH and high-concentration reducing glutathione. The Dox-micelles also exhibited enhanced internalization at extracellular pH, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Excellent tumor-penetrating efficacy was also found in A549 tumor spheroids and solid tumor slices. Moreover, the DA-PLL-LA micelles exhibited excellent tumor-targeting ability in tumor tissues and excellent antitumor efficacy and low systemic toxicity in breast tumor-bearing mice. Therefore, the DA-PLL-LA micelles demonstrated great potential for targeted and efficient drug delivery in cancer treatments.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/química
Doxorrubicina/química
Portadores de Fármacos/química
Polímeros/química
[Mh] Termos MeSH secundário: Células A549
Animais
Antibióticos Antineoplásicos/uso terapêutico
Antibióticos Antineoplásicos/toxicidade
Sobrevivência Celular/efeitos dos fármacos
Doxorrubicina/uso terapêutico
Doxorrubicina/toxicidade
Portadores de Fármacos/síntese química
Liberação Controlada de Fármacos
Seres Humanos
Concentração de Íons de Hidrogênio
Camundongos
Camundongos Endogâmicos BALB C
Micelas
Microscopia Confocal
Neoplasias/tratamento farmacológico
Neoplasias/patologia
Oxirredução
Fagocitose/efeitos dos fármacos
Polilisina/química
Polímeros/síntese química
Ácido Tióctico/química
Transplante Heterólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Drug Carriers); 0 (Micelles); 0 (Polymers); 25104-18-1 (Polylysine); 73Y7P0K73Y (Thioctic Acid); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE


  10 / 23872 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29304038
[Au] Autor:Madhankumar AB; Mrowczynski OD; Slagle-Webb B; Ravi V; Bourcier AJ; Payne R; Harbaugh KS; Rizk E; Connor JR
[Ad] Endereço:Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, PA, United States of America.
[Ti] Título:Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors.
[So] Source:PLoS One;13(1):e0181529, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/administração & dosagem
Doxorrubicina/análogos & derivados
Neoplasias da Bainha Neural/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antibióticos Antineoplásicos/farmacocinética
Linhagem Celular Tumoral
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacocinética
Sistemas de Liberação de Medicamentos
Seres Humanos
Imuno-Histoquímica
Interleucina-13/administração & dosagem
Subunidade alfa2 de Receptor de Interleucina-13/metabolismo
Antígeno Ki-67/metabolismo
Camundongos
Camundongos Nus
Neoplasias da Bainha Neural/imunologia
Neoplasias da Bainha Neural/metabolismo
Polietilenoglicóis/administração & dosagem
Polietilenoglicóis/farmacocinética
Proteínas S100/metabolismo
Neuropatia Ciática/tratamento farmacológico
Neuropatia Ciática/imunologia
Neuropatia Ciática/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Interleukin-13); 0 (Interleukin-13 Receptor alpha2 Subunit); 0 (Ki-67 Antigen); 0 (Mki67 protein, mouse); 0 (S100 Proteins); 0 (liposomal doxorubicin); 30IQX730WE (Polyethylene Glycols); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181529



página 1 de 2388 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde