Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Apoptosis ; 22(10): 1296-1309, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28766061

RESUMO

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential stromal cells which are regarded as the most feasible stem cell group in cell therapy. The maintenance of cell survival without differentiation is important in cell transplantation and stem cell therapy. However, negative factors exist in cell transplantation. Lysophosphatidic acid (LPA) is a non-antigenic small molecule phospholipid which induced several fundamental cellular responses, such as cell proliferation, apoptosis and migration. In this study we aimed to explore the effects of LPA on the survival and differentiation of MSCs and its availability in cell therapy. We found that LPA stimulated hUC-MSC proliferation and protected hUC-MSCs from lipopolysaccharide (LPS) induced apoptosis. We also observed that CD29, CD44, CD73, CD90 and CD105 were expressed, whereas CD34 and CD45 were not expressed in hUC-MSCs, and these makers have no change in LPA containing medium, which indicated that LPA accelerated the survival of hUC-MSCs in an undifferentiating status. We also demonstrated that higher expressed LPAR1 involved in LPA stimulated cell survival action. LPA stimulated cell proliferation was associated with LPAR1 mediated Gi/o-proteins/ERK1/2 pathway. On the other hand, LPA protected hUC-MSCs from LPS-induced apoptosis through suppressing caspase-3 activation by LPAR1 coupled with a G protein, but not Gi/o or Gq/11 in hUC-MSC. Collectively, this study demonstrated that LPA increased the proliferation and survival of hUC-MSCs without differentiation through LPAR1 mediated manner. Our findings provide that LPA as a anti-apoptotic agent having potential application prospect in cell transplantation and stem cell therapy.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lisofosfolipídeos/fisiologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Receptores de Ácidos Lisofosfatídicos/metabolismo , Cordão Umbilical/citologia , Antígenos de Diferenciação/genética , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Subunidades alfa de Proteínas de Ligação ao GTP/antagonistas & inibidores , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Lisofosfolipídeos/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Receptores de Ácidos Lisofosfatídicos/antagonistas & inibidores , Receptores de Ácidos Lisofosfatídicos/genética
2.
Chem Biodivers ; 13(12): 1685-1690, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27448440

RESUMO

In our continuing program to find new bioactive compounds from the Chinese liverworts, four new kaurane-type diterpenoids, (6ß)-kaur-16-ene-6,9-diol (1), (6ß,12ß)-kaur-16-ene-6,9,12-triol (2), (6ß)-kaur-16-ene-5,6,9-triol (3), and kaur-16-ene-9,19-diol (4), have been isolated from the Chinese liverwort Jungermannia comata Nees. Five known kaurane-type diterpenoids (5 - 9) and four known trachylobane-type diterpenoids (10 - 13) were also obtained. The structures of the new compounds were established unequivocally on the basis of spectroscopic data. The absolute configuration of compound 1 was established by comparing experimental and calculated electronic circular dichroism spectra.


Assuntos
Diterpenos do Tipo Caurano/isolamento & purificação , Hepatófitas/química , China , Dicroísmo Circular , Diterpenos do Tipo Caurano/química , Conformação Molecular
3.
J Nat Prod ; 77(2): 339-45, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24491225

RESUMO

Six new cembrane-type diterpenoids (1-6) were isolated from two species of Chandonanthus: Chandonanones A, B, and D-F (1, 2, and 4-6) were isolated from C. hirtellus, and chandonanones B, C, E, and F (2, 3, 5, and 6) from C. birmensis. Five known diterpenoids, (8E)-4α-acetoxy-12α,13α-epoxycembra-1(15),8-diene (7), isochandonanthone (8), chandonanthone (9), anadensin (10), and 2,10,14-triacetoxy-7,8,18,19-diepoxydolabell-3(E)-ene (11), were also obtained. The structures of the new metabolites were established by analyses of their spectroscopic data (1D NMR, 2D NMR, HRESIMS, and IR). The absolute configurations of compounds 1 and 2 were unequivocally confirmed using single-crystal X-ray diffraction analysis with Cu Kα radiation. Cytotoxicity tests of the isolated diterpenoids against seven cancer cell lines (DU145, PC3, A549, PC12, NCI-H292, NCI-H1299, and A172) revealed that some of the diterpenoids had weak activity.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Diterpenos/isolamento & purificação , Hepatófitas/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
4.
J Nat Prod ; 77(9): 2081-7, 2014 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-25226363

RESUMO

Ten new dolabrane-type diterpenoids, notolutesins A-J (1-10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 µM against the PC3 human prostate cancer cell line.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Diterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Hepatófitas/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Dicroísmo Circular , Cristalografia por Raios X , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Concentração Inibidora 50 , Masculino , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
5.
Tetrahedron Lett ; 55(47): 6500-6503, 2014 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-25574060

RESUMO

A new and efficient total synthesis has been developed to obtain plagiochin G (22), a macrocyclic bisbibenzyl, and four derivatives. The key 16-membered ring containing biphenyl ether and biaryl units was closed via an intramolecular SNAr reaction. All synthesized macrocyclic bisbibenzyls inhibited Epstein-Barr virus early antigen (EBVEA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and, thus, are potential cancer chemopreventive agents.

6.
J Agric Food Chem ; 72(2): 1082-1095, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38169320

RESUMO

Oligomycins are potent antifungal and antitumor agents. Mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based metabolomic fingerprinting analysis of marine-derived actinomycetes in our in-house library provided an oligomycin-producing strain, Streptomyces sp. FXY-T5. Chemical investigation led to the discovery of five new oligomycins, 24-lumooligomycin B (1), 4-lumooligomycin B (2), 6-lumooligomycin B (3), 40-homooligomycin B (4), and 15-hydroxy-oligomycin B (5), together with seven biosynthetically related known derivatives. Their structures were assigned by MS, NMR, electronic circular dichroism (ECD), and single-crystal X-ray diffraction analyses. The biosynthesis pathway of oligomycins was first proposed based on the analysis of a type I modular polyketide synthase (PKS) system and targeted gene disruption. As expected, the isolated oligomycins showed significant antiagricultural fungal pathogen activity and antiproliferative properties from which the possible structure-activity relationships were first suggested. More importantly, oligomycins induced significant G1-phase cell cycle arrest on cancer cells and significantly attenuated their Cyclin D1 and PCNA expression through a ß-catenin signaling pathway.


Assuntos
Antineoplásicos , Streptomyces , Streptomyces/química , Oligomicinas/farmacologia , Oligomicinas/química , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Relação Estrutura-Atividade , Antifúngicos/farmacologia
7.
Cardiovasc Toxicol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008239

RESUMO

Hypertension is a globally prevalent disease, but the pathogenesis remains largely unclear. AMP-activated protein kinase (AMPK) is a nutrition-sensitive signal of cellular energy metabolism, which has a certain influence on the development of hypertension. Previously, we found a down-regulation of the phosphorylated (p-) form of AMPK, and the up-regulation of the angiotensin II type 1 receptor (AT1-R) and that of p-ERK1/2 in the hypothalamic paraventricular nucleus (PVN) of hypertensive rats. However, the exact mechanism underlying the relationship between AMPK and AT1-R in the PVN during hypertension remains unclear. Thus, we hypothesized that AMPK modulates AT1-R through the ERK1/2-NF-κB pathway in the PVN, thereby inhibiting sympathetic nerve activity and improving hypertension. To examine this hypothesis, we employed a renovascular hypertensive animal model developed via two-kidney, one-clip (2K1C) and sham-operated (SHAM). Artificial cerebrospinal fluid (aCSF), used as vehicle, or 5-amino-1-ß-D-ribofuranosyl-imidazole-4-carboxamide (AICAR, an AMPK activator, 60 µg/day) was microinjected bilaterally in the PVN of these rats for 4 weeks. In 2K1C rats, there an increase in systolic blood pressure (SBP) and circulating norepinephrine (NE). Also, the hypertensive rats had lowered expression of p-AMPK and p-AMPK/AMPK, elevated expression of p-ERK1/2, p-ERK1/2/ERK1/2 and AT1-R, increased NF-κB p65 activity in the PVN compared with the levels of these biomarkers in SHAM rats. Four weeks of bilateral PVN injection of AMPK activator AICAR, attenuated the NE level and SBP, increased the expression of p-AMPK and p-AMPK/AMPK, lessened the NF-κB p65 activity, decreased the expression of p-ERK1/2, p-ERK1/2/ERK1/2 and AT1-R in the PVN of 2K1C rats. Data from this study imply that the activation of AMPK within the PVN suppressed AT1-R expression through inhibiting the ERK1/2-NF-κB pathway, decreased the activity of the sympathetic nervous system, improved hypertension.

8.
J Nat Prod ; 76(9): 1647-53, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-24004145

RESUMO

Ten highly oxygenated ent-pimarane-type diterpenoids, pedinophyllols A-J (1-10), were isolated from the Chinese liverwort Pedinophyllum interruptum. Their structures were determined by comprehensive analysis of spectroscopic data together with single-crystal X-ray diffraction analysis. The absolute configurations were elucidated by comparison of experimental and theoretically calculated electronic circular dichroism spectra. Allelopathic testing showed that several new diterpenoids inhibited germination of Arabidopsis thaliana seeds.


Assuntos
Abietanos/isolamento & purificação , Abietanos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Hepatófitas/química , Abietanos/química , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Dicroísmo Circular , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxigênio/química , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento
9.
J Nat Prod ; 76(9): 1700-8, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-24033150

RESUMO

Sixteen new clerodane diterpenoids, cephaloziellins A-P (1-16), and two known analogues (17 and 18) were isolated from an EtOH extract of the Chinese liverwort Cephaloziella kiaeri. The structures of the new compounds were elucidated from extensive spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the structures of 5, 9, and 15 were confirmed by single-crystal X-ray diffraction analyses. The absolute configurations of all new compounds were established by comparing experimental and calculated electronic circular dichroism spectra.


Assuntos
Diterpenos Clerodânicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Hepatófitas/química , Dicroísmo Circular , Cristalografia por Raios X , Diterpenos Clerodânicos/química , Medicamentos de Ervas Chinesas/química , Modelos Químicos , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
10.
Chem Biodivers ; 10(9): 1606-12, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24078594

RESUMO

Chemical investigation of the Chinese liverwort Scapania ciliata led to the isolation of four new cis-clerodane lactones, named ciliatolides A-D (1-4, resp.), among which compound 1 was found to be a tetranorclerodanoid. Their structures were determined by extensive analysis of spectroscopic data, and, in the case of compound 1, together with a single-crystal X-ray diffraction analysis. The absolute configurations were established by analysis of the CD spectra and by quantum-chemical CD calculations. The cytotoxicities of compounds 1-4 were preliminarily tested against the PC3 and MCF-7 cell lines.


Assuntos
Diterpenos Clerodânicos/química , Hepatófitas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Cristalografia por Raios X , Diterpenos Clerodânicos/isolamento & purificação , Diterpenos Clerodânicos/toxicidade , Hepatófitas/metabolismo , Humanos , Isomerismo , Células MCF-7 , Conformação Molecular
11.
J Asian Nat Prod Res ; 15(5): 473-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23614492

RESUMO

Three new pimarane-type diterpenoids, 7ß,11α-dihydroxypimara-8(14),15-diene (1), 1ß,11α-dihydroxypimara-8(14),15-diene (2), and 11α-hydroxypimara-8(14),15-diene (3), five 2,3-secoaromadendrane-type sesquiterpenoids, including a new one, ethyoxyplagiochiline A2 (4), and three known fusicoccane-type diterpenoids were isolated from the Chinese liverwort Plagiochila pulcherrima. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 6 and 7 exhibited moderate inhibitory activity on the proliferation of human cancer cell lines Hela, A172, and H460. Moreover, the cytotoxicity of compound 6 to Hela cells was related to apoptotis as confirmed by DAPI nuclear staining and flow cytometry.


Assuntos
Abietanos/isolamento & purificação , Abietanos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Hepatófitas/química , Abietanos/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Diterpenos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estereoisomerismo
12.
Molecules ; 17(5): 4770-81, 2012 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-22534662

RESUMO

Mycobacterium tuberculosis FabH, an essential enzyme in the mycolic acid biosynthetic pathway, is an attractive target for novel anti-tubercolosis agents. Structure-based design and synthesis of 1-(4-carboxybutyl)-4-(4-(substituted benzyloxy)phenyl)-1H-pyrrole-2-carboxylic acid derivatives 7a-h, a subset of eight potential FabH inhibitors, is described in this paper. The Vilsmeier-Haack reaction was employed as a key step. The structures of all the newly synthesized compounds were identified by IR, ¹H-NMR, ¹³C-NMR, ESI-MS and HRMS. The alamarBlue™ microassay was employed to evaluate the compounds 7a-h against Mycobacterium tuberculosis H37Rv. The results demonstrate that the compound 7d possesses good in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Minimum Inhibitory Concentration value [MIC], 12.5 µg/mL).These compounds may prove useful in the discovery and development of new anti-tuberculosis drugs.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase/antagonistas & inibidores , Antituberculosos/síntese química , Ácidos Carboxílicos/síntese química , Inibidores Enzimáticos/síntese química , Mycobacterium tuberculosis/efeitos dos fármacos , Pirróis/síntese química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Antituberculosos/farmacologia , Sítios de Ligação , Ácidos Carboxílicos/farmacologia , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Modelos Moleculares , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/crescimento & desenvolvimento , Ácidos Micólicos/metabolismo , Oxazinas , Ligação Proteica , Pirróis/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Relação Estrutura-Atividade , Xantenos
13.
Nutrients ; 14(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36235619

RESUMO

BACKGROUND: Aerobic exercise training (ExT) is beneficial for hypertension, however, its central mechanisms in improving hypertension remain unclear. Since the importance of the up-regulation of angiotensin II type 1 receptor (AT-1R) in the paraventricular nucleus (PVN) of the hypothalamic in sympathoexcitation and hypertension has been shown, we testified the hypothesis that aerobic ExT decreases blood pressure in hypertensive rats by down-regulating the AT-1R through reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/nuclear factors κB (NF-κB) pathway within the PVN. METHODS: Forty-eight male Sprague-Dawley (SD) rats were assigned to the following groups: sham operation (SHAM) + kept sedentary (Sed), SHAM + exercise training (ExT), two kidney-one clamp (2K1C) + Sed, and 2K1C + ExT groups. RESULTS: The 2K1C + Sed hypertensive rats showed higher systolic blood pressure (SBP), upregulated ROS, phosphorylated (p-) p44/42 MAPK, p-p38 MAPK, NF-κB p65 activity, and AT-1R expression in the PVN, and increased circulating norepinephrine (NE) than those of SHAM rats. After eight weeks of aerobic ExT, the 2K1C + ExT hypertensive rats showed attenuated NE and SBP levels, suppressed NF-κB p65 activity, and reduced expression of ROS, p-p44/42 MAPK, p-p38 MAPK, and AT-1R in the PVN, relatively to the 2K1C + Sed group. CONCLUSIONS: These data are suggestive of beneficial effects of aerobic ExT in decreasing SBP in hypertensive rats, via down-regulating the ROS/MAPK/NF-κB pathway that targets AT-1R in the PVN, and eventually ameliorating 2K1C-induced hypertension.


Assuntos
Hipertensão , Núcleo Hipotalâmico Paraventricular , Condicionamento Físico Animal , Animais , Masculino , Ratos , Hipertensão/prevenção & controle , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Norepinefrina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/genética , Sistema Nervoso Simpático
14.
Nutrients ; 14(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36235829

RESUMO

BACKGROUND: The hypothalamic paraventricular nucleus (PVN) is an important nucleus in the brain that plays a key role in regulating sympathetic nerve activity (SNA) and blood pressure. Silent mating-type information regulation 2 homolog-1 (sirtuin1, SIRT1) not only protects cardiovascular function but also reduces inflammation and oxidative stress in the periphery. However, its role in the central regulation of hypertension remains unknown. It is hypothesized that SIRT1 activation by resveratrol may reduce SNA and lower blood pressure through the regulation of intracellular reactive oxygen species (ROS) and neurotransmitters in the PVN. METHODS: The two-kidney one-clip (2K1C) method was used to induce renovascular hypertension in male Sprague-Dawley rats. Then, bilaterally injections of vehicle (artificial cerebrospinal fluid, aCSF, 0.4 µL) or resveratrol (a SIRT1 agonist, 160 µmol/L, 0.4 µL) into rat PVN were performed for four weeks. RESULTS: PVN SIRT1 expression was lower in the hypertension group than the sham surgery (SHAM) group. Activated SIRT1 within the PVN lowered systolic blood pressure and plasma norepinephrine (NE) levels. It was found that PVN of 2K1C animals injected with resveratrol exhibited increased expression of SIRT1, copper-zinc superoxide dismutase (SOD1), and glutamic acid decarboxylase (GAD67), as well as decreased activity of nuclear factor-kappa B (NF-κB) p65 and NAD(P)H oxidase (NOX), particularly NOX4. Treatment with resveratrol also decreased expression of ROS and tyrosine hydroxylase (TH). CONCLUSION: Resveratrol within the PVN attenuates hypertension via the SIRT1/NF-κB pathway to decrease ROS and restore the balance of excitatory and inhibitory neurotransmitters.


Assuntos
Hipertensão , Núcleo Hipotalâmico Paraventricular , Animais , Cobre/metabolismo , Glutamato Descarboxilase/metabolismo , Masculino , NADPH Oxidases/metabolismo , NF-kappa B/metabolismo , Neurotransmissores/metabolismo , Norepinefrina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/metabolismo , Resveratrol/farmacologia , Sirtuína 1/genética , Sirtuína 1/metabolismo , Superóxido Dismutase-1/metabolismo , Sistema Nervoso Simpático/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Zinco/metabolismo
15.
Mil Med Res ; 8(1): 56, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34743730

RESUMO

Targeting immune checkpoints has achieved great therapeutic effects in the treatment of early-stage tumors. However, most patients develop adaptive resistance to this therapy. The latest evidence demonstrates that tumor-derived exosomes may play a key role in systemic immune suppression and tumor progression. In this article, we highlight the role of exosomal immune checkpoint proteins in tumor immunity, with an emphasis on programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as emerging evidence on roles of T cell immunoglobulin-3 (TIM-3), arginase 1 (ARG1), and estrogen receptor binding fragment-associated antigen 9 (EBAG9) expressed by exosomes.


Assuntos
Exossomos , Neoplasias , Exossomos/metabolismo , Humanos , Proteínas de Checkpoint Imunológico , Imunoterapia
16.
Acta Haematol ; 121(1): 1-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19246888

RESUMO

In the present study, 90 patients with newly diagnosed acute promyelocytic leukemia (APL) were studied for all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) combination treatment in remission induction and postremission therapy. In addition, 20 APL patients who had achieved complete remission (CR) with an ATRA-based regimen received ATRA/As(2)O(3) combination for consolidation and maintenance were also enrolled. The results showed that ATRA/As(2)O(3) combination therapy yielded a high CR rate of 93.3% and a significantly shorter time to enter CR (median: 31 days; range: 18-59 days) compared to the ATRA-based regimen (n = 72; median: 39 days; range: 25-62 days). With the ATRA/As(2)O(3) combination for CR maintaining, regardless of the way by which CR was attained, the relapse-free survival was significantly better than with an ATRA plus cytotoxic chemotherapy regimen (92.9 +/- 3.2% vs. 72.4 +/- 7.6%, for the 3-year Kaplan-Meier estimate of relapse-free survival). The drug toxicity profile showed that with the use of As(2)O(3), the incidence of hepatotoxicity was obviously high during remission induction but decreased significantly during postremission treatment. We conclude that APL patients may benefit from the early use of the combination of ATRA and As(2)O(3), in either remission induction or consolidation/maintenance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Óxidos/administração & dosagem , Óxidos/efeitos adversos , Indução de Remissão/métodos , Taxa de Sobrevida , Fatores de Tempo , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1058-1063, 2019 Aug.
Artigo em Zh | MEDLINE | ID: mdl-31418357

RESUMO

OBJECTIVE: To detect the expression of CRLF2 in bone marrow mononuclear cells from children with newly diagnosed acute lymphoblastic leukemia(ALL) and to explore its clinical significance in pediatric ALL. METHODS: A total of 218 children with newly diagnosed ALL who achieveal the complete remission and had the complete follow-up information were selected, and the expression level of CRLF2 in bone marrow mononuclear cells of these children was detected by real-time fluorescent quantitative PCR, and the significance of CRLF2 expression level in clinical prognosis of ALL children was analyzed by using statistical method. RESULTS: 28 cases in 218 children with complete data showed high expression of CRLF2. The cumulative recurrence rate in the CRLF2 high expression group was significantly higher than that in the low expression group (53.6% vs 12.6%) (P<0.01). The predicted 5-year recurrence-free survival rate (RFS) of ALL children with CRLF2 high expression was significantly higher than that of low expression group (P<0.01). There was no significant difference in the predicted 5-year RFS between ALL children with CRLF2 low and high expression in the standard-risk(SR) group (P>0.05). The predicted 5-year RFS of ALL children with CRLF2 low expression was higher than that of ALL children with CRLF2 high expression in the intermediate-risk (IR) and high-risk (HR) groups. (P<0.05). Cox analysis showed that CRLF2 high expression is an independent risk factor for the relapse of children with ALL. CONCLUSION: The recurrence rate of pediatric ALL with CRLF2 high expression is high, and CRLF2 high expression is an important prognostic factor for high risk of relapse in ALL children with IR and HR. It is necessary to use CRLF2 expression as an indicator of risk stratification in pediatric ALL.


Assuntos
Medula Óssea , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Citocinas/metabolismo , Criança , Humanos , Prognóstico , Recidiva , Fatores de Risco
18.
Ann Hematol ; 87(2): 121-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17999062

RESUMO

This investigation was designed to assess the effect of DuP-697 on growth and apoptosis in a human chronic myeloid leukemia (CML) cell line (K562 cells) and primary CML cells from CML patient bone marrow. DuP-697 significantly suppressed K562 cells and primary CML cells growth and induced apoptosis in a concentration-dependent manner and the growth-inhibiting effect was independent on Philadelphia chromosome. The IC50 of DuP-697 at 36 h was 31.7 muM. It arrested G1-S phase transmit on cell cycle and its apoptosis activity was partially abrogated by pretreating K562 cells with Z-IETD-fmk, a specific inhibitor of caspase-8. This study suggested that Dup-697 suppresses growth and induces apoptosis on K562 leukemia cells by cell-cycle arrest and caspase-8 activation.


Assuntos
Apoptose/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Tiofenos/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Caspase 8/efeitos dos fármacos , Caspase 8/metabolismo , Ciclo Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Humanos , Células K562
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(1): 94-98, 2017 Feb.
Artigo em Zh | MEDLINE | ID: mdl-28245382

RESUMO

OBJECTIVE: To investigate the effect of icaritin on the proliferation and apoptosis of THP-1 cells and its mechanism. METHODS: After treated with various concentrations of icaritin, cell proliferation was detected by MTS method, and apoptosis was measured with flow cytometry and Hoechst 33258 staining. Expression of BCL-2, BAX and Caspase-3 protein in THP-1 cell was detected by Western blot. RESULTS: After treatment with various concentrations (4-32 µmol/L) of icaritin for 24, 48, 72 h, the inhibition rate of cell growth significantly increased (P<0.05) in time-dose dependent manner(r=0.946); and the apoptotic rate of cells significantly increased (P<0.05) in time-dose dependent manner(r= 0.924). The expression of BCL-2 protein at 48 h decreased significantly in icaritin-treated group, compared with that in control group (P<0.05), while the expression of BAX and Caspase3 protein at 48 h increased significantly in icaritin-treated group, compared with that in control group (P<0.05). CONCLUSION: Icaritin can inhibit proliferation and induce apoptosis of THP-1 in vitro, Icaritin may induce apoptosis in THP-1 cells through the mitochondrial pathway.


Assuntos
Apoptose/efeitos dos fármacos , Flavonoides/farmacologia , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células THP-1
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA