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1.
Acta Pharmacol Sin ; 40(7): 971-979, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30643210

RESUMO

Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A1403, a novel c-Met ADC composed of a humanized IgG2 monoclonal antibody against c-Met conjugated to a novel cytotoxic microtubule inhibitor. SHR-A1403 showed high affinity to c-Met proteins derived from human or monkey and potent inhibitory effects in cancer cell lines with high c-Met protein expression. In mice bearing tumors derived from cancer cell lines or patient HCC tissues with confirmed c-Met overexpression, SHR-A1403 showed excellent anti-tumor efficacy. Antibody binding with c-Met contributed to SHR-A1403 endocytosis; the subsequent translocation to lysosomes and cytotoxicity of the released toxin are speculated to be predominant mechanisms underlying the anti-tumor activity of SHR-A1403. In conclusion, SHR-A1403 showed significant anti-tumor activity in cancer cell lines, xenograft mouse models and an HCC PDX model, which all have high c-Met levels. These data provide references for SHR-A1403 as a potential therapy for the treatment of cancers with c-Met overexpression.

2.
J Thorac Cardiovasc Surg ; 147(3): 863-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24315697

RESUMO

OBJECTIVES: To summarize the clinical outcomes of totally thoracoscopic closure of a ventricular septal defect (VSD). METHODS: Totally thoracoscopic VSD closure was performed in 119 patients (66 boys; mean age, 7.1 ± 3.6 years). An additional 35 patients undergoing open-chest VSD closure were selected as a control group. Using 3 port incisions in the right chest, pericardiotomy, bicaval occlusion, atriotomy, and VSD closure were performed by thoracoscopy without the aid of a robotically assisted surgical system. RESULTS: Cardiopulmonary bypass and aortic crossclamp times were 42.2 ± 9.8 and 32.5 ± 7.3 minutes, respectively. There were no deaths but 1 patient required insertion of a permanent pacemaker as a result of postoperative atrioventricular conduction block. The length of stay in the intensive care unit (11.0 ± 2.6 vs 22.9 ± 4.9 hours, P < .01) or postoperative hospital stay (4.2 ± 1.1 vs 6.6 ± 2.1 days, P < .03) in the thoracoscopic group were shorter than in the control group. The percentage of patients who required postoperative opioid analgesics in the thoracoscopic group was lower than in the control group (31.9% vs 74.2%, P < .001). Rate of blood transfusion during the operation (17.6% vs 65.7%, P = .001) and the postoperative use of opioid analgesics (31.9% vs 74.3%, P = .003) in the thoracoscopic group was lower than in the control group. Transesophageal echocardiographic analysis 4.6 ± 2.3 months after the operation showed complete closure of the defect. CONCLUSIONS: Totally thoracoscopic closure of VSD through a 3-port entry was safe and effective.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Comunicação Interventricular/cirurgia , Toracoscopia , Adolescente , Adulto , Fatores Etários , Analgésicos Opioides/uso terapêutico , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/terapia , Transfusão de Sangue , Peso Corporal , Estimulação Cardíaca Artificial , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Ecocardiografia Transesofagiana , Feminino , Comunicação Interventricular/diagnóstico por imagem , Humanos , Tempo de Internação , Masculino , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Seleção de Pacientes , Pericardiectomia , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/terapia , Toracoscopia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
3.
Zhong Yao Cai ; 34(1): 84-8, 2011 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21818975

RESUMO

OBJECTIVE: To investigate the therapeutic effect of Rheum officinale on acute pancreatitis. METHODS: Buffered sodium taurocholate (3% m/V) was injected into the pancreatico-biliary duct to induce acute pancreatitis. Death rate,coefficient of pancreas, serum amylyse (AMY), hemocuprein (SOD), TNF-alpha and IL-1beta level were examined at 6, 12 and 24 hours after operations. Pathology analysis were also obtained. RESULTS: Compared with corresponding pancreatitis groups,death rate, coefficient of pancreas, serum TNF-alpha and IL-1beta level of drug groups decreased remarkably (P < 0.05), while serum SOD level significantly increased (P < 0.01). Serum AMY level of drug groups increased at 6 h (P < 0.01), decreased at 12 h (P < 0.01) and had no statistics disparity at 24 h (P > 0.05) compared with respective pancreatitis group. Although score points of all drug groups were lower than corresponding pancreatitis groups, the growth tendency of both were similar. CONCLUSION: Rheum officinale Baill has the effect of prevention to pancreas pathological changes in the animal pattern, but not able to reverse the tendency.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Pâncreas/patologia , Pancreatite/tratamento farmacológico , Plantas Medicinais , Rheum , Doença Aguda , Amilases/sangue , Amilases/metabolismo , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Interleucina-1beta/sangue , Masculino , Pâncreas/efeitos dos fármacos , Pancreatite/sangue , Pancreatite/patologia , Ratos , Ratos Wistar , Colato de Sódio/administração & dosagem , Superóxido Dismutase/sangue , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue
4.
Chemosphere ; 82(3): 451-9, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20952045

RESUMO

We characterized fluorescent silica nanoparticles (FNPs), which had been applied in many biological systems, in fish embryo rearing media (ERM) solution and evaluated the potential toxicity to the early development of Oryzias latipes embryos. Distribution of FNPs in embryos and larvae of O. latipes was studied by fluorescent and confocal laser scanning microscopic studies. Embryos exposed to three different concentrations of FNPs in stirred or sonicated ERM solutions were observed up to 2d after hatching. FNPs had a negligible effect on the hatchability of O. latipes embryos; however, compared to controls, more than 30% of eggs were abnormal in 10 and 50 mg FN P L(-1) solutions. We found that the toxic effect was increased in sonicated FNP solution, which seems to be related with the dissolution of FNPs in ERM solutions that could be accelerated by sonication. Further study found that the CaCl2 included in ERM solution might enhance the dissolution of the FNPs and the silicate ion released from FNPs partially contributed to larval toxicity. This study showed that some nanoparticles may not be stable in biological fluids even if they are stable in water. Dissolution factors such as sonication and cellular components should be considered in biological application of nanoparticles.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Nanopartículas/toxicidade , Oryzias/embriologia , Dióxido de Silício/toxicidade , Animais , Fluorescência , Larva/efeitos dos fármacos , Oryzias/crescimento & desenvolvimento , Sonicação
5.
J Ethnopharmacol ; 130(2): 231-6, 2010 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-20435129

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (Burk) F.H. Chen (Araliaceae) is a well-known and commonly used traditional Chinese herb for treatment of various diseases, such as hemostasis, edema and odynolysis. AIM OF STUDY: Our aim was to investigate the mechanisms of anti-hyperglycemic and anti-obese effects of Panax notoginseng saponins (PNS) in KK-Ay mice, and explore the components in PNS for such effects. MATERIALS AND METHODS: KK-Ay mice received daily intraperitoneal injections of PNS 200mg/kg or vehicle for 30 days while ginsenoside Re 14 mg/kg, Rd 15 mg/kg, Rg1 40 mg/kg, Rb1 60 mg/kg and notoginsenoside R1 6 mg/kg for 12 days. Fasting blood glucose levels (FBGL), glucose tolerance (GT), serum insulin, leptin levels, body weight changes, food intake, adipose tissues and blood fat levels were measured at different time points. RESULTS: The PNS group had significantly lower FBGL, improved GT and smaller body weight incremental percentage after the 30-day treatment. Additionally, Rb1 exhibited significant reduction of FBGL on day 12, and Re also exhibited a decreasing trend after the 12-day treatment. CONCLUSIONS: PNS possess anti-hyperglycemic and anti-obese activities by improving insulin- and leptin sensitivity, and Rb1 is responsible for the anti-hyperglycemic effect among the five saponins in KK-Ay mice.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/farmacologia , Panax notoginseng , Saponinas/farmacologia , Adiposidade , Animais , Fármacos Antiobesidade/farmacologia , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal , Diabetes Mellitus/sangue , Diabetes Mellitus/fisiopatologia , Modelos Animais de Doenças , Ingestão de Alimentos , Teste de Tolerância a Glucose , Hipoglicemiantes/isolamento & purificação , Insulina/sangue , Resistência à Insulina , Leptina/sangue , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Raízes de Plantas , Saponinas/isolamento & purificação , Fatores de Tempo
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 41(2): 203-7, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20506635

RESUMO

OBJECTIVE: To compare the transfection efficiency of two kind of recombinant adeno-associated virus-mediated transfection to rats osteoblasts with enhanced green fluorescent protein and assess the feasibility of it as a vector for gene therapy of osteoblast lesions. METHODS: The osteoblasts of rats were isolated, cultured and identified with type I collagen staged digestion method. According to different multiplicity of infection (MOI) (MOI = 1 x 10(3), 1 x 10(4), 1 X 10(4), 5 x 10(5)), rAAV-EGFP was transfected into osteoblasts with rAAV only and rAAV-ADV co-transfection respectively. The expression of EGFP along with the transfection time was observed under inverted fluorescence microscope. The transfection efficiency and fluorescence intensity was evaluated by flow cytometry. The best MOI value was analysed and the cell growth curves were obtained according to the best MOI value to evaluate the toxic effects of rAAV-EGFP. RESULTS: The cultured cells possessed the biological behaviors of osteoblasts. The transfection efficiency of the rAAV was increased with the increasing of MOI. The EGFP expression reached the maximum on day 5 in ADV(-) group, the transfection efficiency of rAAV2/6-EGFP and rAAV2/9-EGFP was 90.2% and 66.1% respectively when MOI was 1 x 10(5) and no significant increase was observed when MOI was 5 x 10(5). In ADV(+) group, EGFP expression reached its maximum on day 3, the transfection efficiency of rAAV2/6-EGFP and rAAV2/9-EGFP was 47.6% and 30.5% respectively when MOI was 5 x 10(5). And no significant biologic effects on the cyto-activity was observed. CONCLUSION: The transfection efficiency of two kind of virus vectors was both very high and rAAV2/6's is higher than that of rAAV2/9. This suggested the potential of rAAV-EGFP as a safe and efficient vector for gene therapy.


Assuntos
Dependovirus/genética , Proteínas de Fluorescência Verde/biossíntese , Osteoblastos/metabolismo , Transfecção , Animais , Animais Recém-Nascidos , Dependovirus/metabolismo , Terapia Genética/métodos , Proteínas de Fluorescência Verde/genética , Osteoblastos/citologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética
7.
Chemosphere ; 77(3): 325-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19683785

RESUMO

The present study proposes Fridericia peregrinabunda (Michaelsen, 1913) as a new test species for assessment of soil ecotoxicity. Fridericia is the richest genus in the Enchytraeidae family (Oligochaeta: Annelida: Clitellata: Enchytraeidae), and widely distributed. The acute toxicity of cadmium (Cd) and antimony (Sb) on the survival of F. peregrinabunda were investigated in laboratory experiments. Adult survival of F. peregrinabunda in metal spiked soil was reduced. Cadmium was more toxic to F. peregrinabunda than Sb. In the artificial soil toxicity tests, the LC50 values for F. peregrinabunda exposed to Cd and Sb for 48 h were 37, and 446 mg kg(-1), respectively. The NOEC values for Cd and Sb were 20 and 100 mg kg(-1) up to 48 h exposure, respectively. This is the first report on the ecotoxicological assay of contaminated soils using the enchytraeids F. peregrinabunda as a test species. It can be concluded that F. peregrinabunda is a suitable test species to measure the acute toxicity of heavy metals, and this species is more sensitive to Cd and Sb than earthworm. The filter paper contact test and 2 day-artificial soil toxicity test appear to be rapid and cost-effective protocols for the potworm assay.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Oligoquetos/efeitos dos fármacos , Poluentes do Solo/toxicidade , Solo/análise , Testes de Toxicidade/métodos , Animais , Antimônio/toxicidade , Cádmio/toxicidade
8.
Chemosphere ; 75(7): 889-93, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19264343

RESUMO

Antimony is widespread in aquatic environment. Trivalent forms of antimony are known to be more toxic than other chemical species of antimony. In the present study, antimony potassium tartrate (APT), the trivalent inorganic forms of antimony, was selected as a test antimony compound due to its high water solubility. The effects of antimony on Japanese medaka (Oryzias latipes), planktonic crustacea (Moina macrocopa and Simocephalus mixtus), and green algae (Pseudokirchneriella subcapitata) were evaluated. Larval survival and the embryonic development were measured for fish assay. APT was less toxic to larval medaka (24-h LC50, 261; 48-h LC50, 238 mg L(-1)). Simocephalus mixtus was killed by very low concentrations of APT (24-h LC50, 4.92 mg L(-1)), and antimony was also toxic to Moina macrocopa (24-h LC50, 12.83 mg L(-1)). Toxicities of APT to S. mixtus and Moina macrocopa were about 50 and 20 times more toxic to Oryzias latipes larvae, respectively, in terms of 24-h LC50 value. Growth inhibition of Pseudokirchneriella subcapitata was observed in the presence of APT (72-h EC50, 206 mg L(-1)). This study demonstrated that APT is more toxic to planktonic crustacea than fish and green algae, and planktonic crustacea appears a better indicator of antimony pollution in aquatic environment.


Assuntos
Tartarato de Antimônio e Potássio/toxicidade , Clorófitas/efeitos dos fármacos , Crustáceos/efeitos dos fármacos , Oryzias/embriologia , Poluentes Químicos da Água/toxicidade , Animais , Tartarato de Antimônio e Potássio/farmacologia , Clorófitas/crescimento & desenvolvimento , Crustáceos/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/metabolismo , Dose Letal Mediana , Oryzias/crescimento & desenvolvimento , Análise de Sobrevida , Fatores de Tempo , Poluentes Químicos da Água/farmacologia
9.
Zhong Yao Cai ; 32(10): 1571-6, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20112724

RESUMO

OBJECTIVE: To observe the effects of Panax notoginseng saponins (PNS) on anti-hyperglycemic, anti-obese and prevention from kidney pathological changes in a type 2 diabetic KK-Ay gene mice model. METHODS: All animals were divided into 4 groups: Normal control group (C57BL/6J mice) were treated by NS 10 mL/kg, KK-Ay mice were subdivided into 3 groups as DM administrated NS 10 mL/kg, PNS 50 mg/kg, PNS 200 mg/kg respectively. All the animals received daily intraperitoneal injections for 30 days consecutively. All of these following items were determined as the effect of PNS: fasting plasma glucose levels (FPG), intraperitoneal glucose tolerance, body weight, food intake, insulin resistance index (IRI), serum insulin, triglyceride (TG), cholesterol (CH) levels and contribution of glomerulus injury. RESULTS: On the 12th, 22nd and 30th day, PNS-treated group had significantly lower FPG and low body weight incremental percentage. After a 12-day treatment, glucose tolerance was significantly improved. On the 30th day the serum IRI and TG levels of PNS-treated group decreased significantly, and the development of the mice glomerular lesions was prevented significantly. All of these showed a dose-effect relationship. CONCLUSION: PNS has the effects of anti-diabetes, anti-obese and prevention from kidney pathological changes in type 2 diabetic KK-Ay mice.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Hipoglicemiantes/farmacologia , Panax/química , Saponinas/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Teste de Tolerância a Glucose , Insulina/metabolismo , Resistência à Insulina , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/prevenção & controle , Raízes de Plantas/química , Distribuição Aleatória , Saponinas/química
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 15(3): 533-6, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17605860

RESUMO

The aim of this study was to detect the expression and cell cycle specificity of Fas, TNFRI and TNFRII in human peripheral blood lymphocytes (PBL), and to study the potential role of Fas, TNFRIand TNFRII in cell cycle specific apoptosis. The improved double-parameter flow cytometry was used to detect the expressions of Fas, TNFRI and TNFRII and cell cycle specificity in PBL which were incubated for 24 hours in the presence or absence of phytohaematoagglutinin (PHA) respectively. Apoptosis induced by IgM type anti-Fas and TNF-alpha was detected by API method. The results showed that compared with PBL treated in the absence of PHA in G(0) phase, the ratio of Fas, TNFRI and TNFRII expressions in PHA-stimulated PBL entering cell cycle increased (35.55 +/- 6.63)%, (30.63 +/- 2.66)%, (26.62 +/- 5.14)% respectively (P < 0.01), and mainly appeared at G(1)-phase; no apoptosis was induced by anti-Fas and TNF-alpha in G(0)-phase PBL cultured in the absence of PHA. On the contrary, the apoptosis was induced by anti-Fas and TNF-alpha in PBL which entered cell cycle after stimulation with PHA and mainly initiated at G(1)-Phase. It is concluded that there is evident dose-effect relationship between apoptotic receptor and receptor-mediated apoptosis. Moreover, the cell cycle specificity of receptor-mediated apoptosis is correlated with the cell cycle specific expressions of apoptotic receptor. The induction of apoptosis by apoptotic factors (anti-Fas and TNF-alpha) depends on whether cell entering cell cycle or not.


Assuntos
Apoptose , Linfócitos/citologia , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptor fas/metabolismo , Ciclo Celular , Humanos
11.
Ai Zheng ; 25(5): 576-81, 2006 May.
Artigo em Chinês | MEDLINE | ID: mdl-16687077

RESUMO

BACKGROUND & OBJECTIVE: Chondriosome-mediated apoptosis is closely related to cell cycle, however, the correlation of receptor-mediated apoptosis to cell cycle progression is unclear yet. This study was to observe the receptor-mediated apoptosis and cell cycle specificity in cultured normal and tumor lymphocytes, and investigate their correlation. METHODS: Exponentially growing human leukemia cell lines Molt-4 and Jurkat were treated with tumor necrosis factor-alpha (TNF-alpha) or Anti-Fas. Peripheral blood lymphocytes (PBLs) from healthy donors were stimulated by phytohemagglutinin (PHA), and further incubated with the presence of TNF-alpha or anti-Fas. Annexin V/PI was used to detect the apoptosis, and API method was used to illustrate the cell cycle specificity of apoptotic cells. RESULTS: Unstimulated PBLs kept blunt to stimulation with TNF-alpha or anti-Fas, and the apoptotic rate was 6%-8%. Molt-4 cells, Jurkat cells, and stimulated PBLs which were treated with TNF-alpha or anti-Fas went to apoptosis, and the apoptosis rates were 15%-28%. Most receptor-mediated apoptosis happened in early G1 phase. CONCLUSION: Receptor-mediated apoptosis is closely related to cell cycle and presents cell cycle specificity.


Assuntos
Anticorpos Monoclonais/farmacologia , Apoptose , Leucemia de Células T/patologia , Linfócitos/citologia , Fator de Necrose Tumoral alfa/farmacologia , Anticorpos Monoclonais Murinos , Ciclo Celular , Linhagem Celular Tumoral , Fase G1 , Humanos , Células Jurkat , Fito-Hemaglutininas/farmacologia
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