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1.
J Biochem Mol Toxicol ; : e22158, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29719090

RESUMO

Here, we aimed to investigate the carcinogenic effects of apolipoprotein C1 (APOC1) in prostate cancer (PCa). APOC1 expression was evaluated in PCa and normal prostate specimens, and lentivirus-mediated RNA interference was used to knockdown APOC1 in DU145 cells. The effects of APOC1 silencing on cell proliferation, cell cycle arrest, and apoptosis were assessed. APOC1 expression was much higher in PCa tissues than in normal tissues. Moreover, APOC1 silencing inhibited cell proliferation and colony formation, arrested cell cycle progression, and enhanced apoptosis in DU145 cells. Additionally, APOC1 silencing decreased survivin, phospho-Rb, and p21 levels and increased cleaved caspase-3 expression. These data supported the procarcinogenic effects of APOC1 in the pathogenesis of PCa and suggested that targeting APOC1 may have applications in the treatment of PCa.

2.
Gynecol Endocrinol ; 33(8): 621-624, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28361552

RESUMO

OBJECTIVE: To analyze the concentrations of nesfatin-1 in maternal and cord serum, to evaluate the expression of nesfatin-1 in subcutaneous adipose tissue (SAT) from pregnant women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT). METHODS: We studied a total of 50 GDM and 50 NGT subjects. The clinical features, serum nesfatin-1, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles were measured at the third trimester of pregnancy. The expression of nesfatin-1 in the SAT was determined by western blot. RESULTS: Compared with the NGT group, the GDM group showed greater levels of serum nesfatin-1, adipocyte fatty acid binding protein (AFABP), and leptin; a greater level of cord blood nesfatin-1; and a higher level of expression in SAT (p < 0.05 or p < 0.01). Fasting insulin (FI) (b = 0.317, p= 0.022) and body mass index (BMI) before delivery (b = 0.367, p=0.008) were independently associated with serum nesfatin-1. Nesfatin-1 was the independent risk factor for GDM. CONCLUSIONS: The GDM group had higher levels of maternal serum and cord blood nesfatin-1, and greater nesfatin-1 expression in SAT. Nesfatin-1 is closely related to obesity and IR in pregnancy.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação a DNA/sangue , Diabetes Gestacional/sangue , Proteínas do Tecido Nervoso/sangue , Regulação para Cima , Adulto , Povo Asiático , Biomarcadores/sangue , Biomarcadores/metabolismo , Glicemia/análise , Índice de Massa Corporal , Proteínas de Ligação ao Cálcio/metabolismo , China , Proteínas de Ligação a DNA/metabolismo , Diabetes Gestacional/metabolismo , Ensaio de Imunoadsorção Enzimática , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Sangue Fetal/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Leptina/sangue , Leptina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Nucleobindinas , Gravidez , Gordura Subcutânea Abdominal/metabolismo , Adulto Jovem
3.
J BUON ; 20(2): 505-13, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26011343

RESUMO

PURPOSE: To observe the efficacy and side effects of adjuvant dendritic cells' (DCs) vaccine combined with cytokine-induced killer cell (CIK) therapy after renal cell carcinoma (RCC) surgery (RCCS). METHODS: DCs vaccine and CIK that loaded the autologous tumor cell lysate were prepared in vitro. Four hundred and ten RCC patients were recruited, and the study group was given DCs-CIK immunotherapy, while the control group was given IFN-α therapy. RESULTS: Disease progression (recurrence, metastasis or death) showed significant differences between the two groups in clinical stage I and II patients, as well as in highly and moderately differentiated disease (p<0.05), while there was no significant difference between the two groups in patients with poorly differentiated disease (p>0.05). The 3- and 5-year overall survival rates of the DCs-CIK group (96% and 96%, respectively) exhibited significant difference compared to the IFN-α group (83% and 74%, respectively (p<0.01). Progression-free survival (PFS) between the two groups was significantly different (p<0.01). Tumor stage and DCs-CIK treatment were independent factors concerning prognosis of RCC (p<0.05). There was no severe toxicity observed in the DCs-CIK treatment group. CONCLUSIONS: Adjuvant post-RCCS DCs-CIK treatment prolonged PFS and reduced mortality, showing better overall activity compared to interferon treatment.


Assuntos
Vacinas Anticâncer/imunologia , Carcinoma de Células Renais/terapia , Células Matadoras Induzidas por Citocinas/imunologia , Células Dendríticas/imunologia , Neoplasias Renais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacinas Anticâncer/efeitos adversos , Carcinoma de Células Renais/mortalidade , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade
4.
Heliyon ; 10(13): e33864, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39071607

RESUMO

Background: Rotor syndrome (RS, OMIM#237450) is an extremely rare autosomal digenic recessive disorder characterized by mild non-hemolytic hereditary conjugated hyperbilirubinemia, caused by biallelic variation of SLCO1B1 and SLCO1B3 genes that resulted in OATP1B1/B3 dysfunction in the sinusoidal membrane leading to impaired bilirubin reuptake ability of hepatocytes. Methods: One RS pedigree was recruited and clinical features were documented. Whole genome second-generation sequencing was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations. Results: This study detected a homozygous nonsense variant c.1738C > T (p.R580*) in the coding region of the SLCO1B1 (NM006446) gene in a family with RS and hepatitis B virus infection by Variants analysis and Sanger sequencing, and confirmed by Copy Number Variation (CNV) analysis and Long Range PCR that there was a homozygous insertion of intron 5 of the SLCO1B3 gene into intron 5 of long-interspersed element 1 (LINE1). A few cases of such haplotypes have been reported in East Asian populations. A hepatitis B virus infection with fatty liver disease was indicated by pathology, which revealed mild-moderate lobular inflammation, moderate lobular inflammation, moderate hepatocellular steatosis, and fibrosis stage 1-2 (NAS score: 4 points/S1-2) alterations. Heterozygotes carrying p.R580* and LINE1 insertions were also detected in family members (I1, I2, III2, III3), but they did not develop conjugated hyperbilirubinemia. Conclusion: The mutations may be the molecular genetic foundation for the presence of SLCO1B1 c.1738C > T(p.R580*) and SLCO1B3 (LINE1) in this RS pedigree.

5.
BMC Cell Biol ; 14: 18, 2013 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-23510080

RESUMO

BACKGROUND: The objective of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of granulosa cells (GCs) in rats. RESULTS: Cisplatin increased GC apoptosis from 0.59% to 13.04% in the control and cisplatin treatment groups, respectively, which was significantly reduced upon co-culture with BMSCs to 4.84%. Cisplatin treatment increased p21 and bax and decreased c-myc mRNA expression, which was reversed upon co-culture with BMSCs. As compared to young rats, increased apoptosis was observed in the perimenopausal rats (P < 0.001). After 3 months, the apoptosis rate in the BMSC group was significantly lower than that of the control group (P = 0.007). CONCLUSIONS: BMSC therapy may protect against GC apoptosis induced by cisplatin and perimenopause. Further studies are necessary to evaluate therapeutic efficacy of BMSCs.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Cisplatino/administração & dosagem , Técnicas de Cocultura/métodos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células da Granulosa/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Perimenopausa/fisiologia , Animais , Apoptose/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Estrogênios/administração & dosagem , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/fisiologia , Células-Tronco Mesenquimais/fisiologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
6.
Pediatr Rheumatol Online J ; 21(1): 130, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872565

RESUMO

OBJECTIVES: Systemic lupus erythematosus is an autoimmune disease that involves multiple organ systems. One of its major complications, lupus nephritis (LN), is associated with a high mortality rate, and children-onset LN have a more severe course and worse prognosis than adults. Oxidative stress and inflammatory responses are involved in LN development and pathogenesis. Thus, this study aimed to explore the role of signaling regulation of the Nrf2/HMGB1/TLR/NF-κB pathway in LN pathogenesis and unravel the expression of TLR4+CXCR4+ plasma cells subset (PCs) in LN. METHODS: C57BL/6 and MRL/lpr mice were divided into four groups: control, model, vector control, and Nrf2 overexpression groups. The vector control and Nrf2 overexpression groups were injected with adenoviral vectors into the kidney in situ. Pathological changes in kidney tissues were observed by hematoxylin-eosin staining. The expression of Nrf2, HMGB1, TLR4, NF-κB, and downstream inflammatory factors in kidney samples was analyzed by quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The ratios of TLR4+CXCR4+ PC subsets in the blood and kidneys of mice were determined by flow cytometry. RESULTS: In MRL/lpr mice, Nrf2 was downregulated while HMGB1/TLR4/NF-κB pathway proteins were upregulated. Nrf2 overexpression decreased the expression of HMGB1, TLR4, NF-κB, and its downstream inflammatory cytokines (IL-1ß and TNFα). These cytokines were negatively correlated with an increase in Nrf2 content. PC and TLR4 + CXCR4 + PCs in the blood and kidney samples were significantly increased in MRL/lpr mice; however, they were decreased upon Nrf2 overexpression. CONCLUSION: This study showed severe kidney injury in an LN mouse model and an increased ratio of TLR4 + CXCR4 + PCs. Furthermore, we observed that Nrf2 regulates LN immune response through the Nrf2/HMGB1/TLR4/NF-κB pathway, which can be considered an important target for LN treatment. The clinical value of the findings of our study requires further investigation.


Assuntos
Nefrite Lúpica , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Animais , Criança , Humanos , Camundongos , Citocinas/metabolismo , Proteína HMGB1/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo
7.
Yao Xue Xue Bao ; 47(7): 878-83, 2012 Jul.
Artigo em Zh | MEDLINE | ID: mdl-22993851

RESUMO

The effect of CYP3A4*18B and CYP3A5*3 on concentration/dosage x body surface area ratios (C/D'), adverse effects and acute rejection of tacrolimus in renal transplant patients were investigated. The CYP3A4*18B genotypes of 227 renal transplant patients were determined by PCR-RFLP method. The differences of C/D' ratios, adverse reactions and acute rejection were compared among all of the genotype groups treated with tacrolimus. The frequencies of CYP3A4*18 and CYP3A5*3 alleles in renal transplant patients were 30.8% and 74.2%, respectively. No significant association was found between the C/D's of tacrolimus and CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P > 0.05). While after the effects of CYP3A4*18B genotype were eliminated, the C/D' ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was significantly lower than those with CYP3A5*3/*3 genotype groups (P < 0.01). There is no significant difference in adverse effects and acute rejection among different genotypes (P > 0.05).


Assuntos
Citocromo P-450 CYP3A/genética , Imunossupressores/sangue , Transplante de Rim , Tacrolimo/sangue , Adulto , Alelos , Doenças do Sistema Digestório/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Genótipo , Rejeição de Enxerto/genética , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico
8.
Zhonghua Yi Xue Za Zhi ; 92(24): 1711-4, 2012 Jun 26.
Artigo em Zh | MEDLINE | ID: mdl-22944165

RESUMO

OBJECTIVE: To investigate the effect and potential mechanism of atorvastatin against H2O2-induced apoptosis of human umbilical vein endothelial cells (ECV-304). METHODS: ECV-304 cells were pretreated with different concentrations of atorvastatin (0.1, 1 and 10 µmol/L) for 2 h, followed by an exposure to 100 µmol/L H2O2 for 18 h. Cellular morphology was observed under fluorescence microscope. Cellular viability and apoptosis were evaluated by methyl thiazolyl tetrazolium (MTT) and flow cytometry. Finally the expressions of cleaved caspase-3 and caspase-9 were measured by Western blot. RESULTS: H2O2 treatment caused an obvious apoptosis of ECV-304 cells and significantly decreased the cellular viability as characterized by a high percentage (50.71%) of apoptotic cells. Atorvastatin pretreatment inhibit cellular apoptosis induced by H2O2 (39.45%, 20.53% and 7.83%). Western blot assay showed that H2O2 treatment caused a high expression of cleaved caspase-3 and caspase-9 while atorvastatin pretreatment obviously inhibited the expression in a dose-dependent manner. CONCLUSIONS: Atorvastatin inhibits the H2O2-induced apoptosis of ECV-304 cells in a dose-dependent manner. This effect may be associated with the down-regulation of cleaved caspase-9/caspase-3.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Células Endoteliais/efeitos dos fármacos , Ácidos Heptanoicos/farmacologia , Pirróis/farmacologia , Atorvastatina , Células Cultivadas , Regulação para Baixo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Peróxido de Hidrogênio
9.
Transpl Immunol ; 20(3): 150-4, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18848988

RESUMO

Second renal transplants are historically associated with a poor prognosis. The aim of the present study was to assess long-term survival of second renal grafts from deceased donors performed at our center and to analyze risk factors associated with long-term graft outcome. Sixty-five second renal grafts were enrolled into this study, and compared to primary ones performed during the same period. Kaplan-Meier curve showed a graft survival rate of 89.2% at 1 year, 80% at 3 years, and 63.1% at 5 years, which were similar to that of primary graft. Univariate analysis showed that time to first graft loss, cold ischaemia time, HLA mismatch, primary maintenance immunosuppressant, acute rejection episodes, and serum creatinine at 1 year were significantly associated with regraft survival. Cox regression demonstrated the dominant effect of acute rejection episodes, primary maintenance immunosuppressant, serum creatinine at 1 year, and time to first graft loss as predictor of second graft outcome. However, when long-term survival of second graft was examined on the basis of Kaplan-Meier estimates, HLA mismatch was found to be significant. The second graft had more benefits of improved pre-transplant screening and post-transplant management, and its survival rate was satisfactory and similar to that of primary one. Immunologic factors such as acute rejection and primary immunosuppressant are the main determinants of long-term renal transplantation outcome.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim , Adulto , China , Feminino , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transplante Homólogo , Adulto Jovem
10.
Transpl Immunol ; 18(3): 281-5, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18047938

RESUMO

Presensitized renal allograft recipients require special management to improve their outcome, and there is no consensus on the optimal immunosuppressive strategy. We retrospectively analyzed clinical data of 82 patients, who were PRA positive pre-transplant (above 10%) and received single bolus ATG and basiliximab as induction therapy, and assessed safety and efficacy of two kinds of induction therapies. Patients of ATG group (n=40) received single bolus ATG (Fresenius, 9 mg/kg preoperatively) and those of basiliximab group (n=42) were given two doses of basiliximab (Simulect, Novartis, 20 mg) on days 0 and 4 post-transplant. All patients received standard triple immunosuppressive therapy with tacrolimus (FK-506), mycophenolate mofetil (MMF), and steroids. The follow-up time was 12 months. There was no hyperacute rejection in two groups, and delayed graft function occurred in two patients of ATG group and three of basiliximab group. After 12-month follow-up, more acute rejection (AR) episodes were observed in basiliximab group than ATG group (35.7% vs. 15%, P=0.032). Although highly significant differences were observed between ATG group and basiliximab group with respect to the incidence of thrombocytopenia (P=0.001), single bolus ATG was well tolerated. Incidences of other adverse events and infection episodes did not differ between two groups (P>0.05). One-year patient and graft survival was 95%, 92.5% and 95.2%, 88.1% in ATG and basiliximab group respectively (P>0.05). Both single bolus ATG and basiliximab induction therapy achieved similar one-year graft/patient survival. However, single bolus ATG yielded much lower AR rate than basiliximab without increase in infection episodes and severe adverse events.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Basiliximab , Feminino , Sobrevivência de Enxerto/imunologia , Humanos , Terapia de Imunossupressão , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico
11.
Pediatr Transplant ; 12(2): 215-8, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18307671

RESUMO

To explore the long-term outcomes of paediatric kidney transplantation and the effects of renal allograft on growth, education, employment, marriage and procreation. Twenty-seven children with ESRD received the renal allograft from 1985 to 2001. The patient and kidney survival rate, renal function, growth and employment, etc., were reviewed retrospectively. The average follow-up period was 10.3 +/- 4.4 yr. The one-, three-, five- and 10-yr graft survival rates were 96.3%, 88.9%, 81.5% and 66.7%, respectively, and the corresponding patient survival rates were 100%, 92.6%, 85.2% and 68.8%. The body weight gain was 4-10 kg in one-yr post-operative and the height increased 0-2 cm for girls and 2-5 cm for boys. A total of 44.4% of the recipients accomplished their education above junior high school. The employment rate was 46.2% in males, and 57.2% in females. Twelve patients were married. Non-adherence occurred in 30% of the recipients. Forty percent of the surviving recipients developed complications. Seven patients died. More attention should be paid to non-adherence of medications and more supports from the society are required to improve the life quality of paediatric recipients, especially in employment and education.


Assuntos
Desenvolvimento Infantil , Escolaridade , Emprego , Transplante de Rim/estatística & dados numéricos , Estado Civil , Qualidade de Vida , Adolescente , Adulto , Criança , China , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Fatores de Tempo , Resultado do Tratamento
12.
EBioMedicine ; 34: 85-93, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30078736

RESUMO

BACKGROUND: Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers. METHODS: mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model. FINDINGS: ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p < 0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo. INTERPRETATION: Taken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent. FUND: This work was supported in part by The National Natural Science Foundation of China (No. 81570748) and Natural Science Foundation of Fujian Province (No. 2018J01345, 2017XQ1194).


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Renais/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/antagonistas & inibidores , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico
13.
Kaohsiung J Med Sci ; 34(10): 576-582, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30309486

RESUMO

To explore the influence of prostate size on the outcome of Plasmakinetic enucleation of the prostate (PkEP) for the treatment of benign prostate hyperplasia (BPH), The data of 892 patients with symptomatic BPH who underwent PkEP were retrospectively reviewed. Among them, 199 (22.31%) had the prostate size smaller than 40 g (Group 1), 409 (45.85%) between 40 and 79 g (Group 2), 197 (22.09%) between 80 and 120 g (Group 3), and 87 (9.75%) larger than 120 g (Group 4). Perioperative variables, perioperative and postoperative complications were recorded. Patients were followed up for 36 months postoperatively. The efficiency of the surgery increased as the prostate size increased. Greater decreases in hemoglobin were noted in groups with larger prostates, while the duration of catheterization after the operation was similar across all groups. During the 3-year follow-up, the postoperative improvement in International Prostate Symptom Score (IPSS), Quality of Life (QOL), maximal flow rate (Qmax) and post-void residual urine volume (PVR), as well as longterm complications including urethral stricture and bladder-neck contracture were comparable across the 4 groups. These findings revealed that PkEP is more efficient for large prostate and can treat all prostates regardless of the size with equivalent symptom relief and micturition improvement.


Assuntos
Próstata/patologia , Próstata/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Hiperplasia Prostática/fisiopatologia , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
14.
Transpl Immunol ; 17(4): 278-82, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17493531

RESUMO

Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.


Assuntos
Rejeição de Enxerto/diagnóstico , Antígeno Ki-1/sangue , Transplante de Rim , Monitorização Imunológica , Adulto , Estudos de Coortes , Feminino , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
15.
Zhonghua Nan Ke Xue ; 13(1): 8-12, 2007 Jan.
Artigo em Zh | MEDLINE | ID: mdl-17302025

RESUMO

OBJECTIVE: To study and compare the biologic activity of two anti-PSA/anti-CD3 bispecific single-chain antibodies. METHODS: Flow cytometry (FCM) was used to detect the binding activity of two antibodies to CD3-positive cell line Jurkat and prostate carcinoma cell line LNCaP. The effect of the two antibodies in mediating tumor cell lysis in vitro was determined by using the 51Cr-release test. For in vivo evaluation of the two antibodies activity, a nude mouse model was used. The mice were inoculated with LNCaP prostate cancer cells. RESULTS: FCM showed that both the antibodies could bind Jurkat and LNCaP cells with high specificity. The percentages of the cells bond by the bispecific single-chain antibodies were 56.3% and 55.4%, and those by the multivalent antibodies were 74.0% and 83.0% respectively. Both the antibodies mediated a specific lysis of LNCaP cells in vitro, with activated CTLs as effector cells, and significantly reduced tumor growth of nude mice in vivo as compared with the untreated controls and the group treated with CTLs only (P <0.05). The experiment also showed that the multivalent antibody had a better activity than the bispecific antibody in binding antigens, mediating lysis of LNCaP cells and reducing tumor growth (P < 0.05). CONCLUSION: Both the anti-PSA/anti-CD3 bispecific single-chain antibody and multivalent antibody have good biologic activity, and the formation of the tetramerization of single-chain antibody can improve its biologic activity.


Assuntos
Anticorpos Biespecíficos/farmacologia , Neoplasias da Próstata/patologia , Animais , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Biespecíficos/imunologia , Complexo CD3/imunologia , Citotoxicidade Imunológica/imunologia , Citometria de Fluxo , Humanos , Células Jurkat , Masculino , Camundongos , Camundongos Nus , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/imunologia
16.
World J Gastroenterol ; 23(11): 1990-2001, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28373765

RESUMO

AIM: To determine the role of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance imaging (MRI) using a bi-exponential model in chemotherapy response evaluation in a gastric cancer mouse model. METHODS: Mice bearing MKN-45 human gastric adenocarcinoma xenografts were divided into four treated groups (TG1, 2, 3 and 4, n = 5 in each group) which received Fluorouracil and Calcium Folinate and a control group (CG, n = 7). DW-MRI scans with 14 b-values (0-1500 s/mm2) were performed before and after treatment on days 3, 7, 14 and 21. Fast diffusion component (presumably pseudo-perfusion) parameters including the fast diffusion coefficient (D*) and fraction volume (fp), slow diffusion coefficient (D) and the conventional apparent diffusion coefficients (ADC) were calculated by fitting the IVIM model to the measured DW signals. The median changes from the baseline to each post-treatment time point for each measurement (ΔADC, ΔD* and Δfp) were calculated. The differences in the median changes between the two groups were compared using the mixed linear regression model by the restricted maximum likelihood method shown as z values. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. The median percentage changes were compared with the histopathological analyses between the pre- and post-treatment for each measurement. RESULTS: Compared with the control group, D* in the treated group decreased significantly (ΔD*treated% = -30%, -34% and -20%, with z = -5.40, -4.18 and -1.95. P = 0.0001, 0.0001 and 0.0244) and fp increased significantly (Δfptreated% = 93%, 113% and 181%, with z = 4.63, 5.52, and 2.12, P = 0.001, 0.0001 and 0.0336) on day 3, 7 and 14, respectively. Increases in ADC in the treated group were higher than those in the control group on days 3 and 14 (z = 2.44 and 2.40, P = 0.0147 and P = 0.0164). CONCLUSION: Fast diffusion measurements derived from the bi-exponential IVIM model may be more sensitive imaging biomarkers than ADC to assess chemotherapy response in gastric adenocarcinoma.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Modelos Animais de Doenças , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Processamento de Imagem Assistida por Computador , Marcação In Situ das Extremidades Cortadas , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Funções Verossimilhança , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Aleatória , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Chin Med J (Engl) ; 119(20): 1683-8, 2006 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-17097014

RESUMO

BACKGROUND: Immunological sensitization remains a major problem following renal transplantation. There is no consensus for the management of sensitized renal allograft recipients. The patients become tethered to dialysis while waiting for compatible donors. This study was designed to evaluate the efficacy and safety of preoperative single-bolus high-dose antithymocyte globulin (ATG) as induction therapy in sensitized renal transplant recipients. METHODS: A total of 56 patients were divided into two groups according to the level of panel reactive antibody (PRA): non-sensitized group (PRA < 10%, n = 30) and sensitized group (PRA > or = 10%, n = 26). The characteristics of the recipients and donors were comparable between the two groups. Mycophenolate mofetil (MMF, 1 g) or ATG (iv. 9 mg/kg) were given preoperatively in the two groups as induction therapy. After the transplantation, the patients were treated with standard triple therapy regimen consisting of tacrolimus (FK-506) or cyclosporine A, MMF, and prednisolone. Acute rejection (AR) and infection episodes were recorded and renal function was monitored during a 12-month follow-up. Chi(2) test and t test were used to analyze the data. RESULTS: During the follow-up, 6 patients (20.0%) suffered AR episodes in the non-sensitized group and 4 (15.4%) in the sensitized group (P = 0.737); 8 patients (26.7%) experienced 11 infection episodes (average, 1.4 episodes per infected patient) in the non-sensitized group, and 6 (23.1%) experienced 10 infection episodes (average, 1.7 episodes per infected patient) in the sensitized group (P = 0.757, 0.890). The safety of the drugs, which was assessed by the occurrence of side effects, was comparable between the two groups. The hospital stay was 13 - 25 days (mean, 16.7 +/- 3.3) in the non-sensitized group and 14 - 29 days (mean, 16.2 +/- 3.1) in the sensitized group, respectively (P = 0.563). No delayed graft function (DGF) was observed in all the patients. Both the 12-month actuarial patient and graft survival rates were 100% in the two groups. CONCLUSION: Preoperative single-bolus high-dose ATG is an effective and safe induction therapy yielding acceptable acute rejection rate in sensitized renal transplant recipients.


Assuntos
Soro Antilinfocitário/uso terapêutico , Transplante de Rim , Adulto , Soro Antilinfocitário/efeitos adversos , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores , Masculino , Pessoa de Meia-Idade
18.
J Diabetes Investig ; 7(5): 797-804, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27181269

RESUMO

AIMS/INTRODUCTION: To observe the longitudinal changes in serum adipocyte fatty acid-binding protein (AFABP), carbohydrate, and lipid metabolism parameters in women with and without gestational diabetes mellitus (GDM) during mid- and late pregnancy periods, as well as to identify whether there is any association between AFABP and development of GDM. MATERIALS AND METHODS: A total of 40 GDM and 240 normal glucose tolerance participants were enrolled at 24-28 weeks and completed the study. The clinical features, serum AFABP, other adipocytokines (leptin, adiponectin, retinol-binding protein 4), homeostasis model assessment of insulin resistance, and lipid profiles were measured in the second and third trimesters of pregnancy. RESULTS: Compared with the normal glucose tolerance group, the GDM group showed greater levels of AFABP, leptin and retinol-binding protein 4; and a decreased level of adiponectin (P < 0.05 or P < 0.01) during mid- and late pregnancy periods. Prepregnancy body mass index was the independent factor impacting serum AFABP levels in the second (ß = 0.567, P = 0.004) and third trimesters (ß = 0.619, P = 0.001). Furthermore, GDM was independently associated with AFABP concentrations in multiple regression analysis in the second and third trimester (all P < 0.01). Serum AFABP, leptin and retinol-binding protein 4 are risk factors for GDM; adiponectin is a protective factor for GDM (P < 0.05 or P < 0.01). CONCLUSIONS: The GDM group had a higher level of AFABP during mid- and late stages of pregnancy; prepregnancy body mass index and GDM were the independent factors with respect to serum AFABP. AFABP might be closely related to obesity, insulin resistance and leptin resistance in pregnancy, and is a major risk factor for GDM.


Assuntos
Diabetes Gestacional/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Adipocinas/sangue , Adulto , Feminino , Idade Gestacional , Humanos , Metabolismo dos Lipídeos , Gravidez , Adulto Jovem
19.
Nutrients ; 7(8): 7085-105, 2015 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-26305254

RESUMO

In this study, we examined the effects of apple polyphenols (APs) on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE(-/-) mice were fed a western-type diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.


Assuntos
Aterosclerose/prevenção & controle , Fígado Gorduroso/prevenção & controle , Malus/química , NF-kappa B/genética , Polifenóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL2/sangue , Quimiocina CCL2/genética , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Lipoproteínas LDL/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/genética
20.
Zhonghua Yi Xue Za Zhi ; 83(15): 1292-5, 2003 Aug 10.
Artigo em Zh | MEDLINE | ID: mdl-12930679

RESUMO

OBJECTIVE: To construct a recombinant vector that expresses anti-CD 3/anti-prostate-cancer bispecific single-chain antibody (BsAb), and study its biological activities and clinical significance. METHODS: An anti-CD 3/anti-prostate-cancer BsAb was constructed by PCR and molecular biological technique of DNA cloning. The fusion gene, confirmed by sequencing, was subcloned into the pSectag2-B plasmid from the pUC18 vector by digestion with EcoR I and Hind III restriction endonucleases, whose sites exist in both the vectors. Then the recombinant plasmid was transfected into HeLa cells. The expression products in the supernatant were analyzed by both SDS-PAGE and Western blot technique, then were purified with Ni(2+)-NTA superflow affinity chromatography. Its biological activities were examined by flow cytometry (FCM). RESULTS: A fragment of 1.5 kb was inserted into the pUC18 vector, which was sequenced and verified to be identical with that designed. The expression of anti-CD 3 x anti-prostate-cancer BsAb yielded a soluble protein with an apparent molecular mass of 61 KD. The purification rate of the expressed BsAb was up to 90.537% and the yield of purified BsAb from this procedure was 0.09 mg/ml. The positive binding rates of BsAb to PBMC and to PC-3 cell were 54.1% and 53.7% respectively. CONCLUSION: The anti-CD 3 x anti-prostate-cancer BsAb thus constructed exhibits beneficial biological activities and may play an important role in the treatment of prostate cancer.


Assuntos
Anticorpos Biespecíficos/biossíntese , Anticorpos Antineoplásicos/biossíntese , Complexo CD3/imunologia , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/imunologia , Proteínas Recombinantes de Fusão/biossíntese , Anticorpos Biespecíficos/isolamento & purificação , Anticorpos Biespecíficos/uso terapêutico , Escherichia coli/genética , Células HeLa , Humanos , Masculino , Antígeno Prostático Específico/isolamento & purificação , Antígeno Prostático Específico/uso terapêutico , Neoplasias da Próstata/terapia , Linfócitos T/imunologia
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