RESUMO
Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous non-Hodgkin lymphoma that is extremely aggressive and has an intermediate to high malignancy. Some patients still experience treatment failure, relapse, or resistance to rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) therapy. Therefore, there is an urgent need for further research on new agents for the treatment of DLBCL. AP-48 is an aaptamine alkaloid analog with potent anti-tumor effects that originates from marine natural products. In this study, we found that AP-48 exhibits dose-dependent cytotoxicity in DLBCL cell lines. Flow cytometry showed that AP-48 induced cell cycle arrest in the G0/G1 phase in SU-DHL-4 and Farage cells and in the S phase in WSU-DLCL-2 cells. AP-48 also accelerated apoptosis via the caspase-3-mediated intrinsic apoptotic pathway. Further experiments demonstrated that AP-48 exerted its anti-DLBCL effects through the PI3K/AKT/mTOR pathway, and that the PI3K agonist YS49 partially alleviated the inhibition of cell proliferation and apoptosis induced by AP-48. Finally, in a tumor xenograft model, AP-48 inhibited tumor growth and promoted apoptosis in tumor tissues, indicating its therapeutic potential in DLBCL.
Assuntos
Alcaloides , Apoptose , Linfoma Difuso de Grandes Células B , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Ensaios Antitumorais Modelo de Xenoenxerto , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/metabolismo , Humanos , Serina-Treonina Quinases TOR/metabolismo , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Alcaloides/farmacologia , Linhagem Celular Tumoral , Camundongos , Apoptose/efeitos dos fármacos , Poríferos/química , Camundongos Nus , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Antineoplásicos/farmacologiaRESUMO
<p><b>OBJECTIVE</b>To explore the perpetual impact of pregnancy-induced hypertension on blood pressure.</p><p><b>METHODS</b>This retrospective cohort study included 782 cases of pregnant women who hospitalized at Kailuan Linxi hospital between October 1976 and August 2001. Patients were divided to with pregnancy induced hypertension (PIH, n = 77) group and non pregnancy induced hypertension (NPIH, n = 705) group. Patients were followed for 5 to 34 years (mean 18.8 +/- 5.3 years), the incidence of essential hypertension was obtained in July 2006-September 2007.</p><p><b>RESULTS</b>(1) The cumulative incidence of essential hypertension during follow up was significantly high in PIH group (29.87%) than that in NPIH group 18.87% (P = 0.022). (2) At the final follow up, waist circumference; [(86.06 +/- 10.15) cm vs. (83.07 +/- 8.19) cm, P = 0.015], BMI [(24.83 +/- 4.01) kg/m(2) vs. (23.50 +/- 3.39) kg/m(2), P = 0.006], TC [(5.11 +/- 0.88) mmol/L vs. (4.89 +/- 0.94) mmol/L, P = 0.045] and GLU [(5.57 +/- 1.78) mmol/L vs. (5.20 +/- 1.38) mmol/L, P = 0.010] were all significantly higher in PIH group than those in NPIH group. (3) After adjustment of age and BMI, PIH was still significantly correlated with long-term systolic blood pressure levels (P = 0.048), fasting glucose level was also significantly associated with long-term systolic blood pressure. Age, BMI, white blood cell count and uric acid were also predictors for perpetual systolic and diastolic blood pressure levels.</p><p><b>CONCLUSIONS</b>Incidence of essential hypertension in women with PIH was higher than that in women without PIH. After adjustment of covariates including age, BMI, and glucose, PIH was significantly associated with the level of systolic blood pressure. BMI, fasting glucose and cholesterol levels might contribute to the increase of systolic blood pressure in patients with PIH.</p>
Assuntos
Adulto , Feminino , Humanos , Gravidez , Adulto Jovem , Pressão Sanguínea , China , Epidemiologia , Estudos de Coortes , Hipertensão Induzida pela Gravidez , Epidemiologia , Incidência , Estudos RetrospectivosRESUMO
<p><b>OBJECTIVE</b>To examine the association between polymorphism of vascular endothelial growth factor(VEGF)1498 C/T,936 C/T and colorectal adenoma genetic susceptibility.</p><p><b>METHODS</b>A case-control study of 224 colorectal adenomas and 200 controls was conducted and VEGF genotypes were determined based on TaqMan-probe assay. The epidemiological factors were collected through questionnaire. Accordingly, the clinicopathological data of each sample were also investigated.</p><p><b>RESULTS</b>The carriage of 936 CT and CT+TT genotypes had significantly higher risk of colorectal adenoma (CT vs. CC, OR=2.00, 95% CI: 1.23-3.25, P=0.006; CT+TT vs. CC, OR=2.04, 95% CI:1.28-3.26, P=0.003). 936-T allele carriage had increased risk of colorectal adenoma (OR=1.91, 95% CI:1.25-2.91, P=0.003). The genotypes of 1498 C/T and the frequency of C/T allele showed no differences between healthy persons and patients (P>0.05). In patients with 936 CT+TT and 936-T allele implied a tendency of villous adenoma category (CT+TT vs. CC, OR=2.54, 95% CI:1.12-5.75, P=0.040; T allele vs. C allele, OR=3.08, 95% CI, 1.64-5.80, P=0.001).</p><p><b>CONCLUSION</b>VEGF 936 C/T polymorphism can influence susceptibility to colorectal adenoma.</p>
Assuntos
Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adenoma , Genética , Estudos de Casos e Controles , Neoplasias Colorretais , Genética , Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular , GenéticaRESUMO
0.05);2)After 12,24,36 months' treatment,BP was decreased significantly in each group (P0.05).Conclusion Both combined spirono- lactone/HCTZ and captopril/HCTZ significantly reduced BP and LVMI or LVMI and the maguitude of reduction was further enhanced after prolonged treatment.
RESUMO
<p><b>OBJECTIVE</b>To explore the association between G614T single nuclear polymorphism (SNP) of the alpha-adducin gene and the antihypertensive effect of hydrochlorothiazide (HCTZ) in essential hypertensive (EH) patients.</p><p><b>METHODS</b>Eight hundred twenty nine EH patients were given 12.5 mg HCTZ/d for six weeks. Alpha-adducin gene G614T SNP in the tenth exon was determined by PCR-RFLP in 754 patients with complete records. All the patients were grouped according to TT, GT and GG genotypes.</p><p><b>RESULTS</b>After 6 weeks of HCTZ treatment, the decreases in DBP and MAP of patients carrying 614T allele of alpha-adducin were significantly greater than that of those carrying GG homozygotes (P < 0.05). The decreases in SBP and MAP were significantly greater in patients with the TT genotype as compared with GT or GG genotype (P < 0.05). The effective rate of BP fall by HCTZ was higher in patients with TT genotype than those with GT or GG genotype (P < 0.05). Multivariate stepwise regression analysis showed that the TT genotype and the baseline SBP were the two major predictors affecting the decrease in SBP.</p><p><b>CONCLUSION</b>The present study suggests that the alpha-adducin G614T polymorphism is associated with the antihypertensive effect of HCTZ, which is more effective in patients with TT genotype.</p>