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1.
Oncol Rep ; 30(5): 2042-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24002681

ABSTRACT

Tumor angiogenesis, a pivotal process for cancer growth and metastasis, requires both upregulation of pro­angiogenic molecules and downregulation of anti­angiogenic molecules. Anti-angiogenesis therapy represents a promising way for cancer treatment. Tumstatin, a novel endogenous angiogenesis inhibitor, inhibits endothelial cell proliferation, pathological angiogenesis and tumor growth. Ornithine decarboxylase (ODC), overexpressed in various cancers, is associated with cell transformation, tumor invasion and angiogenesis. We found that the expression of tumstatin was suppressed in ODC-overexpressing human cancer cells and renal carcinoma tissues. We presumed that ODC overexpression may downregulate the expression of tumstatin. To be able to test this hypothesis, we generated HEK293 cells that overexpress ODC (ODC transfectants) and characterized the following experimental groups: PBS-treated group, mock transfectants, ODC transfectants, ODC transfectants transfected with pcDNA-ODCr (an antisense ODC-expressing plasmid) group and putrescine-treated group. The effect of ODC overexpression on tumstatin expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot analysis and dual luciferase reporter assay. ODC-overexpressing cells and putrescine-treated cells showed suppressed tumstatin mRNA and protein expression, and decreased tumstatin gene promoter activity. Thus, ODC overexpression suppresses the expression of tumstatin, which may provide fundamental evidence for the combination of anti-angiogenic therapy and conventional therapy for cancer treatment.


Subject(s)
Autoantigens/administration & dosage , Carcinoma, Renal Cell/enzymology , Cell Proliferation/drug effects , Collagen Type IV/administration & dosage , Ornithine Decarboxylase/biosynthesis , Angiogenesis Inhibitors/administration & dosage , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Down-Regulation , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Ornithine Decarboxylase/genetics
2.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(8): 645-51, 2012 Aug.
Article in Chinese | MEDLINE | ID: mdl-23141007

ABSTRACT

OBJECTIVE: To compare the incidence of cardio-cerebral vascular events between pregnancy induced hypertension (PIH) women and non-PIH(NPIH) women. METHODS: Ambispective cohort study method was used and 4630 pregnant women giving birth during October 1976 to December 2008 in our hospital and participated the healthy examination between July 2006 and October 2007 at Kailuan medical group were included and divided into PIH group (n = 694) and NPIH group (n = 3936) by the history of PIH. Incidence of cardio-cerebral vascular events (myocardial infarction, cerebral infarction and cerebral hemorrhage) was obtained during follow-up. Multivariable Cox proportional hazards regression models was used to assess the relative risk of cardio-cerebral vascular events. RESULTS: (1) The follow-up time was 2 to 34 (15.32 ± 7.94) years. (2) The childbearing age, systolic blood pressure and diastolic blood pressure before delivery were significantly higher while gestational weeks and weight of newborn were significantly less in PIH group than in NPIH group (all P < 0.01). Levels of systolic blood pressure, diastolic blood pressure, waist circumference, body mass index, triglyceride, total cholesterol and fasting blood glucose during healthy examination between July 2006 and October 2007 were significantly higher in PIH group than in NPIH group (P < 0.05 or P < 0.01). (3) There were 71 cardio-cerebral vascular events during the follow-up. In PIH group, the incidence rate of cardio-cerebral vascular events, myocardial infarction and cerebral infarction was 20.64%, 11.08% and 8.67%, respectively, while the corresponding incidence rate was 7.82%, 4.02% and 2.67% in NPIH group (all P < 0.01). After adjustment for other traditional cardiovascular risk factors, the risk of total cardio-cerebral vascular events, myocardial infarction and cerebral infarction in PIH group was 2.99 fold (95%CI: 1.80 - 4.95), 3.91 fold (95%CI: 1.71 - 8.91) and 3.96 fold (95%CI: 1.95 - 8.05) higher than in NPIH group. CONCLUSION: PIH is an independent risk factor for cardio-cerebral vascular events.


Subject(s)
Cardiovascular Diseases/epidemiology , Hypertension, Pregnancy-Induced/epidemiology , Adult , Case-Control Studies , Cohort Studies , Female , Humans , Middle Aged , Pregnancy , Risk Factors
3.
Zhonghua Nei Ke Za Zhi ; 49(6): 469-72, 2010 Jun.
Article in Chinese | MEDLINE | ID: mdl-20979730

ABSTRACT

OBJECTIVE: To study the risk prediction for new intracerebral hemorrhage (ICH) with high sensitivity C-reactive protein (hs-CRP) level. METHODS: In a retrospective, nested, case-controlled study, 323 cases of ICH were identified and matched with 646 controls. The hs-CRP levels at baseline were compared between the two groups. The relevance of different hs-CRP levels and the risk of ICH were analyzed. RESULTS: The ICH group had a higher median hs-CRP levels (1.10 mg/L) as compared with the control group (0.66 mg/L) with significant difference (P<0.01). In addition, the increase of risk associated with hs-CRP levels was primarily observed in the individuals with the highest quartile of hs-CRP levels (>2.12 mg/L). These patients had an increased risk of ICH (OR 2.58, 95%CI 1.77 to 3.76) as compared with those in the lowest quartile (≤0.30 mg/L). Individuals with baseline hs-CRP levels above the specified cut point of 3 mg/L or more and those in the 80th percentile were at a markedly increased risk of ICH (for specified cut point of 3 mg/L, OR 2.26, 95%CI 1.60 - 3.20, P<0.01; for 80th percentile, OR 2.24, 95%CI 1.60 - 3.13, P<0.01, respectively). CONCLUSIONS: Risk of ICH might be predicted with the level of hs-CRP. With the increase of hs-CRP level at baseline, the risk of ICH was increased.


Subject(s)
C-Reactive Protein/metabolism , Intracranial Hemorrhages/diagnosis , Stroke/diagnosis , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Factors
4.
Chin Med J (Engl) ; 123(16): 2269-73, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20819678

ABSTRACT

BACKGROUND: Tumstatin is a novel endogenous angiogenesis inhibitor which is widely studied using purified protein. The current study evaluates the antiangiogenic effects of tumstatin-overexpression plasmid in vitro, reveals the mechanism underlying the vascular endothelial cell growth inhibition and searches for a novel method administering tumstatin persistently. METHODS: The eukaryotic expression plasmid pcDNA-tumstatin encoding tumstatin gene was constructed and transfected to human umbilical vein endothelial cell ECV304 and human renal carcinoma cell ACHN. Expression of tumstatin in the two cell lines was determined by RT-PCR and Western blotting. Vascular endothelial cell proliferation was assessed by CCK-8 assay and cell cycle was analyzed by flow cytometry. To investigate the mechanism by which pcDNA-tumstatin inhibited vascular endothelial cell proliferation in vitro, cyclin D1 protein was detected by Western blotting. RESULTS: DNA sequence confirmed that pcDNA-tumstatin was successfully constructed. RT-PCR and Western blotting indicated that tumstatin could express in the two cell lines effectively. After tumstatin gene transfer, ECV304 cell growth was significantly inhibited and the cell cycle was arrested in G1 phase. And Western blotting showed that pcDNA-tumstatin decreased the level of cyclin D1 protein. CONCLUSIONS: Overexpression of tumstatin mediated by pcDNA 3.1 (+) specially inhibited vascular endothelial cells by arresting vascular endothelial cell in G1 phase resulting from downregulation of cyclin D1 and administration of tumstatin using a gene therapy might be a novel strategy for cancer therapy.


Subject(s)
Autoantigens/genetics , Autoantigens/metabolism , Collagen Type IV/genetics , Collagen Type IV/metabolism , Endothelial Cells/cytology , Endothelial Cells/metabolism , Blotting, Western , Cell Cycle/genetics , Cell Cycle/physiology , Cell Line , Cell Line, Tumor , Cell Proliferation , Flow Cytometry , Humans , Plasmids/genetics , Reverse Transcriptase Polymerase Chain Reaction
5.
Mol Biol Rep ; 37(5): 2273-7, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19688274

ABSTRACT

Tumstatin is the 28 kDa NC1 domain of the alpha3 chain of type IV collagen that inhibits pathological angiogenesis and suppresses endothelial cell proliferation and tumor growth. In the present paper, we expressed and purified recombinant human tumstatin protein and then prepared the anti-tumstatin polyclonal antibody. To investigate the expression of tumstatin in renal carcinoma, tumstatin protein was detected by western blotting using the prepared anti-tumstatin antibody and tumstatin mRNA levels were assayed by RT-PCR. The results showed that the expression of tumstatin gene was down-regulated in renal carcinoma tissues and cells. Our study suggests that as a novel endogenous angiogenesis inhibitor, tumstatin gene expression may be a marker for diagnosis, therapy and prognosis of renal carcinoma.


Subject(s)
Autoantigens/genetics , Collagen Type IV/genetics , Down-Regulation/genetics , Kidney Neoplasms/genetics , Antibodies, Neoplasm/biosynthesis , Autoantigens/immunology , Autoantigens/isolation & purification , Autoantigens/metabolism , Cloning, Molecular , Collagen Type IV/immunology , Collagen Type IV/isolation & purification , Collagen Type IV/metabolism , Gene Expression Regulation, Neoplastic , Humans , Kidney/metabolism , Kidney/pathology , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology
6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 36(12): 1078-82, 2008 Dec.
Article in Chinese | MEDLINE | ID: mdl-19134274

ABSTRACT

OBJECTIVE: To explore the impact of patient compliance on the long-term outcomes in hypertensive patients receiving hydrochlorothiazide (HCTZ) based combination therapy with spironolactone or captopril. METHODS: A total of 853 patients with mild to moderate hypertension were recruited and randomly divided into HCTZ group (HCTZ 12.5 mg q.d), spironolactone group (HCTZ 12.5 mg q.d and spironolactone 20 mg q.d), and captopril group (HCTZ 12.5 mg q.d and captopril 25 mg bid) after 2-week placebo washout period and 6-week loading period for HCTZ. Since the efficacy of combination therapy was proven to be better than monotherapy 1 year after therapy beginning, patients in HCTZ group were randomly assigned to spironolactone group or captopril group. The patients were followed up for 4 years. Patients were divided to compliance (n = 424) or non-compliance group (n = 429) according test drug taking questionnaire. During the follow-up time, the blood pressure and the outcomes were recorded monthly, and blood biochemical parameters were determined once a year. RESULTS: At the end of follow up, incidence of cardio-cerebral vascular events was significantly lower in compliance group (2 fatal, 8 non-fatal) than that in noncompliance group (7 fatal, 21 non-fatal, P < 0.05). Systolic blood pressure [-(19.4 +/- 20.6) mm Hg, 1 mm Hg = 0.133 kPa] and diastolic blood pressure [-(10.7 +/- 13.5) mm Hg] were significantly reduced compared values at baseline and noncompliance group (all P < 0.001) while the reduction did not reach statistically significance in noncompliance group [-(7.3 +/- 18.2) mm Hg and -(3.5 +/- 10.2) mm Hg, all P > 0.05 vs. baseline]. The serum BUN, Cr and UA levels in the compliance group were significantly higher and the serum K(+), CHO, LDL-C level were significantly lower than baseline values. The serum BUN, UA levels in the compliance group were significantly higher while the serum K(+), cholesterol levels were significantly lower than those in the noncompliance group (all P < 0.05). CONCLUSIONS: This study indicates that patient compliance could affect the long-term outcome and antihypertensive efficacy in hypertensive patients receiving HCTZ based combination therapy with spironolactone or captopril.


Subject(s)
Hypertension/drug therapy , Patient Compliance , Aged , Antihypertensive Agents/therapeutic use , Captopril/therapeutic use , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Hydrochlorothiazide/therapeutic use , Male , Middle Aged , Spironolactone/therapeutic use , Treatment Outcome
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 33(7): 595-8, 2005 Jul.
Article in Chinese | MEDLINE | ID: mdl-16080804

ABSTRACT

OBJECTIVE: To determine whether the blood pressure (BP) response to hydrochlorothiazide (HCTZ) was associated with the angiotensin converting-enzyme (ACE) I/D and aldosterone synthase (CYP11B2)-344T/C polymorphisms. METHODS: The BP response to HCTZ 12.5 mg once daily for 6 weeks was assessed in 829 subjects with mild or moderate essential hypertension, and compared across the ACE and CYP11B2 genotypes. RESULTS: Of the 829 enrolled subjects, 785 completed the study. The systolic BP response differed according to the ACE (DD 9.4 +/- 15.7 mm Hg, ID 4.8 +/- 16.3 mm Hg, and II 5.1 +/- 14.8 mm Hg, P < 0.01), but not the CYP11B2 genotype (P > 0.05). Subjects with the combination of ACE DD and CYP11B2 CC genotypes tended to have a more pronounced systolic BP reduction than the other genotypic combinations of these 2 genes. Multiple linear regression analyses showed that the ACE DD genotype and serum aldosterone concentration at baseline were associated with the systolic BP reduction after treatment. None of the genetic associations with changes in diastolic BP or mean arterial pressure reached statistical significance (P > 0.05). CONCLUSIONS: The present study suggested that the ACE DD genotype was associated with the systolic BP response to HCTZ, and that the subjects with the combination of ACE DD and CYP11B2 CC genotypes might have a better BP response to HCTZ than the other genotypic combinations of these 2 genes.


Subject(s)
Cytochrome P-450 CYP11B2/genetics , Hydrochlorothiazide/therapeutic use , Hypertension/drug therapy , Peptidyl-Dipeptidase A/genetics , Sodium Chloride Symporter Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Humans , Hypertension/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide
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