Adolescent ; Adult ; Dust ; Female ; Humans ; Male ; Mental Health ; statistics & numerical data ; Middle Aged ; Occupational Exposure ; Steel ; Surveys and Questionnaires

Objective: The expression of WNT5A is associated with aggressive tumor biology and poor clinical outcomes of various types of cancer. However, its function in the cell migration of small cell lung cancer (SCLC) should be elucidated. Methods:The expres-sion of WNT5A in SCLC and normal lung tissues was detected by immunohistochemisty. The correlation between the expression and clinical characteristics of WNT5A was analyzed. The function of WNT5A in regulating cell migration was studied in DMS153 cell line in vitro. Small interfering RNA (SiRNA) was used to knock down WNT5A. Wound healing and Transwell tests were used to determine the migration rate of DMS153. The phosphorylated JNK expression was detected by Western blot analysis. Results:The WNT5A expression was higher in SCLC tissues than that of normal lung tissues. WNT5A was correlated with clinical stages, lymph nodes, and distance me-tastasis in SCLC. The high expression of WNT5A was accompanied by abnormal levels of NSE and Pro-GRP. The WNT5A phosphoryla-tion of JNK promoted cell migration in vitro. Conclusion:The expression of WNT5A in SCLC is high and correlated with tumor metasta-sis. The influence of WNT5A/JNK on the cell migration property of DMS153 supports the concept that WNT5A can initiate the cell mi-gration of SCLC, which suggested that WNT5A may be a marker and can be potentially used as an effective therapeutic target for the SCLC metastasis.

This study is to investigate the effects of ubenimex on tumor cell invasion and apoptosis, dose relationship and mechanism. Immunofluorescence staining was performed to detect the expression of CD13 in HT-1080 cells. MTT assay was used to analyze the effect of ubenimex on cell proliferation. Annexin V-EGFP/PI was used to detect apoptotic cells by flow cytometry. Cell cycle was analyzed using flow cytometry. Ala-pNA was used as substrate to evaluate the effect of ubenimex on the aminopeptidase activity. Transwell assay was used to analyze the effect of ubenimex on cell invasion and migration ability. Western blotting was used to detect the expression level of CD13. MMP activity was analyzed using gelatin zymography. The results showed that ubenimex at high concentration inhibited the proliferation of HT-1080 cells (IC50: 3.8 mg x mL(-1)), and induced cell apoptosis. Cell cycle was blocked at G1 phase. Ubenimex at low concentration inhibited the aminopeptidase activity of HT-1080 cells (IC50: 8.3 microg x mL(-1)) and inhibited cell invasion, but it had no effects on the cell migration and proliferation. Ubenimex had no effects on CD13 expression and MMP activity. In conclusion, ubenimex at low concentration can inhibit the invasion ability of tumor cells by directly inhibiting the aminopeptidase activity; ubenimex at high concentration can inhibit the proliferation of tumor cells and induce cell apoptosis by a CD13-independent pathway.
Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; CD13 Antigens ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Fibrosarcoma ; metabolism ; pathology ; Humans ; Leucine ; analogs & derivatives ; pharmacology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness

Ventricular fibroblasts were cultured using conditioned growth medium for ventricular fibroblasts (FCGM). The rate of the total collagen synthesis of ventricular fibroblasts was measured by assaying the incorporation rate of ［3H］-proline, whereas the proliferation of ventricular fibroblasts was assessed by determining the incorporation rate of ［3H］-TdR and the expression of c-fos genes. FCGM significantly increased the ［3H］-proline incorporation rate and ［3H］-TdR incorporation rate of fibroblasts in a dose-dependent manner. Furthermore, FCGM promoted the c-fos gene expression of fibroblasts, which attained its maximum in 1 h. BQ123, an ETA receptor antagonist, partially blocked the above effects of FCGM, but AT1 receptor antagonist CV11974 and α-adrenergic receptor antagoist regitin did not. It is suggested that the ventricular fibroblast has an autorine function in promotion of collagen synthesis and proliferation of fibroblasts by secreting endothelin and other bioactive substances.

Using cell culture, radioimmunoassay for endothelin and RT-PCR, the effect of aldosterone on the endothelin secretion of ventricular fibroblasts was studied. The results showed that aldosterone (1×10－7 mol/L) promoted the expression of ppET-1 mRNA, which began to increase in 2 hours and attained the highest level in 4 hours, thereafter decreased; aldosterone increased the endothelin level in ventricular fibroblasts and fibroblast conditioned growth medium (FCGM) as well, which was blocked by spironolactone (1×10－6 mol/L), an aldosterone receptor antagonist. The results suggest that aldosterone can increase endothelin secretion by ventricular fibroblasts, which can be inhibited by its receptor antagonist spironolactone.

The aim of this study was to examine the effects of L-arginine, a nitric oxide (NO) precursor, on protein expression of endothelial nitric oxide (eNOS), nitrite/nitrate content, protein expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) and the activity of mitogen-activated protein kinase (MAPK) in cardiac tissues in renovascular hypertensive rats (RHR). The Goldblatt renovascular hypertensive model was established by two-kidney one clip method. The rats were divided into four groups, respectively treated with 50, 150 and 450 mg/kg L-arginine and 150 mg/kg L-arginine plus 10 mg/kg L-NAME (an eNOS inhibitor) (ip). Another group did not receive specific treatment from the 5th week after renal artery constriction. Control group was sham-operated. Mean arterial blood pressure (MABP) and the ratio of left ventricular weight to body weight (LVW/BW) were measured 8 weeks after treatment. eNOS protein expression, nitrite/nitrate content, MKP-1 protein expression and MAPK activity in cardiac tissues were detected using Western blot analysis, enzyme-reduction method and substrate in-gel kinase assay, respectively. It was found that L-arginine significantly inhibited the increase of MABP and LVW/BW, attenuated the activity of MAPK, increased protein expression of eNOS and MKP-1 and potentiated production of NO in cardiac tissue with the most effective dosage of 150 mg/kg, and these effects of L-arginine could be inhibited by L-NAME. These results suggest that MKP-1 may play an important role in the NO-induced inhibition of myocardial hypertrophy. The anti-hypertrophic effects of L-arginine may involve increase of eNOS protein expression and NO production, poten- tiation of MKP-1 protein expression, and inhibition of MAPK activity in the cardiac tissue of RHR.

Adult ; Base Sequence ; Carcinoma, Hepatocellular ; metabolism ; Female ; Humans ; Insulin-Like Growth Factor II ; biosynthesis ; genetics ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; Molecular Sequence Data ; RNA, Messenger ; biosynthesis ; genetics ; Sequence Analysis, DNA

ObjectiveTo study the epidemiological characteristics of diabetes mellitus and awareness rate in Zhejiang adults.MethodA total of 17 437 adults from 15 counties were randomly selected with stratified multi-stage cluster sampling method from July to November,2010.Each participant was required to complete a set of standardized questionnaire,physical examination,and blood specimen collection.ResultsThe overall standardized rate of diabetes mellitus was 5.94％ ( crude prevalence 8.80％ ).It was increased by 96.67％ during past 8 years,as compared with the prevalence 3.02％ in 2002.The standardized rate of diabetes mellitus of the urban and rural area were 7.52％ and 5.19％ ( crude prevalence 11.33％ and 7.09％ ),respectively.The standardized rate of diabetes mellitus in the urban was higher than rural ( u =6.58,P＜0.05 ).The standardized rate of diabetes mellitus of the male and the female were 5.74％ and 6.15％ ( crude prevalence 8.36％ and 9.13％ ),respectively,without significant difference ( u =1.39,P＞0.05 ).The awareness rate of diabetes mellitus was 59.19％ ( 56.66％ in male and 61.23 ％ in female,x2 =3.26,P＞0.05 ).The awareness rate of the urban was higher than the rural (63.47％ vs 54.69％,x2=12.20,P＜0.01 ).ConclusionThe prevalence of diabetes mellitus showed a rapidly rising trend in Zhejiang province.The effective intervention should be taken at its early stage.

Objective:To investigate the clinical biological characteristics of EVI1 positive acute myeloid leukemia (AML) and its effect on early chemotherapy.Methods:The clinical and biological characteristics of 33 AML patients with EVI1 positive were retrospectively analyzed in 361 AML patients who were diagnosed and treated in our institute from March 2015 to July 2016,and the clinical and biological features,and rates of the induced remission were compared between the intermediate risk and poor risk with EVI1 positive AML,moreover,the influential factors on complete remission (CR) were analyzed.The expression of EVI1/ABL was tested in 32 healthy donors to confirm the abnormal threshold of EVI1 expression.Results:The definition of EVI1 positive was that the quantitative expression of EVI1/ABL was more than 8.0％.The 33 AML patients with EVI1 positive were found in 361 newly diagnosed AML patients,in which the female and male patients were 17 and 16 respectively,the median age was 45 (18-67) years,with a median follow-up of 6.6 (0.7-13.2) months.Intermediate karyotype was found in 17 patients (including 9 patients with normal karyotypes,1 patient with + 8);unfavorable karyotype was found in 14 patients [including 7 patients with-7/7q-,4 patients with t (v;11q23),3 patients with inv (3)/t (3;3),and 2 patients without mitotic figures].The rate of CR in the first induction chemotherapy was 42.4％,and the rate of total CR was 60.6％.According to the NCCN,16 intermediate risk patients and poor risk patients were divided,without favorable risk patients.The rate of CR in the first induction chemotherapy were 68.8％ and 17.6％ (P =0.005) in the intermediate risk and poor risk respectively,that of total CR were 81.3％ and 41.2％ (P =0.032),and the rates of relapse were 7.7％ and 14.3％.Univariable analysis revealed that unfavorable karyotype could affect the rate of CR in the first reduction chemotherapy and that of total CR (P =0.004,0.029).The poor risk patients had higher mortality (41.2％ vs.6.3％,P =0.039) and lower overall survival (OS) (P =0.012).Conclusion:EVI1 may be not an independent prognostic factor for the AML patients considering the appearance in the intermediate and poor risk patients.It predicts poor outcome in the EVI1 positive AML patients who have unfavorable karyocytes,such as-7/7q-,t (v;11 q23),and inv (3)/t (3;3),and also a low rate of both CR in the first induction chemotherapy and total CR.It also has a low rate of long-term survival and high mortality in the AML patients with EVI1 positive,who may benefit from allogeneic bone marrow transplantation as soon as possible.

OBJECTIVETo study the effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer.

METHODSIn vitro, the inhibitory effects of YH-16 and 5-FU on the growth of vascular endothelial cells and colorectal cancer cells were examined by MTT assay. In vivo, colorectal cancer cells were transplanted into BALB/c mice, and the mice were divided into six groups randomly:control group, low-dose YH-16 group, middle-dose YH-16 group, high-dose YH-16 group, 5-FU group and combination group. The number of liver metastases, the size of primary tumor and the toxicity were examined after 2 weeks postoperatively. The expression of vascular endothelial growth factor (VEGF) in liver metastases was detected by immunohistochemistry, and tumor microvessel density (MVD) was measured by immunostaining with CD34 and factor VIII (monoclonal antibodies.

RESULTSIn vitro, YH-16 inhibited the growth of colon cancer cells and vascular endothelial cells, with the IC50 at (2.16+/-0.28) microg/ml and (0.64+/-0.10) microg/ml respectively. In vivo high-dose YH-16 and 5-FU had a remarkable inhibitory effect on liver metastasis, and the combination group showed significant enhancement on this effect (P< 0.05). The combination group and 5-FU group could inhibit the growth of primary tumor, but not found in YH-16 group. The toxicity of YH-16 was lower than that of 5-FU (P< 0.05), and the difference was not found in the toxicity between combination group and 5-FU group (P > 0.05). Expression of VEGF in liver metastases was clearly inhibited by YH-16 in combination with 5-FU or 5-FU alone compared to the control group, and MVD in middle-dose and high-dose YH-16 group, 5-FU group and combination group was lower than that in control group (P< 0.05).

CONCLUSIONSThe angiogenesis inhibitor YH-16 can inhibit liver metastasis of colorectal cancer through inhibiting the growth of vascular endothelial cells. YH-16 in combination with 5-FU has additive effect on inhibitory activity against liver metastasis.

Angiogenesis Inhibitors ; therapeutic use ; Animals ; Cell Line, Tumor ; Colorectal Neoplasms ; drug therapy ; pathology ; Drug Therapy, Combination ; Female ; Fluorouracil ; therapeutic use ; Liver Neoplasms ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Vascular Endothelial Growth Factor A ; metabolism