Modified HindⅢ fragment of IFN-?B gene was treated by nuclease S1 inserted into the HindⅢ site of plasmid YFD18 and fused with leader sequence of ?-factor gene,Resultant plasmid YFD33 was transformed into ?-type yeast strain Y33.The transforments could synthesize and secrete IFN-?B.More than 1.4?107 units/liter of interferon antiviral activity were in the medium and about 1.1?107 units/liter were in the cell.

Objective To investigate the effect of 188Re-IGF-1 analogue (IGF-1A) in proliferation inhibition and apoptosis induction in human pancreatic carcinoma cell line Patu8988.Methods IGF-1A was labeled with 188Re.Patu8988 cells were divided into an un-treated control group,IGF-1A group (1,5,10,20 μg),188ReO4-group (0.37,1.85,3.70,7.40 MBq) and 188Re-IGF-1A group (0.37,0.74,1.85 MBq).The cell proliferation inhibition effects by the 188Re-IGF-1A and 188ReO4-were detected every day by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test from 1 d to 7 d after administration,while the IGF-1 A group was tested every day from 1 d to 6 d after treatment.Inhibition rates were calculated.At 3 d after treatment with 188ReO4-and 188Re-IGF-1A (1.85,3.70,7.40 MBq),cell apoptosis was detected by flow cytometry.For biodistribution studies of 188Re-IGF-1A,36 nude mice bearing Patu8988 cell xenografts were divided into6 groups.At different time points (15 min,1 h,4 h,1 d,3 d and5 d),36 mice (n =6 per time point) were sacrificed and organs of interest were removed,weighted and measured for radioactivity by a gamma counter.The absorbed doses of organs were calculated as ％ ID/g.One-way analysis of variance was used.Results After 4 d,inhibition rate of Patu8988 cell proliferation in the 188 Re-IGF-1A group (1.85 MBq) was (90.75 ±5.20) ％,higher than that in 188ReO4-group or IGF-1A group ((49.50±2.39)％,(23.00±4.21)％; F=554.724,P＜0.01).At 3 d after treatment with different doses of 188 Re-IGF-1A (1.85,3.70,7.40 MBq),floating cell ratios were (16.56 ± 0.95) ％,(33.39 ±5.93) ％ and (43.76 ± 1.38) ％,respectively.Apoptosisratios in the floating cells treated by 188 Re-IGF-1A (1.85,3.70,7.40 MBq) were (12.70±2.27)％,(17.80±1.51)％ and (23.23 ±1.22)％,respectively.Distribution in tumors was (39.30 ± 17.98),(10.59 ± 9.39),(5.32 ± 1.53) and (5.30 ±2.28) ％ ID/g at the 15 min,1 d,3 d,and 5 d timepoints after intratumoral injection,respectively.The absorbed dose of tumors was 5165.8 mGy/MBq.Conclusions Proliferation of human pancreatic carcinoma cell line Patu8988 can be inhibited and apoptosis can also be induced by 188Re-IGF-1A.The tumor region is the major distribution site in nude mice bearing human pancreatic cancer xenografts after intratumoral injection of 188 Re-IGF-1A.

Diabetes mellitus is a typical metabolic disease.Its complications cause the main damage and lead to high mortality and disability eventually.The exact mechanism of diabetes is still unknown at present,and no radical cure of it is available.Therefore,the prevention of diabetes has become a priority.Metabolomics as a new technology can identify and measure the entire metabolic changes in the organism,and therefore has been widely applied to diabetes related studies with its enormous potential.

Objective To evaluate the effect of P-gp inhibitors of verapamil (VER) and GF120918 on 18F-FDG uptake in Bcap37 and Bcap37/multidrug resistancce (MDR)1 cell lines in vitro,and to explore the relationship between 18F-FDG uptake and P-gp expression at cellular level.Methods Bcap37 and Bcap37/MDR1 cells were seeded into 6-well plates at a density of 1 × 106 per well.Three days later,37 kBq/ml 18F-FDG,or 37 kBq/ml 18F-FDG + 100 μmoL/L VER,or 37 kBq/ml 18F-FDG + 50 μmol/L GF120918 were added into each well.Mter incubated for 10,30,60 and 120 min at 37 ℃ and in 5％ CO2,the medium was removed and the cells were washed three times with 1 ml ice-cold PBS immediately.The radioactivity of 18 F-FDG was measured using a gamma counter.The uptake of 18F-FDG was expressed as the ratio of 18F-FDG radioactivity in Bcap37 or Bcap37/MDR1 cells and the overall radioactivity added to the cells in each well.The t test was used for statistical analysis.Results 18F-FDG uptake was higher in Bcap37/MDR1 cells than that in Bcap37 cells after incubated for 10 min.The uptake rate was (1.88 ±0.19) ％ in Bcap37/MDR1 cells and (1.37 ± 0.18) ％ in Bcap37 cells (t =7.832,P ＜ 0.05).On the contrary,18 F-FDG uptake was significantly higher in Bcap37 cells than that in Bcap37/MDR1 cells after incubated for 60 and 120 min.The uptake rates were (2.29 ±0.23)％ and (2.34 ±0.15)％ in Bcap37 cells,(1.47 ±0.14)％ and (1.53 ±0.22)％ in Bcap37/MDR1 cells (t =8.437,8.283,both P ＜ 0.05).18 F-FDG uptake was significantly higher with VER or GF120918 in Bcap37/MDR1 cells than that without VER or GF120918 after the incubation of 60 and 120 min (t =9.032,9.243 and 8.765,8.803,all P ＜ 0.05).The uptake rates with VER or GF120918 were (2.45 ±0.21)％ and (2.46 ±0.25)％,(2.50 ±0.24)％ and (2.48 ±0.27)％.There was no significant difference of 18F-FDG uptake in Bcap37 cells with or without VER or GF120918.Conclusions 18F-FDG is a substrate of P-gp at cellular level.P-gp may act as an efflux pump to reduce 18F-FDG uptake in Bcap37/MDR1 cells.The uptake of 18F-FDG can be used to evaluate the function of P-gp in tumor cells.

Objective To assess the results of surgical intervention on patients with medullary thyroid carcinoma(MTC), and determine the value of measuring plasma calcitonin concentration postoperatively. Methods The diagnosis and treatment of 14 patients with MTC from January 1992 to December 1998 were analysed retrospectively. Results The diagnosis of MTC in the 14 patients was confirmed by pathology. Of them, 64.3% of patients had lymph node metastases. According to AJCC staging system, 1 patient was in stage Ⅰ, 7 in stage Ⅱ, 5 in stage Ⅲ and 1 in stage Ⅳ. Of nine patients measured plasma calcitoinin after initial operation, 4 had persisted hypercalcitoninemia. In the 4 patients, MTC in residual thyroid and enarged lymph node were comfirmed by B mode ultrasounography. After re operation, the calcitonin level returned to normal in 3 cases, but one remained in higher level. Postoperative follow up ranged from 2 to 8 years, 2 patients died of the disease. Twelve patients still lived, 6 of them survived more than 5 years. Conclusions The clinical stage of MTC at the time of diagnosis is an important prognostic factor. An aggressive surgical approach at the initial operation is essential to achieve a curative effect in patient with MTC. Measuring plasma calcitonin postoperatively helps to detect residuled MTC or recurrent MTC.

Objective:To investigate the protective effects of nuclear factor ?B inhibition on liver graft reperfusion injury during transplantation.Methods:Orthotopic liver transplantation using modified cuff technique was established in rats,animals were divided according to the grafts cold storaged in 4℃ Ringer's lactated solution with(PDTC group)or without 0.1 mol/L PDTC(control group)for 6 h.During the early stage of reperfusion,DNA binding activities of NF ?B in liver grafts were analyzed by EMSA(electrophoretic mobility shift assay),mRNA level of TNF ? and ICAM 1 by RT PCR,and activities of ALT and LDH were also detected.Results:NF ?B in liver grafts was activated at early stage of reperfusion during transplantation; PDTC treated liver displayed lower activation of NF ?B 1 h after reperfusion,whereas no difference was shown between 2 groups 6 h after reperfusion.Up regulation of TNF ? and ICAM 1 transcription,high level of ALT and LDH activities were observed in both groups during reperfusion,whereas the transcriptional up regulation and the activities of ALT and LDH in PDTC group were reduced compared with those of control group( P

Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice.Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice (1× 107cells/ml,0.2 ml/mouse) to construct mice models.Bcap37 (n=5) or Bcap37/MDR1 (n=5) tumor-bearing mice fasted for 6 h before imaging.After anesthesia,the mice were injected with 7.4 MBq of 18F-FDG via tail vein.The dynamic microPET scans were carried out for 90 min.On the microPET images,the ROI was drawn and the TAC was obtained.The next day,those 10 mice underwent dynamic microPET scans after injected with elacridar (GF120918) and 18F-FDG.Another 10 mice,5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors,were used.After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein,microPET images were acquired at 60 min.ROI was drawn over the tumors and SUV was obtained.Two-sample t test was used to analyze the data.Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors,but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors.GF120918 did not influence 18F-FDG uptake (SUV) in Bcap37 tumors (1.052±0.028,1.028±0.045,t =1.792,P＞0.05),but significantly increased the SUV in Bcap37/MDR1 tumors (1.015±0.043,0.712±0.031,t=3.365,P＜0.05);The SUV of 18 F-FDG in Bcap37 tumors was significantly higher than that in Bcap37/MDR1 tumors without injection of GF120918 (t =3.952,P＜0.05).The SUV was not significantly different when GF120118 was injected (t=1.835,P＞0.05).Conclusions 18F-FDG is a substrate of P-gp.18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor's MDR.

Objective To evaluate the capability of 18 F-FLT uptake and investigate the early radiation response of human colorectal cancer cells HCT116 exposed to 6 MV X-rays.Methods 3.7 kBq 18F-FLT was added to HCT116 cells with different cell numbers (1.0 × 105-1.5 × 106) and cultured with different times (36,60,84 h).The 18F-FLT uptake rate was measured with a γ-counter after exposed to different does of 6 MV X-rays (0,2,4,6,8 Gy) after 24,48,and 72 h of irradiation.Then the cell uptake inhibition rate,cell proliferation,and cell cycle phase were measured.Results The uptake rate of 18F-FLT in HCT116 was (18.97 ± 1.16)％.The 18F-FLT uptake inhibition rates at 24 h after different does of irradiation (2,4,6,8 Gy) were (32.10±0.02)％,(54.46 ±0.04)％,(62.74 ±0.04)％,and (65.81 ±4.81)％,respectively,which was positively correlated with radiation dose.Conclusions The 18F-FLT uptake rate of human colorectal cancer HCT116 cells could be used to evaluate the early radiation response.

Objective: To investigate the clinicopathological features and immunophenotype of inflammatory myofibroblastic tumor (IMT) and their relationship with IMT diagnosis and prognosis. Methods:A total of 11 IMT cases with follow-up were analyzed morpho-logically and immunohistochemically. Results:The patients included 6 men and 5 women aged 13-66 years. The tumors were found in various anatomical sites, including lung, mediastinum, liver, intra-abdominal, and bladder. Histologically, the majority of the cases com-prised spindled fibroblastic and myofibrobalstic cells accompanied by chronic inflammatory cells in a myxoid or hyalinized stroma;the rest were individual cases of abscess formation. Prognosis mala was indicated for cases with features including atypia tumor cells with two cases demonstrating epithelioid morphology and nucleoli. Immunohistochemical study showed that vimentin, ALK, SMA, S-100, CD117, and CD34 were expressed in 91%(10/11), 55%(6/11), 100%(11/11), 27%(3/11), 18%(2/11), and 9%(1/11) of IMT, respective-ly. Ki-67 was expressed from 3%-40%respectively. CK, H-caldesmon, and DOG1 were negative in all cases. Follow-up data were avail-able for 11 patients and ranged from 4 to 22 months. Data showed that 7 patients were alive with no evidence of disease;4 patients were alive with tumor, whereas 3 showed aggressive biological behavior. Conclusion:IMTs had intermediate behavior or malignant po-tential. Most IMTs with aggressive behavior showed a minority of tumor cells with atypia, epithelioid morphology, and nucleoli. High proliferation index expression, ALK, SMA, and H-caldesmon can aid in IMT diagnosis.

Objective To investigate the effects of Skp2 overexpression on the sensitivity of troglitazone (TRG) in breast cancer cells and to devote to develop a novel drug for increasing the patient survival rate and eventually reaching the cure goal .Methods The transcription activities of PPARγ were analyzed on peroxisome proliferators response element(PPRE) luciferase reporter .The flow cytometry analysis and CCK‐8 assay were adopted to study that overexpression of Skp2 was associated with resistance to TRG‐mediated inhibition growth and apoptosis of breast cancer cells .Results Our study found that overexpression of Skp2 inhibi‐ted the transcriptional activity of the endogenous PPARγ and resisted to TRG‐mediated inhibition growth and apoptosis of breast cancer cells .Conclusion Overexpressed Skp2 breast cancer cells is able to be resistant to TRG‐induced sensitivity of breast cancer cells .Furthermore down‐regulating Skp2 will significantly enhance the growth inhibition of TRG on breast cancer cells .