ObjectiveTo investigate the relationship between insulin-like growth factor binding protein (IGFBP) gene with pancreatic cancer. MethodsThe relevant literatures at home and abroad in recent years were reviewed. From the pancreatic cancer related genes, IGFBP related tumors and the correlation between IGFBP and pancreatic cancer research and other aspects of the previous research results were summaried. ResultsMost of the studies suggested that IGFBP could inhibit the function of tumor cells through the IGF dependent pathway, but the deletion or mutation of IGFBP gene and its regulation mechanism are still unclear. ConclusionIGFBP is closely related to the tumor, but its specific effects and mechanism of pancreatic cancer has not been settled. In order to affect the degree of cell differentiation, regulation of tumor growth and metastasis probability through the change of endogenous IGFBP gene level, the further studie is needed.
Objective To investigate the ability of repairing bone defect with the compound of recombinant human insulinlike growth factor 1 (rhIGF-1), coralline hydroxyapatite(CHA) and autogeneous red bone marrow(ARBM), and to study the feasibility of the compounds being used as bone substitute materials. Methods Bilateral radius bone defects(11 mm in length) were created in 54 Chinese rabbits,which were randomly divided into 3 groups, and two different materials were randomly transplanted into the bilateral defects:in group 1, with material A(rhIGF-1/CHA/ARBM) and material B(CHA/ARBM); in group 2, with material C(rhIGF-1/CHA) and material D(CHA); in group 3, with E(autograft) and F(no implant) as controls. At 2, 4, 8 and 12 weeks, the effects were assessed by X-ray andimage analysis, biomechanics(at 12 weeks), as well as histological observation. Results X-ray and image analysis showed that material A of group 1was significantly superior to any other materials(P＜0.01). Antibending biomechanic detection showed that material A and Ewas significantly superior to the other materials(Plt;0.01), but no significant difference was found between A and E in the 12th week(Pgt;0.05). And by histological observation, in analogical bone morphological progress, materials C and D obviously inferior to materials A, B and E, but there was no significant difference between materials C and D. F had no evidence of new bone rebridging. Conclusion The recombinant compound CHA/ARBM(rhIGF-1),which posseses the potential ability of osteogenesis,osteoconduction and osteoinduction for bone defect repairing,can serve as a new type of autogenous bone substitute material.
Objective To study the effect of two cytokines, basic fibroblast growth factor(bFGF) and insulin-like growth factor-I(IGF-I), on cell proliferation in chondrocytes of adult rabbits. Methods The primary chondrocytes of adult rabbits were harvested and cultured with bFGF and IGF-I at different concentrations,respectively, as well as with the mixture of the two cytokines; the quantity of cultured chondrocytes was detected by MTT assay at the 24th, 48th and 72th hours; and the final fold increase of different groups was measured by cell count for the 3rd passage; and the proliferation index of the groups was recorded by flowing cytometer on the 14th day. Results ① The cultured chondrocytes with either bFGF, IGF-I or their mixture were significantly more than that of control group at the 24th, 48th and 72th hours (P＜0.01). ② After the 3rd passage, the final folds of proliferation were significantly higher in the groups with cytokinesthan in the control group (P＜0.01); and the final fold with the mixture ofcytokines was significantly higher than that of both IGF-I and bFGF (P＜0.01). ③ Theproliferation index was significantly higher in the groups with cytokines than in the control group (P＜0.01); the proliferation index with the mixture of cytokines was significantly higher than that of both IGF-I and bFGF (P＜0.05); besides, proliferation index was higher when cytokine was applied twice than once (P＜0.05). Conclusion bFGF and IGF-I could promote chondrocytes proliferation of adult rabbits obviously and they are synergistic in cell proliferation.
OBJECTIVE: To investigate the effect of combined treatment of recombinant human growth hormone (rhGH) and insulin-like growth factor-1 (IGF-1) on wound healing and protein catabolism in burned rats. METHODS: Forty Wistar rats with deep II degree scald injury were divided randomly into four groups and received rhGH (0.1 U/kg.d), rhGH (0.1 U/kg.d) plus IGF-1 (2.0 mg/kg.d), IGF-1 (2.0 mg/kg.d) and Ringer’s solution (2 ml/kg.d, as control group) respectively. The wound healing time and protein catabolism levels of every groups were compared after 2 weeks. RESULTS: Total body weight began to increase after 2 weeks in rhGH group and rhGH plus IGF-1 group, but in control group, it was occurred after 4-5 weeks. The body weight of rhGH plus IGF-1 group was 1.65 times than that of rhGH group. The wound healing time in rhGH plus IGF-1 group (17.1 +/- 4.4) days was significantly lower than that of rhGH (20.5 +/- 4.8) days and control group (29.7 +/- 6.3) days. The protein level of rhGH plus IGF-1 group was significantly higher than that of control group and rhGH group. CONCLUSION: It suggests that rhGH plus IGF-1 with synergism is more effective in promoting wound healing and increasing the protein catabolism.
Objective To establish hepatocellular carcinoma (HCC) cell lines which olig-expressed IGF1R gene stably． Methods An eukaryotic expressing vector pSUPER-IGF1R-siRNA that could block IGF1R expressing was transferred into hepatocellular carcinoma cell lines SMMC7721 and Hep3B with Lipofectamine 2000 reagents． After transferred, cells were selected with G418 to obtain positive clones. The expressions of IGF1R, cyclin D1 and cyclin B1 were detected by RT-PCR and Western-blot． Cell growth curve were painted. Results Two cell lines clones were screened olig-expressing IGF1R gene stably． The experimental cell lines grew more slowly than control cell lines and the expression of cyclin D1 decreased (P＜0.05). Conclusion The HCC cell lines for olig-expressing IGF1R gene stably are established successfully．The plasmid pSUPER-IGF1R-siRNA can inhibit the growth of SMMC7721 and Hep3B cell lines, and the expression of cyclin D1.
Objective To investigate the relationship between the level of serum-insulin like growth factor-1( IGF-1) and the nut ritional status of cancerous cachexia. Methods Colon cancer CT-26 cells were implanted subcutaneously to 30 liver2specified IGF-1 gene deleted (L ID) C57BL/ 6 mice to establish cancerous cachexia model and theother 30 C57BL/ 6 mice were included as cont rol group. The serum levels of IGF-1 , cytokine TNF-αand IL-6 , bloodglucose , albumin and t riglyceride were detected respectively on day 14 , 18 and 22 af ter the plantation of tumor. Thebody weight of mice , tumor weight and the weight af ter tumor removed in two group s were measured respectively.Results Af ter the plantation , the levels of IGF-1 in L ID group at different times were all significantly lower thanthose in cont rol group ( Plt; 0. 05) . The serum levels of TNF-α, IL-6 , blood glucose and t riglyceride were ascendinggradually over time ( Plt; 0. 05) , but weight s af ter tumor removed and the level of albumin were descending in twogroup s ( Plt; 0. 05) . Compared with the cont rol group , the serum levels of IL-6 , TNF-α, blood glucose and t riglyceride in L ID tumor-bearing mice were all significantly higher at different time point s ( P lt; 0. 05) . On day 18 and 22 ,the weight s af ter tumor removed and the amount of ingestion in L ID group were significantly lower than those in thecont rol group ( Plt; 0. 05) . Conclusion Compared with the low level of IGF-1 in cancerous cachexia , normal level ofserum IGF-1 may represent lower degree of cancerous cachexia2related cytokines and better nut ritional state , whichmay provide a novel idea of the therapy of cancerous cachexia.
Objective To investigate the effects of insulin-like growth factor 1（IGF-1） and ethanol (EtOH) on the changes in the osteoblast proliferation and the osteoblast function under the normal serum concentration and serum starvationMethodsThe osteoblasts harvested from the SD rat calvaria were incubated in the following six conditions according to the supplements in DMEM: the F15group：15% newborn calf serum (NCS)； the F15/EtOH group：100 mmol/L of EtOH added to 15% NCS； the F2 group：2% NCS； the F2/EtOH group：100 mmol/L of EtOH added to 2% NCS；the F2/IGF-1 group：25ng/ml of IGF-1 added to 2% NCS；the F2/IGF-1/EtOH group：100 mmol/L EtOH added to 25 ng/ml IGF-1 and 2% NCS. The osteoblasts were analyzed by the MTTassay, alkaline phosphatase（ALP） activity, and RTPCR at 24, 48, 72 and 96h ours after the culture. Results The absorbance (A), the ALP activity, and the expression of BGP mRNA (the proliferation and function indicators of the osteoblasts) were significantly decreased in the F15/EtOH group at all the time points when compared with those in the F15the group (P＜ 0.05); the above 3 indicators were significantly decreased in the F2 groupwhen compared with those in the F15 group (P＜0.05); they were significantly decreased in the F2/EtOH group when compared with those in the F2 group (P＜0.05); however, the indicators in the F2/IGF-1 group were significantly increased when compared with those in the F2 group (P＜0.05); the A value in the F2/IGF-1/EtOH group was not significantly decreased when compared with that in the F2/IGF-1 group, with an exception of the A value at 24 hours (P＞0.05); however, ALP and BGP mRNA were significantly decreased (P＜0.05). All the indicators were significantly increased when compared with those in the F2/EtOH group (P＜0.05) Conclusion Ethanol can inhibit the osteoblast proliferation and the osteoblast function, and can increase the inhibition when the osteoblasts were cultured under the serum starvation. This may be one of the mechanisms for alcoholic bone disease. IGF-1 can prevent the inhibition of the osteoblasts under the serum starvation and counteract the ethanolinduced proliferation inhibition; therefore, IGF-1 is an alternaive therapeutic intervention for alcoholic bone disease.
【Abstract】 Objective To explore the new therapy for pulmonary fibrosis by observing the effects of insulin-like growth factor 1 ( IGF-1) treated mesenchymal stemcells ( MSCs) in rats with bleomycin-induced pulmonary fibrosis. Methods Bone marrowmesenchymal stemcells ( BMSCs) were harvested from6-week old male SD rats and cultured in vitro for the experiment. 48 SD rats were randomly divided into 4 groups, ie.a negative control group ( N) , a positive control group/bleomycin group ( B) , a MSCs grafting group ( M) ,and an IGF-1 treated MSCs grafting group ( I) . The rats in group B, M and I were intratracheally injected with bleomycin ( 1 mL,5 mg/kg) to induce pulmonary fibrosis. Group N were given saline as control. Group M/ I were injected the suspension of the CM-Dil labled-MSCs ( with no treatment/pre-incubated with IGF-1 for 48 hours) ( 0. 5mL,2 ×106 ) via the tail vein 2 days after injected bleomycin, and group B were injected with saline ( 0. 5 mL) simultaneously. The rats were sacrificed at 7,14,28 days after modeling. The histological changes of lung tissue were studied by HE and Masson’s trichrome staining. Hydroxyproline level in lung tissue was measured by digestion method. Frozen sections were made to observe the distribution of BMSCs in lung tissue, and the mRNA expression of hepatocyte growth factor ( HGF) was assayed by RTPCR.Results It was found that the red fluorescence of BMSCs existed in group M and I under the microscope and the integrated of optical density ( IOD) of group I was higher than that of group M at any time point. But the fluorescence was attenuated both in group M and group I until day 28. In the earlier period, the alveolitis in group B was more severe than that in the two cells-grafting groups in which group I was obviously milder. But there was no significant difference among group I, M and group N on day 28.Pulmonary fibrosis in group B, Mand I was significantly more severe than that in group N on day 14, but itwas milder in group M and I than that in group B on day 28. Otherwise, no difference existed between the two cells-grafting groups all the time. The content of hydroxyproline in group B was significantly higher than that in the other three groups all through the experiment, while there was on significant difference betweengroup I and group N fromthe beginning to the end. The value of group M was higher than those of group I and group N in the earlier period but decreased to the level of negative control group on day 28. Content of HGF mRNA in group Nand group I was maintained at a low level during the whole experiment process. The expression of HGF mRNA in group I was comparable to group M on day 7 and exceeded on day 14, the difference of which was more remarkable on day 28. Conclusions IGF-1 can enhance the migratory capacity of MSCs which may be a more effective treatment of lung disease. The mechanismmight be relatedto the increasing expression of HGF in MSCs.
【Abstract】Objective To study the changes of insulin-like growth factor-1(IGF-1) in serum of patients with obstructive jaundice.Methods The clinical data of 20 patients with obstructive jaundice were collected and the measurement of serum TNFα,ALT, ALP, endotoxin and IGF-1 were performed. Results The serum IGF-1 in obstructive jaundice was significantly lower than that in gallbladder stone(P＜0.01), while endotoxin, TNF-α, ALT，ALP and TB were higher(P＜0.01). After the biliary duct obstruction was removed, the serum IGF1 in obstructive jaundice was significantly higher than that before operation and serum endotoxin， TNF-α, ALT， ALP and TB were significantly lower than that before operation(P＜0.01). A significant negative correlation was found between serum IGF-1 and serum endotoxin in benign obstructive jaundice(r=-0.761, P＜0.01). ConclusionIn obstructive jaundice, endotoxemia can affect the secretion of IGF-1 from liver. IGF-1 can be used as an index to judge the liver function in obstructive jaundice.
ObjectiveTo evaluate the prognostic significance of serum levels of vascular endothelial growth factor (VEGF) and insulin-like growth factors-Ⅰ (IGF-Ⅰ) in advanced gastric cancer patients who were treated with oxaliplatin/5-fluorouracil (FOLFOX). MethodsNinety-six advanced gastric cancer patients who were treated with FOLFOX in our hospital between March 2007 to August 2010 were enrolled in this study. All of the patients were treated with oxaliplatin (85 mg/m2) as a 2-hour infusion on day 1, and leucovorin (20 mg/m2, about 10 min) on day 1 and day 2, followed by a 5-fluorouracil bolus (400 mg/m2) and 22 hours of continuous infusion of 600 mg/m2. Treatment was repeated in 2-week intervals, and patients received 4 chemotherapy cycle in total. The levels of serum VEGF and IGF-Ⅰ were measured using enzyme-linked immunoassays. The relationship between serum levels of VEGF/IGF-Ⅰ and the clinicopathological characteristics of patients, the relationship between serum levels of VEGF/IGF-Ⅰ and prognosis of patients, were analyzed. ResultsThe serum levels of VEGF and IGF-Ⅰ were (464.4±57.4) pg/mL and (33.5±7.3) ng/mL, respectively. The serum level of VEGF was related with surgical history, Lauren's classification, TNM staging before treatment, and pathological type (P < 0.05), and serum level of IGF-Ⅰ was related with TNM staging before treatment and number of transferred organs (P < 0.05). The serum levels of VEGF and IGF-Ⅰ in stable disease (SD) +progressive disease (PD) patiens were higher than those of complete response (CR) +partial response (PR) patients (P < 0.05). The results of Cox proportional hazard regression model showed that, effect of chemotherapy (HR=1.764, P=0.006), number of transferred organs (HR=1.662, P=0.015), serum level of VEGF (HR=1.834, P=0.012) and IGF-Ⅰ (HR=1.855, P=0.008), were all significantly related with time to progression (TTP); serum level of VEGF (HR=2.205, P=0.002) and IGF-Ⅰ (HR=1.931, P=0.004) were all significantly related with overall survival (OS). ConclusionLevels of serum VEGF and IGF-Ⅰ are independent prognostic factors in patients with advanced gastric cancer who were treated with FOLFOX chemotherapy.