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 expression of transforminggrowth factor β1(TGF-β1) and insulin-like growth factorⅠ(IGF-Ⅰ)in new bone after low frequency micromovement. Methods Fifteen female sheep from Shandong province were involved in the study and their bilateral tibias transversely osteotomized in the middle shafts with a defect of 2 mm.The hind limbs were fixed with unilateral external fixators connected to a controlled micromovement device. Ten days after osteotomy, one hind limb of each sheep randomlywas selected to perform micromovement at an amplitude of 0.25 mm and a frequency of 1 Hertz, 30 min a day for 4 weeks ( micromovement group). The other hindlimb served as the control group. Five sheep were sacrificed at 3,4 and 6 weeks after osteotomy, respectively, and specimens were harvested for detecting the expression of TGF-β1 and IGF-Ⅰby immunohistochemistry and RT-PCR. Results Immunohistochemistry: In the third postoperative week in the micromovement group, the expression of TGF-β1 was detected in different areas of new chondrocytes at the margin of callus, mainly in proliferating area, and IGF-Ⅰexpressed in osteoblasts at the margin of endochondral ossification area, calcified and mature chondrocytes and osteocytes. There was seldom expression ofIGF-Ⅰ and little expression of TGF-β1 in the corresponding area in the control one. In the 4th postoperative week in the micromovement group, theexpression of TGF-β1 diminished gradually with the mature of new bone and be located in extracellular matrix and osteoblasts around ossified areas; The expression ofIGF-Ⅰ reached the peak and be located mainly in osteoblasts of new bone surface, maturing osteocytes and calcifing osteoid. But there was little expression of them in the control group. In the sixth postoperative week in the micromovement group, there was a little expression of IGF-Ⅰ expression but little expression of TGF-β1; there was nearly no expression of them in the control group. In the micromovement group, the absorbance values of TGF-β1 at 3 and 4 weeksand of IGF-Ⅰat 3, 4 and 6 weeks were significantlyhigher than those in control group（P＜0.05）. RTPCR: In the third and fourth postoperative weeks in the micromovement group, there was higher expression of mRNA of TGF-β1 and TGF-I than those in control group; in the sixth postoperative week, the expression diminished gradually, but was higher than that in control group. The absorbance values of TGF-β1 at 3 and 4 weeks and IGF-Ⅰat 3, 4 and 6weeks were significantly higher than those of control group（P＜0.05）. Conclusion Low frequency and controlled micromovement in the early stage of the fracture healing can promote the expression of TGF-β1 and IGF-Ⅰ.They worked together to regulate the process of the endochondral ossification, while in the late stage the differentiation of osteocytes and mineralization of osteoid were regulated mainly by IGF-Ⅰ, which played an important role in regulating the cell biological behavior during micromovement.
Objective To investigate the impacts of neoadjuvant chemotherapy on the expression of insulin-like growth factor-1 receptor (IGF-1R) and on operation procedure and the significance of prognosis. Methods The expression of IGF-1R in 40 patients with breast cancer before and after neoadjuvant chemotherapy was measured by immunohistochemistry. The diagnosis was proved by core biopsy. All the patients took the TAC chemotherapy regimen. Modified radical operation was performed after two chemotherapy cycles and the IGF-1R expression was measured again. The clinical effect of neoadjuvant chemotherapy was assessed according to WHO criterion by measuring the size of tumor by physical examination and B type ultrasound. Results After neoadjuvant chemotherapy the tumor size shrank in 29 patients, there was no CR (complete response) or PD (progressed disease) to be documented. IGF-1R expression could be downregulated in 25 patients. Conclusion Neoadjuvant chemotherapy can inhibit the tumor growth by downregulation of the expression of IGF-1R.
ObjectiveTo investigate the effects of micro-fracture and insul in-l ike growth factor 1 (IGF-1) in treatment of articular cartilage defect in rabbits. MethodsTwenty-four New Zealand white rabbits (aged, 4-6 months; weighing, 2.5-3.5 kg) were randomly divided into 4 groups (n=6):micro-fractures and recombinant human IGF-1 (rhIGF-1) treatment group (group A), micro-fracture control group (group B), rhIGF-1 treatment control group (group C), and blank control group (group D). Full thickness articular cartilage defects of 8 mm×6 mm in size were created in the bilateral femoral condyles of all rabbits. The micro-fracture surgery was performed in groups A and B. The 0.1 mL rhIGF-1 (0.01 μg/μL) was injected into the knee cavity in groups A and C at 3 times a week for 4 weeks after operation, while 0.1 mL sal ine was injected in groups B and D at the same time points. At 4, 12, and 24 weeks, the gross, histological, and immunohistochemical observations were performed, and histological score also was processed according to Wakitani's score criteria. The collagen contents in the repair tissues and normal patellofemoral cartilage were detected by the improved hydroxyproline (HPR) method at 24 weeks. Electron microscope was used to observe repair tissues of groups A and B at 24 weeks. Results All animals were survival at the end of experiment. At 24 weeks after operation, defect was repaired with time, and the repair tissue was similar to normal cartilage in group A; the repair tissue was even without boundary with normal cartilage in group B; and the repair tissue was uneven with clear boundary with normal cartilage in groups C and D. Histological staining showed that the repair tissues had no difference with normal cartilage in group A; many oval chondrocytes-l ike cells and l ight-colored matrix were seen in the repair tissues of group B; only a few small spindle-shaped fibroblasts were seen in groups C and D. Moreover, histological scores of group A were significantly better than those of groups B, C, and D (P<0.05) at 4, 12, and 24 weeks. Electron microscope observation showed that a large number of lacuna were seen on the surface of repair tissue in group A, and chondrocytes contained glycogen granules were located in lacunae, and were surrounded with the collagen fibers, which was better than that in group B. Collagen content of the repair tissue in group A was significantly higher than that in groups B, C, and D (P<0.05), but it was significantly lower than that of normal cartilage (P<0.05). Conclusion Combination of micro-fracture and rhIGF-1 for the treatment of full thickness articular cartilage defects could promote the repair of defects by hyaline cartilage.
Objective To investigate the mechanismof lung injury caused by paraquat poisoning by observing the changes of fibrogenic cytokines in acute paraquat poisoned rats and the effects of pyrrolidine dithiocarbamate ( PDTC) . Methods Sprague-Dawley rats were randomly divided into three groups, ie. acontrol group ( n =6) , a PDTC group ( n =36) , a paraquat group ( n = 36) , and a paraquat + PDTC group( n =36) . The rats in the PDTC group, the paraquat group, and the paraquat + PDTC group were subdivided into 6 subgroups sacrificed respectively on 1st, 3rd,7th,14th, 28th and 56th day after the treatment. The levels of transforming growth factor-β1( TGF-β1 ) , platelet-derived growth factor ( PDGF) , insulin-like growthfactor-1 ( IGF-1) in serum were measured. Meanwhile the expression of connective tissue growth factor ( CTGF) and hydroxyproline in lung tissues were detected. The relationship of above cytokines with hydroxyproline was analyzed. Results The destructive phase in early ( 1 ～7 d) was characterized by hemorrhage, alveolar edema, and inflammatory cell infiltration. The proliferous phase in later stage ( 14 ～56 d) was characterized by diffused alveolar collapse with fibroblast proliferation and patchy distribution of collagen fibers. Compared with the control group, the level of TGF-β1 on all time points, the level of PDGF from7th to 56th day, the level of IGF-1 from3rd to 56th day in the paraquat group all significantly increased ( P lt;0. 01) . Immunohistochemistry results showed CTGF positive cells mainly located in aleolar epithelialcells, endothelial cells,macrophages in early stage, and fibroblasts were main positive cells on the 28th and the 56th day. The expression of CTGF in the paraquat group increased gradually compared with the control group on different time points ( P lt; 0. 05 or P lt; 0. 01) . Meanwhile, the levels of above cytokines were positively correlated with the level of hydroxyproline. Noteworthy, PDTC treatment led to significant decreases of above cytokines compared with the paraquat group in corresponding time points ( P lt;0. 05 or P lt;0. 01) .Conclusions Over expressions of IGF-1, TGF-β1 , PDGF, IGF-1 and CTGF may play important roles in lung fibrosis of paraquat poisoned rats. PDTC, as a b NF-κB inhibitor, may inhibits NF-κB activity and further significantly decreases expressions of cytokines, leading to significantly attenuated pulmonary inflammation and fibrosis. However, the mechanisms of PDTC intervention still remain to be explored.
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.
For the purpose of understanding the distribution of insulin-like growth factor-1 (IGF-1) receptor on the tendon cell, the continuous cultured tendon cell line was studied by following experiments. With the methods of immunohistochemical study and flow cytometric study, the density of IGF-1 receptor of the primary, 6th and 13th generation of tendon cell was analyzed. The results showed that there was no difference of the receptor density among those generations. However, in the cell cycle, the numbers of IGF-1 receptor in G2M phase tendon cells were more than that in G1 phase cells (P lt; 0.01). These works provided sufficient evident which suggested there were stable density of IGF-1 receptor on the tendon cell though out the life span of tendon cell. This may build some foundation in growth control of tendon cell by growth factor in the research of tendon tissue engineering.
【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.
Objective To investigate the effect of short-term administration of growth hormone (GH) on serum insulin-like growth factor-1 (IGF-1) level and nutritional status in patients after gastrointestinal operation, and evaluate whether postoperative application of GH rise the risk of tumor recurrence. Methods Forty-eight patients undergoing major gastrointestinal operation were randomly divided into two groups: GH group （n=24） and control group （n=24）. The two groups received isocaloric isonitrogenous nutrition with daily injection of either GH 0.15 U/kg or placebo for a period of day 3-9 postoperatively. Serum albumin, fibronectin, and IGF-1 were measured before operation as a baseline, and day 3 and 10 after operation using standard laboratory techniques. Nitrogen balance was measured daily from day 3 to day 9 after operation. Postoperative complications and adverse reaction were observed. All cancer patients received regular abdominal B-type ultrasonography and chest X-ray examination during 2 years of follow-up. Results Compared with control group, GH treatment did not influence serum IGF-1 and serum albumin level （Pgt;0.05）, but improved significantly the rise from day 3 to day 10 of serum fibronectin level 〔(22.8±5.8) mg/L vs.（9.6±3.6） mg/L， P＜0.05〕 and the cumulative nitrogen balance 〔（11.37±16.82） g vs.（－9.11±17.52） g， P＜0.01〕 postoperatively. There was no severe adverse effects and complications during GH treatment. The tumor-recurrence rates were not statistically different between two groups during follow-up. Conclusions Short-term administration of low-dose GH combined with early nutrition support can improve total nitrogen retention and protein metabolism, but not influence serum IGF-1 level after major abdominal surgery. Short-term administration of low-dose GH may not cause the tumor-recurrence.
Objective To determine the effect of methimazole (MMI) on retinal vascular development in neonatal rats, and to investigate the relationship between the concentration of insulin-like growth factor-I (IGF-I) in serum and the development of normal blood vessels and between the concentration of IGF-I and the formation of abnormal blood vessels. Methods There were 75 neonatal SpragueDawley rats in experimental group whose mothers were raised with water with 0.1% MMI at the first day of parturition. Another 50 neonatal rats were in the control group whose mothers were raised with normal water. The rats in the two groups were sub-divided into 4day and 10day subgroup, respectively. The retinal flatmount of the right eyes were stained with adenosine diphosphatase (ADPase); with the paraffin section of the left eyes, the number of nucleolus breaking through retinal inner limiting membrane was counted and the retinal blood vessels were evaluated. Serum IGF-I levels were detected by radioimmunoassay, and the weight of the neonatal rats in each group were observed and recorded. Results The incidence of retinal neovascularization in 10 day MMI group was 27%, and 0% in 4-day MMI group and control group. The serum IGF-I level in 4-day and 10-day MMI group (73.07 ng/ml, 175.13 ng/ml) was obviously lower than which in the 4-day and 10-day control group (168.73 ng/ml,306.38 ng/ml) （P=0.00）. Obvious slow growth of the neonatal rats was found in MMI group compared with which in the control group. Conculsions MMI may inhibit the normal growth of retinal blood vessels and lead neovascularization, which may relate to the initial decrease of the serum IGF-I level. (Chin J Ocul Fundus Dis, 2007, 23: 198-201)