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Objective@#To explore the correlation between serum uric acid level and disease activity in patients with growth hormone-secreting pituitary adenoma.@*Methods@#The clinical data of 76 patients with growth hormone-secreting pituitary adenoma in the Department of Endocrinology of Beijing Tiantan Hospital, Capital Medical University from 2012 to 2018 were retrospectively analyzed. The patients were divided into 4 groups according to serum uric acid quartiles with 19 cases each, uric acid <233.9 μmol/L in Q1 group, uric acid 233.9 to 275.9 μmol/L in Q2 group, uric acid 276.0 to 366.7 μmol/L in Q3 group, uric acid >366.7 μmol/L in Q4 group. The sex, age, duration of disease, height, weight and blood pressure were collected, and the body mass index (BMI) was calculated. The fasting blood glucose (FBG), glycated hemoglobin, fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), uric acid, basal growth hormone, insulin-like growth factor-1 (IGF-1) were examined, and the IGF-1 index and homeostasis model assessment of insulin resistance (HMOA-IR) were calculated. Pearson correlation analysis was performed to explore the correlation between serum uric acid levels and disease activity.@*Results@#In 76 patients, 8 cases were diagnosed with hyperuricemia, accounting for 10.5%. There were no statistical differences in sex constituent, duration of disease, systolic blood pressure, diastolic blood pressure, FBG, glycated hemoglobin, TG, TC, LDL-C, growth hormone and IGF-1 index among 4 groups (P>0.05). As uric acid level increased, age and HDL-C decreased gradually from Q1 group to Q4 group: (43.58 ± 8.95), (42.58 ± 10.89), (36.58 ± 9.79), (35.37 ± 11.51) years, (1.28 ± 0.22), (1.29 ± 0.23), (1.17 ± 0.28), (1.04 ± 0.22) mmol/L; while BMI, uric acid, IGF-1 and HOMA-IR increased gradually: (25.75 ± 2.86), (27.33 ± 3.94), (26.16 ± 2.94), (28.76 ± 3.69) kg/m2, (190.73 ± 28.80), (249.57 ± 12.00), (325.75 ± 25.61), (430.39 ± 58.41) mmol/L, (594.50 ± 222.45), (733.06 ± 212.42), (774.90 ± 287.87), (962.00 ± 323.36) μg/L, 2.09 (1.64, 2.09), 3.02 (0.94, 3.55), 3.53 (2.31, 6.48), 4.09 (2.52, 5.41), there were statistical differences (P<0.05 or <0.01). Pearson correlation analysis result showed that uric acid was positive correlation with IGF-1, IGF-1 index, HOMA-IR, TG and systolic blood pressure (r = 0.491, 0.341, 0.372, 0.240 and 0.266; P<0.01 or <0.05), and uric acid was negative correlation with HDL-C (r = -0.367, P<0.01). After adjustment for sex, age, duration of disease and BMI, uric acid was still positive correlation with IGF-1 and IGF-1 index (r = 0.352 and 0.318, P<0.01).@*Conclusions@#Serum uric acid level is associated with disease activity in patients with growth-hormone secreting pituitary adenoma.
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Objective To explore the correlation between serum uric acid level and disease activity in patients with growth hormone-secreting pituitary adenoma. Methods The clinical data of 76 patients with growth hormone-secreting pituitary adenoma in the Department of Endocrinology of Beijing Tiantan Hospital, Capital Medical University from 2012 to 2018 were retrospectively analyzed. The patients were divided into 4 groups according to serum uric acid quartiles with 19 cases each, uric acid﹤233.9 μmol/L in Q1 group, uric acid 233.9 to 275.9 μmol/L in Q2 group, uric acid 276.0 to 366.7 μmol/L in Q3 group, uric acid＞366.7 μmol/L in Q4 group. The sex, age, duration of disease, height, weight and blood pressure were collected, and the body mass index (BMI) was calculated. The fasting blood glucose (FBG), glycated hemoglobin, fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), uric acid, basal growth hormone, insulin-like growth factor-1 (IGF-1) were examined, and the IGF-1 index and homeostasis model assessment of insulin resistance (HMOA-IR) were calculated. Pearson correlation analysis was performed to explore the correlation between serum uric acid levels and disease activity. Results In 76 patients, 8 cases were diagnosed with hyperuricemia, accounting for 10.5% . There were no statistical differences in sex constituent, duration of disease, systolic blood pressure, diastolic blood pressure, FBG, glycated hemoglobin, TG, TC, LDL-C, growth hormone and IGF-1 index among 4 groups (P＞0.05). As uric acid level increased, age and HDL-C decreased gradually from Q1 group to Q4 group: (43.58 ± 8.95), (42.58 ± 10.89), (36.58 ± 9.79), (35.37 ± 11.51) years, (1.28 ± 0.22), (1.29 ± 0.23), (1.17 ± 0.28), (1.04 ± 0.22) mmol/L; while BMI, uric acid, IGF-1 and HOMA-IR increased gradually: (25.75 ± 2.86), (27.33 ± 3.94), (26.16 ± 2.94), (28.76 ± 3.69) kg/m2, (190.73 ± 28.80), (249.57 ± 12.00), (325.75 ± 25.61), (430.39 ± 58.41) mmol/L, (594.50 ± 222.45), (733.06 ± 212.42), (774.90 ± 287.87), (962.00 ± 323.36) μg/L, 2.09 (1.64, 2.09), 3.02 (0.94, 3.55), 3.53 (2.31, 6.48), 4.09 (2.52, 5.41), there were statistical differences (P﹤0.05 or﹤0.01). Pearson correlation analysis result showed that uric acid was positive correlation with IGF-1, IGF-1 index, HOMA-IR, TG and systolic blood pressure (r=0.491, 0.341, 0.372, 0.240 and 0.266; P﹤0.01 or﹤0.05), and uric acid was negative correlation with HDL-C (r =-0.367, P﹤0.01). After adjustment for sex, age, duration of disease and BMI, uric acid was still positive correlation with IGF-1 and IGF-1 index (r=0.352 and 0.318, P﹤0.01). Conclusions Serum uric acid level is associated with disease activity in patients with growth-hormone secreting pituitary adenoma.
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Objective: To investigate the effects of NVP-AEW541, an inhibitor of insulin-like growth factor 1 receptor (IGF-1R), on the proliferation and apoptosis of dormant SKOV3-PKH26hi cells isolated from ovarian cancer xenografts, and to explore the possible mechanism. Methods: The effect of NVP-AEW541 (1, 5, 10, 15 μmol/L) on the proliferation of SKOV3-PKH26hi cells was detected by CCK-8 assay. After the SKOV3-PKH26hi cells were treated with NVP-AEW541 for 48 h, FCM was performed to detect the cell cycle and apoptosis. The effects of NVP-AEW541 on the expressions of cyclin D1, caspase-3, Bax, Bcl-2, phospho-protein kinase B (p-PKB, also known as p-Akt), phospho-IGF-1R (p-IGF-1R) and phospho-glycogen synthase kinase-3β (p-GSK-3β) in SKOV3-PKH26hi cells were detected by Western blotting. Results: NVP-AEW541 had anti-proliferative effect on the SKOV3-PKH26hi cells in a dose-and time-dependent manner (both P < 0.01). NVP-AEW541 arrested the cell cycle at G0/G1 phase, and promoted the early and late apoptosis (all P < 0.01). The expressions of cyclin D1 and Bcl-2 proteins were decreased (both P < 0.05), and the expressions of caspase-3 and Bax proteins were increased (both P < 0.05) as compared with the control group (SKOV3-PKH26hi cells without any treatment). NVP-AEW541 downregulated significantly the expression levels of p-IGF-1R, p-Akt and p-GSK-3β proteins (all P < 0.01). Conclusion: IGF-1R inhibitor NVP-AEW541 is effective to inhibit the proliferation of SKOV3-PKH26hi cells and to promote apoptosis by reducing the phosphorylation level of Akt.
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Malignancies threaten human health seriously.Recently studies show that intercellular signal transduction influences the biological characteristics of tumor cells.It has closely relationship with tumor growth and metastasis.Insulin-like growth factor ( IGFs ) signal transduction system is a potential mitogen that distributed in the body′s tissues, organs and blood.Researches show that the abnormal expression of IGFs exists in many tissues, such as breast cancer, colorectal cancer, gastric carcinoma, lung carcinoma, pancreatic cancer and so on, which may play an important role in occurrence and metastasis as a novel tumor marker.
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Objective To observe the effect of L-carnitine on plasma soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) protein in maintenance hemodialysis (MHD) patients.Methods Forty-six cases of MHD patients were enrolled as MHD group,and 40 cases of the same period healthy subjects were enrolled as control group.The levels of plasma sTWEAK protein,high-sensitivity C-reactive protein (hs-CRP),interleukin (IL)-6 and insulin-like growth factor (IGF)-1 were measured by enzyme-linked immunosorbent assay (ELISA).Twenty-six MHD patients with the levels of sTWEAK protein higher than control group mean value as treatment group,were treated for L-carnitine 1.0 g in 0.9％ sodium chloride solution 20 ml after hemodialysis by intravenous injection one time per week.Twenty MHD patients with the levels of sTWEAK protein lower than or equal to control group mean value as non-treatment group.The changes of sTWEAK protein,IGF-1,grip strength and protein energy waisting (PEW) were observed after 3 months treatment.Results The levels of plasma sTWEAK protein,IL-6 and hs-CRP in MHD group were higher than those in control group [(464 ± 102) ng/L vs.(346 ± 159) ng/L,(986.54 ± 123.12) ng/L vs.(407.12 ± 180.25) ng/L,(18.8 ± 2.9) mg/L vs.(1.0 ± 1.2) mg/L],there were significant differences (P＜ 0.05).Compared with non-treatment group,the levels of plasma sTWEAK protein,IL-6 and hs-CRP in treatment group after treatment of 3 months were decreased [(126 ± 92) ng/L vs.(243 ± 103) ng/L,(799.45 ± 105.34) ng/L vs.(966.04 ± 113.11) ng/L,(13.7 ± 1.9) mg/L vs.(26.8 ± 2.8) mg/L],IGF-1 was increased,grip strength was increased,PEW was improved,there were significant differences (P ＜ 0.01 or ＜ 0.05).The body mass index in treatment group was more than that in non-treatment group,but there was no significant difference (P ＞ 0.05).Conclusions L-carnitine can reduce the levels of plasma sTWEAK protein in MHD patients,reduce inflammatory reaction,improve the levels of IGF-1,increase strength,improve the PEW.
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Objective To observe the different expression of somatomedin-receptor in cell membrane of prostate epithelial cells at anoxic or normoxic condition.Methods Human prostate epithelial cells line RWPE-1 were cultured in vitro.At 4,8,12,24,48 h after cells had been seeded,the gene and protein expression of epidermal growth factor receptor (EGFR),fibroblast growth factor receptor (FGFR),transforming growth factor β1 receptor (TGF- β 1R),insulin-like growth factor-1 receptor (IGF-1 R) and vascular endothelial growth factor receptor (VEGFR) in prostate epithelial cells were tested by RT-PCR and immunohistochem-istry methods,respectively.Results The expression of mRNA and protein of EGFR,FGFR,IGF-1R,TGF- β1R,VEGFR were significantly increased in anoxic and normoxic prostate epithelial cells (P ＜ 0.01 ).At different time point,the expression of mRNA and protein of EGFR,FGFR,IGF-1R,TGF- β1R,VEGFR significantly higher in anoxic than those in normoxic prostate epithelial cells (P＜ 0.01 )besides 4 h EGFR mRNA,12 h EGFR protein,4 h IGF-1R mRNA,4 and 8 h IGF-1R protein,4 and 8 h TGF-β 1R mRNA,4 and 8 h TGF-β 1R protein,4 h VEGFR mRNA (P ＞ 0.05).Conclusion Anoxic prostate epithelial cell can up-regulate the expression of somatomedin-receptor.
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Erythropoietin(EPO) is a main growth factor that regulates the erythropoiesis under the physiological conditions and after blood loss. At present, it is one of the special effective clinical drugs for treating anemia due to renal failure, chronic infection, AIDS, tumor and some other causes. However, its short plasma half-life makes more frequent administration, which increases the burden and pain on patients. Therefore, development of long-acting agents is a hot. Continuous erythropoietin receptor activator(CERA) is a third-generation erythropoiesis-stimulating agents(ESA). It has a largely prolonged plasma half-life and extended administration intervals, which are different from other ESAs. This review gives a detail demonstration about the development, molecular structure, biochemical characteristics and the most common adverse effects of CERA, as well as the international attention when CERA works as a doping.
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Insulin-like growth factors (IGF), regulated by their receptors and binding proteins, play a pivotal role in human cell proliferation, differentiation and apoptosis. Increasing evidence has revealed that IGF system is involved in the genesis and progress of various malignancies including lung cancer. Recent studies in regard to IGF axis expression in the lung cancer cell lines, pulmonary tissue samples and blood circulation of lung cancer patients have shown that the IGF axis may contribute to the transformation and progression of lung cancer. Several researches have shown that a number of drugs targeting the IGF receptor are being investigated in clinical trials and suggest a potential therapeutic efficacy. This article reviews the updates and progress in the research of IGF axis in lung cancer.
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Objective To study the impact of exogenous growth hormone (GH) on the levels of insulin-like growth factor-Ⅰ and -Ⅱ (IGF-Ⅰ, -Ⅱ) of the pancreatic cancer tissue and the small intestine mucosa of the host. Methods In situ hybridization was performed on pancreatic cancer cell lines (SW-1990) and inoculation tumor of the host to determine the location of the mRNA transcript encoding IGF R-Ⅰ,-Ⅱ. Athymic nude Balb/c mice were inoculated with SW-1990 cells. After inoculated tumors have become palpable, animals were randomized to receive GH (4 mg/kg once daily for 2 weeks) versus saline control. After the animals were killed at time point, tissues (tumor and small intestine) were rapidly incised for subsequent immune blotting analysis. Results Strong IGF R-Ⅰ,-Ⅱ mRNA hybridization signal could be detected in pancreatic cancer cell. There was no statistically significant difference between the level of IGF-Ⅰ, Ⅱ in the tumor of the GH and NS groups after 1 hours of GH injection (P>0.05). GH augmented the expression of IGF-Ⅰ(1 h : 0.33±0.05, P<0.05 ; 2 h : 0.34±0.04, P<0.05 ; 6 h:0.34±0.05, P<0.05), -Ⅱ(1 h : 0.36±0.05, P<0.05) in the small intestine mucosa of the host. Conclusions The expression of IGF-Ⅰ, Ⅱ in the small intestine mucosa of the host was elevated by GH, but not in the inoculation tumor in vivo. The discrepancy of GH-IGF pathway between inoculation tumor and small intestine of the host may help to explain the phenomena that GH doesn't accelerate growth of pancreatic tumor in vivo.
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A interação entre as vias de sinalização do ER, do IGF-I e da integrina 1 é essencial para a manutenção da homeostase da glândula mamária normal, e alterações nessas vias de sinalização estão associadas ao processo de tumorigênese da mama. Portanto, o objetivo deste trabalho foi investigar a influência e inter-relação entre as vias de sinalização do IGF-I, do ER e da integrina 1 na regulação da transcrição dos genes PHLDA1 e PAWR. Para isso, células MCF-7 foram tratadas, por diferentes tempos, com 10nM de 17- estradiol (E2), 12,5nM de IGF-I, 30M de LY294002 (inibidor da PI-3K), 30M de SB202190 (inibidor da p38MAPK) e 1M de ICI182780 (antagonista do ER), ou transfectadas com 40nM de siRNA para integrina 1. A expressão gênica foi avaliada por PCR em tempo real e a expressão protéica por Western Blot. A expressão do gene PHLDA1 aumentou após tratamento com E2 por 6h (p=0,05), e esse efeito foi inibido pelo tratamento com ICI (p<0,05). O tratamento com E2 por 24h inibiu a expressão do gene PAWR (p<0,05), e esse efeito foi dependente de ER, pois foi inibido pelo tratamento com ICI (p<0,05). O tratamento com IGF-I por 1,5h causou aumento na expressão do gene PHLDA1 (p<0,05); e o tratamento com IGF-I por 24h causou diminuição na expressão do gene PAWR (p<0,05). Foi observado aumento na expressão protéica de PHLDA1 após tratamento das MCF-7 com E2 ou IGF-I por 1:30h. A regulação da expressão do PAWR pelo IGF-I ocorreu através das vias da PI-3K e p38MAPK. O efeito do IGF-I sobre a expressão dos dois genes foi independente da ativação do ER, mas foi observado sinergismo entre E2 e IGFI na inibição da expressão dos transcritos do PAWR, com diminuição na expressão para nível menor do que o observado após tratamento com E2 ou IGF-I sozinhos (p<0,05). A repressão da expressão da integrina 1 resultou na diminuição dos níveis de expressão dos genes PHLDA1 e PAWR. Não foi observada interação entre o IGF-I e a integrina 1 na regulação dos genes PHLDA1 e PAWR. Portanto, o gene...
The interactions among ER, IGF-I and 1 integrin signaling pathways are essential for the maintenance of normal mammary gland homeostasis, and alterations in these pathways have been associated with mammary tumorigenesis. Therefore, the goal of this work was to investigate the influence and interaction among IGF-I, ER and 1 integrin signaling pathways on the regulation of PHLDA1 and PAWR transcription regulation. To accomplish that, MCF-7 cells were treated with 10nM 17-estradiol (E2), 12.5nM IGF-I, 30M LY294002 (a PI3-K inhibitor), 30M SB202190 (a p38MAPK inhibitor) and 1M ICI182,780 (ICI an ER antagonist), or transfected with 40nM siRNA aiming 1 integrin. Real time PCR and western blot were used to evaluate gene and protein expression, respectively. PHLDA1 mRNA expression increased after 6h of treatment with E2 (p=0.05), and this effect was inhibited by ICI (p<0.05). Treatment with E2 for 24h repressed PAWR gene expression (p<0.05) and this effect was dependent on ER, since treatment with ICI inhibited it (p<0.05). Treatment with IGF-I for 1.5h resulted in increased PHLDA1 gene expression (p<0,05) and also PHLDA1 protein expression; and treatment with IGF-I for 24h inhibited PAWR mRNA expression (p<0.05). IGF-I regulation of PAWR expression was dependent on PI3-K and p38MAPK activation. The regulation of both genes by IGF-I was independent of ER activation; however, IGF-I acted in synergism with E2 on PAWR expression resulting in lower PAWR expression than the observed after the treatments alone (p<0.05). Repression of 1 integrin expression resulted in downregulation of PHLDA1 and PAWR expression levels. No interaction was observed between IGF-I and 1 integrin on PHLDA1 and PAWR gene expression. In conclusion, PHLDA1 is positively regulated by E2 and IGF-I, but there is no interaction between them on PHLDA1 regulation. On the other hand, PAWR is negatively regulated by E2 and IGF-I; IGF-I effect is dependent on PI3-K and p38MAPK, but not on ER...
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Humans , Apoptosis , Breast Neoplasms , Gene Expression , Integrins , Receptors, Estrogen , SomatomedinsABSTRACT
Objective To investigate relationship of serum insulin like growth factors(IGFs) and catch up growth. Methods The model of rats intrauterine growth retardation (IUGR) was built by clamping bilateral uterine arteries and veins of pregnant rats. The growth parameters (body weight and length), organs weights (brain, lungs and liver) and serum concentrations of IGF Ⅰ, Ⅱ of all neonatal rats was measured at birth and postnatal day 3 and day 5, respectively. Results (1)At birth, the serum levels of IGF Ⅰ, Ⅱ and the average growth parameters, organs weights in IUGR rats were significantly lower than those in control group( P 0.05). The serum of IGF Ⅱ in high catch up group was significantly higher than that at birth( P 0.05). Conclusion Both IGF Ⅰ, Ⅱmay play an important role in the regulation of catch up growth and the decrease of IGF Ⅰ, Ⅱlevels may be the internal factors contributing to the absence of postnatal catch up growth in IUGR rats.
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Objective To investigate the role of insulin-like growth factor (IGF)-Ⅰ , ⅠⅠ , platelet-derived growth factors (PDGF)-AA,-BB and keratinocyte growth factor (KGF) in various stages of the pulmonary development in rats. Methods All lung tissues of fetal and neonatal rats were collected at the gestational age 18, 20, 21 d, and 1, 4, 7, 10 and 21 d after birth. The expression of IGF-Ⅰ , IGF- ⅠⅠ , PDGF-AA and PDGF-BB was detected by immunohistochemistry and Western blot, respectively. The levels of IGF- Ⅰ , IGF-ⅠⅠ , PDGF-A, PDGF-B and KGF mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). Results The peak expression of IGF-Ⅰ was at 4, 7 and 10 d after birth. IGF-ⅠⅠ was detectable early in fetal lung development and decreased gradually until 21 d after birth. The changes of IGF- Ⅰ , ⅠⅠ mRNA were similar to IGF- Ⅰ , ⅠⅠ polypeptides. The PDGF-A,PDGF-B mRNA were abundant early in fetal lung development. The steady state of PDGF-A chain mRNA was significantly different only at 7 d (0. 97?0. 23,P0. 05). The PDGF-AA polypeptide was abundant early in fetal lung development, and the expression peak was found in 1, 4 and 7 d after birth. KGF mRNA was higher in the fetal samples than that of rats after birth, but no difference in postnatal rats at all time points. Conclusions Peptide growth factors may play a critical role in the development of lung in rats.
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To determine the effect of recombinant human growth hormone (rhGH) on postburn hypermetabolism postburn, sixteen male minipigs were inflicted with 35% TBSA full thickness burns, and the burned minipigs were then randomly divided into two groups: rhGH group and control group. REEs were monitored by means of Cardiorespiratory Diagnostic Systems (Medical Graphics Corporation, USA). The sequential changes in serum levels of GH, IGF 1,insulin,glucagon,cortisol,albumin were analyzed. The level of REE is significantly lower in rhGH treated groupas as compared with that of control, while the serum concentrations of GH, IGF 1, albumin are higher in the former, Body weighf gain is observed in rhGH treated group with no significant effect on serum concentration of insulin,glucagon and cortisol. RhGH therapy is thus helpful in the control of hypermetabolism after extensive burn.