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Growth Factor System (growth + factor_system)
Selected AbstractsVarious components of the insulin-like growth factor system in tumor tissue, cerebrospinal fluid and peripheral blood of pediatric medulloblastoma and ependymoma patientsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Judith M. de Bont Abstract The insulin-like growth factor (IGF) system plays an important role in neuronal development and may contribute to the development of brain tumors. In this study, we studied mRNA expression levels of IGFs, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor receptors (IGFRs) in 27 pediatric medulloblastomas, 13 pediatric ependymomas and 5 control cerebella. Compared to normal cerebellum, mRNA levels of IGFBP-2 and IGFBP-3 were significantly increased in medulloblastomas and ependymomas. IGFBP-2 expression was indicative of poor prognosis in medulloblastomas, whereas IGFBP-3 mRNA levels were especially high in anaplastic ependymomas. IGFBP-5 and IGF-II mRNA levels were significantly increased in ependymomas compared to control cerebellum. Protein expression levels of IGFs and IGFBPs were analyzed in the cerebrospinal fluid (CSF) of 16 medulloblastoma, 4 ependymoma and 23 control patients by radioimmuno assay to determine whether they could be used as markers for residual disease after surgery. No aberrant CSF protein expression levels were found for ependymoma patients. In medulloblastoma patients, the IGFBP-3 protein levels were significantly higher than in ependymoma patients and controls. Moreover, enhanced levels of proteolytic fragments of IGFBP-3 were found in the CSF of medulloblastoma patients, being in concordance with a significantly increased IGFBP-3 proteolytic activity in the CSF of these patients. In conclusion, our data suggest that the IGF system is of importance in pediatric medulloblastomas and ependymomas. Larger studies should be conducted to validate the predictive values of the levels of intact IGFBP-3 and proteolytic fragments in CSF in the follow-up of medulloblastomas. © 2008 Wiley-Liss, Inc. [source] Hind-limb paraparesis in a rat model for neurolathyrism associated with apoptosis and an impaired vascular endothelial growth factor system in the spinal cordTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2010Kuniko Kusama-Eguchi Abstract Neurolathyrism is a motor neuron disease characterized by lower limb paraparesis. It is associated with ingestion of a plant excitotoxin, ,-N-oxalyl-L-,,-diaminopropionic acid (L -,-ODAP), an agonist of ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate-type glutamatergic receptors. Previously, a limited model of neurolathyrism was reported for the rat. To improve upon the model, we stressed rat pups by separation from their mothers, followed by the subcutaneous L -,-ODAP treatment, resulting in a 4.6-fold higher incidence (14.0,15.6%) of the paraparesis compared with the prior study. The number and size of motor neurons in these rats were decreased only in the lumbar and sacral cord segments, at approximately 13,36 weeks after treatment. Only lumbar and sacral spinal cord tissue revealed pathological insults typical of physical and ischemic spinal cord injury in the surviving motor neurons. In addition, extensive but transient hemorrhage occurred in the ventral spinal cord parenchyma of the rat, and numerous TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive cells were also observed. In parallel, vascular endothelial growth factor receptor (VEGFR)-2 (Flk-1) levels were significantly lowered in the lumbosacral spinal cord of the paraparetic rats compared with their controls, suggesting a failure of the VEGF system to protect neurons against L -,-ODAP toxicity. We propose, based on these data, a novel pathological process of motor neuron death induced by peripheral L -,-ODAP. For the first time, we present a model of the early molecular events that occur during chemically induced spinal cord injury, which can potentially be applied to other neurodegenerative disorders. J. Comp. Neurol. 518:928,942, 2010. © 2009 Wiley-Liss, Inc. [source] Review article: The impact of obesity on reproduction in women with polycystic ovary syndromeBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2006R Pasquali The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS. [source] Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system?BJU INTERNATIONAL, Issue 9 2001L.A. Mucci Objectives,To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin-like growth factor 1 (IGF-1). Patients and methods,In the context of a case-control study, 112 men were admitted to three teaching hospitals in Athens, Greece, for disorders other than cancer. Sociodemographic data and detailed histories of smoking, alcohol and coffee consumption were recorded. A validated food-frequency questionnaire was administered by an interviewer and serological measurements of IGF-1 and its binding protein-3 conducted. Results,IGF-1 declined significantly by almost 25% among men aged >75 years and there was a small reduction in IGF-1 levels with increased alcohol intake, with a mean (95% confidence interval, CI) change of ,1.6 (, 2.2 to ,0.9)% for an increment of one drink per day. There was no evidence for an effect of either smoking or coffee consumption on IGF-1 level. Among foods, the consumption of cooked tomatoes was substantially and significantly inversely associated with IGF-1 levels, with a mean (95% CI) change of ,31.5 (, 49.1 to ,7.9)% for an increment of one serving per day. Conclusions,The strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) and an important endocrine factor in the aetiology of this disease (IGF-1) seem to be related in a way that suggests that at least one, and perhaps more, exogenous factors in the development of prostate cancer may be mediated through the IGF-1 system. [source] Expression of insulin-like growth factors systems in cloned cattle dead within hours after birthMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2007Shijie Li Abstract Cloning by somatic nuclear transfer is an inefficient process in which many of the cloned animals die shortly after birth and display organ abnormalities. In an effort to determine the possible roles IGFs played in neonatal death and organ abnormalities, we have examined expression patterns of eight genes in insulin-like growth factor (IGF) systems (IGF1, IGF2, IGF1R, IGF2R, IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4) in six organs (heart, liver, spleen, lung, kidney, and brain) of both neonatal death cloned bovines (n,=,9) and normal control calves (n,=,3) produced by artificial insemination (AI) using real-time quantitative RT-PCR. The effect of the age of the fibroblast donor cell on the gene expression profiles was also investigated. Aberrant expressions of six genes (IGF2, IGF1R, IGF2R, IGFBP-2, IGFBP-3, and IGFBP-4) were found in some studied tissues, but the expression of two genes (IGF1 and IGFBP-1) had similar levels with the normal controls. For the studied genes, kidney was the organ that was most affected (five genes) by gene downregulation, whereas spleen was the organ that was not affected. The two upregulation genes were in brain, but both of downregulation and upregulation were found in the heart, liver, and lung. The expression of three genes (IGF2R, IGFBP-4, and IGF2) in some tissues showed significant differences between AF cell-derived and FF cell-derived clones. Our results suggest that aberrations in gene expression within IGF systems were found in most cloned bovine tissues of neonatal death. Because IGF systems play an important role in embryo development and organogenesis, the aberrant transcription patterns detected in these clones may contribute to the defects of organs reported in neonatal death of clones. Mol. Reprod. Dev. 74: 397,402, 2007. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||