| 1. |
- Sami, Manal M., et al.
(författare)
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Expression of epidermal growth factor receptor and human epidermal growth factor receptor 2 in urothelial bladder carcinoma in an Egyptian cohort: Clinical implication and prognostic significance
- 2023
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Ingår i: UROLOGIA JOURNAL. - : SAGE PUBLICATIONS LTD. - 0391-5603 .- 1724-6075. ; 90:2, s. 246-260
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bladder cancer (BC) has a particular importance in Egyptian patients due to aggressive behavior and absence of prognostic markers. Objective: To evaluate the expression of gene and protein expression of HER2 and epidermal growth factor (EGFR) in Egyptian patients with BC and ultimately to investigate their clinical implication and prognostic significance. Material and methods: The study was carried out on 46 patients with urothelial bladder BC. Tissue were obtained from transurethral resection (N = 22) and radical cystectomy (N = 24) specimens. The original hematoxylin and eosin slides were re-evaluated and the formalin fixed, paraffin-embedded (FFPE) tissues which had sufficient tumor tissue (>75%) and minimal or absent tumor necrosis were selected for immunohistochemistry (IHC) and RNA extraction. Furthermore, five control biopsies were obtained from patients with cystitis. Follow-up data were retrieved from the medical records which included the treatment regimen, disease recurrence and/or progression, and survival. Results: EGFR and HER2 protein were overexpressed in 35% and 46% of patients respectively. EGFR was correlated with the tumor size, grade and pathological stage, with a similar trend for HER2. The recurrence rate was higher in patients with expression of any of the markers. Gene expression was significantly higher (10.6-folds) for EGFR and (21-folds) for HER2 in patients with BC in comparison to control patients. Survival analysis showed lower median disease-free survival in association with HER2 protein overexpression. Conclusions: Our data highlighted the prognostic significance of EGFR and HER in BC and proposed their possible use as predictive markers and potential therapeutic targets.
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| 2. |
- Isgaard, Jörgen, 1959, et al.
(författare)
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Protective and regenerative effects of the GH/IGF-I axis on the brain.
- 2007
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Ingår i: Minerva endocrinologica. - 0391-1977. ; 32:2, s. 103-13
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Tidskriftsartikel (refereegranskat)abstract
- Apart from regulating somatic growth and metabolism, evidence suggest that the GH/ IGF-I axis is involved in the regulation of brain growth, development and myelination. Moreover, growth hormone (GH) and particularly IGF-I have been attributed neuroprotective effects in different in vitro and in vivo experimental models. In addition, both GH and IGF-I affect cognition and biochemistry in the adult brain. Some of the effects of GH are suggested to be mediated by circulating IGF-I, while other effects may be due to locally produced IGF-I within the brain. It is also possible that GH may act directly on the central nervous system (CNS) without involving IGF-I (either circulating or locally). Plasticity in the CNS may be viewed as changes in the functional interplay between the major cell types neurons, astrocytes and oligodendrocytes. GH and IGF-I affect all these cell types in several aspects. Apart from neuroprotective effects of GH and IGF-I in different experimental models of CNS injury, IGF-I has been found to increase progenitor cell proliferation and new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. In the adult cerebral cortex, it appears that only oligodendrogenesis is affected. The increase of IGF-I on endothelial cell phenotype may explain the increase in cerebral arteriole density observed after GH treatment. In the present review, different aspects of the GH/IGF-I axis effects on the brain will be discussed with particular emphasis on neuroprotection, regeneration and brain plasticity. Moreover, recent findings describing neuroprotective effects and effects on synaptic plasticity by GH secretagogues will be reviewed.
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| 3. |
- Lagerquist, Marie, et al.
(författare)
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Androgens and the skeleton.
- 2005
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Ingår i: Minerva endocrinologica. - 0391-1977. ; 30:1, s. 15-25
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Tidskriftsartikel (refereegranskat)abstract
- Loss of estrogens or androgens causes bone loss by increasing the rate of bone remodeling, and also causes an imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, treatment with androgens, as well as estrogens, maintains cancellous bone mass and integrity, regardless of age or sex. Both androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs) can exert these effects, but the relative contribution of these 2 pathways remains uncertain. Androgens, like estrogens, stimulate endochondral bone formation at the start of puberty, whereas they induce epiphyseal closure at the end of puberty, thus, they have a biphasic effect. Androgen action on the growth plate is, however, clearly mediated via aromatization into estrogens and interaction with ER alpha. Androgens increase, while estrogens decrease radial growth. This differential effect of the sex steroids may be important because bone strength in males seems to be determined by higher periosteal bone formation and, therefore, greater bone dimensions. Experiments in mice suggest that both the AR and ER alpha pathways are involved in androgen action on radial bone growth. ER beta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. This androgen action on bone is mediated by the AR and ER alpha.
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| 4. |
- Sjögren, Klara, 1970, et al.
(författare)
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A transgenic model to determine the physiological role of liver-derived insulin-like growth factor I.
- 2002
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Ingår i: Minerva endocrinologica. - 0391-1977. ; 27:4, s. 299-311
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-I (IGF-I) has important growth promoting and metabolic effects and is expressed in virtually every tissue of the body. The highest expression is found in the liver but the physiological role of liver-derived IGF-I is unknown. It has been difficult to separate the endocrine effects of liver-derived IGF-I from the autocrine/paracrine effects of locally produced IGF-I in peripheral tissues. Therefore, we have developed a mouse model with a liver-specific inducible deletion of the IGF-I gene. The liver-IGF-I deficient mouse have dramatically reduced (>80%) serum IGF-I levels, demonstrating that the major part of serum IGF-I is liver-derived. Surprisingly, liver-IGF-I deficient mice demonstrate a normal appendicular skeletal growth up to at least 12 months of age despite the dramatic decrease in circulating IGF-I levels, indicating that liver-derived IGF-I is not required for appendicular skeletal growth. However, the adult axial skeletal growth is clearly reduced in the liver-IGF-I deficient mice. Furthermore, the amount of cortical bone is reduced due to decreased radial growth of the cortical bone while the amount of trabecular bone is unchanged in the liver-IGF-I deficient mice. The decreased levels of circulating IGF-I are associated with increased serum levels of growth hormone (GH), indicating a role for liver-derived IGF-I in the negative feedback regulation of GH secretion. Measurements of factors regulating GH-secretion in the pituitary and in the hypothalamus revealed an increased expression of growth hormone releasing hormone (GHRH) and growth hormone secretagogue (GHS) receptors in the pituitary of liver-IGF-I deficient mice. This in turn results in an increased sensitivity to systemically administered GHRH and GHS, demonstrating that the regulatory action of liver-derived IGF-I on GH secretion is at the pituitary rather than at the hypothalamic level. The liver is an important metabolic organ and liver-IGF-I deficient mice are markedly hyperinsulinemic and yet normoglycemic, consistent with an adequately compensated insulin resistance. Interestingly, liver-IGF-I deficient mice display a reduced age-dependent fat mass accumulation compared with control mice. In conclusion, liver-derived IGF-I is important for carbohydrate- and lipid-metabolism and for the regulation of GH-secretion at the pituitary level. Furthermore, it regulates adult axial skeletal growth and cortical radial growth while it is not required for appendicular skeletal growth.
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| 5. |
- Svensson, Johan, 1964, et al.
(författare)
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Growth hormone and the cardiovascular function.
- 2005
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Ingår i: Minerva endocrinologica. - 0391-1977. ; 30:1, s. 1-13
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Forskningsöversikt (refereegranskat)abstract
- In this review, the great importance of growth hormone (GH) for the maintenance of cardiac function in adult life is discussed. Physiological effects of GH are discussed as well as the cardiac dysfunction caused both by GH excess (acromegaly) and by GH deficiency in adult hypopituitary patients. In both acromegaly and adult GH deficiency, there is also increased cardiovascular morbidity and mortality. Finally, the effect of GH treatment in heart failure is discussed.
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