Sarreal, Antero S.
Hernando, Raymundo T.
Saint-Louis, Leslie A.
Ginsberg, Stephen D.
Mehta, Pankaj D.
Buckley, Peter F.
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AbstractBrain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression as well as neuropsychiatric and neurodegenerative disorders. Recent studies show a role of BDNF in energy metabolism and body weight regulation. We examined BDNF levels in plasma and cerebrospinal fluid (CSF) samples from age matched elderly depressed and control subjects. Also, the association of BDNF levels with age, gender, body weight, body mass index (BMI), and cognitive performance was evaluated. We did not find any significant differences in plasma and CSF BDNF levels between depressed and control subjects. Plasma BDNF levels were negatively correlated with age (but not with BMI and body weight), when analyses were performed including both depressed and control subjects. A significant reduction in plasma BDNF levels was observed in females as compared to male subjects, and the change in BDNF levels were significantly and positively related to body weight in females. Furthermore, significant increases in Total Recall and Delayed Recall values were found in females as compared to males. In conclusion, the lower BDNF levels observed in females suggest that changes in peripheral BDNF levels are likely secondary to an altered energy balance. However, further studies using larger sample size are warranted.
CitationPLoS One. 2012 Jul 2; 7(7):e39358
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Insulin-like Growth Factor-1 Receptor as a Prognostic Factor for Breast Cancer: A Systematic Review and Meta-AnalysisDu, Helen; Koranteng, Patience; Stuart, Ansley; Sloan, Gloria; Weintraub, MJ; Cannon, Joseph; College of Allied Health Sciences - Clinical Laboratory Sciences (2017-03-10)Breast cancer is the “malignant proliferation of epithelial cell lining the ducts or lobules of the breast” (1). Breast cancer is the most common form of cancer affecting women and the second leading cause of cancer death among women. Insulin-like growth factors are potent mitogens that have a role in cell proliferation, differentiation, and apoptosis. Overexpression of IGF-1R is thought to cause an increased risk in tumor metastasis and tumorigenesis. The aim of this project is to conduct a systematic review of IGF-1R expression in breast cancer and its relationship to patient survival. Our hypothesis is that increased insulin-like growth factor-1 receptor expression leads to poor prognosis in breast cancer patients.
Molecular Mechanisms of High Glucose-Induced Vascular Endothelial Growth Factor Expression in Retinal Endothelial CellsPlatt, Daniel H.; Vascular Biology Center (2004-10)Studies in diabetic patients, experimental animal models and tissue culture cells treated with high glucose have shown a close association between pathologic vascular growth, over-expression o f the angiogenic factor vascular endothelial growth factor .5 (VEGF) and oxidative stress. Studies o f diabetic patients and high glucose treated cells have also shown increased levels o f tyrosine nitration, a marker for the formation o f the reactive nitrogen species peroxynitrite. Excess formation o f reactive oxygen/nitrogen species has been shown to activate two transcription factors that regulate the expression o f VEGF, hypoxia-inducible factor-1 (HIF-1) and signal transducer and activator o f transcription 3 (STAT3). These observations suggest that diabetes causes increases in VEGF expression due to the effects o f high glucose in stimulating the formation o f peroxynitrite, which leads to the activation o f the transcription factors HIF-1 and/or STAT3 and increases in VEGF expression. This hypothesis was tested by experiments using primary cultures o f retinal endothelial cells treated with peroxynitrite or high glucose. Both treatments increased VEGF mRNA and protein levels. Further, pretreatment with the specific peroxynitrite decomposition catalyst FeTPPs blocked the increase in VEGF expression. To determine if HIF-1 and/or STAT3 play a role in the peroxynitrite-induced VEGF expression, studies were done to analyze the activation patterns o f both transcription factors. These studies showed that peroxynitrite had no effect on the activation or nuclear translocation o f HIF-1 a , but did induce a rapid activation and nuclear translocation o f STAT3. To further explore the role o f STAT3 in the VEGF expression, cells were treated with peroxynitrite or high glucose in the presence or absence o f an adenoviral vector expressing dominant-negative STAT3. Overexpression o f the dominant-negative STAT3 blocked the effects o f either peroxynitrite or high glucose in increasing VEGF mRNA. Further, treatment with FeTPPS blocked the effects o f high glucose in stimulating activation o f STAT3. A non-receptor tyrosine kinase, cSrc, has been shown to play a role in the activation o f STAT3 as well as the induction o f VEGF expression during tumor angiogenesis. To determine if cSrc plays a role in STAT3 regulated VEGF transcriptional activation, retinal endothelial cells were transduced with an adenovirus over-expressing a constitutively active Src (vSrc). The vSrc transduction induced activation o f STAT3 and increased VEGF expression. Further, FeTPPs blocked the effects o f peroxynitrite and high glucose in stimulating activation o f cSrc. Additionally, the Src inhibitor PP1 blocked the effects o f peroxynitrite and high glucose in increasing VEGF mRNA and protein expression. This work is the first to show that 1) high glucose-induced peroxynitrite formation increases VEGF expression, 2) STAT3 activation by high glucose-induced peroxynitrite formation regulates VEGF expression and 3) cSrc activation by high glucose-induced peroxynitrite formation activates STAT3 and increases VEGF expression.
Sustained Release Formulation for Vascular Endothelial Growth FactorElzinga, Jennifer Lynn; Department of Oral Biology (2013-03)Necrosis of tissue due to trauma or a surgical procedure is a complication of wound healing. This necrosis, or tissue death, occurs when the vasculature is unable to perfuse involved tissue with the oxygen and nutrients necessary to maintain viability. To provide adequate access, reflecting a flap of tissue is often necessary in a variety of surgical procedures, including periodontal surgeries. The success of these procedures is limited by the development of tissue flap necrosis. The survival of these tissue flaps is dependent upon adequate perfusion by the blood vessel supply at the base of the flap, followed by the growth of new vascular channels from the recipient site. However, if angiogenesis does not promptly reach the distal extent of the flap, this portion becomes ischemic, leading to necrosis. Loss of the protective flap delays healing and increases the risk of scarring and infection. Necrosis of this distal region of a tissue flap begins as early as 24 hours following the surgical procedure and progresses rapidly until day 3 when the unaffected tissue begins to stabilize.1 A variety of pharmacological strategies to enhance tissue flap perfusion have been tested in an attempt to prevent necrosis. One such strategy is the administration of angiogenic growth factors such as vascular endothelial growth factor (VEGF). VEGF is known to stimulate the proliferation of endothelial cells from existing vasculature to create new blood vessels, thus enhancing 8 tissue survival.2-7 In addition, VEGF contributes to other aspects of wound healing, including inflammation, granulation tissue formation, reepithelialization, matrix formation, and remodeling.2 Administration of VEGF to wound healing models has shown promising results by increasing vascular formation, leading to enhanced tissue perfusion. However, its short duration of action and rapid dissipation from the target site reduces its effectiveness.8 Maintaining therapeutic concentrations of VEGF at the target site to maximize new vessel growth and reduce necrosis, either multiple applications or an extended-release delivery system is required. An ideal system would provide ease of use and delivery kinetics for sustained therapeutic dosing of VEGF to the wound environment for the duration of healing, thereby minimizing tissue necrosis. A variety of application methods and delivery systems are under investigation in the search to develop one that provides utility as well as improved clinical outcome.