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    Beta-Hydroxy-Beta-Methyl-Butyrate, L-glutamine, and L-arginine Supplementation Improves Radiation-Induce Acute Intestinal Toxicity
    (Taylor & Francis Ltd, 2019) Yavas, Cagdas; Yavas, Guler; Celik, Esin; Buyukyoruk, Ahmet; Buyukyoruk, Cennet; Yuce, Deniz; Ata, Ozlem
    We aimed to evaluate effects of beta-hydroxy-beta-methylbutyrate, L-glutamine, and L-arginine (HMB/GLN/ARG) on radiation-induced acute intestinal toxicity. Forty rats were divided into four groups: group (G) 1 was defined as control group, and G2 was radiation therapy (RT) control group. G3 and G4 were HMB/GLN/ARG control and RT plus HMB/GLN/ARG groups, respectively. HMB/GLN/ARG started from day of RT and continued until the animals were sacrificed 10 days after RT. The extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis were quantified on histological sections of intestinal mucosa. Statistical analyses were performed using the analysis of variance (ANOVA) test. There were significant differences between study groups regarding extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis and crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis (p values were 0.019 for fibrosis, <.001 for the others). Pair-wise comparisons revealed significant differences regarding surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, vascular dilatation, and congestion between G2 and G4 (p values were <.001, .033, <.001, .007, and <.001, respectively). Fibrosis score was significantly different only between G1 and G2 (p = .015). Immunohistochemical TGF-beta score of G2 was significantly higher than G1 and G3 (p values were .006 and .017, respectively). There was no difference between TGF-beta staining scores of G2 and G4. Concomitant use of HMB/GLN/ARG appears to ameliorate radiation-induced acute intestinal toxicity; however, this finding should be clarified with further studies.
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    The effect of Halofuginone in the amelioration of radiation induced-lung fibrosis
    (Churchill Livingstone, 2013) Yavas, Guler; Calik, Mustafa; Calik, Goknil; Yavas, Cagdas; Ata, Ozlem; Esme, Hidir
    The lung is one of the most sensitive organs to ionizing radiation, and damage to normal lung tissue remains a major dose limiting factor for patients receiving radiation to the thorax. Radiation induced lung injury (RILI) which is also named as radiation pneumonpathy is a continuous process and regarded as the result of an abnormal healing response. It has been shown that transforming growth factor beta-1 (TGF-beta 1) plays an integral role in the radiation induced lung fibrosis formation by promoting the chemoattraction of fibroblasts and their conversion to myofibroblasts. Halofuginone is a, low molecular weight plant derived alkaloid, isolated from the Dichroa febnfuga plant that exhibits antifibrotic activity and inhibition of type I collagen synthesis. Halofuginone has been shown to protect against radiation induced soft tissue fibrosis by virtue of inhibiting various members of TFG-beta signaling pathway. By the light of these findings, we hypothesize that Halofuginone may be able to ameliorate the radiation induced lung fibrosis. (C) 2013 Elsevier Ltd. All rights reserved.
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    Effects of Adipose-Derived Stem Cells and Platelet-Rich Plasma for Prevention of Alopecia and Other Skin Complications of Radiotherapy
    (Lippincott Williams & Wilkins, 2021) Evin, Nuh; Tosun, Zekeriya; Aktan, Tahsin Murad; Duman, Selcuk; Harmankaya, Ismail; Yavas, Guler
    Background Radiotherapy (RT) involves the use of ionizing radiation in treating malignancies and benign disorders. However, RT damages target and healthy surrounding tissues in a dose-dependent manner. This effectively reduces patient compliance and quality of life, thereby warranting the prevention of RT-induced adverse effects on skin. Adipose-derived stem cells (ASCs) are used to treat RT-induced damage and platelet-rich plasma (PRP) provides a scaffold that potentiates the effects of ASCs. Thus, the aim of this study was to determine the mechanism employed by ASCs and PRP in protecting against RT-induced adverse effects. Methods We have established an immunodeficient mouse transplantation model using which human hair follicular units were implanted. When the follicular units were macroscopically and microscopically mature and anagenic, we administered localized RT. Subsequently, the mice were randomly divided into 4 groups based on the subcutaneous injection of the following to the irradiated transplantation site: saline, PRP, ASCs, and a combination of ASCs and PRP. Next, we used macroscopic and microscopic analyses to determine the protective effects of the injected solutions on skin and hair follicles. Results Adipose-derived stem cells reduced RT-induced adverse effects, such as impaired wound healing, alopecia, skin atrophy, and fibrosis by suppressing inflammation, dystrophy, degeneration, connective tissue synthesis, and apoptosis and increasing cellular proliferation, differentiation, and signaling. Moreover, these effects were augmented by PRP. Conclusions Thus, co-administering ASCs with PRP in mice prevented RT-induced adverse effects and can be tested for use in clinical practice.