Radiation-Induced Liver Fibrosis Is Mitigated by Gene Therapy Inhibiting Transforming Growth Factor-β Signaling in the Rat

Pretreatment with A Small-Molecule Tumor Necrosis Factor-Alpha (TNF-a) Inhibitor, UTL-5g, Reduced Radiation-Induced Acute Liver Toxicity in Mice

“…Thus, radioprotective effect of UTL-5g for long-term hepatic damage is not known at present. Recent studies suggest that much of the delayed damage may be caused by aberrant and prolonged production of wound healing proinflammatory cytokines including TNF-α in situ [2,16,19]. Since the production of these cytokines is regulated by identical and interrelated inflammatory signaling pathways, it is reasonable to speculate that UTL-5g may have long-term radioprotective effect as well, but further studies are needed to investigate the long-term effect of UTL-5g.…”

“…Radiation-induced toxicity results from a series of pathological changes at both cellular and biochemical levels, which include DNA damage, early cell apoptosis, inflammation and, ultimately, radiation-induced latent fibrosis and loss of liver function. Many strategies and compounds have been studied for their protective effects against radiation [2][3][4]. Ethyol® (amifostine) is the only radioprotector approved by the FDA to reduce xerostomia associated with radiotherapy of head-and-neck cancer.…”

Potential Role of Hedgehog Signaling in Radiation-induced Liver Fibrosis

“…방사선치료는 복부 질환(celiopathy) 환자 중 악성 림프종(malignant lymphoma), 간세포암(hepatocellular carcinoma), 담관암(cholangiocarcinoma), 위암(stomach cancer) 등의 환자에 사용되고 있고 [16], 보건복지부, 대한방사선 종양학회가 제공한 자료에 의하면 국내 유방암(breast cancer), 뼈 전이암, 뇌 전이암과 같은 전이암(metastatic cancer), 두경 부암(head and neck cancer), 폐암(lung cancer), 직장암(rectal cancer), 뇌종양(encephaloma), 췌장암(pancreatic cancer) 등 에서 방사선 치료를 시행하고 있다. 방사선 치료는 종양의 크 기가 작거나, 조직내부에 침투해 있어 외과적 수술을 통해 제 거가 불가능하거나, 혹은 외과적 수술 후 제거하지 못한 한정 된 부위를 치료하는데 가장 효과적인 항암치료법으로 알려져 있다.…”

“…저산소환경은 TGF (transforming growth factor)-β1에 의 존적으로 콜라겐(collagen) 및 다른 세포외기질(extracellular matrix) 단백질들의 합성을 자극시켜, 섬유화 진행에 관여한 다 [15]. 마지막으로, 방사선이 활성 산소종(reactive oxygen species, ROS)의 과잉 생산을 유발하여 생체 내 항산화 방어계 의 균형을 깨트리는 산화적 스트레스를 유발한다는 것이다 [18,66,84] [16,32,49,73]. 최근 본 연구팀은 방사선에 의한 간 섬유화 진행에 헤지호그와의 관련성을 제시하였다 (Fig.…”

In Regard to “Radiation-Induced Liver Fibrosis is Mitigated by Gene Therapy Inhibiting Transforming Growth Factor-β Signalling in the Rat” by Shi-Suo Du et al. (Int J Radiat Oncol Biol Phys 2010;78:1513–1523)

“…To the Editor: We read with interest the article by Du et al (1). They determined whether anti-transforming-growth-factor-b (TGF-b) intervention could halt the progression of radiation-induced-liver-fibrosis in a rat model.…”