Low-dose radiation therapy of cancer: role of immune enhancement

Farooque, Abdullah; Mathur, Rohit; Verma, Amit; Kaul, Vandana; Bhatt, Anant Narayan; Adhikari, Jawahar Singh; Afrin, Farhat; Singh, Saurabh; Dwarakanath, Bilikere S.

doi:10.1586/era.10.217

Cited by 67 publications

(65 citation statements)

References 91 publications

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“…Although LDR was also considered dangerous according to the linear no-threshold (LNT) hypothesis (32), increasing evidence has suggested that LET radiation at dose levels Ͻ100 mGy could induce beneficial effects, including extending life span, enhancing immunity, and improving DNA repair (17,23,36). Epidemiological surveys have analyzed individuals exposed to Ͻ100 mGy radiation.…”

Section: Discussionmentioning

confidence: 99%

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

Shao

Zhang

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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-The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways. low-dose radiation; fibroblast growth factor-21; insulin resistance; inflammation; oxidative stress DIABETIC NEPHROPATHY (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease (38). DN initiates with the thickening of the glomerular basement membrane, which is followed by mild and moderate mesangial expansion, capillary collapse in the renal tubule, epithelial cell degeneration, and a gradual increase in proteinuria, and finally leads to renal fibrosis and kidney failure (43, 56). Hyperglycemia, hyperlipidemia, and subsequent insulin resistance are the initial and systemic pathogeneses of DN, which is also associated with renal pathogeneses, such as oxidative stress, inflammation, and fibrosis. There are currently multiple therapies to treat patients with DN, including reducing blood sugar levels, lowering lipid levels, enhancing insulin sensitivity, and reducing oxidative stress, inflammation, or fibrosis (1, 19, 50). However, most of these treatments just slow rather than arrest the progression toward DN, since blocking any single pathway is not sufficient to prevent the development of DN (8,19). Therefore, identifying a treatment that inhibits both the systemic and renal pathogeneses will prevent the development of DN efficiently.Fibroblast growth factor (FGF)-21 is a novel member of the FGF family that functions as an endocrine hormone rather than regulating cellular prolifera...

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Section: Discussionmentioning

confidence: 99%

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

Shao

Zhang

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…One approach to this end is the identification of adjuvants that can increase the effectiveness of current therapies [4][5][6][7]. Ideally, an adjuvant should be non-toxic, easy to administer and have known pharmacological properties.…”

Section: Introductionmentioning

confidence: 99%

Sodium tungstate modulates ATM function upon DNA damage

et al. 2013

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Edited by Varda RotterKeywords: DNA damage Antitumoral Double-strand break Phosphatase inhibition a b s t r a c t Both radiotherapy and most effective chemotherapeutic agents induce different types of DNA damage. Here we show that tungstate modulates cell response to DNA damaging agents. Cells treated with tungstate were more sensitive to etoposide, phleomycin and ionizing radiation (IR), all of which induce DNA double-strand breaks (DSBs). Tungstate also modulated the activation of the central DSB signalling kinase, ATM, in response to these agents. These effects required the functionality of the Mre11-Nbs1-Rad50 (MRN) complex and were mimicked by the inhibition of PP2A phosphatase. Therefore, tungstate may have adjuvant activity when combined with DNA-damaging agents in the treatment of several malignancies.

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“…adverse side effects (Sakamoto, 2004;Farooque et al, 2011). Several retrospective human studies have shown a reduced cancer incidence from low dose radiation, however such studies are subject to many confounding factors, and so they are not discussed here.…”

Section: Shifting the Paradigm In Radiation Safetymentioning

confidence: 99%

Shifting the Paradigm in Radiation Safety

Doss¹

2012

Dose-Response

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ᮀ The current radiation safety paradigm using the linear no-threshold (LNT) model is based on the premise that even the smallest amount of radiation may cause mutations increasing the risk of cancer. Autopsy studies have shown that the presence of cancer cells is not a decisive factor in the occurrence of clinical cancer. On the other hand, suppression of immune system more than doubles the cancer risk in organ transplant patients, indicating its key role in keeping occult cancers in check. Low dose radiation (LDR) elevates immune response, and so it may reduce rather than increase the risk of cancer. LNT model pays exclusive attention to DNA damage, which is not a decisive factor, and completely ignores immune system response, which is an important factor, and so is not scientifically justifiable. By not recognizing the importance of the immune system in cancer, and not exploring exercise intervention, the current paradigm may have missed an opportunity to reduce cancer deaths among atomic bomb survivors. Increased antioxidants from LDR may reduce aging-related non-cancer diseases since oxidative damage is implicated in these. A paradigm shift is warranted to reduce further casualties, reduce fear of LDR, and enable investigation of potential beneficial applications of LDR.

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Low-dose radiation therapy of cancer: role of immune enhancement

Cited by 67 publications

References 91 publications

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

Sodium tungstate modulates ATM function upon DNA damage

Shifting the Paradigm in Radiation Safety

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