Journal ArticleDOI
Metformin as a Radiation Modifier; Implications to Normal Tissue Protection and Tumor Sensitization.
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TLDR
The interesting properties of metformin such as radioprotection, radiomitigation and radiosensitization could make it an interesting adjuvant for clinical radiotherapy, as well as an interesting candidate for mitigation of radiation injury after a radiation disaster.Abstract:
BACKGROUND: Nowadays, ionizing radiation is used for several applications in medicine, industry, agriculture, and nuclear power generation. Besides the beneficial roles of ionizing radiation, there are some concerns about accidental exposure to radioactive sources. The threat posed by its use in terrorism is of global concern. Furthermore, there are several side effects to normal organs for patients who had undergone radiation treatment for cancer. Hence, the modulation of radiation response in normal tissues was one of the most important aims of radiobiology. Although, so far, several agents have been investigated for protection and mitigation of radiation injury. Agents such as amifostine may lead to severe toxicity, while others may interfere with radiation therapy outcomes as a result of tumor protection. Metformin is a natural agent that is well known as an antidiabetic drug. It has shown some antioxidant effects and enhances DNA repair capacity, thereby ameliorating cell death following exposure to radiation. Moreover, through targeting endogenous ROS production within cells, it can mitigate radiation injury. This could potentially make it an effective radiation countermeasure. In contrast to other radioprotectors, metformin has shown modulatory effects through induction of several genes such as AMPK, which suppresses reduction/ oxidation (redox) reactions, protects cells from accumulation of unrepaired DNA, and attenuates initiation of inflammation as well as fibrotic pathways. Interestingly, these properties of metformin can sensitize cancer cells to radiotherapy. CONCLUSION: In this article, we aimed to review the interesting properties of metformin such as radioprotection, radiomitigation and radiosensitization, which could make it an interesting adjuvant for clinical radiotherapy, as well as an interesting candidate for mitigation of radiation injury after a radiation disaster. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.read more
Citations
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Journal ArticleDOI
Steps in metastasis: an updated review.
Jamal Majidpoor,Keywan Mortezaee +1 more
TL;DR: In this article, the tumor cells isolated from the primary tumor exploit several mechanisms to maintain their survival including rewiring metabolic demands to use sources available within the new environments, avoiding anoikis cell death when cells are detached from extracellular matrix (ECM), adopting flow mechanic by acquiring platelet shielding and immunosuppression by negating the activity of suppressor immune cells, such as natural killer (NK) cells.
Journal ArticleDOI
Radioprotection and Radiomitigation: From the Bench to Clinical Practice.
Elena Obrador,Rosario Salvador,J. I. Villaescusa,José Miguel Soriano,José M. Estrela,Alegría Montoro +5 more
TL;DR: Molecules under development with the aim of reaching clinical practice and other nonclinical applications are discussed and differentiates radioprotectors and radiomitigators (minimize toxicity even after radiation has been delivered).
Journal ArticleDOI
Targeting of oxidative stress and inflammation through ROS/NF-kappaB pathway in phosphine-induced hepatotoxicity mitigation
Hamed Haghi Aminjan,Seyed Reza Abtahi,Ebrahim Hazrati,Mohsen Chamanara,Maryam Jalili,Babak Paknejad +5 more
TL;DR: Targeting ROS/NF-kappaB signalling pathway by resveratrol may have a significant effect on the improvement of hepatic injury induced by phosphine, suggesting it may be a possible candidate for the treatment of phosphine-poisoning.
Journal ArticleDOI
Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer
TL;DR: The biology of metformin and its molecular mechanism of action is discussed, the existing cellular, pre-clinical, and clinical studies that have tested the anti-tumor potential of meetformin as a potential anti-cancer/anti-Tumor agent in breast cancer therapy are discussed, and the future prospects and directions for a better understanding and re-purposing of met formin as an anti- cancer drug in the treatment of breast cancer are outlined.
Journal ArticleDOI
Enriched cancer stem cells, dense stroma, and cold immunity: Interrelated events in pancreatic cancer.
TL;DR: In this article, the authors investigated how desmoplastic aggregates can influence the functionality of CSCs for promoting a cold pancreatic tumor immunity, which can be an effective strategy for improving responses from cold tumors to immunotherapy.
References
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Journal Article
Survival Advantage Associated with Metformin Usage in Hepatocellular Carcinoma Patients Receiving Radiotherapy: A Propensity Score Matching Analysis.
Won Il Jang,Mi-Sook Kim,Jung Sub Lim,Hyung Jun Yoo,Young Seok Seo,Chul Han,Su Cheol Park,Chul Seung Kay,Myungsoo Kim,Hong Seok Jang,Dong Soo Lee,Ah Ram Chang,Hae Jin Park +12 more
TL;DR: The use of metformin in patients with hepatocellular carcinoma receiving radiotherapy was associated with higher overall survival and the adjusted Cox proportional hazards model revealed that met formin usage was a significant factor for mortality.
Journal ArticleDOI
Intraoral Mitochondrial-Targeted GS-Nitroxide, JP4-039, Radioprotects Normal Tissue in Tumor-Bearing Radiosensitive Fancd2–/– (C57BL/6) Mice
Ashwin Shinde,Hebist Berhane,Byung Han Rhieu,Ronny Kalash,Karen M. Xu,Julie P. Goff,Michael W. Epperly,Darcy Franicola,Xichen Zhang,Tracy Dixon,Donna Shields,Hong Wang,Peter Wipf,Kalindi Parmar,Eva C. Guinan,Valerian E. Kagan,Vladimir A. Tyurin,Robert L. Ferris,Xiaolan Zhang,Song Li,Joel S. Greenberger +20 more
TL;DR: Mitochondrial targeting makes F15/JP4-039 an effective normal tissue radioprotector for Fancd2–/– mice, as well as wild-type mice.
Journal ArticleDOI
Mitigation of Lung Injury after Accidental Exposure to Radiation
Javed Mahmood,Salomeh Jelveh,Victoria L Calveley,Asif Zaidi,Susan R. Doctrow,Richard P. Hill,Richard P. Hill +6 more
TL;DR: It is found that genistein had promising mitigating effects on oxidative damage, pneumonitis and fibrosis even at late times (36 weeks) when drug treatment was initiated 1 week after irradiation and stopped at 28 weeks postirradiation.
Journal ArticleDOI
Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis.
Yanyong Yang,Bailong Li,Cong Liu,Yunhai Chuai,Jixiao Lei,Fu Gao,Jianguo Cui,Ding Sun,Ying Cheng,Chuanfeng Zhou,Jianming Cai +10 more
TL;DR: H2 protected the immune system and alleviated the hematological injury induced by IR, and rescued the radiation-caused depletion of white blood cells and platelets.
Journal ArticleDOI
Novel Treatment for Mantle Cell Lymphoma Including Therapy-Resistant Tumor by NF-κB and mTOR Dual-Targeting Approach
Nagendra K. Chaturvedi,Rajkumar N. Rajule,Ashima Shukla,Prakash Radhakrishnan,Gordon L. Todd,Amarnath Natarajan,Julie M. Vose,Shantaram S. Joshi +7 more
TL;DR: Results suggest that 13-197 as a single agent disrupts the NF-κB and mTOR pathways leading to suppression of proliferation and increased apoptosis in malignant MCL cells including reduction in tumor burden in mice.