scholarly journals Radiation-Stimulated Epigenetic Reprogramming of Adaptive-Response Genes in the Lung: An Evolutionary Gift for Mounting Adaptive Protection against Lung Cancer

Dose-Response ◽  
2008 ◽  
Vol 7 (2) ◽  
pp. dose-response.0 ◽  
Author(s):  
Bobby R. Scott ◽  
Steven A. Belinsky ◽  
Shuguang Leng ◽  
Yong Lin ◽  
Julie A. Wilder ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adaptive Response ◽  
Risk Model ◽  
Epigenetic Reprogramming ◽  
Histone Deacetylation ◽  
Early Years ◽  
High Dose ◽  
Alpha Radiation ◽  
Adaptive Protection ◽  
Radiation Induced

Humans are continuously exposed to low-level ionizing radiation from natural sources. However, harsher radiation environments persisted during our planet's early years and mammals survived via an evolutionary gift - a system of radiation-induced natural protective measures (adaptive protection). This system includes antioxidants, DNA repair, apoptosis of severely damaged cells, epigenetically regulated apoptosis ( epiapoptosis) pathways that selectively remove precancerous and other aberrant cells, and immunity against cancer. We propose a novel model in which the protective system is regulated at least in part via radiation-stress-stimulated epigenetic reprogramming (epireprogramming) of adaptive-response genes. High-dose radiation can promote epigenetically silencing of adaptive-response genes ( episilencing), for example via promoter-associated DNA and/or histone methylation and/or histone deacetylation. Evidence is provided for low linear-energy-transfer (LET) radiation-activated natural protection (ANP) against high-LET alpha-radiation-induced lung cancer in plutonium-239 exposed rats and radon-progeny-exposed humans. Using a revised hormetic relative risk model for cancer induction that accounts for both epigenetic activation ( epiactivation) and episilencing of genes, we demonstrate that, on average, >80% of alpha-radiation-induced rat lung cancers were prevented by chronic, low-rate gamma-ray ANP. Interestingly, lifetime exposure to residential radon at the Environmental Protection Agency's action level of 4 pCi L−1 appears to be associated with on average a > 60% reduction in lung cancer cases, rather than an increase. We have used underlined italics to indicate newly introduced terminology.

scholarly journals Impact of [18F]FDG-PET and [18F]FLT-PET-Parameters in Patients with Suspected Relapse of Irradiated Lung Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 279
Author(s):  
Tine N. Christensen ◽  
Seppo W. Langer ◽  
Gitte Persson ◽  
Klaus Richter Larsen ◽  
Annemarie G. Amtoft ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Fdg Pet ◽  
Tumor Volume ◽  
High Dose ◽  
Flt Pet ◽  
Pet Ct ◽  
Radiation Induced ◽  
Fdg Pet Ct ◽  
Induced Changes

Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-uptake. The 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUVmax and FLT-SUVmax were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUVmax: 12.8 vs. 4.2; p < 0.001; median FLT-SUVmax 3.9 vs. 2.2; p < 0.001). A relapse within HDV had higher FDG-SUVpeak (median FDG-SUVpeak: 7.1 vs. 3.5; p = 0.014) and was larger (median metabolic tumor volume (MTV50%): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV50%) was prognostic for the overall survival (hazard ratio: 1.07 pr cm3 [1.01–1.13]; p = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUVmax and FLT-SUVmax may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.

Radiation-Induced Sarcoma After High-Dose Thoracic Radiation Therapy in Non–Small-Cell Lung Cancer

2007 ◽  
Vol 25 (12) ◽  
pp. 1621-1623 ◽  
Author(s):  
Thomas E. Stinchcombe ◽  
Ruth Walters ◽  
Amir H. Khandani ◽  
Mark A. Socinksi
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Thoracic Radiation ◽  
Radiation Induced

THE PREVALENCE OF HEPATITIS B REACTIVATION (HBV) IN CANCER PATIENTS TREATING WITH CHEMOTHERAPY

2016 ◽  
pp. 74-80
Author(s):  
Phuong Phung ◽  
Thi Thuy Nguyen
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Hepatitis B ◽  
Cancer Patients ◽  
Positive Control ◽  
High Dose ◽  
Hbv Reactivation ◽  
Endemic Region ◽  
Hepatitis B Reactivation ◽  
Cancer Breast

ackground and Objectives: Nowadays, the incidence of cancer is constantly increasing in the world as well as in Vietnam. The treatment of cancer is based on multimodality principle. Among those principal modalities, chemotherapy is widely used for different purposes such as neoadjuvant, andjuvant and palliation. However, chemotherapy can induce activation of latent infections, including hepatitis B. Vietnam is in the endemic region of hepatitis B so the reactivation of hepatitis B on cancer patients with chemotherapy has emerged a concerned problem. However, few interests were gained on this problem in the aspect of clinical setting or researching. Aims: to determine the prevalence of hepatitis B reactivation (HBV) in cancer patients treating with chemotherapy and to detect some risks factors of this situation. Subjects and methods: descriptive prospective. The study included 33 cancer patients with inactive HBV infection who are treating with chemotherapy. We define HBV reactivation by ALT > 3 ULN and HBV DNA copies > 10 positive control limit. Results: We found 6 patients with reactivated HBV, accounting for 18.18 %. Among reactivated HBV patients, age less than 60 accounts 83,33%. Rate of reactivated HBV in males was 25,00% while this rate in females was 14,28%. Rate of reactivated HBV in lymphoma, lung cancer and breast cancer was 33,33%, 25% và 22,22% respectively. Clinial manifestation of reactivated HBV includes jaundice (33,33%), fulminant hepatic failure (6%) and death (5%). The reactivated rate was higher in patients got high dose of corticoid (28,57%) vs low dose (15,38%). This rate was 29,41% in patients treated with anthracyclines which was higher than in group without anthracyclines. The reactivated rate of HBV was dramatically higher in patients treated with rituximab (75%). Conclusion: the reactivation of hepatitis B on cancer patients with chemotherapy is common. We found 6 patients with reactivated HBV of 33 subjects of the study which accounts 18.18 %. We recognized that reactivated HBV rate was higher subgroups of age < 60 years old, males, patients with lymphoma, lung cancer, breast cancer. Reactivated HBV may be more prevalent in patients with high-dose corticotherapy, anthracyclines and Rituximab. Key words: HBV reactivation, chemotherapy, cancer, hepatitis B

Recombinant adeno-associated virus 9-mediated expression of Kallistatin suppresses lung tumor growth in mice

2020 ◽  
Vol 20 ◽  
Author(s):  
Weihong Qu ◽  
Jianguo Zhao ◽  
Yaqing Wu ◽  
Ruian Xu ◽  
Shaowu Liu
Keyword(s):  
Lung Cancer ◽  
Gene Therapy ◽  
Tumor Growth ◽  
Lung Tumor ◽  
Control Group ◽  
High Dose ◽  
Blank Control Group ◽  
Adeno Associated Virus ◽  
Tumor Tissues ◽  
Subcutaneous Xenograft

Background:: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure although gene therapy may be a promising future alter-native. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgen-ic expression. Objective:: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice. Method:: The subcutaneous xenograft mode were induced by subcutaneous injection of 2×106 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single-stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9）by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 stain-ing to evaluate tumor angiogenesis. Results:: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased. Conclusion:: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and impli-cate rAAV9-Kal as a candidate for gene therapy of lung cancer.

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