“…[ 41 , 42 ]. In traditional radiotherapy, irradiation field includes the lymph region and the large blood vessel, which results in the apoptosis of lymphocytes in the blood vessels at a dose of around 2 Gy [ 43 ]. This increases total cfDNA, but hinders sequencing of tumor-derived DNA.…”
We investigated the plasma levels of tumor-specific cell-free DNA (cfDNA) in 17 stage I–II (early) and IV (advanced) non-small cell lung cancer (NSCLC) patients who underwent radiotherapy. Digital polymerase chain reaction (PCR) and targeted sequencing showed that total and tumor-specific cfDNA levels increased in response to radiotherapy in both early- and advanced-stage NSCLC patients. We detected high copy numbers of epidermal growth factor receptor mutations (L858R and T790M) in the cfDNA samples from stage IV NSCLC patients who underwent stereotactic body radiation therapy to treat brain metastasis related to tyrosine kinase inhibitor (TKI) treatment failure. In conclusion, our study demonstrates that radiotherapy increases tumoral cfDNA levels in the plasma and shows potential to serve as an indicator for diagnosing drug-resistant tumor-related gene mutations in early-stage NSCLC patients or those undergoing molecular targeted therapy.
“…[ 41 , 42 ]. In traditional radiotherapy, irradiation field includes the lymph region and the large blood vessel, which results in the apoptosis of lymphocytes in the blood vessels at a dose of around 2 Gy [ 43 ]. This increases total cfDNA, but hinders sequencing of tumor-derived DNA.…”
We investigated the plasma levels of tumor-specific cell-free DNA (cfDNA) in 17 stage I–II (early) and IV (advanced) non-small cell lung cancer (NSCLC) patients who underwent radiotherapy. Digital polymerase chain reaction (PCR) and targeted sequencing showed that total and tumor-specific cfDNA levels increased in response to radiotherapy in both early- and advanced-stage NSCLC patients. We detected high copy numbers of epidermal growth factor receptor mutations (L858R and T790M) in the cfDNA samples from stage IV NSCLC patients who underwent stereotactic body radiation therapy to treat brain metastasis related to tyrosine kinase inhibitor (TKI) treatment failure. In conclusion, our study demonstrates that radiotherapy increases tumoral cfDNA levels in the plasma and shows potential to serve as an indicator for diagnosing drug-resistant tumor-related gene mutations in early-stage NSCLC patients or those undergoing molecular targeted therapy.
“…Some of these compounds needed to be administered at high doses to protect against radiation induced adverse effects, hence, producing various side effects by themselves. However, it is believed combining two or more compounds with different and or complementary mechanisms of action might lead to reduced toxicity and greater efficacy (3,4) . Moreover, most of agents were tested on normal cells or tissues for their radioprotective potential.…”
Background: Radioprotective effects of melatonin and famotidine were reported in previous studies. In this study, modulating effects of these agents alone or in combination were tested on high dose radiation induced cell lethality in MRC5 and Hela cells. Materials and Methods: DPPH (2,2-Diphenyl-1-picrylhydrazyl) was used to measure antioxidant property of famotidine and melatonin at different concentrations. Famotidine at a concentration of 80 µg/ml and melatonin at a concentration of 80 µg/ml was added to culture flasks containing MRC5 and Hela cells two hr prior to gamma-irradiation. Treated and untreated cells were irradiated with doses of 4 and 8 Gy gammarays. MTT assay was used to measure cell viability 48 and 72 hours after irradiation. Data were analyzed using nonparametric one way analysis of variance (ANOVA). Results: DPPH assay showed high antioxidant potential for melatonin. Presence of melatonin led to significant elevation of cell viability of both MRC5 and Hela cell lines after 4 and 8 Gy gamma-irradiation at both sampling times (p<0.01). However, for Hela cells exposed to 4 Gy, melatonin led to reduced cell viability (p<0.05). Famotidine, did not improve radiation induced cell lethality for both MRC5 and Hela cells exposed to 4 and 8 Gy. Conclusion: Except for 4 Gy irradiated Hela cells, presence of melatonin led to a significant radioprotection against radiation induced cell lethality of cells, Famotidine failed to improve cell viability in both cell lines. The mechanism of radioprotection of melatonin might be attributed to its radical scavenging potential.
“…Thiols and disulfides such as glutathione and glutathione disulfide participate in the regulation of oxidative metabolism and favor the defense against deleterious effects of reactive oxidative intermediates and ionizing radiation. , The importance of redox systems with sulfur-centered species is largely dependent on their potential actions toward proteins and the repair of nucleic acids. , The present contribution is devoted to the microscopic investigation of primary radical processes in the presence of cystamine (Figure ). The interest in this biological disulfide is 2-fold: the limited number of atoms would favor a synergy between experimental data on transient electronic states and further semiquantum simulations, the radioprotective and clinical properties of cystamine in living systems. − 1 Structure of the disulfide molecule investigated in the present work.…”
The primary steps of a one-electron reduction of a disulfide molecule (cystamine) by the infrared
p-like state of an excited hydrated electron have been investigated by femtosecond laser spectroscopy. The
initial electron photodetachment from chloride ion or phenothiazine is triggered by a two-photon ultraviolet
excitation. In homogeneous aqueous cystamine solution, a subpicosecond univalent reduction of the disulfide
molecule by an infrared prehydrated electron competes with the nonadiabatic relaxation of trapped electrons
(electron solvation process). This presolvation one-electron reduction occurs with a characteristic time of 160
± 20 fs at 294 K. Within the electron solvation regime, this elementary redox process is totally achieved in
less than 1 × 10-12 s and exhibits a probability 9 times higher than the radiationless relaxation of an infrared
excited electron. In aqueous organized assemblies (cationic micelles) the partitioning of reactants does not
influence the frequency rate of a prehydration reaction but modifies the early branching between reactive and
nonreactive IR electronic channels. The real-time UV probing of a nascent sulfur-centered radical anion
(RS∴SR-)aq is discussed in the framework of a two-center-three-electron bond.
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