International Journal of Radiation Biology最新文献

Purpose: Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality. Although HNSCC is mainly caused by tobacco and alcohol consumption, infection by Human Papilloma Virus (HPV) has been also associated with the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCC) during the past decades. HPV-positive HNSCC is characterized by a higher radiosensitivity compared to HPV-negative tumor. While several clinical trials are evaluating de-escaladed radiation doses strategies in HPV-positive HNSCC, molecular mechanisms associated with relative radioresistance in HPV-negative HNSCC are still broadly unknown. Our goal was to review recently proposed biomarkers of radioresistance in this setting, which may be useful for stratifying tumor's patient according to predicted level of radioresistance.

Conclusions: most of biomarkers of radioresistance in HPV-negative HNSCC are identified using a hypothesis-driven approach, based on molecular mechanisms known to play a key role during carcinogenesis, compared to an unsupervised data-driven approach regardless the biological rational. DNA repair and hypoxia are the two most widely investigated biological and targetable pathways related to radioresistance in HNSCC. The better understanding of molecular mechanisms and biomarkers of radioresistance in HPV-negative HNSCC could help for the development of radiosensitization strategies, based on targetable biomarkers, in radioresistant tumors as well as de-escalation radiation dose strategies, based on biological level of radioresistance, in radiosensitive tumors.

Purpose: To encourage the use of the NTCP0 for evaluating safety as a new alternative of assessing the S-Es of the radiation oncology treatments; and the use of the 'NTCP0cal' methodology that calculates/estimates NTCP0.

Method: Revisions of studies related to use of the NTCP in the evaluations of S-Es. Development of the first version of the Matlab application of our methodology, which provides three options, two of them employ the well-known aspects of a phenomenological model, or the relationship with the TNTCP; where NTCP0 = 100%-TNTCP; and the third option determines NTCP0 from an assumed NTCP discrete probabilistic distribution from the binomial distribution, where one of its parameters is automatically defined from a databased of the Disease locations Vs. Late complications.

Result: As result of revisions of some QUANTEC studies, we can say that: (1) The majority of current NTCP models are DVH-based; (2) The risk of toxicity is the way of evaluating the S-Es of the radiation oncology treatments; and (3) The NTCP are used mainly for evaluations of individual or principal complications or Endpoints of the radiation treatments. The 'NTCP0cal' Matlab application developed in this study has three calculation options. Two of the options provide additional graphical information about the distributions.

Conclusions: The NTCP0 is a new radiobiological concept, its introduction let to correct some current P + and UTCP formulations, and will allow evaluating S-Es in whatever activity involving ionizing radiation, like radiation treatments; and its phenomenological model function of dose prescribed (D = n*d) will allow calculating values of NTCP0 for a range of dose per fraction (d) in a treatment with a determined number of fractions (n), or for range of n for a constant d. The DVH is irrelevant for this model. For whatever radiation treatment given to a population of similar patients under similar circumstances, the NTCP0 is calculated as ratio of the number of patients without acute/late complications and total of them. When this number is unknown, then NTCP0 can be obtained using the 'NTCP0cal' application.

Purpose: We studied the effects of computed tomography (CT) scan irradiation on proliferation and differentiation of human embryonic stem cells (hESCs). It was reported that hESC is extremely radiosensitive; exposure of hESC in cultures to 1 Gy of ionizing radiation (IR) results in massive apoptosis of the damaged cells and, thus, they are eliminated from the cultures. However, after recovery the surviving cells proliferate and differentiate normally. We hypothesized that IR-exposed hESC may still have growth rate disadvantage when they proliferate or differentiate in the presence of non-irradiated hESC, as has been shown for mouse hematopoietic stem cells in vivo.

Materials and methods: To study such competitive proliferation and differentiation, we obtained cells of H9 hESC line that stably express green fluorescent protein (H9GFP). Irradiated with 50 mGy or 500 mGy H9GFP and non-irradiated H9 cells (or vice versa) were mixed and allowed to grow under pluripotency maintaining conditions or under conditions of directed differentiation into neuronal lineage for several passages. The ratio of H9GFP to H9 cells was measured after every passage or approximately every week.

Results: We observed competition of H9 and H9GFP cells; we found that the ratio of H9GFP to H9 cells increased with time in both proliferation and differentiation conditions regardless of irradiation, i.e. the H9GFP cells in general grew faster than H9 cells in the mixtures. However, we did not observe any consistent changes in the relative growth rate of irradiated versus non-irradiated hESC.

Conclusions: We conclude that population of pluripotent hESC is very resilient; while damaged cells are eliminated from colonies, the surviving cells retain their pluripotency, ability to differentiate, and compete with non-irradiated isogenic cells. These findings are consistent with the results of our previous studies, and with the concept that early in pregnancy omnipotent cells injured by IR can be replaced by non-damaged cells with no impact on embryo development.

Purpose: While some evidence of an effect of radiation exposure on respiratory disease at low dose levels has now emerged, there is heterogeneity in the risks between different studies and countries. In this paper, we aim to show the effect of radiation on three different sub-types of respiratory disease mortality through the analysis of the NRRW cohort in UK.

Materials and methods: The NRRW cohort consisted of 174,541 radiation workers. Doses to the surface of the body were monitored using individual film badges. Most of the doses are associated with X-rays and gamma rays and to a less extent of beta and neutron particles. The overall mean 10-year lagged lifetime external dose was 23.2 mSv. Some workers were potentially exposed to alpha particles. However, doses from internal emitters were not available for the NRRW cohort. 25% of male workers and 17% of female workers were identified as being monitored for internal exposure. The Poisson regression methods for grouped survival data with a stratified baseline hazard function were used to describe the dependence of the risk on cumulative external radiation dose. The disease was analyzed by the following subgroups: Pneumonia (1066 cases including 17 cases of influenza), COPD and allied disease (1517 cases) and other remaining respiratory diseases (479 cases).

Results: There was very little radiation effect on pneumonia mortality, but evidence of a reduction in mortality risk for COPD and allied disease (ERR/Sv= -0.56, 95%CI: -0.94, -0.06; p = .02) and an increase in risk for other respiratory disease mortality (ERR/Sv = 2.30, 95%CI: 0.67, 4.62; p = .01) with increasing cumulative external dose were observed. The effects of radiation were more prominent amongst workers monitored for internal exposure. The reduction in mortality risk of COPD and allied disease per cumulative external dose was statistically significant for the radiation workers monitored for internal exposure (ERR/Sv= -0.59, 95%CI: -0.99, -0.05; p = .017) but not significant among the workers who were not monitored (ERR/Sv= -0.43, 95%CI: -1.20, 0.74; p = .42). A statistically significant increased risk was observed for other respiratory diseases among monitored radiation workers (ERR/Sv = 2.46, 95%CI: 0.69, 5.08; p = .019), but not among unmonitored workers (ERR/Sv = 1.70, 95%CI: -0.82, 5.65; p = .25).

Conclusion: The effects of radiation exposure can be different depending on the type of respiratory disease. No effect was seen in pneumonia; a reduction in mortality risk of COPD, and increased mortality risk of other respiratory diseases were observed with cumulative external radiation dose. More studies are needed to verify these findings.

Background: The most attractive features of Auger electrons (AEs) in cancer therapy are their extremely short range and sufficiently high linear energy transfer (LET) for a majority of them. The cytotoxic effects of AE emitters can be realized only in close vicinity to sensitive cellular targets and they are negligible if the emitters are located outside the cell. The nucleus is considered the compartment most sensitive to high LET particles. Therefore, the use of AE emitters could be most useful in specific recognition of a cancer cell and delivery of AE emitters into its nucleus.

Purpose: This review describes the studies aimed at developing effective anticancer agents for the delivery of AE emitters to the nuclei of target cancer cells. The use of peptide-based conjugates, nanoparticles, recombinant proteins, and other constructs for AE emitter targeted intranuclear delivery as well as their advantages and limitations are discussed.

Conclusion: Transport from the cytoplasm to the nucleus along with binding to the cancer cell is one of the key stages in the delivery of AE emitters; therefore, several constructs for exploitation of this transport have been developed. The transport is carried out through a nuclear pore complex (NPC) with the use of specific amino acid nuclear localization sequences (NLS) and carrier proteins named importins, which are located in the cytosol. Therefore, the effectiveness of NLS-containing delivery constructs designed to provide energy-dependent transport of AE emitter into the nuclei of cancer cells also depends on their efficient entry into the cytosol of the target cell.

Purpose: To clarify the radiosensitization mechanism masking the Auger effect of the cells possessing brominated DNA, the electronic properties of DNA-related molecules containing Br were investigated by X-ray spectroscopy and specific heat measurement.

Materials and methods: X-ray absorption near-edge structure (XANES) and X-ray photoemission spectroscopy (XPS) were used to measure the electronic properties of the nucleotides with and without Br. We determined the specific heat of 5-bromouracil crystals with thymine as a reference molecule at low temperatures of 3-48 K to calculate the microscopic state numbers.

Results: Obtained XANES and XPS spectra indicated that both the lowest unoccupied molecular orbital (LUMO) and the core-levels were not affected by the Br incorporation. The state numbers of 5-bromouracil calculated from the specific heats obtained around 25 K was about 1.5 times larger than that for thymine below 20 K, although the numbers were almost the same below 5 K.

Discussion: Our results suggest that the Br atom may not contribute substantially to the LUMO and core-level electronic states of the molecule, but rather to the microscopic states related to the excitation of lattice vibrations, which may be involved in valence electronic states.