Single-Ion Microbeam for Applications in Radiobiology:State of the Art

Single-Ion Microbeam (SIM) is uniquely capable of precisely delivering a predefined number of charged particles (precise doses of radiation) to individual cells or sub-cellular targets in situ. Since the early 1990's, there has been an ever-increasing interest in developing and applying the SIM technique to problems in radiobiology for studies of cell and tissue damaged by ionizing radiations. Potential applications for SIM in radiobiology continues to grow and have been diversified. There are currently more than 14 SIM facilities worldwide, and they have been in a constant state of evolution. This paper reviews the current state of SIM research worldwide and the related pivotal technological developments in the fields of both biophysics and radiobiology. Representative applications and the perspective of SIM are also introduced and discussed.

3-73 Progress on Radiation Risk Assessment in the Department of Space Radiobiology

Due to the uncertainties of exposure and different radiosensitivity of individuals, development of novel biodosemeters to assess radiation risk is necessary. Researches related to the biodosimetry after X-ray and energized particle exposure have been carried out during the past year. An International Symposium on Bone Science and Space Radiobiology was successfully held in Institute of Modern Physics.

The challenges of precision radiotherapy technology to the traditional theory of radiobiology

With the development of modern computing technology and medical physics,radiotherapy has made great progress.The theoretical basis of radiobiology seems to lag behind the clinical application of radiotherapy,which hampers the further improvement of treatment efficacy and the optimization of treatment modality.In this paper,some emerging challenges of precision radiotherapy technology to the traditional theory of radiobiology,such as radiosensitivity,dose-response curve and survival curve,linear-quadratic model,4Rs theory,as well as the interaction between cancer and microenvironment,radiation-induced second primary cancers(RISPC),will be discussed.The interplay between precision radiotherapy and traditional radiobiology theories will be addressed with the aim to potentially solve some of the challenging problems.

Comparison of the effects of two typesof multileaf collimators on tumor control probabilityin radiotherapy for breast cancer after conservativesurgery based on the EUD model

Objective To compute and compare the tumor control probability(TCP) of volumetric modulated arc therapy(VMAT) for breast cancer after conservative surgery based on two types of multileaf collimator(MLC) through a retrospective planning study.Methods For a group of 9 patients diagnosed with left breast cancer,VMAT plan based on Agility MLC and beam modulator(BM) MLC were designed.The prescription dose was 50 Gy covering at least 95% of the planning target volume,2 Gy per fraction.TCPs were calculated according to dose-volume histogram(DVH) analysis.Results The TCP of the BM VMAT plan was slightly higher than that of the Agility VMAT plan(94.61% vs 94.23%) but was inferior with respect to delivery efficiency;the delivery time was reduced for Agility VMAT plan by 35% compared to BM VMAT plan.Conclusion For breast cancer radiation therapy after conservative surgery,BM VMAT plans provide slightly higher TCP while the delivery of Agility VMAT plans is significantly faster than the BM VMAT plans.

THE RADIOBIOLOGIC CHARACTERISTICS OF DNA POLYMERASE β IN HEPATOMAS

To investigate the effects of γ rays on DNA polymerase β properties and its DNA repair functions before or after γ rays exposure, DNA polymerase βactivity, gene expression and mRNA levels in SMMC-LTNM hepatomas horn on nude mice or the samples of the liver cancer tissues from 15 patients were measured with 3H-TTP incorporation test, immunocytochemistry and cytoplasmic dot hybridization analysis, respectively.Irradiation was carried out with 60Co-γ rays at ice bath. It was found that DNA polymerase β activity, gene expression and the amount of mRNA were much higher in hepatoma cells than those in normal hepatocytes (P<0.01). In vitro studies, the enzyme activity both in hepatoma and normal liver cells appeared unchanged within 40 Gy γ-ray exposure. Following whole-body exposure of the nude mice bearing SMMC-LTNM with 2 Gy or 4 Gy of γ rays, DNA polymerase β activity in hepatoma increased temorarily at 48 hours postirradiation, and its gene expression seemed more active.The euzyme mRNA increased to 1.76-fold of the control group. 72 hours after exposure, all of these changes returned to normal levels. DNA polymerase βparticipated in DNA repair synthesis and this effect was different between hepatoma and hepatocytes because there were some biologic differences of the enzyme between hepatoma cells and normal liver cells. These data suggested that DNA polymeraseβactivity, its gene expression and mRNA level in hepatomas could increased temporarily after γ rays exposure, which may facilitate the cells to repair DNA damages from radiation.

Radiobiological effect of abdominal X-ray hypo-fraction irradiation on Wistar rats liver

Objective: The aim of our study was to investigate the impact of abdominal hypo-fraction irradiation on liver damage in rats so as to provide a reference for its clinical application. Methods: A total of 100 Wistar rats were equally randomized to five groups as control, 4 Gy, 6 Gy, 8 Gy and 12 Gy group, and the corresponding fractionated doses were offered. Liver functions were examined at the 2nd, 4th, 6th, 8th and 10th week after irradiation. Morphological changes were observed by HE staining. Expressions of Bcl-2 and Bax were examined by immunohistochemical technique. Results: In all irradiation groups, hepatocellular swell, degeneration, necrosis and even hepatic fibrosis could be seen. The differences of the liver coefficient, Glutamyl pyruvic transaminase (GPT), Glutamyl oxaloacetic transaminase (GOT) were significant among the groups and different time points (F = 11.833-781.972, F = 20.857-264.692, P < 0.001). Expressions of Bcl-2 and Bax were significantly different between each group (F = 211.607, 116.577; P < 0. 001), and between each time point (F = 54.083, 68.749; P < 0. 001). Conclusion: Compare with conventional fraction, abdominal hypo-fraction irradiation may cause radiation damage to rat liver, being dose-and-time dependent. Up-regulation of activating apoptosis protein Bax and down-regulation of inhibiting apoptosis protein Bcl-2 may involve in the process.

Radiotherapy and the cellular DNA damage response: current and future perspectives on head and neck cancer treatment

Incidences of head and neck squamous cell carcinoma(HNSCC)have been on the rise in the last few decades,with a significant risk factor being human papillomavirus(HPV)type-16/18 infection,particularly in the development of oropharyngeal cancers.Radiotherapy(RT)is an important treatment modality for HNSCC,where it promotes extensive cellular DNA damage leading to the therapeutic effect.It has been well-established that HPV-positive HNSCC display better response rates and improved survival following RT compared to HPV-negative HNSCC.The differential radiosensitivity has been largely associated with altered cellular DNA damage response mechanisms in HPV-positive HNSCC,and particularly with the signaling and repair of DNA double strand breaks.However,other factors,particularly hypoxia present within the solid cancer,have a major impact on relative radioresistance.Consequently,recent approaches aimed at enhancing the radiosensitivity of HNSCC have largely centered on targeting key proteins involved in DNA repair,DNA damage checkpoint activation,and hypoxia signaling.These studies have utilised in vitro and in vivo models of HPV-positive and HPV-negative HNSCC and examined the impact of specific inhibitors against the targets in combination with radiation in suppressing HNSCC cell growth and survival.Here,accumulating evidence has shown that targeting enzymes including poly(ADP-ribose)polymerase,ataxia telangiectasia and Rad-3 related,DNA-dependent protein kinase catalytic subunit,and checkpoint kinase 1 can radiosensitise HNSCC cells which should be taken forward in further preclinical studies,with the goal of optimizing the future effective RT treatment of HNSCC.

Secondary malignancy estimation in patients after mastectomy and adjuvant therapy

Aim:Secondary malignancy estimation after radiotherapy of post mastectomy patients is becoming an important subject for comparative treatment planning.The data from modern treatment planning systems provide accurate three-dimensional dose distributions for each individual patients,thereby opening up new possibilities for more precise estimates of secondary cancer incidence rates in the irradiated organs.Methods:This study estimates the probability of secondary malignancy using radiobiological model for post mastectomy patients in a low-resource center,Nigeria.The secondary cancer complication probability(SCCP)was computed for linear,linear-exponent and linear-plateau models.Results:The result shows that comparing the three models the mean SCCP for the contralateral breast ranged between 0.41%-0.93%;for the lung(0.34%-5.93%);while for the chest wall is between 0.65%-31.95%.Also,the result showed that based on the differential dose volume histogram,the SCCP in the chest wall is highest compared to the lung and contralateral breast;while the linear model overestimate the risk of secondary malignancy,the linear-exponent and the linear plateaus gave values not outrageously high.Conclusion:The models in this study have shown that the risk of secondary malignancy in these post mastectomy patients is low.