Low-dose hyper-radiosensitivity (HRS) is the phenomenon whereby cells exposed to radiation doses of less than ∼0.5 Gy exhibit increased cell killing relative to that predicted from back-extrapolating high-dose survival data using a linear-quadratic model. While the exact mechanism remains to be elucidated, the involvement of several molecular repair pathways has been documented. These processes in turn are also associated with the response of cells to O6-methylguanine (O6MeG) lesions. We propose a model in which the level of low-dose cell killing is determined by the efficiency of both pre-replicative repair by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT) and post-replicative repair by the DNA mismatch repair (MMR) system. We therefore hypothesized that the response of cells to low doses of radiation is dependent on the expression status of MGMT and MMR proteins. MMR (MSH2, MSH6, MLH1, PMS1, PMS2) and MGMT protein expression signatures were determined in a panel of normal (PWR1E, RWPE1) and malignant (22RV1, DU145, PC3) prostate cell lines and correlated with clonogenic survival and cell cycle analysis. PC3 and RWPE1 cells (HRS positive) were associated with MGMT and MMR proficiency, whereas HRS negative cell lines lacked expression of at least one (MGMT or MMR) protein. MGMT inactivation had no significant effect on cell survival. These results indicate a possible role for MMR-dependent processing of damage produced by low doses of radiation.
Lynn Martin, Brian Marples, Mary Coffey, Mark Lawler, Donal Hollywood, and Laure Marignol
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Publications
Courtship raises male fertilization success through post-mating sexual selection in a spider.
Courtship is well known for its positive effects on mating success. However, in polyandrous species, sexual selection continues to operate after copulation. Cryptic female choice is expected under unpredictable mating rates in combination with sequential mate encounters. However, there are very few accounts of the effects of courtship on cryptic female choice, and the available evidence is often correlative.
Mature Argiope bruennichi females are always receptive and never attack or reject males before mating, although sexual cannibalism after mating occurs regularly. Still, males usually perform an energetic vibratory display prior to copulation. We tested the hypothesis that beneficial effects of courtship arise cryptically, during or after mating, resulting in increased paternity success under polyandry. Manipulating courtship duration experimentally, we found that males that mated without display had a reduced paternity share even though no differences in post-copulatory cannibalism or copulation duration were detected. This suggests that the paternity advantage associated with courtship arose through female-mediated processes after intromission, meeting the definition of cryptic female choice.
Jutta M Schneider and Kristiani Lesmono
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Palliative radiotherapy: modelling and evaluating the impact of factors in the treatment times and workload of orthovoltage units–a pilot study
Patients treated with palliative intent present a complex issue for radiotherapy departments in terms of their specific care needs, treatment times, and the productivity of orthovoltage resources. This study seeks to evaluate and quantify patient-related factors,...
Towards real-time radiation therapy: GPU accelerated superposition/convolution.
We demonstrate the use of highly parallel graphics processing units (GPUs) to accelerate the superposition/convolution (S/C) algorithm to interactive rates while reducing the number of approximations. S/C first transports the incident fluence to compute the total...
A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform
Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP's treatment...
Strategies for treating cutaneous T-cell lymphoma: part 1: remission.
In this article, the management of cutaneous T-cell lymphoma will be presented in terms of the strategies that guide treatment. With the strategies and goals in mind, treatment options to achieve a measurable goal will be presented. The treatments presented in this...
Dose-effect relationships for recurrence of keloid and pterygium after surgery and radiotherapy
PURPOSE: To show radiation dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. METHODS AND MATERIALS: Using PubMed, we performed a retrospective review of articles reporting incidences and/or dose-response...
Practical aspects of commissioning and calibration of clinical orthovoltage units
Despite the emphasis on megavoltage radiation therapy, kV units are still being acquired and used in clinical radiation therapy for superficial lesions and specialized treatment techniques. The dosimetry of kV X-ray beams is tricky and subject to increased...
Hypoxia response element-driven cytosine deaminase/5-fluorocytosine gene therapy system: a highly effective approach to overcome the dynamics of tumour hypoxia and enhance the radiosensitivity of prostate cancer cells in vitro.
We proposed to exploit hypoxia-inducible factor (HIF)-1alpha overexpression in prostate tumours and use this transcriptional machinery to control the expression of the suicide gene cytosine deaminase (CD) through binding of HIF-1alpha to arrangements of hypoxia response elements. CD is a prodrug activation enzyme, which converts inactive 5-fluorocytosine to active 5-fluorouracil (5-FU), allowing selective killing of vector containing cells.
Laure Marignol, Ruth Foley, Thomas Southgate, Mary Coffey, Donal Hollywood and Mark Lawler
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