Jolyon Hendry

Jolyon Hendry
The University of Manchester · Faculty of Medical and Human Sciences

BSc, MSc, PhD, DSc

About

391
Publications
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11,395
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Publications

Publications (391)
Article
Full-text available
There has been a recent revival of interest in the FLASH effect, after experiments have shown normal tissue sparing capabilities of ultra-high-dose-rate radiation with no compromise on tumour growth restraint. A model has been developed to investigate the relative importance of a number of fundamental parameters considered to be involved in the oxy...
Article
Full-text available
In human skin, keratinopoiesis is based on a functional hierarchy among keratinocytes, with rare slow-cycling stem cells responsible for the long-term maintenance of the tissue through their self-renewal potential, and more differentiated daughter progenitor cells actively cycling to permit epidermal renewal and turn-over every month. Skin is a rad...
Article
The response of the intestine to (low linear-energy-transfer) ionising radiation is reviewed regarding the cellular basis to the reactions, the regenerative processes which restore the tissue, and external agents which aid its recovery. In the steady-state, it is generally considered that the crypt cell lineages in both small and large intestine ar...
Conference Paper
The radiological protection system for cancer risk is based on a conceptual framework involving the linear-no-threshold and relative risk models, cancer risk differences among tissues, dose-rate effects, and changes in the risk of radiation carcinogenesis by age at exposure and attained age. Human epidemiological data for cancer incidence versus do...
Article
Full-text available
Background: A recent paper by Tomasetti and Vogelstein (Science 2015 347 78-81) suggested that the variation in natural cancer risk was largely explained by the total number of stem-cell divisions, and that most cancers arose by chance. They proposed an extra-risk score as way of distinguishing the effects of the stochastic, replicative component...
Data
Datasets used for analysis. (ZIP)
Data
R code and output files used for analysis. (ZIP)
Data
Supplementary Analysis. Tables A, B, Analogs of Tables 4 and 5, omitting tumors with short latency (leukemia, thyroid, bone). (DOCX)
Data
Supplementary Figures A, B. (DOCX)
Article
Full-text available
Current knowledge of stem cell characteristics, maintenance and renewal, evolution with age, location in 'niches', and radiosensitivity to acute and protracted exposures is reviewed regarding haematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone. The identity of the target cells for carcinogenesis continues to point t...
Article
Tissue reactions (deterministic effects) become manifest either early or late after doses above a threshold dose, which is the basis for recommended dose limits for avoiding such effects. Threshold doses have been defined for comparative purposes at 1% incidence of an effect, although the choice of incidence level may be scenario-dependent in pract...
Article
Current knowledge of stem cell characteristics, maintenance and renewal, evolution with age, location in ‘niches’, and radiosensitivity to acute and protracted exposures is reviewed regarding haematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone. The identity of the target cells for carcinogenesis continues to point t...
Article
This 2014 volume (Akleyev 2014) is the English translation of a book published in the Russian language in 2012. The author is Alexander Akleyev, who has been Director of the Urals Research Center for Radiation Medicine (URCRM) of the Federal Medical-Biological Agency of Russia since 1990. He describes all aspects of the chronic radiation syndrome (...
Article
Background and purpose To analyse biochemical relapse-free-survival results for prostate cancer patients receiving combined external beam and high-dose-rate brachytherapy, in comparison with expected results using projections based on dose/fractionation/response parameter values deduced from a previous external-beam-alone 5969-patient multicentre d...
Article
Objective: To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma. Methods: Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair...
Article
Aims: This paper details the considerations and calculations made by this centre for the implementation of the biologically equivalent dose in 2 Gy fractions (EQD2) radiobiology calculations recommended by the Gynaecological Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology, in converting our cervix, body o...
Article
For protection purposes, the biological effects of radiation are separated into stochastic effects (cancer, hereditary effects) presumed to be unicellular in origin, and tissue reactions due to injury in populations of cells. The latter are deterministic effects, renamed 'tissue reactions' in the 2007 Recommendations of the International Commission...
Article
New developments in knowledge of radiation effects on tissue stem cells were discussed in a Workshop held at the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan, 18-19 January 2012. Stem cells and their niche in intestinal mucosa, haemopoietic tissue, hair follicles, and spermatogenesis were discussed variously with regard to radio...
Article
This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of ‘practical’ threshold doses for tissue injury defined at the level of 1% incidence. Estimates are g...
Article
Full-text available
Purpose: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this hasprompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will providea significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionationsensi...
Article
There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this has prompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will provide a significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionation sensitiviti...
Article
Full-text available
When reporting radiation therapy procedures, International Commission on Radiation Units and Measurements (ICRU) recommends specifying absorbed dose at/in all clinically relevant points and/or volumes. In addition, treatment conditions should be reported as completely as possible in order to allow full understanding and interpretation of the treatm...
Book
Full-text available
This report is based on work conducted by the AGIR Subgroup on Circulatory Disease Risk. The report reviews the epidemiological, experimental and medical evidence for radiation exposure elevating the incidence of circulatory diseases. Increased evidence of an association between circulatory diseases and radiation exposures has become available over...
Article
This AGIR report (RCE-16) reviews the epidemiological, experimental and medical evidence for radiation exposure elevating the incidence of circulatory diseases. This report is based on work conducted by the Advisory Group on Ionising Radiation (AGIR) subgroup on circulatory disease risk. Increased evidence of an association between circulatory di...
Article
To examine the effect of the human papillomavirus (HPV) type 16-E6 (HPV 'early' gene) oncoprotein on in vitro radiosensitivity of HPV-negative/p53 mutant C33a cervical cancer cells. The human cervical cancer cell line C33a was stably transfected with either the HPV16 E6 cDNA cloned into the vector pcDNA3.0 (C33aE6) or the empty-vector control (C33a...
Article
Full-text available
Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of (222)Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects...
Article
From the data available, PDR is a safe and effective form of brachytherapy. It is also likely to have the radiobiologic advantages associated with LDR over the large doses per fraction used with HDR brachytherapy. There are practical advantages of using PDR in terms of a requirement for less shielding and, in general, the use of two rather than the...
Article
The types and levels of risk associated with certain ranges of radiation dose are summarised from recommendations of the International Commis sion on Radiological Protection in 2007. There are estimates of threshold doses for various lethal radiation-induced syndromes, and for reactions in various tissues and organs including the lens (concerning c...
Article
Radiation oncology addresses the use of ionizing irradiation in therapeutic purposes in malignant and some non-malignant diseases. Its aim is either curative or palliative, achieved either alone or in a combination with other treatment modalities. Its foundation lies in the field of radiation biology, while medical physics and dosimetry ensure tech...
Article
The testes of prepubertal rats were locally irradiated with 300 kVp x-rays to doses of between 1 and 15 Gy. Leydig cell function was assessed between 2 and 36 weeks post-irradiation. Dysfunction was observed at two weeks as evidenced by a reduction in serum levels of testosterone to between 40 and 70% of control, with a threshold dose of about 5 Gy...
Article
The International Atomic Energy Agency organized an international conference called, "Quality Assurance and New Techniques in Radiation Medicine" (QANTRM). It dealt with quality assurance (QA) in all aspects of radiation medicine (diagnostic radiology, nuclear medicine, and radiotherapy) at the international level. Participants discussed QA issues...
Article
The prescribed total radiation dose should be administered within a specific time. In daily clinical practice, however, unplanned treatment interruptions resulting in prolongation of the overall treatment time are predictable. The present review evaluated the existing published data regarding the affect of the prolongation of the overall treatment...
Article
Full-text available
This paper describes the biological mechanisms of normal tissue reactions after radiation therapy, with reference to conventional treatments, new treatments, and treatments in developing countries. It also describes biological reasons for the latency period before tissue complications arise, the relationship of dose to incidence, the effect of incr...
Article
The International Atomic Energy Agency (IAEA) held a Technical Meeting of Consultants to (1) discuss a selection of relatively new agents, not those well-established in clinical practice, that operated through a variety of mechanisms to sensitize tumors to radiation and (2) to compare and contrast their tumor efficacy, normal tissue toxicity, and s...
Article
This paper summarises the conclusions of a working group established jointly by the International Atomic Energy Agency (IAEA) and the International Commission on Radiation Units and Measurements (ICRU) to address some of the relative biological effectiveness (RBE) issues encountered in ion-beam therapy. Special emphasis is put on the selection and...
Chapter
Sterilisation of tissues means the inactivation of harmful bacteria and possibly viruses in the tissue. The tissue consists of many cell populations that already are reproductively inert, as well as structural extracellular matrices. Inactivation of these organisms is caused by ionisations that break the DNA molecule irreparably.About 40% of the DN...
Article
There is increasing interest in radiogenomics and the characterization of molecular profiles that predict normal tissue and tumor radioresponse. A meeting in Amsterdam was organized by the International Atomic Energy Agency to discuss this topic on an international basis. This report is not completely exhaustive, but highlights some of the ongoing...
Article
Depleted uranium (DU) has been claimed to contribute to health problems both in military personnel directly involved in war actions as well in military and civilian individuals who resided in areas where DU ammunition was expended. Due to the low specific radioactivity and the dominance of alpha-radiation, no acute health risk can be attributed to...
Article
Full-text available
The epidermal growth factor receptor (EGFR) is expressed in a wide variety of epithelial tumours including carcinoma of the bladder. Stimulation of the EGFR pathway is blocked by ZD1839 (Iressa), a highly selective EGFR tyrosine kinase inhibitor. Radical radiotherapy is an established organ sparing treatment option for muscle invasive bladder cance...
Article
The rationale for introducing ion beams in cancer therapy is the high level of physical selectivity that can be achieved with ions, equal or even better than with proton beams or modern photon techniques, as well as the potential advantage of high-LET radiations for some tumour types and sites. The radiobiological arguments for high-LET radiation i...
Article
Based on recent advances, this article aims to review the biological basis for the use of either radiation or drug-eluting stents for the prevention of restenosis, and to elucidate the complementary role that they may play in the future. Vascular restenosis is a multifactorial process primarily driven by the remodeling of the arterial wall, as well...
Article
RH1 is a new bioreductive agent that was developed as a cytotoxic agent with selectivity for tumour cells expressing high levels of the enzyme DT-diaphorase (DTD). The aim of the present study was to investigate the cytotoxicity of RH1 in relation to cellular levels of reducing enzymes and any interaction of RH1 with ionizing radiation under oxic a...
Article
Purpose: RH1 is a newly developed bioreductive agent, and its bioactivation is mediated by the enzyme DT-diaphorase (DTD). We have shown previously that RH1 is highly cytotoxic against cells expressing high DTD, using the p53-mutated MDA231 human breast cancer cell line transfected with the DTD gene (D7 cells). We now report that both RH1 and gamm...
Article
The diaziridiny/benzoquinone RH1 is shortly to enter a phase I clinical trial. The drug was originally designed as a substrate for the enzyme DT-diaphorase (DTD) such that metabolic activation of the drug would lead to toxicity. To evaluate this, we have measured the toxicity of RH1 in a pair of non-small cell lung cancer (NSCLC) cell lines of wide...
Article
This study reanalysed the results of the Cs-137 low-dose-rate brachytherapy trials for stage I and II cervix carcinoma at the Christie Hospital, Manchester, UK, in order to quantify the clinical outcome as a function of dose, and to extract radiobiological parameter values by modelling the data for local control and morbidity. Kaplan-Meier survival...
Article
Full-text available
The aim of this study was to establish the radiosensitising properties of gemcitabine in a pair of related bladder tumour cell lines with differential radiosensitivity. The radioresistant bladder tumour cell line MGH-U1 and its radiosensitive mutant clone, S40b (both p53 mutant), had SF(2) values (surviving fraction at 2 Gy) of 0.98 and 0.64, respe...
Article
To examine the contribution of endonuclease III (Nth)-repairable lesions to the cytotoxicity of ionizing radiation (IR) and hydrogen peroxide (H2O2) in the yeast Saccharomyces cerevisiae. A selectable expression vector containing the E. coli nth gene was transformed into two different wild-type strains (7799-4B and YNN-27) as well as one rad52 muta...
Article
Estimates of the clonogen content (number of microcolony-forming cells) of murine intestinal crypts using microcolony assays show an apparent dependence on the radiation dose used in the assay of clonogen content. Crypt radiation survival curves often show increased curvature beyond that expected on the basis of the conventional linear-quadratic mo...
Article
To estimate the benefits of dose escalation in hypofractionated intensity-modulated radiotherapy (IMRT) for prostate cancer, using radiobiologic modeling and incorporating positional uncertainties of organs. Biologically based mathematical models for describing the relationships between tumor control probability (TCP) and normal-tissue complication...
Article
The effects on persons of ionizing radiation can be quantified on three major pathways. At the present time, it is not possible to understand fully the basis of mechanistic principles of the interaction of ionizing radiation with the critical macromolccules, i.e. DNA, cell nuclei, cells, and body tissue, also because of the stochastic methods to be...
Article
Full-text available
Unscheduled interruption of a radiotherapy treatment can lead to significant loss in local tumour control, particularly in tumours that repopulate rapidly. General guidelines for dealing with such treatment gaps have been issued by the Royal College of Radiologists and more specific advice on the use of compensation methods has been published previ...
Article
Full-text available
The single-cell gel electrophoresis (Comet) assay has been widely used to measure DNA damage in human sperm in a variety of physiological and pathological conditions. We investigated the effects of in vivo radiation, a known genotoxin, on spermatogenic cells of the mouse testis and examined sperm collected from the vas deferens using the neutral Co...
Article
To characterize the role of various cellular damagesensing, processing and survival genes in the in-vitro radiosensitivity of haemopoietic colony-forming cells. Bone marrow cells from a range of different gene-knockout mice were irradiated in vitro with graded radiation doses and assayed for colony-forming efficiency. Colony-forming efficiency in t...
Article
A question pertinent to carcinogenesis after low doses and tissue response after high doses is whether the apoptotically sensitive cells in cell lineages are a part of the stem cell population or a daughter population, and whether mutations that affect stem cell response also affect the cell population susceptible to apoptosis. This has now been ad...
Article
Full-text available
Cellular survival following ionising radiation-mediated damage is primarily a function of the ability to successfully detect and repair DNA double-strand breaks (DSBs). Previous studies have demonstrated that radiosensitivity, determined as a reduction in colony forming ability in vitro, may be related to the incorrect repair (misrepair) of DSBs. T...
Article
The large patient-to-patient variability in the grade of normal tissue injury after a standard course of radiotherapy is well established clinically. A better understanding of this individual variation may provide valuable insights into the pathogenesis of radiation damage and the prospects of predicting the outcome. To estimate the relative import...
Article
Unconventional, more aggressive irradiation protocols are usually associated with aggravation of acute reactions. In recent clinical studies, this has resulted in modulation of late effects in the same organ. This phenomenon has been termed consequential late effect (CLE). Correlations between acute and late effects have been reported in a number o...
Article
To use radiobiological modelling to estimate the number of initial days of treatment imaging required to gain most of the benefit from off-line correction of systematic errors in the conformal radiation therapy of prostate cancer. Treatment plans based on the anatomical information of a representative patient were generated assuming that the patien...