Radiation signatures in childhood thyroid cancers after the Chernobyl accident: Possible roles of radiation in carcinogenesis

After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident, cancer risk from low-dose radiation exposure has been deeply concerning. The linear no-threshold model is applied for the purpose of radiation protection, but it is a model based on the concept that ionizing radiation induces stochastic oncogenic alterations in the target cells. As the elucidation of the mechanism of radiation-induced carcinogenesis is indispensable to justify the concept, studies aimed at the determination of molecular changes associated with thyroid cancers among children who suffered effects from the Chernobyl nuclear accident will be overviewed. We intend to discuss whether any radiation signatures are associated with radiation-induced childhood thyroid cancers

How much do health care providers value a community-based asthma care program? – a survey to collect their opinions on the utilities of and barriers to its uptake

<p>Abstract</p> <p>Background</p> <p>A comprehensive asthma care program (ACP) based on Canadian Asthma Consensus Guidelines was implemented in 8 primary care sites in Ontario, Canada. A survey was distributed to health care providers' (HCPs) to collect their opinions on the utilities of and barriers to the uptake of the ACP.</p> <p>Methods</p> <p>A 39-item self-administered survey was mailed to 184 HCPs and support staff involved in delivering the ACP at the end of implementation. The items were presented in mixed formats with most items requiring responses on a five-point Likert scale. Distributions of responses were analyzed and compared across types of HCPs and sites.</p> <p>Results</p> <p>Of the 184 surveys distributed, 108 (59%) were returned, and of that, 83 were completed by HCPs who had clinical contact with the patients. Overall, 95% of the HCPs considered the ACP useful for improving asthma care management. Most HCPs favored using the asthma care map (72%), believed it decreased uncertainties and variations in patient management (91%), and considered it a convenient and reliable source of information (86%). The most commonly reported barrier was time required to complete the asthma care map. Over half of the HCPs reported challenges to using spirometry, while almost 40% identified barriers to using the asthma action plan.</p> <p>Conclusion</p> <p>Contrary to the notion that physicians believe that guidelines foster cookbook medicine, our study showed that HCPs believed that the ACP offered an effective and reliable approach for enhancing asthma care and management in primary care.</p

Mdm2-SNP309 polymorphism in prostate cancer: no evidence for association with increased risk or histopathological tumour characteristics

The search for inherited cancer susceptibility factors is a major focus of epidemiologic cancer studies. Analyses of single-nucleotide polymorphisms (SNP) in a variety of genes revealed a correlation between a specific allele variant and cancer predisposition. Human mouse double-minute 2 protein (Mdm2) is a cellular E3 ligase capable of ubiquitination and degradation of p53. Therefore, Mdm2 is a crucial factor of cell cycle control and cell survival. The Mdm2 promoter SNP309 was shown to increase Mdm2 expression and can, thereby, inhibit the p53 pathway. This SNP was found to be associated with increased risk and early onset of various malignancies. For prostate cancer no studies are reported to date. In a case–control study we determined the distribution of the Mdm2 SNP309 in 145 male subjects with prostate cancer and in 124 male controls without any malignancy using RFLP analysis. Cases and controls showed a similar distribution of the SNP (P=0.299). Genotype distribution showed neither an association with histopathological characteristics of the tumours nor with prognosis. Age at disease onset was also not modified by the SNP. This first study of the Mdm2 SNP309 in prostate cancer patients suggests no correlation between a certain allelic variant and an increased cancer risk

Chromosomal radiosensitivity and acute radiation side effects after radiotherapy in tumour patients - a follow-up study

Radiotherapists are highly interested in optimizing doses especially for patients who tend to suffer from side effects of radiotherapy (RT). It seems to be helpful to identify radiosensitive individuals before RT. Thus we examined aberrations in FISH painted chromosomes in in vitro irradiated blood samples of a group of patients suffering from breast cancer. In parallel, a follow-up of side effects in these patients was registered and compared to detected chromosome aberrations. METHODS: Blood samples (taken before radiotherapy) were irradiated in vitro with 3 Gy X-rays and analysed by FISH-painting to obtain aberration frequencies of first cycle metaphases for each patient. Aberration frequencies were analysed statistically to identify individuals with an elevated or reduced radiation response. Clinical data of patients have been recorded in parallel to gain knowledge on acute side effects of radiotherapy. RESULTS: Eight patients with a significantly elevated or reduced aberration yield were identified by use of a t-test criterion. A comparison with clinical side effects revealed that among patients with elevated aberration yields one exhibited a higher degree of acute toxicity and two patients a premature onset of skin reaction already after a cumulative dose of only 10 Gy. A significant relationship existed between translocations in vitro and the time dependent occurrence of side effects of the skin during the therapy period. CONCLUSIONS: The results suggest that translocations can be used as a test to identify individuals with a potentially elevated radiosensitivity

Family physicians' perspectives on practice guidelines related to cancer control

BACKGROUND: Family physicians (FPs) play an important role in cancer control. While FPs' attitudes towards, and use of guidelines in general have been explored, no study has looked at the needs of FPs with respect to guidelines for the continuum of cancer control. The objective of this study was to understand which guideline topics FPs consider important. METHODS: Five group interviews were conducted by telephone with FPs from across Ontario, Canada. Transcripts were analyzed inductively. Content analysis identified emergent themes. Themes are illustrated by representative quotes taken from the transcripts. RESULTS: The main areas where FPs felt guidelines were needed most included screening – a traditional area of responsibility for FPs – and treatment and follow-up – areas where they felt they lacked the knowledge to best support patients. Confusion over best practice when faced with conflicting guidelines varied according to disease site. FPs defined good guideline formats; the most often cited forms of presentation were tear-off sheets to use interactively with patients, or a binder. Computer-based dissemination was acknowledged as the best way of widely distributing material that needs frequent updates. However, until computer use is a common aspect of practice, mail was considered the most viable method of dissemination. Guidelines designed for use by patients were supported by FPs. CONCLUSIONS: Preferred guideline topics, format, dissemination methods and role of patient guidelines identified by FPs in this study reflect the nature of their practice situations. Guideline developers and those supporting use of evidence-based guidelines (e.g., Canadian Strategy for Cancer Control) have a responsibility to ensure that FPs are provided with the resources they identify as important, and to provide them in a format that will best support their use

Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays

To identify candidate genes relevant for prostate tumour prognosis and progression, we performed an exhaustive gene search in seven previously described genomic-profiling studies of 161 prostate tumours, and four expression profiling studies of 61 tumours. From the resulting list of candidate genes, six were selected for protein-expression analysis based on the availability of antibodies applicable to paraffinised tissue: fatty acid synthase (FASN), MYC, β-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1α (PPP1CA) and PP2A (PPP2CB) and metastasis suppressor NM23-H1. These candidates were analysed by immunohistochemistry (IHC) on a tissue microarray containing 651 cores of primary prostate cancer samples and benign prostatic hyperplasias (BPH) from 175 patients. In univariate analysis, expression of PP1α (P=0.001) was found to strongly correlate with Gleason score. MYC immunostaining negatively correlated with both pT-stage and Gleason score (P<0.001 each) in univariate as well as in multivariate analysis. Furthermore, a subgroup of patients with high Gleason scores was characterised by a complete loss of BARK1 protein (P=0.023). In conclusion, our study revealed novel molecular markers of potential diagnostic and therapeutic relevance for prostate carcinoma

FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome

This study examines the clinical impact of PTEN genomic deletions using fluorescence in situ hybridisation (FISH) analysis of 107 prostate cancers, with follow-up information covering a period of up to 10 years. Tissue microarray analysis using interphase FISH indicated that hemizygous PTEN losses were present in 42/107 (39%) of prostatic adenocarcinomas, with a homozygous PTEN deletion observed in 5/107 (5%) tumours. FISH analysis using closely linked probes centromeric and telomeric to the PTEN indicated that subband microdeletions accounted for ∼70% genomic losses. Kaplan–Meier survival analysis of PTEN genomic losses (hemizygous and homozygous deletion vs not deleted) identified subgroups with different prognosis based on their time to biochemical relapse after surgery, and demonstrated significant association between PTEN deletion and an earlier onset of disease recurrence (as determined by prostate-specific antigen levels). Homozygous PTEN deletion was associated with a much earlier onset of biochemical recurrence (P=0.002). Furthermore, PTEN loss at the time of prostatectomy correlated with clinical parameters of more advanced disease, such as extraprostatic extension and seminal vesicle invasion. Collectively, our data indicates that haploinsufficiency or PTEN genomic loss is an indicator of more advanced disease at surgery, and is predictive of a shorter time to biochemical recurrence of disease

Lifetime study in mice after acute low-dose ionizing radiation: a multifactorial study with special focus on cataract risk

Because of the increasing application of ionizing radiation in medicine, quantitative data on effects of low-dose radiation are needed to optimize radiation protection, particularly with respect to cataract development. Using mice as mammalian animal model, we applied a single dose of 0, 0.063, 0.125 and 0.5 Gy at 10 weeks of age, determined lens opacities for up to 2 years and compared it with overall survival, cytogenetic alterations and cancer development. The highest dose was significantly associated with increased body weight and reduced survival rate. Chromosomal aberrations in bone marrow cells showed a dose-dependent increase 12 months after irradiation. Pathological screening indicated a dose-dependent risk for several types of tumors. Scheimpflug imaging of the lens revealed a significant dose-dependent effect of 1% of lens opacity. Comparison of different biological end points demonstrated long-term effects of low-dose irradiation for several biological end points