Mortality among Thorotrast-exposed patients and an unexposed comparison group in the German Thorotrast study

Becker, Nikolaus; Liebermann, D.; Wesch, H.; Kaick, G. van

doi:10.1016/j.ejca.2008.02.050

Cited by 42 publications

(22 citation statements)

References 12 publications

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“…Known risk factors for BTC are the liver flukes O. viverrini and C. sinensis in high prevalence endemic regions in southeast Asia [1]–[3], as well as primary sclerosing cholangitis [4]–[7], Caroli's disease [8], hepatitis B and hepatitis C [9]–[14], obesity [13], hepatolithiasis [15], [16] and thorotrast contrast exposure [17], [18]. Surgical approaches such as resection and liver transplantation represent the only curative treatment approaches for BTC [19].…”

Section: Introductionmentioning

confidence: 99%

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

et al. 2014

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Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.

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Section: Introductionmentioning

confidence: 99%

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

et al. 2014

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“…IR has been associated with various age-related effects, such as cardiovascular diseases [76, 77], cataracts [78], osteoporosis [79], digestive and respiratory diseases [77]. Exposure to IR shortened the life span of radiologists, radium dial painters, Thorotrast patients and atomic bomb survivors [80, 81]. IR-induced oxidative damage is acknowledged to contribute to ageing in the brain and other organs [82].…”

Section: Radiation and Ageingmentioning

confidence: 99%

Does ionizing radiation influence Alzheimer's disease risk?

Begum

Wang²,

Mori³

et al. 2012

Journal of Radiation Research

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Alzheimer's disease (AD) is a human neurodegenerative disease, and its global prevalence is predicted to increase dramatically in the following decades. There is mounting evidence describing the effects of ionizing radiation (IR) on the brain, suggesting that exposure to IR might ultimately favor the development of AD. Therefore better understanding the possible connections between exposure to IR and AD pathogenesis is of utmost importance. In this review, recent developments in the research on the biological and cognitive effects of IR in the brain will be explored. Because AD is largely an age-related pathology, the effects of IR on ageing will be investigated.

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“…Epidemiological investigations extracting disease-specific and total risk-factors associated with the use of Thorotrast have been carried on and frequently updated in several countries, with especially large cohorts in Portugal [6], Denmark [7], Sweden [8], Japan [9], Germany [10]. These studies pose the problem of the distribution of the incubation periods over a life-long time scale.…”

Section: Introductionmentioning

confidence: 99%

Thorotrast and in vivo thorium dioxide: Numerical simulation of 30 years of α radiation absorption by the tissues near a large compact source

Bianconi

2014

Physica Medica

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Background:The epidemiology of the slightly radioactive contrast agent named Thorotrast presents a very long latency period between the injection and the development of the related pathologies. It is an example of the more general problem posed by a radioactive internal contaminant whose effects are not noteworthy in the short term but become dramatic in the long period. A point that is still to be explored is fluctuations (in space and time) in the localized absorption of radiation by the tissues. Methods:A Monte Carlo simulation code has been developed to study over a 30-year period the daily absorption of α radiation by µm-sized portions of tissue placed at a distance of 0-100 µm from a model source, that approximates a compact thorium dioxide source in liver or spleen whose size is 20 µm. The biological depletion of the daughter nuclei of the thorium series is taken into account. The initial condition assumes chemically purified natural thorium. Results:Most of the absorbed dose is concentrated in a 25-µm thick layer of tissue, adjacent to the source boundary. Fluctuations where a target region with a volume of 1 µm 3 is hit by 3-5 α particles in a day or in a shorter period of time are relevant in a 1-10 µm thick layer of tissue adjacent to the source boundary, where their frequency is larger than the Poisson-law prediction.

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Mortality among Thorotrast-exposed patients and an unexposed comparison group in the German Thorotrast study

Cited by 42 publications

References 12 publications

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

Does ionizing radiation influence Alzheimer's disease risk?

Thorotrast and in vivo thorium dioxide: Numerical simulation of 30 years of α radiation absorption by the tissues near a large compact source

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