Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa)

Breast Cancer Research and Treatment - Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques...     

Validation of ADAM10 metalloprotease as a Bacillus thuringiensis Cry3Aa toxin functional receptor in Colorado potato beetle (Leptinotarsa decemlineata)

Bacillus thuringiensis parasporal crystal proteins (Cry proteins) are insecticidal pore‐forming toxins that bind to specific receptor molecules on the brush border membrane of susceptible insect midgut cells to exert their toxic action. In the Colorado potato beetle (CPB), a coleopteran pest, we previously proposed that interaction of Cry3Aa toxin with a CPB ADAM10 metalloprotease is an essential part of the mode of action of this toxin. Here, we annotated the gene sequence encoding an ADAM10 metalloprotease protein (CPB‐ADAM10) in the CPB genome sequencing project, and using RNA interference gene silencing we demonstrated that CPB‐ADAM10 is a Cry3Aa toxin functional receptor in CPB. Cry3Aa toxicity was significantly lower in CPB‐ADAM10 silenced larvae and in vitro toxin pore‐forming ability was greatly diminished in lipid planar bilayers fused with CPB brush border membrane vesicles (BBMVs) prepared from CPB‐ADAM10 silenced larvae. In accordance with our previous data that indicated this toxin was a substrate of ADAM10 in CPB, Cry3Aa toxin membrane‐associated proteolysis was altered when CPB BBMVs lacked ADAM10. The functional validation of CPB‐ADAM10 as a Cry3Aa toxin receptor in CPB expands the already recognized role of ADAM10 as a pathogenicity determinant of pore‐forming toxins in humans to an invertebrate species.     

Radiotherapy for childhood cancer and subsequent thyroid cancer risk: a systematic review

Most of the pooled analyses and reviews reported an association between radiotherapy for childhood cancer and an increased thyroid cancer risk. Up to now this article presents the first systematic literature review on this association combined with a critical assessment of the methodological quality of the included articles. PubMed and Web of Science databases were searched for relevant articles until May 2016. We included peer-reviewed cohort and case–control studies that investigated an association between radiotherapy for childhood cancer and the occurrence of subsequent thyroid cancer. A systematic overview is presented for the included studies. We identified 17 retrospective cohort studies, and four nested case–control studies, representing 100,818 subjects. The age range at first cancer diagnosis was 0–25.2 years. Considerable variability was found regarding study sizes, study design, treatment strategies, dose information, and follow-up periods. 20 of the 21 identified studies showed increased thyroid cancer risks associated with childhood radiation exposure. The large majority showed an increased relative risk or odds ratio confirming the association between radiotherapy and thyroid cancer although the variation in results was large. Additionally to a pooled analysis that has been published recently, we systematically included 17 further studies, which allowed us to cover information from countries that were not covered by large-scale childhood cancer survivor studies. The methodological limitations of existing studies and inconsistencies in findings across studies yielded a large study heterogeneity, which made a detailed comparison of study results difficult. There is a need to strengthen standardisation for reporting.     

Proprioceptive input overrides vestibulo-spinal drive during human locomotion

The aim of this study was to evaluate the influence of vestibulo-spinal drive on the performance of various locomotor-like movements. The extent of body rotation was assessed during walking (1 Hz and 2 Hz), running and hopping in place after vestibular stimulation (10 body rotations; 0.5 Hz). Compared to the controls, body rotations with eyes closed were larger during hopping than while running and smallest during walking independent of stepping frequency. A close correlation existed between the absolute duration of stance phase of the two legs and the rotation of the body. It is suggested that the amount of proprioceptive feedback from the legs determines the influence of vestibulo-spinal input on body movement.     

Mortality risk among 5-year survivors of childhood cancer in Germany—Results from the CVSS study (Cardiac and Vascular late Sequelae in long-term Survivors of childhood cancer study)

The growing population of long-term childhood cancer survivors is at increased risk for severe, therapy-related late effects and premature mortality. The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS) study is a cohort of patients from Germany diagnosed with a neoplasia prior to 15 years of age in the time period 1980 to 1990. Late mortality was evaluated in a total of 4505 individuals who survived 5 years or more after the initial diagnosis (5-year survivors). Survivors with a second primary tumor were excluded. Standardized mortality ratios (SMRs) were calculated. By December 2014, 400 patients had died. Available cause of death information from 188 individuals was used to estimate cause-specific mortality for all deceased persons. Compared to the population of (former) West Germany, we observed an excess overall mortality risk (SMR = 9.53, 95% confidence interval [CI] = 8.62-10.51). After correcting for missing cause of death information, an increased cancer mortality (SMR = 43.50, 95% CI = 25.79-73.50) in the 5-year survivors was detected. Cardiac death was ascertained in 14 individuals, resulting in an SMR of 10.85 (95% CI = 2.80-32.02) after correcting for missing values. In conclusion, childhood cancer survivors diagnosed in Germany in 1980 to 1990 have a higher mortality risk overall and an elevated risk of dying from cancer and cardiac causes in particular. The results are consistent with those of international cohort studies. However, the reported results are based on few cases and individuals with secondary cancers were excluded.