Occupational UV-Exposure is a Major Risk Factor for Basal Cell Carcinoma

The aim of this study was to investigate the role of occupational and nonoccupational ultraviolet (UV)-exposure concerning the development of basal cell carcinoma (BCC).We undertook a population-based multicenter case-control study. Patients with first incident BCC (n = 836) were propensity score matched by age and sex to controls without skin cancer (n = 836). Sociodemographic characteristics, clinical characteristics, and lifetime UV-exposure were assessed by trained investigators. The differential estimation of occupational and nonoccupational UV-exposure dosages was based on validated instruments and established reference values. Associations were assessed using multivariable-adjusted c…

Generation and characterization of an ABCC1 humanized mouse model (HABCC1<sup>FLX/FLX</sup>) with knockout capability

ATP-binding cassette (ABC) transporters such as ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP) are well known for their role in rendering cancer cells resistant to chemotherapy. Additionally, recent research provided evidence that, along with other ABC transporters (ABCA1 and ABCA7), they might be cornerstones to tackle neurodegenerative diseases. Overcoming chemoresistance in cancer, understanding drug-drug interactions, and developing efficient and specific drugs that alter ABC transporter function are hindered by a lack of in vivo research models, which are fully predictive for humans. Hence, the humanization of ABC transporters in mice has become a major focus in pharmaceutical …

15. Mainzer Allergie-Workshop 2003

External and internal exposure to polycyclic aromatic hydrocarbons (PAH) among workers in the production of fire-proof materials – Proposal of a biological monitoring guidance value

In 1999, we introduced the German polycyclic aromatic hydrocarbons (PAH) study. The study was designed as a nation-wide investigation on workers exposed to PAH. One aim of the study was to establish biological monitoring guidance values (BMGVs) for different branches. Here, we report on the production of fire-proof materials. This branch of industry is typically confronted with high exposure to PAH and with PAH-induced occupational (cancer) diseases. One hundred and thirty-five employees participated in the course of seven sampling dates in four different plants in Germany. External exposure was determined by personal air monitoring of the 16 EPA-PAH. Human biological monitoring was accompl…

A New Tool for the Analysis of the Effect of Intracerebrally Injected Anti-Amyloid-β Compounds

Background: A wide range of techniques has been developed over the past decades to characterize amyloid-β (Aβ) pathology in mice. Until now, no method has been established to quantify spatial changes in Aβ plaque deposition due to targeted delivery of substances using ALZET® pumps. Objective: Development of a methodology to quantify the local distribution of Aβ plaques after intracerebral infusion of compounds. Methods: We have developed a toolbox to quantify Aβ plaques in relation to intracerebral injection channels using Zeiss AxioVision® and Microsoft Excel® software. For the proof of concept, intracerebral stereotactic surgery was performed in 50-day-old APP-transgenic mice injected wit…

Improved method for cannula fixation for long-term intracerebral brain infusion

Abstract Background Implanted osmotic minipumps are commonly used for long-term, brain-targeted delivery of a wide range of experimental agents by being connected to a catheter and a cannula. During the stereotactical surgery procedure, the cannula has to be placed correctly in the x-y directions and also with respect to the injection point in the z-direction (deepness). However, the flat fixation base of available cannula holders doesn’t allow an easy, secure fixation onto the curve-shaped skull. New method We have developed a modified method for a better fixation of the cannula holder by using an easy-to-produce, skull-shaped silicone spacer as fixation adapter. Results We describe the ap…

Homozygous mutations incaveolin-3cause a severe form of rippling muscle disease

Heterozygous missense mutations in the caveolin-3 gene (CAV3) cause different muscle disorders. Most patients with CAV3 alterations present with rippling muscle disease (RMD) characterized by signs of increased muscle irritability without muscle weakness. In some patients, CAV3 mutations underlie the progressive limb-girdle muscular dystrophy type 1C (LGMD1C). Here, we report two unrelated patients with novel homozygous mutations (L86P and A92T) in CAV3. Both presented with a more severe clinical phenotype than usually seen in RMD. Immunohistochemical and immunoblot analyses of muscle biopsies showed a strong reduction of caveolin-3 in both homozygous RMD patients similar to the findings in…

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

Journal article TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10!-7), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10!-8) and BRCA1 mutation carrier (P = 1.1 × 10!-5) breast cancers and altered promot…

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181

Background Squamous cell carcinoma (SCC) is among the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting UV-exposure during leisure time. However, the relative impact of occupational and non-occupational UV-exposure for SCC occurrence is unclear. Objectives To investigate the association between occupational and non-occupational UV-exposure with SCC in a multicenter population-based case-control study hypothesizing that high occupational UV-exposure increases the risk for SCC. Methods Consecutive patients with incident SCC (n=632) were recruited from a German national dermatology network. Population-based controls (n=996) w…

Genome-wide association studies identify four ER negative-specific breast cancer risk loci

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environm…

Expression of endogenous mouse APP modulates β-amyloid deposition in hAPP-transgenic mice

Amyloid-β (Aβ) deposition is one of the hallmarks of the amyloid hypothesis in Alzheimer’s disease (AD). Mouse models using APP-transgene overexpression to generate amyloid plaques have shown to model only certain parts of the disease. The extent to which the data from mice can be transferred to man remains controversial. Several studies have shown convincing treatment results in reducing Aβ and enhancing cognition in mice but failed totally in human. One model-dependent factor has so far been almost completely neglected: the endogenous expression of mouse APP and its effects on the transgenic models and the readout for therapeutic approaches. Here, we report that hAPP-transgenic models of …