Rüdiger Greinert

Far-UVC radiation for disinfection in the presence of people in public indoor spaces through unshielded open radiation sources has been promoted for several years, claiming to be a simple solution to reduce infections from airborne pathogens such as bacteria and viruses. This literature review summarizes the existing research on the effectiveness of far-UVC radiation for inactivating pathogens, as well as potential risks to skin and eyes associated with exposure to far-UVC radiation. Further, it discusses radiation protection aspects of using far-UVC radiation in the presence of people, and addresses possible effects of far-UVC radiation on the human environment as well. The literature review shows that despite its antimicrobial and antiviral effectiveness, there is so far no sufficient evidence that far-UVC radiation can be used for disinfection in the presence of people in public indoor spaces without risks for humans and the environment. There are particular concerns about the safety of vulnerable groups such as children, the elderly and people with pre-existing medical conditions. The authors recommend further and extended studies in this field concerning potential risks of far-UVC radiation.

Humanized tumor mice (HTM) allow for preclinical cancer treatment studies of breast cancer (BC) under human-like conditions. This study utilized HTM for the first time to investigate potential miRNA biomarker candidates for treatment response in sera and extracellular vesicles (EVs), following X-irradiation and atezolizumab (anti-PD-L1) treatment. We identified the changes of human-specific miRNAs (miR-23b-3p and miR-155-5p) after irradiation and anti-PD-L1 treatment in HTMs with human epidermal growth factor receptor 2 positive (HER2⁺ BC) and triple-negative breast cancer (TNBC). The high degree of conserved, circulating free miRNA in mice and men represents a challenge of our assay; however, miRNAs with ≥2 nucleotide mismatches can be employed for human-specific analysis, and even conserved miRNAs may be utilized under clearly defined conditions of human tumor growth in HTM. A comparative analysis of extracellular vesicle miRNA cargo and free-circulating serum miRNAs revealed several exosome-specific miRNAs (miR-29b-3p, miR-34c-5p, miR-203a-3p, miR-378g, and miR-382-5p) in HTMs, which are known to play roles in BC. Our findings demonstrate that HTMs are a suitable model to identify treatment-induced changes in free-circulating and exosomal miRNAs that influence tumor progression and immunological tumor defense, both locally and at distant sites. This study presents a proof-of-principle approach to analyzing cell-free nucleotides and exosomes in a human-like, preclinical in vivo setting. Further refinements are necessary to enhance the sensitivity and the specificity of the HTM-based approach.

Solar radiation is the main risk factor for cSCC development, yet it is unclear whether the progression of cSCC is promoted by solar radiation in the same way as initial tumorigenesis. Additionally, the role of miRNAs, which exert crucial functions in various tumors, needs to be further elucidated in the context of cSCC progression and connection to solar radiation. Thus, we chronically irradiated five cSCC cell lines (Met-1, Met-4, SCC-12, SCC-13, SCL-II) with a custom-built irradiation device mimicking the solar spectrum (UVB, UVA, visible light (VIS), and near-infrared (IRA)). Subsequently, miRNA expression of 51 cancer-associated miRNAs was scrutinized using a flow cytometric multiplex quantification assay (FirePlex^®, Abcam). In total, nine miRNAs were differentially expressed in cell-type-specific as well as universal manners. miR-205-5p was the only miRNA downregulated after SSR-irradiation in agreement with previously gathered data in tissue samples. However, inhibition of miR-205-5p with an antagomir did not affect cell cycle, cell growth, apoptosis, or migration in vitro despite transient upregulation of oncogenic target genes after miR-205-5p knockdown. These results render miR-205-5p an unlikely intracellular effector in cSCC progression. Thus, effects on intercellular communication in cSCC or the simultaneous examination of complementary miRNA sets should be investigated.

Dermal stem cells (DSCs), which are progenitor cells of melanocytes, are isolated from human foreskin and cultivated as mixed cultures containing both DSCs and fibroblasts in varying proportions. These contaminating fibroblasts may have an impact on the results of experimental studies and are a serious limitation for certain applications. The aim of the present study was to purify or enrich DSCs—an indispensable step towards future investigations. Applying different methods, we demonstrated that highly enriched DSCs with a good recovery rate can be obtained through positive selection with MACS^® immunomagnetic cell sorting. These DSCs remain vital and proliferate constantly in culture, maintaining a high level of purity after enrichment. Other approaches such as treatment with Geneticin or selective detachment were not suitable to purify DSC-fibroblast co-cultures. Overall, enriched DSCs represent a novel and unique model to study the effects of UV radiation on the differentiation of DSCs into melanocytes and their potential relevance in the genesis of malignant melanoma.

Outdoor and indoor tanning are considered as risk factors for the development of skin cancer. The aims of this nationwide representative study were to quantify both behaviors in a sample with a wide age range, to identify those showing both behaviors and to explore and compare determinants of both behaviors. We used data from the fifth wave (2019) of the National Cancer Aid Monitoring (NCAM). We surveyed the representative sample including 4000 individuals, aged 16–65 years, living in Germany. Data were collected through telephone interviews. In addition to descriptive statistics, we used logistic regression analyses to identify determinants. The one-year-prevalence of tanning bed use was 7.5%, while 31.9% tanned (very) often intentionally outdoors in at least one situation (weekdays, holidays, and weekends). A total of 3.2% reported both risk behaviors. Regression analyses revealed that tanning bed use is associated with employment, an increased number of naevi, and lack of risk awareness. Intentional outdoor tanning was associated with male sex, younger age, past tobacco use, and low risk awareness of UV radiation. Our findings suggest that only a minority of subjects showed both risk behaviors. This implies that individuals seem to perform either one behavior or the other. In addition, the associated determinants differed between both behaviors, implying that specific preventive measures tailored to address to each tanning behavior are needed.

Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as prognostic markers for BM. We show that a size-based microfluidic approach in combination with a semi-automated cell recognition system are well suited for CTC detection in BM patients and allow further characterization of tumor cells potentially derived from BM. CTCs were found in 50% (7/14) of breast cancer, 50% (9/18) of non-small cell lung cancer (NSCLC) and 36% (4/11) of melanoma patients. The next-generation sequencing (NGS) analysis of nine single CTCs from one breast cancer patient revealed three different CNV profile groups as well as a resistance causing ERS1 mutation. CD44 and CD74 were expressed on most CTCs and their expression was strongly correlated, whereas matched breast cancer BM tissues were much less frequently expressing CD44 and CD74 (negative in 46% and 54%, respectively). Thus, plasticity of CD44 and CD74 expression during trafficking of CTCs in the circulation might be the result of adaptation strategies.

Purpose UV exposure is the main risk factor for development of cutaneous squamous cell carcinoma (cSCC). While early detection greatly improves cSCC prognosis, locally advanced or metastatic cSCC has a severely impaired prognosis. Notably, the mechanisms of progression to metastatic cSCC are not well understood. We hypothesized that UV exposure of already transformed epithelial cSCC cells further induces changes which might be involved in the progression to metastatic cSCCs and that UV-inducible microRNAs (miRNAs) might play an important role. Methods Thus, we analyzed the impact of UV radiation of different quality (UVA, UVB, UVA + UVB) on the miRNA expression pattern in established cell lines generated from primary and metastatic cSCCs (Met-1, Met-4) using the NanoString nCounter platform. Results This analysis revealed that the expression pattern of miRNAs depends on both the cell line used per se and on the quality of UV radiation. Comparison of UV-induced miRNAs in cSCC cell lines established from a primary tumor (Met-1) and the respective (un-irradiated) metastasis (Met-4) suggest that miR-7-5p, miR-29a-3p and miR-183-5p are involved in a UV-driven pathway of progression to metastasis. This notion is supported by the fact that these three miRNAs build up a network of 81 potential target genes involved e.g. in UVA/UVB-induced MAPK signaling and regulation of the epithelial–mesenchymal transition. As an example, PTEN, a target of UV-upregulated miRNAs (miR-29a-3p, miR-183-5p), could be shown to be down-regulated in response to UV radiation. We further identified CNOT8, the transcription complex subunit 8 of the CCR4-NOT complex, a deadenylase removing the poly(A) tail from miRNA-destabilized mRNAs, in the center of this network, targeted by all three miRNAs. Conclusion In summary, our results demonstrate that UV radiation induces an miRNA expression pattern in primary SCC cell line partly resembling those of metastatic cell line, thus suggesting that UV radiation impacts SCC progression beyond initiation.

Indoor tanning is an important risk factor for the development of melanoma and non-melanoma skin cancer. With our nationally representative monitoring, we aimed at describing tanning bed use, user characteristics, reasons for use, and risk awareness over time. In the framework of the National Cancer Aid Monitoring (NCAM), we collected representative data on 12,000 individuals aged 14 to 45 years in annual waves of n = 3,000 participants in Germany between 2015 and 2018. We used descriptive statistics and chi²-tests to uncover group differences. To compare data from the different waves, we calculated confidence intervals. The use of tanning beds decreased from 2015 (11.0%, 95%-CI: 9.9%–12.1%) to 2018 (8.8%, 95%-CI: 7.8%–9.8%). However, this decrease did not affect all subgroups. For instance, there was an (non-significant) increase in minors and the prevalence remained stable for individuals with immigrant background and males. Attractiveness was an important reason for tanning bed use in each wave. Over time, there was an increase in medical-related reasons for use. Furthermore, monitoring showed a decrease in risk awareness regarding tanning bed use and ultraviolet (UV) radiation. While it is a positive development that the overall use of tanning beds in Germany has decreased over time, the increasing use by minors despite the legal ban is alarming. Due to the declining risk awareness it is necessary to implement prevention and education campaigns specifically targeted at this group.

Beim malignen Melanom (MM) handelt es sich um ein komplexes, heterogenes Krankheitsbild in dessen Tumorgenese Störungen unterschiedlicher molekularer Signaltransduktionswege involviert sind. Dabei können sowohl genetische Modifikationen als auch epigenetische Veränderungen von Bedeutung sein. Eine der wichtigsten Erkenntnisse im zurückliegenden Jahrzehnt war der Befund, dass BRAF-Mutationen (BRAF V600) im RAS-RAF-MEK-ERK Signalweg eine bedeutende Rolle für die Ätiologie des MM spielen. Zusätzlich gibt es vermehrte Evidenz für epigenetische Veränderungen, die ebenfalls an der Entstehung, Promotion und Progression des MM beteiligt sein können. Experimentelle Untersuchungen unterstützen epidemiologische Daten, dass UV-Strahlung der Haupt-Risikofaktor für die Entstehung des MM ist. Das wird durch Sequenzanalysen von MM-Genomen untermauert, die zeigen, dass es sich beim Großteil der Mutationen um UV-induzierte signature-mutations handelt.