Comparison of the Biological Effects of Long-Term Exposure of Human Bronchial Epithelial Cells to Total Particulate Matter from 3R4F Cigarette Smoke or Aerosol from the Candidate Modified Risk Tobacco Product (cMRTP) THS2.2
Poster Jan 24, 2017
M. van der Toorn, D. Marescotti, S. Johne, K. Baumer, D. Bornand, R. Dulize, C. Merg, A. Sewer, P. Leroy, N. Ivanov, M. Peitsch, J. Hoeng, and K. Luettich
Chronic cigarette smoke exposure leads to airway epithelial changes underlying lung tumorigenesis, although the molecular events are not fully elucidated. We mimicked chronic exposure in smokers’ airways by continuously exposing BEAS-2B cells to TPM from 3R4F cigarette smoke or aerosol of the Tobacco Heating System 2.2 (THS2.2), a cMRTP, for 12 weeks.
Several endpoints including proliferation, DNA damage, oxidative stress, epithelial-mesenchymal transition (EMT) and wound repair were assessed monthly. Soft-agar assays were performed after 12 weeks, and resulting clones were tested for invasion. Cells were also collected regularly for systems toxicological analysis. Increased oxidative stress and DNA damage were noticeable within the first 2 weeks of 3R4F TPM treatment, but subsided thereafter, indicating adaptation.
Four-week 3R4F TPM treatment resulted in crisis and EMT. By week 8, cells regained E-cadherin expression, suggesting EMT was reversible. Increased MMP levels and decreased wound repair were noted in 3R4F TPM-treated cells at week 12.
However, these changes were not observed following prolonged treatment of BEAS-2B cells with the same or a 5-fold higher concentration of THS2.2 TPM, while a 20-fold higher concentration also increased oxidative burden, DNA damage and caused reversible EMT. In addition, anchorage-independent growth was observed in 3R4F and THS2.2 TPM-treated BEAS-2B cells. 3R4F TPM-derived clones were invasive, while THS2.2 TPM clones were not. Systems toxicological analysis indicated an overall smaller biological impact of THS2.2 compared with 3R4F TPM, confirming a differential effect of the two TPMs. Further analysis by DNA sequencing and in vitro xenograft assay is currently underway.
T-helper cell phenotype expression in cutaneous lesions of angioimmunoblastic T-cell lymphomaPoster
Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma. AITL can be missed until lymphadenopathy develops in patients initially presenting with skin lesions, as skin biopsy may lack conclusive findings. Our case highlights the extranodal presentation of AITL with cutaneous lesions displaying the TFH phenotype.READ MORE
Novel Role of the Innate Immune DNA Sensor IFI16 (Interferon Gamma Inducible Protein 16) as a Major Epigenetic Modulator During KSHV Infection and Lytic ReactivationPoster
Studies have shown that IFI16 acts as an antiviral restriction factor against a number of DNA viruses, by inhibiting viral replication or transcription through epigenetic modifications. However, till date, no specific epigenetic function of IFI16 has been identified. Here, we have discovered that IFI16 recruits two histone methyltransferases on the KSHV episome leading to altered Histone H3K9 methylation, thus regulating its lifecycle.READ MORE
Liver Transplantation for Hepatocellular Carcinoma Outperform Other Populations in the New Hepatitis C EraPoster
Long term results of HCC liver transplants (LTx) in the recent era of direct-acting antivirals (DAA) against hepatitis C (HCV) are not available. We aimed to examine the access, treatments and cure rates with DAA’s utilized in HCC LTx with HCV. Secondarily, we aimed to determine the long term impact of the Liver Cancer Program and DAA therapies on survival of HCC LTx.READ MORE