Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

Cyt‐Geist: Current and Future Challenges in Cytometry: Reports of the CYTO 2019 Conference Workshops

The need for cytometry instrumentation, reagents, training and scientific collaborations in the nations of Africa remains high despite strong efforts by both the African and foreign biomedical and cytometry research communities. Dr. Tesfa and Dr. Blanco therefore organized the first Cytometry in Africa Workshop at CYTO2019. This workshop had several goals. The first goal was to present the results of a pre-workshop survey aimed at assessing flow cytometry resources, personnel, experience and training in Africa. The results of this survey demonstrated important strengths in the African cytometry community, but also pinpointed areas where instrument access, reagent availability and training could be improved. The second goal was to present several collaborative scientific projects in Africa with participation by ISAC members. Third, both existing and proposed strategies for improving collaborative efforts and research support were presented, including cytometer donations, research collaborations and training programs. Finally, an open roundtable discussion was held with workshop attendees, many with experience in working in Africa. A diverse array of investigators from government, academia and industry attended and contributed to the workshop. A key outcome of the workshop was the establishment an African Working group in collaboration with the ISAC Instruments 4 Science Task Force, the ISAC Live Education Task Force, and the ISAC Education Committee. The workshop also marked the establishment of I4S, with the goal of advancing flow cytometry in the international research communit