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

Developing governance of procurement department in hospitals

In for-profit and nonprofit companies, procurement and accounting departments are very tricky in terms of fraud. Transactions in these two units’ and their relationship should be audited meticulously and continuously by auditors. If the hospital management doesn’t like to hire an internal auditor or certified fraud examiner, they should be ready to face. As in the other sectors, various irregularities can also be seen in health institutions. Purchasing and accounting departments are the leading departments in the health companies where fraud activities happen frequently. It can be observed that the employees have misconduct towards the companies they work for. Especially the employees who are not happy with their salary think she/he works more than other employees may commit the crime. There is a need for a rigorous and practical audit and control mechanism in the purchasing department where fraudulent incidents can be seen in many different ways. In this chapter, the procurement procedure in hospitals, a procedure in procurement departments, fraud prevention techniques in the procurement department, and cases from Turkey are discussed in the chapter. © 2020, Springer Nature Singapore Pte Ltd