Refine
H-BRS Bibliography
- yes (2)
Departments, institutes and facilities
Document Type
Language
- English (2)
Keywords
- CDH1 (1)
- Corporate Organization (1)
- E-cadherin (1)
- Familial glioma (1)
- Intercultural Project Management (1)
- Leadership (1)
- MBA Essentials (1)
- Oligodendroglioma (1)
- Project Management (1)
- Whole-genome sequencing (1)
The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced β-catenin binding resulting in increased cytosolic and nuclear β-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/β-catenin signaling.
Project Management
(2023)
Companies are increasingly developing into dynamic and project-oriented organizations. Globalization, innovations and organizational dynamics require more and more projects, and thus a more project-oriented corporate organization and management. As a rule, managers as well as employees already work parallel to their line function in projects or completely from project to project.
At the same time, cross-company and especially international value chains lead to the cooperation of cross-departamental and intercultural teams. For this, the specialists and executives need above all knowledge and experience in project management and the corresponding concepts as well as in the special form of cooperation, team development and communication. Because the most problems in project management are not caused by project goals and methods, but by the many different problem-solving behavior and attitudes, e.g. between engineers and business people, different departments or the different country cultures. The international IT project specialist Tom DeMarco puts it in a nutshell (in Peopleware - Productive Projects and Teams: The major problems of our work are not so much technological as socio-logical in nature. In terms of content here, in contrast to traditional professional textbooks, not only the technologies are priority, but also the social and intercultural aspects of project work.
The book is aimed equally at students of all disciplines with a focus on managerial and project-related work as well as practitioners and entrepreneurs in all private business sectors as well as in NGOs, public projects or PPPs as public-private partnership.