«Let’s Biodesign!» : vom Operationssaal zum disruptiven Medizinprodukt

Der Biodesign-Ansatz ist eine innovative Ausbildungsmethodik für die Entwicklung radikaler Produktinnovationen in Healthcare-Unternehmen. Sie zielt konsequent auf die Praxis und vermittelt Studierenden unternehmerische Kompetenzen

Hippo signaling mediates proliferation, invasiveness, and metastatic potential of clear cell renal cell carcinoma

Recent work has identified dysfunctional Hippo signaling to be involved in maintenance and progression of various human cancers, although data on clear cell renal cell carcinoma (ccRCC) have been limited. Here, we provide evidence implicating aberrant Hippo signaling in ccRCC proliferation, invasiveness, and metastatic potential. Nuclear overexpression of the Hippo target Yes-associated protein (YAP) was found in a subset of patients with ccRCC. Immunostaining was particularly prominent at the tumor margins and highlighted neoplastic cells invading the tumor-adjacent stroma. Short hairpin RNA-mediated knockdown of YAP significantly inhibited proliferation, migration, and anchorage-independent growth of ccRCC cells in soft agar and led to significantly reduced murine xenograft growth. Microarray analysis of YAP knockdown versus mock-transduced ccRCC cells revealed down-regulation of endothelin 1, endothelin 2, cysteine-rich, angiogenic inducer, 61 (CYR61), and c-Myc in ccRCC cells as well as up-regulation of the cell adhesion molecule cadherin 6. Signaling pathway impact analysis revealed activation of the p53 signaling and cell cycle pathways as well as inhibition of mitogen-activated protein kinase signaling on YAP down-regulation. Our data suggest CYR61 and c-Myc as well as signaling through the endothelin axis as bona fide downstream effectors of YAP and establish aberrant Hippo signaling as a potential therapeutic target in ccRCC

MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I.

Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8+ T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients

The chinese medtech sector with focus on new regulatory rules

Even though 95 per cent of the population is insured by basic medical insurance, the scheme does not address chronically ill patients who need long term treatment. China spends 5.8 per cent of its GDP on healthcare and the per capita expenditure is US$650, which is inadequate to provide for chronically ill patients. Since there is no gatekeeper in the Chinese healthcare system, the government is trying to channel patients to community health centers. The development of the private healthcare market is slow, because most doctors do not want to leave careers at public hospitals. Outbound medical tourism has reached a size of US$ 10 billion in 2015, as affluent people tend to avoid treatment in China. It seems obvious that in the future two different healthcare systems will coexist in China, namely: a large high-volume, low-priced public system and a small low-volume, high-priced private system. Since the large public system is controlled by the government, tender prices are bound to get lower

Systematization of digital twins : ontology and conceptual framework

The development and progress in information and communication technologies will transform traditional products into smart products and allow to offer novel smart services [1]. Herein, the digital twin (DT) concept is regarded as a key technology to create value with smart services [2]. Although the research and applications of DTs emerge continuously many concerns are to be scrutinized [3]. The lack of a shared conceptual framework for DTs with an unambiguous terminology [4] complicates cross-functional discussions. Therefore, a systematization of the main dimensions of DTs is proposed in the form of an ontology and a conceptual framework thereof derived. The research questions addressed in this paper are a) «Which dimensions are used to classify and structure DTs in academic literature?», b) «What are the fundamental differences or specifications within these dimensions?» and c) «How do these different specifications relate to each other?» The focus of the research is on the objective to find classification systematics that are a) representing the entire spectrum of DTs, b) universally valid in all DT related domains and c) applicable in research and practice. A systematic literature review on the relevant aspects of DTs was conducted and the findings iteratively advanced within workshop sessions with academic experts. DTs are considered as integrators of physical and digital worlds as well as internal and external value creation. Further, the creation of DTs requires per definition the use of digital data. Hence, the proposed ontology and conceptual framework for DTs include the following main dimensions to consider for every DT: Data resources, external value creation and internal value creation. The main subdimensions of the data resources are the data sources to obtain the data, the data categories and the data formats. The main subdimension of the external value creation are the attributes of the services as the basis of the value propositions, the level of smartness of the connected products and the actors on the different levels of the ecosystem. The main subdimensions of the internal value creation are the lifecycle phases of products, the product management levels and the different generations of both. The proposed ontology and conceptual framework support researchers and practitioners in positioning and structuring their intended DT activities and communicating them to internal and external stakeholders. The holistic view on the data resource dimension further allows to easily deduct the needed data for certain applications or deduct possible applications from already available data