What are the bottlenecks to health data sharing in Switzerland? An interview study.

Background: While health data sharing for research purposes is strongly supported in principle, it can be challenging to implement in practice. Little is known about the actual bottlenecks to health data sharing in Switzerland.

Aims Of The Study: This study aimed to assess the obstacles to Swiss health data sharing, including legal, ethical and logistical bottlenecks.

Prevalence and clinical association of MET gene overexpression and amplification in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape project.

Introduction: In a well-defined NSCLC cohort of the ETOP Lungscape program, we explored the epidemiology of IHC MET overexpression and amplification, their inter-correlation, and their association to outcome.

Methods: Resected NSCLC were assessed for MET gene copy number (GCN) and expression using silver in-situ hybridization (SISH) and immunohistochemistry (IHC) on TMAs in a multicenter setting. MET amplification was defined as MET/centromere ratio≥2 (with average MET GCN≥4), high MET GCN as CGN≥5 and MET IHC+ as ≥2+ intensity in ≥50% of tumor cells.

Immunocompetent mouse allograft models for development of therapies to target breast cancer metastasis.

Effective drug development to combat metastatic disease in breast cancer would be aided by the availability of well-characterized preclinical animal models that (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame, (c) have an intact immune system, and (d) capture some of the heterogeneity of the human disease. To address these issues, we have assembled a panel of twelve mouse mammary cancer cell lines that can metastasize efficiently on implantation into syngeneic immunocompetent hosts. Genomic characterization shows that more than half of the 30 most commonly mutated genes in human breast cancer are represented within the panel.

A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2.

Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.

Functional analysis of prognostic gene expression network genes in metastatic breast cancer models.

Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer.

BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.

Recent studies suggest that BET inhibitors are effective anti-cancer therapeutics. Here we show that BET inhibitors are effective against murine primary mammary tumors, but not pulmonary metastases. BRD4, a target of BET inhibitors, encodes two isoforms with opposite effects on tumor progression.

Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis.

Metastasis confronts clinicians with two major challenges: estimating the patient's risk of metastasis and identifying therapeutic targets. Because they are key signal integrators connecting cellular processes to clinical outcome, we aimed to identify transcriptional nodes regulating cancer cell metastasis. Using rodent xenograft models that we previously developed, we identified the transcription factor Fos-related antigen-1 (Fra-1) as a key coordinator of metastasis.

Deletion of the proline-rich region of the murine metastasis susceptibility gene Brd4 promotes epithelial-to-mesenchymal transition- and stem cell-like conversion.

The bromodomain-containing chromatin-modifying factor BRD4 is an inherited susceptibility gene for breast cancer progression and metastasis, but its functionality in these settings has yet to be explored. Here we show that deletion of either of the BRD4 bromodomains had modest effects on the metastatic suppression ability of BRD4. In contrast, expression of the natural short isoform of BRD4 that truncates the protein after the SEED domain restored progression and metastatic capacity.

Functional characterization of human cancer-derived TRKB mutations.

Cancer originates from cells that have acquired mutations in genes critical for controlling cell proliferation, survival and differentiation. Often, tumors continue to depend on these so-called driver mutations, providing the rationale for targeted anticancer therapies. To date, large-scale sequencing analyses have revealed hundreds of mutations in human tumors.

Metastasis mechanisms.

Metastasis, the spread of malignant cells from a primary tumor to distant sites, poses the biggest problem to cancer treatment and is the main cause of death of cancer patients. It occurs in a series of discrete steps, which have been modeled into a "metastatic cascade". In this review, we comprehensively describe the molecular and cellular mechanisms underlying the different steps, including Epithelial-Mesenchymal Transition (EMT), invasion, anoikis, angiogenesis, transport through vessels and outgrowth of secondary tumors.

A Twist-Snail axis critical for TrkB-induced epithelial-mesenchymal transition-like transformation, anoikis resistance, and metastasis.

In a genomewide anoikis suppression screen for metastasis genes, we previously identified the neurotrophic receptor tyrosine kinase TrkB. In mouse xenografts, activated TrkB caused highly invasive and metastatic tumors. Here, we describe that TrkB also induces a strong morphological transformation, resembling epithelial-mesenchymal transition (EMT).

Critical role for TrkB kinase function in anoikis suppression, tumorigenesis, and metastasis.

Anoikis, or cell death induced by cell detachment, provides protection against the metastatic spread of tumor cells. We have previously shown that the neurotrophic receptor tyrosine kinase TrkB suppresses anoikis in rat intestinal epithelial cells and renders them highly tumorigenic and metastatic. Because TrkB is overexpressed in several aggressive human cancers, first attempts are being made to target TrkB in cancer therapy.

The neurotrophic receptor TrkB in anoikis resistance and metastasis: a perspective.

Resistance to anoikis ("detachment-induced apoptosis") has been suggested to be a prerequisite for cancer cells to metastasize. In a functional screen for suppressors of anoikis, we identified the neurotrophic receptor TrkB. Upon s.