Health policy developments in the Western Balkan Countries 2000-19: towards European Health and Health Care Policies.

BACKGROUND: Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia have committed to becoming European Union (EU) member states. This, among others, implies that candidate/potential candidate states adopt legally authorized EU policies, including health. The study aims to identify the main country-specific health policy areas critical to the EU accession health policy dimension and present the change in associated selected health indicators from 2000 to 2019. METHODS: The study draws on published reports and analyses of official statistics over time and cross-country. Health care policy adherence to the European Commission's recommended country-specific health actions was classified into five health policy areas: financing, payment, organization, regulation and persuasion. Key health policy areas for Western Balkan countries (WBCs) were identified. Health progress or lack thereof in catching up to the EU15 population health, health expenditure and the number of health professionals are measured. RESULTS: The European Commission prioritized financing and regulation for all WBCs in the five policy areas. Nine of the 18 analyzed selected health indicators showed divergence, and the other nine converged towards the EU15 averages. WBCs continue to face diverse public health challenges in improving life expectancy at birth, death rates caused by circulatory system diseases, malignant neoplasms, traffic accidents, psychoactive substance use, tuberculosis incidence, tobacco smoking prevalence and public-sector health expenditure. CONCLUSIONS: By 2019, there is limited evidence of WBCs catching up to the average EU15 health levels and health care policies. Closer attention towards EU health and health care policies would be favourable.

FOXC2 promotes vasculogenic mimicry and resistance to anti-angiogenic therapy.

Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood vessels, and their presence is generally associated with poor patient prognosis. Here we show that the transcription factor, Foxc2, promotes VM in diverse solid tumor types by driving ectopic expression of endothelial genes in tumor cells, a process that is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy, and suppression of Foxc2 augments response. This work establishes co-option of an embryonic endothelial transcription factor by tumor cells as a key mechanism driving VM proclivity and motivates the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics.

Imaging and Molecular Annotation of Xenographs and Tumours (IMAXT): High throughput data and analysis infrastructure.

With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.

Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response.

The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.