Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

BACKGROUND: We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. METHODS: Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-alpha (ERalpha)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERalpha or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. RESULTS: Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2alpha and CAIX, but not to HIF-1alpha or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERalpha or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. CONCLUSION: We conclude that in breast cancer, Mb is co-expressed with ERalpha and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours

Влияние фосфатных связующих на физико-механические свойства периклазохромитовых огнеупоров

У данній статті наведено та порівняно фізико-механічні властивості периклазо-хромітових матеріалів в залежності від різних типів фосфатних зв’язуючих та введення різних домішок. Визначено, що найбільш раціональним є введення триполіфосфату натрію.In given clause are resulted and the physycal-mechanical properties periclase-cgromite of materials are compared depending on different of types phosphate binding and introduction of the various additives. Is determined, that most rational is the introduction treepolyphosphate sodume

Advancing the science behind human resources for health: highlights from the Health Policy and Systems Research Reader on Human Resources for Health

Health workers are central to people-centred health systems, resilient economies and sustainable development. Given the rising importance of the health workforce, changing human resource for health (HRH) policy and practice and recent health policy and systems research (HPSR) advances, it is critical to reassess and reinvigorate the science behind HRH as part of health systems strengthening and social development more broadly. Building on the recently published Health Policy and Systems Research Reader on Human Resources for Health (the Reader), this commentary reflects on the added value of HPSR underpinning HRH. HPSR does so by strengthening the multi-disciplinary base and rigour of HRH research by (1) valuing diverse research inferences and (2) deepening research enquiry and quality. It also anchors the relevance of HRH research for HRH policy and practice by (3) broadening conceptual boundaries and (4) strengthening policy engagement. Most importantly, HPSR enables us to transform HRH from being faceless numbers or units of health producers to the heart and soul of health systems and vital change agents in our communities and societies. Health workers’ identities and motivation, daily routines and negotiations, and training and working environments are at the centre of successes and failures of health interventions, health system functioning and broader social development. Further, in an increasingly complex globalised economy, the expansion of the health sector as an arena for employment and the liberalisation of labour markets has contributed to the unprecedented movement of health workers, many or most of whom are women, not only between public and private health sectors, but also across borders. Yet, these political, human development and labour market realities are often set aside or elided altogether. Health workers’ lives and livelihoods, their contributions and commitments, and their individual and collective agency are ignored. The science of HRH, offering new discoveries and deeper understanding of how universal health coverage and the Sustainable Development Goals are dependent on millions of health workers globally, has the potential to overcome this outdated and ineffective orthodoxy