Differential expression of heat shock protein family B (small) member 2 in cancers of the breast.

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding heat shock protein family B (small) member 2, HSPB2, when comparing primary tumors of the breast to the tissue of origin, the normal breast. HSPB2 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of HSPB2 in primary tumors of the breast was correlated with overall survival in patients with basal-like and normal-like subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. HSPB2 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

Differential expression of heat shock protein family B (small) member 7 in cancers of the breast.

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding heat shock protein family B (small) member 7, HSPB7, when comparing primary tumors of the breast to the tissue of origin, the normal breast. HSPB7 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of HSPB7 in primary tumors of the breast was correlated with overall survival in patients with basal-like and HER2+ subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. HSPB7 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

THE FUTURE OF THE COMMON SECURITY AND DEFENCE POLICY AND SMALL MEMBER STATES

Povzetek Dvaindvajset let po srečanju na vrhu v Kölnu, ki velja za zgodovinsko za SVOP, danes še vedno ne moremo govoriti o popolnoma funkcionalni in operativni SVOP. Prispevek analizira PESCO, CARD, CDP in EDF ter nekatere najpomembnejše težave evropskega obrambnega prizorišča, ki mu primanjkuje skladnosti in ostaja razdrobljeno v številnih vidikih. Države članice še vedno namenjajo veliko več finančnih sredstev za druge varnostne okvire, ki niso del EU, kot je na primer Nato. Prav tako države članice ohranjajo nacionalni fokus na področju obrambnega načrtovanja in v resnici zelo slabo izpolnjujejo dane obljube. Vprašanje je, kaj in koliko v trenutni evropski arhitekturi majhna država članica sploh lahko doseže. Prispevek osvetli vlogo majhnih držav skozi institucijo predsedovanja Evropskemu svetu. Ključne besede SVOP, Slovenija, PESCO, CARD, EDF. Abstract Twenty-two years after the EC meeting in Cologne where the CSDP came to life, we still cannot talk about a fully functional and operational CSDP. This article reflects on PESCO, CARD, the CDP and the EDF, and on some of the main issues in the European defence landscape today, which continues to be fragmented and lacks coherence in several aspects. Member States are still investing more in non-EU frameworks such as NATO, and still retain a national focus in their defence planning, showing very little discipline in meeting the commitments that they have undertaken. The question arises of what a small state can achieve in the current European architecture, if anything. The role of the small state is reflected through the Presidency of the European Council. Key words CSDP, Slovenia, PESCO, CARD, EDF.

Differential expression of heat shock protein family B (small) member 3 in human epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding heat shock protein family B (small) member 3, HSPB3, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. HSPB3 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. HSPB3 expression correlated with progression-free survival in patients with p53 mutant ovarian cancer. These data indicate that expression of HSPB3 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. HSPB3 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

HSPB7 Protected the Osteogenic Differentiation of Mesenchymal Stem Cells From TNF-α Through Chaperone-mediated Autophagy/beta-catenin Pathway

Background Managing healing of impaired bone fracture has long been a subject of concern. Prolonged or uncontrolled inflammation exerts detrimental effects on bone healing. Tumor necrosis factor (TNF)-α is a critical inflammatory factor, whose absence impairs normal bone formation. However, TNF-α exposure for longer duration inhibits bone regeneration. In this study, we aim to find a new therapeutic target for the impaired osteogenesis induced by long exposure of TNF-α.MethodsIn vitro, mRNA microarray analysis was used to identify differentially expressed genes. Cell proliferation assay was used to assess the proliferation of cells. qPCR and Western blotting analysis were applied to detect the expression of target genes and proteins respectively. ALP staining and Alizarin Red staining (ARS) were used to evaluate ALP activity and mineral deposition respectively. Co-immunoprecipitation was used to detect the interaction of proteins. In vivo, a murie tibial fracture model was established, histological evaluation and radiographic analysis was used to confirm bone regeneration in fracture healing. statistical significance between two groups was determined by Student’s t test, one-way ANOVA or Bonferroni’s post-hoc test according to the distribution of the tested population.ResultsIn this study, we show that heat shock protein family B (small) member 7 (HSPB7) mitigates negative impact of long-term TNF-α exposure on bone formation by binding heat shock protein family H (small) member 1 (HSPH1). HSPH1, in turn, inhibits the ATPase of heat shock cognate A8 (HSCA8), one of the key components involved in chaperone-mediated autophagy (CMA). Deletion of genes encoding for either HSCA8 or lysosome-associated membrane protein 2A (LAMP2A), another component of CMA, failed to reverse the osteogenic differentiation of hBMSCs induced by TNF-α by deleting HSPH1. Moreover, LAMP2A overexpression reverse the impaired osteogenesis induced by TNF-α, and this effect was attenuated by DKK1, a specific Wnt/β-catenin signaling pathway inhibitors. Thus, a heat shock protein family network composed by HAPB7, HSPH1 and HSCA8 rescued the impairment of bone healing by TNF-α through the CMA/β-catenin pathway, making it a potential therapeutic agent for bone regeneration in cases of prolonged or severe inflammation in the clinical settings. ConclusionsTaken together, these findings indicate that a heat shock protein family network including HSPB7, HSPH1 and HSCA8 protects the impaired osteogenesis induced by TNF-α via the CMA/β-catenin pathway. And in vivo, HSPB7 overexpression lentiviral particles effectively protects the impaired fracture healing induced by TNF-α in a mouse tibia fracture healing model.

HSPB6 is differentially expressed in metastatic breast cancer, both in metastases to the brain and to the lymph nodes.

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that heat shock protein family B (small) member 6, encoded by HSPB6, was among the genes whose expression was most different in the metastatic tumor tissues of patients with metastatic breast cancer, both in metastases to brain and to the lymph nodes when compared to primary tumors of the breast or normal breast tissue, respectively. We observed significant down-regulation of HSPB6 in metastasis to the brain. Molecular functions and down-regulation of heat shock protein family B (small) member 6 may be important for metastasis of primary tumor-derived cancer cells to the lymph nodes and to the brain in humans with metastatic breast cancer and suggests some level of common origin for metastases that reside in the lymph nodes and colonize the brain.

Lilliput Effect Revisited: Small States and EU Foreign Policy

The role of small member states in EU foreign policy is increasingly being challenged, especially in view of the reforms being proposed to make the EU more effective as an international actor. These reforms, if adopted, will require the small Central and Eastern European member states, such as Bulgaria, to rethink their old foreign-policy strategies and practices. Instead of band-wagoning and balancing conflicting interests, these small member states will have to learn to be more proactive, to build their reputations and to form alliances if they want to continue to have any influence on EU foreign policy. These issues are discussed in the light of the EU sanctions adopted against Russia in the aftermath of the Ukrainian–Russian conflict of 2014.