The challenge of return to work in workers with cancer : employer priorities despite variation in social policies related to work and health

This study explored employer's perspectives on (1) their experience of good practice related to workers diagnosed with cancer and their return to work (RTW), and (2) their perceived needs necessary to achieve good practice as reported by employers from nine separate countries. Twenty-five semi-structured interviews were held in eight European countries and Israel with two to three employers typically including HR managers or line managers from both profit and non-profit organisations of different sizes and sectors. Interviews were recorded and transcribed verbatim. A grounded theory/thematic analysis approach was completed. Employers' experience with RTW assistance for workers with cancer appears to be a dynamic process. Results indicate that good practice includes six phases: (1) reacting to disclosure, (2) collecting information, (3) decision-making related to initial actions, (4) remaining in touch, (5) decision-making on RTW, and (6) follow-up. The exact details of the process are shaped by country, employer type, and worker characteristics; however, there was consistency related to the need for (1) structured procedures, (2) collaboration, (3) communication skills training, (4) information on cancer, and (5) financial resources for realizing RTW support measures. Notwithstanding variations at country, employer, and worker levels, the employers from all nine countries reported that good practice regarding RTW assistance in workers with a history of cancer consists of the six phases above. Employers indicate that they would benefit from shared collaboration and resources that support good practice for this human resource matter. Further research and development based on the six phases of employer support as a framework for a tool or strategy to support workers with a history of cancer across countries and organisations is warranted

Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma

Background: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. Objectives: To determine whether HIF1/mTOR signalling is involved in BCC and TE. Methods: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%). Results: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1 alpha), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. Conclusions: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE

Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a metalloprotease-dependent process regulated by TACE/ADAM17

Carbonic anhydrase IX (CA IX) is a transmembrane protein whose expression is strongly induced by hypoxia in a broad spectrum of human tumours. It is a highly active enzyme functionally involved in both pH control and cell adhesion. Its presence in tumours usually indicates poor prognosis. Ectodomain of CA IX is detectable in the culture medium and body fluids of cancer patients, but the mechanism of its shedding has not been thoroughly investigated. Here, we analysed several cell lines with natural and ectopic expression of CA IX to show that its ectodomain release is sensitive to metalloprotease inhibitor batimastat (BB-94) and that hypoxia maintains the normal rate of basal shedding, thus leading to concomitant increase in cell-associated and extracellular CA IX levels. Using CHO-M2 cells defective in shedding, we demonstrated that the basal CA IX ectodomain release does not require a functional TNFα-converting enzyme (TACE/ADAM17), whereas the activation of CA IX shedding by both phorbol-12-myristate-13-acetate and pervanadate is TACE-dependent. Our results suggest that the cleavage of CA IX ectodomain is a regulated process that responds to physiological factors and signal transduction stimuli and may therefore contribute to adaptive changes in the protein composition of tumour cells and their microenvironment

PPARδ Activation Acts Cooperatively with 3-Phosphoinositide-Dependent Protein Kinase-1 to Enhance Mammary Tumorigenesis

Peroxisome proliferator-activated receptorδ (PPARδ) is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1). PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling

Diagnostyka warystorów z ZnO z zastosowaniem metod nieniszczących

Standard industrial testing of high-voltage varistors for surge arresters demands application of high voltages and intensive currents. Nondestructive methods for varistor quality and endurance evaluation have been proposed and described. They rely on the application of resonant ultrasound spectroscopy, electroultrasonic spectroscopy, noise measurement and nonlinearity testing at voltages lower than continuous operating range. The achieved results show that these methods could be successively applied for varistor specimens at the production stage and in laboratory circumstances.Normatywne testy przemysłowe warystorów wysokonapięciowych stosowanych w ogranicznikach przepięć wymagają użycia wysokich napięć oraz prądów o odpowiednio dużych wartościach. Zaproponowano i opisano metody nieniszczące do oceny jakości i trwałości warystorów. Polegają one na zastosowaniu rezonansowej spektroskopii ultradźwiękowej, spektroskopii elektro-ultradźwiękowej, pomiarów szumów i testowaniu nieliniowości w zakresie napięć mniejszych od ciągłego napięcia pracy. Uzyskane wyniki wskazują, że metody nieniszczące mogą być z powodzeniem stosowane w odniesieniu do struktur warystorowych, zarówno w warunkach produkcyjnych jak i laboratoryjnych