Социальная политика предприятий

Материалы III Междунар. науч. конф. студентов, аспирантов и молодых ученых, Гомель, 20 мая 2010 г

Studies of transforming growth factor alpha in normal and abnormal growth

Regulation of growth is of fundamental importance for development of the organism and to maintain health. The induction of cell proliferation and matrix production are influenced by several different signaling systems, most importantly by growth factors. The human HER-family of growth factor ligands and receptors is one of the most studied and, at present, one of the most complex including 4 tyrosine kinase receptors and at least 11 different ligands cooperating in the transfer of signals. The HER-family growth responses are also influenced by other intercellular and extracellular signals, including matrix components, cytokines and hormones mediating e.g. inflammation. HER-1 (EGFR) is one of the best known and most extensively studied growth factor receptors. TGF-alpha is possibly the most potent HER-1 ligand and influences wound healing, epidermal maintenance, gastrointestinal function, lactation, pulmonary function and more. Several studies have shown important regulatory functions for some inflammatory cytokines on TGF-alpha production in white blood cells. HER-1 is widespread in epithelial cells but also in mesenchymal cells such as fibroblasts, osteogenic and chondrogenic cells. Consequently, many tumors arising from these cell types express HER family members and often show TGF-alpha and/or HER activation. Indeed, mammary cancer development has been shown when over expressing both TGF-alpha and HER-2 in mouse mammary cells in vivo. In recent years the first HER-1 and HER-2 inhibitors have come into clinical practice for treatment of breast cancer, lung cancer and gastrointestinal cancers, sometimes with great success. However, more knowledge is needed concerning the inflammatory regulation of HER-family expression including where and how the ligands and receptors cooperate. Therefore we were interested in studying the role of TGF-alpha in normal and abnormal growth. First we showed that the acute inflammatory cytokine IL-6 regulates TGF-alpha expression in U-937-1 monocytoid cells. Secondly, we detected a possible long-term enhancing influence of singledose UVR on HER-1 expression in normal human melanocytes. We continued thirdly by revealing TGF-alpha production concomitant with HER-2 in normal human synovia and release of soluble TGF-alpha into the synovial fluid. Both TGF-alpha and HER-2 production were significantly increased in inflammatory joint conditions, e.g. RA. Fourthly, we demonstrated expression of TGF-alpha, HER-1 and HER-2 in synovial sarcoma cells in culture; the observed HER-2 phosphorylation was dependent on ligand induced HER-1 activation. The presented results indicate that TGF-alpha expression can be enhanced by acute inflammatory cytokine IL-6, possibly contributing to growth stimulatory effects assigned to IL-6 itself. The acute effects of UVR on melanocytes mediate up-regulated steady-state expression of HER-1, constituting a potential target for locally produced TGF-alpha that may induce melanocyte proliferation. TGF-alpha and HER-2 seem to have a role in the maintenance of synovial joint tissues. Upregulation of TGF-alpha and HER-2 in inflammatory joint conditions, e.g. RA, represents a novel mechanism for synovial proliferation contributing to joint deterioration. TGF-alpha, HER1 and HER-2 may have a role in synovial sarcoma proliferation; further investigation is needed to evaluate HER-family inhibitors as a possible treatment alternative in this type of cancer

Linköping University medical dissertations, No. 1025 Studies of Transforming Growth Factor Alpha in Normal and Abnormal Growth

This thesis is based on studies presented in the following four papers, referred to in the text by their roman numerals. I. Hallbeck, A-L., Walz, T.M. and Wasteson, Å. (2001). Interleukin-6 enhances transforming growth factor-alpha mRNA expression in macrophage-like human monocytoid (U-937-1) cells. Bioscience Reports; Vol. 21(3):325-339. II. Hallbeck, A-L., Lirvall, M., Briheim, K. and Wasteson, Å. Single physiologic dose UVB radiation increases EGFR expression in cultured normal melanocytes. Manuscript. III. Hallbeck, A-L., Walz, T.M., Briheim, K. and Wasteson, Å. (2005). TGF-alpha and ErbB2 production in synovial joint tissue: increased expression in arthritic joints. Scandinavian Journal of Rheumatology; 34(3):204-211. IV. Hallbeck, A-L., Walz, T.M., Wasteson, Å. and Lindström, A. Cooperation of endogenous HER-family members in synovial sarcoma cells: stimulation of HER-2/ErbB2 is dependent on EGF-R activation. Submitted

Närståendes upplevelser och behov

Sjuksköterskeyrket innebär möten med patienter såväl som närstående tillpatienterna. Sjukdom och dödsfall är inte något som bara drabbar den enskildapersonen utan händelsen kan vara lika svår eller svårare för den drabbades familjoch närstående. Det är viktigt för sjuksköterskan att ha insikt i de närståendesupplevelser och behov för att bättre kunna möta dessa. Denna studies syfte är attbeskriva upplevelser och behov hos närstående till kritiskt sjuka patienter samt attbeskriva hur sjuksköterskan kan möta dessa behov. Genom en litteraturstudie harkvalitativa och kvantitativa vetenskapliga artiklar granskats. Studienshuvudresultat visar att de närstående är i behov av information, tillförsikt, närhet,familjens stöd och bekvämlighet. Studiens slutsats är att sjuksköterskan behöverkunskap och insikt beträffande dessa resultat för att på ett bra sätt möta denärståendes behov.When working with critical ill patients the nurse also get in contact withsignificant others related to the patient. Illness and accidents don’t strike only atthe patient it also strikes just as hard or harder at the significant others of thepatient. It’s important that the nurse has knowledge about the related person’sexperiences and needs in these situations, to better be able to meet these needs.This study aimed to describe experiences and needs of significant others whenthey have a critical ill person hospitalized. It also aimed to describe how the nursecan meet these needs. Through a literature review has both quantitative andqualitative scientific articles been reviewed. The study’s main results show thatthe needs of the related are information, assurance, proximity, family support andcomfort. The study concludes that the nurse needs knowledge and understandingsregarding these results to in a good way meet the relative’s needs

Närståendes upplevelser och behov

Sjuksköterskeyrket innebär möten med patienter såväl som närstående till patienterna. Sjukdom och dödsfall är inte något som bara drabbar den enskilda personen utan händelsen kan vara lika svår eller svårare för den drabbades familj och närstående. Det är viktigt för sjuksköterskan att ha insikt i de närståendes upplevelser och behov för att bättre kunna möta dessa. Denna studies syfte är att beskriva upplevelser och behov hos närstående till kritiskt sjuka patienter samt att beskriva hur sjuksköterskan kan möta dessa behov. Genom en litteraturstudie har kvalitativa och kvantitativa vetenskapliga artiklar granskats. Studiens huvudresultat visar att de närstående är i behov av information, tillförsikt, närhet, familjens stöd och bekvämlighet. Studiens slutsats är att sjuksköterskan behöver kunskap och insikt beträffande dessa resultat för att på ett bra sätt möta de närståendes behov.When working with critical ill patients the nurse also get in contact with significant others related to the patient. Illness and accidents don’t strike only at the patient it also strikes just as hard or harder at the significant others of the patient. It’s important that the nurse has knowledge about the related person’s experiences and needs in these situations, to better be able to meet these needs. This study aimed to describe experiences and needs of significant others when they have a critical ill person hospitalized. It also aimed to describe how the nurse can meet these needs. Through a literature review has both quantitative and qualitative scientific articles been reviewed. The study’s main results show that the needs of the related are information, assurance, proximity, family support and comfort. The study concludes that the nurse needs knowledge and understandings regarding these results to in a good way meet the relative’s needs

OPPONENT

Canertinib-induced leukemia cell death signaling – effects of a pan-ERBB inhibito

TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma

Telomerase reverse transcriptase (TERT) activity is up-regulated in several types of tumors including glioblastoma (GBM). In the present study, 128 primary glioblastoma patients were examined for single nucleotide polymorphisms of TERT in blood and in 92 cases for TERT promoter mutations in tumors. TERT promoter mutations were observed in 86% of the tumors and of these, C228T (-124 bp upstream start codon) was detected in 75% and C250T (-146 bp) in 25% of cases. TERT promoter mutations were associated with shorter overall survival (11 vs. 20 months p = 0.002 and 12 vs. 20, p = 0.04 for C228T and C250T, respectively). The minor alleles of rs2736100 and rs10069690 SNPs, located in intron 2 and the promotor regions, respectively, were associated with an increased risk of developing GBM (p = 0.004 and 0.001). GBM patients having both TERT promoter mutations and being homozygous carriers of the rs2853669 C-allele displayed significantly shorter overall survival than those with the wild type allele. The rs2853669 SNP is located in a putative Ets2 binding site in the promoter (-246 bp upstream start codon) close to the C228T and C250T mutation hot spots. Interleukin-6 (IL-6) expression regulated by TERT promoter status and polymorphism, what leads us to think that TERT and IL-6 plays a significant role in GBM, where specific SNPs increase the risk of developing GBM while the rs2853669 SNP and specific mutations in the TERT promoter of the tumor lead to shorter survival.Funding Agencies|Swedish Cancer foundation; Region Ostergotland research fund; FORSS</p

Wallenbergs jubileumsfond.

S6K1, S6K2 and 4EBP1 in breast cance