8 resultados para therapeutic alliance
em Doria (National Library of Finland DSpace Services) - National Library of Finland, Finland
Resumo:
Tyss oli selkesti kaksi tavoitetta. Ensimmisen tavoitteena oli tutkia, millaisesta kumppanuudesta Drives Alliance Partner -konsepti (DAP) muodostuu. Tyn toisena tavoitteena oli selvitt ja analysoida DAP-konseptin informaation jakamiseen liittyvt tietotyypit, ja tehd esitys siit, mit tietoa ABB:nja kumppaneiden vlill tulisi vaihtaa. Jotta kumppanuuden tila saatiin selville, tehtiin ABB:n sisisi haastatteluja sek kytettiin hyvksi DAP-konseptista tehty dokumentaatiota. Informaation jakamiseen liittyv tietotarpeiden kartoitus toteutettiin web-pohjaisen kyselyn avulla. Kysely toimitettiin osalle ABB:n nykyisist kumppaneista sek sellaisille ABB:n tyntekijille, jotka liittyvt DAP- konseptiin. Tyss luotiin malli kuvaamaan informaation vaihtoa partnereiden j a ABB :n vlill. Malliin otettiin mukaan ne tietotarpeet, jotka tehdyn kyselyn mukaan osoittautuivat tarpeellisiksi. Kumppanuuksiin syventymisen myt tiedonvaihdon merkitys tulee entisestn korostumaan, mik asettaa uusia haasteita ABB:lle.
Resumo:
The focus of this study has been comovement of stock price risk level between two companies as they form strategic alliance. Thus the main reason has been to shed more light to possible increased risk level that the stockholder confronts when a company he owns forms a strategic alliance with another company. This study has centralized to interfirm cooperation between mobile and internet companies, which have furthered the development of mobile internet. The study has been divided into theoretical and empirical part. In theoretical part the main concepts riskiness of a stock (volatility), comovement and strategic alliance have been run through. In empirical part seven strategic alliances formed by mobile internet companies have been examined. Based on this, strategic alliance seems to increase comovement of stock price risk in some degree. This comovement seems to be stronger when core businesses or operating environments of cooperating companies differ more from each other.
Resumo:
The question of why some firms perform better in managing their alliances has raised interest among scholars and managers. Whereas inter-firm factors influencing the alliance performance such as strategic fit between partners and the existence of complementarities have been studied extensively, research on firm-level antecedents is rather scarce. Therefore this study investigates the role of firms alliance capability in the alliance success equation. Particularly it analyses the specialized mechanisms and processes set up by firm in order to facilitate alliancerelated know-how leverage organization-wise. Evidence from a cross-industry sample of R&D intensive Finnish companies supports the fact that firms which have invested in institutionalizing alliance capabilities outperform their counterparts in alliance portfolio management. Results also suggest that firms need to adjust alliance management tools depending on the alliance portfolio size, prior experience with inter-firm partnerships and the strategic importance of alliances. Furthermore, absorptive capacity is found to be crucial for successful alliance management, its role being complementary to that of alliance capability. Finally, firms that have successful alliances also enjoy higher financial, market and innovation performance.
Resumo:
The aim of this study was to characterize the cellular mechanisms leading to the beneficial effect of anti-oxidative gene therapy and pro-angiogenic stem cell therapy in acute peripheral ischemia. Post-ischemic events aim to re-establish tissue blood perfusion, to clear cellular debris, and to regenerate lost tissue by differentiation of satellite cells into myoblasts. Although leukocytes have an essential role in clearing cellular debris and promoting angiogenesis, they also contribute to tissue injury through excessive ROS production. First, we investigated the therapeutic properties of extracellular superoxide dismutase (SOD3) gene transfer. SOD3 was shown to reduce oxidative stress, to normalize glucose metabolism, and to enhance cell proliferation in the ischemic muscle. Analysis of the mitogenic Ras-Erk1/2 pathway showed SOD3 mediated induction offering a plausible explanation for enhanced cell proliferation. In addition, SOD3 reduced NF-B activity by enhancing IB expression thus leading to reduced expression of inflammatory cytokines and adhesion molecules with consequent reduction in macrophage infiltration. Secondly, we sought to determine the fate and the effect of locally transplanted mesenchymal stem/stromal cells (MSCs) in acute ischemia. We showed that a vast majority of the transplanted cells are cleared from the injury site within 24 hours after local transplantation. Despite rapid clearance, transplantation was able to temporarily promote angiogenesis and cell proliferation in the muscle. Lack of graft-derived growth factor expression suggests other than secretory function to mediate this observed effect. In conclusion, both SOD3 and MSCs could be utilized to alleviate peripheral ischemia induced tissue injury. We have described a previously unidentified growth regulatory role for SOD3, and suggest a novel mechanism whereby transplanted MSCs enhance the reparative potential of the recipient tissue through physical contacts.
Resumo:
Breast cancer that has metastasized to bone is currently an incurable disease, causing significant morbidity and mortality. The aim of this thesis work was to elucidate molecular mechanisms of bone metastasis and thereby gain insights into novel therapeutic approaches. First, we found that Lserine biosynthesis genes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH), were upregulated in highly bone metastatic MDAMB231(SA) cells as compared with the parental breast cancer cell line. Knockdown of serine biosynthesis inhibited proliferation of MDAMB231(SA) cells, and Lserine was essential for the formation of bone resorbing osteoclasts. Clinical data demonstrated that high expression of PHGDH and PSAT1 was associated with decreased relapsefree and overall survival and with features typical of poor outcome in breast cancer. Second, RNA interference screening pointed out heparan sulfate 6Osulfotransferase 2 (HS6ST2) as a critical gene for transforming growth factor (TGF)induced interleukin 11 (IL11) production in MDAMB231(SA) cells. Exogenous heparan sulfate glycosaminoglycans heparin and K5NSOS also inhibited TGFinduced IL11 production in MDAMB231(SA) cells. Furthermore, K5NSOS decreased osteolytic lesion area and tumor burden in bone in mice. Third, we discovered that the microRNAs miR204, 211 and 379 inhibited IL11 expression in MDAMB231(SA) cells through direct targeting of the IL11 mRNA. MiR379 also inhibited Smadmediated signaling. Gene expression profiling of miR204 and 379 transfected cells indicated that these microRNAs downregulate several bone metastasisrelevant genes, including prostaglandinendoperoxide synthase 2 (PTGS2). Taken together, this study identified three potential treatment strategies for bone metastatic breast cancer: inhibition of serine biosynthesis, heparan sulfate glycosaminoglycans and restoration of miR204/211/379.
Resumo:
Recurrent castration resistant prostate cancer remains a challenge for cancer therapies and novel treatment options in addition to current anti-androgen and mitosis inhibitors are needed. Aberrations in epigenetic enzymes and chromatin binding proteins have been linked to prostate cancer and they may form a novel class of drug targets in the future. In this thesis we systematically evaluated the epigenenome as a prostate cancer drug target. We functionally silenced 615 known and putative epigenetically active protein coding genes in prostate cancer cell lines using high throughput RNAi screening and evaluated the effects on cell proliferation, androgen receptor (AR) expression and histone patterns. Histone deacetylases (HDACs) were found to regulate AR expression. Furthermore, HDAC inhibitors reduced AR signaling and inhibited synergistically with androgen deprivation prostate cancer cell proliferation. In particular, TMPRSS2- EGR fusion gene positive prostate cancer cell lines were sensitive to combined HDAC and AR inhibition, which may partly be related to the dependency of a fusion gene induced epigenetic pathway. Histone demethylases (HDMs) were identified to regulate prostate cancer cell line proliferation. We discovered a novel histone JmjC-domain histone demethylase PHF8 to be highly expressed in high grade prostate cancers and mediate cell proliferation, migration and invasion in in vitro models. Additionally, we explored novel HDM inhibitor chemical structures using virtual screening methods. The structures best fitting to the active pocket of KDM4A were tested for enzyme inhibition and prostate cancer cell proliferation activity in vitro. In conclusion, our results show that prostate cancer may efficiently be targeted with combined AR and HDAC inhibition which is also currently being tested in clinical trials. HDMs were identified as another feasible novel drug target class. Future studies in representative animal models and development of specific inhibitors may reveal HDMs full potential in prostate cancer therapy
