The PI3K/mTOR signalling pathway plays a major role in biology and disease. Therefore, effective inhibitors that target proteins of this pathway have been developed. However, acquired resistance of cancer cells is a prevalent phenomenon that limits the durable response of these compounds. It is becoming apparent that experimental approaches for comprehensive biochemical analysis contribute to understand the complex mechanisms that confer drug resistance, and advances in largescale technologies including genomic sequencing and proteomics allow unprecedented molecular coverage without being biased for specific genes/cellular pathways. Initially, the phenotypic response of sensitive and resistant cells to the absence or presence of a PI3K inhibitor (PI3Ki), as well as other kinases, was examined. This study revealed that PI3Ki-resistant cells experience extensive phenotypic changes upon withdrawal of the PI3Ki from the culture media. The regulation of the proteome and phosphoproteome of sensitive and PI3Ki-resistant cells grown with or without the PI3Ki was analysed by shotgun mass spectrometry-based label-free quantitative technology. This analysis demonstrated that the proteomes and phosphoproteomes of drug-resistant cells are remodelled conditional to the presence of PI3Ki, and that the levels of enzymes with metabolic roles are modulated in resistant cells. Functional analysis of the metabolism of cells capable to survive in absence of PI3K/mTOR activity demonstrated that the bioenergetic activity of these cells is contingent on the presence of the selection drug. The complete set of protein-coding regions of the genome (exome) of sensitive and PI3Ki-resistant cells was then sequenced. This study unveiled common alterations in exome regions across PI3Kiresistant cell lines, as well as a degree of genomic heterogeneity between them. Lastly, the impact of lactic acid, a metabolic product, on a defined signalling network of the MCF7 breast cancer cell line was analysed. This study described the capacity of this metabolite to change the activity of signalling network branches.

Thesis (Ph. D. in Interdisciplinary Studies: Engineering Management)--Vanderbilt University, Dec. 2008. / Title from title screen. Includes bibliographical references.

The first part introduces the RFID technology and its application in the healthcare and pharma. The second part deals with the particular RFID application in the process of preparation and aplication of cytostatics at MOU. It includes process analysis, identification of areas where there is a lack in usage of technology potential, suggestions on how to increase the benefits of the implementation, as well as identification of factors that have impact on the valuation of RFID projects.

Thesis (Ph. D.)--Case Western Reserve University, 1995. / Includes bibliographical references (leaves 191-203). Issued also online.

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Source: Masters Abstracts International, Volume: 47-03, page: 1618. Adviser: Victor M. Cardenas. Includes bibliographical references.

The subject of the diploma thesis is a project of Centre for Prevention and an extension of the Clinic of Radiational oncology on the edge of Masaryk Memorial Cancer Institute in Brno. The project completes pavilions composition. It responses to the future development designed in nearest surrounding. The project creates a new public space with a view towards Brno and the Pálava area. The project also proposes a sequential building – the Prevention centre at first and the Proton centre later.

A project deals with a proposal of a new cancer-prevention centre located at the Masaryk Memorial Cancer Institute in Brno. The design proposal includes the cancer prevention centre itself with outpatients’ department, inpatient ward department, adjacent commercial and administrative programme and with a proton therapy centre.