The role of p73 in cancer – a pathway towards more effective cancer therapy

The p53-family consists of three transcription factors, p53, p73 and p63. The family members have similar but also individual functions connected to cell cycle regulation, development and tumorigenesis. p53 and p73 act mainly as tumor suppressors. During DNA damage caused by anticancer drugs or irradiation, p53 and p73 levels are upregulated in cancer cells leading to apoptosis and cell cycle arrest. p53 is mutated in almost 50 per cent of the cancers, causing the cancer cells unable to undergo cell death. Instead, p73 is rarely mutated in cancer cells and because of that could be more viable target for anticancer therapy. The network surrounding the regulation of p73 is extensive and has several potential targets for cancer therapy. One of the most studied is Itch ligase, the negative regulator of p73 levels. Gene therapy directed towards knockdown of Itch ligase is a potential approach but in need for more in vivo proof. p73 has two isoforms, transactivating TA-forms and dominant-negative ΔN-forms. The specific regulation of these isoforms could also offer a possible way for more effective cancer treatment. The literature work includes information of structures, isoforms, functions and possible therapeutic targets of p73. Also the main therapeutic approaches to date are introduced. The experimental part is based on transfection and cytotoxicity studies done e.g. in pancreatic cancer cells (Mia PaCa-2, PANC1, BxPc-3 and HPAC). The aim of the experimental work was to optimize the conditions for effective transfection with DAB16 dendrimer nanoparticles and to measure the cytotoxicity of plain dendrimers and DAB16-pDNA complexes. Also the protein levels of p73 and Itch ligase were measured by Western blotting. The work was done as a part of a bigger project, which was aiming to down regulate Itch ligase (negative regulator of p73) by siRNA/shRNA. Tranfection results were promising, showing good transfection efficacy with DAB16 N/P30 in pancreatic cancer cells (except in BxPc-3). Pancreatic cancer cells showed recovery in 3 days after they were exposed to plain dendrimer solution or to DAB16-pDNA. Measurement of protein levels by Western blotting was not optimal and the proposals for the improvement regarding e.g. the gels and the extracted protein amounts have been done.

Women, Management and Leadership - Naiset ja johtajuus : NASTA Women's Leadership Project Final Report

Leadership without the full participation of women not only excludes women individually and collectively, but is also a huge waste of talent, knowledge and expertise. And crucially, given the current state of society and the world, this aspect of gender inequality is likely to become even more important in the future. NASTA - Women’s Leadership: A Research and Education Development Project was established in 2005 as a national multi-university project mainly and generously funded by Finnish Ministry of Education. The project aims at producing new knowledge and increasing understanding about women’s leadership, as well as promoting women’s leadership through research, development of teaching, and public outreach. NASTA is a joint effort of three Finnish universities – Hanken School of Economics, University of Jyväskylä School of Business and Economics, and the Helsinki School of Economics (now part of Aalto University) – and has been coordinated by Hanken. This report presents research and activities conducted within and around the project. NASTA activities have been many and various. They have examined the position and experiences of women in relation to leadership, management, organisation and work more generally. They have sought new knowledge about gender and leadership, on women leaders’ values, attitudes and behaviour, as well as about values, attitudes and behaviour in relation to women’s leadership. NASTA activities have included teaching, student supervision, research theses, research projects, publishing, networking, seminars, meetings, an international conference, and knowledge transfer into other sectors of society. The first section of the book introduces NASTA joint projects, including web-based teaching material, a survey of gender staffing and teaching on gender in business schools, critical review of previous research literature, and new empirical research. The next section includes research articles on different aspects of gender, leadership and manage¬¬ment from more individual projects conducted by participating researchers and research groups linked to NASTA across the three universities. The final section includes short presentations of other research in progress. The appendix lists publications by NASTA members – journal articles, research reports, books, chapters, journal special issues, popular journal articles, magazine articles - and masters, licentiate and doctoral theses that have been produced. These matters of women, leadership and management are not simply academic concerns but urgent matters for practice, organisations, management, policy, and society more generally.