Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways

<p>Abstract</p> <p>Background</p> <p>Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI) anchored protein expressed not only in prostate but also in pancreas and bladder cancer as shown by immunohistochemistry and mRNA analysis. It has been targeted by monoclonal antibodies in preclinical animal models and more recently in a clinical trial in prostate cancer patients. The biological role played in tumor growth is presently unknown. In this report we have characterized the contribution of PSCA expression to tumor growth.</p> <p>Methods</p> <p>A bladder cell line was engineered to express a doxycycline (dox) regulated shRNA against PSCA. To shed light on the PSCA biological role in tumor growth, microarray analysis was carried out as a function of PSCA expression. Expression of gene set of interest was further analyzed by qPCR</p> <p>Results</p> <p>Down regulation of the PSCA expression was associated with reduced cell proliferation <it>in vitro </it>and <it>in vivo</it>. Mice bearing subcutaneous tumors showed a reduced tumor growth upon treatment with dox, which effectively induced shRNA against PSCA as revealed by GFP expression. Pathway analysis of deregulated genes suggests a statistical significant association between PSCA downregulation and activation of genes downstream of the IFNα/β receptor.</p> <p>Conclusions</p> <p>These experiments established for the first time a correlation between the level of PSCA expression and tumor growth and suggest a role of PSCA in counteracting the natural immune response.</p

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Økt selvbestemmelse? - Har det nye vilkåret om samtykkekompetanse i psykisk helsevernloven § 3-3 nr. 4 fungert etter sin hensikt?

Oppgaven omhandler kravet til manglende samtykkekompetanse i phvl. § 3-3 nr. 4. I 2017 ble det vedtatt at pasienter som skal underlegges tvungent psykisk helsevern må mangle samtykkekompetanse. Lovgiver ønsket å redusere bruk av tvang og gi pasientene økt selvbestemmelse og rettssikkerhet. I oppgaven vurderer jeg om vilkåret har fungert etter sin hensikt. Vilkåret er vagt og upresist. Styrende for vurderingen er derfor et rundskriv fra Helsedirektoratet (IS-1/2017). For å besvare problemstillingen har jeg blant annet analysert 40 dommer fra lagmannsretten, sammen med de to sentrale avgjørelsene fra Høyesterett i HR-2018-2204-A og HR-2020-1167-A. Det åpenbarte seg et tydelig motsetningsforhold mellom pasientens autonomi og integritetsvern holdt opp mot den medisinskfaglige vurderingen. Lagmannsrettspraksis indikerer at hensynet til å behandle pasienten og det som antas å være til pasientens medisinskfaglig beste ofte tillegges avgjørende vekt, i strid med intensjonen bak lovbestemmelsen

Examination of the roles and capacities of duty bearers responsible for protecting the human rights to adequate food, nutritional health and wellbeing in Ugandan children’s homes

Background The majority of Ugandan children face vulnerability and malnutrition. As a State Party to international human rights treaties, Uganda has legal obligations of guaranteeing the fundamental rights and the best interest of the nation’s children. Despite being protected under international and national law, Uganda is not providing adequate child protection, including safeguarding children’s food security. Numerous privately owned and unregulated children’s homes face this problem. The overall aim of the study was to examine to what extent children’s homes’ operations are consistent with the right to adequate food, nutritional health and wellbeing of children. Methods We performed a qualitative role- and capacity analysis of duty bearers with human rights duties towards children living in children’s homes. We studied three groups of duty bearers: caretakers working in private children’s homes, State actors working in government and its institutions, and non-State actors working in civil society organizations. A human rights based approach guided all aspects of the study. An analysis of the roles, performance and capacities of duty bearers was employed, with individual face-to-face structured qualitative in-depth interviews, self-administered structured questionnaires, and a structured observational study, as well as a desk review of relevant literature. Results The State of Uganda’s efforts to respect and realize its obligations towards children living in children’s homes is inadequate. There are numerous capacity gaps among the duty bearers, and the concepts of human rights and the best interest of the child are not well understood among the duty bearers. Conclusion The efforts of the State of Uganda to realize its human rights obligations towards children in children’s homes are lacking in important areas. Hence the State does not fulfill its minimum obligations under the International Covenant on Economic, Social and Cultural Rights to ensure all children freedom from hunger. There is a need for capacity development at all levels in the Ugandan state and the international society to delimit capacity gaps in order to realize these human rights’ obligations

Additional file 1 of Examination of the roles and capacities of duty bearers responsible for protecting the human rights to adequate food, nutritional health and wellbeing in Ugandan children’s homes

Information on relevant international treaties, general comments as well as national legislation and policy framework included in 4 tables. (PDF 389 kb

Additional file 4 of Examination of the roles and capacities of duty bearers responsible for protecting the human rights to adequate food, nutritional health and wellbeing in Ugandan children’s homes

Guide for study of equity gaps in the children’s homes. (PDF 408 kb

Additional file 2 of Examination of the roles and capacities of duty bearers responsible for protecting the human rights to adequate food, nutritional health and wellbeing in Ugandan children’s homes

Interview guide for staff working in the children’s homes. (PDF 294 kb