Framework for better living with HIV in England

1 Introduction and overview 1.1 The goal, purpose and scope of the framework This framework is the first of its kind in the UK. It describes the shared aspirations of a group of agencies for the lives of people diagnosed with HIV in England. The overarching goal of the framework is: All people with HIV are enabled to have the maximum level of health, well-being, quality of life and social integration. This is no less than the majority of people in the country expect for themselves. However, numerous obstacles prevent people with HIV from achieving this goal. These obstacles are not about having the virus but about how people with the virus are treated. This overarching goal is the situation we want to bring about. We detail this goal in seventeen subsidiary goals (what we want to happen). Each of these has a number of related aims and target groups (what we want individuals and groups to do to bring about the goal). The framework starts with the individual and seeks to bring about the conditions most favourable to individual self-determination and self-empowerment. The purpose of the framework is to: • Promote and protect the rights and well-being of all people with HIV in England. • Maximise the capacity of individuals and groups of people with HIV to care for, advocate and represent themselves effectively. • Improve and protect access to appropriate, effective and sufficient information, social support and social care services. • Minimise social, economic, governmental and judicial change detrimental to the rights and well-being of people with HIV. • Build consensus among those with a responsibility for promoting the well-being and rights of people with HIV. • Provide benchmarks against which the activities of a range of key stakeholders can be assessed, critiqued and coordinated. The framework does not describe all the activities of the organisations represented in the Framework Development Group (see section 1.4). Nor can these organisations undertake all the interventions necessary within the framework. Rather, the framework seeks to mobilise and coordinate the actions of a broad range of individuals and groups, from people with HIV themselves to government ministers. The framework primarily seeks to benefit people with diagnosed HIV infection. It is concerned with the health and well-being of those diagnosed with HIV and not those with undiagnosed HIV or those who might become infected (HIV prevention).As we are concerned with the lives of people with HIV after diagnosis, this framework is not focused on increasing HIV testing or HIV diagnosis nor does it attend to the needs of the broader population affected by HIV except where they relate to people with diagnosed HIV

KAT5 (Tip60) is a potential therapeutic target in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Lysine acetyltransferases (KATs) including KAT5 have been linked with the development of cisplatin resistance. This gene may therefore be altered in MPM and could represent a novel candidate target for intervention. Using RT-PCR screening the expression of all known KAT5 variants was found to be markedly increased in malignant tumors compared to benign pleura. When separated according to histological subtype, KAT5 was significantly overexpressed in both the sarcomatoid and biphasic subgroups for all transcript variants. A panel of MPM cell lines including the normal pleural cells LP9 and Met5A was screened for expression of KAT5 variants. Treatment of cells with a small molecule inhibitor of KAT5 (MG-149) caused significant inhibition of cellular proliferation (p<0.0001), induction of apoptosis and was accompanied by significant induction of pro-inflammatory cytokines/chemokines

Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes. As such these genes could potentially represent novel candidate targets for intervention in MPM. Using RT-PCR we examined the expression of Kdm6aA and Kdm6b in a panel of MPM cell lines and in a cohort of snap-frozen patient samples isolated at surgery comprising benign, epithelial, biphasic and sarcomatoid histologies. Both Kdm6a and Kdm6b were found to be significantly overexpressed in MPM at the mRNA level. However, tests examining if targeting therapeutically Kdm6a/b using a specific small molecule inhibitor (GSK-J4) was potentially useful for treating MPM, revealed that anti-proliferative activity was higher at lower drug concentrations in cell lines derived from normal mesothelial cells compared to those derived from malignant cells. Treatments with GSK-J4 were found to be associated with the induction of apoptosis and increased expression of pro-inflammatory cytokines. As such our results demonstrate that whilst members of the Kdm6 family are overexpressed in MPM they may not be suitable candidates for therapy and may elicit a cytokine storm