MTI-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression

Membrane type 1 metalloprotease (MT1-MMP) is a transmembrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly by activating pro-MMP2. We investigated the effects of MT1-MMP overexpression on in vitro and in vivo properties of human breast adenocarcinoma MCF7 cells, which do not express MT1-MMP or MMP-2. MT1-MMP and MMP-2 cDNAs were either transfected alone or cotransfected. All clones overexpressing MT1-MMP 1) were able to activate endogenous or exogenous pro-MMP-2, 2) displayed an enhanced in vitro invasiveness through matrigel-coated filters independent of MMP-2 transfection, 3) induced the rapid development of highly vascularized tumors when injected subcutanously in nude mice, and 4) promoted blood vessels sprouting in the rat aortic ring assay. These effects were observed in all clones overexpressing MT1-MMP regardless of MMP-2 expression levels, suggesting that the production of MMP-2 by tumor cells themselves does not play a critical role in these events. The angiogenic phenotype of MT1-MMP-producing cells was associated with an up-regulation of VEGF expression. These results emphasize the importance of MT1-MMP during tumor angiogenesis and open new opportunities for the development of antiangiogenic strategies combining inhibitors of MT1-MMP and VEGF antagonists. - Sounni, N. E., Devy, L., Hajitou, A., Frankenne, F., Munaut, C., Gilles, C., Deroanne, C., Thompson, E. W., Foidart, J. M., Noel, A. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression.

Regulation of breast cancer cells by hormones and growth factors : effects on proliferation and basement membrane invasiveness

The current understanding of the regulation of breast cancer cell proliferation and invasiveness by hormones and growth factors is reviewed. It has been shown that polypeptide growth factors are involved in hormone-independent breast cancer, and are sometimes oestrogen-regulated in hormone-responsive models. Basement-membrane invasiveness, relating to the metastatic potential of these cells, is also stimulated by oestrogen in hormone-dependent models, elevated in hormone-independent models, and is growth factor sensitive. Further understanding of the differential effects of growth factors on breast cancer cell proliferation and invasiveness should facilitate better therapeutic exploitation of regulation at this level.

Regulation of proliferation, invasion and growth factor synthesis in breast cancer by steroids

Endogenous ovarian estrogens and progestins appear to play a critical role in the development and progression of breast cancer. Local productions of growth factors probably also contribute to malignant proliferation, while production and activation of collagenolytic enzymes may be equally critical for local invasive processes. The current review focusses on characterization of growth factor-receptor systems operant in normal and malignant breast epithelium. In addition, the determinants of local invasion are reviewed: attachment, modality, and proteose secretion. Finally, data are discussed concerning the regulation of both proliferation and invasion by hormones and antihormonal agents in hormone-dependent breast cancer. The results suggest new potential pharmacologic targets to explore to suppress onset and progression of breast cancer.

Vulnerability to loneliness in people with intellectual disability: an explanatory model

Research with typically developing groups has identified loneliness as a significant predictor of a range of physical and mental health problems. This paper reviews research about loneliness in children and adults with intellectual disability. Although a considerable body of evidence has highlighted the difficulties individuals with intellectual disability have with friendships, there is a relative scarcity of research focused explicitly on loneliness. The available evidence suggests that up to half of those with intellectual disability are chronically lonely, compared with around 15-30% of people in the general population. The cognitive, physical and mental health problems already associated with intellectual disability are likely to be compounded by experiences of chronic loneliness. We argue that people with intellectual disability are highly vulnerable to loneliness and present a theoretical model of vulnerability that comprises three reciprocally influencing domains: social attitudes and expectations; opportunities and experiences; and skill deficits associated with intellectual disability. We propose that societal views which have traditionally devalued and stigmatised those with intellectual disability limit their opportunities for experiencing social and emotional connectedness with others. Individual skill deficits in areas such as communication, self-regulation and social understanding, as well as functional difficulties associated with intellectual disability, also potentially influence the opportunities and experiences of people with intellectual disability, both directly and via multiple layers of the social context. In turn, limited opportunities will entrench particular skill deficits and reinforce negative attitudes towards intellectual disability. Future research about loneliness and intellectual disability needs to address the difficulties of measuring emotional isolation in this population, as well as the possibility that people with intellectual disability may understand, experience and interpret loneliness somewhat differently from others. The model proposed in this paper provides a starting point for developing a more sophisticated understanding of the experience of loneliness for individuals with intellectual disability.

The educational pipeline for health care professionals : understanding the source of racial differences

The underrepresentation of blacks in the healthcare professions may have direct implications for the health outcomes of minority patients, underscoring the importance of understanding movement through the educational pipeline into professional healthcare careers by race. We jointly model individuals' postsecondary decisions including enrollment, college type, degree completion, and choosing a healthcare occupation requiring an advanced degree. We estimate the parameters of the model with maximum likelihood using data from the NLS-72. Our results emphasize the importance of pre-collegiate factors and of jointly examining the full chain of educational decisions in understanding the sources of racial disparities in professional healthcare occupations.

Regulation of microRNA-1288 in colorectal cancer : altered expression and its clinicopathological significance

We aim to examine the miR-1288 expression in cancer cell lines and a large cohort of patients with colorectal cancer. Two colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The miRNA expressions of miR-1288 were tested on these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). An exogenous miR-1288 (mimic) was used to detect cell proliferation and cell cycle changes in SW480 using MTT calorimetric assay and flow cytometry, respectively. In addition, tissues from 122 patients with surgical resection of colorectum (82 adenocarcinomas, 20 adenomas, and 20 non-neoplastic tissues) were tested for miR-1288 expression by qRT-PCR. The colon cancer cell lines showed reduced expression of miR-1288 compared to normal colonic epithelial cell line. Over expression of miR-1288 in SW480 cell line showed increased cell proliferation and increased G2-M phase cells. In tissues, reduced miR-1288 expression was noted in majority of colorectal adenocarcinoma compared to colorectal adenoma and non-neoplastic tissues. Reduced or absent expression of miR-1288 was noted in 76% (n = 62/82) of the cancers. The expression levels of miR-1288 were higher in distal colorectal adenocarcinomas (P = 0.013) and in cancers of lower T staging (P = 0.033). To conclude, alternation of miR-1288 expression is important in the progression of colorectal cancer. The differential regulation of miR-1288 was found to be related to cancer location and pathological staging in colorectal cancers.

Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation

Ataxia oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin, a putative DNA/RNA helicase which shares high homology to the yeast Sen1p protein and has been shown to play a role in the response to oxidative stress. To investigate further the function of senataxin, we identified novel senataxin-interacting proteins, the majority of which are involved in transcription and RNA processing, including RNA polymerase II. Binding of RNA polymerase II to candidate genes was significantly reduced in senataxin deficient cells and this was accompanied by decreased transcription of these genes, suggesting a role for senataxin in the regulation/modulation of transcription. RNA polymerase II-dependent transcription termination was defective in cells depleted of senataxin in keeping with the observed interaction of senataxin with poly(A) binding proteins 1 and 2. Splicing efficiency of specific mRNAs and alternate splice-site selection of both endogenous genes and artificial minigenes were altered in senataxin depleted cells. These data suggest that senataxin, similar to its yeast homolog Sen1p, plays a role in coordinating transcriptional events, in addition to its role in DNA repair.

Health law : scope, sources and forces

• For the purposes of this chapter, “health law” encapsulates regulation of the medical and health professions, the administration of health services and the maintenance of public health to the extent that it is connected to the provision of health services. • There are diverging views as to whether health law can be regarded as a discrete “area of law”. • Health law draws on other areas of law such as tort law, criminal law and family law. It also draws upon other disciplines, most notably medical and health ethics. • Social and economic forces have influenced the development and direction of health law, and these forces may become even more influential in the future. • The increasingly globalised world has implications for Australia's health systems and raises questions and creates commitments in respect of the international community. • Technological developments, including in respect of treatment, diagnosis and information management, create ongoing challenges for health law. • Patient rights, human rights and consumerism are increasingly key drivers in the development of health law. • Health law is significant to contemporary Australian society because of the gravity of the topics that fall within its ambit, its social relevance to so many aspects of human existence and endeavour, the important role it plays in protecting the vulnerable, and the extent to which it engages with fundamental principles of justice.

Beliefs about infant regulation, early infant behaviors and maternal postnatal depressive symptoms

Background: Young infants may have irregular sleeping and feeding patterns. Such regulation difficulties are known correlates of maternal depressive symptoms. Parental beliefs regarding their role in regulating infant behaviours also may play a role. We investigated the association of depressive symptoms with infant feeding/sleeping behaviours, parent regulation beliefs, and the interaction of the two. Method: In 2006, 272 mothers of infants aged up to 24 weeks completed a questionnaire about infant behaviour and regulation beliefs. Participants were recruited from general medical practices and child health clinics in Brisbane, Australia. Depressive symptomology was measured using the Edinburgh Postnatal Depression Scale (EPDS). Other measures were adapted from the ALSPAC study. Results: Regression analyses were run controlling for partner support, other support, life events, and a range of demographic variables. Maternal depressive symptoms were associated with infant sleeping and feeding problems but not regulation beliefs. The most important infant predictor was sleep behaviours with feeding behaviours accounting for little additional variance. An interaction between regulation beliefs and sleep behaviours was found. Mothers with high regulation beliefs were more susceptible to postnatal depressive symptoms when infant sleep behaviours were problematic. Conclusion: Mothers of young infants who expect greater control are more susceptible to depressive symptoms when their infant presents challenging sleep behaviour.

Health education action research (HEAR) framework

As a mandatory assessment technique of the Health Education Senior Syllabus (QSA, 2010), action research provides an opportunity for unique insights into health related knowledge, behaviours, beliefs, attitudes and values. It has the potential to be a very motivating and engaging form of learning and assessment. Despite these benefits, action research can be a daunting prospect for some students and a challenging form of assessment for teachers to conceptualise and construct. Session participants will be provided with a visual framework for understanding, structuring and sequencing action research projects. This framework will present a series of action research phases and map them against the four general objectives and three assessable dimensions of the syllabus (QSA, 2010. Participants are strongly encouraged to bring a copy of the syllabus for reference and use during this session. Reference Queensland Studies Authority. (2010). Health Education Senior Syllabus 2010. Brisbane: QSA.

The BRAKE Driver Awareness Program & Senior Health Education

The BRAKE Driver Awareness Program provides evidence-based behaviour, risk, attitude and knowledge education for young drivers. BRAKE was founded during 2006 by Queensland Police Sergeant Rob Duncan and has been delivered to more than 35,000 senior secondary students since 2007. BRAKE is a participant directed program supported by resources provided at no cost. It includes eight parts able to be delivered in different configurations. BRAKE is endorsed by the Queensland Police and Queensland Ambulance Services. It is recognised by the Queensland Studies Authority as a Queensland Certificate of Education registered life skills course. This session is a must attend for secondary teachers, coordinators, staff in senior leadership positions and other stakeholders seeking a unique approach to adolescent road safety education. It will conclude with an opportunity to consider how BRAKE can be integrated into the senior secondary Health Education curriculum or pastoral care, social action and personal development programs.

School based youth health nurses and attrition : the reasons for moving on

Like the UK, Australia has a number of school nursing models and programmes. The School Based Youth Health Nurse Program (SBYHNP) is a new and unique model of school nursing in Queensland, Australia. The SBYHNP represents a philosophical and structural shift from traditional school nursing programmes. The purpose of this qualitative case study is to explore the reasons School Based Youth Health Nurses (SBYHN) leave school nursing. Sixteen in-depth interviews were conducted with participants who practiced as SBYHN and left the SBYHNP. This case study reveals six themes: The politics’: Navigating the organisational divide, 'Unconditional positive regard’: Surviving without team cohesion, 'Absolutely exhausted’: Maintaining physical and emotional strength, ‘Definitely geographical’: Managing the tyranny of time and distance, ‘If things fell into place’: Thinking about what could have been, and ‘A stepping stone’: Moving on to the next nursing position. This case study suggests nurses considering school nursing as a specialty should seek opportunity to understand this complex role, ensure realistic expectations and ndertake relevant qualifications. This approach may secure the investment made by nurses and schools and create demand for a highly sort after position.

Health and safety regulatory reform in Australia : challenges and issues for smaller ethnic firms

In recent times significant change has occurred to the Australian health and safety regulatory context. In this paper we consider the potential response of smaller firms in general, and ethnic owned and/or operated smaller firms in particular. We draw on literature examining smaller firms' responses to regulation and apply this to what little we know about smaller ethnic firms in Australia in the context of the regulatory change. We highlight the challenges to owner managers and what could be done to engage and support smaller ethnic firms to realise the opportunities resulting from this regulatory change.