The melanoma differentiation associated gene-7 (mda-7) has a potential inhibitory role in melanoma progression, although the mechanisms underlying this effect are still unknown. mda-7 mRNA has been found to be present at higher levels in cultured normal melanocytes compared with metastatic melanoma cell lines. Furthermore, levels of mda-7 message have shown an inverse correlation with melanoma progression in human tumor samples, suggesting that mda-7 may be a novel tumor suppressor gene. We have designed this study to investigate MDA-7 protein expression in different stages of melanoma progression and to examine its antiproliferative effects in vitro. Our data demonstrate that MDA-7 protein can be found in normal melanocytes and early stage melanomas. It is also observed in smooth muscle cells in the skin. However, in keeping with a possible role as a tumor suppressor, MDA-7 expression is decreased in more advanced melanomas, with nearly undetectable levels in metastatic disease. We also investigated antitumor effects of overexpressed MDA-7 on human melanoma cells in vitro. A feature of malignant tumors that is considered therapeutically exploitable is the loss of cellular differentiation. This has lead to a search for tissue-specific differentiation factors that might be reintroduced into tumors in order to modify their growth and ability to metastasize. In the case of melanoma, several unique genes have been isolated by Jiang et al. 1 from a melanoma cell line induced to differentiate by interferon-␤ and mezerein. One of the most interesting and promising of these genes is the melanoma differentiation associated gene-7 (mda-7). Since its initial isolation from melanoma cells and subsequent molecular characterization, the mda-7 gene and MDA-7 protein have been studied in numerous other tumor types, some of which have included carcinoma of the lung, breast, prostate and cervix. 2 Experiments using an adenovirus/mda-7 vector construct (Ad-mda-7) to infect normal and malignant cells have consistently demonstrated growth-inhibitory effects on various tumor types, but no inhibitory effects on normal cells. 3,4 These findings have prompted the development of the Ad-mda-7 as a potential therapeutic agent, and plans for a phase I clinical trial are under way. Although the initial description of mda-7 occurred in melanoma, most of the clinically relevant research has focused on the more prevalent malignancies. Our results demonstrate that Ad-mda-7 induces apoptosis and G2/M cell cycle arrest in melanoma cellsOur laboratory has an ongoing interest in the development of prognostic tools and therapeutic interventions for advanced melanoma. We have therefore undertaken a study to better define the significance of MDA-7 in this disease. We describe in this paper our data from human tumors and cell lines demonstrating that MDA-7 protein can be found in normal melanocytes, early stage melanomas and smooth muscle cells. However, in keeping with a role as a tumor suppressor, MDA-7 expression is decreased in more advanced melanom...

No abstract

No abstract

Objective: To assess middle‐aged Australian women's retrospective reports of how intended and wanted were their pregnancies, and the degree of happiness associated with these pregnancies. Methods: A self‐administered questionnaire was sent to 1000 participants in the Mid‐Age cohort of the Australian Longitudinal Study on Women's Health. Results: Responses from 811 women (81%) showed that, although 32% of first pregnancies were unplanned and 29% were unwanted, most women recall being happy with their pregnancies and termination rates were very low. The second pregnancy was the most planned and wanted and associated with the highest levels of happiness. Conclusions: While the majority of middle‐aged women report having been happy to be pregnant, and the majority of pregnancies are described retrospectively as planned and wanted, a significant proportion of pregnancies are unwanted, unplanned or resulting from unintended contraceptive failure. Implications: The data support the continuing need for widely available, affordable and sensitive fertility control services.

Purpose The purpose of this paper is to argue, using the New Zealand context as reference, that heterogeneous societies with diverse cultures have an expanded space of possibilities for developing social innovations. Design/methodology/approach Incorporation of the cultural context is integral to finding innovative, collective solutions for mitigating complex social problems and sparking transformational social change. Empirical support for this contention draws on examples of social innovations that embed the cultural values of Māori, New Zealand’s indigenous people. Findings Using illustrative cases, the authors highlight the capacity of Māori values, encompassed in an ecosystem of Māori social institutions, to catalyse social innovation in New Zealand. The authors position these examples within two paradigms of social innovation. Research limitations/implications The paper limits its focus to the implications of Māori cultural values for social innovation. However, it serves to highlight that appreciation of indigenous and minority cultural values can provide a foundation for social innovations in other contexts too. Practical implications Recognising cultural values increases the range of possibilities for innovatively addressing social and environmental challenges. Social implications Respect and recognition of indigenous culture and knowledge offers potential for sustainable solutions to complex social challenges. Originality/value This is one of the few papers to explore the cultural embeddedness of social innovation and highlight public policy social innovations.