DNA alkylation and interstrand cross-linking by treosulfan

The anti-tumour drug treosulfan (L-threitol 1,4-bismethanesulphonate, Ovastat) is a prodrug for epoxy compounds by converting non-enzymatically to L-diepoxybutane via the corresponding monoepoxide under physiological conditions. The present study supports the hypothesis that this conversion of treosulfan is required for cytotoxicity in vitro. DNA alkylation and interstrand cross-linking of plasmid DNA is observed after treosulfan treatment, but this is again produced via the epoxide species. Alkylation occurs at guanine bases with a sequence selectivity similar to other alkylating agents such as the nitrogen mustards. In treosulfan-treated K562 cells, cross-links form slowly, reaching a peak at approximately 24 h. Incubation of K562 cells with preformed epoxides shows faster and more efficient DNA cross-linking. © 1999 Cancer Research Campaig

ASSAY OF MATRIX METALLOPROTEASES TYPE-8 AND TYPE-9 BY ELISA IN HUMAN BREAST-CANCER

DUFFY MJ, BLASER J, DUGGAN C, et al. ASSAY OF MATRIX METALLOPROTEASES TYPE-8 AND TYPE-9 BY ELISA IN HUMAN BREAST-CANCER. BRITISH JOURNAL OF CANCER. 1995;71(5):1025-1028.Results from model tumour systems suggest that either increased levels of certain metalloproteases (MMPs) or decreased levels of their inhibitors correlate with metastatic potential. In this study, levels of two MMPs, i.e. MMP-8 and -9, and their inhibitor tissue inhibitor of metalloprotease type 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay in human breast tumours. Levels of MMP-8 and -9 correlated significantly with each other, but neither MMP correlated with urokinase plasminogen activator. Levels of both MMP-8 and -9 were also significantly related to levels of TIMP-1. In contrast, neither MMP correlated with plasminogen activator inhibitor. No relationship was found between MMP-8, MMP-9 or TIMP-1 and either tumour size or metastasis to axillary nodes. MMP-8 and -9 levels were inversely related to levels of oestrogen receptors. MMP-8 but not MMP-9 levels were also inversely correlated with progesterone receptor levels. It is concluded that the assay for MMP-8 and -9 described here will permit the evaluation of these proteases as prognostic markers in cancer

Examining Physical Activity Service Provision to Culturally and Linguistically Diverse (CALD) Communities in Australia: A Qualitative Evaluation

Strong evidence exists for the role of physical activity in preventing and managing a range of chronic health conditions. A particular challenge in promoting physical activity as a health strategy exists in culturally and linguistically diverse (CALD) groups, as such groups demonstrate high risk for a range of non-communicable diseases. The aim of this research was to examine the perspective of multicultural health service providers for CALD groups with respect to the physical activity services/initiatives on offer, access barriers to these services, and ideas for future service delivery in this area. Semi-structured interviews were conducted with 15 multicultural health service providers across the capital cities of the three most populous states in Australia (New South Wales, Queensland, and Victoria), and thematic content analysis was used to examine the data. Findings indicated that the majority of physical activity initiatives were associated with organizations offering other social services for CALD communities but were greatly restrained by resources. As well, it was found that most services were not designed by taking into account specific cultural requirements for CALD communities or their cultural expectations. Common barriers identified to service uptake were classified as socio-cultural (e.g., gender, language, context of health) and environmental (e.g., transportation) in nature. These findings should be utilized when planning future physical activity and health promotion initiatives for increasing CALD participation. In particular, programs need to be culturally tailored to the specific expectations of CALD groups, addressing cultural safety and sensitivity, and should be in partnership with other organizations to extend the reach and capacity