Maspin is a tumour suppressor that inhibits breast cancer tumour metastasis in vivo

Maspin is a member of the serpin family of serine proteases and functions as a tumour suppressor. A study using a new syngeneic mouse model for breast cancer suggests that maspin can inhibit metastasis in vivo

Expression of a protease-resistant insulin-like growth factor-binding protein-4 inhibits tumour growth in a murine model of breast cancer

BACKGROUND: Insulin-like growth factor 1 (IGF1) promotes breast cancer and disease progression. Bioavailability of IGF1 is modulated by IGF-binding proteins (IGFBPs). IGFBP4 inhibits IGF1 activity but cleavage by pregnancy-associated plasma protein-A (PAPP-A) protease releases active IGF1. METHODS: Expression of IGF pathway components and PAPP-A was assessed by western blot or RT-PCR. IGFBP4 (dBP4) resistant to PAPP-A cleavage, but retaining IGF-binding capacity, was used to block IGF activity in vivo. 4T1.2 mouse mammary adenocarcinoma cells transfected with empty vector, vector expressing wild-type IGFBP4 or vector expressing dBP4 were implanted in the mammary fat pad of BALB/c mice and tumour growth was assessed. Tumour angiogenesis and endothelial cell apoptosis were assessed by immunohistochemistry. RESULTS: 4T1.2 cells expressed the IGF1R receptor and IGFBP4. PAPP-A was expressed within mammary tumours but not by 4T1.2 cells. Proliferation and vascular endothelial growth factor (VEGF) production by 4T1.2 cells was increased by IGF1(E3R) (recombinant IGF1 resistant to binding by IGFBPs) but not by wild-type IGF1. IGF1-stimulated microvascular endothelial cell proliferation was blocked by recombinant IGFBP4. 4T1.2 tumours expressing dBP4 grew significantly more slowly than controls or tumours expressing wild-type IGFBP4. Inhibition of tumour growth by dBP4 was accompanied by the increased endothelial cell apoptosis. CONCLUSION: Protease-resistant IGFBP4 blocks IGF activity, tumour growth and angiogenesis

Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone

INTRODUCTION: Studies in xenograft models and experimental models of metastasis have implicated several β3 integrin-expressing cell populations, including endothelium, platelets and osteoclasts, in breast tumor progression. Since orthotopic human xenograft models of breast cancer are poorly metastatic to bone and experimental models bypass the formation of a primary tumor, however, the precise contribution of tumor-specific αvβ3 to the spontaneous metastasis of breast tumors from the mammary gland to bone remains unclear. METHODS: We used a syngeneic orthotopic model of spontaneous breast cancer metastasis to test whether exogenous expression of αvβ3 in a mammary carcinoma line (66cl4) that metastasizes to the lung, but not to bone, was sufficient to promote its spontaneous metastasis to bone from the mammary gland. The tumor burden in the spine and the lung following inoculation of αvβ3-expressing 66cl4 (66cl4beta3) tumor cells or control 66cl4pBabe into the mammary gland was analyzed by real-time quantitative PCR. The ability of these cells to grow and form osteolytic lesions in bone was determined by histology and tartrate-resistant acid phosphatase staining of bone sections following intratibial injection of tumor cells. The adhesive, migratory and invasive properties of 66cl4pBabe and 66cl4beta3 cells were evaluated in standard in vitro assays. RESULTS: The 66cl4beta3 tumors showed a 20-fold increase in metastatic burden in the spine compared with 66cl4pBabe. A similar trend in lung metastasis was observed. αvβ3 did not increase the proliferation of 66cl4 cells in vitro or in the mammary gland in vivo. Similarly, αvβ3 is not required for the proliferation of 66cl4 cells in bone as both 66cl4pBabe and 66cl4beta3 proliferated to the same extent when injected directly into the tibia. 66cl4beta3 tumor growth in the tibia, however, increased osteoclast recruitment and bone resorption compared with 66cl4 tumors. Moreover, αvβ3 increased 66cl4 tumor cell adhesion and αvβ3-dependent haptotactic migration towards bone matrix proteins, as well as their chemotactic response to bone-derived soluble factors in vitro. CONCLUSION: These results demonstrate for the first time that tumor-specific αvβ3 contributes to spontaneous metastasis of breast tumors to bone and suggest a critical role for this receptor in mediating chemotactic and haptotactic migration towards bone factors

Using a remote system to study the thermal properties of a vegetable oil filled power transformer: how does operation differ from mineral oil

There has been much discussion on the properties of natural esters and how they can be best applied as a transformer dielectric. The thermal properties of natural esters are different from those of mineral oil. A difficulty with investigating the thermal properties is that it is uncommon to find the same transformer design filled with different fluids. Two 90MVA power transformers were manufactured to the same design and installed in the south east of England, UK, where they were connected to the internet via a private connection. The transformers have been filled with different dielectrics, one being mineral oil and the other a natural ester. Remote monitoring has allowed us to perform a field study on the thermal properties of a natural ester and their effect on the operation of the transformer. The investigation shows that despite the viscosity affecting the cooling capability a power transformer can be designed so that there is little effect on its temperature. This study also demonstrates the advantage of remote monitoring, where a team in Australia can oversee a transformer on the other side of the world

A zero carbon future: based on current initiatives, how long before Australia meets its energy needs from renewable energies?

The Australian government has a target for 20% of electricity to be generated from renewable sources by 2020. In this paper we review the progress of installing renewable generation in Australia and ask, firstly, whether Australia is on track to meet its target and secondly, whether a goal should be set to generate all of Australia's electricity needs from renewables. If it is concluded that there is the potential for 100% generation by renewable how should this be accomplished? We found that progress on the state level was not consistent. It was also notable that while all states had a plan to reach the federal government's target, none appeared to have concrete plans to manage the reduction of fossil fuel usage by retiring old power stations. There seemed to be an expectation that the renewables target would be reached by installing new capacity. In order to reach the federal government 20% target, an annual growth of 10% in renewable energy production is required. Extrapolating this rate of increase in renewable energy share into the future suggests that Australia could achieve 100% renewable generation by the 2040s. With respect to the obvious technical hurdles in reaching full renewable coverage (e.g. intermittency and reliability), geothermal appears as a valuable option for exploitation, and as such its use is currently being explored in Australia

Life estimation techniques for transformer insulation

A significant proportion of power transformers are approaching the end of their designed life. However, the Utilities are coming under increasing pressure to delay asset upgrade costs. Therefore, in order to determine whether delaying a replacement for a particular power transformer is safe the Utilities require tools to help them reach this decision

Exposure of vegetable oil impregnated transformer windings to air

A large quantity of research into the use of vegetable oils as transformer dielectrics has been performed over the years. Together with over ten years of practical experience, vegetable oil based dielectrics have been demonstrated to be effective for use within a transformer. One of the practical issues of maintaining transformers filled with these fluids is that a Utility is likely to extensively service the unit twenty or so years into its operating life. During this service the fluid impregnated cellulosic structure is exposed to the air. We have therefore been conducting investigations into the effect of air on the windings. Specifically, whether the rate of water adsorption and the formation of residues on the surface of the paper insulation is different when a vegetable oil is used instead of mineral oil. We are firstly investigating residue formation in the laboratory setting, by studying the interactions between paper, vegetable oil and air. Secondly we will apply the findings of the laboratory studies to small transformers, by exposing their windings to the atmosphere under controlled conditions then searching for gelling. In this paper we present some preliminary findings of the project