The prognosis for patients with high-grade cerebral glioma is poor. Most treatment failures are due to local recurrence of tumor, indicating that a more aggressive local therapy could be beneficial. Adjuvant treatments such as porphyrin-sensitized photodynamic therapy (PDT) or boron neutron capture therapy (BNCT) have the potential to control local recurrence. The selective tumor uptake of a boronated porphyrin was studied in CBA mice bearing an implanted intracerebral glioma. Biopsy samples of tumor, normal brain, and blood were analyzed by a fluorometric assay following intraperitoneal and intravenous administration of boronated protoporphyrin (BOPP). This compound was selectively localized to tumor at ratios as high as 400:1 relative to normal brain.Confocal laser scanning microscopy of glioma cells in vitro and in vivo showed that BOPP was localized within mitochondria and excluded from the nucleus of these cells. This discrete subcellular localization was confirmed by density gradient ultracentrifugation after homogenization of mouse tumor biopsies. The selective discrete localization of these compounds within the tumor suggests that this compound may be used as a dual PDT/BNCT sensitizer.Primary cerebral tumors are responsible for -2% of all cancer deaths, with =10,000 persons dying per annum in the United States (1). The majority of these deaths are due to the high-grade gliomas-anaplastic astrocytoma and glioblastoma multiforme. At present there is no satisfactory treatment for these tumors. Surgery provides a definitive histological diagnosis and relief of symptoms of raised intracranial pressure. Radiotherapy and adjuvant chemotherapy are of limited value and most studies utilizing these treatments report median survival times of <1 year (1, 2). Most treatment failures are due to local recurrence of the tumor, suggesting that more aggressive local therapy could be beneficial. Two adjuvant therapies with the potential to control local recurrence are photodynamic therapy (PDT) and boron neutron capture therapy (BNCT).PDT relies on the selective uptake or retention of a photosensitizing chemical in the tumor relative to surrounding normal tissue, followed by treatment with light of the appropriate wavelength to activate the photosensitizer (3). The photoactivation of this sensitizer results in generation of a cytotoxic chemical species, probably singlet excited state oxygen, which leads to selective tumor necrosis (3). Photosensitizers that have been used in most clinical and experimental studies to date are hematoporphyrin derivative (HpD) and its enriched commercial preparation Photofrin II (3), both of which have been shown to selectively localize in glioblastoma multiforme (4, 5). Reports of PDT in the treatment of animal (5-7) and human (5, 7-9) gliomas have been encouraging, although the use of a more tumor-selective photosensitizer than HpD or Photofrin II would be desirable.Like PDT, BNCT is based on selective tumor localization of a sensitizing agent, a compound containing 10B atoms, fo...

Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma (IDC). Annotation of the genetic differences between the two lesions may assist in the identification of genes that promote the invasive phenotype. Synchronous DCIS and IDC cells were microdissected from FFPE tissue and analysed by molecular inversion probe (MIP) copy number arrays. Matched IDC and DCIS showed highly similar copy number profiles (average of 83% of the genome shared) indicating a common clonal origin although there is evidence that the DCIS continues to evolve in parallel with the co-existing IDC. Four chromosomal regions of loss (3q, 6q, 8p and 11q) and four regions of gain (5q, 16p, 19q and 20) were recurrently affected in IDC but not in DCIS. CCND1 and MYC showed increased amplitude of gain in IDC. One region of loss (17p11.2) was specific to DCIS. IDC-specific regions include genes with previous links to breast cancer progression and potential therapeutic targets such as AXL, SPHK1 and PLAUR.

Growing climate change challenges and increasingly strict sustainability standards have led to a significant growth in the need for building refurbishment projects which are essentially focused on retrofitting in order to make them low carbon, energy efficient and environmentally friendly. The Waste and Resources Action Programme (WRAP) suggested that Building Information Modelling (BIM) should be used to achieve sustainability requirements during refurbishment projects as a correspondence to the National Audit Office (NAO) sustainability report. BIM is now widely advocated as the preferred tool for the management and co-ordination of design and construction data using object-oriented principles. The successful integration of environmental assessment into BIM for the whole of the construction lifecycle has not yet been achieved. The potential for using BIM in refurbishment projects specifically for achieving and managing sustainability requirements has not been yet critically reviewed or put into practice. This paper focuses on the use of BIM sustainability design tools in refurbishment projects, to achieve energy efficient buildings and achieve sustainability criteria for refurbishing non-domestic buildings. A critical lens is cast on the current literature in the domains of sustainable designs and the associated implications of the sustainability decision-support tools in BIM. The research also reviews the practicality of the existing sustainability decisionsupport tools that are currently used to assist with achieving environmental scheme certifications such as BREEAM and LEED for refurbishment projects.

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