Medicine (St Vincent's) - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/205

Filters

2003 4
4
Reset filters

Settings
Statistics
Citations
Start date: 2003 × End date: 2003 ×

Search Results

Now showing 1 - 4 of 4
  • Item
    No Preview Available
    Generation and analysis of Siah2 mutant mice
    Frew, IJ ; Hammond, VE ; Dickins, RA ; Quinn, JMW ; Walkley, CR ; Sims, NA ; Schnall, R ; Della, NG ; Holloway, AJ ; Digby, MR ; Janes, PW ; Tarlinton, DM ; Purton, LE ; Gillespie, MT ; Bowtell, DDL (AMER SOC MICROBIOLOGY, 2003-12)
    Siah proteins function as E3 ubiquitin ligase enzymes to target the degradation of diverse protein substrates. To characterize the physiological roles of Siah2, we have generated and analyzed Siah2 mutant mice. In contrast to Siah1a knockout mice, which are growth retarded and exhibit defects in spermatogenesis, Siah2 mutant mice are fertile and largely phenotypically normal. While previous studies implicate Siah2 in the regulation of TRAF2, Vav1, OBF-1, and DCC, we find that a variety of responses mediated by these proteins are unaffected by loss of Siah2. However, we have identified an expansion of myeloid progenitor cells in the bone marrow of Siah2 mutant mice. Consistent with this, we show that Siah2 mutant bone marrow produces more osteoclasts in vitro than wild-type bone marrow. The observation that combined Siah2 and Siah1a mutation causes embryonic and neonatal lethality demonstrates that the highly homologous Siah proteins have partially overlapping functions in vivo.
  • Item
    No Preview Available
    Beyond FDG: novel PET tracers for cancer imaging.
    Hicks, RJ (E-MED LTD, 2003-09-02)
    Despite the excellent clinical performance of fluorodeoxyglucose (FDG) as a cancer-imaging agent for positron emission tomography (PET), false positive and false negative results can be problematic in some clinical settings. Radiopharmaceutical development has recently focussed on the search for new PET tracers that could complement or replace FDG in such settings. Due to the general availability and favourable physical properties of fluorine-18, much effort has been directed to fluorinated compounds. The most promising of these are discussed.
  • Item
    Thumbnail Image
    Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation
    Leong, T ; Michael, M ; Foo, K ; Thompson, A ; Joon, DL ; Weih, L ; Ngan, S ; Thomas, R ; Zalcberg, J (NATURE PUBLISHING GROUP, 2003-10-20)
    Chemoradiation is now used more commonly for gastric cancer following publication of the US Intergroup trial results that demonstrate an advantage to adjuvant postoperative chemoradiotherapy. However, there remain concerns regarding the toxicity of this treatment, the optimal chemotherapy regimen and the optimal method of radiotherapy delivery. In this prospective study, we evaluated the toxicity and feasibility of an alternative chemoradiation regimen to that used in the Intergroup trial. A total of 26 patients with adenocarcinoma of the stomach were treated with 3D-conformal radiation therapy to a dose of 45 Gy in 25 fractions with concurrent continuous infusional 5-fluorouracil (5-FU). The majority of patients received epirubicin, cisplatin and 5-FU (ECF) as the systemic component given before and after concurrent chemoradiation. The overall rates of observed grade 3 and 4 toxicities were 38 and 15%, respectively. GIT grade 3 toxicity was observed in 19% of patients, while haematologic grade 3 and 4 toxicities were observed in 23%. Our results suggest that this adjuvant regimen can be delivered safely and with acceptable toxicity. This regimen forms the basis of several new studies being developed for postoperative adjuvant therapy of gastric cancer.
  • Item
    Thumbnail Image
    Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiation
    Chong, MMW ; Cornish, AL ; Darwiche, R ; Stanley, EG ; Purton, JF ; Godfrey, DI ; Hilton, DJ ; Starr, R ; Alexander, WS ; Kay, TWH (CELL PRESS, 2003-04)
    To determine the tissue-specific functions of SOCS-1, mice were generated in which the SOCS-1 gene could be deleted in individual tissues. A reporter gene of SOCS-1 promoter activity was also inserted. Using the reporter, high SOCS-1 expression was found at the CD4(+)CD8(+) stage in thymocyte development. To investigate the function of this expression, the SOCS-1 gene was specifically deleted throughout the thymocyte/T/NKT cell compartment. Unlike SOCS-1(-/-) mice, these mice did not develop lethal multiorgan inflammation but developed multiple lymphoid abnormalities, including enhanced differentiation of thymocytes toward CD8(+) T cells and very high percentages of peripheral CD8(+) T cells with a memory phenotype (CD44(hi)CD25(lo)CD69(lo)). These phenotypes were found to correlate with hypersensitivity to the gamma-common family of cytokines.