Science

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Now showing 1 - 10 of 77
  • (2006) Hitchins, Megan; Suter, C; Wong, Jenny; Cheong, Kay; Hawkins, Nicholas; Leggett, B; Scott, R; Spigelman, Allan; Tomlinson, Ian; Martin, David; Ward, Robyn
    Journal Article

  • (2003) Welsh, John; Sapinoso, Lisa; Kern, Suzanne; Brown, David; Liu, Tao; Bauskin, Asne; Ward, Robyn; Hawkins, Nicholas; Quinn, David; Russell, Pamela; Sutherland, Robert; Breit, Samuel; Moskaluk, Christopher; Frierson Jr, Henry; Hampton, Garret
    Journal Article
    Genetic alterations in tumor cells often lead to the emergence of growth-stimulatory autocrine and paracrine signals, involving overexpression of secreted peptide growth factors, cytokines, and hormones. Increased levels of these soluble proteins may be exploited for cancer diagnosis and management or as points of therapeutic intervention. Here, we combined the use of controlled vocabulary terms and sequence-based algorithms to predict genes encoding secreted proteins from among ≈12,500 sequences represented on oligonucleotide microarrays. Expression of these genes was queried in 150 carcinomas from 10 anatomic sites of origin and compared with 46 normal tissues derived from the corresponding sites of tumor origin and other body tissues and organs. Of 74 different genes identified as overexpressed in cancer tissues, several encode proteins with demonstrated clinical diagnostic application, such as α-fetoprotein in liver carcinoma, and kallikreins 6 and 10 in ovarian cancer, or therapeutic utility, such as gastrin-releasing peptide/bombesin in lung carcinomas. We show that several of the other candidate genes encode proteins with high levels of tumor-associated expression by immunohistochemistry on tissue microarrays and further demonstrate significantly elevated levels of another novel candidate protein, macrophage inhibitory cytokine 1, a distant member of the tranforming growth factor-β superfamily, in the serum of patients with metastatic prostate, breast, and colorectal carcinomas. Our results suggest that the combination of annotation/protein sequence analysis, transcript profiling, immunohistochemistry, and immunoassay is a powerful approach for delineating candidate biomarkers with potential clinical significance and may be broadly applicable to other human diseases.

  • (2003) Brown, David; Ward, Robyn; Buckhaults, Philip; Liu, Tao; Romans, Katherine; Hawkins, Nicholas; Bauskin, Asne; Kinzler, Kenneth; Vogelstein, Bert; Breit, Samuel
    Journal Article
    Purpose: Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the tumor growth factor ß (TGF-ß) superfamily. Several observations suggest that it plays a role in colorectal carcinoma (CRC). In particular, MIC-1 is markedly up-regulated in colorectal cancers as well as in premalignant adenomas. This study examines the relationship of serum MIC-1 levels and genotypes to clinical and pathologic features of colonic neoplasia. Experimental Design: We confirmed the presence of MIC-1 in CRC tissue and the cell line CaCo-2. The normal range for serum MIC-1 levels was defined in 260 healthy blood donors, and the differences between normal subjects and 193 patients having adenomatous polyps or CRC were then determined. In a separate cohort of 224 patients, we evaluated the relationship of MIC-1 serum level and genotype to standard tumor parameters and outcome measures. Results: MIC-1 was expressed in CRC tissue and the cancer cell line CaCo-2. There was a progressive increase in serum MIC-1 levels between normal individuals [mean (M) = 495 pg/ml, SD = 210), those with adenomatous polyps (M = 681 pg/ml, SD = 410), and those with CRC (M = 783 pg/ml, SD = 491)]. Serum MIC-1 level was correlated with the extent of disease so that the levels were higher in patients with higher Tumor-Node-Metastasis stage. There were significant differences in time to relapse and overall survival between subjects with different MIC-1 levels and genotypes. Conclusions: This study identifies a strong association between MIC-1 serum levels and neoplastic progression within the large bowel. We suggest that the measurement of serum MIC-1 levels and determination of MIC-1 genotype may have clinical use in the management of patients with CRC.

  • (1998) Bradley, Peter; Rozenfeld, Anatoly; Lee, Kevin; Jamieson, Dana; Heiser, Gernot; Satoh, S
    Journal Article
    The first results obtained using a SOI device for microdosimetry applications are presented. Microbeam and broadbeam spectroscopy methods are used for determining minority carrier lifetime and radiation damage constants. A spectroscopy model is presented which includes the majority of effects that impact spectral resolution. Charge collection statistics were found to substantially affect spectral resolution. Lateral diffusion effects significantly complicate charge collection

  • (1998) Lutze, J; Roden, J; Holly, C; Wolfe, Joseph; Egerton, J; Ball, Malcolm
    Journal Article
    Growth under elevated [CO2] promoted spring frost damage in field grown seedlings of snow gum (Eucalyptus pauciflora Sieb. ex Spreng.), one of the most frost tolerant of eucalypts. Freezing began in the leaf midvein, consistent with it being a major site of frost damage under field conditions. The average ice nucleation temperature was higher in leaves grown under elevated [CO2] (– 5.7 oC versus – 4.3 oC), consistent with the greater incidence of frost damage in these leaves (34% versus 68% of leaves damaged). These results have major implications for agriculture, forestry and vegetation dynamics, as an increase in frost susceptibility may reduce potential gains in productivity from CO2 fertilization and may affect predictions of vegetation change based on increasing temperature.

  • (2008) Gattellari, Melina; Worthington, John; Zwar, N; Middleton, Susan
    Journal Article
    Background and Purpose: Anticoagulation reduces the risk of stroke in nonvalvular atrial fibrillation yet remains underused. We explored barriers to the use of anticoagulants among Australian family physicians. Methods: The authors conducted a representative, national survey. Results: Of the 596 (64.4%) eligible family physicians who participated, 15.8% reported having a patient with nonvalvular atrial fibrillation experience an intracranial hemorrhage with anticoagulation and 45.8% had a patient with known nonvalvular atrial fibrillation experience a stroke without anticoagulation. When presented with a patient at `very high risk` of stroke, only 45.6% of family physicians selected warfarin in the presence of a minor falls risk and 17.1% would anticoagulate if the patient had a treated peptic ulcer. Family physicians with less decisional conflict and longer-standing practices were more likely to endorse anticoagulation. Conclusion: Strategies to optimize the management of nonvalvular atrial fibrillation should address psychological barriers to using anticoagulation.

  • (2006) Gattellari, Melina; Zwar, N; Worthington, John; Middleton, Susan
    Journal Article
    Background and Purpose: Anticoagulation reduces the risk of stroke in nonvalvular atrial fibrillation yet remains underused. We explored barriers to the use of anticoagulants among Australian family physicians. Methods: The authors conducted a representative, national survey. Results: Of the 596 (64.4%) eligible family physicians who participated, 15.8% reported having a patient with nonvalvular atrial fibrillation experience an intracranial hemorrhage with anticoagulation and 45.8% had a patient with known nonvalvular atrial fibrillation experience a stroke without anticoagulation. When presented with a patient at "very high risk" of stroke, only 45.6% of family physicians selected warfarin in the presence of a minor falls risk and 17.1% would anticoagulate if the patient had a treated peptic ulcer. Family physicians with less decisional conflict and longer-standing practices were more likely to endorse anticoagulation. Conclusion: Strategies to optimize the management of nonvalvular atrial fibrillation should address psychological barriers to using anticoagulation.

  • (1997) Das, T; Munroe, Paul; Bandyopadhyay, Srikanta; Bell, Toby; Swain, M
    Journal Article

  • (1995) Bandyopadhyay, Srikanta; Mukherjee, S; Perera, D; Mori, K; Swain, M; Bell, Toby
    Conference Paper

  • (2008) Wakefield, Claire; Meiser, Bettina; Homewood, J; Peate, Michelle; Taylor, Adrian; Lobb, Elizabeth; Kirk, J; Young, Mark; Williams, Robyn; Dudding, T; Tucker, Katherine
    Journal Article
    Purpose To measure the effectiveness of a tailored decision aid (DA) designed to help women make informed decisions about genetic testing for breast/ovarian cancer risk. Methods A total of 145 women were randomized to receive the DA or a control pamphlet at the end of their first genetic counseling consultation. Of these, 120 (82.8%) completed two questionnaires, 1 week and 6 months post-consultation. Results While the DA had no effect on informed choice, post-decisional regret or actual genetic testing decision, the trial showed that women who received the DA had higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet (chi(2)(2) = 6.82; P = 0.033; chi(2)(1) = 4.86; P = 0.028 respectively). The DA also helped women who did not have blood drawn at their first consultation to clarify their values with regards to genetic testing (chi(2)(1) = 5.27; P = 0.022). Women who received the DA were less likely to share the information with other family members than women in the control condition (chi(2)(1) = 8.78; P = 0.003). Conclusions Decision aids are an effective decision-support strategy for women considering genetic testing for breast/ovarian cancer risk, and are most effective before the patient has made a decision, which is generally at the point of having blood drawn.