Science handbook

1999 handbook for the faculty of Scienc

‘With Friends Like These’: Human Rights, Neoconservatism and U.S. Foreign Policy from Carter to Reagan.

This thesis engages with two emerging bodies of scholarship: the history of human rights and the history of U.S. neoconservatism. It begins with an exploration of the genesis of the contemporary international human rights movement, arguing that human rights as we know and understand them today were a product of the latter half of the twentieth century. Their path, however, was not a clear one. The emergence of neoconservative ideology in U.S. domestic politics would greatly impact upon the trajectory of the human rights movement under the presidencies of Jimmy Carter and Ronald Reagan. The latter period witnessed a conflict between America’s Watch and the Reagan administration over human rights as an ‘idea’ and as praxis, with U.S. policy towards Latin America as the primary battle field

Studies on breeding dwarf poinsettias (Euphorbia pulcherrima Willd.) and the influence of infective agents

BACKGROUND: Hypoxia, metabolism, and growth factor signaling are important prognostic features in most solid tumors. The purpose of this study was to determine whether head and neck squamous cell carcinoma (HNSCC) xenografts show similar biological and molecular characteristics as the primary tumor they originate from. METHODS: Eighteen HNSCC primary tumor-xenograft pairs were immunofluorescently stained for pimonidazole (hypoxia), carbonic anhydrase IX (CAIX), glucose transporter-1 (GLUT-1), monocarboxylate transporter-1 (MCT-1), monocarboxylate transporter-4 (MCT-4), epidermal growth factor receptor (EGFR), and phosphorylated protein kinase B (pAKT). RESULTS: Although no correlation was found for the amount of hypoxia, significant correlations between primary tumors and xenografts were observed for both the percentage of cells positive for expression and the hypoxia-related expression pattern of CAIX, GLUT-1, and MCT-1. For EGFR and MCT-4, the intensity of expression was correlated. No correlation was observed for pAKT. CONCLUSION: Xenografts did not always resemble the primary tumor they originate from, but the xenografts did represent the variability in expression levels and patterns observed in the primary tumors

Multiparameter analysis of vasculature, perfusion and proliferation in human tumour xenografts.

A method is presented in this report for concurrent analysis of vascular architecture, blood perfusion and proliferation characteristics in whole-tumour cross-sections of human larynx carcinoma and glioblastoma xenografts. Tumours were implanted subcutaneously in nude mice. After i.v. injection with Hoechst 33342 and bromodeoxyuridine (BrdUrd) as perfusion and proliferation markers, animals were killed. An antiendothelial antibody (9F1) was used to delineate vascular structures. Cross-sections were analysed by a multistep immune staining and a computer-controlled microscope scanning method. Each tumour section was stained and scanned four times (Hoechst, 9F1, BrdUrd and Fast Blue for all nuclei). When these images were combined, vasculature, perfusion and proliferation parameters were analysed. The labelling index (LI) was defined as the ratio of the BrdUrd-labelled area to the total nuclear area. The LI based on manual counting and the LI calculated by flow cytometry (FCM) were in good agreement with the LI based on surface analysis. LI decreased at increasing distance from its nearest vessel. In the vicinity of perfused vessels, the LI was 30-70% higher than near non-perfused vessels. This method shows that both vasculature/perfusion and proliferation characteristics can be measured in the same whole-tumour section in a semiautomatic way. This could be applied in clinical practice to identify combined human tumour characteristics that predict for a favourable response to treatment modifications

Prevalence and clinical and psychological correlates of high fear of cancer recurrence in patients newly diagnosed with head and neck cancer

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Correlation and colocalization of HIF-1a and pimonidazole staining for hypoxia in laryngeal squamous cell carcinomas:A digital, single-cell-based analysis

OBJECTIVE: Tumor hypoxia results in worse local control and patient survival. We performed a digital, single-cell-based analysis to compare two biomarkers for hypoxia (hypoxia-inducible factor 1-alpha [HIF-1α] and pimonidazole [PIMO]) and their effect on outcome in laryngeal cancer patients treated with accelerated radiotherapy with or without carbogen breathing and nicotinamide (AR versus ARCON). MATERIALS AND METHODS: Immunohistochemical staining was performed for HIF-1α and PIMO in consecutive sections of 44 laryngeal cancer patients randomized between AR and ARCON. HIF-1α expression and PIMO-binding were correlated using digital image analysis in QuPath. High-density areas for each biomarker were automatically annotated and staining overlap was analyzed. Kaplan-Meier survival analyses for local control, regional control and disease-free survival were performed to predict a response benefit of ARCON over AR alone for each biomarker. RESULTS: 106 Tissue fragments of 44 patients were analyzed. A weak, significant positive correlation was observed between HIF-1α and PIMO positivity on fragment level, but not on patient level. A moderate strength correlation (r = 0.705, p < 0.001) was observed between the number of high-density staining areas for both biomarkers. Staining overlap was poor. HIF-1α expression, PIMO-binding or a combination could not predict a response benefit of ARCON over AR. CONCLUSION: Digital image analysis to compare positive cell fractions and staining overlap between two hypoxia biomarkers using open-source software is feasible. Our results highlight that there are distinct differences between HIF-1α and PIMO as hypoxia biomarkers and therefore suggest co-existence of different forms of hypoxia within a single tumor

Whose national emergency? Caboolture and Kirribili? or Milikapiti and Mutitjulu?

Keynote Address - Ms Marion Scrymgour MLA Member for Arafura, Northern Territory Government. Other Speakers - Professor Gavin Brown AO FAA, Vice-Chancellor and Principal, University of Sydney; Mr Neville Perkins OAM, Master of Ceremonies; Mr Charles Madden, Welcome to country; Ms Michelle Blanchard, Acting Director, Koori Centre; Mr Nicholas Beeton, Ms Kerry Wallace-Massone, Ms Jade Swan Prize winners, Dr Charles Perkins AO Annual Memorial Prize

Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model

BACKGROUND AND PURPOSE: Carbonic anhydrase IX (CAIX) plays a pivotal role in pH homeostasis, which is essential for tumor cell survival. We examined the effect of the CAIX inhibitor 4-(3'(3",5"-dimethylphenyl)-ureido)phenyl sulfamate (S4) on the tumor microenvironment in a laryngeal tumor model by analyzing proliferation, apoptosis, necrosis, hypoxia, metabolism and CAIX ectodomain shedding. METHODS: SCCNij202 tumor bearing-mice were treated with S4 for 1, 3 or 5 days. CAIX ectodomain shedding was measured in the serum after therapy. Effects on tumor cell proliferation, apoptosis, necrosis, hypoxia (pimonidazole) and CAIX were investigated with quantitative immunohistochemistry. Metabolic transporters and enzymes were quantified with qPCR. RESULTS: CAIX ectodomain shedding decreased after treatment with S4 (p<0.01). S4 therapy did neither influence tumor cell proliferation nor the amount of apoptosis and necrosis. Hypoxia (pimonidazole) and CAIX expression were also not affected by S4. CHOP and MMP9 mRNA as a reference of intracellular pH did not change upon treatment with S4. Compensatory mechanisms of pH homeostasis at the mRNA level were not observed. CONCLUSION: As the clinical and biological meaning of the decrease in CAIX ectodomain shedding after S4 therapy is not clear, studies are required to elucidate whether the CAIX ectodomain has a paracrine or autocrine signaling function in cancer biology. S4 did not influence the amount of proliferation, apoptosis, necrosis and hypoxia. Therefore, it is unlikely that S4 can be used as single agent to influence tumor cell kill and proliferation, and to target primary tumor growth