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  • 1
    ISSN: 1573-8280
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sixty-six patients with disseminated malignancy were treated with recombinant interleukin-2 (IL-2) on a three times a week (M, W, F) IV-bolus injection schedule. Doses ranged from 0.001 to 14.0 × 106 units/M2 body surface area. Consecutive groups of 3-5 patients were placed on each dose level and were maintained on that level except for dosage de-escalation for toxicity. Toxicity to all major organ systems were noted with major toxicity including fever and chills, anorexia, fatigue and malaise, arthralgias and arthritis as well as hepatic and renal toxicity. All toxicity reversed within one week of drug cessation. Renal toxicity manifested by azotemia, arthritis and fatigue were the common dose limiting toxicities and the maximally tolerated dose was 12 × 106 units/M2. Pharmacokinetic studies indicated a short half-life (T 1/2α = 7–23 minutes). At doses over 0.5 × 106 units/M2 increases in absolute lymphocytes and eosinophil counts were noted. All T lymphocyte subsets increased. Maximal increases were seen at 4–8 × 106 units/M2 with a lesser increase at 10–14 × 106 units/M2 dosage level. Circulating NK cells also increased while circulating LAK cells were detected during therapy. Partial responses were noted in 3 patients with melanoma. These lasted 4, 6 and 16 months and involved pulmonary, pulmonary plus mesenteric and retro-orbital plus hepatic metastases respectively in these patients.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 57-62 
    ISSN: 0730-2312
    Keywords: cancer risk ; genetic instability ; in situ hybridization ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Many human tumors are thought to develop along a multistep pathway in tissues that have encountered long periods of carcinogen exposure and thus have accumulated genetic hits in functional targets relevant to tumor evolution. The cumulative degree of genetic change is dependent on both exogenous (e.g., degree of carcinogen exposure) and endogenous factors (e.g., metabolism of procarcinogens, repair or misrepair capacity, proliferation properties of the tissue, capability of damaged cells to survive). Thus one approach to risk estimation is to measure the accumulated amount of genetic damage in a target tissue at risk for tumor development. Since one cannot predict the exact site of the future tumor, the risk assay must detect a generalized ongoing process of genetic instability from small, random biopsies. The technique of chromosome in situ hybridization involves the use of chromosome- or region-specific probes and provides an ability to directly visualize genetic change (e.g., random or clonal chromosome polysomy and monosomy) on thin tissue sections (where tissue architecture is maintained) or exfoliated cells. Analyses of normal and premalignant lesions adjacent to tumors (e.g., head and neck, lung, bladder, cervix, breast) have demonstrated that chromosome instability can be detected in the field of the tumor (i.e., in normal and premalignant cells in a tissue at 100% risk of tumor development) and the degree of chromosome instability increases with the degree of histologic progression toward cancer. Analyses of premalignant lesions (e.g., oral leukoplakia and erythroplakia from individuals at risk for aerodigestive tract cancer) by chromosome in situ hybridization have uncovered varying degrees of chromosome instability. However, approximately half of those individuals who showed a high degree of chromosome instability in biopsies subsequently developed aerodigestive tract cancer. Of interest, half of these tumors have developed away from the biopsied site, suggesting that the detection of a chromosome instability process in one aspect of the tissue might yield risk information for the total tissue field. These studies also suggest that chromosome in situ hybridization might be useful for identifying individuals with high tumor risk who might benefit from chemopreventive intervention. J. Cell. Biochem. 25S:57-62. © 1997 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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