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  • 1
    Electronic Resource
    Electronic Resource
    Alteration in interactions between tumor-infiltrating lymphocytes and tumor cells in human melanomas after chemotherapy or immunotherapy (1991)
    Springer
    Cancer immunology immunotherapy 33 (1991), S. 238-246 
    Details
    ISSN: 1432-0851
    Keywords: Tumor-infiltrating lymphocytes ; Human melanomas ; Chemotherapy ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alteration in interactions between tumor-infiltrating lymphocytes (TILs) and tumor cells after chemotherapy or immunotherapy was studied in metastatic melanoma patients. Tumors were harvested from surgical specimens 17 days after the end of chemotherapy with cisplatin, vinblastine, and dacarbazine (CVD). Tumors of nonlymph-node metastases from two responders yielded neither TILs nor tumor cells, whereas those from all four nonresponders had both TILs [(1.1−13.8) × 106 cells/g tumor] and tumor cells [(2.8−30.8) × 106 cells/g tumor). Tumors of lymph node metastases from nine patients yielded substantial numbers both of TILs and tumor cells, regardless of different clinical responses, except with one complete responder, whose tumor did not contain tumor cells. The mean increase of TILs from these tumors (n = 14) 3–4 weeks after incubation with 200 U/ml recombinant interleukin-2 (rIL-2) was 2.5-fold, whereas there was a 56-fold increase in TILs from untreated tumors (n = 3). CD3+ T cells predominated in TILs before and after expansion with IL-2. IL-2-activated TILs from five of six tumors tested displayed higher cytotoxicity against autologous tumor cells than against cells from any of three allogeneic tumors. Mean tumor cell numbers (106 cells/trial) obtained by serial needle biopsies for the same tumor in five patients decreased from 1.2 before therapy to 0.25 at day 4 of therapy (interferon α alone), and to 0.02 at day 8 (interferon α and IL-2). This decrease did not correlate with clinical responses. Yields (× 106 cells/g tumor) of TILs and tumor cells in subcutaneous melanomas obtained by excisional biopsies in one nonresponder under IL-2 therapy were respectively 0.2 and 1.1 before therapy (day 0), 0.1 and 〈0.01 during (day 7), 0.2 and 〈0.01 at the end of therapy (day 21), and 0.5 and 0.5 at the time of tumor progression (day 66). Yields of TILs and tumor cells in the other nonresponder were respectively 3 and 26 before (day 0), 16 and 3 during (day 7), and 0.4 and 〈0.01 at the end of IL-2 therapy (day 17), and 2.5 and 6 at the time of progression (day 62). TILs in these two patients before therapy proliferated well in culture with IL-2 (570-and 720-fold, respectively), and showed higher cytotoxicity against autologous tumor cells, whereas none of those from the five tumors biopsied during or at the end of IL-2 therapy proliferated. TILs at the time of progression showed modest proliferation (54- and 76-fold, respectively) and showed major-histocompatibility-complexnonrestricted cytotoxicity. In summary, a decrease in the number of live tumor cells did not always correlate with clinical response in either therapy. CVD chemotherapy may simply impair IL-2-induced proliferation of TILs. IL-2 therapy may induce transient unresponsiveness of TILs to IL-2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01744943
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  • 2
    Electronic Resource
    Electronic Resource
    Nuclear binding of the estrogen receptor: A potential predictor for hormone response in metastatic breast cancer (1990)
    Springer
    Breast cancer research and treatment 16 (1990), S. 273-278 
    Details
    ISSN: 1573-7217
    Keywords: estrogen receptor ; hormone therapy ; immunohistochemistry ; nuclear binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously described anin vitro immunohistochemical test employing anti-receptor antibodies, for demonstrating the nuclear binding characteristics of estrogen receptors (ER) in breast carcinomas. Based on a retrospective analysis of twenty-five patients with estrogen receptor-positive (ER+) breast cancer who were treated with hormone therapy and whose clinical responses were evaluable, we were able to demonstrate that this test may be valuable to predict which, among the ER+ tumors (whether or not they are progesterone receptor positive, PR+), are likely to respond to hormone therapy and which may fail. While tumors in which ER exhibited abnormalities in nuclear binding behavior (ligand-independent nuclear binding or no nuclear binding) failed hormone therapy (16 out of 19 patients), those in which nuclear binding of ER appeared normal (ligand-dependent) in thein vitro test, responded to hormone therapy (5/6 patients). While our previous report dealt with the procedural details, specificity of the reagents, and the design of the study, this report addresses the clinical aspects of this study and response correlation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01806335
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  • 3
    Electronic Resource
    Electronic Resource
    Unique allelic restriction fragments of the human Ha- ras locus in leukocyte and tumour DNAs of cancer patients (1985)
    [s.l.] : Nature Publishing Group
    Nature 313 (1985), S. 369-374 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] White blood cell DNA from cancer patients and DNA from tumours and tumour-derived cell lines frequently demonstrated allelic restriction fragments of the Harvey ras oncogene locus not found in the unaffected population. The presence of such unusual alleles may be linked to susceptibility to ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/313369a0
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  • 4
    Electronic Resource
    Electronic Resource
    Induction of circulating tumor necrosis factor (TNFα) as the mechanism for the febrile response to interleukin-2 (IL-2) in cancer patients (1988)
    Springer
    Journal of clinical immunology 8 (1988), S. 426-436 
    Details
    ISSN: 1573-2592
    Keywords: Interleukin-2 ; tumor necrosis factor ; fever
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fever is frequently observed in cancer patients treated with high-dose recombinant human interleukin-2 (rIL-2). The preincubation of rIL-2 with polymyxin B, an antibiotic that inhibits the biologic effects of endotoxins, did not diminish the pyrogenicity of IL-2 in New Zealand rabbits, indicating that IL-2-induced fever is not due to contaminating endotoxins. In contrast to interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon α, which cause fever through their effects on arachidonic acid metabolism in the hypothalamus, IL-2 was unable to induce prostaglandin E2 synthesis in hypothalamic cells or fibroblastsin vitro, suggesting that IL-2 is not intrinsically pyrogenic. To determine if IL-2-induced fever is mediated indirectly through the generation of pyrogenic cytokines, culture supernatants from IL-2-stimulated human peripheral blood mononuclear cells were screened for the presence of pyrogens by direct injection into rabbits and by measuring the amounts of IL-1α, IL-1β, and TNFα by specific radioimmunoassays (RIA). All three cytokines were readily detected by RIA in these supernatants, which in turn caused fever when injected into rabbits. Furthermore, in six of six cancer patients treated with rIL-2, elevated levels of TNFα were detected in the plasma by RIA 2 hr after IL-2 administration. Plasma TNF levels increased from pretreatment values of 14±7 to 765±150 pg/ml 2 hr after an IL-2 injection. These results strongly implicate IL-2-induced pyrogenic cytokines, in particular TNFα, as a major cause of the fever and possibly other aspects of the acute-phase response associated with IL-2 therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00916947
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  • 5
    Electronic Resource
    Electronic Resource
    Strategy and planning for chemopreventive drug development: Clinical development plans (1994)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 56 (1994), S. 55-62 
    Details
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: At the National Cancer Institute, Division of Cancer Prevention and Control, the Chemoprevention Branch and Agent Development Committee develop strategies for efficiently identifying, procuring, and advancing the most promising drugs into clinical trials. Scientific expertise is applied at each phase of development to critically review the testing methods and results, and to establish and apply criteria for evaluating the agents for further development. The Clinical Development Plan, prepared by the Chemoprevention Branch and the Agent Development Committee, is a summary of the status of the agent regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. It also contains the strategy for further development of the drug that addresses pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen Clinical Development Plans are presented here: N-acetyl-l-cysteine (NAC), aspirin, calcium, β-carotene, 2-difluoromethylornithine (DFMO), DHEA analog 8354, 18β-glycyrrhetinic acid, N-(4-hydroxyphenyl)retinamide (4-HPR), ibuprofen, oltipraz, piroxicam, Proscar®, sulindac, tamoxifen, vitamin D3 and analogs and vitamin E. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing chemopreventive drugs. 1994 Wiley-Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240560906
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  • 6
    Electronic Resource
    Electronic Resource
    Human restriction fragment length polymorphisms and cancer risk assessment (1986)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 30 (1986), S. 319-329 
    Details
    ISSN: 0730-2312
    Keywords: oncogenes ; Ha-ras ; restriction fragment length polymorphism ; human genetics ; cancer risk assessment ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The polymorphic restriction fragments of the human Ha-ras locus, produced by the variable tandem repetition (VTR) of a short consensus sequence, fall into three classes based on allelic frequencies. Alleles of the “rare” class (individual frequencies 〈 0.5%) have been detected only in white blood cell and tumor DNA of cancer patients. This phenomenon is independent of ethnic origin. No significant association of rare alleles with cancer patients has been demonstrated at an independent tandem repeat locus, VTR4.1. The results suggest that the Ha-ras restriction fragment length polymorphism is useful in cancer risk assessment.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240300405
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  • 7
    Electronic Resource
    Electronic Resource
    Strategy and planning for chemopreventive drug development: Clinical development plans II (1996)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 54-71 
    Details
    ISSN: 0730-2312
    Keywords: Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l-selenomethionine and 1,4-phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs. © 1997 Wiley-Liss, Inc.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240630705
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