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  • 1
    ISSN: 1573-7373
    Keywords: apoptosis ; neuroblastoma ; N-myc ; DNA fragmentation ; Terminal deoxynucleotidyl Transferase ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuroblastoma (NB) is a tumor of pediatric age that is associated with high mortality in metastatic stages, although stage IVS patients undergo frequent spontaneous regression. Since apoptosis has been proposed as a possible cause of remission among cancer patients, we tested this hypothesis among both localized and metastatic NB and, in particular, NB metastatic stage IVS. We have assayed 36 localized and 117 metastatic neuroblastomas for evidence of internucleosomal DNA degradation and confirmed DNA fragmentation by the flow cytometric Terminal deoxynucleotidyl Transferase method, which also allowed us to measure DNA content and cell cycle phases. These techniques provided evidence of apoptosis in 18 out of 153 samples (11.8%), that were equally distributed among all stages except IVS, i.e., 11.1% in stage I (2/18), 11.1% in stage II (2/18), 13.2% in stage III (5/38), 13.4% in stage IV (9/67), and 0% in stage IVS (0/12). Tumor tissue samples collected at ons et and also at relapse for the same patients showed that apoptosis may occur at relapse. In addition, cells appear to undergo apoptosis independently from N-myc amplification, cell cycle phase and DNA ploidy. In conclusion, apoptosis seems to take place with about an equal frequency for both favourable and unfavourable stages with an exception for IVS. Since DNA fragmentation remained undetected in stage IVS, we suggest that apoptosis is not a mechanism of spontaneous regression for these patients. A better basic understanding of the complex molecular mechanisms and biochemical pathways that control apoptosis in neuroblastoma appears to be necessary.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0730-2312
    Keywords: 4-HPR ; bladder cancer ; chemoprevention ; DNA flow cytometry ; intermediate endpoints ; retinoids ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The ability ofthesynthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) to affect the outcome of previously resected superficial bladder cancer was investigated in apilot study using DNA content flow cytometry and conventional cytology as intermediate endpoints. Twelve patients were treated with oral 4-HPR (200 mg daily) and compared with 17 non-randomized, untreated controls. The median interval between transurethral resection and 4-HPR administration was 5.5 months (rangs 0-36). The median follow-up period was 12 months (rang 3-31) in the4-HPR group and 9 months (range 2-22) in the control group. The proportion of patients with DNA aneuploid stemlines in bladder-washed cells decreased form 7/12 (58%) to5/11 (45%) in the 4-HPR group, but increased form 7/17 (41%) to 10/17(59%) in the control group. In patients with stable diploid profiles, mean (±SE) S-phase and G2-M-phase fractions decreased in the course of retinoid treatment from basal levels of 15.2±4.1% to 7.5±3.3% and 10.3±2.2% to 5.2 ±0.4%, respectively. The same parameters in the control group changes from basal levels of 14.6±3.4% to 12.4±2.7% and 9.8±1.6% to 12.6±1.6%, respectively. Positive or suspicious cytologic examinations were present in 3/12 (25%) treated cases prior to 4-HPR) administration and all subsequently reverted to normal. The same parameter in the control group increased from 4/17 (24%) to 6/17 (35%)during follow-up. Impaired adaptation to darekness was recorded in 4 patients, and transient dermatologic alterations were observed in one-third of the patients, requiring dose reduction in one case. Our preliminary data suggest that4-HPR may affect theDNA content and abnormal cytology in patients with previously resected superficial bladder cancer. © 1992 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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