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  • biochemical modulation  (2)
  • Cell & Developmental Biology  (1)
  • 1
    ISSN: 1569-8041
    Keywords: advanced colorectal cancer ; biochemical modulation ; 5-fluorouracil ; schedule of administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:We have recently suggested that bolus 5-fluorouracil(5-FU) may work via a RNA directed mechanism while continuous infusion 5-FUmay kill cells via a thymidylate synthase related pathway. It may thus bepossible to selectively modulate each schedule biochemically. We have comparedan alternating regimen of bolus and continuous infusion 5-FU, selectivelymodulated for the schedule of administration, with modulated bolus 5-FU inadvanced colorectal cancer patients. Patients and methods:Two hundred fourteen patients from nineteenItalian centers were randomized to the control arm consisting of biweeklycycles of MTX, 200 mg/m2 on day 1, followed by bolus 5-FU 600mg/m2 on day 2 and 6-S-leucovorin rescue, or to the experimentalarm consisting of two biweekly cycles of the same regimen as in the controlarm alternated to three weeks of continuous infusion 5-FU (200mg/m2 day) + weekly bolus 6-S-leucovorin, 20 mg/m2. Results:Nine CR and twenty-seven PR were obtained on one hundredeleven evaluable patients treated in experimental arm (RR = 32%,95% confidence interval (95% CI): 24%–42%),while two CR and eleven PR were observed among one hunderd three evaluablepatients in control arm (RR = 13%, 95% CI:7%–21%). WHO grade 3–4 toxicity occurred in13% of cycles of experimental arm and in 8% of cycles in controlarm. The PFS was significantly longer in experimental arm (6.2 vs. 4.3 months,odds ratio 0.66, P = 0.003), while the overall survival was similarin both arms (14.8 months in experimental arm vs. 14.1 months in control arm);quality of life was similar as well. Eighty percent of patients receivingsecond-line chemotherapy in control arm were treated with continuous infusion5-FU. Conclusions:Alternating, schedule-specific biochemical modulationof FU is more active than MTX → 5-FU as first-line treatment of advancedcolorectal cancer. However, the overall survival was similar suggesting thatalternating bolus and infusional 5-FU upfront may be as effective as givingthem in sequence as first- and second-line treatment.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: biochemical modulation ; colorectal cancer ; 5-fluorouracil ; high- versus low-dose ; L-leucovorin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Although leucovorin (LV) + 5-fluorouracil (5-FU) isconsidered the treatment of choice for advanced colorectal cancer in mostcountries, the optimal schedule of this combination has not yet beenestablished. Low-dose LV appears to be as active as high-dose LV in thedaily-times-five regimen, but no randomized study of the levorotatorystereoisomer (6S-LV) given at two different dose levels has been published. Patients and methods: Between November 1991 and June 1994, 422patients (all with measurable disease previously untreated with chemotherapy)were randomized to 6S-LV (100 mg/sqm/i.v.) + 5-FU (370 mg/sqm/15 min i.v.infusion), both administered for 5 days every 28 days (arm A), or to 6S-LV (10mg/sqm/i.v.) + 5-FU (doses as above), also given for 5 days every 28 days (armB). The primary endpoint of the study was the comparison of response rates(WHO criteria); the secondary endpoint was the assessment of survival andtolerability. No evaluation of the quality of life or the symptomatic effectof treatment was planned. Results: The response rate was 9.3% in arm A (95% CI:5.4–13.1), with 2 CR and 18 PR, and 10.7% in arm B (95%CI: 6.5–14.9), with 3 CR + 19 PR, without any significant difference(P = 0.78). The median time to progression was eight months in bothgroups and overall survival was 11 months, with no difference betweentreatments. Toxicity mainly consisted of gastrointestinal side effects(mucositis and diarrhoea), which were rarely severe (grade 3–4:5%–10% of patients) and similar in the two groups. Conclusions: In this large-scale multicentre trial, the low and highdoses of 6S-LV appeared to be equivalent in terms of the biochemicalmodulation of 5-FU in advanced colorectal cancer although, for several reasons(including the timing and the strict criteria of response evaluation, the highnumber of patients with unfavourable prognostic factors, themulti-institutional nature of the study, the dose and modality of 5-FUadministration), the response rate was lower than that reported in some of theother published studies. Given the considerable difference in economic costbetween the two dosages, the use of high-dose 6S-LV in the daily-times-fiveregimen is not recommended in clinical practice.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 191 (1987), S. 25-36 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The major anatomical divisions of the cerebellum of the European eel, i.e., corpus cerebelli, lobus vestibulolateralis, and valvula, were studied morphologically and morphometrically. There were differences in cerebellar cytoarchitecture and gross morphology in two stages of the eel life cycle, the trophic stage (yellow eel), and the reproductive stage (silver eel), which are characterized by different degrees of swimming activity. The principal differences between silver and yellow eels in the cytoarchitecture of the corpus cerebelli and the lobus vestibulolateralis were in distribution of Purkinje or Purkinje-like cells in the molecular layer, which is wider in silver eels, in part because of a decreased thickness of the granular cell layer. In the silver eel, the scattering of Purkinje cells was more evident in the lobus vestibulolateralis where the molecular layer is also thicker. The data indicate the transition from the yellow eel to the silver eel is characterized by a migration of granule cells from the ganglionic cell layer to the internal granular layer and by a further development of molecular layer components, e.g., parallel fibers, Purkinje-cell dendrites, etc. In contrast, the thickness of the granular layer and of the Purkinje cell layer, limited to the lower part of the valvula, decreased. There is also a slight increase of cerebellar volume in the silver eel. The volume of the lobus vestibulolateralis was constant. Hypertrophy of the valvula and eminentiae granulares is observed and is due to the migration of cells from the granular layer of the corpus cerebelli whose volume slightly decreases. Perhaps the lobus vestibulolateralis also contributes to the increased volume of eminentiae granulares. Our findings suggest that the cerebellum continues to develop during the passage from the trophic to the reproductive stage of the eel. The appearance of new afferents from the lateral line which becomes more visible in the silver eel probably completes cerebellar ontogeny.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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