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  • 1
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 89 (1988), S. 227-230 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A single dose of the DNA-binding cytostatic agent bleomycin (100 μg/g body weight, subcutaneously) was given to 10-day-old rats to study unscheduled repair DNA synthesis in nucleolar and in bulk nuclear chromatin of postmitotic Purkinje neurons. The Feulgen reaction and Hoechst 33342 staining were used for quantitative evaluation of nuclear DNA content and chromatin structure. The repair synthesis of DNA was detected by 3H-thymidine autoradiography. The data showed a lesser staining of Purkinje as well as granule cell DNA by Hoechst 33342 in bleomycin-treated animals than in controls, but there was no difference in staining with the Feulgen reation. The mechanisms of DNA staining by both cytochemical methods suggest that bleomycin reacted preferentially with AT-rich and single stranded DNA in cerebellar cells in vivo. Weak 3H-thymidine labelling was found in Purkinje cells of both control and treated rats, but in the latter group the labelling was more pronounced near or over the nucleolus. The enhanced unscheduled DNA synthesis in the nucleolar region of Purkinje cells of treated animals may be due to greater damage of DNA in this region or may indicate a greater ability of the nucleolar chromatin to repair its DNA.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1569-8041
    Keywords: gemcitabine ; infusion schedule ; pancreatic cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Laboratory evidences suggest the possibility that aninfusion rate of 10 mg/m2/min may be more effective than thestandard 30-min infusion of Gemcitabine (GEM). Patients and methods:Thirty-four patients with histologicallyverified locally unresectable and/or metastatic pancreatic carcinoma receivedGEM at the dose of 1,500 mg/m2 with an infusion rate of 10mg/m2/min, associated to 5-fluorouracil (5-FU) at the dose of 600mg/m2. Both drugs were administered weekly for two consecutiveweeks out of every three weeks. Results:One complete and five partial responses have beenobserved for an overall response rate of 17% (95% CI:3%–27%). The time to progression was 3.7 months with amedian survival of 5.7 months. A clinical benefit was obtained in 5 of 29patients (17%). Grade 3–4 WHO toxicities included neutropenia(35%) and thrombocytopenia (10%). Conclusion:It is unlikely that a fixed dose rate infusion of GEM,at least with this dose, can improve palliation in comparison with thestandard 30-min infusion schedule in advanced pancreatic cancer.
    Type of Medium: Electronic Resource
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  • 4
    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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  • 5
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; colorectal cancer ; p53 ; thymidylate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:We assessed the hypothesis that a compromised p53function could account for the non response of colon cancer patients withlow thymidylate synthase (TS) expression receiving a bolus 5-fluorouracil(5-FU)–leucovorin (LV) combination. Patients and methods:The study population consisted of 41patients with unresectable metastatic colon cancer, homogeneosuly, treatedwith bolus 5-FU and LV. Results:Twenty-seven patients (66%) showed high levels ofTS expression. The difference in the proportion of objective responses betweenpatients with low (CR + PR: 7 of 14, 50%) and high (CR + PR: 0 of 27)TS levels was statistically significant (P = 0.0001, chi-squaretest). p53nuclear overexpression was found in 27 of 41 patients(66%). No differences were observed in p53overexpression inpatients with high (66%) or low (66%) TS expression. p53status was not found to be associated with response even in patients withlow TS expression. Conclusions: p53status measured by immunohistochemistrydoes not seem to be useful to identify unresponsive patients with low TSexpression.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1569-8041
    Keywords: adjuvant ; chemotherapy ; gastric cancer ; meta-analysis ; randomised clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Several studies have investigated the possible roleof the adjuvant chemotherapy after curative resection for gastric cancerfailing to show a clear indication; previous meta-analyses suggested smallsurvival benefit of adjuvant chemotherapy, but the statistical methods usedwere open to criticisms. Materials and methods:Randomised trials were identified by meansof Medline and CancerLit and by selecting references from relevant articles.Systematic review of all randomised clinical trials of adjuvant chemotherapyfor gastric cancer compared with surgery alone, published before January 2000,were considered. Pooling of data was performed using the fixed effect model.Death for any cause was the study endpoint. The hazard ratio and its95% confidence intervals (95% CI), derived according to themethod of Parmar, were the statistics chosen for summarising the relativebenefit of chemotherapyversuscontrol. Results:Overall 20 articles (21 comparisons) were considered foranalysis. Three studies used single agent chemotherapy, seven combination of5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU withoutanthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82,95% CI: 0.75–0.89, P 〈 0.001). Association ofAnthracyclines to 5-FU did not show a statistically significant improvementwhen compared with the effect of the other regimens. Conclusions:Chemotherapy produces a small survival benefit inpatients with curatively resected gastric cancer. However, taking into accountthe limitations of literature based meta-analyses, adjuvant chemotherapy isstill to be considered as an investigational approach.
    Type of Medium: Electronic Resource
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  • 7
    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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