Bleomycin Induction Research Articles

Increase in p21 expression independent of the p53 pathway in bleomycin-induced lung fibrosis

Although a number of animal models have been used to study the pathogenesis of lung disease, to date few studies have looked at changed in the expression of cell cycle regulatory genes. We have studied the variation in the expression of p21, p53, p27 and PCNA in bleomycin-induced lung fibrosis using animal mouse models using immuno-histochemistry and gene-expression analysis. No difference in the p53, PCNA and p27 expressions were observed from the bleomycin-induced fibrosis when compared to saline-induced non-fibrotic lungs. Although no difference in nuclear p21 expression was observed, the level of cytoplasmic p21 expression was found to be higher in fibrotic lungs at day 14 after bleomycin injection. p21 expression was found to increase independent of p53 in fibrotic lungs at 14 days after bleomycin induction.

Roles of the AtErcc1 protein in recombination.

Summary Atercc1, the recently characterized Arabidopsis homologue of the Ercc1 (Rad10) protein, is a key component of nucleotide excision repair as part of a structure-specific endonuclease which cleaves 5' to UV photoproducts in DNA. This endonuclease also acts in removing overhanging non-homologous DNA 'tails' in synapsed recombination intermediates. We have previously demonstrated this recombination function of the Arabidopsis thaliana Xpf homologue, AtRad1p, and show here that recombination between plasmid DNA substrates containing non-homologous tails is specifically reduced 12-fold in atercc1 mutant plants compared with the wild type. Furthermore, using chromosomal tandem-repeat recombination substrates, we show that AtErcc1p is required for bleomycin induction of mitotic recombination in the chromosomal context. This work thus confirms both the specific and general recombination roles of the Atercc1 protein in recombination in Arabidopsis.

Alveolar macrophage apoptosis and TNF-alpha, but not p53, expression correlate with murine response to bleomycin.

Apoptosis is considered to be a protective mechanism that limits lung injury. However, apoptosis might contribute to the inflammatory burden present in the injured lung. The exposure of mice to bleomycin (BLM) is a well-established model for the study of lung injury. BLM exposure induces DNA damage and enhances tumor necrosis factor (TNF)-alpha expression in the lung. To evaluate the importance of alveolar macrophage (AM) apoptosis in the pathogenesis of lung injury, we exposed BLM-sensitive (C57BL/6) and BLM-resistant (BALB/c) mice to BLM (120 mg/kg) and studied the induction of apoptosis [by light-microscopy changes (2, 8, 12, 24, 48, and 72 h) and annexin V uptake by flow cytometry (24 h)], the secretion of TNF-alpha (measured by ELISA), and the expression of p53 (by immunoblotting) in AM retrieved from these mice. BLM, but not vehicle, induced apoptosis in AM from both murine strains. The numbers of apoptotic AM were significantly greater (P < 0.001) in C57BL/6 mice (52.9%) compared with BALB/c mice (40.8%) as demonstrated by annexin V uptake. BLM induction of apoptosis in AM was preceded by an increased secretion of TNF-alpha in C57BL/6 but not in BALB/c mice. Furthermore, double TNF-alpha receptor-deficient mice, developed on a C57BL/6 background, demonstrated significantly (P < 0.001) lower numbers of apoptotic AM compared with C57BL/6 and BALB/c mice. BLM also enhanced p53 expression in AM from both murine strains. However, p53-deficient mice developed BLM-induced lung injury, exhibited similar lung cell proliferation (measured as proliferating cell nuclear antigen immunostaining), and accumulated similar amounts of lung hydroxyproline (65 +/- 6.9 microgram/lung) as did C57BL/6 (62 +/- 6.5 microgram/lung) mice. Therefore, AM apoptosis is occurring during BLM-induced lung injury in a manner that correlates with murine strain sensitivity to BLM. Furthermore, TNF-alpha secretion rather than p53 expression contributes to the difference in murine strain response to BLM.tumor necrosis factor; strain susceptibility

Chemo-radiotherapeutic management of advanced head and neck cancer.

Stage III and IV head and neck cancer patients usually achieve poor therapeutic results after radiotherapy. The search for more effective treatment modalities is justified, provided that tolerance is not lower than that of the usual radiation therapy schedules. Chemotherapy has been shown to be effective, and cis-platinum and bleomycin based treatments are reported to result in objective remissions in a substantial proportion of cases. There is also experimental evidence of a radiosensitizing activity of cis-platinum. Thirty-five locally advanced head and neck cancer patients were given combined chemo-radiotherapeutic treatment consisting of a cis-platinum and bleomycin induction followed by a standard radiotherapy course integrated with weekly administrations of cis-platinum. Before radiotherapy, an overall 48.5% objective remission rate was achieved, that rose to 85.8% after completion of the entire treatment, with a 31.5% complete response rate. Incidence and severity of radiation mucositis seem not to be increased, and systemic toxicity is very low, with the adopted drug administration schedule. Overall results do not show any obvious superiority over those of radiotherapy alone.

Cis-diamminedichloroplatinum (II) and bleomycin induction chemotherapy as an adjuvant to conventional treatment modalities in advanced head and neck cancer preliminary report of the results of a non-randomized trial and control series

cis-diamminedichloroplatinum (II) and bleomycin induction chemotherapy as an adjuvant to conventional treatment modalities in advanced head and neck cancer preliminary report of the results of a non-randomized trial and control series