Effect of oxygen concentration on pulmonary fibrosis caused by peplomycin in mice.
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The pulmonary fibrosis caused by peplomycin (PEP) was studied in terms of oxygen toxicity using ICR mice. When 16 micrograms of PEP was administered intratracheally in mice after exposure to the air containing 75% O2 for 10 days, the pulmonary fibrosis was completely suppressed, while when mice were exposed to 75% O2 after the administration of PEP, the fibrosis was much severe than that of mice raised in atmospheric air. In 50% O2, similar oxygen effect was also observed, but it was weaker than that in 75% O2. In 90% O2, the oxygen toxicity was observed in mice without administration of PEP. When mice were exposed to 75% O2, the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which are relevant to the detoxication of active oxygen species, were not increased in the lung, but the levels of reducing agents such as glutathione and ascorbic acid, and high molecular substances having 1O2-scavenging activity were enhanced. The results suggest that these materials have some roles to decrease the pulmonary fibrosis caused by PEP. (+info)
Initial prognostic factors in small-cell lung cancer patients predicting quality of life during chemotherapy. Swiss Group for Clinical Cancer Research (SAKK).
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The question of whether initial prognostic factors in small-cell lung cancer patients have a predictive value for patients' quality of life (QL) during chemotherapy is addressed in the context of a randomised clinical trial comparing early and late alternating chemotherapy (SAKK protocol 15/84). The relative impact of initial tumour stage and performance status, previous weight loss, sex and age on patient-rated QL was analysed over six chemotherapy cycles in 124-130 patients (according to available QL data) with more than 400 questionnaires. Fatigue/malaise, personal functioning, emotional and general well-being were prospectively selected as QL indicators. Predefined summary measures (average QL score over chemotherapy cycles, 'minimum', 'maximum' and 'final' improvement) were analysed separately by scale in various patient groups. General linear models adjusted for treatment arm and response were used to confirm the univariate findings. Within the overall sample, the average QL scores over six cycles were predicted by initial prognostic factors. Patients with poor prognostic factors reported worse QL. Within a limited sample (with baseline QL), patients with poor prognostic factors reported worse QL at baseline and greater improvement under treatment. Graphical comparison of QL patterns over cycles showed permanent discrimination by levels of prognostic factors. The impact of initial prognostic factors was consistently confirmed in the three analyses. Levels of performance status and weight loss best discriminated QL. Initial tumour stage, performance status and previous weight loss can predict QL in small-cell lung cancer during chemotherapy, even after controlling for response to treatment. Our results may contribute to clinical decision-making with regard to the intensity of chemotherapy and QL outcome, especially in patients with extensive disease. (+info)
Anaplastic Ki-1-positive large cell lymphoma of the pancreas: a case report and review of the literature.
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A case of Ki-1-positive anaplastic large cell lymphoma of the pancreas is presented. The patient complained of abdominal pain and was jaundiced. Examination of a biopsy specimen obtained by duodenal endoscopy revealed malignant lymphoma, and surgery confirmed a large mass located in the region from the intra-pancreatic tissue around the lower common bile duct to the peri-pancreatic lymph nodes. Histologically, this tumor was composed mainly of large and giant neoplastic cells. Immunohistochemically, these cells were diffusely positive for Ki-1 and CD45RO antigens, indicating the features of Ki-1 anaplastic large cell lymphoma with a T-cell phenotype among non-Hodgkin's lymphoma. The histologic types of the majority of malignant lymphomas of the pancreas reported previously were considered to be diffuse-type non-Hodgkin lymphoma (probably with predominance of the B-cell phenotype), except for a single Japanese lymphoma case with a T-cell phenotype. This is therefore the first known case of Ki-1 anaplastic large cell lymphoma of the pancreas. (+info)
Structures of cobalt(III)-pepleomycin and cobalt(III)-deglycopepleomycin (green forms) determined by NMR studies.
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Pepleomycin (PEP) is a metalloglycopeptide that has stronger anticancer activity and less pulmonary toxicity than bleomycin (BLM). PEP, like BLM, exerts its action by binding to and degrading DNA in the presence of oxygen and certain metals. Obtaining detailed structural information of PEP and PEP-DNA complexes is crucial to understanding its anticancer activity. The structures of two green forms of cobalt-PEP species, HO2-Co(III)-PEP (denoted CoPEP) and deglycosylated HO2-Co(III)-PEP (denoted CodPEP) have been obtained by NOE restrained refinements. Earlier studies of the related HO2-Co(III)-BLM A2 proposed that two chiral conformers (form A or B) could exist with either the beta-aminoalanine primary amine (A,NH2) or the mannose carbamoyl nitrogen (M,NH2) as the axial ligand. Analysis of our NOESY data shows convincingly that form A is the most probable conformer with the mannose carbamoyl M,NH2 and the beta-aminoalanine primary amine A,NH2 as the axial ligands in CoPEP and CodPEP, respectively. The NOE cross-peaks resulting from the interactions between the N-terminus (i.e., the metal-binding domain) and the C-terminus of CoPEP and CodPEP have similar patterns, suggesting that they both adopt compact structures with the bithiazole group folded back over the N-terminus. (+info)