p53 mutations in early neoplastic lesions of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine

Rat experimental models using Ar-butyl-Af-(4-hydroxybutyl) nitrosamine(BBN) as an initiating agent have been widely used to studycarcinogenic processes in the urinary bladder. In this study,early neoplastic lesions from 10 male F344 rats treated with0.05% BBN for 16 weeks were analyzed for changes in the H-rasor p53 genes by polymerase chain reaction (PCR)-single strandconformation polymorphism (SSCP) analysis and subsequent DNAsequencing. Lesions were pooled for each of the 10 rats andsix showed point mutations in the p53 gene and one in the H-rasgene. These results would indicate that BBNinduced rat urinarybladder carcinomas are similar to human urinary bladder carcinomaswith respect to alterations in the p53 and H-ras genes and thatp53 gene alterations are relatively early events in rat urinarybladder carcinogenesis induced by BBN treatment     

Frequent mutations of the p53 gene and infrequent H- and K-ras mutations in urinary bladder carcinomas of NON/Shi mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine

To elucidate whether common genetic events in human urinarybladder carcinogenesis also occur in rodent models, we investigatedthe presence of p53, H- and K-ras mutations in 18 urinary bladdercarcinomas induced by various concentrations of N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) in male NON/Shi mice. Histopathologically, all were invasive,11 being squamous cell carcinomas (SCCs) and the remaining sevenbeing transitional cell carcinomas (TCCs). Using polymerasechain reaction single-strand conformation polymorphism (PCR-SSCP)analysis followed by DNA sequencing, p53, H- and K-ras mutationswere observed in 14 (78%; exons 5–7), two (11%; one eachon exons 1 and 2) and one (5.6%; exon 1) animals respectively.The frequencies of mutations in p53 exons 5, 6 and 7 were 7(39%), 4 (22%), and 9 (50%) respectively, and no mutation wasfound in exon 8. All mutations involved one base-pair substitutionwith or without amino acid changes and the types of base-pairsubstitution were random. No evident association was observedbetween mutation sites and the histological phenotypes. In conclusion,p53 mutations are frequent in BBN-induced mouse invasive urinarybladder tumors, at similar levels to those observed for humanhigh-grade invasive carcinomas, and this plus their distributionsuggests their possible participation in this model of urinarybladder carcinogenesis.     

Fatal hemorrhage after radiochemotherapy for leptomeningeal dissemination of glioma: report of two cases

BACKGROUND: Dissemination of malignant gliomas is often observed, but the treatment of choice for leptomeningeal dissemination has not been established. CASE DESCRIPTIONS: A 55-year-old man suffered fatal hemorrhage 1 day after whole brain irradiation (2 Gy) along with intravenous administration of 150 mg of nitrosourea (ACNU) for leptomeningeal dissemination of glioblastoma. A 14-year-old boy suffered hemorrhage after intrathecal administration of 10 mg of methotrexate for recurrence of leptomeningeal dissemination of anaplastic astrocytoma 4 months after local brain irradiation and ACNU administration, and died 19 days later. CONCLUSION: Massive fatal hemorrhage is an unusual but possible acute complication after radiochemotherapy for leptomeningeal dissemination of gliomas.     

SN-38 induces cell cycle arrest and apoptosis in human testicular cancer

OBJECTIVE: CPT-11 is one of the most widely used camptothecin analogues and is converted to form the active metabolite SN-38. Clinical trials are ongoing to better characterize its spectra of clinical activity, to determine the optimal schedules of administration, and to define the usage in combination with other chemotherapeutic compounds. MATERIALS AND METHODS: KU-MT, an AFP-producing testicular carcinoma cell line, was exposed to SN-38, etoposide, or cisplatin for 24 h, and the resulting cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay. This paper describes the effects of SN-38 on the cell proliferation and cell cycle of testicular tumor cells in culture. RESULTS: SN-38 was shown to inhibit KU-MT cell growth more potently than either etoposide or cisplatin. A marked decrease in the percentage of S phase cells was accompanied by the enhancement of cyclin E levels. In concentrations of >30 nmol/l, SN-38 arrested the cell cycle in G2 and induced cell death via apoptosis. The apoptosis was promoted by Bax and p53 protein, which were both shown to be present by flow cytometric and Western blot analyses. CONCLUSION: These results suggest that CPT-11, a pro-drug of SN-38, may be clinically useful for the treatment of testicular cancer, and that the mechanism of this agent's cytotoxicity consists of cell cycle arrest and concomitant apoptosis.     

Neuronal expression of αB crystallin in cerebral infarction

alphaB crystallin (alphaBC) is one of the heat shock proteins that are induced under stressful conditions. In normal brains, alphaBC is present in oligodendrocytes and astrocytes, but not in neurons. Neuronal alphaBC expression in the central nervous system under pathological conditions has been investigated in several previous studies, most of which dealt with various neurodegenerative diseases with and without ballooned neurons. Neuronal expression of alphaBC has seldom been studied in cerebral infarction (CI), and the frequency of alphaBC-positive neurons in the various stages of CI is unknown. To investigate this issue, we examined 48 autopsy brains of patients with CI, and found neuronal expression of alphaBC in 68.8% of the cases. We found three types of alphaBC-positive neurons: normal morphological, convex, and ballooned neurons. Although alphaBC-positive neurons were present in the every stage of CI, they were more frequent later than 10 days after the onset of CI, and the frequency of alphaBC-positive ballooned neurons was particularly increased in the later stages of CI. This may indicate that morphologically normal neurons gradually swelled up through convex neurons, finally forming ballooned neurons. Previous studies indicated that alphaBC might have a cytoprotective function as a molecular chaperone, and we speculate that alphaBC is expressed in neurons subjected to ischemic stress, and exerts a cytoprotective effect on the neurons.     

Pulmonary artery stenting for recurrent lung cancer after left pneumonectomy

We present a case of a patient with stenosis of the pulmonary artery which was successfully treated by implantation of a vascular endoprosthesis. A 50-year-old man underwent left pneumonectomy for lung cancer. Eleven months later, a computed tomographic scan revealed a soft tissue mass in the mediastinum and there was severe stenosis of the remaining right main pulmonary artery. A self-expandable vascular endoprosthesis was implanted in the stenotic portion. We used percutaneous cardiopulmonary support (PCPS) during the procedure. We recommend the technique of pulmonary artery stenting using PCPS as efficacious and safe.     

Time-dependent contribution of the hippocampal complex when remembering the past: a PET study

Previous studies of brain-damaged patients and functional neuro-imaging have consistently shown the importance of the hippocampal complex, i.e. the hippocampus and parahippocampal gyrus, in episodic memory retrieval. We wished to determine whether patterns of brain activation during memory retrieval as measured by PET are same or different when the oldness of a to-be-retrieved episode is manipulated. Using cue words, subjects remembered related episodes from three periods of their life, childhood, adolescence and recent period. The results showed an increase of parahippocampal activities during recall of episodes from childhood and recent period, but not from adolescence. These data suggest a possibility of time-dependent hippocampal contribution in episodic recall, which cannot be understood in simple terms of recent remote memory dichotomy.