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Other Alterations (other + alteration)
Selected AbstractsAstroblastoma: Clinicopathologic Features and Chromosomal Abnormalities Defined by Comparative Genomic HybridizationBRAIN PATHOLOGY, Issue 3 2000Daniel J. Brat M.D., Ph.D. Astroblastomas are uncommon brain tumors whose classification and histogenesis have been debated. Precise criteria for diagnosis have been described only recently, but have not found wide acceptance. We report the clinical, radiographic, and histopathologic features of 20 astroblastomas, and the chromosomal alterations in seven cases as detected by comparative genomic hybridization (CGH). The tumors occurred both in children and young adults (average age, 14 years), most often as well circumscribed, peripheral, cerebral hemispheric masses. Radiographically, the lesions were contrastenhancing and solid, often with a cystic component. All were characterized histologically by astroblastic pseudorosettes, and most displayed prominent perivascular hyalinization, regional hyaline changes, and pushing borders in regard to adjacent brain. Tumor cells were strongly immunoreactive for S-100 protein, GFAP, and vimentin. Staining for EMA was focal. Ten of 20 astroblastomas were classified as "well differentiated" and 10 were classified as "malignant," largely on the basis of hypercellular zones with increased mitotic indices, vascular proliferation, and necrosis with pseudopalisading. All 10 well differentiated lesions and 8 of 10 malignant lesions were completely resected. None of the well differentiated astroblastomas recurred within the limited follow-up period. Three malignant astroblastomas recurred, including two incompletely resected tumors, and one that had been totally resected. One patient died of disease following recurrence. The most frequent chromosomal alterations detected by CGH were gains of chromosome arm 20q (4/7 tumors) and chromosome 19 (3/7). The combination of these gains occurred in three, including two well differentiated and one malignant astroblastoma. Other alterations noted in two tumors each were losses on 9q, 10, and X. These chromosomal alterations are not typical of ependymoma or infiltrating astrocytic neoplasms, and suggest that astroblastomas may have a characteristic cytogenetic profile in addition to their distinctive clinical, radiographic, and histopathologic features. [source] Oncogenetic tree model of somatic mutations and DNA methylation in colon tumorsGENES, CHROMOSOMES AND CANCER, Issue 1 2009Carol Sweeney Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and TP16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population-based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and TP16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis. © 2008 Wiley-Liss, Inc. [source] New established melanoma cell lines: genetic and biochemical characterization of cell division cycleJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2003A Vozza ABSTRACT Background Cancer might be envisaged as the result of a genetic process causing the unregulated proliferation of a given cell as well as its inability to undergo differentiation and/or apoptosis. Alterations of genes regulating cell division cycle appear to play a key role in the development of human cancer. Objective On the bases of the above considerations, we decided to establish new cell lines from human melanoma specimens, in order to analyse the molecular alterations in primary preparations of malignant cells. Results The present paper describes two new established cell lines and their genetic and biochemical features. Both the melanoma cell lines show inactivation of the cyclin-dependent kinase inhibitor gene, CDKN2A/p16INK4A, thus demostrating that this alteration occurs in primary human melanomas. No other alterations were observable when we investigated several different cell cycle genes including those encoding cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors. Analyses at protein level by means of immunoblotting confirmed the results obtained at the genetic level. Moreover, the inducibility of a pivotal cyclin-dependent kinase inhibitor gene, namely p21CIP1 gene, was obtained by treating the cells with histone deacetylase inhibitors, namely butyrate and phenylbutyrate. Conclusions Our results suggest a primary role of cyclin-dependent kinase inhibitor genes inactivation in the origin of human melanoma and allow the proposal of new therapeutic strategies based on the transcriptional activation of p21CIP1 gene. [source] Sulphated Polysaccharides: New Insight in the Prevention of Cyclosporine A-Induced Glomerular InjuryBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2007Anthony Josephine Nephrotoxicity induced by cyclosporine A continues to be a major problem despite its potent immunosuppressive action. Adult male albino rats of Wistar strain were categorized into four groups. Two groups (II and IV) were administered cyclosporine A (25 mg/kg body weight, orally) for 21 days, in which Group IV rats were also treated simultaneously with sulphated polysaccharides (5 mg/kg body weight, subcutaneously) for the same period. A significant loss in body weight was noted in the cyclosporine A-induced rats. Renal damage was assessed in terms of decreased creatinine clearance and increased activity of lysosomal enzymes. The levels of glycoproteins were found to be decreased in the renal tissue, and a noticeable rise in glycosaminoglycanuria coupled with marked proteinuria was more prominent in the cyclosporine A-induced animals. Furthermore, the extent of kidney damage was assessed by histopathological findings. Toxic manifestations were also confirmed by transmission electron microscopic studies. These morphological abnormalities and other alterations in the renal tissue were significantly offset by sulphated polysaccharides supplementation. These findings underline that restoration of normal cells accredits sulphated polysaccharides, from Sargassum wightii, with nephroprotective role, against cyclosporine A-induced renal injury. [source] | ||||||||||