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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We are now beginning to understand the development of bladder cancer at the molecular level. Tumor evolution involves the interaction of both oncogenes and tumor suppressor genes. One of the key tumor suppressor genes in this process is the retinoblastoma (RB) gene. Much has been learned recently about the role of this gene in the tumor progression and prognosis of bladder cancer, although several questions are still unanswered. The progress made on this subject in our laboratory as well as others will be the focus of this report.
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PMID:Altered RB expression is a prognostic clinical marker involved in human bladder tumorigenesis. 130 91

In a previously studied family with inherited renal cell carcinoma (RCC), RCC was shown to segregate with a constitutional balanced t(3;8)(p14.2;q24.1). In addition, we recently showed that in a RCC tumor from this family the constitutional translocation became unbalanced, suggesting a genetic mechanism that may be associated with the primary genetic events of tumorigenesis. We now report that the RCC tumor cells from this case showed additional cytogenetic alterations, possibly related to tumor progression, which include an additional tumor-specific translocation involving band 14 of chromosome 13. Because this band contains the retinoblastoma (RB) gene, we examined the tumor for aberrations in the RB gene using DNA sequence polymorphism analysis and pulsed-field gel electrophoresis (PFGE), but did not detect alterations in the RB gene.
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PMID:Cytogenetic and molecular studies of a familial renal cell carcinoma. 142 22

Cytogenetic alterations that characterize different histologic subtypes of soft tissue sarcomas have been identified. In a few situations, more precise chromosomal mapping has allowed identification of certain genes that may be involved in the development or tumor progression of sarcomas. Careful family histories must be elicited in sarcoma patients. While "cancer families" are rarely identified when screening close relatives of sarcoma patients, the discovery of the currently known tumor suppressor gene syndromes associated with germ line retinoblastoma gene and p53 gene defects were made possible by their association with sarcomas. Optimal management of primary sarcomas includes function-sparing complete resection and radiotherapy. Innovative radiotherapy, utilizing radiation sensitizers or brachytherapy, may increase local control in patients with unresectable tumors. New drugs are needed. Epirubicin and other anthracycline analogues do have significant activity; however, no other novel drugs have documented efficacy. Dose intensity is being explored with sarcoma trials providing the "vehicle" to evaluate new cytokines. Several mechanisms of doxorubicin resistance have been identified in cell lines and fresh tumors, including alterations in glutathione peroxidase activity and MDR-1 gene expression. These observations need to be taken to the clinic.
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PMID:Advances in the diagnosis and management of sarcomas. 151 Oct 24

The two-stage murine skin tumorigenesis model is widely used to study the development of squamous cell neoplasias. We have investigated expression of the p53 and retinoblastoma tumor suppressor genes in eight murine skin tumor cell lines of varied histopathology and malignant potential, in seven in vivo-derived clones from these cell lines, and in 39 primary short-term cultures of similarly induced skin tumors at various stages of tumor progression. One squamous cell carcinoma cell line and three more malignant clones derived from it revealed mutations of the p53 protein by immunoprecipitation analyses despite normal-sized p53 transcripts. Sequence analysis identified the nature of the point mutations in these lines, a G----C transversion in codon 132. Mouse retinoblastoma transcripts and protein were unaltered in all the cell lines examined. Among short-term cultures of skin tumors, the p53 gene appeared normal in all papillomas and early well-differentiated carcinomas by Southern and immunoprecipitation analyses. In contrast, four of eight tumors from later stages of promotion (50-60 weeks) possessed alterations in p53, including loss of the p53 product, and loss of immunoreactivity with a murine-specific antibody recognizing only wild-type p53 protein. Loss of heterozygosity at the p53 locus was similarly observed in several more malignant tumors from later stages of promotion. In contrast retinoblastoma expression was normal regardless of the stage of promotion or histological grade of the tumor. Direct sequence analyses of exons 5 through 8 of the p53 gene in eight advanced murine skin tumors revealed a 25% incidence of p53 mutations. These point mutations were located in codons 245 and 263. Collectively, these data indicate that alterations in the p53 gene occur in 25 to 50% of murine skin tumors induced by the two-stage tumorigenesis protocol and are later events in murine skin tumor progression. Moreover, these alterations are associated with tumors possessing a more malignant and/or poorly differentiated phenotype.
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PMID:Alterations of the p53 tumor suppressor gene during mouse skin tumor progression. 174 35

Cobalt60 plaque irradiation is one treatment option for patients with recurrent retinoblastoma following conventional external beam irradiation (ERT). Tumorocidal doses can be delivered without excessive risk of normal tissue injury. In patients not considered candidates for xenon arc or cryotherapy, 60Co is an alternative to enucleation. Between 1968 and 1987, 85 patients were treated with 60Co plaques, 72 of whom had failed prior ERT. Age at diagnosis ranged from 1 week to 4 years. There are 37 males and 35 females. Seventy-one patients had bilateral disease and one had unilateral. Three patients had both eyes plaqued. Prior ERT ranged from 30 to 70 Gy (mean 4200 Gy). Time from initial therapy to failure ranged from 13 to 60 months. Cobalt plaques of 10 mm, 15 mm, or 10 x 15 mm were used depending on tumor size and location. Dose prescribed to the apex of the tumor ranged from 30 to 50 Gy (median 40 Gy) given over 3 to 8 days. Twelve patients had two plaque applications; three patients had three plaque applications. All patients were followed with routine ophthalmoscopic examinations. Follow-up ranged from 2 to 22 years (mean 8.7). Seven patients died of metastatic disease; 10 patients developed non-ocular second tumors. Thirty patients required enucleation. Twenty-two patients had clear tumor progression, two patients had radiation complications, and six patients had a combination of tumor growth and complications. Cobalt60 can salvage eyes in retinoblastoma patients failing ERT. Currently, we are using I125 in an attempt to spare normal ocular tissue and reduce subsequent complications.
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PMID:Cobalt60 plaques in recurrent retinoblastoma. 186 58

The development of human cancer is generally thought to entail a series of events that cause a progressively more malignant phenotype. Such a hypothesis predicts that tumor cells of the ultimate stage will carry each of the events, cells of the penultimate stage will carry each of the events less the last one and so on. A dissection of the pathway from a normal cell to a fully malignant tumor may thus be viewed as the unraveling of a nested set of aberrations. In experiments designed to elucidate these events we have compared genotypic combinations at genomic loci defined by restriction endonuclease recognition site variation in normal and tumor tissues from patients with various forms and stages of cancer. The first step, inherited predisposition, is best described for retinoblastoma in which a recessive mutation of a locus residing in the 13q14 region of the genome is unmasked by aberrant, but specific, mitotic chromosomal segregation. Similar mechanisms involving the distal short arm of chromosome 17 are apparent in astrocytic tumors and the events are shared by cells in each malignancy state. DNA sequencing indicates that these events accomplish the homozygosis of mutant alleles of the p53 gene. Copy number amplification of the epidermal growth factor receptor gene occurs in intermediate and late-stage tumors whereas loss of heterozygosity for loci on chromosome 10 is restricted to the ultimate stage, glioblastoma multiforme. These results suggest a genetic approach to defining degrees of tumor progression and the locations of genes involved in the pathway as a prelude to their molecular isolation and characterization.
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PMID:Molecular genetics of human cancer predisposition and progression. 201 Nov 37

The development of human cancer is generally thought to entail a series of events that cause a progressively more malignant phenotype. This hypothesis predicts that tumor cells of the ultimate stage will carry each of the events, cells of the penultimate stage will carry each of the events less the last one and so on. That is to say, a dissection of the pathway form a normal cell to a fully malignant tumor may be viewed as the unraveling of a nested set of aberrations. In experiments designed to elucidate these events, we have compared genotypic combinations at genomic loci defined by restriction endonuclease recognition site variation in normal and tumor tissues from patients with various forms and stages of cancer. The first step, inherited predisposition, is best described for retinoblastoma in which a recessive mutation of a locus residing in the 13q14 region of the genome is unmasked by aberrant, but specific, mitotic chromosomal segregation. A similar mechanism involving the distal short arm of chromosome 17 is apparent in astrocytic tumors and the event is shared by cells in each malignancy stage. This is distinct from a loss of heterozygosity for loci on chromosome 10 which is restricted to the ultimate stage, glioblastoma multiforme. Further, this approach has has been extended to a wide variety of human cancers and shown to be generally applicable. The results suggest a genetic approach to defining degrees of tumor progression and a means for determining the genomic locations of genes involved in the pathway as a prelude to their molecular isolation and characterization. They have provided a molecular genetic-based oncology with clinical utility in differential pathology, in disease groupings for therapeutic purposes and in prenatal identification of latent disease carriers.
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PMID:Tumor progression stage: specific losses of heterozygosity. 248 36

The development of human cancer is generally thought to entail a series of events that cause a progressively more malignant phenotype. Such a hypothesis predicts that tumor cells of the ultimate stage will carry each of the events, cells of the penultimate stage will carry each of the events less the last one, and so on. That is to say a dissection of the pathway from a normal cell to a fully malignant tumor may be viewed as the unraveling of a nested set of aberrations. In experiments designed to elucidate these events, we have compared genotypic combinations at genomic loci defined by restriction endonuclease recognition site variation in normal and tumor tissues from patients with various forms and stages of cancer. The first step, inherited predisposition, is best described for retinoblastoma in which a recessive mutation of a locus residing in the 13q14 region of the genome is unmasked by aberrant, but specific, mitotic chromosomal segregation. A similar mechanism involving the distal short arm of chromosome 17 is apparent in astrocytic tumors and the event is shared by cells in each malignancy stage. This is distinct from a loss of heterozygosity for loci on chromosome 10 which is restricted to the ultimate stage, glioblastoma multiforme. These results suggest a genetic approach to defining degrees of tumor progression and means for determining the genomic locations of genes involved in the pathway as a prelude to their molecular isolation and characterization.
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PMID:Mitotic abnormalities leading to cancer predisposition and progression. 255

Medullary thyroid carcinoma (MTC) is an important human cancer for the study of molecular abnormalities that underlie initiation of neoplasia and subsequent cellular changes during tumor progression. This tumor can occur in different inherited forms, each mediated by autosomal dominant genetic events. Germline abnormalities on chromosome 10 are linked to at least one type of genetic MTC, multiple endocrine neoplasia type II. Our studies of chromosome 10 in DNA from MTC tumors failed to detect frequent loss of polymorphic DNA markers, suggesting that the genetic mechanisms involved in MTC development may be different from those for other inherited cancers such as retinoblastoma. During tumor progression of MTC, abnormalities develop in expression of the mature phenotype of the endocrine cell from which the tumor arises. In cell culture, chemical modulation or gene insertion can lead to partial correction of these defects in differentiation capacity by activating cellular signaling processes. These studies offer opportunities to dissect the molecular events that regulate endocrine cell differentiation, to determine the precise abnormalities that may underlie the initiation and tumor progression events in MTC and related cancers, and, thereby, to identify new targets for therapeutic intervention.
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PMID:The molecular biology of medullary thyroid carcinoma. A model for cancer development and progression. 265 32

Cellular oncogenes (c-oncs) have been highly conserved throughout evolution and subserve important roles in growth and development. Both in development and the neoplastic state, c-oncs appear to collaborate rather than function independently. Cellular oncogenes are activated in the neoplastic process by four (nonviral) mechanisms; (a) chromosomal translocations; (b) gene amplifications; (c) point mutations; and (d) DNA rearrangements. The timing of c-onc gene product expression may be as important in oncogenesis as the level of expression. At this writing, mutant oncogenes have not been shown to be inherited. Oncogene amplification, if important in oncogenesis, is more likely to be involved with tumor progression rather than initiation. Chromosomal/molecular aberrations tend to be characteristic for a given type of cancer. These genetic alterations are often situated near heritable fragile sites, tumor-suppressor gene loci and/or oncogene loci. Similar molecular mechanisms involving translocations and inversions may underly the common T and B cell neoplasms. The loss/inactivation of both normal alleles at a locus thought to encode for tumor-suppressing activities (antioncogenes) may represent an event common to many childhood and adult neoplasms. The consistency and cell specificity with which this has been identified is consistent with a role for such genes in cellular differentiation. At this writing, the paradigm for such a controlling locus is 13q14, the site of the retinoblastoma gene. Based on recent studies in familial and sporadic Wilms' tumor which suggest etiological heterogeneity, theoretical modifications of the carcinogenesis model which has been central to understanding retinoblastoma may soon be forthcoming to explain molecular mechanisms operative in other cancer. The role of genomic imprinting in carcinogenesis is only recently being explored. Further study of this process may prove to be a fruitful area of future research.
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PMID:Molecular mechanisms of oncogenesis. 265 71


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