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

The myelodysplastic syndrome (MDS) or preleukaemia is a haematological disorder characterized by low blood counts, bone marrow cells of abnormal appearance and progression to acute leukaemia in as many as 30% of patients. The distinctive preleukaemic and leukaemic phases of this disease make it an attractive model for neoplastic progression in human tumours. We reasoned that, because dominantly transforming genes (such as mutant alleles of ras proto-oncogenes) are found so frequently in acute leukaemia, the search for these genetic lesions during the clinical course of patients with MDS might give us insight into the function of oncogenes in leukaemogenesis. We report here that bone marrow cells from two of four patients with preleukaemia, and from one patient who progressed to acute leukaemia from MDS, contained a transforming allele of the Ki-ras proto-oncogene. In one preleukaemic patient, a novel mutation in codon 13 of this ras gene was detected in bone marrow cells harvested 1.5 years before the acute leukaemia developed. Our findings provide evidence that ras mutations may be involved in the early stages of human leukaemia.
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PMID:Mutations of the Kirsten-ras proto-oncogene in human preleukaemia. 331 61

We demonstrated previously that carcinogen-induced neoplastic transformation of Syrian hamster embryo (SHE) cells requires multiple steps. Normal, diploid SHE cells and carcinogen-induced preneoplastic cells were transfected with different oncogenes. The normal, early-passage cells were not transformed by the v-Ha-ras or v-myc oncogenes alone, but the two oncogenes combined caused tumors in nude mice and syngeneic hamsters. Cytogenetic analysis of the ras-plus-myc-induced tumors showed a nonrandom chromosome loss (monosomy of chromosome 15) in the ras/myc tumor cells. Tumorigenicity of the ras/myc tumor cells was suppressed following hybridization with normal SHE cells; reexpression of tumorigenicity at later passages correlated with loss of chromosome 15. The hybrid cells in which tumorigenicity was suppressed still expressed the ras and myc oncogenes. An early change in carcinogen-induced neoplastic progression of SHE cells is induction of immortality. At early passages, immortal cells retain the ability to suppress tumorigenicity in cell hybrids. This ability decreases with passaging of immortal cell lines. The susceptibility of immortal cell lines to neoplastic transformation by DNA transfection with the v-Ha-ras oncogene or tumor DNA inversely correlated with the tumor-suppressive ability of the cells in cell hybrids. These observations indicate that neoplastic transformation of SHE cells involves at least three steps: (1) induction of immortality, (2) activation of a transforming gene or oncogene, and (3) loss of or inactivation of a tumor-suppressor gene.
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PMID:Role of oncogenes and tumor suppressor genes in a multistep model of carcinogenesis. 332 9

In order to test the hypothesis that tumor cells with greater malignant potential should have an increased sensitivity to mutagens, four individual murine cell lines, each paired for their metastatic and nonmetastatic potentials, were compared with respect to the prevalence at which ouabain-resistant mutants could be obtained after treatment of the cells with the mutagen MNNG. No increase in the prevalence of induced mutation in metastatic cells was observed; and, in fact, in two cases (h-ras-transfected 3T3 and SP1 cells), nonmetastatic cells had a higher prevalence of mutations after MNNG treatment than did their metastatic counterparts. We suggest that the absolute level of genomic instability, measured by this means, is not critical to malignant potential and tumor progression.
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PMID:The prevalence of ouabain-resistant variants after mutagen treatment. Lack of correlation between the frequency of variant expression and the metastatic phenotype. 336 May 93

In Xiphophorus the causative, primary cellular oncogene for melanoma formation has been assigned by classical genetics to a sex-chromosomal locus, designated Tu. Activation of Tu was proposed to be the result of the elimination of Tu-specific regulatory genes which normally suppress the transforming function in the non-tumorous state. In order to understand the role which known proto-oncogenes might play in this process, we have analysed the expression of src, erb A, erb B, ras, abl, sis and mil related genes from Xiphophorus during embryogenesis, in non-tumorous organs and in melanoma cells. For src, ras, erb B and sis a differential expression during embryogenesis and/or in normal organs was detected, with preferential expression of src in neural tissues, a high abundance of sis transcripts in an embryonal epitheloid cell line and of erbB transcripts in the head nephros. In melanoma cells ras, src and a v-erb B related gene were found to be expressed. The src gene most likely is more involved in secondary processes during tumor progression, while the expression of the v-erb B related gene might be transformation-specific because recently such a sequence was found to map to the close vicinity of the Tu-locus.
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PMID:Expression of proto-oncogenes in embryonic, adult, and transformed tissue of Xiphophorus (Teleostei: Poeciliidae). 337 60

Cell hybrids between normal, early-passage Syrian hamster embryo cells and a highly tumorigenic, chemically transformed hamster cell line, BP6T, were formed, selected, and analyzed. Tumorigenicity and anchorage-independent growth were suppressed in the hybrid cells compared to the tumorigenic BP6T cells. These two phenotypes segregated coordinately in these cells. To determine at what stage in the neoplastic process this tumor-suppressive function was lost, two chemically induced immortal cell lines were examined at different passages for the ability to suppress the tumorigenic phenotype of BP6T cells following hybridization. Hybrids of BP6T cells with the immortal, nontumorigenic cell lines at early passages were suppressed for tumorigenicity and anchorage-independent growth. This tumor-suppressive ability was reduced in the same cells at later passages and in some cases nearly completely lost, prior to the neoplastic transformation of the immortal cell lines. Subclones of the cell lines were heterogeneous in their ability to suppress tumorigenicity in cell hybrids; some clones retained the tumor-suppressive ability and others lost this function. The susceptibility to neoplastic transformation of these cells following DNA transfection with the viral ras oncogene or BP6T DNA inversely correlated with the tumor-suppressive ability of the cells. These results suggest that chemically induced neoplastic progression of Syrian hamster embryo cells involves at least three steps: induction of immortality, activation of a transforming oncogene, and loss of a tumor-suppressive function.
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PMID:Loss of tumor-suppressive function during chemically induced neoplastic progression of Syrian hamster embryo cells. 346 73

Analyses of the cellular and viral Kirsten ras genes (c-Ki-ras and v-Ki-ras, respectively) during malignant tumor progression were performed by using Kirsten murine sarcoma virus-transformed BALB/c 3T3 cells that harbor a replication-defective provirus. After injection into athymic nude mice by four different routes, primary tumors and secondary lung metastases were isolated, adapted to in vitro growth, and analyzed for DNA levels and mRNA expression of both genes for comparison with the originally injected transformed cells and untransformed 3T3 cells. For all tumors (primary or secondary), the v-Ki-ras gene was amplified and v-Ki-ras mRNA expression was highly elevated above that observed in the original transformed cell population. In two of five lung metastases from the i.v. and footpad injection routes, rearranged Ki-ras DNA sequences were observed. Micrometastases from the s.c. route of injection did not display these alterations. Injection of footpad lung tumor cells with rearrangements into a second group of animals led to multiple lung metastases with even further rearrangements correlating with more effective lung colonization/growth ability (overt lung tumors in five of eight animals less than 20 days after injection). However, reinjection of an i.v. lung tumor with rearranged Ki-ras led to no further rearrangements in the lung microfoci tumors isolated greater than 40 days after injection. These data suggest (i) the significance of amplification and elevated expression of v-Ki-ras in tumor formation, (ii) correlation of this amplification with more effective tumor progression, and (iii) the selective advantage that cells with Ki-ras DNA sequence additions have in the formation of overt lung tumors.
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PMID:Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression. 347 46

To determine the frequency and clinical significance of oncogene abnormalities in colon cancer, deoxyribonucleic acids from 45 colon carcinomas and 15 benign adenomas were hybridized with 14 different protooncogene probes. Abnormalities of oncogenes were found in 22% of cancers at the time of resection. Amplification of c-myc or c-erbB-2 and allelic deletion of c-ras-Ha or c-myb were the most frequent abnormalities. The presence of altered oncogenes did not correlate with Dukes' stage, tumor progression, or patient survival after resection. One adenoma had an allelic deletion of the c-myb oncogene which was not seen in either the normal colon or an adjacent carcinoma. These data indicate that the spectrum of altered protooncogenes in colon carcinoma is similar to that of other adenocarcinomas, and that unstable oncogenes can be found before overt malignancy develops.
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PMID:Protooncogene abnormalities in colon cancers and adenomatous polyps. 355 13

The hypothesis of tumor progression proposed by Nowell [P. C. Nowell, Science (Wash. DC), 194: 23-28, 1976] states that one mechanism for the development of the metastatic phenotype could be the induction of chromosomal instability. We have developed a new experimental system for studying the induction of the metastatic phenotype using early passage fibroblasts which become metastatic in nude mice after transformation with the Harvey ras oncogene [R. J. Muschel et al., Am. J. Pathol., 121: 1-8, 1985; R. Pozzatti et al., Science (Wash. DC), 232: 223-227, 1986]. Since the early passage fibroblasts themselves are diploid, we reasoned that this might be a system in which karyotypic change after tumor formation or metastasis might easily be evaluated. Thus, we performed cytogenetic analysis on multiple metastases and tumors which had been derived from cells transformed with the cellular Harvey ras1 oncogene and compared their karyotypes. The karyotypes of the cells isolated from 5 tumors and 14 metastases were, as far as we could determine, identical to those of the injected cells. This could easily be evaluated because of the two clones studied one was diploid; the other has a trisomy of chromosome 4 without any other detectable abnormality. These results suggest that in this system using nude mice, selection for a necessary or even advantageous chromosomal aberration does not occur during tumor formation or metastasis. Furthermore, they indicate that the presence of the ras gene itself does not induce chromosomal rearrangements or aneuploidy and that a cell can be both tumorigenic and metastatic yet remain diploid.
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PMID:Karyotypic analysis of diploid or near diploid metastatic Harvey ras transformed rat embryo fibroblasts. 373 Oct 77

The human lung tumor-derived cell lines A549, Calu-1, Calu-3, HuT292, and SW900 and the transformed human bronchial epithelial cell line TBE-1, that was transfected with the v-Harvey-ras oncogene, were inoculated into deepithelialized Fisher 344 rat tracheas (5 X 10(5) cells/trachea). After the ends of the tracheas were sealed, the tracheas were transplanted into s.c. tissues of nude mice. In a parallel experiment, 1 X 10(6) cells from each of these cell lines were injected s.c. Histological examination of the tracheal transplants 2, 4, 8, 12, and 16 weeks after cell inoculation proved to be of greater usefulness than either clinical or histological observation of the s.c. injection sites. A549, Calu-1, and TBE-1 produced intratracheal neoplastic nodules as early as 2 weeks after cell inoculation. Calu-3, HuT292, and SW900 grew relatively slowly in the tracheas, and simple or stratified epithelia with slight or moderate atypia (preneoplastic lesions) were seen at 2 weeks. After the 4th week, they produced tumor nodules in the tracheal transplants, whereas no tumor cells could be seen at the s.c. injection sites. The human derivation of the cells was confirmed by in situ hybridization using human-specific DNA probes. The intratracheal inoculation and xenotransplantation of human-derived cell lines offers a time-saving alternative to the s.c. inoculation assay for tumorigenicity and is at the same time a potentially valuable approach to studying preneoplastic and neoplastic progression with human cell subpopulations.
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PMID:Preneoplastic and neoplastic growth of xenotransplanted lung-derived human cell lines using deepithelialized rat tracheas. 379 Dec 42

Activation of the cellular oncogene ras has been implicated in many types of human malignancies. In this study, the relative levels of p21 protein product of ras (p21ras) in primary and metastatic colon tumors were compared to those in adjacent normal tissues. Nine of the 17 primary tumors had substantially elevated levels of p21ras with respect to adjacent normal tissues. Eight of these tumors were from Dukes' B and C stages. Four of the five tumors classified as "D" stage (in which distant metastases are present) did not show elevated levels of p21ras. In metastases from primary colon tumors, nine of nine were considerably reduced in p21ras expression regardless of the site of metastasis. These data suggest that elevation of p21ras may be a common event in early stages of colon tumors, and tumor progression may lead to a more autonomous population of cells in which other growth factors supplant the role of this protein.
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PMID:Expression of p21ras in fresh primary and metastatic human colorectal tumors. 388 18


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