Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In these studies, Syrian hamster embryo cells (SHE), which were isolated at different stages of neoplastic progression, were used to test the ability of the protein phosphatase inhibitors, okadaic acid and sodium orthovanadate (Na3VO4) to induce neoplastic progression. We observed that these chemicals can induce transition of the cells from one stage to the other at different points in the multistep process of neoplastic transformation. Three steps in this multistep process were studied: escape from cellular senescence, loss of a tumor suppressor gene function in immortal cells, and aquisition of anchorage-independent growth. Treatment of normal, primary SHE cells with okadaic acid or Na3VO4 allowed the cells to escape senescence and become immortal at a low frequency. The induction of immortality was associated with nonrandom chromosome changes, including trisomy 8 and 11 and monosomy 13 and Xq. The transition of preneoplastic cells to more advanced stages was also studied in immortal, nontumorigenic cells that either have retained (supB+) or have lost (supB-) the ability to suppress tumorigenicity of a transformed cell line in cell hybrids. SupB+ and supB- cells do not normally grow in agar, but supB- cells will grow in agar if additional growth factors are added. However, upon addition of protein phosphatase inhibitors, supB+ cells exhibited the supB- phenotype; for example, colony formation of supB+ cells was observed in agar supplemented with growth factors and protein phosphatase inhibitors. Following treatment, selection of these colonies showed that 89% of these cells heritably acquired the phenotype of cells that have lost the suppressor gene function (supB-). SupB- cells were also treated with protein phosphatase inhibitors in soft agar in the presence of additional growth factors. While the frequency of colonies in agar supplemented with growth factors in agar was not greatly enhanced, approximately 50% of the colonies acquired the ability to grow in agar autonomously without the supplemented growth factors, similar to tumorigenic cells. These studies suggest that Na3VO4 and okadaic acid induce progression of cells through various stages in this multistep system.
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PMID:Induction of neoplastic progression in Syrian hamster embryo cells treated with protein phosphatase inhibitors. 838 70

We identified cytogenetically unrelated clones in the bone marrow of 12 of 240 patients with myelodysplastic syndrome (MDS) and in 3 of 232 patients with acute myeloid leukemia (AML). In addition, unrelated single-cell abnormalities were found in six MDS and two AML patients. The most commonly encountered abnormalities present in the unrelated clones in patients with refractory anemia (RA) were del(5q), +8, and -7. In blastic types of MDS and AML trisomy 8 was found in two of eight patients while in the remaining cases the chromosome abnormalities were diverse and nonspecific. The presence of the chromosomally unrelated clones, together with recent data on the early appearance of monoclonality provided by molecular biology studies, support the interpretation that aberrations such as +8 and del(5q) are actually secondary abnormalities that develop during tumor progression in a cell with a primary submicroscopic genomic rearrangement.
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PMID:Multiple unrelated clones in myelodysplastic syndrome and in acute myeloid leukemia. 864 Jul 23

Ewing sarcoma (ES) is the second most common primary malignant tumor of bone in children and young adolescents. Most ES contain a pathognomonic translocation t(11;22)(q24;q12) that is likely a pivotal event in the tumorigenesis of these neoplasms. Many ES also contain nonrandom, numerical chromosomal aberrations, the most common of which are trisomies 8 and 12. In this study we evaluated the hypothesis that these trisomies might occur during neoplastic progression and might be associated with differences in biologic behavior. We tested this hypothesis using a combined cytogenetic and dual color fluorescence in situ hybridization approach to determine chromosome 8 and 12 copy number in 52 ES. Relative gains, primarily trisomies, of chromosomes 8 and 12 were found in 24 (46%) and 17 (33%) cases, respectively. Trisomy 8 and trisomy 12 were independent events acquired in a flexible order during ES genetic progression. Our preliminary findings also suggest a higher frequency of trisomies 8 and 12 in relapses than in primary tumors. Prospective studies will be required to determine whether either trisomy is prognostic in newly-diagnosed ES.
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PMID:Frequency and implications of chromosome 8 and 12 gains in Ewing sarcoma. 942 52

Acute myeloid leukemia (AML) cases with monosomy 7 (-7) and del(7q) comprise a heterogeneous subgroup. The association of losses in 7q with myeloid leukemia suggests that this region contains a tumor suppressor gene or genes whose loss of function contributes to leukemic transformation or tumor progression. The -7/del(7q) aberrations frequently coexist with complex karyotypes such as -5/del(5q) and trisomy 8. In the present case, we identified a rare abnormality involving deletion of both arms of chromosome 7 presenting with a marker chromosome-like appearance in an AML patient. Bone marrow aspiration and biopsy revealed acute myelomonocytic leukemia. Immunophenotyping study showed CD13, CD14, CD33, CD117, and myeloperoxidase positivities. Analysis of 20 metaphases indicated a diploid cell number with an unidentifiable tiny marker chromosome instead of one normal chromosome 7, described as 46,XY,-7,+mar[20]. Array comparative genomic hybridization test confirmed the chromosome 7 origin of the marker chromosome with deletions of 7p and 7q. The evaluation after remission induction treatment indicated morphological and cytogenetic remissions. There is evidence that the outcome is better when -7 or del(7q) occurs in patients with a simple karyotype, compared with a complex karyotype.
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PMID:Deletions of chromosome arms 7p and 7q in adult acute myeloid leukemia: a marker chromosome confirmed by array comparative genomic hybridization. 1978 38

Trisomy of chromosome 8 is frequently reported in myeloid lineage disorders and also detected in lymphoid neoplasms as well as solid tumors suggesting its role in neoplastic progression in general. It is likely to be a disease-modulating secondary event with underlying cryptic aberrations as it has been frequently reported in addition to known abnormalities contributing to clinical heterogeneity and modifying prognosis. Here, we share our findings of trisomy 8 in leukemia patients referred for diagnostic and prognostic cytogenetic assessment. Total 60 cases of trisomy 8, as a sole anomaly or in addition to other chromosomal aberrations, were reported (January 2005-September 2008). Unstimulated bone marrow or blood samples were cultured, followed by GTG banding and karyotyping as per the ISCN 2005. Patients with +8 were chronic myeloid leukemia (CML) (36), acute myeloid leukemia (AML) (17), and acute lymphoblastic leukemia (ALL) (7). In 7 patients, trisomy 8 was the sole anomaly, whereas in 6 patients +8 was in addition to normal clone, in 47 patients, the +8 was in addition to t(9;22), t(15;17), and others, including 3 with tetrasomy 8. Only one patient showed constitutional +8. The present study will form the basis of further cumulative studies to correlate potential differential effects of various karyotypic anomalies on disease progression and survival following a therapeutic regime. To unravel the role of extra 8 chromosome, constitutional chromosomal analysis and uniparental disomy will be considered.
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PMID:Trisomy 8 in leukemia: A GCRI experience. 2275 32