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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past few decades medical science has accepted the concept that cancer is a fundamental disorder of cellular growth control. A disorder can originate in some cells through changes in genes (DNA level: gene amplification, mutation and rearrangement) or their expression (RNA and protein levels), and stimulates growth in contrast to surrounding cells. Over the last decade genes affected in the cancer cell have been identified as well as the nature of changes undergone. Only a few of the known oncogenes play a role in head and neck cancer. These are epidermal growth factor receptor, c-myc, the ras gene family, int-2, hst-1 and bcl-1. In some clinical disorders, such as childhood neuroblastoma and breast cancer, oncogenes have been shown to play an important role in tumor staging or as a prognostic parameter. The aim for future therapy is the effective application of oncogenes (or "gene therapy") in clinical practice.
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PMID:[Oncogenes and their significance for head and neck cancers]. 151 16

Expression of the c-myb nuclear oncogene during the cell proliferation and differentiation of HL-60 human promyelocytic leukemia cells was characterized and compared to the expression of c-fos, another nuclear oncogene with transcriptional regulatory activity. During progression through the cell cycle, the amount of c-myb protein increased. The increase was commensurate with total cell size, thus preserving the relative abundance of c-myb protein present at the onset of the cell cycle. In HL-60 cells, the induced metabolic cascade leading to terminal myeloid or monocytic differentiation segregates into two steps occurring over two division cycles. Expression of c-myb did not diverge from the control until late in this metabolic cascade when it declined prior to onset of terminal differentiation. This course of expression was similar for both the retinoic acid induced myeloid or the 1,25-dihydroxy vitamin D2 induced monocytic terminal differentiation of the cells. Bromodeoxyuridine, which induces proliferative arrest but not phenotypic differentiation of these cells, induced the same course of c-myb expression as the inducers of terminal differentiation. The same course of c-myb expression with growth arrest induced by these three different means is consistent with a potential proliferation regulatory role for c-myb in late but not early events leading to terminal differentiation. The dynamics of c-myb expression during this process were qualitatively, but not quantitatively, similar to the course of c-fos expression. Thus, taken with previous results, then amongst the nuclear oncogenes or tumor suppressor genes, c-myc, RB, c-fos, and c-myb, only c-myc and RB expression exhibit early regulation during induced HL-60 cell differentiation.
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PMID:Regulation of cell proliferation: late down-regulation of c-myb preceding myelo-monocytic cell differentiation. 152 28

We established an androgen-sensitive cell line (BR31-5) from a ras + myc-induced mouse prostate carcinoma and used this cell line together with a previously reported transplantable androgen-independent mouse prostate carcinoma to investigate patterns of expression for apoptosis-related genes in an androgen-deprived environment. Single cell suspensions derived from the BR31-5 cell line were inoculated into the flank of intact or castrated adult male C57BL/6 mice and tumors were harvested 12 days post-inoculation for Northern blotting. A transplantable androgen-independent prostate cancer was also inoculated into intact or castrated mice and tumors harvested 21 days later. Tumor volume analyses showed that BR31-5 carcinomas were androgen-sensitive. Northern blotting showed that mRNA levels for two apoptosis-related genes, transforming growth factor-beta 1 and c-myc, were significantly elevated to a similar extent in carcinomas grown in castrated hosts compared to intact hosts for both the androgen-sensitive BR31-5 and androgen-independent carcinomas. Levels of mRNA for tissue type plasminogen activator, shown previously to be elevated in androgen-independent carcinomas following growth in castrates, were also increased in BR31-5 carcinomas under similar androgen-deprived conditions but to a lesser extent. Interestingly, testosterone repressed prostate mRNA No. 2 levels shown previously to be similar in both the intact and castrated groups for androgen-independent carcinomas were significantly increased in the castrated group compared to the intact group for BR31-5 carcinomas. Therefore, specific patterns of expression for apoptosis-related genes may be able to discriminate androgen-sensitive and androgen-independent prostate cancer under androgen-deprived conditions.
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PMID:Androgen sensitivity and gene expression in ras + myc-induced mouse prostate carcinomas. 152 69

We present four cases of infantile cerebellar neoplasms composed of cells with large vesicular nuclei with prominent nucleoli. All four cases were strongly immunoreactive for synaptophysin, and one case showed immunoreactivity for neurofilaments. Filter hybridization for N-myc and c-myc oncogenes showed a 27-fold c-myc amplification in one case. The cytogenetic analysis in this case showed Double-Minutes and isochromosome 17q. An intracerebral xenograft in nude mice obtained from one such tumor showed a similar morphology to that of the original tumor as well as strong immunoreactivity for synaptophysin and neurofilaments. All the neoplasms were characterized by highly aggressive behavior leading to early cerebrospinal fluid dissemination despite radiotherapy and chemotherapy. We conclude that large-cell medulloblastoma represents a distinct and more aggressive variant of medulloblastoma that requires more aggressive therapy.
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PMID:Large-cell medulloblastomas. A distinct variant with highly aggressive behavior. 153 Jan 8

A highly malignant human T-cell leukemia was identified by cell surface analysis as a member of the T-cell receptor (TCR) gamma delta lineage. Cytogenetic and molecular analysis showed a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on chromosome 14 and the distal end of chromosome 8 near the c-myc proto-oncogene locus. The gamma delta TCR of the leukemia blasts was functionally intact and could be activated to generate intracellular calcium flux and to target Fc receptor-mediated redirected tumor cell lysis. In addition, non-major histocompatibility complex restricted lysis of a limited target cell panel was shown by fresh leukemic blasts and by the in vitro-maintained leukemia cells that was comparable to known T-cell lines with natural killer-like activity. These data suggest that the T-cell leukemia potentially had in vivo functional cytolytic activity. However, whether this activity did contribute to the patient's clinical condition could not be determined.
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PMID:A gamma delta+ T-cell leukemia bearing a novel t(8;14)(q24;q11) translocation demonstrates spontaneous in vitro natural killer-like activity. 153 37

A systematic study of primary human breast tumor DNA demonstrated that three proto-oncogenes or regions of the genome (c-myc, int-2, and c-erbB2) are frequently amplified and that there is loss of heterozygosity (LOH) on chromosomes 1p(37%), 1q(20%), 3p(30%), 7(41%), 11p(20%), 13q(30%), 17p(49%), 17q(29%), and 18q(34%). Specific subsets of tumors can be defined based on the particular collection of mutations they contain. For instance, LOH on chromosomes 11p, 17p, and 18q frequently occurs in the same tumor. A search for putative tumor suppressor genes within the regions of the genome affected by LOH has been started. In a comprehensive molecular analysis of the p53 gene on chromosome 17p, 46% of the tumors contained a point mutation in the p53 gene.
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PMID:Somatic mutations and human breast cancer. A status report. 154 Aug 99

Six human colon tumor cell lines were analyzed for their constitutive levels of the c-myc protein. The nuclear proto-oncogene, c-myc, was detected as an expressed product in all of the human colon tumor cell lines analyzed. The poorly differentiated cell lines HCT116, RKO and C showed c-myc levels that averaged 2-fold greater than their well-differentiated counterparts, i.e., GEO, CBS and FET. When c-myc levels and responses to serum induction were analyzed in the presence of inducers of differentiation, i.e., dimethylformamide, retinoic acid, sodium butyrate and TGF-beta, distinct patterns of sensitivity and resistance emerged. Nuclear c-myc levels were reduced in all the colon cell phenotypes treated with dimethylformamide or sodium butyrate. Only the well-differentiated human colon tumor cell lines were responsive to transforming growth factor-beta. Only one of the human colon tumor cell lines (GEO) responded to retinoic acid. Increased levels of c-myc protein were found to correlate well with greater growth rates and with poor differentiation class. Similarly, a parallel sensitivity to down-regulation of c-myc levels and attenuation of c-myc induction curves for inducers of differentiation were observed in growth sensitive human colon tumor cell lines.
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PMID:Sensitivity of nuclear c-myc levels and induction to differentiation-inducing agents in human colon tumor cell lines. 154 Sep 46

Expression of c-myc protein was studied immunohistochemically in colorectal cancers using a monoclonal antibody, MYC-1. Immunoblotting assays with cellular lysates demonstrated a band of the gene products at the level of 60 kDa. c-myc-protein-positive tumor cells were observed in 43 (43.4%) of 99 specimens of colorectal cancers. There was no significant correlation between the incidence of MYC-1-positive tumors and clinicopathological findings. The rate of MYC-1 proteins occurring in patients with liver metastasis was significantly higher than that in patients without the metastasis. The rate of occurrence of DNA polymerase-alpha-positive cells in MYC-1 protein-positive tumors was significantly higher than in MYC-1 negative ones. The results suggested that MYC-1 immunoreactivity might possibly be a useful prognostic marker of colorectal cancers.
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PMID:Immunohistochemical detection of c-myc products in colorectal cancer and proliferative cell rate. 154 92

A clonal mouse prostate carcinoma was established by the introduction of the ras and myc oncogenes via the recombinant retrovirus Zipras/myc 9 using a mouse prostate reconstitution model system. A single-cell suspension derived from an early passage ras+myc-induced carcinoma was inoculated into the flanks of intact or castrated adult male C57BL/6 mice, and tumors were harvested 3 wk postinoculation for northern and Southern blotting. Tumor volume analysis showed that this carcinoma was not dependent on testicular androgens for growth. Southern blot analysis of virus-cell DNA junction fragments revealed that tumor cell populations recovered from both intact and castrated mice were progeny of the same virus-infected cell. Northern blotting showed that mRNA levels for the four growth-related genes transforming growth factor-beta 1 (TGF-beta 1), transforming growth factor-beta 3 (TGF-beta 3), tissue-type plasminogen activator (tPA), and c-myc were significantly elevated in clonal mouse prostate carcinomas grown in castrated hosts. In contrast, androgen receptor mRNA levels were significantly reduced under the same conditions. The response of TGF-beta 1, tPA, and c-myc mRNA levels in the carcinomas grown in castrated hosts was similar to that shown previously in normal rat ventral prostate. However, unlike normal rat ventral prostate after castration, increased numbers of apoptotic cells were not seen in the castrated group relative to the intact group at the time of analysis, indicating that the altered gene expression was not associated with cell death. In addition, testosterone-repressed prostate mRNA number 2 levels, shown previously to be elevated after castration in normal rat ventral prostate, were not increased in the androgen-deprived clonal mouse prostate carcinomas. Therefore, this early passage clonal ras+myc-induced prostate carcinoma demonstrates unique patterns of expression for a set of growth-related genes in an androgen-deprived environment.
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PMID:Alterations in mRNA levels for growth-related genes after transplantation into castrated hosts in oncogene-induced clonal mouse prostate carcinoma. 154 41

Lipotrope-deficient (methyl-deficient) diets cause fatty livers and increased liver-cell turnover and promote carcinogenesis in rodents. In rats prolonged intake of methyl-deficient diets results in liver tumor development. The mechanisms responsible for the cancer-promoting and carcinogenic properties of this deficiency remain unclear. The results of the experiments described here lend support to the hypothesis that intake of such a diet, by causing depletion of S-adenosylmethionine pools, results in DNA hypomethylation, which in turn leads to changes in expression of genes that may have key roles in regulation of growth. In livers of rats fed a severely methyl-deficient diet (MDD), lowered pools of S-adenosylmethionine and hypomethylated DNA were observed within 1 week. The extent of DNA hypomethylation increased when MDD was fed for longer periods. The decreases in overall levels of DNA methylation were accompanied by simultaneous alterations in gene expression, yielding patterns that closely resembled those reported to occur in livers of animals exposed to cancer-promoting chemicals and in hepatomas. Northern blot analysis of polyadenylated RNAs from livers of rats fed control or deficient diets showed that, after 1 week of MDD intake, there were large increases in levels of mRNAs for the c-myc and c-fos oncogenes, somewhat smaller increases in c-Ha-ras mRNA, and virtually no change in levels of c-Ki-ras mRNA. In contrast, mRNAs for epidermal growth factor receptor decreased significantly. The elevated levels of expression of the c-myc, c-fos, and c-Ha-ras genes were accompanied by selective changes in patterns of methylation within the sequences specifying these genes. Changes in DNA methylation and in gene expression induced in livers of rats fed MDD for 1 month were gradually reversed after restoration of an adequate diet. In hepatomas induced by prolonged dietary methyl deficiency, methylation patterns of c-Ki-ras and c-Ha-ras were abnormal. Although human diets are unlikely to be as severely methyl deficient as those used in these experiments, in some parts of the world intake of diets that are low in methionine and choline and contaminated with mycotoxins, such as aflatoxin, are common. Even in industrialized nations, deficiencies of folic acid and vitamin B12 are not uncommon and are exacerbated by some therapeutic agents and by substance abuse. Thus, it seems possible that interactions of diet and contaminants or drugs, by inducing changes in DNA methylation and aberrant gene expression, may contribute to cancer causation in humans.
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PMID:Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. 154 43


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