Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the cellular oncogene c-N-ras has been frequently observed in DNA from leukemic cells in acute myeloid leukemia (AML). Ras gene activation sufficient to mediate in vitro transformation and rodent tumorigenesis usually results from point mutations and amino acid substitutions in the 12th or 61st codons. In AML and the related myelodysplastic syndromes, amino acid substitution at the 13th codon has been observed. An activated c-N-ras gene from a 45-year-old patient with AML was isolated by transfection analysis and subjected to molecular cloning and sequence analysis. A point mutation of the 12th codon (GGT to GAT) resulting in aspartic acid substitution for glycine was observed. In other neoplasms such as colon cancer, specific ras mutations occur predominantly (e.g., K-ras, codon 12). This predominance has been of demonstrable value in analyzing large cohorts for ras activation with techniques that are rapid and economical, such as oligonucleotide hybridization. It had previously been thought that such a predominance for activation of c-N-ras at codon 13 existed in AML; however, this study in concert with others underscores the importance of 12th codon c-N-ras mutations, along with 13th and 61st codon mutations in the molecular pathogenesis of AML. Guanylate to adenylate transition mutations are commonly observed in AML and may provide insight into potential environmental leukemogens. Addressing all commonly prevalent ras activating mutations bears impact in the future design of molecular surveys of the role of ras activation in leukemogenesis.
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PMID:12th codon mutation resulting in c-N-ras activation in acute myelogenous leukemia. 327 72

Recently an increase of the elderly patients with hematological malignancies has been pointed out. We analyzed second malignancies in elderly patients with hematological malignancies (95 age 65 or more), and made a comparative study with non-elderly case for the past 5 years. Second malignancies were observed in 26 cases out of the total of 282 hematological malignancies (9.2%). The percentage of patients with second malignancies in the elderly group (19/95; 20%) was significantly higher than that of the non-elderly group (7/187; 3.7%). Among the all kinds of hematological malignancies, the second malignancies were mainly observed in cases with myelodysplastic syndrome and chronic myelo-proliferative disorder. Colon carcinoma, gastric carcinoma and lung carcinoma accounted for nearly half of all the second malignancies. On 11 of the 26 cases with second malignancies, the first malignancies had been treated with some anti-cancer drug such as alkylating agents. Development of a second cancer was greater in cases in which the first hematological malignancy was treated with alkylating agents more than in cases in which the first carcinoma was not treated with alkylating agents.
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PMID:[Elderly cases of hematological malignancies with second malignancies]. 823 Jul 94

Using flow cytometry and immunoprecipitation (IP), we have investigated the deleted in colon cancer (DCC) protein expression on the bone marrow (BM) and peripheral blood (PB) cells of 16 normal subjects, 17 myelodysplastic syndrome (MDS) patients, and 10 acute myelogenous leukemia (AML) patients. With regard to the BM mononuclear cells (BM-MNCs) of normal subjects, the DCC protein expression ranged from 6.6 to 57.0%. Two-color flow cytometry revealed that among the IBM-MNCs the DCC protein was clearly expressed on the CD14+, CD13+, and factor 8+ cells, whereas it was low on the CD19+ and CD7+ cells and did not express on the CD34+, CD8+, and the glycophorin A+ cells. Further, the DCC protein expression was not seen on the PB CD11b+ and CD13+ cells. The IP results revealed that the 180-kD DCC protein was detected on the MNCs of both the BM and PB cells by the antibodies AF5, specific for the DCC extracellular domain, and G97-449, specific for the cytoplasmic domain. In contrast, flow cytometry did not detect the DCC protein on any BM-MNC MDS lineages (0.1-1.5%) or on AML leukemic cells (0.1-0.9%). The IP results indicated that the AF5 antibody did not detect the DCC protein on BM-MNCs of three of five MDS patients and four of five AML patients; however, the G97-449 antibody detected the 180-kD DCC protein in two MDS patients in whom AF5 had detected greatly reduced DCC band. These findings suggest that the DCC protein presence appears to be associated with normal hematopoiesis, and that its absence on the surfaces of the BM-MNCs and AML cells may contribute to the MDS and AML pathogenesis.
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PMID:DCC protein expression in hematopoietic cell populations and its relation to leukemogenesis. 860 44

The occurrence of multiple malignancy was studied in 674 patients with hematologic malignancies who were admitted to this department during the past 10 years. Of the 674 patients, 205 were aged 65 years or older, and 56 (8.3%) had another cancer. The frequency of multiple malignancy was significantly higher in older patients than in younger patients: 44 (21.5%) vs. 12 (2.6%). The major hematologic conditions in patients with multiple malignancy were multiple myeloma, myelodysplastic syndromes, non-Hodgkin's lymphoma, and chronic myelogenous leukemia. The major sites of cancers other than hematological malignancies were the stomach, colon, breast, and esophagus. Many of the older patients had gastric cancer or colon cancer, and gastric cancer was common in the younger patients. The multiple malignant neoplasms were synchronous in as many as 20 of the 44 older patients. There was only one such case among the younger patients. Of the 56 patients, nine had received alkylating agents, and one has received etoposide. In brief, elderly patients with hematologic malignancies are likely to have multiple malignant neoplasms. If they are synchronous, the patient's prognosis may be adversely affected, because simultaneous management of multiple malignant neoplasms is not easy.
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PMID:[Double cancer in elderly patients with hematologic malignancies]. 875 14

Somatic mutations of the adenomatous polyposis coli (APC) gene have been frequently found in sporadic colorectal tumors, and the frequency of such mutations remain constant as tumors progress from benign adenomas to malignant cancers. Thus the mutations of the APC gene may have a major role in the early development of sporadic colorectal tumors. Whether inactivation of the APC gene accounts for other types of primary tumors is still being investigated. We investigated for APC mutations within the mutation cluster region (a 684-bp region containing most of the mutations found in colorectal tumors) in 317 samples from a wide variety of human malignant and premalignant tissues, including 40 lung cancers, 47 renal cell carcinomas, 41 osteosarcomas and 21 other types of sarcomas, 45 acute lymphoid leukemias/lymphomas, 33 acute myeloid leukemias, 27 myelodysplastic syndrome samples, and 20 chronic colitis (ulcerative colitis and Crohn's disease) associated cancers and dysplasias, and 43 human malignant cell lines. We used single-strand conformation polymorphism assay following polymerase chain reaction. Samples with abnormal assay results were reamplified and analyzed by the direct DNA sequencing method. We detected a total of two cases with a base substitution. A silent mutation was detected in a case of myelodysplastic syndrome, and a novel nonsense mutation was discovered in a colorectal cancer cell line, SW837. In summary, we did not detect any functional mutations of the APC gene in a wide variety of tumors except for a colon cancer cell line, suggesting that alterations of the APC gene do not have a major role in the development of lung and renal cancers, various types of sarcomas, or hematological malignancies.
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PMID:Molecular analysis of the adenomatous polyposis coli gene in sarcomas, hematological malignancies and noncolonic, neoplastic tissues. 908 31

The human genome contains at least 50 copies of the human endogenous retrovirus K (HERV-K) family which is related to the mouse mammary tumor virus (MMTV). Some members have been shown to be transcriptionally active and to have large open reading frames. Using the RT-PCR method we have investigated the HERV-K env transcription pattern in several malignant tissues and in peripheral blood mononuclear cells PBMCs). Samples were derived from chronic myelogenous leukemia (CML), breast cancer, colon cancer, high and low grade non-Hodgkin's lymphomas, Hodgkin's disease, myelodysplastic syndrome, thyroid adenoma (TA) and from PBMCs of patients with breast cancer, gastric cancer, and of healthy individuals. We found abundant HERV-K env transcripts in all tissues under investigation. Using HERV-K 10 specific primers for amplification we detected in addition to transcripts with high homology to HERV-K 10 (ca. 96% homology on the amino acid level) also transcripts of low homology to HERV-K10 (ca. 71%). Interestingly, all solid tissues containing high percentages of malignant cells such as breast cancer, colon carcinoma, low and high grade non-Hodgkin's lymphomas showed exclusively HERV-K env related transcripts with low homology to HERV-K 10. In contrast, in samples containing only a low proportion of malignant cells or no malignant cells at all we observed both types of transcripts. Thus, our data suggest that the expression pattern of HERV-K elements in human cells is very heterogenous and subjected to a complex transcriptional regulation.
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PMID:Two groups of endogenous MMTV related retroviral env transcripts expressed in human tissues. 942 77

It has become clear that several polymorphisms of human drug-metabolizing enzymes influence an individual's susceptibility for chemical carcinogenesis. This review gives an overview on relevant polymorphisms of four families of drug-metabolizing enzymes. Rapid acetylators (with respect to N-acetyltransferase NAT2) were shown to have an increased risk of colon cancer, but a decreased risk of bladder cancer. In addition an association between a NAT1 variant allele (NAT*10, due to mutations in the polyadenylation site causing approximately two fold higher activity) and colorectal cancer among NAT2 rapid acetylators was observed, suggesting a possible interaction between NAT1 and NAT2. Glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) are polymorphic due to large deletions in the structural gene. Meta-analysis of 12 case-control studies demonstrated a significant association between the homozygous deletion of GSTM1 (GSTM1-0) and lung cancer (odds ratio: 1.41; 95% CI: 1.23-1.61). Combination of GSTM1-0 with two allelic variants of cytochrome P4501A1 (CYP1A1), CYP1A1 m2/m2 and CYP1A1 Val/Val further increases the risk for lung cancer. Indirect mechanisms by which deletion of GSTM1 increases risk for lung cancer may include GSTM1-0 associated decreased expression of GST M3 and increased activity of CYP1A1 and 1A2. Combination of GST M1-0 and NAT2 slow acetylation was associated with markedly increased risk for lung cancer (odds ratio: 7.8; 95% CI: 1.4-78.7). In addition GSTM1-0 is clearly associated with bladder cancer and possibly also with colorectal, hepatocellular, gastric, esophageal (interaction with CYP1A1), head and neck as well as cutaneous cancer. In individuals with the GSTT1-0 genotype more chromosomal aberrations and sister chromatid exchanges (SCEs) were observed after exposure to 1,3-butadiene or various haloalkanes or haloalkenes. Evidence for an association between GSTT1-0 and myelodysplastic syndrome and acute lymphoblastic leukemia has been presented. A polymorphic site of GSTP1 (valine to isoleucine at codon 104) decreases activity to several carcinogenic diol epoxides and was associated with testicular, bladder and lung cancer. Microsomal expoxide hydrolase (mEH) is polymorphic due to amino acid variation at residues 113 and 139. Polymorphic variants of mEH were associated with hepatocellular cancer (His-113 allele), ovarian cancer (Tyr-113 allele) and chronic obstructive pulmonary disease (His-113 allele). Three human sulfotransferases (STs) are regulated by genetic polymorphisms (hDHEAST, hM-PST, TS PST). Since a large number of environmental mutagens are activated by STs an association with human cancer risk might be expected.
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PMID:Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. 1002 93

Mutations of the mitochondrial DNA (mtDNA) are associated with a number of human diseases. To become relevant in terms of pathology, a mutation must generally affect at least 50-70% of mtDNA molecules in a tissue. One way to reach this level is by inheritance. Mitotic segregation of mtDNA in the female germline can result in large increases in the percentage of mutant mtDNA between generations. A different explanation is required if a particular mtDNA mutation accumulates over time in somatic cells. We discuss the possibility that mutant mtDNA, by causing deficient oxidative phosphorylation, may become preferentially replicated and may thus thrive in the cell like a cuckoo in the nest. However, despite preferential replication, a de novo mtDNA mutation will be confined to that particular cell or a small clone of daughter cells. Significant accumulation can only occur if the cell harbouring the mutant mtDNA undergoes malignant transformation and therefore starts proliferating continuously. This type of amplification of mutant mtDNA has recently been demonstrated in certain bone marrow disorders (myelodysplastic syndromes) and in colon cancer cell lines. Finally, in postmitotic tissues, an inherited mutation which is present in virtually all cells of the tissue, may accumulate through replicative advantage. This may contribute to the development of degenerative diseases.
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PMID:Mitochondria harbouring mutant mtDNA--a cuckoo in the nest? 1049 36

In addition to immunomodulatory and cytokine-modulatory properties, thalidomide has antiangiogenic activity. It has been investigated in a number of cancers including multiple myeloma, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Its role has been best explored in myeloma, where, at daily doses of 100 to 800 mg, it is remarkably active, causing clinically meaningful responses in one-third of extensively pretreated patients and in over half of patients treated early in the course of the disease. It also acts synergistically with corticosteroids and chemotherapy in myeloma. Thalidomide produces improvement of cytopenias characteristic of myelodysplastic syndrome, resulting in the reduction or elimination of transfusion dependence in some patients. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high grade glioma and, in combination with irinotecan, in some patients with colon cancer. Thalidomide is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation and fatigue are common adverse effects seen in 75% of patients. Symptoms of peripheral neuropathy and skin rash are seen in 30%. A minority of patients experience bradycardia and thrombotic phenomena. Despite the high frequency of adverse effects, those severe enough to necessitate cessation of therapy are seen in only 10 to 15% of patients. A therapeutic trial of thalidomide should be considered in all patients with myeloma who are unresponsive to or relapse after standard therapy. In other malignant diseases, the most appropriate way to use the drug is in the setting of well designed clinical trials. In the absence of access to such studies, thalidomide could be considered singly or in combination with standard therapy in patients with no meaningful therapeutic options.
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PMID:Thalidomide in cancer: potential uses and limitations. 1143 82

A 59-year-old man was admitted to our hospital because of disturbance of consciousness and hyponatremia. The patient had suffered from acute myelogenous leukemia (AML) with 46,XY and received chemotherapy for 5 years. Meningeal carcinomatosis was diagnosed due to the detection of carcinoma cells in the cerebrospinal fluid (CSF). Hyponatremia was caused by syndrome of inappropriate secretion of anti-diuretic hormone (SIADH). Bone marrow examination revealed myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 7. Emergence of a new abnormal clone was suggested. The patient died from brain herniation. Post mortem examination showed adenocarcinoma in the colon. An association between chemotherapy and both colon cancer and MDS was suggested.
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PMID:Colon cancer with meningeal carcinomatosis and myelodysplastic syndrome in a patient who underwent intensive chemotherapy for acute myelogenous leukemia: a case report. 1145 Sep 98


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