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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two human ovarian (OV-MZ-10, OV-MZ-15) and two colon cancer cell lines (CO-MZ-5, CO-MZ-6) were newly established in permanent cell culture. These cell lines have been maintained in vitro for 5-6 years, the passage number varying from 25 to 228. They were established from ascites or solid tumours at the time of primary surgery. By clinical and histopathological judgement alone all four cell lines would have been interpreted as ovarian cancer cell lines. Morphological criteria or the expression of the tumour-associated antigens CA-125 and CEA allowed no differential diagnosis. Only the analysis of the expression of different cytokeratins and vimentin enabled us to verify the different origin of the cell lines. Ovarian cancer cell lines, in contrast to the colon cancer cell lines, are positive for the expression of cytokeratin (CK) 7 and for vimentin. CK 20 proved to be the marker with the best discrimination. CK 20 was found exclusively in the colon carcinoma cell lines, but not in the ovarian carcinoma cell lines. The evaluation of cytokeratin expression is a helpful diagnostic modality in differentiating between adenocarcinoma cell lines derived from ovarian and colon tumours.
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PMID:Establishment of new ovarian and colon carcinoma cell lines: differentiation is only possible by cytokeratin analysis. 751 Jan 15

For the detection of circulating colorectal carcinoma cells, we investigated the presence of cytokeratin 20 (CK 20) mRNA in the peripheral blood of colorectal carcinoma patients. Application of our published technique resulted in analysis by reverse transcription followed by three-step nested polymerase chain reaction. This analysis could detect a single Colo 205 colon cancer cell mixed with 1 ml of blood. Our system also successfully detected the presence of CK 20 mRNA in actual patients' peripheral blood samples. Our highly sensitive and specific system for the detection of CK-20 mRNA from patients' peripheral blood thus seems to be useful for screening for circulating colorectal carcinoma cells.
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PMID:Detection of colorectal carcinoma cells in circulating peripheral blood by reverse transcription-polymerase chain reaction targeting cytokeratin-20 mRNA. 904 67

The immunophenotype of HT29 human colon cancer cells implanted into severe combined immunodeficient mice was assessed in primary tumours and their metastases in the lungs using an indirect immunohistochemical method. After primary tumours were surgically removed, the metastases were given time to develop, thus paralleling the clinical situation. While vimentin was negative in both primary and secondary tumours, E-cadherin was present as membrane-bound labelling in the primary tumours only. Whereas the markers p53, MIB1, PCNA and CEA were consistently positive in both primary and metastatic tumours, CD44 variant 6 and CA125 were negative in metastases but positive in the primary tumours. There was a significant increase in the percentage of cells labelled for p53 in the primary tumours compared with the metastases. For the proliferation markers, there was no significant difference in labelling between primary tumours and metastases for MIB1. Of the cytokeratins examined, CK 20 gave the strongest and most consistent reaction in both primary and secondary tumours. The results indicate that, for certain immunohistochemical markers, results are the same in both primary tumours and metastases. Hence, in these cases, antigens that are expressed on the primary tumour as well as on the metastases can serve as target molecules for immunologically based forms of treatment of metastases.
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PMID:Immunophenotyping of human HT29 colon cancer cell primary tumours and their metastases in severe combined immunodeficient mice. 918 53

The presence of colonic tumor cells in the circulation may predict colorectal carcinoma recurrence and metastases. We have developed a highly sensitive nested RT-PCR assay, with primers derived from the cytokeratin 20 (CK20) and the carcinoembryonic gene CGM2, to detect occult microdisseminated enterocytes in blood of colorectal cancer patients. Among 82 healthy controls analyzed, 40.2% (33/82) have a positive expression of CK20 mRNA which is not statistically different from the 45.5% (15/33) of positive results found in colon cancer patients. This sensitive method may detect non-tissue specific constitutive low level (illegitimate) expression of CK20 mRNA in peripheral nucleated blood cells (PNBC) of a significant number of healthy control as well as in a number of normal bone marrow. The low specificity of this assay therefore hampers its value to detect blood colon cancer dissemination. In 47 patients with colorectal carcinoma, CGM2 primers detected circulating enterocytes in 25 of them (53%). In disseminated Dukes' stage C disease patients, 17 out of 29 (59%) were found positive whereas in localized adenocarcinoma (Dukes's stage A and B), CGM2 primers detected enterocytes in 44% suggesting that an hematogenous spillage of colonic cells may be a relatively early event in colon cancer. None of the patients suffering from benign colonic pathologies or from diverticulitis were found positive for this assay. The analysis of 56 healthy individuals without known colorectal cancer, of 20 non-colorectal cancer patients and of 6 normal bone marrows provide evidence that this assay is highly specific and may predict an hematogenous spread of colonic cells in patients with organ-confined disease. Nevertheless, the clinical significance of enterocyte detection and the potential applications of this molecular tool merit longer term follow-up.
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PMID:[Evaluation and interest in new molecular markers in colon cancer]. 977 30

Surgery is the main therapy for malignancies of the gastrointestinal tract. Lymph node metastasis is one of the major factors in predicting patients' clinical course and choosing appropriate adjuvant therapy after surgery. The concept of micrometastasis to regional lymph nodes emerged over 10 years ago, but its significance has been controversial. To clarify the relevance of micrometastasis of gastrointestinal tract cancers, we have established RT-PCT based-diagnostic methods using multi-markers such as CEA, CK20, and Mage 3. Prospective studies have shown that not a few micrometastasis-positive patients with carcinoma of the colon, stomach, and esophagus suffered disease recurrence, even though they did not show histologically positive lymph node metastasis. They were initially diagnosed as node-negative, and thus predicted to be disease free. A retrospective study of 62 patients with stage II node-negative colorectal cancer showed that 5-year overall survival was 78.2% among micrometastasis-positive patients, against 95.3% micrometastasis-negative patients. Moreover, there was a marked difference in 5-year disease-free survival, with 61.4% versus 88.4%, respectively. These data warrant further prospective study with a large population since RT-PCR based detection systems for micrometastasis appear to have the potential to improve conventional diagnosis and therapy for colorectal cancer.
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PMID:[Clinical significance of micrometastasis to lymph nodes in gastrointestinal tract cancers]. 1143 44

Quantification of circulating cancer cells in whole blood samples by real time quantitative RT-PCR might be of clinical value for monitoring therapeutic effectiveness. In colon cancer patients, carcinoembrynic antigen (CEA) and cytokeratin 20 (CK20) have been frequently used for RT-PCR based tumor cell detection, but the specificity in particular for CEA has been questioned. In this study, we compared real-time RT-PCR for CEA and CK20 and analysed patients with metastatic disease (n=32) and healthy volunteers (n=17). CK20 mean values were elevated in cancer patients (P<0.001) and defined a subgroup (38%) who showed CK20 levels at least 100-fold above the highest value of the healthy control group. In contrast, only two cancer patients (6%) showed elevated CEA levels. Samples of the healthy control group showed exclusively a CEA-PCR product of 79 degrees C melting temperature. Thirty per cent of the colon cancer patients showed an additional product of 82 degrees C melting temperature. The 82 degrees C product was identical with the amplification product of CEA-cDNA and cDNA from different colon cancer cell lines. Colon cancer cells were spiked into normal blood in 10-fold dilutions that resulted in a dose dependent shift of the melt curve from 79 degrees C to the 82 degrees C. Sequencing of the PCR products showed that white blood cells express a splice variant of CEA, which hinders detection of tumor cell cDNA in whole blood samples. Our findings have implications for the use of CEA as a diagnostic molecule (e.g. by RT-PCR). The discovery of a physiologically expressed CEA splice variant might lead to a better understanding of the biological function of CEA and its family members.
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PMID:Differential expression of carcinoembryonic antigen (CEA) splice variants in whole blood of colon cancer patients and healthy volunteers: implication for the detection of circulating colon cancer cells. 1242 Feb 18

Expression of genes such as cytokeratin 19 (CK19), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) has been investigated at mRNA level in peripheral blood of carcinoma patients to detect the presence of circulating tumor cells (CTC). We performed this study because recent literature emphasizes that the importance of CK19, 20 and EGFR mRNAs in CTC as prognostic factors remains unclear especially for breast, head and neck and colon cancer patients. Reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization was performed in blood samples from 47 subjects (12 colorectal, 15 head and neck and 20 breast carcinoma patients), as well as in 35 healthy donors. The CK19 expression was found in 36/47 patients (9 colorectal, 9 head and neck and 18 breast cancer), two patients (one affected by colorectal and one by head and neck cancer) were positive for CK20 whereas EGFR was found expressed in 9 patients (3 colorectal, 5 head and neck and one breast cancer). Seven of 35 and 4/35 healthy donors displayed positivity for the expression of CK19 and CK20 genes respectively, whereas no EGFR mRNA was found in this group. The correlation of the detection of CTC in peripheral blood with progression of the disease in a follow-up period of 40 months did not show any prognostic value to the presence of mRNAs of these biomarkers in blood. We believe that research should be addressed, at least for breast cancer, to the identification of occult metastases in sentinel lymph nodes, such as recently performed in melanoma patients.
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PMID:Detection of CK19, CK20 and EGFR mRNAs in peripheral blood of carcinoma patients: correlation with clinical stage of disease. 1246 72

Peritoneal recurrence after curative resection of malignant tumor with negative cytology is considered to be caused by microscopic dissemination of the exfoliated cancer cells from primary tumors to serosal surfaces at the time of operation, not detectable with conventional diagnostic tools. We applied the reverse transcriptase-polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK 20) to detect micrometastatic foci in the peritoneal cavity of colon cancer patients. Cytological samples taken by peritoneal lavage from a series of 79 colon cancer patients were analyzed microscopically, for CEA levels, and by RT-PCR analysis using nested primers for CEA and CK 20. Cases with both CEA and CK 20 signals were defined as PCR-positive. This RT-PCR method proved both sensitive (1 tumor cell/10(6) non-tumor cells on preparation of serial colorectal cancer cell dilutions) and specific (no false positive results, 0/23 tested in our control experiment). Intraperitoneal micrometastatic cells were detected in peritoneal lavage 7.6% by cytology, 17.7% by CEA levels, and 24.1% by RT-PCR (significantly higher than by cytology: p=0.0046). RT-PCR detection rate increased in parallel with pathological depth of tumor invasion, and also a pathological stage-dependence was suggested according to the tumor-node-metastasis classification of the International Union Against Cancer. Our results suggest that CEA and CK 20 mRNA identification by RT-PCR appeared to be reliable and may be useful for early diagnosis in peritoneal dissemination of colon cancer.
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PMID:Detection of peritoneal micrometastases by reverse transcriptase-polymerase chain reaction targeting carcinoembryonic antigen and cytokeratin 20 in colon cancer patients. 1263 2

Colon and ovarian cancers can be difficult to distinguish in the abdomen, and the distinction is important because it determines which drugs will be used for therapy. To identify molecular markers for that differential diagnosis, we developed a multistep protocol starting with the 60 human cancer cell lines used by the National Cancer Institute to screen for new anticancer agents. The steps included: (a) identification of candidate markers using cDNA microarrays; (b) verification of clone identities by resequencing; (c) corroboration of transcript levels using Affymetrix oligonucleotide chips; (d) quantitation of protein expression by "reverse-phase" protein microarray; and (e) prospective validation of candidate markers on clinical tumor sections in tissue microarrays. The two best candidates identified were villin for colon cancer cells and moesin for ovarian cancer cells. Because moesin stained stromal elements in both types of cancer, it would probably not have been identified as a marker if we had started with mRNA or protein profiling of bulk tumors. Villin appears at least as useful as the currently used colon cancer marker cytokeratin 20, and moesin also appears to have utility. The multistep process introduced here has the potential to produce additional markers for cancer diagnosis, prognosis, and therapy.
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PMID:Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling. 1450 Mar 54

In the previous 500 2-year chemical bioassays within the National Toxicology Program, large intestinal tumors (cecal carcinomas) related to chemical exposure have not been observed in B6C3F1 mice. The recently completed o-nitrotoluene study provided the first cecal tumor response and an opportunity to evaluate the morphology and molecular profile of oncogenes and tumor suppressor genes that are relevant to humans. Morphologically, the carcinomas were gland-forming tumors lined by tall columnar epithelial cells that were positive for cytokeratin 20 and negative for cytokeratin 7. Using immunohistochemistry beta-catenin (encoded by Catnb) protein accumulation was detected in 80% (8/10) of the cecal carcinomas, while increased cyclin D1 and p53 protein expression was detected in 73% (8/11), respectively. There was no difference in adenomatous polyposis protein expression between normal colon and cecal carcinomas. All tumors examined exhibited mutations in exon 2 (corresponds to exon 3 in humans) in the Catnb gene. Mutations in p53 were identified in nine of 11 carcinomas, and all were in exon 7. Analysis of the K-ras gene revealed mutations in 82% (9/11) of carcinomas; all had specific G --> T transversions (Gly --> Val) at codons 10 or 12. The alterations in cancer genes and proteins found in the mouse large intestinal tumors included mutations that activate signal transduction pathways (K-ras and Catnb) and changes that disrupt the cell-cycle and bypass G(1) arrest (p53, cyclin D1). These alterations, which are hallmarks of human colon cancer, probably contributed to the pathogenesis of the large intestinal carcinomas in mice following o-nitrotoluene exposure.
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PMID:o-Nitrotoluene-induced large intestinal tumors in B6C3F1 mice model human colon cancer in their molecular pathogenesis. 1468 30


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