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)

CD44 variant 6 (CD44 v6) is well known as a useful marker of tumor progression; however, its relationship to prognosis has not yet been elucidated. In this study, we investigated the expression of CD44 v6 in colorectal cancer to analyze its relationship to hepatic metastasis as well as to prognosis. Tumor tissues were obtained from 42 patients with colorectal cancer who underwent curative resection with follow-up periods ranging from 5.9 to 71.3 months. There were 21 patients (50%) whose tumors were positive for CD44 v6, with no significant difference between colon and rectal cancer. CD44 v6 staining was significantly related to Dukes' classification as well as to hepatic metastasis. The 5-year survival rate was significantly higher in patients with CD44 v6 negative cancer (84%) than in those with CD44 v6 positive cancer (31%). Thus, we concluded that CD44 v6 could be a reliable prognostic indicator, as well as a predictor of metastatic potential after curative surgery for colorectal cancer.
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PMID:The positive relationship between the expression of CD44 variant 6 and prognosis in colorectal cancer. 888 58

The peptides encoded by the rat liver oncofetal cDNA TA1 and the human lymphocyte activation gene E16 display a high degree of homology with coding regions recently identified in Schistosoma mansoni and Caenorhabditis elegans. Previous studies showed that up-regulation of TA1/ E16 expression was associated with rat hepatocarcinogenesis and human tumor cell lines; therefore, we analyzed several primary human tumors including a panel of 20 colon carcinomas to evaluate the relationship of TA1/E16 RNA and protein expression to neoplasia. A 4.0-kb transcript was detected in all but one colorectal carcinoma but not in normal colon or specimens of inflammatory bowel disease. Steady-state TA1/E16 mRNA levels varied considerably between carcinomas and did not correlate simply with mitotic index, modified Dukes' stage, or tumor size. TA1/E16 message also was detected in adenocarcinomas from breast, endometrium, salivary gland, and esophagus. Western blot analysis using antibodies against TA1/E16-deduced peptides identified major reactive bands of approximately 35 and 19 kDa in neoplasms but not in normal tissue. Immunoperoxidase staining localized the protein primarily to the supranuclear region of colon carcinoma cells, whereas normal epithelial cells were negative. Heterogeneous staining was found in villous adenomas with focal intramucosal adenocarcinoma but was negative in tubular adenomas, suggesting that expression of TA1/E16 may correlate with neoplastic progression in the colon. Up-regulation of this gene in various human cancers suggests a common role in the carcinogenic process and possible application as a tumor marker.
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PMID:Expression of a highly conserved oncofetal gene, TA1/E16, in human colon carcinoma and other primary cancers: homology to Schistosoma mansoni amino acid permease and Caenorhabditis elegans gene products. 889 58

Numerical aberration of chromosome 17 of 14 cases of colorectal carcinoma with multiple primary cancer (: multiple cancer) was compared with that of 35 cases of colorectal carcinoma without any other cancer (: single cancer). Fluorescence in situ hybridization with p17H8 was performed on touch smear from fresh materials. The proportion of aneusomy 17 (NCAI: numerical chromosome aberration index) in multiple cancers was significantly higher than that of single cancers (37.7 +/- 10.5% VS 46.1 +/- 8.0%; p < 0.01). Although NCAI of single cancers conformed to cancer progression (26.1 +/- 4.7% in Dukes A, 33.1 +/- 7.1% in Dukes B, 39.9 +/- 6.9% in Dukes C, and 45.7 +/- 12.0% in Dukes D), that of multiple cancers was high in all stages (44.7 +/- 7.3%, 44.4 +/- 6.8%, 50.4 +/- 11.2%, and 49.6 +/- 5.6%, respectively). Furthermore, the multiple numerical aberration of chromosome 17 in multiple cancers was more often than that of single cancers (64.3% VS 22.9%; p < 0.01).
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PMID:[Numerical aberration of chromosome 17 is correlated with multiple primary cancer in colorectal carcinoma]. 927 9

Microsatellite instability (MSI) is intrinsic to most colorectal carcinomas (CRC) from patients with hereditary nonpolyposis colorectal cancer (HNPCC), reflecting germline mutations in the mismatch-repair (MMR) genes. Its occurrence and chronological sequence of development in sporadic CRC appears less well defined. To explore the time sequence in acquisition of MSI, and the role it plays during tumor progression in sporadic CRC, we compared the incidence of MSI in tissue samples from 40 Dukes'-B and 30 Dukes'-D CRC patients with liver metastases, at 4 different microsatellite loci, representing sites on the APC, DCC and p53 genes respectively as well as the D2S123 site. Among the 30 patients with hepatic metastases, MSI was found in 9 (30%) of the primary, and 13 (43.3%) of the metastatic tumors. In comparison, among the 40 Dukes'-B CRC, MSI was found in only 8 cases (20%). CRC with MSI were more frequently located in the right colon, less frequently on the left side, and seldom in the rectum. Tumor ploidy analysis shows that 46.2% of Dukes'-D primary tumors with MSI are diploid (chi2 = 4.46, p = 0.035). With a mean follow-up time of 4.2 years for the Dukes'-B CRC, there were no recurrences in the 8 patients with MSI, whilst 6 (18.8%) relapses occurred amongst the 32 patients without MSI, average time to recurrence being 15 months. In Dukes'-D CRC, mean survival time for patients with MSI was 37 months (95% CI, 24 to 51 months), for those without MSI 26 months (95% CI, 18 to 35 months), although this was not statistically significant. Our data suggest that tumor progression may involve increased genetic instability.
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PMID:Microsatellite instability in sporadic-colon-cancer patients with and without liver metastases. 929 42

Western blots, enzyme assays, protein glycosylation studies, and immunohistochemical staining were used to characterize cathepsin B expression at successive stages of colorectal tumor progression. In normal colon mucosa and premalignant adenomas, cathepsin B expression was predominantly due to mature two-chain protein detected on Western blots as the nonglycosylated 27-kDa form, with overexpression of this protein occurring in only 4 of 18 adenomas. Overexpression increased significantly in Dukes A and B carcinomas (26 of 37 cases), with cathepsin B protein generally detectable in carcinomas as a combination of both 27-kDa nonglycosylated and 28-kDa glycosylated mature two-chain forms. Glycosylated cathepsin B protein in carcinoma extracts was sensitive to PNGase F but resistant to Endo H, indicating a pattern consistent with complex rather than high mannose type glycosylation. When sorted by advancing tumor stage, peak expression of cathepsin B protein occurred in carcinomas involved in local invasion compared with adenomas or metastatic cancers. At all stages, cathepsin B activity correlated significantly with the levels of heavy chain mature cathepsin B protein (r = 0.6682, p < 0.0001) irrespective of glycosylation. Immunohistochemical staining of cathepsin B protein revealed fine diffuse cytoplasmic staining in both adenomas and carcinomas compared with coarse granular cytoplasmic staining (typical of lysosomes) seen in matched normal mucosa. Our results demonstrate several sequential, apparently independent changes in cathepsin B expression during colorectal tumor progression including early changes in subcellular localization, up-regulation of cathepsin B protein and activity in invasive cancers, and altered protein glycosylation detected in malignant tumors at all stages.
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PMID:Elevations in cathepsin B protein content and enzyme activity occur independently of glycosylation during colorectal tumor progression. 936 Sep 97

The down-regulated in adenoma (DRA) gene was originally identified as a gene that was down-regulated in colon tumors. It encodes a protein with anion transporter function that is expressed predominantly in the mucosa of the lower gastrointestinal tract. In this study, expression of DRA and its cellular distribution have been investigated in a series of benign adenomatous polyps and malignant colorectal tumors and in corresponding normal colonic mucosa. We show that DRA mRNA and protein are expressed in all normal colonic tissue specimens with the protein restricted primarily to the terminally differentiated columnar epithelium and some goblet cells. Apical membrane localization was especially apparent in the columnar epithelium. The levels of DRA mRNA transcripts were down-regulated in all colon tumors examined relative to matched normal mucosa, with most specimens showing undetectable levels of DRA mRNA (77 of 104 tumors). DRA down-regulation was positively associated with colonic tumor progression according to Dukes' stage and was particularly significant in the early transition from normal mucosa to polyp to adenocarcinoma. DRA expression does not appear to be strictly associated with colonic cell differentiation; rather, its absence and down-regulation were associated with the proliferating component of the crypt epithelium and with neoplastic transformation, respectively.
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PMID:Down-regulation of the down-regulated in adenoma (DRA) gene correlates with colon tumor progression. 971 12

Telomerase and telomere length are increasingly studied as prognostic markers in malignancy. Telomerase is also known to be expressed in certain nonmalignant cells, although generally at low levels. We investigated telomerase activity and telomere length in premalignant, malignant, inflammatory, and normal colon specimens to determine whether significant differences exist and whether telomerase may serve as a marker for early- or late-stage colorectal cancer. Telomerase activity was evaluated in 130 frozen specimens from human colon cancer (n = 50), adjacent normal colon tissue (n = 50), colon polyps (n = 20), and colitis (n = 10) using a modified telomeric repeat amplification protocol assay, and telomere length was assessed by terminal restriction fragment analysis. High to moderate levels of telomerase activity were detected in 90% of colorectal tumors. Weakly positive activity was detected in 10%. None of the normal tissues exhibited telomerase activity. In polyps and colitis, telomerase activity was found in 60% (12 of 20) and 40% (4 of 10), respectively. Telomerase activity in both nonmalignant lesions was 25- to 54-fold lower than that detected in colon cancer (P < 0.001). We found a positive correlation between tumor cell infiltration determined in cryostat sections and telomerase activity (r = 0.886; P > 0.0001). Late-stage tumors (Dukes C + D) demonstrated increased telomerase activity compared to early-stage tumors (Dukes A + B). Telomere restriction fragments in colon tumors had peak values of 4.8 +/- 1 kbp that were significantly and consistently shorter than those of the adjacent normal tissues (7.54 +/- 1.3 kbp), polyps (7.5 +/- 0.7 kbp), and colitis specimens (7.7 +/- 0.5kbp; P < 0.0001). Telomeres were 0.6 kbp longer in tumors with high telomerase activity and in late-stage cancers (Dukes C + D) compared to those in tumors with low telomerase activity and in early-stage cancers (Dukes A + B). Our data demonstrate that telomerase in colon cancer was commonly acquired, and activity was higher than that in polyps and colitis. However, weak telomerase activity was detected in premalignant and inflammatory lesions. Telomeres in colon cancer were considerably shorter, an indication of extensive cell proliferation and population divisions, whereas adjacent normal colon specimens, polyps, and colitis had comparable telomere lengths. Our results indicate that increased telomerase activity occurs in colon cancer cells that have undergone extensive telomere shortening relative to surrounding normal tissues and in which telomerase-induced stabilization of telomeres may be critical for the continued proliferation of the malignant clone. The link between telomerase activity and stage suggests that telomerase is up-regulated as a function of increased tumor cell invasion, tumor progression, and metastatic potential in colon cancer.
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PMID:Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. 981 82

Dukes' classification is a useful staging system in patients with colorectal cancer. The aim of this study was to present clinicopathologic characteristics and survival of patients with gastric cancer based on Dukes' classification. A total of 273 patients with gastric cancer curatively treated by radical gastrectomy and lymph node dissection (D2, D3) were studied. With the modified Dukes' classification, A includes tumors limited to the mucosa, submucosa, or muscularis propria; B includes tumors extending into the subserosa or serosa; Ca includes tumors with one to six positive lymph nodes; and Cb includes tumors with seven or more positive lymph nodes. Dukes' classification modified by the number of positive lymph nodes well correlated with the tumor size (p < 0.01), depth of wall invasion (p < 0.01), level of lymph node metastasis (p < 0.01), and degree of lymphatic permeation (p < 0.01) and venous permeation (p< 0.01). The 5-year survival rate was significantly different among Dukes' A (98%), Dukes' B (90%), Dukes' Ca (75%), and Dukes' Cb (44%) cases. The results indicate that Dukes' classification modified by the number of positive lymph nodes (Dukes' A, B, Ca, an Cb) significantly correlates with tumor progression and patient survival; and it may be a simple and useful staging system for gastric cancer.
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PMID:Clinicopathologic study of gastric cancer based on Dukes' classification. 1008

Background: Topographic genotyping is a system of solid tissue molecular analysis designed to correlate microscopic alterations with specific forms of gene damage. In this system, microscopic targets are selected on the basis of cellular and immunohistochemical features. Minute tissue samples corresponding to these targets are precisely removed and analyzed for the presence and specific type of oncogene/tumor suppressor gene damage by means of polymerase chain reaction (PCR) followed by DNA sequencing. In this study, topographic genotyping was used to investigate the prognostic value of p53 and K-ras-2 mutational damage in 204 patients with colorectal cancer from two tertiary care centers. Methods and Results: The intensity and distribution of p53 immunohistochemical staining were correlated with the presence and specific type of mutational change, which resulted in a better understanding of the highly variable nature of p53 immunostaining patterns. Molecular genotype was correlated with the depth and extent of colorectal cancer spread (Dukes B and C) and with survival for follow-up periods of up to 10 years. An algorithm for p53/K-ras-2 genotyping was formulated to include p53 immunohistochemistry and DNA sequencing both of p53 exons 5-8 and of K-ras-2 exons 1 and 2. By using this algorithm, survival was shown to be significantly better in those patients whose tumors manifested normal p53 and K-ras-2 genes (P >.01). Patients with p53-mutated tumors composed a poor prognostic group, characterized by a high rate of intra-abdominal recurrence in the form of peritoneal seeding. Patients with K-ras-2-mutated tumors also composed a poor prognostic group, marked by a tendency for distant hematogenous metastasis involving lung, bone, and brain. Conclusions: Topographic genotyping's molecular diagnostic approach to colorectal cancer combines immunohistochemistry, PCR, and DNA sequencing. It is informative, cost-effective, timely, and yet fully integrated with standard histopathology. The use of this approach by pathologists as a model system for molecular diagnosis of colorectal cancer and other forms of solid tumor malignancy is recommended. As new prognostic molecular lesions are documented for tumor progression and metastasis, topographic genotyping will be well suited to facilitate their clinical application.
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PMID:Prediction of Biologic Aggressiveness in Colorectal Cancer by p53/K-ras-2 Topographic Genotyping. 1033 Jan 94

We have previously demonstrated that the increased expression of angiogenin (ANG) in pancreatic cancer is related to cancer aggressiveness; however, the relationship between ANG expression and its clinical relevance in colorectal cancer has not been demonstrated. We therefore investigated the correlation between serum ANG (sANG) concentration and colorectal cancer progression or the changes in sANG concentrations before and after cancer resection. To determination sANG concentration by ELISA, sera were obtained from colorectal cancer patients (the cancer group) preoperatively (n = 34) and postoperatively (n = 25), from hernia patients (the nonneoplastic group) preoperatively (n = 9) and postoperatively (n = 4), and from 23 healthy volunteers. The amount of ANG in the colorectal cancer tissues (n = 19) was determined by the same method. Before surgery, the mean sANG concentration in the cancer group (411.8 +/- 106.3 ng/ml) was significantly higher than that in both the nonneoplastic group (344.0 +/- 60.7 ng/ml; P = 0.04) and in the healthy volunteers (321.7 +/- 59.7 ng/ml; P = 0.0001). The degree of elevation of sANG concentration in the cancer group was more significant in the more progressed subgroups as compared with that in the normal group (versus T(is) + T1 + T2 cancer, P = 0.01; versus T3 + T4 cancer, P = 0.002; versus stage 0 + I cancer, P = 0.02; versus >stage III cancer, P = 0.001; versus Dukes' A cancer, P = 0.02; versus Dukes' C cancer, P = 0.006). After cancer resection, the mean sANG concentrations in each subgroup decreased to the same levels as those of the normal group; the degrees of reduction were more significant in the more progressed subgroups. The tissue ANG amount correlated significantly with sANG concentration (P = 0.007). These results suggest that the increased concentration of sANG that is derived from colorectal cancer correlates with cancer progression.
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PMID:Increased serum angiogenin concentration in colorectal cancer is correlated with cancer progression. 1058 92


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