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

Tumor invasion and metastasis involve the interaction between tumor cells and basement membrane, which is mediated in part by laminin receptors. To search for tumor-associated-genes which can be used as new markers in colon cancers with known poor prognosis, cDNA libraries from a colon cancer cell line and colonic tissues were constructed and screened. We selected a cDNA clone which encodes 32-kD laminin-binding protein (LBP-32), and showed increased mRNA expression of LBP-32 in colon carcinoma. This mRNA expression was also correlated with clinical tumor staging. Furthermore, to investigate the role of LBP-32 in cancer invasion and metastasis, cell adhesion assays and in vitro invasion assays were performed, using anti-sense RNA of LBP-32 to block the synthesis of LBP-32. Results showed that anti-sense RNA of LBP-32 inhibits tumor cell attachment and invasiveness in vitro in transfectants of a colon cancer cell line. These data suggest that LBP-32 may play an important role in colon cancer progression, and that LBP-32 may be used as a marker of biological aggressiveness. These findings also imply that laminin receptors may provide a target for novel therapeutic strategies: modulating LBP-32 expression by anti-sense RNA or monoclonal antibodies may have clinical application in colorectal cancer therapy.
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PMID:[Cellular and molecular biological study of the laminin-binding protein and its clinical application]. 147 Jan 61

P-glycoprotein mediates classic multidrug resistance by functioning as an efflux pump that excretes lipophilic chemotherapeutic drugs from cancer cells. We now report an association of P-glycoprotein in colon carcinomas with another tumor property, i.e., enhancement of local tumor aggressiveness. P-glycoprotein was detected with monoclonal antibody immunohistochemistry in 65 of 95 primary colon adenocarcinomas, which were stage B1 or greater. In all but 1 of the 95 cases, solitary invading carcinoma cells were present at the leading edge of the tumor. This subpopulation of invasive carcinoma cells expressed P-glycoprotein (P-Gp+) in 47 of the 95 surgically resected colon specimens. Cases were grouped on the basis of the presence (Group 1, 47 cases) or absence (Group 2, 48 cases) of P-Gp+ invasive carcinoma cells. There was a significantly greater incidence of vessel invasion (P less than 0.001) and lymph node metastases (P less than 0.01) in Group 1 cases. Groups 1 and 2 did not differ with respect to tumor size, depth of invasion of the bowel wall, histological grade, maximum tumor size, mitotic index, mucin production, or presence of perineural invasion (P greater than 0.1). Our findings indicate that P-Gp+ invasive colon cancer cells may have an increased potential for dissemination, suggesting that P-glycoprotein may influence cell behavior.
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PMID:Relationship of the expression of the multidrug resistance gene product (P-glycoprotein) in human colon carcinoma to local tumor aggressiveness and lymph node metastasis. 167 39

Cell surface receptors for laminin may play an important role in tumor migration and metastasis. To evaluate laminin receptor/laminin-binding protein expression in human colon carcinoma, surgical specimens of primary colon cancers and liver metastases were examined by blot hybridization of total RNA with a complementary DNA clone which encodes a Mr 32,000 human laminin-binding protein. The mRNA level of the laminin-binding protein was higher in primary colon carcinoma than in adjacent normal colonic epithelium in 20 of 21 cases. In all 6 cases of colon cancer liver metastases, the laminin-binding protein mRNA level was more than 3-fold greater in tumor than in adjacent normal liver tissue. The tumor/normal ratio of this laminin-binding protein mRNA expression in primary colon cancer has significant correlation with Dukes' classification (P less than 0.001). Our results suggest that mRNA expression of the laminin-binding protein may be a marker of human colorectal cancer progression and biological aggressiveness.
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PMID:Expression of a Mr 32,000 laminin-binding protein messenger RNA in human colon carcinoma correlates with disease progression. 214 Dec 94

Several genes have identified that play a role in colon cancer development. However, less is known about factors that increase the rate of progression of colon cancers to metastasis. One candidate is transforming growth factor beta 1 (TGF beta 1), which can enhance the aggressiveness of human colorectal cell lines in vitro and in vivo. The amount of TGF beta 1, TGF beta 2, and TGF beta 3 protein isoforms expressed in primary site colorectal cancers were measured to determine whether any correlation existed between protein levels and disease recurrence in a series of Memorial Sloan-Kettering Hospital patients who underwent potentially curative resections. Intense staining for TGF beta 1 correlated significantly (P < 0.0013; odds ratio, 18) with disease progression to metastasis and was independent of nodal status and the degree of differentiation of the primary tumor. Therefore, in this study, patients with high TGF beta 1 protein levels in their primary site colorectal cancer were 18 times more likely to experience recurrence of their disease than were patients whose tumors exhibited low levels of TGF beta 1. In this case-control study, patients whose cancer recurred and those remaining cancer free were age and sex matched. The disease recurred at a mean of 26.8 +/- 4.3 (SE) months, whereas the mean follow-up time in patients whose disease did not recur was over twice as long, 57.3 +/- 6.6 months. Ninety-four % of the patients in each group were node positive at the time of resection, with equal mean numbers of positive nodes per patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High levels of transforming growth factor beta 1 correlate with disease progression in human colon cancer. 754 13

The overview of apoptosis presented here emphasizes cell deletion in the immune system, with particular reference to T- and B-lymphocyte development, and the in vivo and in vitro senescence of human neutrophils. Some biochemical criteria that are used to identify apoptotic cells are described. Pitfalls in using agarose gel electrophoresis as the sole method for the identification of apoptotic cells are discussed. There are multiple modes of cell death that can be identified at the morphologic level. Thus the central role of microscopic methods, and in particular, electron microscopy, as an important tool in the study of cell death mechanisms, is presented. Apoptosis has a protective role against disease and could, a priori, have an important role in either the initiation or progression of cancer. Two paradoxes concerning the relationship of tumor aggressiveness at the clinical level to mitotic activity have been explained by an evaluation of apoptotic index. In the first case, basal cell carcinomas grow slowly but show a high rate of mitosis. Here, the apoptotic rate is quite high, but just below the mitotic rate, thereby accounting for the slow rate of growth. A second instance is follicular lymphoma, which has a low rate of mitosis that is less than that described for reactive germinal centers. However, apoptosis is markedly reduced in follicular lymphomas compared with that seen in reactive germinal centers, thus providing an explanation for the progressive growth of the follicle. We present a brief description of recent work from our laboratory that indicates that apoptosis may play an important role in colon carcinogenesis. We have shown that sodium deoxycholate, the particular bile salt present in highest concentration in the colon, induces apoptosis in the goblet cells of the human colonic mucosa in an in vitro assay. The intriguing finding is that cells of the normal-appearing mucosa of colon cancer patients are resistant to bile salt-induced apoptosis. This suggests a novel hypothesis about the etiologic role of bile salts in colon cancer. The chronic presence of bile salts that accompany a high-fat diet could select for apoptosis-resistant epithelial cells in the colon over time. Thus, a resistance-to-apoptosis bioassay may prove useful as an intermediate biomarker for determining which individuals are at high risk for colon cancer.
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PMID:Role of apoptosis in biology and pathology: resistance to apoptosis in colon carcinogenesis. 757 Oct 81

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of galectin-3 during the interactions between cells and laminin is not yet known, it has recently been observed that its expression is down-regulated at both the protein and the mRNA level in colon cancer tissues in correlation with progression of the disease. This study investigated the possibility that breast cancer cells might also exhibit decreased galectin-3 expression in association with their aggressiveness. The expression of galectin-3 was examined by immunoperoxidase staining, using a polyclonal antibody raised against recombinant galectin-3, in a collection of 98 human breast lesions including 12 fibroadenomas, 15 fibrocystic disease lesions, 22 in situ carcinomas, and 49 infiltrating ductal carcinomas, 19 of which had positive axillary lymph nodes. Normal breast tissue adjacent to the lesions was present in 59 biopsies. Normal breast tissue expressed high levels (3+) of galectin-3. High expression (2+ to 3+) was also found in most benign lesions examined. The expression of galectin-3 was significantly decreased in in situ carcinoma and this down-regulation was more pronounced in invasive ductal carcinoma, particularly when associated with infiltration of axillary lymph nodes. These data constitute the first observation that galectin-3 is down-regulated in breast cancer and suggest the decreased expression of this galactoside-binding lectin is associated with the acquisition of the invasive and metastatic phenotype.
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PMID:Decreased expression of galectin-3 is associated with progression of human breast cancer. 869 44

The expression of HLA class I antigens was studied by immunohistochemistry in various tumors in correlation with clinicopathologic characteristics. Reduced expression was observed in germ cell testicular cancer, kidney, prostate, gastric and colon cancer, and was associated with tumor aggressiveness, grade and penetration of the tumor through the organ wall. In bladder cancer reduced expression was associated with poor survival. Irradiation of brain tumors resulted in an increase in class I expression. Soluble class I levels were studied in breast and colon cancer patients and were found to be high in those with metastatic disease. The clinical relevance of reduced class I levels are discussed.
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PMID:HLA class I antigen expression in human solid tumors. 900 63

A transforming growth factor beta1 (TGF beta1) antisense expression plasmid under constitutive control of the Rous sarcoma virus promoter was introduced into the highly tumorigenic and invasive colon carcinoma U9A cell line, which uses its autocrine TGF beta1 as a growth-stimulating factor. Stable transfectants were infrequent, and only the K6 transfectant exhibited 39 and 33%, respectively, of the levels of TGF beta1 mRNA and active, secreted TGF beta1 protein of the parental line. K6 exhibited no change in TGF beta2 expression, and TGF beta3 expression was not detected in either parental or transfectant cells. Compared to the parental line, the K6 antisense transfectant exhibited a 3-fold increase in lag time in anchorage-dependent colony formation. The parental line was 44 times as invasive through a collagen l-coated polycarbonate membrane in vitro as K6 cells and, after s.c. injection at low-cell inocula, U9A cells induced tumors 75 times as large in vivo as did the K6 antisense transfectant. The decreases in in vitro invasion and anchorage-dependent colony formation seen in K6 cells were largely reversed by the addition of TGF beta1. Tumors that did arise from the K6 antisense transfectant cells had lost antisense TGF beta1 expression and expressed the same TGF beta1 mRNA levels as controls. U9A cells were more metastatic to the liver after intrasplenic injection than K6 cells. These findings demonstrate a role for autocrine TGE beta1 in colon cancer tumorigenicity and invasion. They also show that a relatively small decrease in TGF beta1 levels was enough to markedly decrease colon carcinoma cell aggressiveness. This is not unprecedented, as we had found in an earlier study that a small, 2-4-fold increase in TGF beta1 protein levels in human colon cancers correlated with disease progression to metastases (E. Friedman et al., Cancer Epidemiol, Biomarkers & Prev., 4:549-554, 1995).
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PMID:Transforming growth factor beta 1 (TGF beta 1) is an autocrine positive regulator of colon carcinoma U9 cells in vivo as shown by transfection of a TGF beta 1 antisense expression plasmid. 901 69

Black patients with colon cancer in the Black/White Cancer Survival Study were found to have a poorer survival than white patients. More advanced-stage disease at diagnosis was the primary determinant, accounting for 60% of the excess mortality. After adjusting for stage, factors such as poverty, other socioeconomic conditions, and treatment did not further explain the remaining survival deficit. This study examined the aggressiveness of colon tumors in blacks and whites to explore its role in the racial survival differences. Tumor characteristics of 703 cases of newly diagnosed invasive colon adenocarcinoma were centrally evaluated by a gastrointestinal pathologist, blinded in regard to the age, race, and sex of the patients. Blacks were less likely to have poorly differentiated (grade 3) tumors [odds ratio (OR), 0.44; 95% confidence interval, 0.22-0.88] and lymphoid reaction (OR, 0.49; 95% confidence interval, 0.26-0.90) when compared with whites. These black/white (B/W) differences remained statistically significant after adjusting for age, sex, metropolitan area, summary stage, socioeconomic status, body mass index, and health care access and utilization. In addition, blacks were less likely to have high-grade (grade 3) nuclear atypia, mitotic activity, and tubule formation, although these ORs did not reach a statistical significance level of 0.05. Similar B/W differences were observed for patients with advanced disease but not with early stage. Comparison by anatomical subsite showed that blacks had statistically significantly better differentiated tumors for cancers of the proximal and transverse colon but not for the distal. No racial differences were found for blood vessel and lymphatic invasion, necrosis, fibrosis, and mucinous type of histology. The findings, therefore, are the opposite of those hypothesized. After adjusting for stage, more aggressive tumor characteristics do not explain the adverse survival differential in blacks. This suggests that there may be racial differences in environmental exposure, and that the intensity and mode of delivery of carcinogen insult as well as host susceptibility may differ by race and anatomical subsite. Future studies should explore the B/W differences in tumor biology using molecular markers that precede the conventional histological parameters evaluated here.
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PMID:Aggressiveness of colon carcinoma in blacks and whites. National Cancer Institute Black/White Cancer Survival Study Group. 941 8

Port-site metastasis has been an unexpected finding after laparoscopic surgery in gastrointestinal cancer patients. No clear explanation exists for this phenomenom. The aims of this study were to evaluate the dissemination pattern in an experimental model of hepatocarcinoma in the rat and summarize current knowledge about the risks and the results of experimental studies on cancer dissemination during laparoscopic surgery. NDA-induced hepatocarcinoma was obtained in Sprague-Dawley rats. Tumors were manipulated during laparoscopy (group 1, n = 11) or laparotomy (group 2, n = 12). A Medline review of all experimental studies about the risk of cancer dissemination during laparoscopic surgery was undertaken. Both models were associated with implants in parietal wounds [1/11 in group 1 (9%) vs. 1/12 in group 2 (8%), p = NS]. Analysis of the current literature confirms that laparoscopy is associated with abdominal cell mobilization, and cells can be recovered in trocars, filtered exhaust gas, and instruments. Postoperative immunosuppression, the biologic aggressiveness of the tumor, and the gas used for laparoscopy also influence tumoral growth. Port-site metastases are secondary to multiple factors, including the technical skill of the surgeon, the biologic properties of the tumors, and local environmental aspects. Undoubtedly, laparoscopy can help disseminate aggressive tumors and should be reserved for diagnostic and staging procedures or for treatment of low-grade malignant tumors. Therapeutic resection, especially of colon cancer, should be restricted to prospective and randomized trials until there are enough hard data to rule out the clinical importance of this potentially severe complication.
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PMID:Cancer dissemination during laparoscopic surgery: tubes, gas, and cells. 1107 77


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