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

A 3 x 3 factorial experiment was conducted to examine how dietary fiber (wheat bran) and fat (lard) interactively affect the genesis of N-methyl-N'-nitro-N-nitrosoguanidine-induced colon cancer in rats. Groups of 30 male 4-week-old Wistar rats were fed ad libitum one of nine experimental diets containing either 15 (low), 27.5 (medium), or 40% (high) energy as fat in combination with 0.7 (low), 2.2 (medium), or 3.8 g (high) fiber/100 kcal for a period of 37 weeks. After 4 weeks, each rat received a total of five weekly intrarectal instillations of 6 mg N-methyl-N'-nitro-N-nitrosoguanidine/kg. The highest colon carcinoma incidence and the highest total number of carcinomas of the colon were observed in the animals fed the medium-fat/medium-fiber diet. The highest number of polyps and a relatively high polyp incidence occurred in the animals on the high-fat/low-fiber diet. An enhancing effect of fat on both the tumor incidence and tumor multiplicity was clearly present for the low-fiber diets, whereas fat had no effect when the fiber content of the diet was high. In general, the results showed a nonlinear dose-response relationship for fiber and fat. These results indicate that both dietary fiber and fat affect colon carcinogenesis in a complex, interactive manner.
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PMID:Interactive effects of dietary wheat bran and lard on N-methyl-N'-nitro-N-nitrosoguanidine-induced colon carcinogenesis in rats. 215 49

The connective tissue stroma of malignant tumors is a newly formed tissue that supports the growth and progression of neoplastic cells. Proteoglycans are intrinsic components of this complex structure and molecular changes in this class of macromolecules can significantly affect behavioral properties of transformed cells. We report that human colon carcinoma contained increased levels of a chondroitin sulfate proteoglycan that exhibited an altered glycosaminoglycan structure in which 0- and 6-sulfated units, as detected by specific monoclonal antibodies, predominated. Proteoglycans with such epitopes were localized primarily to the connective tissue stroma surrounding the tumor cells but not to the tumor cells themselves or the native, non-cancerous connective tissue. Analysis of mRNA encoding PG-40, the main chondroitin sulfate proteoglycan of colon tissue, revealed a 7-fold increase in the two transcripts encoding this gene product. This increase was evident whether the data were normalized to total RNA content or beta-actin mRNA levels. The altered steady state levels of PG-40 mRNA did not correlate with any significant gene amplification or rearrangement of PG-40 in human colon cancer. However, when genomic DNA was tested for degree of methylation, the colon carcinoma tissue showed a marked hypomethylation of PG-40 gene locus, a finding that has been associated with increased gene activation. Interestingly, PG-40 gene was also hypomethylated in cultured colon fibroblasts, which express PG-40, but not in colon carcinoma cells which do not express this gene. These results indicate that specific proteoglycan changes occur in colon carcinoma and that these alterations are the product of stromal cells that are topologically associated with and functionally respondent to the growing malignant cells. This is the first evidence that enhanced PG-40 expression in a human malignant tissue is associated with a hypomethylated gene and suggests that the control of PG-40 gene expression may represent an important factor in the progression of colon carcinoma.
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PMID:Altered expression of chondroitin sulfate proteoglycan in the stroma of human colon carcinoma. Hypomethylation of PG-40 gene correlates with increased PG-40 content and mRNA levels. 216 45

Mutations in the first exon of the c-Ki-ras protooncogene were analyzed in carcinomas and dysplasias from patients with sporadic colon cancer and chronic ulcerative colitis by a combination of histological enrichment, cell sorting, polymerase catalyzed chain reaction, and direct sequencing. In contrast to sporadic colon carcinomas, where 52% (11 of 21) contained mutations in codon 12, only 1 of 28 samples of ulcerative colitis associated carcinoma or dysplasia contained a c-Ki-ras mutation, despite the presence of aneuploid cell populations. These results suggest that a different genetic pathway for tumor progression may exist between sporadic colon carcinoma and carcinomas arising in chronic ulcerative colitis.
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PMID:c-Ki-ras mutations in chronic ulcerative colitis and sporadic colon carcinoma. 219 96

Total, free, and acetylated polyamine concentrations were measured simultaneously in colon tissue, serum, and urine of 50 patients with histologically proven colorectal cancer, 40 patients with nonmalignant gastrointestinal diseases, and 30 healthy volunteers. Compared with histologically unaffected colon tissue, concentrations were significantly (P less than 0.001) higher for putrescine, elevated for cadaverine, and nearly identical for spermidine and spermine in colon carcinoma, whereas N1-acetylated and N8-acetylated spermidine were detectable in cancer tissue only. Serum and urine concentrations of all polyamines except total cadaverine and spermine in serum and free spermine in urine were significantly elevated compared with healthy controls and highest sensitivity for colon cancer was found for total spermidine (89.15%) in serum and acetylputrescine (84.5%), total putrescine (84.0%), N1-acetylspermidine (79.3%), and total spermidine (92.1%) in urine. However, nonmalignant gastrointestinal diseases partly showed similar elevations which resulted in a low specificity for polyamines in colorectal cancer. Therefore, polyamines are of little value only as diagnostic markers in colorectal carcinoma. Since polyamine concentrations in serum and urine normalized in patients after curative operation while they were further elevated in patients with proven tumor relapse or metastases, these substances might play a clinical role in predicting therapeutic success or indicating relapse of the tumor. Although a significant dependency of polyamine concentrations in serum or urine to Dukes' classification, tumor localization, CEA, CA 19-9, or CA 125 did not exist, a significant linear correlation was found for tumor size.
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PMID:Polyamines in colorectal cancer. Evaluation of polyamine concentrations in the colon tissue, serum, and urine of 50 patients with colorectal cancer. 229 64

Intrasplenic injection of the HT-29 LMM metastatic human colon cancer line reproducibly results in hepatic metastasis formation in congenitally athymic mice. HT-29-15, a murine monoclonal antibody (mAb) of the IgG1 class reactive with the HT-29 LMM line, and BL-3, an isotype-matched control antibody, were labeled with 125I. Labeled mAbs were injected i.v. in mice with hepatic metastases, and animals were sacrificed on days 3, 5, and 7. Specific mAb uptake by tumor was significantly greater than nonspecific mAb uptake, as evidenced by specific/nonspecific tumor/blood ratios (radiolocalization indices) of 3.47/1-25.6/1. Relative mAb uptake was greater by the hepatic tumors than by the splenic tumors from day 3 to day 7, although this was significant (P less than 0.05) only on day 7 (5.12 +/- 2.97 versus 1.79 +/- 0.71). Tumor/uninvolved tissue ratios were also significantly greater (P less than 0.05) for the hepatic metastases than for the splenic tumors on day 7 (12.23 +/- 3.85 versus 6.63 +/- 2.63). This murine hepatic metastasis model appears useful for evaluation of localization of mAbs to hepatic metastases from human colon carcinoma.
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PMID:Radiolocalization of monoclonal antibodies in hepatic metastases from human colon cancer in congenitally athymic mice. 229 35

Methods of single-tracer whole-body autoradiography (WBAR) have been developed in our laboratory which allow imaging and measurement of the zonal distribution of radioiodinated antibodies and their fragments within GW-39 colon carcinoma xenografts varying in size from large, cystic masses with necrotic cores to micrometastases. The whole-animal distribution of 90Y-labeled anti-carcinoembryonic antigen monoclonal antibody NP-2 was evaluated by WBAR in nude mice bearing s.c. implants of GW-39 colon cancer and revealed antitumor uptake specifically as well as significant accumulation of 90Y in the bones. Dual-tracer qualitative WBAR methods have also been applied in order to examine the biodistribution of labeled immunoglobulins in the GW-39 animal tumor model as a function of the underlying rapid cell proliferation index ([3H]-thymidine assay) in the same tumor. In addition, extension of the WBAR method was made to permit imaging of the biodistribution of 10B compounds in mice bearing Harding-Passey melanoma implants by using a track-etch procedure to produce alpha-particle WBAR. Further applications of single and multiple radionuclide WBAR are offered and discussed as an effective means of assessing the degree of penetration of immunoglobulins in tumors in which vascular patterns, local glucose metabolism, protein synthesis, and rapid cell proliferation indices may be characterized.
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PMID:Use of whole-body autoradiography in cancer targeting with radiolabeled antibodies. 229 39

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2). Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P less than 0.0001). The overall death rate was reduced by 33 percent (P approximately 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone--i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia. These reactions were usually not severe and did not greatly impede patients' compliance with their regimen. We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for Stage C colon carcinoma. Since most patients in our study were treated by community oncologists, this approach should be readily adaptable to conventional medical practice.
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PMID:Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. 236 11

Two independent multidrug-resistant (MDR) sublines, AdR1.2 and SRA1.2, were developed from the established human colon carcinoma cell line LoVo. AdR1.2 was developed by a long-term continuous exposure of LoVo cells to Adriamycin in stepwise increments of concentration; SRA1.2 was selected/induced by pulse treatments by using a single concentration of Adriamycin. The two resistant sublines were cross-resistant and cross-sensitive to a similar spectrum of cytotoxic agents. However, AdR1.2 was most resistant to Adriamycin among the nine agents tested, and SRA1.2 was most resistant to Vinca alkaloids. Although SRA1.2 had biological characteristics similar to those of LoVo, AdR1.2 had remarkably altered biological properties, including no detectable carcinoembryonic antigen secretion, a smaller proportion of proliferating cells and a lower growth rate, lower fraction of cells in S phase, a lower colony-forming ability, and smaller colonies. In addition, the resistant phenotype of AdR1.2 was reversed when the cells were grown in a drug-free medium, whereas SRA1.2 maintained its resistance for at least 10 months under similar conditions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the plasma membrane proteins demonstrated overproduction of an Mr 130,000 protein in both the resistant sublines. The Mr 130,000 protein was not immunoreactive with C219 monoclonal antibody against p170, but the absence of Mr 130,000 protein in an AdR1.2 revertant and the parental LoVo suggests that it is an MDR-related plasma membrane protein. The absence of a 46-kDa cytosolic protein and the presence of a Mr 150,000 plasma membrane protein were found in AdR1.2 but not in SRA1.2. This Mr 150,000 protein immunoreacted with C219. This protein was also present, although in a reduced amount, in an AdR1.2 revertant that retained three times the MDR of LoVo cells and was thus comparable to SRA1.2. The two MDR sublines thus may represent two independent subclones which may serve as two different models for the study of multidrug resistance in human colon cancer.
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PMID:Biological characterization of multidrug-resistant human colon carcinoma sublines induced/selected by two methods. 233 17

Autocrine stimulation of the epidermal growth factor receptor (EGF-R), by coexpression of transforming growth factor-alpha (TGF-alpha), causes malignant transformation of some fibroblast cell lines. TGF-alpha and EGF-R are both known to be expressed in colon carcinoma tissue and have been shown coexpressed in colon carcinoma cell lines. TGF-alpha autocrine activation of EGF-R has been suggested as a potential mechanism contributing to abnormal growth control in colon cancer. We now report coexpression of TGF-alpha and EGF-R transcripts in morphologically normal colonic epithelium from five individuals, in colonic adenomas from three individuals, and in a nontumorigenic colon adenoma cell line, VACO-330. Functional studies demonstrate VACO-330 growth is stimulated by exogenous TGF-alpha and is completely abolished by a blocking anti-EGF-R antibody. Autocrine stimulation of EGF-R by TGF-alpha is therefore required for growth of the adenoma cell line. Autocrine stimulation of EGF-R by TGF-alpha does not cause malignant transformation of the colonic epithelial cell. In normal and adenomatous human colon TGF-alpha, via either an autocrine or paracrine mechanism, is likely an important physiologic stimulant of epithelial proliferation.
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PMID:Growth stimulation by coexpression of transforming growth factor-alpha and epidermal growth factor-receptor in normal and adenomatous human colon epithelium. 236 25

The monoclonal antibody A7 (MoAb A7), which belongs to IgG1, was digested with pepsin to yield F(ab')2 fragments. The maximum binding to the human colon cancer cell line, SW1116, was 27% with 125-I labeled whole MoAb A7 and 24% with 125-I labeled F(ab')2 fragments using an in vitro binding assay. The results showed that the binding activity of F(ab')2 to SW1116 was practically the same as that of whole MoAb A7. The preferred localization of the fragments to tumor tissue, compared with normal mouse tissue, was demonstrated in mice carrying SW1116 xenografts. The tumor:blood ratio three days after injection was 2.64:18.5 for whole MoAb A7:F(ab')2, respectively. The tissue:blood ratios for the F(ab')2 fragments showed a value of 18.5 in tumors, whereas its was a value less than 1.0 in normal organs. The tumor accumulation of F(ab')2 fragments was also dependent on the antigenic expression of each tumor among xenografts of colon carcinoma SW1116 and WiDr, and squamous cell carcinoma KB. In kinetic experiments with whole MoAb A7 and its F(ab')2 fragments, whole MoAb A7 was lost, with a half-life of 4 days, in both blood and tumors, whereas F(ab')2 fragments were rapidly lost with a half-life of 1.5 days. These results suggested that the F(ab')2 fragments were cleared from the blood faster than was whole MoAb A7.
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PMID:Monoclonal antibody A7 tumor localization enhancement by its F(ab')2 fragments to colon carcinoma xenografts in nude mice. 237 Jun 92


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