UMLS:C0699790 - FACTA Search

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

Although the thymidine analogues 5-bromo-2'-deoxyuridine (BrdUrd) and 5-iodo-2'-deoxyuridine (IdUrd) have been used successfully as radiation sensitizers in clinical trials, it is not clear which of these agents is the more promising to pursue. To begin to assess this question with regard to colorectal cancer metastatic to the liver, a study was carried out using HT29 human colon cancer cells in culture and implanted in nude mice as xenografts. Cells and animals were treated with BrdUrd +/- the thymidylate synthase inhibitor 5-fluoro-2'-deoxyuridine (FdUrd), and the results compared to our previous studies with IdUrd +/- FdUrd (T. S. Lawrence, M. A. Davis, P. E. McKeever, J. Maybaum, P. L. Stetson, D. P. Normolle, and W. D. Ensminger. Cancer Res., 51: 3900-3905, 1991). Using cultured cells, it was found that FdUrd (at concentrations of greater than 10 nM) increased: (a) the incorporation of BrdUrd into the DNA of cultured tumor cells; (b) BrdUrd-mediated radiosensitization; (c) BrdUrd-mediated increase in radiation-induced DNA damage; and (d) BrdUrd-mediated decrease in the repair of radiation-induced damage. The incorporation of BrdUrd was greater than or equal to the incorporation of IdUrd previously determined under the same exposure conditions. Studies using nude mice bearing HT29 xenografts showed that FdUrd increased BrdUrd incorporation more into tumors than into the normal liver. Most tumor cells incorporated BrdUrd (labeling index after a 4-day infusion = 87 +/- 2%; SE); in the liver, labeling was confined chiefly to nonparenchymal cells. In both the presence and absence of FdUrd, the incorporation of BrdUrd into tumors was significantly and consistently greater than the incorporation of IdUrd measured under the same conditions of drug administration (by a factor of 1.2-3.6). Furthermore, the administration of BrdUrd +/- FdUrd tended to produce less weight loss and hematological toxicity than IdUrd +/- FdUrd. These findings suggest that BrdUrd may be superior to IdUrd as a radiation sensitizer in the treatment of colorectal cancer metastatic to the liver.
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PMID:The potential superiority of bromodeoxyuridine to iododeoxyuridine as a radiation sensitizer in the treatment of colorectal cancer. 161 42

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common form of hereditary colon cancer. Autosomal dominant inheritance is evident from pedigrees but the genetic basis of the disorder is otherwise unknown. Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and APC was shown to be the gene predisposing to familial adenomatous polyposis. To determine if these genes also confer susceptibility to HNPCC we performed linkage analyses in nine affected families. The MCC-APC region could be formally excluded as the locus for HNPCC in seven families. In one family the results were suggestive of exclusion, although they were not conclusive. The remaining family was uninformative. We used two alternative definitions of affected status. Based on haplotypes for MCC and APC the added pairwise logarithm-of-odds score for all nine families was -22.57 at the recombination fraction of 0.00 using more stringent criteria for the HNPCC phenotype and -22.67 for less stringent criteria. In addition to blood DNA samples from living family members, DNA from formaldehyde-fixed archival pathology specimens from decreased individuals contributed to these linkage results.
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PMID:Evidence that the MCC-APC gene region in 5q21 is not the site for susceptibility to hereditary nonpolyposis colorectal carcinoma. 164 45

The effects of unsaturated fat and fiber (cellulose) on the growth of human colon cancer explanted to athymic nude mice was evaluated. Eighty-seven male nude mice bearing xenografts of human HT29 or WiDr colon cancer were divided into three groups of equal weight and tumor volume. Each group was fed one of three diets: normal fat/no fiber (N/N), high fat/no fiber (H/N) or high fat/high fiber (H/H). To equalize caloric intake, animals in the H/N group received 4 g of food per day and the other animals were fed 5 g of food per day. At sacrifice tumor volume and weight was recorded, and tumors were analyzed for protein and DNA content and ornithine decarboxylase activity. Tumor volume, weight, and protein were greater in the H/N group compared to the N/N group for both colon cancer cell lines. Tumor DNA content was greater in the HT29 H/N group compared to the N/N group (P less than 0.05) and tumor ornithine decarboxylase activity in the WiDr H/N group was greater than the N/N animals (P less than 0.002). The tumor growth-promoting effects of the high unsaturated fat diet were attenuated by the addition of fiber. Animal weight was higher in the H/N group compared to the N/N and H/H groups. This study suggested that a high-fat diet stimulated and fiber decreased the growth of human colon cancer explanted to athymic nude mice. The growth-promoting effects of a high-fat diet in colorectal cancer may be due in part to a circulating trophic factor since these tumors were remote from the large intestine.
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PMID:Effects of fat and fiber on human colon cancer xenografted to athymic nude mice. 165 57

The effect of somatostatin analogue RC-160 on the growth of DHD/K12 rat colon cancer has been investigated in vivo as well as in vitro. Twenty syngeneic BDIX rats with s.c. implanted tumors were divided randomly into 2 groups. The rats from each group received a daily s.c. injection of either RC-160 (100 micrograms/kg/day) or injection vehicle as control for 37 days starting from the day of tumor inoculation. Tumor volumes were measured every 3-4 days. At the end of the treatment, the mean tumor volume was 504.5 +/- 97.0 mm3 in the control group and 177.8 +/- 60.5 mm3 in the RC-160 treated group (p less than 0.01). The tumor volume doubling time was calculated to be 11 days in the control group and 13.5 days in the RC-160 group, respectively. The tumor growth delay time was 18 days. Using bromodeoxyuridine labelling in vivo, the mean labelling index in the tumors was decreased by 35% (p less than 0.01) after RC-160 treatment. Total protein and total DNA contents in the tumors were decreased by 70.1% (p less than 0.05) and 68.7% (p less than 0.05), respectively. The data indicate that somatostatin analogue RC-160 inhibits the growth of DHD/K12 colon cancer in vivo. In 2 studies in vitro, DHD/K12 cells were cultured for 72 hr with RC-160 and natural somatostatin-14 (S-S-14) at concentrations ranging from 62.5 ng/ml to 2,000 ng/ml. Tumor-cell growth was measured spectrophotometrically by the crystal violet staining assay. No direct effect on tumor cell growth in vitro was observed with either RC-160 or S-S-14, possibly because of the loss of somatostatin receptors in previous passages of the DHD/K12 cell line.
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PMID:Somatostatin analogue RC-160 inhibits the growth of transplanted colon cancer in rats. 167 6

The effectiveness of liposome-encapsulated doxorubicin in overcoming multidrug resistance was studied in various human colon cancer cells. Colon-cancer cell lines SW403, HT29, SW620, and SW620/R overexpressed P-glycoprotein as determined by immunoflow cytometry, thereby confirming the presence of the multidrug-resistant phenotype. Important differences were observed in the cytotoxicity of free doxorubicin as represented by IC50 values of 0.168, 0.058, 0.023, and 9.83 microM for SW403, HT29, SW620, and SW620/R, respectively. Liposomally encapsulated doxorubicin provided an IC50 that was 1.4 times lower than that of the free drug in the doxorubicin-resistant SW 620/R cell line, whereas no difference was evident in the sensitive parental SW620 cells. In addition, liposome-encapsulated doxorubicin exhibited 1.31- and 2.33-fold cytotoxicity to HT-29 and SW403 cells, respectively. The intracellular drug accumulation in SW620/R cells was enhanced by liposomally encapsulated doxorubicin, whereas it was reduced in all other cell lines as compared with that of free drug. The colon-cancer cell lines demonstrated different degrees of doxorubicin-induced DNA strand breakage that correlated with their sensitivities to drug-induced cytotoxicity. However, no difference was observed between DNA breakage caused by the free drug and that induced by liposome-encapsulated doxorubicin in any of the cell lines. The results suggest that the enhanced cytotoxicity of liposomal doxorubicin to colon cancer cells was due to some secondary non-DNA target. However, liposomally encapsulated doxorubicin appears to be effective in diminishing the multidrug-resistant phenotype and may have clinical applications.
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PMID:Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes. 167 95

The serum-free medium conditioned by the human colon cancer cell line HT-29 contains insulin-like growth factors (IGF) that are entirely complexed to binding proteins (IGF-BP). Gel filtration in acid conditions of the cell-conditioned medium permits separation of IGF-BP from two molecular forms of IGF of 15,000 and 7,500 Mr. As determined by ligand blotting, IGF-BP are heterogeneous and constituted of three molecular forms of 31,000, 28,000, and 26,000 Mr. Using IGF-I and IGF-II radioreceptor assays, IGF-I radioimmunoassay (RIA), and competitive protein-binding assay specific for IGF-II, it is shown that the IGF-type eluting in 15 K and 7.5 K position from gel filtration is restricted to IGF-II. Its concentration is approximately 6 ng/10(6) HT-29 cells with 60% present as a high-molecular-weight form of IGF-II. This large 15 K IGF molecule is devoided of any IGF-binding activity and might represent incomplete processing of pro-IGF-II peptide. By contrast, the level of IGF-I detected by RIA is barely measurable and considered negligible (0.57 pg/10(6) HT-29 cells). Although these IGF-II-like peptides exhibit a growth-promoting activity on FR3T3 fibroblasts, they cannot stimulate, as recombinant IGF-I or IGF-II, 3H-thymidine incorporation into DNA of HT-29 cells, whatever the experimental conditions used. Finally, we have shown that IGF binding is restricted predominantly to the basolateral domain of the cell membrane by using HT-29-D4 clonal cells, derived from the parental HT-29 cell line, maintained in a differentiated state by culture in a medium in which glucose is replaced by galactose.
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PMID:Production of insulin-like growth factor II (IGF-II) and different forms of IGF-binding proteins by HT-29 human colon carcinoma cell line. 169 80

A soluble substance (HT29 factor) produced by HT29 colon cancer cells markedly suppresses mitogen-induced T-cell proliferation and interleukin-2 production. In this study the range of T-cell functions susceptible to the inhibitory effects of the HT29 factor was evaluated. Serum-free conditioned medium was collected from confluent cultures of HT29 cancer cells, concentrated, and subjected to gel filtration chromatography and anion exchange chromatography, resulting in 24.4-fold purification of the HT29 factor with 31% yield. This factor abolished the development of lymphokine-activated killer cells when present during activation of peripheral blood lymphocytes by interleukin-2 but did not affect the lysis of target cells by normal effectors when added in the lysis stage only. The HT29 factor did not affect the generation of concanavalin A-induced suppressor lymphocytes, even though it markedly inhibited synthesis of DNA, RNA, and protein as well as expression of the CD25 (Tac) antigen during mitogen activation of T-cells. The HT29 factor itself did not induce suppressor cells. These results indicate that the immunosuppressive action of the HT29 factor is selective.
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PMID:Selective immunosuppressive action of a factor produced by colon cancer cells. 169 19

The cell cycle of Familial Polyposis Coli (FPC) has been determined by a flow cytometric (FCM) DNA/bromodeoxyuridine (BrdUrd) bivariate analysis. Specimens were obtained from one FPC cancer patient and, for our controls, from 8 single colon cancer patients and from 8 gastric cancer patients who underwent a colectomy. Procedurally, 1 g i.v. injection of BrdUrd was administered 5 to 7 hours before the resection. Later, the BrdUrd-labeling index (BULI) and the potential doubling time (Tpot) were measured by FCM. No significant differences were uncovered between the BULI of the cancer in the FPC patient and that of our controls, or between the BULI of the unaffected mucosa of the FPC patient and that of the controls. Further, with regard to the FPC patient, the mean BULI of the cancer was significantly higher than that of the adenoma and than that of the unaffected mucosa. Also, the mean Tpot of the cancer was significantly shorter than that of the unaffected mucosa. These results suggest that the BULI and the Tpot may change when an adenoma is generated from the unaffected mucosa in FPC patients.
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PMID:[A flow cytometric cell cycle analysis of familial polyposis coli]. 170 Jan 68

A series of Adriamycin-resistant human breast MCF-7 and human colon DLD-1 cancer cell lines were established by stepwise selection. The concentration of Adriamycin required to inhibit cell proliferation by 50% (IC50) in the parent breast line (MCF-7), Adriamycin-resistant lines (MCF-Ad5 and MCF-Ad10), and a 5-fluorouracil (5-FU)-revertant line (MCF-R) was 0.005, 3.3, 6, and 4.9 microM, respectively. The Adriamycin IC50 value for the resistant colon line (DLD-Ad) was 8.2 microM, 68-fold higher than that for its parent line (DLD-1) (IC50 = 0.12 microM). The MCF-Ad5 and MCF-Ad10 cells were cross-resistant to 5-FU, with respective 5-FU IC50 values of 11.7 and 22.5 microM, or 7.3- and 14-fold less sensitive than their parent MCF-7 (IC50 = 1.6 microM) line. The MCF-R line completely reverted in sensitivity to 5-FU, with an IC50 of 1.7 microM. The resistant DLD-Ad line was 3.5-fold more resistant to 5-FU than was the parent DLD-1 line. Using both the 5-fluoro-2'-deoxyuridine-5'-monophosphate binding and catalytic assays for measurement of thymidylate synthase (TS) activity, there was significantly increased TS activity in the resistant MCF-Ad5 (2.4- and 2.5-fold), MCF-Ad10 (11.5- and 6.8-fold), and DLD-Ad (4.8- and 10.7-fold) lines, for binding and catalytic assays, respectively, compared with their parent MCF-7 and DLD-1 lines. The level of TS in cytosolic extracts, as determined by Western immunoblot analysis, was markedly increased for the resistant MCF-Ad5 (31-fold), MCF-Ad10 (46-fold), and DLD-Ad (52-fold) cells. Measurement of TS mRNA levels by Northern analysis revealed elevation of TS mRNA in the resistant MCF-AD5 (16.7-fold), MCF-Ad10 (31-fold), and DLD-Ad (55-fold) cells. Southern analysis showed that this increase in TS mRNA was not accompanied by any major rearrangements or amplification of the TS gene. Incorporation of 5-FU into the RNA and DNA of the resistant MCF-Ad10 cells was not significantly different, compared with that for parent MCF-7 cells. These studies suggest that exposure of human breast and human colon cancer cells to Adriamycin leads to overexpression of TS, with concomitant development of resistance to 5-FU.
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PMID:Induction of thymidylate synthase associated with multidrug resistance in human breast and colon cancer cell lines. 170 99

We have previously reported that the connective tissue stroma of human colon carcinoma contains elevated amounts of decorin, a small proteoglycan involved in the regulation of matrix formation and cell proliferation. These biochemical changes were correlated with increased mRNA levels and general hypomethylation of the decorin gene in human colon cancer DNA. In this report we use a quantitative polymerase chain reaction method coupled with digestion of the DNA template by methylation-sensitive restriction endonucleases to investigate in detail the location of hypomethylated sites in decorin gene. We demonstrate that a specific site in the 3' region of the gene, encompassing codons 360-361, is specifically hypomethylated in both colon carcinoma and benign polyp. In contrast, three HpaII sites, clustered in the 5' untranslated region, show full methylation in normal and neoplastic DNA. The lack of such changes in ulcerative colitis DNA suggests that chronic inflammation alone is not sufficient to alter cytosine methylation in the decorin gene. These results suggest the possibility that the 3' region of the decorin-coding sequence may be involved in the control of decorin gene expression.
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PMID:Hypomethylation of the decorin proteoglycan gene in human colon cancer. 171 Aug 88

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