Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human gamma-interferon (IFN-gamma) has recently been shown to enhance localization of radiolabeled monoclonal antibodies (MAb) to human colon carcinoma xenografts in athymic mice. The present study investigates the ability of gamma-interferon to enhance radioimmunotherapy of a low carcinoembryonic antigen-expressing human colon cancer (WiDr) in athymic mice. Growth curve analysis, antibody localization, and dose estimation studies were performed. A significant tumor growth delay, measured as the time to reach 1.0 g, was noted for animals receiving specific anti-carcinoembryonic antigen 90Y-MAb (ZCE025, 120 microCi) plus IFN-gamma (61.8 days) as compared to animals that received specific 90Y-MAb with phosphate-buffered saline (34.9 days; P less than 0.005). IFN-gamma (100,000 units) was given i.p. every 8 h for 2 days before and 4 days after 90Y-MAb therapy. The time required to reach 1.0 g for animals treated with nonspecific 90Y-MAb (ZME018) was significantly less either with (38.3 days) or without (34.4 days) IFN-gamma. The difference was more apparent when compared to animals receiving IFN-gamma alone (30.0 days) or phosphate-buffered saline alone (28.9 days; P less than 0.001). Increased antibody localization in the tumors of animals treated with IFN-gamma plus specific 90Y-MAb (43.2% injected dose/g) was seen in comparison to animals treated with specific 90Y-MAb without IFN-gamma (18.2% injected dose/g). The estimate of radiation dose delivered to the tumors, based on biodistribution data over time, revealed significantly higher levels in animals treated with specific 90Y-MAb with IFN-gamma (2477 cGy) compared to animals treated without IFN-gamma (1217 cGy). These results provide support for the use of gamma-interferon as an immunomodulating agent prior to radioimmunotherapy.
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PMID:Interferon enhancement of radioimmunotherapy for colon carcinoma. 190 60

Six established human colon carcinoma cell lines that segregated into three groups with different degrees of differentiation were treated using three subclasses of interferons as single agents and in combination with either 5-fluorouracil, cis-platinum, or adriamycin. The cytotoxicities of the combination treatments were heterogeneous and did not relate to the cell's levels of differentiation. Our data suggest that the optimal combinations of interferons and chemotherapeutic agents are independent of the differentiation state of the colon cancer cells.
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PMID:Heterogeneous effects of interferon on antitumor agents' cytotoxicities to human colon carcinoma cell lines. 190 77

We have synthesized 90Y-labeled immunotoxin (IT) containing ricin A chain and C110 anti-carcinoembryonic antigen monoclonal antibody (MAb) to produce a therapeutic immunoconjugate for human colon cancer. The C110 IT was labeled with 90Y via a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid. The efficiency of 90Y labeling was consistently 90 to 98%, with a specific activity of about 1 microCi/microgram. In in vitro stability studies, more than 80% of 90Y remained bound to the C110 IT for up to 5 days after incubation. The percentage of binding of 90Y-labeled C110 IT to carcinoembryonic antigen-coated microbeads was 86%, indicating good retention of the initial immunoreactivity of the C110 MAb. In in vitro protein synthesis inhibition assays, 90Y-labeled C110 IT was approximately 3.7-fold more toxic to the LS174T human colon carcinoma cell line than unmodified C110 IT and 1380-fold more toxic than 90Y-labeled C110 MAb. Biodistribution studies of 90Y-labeled C110 IT in LS174T tumor-bearing mice showed that, at 24 h following i.p. injection, high accumulation of radioactivity was seen in the i.p. tumor and liver and, thereafter, high accumulation in these tissues remained almost unchanged until up to 168 h, with percentage of injected dose/g ranging from 15 to 18% in the tumor and 10 to 15% in the liver. The radioactivity in the spleen and bone gradually increased with time and reached their highest levels (approximately 8% of injected dose/g) at 168 h. Estimation of absorbed radiation doses to the tissues showed that i.p. tumor would have received an approximately 1.5 to 7 times higher radiation dose than normal organs. In in vivo therapeutic trials, 90Y-labeled C110 IT provided survival prolongation of LS174T tumor-bearing mice superior to that with either unmodified C110 IT or 90Y-labeled C110 MAb (4 less than 0.01; Mann-Whitney U test). These results indicate that 90Y-labeled C110 anti-carcinoembryonic antigen IT may be a potent therapeutic immunoconjugate for human colon cancer and that it may have direct relevance for i.p. treatment of peritoneal carcinomatosis from colon cancers.
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PMID:Preclinical assessments of 90Y-labeled C110 anti-carcinoembryonic antigen immunotoxin: a therapeutic immunoconjugate for human colon cancer. 198 87

Patients with mucinous colorectal cancers characteristically present with advanced disease, however, the relationship between mucin production by colon cancer cells and their metastatic potential remains unclear. We therefore sought to define the relationship between mucin production by human colon cancer cells and metastatic ability by employing animal models of colon cancer metastasis. LS LiM 6, a colon carcinoma cell line with high liver metastasizing ability during cecal growth in nude mice produced twofold more metabolically labeled intracellular mucin and secreted four- to fivefold more mucin into the culture medium compared to poorly metastatic parental line LS174T. This was accompanied by a similar elevation in poly(A)+ RNA detected by blot hybridization with a human intestinal mucin cDNA probe, and increases in mucin core carbohydrate antigens determined immunohistochemically. Variants of LS174T selected for high (HM 7) or low (LM 12) mucin synthesizing capacity also yielded metastases after cecal growth and colonized the liver after splenic-portal injection in proportion to their ability to produce mucin. Inhibition of mucin glycosylation by the arylglycoside benzyl-alpha-N-acetyl-galactosamine greatly reduced liver colonization after splenic-portal injection of the tumor cells. These data suggest that mucin production by human colon cancer cells correlates with their metastatic potential and affects their ability to colonize the liver in experimental model systems.
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PMID:Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis. 199 84

The tumoricidal properties of an anti-human colon carcinoma monoclonal antibody (MAb), designated D612 (IgG2a), alone and in combination with IL-2-activated human lymphocytes were investigated in athymic mice bearing LS-174T colon tumor xenografts. Treatment of mice bearing LS-174T tumors (1 day, s.c.) with a single i.v. dose of 400 micrograms of D612 alone resulted in a significant inhibition of tumor growth. Lower doses of D612 had an intermediate effect on tumor growth. Similar inhibition of tumor growth was obtained when D612 was administered in three doses of 400 or 800 micrograms each during the first week after tumor implantation. Mouse macrophages but not splenocytes mediated antibody-dependent cellular cytotoxicity with D612, suggesting that tumor inhibition was due to the participation of host macrophages with D612. Human lymphokine-activated killer (LAK) cells were generated by incubating human peripheral blood mononuclear cells (PBLs) from normal donors with 100 U/ml of IL-2 for 24 h. An administration of human LAK cells did not significantly inhibit the growth of the human xenograft tumor. Adoptive transfer of a single dose of human LAK cells (2 x 10(7), i.v.) into mice treated with a suboptimal dose of D612 (200 micrograms) significantly inhibited tumor growth compared to that obtained with either D612 or LAK cells alone. Similar results were obtained with three doses of D612 plus human LAK cells although there was a tendency for multiple doses of LAK cells alone to show some antitumor effects. LAK cells or PBLs had similar antitumor activities when used in conjunction with D612. When larger established tumors were treated, single or multiple doses of D612 or LAK cells alone were without effect; however, LAK cells plus D612 elicited significant growth inhibition. These results demonstrate that the tumoricidal properties of LAK cells and the D612 MAb can be augmented when used together in the immunotherapy of human colon cancer xenografts.
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PMID:Human lymphokine-activated killer cells augment immunotherapy of human colon carcinoma xenografts with monoclonal antibody D612. 201 97

The biokinetics of seven 131I-labelled monoclonal antibodies (MAbs), directed against human colon carcinoma and one 125I-labelled unspecific MAb have been examined. The study in nude mice, carrying human colon carcinoma, was intended to be a step in the selection of the most suitable antibody for clinical scintigraphy. The biological half-life in blood was found to be between 1.3 and 7.4 days for the different MAbs. Chromatography of plasma samples showed that the radioiodine was mainly bound to IgG-sized molecules. The (normal tissue)/blood ratios were similar for all the MAbs. The tumour/blood ratio was 0.41 for the unspecific MAb and 0.49-1.1 for the specific MAbs, and the tumour/muscle ratio was between 3.2 and 6.8 for the specific MAbs 6 days after injection. For one MAb tumour/blood and tumour/muscle ratios were 3.9 and 9.8 respectively 9 days after injection. Localization indices were at their highest 2.6 6 days after injection. For at least two of the monoclonal antibodies the tumour/blood and tumour/muscle ratios found are high enough to justify clinical trials regarding their usefulness for scintigraphy of colon cancer in man.
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PMID:Comparison of seven iodine-labelled monoclonal antibodies in nude mice with human colon carcinoma xenografts. 203 51

Over recent years, the interest in the development of experimental models of colorectal liver metastases has increased due to the need for new adjuvant therapies to improve the treatment of both colorectal cancer and liver metastases. The induction of colon cancer by carcinogens in the rat with spontaneous liver metastases fairly closely mimicks the natural history of colon cancer but a low yield of both colonic cancer (less than 50%) and liver metastases (approx. 25%) is obtained after 6 months of latency. Direct intraportal injection of cells derived from a colon carcinoma cell line is the experimental model most often used. Although it bypasses the natural history of cancer this simple model produces up to 100% of liver metastases 6 weeks after injection of cells. These two models have been used for several studies of liver metastases concerning their morphology, their modulating factors and their vascularisation. They have been used to test new adjuvant therapies for colorectal cancer.
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PMID:[Experimental models for hepatic metastases from colorectal tumors]. 204 14

An experimental model is proposed to study suture line recurrence. By giving enemas with K12 colon carcinoma cells, derived from a 1,2-dimethylhydrazine-induced colon cancer in male syngeneic BDIX rats, we were able to obtain a suture implantation in about 30% of the control animals. Possible systemic and local factors which might influence this implantation rate could be studied using this model. Only local irrigations of the colon lumen with sodium hypochlorite 0.2% prior to anastomosis produced a significant decrease in implantation rate. Irrigations with chlorhexidine-cetrimide 2.5%, the use of iodized suture material and altering the cellular immune system of the hosts by ciclosporin or excessive surgical stress, had no significant effect on the implantation rate.
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PMID:Factors influencing the implantation of colon cancer cells on the colonic suture line in rats. 207 96

We describe a patient in whom Hodgkin's disease affecting the mesenteric lymph nodes was discovered incidentally at laparotomy for carcinoma of the colon. The occurrence of Hodgkin's disease and colon carcinoma in the same patient is rare, as is Hodgkin's disease in the mesenteric lymph nodes. In cases in which Hodgkin's disease is discovered incidentally at laparotomy, staging is usually done by using computerized tomography and lymphangiographic studies.
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PMID:Hodgkin's disease in the mesenteric lymph nodes in a patient with colon carcinoma. 207 55

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


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