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

The therapy of colorectal cancer may be improved by biologic response modifiers that enhance natural killer (NK) cell and antibody-dependent tumoricidal mechanisms. This study examined the effect of a recently discovered cytokine purified from the supernatant of an Ebstein-Barr virus-transformed B-lymphoblastoid cell line (RPMI-8866), natural killer cell stimulatory factor (NKSF), on NK and antibody-dependent cellular cytotoxicity (ADCC) of human colon adenocarcinoma cell lines. Human peripheral blood lymphocytes were cultured for 24 hr in the presence or absence of NKSF (3.6 pM) or interleukin-2 (1 nM). The cultured lymphocytes were analyzed for lytic potential toward chromium-51-labeled colon carcinoma targets SW 1116, 498 LI, and WC 1. ADCC was measured by incubating chromium-51-labeled SW 1116 or WC 1 targets with the monoclonal antibody CO17-1A, an IgG2a antibody reactive with gastrointestinal cancer-associated cell antigen, or control mouse IgG prior to testing NKSF-treated or control PBL effectors in a 6-hr cytotoxicity assay. NKSF significantly enhanced NK cytolysis of colon carcinoma and NK-resistant lymphoma cell lines, and on a molar basis was approximately 300 times more potent than interleukin-2 in generating NK cytotoxicity. Furthermore, NKSF significantly augmented lymphocyte-mediated ADCC against colon carcinoma targets, and the combination of NKSF with the antibody CO17-1A had an additive effect on lymphocyte tumoricidial capacity. Thus, NKSF may have a potential role in the treatment of colon cancer.
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PMID:Natural killer cell stimulatory factor (NKSF) augments natural killer cell and antibody-dependent tumoricidal response against colon carcinoma cell lines. 167 86

Four human colon cancer cell lines (SW620, LS 180, DLD-I, and HCT-15) and sub-lines isolated in vitro by selection with Adriamycin were studied for reversal of intrinsic and acquired Adriamycin resistance, using buthionine sulfoximine (BSO) to deplete cellular glutathione alone and in combination with the P-glycoprotein antagonist verapamil. GSH levels varied among the parental cell lines but did not increase with resistance. In the parental SW620, DLD-I and HCT-15 and their drug-resistant derivatives, there was no relation between the effect of the glutathione-depleting agent BSO, the mRNA expression of both selenium-dependent glutathione peroxidase (GPx) and glutathione S-transferase pi (GST pi), bulk glutathione S-transferase (GST) activity, and the degree of resistance. However, in LS 180 and its derivative sub-lines, which do not principally rely on P-glycoprotein (Pgp) for Adriamycin resistance, treatment with BSO demonstrated a relatively diminished GSH depletion and enhanced recovery. In comparison with the other acquired cell lines, BSO specifically reversed acquired resistance in the LS 180 Adriamycin-resistant subline (LS 180 Ad150) after short-term drug exposure. Furthermore, the LS 180 Ad150 cells demonstrated an increase in both GPx and GST pi mRNA expression. These observations suggest that glutathione-mediated detoxification of Adriamycin may play a role in the resistance of this sub-line. Verapamil enhanced Adriamycin cytotoxicity 1.2- to 12-fold in the intrinsically resistant cells and as much as 15-fold in cell lines with acquired resistance. Combination of BSO with verapamil resulted in additive, but not synergistic, reversal of resistance. The results underscore the complex nature of Adriamycin resistance, and suggest a role for drug-resistance-modulating agents in the treatment of colon carcinoma.
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PMID:Contribution of glutathione and glutathione-dependent enzymes in the reversal of adriamycin resistance in colon carcinoma cell lines. 168 79

Four human colon cancer cell lines (SW620, LS 180, DLD-I, and HCT-15) and Adriamycin-resistant sub-lines with varying degrees of P-glycoprotein expression were studied to evaluate the reversibility of Adriamycin resistance in human colon cancer. Two groups of cell lines were studied. In the first, including a series of Adriamycin-resistant SW620 and DLD-I sub-lines, and in parental HCT-15 cells, P-glycoprotein has a major role in Adriamycin resistance, as evidenced by a correlation between Adriamycin resistance, expression of the multidrug-resistance gene mdr-I and its product, P-glycoprotein (Pgp), decreased drug accumulation and reversibility by verapamil. In these cell lines, increasing doses of verapamil are required to fully reverse increasing levels of resistance. In the second group, including parental SW620, DLD-I and LS 180 cells and Adriamycin-selected LS 180 sub-lines, P-glycoprotein does not have a major role in Adriamycin resistance. There was correlation between the schedule dependence of Adriamycin cytotoxicity and the role of P-glycoprotein in modulating resistance. In the cell lines in which P-glycoprotein was a major determinant of Adriamycin resistance, the drug exposure (defined as the product of the concentration and the time of treatment) needed to achieve a given percent cell kill was reduced as much as 9-fold when cells were treated for 7 days as compared with 3 hr. By comparison, in cell lines in which P-glycoprotein played a lesser role, the drug exposure necessary to achieve a given percent kill increased under conditions of continuous treatment. In some human colon carcinoma cell lines Pgp appears to play a significant role in resistance to Adriamycin, and this can be overcome by the use of competitive inhibitors of Pgp. The increased sensitivity with continuous treatment observed in cell lines with P-glycoprotein-mediated resistance suggests that administration of drugs by continuous infusion may be valuable in reversing clinical drug resistance mediated predominantly by P-glycoprotein.
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PMID:P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines. 168 80

Tumor targeting by monoclonal antibodies (MAbs) can be enhanced by (a) increasing the percentage of injected dose taken up by the tumor and/or (b) increasing the tumor:nontumor ratios. Several groups have demonstrated that one can increase tumor to nontumor ratios by the use of antibody fragments or the administration of second antibodies. Several other modalities are also possible: (a) the use of recombinant interferons to up-regulate the expression of specific tumor associated antigens such as carcinoembryonic antigen or TAG-72 on the surface of carcinoma cells and thus increase MAb tumor binding has proved successful in both in vitro and in vivo studies; (b) the intracavitary administration of MAbs. Recent studies have demonstrated that when radiolabeled B72.3 is administered i.p. to patients with carcinoma of the peritoneal cavity, it localizes tumor masses with greater efficiency than does concurrent i.v. administered antibody. Studies involving the comparative pharmacology of intracavitary administration of radiolabeled MAb in patients and several animal models will be discussed; (c) it has been reported that prior exposure of hepatoma to external beam radiation will increase radiolabeled MAb tumor targeting. We and others have not been able to duplicate this phenomenon with a human colon cancer xenograft model and radiolabeled MAbs to two different colon carcinoma associated antigens. The possible reasons for these differences will be discussed; (d) the cloning and expression of recombinant MAbs with human constant regions and subsequent size modification constructs will also undoubtedly alter the pharmacology of MAb tumor binding in both diagnostic and therapeutic applications.
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PMID:Innovations that influence the pharmacology of monoclonal antibody guided tumor targeting. 168 34

The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven-week-old BALB/c-nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous-cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5-Fluoro-uracil (5-FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5-FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5-125I-Iodo-2'deoxyuridine, and of Ki-67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium-induced prolongation of tumor-cell cycle times and a reduction of the growth fraction.
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PMID:Heavy water enhances the antineoplastic effect of 5-fluoro-uracil and bleomycin in nude mice bearing human carcinoma. 168 3

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

From 1977 to 1984, 56 patients with colon cancer adherent to other organs were operated upon. Twenty-three (41 percent) underwent palliative treatment without resection. The mean survival in this group was 6 months. The results of en bloc resection were evaluated in 33 patients (59 percent) with colon carcinoma and tumor growth in adjacent organs. Pathologic staging was based on Dukes' (Astler and Coller) classification. Dukes' B carcinoma was shown in 15 patients. Dukes' C in 14 patients, and Dukes' D in four patients. The 4-year survival rate was as follows: Dukes' B, 47 percent; Dukes' C, 29 percent; and Dukes' D, 0 percent. The 4-year survival rate for the whole group was 33 percent. The postoperative morbidity and mortality were 6 percent and 3 percent, respectively. Colon cancer with involvement of adjacent structures should not be regarded as an incurable Dukes' D carcinoma; en bloc resection is indicated and can be performed with acceptable morbidity and mortality.
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PMID:En bloc resection of colon carcinoma adherent to other organs: an efficacious treatment? 171 11

Between 1978 and 1983 we performed 19 ureterosigmoidostomies (25% of all urinary diversions). We try to realise a reevaluation of this technique by means of clinical data, laboratory findings, U.S.- and X-ray examinations. The mean follow-up time is 7.5 years. All patients mention a comfortable life-style. By routine administration of sodium bicarbonate, no electrolyte disturbances occur. Only 5 kidneys (on a total of 32 renal units) show major deformities. Colon carcinoma is not reported. Since the introduction of the ileal conduit by Bricker in 1950 (1), together with the repeatedly published higher incidence of colon carcinoma (2), a certain revulsion for the traditional Coffey-technique arose. Yet there are some important advantages in this peculiar surgical method. We think that, after a rather premature condemnation, the time is ripe for a reevaluation and a reevaluation of the ureterosigmoidostomy.
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PMID:Ureterosigmoidostomy: reevaluation of a "forgotten" continent urinary diversion. 181 95

It has been proposed that among the various cell-surface proteins capable of interacting with laminin, the 67-kd high-affinity laminin receptor plays a crucial role during tumor invasion and metastasis. In this study, the expression of laminin-receptor-precursor messenger RNA (mRNA) and 67-kd protein was analyzed in human colon adenocarcinoma. In 22 of 23 patients with colon cancer, we found a 2- to 23-fold increase in levels of laminin-receptor-precursor mRNA in the cancer tissues compared with those in matched normal adjacent colonic mucosa. In 10 of 11 cases studied, the level of 67-kd laminin receptor, detected by affinity-purified anti-laminin-receptor synthetic peptide antibodies on immunoblots of matched tumor and normal tissue extracts, was higher in the colon carcinoma tissue. Immunodetection of laminin receptor in tissue sections using anti-laminin-receptor-peptide antibodies confirmed that the increased expression of laminin receptor was specifically associated with the cancer cells. In a series of 72 paraffin sections of colon lesions, we observed a correlation between the expression of the laminin receptor and the Dukes' classification. Our observations indicate that increased expression of laminin-receptor-precursor mRNA is associated with enhanced levels of the 67-kd laminin receptor as well as with the invasive phenotype of colon carcinoma. Detection of this metastasis-associated gene product may be a valuable adjunct in the evaluation of human colon cancer.
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PMID:Increased expression of the laminin receptor in human colon cancer. 182

A quantitative overview of 14 studies of rat colon carcinogenesis was undertaken to examine the relationship between fat intake, and fat intake by degree of saturation, on the incidence of colon carcinoma while controlling for calorie consumption. Calorie consumption was not recorded in 11 of the 14 studies. Hence, two types of analyses were conducted. The first examines carcinoma incidence as a function of percent fat (by weight), with calories controlled for by including weight gain per week in the analysis. The second estimates calories per day, for studies not providing such information, using weight gain per week and age at death, followed by a joint analysis of estimated fat calories and estimated total calories. With either approach, a rather strong positive relationship between colon carcinoma incidence and fat intake is indicated for Fischer 344 rats, but no association is apparent for Sprague-Dawley rats. This situation is somewhat clarified when the degree of saturation is taken into account: both strains gave results that suggest a negative relationship between colon cancer incidence and omega-3 fatty acids intake and a positive relationship with non-omega-3 polyunsaturated fat intake among Fischer 344 rats. These analyses suggest an important and specific role for dietary fat in the promotion of rat colon carcinoma.
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PMID:Quantitative review of studies of dietary fat and rat colon carcinoma. 186 11


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