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

Colon carcinoma is one of the most frequent causes of cancer death in industrialized countries. The patients generally die of the metastases. In a colon cancer rat model, the authors have shown that lipopolysaccharides from Escherichia coli induced the regression of carcinomatosis and cured 20%-30% of the rats. Some synthetic derivatives of lipid A, which are less toxic than lipopolysaccharides, were injected 14 days after the tumor cells. They induced the complete regression of peritoneal carcinomatosis consisting of numerous nodules measuring 1-5 mm in 20%-30% of rats. Only compounds with three or more hydroxymyristic acid residues were effective. In vivo effects were correlated with the capacity to induce the production of interleukin 1 and tumor necrosis factor but not with the capacity to induce macrophage-mediated cytolysis. It is therefore possible to synthesize weakly toxic derivatives of lipopolysaccharides retaining their antitumoral property in vivo.
Gastroenterology 1991 Sep
PMID:Antitumor effect of synthetic derivatives of lipid A in an experimental model of colon cancer in the rat. 186 Jun 36

A selective gastrin receptor (GR) antagonist, L-365,260 is bound to the GR on AR42J cells with a potency 7.5-fold less than G17 (50% inhibitory concentration [IC50] G17, 6 x 10(-9) mol/l; IC50 L365-260, 4.5 x 10(-8) mol/l). G17 is mitogenic for AR42J cells, as assessed by 75Se-selenomethionine uptake and L-365,260 at concentrations of 2.5 x 10(-6) mol/l and 2.5 x 10(-7) mol/l, (55X and 5.5 X the dose required to displace 50% 125I G17, respectively), and reduced optimal G17 stimulated mitogenesis in 75% of experiments. The basal growth of two human colon cancer cell lines, LoVo and C146 was reduced by L-365,260 (2.5 x 10(-7) mol/l) after 5 days of treatment to 44% and 64% of the control, respectively. However, inhibition was followed by a rebound of growth to control levels. The growth of AR42J xenografts in nude mice was increased by administration of G17 (10 micrograms/mouse/d, P less than 0.027). This increase was blocked by coadministration of oral L-365,260 (5 mg/kg/d, P less than 0.034). L-365,260 could be an important therapeutic agent in slowing the growth of GR-positive, G17-sensitive gastrointestinal tumors.
Cancer 1991 Sep 15
PMID:Inhibitory effects of the gastrin receptor antagonist (L-365,260) on gastrointestinal tumor cells. 187 78

An astoundingly high frequency of micrometastatic cells have been found in bone marrow aspirates of patients with colon carcinomas (G. Schlimok et al., J. Clin. Oncol., 8:831-837, 1990), although these tumors very rarely metastasize to the skeleton. This observation has raised questions about the malignant potential of such cells. In a first attempt to characterize this potential, we have assessed the expression of major histocompatibility complex (MHC) class I antigens on bone marrow micrometastases, inasmuch as down-regulation of these molecules is a potential mechanism to escape from MHC class I-restricted lysis by cytotoxic T-cells. The two groups of cancer patients compared were those with tumors known to rarely (stomach and colon cancer) or frequently (breast cancer) manifest skeleton metastases. Bone marrow aspirates taken from these patients were probed for individual disseminated tumor cells using the immunoalkaline phosphatase technique with monoclonal antibody CK2 to the epithelial differentiation antigen cytokeratin 18 (CK-18), as described previously (G. Schlimok et al., Proc. Natl. Acad. Sci. USA, 84:8672-8676, 1987). Specimens containing CK18-positive cells were colabeled with monoclonal antibody W6/32 directed to a framework (or nonpolymorphic) antigenic determinant of MHC class I heavy chains associated with beta 2-microglobulin. W6/32-positive CK-18-positive cells could be detected in 25 of 54 patients (46.3%) with significantly higher incidences in 26 breast cancer patients (61.9%) as compared to 28 patients with carcinomas of the stomach and colon (27.3 and 29.4%). Independent from the origin of the primary carcinoma, the incidence of W6/32-negative CK18-positive cells was positively correlated to both the differentiation grade of the primary tumor (P less than 0.05) and appeared to be linked to the occurrence of regional lymph node metastases (statistically not significant) determined by conventional histological examination. The present results demonstrate for the first time that down-regulation of MHC expression on individual micrometastatic cells correlates to the differential pattern of metastasis obtained by comparing breast and gastrointestinal carcinomas. This finding together with the suggestive link to clinical risk factors supports the significance of reduced MHC class I expression for the survival of residual metastatic cells which is a major determinant of prognosis for patients with solid tumors.
Cancer Res 1991 Sep 01
PMID:Frequent down-regulation of major histocompatibility class I antigen expression on individual micrometastatic carcinoma cells. 187 15

Leucovorin potentiates the cytotoxicity of fluorouracil (5-FU) in experimental tumor systems and appears to enhance the effectiveness of 5-FU in patients with colon cancer. Twenty-two eligible patients (18 previously untreated) with advanced pancreatic adenocarcinoma were treated in a phase II trial of leucovorin 500 mg/m2/d for 6 days by continuous intravenous infusion with 5-FU 370 mg/m2/d by rapid intravenous injection on 5 consecutive days, beginning 24 hours after initiation of leucovorin infusion. Among the 20 assessable patients, there were no complete or partial regressions, although there was one minor response lasting 4 months. Three patients had stable disease for 5, 20, and 21 months, respectively. Median survival was 10 weeks. Toxicity was predominantly mucosal; stomatitis grade 2 or worse was seen in five patients, and diarrhea grade 2 or worse was seen in four. Hospitalization for toxicity was necessary in four previously untreated patients and three previously treated patients. The median WBC nadir was 4.6 (range, 1.4 to 9.6) x 10(3)/microL, and the median platelet nadir was 147.0 (range, 69.0 to 240.0) x 10(3)/microL. This combination of leucovorin and 5-FU did not demonstrate meaningful therapeutic activity in patients with adenocarcinoma of the pancreas and was associated with moderate to severe toxicity. It should not be considered a standard treatment for patients with this disease.
J Clin Oncol 1991 Sep
PMID:Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma. 187 24

Regular physical activity increases a person's ability to perform daily activities with greater vigor and may reduce the risk for specific health problems, including coronary heart disease (1), hypertension (2), noninsulin-dependent diabetes mellitus (3), colon cancer (4), and depression (5), as well as lower all-cause death rates (6). In addition to extracurricular activities (e.g., sports and recreational organizations), high school physical education (PE) classes provide an opportunity to ensure a minimal, regular amount of desirable physical activity and help establish physical activity patterns that may extend into adulthood. This report examines the prevalence of self-reported enrollment, attendance, and participation in PE classes by students in grades 9-12.
MMWR Morb Mortal Wkly Rep 1991 Sep 06
PMID:Participation of high school students in school physical education--United States, 1990. 188 83

MUC-2, the first described intestinal mucin gene, has become important as a prototype for secreted mucins in several organ systems. However, little is known about its protein backbone structure and hence its role in diseases such as colon cancer, ulcerative colitis, and cystic fibrosis, which are known to have mucin abnormalities. Studies in this manuscript show that MUC-2 contains two distinct regions with a high degree of internal homology, but the two regions bear no significant homology to each other. Region 1 consists mostly of 48-bp repeats which are interrupted in places by 21-24-bp segments. Several of these interrupting sequences show similarity to each other, creating larger composite repeat units. Region 1 has no length polymorphisms. Region 2 is composed of 69-bp tandem repeats arranged in an uninterrupted array of up to 115 individual units. Southern analysis of genomic DNA samples using TaqI and HinfI reveals both length and sequence polymorphisms which occur within region 2. The sequence polymorphisms have different ethnic distributions, while the length polymorphisms are due to variable numbers of tandem repeats.
J Clin Invest 1991 Sep
PMID:MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism. 188 63

The assessment of physical activity at a single time to evaluate its association with cancer may be limited, since such a measure may not adequately reflect activity over the long term. To overcome this limitation, we studied 17,148 Harvard alumni aged 30-79 years who were followed prospectively for the occurrence of colon cancer (n = 225) and rectal cancer (n = 44) from 1965 through 1988. Physical activity, based on self-reported stair climbing, walking, and sports play, was assessed in either 1962 or 1966 (1962/1966) and again in 1977. The increased activity evaluated using either assessment (1962/1966 or 1977) taken alone was not associated with risk of colon cancer. However, alumni who were highly active (energy expenditure of greater than 2500 kilocalories/wk) at both assessments had half the risk of developing colon cancer relative to those who were inactive (less than 1000 kilocalories/wk) at both assessments (age-adjusted rate ratio = 0.50; 90% confidence interval = 0.27-0.93), whereas those who were moderately active (1000-2500 kilocalories/wk) at both assessments had an age-adjusted rate ratio of 0.52 (90% confidence interval = 0.28-0.94). We conclude that either consistently higher levels of activity are necessary to protect against colon cancer or combining two assessments increased the precision of physical activity measurement. We found no evidence that increased physical activity protected against rectal cancer.
J Natl Cancer Inst 1991 Sep 18
PMID:Physical activity and risk of developing colorectal cancer among college alumni. 188 58

Analysis of cell kinetics may be beneficial for evaluation of the therapeutic effect of anticancer agents. Therefore, using flow cytometry, the authors could classify perturbations of DNA histogram of cultured colon cancer cells treated with 5-FU into 4 types. Perturbation of DNA histogram of cancer cells treated with 5-FU of different concentrations was closely associated with the degree of cell damage indicated by the growth curve. Then, tumor samples before and after injection of 5-FU were collected from 9 preoperative patients with colon cancer and classified into the above 4 types. The results show that 2 cases were classified into type I (S/G1 ratio: 1.5 greater than, G1.G2M comparison: G1 greater than G2M) and another two into type IV (CV ratio: 1.5 less than or equal to, S/G1 ratio: 1.5 less than or equal to, G1.G2M comparison: G1 greater than G2M). However, 5 cases could not be classified (not evaluated) because of the absence of stemline and the presence of heterogeneity in tumor samples. The authors consider that the classification of perturbation of DNA histogram is a useful method to evaluate the degree of cell damage with 5-FU, if tumor samples are appropriately selected and analysis is made with careful attention.
Gan To Kagaku Ryoho 1991 Sep
PMID:[Classification of DNA histogram perturbed with 5-FU and its clinical application]. 188 80

Human intestinal mucins are large glycoconjugates (greater than 1,000,000 D) that coat the epithelium, serving to lubricate and protect. Apart from this physiologic function, mucins are important in that they are frequently altered in cancer; thus, they have potential usefulness as tumor markers. We have isolated mucins from human LS174T colon cancer cells and small intestine, deglycosylated these highly purified glycoconjugates, produced polyclonal antibodies to the apomucins, and used these antibodies to isolate two different types of cDNA clones that encode different apomucins. The first class of cDNA clones was isolated using antibodies to deglycosylated LS174T mucin. These cDNA, designated SMUC or MUC2, contain 69 nucleotide tandem repeats that encode a repetitive peptide that is extremely rich in threonine and proline. Northern blots using MUC2 cDNA as probes exhibit large (7,600 bases) and polydisperse hybridization bands. This gene is polymorphic within the human population and is located on chromosome 11. The second class of cDNA was isolated using antibodies to deglycosylated small intestinal mucin. These cDNA, designated SIB or MUC3, have 51 nucleotide tandem repeats that encode a threonine- and serine-rich repetitive peptide. This mucin also is encoded by a large, polydisperse message, but it is clearly distinct from MUC2 as it is located on chromosome 7. Both the MUC2 and MUC3 mucins are expressed in colonic tumors; however, the level of their expression is quite variable. Thus, at least two mucins are expressed by the human gastrointestinal tract. Elucidation of the regulation of these two genes will be important in understanding the physiology and pathophysiology of the human intestine.
Am Rev Respir Dis 1991 Sep
PMID:The structure of human intestinal apomucins. 189 19

A perfluorocarbon blood substitute, Fluosol, is undergoing clinical trials as an adjunct to chemotherapy. The adverse effects associated with its administration have been postulated to result from complement activation. When gel electrophoresis and Western blotting of Fluosol are used after its incubation with serum, activated C3 and factors Bb and H are bound to the Fluosol particles in a time-dependent fashion, which suggests that complement activation with Fluosol, as does that with zymosan, occurs on the surface of the particles. Paradoxically, it is found, both by the measurement of Fluosol-bound C3d and by fluid-phase C5a, that lower concentrations of Fluosol cause greater amounts of complement activation, which suggests a complex interaction of activators and inhibitors that changes as the available surface area is decreased. Studies performed with bystander red cell-bound C3d demonstrated in vivo complement activation occurring in six patients receiving Fluosol as an adjunct to chemotherapy for colon cancer. In two patients, there was a marked increase in red cell-bound C3d after Fluosol infusion; these two patients also developed adverse reactions during Fluosol infusion. These studies suggest that the Fluosol surface plays a major role in the initiation and regulation of complement activation that is seen during Fluosol infusion.
Transfusion 1991 Sep
PMID:Complement activation by artificial blood substitute Fluosol: in vitro and in vivo studies. 190 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>