Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three complementary DNA encoding S19 ribosomal protein (S19), laminin-binding protein (LBP), and HLA class I (HLA-I) genes were isolated from a colon tumor-enriched subtraction library. To evaluate this mRNA expression, surgically removed colon tumors as well as matched normal tissue and human colon carcinoma cell lines showing various differentiation states, anchorage dependence, and proliferation states were examined by Northern blot analysis. The mRNA level of S19 mRNA (0.6 kilobase) was higher in primary colon carcinoma tissue than in matched normal colon tissue in 5 of 6 cases. In 2 of 4 cases, the expression of LBP mRNA (1.2 kilobases) was higher in carcinoma than in normal tissue. In 12 human colon cell lines, the level of LBP mRNA was higher in poorly differentiated cells. On the other hand, HLA-I mRNA (1.7 kilobases) was higher in well-differentiated cells. Although the S19 mRNA was expressed in both well- and poorly differentiated cells, a concomitant increase with tumor progression was observed in two pairs of cell lines derived from the same patients (SW480 and SW620; COLO201 and COLO205). Anchorage dependence of butyrate-treated HT29 colon carcinoma cells was correlated with lower levels of S19 and LBP mRNAs and higher levels of HLA-I mRNA expression compared with untreated cells. While the expression of S19 and LBP mRNAs was not changed due to cell growth states, HLA-I mRNA levels were found to be low in proliferating HT29 cells but highly induced in contact-inhibited cells. In summary, therefore, high expression of S19 and LBP combined with low expression of HLA-I were well correlated with colon carcinoma cells of higher malignant potential.
Cancer Res 1992 Feb 15
PMID:Differential expression of S19 ribosomal protein, laminin-binding protein, and human lymphocyte antigen class I messenger RNAs associated with colon carcinoma progression and differentiation. 133 4

Because tumor size has been shown to influence the specific accumulation of radiolabeled anti-tumor-associated antigen monoclonal antibodies (mAb), the present study has investigated the effect of the tumor size on the enhancement by gamma interferon (IFN-gamma) of the accumulation of radiolabeled mAb in malignant lesions. Intercellular adhesion molecule-1 (ICAM-1) has been used as a marker because of its high susceptibility to modulation by IFN-gamma. F(ab')2 fragments of anti-ICAM-1 mAb CL207.14 have been selected to visualize malignant lesions, because they had been shown to be more sensitive probes for our experiments than whole IgG. Administration of IFN-gamma to human colon carcinoma-bearing nude mice increased the expression of ICAM-1 in the xenografts and the specific accumulation of 125I-F(ab')2 fragments of anti-ICAM-1 mAb CL207.14. The latter effect is influenced by the size of the lesions, because it was observed only in tumors with an approximate diameter of 8 mm and an approximate weight of 250 mg. If these results obtained in an animal model system are applicable to patients with malignant diseases, the present investigation suggests that administration of IFN-gamma enhances the sensitivity of immunoscintigraphy and the efficacy of immunotherapy with radiolabeled mAb which recognize tumor-associated antigens that are susceptible to modulation by IFN-gamma. However, the effect of IFN-gamma is not a general phenomenon but is influenced by the size of the malignant lesions.
Cancer Res 1992 Mar 01
PMID:Effect of tumor size on the enhancement by gamma interferon of the localization of radiolabeled F(ab')2 fragments of anti-intercellular adhesion molecule-1 monoclonal antibodies in human colon carcinoma cells grafted in nude mice. 134 88

Cytotoxicity of Adriamycin on human colon adenocarcinoma cell lines was investigated. Concentrations of Adriamycin producing 50% inhibition were very similar in HT29, Sw480, Sw620, and Sw1116 cells, whereas Caco-2 cells were relatively insensitive. As compared to the Sw1116 cell line, Caco-2 cells were also insensitive to mitoxantrone. Sensitivity to cisplatin, 5-fluorouracil, or ethacrynic acid was comparable in both cell lines. To find the mechanism for this mitoxantrone and Adriamycin resistance, several potential Adriamycin-detoxifying systems were characterized and quantified in both Sw1116 and Caco-2 cells. No dramatic differences in glutathione content and expression of both selenium dependent- and independent glutathione peroxidase, UDP-glucuronyltransferase, and cytochrome P-450 were found. However, highly significant differences in glutathione S-transferase activity were present, the expression of both class pi and class alpha glutathione S-transferases being much higher in the Caco-2 cell line. In addition, a slightly higher content of P-170 glycoprotein was present in the Caco-2 cells. These findings suggest that glutathione S-transferases, and to a lesser extent the P-170 glycoprotein, may be involved in mitoxantrone and Adriamycin resistance of Caco-2 colon carcinoma cells.
Cancer Res 1992 Apr 01
PMID:Biochemical characterization of resistance to mitoxantrone and adriamycin in Caco-2 human colon adenocarcinoma cells: a possible role for glutathione S-transferases. 134 15

To search for differentially expressed gene products in selected cancers of endodermal origin, cDNA libraries derived from mRNA in human hepatocellular carcinoma and adjacent grossly normal tissue were generated. From these parent libraries, subtracted cDNA libraries of tumor minus normal and normal minus tumor tissues were constructed. After screening these subtracted libraries by +/- hybridization, a cDNA clone that is overexpressed in hepatocellular carcinoma and encodes the human acidic ribosomal phosphoprotein P0 (P0) was identified. We then evaluated the expression of this phosphoprotein P0 in human colon carcinoma samples. Surgical specimens of primary tumors and liver metastases were examined by Northern hybridization of total RNA with one of 2 32P-labeled P0 probes. The mRNA level of the P0 was greater in primary colon carcinoma than in paired adjacent normal colonic epithelium in 36 of 38 cases; the mean tumor/normal ratio was 2.7 (range, up to 13). The tumor/normal ratio, when plotted against the Dukes' stage of disease, gave evidence for increasing P0 expression with increasing stage of colon carcinoma (P = 0.02). In all 8 cases of paired colon carcinoma metastatic to liver and 2 cases of paired primary hepatocellular carcinoma, the P0 mRNA level was greater in tumor than in adjacent normal liver tissue. The mean tumor/normal ratio was 4.0 (range, up to 11) for the colon cancers metastatic to liver and 4.2 for the primary hepatocellular carcinoma samples. These findings support a common increased expression of selected gene products in different tumors of endodermal origin and suggest that increased P0 expression, in line with certain other ribosomal proteins, may be associated with human colorectal cancer progression and biological aggressiveness.
Cancer Res 1992 Jun 01
PMID:Increased expression of human ribosomal phosphoprotein P0 messenger RNA in hepatocellular carcinoma and colon carcinoma. 135 May 8

Monoclonal antibody AM-3 (MAb AM-3) raised against a sialomucin from human colorectal carcinoma has previously been shown to define a carbohydrate epitope, which is detectable by immunocytochemistry on all investigated colonic carcinomas and is expressed in correlation with the grade of dysplasia in colonic adenomas (Hanski et al., J. Clin. Pathol., 43: 379-385, 1990). Epitope analyses in solid-phase enzyme immunoassays revealed that AM-3 antibody recognizes the sialylated Lewis(x) sequence on a branched O-linked glycan and its reductively cleaved alditol from human amniotic mucins. In comparative binding and binding inhibition studies MAbs AM-3 and CSLEX1 displayed reciprocal affinities to mucins versus gangliosides. Correspondingly, the weaker binding activities of AM-3 versus CSLEX to III3-alpha Fuc-IV3-alpha NeuAc-nLcOse4-Cer or to monogangliosides from human granulocytes were measured. Gangliosides from a human colon carcinoma were recognized by MAb CSLEX1 exhibiting a broader specificity to various sialyl-Lewis(x) antigens and by MAb FH6 reactive to sialyl-dimeric Lewis(x) antigen, but not by MAb AM-3. In conclusion, MAb AM-3 is distinguished from other sialyl Lewis(x)-specific MAbs by its selective reactivity to mucin-carried epitopes on the monomeric antigen.
Cancer Res 1992 Jun 01
PMID:Sialyl Lewis(x) antigen as defined by monoclonal antibody AM-3 is a marker of dysplasia in the colonic adenoma-carcinoma sequence. 135 May 9

The biochemical basis of the multidrug-resistant (MDR) phenotype has been investigated in drug-resistant sublines derived from LoVo and SW984 human colon carcinoma cell lines by doxorubicin selection. Besides drug extrusion through the plasma membrane, two further observations, both ascribable to the drug transport property of the gp170 glycoprotein, were made. First drug deposition into cytoplasmic membranous structures which allows cells to tolerate a high intracellular drug concentration since it prevents drugs from reaching their cellular target site(s). Secondly drug removal from the complexes formed by interaction of drug with target cellular macromolecules, a phenomenon which extends its an effect that continues after treatment and appears to be the most important resistance mechanism in MDR cells. Treatments based on the gp170 inhibitory property of verapamil were developed that allowed abrogation of resistance in MDR cell lines, a strategy that may be applicable to therapy treatments.
Eur J Cancer 1992
PMID:Mechanism of multidrug resistance in human tumour cell lines and complete reversion of cellular resistance. 135 96

Tiazofurin is effective in treating end-stage leukemic patients (Tricot et al., Cancer Res 49:3696-3701, 1989). In sensitive tumors, the active metabolite of tiazofurin, TAD, potently inhibits IMP dehydrogenase activity, resulting in reduced guanylate pools. To elucidate tiazofurin activity in human solid tumors, we examined its activity in human colon carcinoma HT-29. Tiazofurin exhibited an LC50 of 35 microM in cultured HT-29 cells. Incubation of HT-29 cells with 100 microM tiazofurin for 2 h resulted in TAD formation (9.3 nmol/g cells) and in a 64% decrease in GTP pools. For biochemical and chemotherapy studies, athymic nude mice were transplanted s.c. with HT-29 cells. Twenty-four days later, mice were injected i.p. with tiazofurin (500 mg/kg); 6 h later, tumors were removed and analyzed. These tumors formed 17 nmol/g of TAD with decreased GTP pools (56%). To study oncolytic activity, transplanted mice were treated 24 h later with tiazofurin (500 mg/kg, once a day for 10 days). To examine the effectiveness of tiazofurin in established tumors, the drug was administered to mice 14 days after tumor implantation (500 mg/kg, once a day for 5 days, course repeated 4 times with a 10-day rest). Both treatment schedules resulted in significant antitumor activity. This study illustrates the potential usefulness of tiazofurin in treating human colon carcinoma.
Cancer Invest 1992
PMID:Antitumor activity of tiazofurin in human colon carcinoma HT-29. 135 9

We now keep HFRSV free WF-Osaka rats and ACI rats together in the separate three animal rooms (animal room 1, 2 and 3) and the incidence of colon carcinoma is still high on the WF-Osaka rats in animal room 1 with the high humidity. Two female ACI rats developed colon carcinomas in the ascending colon. The gross and the histological appearance of the colon carcinoma were completely the same as those of WF-Osaka rats. ACI and WF-Osaka rat strain together have been kept bred in neighborhood of each other in different racks in the identical animal room 1. To obtain HFRSV free ACI rat strain, Antecedents born by cesarean section of ACI female pregnant rat were foster-bred by WF-Osaka female nursing rat incidentally, and at the fourth mating generation after the start of foster-breeding, they developed colon carcinomas at the age of four months. Before five out of eight F1 hybrids by WF-Osaka cancer carrying female rat x male ACI rat had developed the same colon carcinoma, but none of F1 hybrids by the contrary mating had developed colon carcinomas in this same animal room 1. Animal room 1 and 2 where there was a high incidence of colon carcinomas, had happened to be kept moistened. However, after disinfection of these animal rooms, the animal room 2 and 3 occurred to be kept dried, and rats of WF-Osaka strain ceased to develop colon carcinomas in the animal room 2. Thereafter, animal room 2 and 3 were adjusted to be kept moistened again. Subsequently WF-Osaka rats in the animal room 2 began to have colon carcinomas in the ascending colon as before, but none of rats developed colon carcinomas in the animal room 3. Based on these findings, we consider that milk factor at the time of foster-breeding played an important role first and high moistened condition of the animal room resulted in promoting effect on colon carcinogenesis on ACI rats and WF-Osaka rats as well.
 ...
PMID:Adenocarcinoma in the ascending colon of ACI strain rat foster bred by WF-Osaka female rat. 136 50

Intraperitoneal injection of the serum of colon cancer carrying WF rats induced, within two months, colon carcinomas in the ascending colon of LE and Wistar/Shi rats when they were given it during their suckling. We had also induced colon carcinomas in the ascending colon of ACI rats by the same methods. Therefore, it is supported that this serum derived from colon cancer carrying WF rats must have some transmissible agent in itself. In addition, we ultracentrifuged the serum of cancer carrying WF rats and we found, in the sediment, numerous round or oval virus like corpuscles by electron microscopy studies. Negatively stained corpuscles by phosphotungstic acid staining clearly revealed fine spike appearance on their surface. We believe that these virus like corpuscles are the etiological agent for the transmissible colon carcinoma of WF rat strain.
 ...
PMID:Induced adenocarcinoma of the ascending colon on LE and Wistar/Shhi rats and virus like particles in the serum of colon cancer carrying WF rats. 136 56

Two mucin-producing cell clones (16.2 and 12.2) and a mucin-deficient clone (15.2) were selected from the established human adenocarcinoma cell line HT-29 by limiting dilution and Alcian blue staining. The amounts of the mucin antigen detectable on the cell surface with the monoclonal antibody (MAb) AM-3 decreased in the order HT-29 greater than 16.2 greater than 12.2 greater than 15.2 = 0. The binding avidity of AM-3 antibody to cells as well as to mucin extracts from each cell line decreased in the same order, indicating that the epitope density on the cell-bound mucins was highest in HT-29 and lowest in 12.2 cells. The parental line and the mucin-producing cell clones 16.2 and 12.2 showed no contact inhibition and grew as aggregates, while the 15.2 cells were well spread and formed a regular monolayer. The mucin-producing cell lines injected into nude mice yielded solid tumors with different growth rates (HT-29 greater than 16.2 greater than 12.2), while the 15.2 cell clone was not tumorigenic at all. The relative amounts of total mucin-bound hexoses and of the mucin epitope AM-3 decreased in the xenografts in the order HT-29 greater than 16.2 greater than 12.2. The present system is suitable for investigating the role of mucins in growth of colon carcinoma cells and indicates that increased tumorigenicity in nude mice coincides with the increase in total mucin expression and the expression of the AM-3 mucin epitope in tumor tissue.
Int J Cancer 1992 Apr 01
PMID:Tumorigenicity, mucin production and AM-3 epitope expression in clones selected from the HT-29 colon carcinoma cell line. 137 82


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