Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Four perchloric acid-soluble fractions (PASFs) from human liver metastases of sigmoid colon carcinoma (LSCC), pancreas carcinoma (LPC), breast carcinoma (LBC) and human normal liver (NL) were subjected to DEAE-cellulose column chromatography and separated into three glycoprotein fractions, respectively. 2. In chromatography, LSCC-PASF and LBC-PASF gave Thomsen-Friedenreich (T)-active glycoprotein, blood group N antigen precursor glycoprotein with T activity and N antigen precursor glycoprotein, respectively. 3. LPC-PASF gave N antigen precursor glycoprotein with T activity and two N antigen precursor glycoproteins. 4. The three glycoprotein fractions from NL-PASF did not exhibit both T activity and N antigen precursor activity.
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PMID:Blood group N antigen precursor glycoproteins and N antigen precursor glycoproteins with Thomsen-Friedenreich (T) activity from human liver metastatic carcinomas. 164 19

Increased sialylation of cell surface glycoconjugates has been demonstrated in malignant tumors and shown to be correlated with the invasive and metastatic growth of colon carcinoma cells. The authors have applied the Maackia amurensis lectin, which interacts with alpha 2,3-linked sialic acid, and the Sambucus nigra I lectin specific for alpha 2,6-linked sialic acid. In human colon, alpha 2,3-linked sialic acid was detectable in normal and transitional mucosa as well as in adenomas with different degrees of dysplasia and in carcinoma. In contrast, alpha 2,6-linked sialic acid as visualized with Sambucus nigra I lectin was found only in severe dysplasia and carcinoma. Thus expression of binding sites for Sambucus nigra I lectin was associated with the occurrence of histologic features of malignancy. It is concluded that malignant transformation in human colonic epithelium is accompanied by the de novo expression of an alpha 2,6 sialyl-transferase. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing alpha 2,6-linked sialic acid in growth behavior of human colonic epithelial cells.
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PMID:Expression of alpha 2,6-linked sialic acid residues in neoplastic but not in normal human colonic mucosa. A lectin-gold cytochemical study with Sambucus nigra and Maackia amurensis lectins. 166 Oct 75

Development of colon carcinomas can be associated with allelic deletions on several chromosomes, including 5q and 18q. The APC gene on 5q and the DCC gene on 18q have been identified as potential tumour suppressor genes, whose suppression contributes to colon carcinogenesis. To investigate the role of genes in these deleted regions, we have now introduced a single normal human chromosome into a human colon carcinoma cell line, COKFu, through microcell hybridization. Several clones of hybrid cells containing normal chromosome 5, and others containing normal chromosome 18, were obtained. The morphology of the hybrid cells was markedly altered: the hybrids with chromosome 5 exhibited a closely packed polygonal morphology, and the hybrid cells with chromosome 18 were flattened. The cloning efficiency of the hybrid cells in soft agar was reduced from 0.46 to 0% of that of the parental carcinoma cells, and the tumorigenicity of these hybrid cells in athymic nude mice was completely suppressed. The growth properties of the hybrid cells with chromosome 11 were not substantially changed. These results strongly suggest that the genes on normal chromosome 5 and 18 function as tumour suppressors in colon carcinogenesis.
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PMID:Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18. 167 Sep 65

Immunochemical studies of human colorectal carcinoma with various monoclonal antibodies against Le(X)-related carbohydrate antigens previously revealed that the amount of sialyl-dimeric Le(X) antigen (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-R: SLX) associated with metastatic lesions was greater than in the primary tumors. To assess whether an experimental model can be used to study the direct relationship between this carbohydrate antigen and the tumor cell's metastatic behavior, we selected variant cells with increased surface SLX from established human colon carcinoma cell line HT-29. The cells in the upper 5% or lower 5% population in fluorescence intensity after reacting with a monoclonal antibody, FH6, were retrieved separately by a fluorescence-activated cell sorter and propagated. After three- or four-times selection, we obtained stable cell lines with low and high cell surface SLX antigens (HT-29 M1 and HT-29 M2, respectively). Binding of monoclonal antibody FH6 was detected to glycolipids extracted from HT-29 M2 cells but not from HT-29 M1 cells. Glycoprotein components having reactivity with monoclonal antibody FH6 were below the detectable level. HT-29 M2 cells injected intrasplenically into nude mice showed a slightly reduced incidence of metastasis to lung, liver and lymph nodes than did HT-29 M1 cells. Subsequently we found that SLX antigen was not detectable by immunohistochemical examination of these tumor cells grown in nude mice. Re-established cell line from nude mice xenografts expressed SLX antigen in vitro.
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PMID:Metastatic behavior and cell surface properties of HT-29 human colon carcinoma variant cells selected for their differential expression of sialyl-dimeric Le(x)-antigen. 167 54

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

Two human immunoglobulin M (IgM) monoclonal antibodies (MoAbs), 16.88 and 28A32, which react with cytoplasmic (28A32 and 16.88) or cell surface (28A32) determinants on human colon carcinoma cells, were administered intravenously to 26 patients with metastatic colorectal carcinoma to determine if they could localize to sites of metastatic disease, if they had any antitumor or toxic effects, and to determine whether they would elicit an antihuman MoAb response. Serial scans showed tumor uptake of radioisotope in 12 of 16 patients receiving 131I-labeled 28A32 and in nine of 12 patients receiving 131I-labeled 16.88. No antitumor effects were seen with either antibody. No antibody-related toxic effects were observed following administration of 16.88, but two patients developed localized urticarial reactions following injection with antibody 28A32. No patient developed an antibody response to 16.88. Anti-28A32 reactivity was found in five of 12 (42%) normal sera and in seven of 23 (30%) patients before receiving any antibody. Following administration of 28A32, a low titer (1:10 dilution) of anti-28A32 developed in four patients with no preexisting antibody, a decrease in the preexisting titer was seen in three other patients, the titer remained constant in one patient, and no anti-28A32 was ever detected in six patients. In most cases, anti-28A32 activity was lost at dilutions greater than 1:10 and did not appear to affect antibody half-life in the serum or whole body retention of the antibody. We conclude that these human IgM MoAbs are capable of localizing at sites of disease in vivo, are nontoxic, and are poorly immunogenic in humans. Further studies to determine the specificity of targeting and to improve the delivery of antibody to sites of tumor are indicated.
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PMID:Toxicity, immunogenicity, and tumor radioimmunodetecting ability of two human monoclonal antibodies in patients with metastatic colorectal carcinoma. 168 72

We used the method of Rudolph et al. (Clin Chem 1988; 34:2031-8) to find information in the data from correlated determinations of acid phosphatase (PAP, EC 3.1.3.2; DuPont aca) and prostate-specific antigen (PSA, Hybritech). We described there how we assign medical decision limits for two or more correlated variables and convert the database to a binary coded message, allowing separation of a selected disease class with minimum error. The decision point, analogous to a percentile upper limit on the ordered values of each variable in the reference group, satisfies the maximum entropy constraints of reference, producing a minimum entropy for the binary coded patient database. We found maximum entropy decision points at PAP = 0.75 U/L and PSA = 22.8 micrograms/L. Patients with PSA values exceeding 22.8 micrograms/L had no benign prostatic disease except for five patients with benign prostate hyperplasia (BPH) with adjacent colon carcinoma (95.3), BPH with infarction (27.6), BPH (23.4) 28.1), or acute prostatitis (34.6). We consider PSA exceeding 22.8 micrograms/L as indicative of carcinoma of the prostate, stage C or D, in the absence of disconfirming evidence. Another decision value for PSA is 11.3 micrograms/L. This bounds the region between 11.3 and 22.8 micrograms/L, where the frequency of BPH is 1.5 times that for adenocarcinoma. At PSA less than 11.3 micrograms/L there is a high frequency of BPH. PSA concentration is not correlated with prostatic size (mass) or with prostatitis. A metastatic carcinoma is as likely to be nonprostatic as prostatic when the PSA concentration is less than 11.3 micrograms/L.
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PMID:Medically significant concentrations of prostate-specific antigen in serum assessed. 169 92

Monoclonal antibody (MAb) B72.3 has been shown to be of potential utility in the management of human carcinoma via its use in (a) the targeting of carcinoma lesions in colorectal and ovarian cancer patients, (b) immunohistochemical analyses of biopsies and effusions, and (c) serum assays to help define the presence of carcinoma. The B72.3-reactive antigen, designated tumor-associated glycoprotein 72 (TAG-72), has been characterized as a high molecular weight glycoprotein with the properties of a mucin. We report here the utilization of MAb B72.3 and 18 second generation MAbs (generated using purified TAG-72 obtained from a colon carcinoma xenograft as immunogen) to construct a serological map of the TAG-72 molecule. The generation and initial characterization of 10 of the second generation MAbs have been described previously; in addition, eight previously unreported MAbs were used. All 19 MAbs produced immune precipitate lines against purified TAG-72 in double immunodiffusion, indicating that each epitope recognized by a single MAb is present at least twice on the TAG-72 molecule. Immunodepletion analyses utilizing 11 of the anti-TAG-72 MAbs indicated that each recognizes the same molecule or population of molecules. Nineteen competition radioimmunoassays were developed and 19 purified competitor immunoglobulins were used in each assay. The patterns of cross-competition indicated the presence of a complex array of tumor-associated epitopes on the TAG-72 molecule. Some of the MAbs recognized epitopes that were structurally or spatially related to one another, but none appeared to recognize identical epitopes. The spectrum of inhibitory reactivities of these MAbs for TAG-72 binding varied from extremely restricted to more broad inhibition. The serological mapping studies reported here provide information as to the range and nature of the epitopes expressed on the TAG-72 molecule, help form the basis for selecting alternative anti-TAG-72 MAbs for use in potential clinical applications, and further define the nature of this oncofetal antigen.
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PMID:Serological mapping of the TAG-72 tumor-associated antigen using 19 distinct monoclonal antibodies. 169 62

Bleomycin is an agent with significant antitumor efficacy whose major dose limiting toxicity is pulmonary fibrosis. Attempts have thus been made to identify congeners with reduced toxicity and with comparable or greater antitumor activity. Tallysomycin S10b is a bleomycin analogue possessing significantly greater potency, equal or reduced lung toxicity, and slightly greater antineoplastic activity when compared to the parent compound in preclinical studies. This report describes our experience with tallysomycin S10b in 30 patients with a variety of non-hematologic neoplasms. Pulmonary toxicity, occurring in 4 patients, was the major toxicity. The recommended cumulative dose of tallysomycin S10b was difficult to establish from the results of this study, as pulmonary toxicity appeared to be more idiosyncratic than dose- or schedule-dependent. The employment of more sensitive methods for detecting pulmonary toxicity in this study suggest that tallysomycin S10b may have reduced pulmonary toxicity compared to the parent compound. Both bleomycin and tallysomycin S10b have similar t1/2 beta half-lives of 2-4 h. Six patients had prolonged terminal elimination half-lives of tallysomycin S10b, but no clear relationship between this phenomenon and efficacy or toxicity was evident. No complete or partial responses occurred. Disease stabilization occurred in 4 of 15 patients with diagnoses of renal cell carcinoma, rectal cancer and lung cancer. Five of eight patients with non-measurable disease had stable disease, including one with mesothelioma, one with carcinoma of the head and neck, two with renal cell cancer and one with colon carcinoma.
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PMID:Phase I trial of tallysomycin S10b, a bleomycin analogue. 169 67


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