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

Levels of putrescrine, spermidine, and spermine in urine were determined by means of a sensitive ion-exchange chromatographic method in patients with advanced solid tumor malignancies, in patients with diseases other than cancer, and in normal control subjects. Elevation above 2 SDS of the normal mean were found in varying number of patients in each tumor category. For those malignancies studied that involved more than 20 patients, the greatest incidences of increased excretion were 66% for spermine in patients with colon carcinoma and 50% for putrescine and spermidine in patients with bronchogenic carcinoma. The highest levels and greatest frequency of elevated polyamine levels were found in patients with Burkitt's lymphoma, and changes in clinical tumor status associated with treatment appeared to correlate well with polyamine levels in this disease. Abnormal amounts of polyamines were also excreted by some patients with diseases other than cancer, indicating that increased polyamine excretion is not restricted or specific to the neoplastic state. It was also found that the levels of polyamines were apparently not affected by the intake of meat or the diet eaten, and remained in a rather narrow excretion range for any one individual at different time intervals. This study was carried out as part of a program to determine and evaluate biologic materials present in body fluids that may be used to follow and evaluate response or progression of neoplastic disease in patients during treatment regimens. The results suggest that abnormal urinary polyamine levels may be characteristic of neoplastic growth for some patients with malignant disease. Further studies are necessary to determine if these compounds may be helpful in assessing disease status for patients with such solid tumor malignancies as colon and bronchogenic carcinoma although their potential as useful "biologic markers" appears less promising than originally anticipated.
Cancer Chemother Rep
PMID:Urinary excretion of polyamines by patients with advanced malignancy. 122 94

A controlled prospective study was undertaken to determine if fluids which bathe malignancies may contain carcinoembryonic antigen (CEA) earlier in the course of gastrointestinal cancer than does plasma of the same patient and may offer a better means for diagnosis. CEA titers were normal (less than 2.5 ng per ml) in the plasma of 42 healthy volunteers. Normal CEA levels were also found in the plasma and in the colonic mucus of 14, the gastric juice of 18, duodenal drainage of 10, and bile of 11 normal control subjects. The colonic mucus of 3 patients with ulcerative colitis, gastric secretions of 5 benign gastric ulcer patients, bile specimens from 11 normal control subjects and from 5 gallstone patients contained CEA at concentrations below 2.5 ng per ml. Positive CEA titers were found in the fluids bathing tumors of all 23 patients with colonic carcinoma, 9 of 17 patients with gastric carcinoma, and all 6 patients with pancreatic carcinoma. In contrast, positive CEA titers were found in the plasma of only 16 of 23 patients with colon carcinoma, 6 of 17 patients with gastric carcinoma, and 4 of 6 patients with pancreatic carcinoma. Among 46 patients with gastrointestinal malignancies, CEA was detected in significant concentrations in the plasma of 26 patients and in fluids bathing tumors of 38 patients. These results indicate a significant association of adenocarcinoma of the colon with CEA-positive colonic mucus (P less than 0.01) and suggest the usefulness of assaying CEA in fluids bathing tumors for the detection of gastrointestinal malignancies.
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PMID:CEA levels in fluids bathing gastrointestinal tumors. 125 36

In an attempt to identify new tumor markers in human colon carcinoma, we produced antisera in rabbits tolerant to normal human tissue antigens and immunized with zinc glycinate-treated extracts of liver metastases from a colon carcinoma. These antisera reacted with carcinoembryonic antigen and with an additional component present in the tumor extracts but not detected in the extracts of normal tissues. The new component, the zinc glycinate marker (ZGM), had an alpha2 mobility on immunoelectrophoresis, was soluble in 1 M perchloric acid, and had a molecular weight of approximately 2X10(6), as indicated by its elution pattern on Sepharose 6-B chromatography. It differed from alpha fetoprotein, nonspecific cross-reacting antigens (NCA, NGP, or CCA III), ferritin-like molecules, and blood group substances A, B, H, Lewis a, and Lewis b. The ZGM was similarly identified in saline or zinc glycinate extracts of 11 of 23 carcinomas of the colon. With routine hematoxylineosin staining, no histologic differences were apparent between tumors bearing the antigen and those without it.
J Natl Cancer Inst 1976 Feb
PMID:The zinc glycinate marker in human colon carcinoma. 125 60

A human carcinoembryonic antigen-producing colon carcinoma cell line has been established. The cells form acinar structures and signet ring cells. The lumen of the acini presents microvilli and a glycocalyx. Neighboring cells show desmosomes and terminal bars. The cells present an aneuploid karyotype with a modal number of 49. No marker chromosomes are found, although a significant proportion of cells show an altered A2 chromosome and an extra B. Exponentially growing cultures produce 54 ng of carcinoembryonic antigen/10(6) cells. Kinetic parameters are as follows: doubling time, 37 hr; mitotic index, 0.8%; labeling index, 31%; generation time, 30 hr; G1 phase, 7 hr; S phase, 18 hr; G2 phase, 5 hr; growth fraction 90%. This cell line, designated line LoVo, represents an in vitro model for human colon carcinoma.
Cancer Res 1976 Feb
PMID:Establishment of a human carcinoembryonic antigen-producing colon adenocarcinoma cell line. 126 Jul 46

The activity of deoxycytidine kinase (EC 2.7.1.74), an important pyrimidine salvage enzyme, was elevated 5- to 30-fold in human ovarian carcinoma and OVCAR-5 cells, in human colon carcinoma and HT-29 cells, in rat hepatoma 3924A solid tumors and cells, and in rat sarcoma as compared with the respective control normal cells. There was an inverse relationship between cell doubling time and deoxycytidine kinase activity in 8 cancer cell lines, with rapidly growing HL-60 cells (20 hr) showing the highest, and slower-growing lung H69 cells (60 hr) the smallest, increase in enzyme activity. In time-sequence studies in human HL-60, OVCAR-5, PANC-1, and rat hepatoma 3924A cells, there was a significant rise in deoxycytidine kinase activity after 3-6 hr of seeding, with peak increases (3.5- to 4-fold) at 48-72 hr in the log phase in comparison with values of the respective plateau phase cells (96-144 hr). In extracts of various cancer cells, the high deoxycytidine kinase activity was competitively inhibited by difluorodeoxycytidine (DFDC), with Ki = 7 to 30 microM. The Km for deoxycytidine in various carcinoma cell lines ranged from 0.3 to 0.7 mM and addition of DFDC increased the apparent Km from 0.7 to 4 mM. Deoxycytidine kinase activity in human HL-60 cells was inhibited by the end product, dCTP, with IC50 = 3 microM; dCTP elevated the Km for deoxycytidine from 0.35 to 0.9 mM. dTTP reversed the inhibition by dCTP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased deoxycytidine kinase activity in cancer cells and inhibition by difluorodeoxycytidine. 129 79

The 3645-base pair human topoisomerase I complementary DNA (cDNA) clone isolated by D'Arpa et al. (Proc. Natl. Acad. Sci. USA, 85:2543-2547, 1988) and a mutated version of the cDNA encoding a protein with phenylalanine instead of tyrosine at position 723 have been overexpressed 2- to 5-fold in stably transfected baby hamster kidney cells. The overexpressed proteins are the same size as the topoisomerase I present in Hela cells, indicating that the cDNA clone contains the complete topoisomerase I coding sequence. Some human colon carcinoma cells have increased levels of topoisomerase I and are hypersensitive to the drug camptothecin. The overexpressed wild-type topoisomerase I does not affect the cell growth or morphology of the baby hamster kidney cells, suggesting that elevated levels of topoisomerase I alone are not sufficient to cause cell transformation. However, the overexpressed wild-type protein is active, as shown by the hypersensitivity of clonal cell lines to camptothecin. The mutant form of topoisomerase I is enzymatically inactive by two criteria. First, extracts of Escherichia coli cells carrying the mutant cDNA contain no activity capable of relaxing superhelical DNA under conditions where activity is easily detectable in extracts from cells containing the wild-type cDNA. Second, baby hamster kidney cells stably transfected by the mutant cDNA are no more sensitive to camptothecin than control untransfected cells. These results indicate that tyrosine 723 is essential for enzyme activity and are consistent with predictions based on homology comparisons with the yeast enzymes, that this is the active-site tyrosine in the human topoisomerase I.
Cancer Res 1992 Feb 01
PMID:Overexpression of human topoisomerase I in baby hamster kidney cells: hypersensitivity of clonal isolates to camptothecin. 131 66

The effect of the relative affinity (Ka) on the antitumor efficacy of monoclonal antibodies (MAbs) has been questioned. It has previously been shown in experimental models that the use of MAbs with higher relative Kas manifests itself in a higher percentage of injected dose of MAb bound to tumor. On the other hand, mathematical models have proposed that the use of higher affinity MAbs may be disadvantageous for antitumor effects, since higher Ka MAbs would bind more antigen and prevent penetration of MAb through tumor. To test this hypothesis, three MAbs reacting to the human pancarcinoma antigen TAG-72 were used as radioimmunoconjugates for therapeutic efficacy versus the LS-174T human colon carcinoma xenograft. MAbs B72.3, CC49, and CC83 have all been shown by depletion studies to react to the same molecule and to all react with overlapping epitopes. While the relative Ka of B72.3 is 2.5 x 10(9) M-1, the relative Kas of CC49 and CC83 are 16.2 and 27.7 x 10(9) M-1, respectively. Each MAb was radiolabeled with 131I, and each radioimmunoconjugate was assayed at five dose levels for therapeutic efficacy using the human xenograft model. The results of these studies demonstrate substantial therapeutic advantage of the higher affinity MAbs CC49 and CC83 versus B72.3 at every dose level. While 500 microCi of B72.3 were required to reduce tumor growth in only a minority of tumor-bearing animals, the use of the same amount or less of the radioimmunoconjugates of CC49 or CC83 resulted in strong antitumor effects in 80 to 100% of tumor-bearing animals. Thus, stronger antitumor effects were seen using as little as 2.5- to 3-fold less of the higher Ka immunoconjugates CC49 and CC83 as compared with B72.3. While we acknowledge the potential disadvantages of higher Ka MAbs in some situations, at least the experimental studies and model system described here show that a distinct therapeutic advantage exists with the use of higher affinity immunoconjugates.
Cancer Res 1992 Mar 01
PMID:Therapeutic advantage of high-affinity anticarcinoma radioimmunoconjugates. 131 Jun 38

A set of adenosine 3':5'-monophosphate (cAMP) analogues that combine exocyclic sulfur substitutions in the equatorial (Rp) or the axial (Sp) position of the cyclophosphate ring with modifications in the adenine base of cAMP were tested for their effect on the growth of HL-60 human promyelocytic leukemia cells and LS-174T human colon carcinoma cells. Both diasteromeres of the phosphorothioate derivatives were growth inhibitory, exhibiting a concentration inhibiting 50% of cell proliferation of 3-100 microM. Among the analogues tested, Rp-8-Cl-cAMPS and Sp-8-Br-cAMPS were the two most potent. Rp-8-Cl-cAMPS was 5- to 10-fold less potent than 8-Cl-cAMP while Sp-8-Br-cAMPS was approximately 6-fold more potent than 8-Br-cAMP. The growth inhibition was not due to a block in a specific phase of the cell cycle or due to cytotoxicity. Rp-8-Cl-cAMPS enhanced its growth-inhibitory effect when added together with 8-Cl-cAMP and increased differentiation in combination with N6-benzyl-cAMP. The binding kinetics data showed that these Sp and Rp modifications brought about a greater decrease in affinity for Site B than for Site A of RI (the regulatory subunit of type I cAMP-dependent protein kinase) and a substantial decrease of affinity for Site A of RII (the regulatory subunit of type II protein kinase) but only a small decrease in affinity for Site B of RII, indicating the importance of the Site B binding of RII in the growth-inhibitory effect. These results show that the phosphorothioate analogues of cAMP are useful tools to investigate the mechanism of action of cAMP in growth control and differentiation and may have practical implication in the suppression of malignancy.
Cancer Res 1992 May 01
PMID:Unhydrolyzable analogues of adenosine 3':5'-monophosphate demonstrating growth inhibition and differentiation in human cancer cells. 131 95

We compared the cytotoxicity of simultaneous and sequential combination chemotherapy with camptothecin and etoposide, in slowly growing human colon carcinoma, HT-29 cells. Simultaneous treatments of HT-29 cells with etoposide and camptothecin produced no marked enhancement of cytotoxicity over single agent administration. This finding demonstrates antagonism of one drug's cytotoxicity over the other. When these studies were repeated in sequential treatment protocols, we observed that antagonism could be circumvented if the period between individual drug administration was separated by 6-8 h. The cytotoxicity that was observed with this approach was never more than additive and the order of camptothecin or etoposide administration did not significantly affect the extent of combined cytotoxicity observed. The protective effect of simultaneous camptothecin and etoposide exposure was not due to reduced formation or alterations in the rate of cleavable complex reversal, and protection persisted for a considerably longer period of time than DNA strand breaks. Protection correlated with the kinetics of DNA and RNA synthesis inhibition produced by either drug. Remarkably, full cytotoxic protection could be afforded by one drug over the other, in the presence of only partial inhibition of DNA or RNA synthesis (50-60%). Our findings suggest that sequential rather than simultaneous administration of topoisomerase I and II inhibitors in future cancer chemotherapy schedules will enhance cytotoxicity over single-agent administration.
Eur J Cancer 1992
PMID:Sequential administration of camptothecin and etoposide circumvents the antagonistic cytotoxicity of simultaneous drug administration in slowly growing human colon carcinoma HT-29 cells. 132 4

The presence in tumors of numerous cytokines suggests that they potentially modulate tumor cell activities and host tissue remodelling. To investigate the possible involvement of transforming growth factor type beta (TGF beta) in the metastatic process of cancer development, we have studied the effect of this factor on two rat colon carcinoma cell lines. These cell clones had been previously tested and selected for their ability to develop metastases in syngenic animals or lack of it. The two cell lines were characterized for their production of TGF beta. Production of active and latent forms of TGF beta 1 in the medium conditioned by the rat colon cancer cells were quantified using a bioassay. The presence of active TGF beta 1 was demonstrated in conditioned medium from the progressive tumor (PROb) cells and significant expression of latent forms of TGF beta 1 were found in the conditioned media from both cell clones. TGF beta 1 slightly inhibited proliferation of PROb cells which had been previously described as moderately differentiated, and significantly stimulated proliferation of the regressive (REGb) cells, described as poorly differentiated. On the basis of our observations, we suggest that this endogenous factor could be involved in autocrine regulation of tumor cell activities and in paracrine regulation of stroma cell and immune responses. Active and/or latent expression of TGF beta 1 by the two rat colon carcinoma cell lines, and their variable responses to the growth factor, strongly suggest that this polypeptide is involved in the regulation of tumorigenic expression of adenocarcinoma cells.
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PMID:Possible involvement of TGF beta 1 in the distinct tumorigenic properties of two rat colon carcinoma clones. 133 1


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