Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the free-plasma amino acid pattern in 73 healthy volunteers and 156 patients with gastrointestinal carcinomas after an overnight fast. None of the examined persons showed a sign of malnutrition or metabolic illness. Differences of more than +/- 40% in the concentrations of methionine, phenylalanine, glutamic acid, ornithine, taurine, and phosphoserine were found in cancer patients compaired to healthy volunteers. Tumorstage but not localization or grading correlated significantly with most amino acids. From our results we were able to compute a linear model of seven amino acids using computer-based stepwise discriminant analysis. This formula in the form of a tumor-index can be used as a prognostic indicator for the presence or absence of a gastrointestinal carcinoma.
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PMID:[Changes in plasma amino acid level as a possible tumor marker in cancers of the gastrointestinal tract]. 406 7

2-Amino-6-methyldipyrido[1,2-a:3',3'-d]imidazole (Glu-P-1) and 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), which were isolated from a glutamic acid pyrolysate, were proved to be multipotent carcinogens in rats, inducing tumors of the liver, intestine, ear duct and clitoral gland when administered orally to F344 rats. Intestinal tumors were produced for the first time in a series of experiments with heterocyclic amines. Details of the morphologic features of the intestinal tumors induced in F344 rats by Glu-P-1 and Glu-P-2 are described. There were no marked differences between the tumors induced by Glu-P-1 and Glu-P-2. Grossly, the tumors of the small intestine were recognized as papillary, polypoid or umbilicated masses. The most common tumors in the large intestine showed polypoid growth with a short stalk. Histologically, the intestinal tumors were classified as adenomas, adenocarcinomas, and mucinous carcinomas. Several adenocarcinomas were found adjacent to adenomas. Mucinous carcinomas developed only in the small intestine. Most of these tumors showed endophytic growth with extensive mucus production. Tumor tissue from the small intestine transplanted into the subcutis of the flank grew into tumors within 3 months.
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PMID:Intestinal tumors in rats induced by mutagens from glutamic acid pyrolysate. 609 72

The principal limiting feature of the antitumor agent, vincristine, in the clinic has been neurotoxicity; there are no known agents which can routinely prevent or decrease this side effect. Glutamic acid in laboratory and clinical investigations in the early 1960s was found to antagonize vinblastine, another clinically useful vinca alkaloid. Glutamic acid 250 mg/kg/d i.p. was given to normal mice treated with repetitive doses of vincristine 1.5 mg/kg every other day. When glutamic acid was given both before and during vincristine administration, it produced a 49-79% increase in survival compared to control mice receiving vincristine only (p less than 0.01). Other schedules of glutamic acid administration were ineffective. Also, there appeared to be a delay in development of neurotoxic manifestations (toe-walking gait) but the results were not as consistent as the improvement in survival. Glutamic acid given to tumor-bearing mice (P-388 and P-1534 murine leukemia) did not inhibit the antitumor effect of vincristine-induced host toxicity in a schedule-dependent fashion without inhibition of the antitumor effect of vincristine.
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PMID:Glutamic acid modification of vincristine toxicity. 614 15

We investigated the ability of macrophages (M phi) to present the tolerogen fluoresceinated sheep gamma-globulin (FL-SGG) to B cells. M phi pulsed with FL-SGG or murine FL-IgG2 were able to tolerize normal spleen B cells specifically as assessed by the plaque-forming cell (PFC) response to the antigens FL-Brucella abortus (FL-BrA) and FL-polymerized flagellin (FL-POL). Tolerance was not induced when M phi were pulsed with a variety of other FL antigens or the synthetic tolerogen FL-D-glutamic acid-D-lysine (FL-D[G,L]). The ability of M phi to tolerize B cells was not T cell-dependent, because populations of both T-depleted B cells and hapten-specific B cells were tolerizable. M phi-induced B cell tolerance did not exhibit genetic restriction with regard to the H-2 haplotype of the presenting M phi or the responding B cells. A variety of different types of peritoneal M phi, including normal resident M phi and those elicited by thioglycollate or concanavalin A (the latter are predominantly la+), could tolerize B cells after being pulsed with FL-SGG. We compared tolerogen-pulsed M phi to soluble tolerogen for the ability to tolerize B cells and found that tolerogen bound to M phi was more than 10 times as potent as an equivalent amount of soluble tolerogen. In contrast to the ability of M phi to present FL-SGG in a tolerogenic fashion to B cells, the P388AD lymphoid dendritic cell-like tumor line presented FL-SGG in an immunogenic mode to B cells. Tolerogen bound to P388AD cells could specifically augment a PFC response to both FL-BrA and FL-POL. We suggest that certain types of M phi may play a role in unresponsiveness by enhancing the tolerogenicity of soluble antigen, whereas other accessory cells may present the same moieties in an immunogenic fashion.
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PMID:A novel role for macrophages: the ability of macrophages to tolerize B cells. 619 50

Four types of 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates with poly-L-glutamic acid (PLGA) or poly-N5-(2-hydroxyethyl)-L-glutamine (PHEG) were prepared in an attempt to enhance the efficacy of the drug in simple dosage schedules. The conjugates were made by linking ara-C to the carboxyl groups of PLGA directly at N-4 of ara-C (ara-C:PLGA) or indirectly through the 2-aminoethylphosphoryl or 6-aminohexylphosphoryl side chain which had been introduced to C-5' of ara-C, 1-[5'-(2-aminoethylphosphoryl)-beta-D-arabinofuranosyl]cytosine: PLGA [araCMP(C2):PLGA and 1-[5'-(6-aminohexylphosphoryl)-beta-D-arabinofuranosyl]cytosine:++ +PLGA, respectively, or made by converting the remaining carboxyl groups in the PLGA conjugates to the 2-hydroxyethylamide groups [ara-C:PHEG, ara-CMP(C2):PHEG, 1-[5'-(6-aminohexylphosphoryl)-beta-D-arabinofuranosyl]cytosine:++ +PHEG]. Studies in vitro showed that the conjugates had decreased cytotoxicity against L1210 cells when compared with that of ara-C. Studies in vivo showed that all of the conjugates, except ara-CMP(C2):PLGA, had a greater antitumor activity than did ara-C in L1210 tumor-bearing BALB/c X DBA/2 F, (hereafter called CD2F1) mice (inoculum, 1 X 10(5) cells i.p. on Day 0) which were treated by a single i.p. injection of either the conjugates or the control ara-C on Day 1. The largest antitumor activity [increased life span (ILS) 170%] was observed with a dosage of 50 mg (equivalent ara-C per kg) of ara-C:PHEG. When CD2F1 mice which had been inoculated i.p. with 1 X 10(5) L1210 cells were treated with an i.p. injection of 12.5 or 25 mg (equivalent ara-C per kg) of ara-C:PHEG daily for 5 days starting from Day 1, 2 of 5 mice survived more than 42 days, and the ILS of the remaining mice was 153 and 184%. The injections of 3.2 mg (equivalent ara-C per kg) of ara-C:PHEG showed a moderate antitumor activity with an ILS of 113% which was similar to the ILS (119%) found when unconjugated ara-C (400 mg/kg) was used to treat tumor-bearing mice. In in vitro release experiments, ara-C was released slowly from ara-C:PLGA at pH 7.4, and ara-CMP(C2):PLGA was chemically stable but cleaved by phosphodiesterase, acid phosphatase, and alkaline phosphatase to give mainly 1-beta-D-arabinofuranosylcytosine 5'-monophosphate.
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PMID:Antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugated with polyglutamic acid and its derivative. 619 62

The present study was designed to investigate the generation of trinitrophenyl (TNP)-reactive helper T cell activity potent enough to induce the regression of a syngeneic tumor; this occurs by augmenting antitumor-specific immunity through T-T cell interaction. Mice whose skin was painted with trinitrochlorobenzene (TNCB) exhibited a variety of anti-TNP T cell responses, including delayed-type hypersensitivity (DTH) and cytotoxic T cell responses, as well as helper T cell activity. Pretreatment of C3H/He mice with TNP-conjugated copolymer of D-glutamic acid and lysine (TNP-D-GL) or cyclophosphamide, which have been shown, respectively, to inactivate TNP-specific suppressor T cells or suppressor T cells in general, exhibited a slight or marginal augmentation of DTH and cytotoxic potentials when tested 5 wk after TNCB painting. In contrast, the same pretreatment regimens induced an appreciably amplified generation of anti-TNP helper T cell activity. This amplified TNP-helper T cell activity was demonstrated to enhance cytotoxic responses to antigens other than TNP in an antigen-nonspecific way. In fact, such helper T cells enhanced antitumor CTL responses when co-cultured with spleen cells from syngeneic X5563 plasmacytoma-bearing mice in the presence of TNBS-modified X5563 tumor cells. This amplified TNP-helper cell system was utilized for its immunotherapeutic potential. When TNCB was injected into X5563 tumor mass of syngeneic C3H/He mice in which the amplified TNP-helper T cell activity had been generated, an appreciable number of growing tumors was observed to regress. This contrasted with the low incidence of tumor regression observed in mice in which TNP-helper activity had been induced by TNCB painting without inactivation of suppressors. Thus, the present model provides an effective immunotherapeutic manipulation for eliciting enhanced in vivo tumor regression, and emphasizes a role of helper T cells in augmentation of syngeneic tumor immunity.
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PMID:Enhanced TNP-reactive helper T cell activity and its utilization in the induction of amplified tumor immunity that results in tumor regression. 619 97

In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunorubicin [(DM) daunomycin] was conjugated with an affinity-purified horse antibody to rat alpha-fetoprotein (AFP) with a novel derivative of poly-L-glutamic acid (PLGA) as the intermediate drug carrier. A single masked thiol group first was introduced by PLGA, and the thiol group was generated from it after the linking of DM to PLGA at the carboxyl groups of PLGA. The thiol group was used selectively for binding PLGA-DM to antibody that had been modified so as to have the maleimide groups. The conjugates (DM:PLGA:immunoglobulin molar ratio, 19.6:2.8:1 or 11.8:1.1:1) were more potent than DM in in vitro cytotoxicity against the AFP-producing rat ascites hepatoma cell line AH66. In therapeutic experiments, the conjugates were more efficacious in prolonging the lives of AH66 hepatoma-bearing DONRYU rats than DM, antibody, a mixture of DM and antibody, or a conjugate similarly prepared with normal horse immunoglobulin.
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PMID:An anti-alpha-fetoprotein antibody-daunorubicin conjugate with a novel poly-L-glutamic acid derivative as intermediate drug carrier. 620 72

In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunomycin (DM) was first linked to a poly-L-glutamic acid (PLGA) derivative having a single masked thiol group. At the thiol group, DM-linked PLGA was bound to horse anti-rat alpha-fetoprotein (AFP) antibody. The anti-AFP antibody-PLGA-DM conjugate (anti-AFP conjugate, DM/PLGA/Ig molar binding ratio, 7.5/1.2/1.0) retained most of the antigen-binding activity of the parent antibody and was more potent than either unconjugated DM, a conjugate similarity prepared with normal horse immunoglobulin (normal conjugate), or an unconjugated mixture of anti-AFP antibody and DM in an in vitro cytotoxicity assay against the AFP-producing rat ascites hepatoma cell line AH66. Anti-AFP conjugate tended to be less cytotoxic than DM against the AFP-nonproducing rat ascites hepatoma AH272 cells, and in this case there was no difference between the cytotoxicities of anti-AFP conjugate and of normal conjugate.
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PMID:A novel method of conjugation of daunomycin with antibody with a poly-L-glutamic acid derivative as intermediate drug carrier. An anti-alpha-fetoprotein antibody-daunomycin conjugate. 620 94

The present study investigates the role of helper T cells in preventing tolerance in effector T cells responsible for syngeneic tumor immunity. Tolerance in T cell-mediated immune responses against X5563 plasmacytoma was induced in syngeneic C3H/He mice by intravenous (iv) administration of 7,000 R X-irradiated X5563 tumor cells. Since the anti-X5563 tumor tolerance was observed irrespective of whether the tumor cells had been modified with trinitrophenyl (TNP) hapten prior to iv inoculation, the ability of TNP-reactive helper T cells to prevent the tolerance induced by iv inoculation of TNP-X5563 tumor cells was examined. TNP-reactive helper T cell activity was generated in C3H/He mice by immunization with TNP-isologous mouse gamma-globulin after inoculation with the TNP-conjugate of a non-immunogenic co-polymer of D-glutamic acid and D-lysine. Intravenous inoculation with TNP-modified X5563 cells induced tolerance in mice not primed with TNP. However, such tolerance was prevented in mice in which TNP-reactive helper T cell activity had been generated. These results indicate that helper T cells play a crucial role in preventing effector T cell tolerance. The mechanisms by which tolerance induction in effector T cells is circumvented are discussed in relation to the generation and delivery of signals required for T cell activation.
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PMID:Effect of helper T cells on prevention of tolerance induction in effector T cells responsible for syngeneic tumor immunity. 621 8

We have identified the single phosphorylated tyrosine in p60src, the transforming protein of Rous sarcoma virus, as part of the sequence. NH2-Arg-Leu-Ile-Glu-Asp-Asn-Glu-Tyr(P)-Thr-Ala-Arg-COOH. Therefore, this is a sequence that is recognized efficiently by a tyrosine protein kinase in vivo. Phosphorylation of tyrosine in cellular proteins appears to play a role in malignant transformation by four classes of genetically distinct RNA tumor viruses. Phosphorylated tyrosines in several other proteins resemble of the tyrosine in p60src in that they are located 7 residues to the COOH-terminal side of a basic amino acid and either 4 residues to the COOH-terminal side of, or in close proximity to, a glutamic acid residue. Therefore it is possible that these features play a role in the selection of sites of phosphorylation by some tyrosine protein kinases. However, several clear exceptions to this rule exist.
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PMID:Analysis of the sequence of amino acids surrounding sites of tyrosine phosphorylation. 628 Jan 76


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