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)

Irradiation of whole blood with 137Cs gamma rays intensifies the oxidative burst. Oxidant production was used as an indicator of inflammatory cell reactions and was measured by luminol-amplified chemiluminescence after treatment with inflammatory activators including bacteria, the neutrophil taxin formyl-Met-Leu-Phe, the Ca2+ ionophore A23187, the detergent saponin, and the tumor promoter phorbol ester. The irradiation response is dose-dependent up to about 100 microGy, is detectable within minutes, persists at least 1 h, and is transmitted intercellularly by a soluble mediator. The response is completely inhibited by Ca2+ sequestration in the presence of A23187 or by adenosine, indicating its Ca2+ dependency, and by the phospholipase A2 blocker p-bromphenacyl bromide. However, inhibition by the cyclooxygenase blocker aspirin is sporadic or absent. Blood taken after diagnostic examination of lungs with X rays also exhibited intensified chemiluminescence. These reactions implicate a role for specific amplifying mediator pathways, especially metabolites of the arachidonic acid cascade, in the response: "damage and repair" to cells or DNA plays little or no role. Our results provide evidence for a new mechanism of radiation action with possible consequences for the homeostasis of reactions involving inflammation and second messengers in human health and early development.
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PMID:Ionizing radiation at low doses induces inflammatory reactions in human blood. 196 21

Recently, we provided the first direct evidence that the determinant recognized by some alloreactive cytotoxic T lymphocytes (CTL) clones included an endogenous peptide antigen(s), which could be derived by cyanogen bromide cleavage of cytoplasmic proteins. The studies outlined in this report provide three important findings which confirm and extend our previous results. First, the description of peptide-dependent Kb-specific alloreactive CTL clones is now extended to clones isolated from several responders primed with allogeneic EL4 tumor cells. This indicates that the previously reported results were not unique to the original EL4-primed responder. Second, we establish that peptide-dependent Kb-specific alloreactive CTL clones can be identified after priming with normal allogeneic spleen cells. Thus, induction of peptide-dependent CTL clones is not a unique property of EL4 tumor cells. These results suggest that peptide plays an important role in formation of the allogeneic determinants recognized during graft rejection. Third, these studies reveal that a number of alloreactive CTL clones exhibit cell-type-specific recognition of allogeneic murine target cells. This is consistent with the possibility that some CTL clones recognize peptide antigens that are limited in their tissue distribution. The mechanisms and implications of these findings are discussed.
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PMID:Cell-type-specific recognition of allogeneic cells by alloreactive cytotoxic T cells: a consequence of peptide-dependent allorecognition. 199 85

A polymerase chain reaction-based procedure was used for the detection of DNA length polymorphisms generated by naturally occurring genetic deletions or insertions of known sequence. This method consists of a simple one-step assay that does not require any restriction enzyme analysis or Southern blot hybridization, allowing identification in ethidium bromide-stained gels. The procedure described here was used to detect loss of heterozygosity at various loci, including the Hbb beta-globin gene cluster, in chemically induced mouse skin tumors, using a variety of tissue preparations, including microdissection of formalin-fixed, paraffin-embedded specimens, short-term cultures, and fluorescence-activated cell sorting of epithelial populations. This approach may be useful in detecting tumor-specific reduction to homozygosity at polymorphic chromosomal loci, allowing the mapping of putative tumor-suppressor loci involved in carcinogenesis.
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PMID:Detection of loss of heterozygosity in formalin-fixed paraffin-embedded tumor specimens by the polymerase chain reaction. 199 58

A new type of antineoplastic nucleoside, 2'-deoxy-2'-methylidenecytidine (DMDC) has been synthesized from the corresponding 2'-keto pyrimidine nucleosides 3 and 8 by the Wittig reaction. During the course of the reaction, we found that an intermediate betaine could pick a proton from the excess triphenylphosphonium bromide to form the 2'-phosphonium salts 5 and 10, which could be further converted into the 2'-deoxy-2'-methylidene nucleosides 4 and 9 by treatment with sodium hydride. Various 5-substituted DMDC derivatives 19a-e,h and their uracil congeners 16a-h were also synthesized from the corresponding 5-substituted uridines 12a-f,h. Among them, DMDC as well as 2'-deoxy-2'-methylidene-5-fluorocytidine (19a) showed potent antileukemic activity against murine L1210 cells in culture. The activity of DMDC and 19a toward various human tumor cells in culture compared with 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil was also examined. In vivo antitumor activity of DMDC against L1210 was also described.
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PMID:Nucleosides and nucleotides. 97. Synthesis of new broad spectrum antineoplastic nucleosides, 2'-deoxy-2'-methylidenecytidine (DMDC) and its derivatives. 199 5

The hydrogen acceptor 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) is commonly utilized to estimate cellular viability in drug screening protocols. The present investigation was prompted, in part, by observations that reduction of MTT to its colored reaction product, MTT formazan, varied between cell lines and with culture age. A correlation was established between the D-glucose concentration of the culture medium at the time of assay and the production of MTT formazan for cell lines representing seven tumor histologies. A decrease in the concentration of D-glucose from culture medium was accompanied by a decrease in MTT specific activity (MTT formazan/microgram cell protein) for a number of cell lines. Cells which extensively metabolized D-glucose exhibited the greatest reduction in MTT specific activity. Further evidence that the D-glucose concentration of the culture medium played an important role in MTT reduction was provided by experiments which demonstrated that transfer of cells to a glucose-free medium (L-15) was accompanied by an immediate decrease in MTT reduction which was pH independent. These studies suggested that cellular transport and constant metabolism of glucose were required for maximum MTT reduction. Decreases in the cellular concentration of the reduced pyridine nucleotides NADH and NADPH were accompanied by concomitant decreases in MTT formazan production. MTT formazan varied significantly among cell lines in both the kinetics of its formation and the degree of saturability exhibited. Apparent IC50 values for Adriamycin varied, in a cell line-specific manner, with MTT exposure time. These results indicate that MTT specific activity is significantly influenced by a number of parameters and suggest that assay conditions should be established which minimize their effects.
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PMID:Tetrazolium-based assays for cellular viability: a critical examination of selected parameters affecting formazan production. 202 31

The effect of a reticuloendothelial blockade was examined on the tissue distribution of 99mTc-labeled synthetic liposomes prepared from N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide (N+C5Ala2C12) in Ehrlich solid tumor-bearing mice. While a pre-dose of unlabeled phosphatidyl choline liposomes (natural liposomes) hardly influenced the tissue distribution of N+C5Ala2C12 liposomes, the pretreatment of dextran sulfate depressed the uptake in liver accompanied by increasing that in tumor and other tissues except the stomach. However, the extent of liver depression of N+C5Ala2C12 liposomes by dextran sulfate was lower than that of natural liposomes and the pre-dose of unlabeled natural liposomes had a minor effect on the tissue distribution of N+C5Ala2C12 liposomes compared with that of natural liposomes. In the liver uptake of N+C5Ala2C12 liposomes, it was suggested that Kupffer cell phagocytosis was not the main mechanism.
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PMID:Effect of reticuloendothelial blockade on tissue distribution of 99mTc-labeled synthetic liposomes in Ehrlich solid tumor-bearing mice. 204 8

The interaction of 99mTc-labeled liposomes prepared from synthetic amphiphiles containing amino acid residues with Ehrlich ascites tumor cells in vitro and their tissue distributions in Ehrlich solid tumor-bearing mice were investigated. The amphiphiles used were N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide N+C5Ala2C12), N,N-didodecyl-N alpha-(6-[dimethyl(2-carboxyethyl)ammonio]hexanoyl)-L- alaninamide bromide (CAC2N+C5Ala2C12) and S-[1-carboxy-2- ([2,3-bis(hexadecyloxy)propoxy]carbonyl)ethyl]homocysteine (HcyM-G2C1 6). Most of the radioactivity of N+C5Ala2C12 and CAC2N+C5Ala2C12 liposomes was firmly bound to Ehrlich ascites tumor cells in vitro. On the other hand, the accumulation of three 99mTc-labeled liposomes in the tumor of Ehrlich solid tumor-bearing mice was low (about 1% dose per gram of tissue), and most of the liposomes were taken up highly in the liver and spleen of the tumor-bearing mice. However, the radioactivity of the liposomes in the tumor, especially that of N+C5Ala2C12 and CAC2N+C5Ala2C12 liposomes, decreased more slowly with time than in the liver in up to 24 h after injection, suggesting that these liposomes were hard to separate from the tumor cells.
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PMID:Liposomes prepared from synthetic amphiphiles. II. Their interaction with Ehrlich ascites tumor cells and tissue distribution in Ehrlich solid tumor-bearing mice. 207 67

Daunorubicin (DNR) or doxorubicin (DOX) was modified with one of four "linker reagents" to produce electrophilic drug analogues for synthesis of bioconjugates. Synthesis and characterization of two new reagents [p-isothiocyanatobenzoyl chloride and 3-(p-isothiocyanatophenyl) propionyl chloride] are described here for the first time. Adding one of the new reagents, bromoacetyl bromide, or p-(fluorosulfonyl)-benzoyl chloride in chloroform to an alkaline aqueous solution of DNR (or DOX) provided excellent yields of the corresponding, electrophilic 3'-N-amide analogue. The DNR and DOX analogues were characterized by thin-layer chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy. Bioconjugates were produced with the electrophilic DNR or DOX analogues by mixing them with bovine serum albumin (BSA), mouse IgG, or a monoclonal antibody (OC125, which specifically binds to the CA125 antigen from human ovarian carcinoma). The relative reactivity of the 3'-N-substituents toward protein is p-(fluorosulfonyl)benzoyl greater than phenylisothiocyanato greater than bromoacetyl. Overall, the new phenyl isothiocyanate acid chlorides are superior to p-(fluorosulfonyl)benzoyl chloride or bromoacetyl bromide as reagents with which to produce electrophilic DNR or DOX analogues for conjugation with monoclonal antibodies. The bioconjugates DNR-OC125 and DOX-OC125 are selectively toxic to two human ovarian cancer cell lines in vitro (1) and bind with high specificity to human ovarian tumor sections (2) that express the CA125 antigen.
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PMID:Electrophilic analogues of daunorubicin and doxorubicin. 209 17

The polymerase chain reaction (PCR) was used to develop a simple technique for detecting monoclonality at the DNA level in B lymphocyte populations in formalin fixed, paraffin wax embedded material. Sections were dewaxed and dehydrated, and the DNA was extracted by boiling in water for 45 minutes. A semi-nested PCR was performed to amplify the V-D-J region of the immunoglobulin heavy chain gene. The product was electrophoresed and viewed under ultraviolet light after ethidium bromide staining. Specimens from 26 B cell lymphomas produced a monoclonal band in 24 cases and no amplification in two cases; monoclonality was specific for this disorder. Specimens from seven T cell lymphomas produced no amplification; specimens from nine reactive nodes produced a broad smear of polyclonal material; and specimens from 12 cases of carcinoma produced either no amplification or polyclonal material. As detection of monoclonality is strongly suggestive of neoplastic disease, this technique is likely to be of value in routine diagnosis, because of its speed, simplicity, and applicability to fixed, embedded material.
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PMID:Monoclonality in B cell lymphoma detected in paraffin wax embedded sections using the polymerase chain reaction. 212 87

In medium containing low concentrations of serum, rat 13762NF mammary adenocarcinoma cell lines and clones (MTPa and MTC; isolated from the locally growing tumor) of low metastatic potential to lung did not exhibit a growth response to lung-conditioned medium, whereas a highly metastatic cell clone isolated from a spontaneous lung metastasis (MTLn3) did. The major growth-promoting factor for MTLn3 cells from porcine and rat lung-conditioned media was isolated by using a five-step procedure (anion exchange chromatography, Affi-gel blue affinity chromatography, chromatofocusing, size exclusion chromatography, and preparative native gel electrophoresis). The lung-derived factor that stimulated the growth of highly metastatic MTLn3 cells was a glycoprotein of Mr approximately 66,000 (non-reduced) or Mr approximately 72,000 (reduced) and possessed a pI of 6.9-7.0. It preferentially promoted the growth of lung-metastasizing tumor lines over their poorly lung-metastasizing counterparts in three tumor systems: rat 13762NF mammary adenocarcinoma, murine B16 melanoma, and murine RAW117 large-cell lymphoma. The factor's growth-stimulatory affect was inactivated by reduction or exposure to high temperature (95 degrees C). Although the growth factor appears to be glycosylated, its molecular weight was not altered by treatment with the protein-deglycosylating agent, trifluoromethane sulfonic acid. Cleavage of the protein by cyanogen bromide resulted in the formation of five fragments. Malignant cell response to this lung-derived paracrine growth factor may be important in the successful formation of lung metastases.
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PMID:Purification and characterization of a Mr approximately 66,000 lung-derived (paracrine) growth factor that preferentially stimulates the in vitro proliferation of lung-metastasizing tumor cells. 216 61


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