Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular levels of cathepsin B-like cysteine proteinases have been determined in a panel of transplantable mouse leukemias possessing a different potential to metastatize to the liver after i.p. implantation. The higher enzymatic activity observed in L1210 leukemic cells matches their higher capacity for hepatic infiltration. No significant difference is observed for TLX5 lymphoma and P388 leukemia, in spite of their different liver invasiveness, and their enzymatic levels do not significantly differ from that of the non-invasive Ehrlich ascitic carcinoma. The in vivo administration of the antimetastatic drugs ICRF159 and DM-COOK, or of the cytotoxic drugs cyclophosphamide, cisplatin, CCNU and GANU, does not cause a pattern of enzyme inhibition matching the tumor metastatic potential and the increase in life-span of the treated tumor bearing mice, indicating that the inhibition of cathepsin B-like cysteine proteinase is not involved in either their cytotoxic or their antimetastatic action.
 ...
PMID:Activity and inhibition by cytotoxic and antimetastatic drugs of cathepsin B-like cysteine proteinase in transplantable leukemias in mice. 330 99

The int-1 proto-oncogene is the first cellular gene discovered and implicated in tumorigenesis solely on the basis of repeated insertional mutations that activate transcription of the gene. The gene is silent in most tissues but expressed in the embryonic central nervous system, in the late (post-meiotic) stages of spermatogenesis, and in a high proportion of mouse mammary tumor virus-induced carcinomas, when a provirus is inserted upstream or downstream of the coding domain. The functional significance of int-1 in the oncogenic process is supported by the demonstration that murine leukemia virus-based vectors carrying the gene can alter the morphology and growth properties of an established line of mammary epithelial cells. The predicted primary protein product of the int-1 gene is 370 amino acids in length and cysteine-rich; immunoprecipitation with anti-peptide antibodies reveals multiple species of int-1 protein, due to asparagine-linked glycosylations and probable cleavage of a signal peptide. However, the active product of the gene and its biochemical behavior during normal development and mammary tumorigenesis are not known.
 ...
PMID:The int-1 proto-oncogene. 333 19

To verify whether cancer procoagulant (CP), a cysteine proteinase procoagulant distinct from tissue factor (TF), is associated with leukemic cells, we assayed the procoagulant activity of blast cell extracts from 26 patients with different cytological subtypes of acute nonlymphoid leukemia (ANLL) according to the French-American-British classification. All the samples except two shortened the recalcification time of normal human plasma, the effect being significantly greater in the M3 subgroup. The two criteria used to distinguish between CP and TF, independence from factor VII in initiating blood coagulation and sensitivity to cysteine-proteinase inhibitors, were positive in 19 samples from M1, M2, M3, and M4 cytological subtypes. None of the M5 samples fulfilled these criteria. In addition, M1, M2, M3, and M4 samples immunoreacted with an anti-CP goat polyclonal antibody on an Ouchterlony immunodiffusion plate. This study provides the first evidence for a procoagulant other than TF that is associated with leukemic cells.
 ...
PMID:A new procoagulant in acute leukemia. 335 94

Six peptides, representing contiguous amino acid sequences within the C epsilon 2, C epsilon 3 and C epsilon 4 domains of murine IgE, were selected for synthesis on the basis of overall hydropathy, degree of homology to both human and rat IgE and, where possible, inclusion of a native cysteine residue. Antibodies were produced against each peptide by immunizing rabbits with peptide-KLH conjugates. Each anti-peptide antiserum exhibited good reactivity with the corresponding immunizing peptide (titer: 10(-4) to 10(-5] and four of the six antisera exhibited a distinct preferential murine IgE reactivity compared to four other murine immunoglobulin classes (IgG1, IgG2b, IgM and IgA). In addition, one antiserum (anti-epsilon peptide 5), raised against a peptide with 80% homology to human IgE, reacted comparably with both human and murine IgE. Each IgE-reactive antiserum was screened for the ability to stimulate mediator release from IgE-sensitized rat basophilic leukemia (RBL) cells. Two of the four IgE-reactive antisera strongly stimulated 3H-serotonin release (anti-epsilon peptides 4 and 5), one antiserum showed weak activity (anti-epsilon peptide 3) and the remaining anti-peptide serum (anti-epsilon peptide 6), which exhibited the highest anti-IgE reactivity, exhibited no detectable stimulatory activity. Individual anti-peptide antibodies were subsequently tested for the potential to bind to receptor-bound IgE. Anti-epsilon peptide 3 was shown to exhibit the least binding, anti-epsilon peptide 6 showed the highest magnitude of binding while anti-epsilon peptides 4 and 5 exhibited intermediate values. We conclude from this study that sequences defined by epsilon-peptides 4 and 5 are not significantly involved in the receptor binding mechanism whereas epsilon-peptide 3 is likely to be most proximal to the IgE-receptor recognition site of those sequences studied. Finally, we suggest that the epsilon-peptide 6 sequence is in such an orientation in cell-bound IgE that, while it is accessible to external antibody, effective cross-linking of the IgE-receptor complex cannot be achieved through this determinant.
 ...
PMID:IgE structure-function relationships defined by sequence directed antibodies induced by synthetic peptides. 337 91

Murine L1210 leukemia cells resistant to the antineoplastic agent L-phenylalanine mustard have a 1.5-2.0-fold elevation in their cellular GSH and GSSG content as compared to drug-sensitive cells. Cellular uptake of L-[U-14C]cystine and its incorporation into GSH of the resistant tumor are correspondingly elevated. Synthesis of gamma-glutamylcysteine, GSH, and GSSG is elevated 1.5-2.0-fold in cell-free preparations of the resistant tumor. This increased synthesis of GSH is attributed to increased cellular content (1.6-fold) of gamma-glutamylcysteine synthetase. GSH synthetase activity is equivalent in both drug-sensitive and -resistant cells. Investigation into the hydrolysis of selected peptides by cell-free preparations of both sensitive and resistant tumors suggest that aminopeptidase M participates in the formation of L-cysteine from L-Cys-Gly. This is supported by the observation that these preparations readily degrade L-Leu-p-nitroanilide and L-Ala-L-Ala-L-Ala, known substrates for aminopeptidase M, but not dipeptidase. The failure of the tumors to degrade Gly-D-Ala, a dipeptidase substrate, and the marked inhibition of L-Ala-Gly, L-Cys-Gly, and L-Ala-L-Ala-L-Ala hydrolysis by Bestatin further support a role for aminopeptidase M in the generation of L-cysteine from L-Cys-Gly. These results suggest that the drug-resistant tumor cell has developed an efficient mechanism for maintenance of elevated GSH which involves both gamma-glutamyl transpeptidase-initiated catabolism of GSH to cysteine and its reutilization by gamma-glutamylcysteine synthetase.
 ...
PMID:Elevation of glutathione in phenylalanine mustard-resistant murine L1210 leukemia cells. 366 23

Fifteen sulfur-containing compounds were examined for their ability to both protect normal hematopoietic stem cells (NCFU) from the cytotoxic effect of nitrogen mustard (HN2), and potentiate the cytotoxicity of HN2 to AKR leukemia cells (LCFU). All except four agents demonstrated some protection of NCFU with WR-2721 being most active. Five of the agents were also protective for LCFU with cysteine and glutathione being most active. However, a number of agents potentiated the cytotoxicity of HN2 to LCFU, the most active being disulfiram and AET followed by cysteamine, DMSO, WR-638, and WR-3689. The dose-response relationship for the potentiation was defined for DMSO. A second leukemia model, L1210, was also studied for potentiation of HN2 cytotoxicity by four of the most active agents--WR-2721, AET, DMSO, and disulfiram. The first two agents showed no effect (either protection or potentiation) when given either 15 min or 6 hr before HN2 administration. The last two agents, however, potentiated the cytotoxicity to a level similar to that found with the AKR leukemia.
 ...
PMID:Potentiation of nitrogen mustard cytotoxicity to leukemia cells by sulfur-containing compounds administered in vivo. 374 35

Decarbazine (DTIC) is reported to exhibit enhanced clinical toxicity and increased antitumor activity in vitro when exposed to light. Since it was unclear whether light exposure enhanced DTIC antitumor activity or local toxic effects in vivo, a series of experiments was performed in mice given DTIC solutions exposed to light for 2 hours at room temperature. Adenocarcinoma 07/A was implanted by trocar in adult female BALB/c mice. DTIC (50 and 100 mg/kg) was given ip three times per week for 2 weeks. Both drug doses significantly inhibited tumor growth. However, there was no significant difference between light-exposed and -protected drug treatments. In vitro clonogenic assays in L1210 leukemia and Chinese hamster ovary (CHO) cells demonstrated that DTIC cytotoxicity was not increased with light exposure (0.8 J/m2/sec). Both cell lines showed a dose-response relationship to DTIC after 1- or 6-hour exposures in the presence or absence of light. Normal dehaired BALB/c mice were given single intradermal injections of 0.5, 1.75, 5.0, or 10 mg of DTIC in 0.05 ml of saline. Dose-dependent skin ulceration was produced at the 1.75-, 5.0-, and 10.0-mg dose levels. Again, there was no consistent statistical difference in skin ulceration between treatments using light-exposed and -protected DTIC vials. However, when mice were exposed to light following intradermal DTIC, increased skin toxicity was produced (P less than 0.05 by Student-Neuman-Keuls multiple range test). A number of potential local antidotes to DTIC skin ulceration were found to be ineffective. These included: L-cysteine, dimethyl sulfoxide, hyaluronidase, hydrocortisone, and 0.9% saline. Sodium thiosulfate (0.3 M) significantly reduced DTIC skin ulcers as did pre-exposure of DTIC to S-9 rat liver enzymes and NADPH. Neither mild skin heating nor cooling reduced DTIC ulcerations. DTIC appears to synergize with light in vivo to produce increased toxicity. Patients receiving DTIC should avoid intense light exposure after drug injection. However, elaborate precautions to prevent light exposure of DTIC solutions during preparation or injection appear to be unnecessary.
 ...
PMID:Experimental dacarbazine antitumor activity and skin toxicity in relation to light exposure and pharmacologic antidotes. 381 94

Dihydrofolate reductase, purified to homogeneity (as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis), from a subline of L1210 murine leukemia cells resistant to 10(-6) M methotrexate, was resolved into two principal forms (1 and 2) by polyacrylamide gel electrophoresis at pH 8.3 or isoelectric focusing. In the latter procedure, these forms had pI values of 7.4 and 8.2, respectively; both stained for protein and catalytic activity. Form 1 appears to be a single component, comprising ca. 10% of the total protein and at least 20% of the total catalytic activity. It is also more sensitive to inhibition by MTX, more heat-stable, and less susceptible to activation than form 2. Multiple components of 2 were observed by narrowing the pH range in isoelectric focusing, and further resolution was achieved by urea denaturation. Substrate and inhibitor complexes of 1 and 2, differentiated by polyacrylamide gel electrophoresis or isoelectric focusing, provided information about the ability of the enzyme to undergo conformational changes. Interconversion of 1 with one of the components of 2 may also involve conformational isomerism. These conclusions are consistent with the well-known ability of eukaryotic dihydrofolate reductases to exhibit increased catalytic activity (attributed to transformations to more open conformations) when treated with salts, chaotropes, or cysteine-modifying agents. Treatment of the L1210/R6 enzyme preparation with one of these activating agents, 5,5'-dithiobis(2-nitrobenzoic acid), derivatized both 1 and 2 (changing their pI values to 7.3 and 6.9, respectively) and altered the enzyme such that stoichiometric inhibition for MTX was observed.
 ...
PMID:Polymorphism of dihydrofolate reductase from a methotrexate-resistant subline of L1210 cells. 407 99

In avian sarcoma and leukemia viruses, the gag protein p19 functions structurally as a matrix protein, connecting internal components with the viral envelope. We have used a combination of in situ cross-linking and peptide mapping to localize within p19 the regions responsible for two major interactions in this complex, p19 with lipid and p19 with p19. Lipid-protein cross-links were localized near the amino terminus within the first 35 amino acids of the polypeptide. Homotypic protein-protein disulfide bridges were found to originate from near the carboxy terminus of p19, from cysteine residues at amino acids 111 and 153. These results suggest that p19 is divided into domains with distinct functions. The peptide maps constructed for p19, and for the related proteins p23 in avian sarcoma and leukemia viruses and p19 beta in recombinant avian sarcoma viruses, should serve as useful tools for other types of studies involving these proteins.
 ...
PMID:Fine-structure analyses of lipid-protein and protein-protein interactions of gag protein p19 of the avian sarcoma and leukemia viruses by cyanogen bromide mapping. 609 Jun 91

People exposed to type I human T-cell leukemia virus (HTLV-I) develop antibodies to an antigen at the surface of virus-infected cells, designated human T-cell leukemia virus membrane antigen (HTLV-MA). In an earlier study, we demonstrated that the major component of HTLV-MA is gp61, a glycoprotein encoded by the HTLV env gene. In the current study, we found that human antibodies that react with HTLV-MA on cells infected with HTLV-I react equally well with HTLV-MA on C3-44/MO, a target cell infected with type II HTLV. A glycoprotein with an approximate size of 67 kDa, gp67, was identified in C3-44/MO using immunoprecipitation and NaDodSO4/PAGE analysis. The positions of serine and cysteine residues were determined in the amino terminus of gp67 by radiolabel sequencing analysis. Comparison with the amino acid sequence deduced from the primary nucleotide sequence of HTLV-IIMO virus reveals that gp67 is also encoded, at least in part, by the env gene. The gp67 of HTLV-IIMO, like the env gene product of HTLV-ICR, gp61, is recognized both by antibodies from a HTLV-IIMO-infected patient with a variant form of hairy cell leukemia, and by antibodies from patients with HTLV-I-associated adult T-cell leukemia/lymphoma. These results indicate that, despite the divergence between HTLV-I and HTLV-II, the major env gene products of the two types of HTLV are conserved to the degree that they are serologically cross-reactive.
 ...
PMID:Serological cross-reactivity between envelope gene products of type I and type II human T-cell leukemia virus. 609 7


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