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

Southern blot analysis was employed to analyze the structural alterations of the c-myc oncogene in genomic DNA derived from tumor specimens of 35 adults with pathologically classified and immunophenotyped non-AIDS-related, non-Hodgkin's lymphoma in Japan. In this study, seven cases (20%), including one peripheral T-cell lymphoma and six B-cell lymphomas of various histological types, were demonstrated to have additional c-myc fragments. An interesting feature is that c-myc rearrangements were found in three out of eight primary gastrointestinal lymphomas. Analyses with several restriction enzymes revealed that the breakpoints in these cases were clustered in a region spanning the first exon, first intron and nearby 5'-flanking sequences of the c-myc gene, suggesting that the alteration of this region may represent an important molecular event in activating the oncogenic potential of the c-myc gene.
Leukemia 1991 Jun
PMID:Genomic rearrangement of the c-myc proto-oncogene in non-AIDS-related lymphoma in Japan. 205 71

Plasma and tumor cells from 103 patients with leukemia or lymphoma at initial presentation were investigated for the presence of plasminogen activator inhibitor-2 (PAI-2) antigen, a potent inhibitor of urokinase. PAI-2 was detected in plasma and leukemic cells of the 21 patients with leukemia having a monocytic component [acute myelomonocytic (M4), acute monoblastic (M5), and chronic myelomonocytic leukemias], and in the three patients with acute undifferentiated myeloblastic leukemia (M0). In contrast, this serine protease inhibitor was undetectable in 79 patients with other subtypes of acute myeloid leukemia or other hematological malignancies. Serial serum PAI-2 determinations in 16 patients with acute leukemia at presentation, during therapy, remission, and relapse revealed that in the five patients with M4-M5, elevated PAI-2 levels rapidly normalized under therapy and during remission, but increased again in the patients with a relapse associated with an M4-M5 phenotype. Thus, PAI-2 seems to be a marker highly specific for the active stages of monocytic leukemia, i.e. presentation and relapse. The presence of PAI-2 in the plasma and cells of patients with M0 may give a clue to a monocytic origin of these cells.
Leukemia 1991 Jun
PMID:Plasminogen activator inhibitor-2 in patients with monocytic leukemia. 205 72

Leukemia-specific human antibody was detected in a child with acute lymphoblastic leukemia (ALL) treated with chemoimmunotherapy. Chemoimmunotherapy consists of standard chemotherapy and subcutaneous injections of irradiated ALL cells with a biological response modifier. This ALL-specific serum reacted in 60 out of 67 (89.5%) children with ALL and was not reactive with normal cells. Furthermore, this ALL-specific serum showed a different immunofluorescent pattern on dual staining as compared with J-5 monoclonal antibody directed for common ALL antigen (CALLA; CD10). J-5 did not block the reactivity of ALL-specific serum, and vice versa, when CD10-positive ALL cell lines were used as targets. These findings suggest the possibility that there exists an ALL-specific antigen(s) which is different from CALLA and that this antigen(s) elicits a tumor-specific antibody response.
 ...
PMID:Leukemia-specific serum from a child showing an immunofluorescent pattern distinct from J-5 monoclonal antibody directed for CD10 (common ALL antigen). 209 9

Meta-iodobenzylguanidine (MIBG) is a guanidine analogue of the neurotransmitter norepinephrine. Radioiodinated [131I]MIBG is clinically used as a tumor-targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. Moreover, non-radiolabelled MIBG exerts several cell-biological effects, tentatively ascribed to interference with cellular mono(ADP-ribosyl) transferases (Smets, L.A., Bout, B. and Wisse, J. (1988) Cancer Chemother. Pharmacol. 21, 9-13; Smets, L.A., Metwally, E.A.G., Knol, E. and Martens, M. (1988) Leukemia Res. 12, 737-743). In the present study it was investigated whether MIBG could serve as an acceptor for the ribosyl transferase activity of cholera toxin and of erythrocyte membranes. MIBG appeared a substrate for the cholera toxin-catalyzed transfer of the ADP-ribose moiety of NAD to arginine-like residues with the highest affinity for this enzyme reported as yet (Km = 6.5 microM). MIBG was also ADP-ribosylated by the mono(ADP-ribosyl)transferase(s) of turkey erythrocyte membranes. Moreover, the drug appeared a potent affector of the ADP-ribose linkage to membrane proteins by these enzymes. Interference by MIBG was stronger than by related guanyltyramine, the monoamine precursors of MIBG, meta-iodobenzylamine had no effect at all. In contrast, the drug failed to affect endogenous, O-linked poly(ADP-ribose) polymerase, induced in nuclei of S49-leukemia cells by deoxyribonuclease. Since MIBG is the first described drug that specifically interferes with the cellular N-linked mono(ADP-ribosyl) transferase reactions, it may be an important tool to elucidate the physiological role of this posttranscriptional protein modification.
 ...
PMID:Meta-iodobenzylguanidine (MIBG), a novel high-affinity substrate for cholera toxin that interferes with cellular mono(ADP-ribosylation). 210 58

The inhibitors of C1q biosynthesis and secretion, 3,4-dehydro-DL-proline (DHP) and 2,2'-dipyridyl, were previously shown to suppress murine macrophage FcR-dependent phagocytosis and cytolysis of IgG-opsonized RBC targets. Inasmuch as non-antibody macrophage activators also bind C1q to initiate C1 activation, we determined the effects of these same inhibitors of C1q biosynthesis on activation of macrophages for antibody-independent, nonspecific tumor cytotoxicity by lipid A and a variety of other non-antibody activators. Preexposure of mouse inflammatory peritoneal macrophages to either DHP (0.5 to 2.5 mM) or 2,2'-dipyridyl (0.1 to 0.3 mM) for 24 h produced a dose-related suppression of their response to activation by lipid A to mediate tumor cytotoxicity of L1210 mouse leukemia targets. Inhibition of C1q secretion by DHP-treated macrophages was confirmed both by a complement hemolytic assay and by autoradiographic analysis of [35S]methionine-labeled culture supernatants. DHP-treated macrophages were inhibited in their response to direct activation and triggering of IFN-gamma-primed macrophages by lipid A, Poly I:C, and cobra venom factor for tumor cytotoxicity. DHP inhibited macrophage activation for antibody-dependent cellular cytotoxicity of L1210 tumor targets mediated by antitumor target IgG. The addition of exogenous purified C1q (2 micrograms/ml) to macrophages after DHP treatment, reconstituted their response to activation for both antibody-independent and antibody-dependent tumor cytotoxicity. Our results indicate that C1q synthesis and secretion by effector macrophages is a prerequisite for the initiation of their activation by both immune complex and by non-antibody agents that also bind C1q. It now appears that macrophage-derived C1q may act as an auxiliary amplification signal for autocrine-like modulation of the initiation of macrophage activation by both the antibody-dependent and independent pathways.
 ...
PMID:Inhibitors of C1q biosynthesis suppress activation of murine macrophages for both antibody-independent and antibody-dependent tumor cytotoxicity. 210 57

The Friend helper leukemia virus (F-MuLV) induces in mice leukemias of the erythroid, lymphoid, and myeloblastic lineages. Erythroleukemic cell DNAs were examined for genetic alterations at loci described as common proviral integration regions in MuLV-induced myeloid or lymphoid leukemias or in Friend complex-induced erythroleukemias. No alteration of the Fim-1, Fim-2, Fim-3, pvt-1, and Spi-1 loci were detected in 17 erythroleukemias, p53 gene rearrangement was observed in 6 (30%) erythroleukemias and was always associated with a loss of the germ line allele. Interestingly, genetic alterations were also detected at two loci, c-myc and Pim-1, previously described as common provirus integration regions in T lymphoid leukemias. Rearrangements of these two genes were often associated with p53 gene alteration within the same tumor.
Leukemia 1990 Aug
PMID:Rearrangements of the Pim-1, c-myc, and p53 genes in Friend helper virus-induced mouse erythroleukemias. 214 96

The Friend viruses, like the Rauscher virus, cause murine acute erythroleukemias which evolve in a similar multistep process. In previous studies it has been described that the late malignant proerythroblastic transformation induced by the polycythemia-inducing strain of Friend spleen focus-forming virus (SFFVP) is correlated with Spi-1 oncogene activation by insertional mutagenesis. In this paper we report that Spi-1 genomic rearrangements were also observed in 90% of tumors induced by the anemia-inducing strain of Friend spleen focus-forming virus (SFFVA) and in all Rauscher-induced tumors analyzed. SFFVA and Rauscher proviral insertions occurred in the viral integration cluster previously characterized in SFFVP-induced tumors. The Spi-1 1.4-Kb messenger RNA was found highly expressed in all SFFVA and Rauscher-induced malignant cells as compared to normal tissues. The nucleotide sequence of Spi-1 cDNA isolated from a library constructed from SFFVA-induced tumor cells revealed no difference between the Spi-1 gene transcripts expressed in both SFFVP and SFFVA-induced leukemic cells. These results indicate that Spi-1 gene activation is a general feature in the malignant proerythroblastic transformation which occurs in mice infected with Friend and Rauscher viruses.
Leukemia 1990 Jan
PMID:Spi-1 oncogene activation in Rauscher and Friend murine virus-induced acute erythroleukemias. 215 62

The role of B ecotropic recombinant retroviruses in the emergence and the progression of radio-induced thymic lymphomas was evaluated by analyzing the cell populations present in nine primary and in in vivo propagated tumors. For this, tumor DNAs were analyzed by the Southern method using probes specific for newly acquired proviral sequences, T-cell receptor beta-chain, and immunoglobulin heavy chain genes. Our results show that primary radio-induced tumors are composed of several tumoral cell clones but do not support that malignant cell transformation and proliferation are conferred, solely, by the newly acquired ecotropic recombinant retroviral sequences.
Leukemia 1990 Apr
PMID:Identification of malignant cell clones in radio-induced murine thymic lymphomas by viral and cellular probes. 216 22

A study of treated murine acute myeloid leukemia (AML) with an emphasis on the bone marrow stromal function is reported. Leukemia was induced in C57Bl mice through intraperitoneal (i.p.) inoculation of C-1498 myelogenous leukemic cells. The leukemic mice were administered: (1) total body lethal X-irradiation (t.b.i.); (2) two i.p. cytosine-arabinoside (Ara-C) injections followed by X-irradiation. Control mice received similar regimens. Bone marrow of experimental and control mice was processed for stromal cell cultures (SCC) and in vitro engraftment of hematopoietic cells onto the cultures. The results of this study indicate that the bone marrow stromal deficiency which occurs in leukemia is aggravated by Ara-C and irradiation treatments. Moreover, SCC of treated leukemic mice sustain in vitro hematopoiesis only to a limited degree. Stromal deficiency, as possible cause for graft failure in bone marrow transplanted leukemic patients, is discussed.
Med Oncol Tumor Pharmacother 1990
PMID:Cumulative bone marrow stromal damage caused by X-irradiation and cytosine-arabinoside in leukemic mice. 218 23

The synthetic ether lipids ET-18-OCH3 and BM41.440 and a derivative, hexadecylphosphocholine, were tested for inhibition of [3H]-thymidine uptake into a Chinese hamster ovarian cell line (AUXBl) and its multidrug-resistant subline selected for colchicine resistance (CHRC5). The activity of all three compounds against the multidrug-resistant subline was equal to or higher than that against the parent line. The same result was found for their activity against a human leukemic lymphoblastic cell line (CEM/O) and its methotrexate-resistant subline (CEM/MTX). In contrast, two multidrug-resistant cell lines selected for resistance to Adriamycin, the mouse leukemia cell line P388/ADR and the murine sarcoma cell line S180/ADR, expressed modest cross-resistance to the lipids as measured by thymidine uptake. Experiments performed using the trypan-blue dye-exclusion assay yielded comparable results, although this system revealed a slightly different sensitivity in showing the cytotoxicity of the drugs. By this assay, modest cross-resistance for ET-18-OCH3 and BM41.440 to Adriamycin was found only after 24 h incubation and decreased after 48 h incubation, with almost equal sensitivity to both drugs being shown by the parental (P388/W) and resistant lines (P388/ADR). Furthermore, findings from a human tumor-cloning assay were in accordance with these data, although they did not indicate cross-resistance for the P388/ADR cell line. These results suggest that certain ether lipids and derivatives might represent valuable anticancer drugs warranting further study in the setting of resistant disease.
 ...
PMID:Cross-resistance pattern of cell lines selected for resistance towards different cytotoxic drugs to membrane-toxic phospholipids in vitro. 222 15


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