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)

We have implicated histamine as a mediator of proliferation through its binding to novel intracellular receptors (HIC), closely associated with antiestrogen binding sites (AEBS) in microsomes and nuclei. N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE), is a potent ligand for AEBS/HIC. We now demonstrate that DPPE stimulates in vivo tumor growth (DMBA-induced mammary cancer in Sprague-Dawley rats and L5178Y leukemia in DBA/2 mice) and synergizes with phorbol-12-myristate-13-acetate (PMA) to induce inflammation and mitotic activity in mouse epidermis. Thus, ligands for intracellular histamine receptors may represent a new class of tumor promoting agents; this finding lends new credence to an important role for histamine in growth.
 ...
PMID:Stimulation of in vivo tumor growth and phorbol ester-induced inflammation by N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine HCl, a potent ligand for intracellular histamine receptors. 193 Jan 76

Novel 36 derivatives (6), bonding the phenolic hydroxyl group of 7-ethyl-10-hydroxycamptothecin (4) with diamines through a monocarbamate linkage, were synthesized and their antitumor activity was evaluated in vivo. The derivatives were soluble in water as their HCl salts with the E lactone ring intact and exhibited significant antitumor activity. One of the derivatives, 6-27 showed excellent activity against L1210 leukemia and other murine tumors. The structure of its hydrochloride trihydrate (CPT-11) was determined by spectroscopic and crystallographic methods.
 ...
PMID:Synthesis and antitumor activity of 20(S)-camptothecin derivatives: carbamate-linked, water-soluble derivatives of 7-ethyl-10-hydroxycamptothecin. 193 65

Condensation of 3,4,6-tri-O-benzoyl-2,5-anhydro-D-allonyl chloride (4) with ethyl 2-amino-2-cyanoacetate (5) provided 2-[(3',4',6'-tri-O-benzoyl-2',5'-anhydroallonyl)amino]-2-cyanoa cetate (6). Compound 6 was treated with hydrogen chloride gas to give ethyl 5-amino-2-(2',3',5'-tri-O-benzoyl-beta-D- ribofuranosyl)oxazole-4-carboxylate (8). Reductive dediazotization of blocked nucleoside 8 provided ethyl 2-(2',3',5'-tri-O- benzoyl-beta-D-ribofuranosyl)oxazole-4-carboxylate (10), which after deblocking with sodium methoxide and ammonolysis was converted to 2-beta-D-ribofuranosyl-oxazole-4-carboxamide (oxazofurin, 3), an analogue of the antitumor and antiviral C-nucleoside tiazofurin (1). Oxazofurin (3) was found to be cytotoxic toward B16 murine melanoma cells in culture but inactive against murine leukemia P388 and L1210.
 ...
PMID:Synthesis and antitumor activity of 2-beta-D-ribofuranosyloxazole-4-carboxamide (oxazofurin). 212 Apr 42

The therapeutic efficacy of PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl, was evaluated using the transplantable L1210 leukemia and Ridgway osteogenic sarcoma tumor lines and the spontaneous C3H/StRos mammary tumor and AKR leukemia tumor models. Given in a single i.p. dose at 5-10 mg/kg on day 2 or in two injections of 5-7 mg each on days 2 and 9 to BDf1 mice with peritoneal L1210 leukemia grafts, PTT.119 increased the life spans (ILS) of the population dying of tumor by 94%-313%. In addition, 10% of the mice receiving 7 mg PTT.119 on days 2 and 9 were free of L1210 leukemic grafts when autopsied at the end of the 70-day observation period. The average life span of AKR mice with Ridgway osteogenic sarcoma grafts was significantly increased from 36-40 days to greater than 79 days following one or two s.c. injections of 5, 7, or 12.5 mg/kg PTT.119. Administration of PTT.119 at 14 or 14 and 21 days after tumor graft not only induced regression of palpable tumors but resulted in the absence of grafts in 60%-70% of the mice in several of the treated groups on autopsy at 180 days. In contrast, spontaneous mammary tumors were less susceptible to PTT.119; an ILS of only 15%-38% was observed in C3H/StRos mice, which eventually succumbed to tumor. Nevertheless, the total regression of initial tumors and the absence of further tumor incidence (greater than 180 days) was confirmed by autopsy in 5%-10% of the C3H/StRos mice receiving multiple i.p. injections of 5 or 7.5 mg/kg PTT.119. The drug was highly effective against spontaneous AKR leukemia; multiple s.c. or i.p. injections for a total of 15-40 mg/kg PTT.119 increased the average 25-day life span up to 723% and sustained remission in 9%-40% of the animals for greater than 6 months.
 ...
PMID:Evaluation of p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl against transplantable and spontaneous murine neoplasia. 235 70

An aqueous extract from the marine red alga, Schizymenia pacifica has been tested in a cell free system for its effect on reverse transcriptase from avian retrovirus (avian myeloblastosis virus), and mammalian retrovirus (Rauscher murine leukemia virus). The extract inhibited reverse transcriptase from both these retroviruses but showed almost no effect, if any, on the activity of cellular DNA polymerase alpha and RNA polymerase II in vitro. Consequently it is unlikely to have an adverse effect on the growth of cultured cell. The inhibitory activity of the extract was stable over a relatively wide pH range (pH 1-11) and was not lost after pronase digestion. Inhibitory activity of the extract was lost after boiling at 100 degrees C in 0.67 N HCl, and after treatment with 100 mM NaIO4. The active principle in the extract has an apparent molecular weight in excess of 100,000 daltons. This new reverse transcriptase inhibitor is probably a polysaccharide.
 ...
PMID:Antiretroviral activity in a marine red alga: reverse transcriptase inhibition by an aqueous extract of Schizymenia pacifica. 244 71

A method is described herein for the isolation and quantitation of polyglutamates of the thymidylate synthase (TS) inhibitor N10-propargyl-5,8-dideazafolic acid (CB3717) in tumor cells exposed to the drug in vitro. Cells were incubated with 50 microM 3H-CB3717 for 12 h and then disrupted by sonication. CB3717 and its polyglutamates were extracted by boiling in 0.01 M Tris-HCl pH 10. The extract was concentrated by lyophilization and analyzed by reverse phase HPLC (10 x 0.46-cm Polygosil 5-micron C18 column) using linear gradient elution (5-16% acetonitrile in 0.1 M sodium acetate, pH 5, over 15 min, 2 ml/min). Recovery of radioactivity at each stage of the method was greater than 70%. CB3717 and its polyglutamates were identified by co-chromatography with synthetic standards and by inhibition of partially purified TS. Quantitation was by means of radiochemical analysis. The 3H-CB3717 used in these studies was prepared by catalytic tritiation of diethyl-(2-chloro-4-nitrobenzoyl)-L-glutamate followed by consecutive alkylation with propargyl bromide and 2-amino-6-bromomethyl-3,4-dihydro-4-oxoquinazoline hydrobromide. The free diacid was prepared as required by hydrolysis in sodium hydroxide and purified by HPLC. Tritiation in only one position was confirmed by 3H NMR. Following the exposure of L1210 leukemia cells to 50 microM 3H-CB3717 for 12 h the total cellular radioactivity level was approximately 7 microM, of which 27% was present as polyglutamated metabolites with four and five glutamate residues.
 ...
PMID:Development of an assay for the estimation of N10-propargyl-5,8-dideazafolic acid polyglutamates in tumor cells. 246 Nov 14

A growth-inhibitory (GI) factor, that specifically inhibits the growth of mouse monocytic leukemia cells, was found in conditioned medium of mouse lung tissue, but not in that of mouse brain, heart, liver, or kidney tissue. Conditioned medium of spleen or bone marrow cells had low GI activity. Pulmonary macrophages were as active as peritoneal and bone-marrow-derived macrophages in production of the GI activity. The GI factor inhibited the growth of murine monocytic leukemia cell lines Mm-A and J774.1, but scarcely inhibited the growth of other mouse cell lines, such as a myeloblastic leukemia cell line (M1), a Friend erythroleukemia cell line (745A) and a mammary carcinoma cell line (FM3A). It had no significant effect on the growth of human monocytic leukemia cell lines U937 and THP-1 or on the HL-60 promyelocytic leukemia cell line. These results suggest that the GI factor produced by mouse lung tissue preferentially inhibits the growth of mouse monocytic cells. The GI factor was found to be a proteinaceous substance with a molecular mass of 25 kDa. On chromatofocusing, the GI activity was eluted with Polybuffer 96/acetic acid at pH 7.2-7.5. The GI activity was not significantly decreased by heat treatment at 56 degrees C for 30 min or acid treatment (0.01 M HCl, 14 h), but the GI activity in glycosidase-treated conditioned medium of lung tissue was lost on heat treatment. The GI activity could not be neutralized with anti-(interferon alpha + beta) antibody. The activity was produced constitutively by lung tissues and its production was not stimulated appreciably by lipopolysaccharide, lectin, or poly(I).poly(C). The GI factor appears to be a cytokine unrelated to known cytokines such as tumor necrosis factor, interleukin-1, transforming growth factor beta, and interferons. These results suggest that the GI factor may be involved in negative feedback regulation of macrophage production in steady-state conditions in the lungs.
 ...
PMID:Normal mouse lung tissue produces a growth-inhibitory factor(s) preferential for mouse monocytic leukemia cells. 248 Aug 47

High-(Fc epsilon RI) and low-(Fc epsilon RII) affinity IgE receptors were isolated from surface radioiodinated, Nonidet-P40-solubilized rat intestinal mucosal mast cells (IMMC) and compared with those on rat peritoneal mast cells (PMC) and rat basophilic leukemia (RBL) cells. Fc epsilon RII were isolated by affinity chromatography using IgE-Sepharose or by anti-Fc epsilon RII antisera and protein A-Sepharose. The surface-exposed, IgE-binding alpha subunits of Fc epsilon RI [Fc epsilon RI alpha] were isolated by affinity chromatography using IgE and anti-IgE-Sepharose. Fc epsilon RI alpha on IMMC had an apparent molecular mass of 59 kDa, somewhat larger than that of PMC (51 kDa), RBL-2H3 cells (51 kDa) or RBL-CA10.7 cells (46 kDa). Brief (45 s) incubation of IMMC or PMC in glycine-HCl, pH 3, prior to iodination removed much of the surface-bound IgE. This permitted more thorough labeling of the receptors, but had no affect on the estimate of receptor size. Surprisingly and in contrast to acid-treated PMC, upon anti-IgE-Sepharose isolation acid-treated IMMC yielded an intensely radioactive Fc epsilon RI alpha band in the absence of added IgE. Such a finding suggests that IMMC, more so than PMC, may have an intracellular store of IgE, as has been suggested by many others. IMMC also differed from PMC in the number of forms of Fc epsilon RII isolated; 50-kDa and 58-kDa forms of Fc epsilon RII were obtained from IMMC, whereas PMC yielded most often a single 56-kDa Fc epsilon RII band. These results were mimicked by the two RBL cell sublines: RBL-2H3 cells yielded two Fc epsilon RII (46 kDa and 55 kDa), but only one form of Fc epsilon RII (54-kDa) was obtained from RBL-CA10.7 cells. Thus, the two subtypes of rat mast cells, which have previously been shown to differ in mediator profile and responsiveness to secretagogues and antiallergic drugs, are also distinguished by differences in IgER profile.
 ...
PMID:Isolation and characterization of IgE receptors from rat intestinal mucosal mast cells. 253 Oct 89

New reactions of methyl 2,2-difluoro glycosides are described that were utilized for synthesis of some novel nucleoside derivatives. Thus, treatment of methyl 2-deoxy-2,2-difluoro-3,4-O-isopropylidene-alpha (beta)-D-erythro-pyranoside (2) with anhydrous HCl resulted in selective displacement of one fluorine atom with chlorine to give a 2-deoxy-2-chloro-2-fluoro glycoside 3. Reaction of 3 with silylated uracil in the presence of SnCl4 provided a 2-deoxy-2-fluoro-2-uracil-substituted glycoside 4. 2-Fluoro-2-deoxy glycosides substituted with other pyrimidines at C-2 were prepared similarly by the reaction of acylated 2,2-difluoro or 2-fluoro-2-bromo derivatives (5 and 6, respectively) with silylated pyrimidines. The resulting 2'-fluorinated isonucleosides were evaluated for their antitumor and antiviral activities. Compounds 7a,b, 8a,b, and 10a,b demonstrated 50% tumor cell growth inhibition in vitro (IC50) at 10(-4)-10(-5) M. At similar concentrations no antiviral activity was observed in vitro. Therapeutic activity was obtained with 7a,b and 8a,b in DBA/2 mice with L1210 leukemia. Administration of 7a,b at 500 mg/kg, ip daily, for 5 consecutive days, resulted in a 55% increase in life span (% ILS) while administration of 8a,b in the same manner at 200 mg/kg caused a 29% ILS. Treatment with 7a,b to mice with drug-resistant L1210 sublines (5-FU and araC) resulted in 22 and 57% increases in life span, respectively. Lewis lung carcinoma and M5076 sarcoma in mice also responded to the administration of 7a,b with reductions in tumor growth for both tumors and significant increases in life span in mice with Lewis lung carcinoma. Although the mechanism of action of 7a,b is not known, it has been found to be a relatively fast-acting, cell-cycle nonspecific cytotoxic agent that decreases [3H]deoxyuridine incorporation, blocks L1210 cells at the G2 phase of the cell cycle, and is not reversed by exogenous thymidine. These 2'-fluorinated isonucleosides have demonstrated biological activity and may have potential as antitumor drugs.
 ...
PMID:2'-Fluorinated isonucleosides. 1. Synthesis and biological activity of some methyl 2'-deoxy-2'-fluoro-2'-pyrimidinyl-D-arabinopyranosides. 270 26

We have studied Ag-induced membrane potential changes of rat basophilic leukemia cells by using the potential-sensitive dye, bis-(1,3-diethylthiobarbiturate)trimethineoxonol. A rapid membrane depolarization is triggered by a multivalent Ag, and it has a bell-shaped dose dependence that parallels the degranulation response but not the extent of cross-linking of the IgE-receptor complexes. As the temperature is reduced from 37 degrees C, this depolarization response slows and decreases in magnitude until complete inhibition is observed at 15 degrees C, similar to the temperature dependence previously observed for the Ag-stimulated rise in cytoplasmic Ca2+ and for degranulation. The results imply that a highly temperature-dependent step subsequent to Ag binding and cross-linking is necessary for the depolarization response. A partial return to the resting potential is seen to follow the depolarization response to Ag. This repolarization process is inhibited by quinidine.HCl and Ba2+ in parallel with an inhibition of the degranulation response. Repolarization is not affected by 4-aminopyridine or by the absence of K+ in the external buffer. These data suggest that the repolarization is caused by a previously uncharacterized K+ channel.
 ...
PMID:Antigen-triggered membrane potential changes in IgE-sensitized rat basophilic leukemia cells: evidence for a repolarizing response that is important in the stimulation of cellular degranulation. 290 16


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