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

Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was essentially unaffected. A potent inhibitor of PKC, staurosporin, inhibited both moAb- and PMA-induced aggregation responses. The aggregation responses were completely inhibited by low temperatures, cytochalasins B and E, and partly inhibited by EDTA and CD18 moAbs, but unaffected by aphidicolin, mitomycin C, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through CD11a-dependent and independent adhesion pathways.
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PMID:Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion. 128 78

Normal and malignant plasma cells were investigated for the expression of seven cellular adhesion molecules by immunofluorescence microscopy. The antigens investigated were CD2 and its ligand, LFA-3 (CD58). LFA-1 alpha (CD11a) and LFA-1 beta (CD18) and their ligand ICAM-1 (CD54), H-CAM (lymphocyte homing receptor; CD44) and N-CAM (CD56). Marrow from 18 patients with myeloma, two with plasma cell leukaemia (PCL), four with monoclonal gammopathy of uncertain significance (MGUS) and 10 normal allogeneic bone marrow donors was studied. All plasma cells from normals and multiple myeloma patients were negative for CD2, CD11a and CD18. All normal and myeloma marrow plasma cells were positive for ICAM-1. 16/18 myeloma cases tested, and all other samples (normal, MGUS and PCL), contained plasma cells positive for H-CAM. Only one normal, but 12/16 myelomas tested were positive for N-CAM (P less than 0.02). One of four MGUS cases was moderately positive and one other weakly positive for N-CAM. Both PCLs were N-CAM negative. 12/18 myelomas were positive for LFA-3, but only two normals (P less than 0.05). All MGUS cases were negative for LFA-3, as was one PCL, the other being weakly positive. Three cases were negative for both adhesion molecules, three cases expressed only N-CAM or LFA-3 and 10 cases expressed both. LFA-3 and N-CAM are expressed significantly in myeloma rather than normal plasma cells. Cases of MGUS may express N-CAM but not, in this small series, LFA-3. Plasma cells in the peripheral blood (PCL) and plasma cell lines express little or no LFA-3 or N-CAM.
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PMID:Expression of adhesion molecules LFA-3 and N-CAM on normal and malignant human plasma cells. 138 43

Human myeloma plasma cells had been considered to express few surface antigens until recently. The past two International Workshops on Leucocyte Differentiation Antigens have shown that myeloma cells can express a range of surface molecules, and it has become clear that many of these have adhesive functions. The identification of ICAM-1 (CD54) and H-CAM (CD44) on human plasma cells was the initial observation, and other antigens such as N-CAM (CD56) and LFA-3 (CD58) have been confirmed as features of malignant plasma cells in particular. The degree of expression of LFA-1 (CD11a) remains to be characterised fully. It seems probable that the loss of some adhesion structures may be associated with increased malignancy and plasma cell leukaemia. At the present time there are few studies relating to the function of these molecules, although homotypic adhesion appears to occur, and it is likely that such studies will shed light on the pathogenesis of myeloma.
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PMID:The role of adhesion molecules in multiple myeloma. 149 Jan 46

Several mouse aldehyde dehydrogenases catalyze the detoxification of aldophosphamide, the pivotal metabolite of the prodrugs cyclophosphamide, mafosfamide, and other oxazaphosphorines. N-Isopropyl-p-formylbenzamide, a major metabolite of procarbazine, was found to be an excellent substrate (Km = 0.84 microM) for at least one of these enzymes, namely, mouse aldehyde dehydrogenase-2. The Km for mouse aldehyde dehydrogenase-2-catalyzed detoxification of aldophosphamide is 16 microM. Thus, competition between N-isopropyl-p-formylbenzamide and aldophosphamide for the catalytic site on the enzyme should strongly favor the former, and the rate at which aldophosphamide is detoxified should be markedly retarded. Mouse L1210/OAP and P388/CLA leukemia cells are relatively insensitive to the oxazaphosphorines because they contain large amounts of mouse aldehyde dehydrogenase-2. As predicted, N-isopropyl-p-formylbenzamide markedly potentiated the cytotoxic action of mafosfamide against these cells. Mouse L1210/0 and P388/0 lack the enzyme. Again as expected, N-isopropyl-p-formylbenzamide essentially did not potentiate the cytotoxic action of mafosfamide against these cells. Certain mouse and human hematopoietic progenitor cells also contain an aldehyde dehydrogenase that catalyzes the detoxification of aldophosphamide, but the specific identity of this enzyme remains to be established. N-Isopropyl-p-formylbenzamide potentiated the cytotoxic action of mafosfamide against these cells as well. Clinically, procarbazine and the oxazaphosphorines are used to treat certain neoplastic diseases. Frequently, they are used in combination. Our findings demonstrate the potential for both desirable and undesirable drug interactions when these agents are used concurrently. Similar drug interactions can be expected when other substrates for, or inhibitors of, the relevant aldehyde dehydrogenases, e.g., chloramphenicol, chloral hydrate, and methyltetrazolethiol-containing cephalosporins, are co-administered with the oxazaphosphorines.
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PMID:Potentiation of the cytotoxic action of mafosfamide by N-isopropyl-p-formylbenzamide, a metabolite of procarbazine. 186 38

A panel of antibodies recognising lymphoid and epithelial antigens in formalin fixed, paraffin embedded sections was applied to a series of 54 bone marrow trephines decalcified by formic or edetic acids. Normal trephines and cases infiltrated by myeloid, lymphoid, and epithelial tumours were included. Patterns of reactivity were distinct and allowed the different diseases to be distinguished. All lymphoid tumours expressed leucocyte common antigen, with B cell tumours staining with MB1 and MB2, and T cell tumours staining with MT1 and UCHL1. T cell acute lymphoblastic leukaemia (ALL)/lymphoblastic lymphoma all stained with MT1, but some were negative with UCHL1. B cell ALL/lymphoblastic lymphoma also stained with MT1, but could be distinguished by its reactivity with MB1 and MB2. Reed-Sternberg cells did not stain with any reagent. Normal and neoplastic myeloid cells stained with MT1. Carcinomas stained with CAM 5.2 but were negative for lymphoid markers except MB2 staining in some cases. A case of neuroblastoma could be distinguished from ALL/lymphoblastic lymphoma by its lack of reactivity with all antileucocyte antibodies and its staining with antineurone specific enolase. Although not ideal, if used together, this panel of reagents may usefully be applied to routinely fixed and processed, decalcified bone marrow trephines.
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PMID:Demonstration of lymphoid antigens in decalcified bone marrow trephines. 330 63

A newly synthesized mycophenolic acid (MPA) derivative, ethyl O-[N-(p-carboxyphenyl)-carbamoyl]-mycophenolate (CAM, NSC-297879D) was tested for antitumor activity, when given orally, against transplantable murine tumors. The compound was markedly effective against transplantable murine tumors. The compound was markedly effective against leukemia P388 and L1210, lymphoma L5178Y, mastocytoma P815 and sarcoma Meth-A, moderately effective against sarcoma-180, C3MC2 and BAMC1, Ehrlich carcinoma, Lewis lung carcinoma and melanoma B16 and marginally effective against hepatoma MH134. The antitumor effects were manifested not only in growth inhibitory effects on subcutaneously transplanted tumors but also in the prolongation of life span of mice int which the tumors had been inoculated intraperitoneally or subcutaneously. The growth of primary transplants of a mammary tumor which developed spontaneously in a C3H/He mouse was inhibited by consecutive administration of CAM frm the 34th day after the transplantation. Oral CAM was more potent than its mother compound, MPA, in the tumor models examined. These results indicate that orally administered CAM has a wide antitumor spectrum.
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PMID:Antitumor activity of a new compound, ethyl O-[N-(p-carboxyphenyl)-carbamoyl]-mycophenolate, against various experimental tumors upon oral administration. 727 50

The CA (capsid) protein of avian sarcoma and leukemia viruses occurs in multiple species. Only one form has been previously characterized biochemically. We have now determined that the mature CA protein of avian sarcoma and leukemia viruses exists as three species with different C termini, ending in amino acid residues A-476, A-478, and M-479 of the Gag precursor, respectively. These structures were deduced from a combination of cyanogen bromide peptide mapping, sequence analysis of tryptic peptides, and electrospray mass spectrometry. The three forms of CA were detected in the same ratios in Rous sarcoma virus and avian myeloblastosis virus and therefore are likely to represent a common feature of members of this genus of avian retroviruses. The only previously reported CA species, CAM-479, accounts for only about 36% of the total CA protein, while CAA-476 and CAA-478 account for 55 and 9%, respectively. From the analysis of peptides cleaved in vitro by PR, the viral protease, we infer that the cleavage site between A-476 and A-477 not only is recognized by PR but is the preferred site. We were unable to determine if A-478/A-479 is a cleavage site for PR or alternatively if CAA-478 results from further processing of CAM-479 by a carboxypeptidase. To study the biological significance of residues A-477 to M-479, we constructed genetically altered viruses in which deletions removed either residues 477 to 479 or 477 to 488. The resulting virus particles appeared to assembly with normal efficiencies, but the latter mutant showed slowed proteolytic processing. Neither of the mutants was infectious.
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PMID:Differential proteolytic processing leads to multiple forms of the CA protein in avian sarcoma and leukemia viruses. 766 44

To investigate whether the lymphocyte homing receptors, adhesion molecules regulating normal lymphocyte traffic, influence the dissemination of lymphoma cells, 24 lymphoma/leukemia cell lines were inoculated into SCID mice subcutaneously, and the correlation between the expression of the adhesion molecules and the metastatic potential of the cell lines was examined. Among the six adhesion molecules examined (LFA-1, ICAM-1, CLA, VLA-4, L-selectin and CD44), L-selectin increased the incidence of lymph node metastasis, and CD44 expression was related to both lymph node and organ (hematogenous) metastasis. A monoclonal antibody to the standard form of CD44 (CD44s), Hermes-3, inhibited the local growth and remote metastasis of CD44+ cell lines. Thus, it is concluded that at least CD44s expression is important in both lymphatic and hematogenous metastasis.
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PMID:Metastatic potential of lymphoma/leukemia cell lines in SCID mice is closely related to expression of CD44. 895 66

An immortalized implantation site intermediate trophoblastic cell line, IST-1, was established from a human placenta of 7 weeks gestation. IST-1 cells phenotypically resembled the implantation site intermediate trophoblastic cells in situ and expressed Mel-CAM (MUC 18 or CD146). Mel-CAM is a cell adhesion molecule belonging to the immunoglobulin gene superfamily. It is involved in heterophilic cell-cell adhesion and plays a role in several biological processes including tumor progression. We have previously shown that Mel-CAM was highly expressed in the intermediate (extravillous) trophoblast in the human implantation site. In this study we determined the function of Mel-CAM in the interaction of trophoblast and uterine smooth muscle in the implantation site. IST-1 cells failed to adhere to immobilized recombinant Mel-CAM in solid phase whereas the uterine smooth muscle cells did. The presence of the putative Mel-CAM ligand in smooth muscle cells was further supported by the finding that Mel-CAM-transfected but not the mock-transfected U937 leukemia cells bind to the confluent monolayer of uterine smooth muscle cells. IST-1 cells attached efficiently to the monolayer of the uterine smooth muscle cells and acquired a spindle-shaped morphology simulating smooth muscle cells. The cell binding was only marginally affected by Mel-CAM blocking antibodies. However, Mel-CAM blocking antibodies and recombinant Mel-CAM promoted cell migration from IST-1 cell spheroids on the smooth muscle monolayer. Taken together, our results suggest that IST-1 cells express Mel-CAM but not the putative Mel-CAM ligand. In contrast, the uterine smooth muscle cells express the putative Mel-CAM ligand which binds to Mel-CAM on the surface of the IST-1 cells. The interaction between Mel-CAM and its putative ligand confers a stationary phenotype for trophoblastic cells. These observations are consistent with an important role for Mel-CAM in limiting trophoblastic migration within the myometrium in the implantation site.
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PMID:Expression of Mel-CAM in implantation site intermediate trophoblastic cell line, IST-1, limits its migration on uterine smooth muscle cells. 970 64

Two elderly patients with chronic myelomonocytic leukemia were treated with cytosine arabinoside (Ara-C) and aclarubicin (ACR) under simultaneous administrations of macrophage colony-stimulating factor (M-CSF) (CAM), and both obtained good responses. Examination of apoptosis using flow cytometry revealed induction of apoptotic death of leukemia cells by CAM in Patient 2, while neither induction of apoptotic death of leukemia cells nor clinical response were seen with CAG (Ara-C, ACR, and granulocyte colony-stimulating factor) given prior to CAM in Patient 1. These findings suggested that chemotherapy combined with simultaneous administration of M-CSF could effectively reduce monocytic leukemia cells by inducing programmed cell death.
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PMID:Priming effects of macrophage colony-stimulating factor on monocytic leukemia cells in combination with chemotherapy: induction of programmed cell death in vivo. 1078 4


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