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)

Marrow stromal cells are important in normal myelopoiesis and support growth of leukemia/lymphoma (LL) cells in vitro. We have previously described the heterotypic adherence of a human B-lymphoblastic cell line (UTMB-460) to marrow stromal cells (MSC). We have extended these observations to a human T-lymphoblastic cell line (CEM) and characterized the heterotypic adherence of B- and T-lymphoblastic cell lines to human MSC. Electron microscopy demonstrated UTMB-460 cells were in very close apposition to the MSC, but no specific intercellular junctions were noted. Under the conditions employed, these MSC express extracellular fibronectin, collagen types I and IV, intracellular laminin, and vimentin, but no factor VIII-R antigen. In addition, the MSC had receptors for the lectin Ulex europaeus agglutinin I. UTMB-460 and CEM cells do not adhere to extracellular matrix (ECM) proteins secreted by the MSC, i.e., fibronectin, collagen types I, III, or IV, or laminin. Monoclonal antibodies (MoAbs) against CD11a, CD11b, CD18, and CD54 and a polyclonal anti-human fibronectin antibody do not inhibit attachment of either B- or T-lymphoblastic cells to MSC. Peptides GRGES and GRGDS did not inhibit adherence of UTMB-460 and CEM cells to MSC. In contrast, the anti-vascular cell adhesion molecule (VCAM)-1 MoAb (4b9) caused significant inhibition (p < 0.01) of the adherence of both UTMB-460 and CEM cells to normal human MSC monolayers. These data suggest: (1) that MSC to which lymphoblastic cells adhere are specialized mesenchymal cells; (2) that the membrane interactions between T- and B-lymphoblastic cells and MSC involve close apposition of cell membranes of MSC and the lymphoblastic cells; (3) that the heterotypic adherence between B- and T-lymphoblastic cell lines (UTMB-460 and CEM) and MSC does not involve the RGD recognition sequence of the integrin family, the B2 leukocyte integrins, CD44, LAM-1, or the ECM proteins examined; and (4) that VCAM-1 may at least be partially responsible for heterotypic adherence between human MSC and B- and T-lymphoblastic cells.
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PMID:Characterization of heterotypic adherence between transformed human lymphoblastic cells and marrow stromal cells: VCAM-1 is a ligand for one of the leukemia cell adhesion proteins. 128 95

We have previously shown that leukemia/lymphoma (LL) cells adhere to marrow stromal cells (MSC), and MSC induce clonal growth of LL cells. Even though CD11a/18 and CD54 are important in leukocyte and endothelial cell interaction, the literature suggested that these adhesion proteins are not involved in adhesion of hematopoietic stem cells to MSC. We therefore utilized a unique ICAM-1- murine MSC line (MLT) to evaluate the mechanisms of adherence of LL cells (L5178Y and L1210) to MLT. Adherence of LL cells to extracellular matrix (ECM) proteins was also examined. L1210 cells attached to collagen types III and IV, laminin, and fibronectin, but not to collagen type I. L5178Y cells did not attach to any of the ECM proteins tested. The adherence of both L1210 and L5178Y to MSC was unaffected by rat monoclonal antibodies to murine CD11a, CD11b, and CD18. Neoglycoprotein probes, mannosyl-bovine serum albumin (BSA) and galactosyl-BSA, inhibited the adherence of L5178Y and L1210 cells to MSC by 34%-63% of controls at concentrations of 10(-3) and 5 x 10(-3) M. In contrast, fucosyl-BSA had no inhibitory effect on LL cell adherence of MLT. These data suggest that 1) LL cells may adhere to MSC by a lectin mechanism with mannosyl and galactosyl specificities; and 2) other mechanisms of adherence, not yet defined, are also important in this system.
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PMID:Heterotypic adherence between murine leukemia/lymphoma cells and marrow stromal cells involves a recognition mechanism with galactosyl and mannosyl specificities. 134 82

The preliminary results of the LAL-86 protocol applied to 43 patients diagnosed of acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LL) between May 1986 and April 1989 are reported. Induction treatment consisted of one or two courses of vincristine, daunorubicin, prednisone, cytosine arabinoside and 6-thioguanine combination therapy. This phase was followed by consolidation treatment, in which VM-26, cyclophosphamide, BCNU and L-asparaginase were added to the former agents. Central nervous system prophylaxis was done with intrathecal methotrexate. Patients under 45 years of age with HLA identical sibs were subjected to allogeneic bone marrow transplantation (BMT) in the first complete remission (CR); when no HLA-identical sibs were available patients were randomised into autologous BMT or maintenance therapy. The remaining patients received maintenance chemotherapy. CR was achieved in 34 ALL patients (79%), 5 were refractory to treatment and 4 died during remission induction. Allogeneic BMT was carried out in 6 cases, autologous BMT in 3, and the remainders received chemotherapy. When performing this review, 7 patients had relapsed and the actuarial probability of 2-year duration of CR was 70%. Sixteen patients have died with a two-year disease-free survival probability of 60%. The preliminary results of the LAL-86 protocol are encouraging, but greater number of patients is needed, as well as a longer follow-up, to assess the effect of chemotherapy and compare these findings to the results of autologous or allogeneic BMT in the first RC.
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PMID:[Adult acute lymphoblastic leukemia: preliminary results of the LAL-86 protocol]. 233 81

The combinations of tricyclodecan-9-yl-xanthogenate (D 609) with undecanoic acid (C11) and D 609 with myristic acid (C14) were tested in 3 rodent tumor models in vivo. D 609 in combination with C11 or C14 did not show antitumoral efficacy in 3-Lewis lung carcinoma (3-LL) growing in syngeneic C57BL6-mice (primary tumor and metastasis) or in WEHI-3B myelomonocytic leukemia growing in Balb/c mice, when given in a dose range lower than the lethal dose for 10% of the treated animals (LD10). In L 1210 mouse lymphoid leukemia growing in CD2F1 mice the combination of D 609/C11 given intraperitoneally in a concentration of 100 mg/kg for more than 1 day effected a significant difference in the survival curves between the control and therapeutic groups in 1 out of 2 experiments. In conclusion, the treatment schedules of D 609/C11 or D 609/C14 used in this study has not revealed significant therapeutic effects in mouse tumors or leukemias in vivo.
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PMID:Antitumoral activity of a xanthate compound. II. Therapeutic studies in murine leukemia and tumor models in vivo. 275 84

AKR mice, which spontaneously develop greater than 90% incidence of lymphocytic leukemia (LL), crossed with SJL mice, which show greater than 80% incidence of Hodgkin's-like reticulum-cell sarcoma (RCS), produced F1 progeny showing incidences of 30% LL and 0% RCS. Thus, each strain possesses one or more dominant genes capable of interfering with the emergence of the tumor type typical of the other strain. Although mice of reciprocal F1 crosses showed a profound difference in expression of endogenous ecotropic murine leukemia virus (E-MuLV) due to a maternal resistance factor transmitted by SJL females but not males, the two populations did not differ detectably in LL incidence. Like AKR mice, mice of 5 other strains studied (C58, DBA/2, PL, RF and ST/b) possessed one or more genes conferring resistance to RCS in F1 crosses with SJL. Analysis of LL incidences in F1 generations of all possible crosses among these 7 strains revealed 4 different categories of strains with respect to susceptibility/resistance to LL; only ST/b mice, which show no significant incidence of spontaneous LL, lacked genes that could suppress the disease in crosses with high- or moderate-incidence strains. SJL mice treated topically with 3-methylcholanthrene (MCA) developed a 50% incidence of LL, mostly before one year of age; treated mice surviving after one year of age developed a high incidence of RCS.
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PMID:Genetic and epigenetic factors that influence the occurrence of spontaneous lymphoid tumors in crosses of mice of high- and low-incidence strains. 300 Sep 51

Using in situ immunohistological analysis, expression of Leu-8 and its correlation with other B-cell markers were investigated in 21 selected lymphomas of different categories, each one expressing its own typical immunophenotype. These categories included eight follicular centroblastic/centrocytic (CB/CC) lymphomas, eight intermediately differentiated lymphocytic lymphomas (ILL)/mantle zone lymphomas (MZL), and five lymphocytic lymphomas (LL) associated with chronic lymphocytic leukaemia (CLL). Four reactive lymph nodes and three tonsils were also studied using double immunolabelling procedures. Cell suspensions were also performed in three CB/CC and four ILL/MZL cases. Leu-8 was consistently expressed in ILL/MZL and LL but it was absent in most (7/8) CB/CC lymphomas. In reactive tissues, the Leu-8-positive B cells were strictly confined to the mantle zones. A close association emerged between Leu-1 (CD5) and Leu-8, both being present in ILL/MZL and LL but absent in CB/CC. A consistent lack of association was found between Leu-8 or CD5 antigens and common acute lymphoblastic leukaemia antigen (CD10) and BA-2 (CD9) antigen, whereas Leu-8 and CD5 were strictly associated with surface IgD. Reactivity with Leu-8 provides a means of distinguishing between CB/CC and ILL/MZL. Furthermore, shared immunoreactivity for Leu-8 in ILL/MZL and LL may represent a potential clue to the still uncertain cellular derivation of LL/B-CLL.
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PMID:Expression of Leu-8 surface antigen in B-cell lymphomas. Correlation with other B-cell markers. 325 74

Flavone-8-acetic acid (FAA), a new antitumor agent currently undergoing clinical trial, fails to inhibit the growth of early stage Lewis lung (LL) tumors growing in the lung. However, the growth of advanced subcutaneous tumors, arising from inoculation of either the original in vivo LL line or a tissue culture-adapted cell line (LLTC) derived from the LL line was delayed significantly by FAA treatment. Comparison, by clonogenic survival assays, of the cytotoxic effect of FAA on LLTC cells demonstrated that most cell killing occurred between 2 and 8 hours following in vivo exposure but occurred to a much lesser extent and at later times following in vitro exposure. FAA was inactive against LLTC cells growing in vivo in diffusion chambers, suggesting that a host cellular component was necessary for activity. FAA was found to induce hemorrhagic necrosis in the advanced LL tumors, as well as in a number of human tumor xenografts growing in athymic mice. The human cell lines from which the xenografts were derived, as well as the LL tumor lines and P388 leukemia lines, were inhibited by FAA in vitro. However, the ranking of FAA activity in vivo did not parallel that observed in vitro. Together, these observations strongly suggest that FAA has an indirect mode of antitumor action.
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PMID:Effect of flavone acetic acid on Lewis lung carcinoma: evidence for an indirect effect. 335 60

An established in vitro cell line (LLTC), originally derived from the Lewis lung carcinoma (LL), was found to have lost sensitivity to the C-nucleoside antitumor agent tiazofurin (NSC-286193; 2-beta-D-ribofuranosylthiazole-4-carboxamide) both in vitro and in vivo. A new in vitro cell line (LLAK) was derived from LL and compared to LLTC in its growth properties and sensitivity to tiazofurin. LLAK resembled the in vivo tumor in having both a high S-phase fraction and a high rate of cell death at high cell density. In continuous drug exposure growth inhibition assays, the concentration of tiazofurin required to reduce the number of cells in a culture by 50% with respect to control cultures was 0.51 microM for LLAK, 2.6 microM for LLTC, and greater than 10 microM for a range of human cancer cell lines. In cytotoxicity assays involving a 2-hour drug exposure followed by clonogenic assay, tiazofurin was more toxic to LLAK cells than to LLTC cells or L1210 murine leukemia cells, consistent with its high in vivo activity against LL. MM-96 human melanoma cells were highly resistant. Flow cytometry studies indicated that tiazofurin selectively depleted the LLAK cell population of S- and G2-phase cells. In one experiment involving 16 consecutive in vitro passages of LLAK in the absence of tiazofurin, a new line emerged that was resistant to tiazofurin in the clonogenic assay. The results demonstrate the spontaneous emergence of resistance from a tiazofurin-sensitive cell line. If similar processes occur during adaptation of human tumor cells to culture, this may explain the finding of low activity of tiazofurin toward a range of human tumor cell lines.
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PMID:Resistance of cultured Lewis lung carcinoma cell lines to tiazofurin. 347 63

The activity of several clinical agents (5-fluorouracil, methotrexate, adriamycin, daunorubicin, mitoxantrone and amsacrine) and of a number of analogues of amsacrine, including the 4-methyl,5-(N-methyl)carboxamide derivative (CI-921) which is at present in clinical trial, has been compared in vivo against Lewis lung carcinoma (LL) and P388 leukaemia in mice, and against corresponding cell lines in cell culture. All derivatives were active against i.p. inoculated P388 leukaemia whereas only some were active against i.v. inoculated LL cells. The relative in vitro activities in the two cell lines, as measured by growth inhibition (IC50) assays, varied from equitoxic to 26-fold more active with P388 cells than with LL cells. The in vivo activity of these drugs against i.v. inoculated LL relative to i.p. inoculated P388 could be predicted with a high degree of significance from the ratio of in vitro activities in the 2 cell lines. However, this correlation did not appear to reflect cell line selectivity alone, since, when P388 cells were inoculated i.v. rather than i.p., drug sensitivity closely matched that of the LL tumour. This observation suggests a dominant role for pharmacological variables in determining the in vivo activity of amsacrine analogues, and underlines the importance of standardising tumour site in the determination of antitumour spectrum. Nevertheless, the correlation of selective in vitro toxicity for cultured LL cells with high activity against remotely implanted tumours demonstrates the utility of in vitro tests in identifying amsacrine analogues with improved clinical potential.
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PMID:Comparison of in vivo and in vitro drug sensitivities of Lewis lung carcinoma and P388 leukaemia to analogues of amsacrine. 365 85

The modified steroidal alkylating agents, 17 beta-hydroxy-3-aza-A-homo-4 alpha-androsten-4- one(p-[bis(2-chloroethyl)amino]phenyl)butyrate(1),3 alpha-hydroxy- 13,17-seco-5 alpha- butyrate(2),3 beta-hydroxy-13,17-seco-5-androsten-17-oic- 13,17-lactam(p-[bis-(2-chloroethyl)amino]phenyl)butyrate(3) and and (p-[bis(2-chloroethyl)amino]phenyl)butyric acid(4) have been tested against L1210, P388, Ehrlich ascites tumors (EAT), Lewis lung (LL) carcinoma and adenocarcinoma CA-755. Of four compounds evaluated in L1210 leukemia, none displayed antileukemic activity. Almost all of the four compounds were more or less active against P388 leukemia. Compound 2 possesses a slight antitumor activity in EAT, while only compound 1 appears to be active in LL carcinoma. The antitumor activity of the three modified steroidal esters on adenocarcinoma CA-755 seems to be interesting.
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PMID:Further studies on the antineoplastic activity of homo-aza-steroidal esters. 380 65


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