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)

Antitumor activity against the Lewis lung carcinoma in mice is reported for the series of 36 acridine-substituted derivatives of the antileukemia agent amsacrine. This series is the one from which the analogue N,5-dimethyl-9-[(2-methoxysulfonylamino)phenylamino]-4-acridinecarboxamide (CI-921), presently in clinical trial, was chosen. The analogues also were tested in vitro by comparing growth inhibition data [IC50 values (concentration required to reduce growth of cultured cells to 50% of that of untreated cultures)], using L1210 murine leukemia cells and HCT-8 human colon carcinoma cells. Determined IC50 values were highly dependent on the culture medium used, and it was found that the presence of ascorbate in the medium had a major effect on the stability of compounds to oxidation. A survey of 115 analogues of amsacrine indicates that a low ratio of IC50 values (HCT-8/L1210) is necessary but not sufficient for good antitumor activity against the solid tumor. DNA binding constants did not in themselves predict activity, although they were related to dose potency. Other factors, such as drug lipophilicity, acridine base strength, and drug solubility, also are involved, probably in providing effective drug distribution. It is concluded that in vitro assay data provide information useful for drug design but that other factors also are important for in vivo activity.
 ...
PMID:Derivatives of amsacrine: determinants required for high activity against Lewis lung carcinoma. 334 11

Derivatives of the DNA-intercalating agent N-[2-(dimethylamino)ethyl]phenanthridine-4-carboxamide have been prepared and shown to have moderate in vivo antitumor activity against both the P388 leukemia and Lewis lung carcinoma. This demonstrates that the effective pharmacophore in the broad class of tricyclic carboxamides is not limited to linear tricyclic chromophores. Both 7 and the 6-phenyl derivative 10 have identical DNA binding properties, suggesting that the phenyl ring of 10 is not involved in the DNA intercalation site. A series of phenyl-substituted derivatives of 10 was evaluated. Aza substituents led to compounds with the highest in vivo cytotoxicity and in vivo P388 activity, but the in vivo solid tumor activity of the substituted 6-phenylphenanthridine-4-carboxamides was in general low.
 ...
PMID:Potential antitumor agents. 55. 6-Phenylphenanthridine-4-carboxamides: a new class of DNA-intercalating antitumor agents. 335 55

Flavone acetic acid (FAA) is a new antitumor agent with broad activity against transplantable solid tumors of mice but with only scant or no activity against leukemias and lymphomas. The technique of alkaline elution was used to study DNA lesions in s.c. implanted Glasgow osteogenic sarcoma in C57BL/6 x DBA/2 F1 mice treated i.v. with FAA. At efficacious dosages (235 and 200 mg/kg), FAA produced extensive single strand breakage. Formation of single strand breaks was dependent on time of assay after exposure to FAA with only minimal damage occurring prior to 5 h posttreatment. Apparently Glasgow osteogenic sarcoma had no capacity to repair single strand breaks for at least 45 h after drug administration. Thus, FAA differs in its mechanism from other scission agents (e.g., VP-16). Neither interstrand cross-links nor DNA-protein cross-links were detected. DNA single strand breaks did not occur in the bone marrow cells or in the unresponsive P388 leukemia cells at dosages causing extensive DNA damage in solid tumor cells.
 ...
PMID:Flavone acetic acid (NSC 347512)-induced DNA damage in Glasgow osteogenic sarcoma in vivo. 342 92

Rapid in vivo growth of cultured human cancer or leukemia cells was achieved by implantation into the subrenal capsule of mice. A solid structure, necessary for accurate implantation and measurement of tumor growth in this model, was provided by stepwise addition of fibrinogen and thrombin to the tumor cells, leading to rapid enzymatic formation of a solid tumor-fibrin matrix. Human leukemia and epithelial cancers increased in volume between 6- and 40-fold when measured 6-10 days after implantation into normal or immunosuppressed mice. Immunosuppression of host CD-1 mice was achieved by cyclosporine given daily after tumor implantation, cyclophosphamide given preimplantation combined with cyclosporine, or whole-body irradiation given preimplantation. Confirming the validity of tumor measurements, tumor histology in the immunosuppressed mice revealed cell proliferation, invasion, and neovascularization. Similarly, no artifactual measurement of tumor growth was observed by nonviable cancer cells, implanted after in vitro exposure to a known cytotoxic concentration of thiotepa. This model provides an economical, short-term technique for the in vivo study of human tumor growth, for the evaluation of new cancer therapies, and for in vitro - in vivo drug activity correlations in specific types of human cancer or leukemia cell lines.
 ...
PMID:Rapid growth of human cancer cells in a mouse model with fibrin clot subrenal capsule assay. 347 62

Platelet-derived growth factor (PDGF) is one of the most important polypeptide growth factors in human serum. It is composed of two polypeptide chains linked by disulfide bonds. The B-chain is encoded by the c-sis proto-oncogene, which is expressed in several malignant and non-malignant cells including K562 cells differentiating towards megakaryoblasts. Expression of the A-chain has been reported to occur in human solid tumor cell lines independently of c-sis expression. We report here the non-coordinate expression of the A- and B-chains in human leukemia cell lines. The PDGF-A and B-chain (c-sis) RNA expression as well as secretion of PDGF polypeptides are induced in the K562 cell line upon induction of megakaryoblastic differentiation with 12-O-tetradecanoyl phorbol-13-acetate (TPA) whereas erythroid differentiation induced with sodium butyrate is accompanied by c-sis expression only. Simultaneously with megakaryoblastic differentiation the RNA level for another platelet protein, the transforming growth factor-beta was also increased, but in a complex manner. The promyelocytic leukemia cell line HL-60 does not express PDGF-A RNA, whereas the promonocytic cell line U937 does. Preferential induction of the A-chain RNA is obtained in both cell lines after treatment with TPA which causes monocytic differentiation. PDGF-A expression in HL-60 cells is also observed after treatment with the tumor necrosis factor-alpha but granulocytic differentiation of HL-60 cells induced with dimethyl sulfoxide or the granulocyte colony-stimulating factor is not associated with PDGF gene expression.
 ...
PMID:Induction of platelet-derived growth factor gene expression during megakaryoblastic and monocytic differentiation of human leukemia cell lines. 347 2

In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undesirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. We have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell line) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppressing the in vivo growth of the ascitic tumor, we divided 40 nude mice that were injected with Ichikawa cells into four groups. Each group of 10 mice was injected with one of the following mixtures: 40 micrograms of purified control mouse IgG [IgG1(kappa)] (group 1), 40 micrograms of control RA conjugate (group 2), 20 micrograms of purified SN1 antibody [IgG1(kappa)] and 20 micrograms of purified SN2 antibody [IgG1(kappa)] (group 3), or 20 micrograms of SN1-RA and 20 micrograms of SN2-RA (group 4). Mice in groups 1 and 2 formed large ascitic tumors, and died 5.8-7.0 weeks after the transplantation. Group 3 mice also formed large ascitic tumors and died 6.4-7.8 weeks after the transplantation. However, none of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation; these mice were indistinguishable from healthy control nude mice that were not injected with Ichikawa cells. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.
 ...
PMID:Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models. 349 97

Two new monoclonal antibodies (Lym-1 and Lym-2), reactive with the cell surface of B-lymphocytes and derived tumors, have been produced using tumor cell nuclei preparations as immunogens. Specificity screens using live cell radioimmunoassay techniques with 52 well-characterized human lymphoma and leukemia cell lines showed that both Lym-1 and Lym-2 bound to cell lines of B-cell lineage but were unreactive with those of T-cell, myeloid, or erythroid derivation. The B-cell specificity of these reagents was confirmed on 36 lymphoma and 15 leukemia biopsy specimens by using immunoperoxidase or immunofluorescence techniques. Additionally, flow cytometric analysis of 22 lymphoma biopsies showed that the majority of B-cell tumors were Lym-1 and/or Lym-2 positive and that within a given biopsy, a high percentage of the malignant cell population was stained. In both the immunoperoxidase and flow cytometric studies, reactive T-cells or T-cell lymphomas were consistently negative with the exception of Hodgkin's disease tissues which, in some instances, showed a higher than expected positivity with Lym-1 and Lym-2. Approximately 40% of B-cell chronic lymphocytic leukemias were found to be positive with Lym-1 while 80% were positive with Lym-2. Immunoperoxidase staining of frozen sections of human lymphoid tissues showed that both Lym-1 and Lym-2 stained germinal center and mantle zone B-lymphocytes as well as interfollicular histiocytes. Flow cytometric analysis of normal peripheral blood demonstrated specific staining of B-cells which comprised approximately 8% of circulating lymphocytes. Immunoperoxidase staining of nonlymphoid human organs and tissues revealed weak reactivity of Lym-1 with surface colonic epithelium only. Consistent with these findings, 35 solid tumor cell lines of diverse nature were found unreactive with both Lym-1 and Lym-2. Although standard techniques have thus far failed to identify the antigen recognized by Lym-2, the membrane antigen which binds Lym-1 has been shown by immunoprecipitation and competitive radioimmunoassay studies to be a polymorphic variant of the HLA-Dr antigen. Solid-phase radioimmunoassay techniques have shown that the antigens recognized by Lym-1 and Lym-2 are not significantly modulated after antibody exposure nor shed into the circulation of lymphoma patients. Finally, using iodine-125 labeled preparations of purified Lym-1 and Lym-2, we have determined that both reagents have a relatively large number of antibody binding sites per tumor cell and increased avidity for lymphoma cells when compared to normal and reactive lymph node B-cells.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Two new monoclonal antibodies, Lym-1 and Lym-2, reactive with human B-lymphocytes and derived tumors, with immunodiagnostic and immunotherapeutic potential. 354 94

Antitumor effects of Royal Jelly (RJ) were investigated employing the transplantable tumors of mouse advance leukemia L1210 and P388 strains and Ehrlich, Sarcoma-180 ascites and solid tumor strains. RJ was administered orally in a prophylactic-therapeutic (30 days before and 30 days after the transplantations of tumor cells) or a therapeutic (30 days after the transplantations of tumor cells) manner. Tumor cells were transplanted i.p. (ascites tumor) or s.c. (solid tumor). The daily dose of RJ was 0 (control), 10, 100, or 1000 mg/kg. In the case of the therapeutic experiments employing advance leukemia L1210 and P388 strains, which gave quite a short survival period of 8 approximately 9 days, RJ did not show any antitumor effect. In the case of the therapeutic RJ application employing the Sarcoma-180 ascites tumor, which gave a moderate survival period of 16 days, the increased life span was 9.3 approximately 19.3%; and with the Ehrlich ascites tumor (survival period of 22.1 days), the increased life span was 20.4% (RJ 10 mg/kg . day) and 17.6% (RJ 1,000 mg/kg . day), but no antitumor effect was observed at the dose of 100 mg/kg . day. In the case of the therapeutic experiment employing Ehrlich solid tumor, tumor growth inhibition was 25.3 approximately 54.8%, where as the use of the prophylactic-therapeutic regimen gave a tumor growth inhibition of 38.3 approximately 45.7%. In the case of the therapeutic RJ application employing Sarcoma-180 solid tumor, tumor growth inhibition was 45.1 approximately 59.7%, where as the prophylactic-therapeutic regimen gave a tumor growth inhibition of 49.1 approximately 56.1%.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Antitumor effects of royal jelly (RJ)]. 357 Jan 5

The literature data and the authors' findings on second tumors in patients treated for Hodgkin's disease are analyzed. Most patients who subsequently developed acute leukemia and solid tumors received chemoradiation treatment, while only few of them were exposed to radiation alone. Acute leukemia and solid tumor development is attributed to application of alkylating drugs. Out of 420 patients under study, leukemia was registered in 2 and solid tumors--in 4 cases.
 ...
PMID:[Development of second tumors in patients with Hodgkin's disease (review of the literature and personal data)]. 359 Jun 64

Study of a series of aniline-substituted 9-anilinoacridines related to the antileukemic drug amsacrine showed that a 1'-carbamate group provided increased activity against the multidrug-resistant P388/ADR leukemia subline in vivo. Since activity against such resistant tumors is of great clinical significance, a series of acridine-substituted carbamate derivatives were evaluated against both wild-type and ADR/resistant P388 leukemia and the Lewis lung solid tumor in vivo. Structure-activity relationships for all three tumor lines were similar, with 3-halo-5-methyl and 3-halo-5-methoxy compounds proving the most active. This substitution pattern also provided the highest DNA binding. Such compounds (particularly the 3-chloro-5-methyl and 3-chloro-5-methoxy) have in vivo activity against wild-type P388 and Lewis lung comparable to that of the best amsacrine analogues previously developed (greater than 50% cures), as well as P388/ADR activity. This work essentially completes the development of the amsacrine series of antitumor agents.
 ...
PMID:Potential antitumor agents. 52. Carbamate analogues of amsacrine with in vivo activity against multidrug-resistant P388 leukemia. 362 6


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