Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.
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PMID:A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. 16 75

Cancer chemotherapy was purely palliative until the early sixties. Tumor cures have been since obtained, first in malignant trophoblastoma and Burkitt's lymphoma, and more recently in Hodgkin's disease, diffuse histiocytic lymphoma, acute lymphocytic leukemia in children, Wilms's tumor and osteosarcoma. Preliminary data are suggestive of tumor cures in testicular teratomas and, possibly, in small cell carcinoma of the lung. Five patients with trophoblastoma, Hodgkin's disease, melanoma, chronic myelocytic leukemia and anaplastic carcinoma of the lung are briefly presented, all without evidence of tumor relapse 3 years or more after chemotherapy. Theoretical bases for improvement of the curative effect of cancer chemotherapy are discussed, including the development of new agents, and new pharmacological problems concerning drug interactions, complexes of drugs with macromolecules or immunoglobulins and liposomes are considered.
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PMID:[Curability of malignant neoplasms: value and limitations of chemotherapy]. 21 68

One hundred one patients were treated for Ph' positive chronic granulocytic leukemia (CGL) in the blastic phase. In seven of these (6.9 per cent), meningeal leukemia developed. Of the 99 patients who died of their disease, a complete remission was achieved in 12 with a median survival of 12 months (three to 28 months). Incomplete responders had a median survival of only 2.5 months (one to 14 months). In five of the 12 complete responders (42 per cent), but in only two of the incomplete responders (2.3 per cent), meningeal leukemia developed. The principal neurologic signs were cranial nerve palsies and papilledema. All patients had pleocytosis with myeloblasts in the cerebrospinal fluid. As in patients with acute leukemia and diffuse histiocytic lymphoma, increased survival of patients in whom hematologic remission from the blastic phase of CGL is achieved may allow sufficient time for the development of meningeal leukemia. Intrathecal methotrexate is extremely successful in treating this complication. Cerebrospinal fluid pleocytosis was eradicated in all seven of our patients, and neurologic symptoms and signs were completely eliminated in five patients. No evidence of meningeal leukemia was found in three of the five patients in whom an autopsy was performed.
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PMID:Meningeal leukemia in the blastic phase of chronic granulocytic leukemia. 105 28

The possible presence of tumor cells in remission bone marrow (BM) is one of the major problems for the success of autologous BM transplantation (ABMT), because the reinfusion of viable malignant cells may result in relapse. In this study we attempted the purging of the malignant cells by the use of VP-16-213 (VP-16) and nitrogen mustard (NM) either alone or in combination. Four cell lines from various hematological malignancies were utilized: SK-DHL-2 was established from a B-cell diffuse histiocytic lymphoma; RAJI was from an Epstein-Barr virus (EBV)-infected B-cell lymphoma cell line; K-562 were from a chronic myelogenous leukemia (CML) blastic crisis; and HL-60, derived from a human promyelocytic leukemia, were used in exponential growth phase. Four logs of tumor cell-elimination were observed after 1-h incubation of RAJI cells with 25 micrograms/ml of VP-16. K-562 and SK-DHL-2 cells showed a greater than 4 logs reduction after 1-h exposure to 75 micrograms/ml of VP-16, and HL-60 cell line growth was inhibited by 3.2 logs. Under the same conditions (i.e., the treatment with 75 micrograms/ml), we observed a mean recovery of 2.7% of BM granulocyte-macrophage colonies (granulocyte-macrophage colony-forming units, CFU-GM), 3.2% of erythroid (erythroid burst-forming units, BFU-E), and 2.5% of pluripotent (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) progenitors, respectively. More than 3 logs reduction of leukemia and lymphoma cell lines were reached following 1-h treatment with 1 micrograms/ml of NM. After exposure to the same concentration of the drug we obtained 2.5% CFU-GM, 1.2% BFU-E, and 2% CFU-GEMM recovery. A drug mixture containing constant doses of VP-16 (10 and 20 micrograms/ml) and NM (1 micrograms/ml) reduced HL-60 and SK-DHL-2 cell growth to undetectable levels (i.e., 4 and 5 logs elimination) in the presence of an excess of irradiated BM cells, whereas it did not further affect the recovery of the BM precursors as compared to the single drugs used alone. These results suggest that the combination of these two drugs at the selected dose level could provide a better therapeutic index (i.e., higher tumor cell killing coupled with no additional cytotoxic effect on normal BM cells) than the same chemotherapeutic agent used alone and that this mixture may be useful for the "ex vivo" treatment of BM grafts.
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PMID:In vitro cytotoxicity of VP-16-213 and nitrogen mustard: agonistic on tumor cells but not on normal human bone marrow progenitors. 239 48

Adenosine deaminase (ADA) deficiency is associated with a fatal severe combined immunodeficiency. Because most patients do not have a suitable marrow donor, the introduction of a normal ADA gene into the patient's marrow cells is a potentially useful alternative therapy. To identify vectors that provide optimal gene expression in human hematopoietic cells, we investigated retroviral vectors containing the ADA gene under the transcriptional control of the promoter/enhancers of Moloney murine leukemia virus, the simian virus 40 early region, the cytomegalovirus immediate-early gene, the lymphotropic papovavirus, and the human beta-globin gene. ADA expression from these vectors was monitored in the ADA- human histiocytic lymphoma cell line DHL-9, and in the multipotential chronic myeloid leukemia cell line K562. ADA expression in infected K562 cells was also measured after induction of megakaryoblastic differentiation by phorbol ester, and after induction of erythroid differentiation by sodium n-butyrate or hemin. In these hematopoietic cell lines, the vectors that contained ADA controlled by either the Moloney murine leukemia virus promoter (LASN) or the cytomegalovirus promoter (LNCA) expressed ADA at much higher levels than the other vectors tested. Furthermore, in K562 cells infected with LASN and LNCA vectors, induction of terminal differentiation resulted in the same or higher level expression of ADA. These cell lines have permitted the evaluation of transduced gene expression in proliferating and differentiating hematopoietic cells that provide a model for bone marrow-targeted gene therapy.
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PMID:Expression of human adenosine deaminase from various strong promoters after gene transfer into human hematopoietic cell lines. 275 48

An antiserum specific to esterase Ib was produced in a rabbit. The antigen-antibody reaction was visualized by the strong esterase activity in the precipitin band in Ouchterlony double diffusion and immunoelectrophoresis. Immunohistochemical procedure demonstrated strong staining in the monocyte-infiltrated splenic sections and tissue sections of true histiocytic lymphoma. Negative results were observed in T- and B-cell lymphomas, granulocytic sarcoma, and chronic granulocytic leukemia. This antibody may be useful for the identification of monocytes and histocytes in paraffin-embedded tissue sections.
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PMID:Immunohistochemical detection of monocytes by the antiserum specific to monocytic esterase. 388 78

Preparation and characterization of a monoclonal antibody termed M206 directed to a human monocyte lineage are described. The antibody was produced by somatic cell hybridization between BALB/c spleen cells primed with human histiocytic lymphoma cell line U937 and murine myeloma cell line P3U1. The antibody reacted intensely with human peripheral blood monocytes as well as U937 but did not react with peripheral blood T and B cells. Granulocytes were weakly stained with the antibody by indirect immunofluorescence. M206 also reacted intensely with the immature leukemic cells from patients with acute monocytic leukemia but was unreactive with other types of leukemic cells except cells from chronic myelogenous leukemia which showed varied patterns of reactivities. M206 reacted with a single polypeptide chain with a molecular weight of 180,000 on the surface of U937 cells.
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PMID:Preparation of a monoclonal antibody against human monocyte lineage. 633 27

Nineteen patients with advanced refractory lymphoma and 12 patients with acute leukemia, including seven in blastic crisis of chronic myelogenous leukemia (CML), were treated with vindesine in combination with prednisone. Of 16 evaluable patients with lymphocytic or histiocytic lymphoma, one achieved complete remission (6%) and eight achieved partial remissions (50%). Median duration of response was 12 weeks (range, 4-72+). Four of six evaluable patients in blastic crisis of CML showed definite improvement in blood cell counts and symptoms. The major dose-limiting toxic effect was bone marrow suppression, while neurotoxicity was seldom cause for dose modification. The study shows vindesine and prednisone to be active in heavily pretreated patients with non-Hodgkin's lymphoma and blastic phase of CML.
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PMID:Combination of vindesine and prednisone in malignant lymphoma and acute leukemia. 657 59

The effect of thymidine (dThd) and hydroxyurea (HU) on the cellular metabolism of 1-beta-D-arabinofuranosylcytosine (Ara-C) was investigated in the human promyelocytic cell line HL-60. Both dThd and HU increased the cellular uptake and rate of formation of Ara-CTP. Measurement of ribo- and deoxyribonucleotide triphosphate pools implicated a reduction of the dCTP as the mechanism of this effect. dThd and HU had opposite effects on the incorporation of Ara-C into DNA per unit time, but both enhanced the incorporation of Ara-C per unit of newly synthesized DNA. In a Phase I trial Ara-C was given by continuous infusion for five days at 100 mg/m2, and HU by mouth every six hours with dose escalation from 0.375 to 1.78 g/m2 every six hours. Myelosuppression was the dose-limiting toxicity; the major nonhematologic toxicity was skin rash. To date responses have been observed in chronic myelogenous leukemia in blast crisis and diffuse histiocytic lymphoma.
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PMID:Modulation of the cellular pharmacology and clinical toxicity of 1-beta-D-arabinofuranosylcytosine. 676 70

Rabbit antisera have been produced to an acute myelomonocytic leukaemia (AMML)-derived cell line (RC2a) and a histiocytic lymphoma derived cell line (U937) having macrophage characteristics. The antisera were screened by complement-mediated cytotoxicity and immunofluorescence (cytofluorograph analysis) against separated leukaemic (122 patients plus 13 cell lines) and normal haematologic cell populations (60 preparations from 20 donors plus 10 B-lymphoblastoid cell lines). The sera were absorbed with pooled B-lymphoblastoid cell lines including the autologous B-lymphoblastoid cell line to RC2a (CESS-B) or alternatively with B-CLL and T-CLL cells. All leukaemic cell populations were confirmed using the markers SIg, E-rosette receptor, cALL antigen, alpha-naphthyl butyrate esterase and myeloperoxidase. Rabbit anti-RC2a (Adherent cells) (RARC2a(Ad) ) and rabbit anti-U937 (RAU937) recognised antigens common to immature myeloid monocyte and T-lymphocyte lineage but did not react by cytotoxicity, absorption or cytofluorographic analysis with cells of B-lymphocyte lineage (B-lymphoblastoid or B-CLL) and reacted only occasionally with cALL patients' cells (includes pre B phenotype). These sera reacted with peripheral blood monocytes but not with other mature blood leucocytes. RAU937 reacted with a major mononuclear population from normal marrow and with more differentiated myeloid leukaemia cells. RARC2a(Ad) and RAU937 detected overlapping subgroups of myeloid leukaemia (AMoL, AMML, AML and CML) patients and Null-ALL and T-ALL patients. These subgroups are now being examined for prognostic significance.
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PMID:Rabbit antisera to cell lines RC2a and U937: antigens expressed on human leukaemic cells of myeloid, monocyte and T-lymphocyte lineage. 681 43


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