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)

Forty-six cases with hematological malignancies were treated with vindesine sulfate (VDS); a new semisynthetic vinca alkaloid. Six cases with ALL, 5 cases CML in blastic crisis, 3 Hodgkin's disease (HD) and 4 non-Hodgkin's lymphoma (NHL) were treated with VDS alone. Five out of 6 cases ALL, 2 out of 5 CML in blastic crisis were induced into partial remission with VDS alone. All of 3 HD, and 4 NHL were induced in complete remission (CR) or partial remission (PR). Out of 5 cases AML in CR who received VDS as the maintenance therapy in combination with cyclophosphamide, 6-MP and prednisone, one case relapsed during the treatment, but other four cases maintained CR for 4 to 24 months. One case of APL in relapse, which was treated with VDS and 6-MP, reinduced into CR after one month. Out of 16 cases with malignant lymphoma treated by combination chemotherapy including VDS, eleven cases entered in CR or PR. Out of four cases in which the disease became refractory to vincristine (VCR) or vinblastine (VLB) clinically, two achieved PR. VDS was administered intravenously with 3 mg/body/week. When undesirable effect such as leucocytopenia was observed, the dose was reduced to 2-2.5 mg/body/week or 3 mg/body/2 weeks or month. Neurotoxicity (i.e. Paresthesia 21.7%), alopecia (21.7%), leucocytopenia (19.6%), constipation (10.9%) and fever (6.5%) were main side effects of VDS. The neurotoxicity of VDS, however, seemed far less intensive than VCR.
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PMID:[Administration of vindesine sulfate for the treatment of malignant hematological tumors]. 676 3

Studies were undertaken to determine whether leukemia and lymphoma cells would be lysed by autologous and allogeneic interferon (IFN) activated peripheral blood mononuclear cells (PBMC). PBMC from healthy donors and from patients were cultured with and without 500 U of highly purified human fibroblast IFN/ml for 24 hr, and then their cytotoxic activity was assayed by a 5-hr 51Cr-release test. Of primary tumor cells isolated from patients, the cells of 5 of 15 patients with acute nonlymphocytic leukemia (ANLL), 5 of 9 patients with acute lymphocytic leukemia (ALL), 2 of 3 patients with chronic phase chronic myelogenous leukemia (CML), 2 of 3 patients with blastic phase CML, 1 patient with hairy cell leukemia, and 6 patients with diffuse non-Hodgkin's lymphoma were sensitive to IFN-activated PBMC of healthy donors, whereas the cells of 3 of the ANLL patients, 2 of the ALL patients, and 3 of the lymphoma patients were sensitive to unstimulated PBMC. Of the ANLL cells tested, myeloblasts, promyelocytes, and monoblasts were sensitive to either unstimulated or IFN-activated PBMC. Compared with the ANLL cells, the lymphoma cells were statistically significantly sensitive to activated effector cells (p less than 0.025). On the basis of the unlabeled target competition test and the recovery of cytotoxic cells within the fractions enriched in natural killer (NK) cells, NK cells appeared to mediate the above unstimulated and IFN-boosted cytotoxicity. In experiments using autologous effector-target cells from 11 patients, the addition of 500 U of IFN/ml enhanced the lytic activity of PBMC against autologous lymphoma cells in 1 patient, and higher concentrations of IFN, i.e., 2500 or 3500 U/ml, enhanced their cytotoxic activity against autologous leukemia or lymphoma cells in 4 of 8 patients. These data indicate that IFN-activated allogeneic PBMC are able to lyse both myeloid and lymphoid tumor cells, whereas higher concentrations of IFN are required to enhance lytic activity against autologous tumor cells.
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PMID:Lysis of leukemia and lymphoma cells by autologous and allogeneic interferon-activated blood mononuclear cells. 683 Oct 42

A potential application of the human tumor stem cell colony assay is to guide Phase II clinical investigations by identifying classes of tumors (or individual patients) which are sensitive in vitro to a new antitumor compound. We have tested human tumor stem cells from 140 tumor biopsies representing 20 different tumor types for chemosensitivity to the Phase II drug 4'-(9-acridinylamino)methanesulfon-m-anisidide. In vitro sensitivity was defined as a reduction in the number of tumor colony-forming cells to 30% of the control or less after a 1-hr exposure to one-tenth of the pharmacologically achievable plasma concentration of 4'-(9-acridinylamino)methanesulfon-m-anisidide. In vitro sensitivity was found in 29 cases: non-Hodgkin's lymphoma (2 of 2); cervical carcinoma (1 of 1); sarcoma (3 of 6); neuroblastoma (1 of 2); acute myelogenous leukemia (6 of 16); chronic myelogenous leukemia (1 of 3); melanoma (8 of 34); uterine carcinoma (1 of 5); lung carcinoma (1 of 9); ovarian carcinoma (4 of 36); and breast carcinoma (1 of 11). Prospective in vitro-in vivo correlations in eight patients with various tumor types showed that three of three patients sensitive in vitro to 4'-(9-acridinylamino)methanesulfon-m-anisidide responded in vivo, while five of five patients resistant in vitro had no clinical response. The results provide support for further evaluation of the utility of the human tumor stem cell colony assay for targeting Phase II clinical trials.
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PMID:In vitro chemosensitivities of human tumor stem cells to the Phase II drug 4'-(9-acridinylamino)methanesulfon-m-anisidide and prospective in vivo correlations. 689 12

AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.
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PMID:[Phase I-II studies of a new antineoplastic agent, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA)]. 689 58

Serum total lactic dehydrogenase (LDH) levels were examined in 42 patients with acute leukemia, 9 patients with chronic myeloid leukemia, 6 of them in blastic crisis, and 53 patients with lymphoma and other lymphoproliferative disorders. The mean range of serum LDH leveles in Hodgkin's and non-Hodgkin's lymphoma was 402 +/- 210 IU/liter and 313 +/- 113 IU/liter, while that of patients with nonmalignant disorders was 308 +/- 74 IU/liter. In acute nonlymphoblastic leukemia (ANLL), the range was 126-684 IU/liter (mean value 413 +/- 146 IU/liter). In 6 of the patients (11.3%) with lymphoma and in 6 cases (26.8%) with ANLL, the LDH levels were above 500 IU/liter. None of these patients had levels over 900 IU/liter. Patients with acute lymphoblastic leukemia (ALL) had a range of 402-3582 IU/liter (mean value of 1669 + 1038 IU/liter). In 15 of the 19 patients (78.9%) with ALL, serum LDH values were above 900 IU/liter. In addition, 3 patients with chronic myeloid leukemia (CLM) in blastic crisis had levels of 970-1940 IU/liter. One of these 3 patients had lymphoblastic crisis, while the second case responded clinically to vincristine and prednisone, but was not regarded as ALL. The differences in serum LDH levels between ALL and ANLL are statisticaly significant (p < 0.001). It appears that markedly elevated serum LDH levels in acute leukemia are suggestive of ALL, and that in individual patients, the LDH levels were correlated with the number of blasts during remission and relapse.
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PMID:Serum lactic dehydrogenase (LDH) levels in acute leukemia: marked elevations in lymphoblastic leukemia. 693 18

Data from 90 patients with a variety of hematologic malignant neoplasms were studied to determine the relation between changes in serum ferritin concentration and the clinical status of the patients. Patients with Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, blastic crisis of chronic myelocytic leukemia, acute myeloblastic leukemia and acute lymphoblastic leukemia were found to have significantly elevated serum ferritin levels. Further study of serum ferritin concentration in certain hematologic malignant neoplasms might provide a valuable insight into the role of serum ferritin determination in the diagnosis and follow-up of patients with malignant diseases.
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PMID:Serum ferritin levels in hematologic malignant neoplasms. 693 89

A monoclonal antibody designated PI153/3, which reacts with neuroblastoma and fetal brain, is shown to identify also a cell surface determinant shared by pre-B and mature B cells and their corresponding leukemias including chronic lymphocytic leukemia, non-Hodgkin's lymphoma, B acute lymphoblastic leukemia, and hairy cell leukemia, but not plasmacytoma. Almost all non-T, non-B acute "lymphoid" leukemias bind PI153/3. The latter includes 71 of 74 common ALL tested, most but not all "unclassified" or "null" ALL and cases of both acute undifferentiated leukemia and Ph1 positive chronic myeloid leukemia in blast crisis with common ALL phenotypes. The antigen is absent or present at very low density on normal and leukemic T lymphocyte, myeloid and erythroid cells. The determinant appears to co-redistribute with cell surface immunoglobulin in B lymphocytes and segregates independently of other cell surface antigens associated with B cells and/or cALL including HLA-DR (Ia-like antigens) and the cALL (gp 100) antigen.
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PMID:A monoclonal antibody identifying a cell surface antigen shared by common acute lymphoblastic leukemias and B lineage cells. 696 98

Spleen cell production of granulocyte-macrophage colony stimulating activity (CSA) and colony forming capacity (CFU-GM) from 59 patients with Hodgkin's and non-Hodgkin's lymphoma, acute (AML) and chronic myeloid leukemia (CML), and control subjects was quantified to evaluate local cellular potential for modulating splenic granulocytopoiesis. Mononuclear spleen cell conditioned media stimulated myeloid CFU-GM by human nonadherent marrow target cells. In contrast to conditioned media produced by marrow and peripheral blood cells, the vast majority of spleen CSA was generated by nonadherent lymphoid cells rather than adherent monocytic cells. The nonadherent cells producing CSA were non-T cells (assessed by sheep erythrocyte rosetting), with 98% +/- 2% CSA produced by the nonrosetted fraction (B lymphocytes and null cells), and had a peak density heavier than that of the adherent spleen CSA-producing cells. Dose response curves demonstrated significantly increased cellular CSA production from patients with lymphomas and AML in remission. In a high proportion of patients, foci of immature granulocytic cells were found by specific cytochemical staining of histologic sections of spleens. A limited degree of splenic granulocytopoiesis was demonstrated morphologically and by CFU-GM incidence. CSA was not detectable in conditioned medium prepared from nonadherent spleen cells from 5 patients with CML, due to a nondialyzable substances(s) produced by the nonadherent cells which inhibited normal CFU-GM response to CSA. The high CFU-GM incidence and extensive leukemic granulocytopoiesis present in the CML spleens suggests diminished effect of this inhibitor on leukemic as opposed to normal granulocytic precursor cell proliferation.
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PMID:Splenic granulocytopoiesis and production of colony-stimulating activity in lymphoma and leukemia. 696 8

Vindesine (VDS) is an analogue of the vinca alkaloids. Its spectrum of antitumoral activity is similar to that of vincristine (VCR), but with milder experimental neurotoxicity, and it inhibits the polymerization of tubulin. Its terminal half-life is 24 h and its plasma clearance is intermediate between those of vinblastine (VLB) and VCR. The maximal tolerated dose is 4-5 mg/m2/week, the dose-limiting toxicity being myelosuppression (nadir by days 7-8 and recovery by days 11-13). It has already been demonstrated as efficient in childhood acute lymphoid leukemia (ALL), non-Hodgkin's lymphoma, blastic crisis of chronic myeloid leukemia, and esophageal carcinoma. It has also shown activity in Hodgkin's disease, breast and germ cell carcinomas, and melanoma. Intolerance is mainly neurologic, with paresthesias, without motor impairment, or hematologic, with leukopenia, and sometimes alopecia, asthenia, and muscle pains. The results are better if the patients have not been treated previously; continuous infusion could be of interest and there appears to be no cross-resistance with its parent VCR, as documented in ALL.
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PMID:Vindesine: a new vinca alkaloid. 700 62

Deoxynucleotidyl transferase (TdT) is of diagnostic and therapeutic importance in acute leukaemia and malignant lymphoma. Previous methods for determining TdT activity by biochemical assay are complex and require the use of radioactive substances. There now is available a specific antibody for immunofluorescent demonstration of TdT. The two methods were compared on samples from 43 patients with leukemia or malignant lymphoma. There was very good agreement. High TdT activity was found in 12 of 14 patients with acute lymphatic leukemia and in one of two with acute undifferentiated leukaemia. TdT activity was absent with acute and chronic myeloid leukaemia, chronic lymphatic leukaemia and non-Hodgkin's lymphoma of low malignancy. Immunofluorescence assay, although its results are of similar significance to that obtained with the biochemical tests, is simpler to do. Furthermore, it can be done on normal bone-marrow smear or lymph-node preparations and can be correlated with the morphological findings.
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PMID:[Significance of terminal deoxynucleotidyl transferase in patients with acute leukemia and malignant lymphoma: results obtained by immunofluorescence assay (author's transl)]. 701 59


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