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)

The clinical and pathologic features of eight infants with monocytic leukemia are reviewed. The children were all aged 12 months or less at diagnosis and had a high incidence of extramedullary features, skin infiltration being particularly common. The diagnosis was established by conventional morphologic and cytochemical techniques. Using the French-American-British (FAB) classification, five infants had FAB 5a disease, and three had FAB 5b. The difficulties in making the diagnosis from extramedullary sites and the overlap that exists at this age between monocytic leukemia, true histiocytic lymphoma, and malignant histiocytosis are discussed. The treatments given to the group and their response are reviewed. Five of the patients received VP-16-213 and cyclophosphamide as primary induction chemotherapy, a combination that merits further evaluation in leukemia with monocytic features.
 ...
PMID:Monocytic leukemia in infancy. A review of eight children. 386 Dec 30

We have examined the effects of verapamil on the cytotoxicity of etoposide, vincristine, and Adriamycin in human leukemia K562 cells as well as in normal human bone marrow granulocyte-macrophage progenitors (CFU-GM). Etoposide was 10-fold more potent against K562 cells than against normal human bone marrow CFU-GM. Similarly, vincristine cytotoxicity was about 10-fold greater against K562 cells than against human bone marrow CFU-GM. In contrast, Adriamycin exhibited little selectivity for K562 cells versus normal bone marrow CFU-GM during the 1-h incubation period of the experiments. In the presence of verapamil (2.5-10 microM), etoposide cytotoxicity was enhanced in both malignant and normal cells. Verapamil enhanced vincristine (0.1 microM) cytotoxicity in K562 cells but did not potentiate Vinca alkaloid toxicity in normal bone marrow CFU-GM. Adriamycin, on the other hand, did not display any calcium antagonist-mediated potentiation of cytotoxicity in either malignant or normal tissue. These results indicate that short-term (1 h) incubations with etoposide, vincristine, and Adriamycin yield different profiles of toxicities whether used alone or with chemosensitizing agents such as the calcium antagonists. These differences in activities are consistent with different mechanisms for intracellular disposition of these three classes of anticancer agents and are worthy of further investigation, especially with regard to combinations with calcium antagonists.
 ...
PMID:Effects of verapamil on etoposide, vincristine, and adriamycin activity in normal human bone marrow granulocyte-macrophage progenitors and in human K562 leukemia cells in vitro. 386 Dec 38

The antitumor activity of etoposide against a wide variety of transplantable tumors in mice and rats was examined. Etoposide exhibited antitumor activity by both i.p. and p.o. administrations but a much larger effect was obtained in the former case. In addition, the effective dose of etoposide was much less in i.p. administration. In order to further investigate this large difference of etoposide effect the level of etoposide in the blood was followed after administration of 3H-etoposide via i.p. and p.o. routes. Although the maximum levels for both were seen 10 to 20 min after administration, the level in i.p. administration was much higher than that in p.o. administration. For instance, the level seen for i.p. administration at 8 mg/kg was comparable to that for p.o. administration at a much higher dose of 128 mg/kg. The administration schedule dependency of etoposide antitumor activity was examined using L1210 leukemia as the target tumor. When etoposide was administered alone on day, 1, the effect was the smallest obtained in i.p. as well as in p.o. administrations among the schedules examined in this study. Under other schedules where etoposide was administered i.p. and p.o. once a day for 3, 5 and 9 consecutive days from day 1 and on every other day, that is, days 1, 3 and 5, higher antitumor effects were seen.
 ...
PMID:[The antitumor activity of intraperitoneally- or orally-administered etoposide in animals and its administration-schedule dependency]. 407 28

The optimal synergism in combination therapy of leukemia L1210 depends on the sequence and the timing of the agents used. Etoposide (20 mg/kg applied intravenously) 3 h before methotrexate (50 mg/kg administered subcutaneously) results in significantly improved therapeutic action. Simultaneous application of these drugs, or an exceeding of that interval, do not entail synergism. Similar to the results obtained with other transplantable murine tumors, the optimal interval between methotrexate and 5-fluorouracil treatments of leukemia L1210 amounts to 6 h. Sequential treatment with etoposide (20 mg/kg given intravenously) significantly improves the efficacy of combined methotrexate (50 mg/kg applied subcutaneously) and 5-fluorouracil (80 mg/kg administered subcutaneously). The optimal synergism combining etoposide, methotrexate and 5-fluorouracil is achieved when the interval between etoposide and methotrexate amounts to 3 h followed 6 h later by 5-fluorouracil.
 ...
PMID:Timing- and sequence-dependent synergism between etoposide and methotrexate or etoposide, methotrexate and 5-fluorouracil in advanced leukemia L1210. 407 96

Many of the conceptual advances in the treatment of advanced cancer have resulted from studies of the hematologic malignancies: The signal importance of complete remission, the complete disappearance of evident disease, as the major contributor to significant palliation; the first studies of adjuvant therapy, that is chemotherapy given to patients free of disease, which demonstrated prolongation of disease-free periods; the first studies of intensification, including early, intermittent, and late; combination chemotherapy; and finally, the important observation that advanced metastatic malignancies can be cured were made in studies of these important diseases. Because of treatment advances that have occurred over the last 10 to 20 years, the majority of patients with adult hematologic malignancies that were once considered universally fatal can be either cured or have substantial palliation. Treatment for adult acute leukemia has advanced such that 15% to 20% of patients have prolonged disease and treatment-free survivorship; in Hodgkin's disease, over 70% of patients can be cured; and for the lymphomas, the majority or 50% to 60% of patients can be cured with available treatments. Major treatment advances in supportive treatment such as allogeneic transfusion and allogeneic and autologous bone marrow transplantation improve the perspective for control of the hematologic malignancies. In addition, the potential for biologic response modifiers or the biologic products of normal cells that are normally involved in the regulation of both proliferation and differentiation show enormous potential for the treatment of advanced disease. Studies of interferon have shown promising early results in chronic granulocytic leukemia and in hairy cell leukemia. A new class of drugs, the acridine analogs, of which AMSA (4'-[9-acridinylamino]methanesulfon-M-anisidide) is a member, has been introduced and has established activity against acute leukemia. VP-16 (etoposide) has just become commercially available and is an important drug both in leukemia and lymphoma. Finally, the discovery of new knowledge about the biochemical pharmacology of drugs such as arabinosyl cytosine has offered a major advance in salvage treatment and the potential for substantial further improvement in the frontline management of these diseases. The rapid advances in both palliative and curative treatment for the hematologic malignancies have generally found broad application to the management of advanced cancer arising from other organ systems.
 ...
PMID:The hematologic malignancies. Leukemia, lymphoma, and myeloma. 620 91

Acute leukemia with megakaryocytic differentiation has been an uncommonly recognized disorder. We used specific monoclonal and polyclonal antibody reagents (HP1-1D antibody and anti-factor VIII antibody, respectively) and an immunocytochemical staining technique to identify the megakaryocytic nature of the leukemic cells of 12 patients who presented with acute leukemia. The leukemic cells of our patients demonstrated the presence of one or both of these platelet- and megakaryocyte-related antigens, but were negative for all of the commonly employed cytochemical and immunocytochemical staining reactions, except for diffuse acid phosphatase activity and granular PAS positivity. Morphologically, the leukemic cells varied in size from 10 to 40 microns in diameter, frequently had cytoplasmic budding, and contained occasional vacuoles and/or peroxidase-negative azurophilic granules. Five patients presented with syndromes of acute myelofibrosis, and seven patients had otherwise unclassifiable acute leukemias, including three patients who had secondary leukemias. Diffuse reticulin myelofibrosis was present in all cases in which it was sought. Chromosomal abnormalities of leukemic cells were found in five cases. Two patients had deficiencies of plasma coagulation factor V. Study of one patient revealed significant platelet dysfunction. When cytoreductive chemotherapy of leukemia was attempted, the observed response was generally poor, with the exceptions of one patient who has remained in complete remission following treatment with etoposide (VP-16) and a second patient who attained remission following bone marrow transplantation. These cases of acute megakaryoblastic leukemia represented from 3.6% to 9.3% of all acute leukemia cases diagnosed concomitantly in our institution. Acute leukemia with megakaryocytic differentiation may occur more frequently than previously recognized, may present with differing syndromic features, and can be identified by the use of specific antibody reagents and relatively simple immunocytochemical techniques.
 ...
PMID:Acute leukemia with megakaryocytic differentiation: a study of 12 cases identified immunocytochemically. 637 77

The potential interaction of the antitumor agents vincristine and VP-16-213 was investigated in vivo. DBA/2 mice were inoculated with 10(6) P388 murine leukemia cells, after which single IP injections of saline only, vincristine only, VP-16-213 only, or a combination of vincristine and VP-16-213 were administered. Long-term survival (greater than 60 days) was observed in 0/45, 1/45 (2%), 9/135 (7%), and 44/135 (33%) mice, respectively (P less than 0.001). Treatment was most effective when VP-16-213 was administered 0-72 h after vincristine. A similar trend was observed in mice bearing P1534 murine leukemia. These data demonstrate synergistic antitumor activity between vincristine and VP-16-213 in a murine model.
 ...
PMID:Synergistic antitumor activity of vincristine and VP-16-213. 648 38

A vincristine (VCR)-resistant subline of human K562 myelogenous leukemia was established in vitro, and several clones with different susceptibilities to VCR were isolated by the limiting dilution technique. The most resistant clone (H-1) had a 17-fold greater resistance to VCR when compared to the parent K562 cells. The clone gradually lost the resistance during prolonged culture in vitro. These clones generally accumulated smaller amounts of VCR in their cells as compared to the parent cells. The size of H-1 clone cells was almost the same as that of the parent cells. The numbers of potential binding sites of VCR in the K562 cells and the resistant H-1 clone were almost the same. Similar results were obtained for P388 and its VCR-resistant subline. The cells derived from the VCR-resistant H-1 clone were highly cross-resistant to vindesine and moderately resistant to vinblastine. Cells derived from clone H-1 exhibited marginal degrees of cross-resistance to adriamycin, maytansine and VP-16-213, whereas VCR-resistant P388 leukemia cells exhibited significant resistance to these agents, especially to maytansine.
 ...
PMID:Establishment and properties of vincristine-resistant human myelogenous leukemia K562. 658 Feb 55

Nutritional intervention in the cancer patient [e.g., total parenteral nutrition (TPN)] might improve durable survival because of increased tolerance to aggressive tumor therapy. To determine whether this assumption is correct, 42 patients with diffuse histiocytic lymphoma were induced with prednisone, high-dose methotrexate, Adriamycin, cyclophosphamide, and VP-16 (ProMACE). Nitrogen mustard-vincristine-procarbazine-prednisone (MOPP) consolidation was then used, followed by late intensification with ProMACE. Patients were selected randomly to receive adjuvant TPN or a standard diet during ProMACE-MOPP treatment. While TPN patients had a greater median weight gain than did control patients, lean body mass and degree of myelosuppression did not improved as a consequence of TPN. There was no significant difference in tumor response or survival between TPN and control patients, whether or not the patients were initially malnourished. In a second trial, 32 young patients with metastatic or other poor-prognosis sarcomas were randomly allocated to receive TP or a standard diet as an adjunct to one very intensive course of combination chemotherapy or chemotherapy plus total body irradiation; autologous marrow transplantation was used with gain than did controls but remained in a negative nitrogen balance. Response rates and median durable survival did not differ between the two groups. In both trials, the maximum nutritional support permitted by currently available technology was offered. Thus, the limiting factor may not be nutritional status but rather the intrinsic biology of the tumors and the limitations of their response to current therapy. In in vitro studies of the possible influence of nutrition on cancer treatment, we have compared sublines of P388 murine leukemia cells which are sensitive or resistant to Adriamycin. The difference in drug sensitivity correlated with differences in lipid composition, with more intracellular lipid, and with greater membrane rigidity in the resistant cells. Resistant cells have a relatively poor transport of drug into the cell; moreover, intracellular Adriamycin is sequestered in lipid depots away from DNA. These results suggest one possible relationship between nutritional phenomena and drug sensitivity.
 ...
PMID:Controlled clinical trials of nutritional intervention as an adjunct to chemotherapy, with a comment on nutrition and drug resistance. 679 96

Thirteen patients with relapsed acute leukemia, 12 adults with acute nonlymphocytic leukemia, and one child with acute lymphoblastic leukemia were treated with VP 16-213, an epipodophyllotoxin analog, at a dose of 200-300 mg/m2/day X5 as a 2-hour intravenous infusion. Only four patients achieved bone marrow aplasia and three regenerated with leukemic cells. The fourth patient achieved a partial remission for 4 weeks. Toxicities included myelosuppression (WBC nadir 500/microliter), nausea and vomiting (70% of courses), mucositis (23%), esophagitis (12%), which contributed to death in one patient, hypotension (12%), and transient liver function abnormalities (12%). It is concluded that increasing the dose of VP 16-213 as employed in this study did not increase the therapeutic activity of VP 16-213 for the treatment of relapsed leukemia but did increase the risk of toxicity.
 ...
PMID:High-dose VP 16-213 (NSC 141540) for the treatment of patients with previously treated acute leukemia. 693 27


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