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)

1. APP is activated by adenosine kinase to its 5'-phosphate (APP-MP). 2. APP-MP inhibits PRPP synthetase, and depletes cellular PRPP and purine and pyrimidine nucleotides. 3. APP inhibits synthesis of DNA and RNA, and blocks cells in G1 phase of the cell cycle. 4. APP retains full activity against MDR cells. 5. APP is equally active against quiescent and proliferating CHO cells. 6. APP has only weak activity against L1210 leukemia in vivo, but has substantial activity against mammary carcinoma 16/c. 7. In vitro, APP has a relatively high ratio of solid tumor: leukemia activity.
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PMID:Biochemical pharmacology and antitumor properties of 4-amino-8-[beta-D-ribofuranosylamino]pyrimido-[5,4-d]pyrimidine. 256 Mar 25

Taxol, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered to adults with refractory leukemias as a 24-h i.v. infusion in a Phase I study. The primary objectives were to determine the maximum tolerated dose of taxol administered on this schedule to patients with acute leukemias and describe the nonhematological toxicities which became dose limiting. The starting dose, 200 mg/m2, was based on the maximum tolerated dose in solid tumor trials, in which myelosuppression precluded dose escalation. Seventeen patients received 28 evaluable courses at 200, 250, 315, and 390 mg/m2. Severe mucositis limited further dose escalation. Other nonhematological effects included peripheral neuropathy, alopecia, myalgias, arthralgias, nausea, vomiting, diarrhea, and an acute pulmonary reaction that was presumptively due to taxol's Cremophor vehicle. Mean peak taxol plasma concentrations at all dose levels were in the range of concentrations that were previously demonstrated to induce microtubule bundles, a morphological effect associated with cytotoxicity, in leukemia cells in vitro. Pretreatment blasts from 12 patients were incubated with taxol ex vivo. Taxol-induced microtubule bundles were apparent in the blasts of eight patients who also had cytoreduction of tumor, and sensitivity to bundle formation was related to the magnitude of antitumor activity. In contrast, taxol did not induce microtubule bundles ex vivo in the blasts of the other four total nonresponders. Based on this study, the maximum tolerated doses and recommended Phase II doses for taxol, limited by nonhematological toxicity and administered as a 24-h i.v. infusion to patients with refractory leukemias, are 390 and 315 mg/m2. Phase II trials at these myelosuppressive doses are required to determine taxol's activity in the treatment of leukemias. In addition, further evaluation of microtubule bundle formation ex vivo in Phase II studies is necessary to determine the ultimate utility of this assay in assessing tumor sensitivity to taxol.
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PMID:Phase I and pharmacodynamic study of taxol in refractory acute leukemias. 256 75

The risk of second malignant neoplasm (SMN) was evaluated in 979 children with Hodgkin's disease. This cohort was diagnosed between 1955 and 1979 at one of the institutions of the Late Effects Study Group. Solid tumors, non-lymphocytic leukemia, and non-Hodgkin's lymphoma (NHL) developed in 18, 17, and 3 patients, respectively. The estimated cumulative probability of developing any SMN was 2% at 5 years from diagnosis, 5% at 10 years, and 9% at 15 years. The incidence is ninefold greater than the risk of acquiring cancer in 19 year-olds, the median age at which the diagnosis of SMN was made in this study population. For leukemia and NHL the corresponding probabilities were 1%, 3%, and 4% for the group as a whole but were increased (2%, 6%, and 8%) in patients who had suffered one or more recurrences. In order to analyze the risk of leukemia and NHL associated with alkylating agent chemotherapy, each patient was assigned a score of one for each alkylating agent administered for a 6-month period. Scores of 2, 4, 6, and 8 were associated with probabilities of leukemia or NHL of 2%, 3%, 6%, and 10%, respectively. In a multivariate analysis for leukemia/lymphoma that included AAD score, stage, and splenectomy, the effect of AAD score and splenectomy did not change substantially compared to the univariate results. AAD score remained statistically significant (P = .0001), and splenectomy was of borderline significance (P = .09). Of the 18 solid tumor SMNs, 15 developed within the field of radiation, and one other developed in tissue irradiated 34 years earlier for hemangioma. This study of a large and unselected group of children with Hodgkin's disease who received a variety of therapies demonstrates that children are as likely as adults to develop acute leukemia after alkylating agents and solid tumors in the field of radiation therapy.
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PMID:Second malignant neoplasms following childhood Hodgkin's disease: treatment and splenectomy as risk factors. 258 62

Chemotherapy of malignant diseases was introduced into clinical practice during the 1940's. The initial response rate to this type of therapy is high in patients with a variety of cancers but the survival rate is affected in only a few patients, mainly in women with choriocarcinoma. Despite intensive research, the percentage of survivors following chemotherapy, for example in patients with small-cell bronchogenic cancer, has remained almost constant during the last 2 decades. The objective of the present paper is to consider the likelihood of immune mechanisms being active both in the regression and again in the later progression of tumor growth observed during treatment with cytotoxic drugs. Such a dual role for immunity appears to be possible. In contrast to most malignant cells in solid tumors, the leucocytes and leukemia cells are highly sensitive to anti-cancer agents. Thereby the drugs become immunosuppressive at a level in serum lower than that required for a direct interference with the proliferative capacity of the cells in a solid tumor. Furthermore, the cytotoxic drugs selectively influence the immune system. In the first phase of treatment the drugs enhance the effect of T-killer cells relatively by reducing blocking activity in serum; the net result being a regression in the tumor volume. However, continued chemotherapy is inconvenient for cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemotherapy of malignant tumors--a self-defeating form of immunotherapy? 266 36

Iron (Fe) depletion with anti-transferrin (Tf) receptor monoclonal antibodies (MAbs), Fe chelators, or gallium (Ga) salts inhibits in vitro and in vivo growth of tumor cells. The present studies examined the cytotoxic effects of an IgA anti-human Tf receptor MAb, 42/6, combined with parabactin, a powerful Fe chelator, or Ga nitrate. Parabactin inhibited in vitro growth of human hematopoietic and solid tumor cells, and the rank order of their sensitivities to the Fe chelator was identical to their relative sensitivity to MAb 42/6 as demonstrated in previous studies. When the most parabactin and MAb 42/6-sensitive (HL60 leukemia) and -resistant (KB carcinoma) cells were incubated with various concentrations of parabactin, cell killing was time and dose dependent over the first 24 hours. Little additional cytotoxicity occurred, however, when cells were exposed to parabactin for 48 hours. HL60 cells were slightly more sensitive than KB cells to parabactin cytotoxicity. Addition of optimally effective concentrations of anti-Tf receptor MAb 42/6 to parabactin increased cytotoxicity to HL60 cells over a narrow parabactin dose range but had little effect on cytotoxicity to KB cells. Cell cycle analysis of cells treated with parabactin for 24 hours showed that doses causing variable cytotoxicity increased the percentage of cells in S phase, but higher parabactin concentrations consistently arrested cells in G1 phase or at the G1/S interface. MAb 42/6 also increased toxicity of parabactin to granulocyte/macrophage colony-stimulating factors and normal marrow granulocyte/macrophage progenitors. When HL60 or KB cells were treated with MAb 42/6 combined with Ga nitrate, MAb 42/6 increased cytotoxicity of Ga for HL60 cells but had little or no effect on Ga cytotoxicity to KB cells. In contrast, MAb 42/6 had minimal effects on cytotoxicity of the ribonucleotide reductase inhibitor, isoquinaldehyde thiosemicarbazone, to either HL60 or KB cells. Both hematopoietic and solid tumors were killed by Fe depletion, but the present studies suggested that hematopoietic cells are more sensitive than solid tumor cells to cytotoxic effects of Fe depletion. Combined Fe depletion therapy by the use of MAb 42/6 with an Fe chelator or Ga salt increased toxicity to MAb 42/6-sensitive cells, such as HL60, but was not more effective against MAb 42/6-resistant solid tumor cells. Combination Fe depletion therapy of hematopoietic cell tumors merits evaluation in experimental in vivo tumor systems.
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PMID:Combination iron depletion therapy. 266 76

Recent advances of cytogenetics in human hematological malignancies and solid tumors were reviewed. In leukemia and lymphoma, many non-random chromosome aberrations have been found in the last decade. Further specific chromosome aberrations, which existed usually in less than five percent of acute leukemia cases, were recently found, including t (1 ; 3) in MDS or AML M4, +der (1) t (1 ; 7) in MDS, t (1 ; 11) in AML M4 or M5 and +4 in AML M2 or M4. Recurrent chromosome deletions of 17p-, 9q- and 2p- were also found as secondary aberrations in association with tumor development. Accumulation of the data from variant translocation for the 9 ; 22, 8 ; 21 and 15 ; 17 gave us important informations of critical sites of the chromosome in leukemia development. A new trial for the simultaneous analysis of morphology, immunologic phenotype and karyotype on the same metaphase clearly demonstrated stem cell origin of leukemia in some cases, specializing the affected cell lineage. Progress in non-radioactive in situ hybridization techniques now allows approaches to the recognition of particular chromosome abnormality in metaphase and also in interphase cell by means of specific repetitive probes for each chromosome. Though a hypothesis that fragile sites may act as factors predisposing to chromosomal rearrangements have attracted attention in past few years, recent results appear to be conflicting without any direct proof. Cytogenetic studies in solid tumor have been remarkably progressed with advances of methodology. Recurrent chromosome aberrations in solid tumor were found, such as t (X ; 18) in synovial sarcoma, t (12 ; 16) in liposarcoma, and i (12p) in seminoma. Studies on the correlation between specific chromosome changes and histologic subtypes resulted in an useful orientation to the diagnosis and the therapy. Advance in cytogenetics may serve as new concepts for patho-physiology of malignant tumors and contribute to further understandings of molecular genetics in human solid tumors.
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PMID:[Cancer and chromosomes]. 268 17

The authors report on five patients with secondary leukemia (SL) and one of the "specific" chromosomal rearrangements usually encountered in de novo acute nonlymphoblastic leukemia: inv(16), t(15;17), t(8;21), and t(9;11). They were characterized by solid tumor as the primary malignancy in four of five cases, absence of preleukemic phase in all cases, and myelodysplastic features in one of five cases only. All patients achieved complete remission (CR) with aggressive chemotherapy. Only two relapsed, but follow-up is still limited in the three remaining cases. Cytogenetic analysis is important in all younger patients with SL, especially if unusual features (such as absence of preleukemic phase or myelodysplastic features) are found. Aggressive chemotherapy appears to be indicated in those patients if a "specific" rearrangement is found.
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PMID:Favorable cytogenetic abnormalities in secondary leukemia. 272 Jun

We reviewed 135 cases of candidemia occurring between 1983 and 1986 to examine oncologic and nononcologic populations and assess factors for survival. Candida albicans was the most common species (51%); Candida tropicalis occurred most frequently in leukemia patients (57%), whereas Candida parapsilosis and Torulopsis glabrata were associated with solid tumors and nononcologic diseases. Risk factors identified were: preceding surgery, antibiotics, cannulas, and steroids in solid tumor and nononcologic diseases; and chemotherapy and neutropenia with hematologic malignancies. Even transient cannula-associated candidemia was not a benign process. Intravenous cannulas were common portals of entry (39%) in debilitated patients without cancer (59%) and were associated with high mortality (55%). Overall mortality was 59%, candidemia directly contributing to death in 75% of cases. In patients with candidemia, failure to initiate therapy with amphotericin B had a negative influence on outcome, whereas analysis of the entire group identified severity of underlying illness as the dominant cofactor influencing outcome.
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PMID:Fungemia caused by Candida species and Torulopsis glabrata in the hospitalized patient: frequency, characteristics, and evaluation of factors influencing outcome. 274 2

The diagnosis of acute megakaryoblastic leukemia (AMKL) (M7, French-American-British [FAB] classification) has rarely been made in children due, in part, to its pleomorphic morphology and ability to mimic other malignancies common in the pediatric age group. Three infants are described who had thrombocytopenia and the classical criteria of metastatic solid tumor in the bone marrow: patchy infiltration by cohesive clusters of cells with high nuclear cytoplasmic ratio and myelofibrosis in the bone marrow biopsy infiltrated area. This finding prompted clinical evaluation for solid tumor. The megakaryocytic lineage was ascertained by immunocytochemical studies and/or electron microscopic examinations of the bone marrow aspirates. The blasts in all three patients showed cytogenetic abnormalities that also were demonstrated by quantitative DNA analysis. None of the infants had Down's syndrome. Two of the patients are alive; one is off of therapy and the other is in remission. The third patient was transferred to another institution and lost to follow-up. Two children had wheezing that disappeared in remission. It is proposed that the clinical symptoms may be due to a substance produced, stored, or released by the leukemic cells.
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PMID:Three infants with acute megakaryoblastic leukemia simulating metastatic tumor. 276 29

Recent studies concerning cellular and molecular mechanisms of T cell-mediated immunity have revealed the involvement of various types of lymphokines. Irrespective of which types of lymphokines and cell-cell interactions among various T cell subsets are involved in the implementation of host immune responses against tumor, the feasible and practical approach is to use both molecular and cellular mechanisms for the augmented induction of effector T cell activity against tumor-resistant antigens (TRA). We have demonstrated previously that the in vivo effector T cells comprise 2 subsets of TRA-specific non-cytolytic CD4- and CD8-positive helper T cells, both of which release lymphokines and activate macrophages as an ultimate anti-tumor cytocidal effector. We have also defined conditions under which enhanced anti-tumor immunity can be obtained by pre-inducing potent helper T cell activity reactive to a certain antigenic determinant such as trinitrophenyl (TNP) residue of muramyl dipeptide (MDP)-derivatives as hapten, and immunized with tumor cells coupled with the corresponding haptenic determinant. This system induced most efficient and physiological cellular and molecular mechanisms responsible for the generation of tumor-specific effector T cell activity in vivo by virtue of the close linkage of hapten-reactive helper T cells and TRA-specific effector-precursor T cells in the microenvironment of hapten-coupled tumor cells. We have subsequently demonstrated that this protocol resulted in enhanced in vivo tumor protective immunity but also was applicable to the immunotherapy whereby a growing solid tumor as well as disseminated leukemia cells could be effectively eradicated in mice. Thus, these results emphasize the role of hapten-reactive helper T cell in augmenting tumor-specific immunity, and this protocol provides an effective maneuver for tumor-specific immunotherapy in human in future.
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PMID:[Future perspectives on tumor-specific immunotherapy using hapten-reactive T cell activity]. 278 76


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