Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-radiation remains the treatment of choice in most cases of leukemia and lymphoma, but new agents are playing an increasing role in therapy. Radioactive phosphorus does not produce radiation sickness and results with it are comparable to those of x-ray therapy in chronic leukemia. Urethane and nitrogen mustard may produce remissions in patients with chronic leukemia who have become resistant to radiation. Triethylene melamine may be administered orally with nitrogen mustard-like effects and is undergoing further trial. Aminopterin, ACTH and cortisone often cause short remissions in acute leukemia. Urethane is the best treatment available for multiple myeloma. Polycythemia vera is well controlled by radioactive phosphorus combined with venesection. Nitrogen mustard is often effective and triethylene melamine shows promise in Hodgkin's disease. Antianemic substances such as iron and liver extract are of no value in the treatment of anemia caused by leukemia, lymphoma and myeloma.
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PMID:New therapy for leukemia, polycythemia, and lymphoma. 1301 1

The trace element boron is essential for all higher plants and is beneficial or has been established as essential for several animal models of human nutrition. To help identify the biomolecules that require boron for function in humans, we determined whether intracellular boron is retained against a concentration gradient. Cells (Abelson leukemia virus BALB murine monocyte-macrophage RAW 264.7 [RAW] and HL60) and supplemented media (Dulbecco's modified essential media [+ 10% fetal calf serum] and Iscove's modified Dulbecco's medium [+ 5% fetal calf serum], respectively) were analyzed for mineral concentrations after culture and subculture. Special corrections were made for trapped extracellular media in cell pellets and endocytosed media. For RAW cells, the partitioning coefficients (PC; intracellular/extracellular ratios) were, in rank order, as follows: Mn, 110; Fe, 67; P, 65; Zn, 32; K, 15; Cu, 7.1; Mg, 4.3; B, 1.7; Ca, 0.4; Na, 0.3. For HL60 cells, the partitioning coefficients were, in rank order, as follows: Mn, 212; Zn, 211; P, 123; K, 21; Fe, 16; Mg, 11; B, 1.7; Ca, 0.8; Na, 0.3. Trapped extracellular media was estimated to be 6.7 +/- 0.8%; trapped extracellular and endocytosed media together was 24.8 +/- 0.3% of the mass within the isolated cell pellets. The partitioning coefficients indicate a positive gradient for intracellular accumulation of boron, zinc, phosphorus, manganese, magnesium, potassium, iron, and copper in RAW264.7 and HL60 cells. Specifically, the data indicate the existence of a selective boron-binding molecular species within the cell or the existence of a boron-specific membrane transporter.
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PMID:Transmembrane partitioning of boron and other elements in RAW 264.7 and HL60 cell cultures. 1507 15

In order to evaluate potential long-term kidney damage of childhood leukemia and risk factors affecting renal damage, we studied 116 children treated for acute lymphoblastic leukemia (ALL) using the St. Jude Total XI and XIII protocols in 1991-1998. The median follow-up period after the completion of treatment was 35 months. The following parameters were examined: urinalysis, urinary creatinine (Cr), calcium (Ca), phosphorus, beta2-microglobulin, glomerular filtration rate (GFR), tubular phosphorus reabsorption (TPR), and renal function tests. Radiological evaluation included renal ultrasonography (US), and renal scans with DMSA or MAG-3 were performed. Blood chemistry and renal US patients were normal in all patients except two. GFR, TPR, urinary Ca/Cr, beta2-microglobulin, and renal scan were abnormal in 19.0%, 16.4%, 13.8%, 6.0%, and 40.5% of patients, respectively. The abnormality rate in GFR was significantly higher in patients <2 years of age. TPR abnormality was found to be significantly higher in patients who did not have G-CSF. An abnormal renal scan was associated with Hb < 10 g/dL, kidney infiltration, or hypertension at presentation and also occurred patients who underwent methotrexate treatment with frequent intervals during the follow-up period. Patients should be followed-up after cessation of therapy with the conventional tests mentioned above. In case of any abnormality, further detailed tests should be performed; renal scan seems to be more predictive for renal damage.
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PMID:Evaluation of kidney damage in patients with acute lymphoblastic leukemia in long-term follow-up: value of renal scan. 1538 22

Nude rats bearing the LC-6-JCK human lung cancer xenograft displayed cancer-associated wasting syndrome in addition to humoral hypercalcemia of malignancy. In these rats, not only PTHrP but also several other human proinflammatory cytokines, such as IL-6, leukemia-inducing factor, IL-8, IL-5 and IL-11, were secreted to the bloodstream. Proinflammatory cytokines induce acute-phase reactions, as evidenced by a decrease of serum albumin and an increase in alpha1-acid glycoprotein. Tumor resection abolished the production of proinflammatory cytokines and improved acute-phase reactions, whereas anti-PTHrP antibody affected neither proinflammatory cytokine production nor acute-phase reactions. Nevertheless, tumor resection and administration of anti-PTHrP antibody similarly and markedly attenuated not only hypercalcemia but also loss of fat, muscle and body weight. Body weight gain by anti-PTHrP antibody was associated with increased food consumption; increased body weight from anti-PTHrP antibody was observed when animals were freely fed but not when they were given the same feeding as those that received only vehicle. Furthermore, nude rats bearing LC-6-JCK showed reduced locomotor activity, less eating and drinking and low blood phosphorus; and anti-PTHrP antibody restored them. Although alendronate, a bisphosphonate drug, decreased blood calcium, it affected neither locomotor activity nor serum phosphorus level. These results indicate that PTHrP represses physical activity and energy metabolism independently of hypercalcemia and proinflammatory cytokine actions and that deregulation of such physiologic activities and functions by PTHrP is at least in part involved in PTHrP-induced wasting syndrome.
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PMID:Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts. 1580 Sep 41

Leptin has important effects on bone metabolism. Possible relationships between leptin and bone mineral density were evaluated in the survivors of the childhood leukemia and lymphoma. Twenty patients were included the study. Anthropometric parameters, growth hormone response to provocative test, serum calcium, phosphorus, alkaline phosphates, osteocalcin, leptin levels, urinary calcium and deoxyypyridinoline levels, and bone mineral density were obtained. Anthropometric parameters of patients were not significantly different from those of a control group. Growth hormone provocative test was abnormal in 3 patients who received cranial radiotherapy. The osteocalcin levels and bone mineral density of patients were significantly lower than in the control group (p=.001, p=.02). Nine patients were in the osteopenic and 7 were in the osteoporotic range. The leptin levels of patients were significantly lower (p=.01) than in the control group. Bone mineral density (BMD) was significantly correlated with leptin level, age, body mass index, and Tanner stage in simple correlation analysis. However, in multivariate analysis only age was significant (p<.000, r: .752). Markers of bone metabolism, BMD, and leptin levels were not related with the growth hormone status of patients and did not present a correlation with the cumulative doses of drugs. There are a few studies evaluating the relationship between BMD and leptin levels in childhood cancer. Although this study did not find any correlation between the leptin level and BMD, detailed studies of larger numbers of patients are necessary to evaluate causes of decreased leptin level and the possible role of leptin on osteopenia observed in survivors of childhood cancer.
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PMID:Bone mineral metabolism and its relationship to leptin levels in survivors of childhood leukemia and lymphoma. 1616 15

Elemental selenium generated by the photobleaching of selenomerocyanine dyes forms conjugates with serum albumin and serum lipoproteins that are toxic to leukemia and selected solid tumor cells but well tolerated by normal CD34-positive hematopoietic stem and progenitor cells. Serum albumin and lipoproteins act as Trojan horses that deliver the cytotoxic entity (elemental selenium) to tumor cells as part of a physiological process. They exploit the fact that many tumors have an increased demand for albumin and/or low-density lipoprotein. Se(0)-protein conjugates are more toxic than selenium dioxide, sodium selenite, selenomethionine, or selenocystine. They are only minimally affected by drug resistance mechanism, and they potentiate the cytotoxic effect of ionizing radiation and several standard chemotherapeutic agents. The cytotoxic mechanism of Se(0)-protein conjugates is not yet fully understood. Currently available data are consistent with the notion that Se(0)-protein conjugates act as air oxidation catalysts that cause a rapid depletion of intracellular glutathione and induce apoptosis. Drugs modeled after our Se(0)-protein conjugates may prove useful for the local and/or systemic therapy of cancer.
Phosphorus Sulfur Silicon Relat Elem 2005
PMID:ELEMENTAL SELENIUM GENERATED BY THE PHOTOBLEACHING OF SELENOMEROCYANINE PHOTOSENSITIZERS FORMS CONJUGATES WITH SERUM MACROMOLECULES THAT ARE TOXIC TO TUMOR CELLS. 1649 Nov 41

The aim of this research was to examine chemical and biological properties of the products (4a-c/5a-c, 8b-c, 9a-b) of the reaction of methyl chromone-3-carboxylate (2), 3-formyl-4-hydroxycoumarin (3), 3-formylchromone (6) and chromone 3-carbonyl chloride (7) with phosphorus hydrazides (1a-c). For structure and keto-enol tautomerism analyses (1)H, (13)C, (31)P NMR spectroscopy was used. The ring transformation species (4a-c/5a-c) containing the coumarin ring (5a-c) were predominant in the solution. The chromone series 8b-c and 9a-b was obtained in reaction of phosphorus hydrazides (1a-c) with 3-formylchromone (6) and chromone-3-carbonyl chloride (7). Alkylating activity of phosphorohydrazides of coumarin and chromone was determined with in vitro Preussmann test (NBP test). Some of the compounds were examined towards antitumor and antibacterial activity. Compounds 4b-c/5b-c and 9a demonstrated in vitro antitumor activity against P388 leukemia. Antineoplastic activity of the compounds 4b/5b and 9a combined with methotrexate was showed using L1210 murine leukemia.
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PMID:In vivo antitumor, in vitro antibacterial activity and alkylating properties of phosphorohydrazine derivatives of coumarin and chromone. 1690 95

To prevent acute renal failure in children at risk for developing tumor lysis syndrome due to acute lymphoblastic leukemia or non-Hodgkin's lymphoma treated according to international BFM protocols, we investigated recombinant urate oxidase (rasburicase) in the first Central European openlabeled, prospective, multicenter phase IV trial. Rasburicase was administered intravenously, at 0.2 mg/kg for 5 consecutive days to 36 patients. Blood levels of uric acid, creatinine, phosphorus, calcium, lactate dehydrogenase and complete blood count were measured daily during rasburicase treatment and on days 6, 7 and 12. Initial uric acid level decreased significantly by 4 hours (from 343 micromol/L to 58 micromol/L, p<0.001), except for one steroid-resistant patient who required hemodialysis on day 14 after having introduced combined cytostatic treatment. Comparing the data of a subgroup of 12 patients receiving rasburicase with that of a historic cohort of 14 patients treated with allopurinol indicated the superiority of rasburicase over allopurinol in prophylaxis and treatment of hyperuricemia in children with leukemia and lymphoma.
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PMID:Prevention and treatment of hyperuricemia with rasburicase in children with leukemia and non-Hodgkin's lymphoma. 1738 90

The results above reported lead to the conclusion that while in the degenerating cells chemical changes are taking place tending toward a diminution of the hexon bases as a whole, they affect the arginin especially. One may picture the process either as a partial or as a complete breaking down of certain proteid. material more or less rich in hexon bases, leaving behind. proteid matter poorer in bases. The meaning of these changes is, however, obscure, and with the limited number of known facts bearing upon the subject, it would seem idle even to attempt to formulate an hypothesis to explain them. Certain work of other investigators is, however, suggestive in this connection. Kossel and Dakin, for instance, as illustrated by their work upon the simple proteid body clupein, found that a partial destruction of the proteid molecule, involving the arginin group, is brought about by a ferment furnished by the animal organism. When subjected to the hydrolytic action of a mineral acid, clupein yields arginin in considerable abundance. But if the clupein is first acted upon by the ferment arginase found in the liver, and then subjected to acid hydrolysis, the yield of arginin is appreciably diminished. Among the cleavage products in the latter instance are the components of arginin, namely, omithin and urea. It would seem, therefore, as if the ferment had loosened the union between the omithin and urea in the arginin group, so that upon subsequent hydrolysis a diminution of arginin resulted. In the cases studied by me, it may be that the conditions were favorable for some such ferment action as that above described, and hence the relatively low yield of arginin. No attempt, however, was made to ascertain if omithin were present in the urine. Its presence there would seem not wholly unlikely when one considers the diminished power of oxidation of the phosphorus-poisoned cell, although Thompson has shown that arginin or omithin when administered to a healthy dog as food or by hypodermic injection is eliminated for the most part as urea, no ornithin being found. There might seem to be a conflict between this view and the results recently published by Wohlgemuth, but it must be borne in mind that the influences at work causing the breaking down of the proteid molecule are probably quite diverse in character. Wohlgemuth has recently shown for the first time that a diamino acid may actually find its way into the urine in phosphorus poisoning. He found arginin in the urine not only in rabbits poisoned with phosphorus but also in a patient suffering from phosphorus poisoning. On the other hand, he was unable to find lysin in the urine. This fact is of especial interest in view of the evidence set forth in this paper that the arginin base is lost to the proteid molecule more rapidly than the lysin base. The correspondence between the findings in the liver and in the urine is thus a close one. How much of the arginin liberated from the proteid molecule may find its way into the urine is of course uncertain. It seems reasonable to suppose that a portion of the base is acted upon by the arginase ferment in the manner already described. Of the seventeen to eighteen cleavage products of the proteid molecule thus far isolated, the hexon bases are among the most stable. One or more of these bases have been found in practically all proteid matter thus far investigated; in fact arginin is so uniformly present that Kossel has made the suggestion that it is the kernel of the proteid molecule. At all events, the question may be asked, whether, if the influences at work in the altered liver tissue were of a general character causing a diminution of the hexon bases, the monoamino acid groups would not suffer even a greater diminution; and since the pathological condition is undoubtedly associated with impaired oxidation, their presence should not be expected in the urine. As a matter of fact, Ignatowski found considerable quantities of monoamino acids in the urine of patients suffering from gout, pneumonia, and leukaemia, though under normal conditions no monoamino acids were found in the urine, indeed, not even after the subcutaneous injection of glycokoll. Furthermore, the loosening of the amino acids from the proteid molecule is suggested by the fact that Taylor found such acids in the liver of a patient who died from a hepatic disease of obscure etiology, but which he was inclined to attribute to chloroform poisoning. Taylor found not only leucin and tyrosin in the liver, but also arginin, a fact not without interest in view of the diminished arginin content found in the livers of the chloroformed dogs after acid hydrolysis. Moreover, the falling off of the hexon bases under the conditions studied seems quite in accordance with some results recently reported by Levene. He has shown that certain cleavage products obtained by the action of mineral acids upon self-digested pancreas, spleen, and liver, are much diminished when compared with the products obtained from the fresh glands. The lysin and arginin of the digested liver, for example, showed a diminution of over 50 per cent. It is now well established that in course of the process of aseptic autolysis, the proteids of the liver cell undergo decomposition into simpler substances, and Jacoby showed that during life autolysis may go on in portions of the liver in which the circulation has been hindered. But of greater significance still in this connection, is the observation made by Jacoby on the autolytic changes in the liver during phosphorus poisoning. He found that when the normal liver substance is permitted to autolyse the solution of the liver substance is a slow one. On the other hand, under similar conditions the liver of a phosphorus-poisoned animal undergoes rapid and almost complete solution. The difference in the behavior of the normal and damaged liver points to an increase of normal ferment action in the case of the poisoned organ. It thus seems reasonable to suppose that in phosphorus poisoning we have during life an exaggerated breaking down of the proteid molecule associated with an over-action of certain ferments, and among them probably arginase. The pathological process in the liver during life may, therefore, be thought of as proceeding in the same general direction as the process of post-morten autolytic decomposition. By means of further studies along lines indicated in this paper, it should be possible to gain a deeper insight into numerous pathological processes. The changes in amyloid degeneration are among those which promise to be better understood through the application of the new methods of chemical analysis. Moreover, it cannot be doubted that pharmacology as well as toxicology has much to gain from a study of what happens to the proteid molecule under the influence of poisons.
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PMID:ON THE HEXON BASES OF LIVER TISSUE UNDER NORMAL AND CERTAIN PATHOLOGICAL CONDITIONS. 1986 99

Acute tumor lysis syndrome (ATLS) is a potentially lethal condition precipitated by the massive release of intracellular components such as nucleic acids, potassium, and phosphorus, following a rapid and widespread lysis of tumor cells. Herein, the authors describe the high incidence and characteristic histopathologic lesions of acute ATLS in p53-deficient mice used in 2 short-term carcinogenicity studies. ATLS was a frequent cause of early death in p53 (+/-) mice in these studies and was consistently associated with the presence of disseminated lymphoma and leukemia. Although a heavy tumor burden and leukemia were present in all affected mice, the absence of ATLS in other mice with equally severe lymphoma and leukemia indicates that these tumor burdens are necessary but insufficient to cause ATLS in mice. The hallmark histopathologic findings of ATLS in mice are the disseminated microemboli composed of nuclear and cytoplasmic debris derived from lysed tumor cells. The mechanical obstruction of capillary beds by these microemboli appeared to be the proximate cause of the early deaths of mice in these studies. Microemboli may contribute to the pathogenesis of acute renal failure and other clinical signs associated with ATLS in other species. Recognition of ATLS in laboratory animals is critical in studies intended to evaluate the efficacy and/or toxicity of anticancer treatments, where early deaths due to ATLS might otherwise be attributed to test article toxicity. Further studies on the role of microemboli in the pathogenesis of ATLS may elucidate pathogenetic mechanisms and lead to improved approaches to clinical management and treatment of this potentially lethal condition.
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PMID:Spontaneous acute tumor lysis syndrome as a cause of early deaths in short-term carcinogenicity studies using p53 +/- mice. 2043 82


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