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)

Two therapeutic modalities, zidovudine (targeting retroviral replication) and cyclosporin A (targeting immunopathologic consequences of retroviral expression) were evaluated in a murine model of AIDS. In previous studies, cyclosporin A treatment (40 or 60 mg/kg/day) before and after infection with LP-BM5 murine leukemia viruses protected against the development of immunodeficiency disease. The present study extends these findings. First, a low dose of cyclosporin A (20 mg/kg/day) was ineffective, and treatment initiated 5 days after infection did not protect against virus-induced lymphoproliferation and hypergammaglobulinemia. Second, zidovudine added to drinking water (0.1 mg initiated 5 days after infection and continued for 8 weeks) was more effective than 0.2 mg/mL given day 5-12 after infection. This treatment reduced lymph node size, disease severity as determined histologically, retrovirus-induced gp70 expression, and IgE (but not IgM and IgG) levels. Third, combined treatment had an additive, protective effect on lymphocyte proliferative capacity. This successful dual therapeutic strategy in a mouse model has potential applicability for similar approaches in treating human immunodeficiency virus infection.
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PMID:Effect of cyclosporin A and zidovudine on immune abnormalities observed in the murine acquired immunodeficiency syndrome. 163

Mice infected with an immunosuppressive murine leukemia virus (MuLV) mixture, LP-BM5, displayed profound and selective deficits in spatial learning in a modified Morris water maze. These deficits appeared before the appearance of gross neurological impairment or histopathological changes in the central nervous system. Thus, LP-BM5-infected mice displayed deficits in several aspects of trained performance compared to controls. Furthermore, a failure to exhibit any evidence of task acquisition in this maze was observed almost twice as frequently (P less than 0.0005) in infected mice as in uninfected controls. Moreover, in the absence of gross visual, motoric, or motivational impairment, LP-BM5 MuLV-infected animals exhibited neither the target directed search pattern nor the spatial preference characteristic of controls. The spatial learning and memory deficit described here is the first report of cognitive impairment accompanying viral-induced immunosuppression in a nonprimate species.
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PMID:Spatial learning impairment in a murine model of AIDS. 164 64

Natural transmission of bovine leukaemia virus (BLV) infection in south-eastern Queensland dairy herds was slow in 2 herds with a low to moderate (13 to 22%) prevalence of infection. Infection spread much more rapidly in a herd that had a higher prevalence (42%) when first tested. In a 13 month study of this herd, the cumulative incidence of infection was 24%. In one herd new infections were confined almost entirely to calves of uninfected dams. Following the end of feeding bulk milk to calves, a common practice in dairy herds, no more calves in this herd became infected. In laboratory experiments, neither prolonged housing of susceptible calves with infected cattle, consumption of drinking water contaminated with infected blood, nor inoculation of sheep with saliva from infected cattle resulted in transmission of BLV infection. Sheep were infected by subcutaneous inoculation of a suspension of purified lymphocytes from an infected heifer. The minimum infective dose was 10(3) lymphocytes, equivalent to the number of lymphocytes in approximately 0.1 microliter blood. Thus, procedures involving the transfer of a very small volume of blood from animal-to-animal have the potential to transmit infection.
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PMID:Factors affecting the natural transmission of bovine leukaemia virus infection in Queensland dairy herds. 165 25

Topotecan (SK&F 104864), a water-soluble analogue of the topoisomerase I inhibitor camptothecin, is currently in Phase II clinical trial for solid tumors. We have characterized topotecan in terms of its effect upon gamma-radiation-induced cell killing. In colony formation experiments, subtoxic concentrations of topotecan (2 microM) potentiated radiation-induced killing of exponentially growing Chinese hamster ovary or P388 murine leukemia cultured cells. Survival curve shoulders were reduced; the slopes of the exponential portions of the curves were decreased to a small extent. D37 and D10 (radiation dose resulting in 37 and 10% survival of colony-forming ability) values were reduced by approximately 60 and 50%, respectively, in the case of Chinese hamster ovary cells. In P388 cells, topotecan reduced D37 by 35 to 40% and D10 by 20 to 25%. Potentiation of radiation-induced cell killing by topotecan was absolutely dependent upon the presence of the topoisomerase I inhibitor during the first few (less than 30) min after irradiation. Association of topoisomerase I with this effect was confirmed in studies of Chinese hamster ovary cells previously made resistant to camptothecin (and cross-resistant to topotecan), resulting in decreased cellular content of topoisomerase I. These cells were found to be 2- to 3-fold hypersensitive to gamma-radiation-induced killing. P388 camptothecin-resistant cells were further sensitized to the lethal effects of ionizing radiation by nontoxic treatment with the topoisomerase II inhibitor novobiocin, consistent with increased dependence of topoisomerase I-deficient cells upon topoisomerase II.
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PMID:Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK&F 104864). 165 71

The cytotoxic and DNA-damaging effects of a novel alkylating anthracycline, N-(5,5-diacetoxypentyl)doxorubicin, were quantified in HL-60 human leukemia cells and in an intercalator-resistant daughter line, HL-60/AMSA. The new drug was cytotoxic to both lines at doses as low as 50 nM for 1 h. N-(5,5-Diacetoxypentyl)doxorubicin produced DNA interstrand cross-linking in both lines. The cross-linking appeared to increase in both lines following drug treatment, but the increase was greater in the resistant line. This appeared to be due to an underestimation of cross-linking, particularly in sensitive HL-60, secondary to time-dependent DNA fragmentation that followed drug removal. This time-dependent DNA fragmentation was probably endonucleolytic cleavage (a feature of apoptosis) as characteristic nucleosomal ladders were produced by N-(5,5-diacetoxypentyl)doxorubicin treatment in a cotemporal time-dependent fashion. This novel anthracycline is the first of a family of alkylating anthracyclines designed to be water soluble, easy to formulate, and capable of producing DNA interstrand cross-linking. Because this last characteristic has previously been associated with doxorubicin analogues of great potency and low toxicity, these newer, more readily formulated drugs may have great clinical utility.
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PMID:N-(5,5-diacetoxypentyl)doxorubicin: a novel anthracycline producing DNA interstrand cross-linking and rapid endonucleolytic cleavage in human leukemia cells. 166 Mar 46

Patients suffering from malignant disease will probably develop some metabolic abnormality of electrolytes. Hypernatremia is defined as an elevation of serum natrium over 150 mEq/l and caused by decrease of water intake, low level of ADH secretion and impaired response of kidney to ADH. Hyponatremia below 135 mEq/l of serum natrium is caused by SI-DAH, sick cell syndrome and increased loss of natrium from the kidney. On the other hand, hyperkalemia is defined as an elevation of serum kalium over 5.0 mEq/l and caused by acute tumor cell lysis syndrome, adrenal and renal insufficiency. Hypokalemia is caused by kalium loss from kidney and hypersecretion of mineral corticoid. Hypercalcemia is found in the high frequency among patients with malignant disease. Hypercalcemia is defined as an elevation of serum calcium over 11.0 mg/dl, although the most important aspect is the level of ionized calcium. The excess calcium causes defective urinary concentration with polydipsia, nausea and vomiting leading to volume depletion. At serum calcium levels about 13.8 mg/dl, there may be rapid deterioration or renal function, dehydration, coma and cardiac arrhythmias. Hypercalcemia is rarely the first manifestation of cancer. There are three principle pathogenic causes of malignant hypercalcemia, 1) hypercalcemia is a feature of several hematological cancers, including Burkitt's lymphoma, T cell leukemia, but most commonly with myeloma. The hypercalcemia in these myeloma patients is due to the secretion of an osteoclast activator, a lymphokine by the myeloma cells. 2) all patients with bony metastases have biochemical evidence of increased bone resorption. However, not all patients with bony metastases develop hypercalcemia. Probably the hypercalcemia is due partially to increased renal tubular reabsorption of calcium, mediated by a humoral factor, with activity similar to that of parathormone. 3) hypercalcemia in the patients without bony metastases is due to increased bone resorption caused by the ectopic secretion by the tumor. Mildly symptomatic patients will benefit from modest salt loading. They are dehydrated and replacement of the extracellular fluid is the first line of treatment. This may require 4-10 l normal saline/24 h. In addition, frusemide will increase calcium excretion. Calcitonin may be given subcutaneously or intravenously to refuse the mobilisation of calcium from bone. Glucocorticoids are unhelpful, but will prolong the effect of calcitonin. A diphosphonate is also useful.
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PMID:[Palliative therapy in cancer. 4. Palliation of the symptoms from a malignant tumor. (2)]. 169 56

The presence of 10 microM dipyridamole in incubation media of L1210/C2 cells decreased initial rates of zero-trans influx of formycin B (FB, 50 microM), a poorly metabolized inosine analogue, from 4.84 pmol/microliters cell water/s to 0.87 pmol/microliter cell water/s. However, after a 5-min interval of uptake, free FB levels in dipyridamole-treated cells were 165 pmol/microliters cell water, 2.3-fold greater than in dipyridamole-free cultures. This indicated the presence of a concentrative, dipyridamole-insensitive nucleoside transport (NT) system in L1210 cells, in addition to the equilibrative NT systems known to be expressed in these cells. The concentrative system was demonstrable only in the presence of NT inhibitors and required extracellular Na+. The presence of 8 microM 6-[(4-nitrobenzyl)thio]-9-beta-D- ribofuranosylpurine or 15 microM dilazep also induced an accumulation of free FB above steady-state levels, although of a lesser magnitude than that observed with dipyridamole. It appears that NT inhibitors induced nucleoside accumulation by inhibiting bidirectional nucleoside movements mediated by the equilibrative component of nucleoside transport in L1210/C2 cells without interfering with inward FB fluxes mediated by the Na(+)-dependent transporter. The presence of NT inhibitors also enhanced the cellular accumulation and retention of arabinosyladenine and its 5'-triphosphate in these cells. The increased cellular accumulation of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosyladenine triphosphate by dipyridamole was associated with enhanced antiproliferative activity of 9-beta-D-arabinofuranosyladenine towards the leukemia cells.
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PMID:Sodium-dependent and equilibrative nucleoside transport systems in L1210 mouse leukemia cells: effect of inhibitors of equilibrative systems on the content and retention of nucleosides. 169 38

Cytotoxin P4 was isolated from the venom of Naja nigricollis nigricollis in three steps and contained 55% of the crude cytotoxic activity. It had a molecular weight of 8 KD, was stable over a pH range of 1-11 and in boiling water for at least 15 min. It had no measurable enzymatic activities, but was destroyed by proteases. Concentrations of 0.8, 1, 1.2, 25. 20 and 45 ug/ml, were needed to destroy murine melanoma B16 and WEHI 3B leukemia, rat chondrosarcoma, mouse erythrocytes and spleen cells, and human erythrocytes, respectively, thereby showing preferential cytotoxicity to the examined tumor cells. It also prevented the development of the melanoma, leukemia and chondrosarcoma tumors in vivo when mixed with the cells prior to the injection into the animal.
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PMID:Isolation and characterization of a cytotoxin P4 from the venom of Naja nigricollis nigricollis preferentially active on tumor cells. 177 20

ICRF-187 is the (+) enantiomer of the racemic mixture razoxane (ICRF-159). This compound is much more water soluble and thus could be formulated for parental use. The maximum tolerated dose in children after phase I trials was determined to be 3500 mg/M2/day x 3 days. A phase II trial of ICRF-187 was done in 21 children with solid tumors and 35 children with acute leukemia. All these patients were less than 21 years of age, had recovered from previous chemotherapy, had normal liver and kidney functions, and had a life expectancy of greater than 4 weeks. ICRF-187 was administered at a dose of 3 g/M2/day for 3 days as a 4 hour infusion each day. In patients with leukemia, no objective response was seen in the bone marrow although a few patients had a decrease in peripheral blast count. There were no measurable responses seen in patients with a solid tumor. ICRF-187 was well tolerated. The major toxicity was hematopoietic depression. Significant but rare toxicities included moderate to severe nausea and vomiting, and elevation of bilirubin and transaminases. Although inactive in the current study, ICRF-187 might be more active in another schedule.
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PMID:Phase II trial of ICRF-187 in children with solid tumors and acute leukemia. 180 8

Near-infrared emission (1170-1475 nm) was studied from L1210 leukemia cells incubated with polyporphyrin (fractionated hematoporphyrin derivative), suspended in deuterium oxide buffer, and then exposed to light. Following pulsed laser excitation, the near-infrared emission decayed in two phases. The first phase of the emission (0-2 microseconds) was principally due to polyporphyrin fluorescence. The second phase of the emission (20-90 microseconds) was due mainly to singlet oxygen. Evidence supporting the assignment of the second phase emission to singlet oxygen included a spectral analysis showing a peak near 1270 nm and reductions in the second phase emission caused by the singlet oxygen quenchers, histidine, carnosine, and water. The second phase emission decayed in a biexponential manner with lifetimes of 4.5 +/- 0.5 and 49 +/- 4 microseconds. Most of the singlet oxygen in the second phase emission was likely due to singlet oxygen that was generated near the surface of the L1210 leukemia cells and then diffused into the deuterium oxide buffer. Direct measurements of singlet oxygen phosphorescence at 1270 nm may prove to be a useful analytical technique for studying photochemical generation of singlet oxygen in cultured cells.
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PMID:Direct observation of singlet oxygen phosphorescence at 1270 nm from L1210 leukemia cells exposed to polyporphyrin and light. 183 32


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