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)

A modified species of hydroxyethyl starch (HES 350/0.60) possessing a Mw- of 350,000 daltons combined with a molar hydroxyethyl group substitution (MS) of 0.60 (60 hydroxyethyl groups.100 glucose residues) was clinically assessed in seven normal subjects to determine the influence of these chemical modifications on intravascular clearance kinetics concomitantly with effects on the suspension stability (ESR) of blood. Following a standardised intravenous dose (30 gm.m2 BSA), the concentration of HES 350/0.60 in serum fell to half its peak value in 11.8 +/- 1.3 (SD) hours, while the ESR remained elevated for up to 12 hours post-injection. By adopting a Mw- of 350,000 daltons, the critical molecular weight (Cmw) of this colloid was surpassed, while the critical concentration (Cc), below which the suspension stability of blood is not affected, was shown to range between 0.3 and 0.5 gm.dl-1. In comparison to the present species of HES (Mw- 450,000 daltons, MS: 0.70) utilised as a sedimenting agent duirng centrifugal leucapheresis, HES 350,000/0.60 appears to affect the ESR in a similar manner, but is removed from the intravascular space approximately twice as rapidly. This more rapid clearance should be useful in avoiding cumulative build-up of HES in blood concomitant with reducing the total amount of intravascular H2O bound to this colloid, in normal and CML donors undergoing multiple cell collection procedures.
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PMID:The plasma kinetics of hydroxyethyl starch 350/0.60: a potential new adjunct for centrifugal leucapheresis. 9 71

A case of acute nonlymphocytic leukemia (ANLL) with primitive basophilic differentiation is presented. The patient had no antecedent history or concomitant presence of chronic myelogenous leukemia. The leukemic blasts constituted 83% of the peripheral white blood cells and more than 90% of the marrow nucleated cells. Cytoplasmic vacuoles were found in some leukemic cells. About half the leukemic cells showed a few azurophilic granules stained with Wright's stain, whereas exhibited a faint pinkish hue around the cells without cytoplasmic granules (water-soluble granules) by Riu's stain. The cytoplasmic granules failed to be stained with peroxidase but stained positively with toluidine blue. The former result could lead one to misclassify the case as lymphoid leukemia, but the characteristic finding of basophilic cells in Riu's stain should direct one to make the diagnosis of ANLL with basophilic differentiation. The cytochemical findings of this case suggested that basophilic differentiation should be considered when leukemic cells show peroxidase-negative granules. Riu's stain and toluidine blue stain are useful to make the correct diagnosis.
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PMID:Acute basophilic leukemia. A case report. 171 80

The ability of bepridil, a calcium channel blocker, to potentiate the antitumor activity of mitoxantrone (MITO) in human chronic myeloid leukemia (CML) cells was evaluated. MITO and bepridil, when incubated alone with the CML cells for 4 h, indicated a dose-dependent increase in the inhibition of 3H-thymidine incorporation. Incorporation rate of the radiolabeled thymidine into DNA was used as a measure of cell growth. When the CML cells were exposed to MITO (1 microgram/ml) in the presence of bepridil (1 and 5 micrograms/ml), an enhancement in the inhibition of DNA biosynthesis was observed in 14 out of 17 human CML samples studied. This significant inhibition (p less than 0.001) of 3H-thymidine incorporation due to the combination was found to be completely irreversible. Bepridil was identified predominantly in the octanol phase in the octanol/water partitioning studies. This lipophilic property of drug response modulators was implicated in the observed increase in the intracellular uptake of anticancer drugs, which in turn led to an enhanced cytotoxicity correlating well with the MITO activity observed in this study. The results are suggestive of clinical utility of bepridil as an adjuvant to enhance the anticancer ability of MITO in the treatment of CML.
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PMID:Response of human chronic myeloid leukemia cells to mitoxantrone cytotoxicity: potentiation by bepridil, a calcium channel antagonist. 176 84

A high dose of cytosine arabinoside (ara-C) was given to 51 patients during consolidation therapy or with refractory or relapsed acute leukemia. Ara-C was administered as a 3-hour infusion at a dose ranging from 2 to 3 g/m2 every 12 hours, diluted in 500 ml of 5% dextrose in water for 2 to 6 days. Complete remission was attained in 3 (25%) of 12 evaluable patients. Two with blast crisis of chronic myelogenous leukemia of these did not obtain complete remission. Death due to marrow aplasia occurred in five patients, and two of these had relatively good performance status and were given a dose of 3.0 g/m2 x 8 or 12 of ara-C. At a dose of 3.0 g/m2 x 6, the mean duration of granulocytes of less than 100/mm3 was 6.7 days. This duration seemed to be manageable myelosuppression. Therefore, 3.0 g/m2 x 6 was thought to be an adequate dose. Seizure occurred in one patient, and conjunctivitis was seen in another. In conclusion, from the manageable myelosuppression observed, administration of 3.0 g/m2 x 6 of ara-C seemed to be an adequate dose.
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PMID:[High-dose cytosine arabinoside treatment of leukemia with special reference to the optimal number of doses]. 277 89

A new water-soluble nitrosourea derivative, methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), was found to be useful for the treatment of chronic myelogenous leukemia (CML) in the chronic phase. To compare the efficacy of MCNU with that of busulfan, patients were randomized. In the 40 patients administered MCNU, the median time to the achievement of a complete remission (CR) was 50 days. This value was shorter than that observed in 37 patients administered busulfan (126 days, p less than 0.05). There were no differences in the rate of CR achieved, mortality, median time to the onset of blast crisis (BC), BC rate, or survival rate during the observation period. The overall incidence of side effects was higher for MCNU (31%) than for busulfan (15%), but the symptoms were mild, transient and tolerable for most patients. These results suggest that MCNU is a safe and valuable addition to the therapeutic repertoire for the control of CML.
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PMID:A new nitrosourea derivative for the treatment of chronic myelogenous leukemia. 304 11

Serial magnetic resonance (MR) studies of the cervical bone marrow were performed in five patients undergoing bone marrow transplantation for chronic granulocytic leukemia and in four patients with aplastic anemia who were treated with antilymphocytic globulin. Findings were compared with those from a group of healthy volunteers. Chemical shift imaging techniques were used to exploit the presence of protons in fat and water in the red marrow. Characteristic changes were seen in aplastic anemia before treatment, but derivation of images representing fat and water fractions was necessary to distinguish leukemic marrow. Acute changes during the treatment of leukemia may reflect the effects of chemotherapy and radiation therapy, whereas changes in the chronic phase of both diseases may prove useful in predicting treatment outcome. MR studies are likely to be useful in the assessment and treatment of hematologic disorders.
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PMID:Bone marrow in leukemia and aplastic anemia: MR imaging before, during, and after treatment. 354 34

The temperature dependence of the apparent water diffusional exchange through erythrocyte membranes in cases of policitemia vera, chronic granulocytic leukemia and primary myelofibrosis was measured by using a nuclear magnetic resonance method in the presence of Mn2+. The thermal transition shifted to lower temperatures in all cases, regardless of the stage of the disease, suggesting a structural alteration of the membrane. The shift of transition indirectly suggests a lower penetration of the erythrocytes by Mn2+. The water exchange time at 37 degrees C also increased, mainly in the blast crisis; it seems to have a prognostic value of some clinical interest. No simple correlation of the water exchange and the following clinical investigations was observed: the white count, the percentage of promyelocites and myeloblasts, the sedimentation rate of blood, the osmotic fragility of erythrocytes, the total concentration of proteins, albumin and immunoglobulins, respectively, in plasma.
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PMID:Nuclear magnetic resonance investigation of erythrocyte membranes in chronic myeloproliferative disorders. 374 82

In animal models of cancer, an elevation of T1 and T2 in uninvolved tissues and in the blood of tumor bearing animals has been termed "the systemic effect." This study reports T1 values in sera of human patients from Genoa, Italy, with several types of cancer and non-cancerous diseases. T1 values were significantly elevated over normal controls (1628 +/- 113 ms) in colorectal cancers (1725 +/- 149 ms) and stomach cancers (1817 +/- 219 ms). However a systemic effect was not demonstrated in acute myeloid leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, or plasma cell myeloma, or in pancreatic and lung cancers. Noncancerous states of cirrhosis, chronic hepatitis, and monoclonal gammapathies did not show a T1 elevation. In general, T1 values of sera correlated with protein content of the sera; however, a disproportionate contribution of gamma-globulin protein on water proton relaxation times was observed in several cases.
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PMID:The systemic effect of cancers on human sera proton NMR relaxation times. 608 32

The osmotic behavior of control lymphocytes (CL) and polymorphonuclears (CPMN) was compared with that of cells from patients with chronic lymphocytic leukemia (CLL) and chronic myelocytic leukemia (CML), using the method of gradual dialysis against distilled water. The results were evaluated with a fragiligraph, and by scanning (SEM) and transmission (TEM) electron microscopy. The fragiligraphy curves showed that CLL cells are more resistant to osmotic pressure than the CL, whereas the curves for CPMN and CML cells showed an overlap. Surface alterations in CL appeared as early as 1 min of dialysis, while in CLL cells the membrane did not show major alterations even after 5 min of dialysis. CPMN also showed alterations earlier than CML cells, but this difference was not as prominent as in the case of lymphocytes and was observed for a maximum of 3 min of dialysis. The internal structure of the cells was altered earlier than the surface membrane and this was expressed mainly in the nucleus in both control and leukemic cells. Also in this respect, the internal structure of CL was altered earlier than that of CLL cells, whereas no major differences were observed between CPMN and CML cells.
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PMID:SEM and TEM studies on the osmotic behavior of control and leukemic lymphocytes and polymorphonuclears. 612 53

This paper provides an overview of cancer chemotherapy with special reference to the pharmacokinetics of the nitrosoureas. At physiological PH, the chloroethylnitrosoureas can be decomposed into an isocyanate and 2-chloroethyl diazene hydroxide. Therefore, it is clear that they have both alkylation and carbamoylation actions. In addition to the spontaneous chemical dissociation, the nitrosoureas can be metabolized by liver microsomal enzymes to more polar hydroxylated products, and certain nitrosoureas can be denitrosated by these enzymes to the parent urea. Since the lipid-soluble nitrosoureas and some of the water-soluble nitrosoureas such as ACNU and MCNU demonstrated to cross the blood-brain barrier, they have been used in the treatment of primary brain tumors and tumors and tumors of metastatic origin. It has been demonstrated from the results of our study and other reports that the alkylation of DNA by ACNU progresses more slowly as compared with that of other alkylating agents. This is an important finding in relation to the appearance of delayed myelosuppression of the nitrosoureas and in the design of dose schedules of these agents. The major clinical emphasis has been directed towards the more active chloroethylnitrosoureas with reduced myelosuppression, and attempts are now made for this purpose. Unfortunately, the results of phase I and II trials of the newly developed nitrosoureas suggest that these agents produce delayed and cumulative bone marrow toxicity. Antitumor activity of the nitrosoureas is frequestly observed in chronic myelocytic leukemia, malignant lymphoma, brain tumors and small cell carcinoma of the lung, and less frequently in gastrointestinal carcinoma, multiple myeloma and malignant melanoma. In order to enhance clinical effects of the nitrosoureas, further investigation of the design in therapeutic schedules on the basis of their pharmacokinetic characteristics will be needed.
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PMID:[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas]. 622 95


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