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1.
Eur J Cancer ; 41(5): 694-701, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15763644

ABSTRACT

The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen+placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I, and insulin-like growth factor binding protein 1-3 (IGFBP1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment. Combined treatment caused a higher increase in IGFBP-1 and larger suppression of total and free IGF-I, IGF-II, and IGFBP-3 (P<0.01 for all), but less suppression of IGFBP-2 (P<0.05) compared with tamoxifen monotherapy. An increase in IGFBP-2 25% was associated with decreased progression-free survival (PFS) in the total patient population and combined treatment group. Similar response rates and time to progression in the treatment arms suggests moderate suppression of circulating IGF-I has no influence on clinical outcome.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Insulin-Like Growth Factor Binding Proteins/drug effects , Somatomedins/drug effects , Tamoxifen/therapeutic use , Adult , Aged , Aged, 80 and over , Breast Neoplasms/blood , Double-Blind Method , Female , Humans , Insulin-Like Growth Factor Binding Proteins/blood , Middle Aged , Octreotide/administration & dosage , Proportional Hazards Models , Somatomedins/analysis , Tamoxifen/administration & dosage , Treatment Outcome
2.
Am J Med Sci ; 297(2): 114-7, 1989 Feb.
Article in English | MEDLINE | ID: mdl-2919631

ABSTRACT

We describe a new glucose-6-phosphate dehydrogenase mutant, G-6-PD Titusville. The propositus is a 7-month-old black male infant with a transient hemolytic episode. The mutant enzyme is characterized by abnormal electrophoretic mobility, thermolability, Km for NADP, abnormal deamino NADP use and a decreased sensitivity to inhibition by NADPH. G-6-PD activity of hemolysate, as measured under optimal in vitro conditions, was not initially decreased, whereas fibroblasts, granulocytes, and platelets showed a markedly decreased level of enzyme activity. These properties identify G6PD Titusville as a unique variant of this X-linked, housekeeping enzyme. We conclude that although the propositus with G6PD Titusville had a transient hemolytic episode, we cannot be certain whether this association was a causative one.


Subject(s)
Glucosephosphate Dehydrogenase/blood , Enzyme Stability , Erythrocytes/enzymology , Glucosephosphate Dehydrogenase Deficiency/enzymology , Hemolysis , Hot Temperature , Humans , Infant , Male , Mutation
3.
Am J Hematol ; 28(1): 61-2, 1988 May.
Article in English | MEDLINE | ID: mdl-3369438

ABSTRACT

Glucose-6-phosphate-dehydrogenase deficiency is the most common disease-producing enzyme deficiency in man. This paper describes a new glucose-6-phosphate-dehydrogenase variant discovered during the evaluation of an episode of acute hemolytic anemia in a 62-year-old black male, which was temporally related to the ingestion of Tolbutamide. The hemolysis resolved within 10 days despite continuation of Tolbutamide. The erythrocyte glucose-6-phosphate-dehydrogenase activity was significantly decreased, and its electrophoretic mobility was indistinguishable from wild type enzyme, though faster on starch gel with tris, borate, and phosphate buffers. The enzyme had a biphasic pH optimum reduced Km for G-6-P and NADP, decreased utilization of deamino-NADP, and reduced Ki for NADPH. Because the kinetic properties of this enzyme were unique, we have designated it as G6PD Central City.


Subject(s)
Glucosephosphate Dehydrogenase Deficiency/genetics , Glucosephosphate Dehydrogenase/genetics , Mutation , Alabama , Glucosephosphate Dehydrogenase/blood , Glucosephosphate Dehydrogenase Deficiency/blood , Glucosephosphate Dehydrogenase Deficiency/enzymology , Humans , Male , Middle Aged
4.
Am J Med ; 84(3 Pt 1): 517-23, 1988 Mar.
Article in English | MEDLINE | ID: mdl-3348252

ABSTRACT

A six-year-old black boy who had transient hemolysis after a viral infection was found to have mildly decreased red cell glucose-6-phosphate dehydrogenase (G6PD) activity (1.25 IU/g hemoglobin). Two G6PD bands, both slightly faster than normal G6PD B, were seen on electrophoresis in both the propositus as well as in his maternal grandfather. This is an unexpected finding, since the G6PD gene is located on the long arm of the X chromosome that is subject to X-chromosome inactivation, and available evidence indicates that it is present as a single functional copy in the human genome. The obvious possibility of duplication of the X chromosome was eliminated by cytogenetic analysis with G-banding. G6PD duplication is unlikely, since peripheral blood granulocytes, platelets, and lymphocytes; cultured skin and bone marrow fibroblasts; and Epstein-Barr virus-stimulated lymphocytes yielded only a single electrophoretic band with mobility identical to the slower band seen in crude red blood cell hemolysate. Study of partially purified red blood cell hemolysate G6PD also yielded a single band with identical mobility. Kinetic studies of the enzyme in the propositus and in three generations of his family identified a unique, previously unpublished G6PD mutant that is herein designated G6PD Alabama. Red blood cells were separated by density gradient into a reticulocyte-enriched, an intermediate, and a dense, older portion. Two distinct enzyme bands were identified on electrophoresis of hemolysate from the reticulocyte-enriched portion, but not from the other two portions. It is postulated that two transcriptional products of the mutant G6PD gene exist; one with a short half-life and detectable only in young red blood cells, and another with a longer half-life present in all cells. The existence of two distinct mutant genes in the genome or a unique post-translational form of the mutant G6PD detected only in reticulocytes cannot be excluded.


Subject(s)
Genetic Variation , Glucosephosphate Dehydrogenase Deficiency/genetics , Glucosephosphate Dehydrogenase/genetics , Mutation , Blood Protein Electrophoresis , Child , Humans , Male , Transcription, Genetic
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