Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The toxicity and efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) is established in adults, but limited information is available on its use in children. The profound myelotoxicity induced by cisplatin (40 mg/m2 daily x 5) and etoposide (150 mg/m2 daily x 3) provides a model to test the clinical value of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric cancer patients; myelosuppression occurred (absolute neutrophil count [ANC] < 500/microL) during 99 of 118 (84%) courses given to 44 children with refractory solid tumors. Fifty-nine courses (50%) resulted in hospitalizations for fever. Subsequently, rhuGM-CSF was added to this treatment regimen to: (i) determine the dose-limiting toxicity of this agent in children; and (ii) to determine whether it can decrease the duration and severity of neurtropenia and attendant complications. Here we summarize and update our experience with this glycoprotein in children with relapsed solid tumors.
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PMID:Use of GM-CSF in children after high-dose chemotherapy. 130 84

LF, an iron-binding glycoprotein, has myelosuppressive effects in vitro and in vivo. The present study evaluated the mode of LF action in vitro and the effects of various recombinant CSFs and ILs on this action. Normal human low-density BMC, at 2 x 10(6)/ml, were exposed to purified and endotoxin-depleted iron-saturated LF for 2 h, washed three times, and plated for CFU-GM and BFU-E in the presence of rhuCSFs (e.g., GM-CSF, Epo, IL-3) and in the absence and presence of rhuIL-6, rhuIL-1 alpha, or rhuIL-1 beta. LF caused a 40-65% plateau curve of inhibition for CFU-GM and BFU-E that was not apparent when adherent mononuclear cells (monocytes) were removed from the target population of cells. This myelosuppression was ablated by rhuIL-6, but not by rhuIL-1 alpha or rhuIL-beta. These results suggests a role for IL-6 in the accessory cell-mediated suppressive effect of LF on CFU-GM and BFU-E and open up the possibility that IL-6 may have stimulatory/enhancing or cofactor activities necessary for optimal proliferation of hematopoietic progenitor cells.
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PMID:Interleukin-6 ablates the accessory cell-mediated suppressive effects of lactoferrin on human hematopoietic progenitor cell proliferation in vitro. 206 24

Human monocytic colony-stimulating factor (hM-CSF) is a glycoprotein which stimulates monocyte production in the bone marrow. It enhances CSF (such as G- and GM-CSF) production of monocytes and megakaryocyte-potentiating activity (Meg-POT). It also enhances tumor-killing activity of monocytes against several leukemic cell lines such as K562, U937, HL60 and Daudi. In the clinical studies, it was shown that hM-CSF infusions accelerated the recovery from neutropenia as well as thrombopenia after anticancer chemotherapy against hematological, gynecologic and urogenital malignancies. Human M-CSF infusions were tolerable without any serious side effects. It is reported that infusions of G-CSF and GM-CSF cause the increment of leukemic cell counts in some cases, but hM-CSF infusions did not increase leukemic cell counts. These results indicate that hM-CSF may be potentially useful for the treatment of myelosuppression induced by cancer chemotherapy in cancer patients.
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PMID:[Human monocytic colony-stimulating factor]. 268 18

A retrovirus containing the multiple drug resistance (MDR-1) cDNA, was used to transduce cultures of CD34 selected human marrow cells, on stromal monolayers in the presence of hematopoietic growth factors IL-3 and IL-6, following collection from patients recently recovered from chemotherapy-induced myelosuppression. In one experiment, these CD34 selected cells were grown in Dexter cultures for 35 days or more following MDR-1 transduction, and then plated in methylcellulose. Polymerase chain reaction (PCR) analysis of colonies picked after 10-14 days of methylcellulose culture, using a set of primers that are specific for the endogenous or the retrovirally transduced MDR-1, showed that the long-term culture initiating cells (LTCICs) were transduced by the MDR-1 virus. Analysis of the colonies from the CD34 selected MDR-1 transduced cells, with a reverse transcription (RT) PCR assay that could distinguish viral MDR-1 mRNA from endogenous MDR-1 mRNA, showed that the viral MDR-1 mRNA levels were much higher than that of the MDR-1 mRNA from the endogenous MDR-1 gene in the transduced CD34 selected cells. Fluorescence activated cell sorting (FACS) analysis of the CD34 selected transduced marrow cells within 48 h after the transduction, using the C219 and UIC2 monoclonal antibodies for p-glycoprotein, showed that the transduction frequency under these conditions varied from 7 to 20%. Rhodamine efflux studies showed that this additional p-glycoprotein was functional and that the frequency of cells with high p-glycoprotein levels was higher in the transduced cells than in the non-transduced cells. The resistance to taxol of the CD34 selected transduced cells, as judged by the plating efficiency of clonogenic progenitor cells derived from these cells by growth in methylcellulose supplemented with taxol was much higher in the transduced cells than in untransduced cells. In order to test the reproducibility of the transduction frequency of the retroviral supernatants from PA317 MDR-1 viral producer cells on CD34 selected cells, the virus produced from 12 different lots of supernatants from the PA317 MDR-1 producer cell line was used to transduce CD34 selected marrow cells from four different patients, and to transduce the peripheral blood cells of two additional patients collected following chemotherapy-induced myelosuppression. The supernatant lots used for these transduction experiments were tested by Microbiological Associates (Rockville, MD, USA), by the Mus dunni co-cultivation and amplification tests in the S+L-assay and found to be negative for replication-competent retrovirus, and later approved for human use by the Food and Drug Administration.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chemotherapy resistance to taxol in clonogenic progenitor cells following transduction of CD34 selected marrow and peripheral blood cells with a retrovirus that contains the MDR-1 chemotherapy resistance gene. 755 82

Colony-stimulating factors (CSFs) are glycoprotein growth factors that influence the proliferation and differentiation of hematopoietic progenitor cells. Among CFSs granulocyte colony-stimulating factor (G-CSF) is thought to be major stimulator of production of human neutrophilic granulocyte. G-CSF have recently moved from the basic research to the clinical use and have been suggested to have important roles in cancer management. Today two kinds of recombinant G-CSF which have similar specific activity are commercially available, one is derived from ovarian cells of Chinese hamster and the other from E. coli. (Variant type of E. coli is now in trial.) Difference of these two is whether carbohydrate chain primarily seen in molecule of natural form is contained or not. In this report recombinant product of G-CSF for the clinical use is introduced. Preclinical study with recombinant G-CSF have suggested that it would stimulate granulocyte production in cancer patients with myelosuppression due to chemotherapy. Thus, after evaluation of toxicities and possible efficacy recombinant G-CSF has been introduced into phase II trial for the prevention of chemotherapy-induced neutropenia in various cancers. In this setting 2 micrograms/kg of subcutaneous administration for 14 days after aggressive chemotherapy was suggested to be optimal and to be acceptable for toxicities including bone pain or headache. In conclusion recombinant G-CSF is thought to be very useful drug for reduction of nadir of cancer chemotherapy-induced neutropenia and shortening of period of neutropenia.
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PMID:[Recombinant human granulocyte colony-stimulating factor (G-CSF)]. 768 Aug 49

Etoposide has demonstrated highly significant clinical activity against a wide variety of neoplasms, including germ-cell malignancies, small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the important agents in the preparatory regimens given prior to bone marrow and peripheral stem-cell rescue. Despite its high degree of efficacy in a number of malignancies, the optimal dose, schedule, and dosing form remain to be defined. It is possible that continuous or prolonged inhibition of the substrate, i. e., topoisomerase II, may be the key factor for the cytotoxic effects of etoposide. Clinical studies have shown the activity of etoposide to be schedule-dependent, with prolonged dosing, best accomplished by the oral dosing form, offering a therapeutic advantage. This benefit awaits validation by prospective randomized studies, some of which are in progress. Recent clinical investigations have focused on the use of etoposide in combination with (a) cytokines to ameliorate myelosuppression, the dose-limiting toxicity of etoposide; (b) agents such as cyclosporin A and verapamil to alter the p-glycoprotein (mdr1) function; and (c) topoisomerase I inhibitors to modulate the substrate upon which it acts. There is continued interest in the development of etoposide to its maximal clinical dimensions and in the examination of alternative biochemical and mechanistic approaches to further our understanding of this highly active agent.
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PMID:Etoposide: current status and future perspectives in the management of malignant neoplasms. 807 20

The red-cell mass is continuously adjusted to the optimal size for its function as an oxygen carrier by messages transmitted to the bone marrow from an oxygen sensor in the kidney. These messages are mediated by the hormone erythropoietin. Erythropoietin is a glycoprotein growth factor synthesized by cells adjacent to the proximal renal tubule in response to signals from a renal oxygen-sensing device, probably a heme protein (1). In the bone marrow, erythropoietin binds to and activates specific receptors on the erythroid progenitor cells (2). In the presence of this erythropoietin-receptor complex the progenitor cells continue their predestined development into mature erythrocytes. Erythropoietin was the first hemopoietic growth factor to be molecularly cloned in 1985 (3). Our understanding of the biology and physiology of erythropoietin has been considerably improved with the advent of recombinant human erythropoietin (rHuEpo). During the past 7 years, rHuEpo has undergone extensive testing in clinical trials. It has been approved for treatment of the anemia of chronic renal failure, both in progressive renal failure and endstage renal failure (ESRD). In these instances, the administration of rHuEpo has been used in effect as a substitutive therapy, since patients' erythropoietin levels are very low despite severe anemia, due to the failure of affected kidneys to produce adequate amounts of the hormone. However, the application of rHuEpo has now moved largely from the primitive indication of renal diseases, and the hormone is currently under study in a number of anemic states of different etiologies, even with relatively high serum erythropoietin levels. Among these, some of the best documented indications are the anemia associated with malignancies, either due to neoplastic bone marrow infiltration or to chemotherapy-related myelosuppression, the anemia of myelodysplastic syndromes and AIDS, the anemia of chronic inflammatory diseases, prematurity, and bone marrow transplantation (4). The purpose of this review is to provide a summary of our present knowledge regarding rHuEpo therapy for the anemia of renal failure. We provide some clues for the correct use of rHuEpo in the treatment of the anemia of chronic inflammatory diseases. In addition, we address a series of new issues in the attempt to better understand the relationship between erythropoietin and liver disease.
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PMID:Erythropoietin and the anemia of chronic diseases. 840 91

An acidic glycoprotein prepared from a culture of Chlorella vulgaris (CVS) was examined for its protective effect on 5-fluorouracil(5FU)-induced myelosuppression and indigenous infection in mice. Subcutaneous administration of CVS greatly reduced the mortality of non-tumor-bearing mice given a high dose of 5FU, and could increase the LD50 value of 5FU for these mice. After 5FU treatment, indigenous infection developed probably as a result of the impairment of the host defense system. CVS reduced the incidence of indigenous infections and this effect was attributable to the acceleration of recovery from 5FU-induced myelosuppression. Early recovery of hematopoietic stem cells, or cells responding to interleukin-3 or granulocyte/macrophage-colony-stimulating factor, was especially observed in the bone marrow of CVS-treated mice on days 4-9 after the injection of 5FU. When tumor-bearing mice were given CVS during treatment with 5FU, CVS prolonged the survival of mice without affecting the antitumor activity of 5FU. In addition, CVS was itself shown to exert an antitumor effect. These results suggested that CVS may be beneficial for the alleviation of side-effects in cancer chemotherapy without affecting the antitumor activity of the chemotherapeutic agent.
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PMID:Protective effect of an acidic glycoprotein obtained from culture of Chlorella vulgaris against myelosuppression by 5-fluorouracil. 870 47

Interleukin-3 (IL-3) is a glycoprotein produced primarily by activated T-lymphocytes. As a hematopoietic growth factor it affects the proliferation, maturation, and survival of progenitor cells of the myeloid, erythroid, and megakaryocyte lineages. Initial studies in cancer patients with normal bone marrow using IL-3 doses of > 5 micrograms/kg daily produced a doubling of the neutrophil count within 2-3 days and that of platelet counts by days 10-12. Phase I-II clinical trials have examined the response to IL-3 in various clinical states, and ongoing phase III studies are currently assessing the clinical relevance. In the treatment of relapsed lymphoma, small-cell lung cancer, and breast and ovarian cancer, IL-3 at doses of 5-10 micrograms/kg daily given mainly subcutaneously for 5-10 days has been shown to maintain chemotherapy schedules while preserving adequate granulocyte and platelet numbers in the peripheral blood. At these doses, side effects were uncommon. The translation of these observations into clinical phase III studies has been disappointing, with no clear-cut clinical advantage being observed in the treated group. This reflects the relative lack of myelosuppression seen with most current regimens for solid tumors. The role of combined treatment with IL-3 in association with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor after cytotoxic treatment has yet to be established. However, it has been shown that they may act synergistically, resulting in significantly higher numbers of progenitor cells in the peripheral blood than when either is used alone. Combinations with IL-6 are also under study, as is the use of "cocktails" for ex vivo expansion of progenitors. This latter approach would allow single, small collections to be used for multiple infusions of progenitors and could support significant dose-intensification regimens by relieving myelosuppression. It is clear that the place of these newer cytokines in current treatment remains to be clarified.
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PMID:Is interleukin 3 active in anticancer drug-induced thrombocytopenia? 876 24

High-dose chemotherapy is increasingly accepted as a treatment approach in a number of tumour types. However, there are controversies surrounding its efficacy and there is a need to consider its safety. In view of this, much effort has been directed towards the provision of adequate supportive care strategies to prevent toxicities and to ameliorate myelosuppression. Severe anaemia and its associated symptoms, for example, fatigue can have a debilitating effect on a patient's quality of life and often necessitates red blood cell transfusions. Erythropoietin, a glycoprotein hormone which stimulates red blood cell production, has been established for the treatment of anaemia in patients with chronic renal insufficiency. It is currently approved in most countries for treating anaemia associated with cancer, and its role is emerging especially in patients undergoing high-dose chemotherapy. This paper gives an overview of the studies conducted to date with epoetin alfa (recombinant human erythropoietin) in patients receiving allogeneic and autologous bone marrow transplants or peripheral blood stem cells in conjunction with high-dose chemotherapy. In addition, there are some novel clinical applications for epoetin alfa: for example, in delayed anaemia, as a supportive strategy prior to high-dose chemotherapy and as a synergistic enhancer of blood progenitor cell mobilisation in combination with granulocyte-colony-stimulating factor (G-CSF).
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PMID:Haematological toxicities associated with dose-intensive chemotherapy, the role for and use of recombinant growth factors. 934 59


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