Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00035 (CSF)
30,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellulose ester membranes (CEM) were folded into a trilaminar open-ended tube which was implanted into the peritoneal cavity of mice. CEM rapidly acquired a stromal core with many features of marrow such as fat, fibroblasts, an abundant sinusoidal microcirculation and monocyte-macrophage-like cells. CEM took up 59iron, 99technetium sulfur colloid and produced CSF in in vitro culture but their microenvironment supported only granulopoiesis. CEM were coated on their interior surfaces with bone marrow or regenerating medullary cavity mesenchyme or bone but the stromal cores supported only granulopoiesis after 3 weeks to 3 months of implantation. CEM coated with spleen and implanted into mice developed trilineal hematopoiesis within 6 weeks with abundant erythropoiesis and megakaryocytopoiesis in addition to granulopoiesis. These CEM differed from splenic tissue in that only scattered lymphoid tissue was present. CEM coated with bone marrow and bone developed trilineal hematopoiesis but only after3--6 months of peritoneal implantation. CEM coated with regenerating medullary cavity mesenchyme failed to develop trilineal hematopoiesis. Cyclophosphamide injection did not enhance hematopoiesis. These experiments indicate that splenic, marrow and bone tissue contain stromal elements capable of being transferred onto CEM which then develop a microenvironment capable of supporting trilineal hematopoiesis.
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PMID:Hematopoiesis on cellulose ester membranes (CEM). II. Enrichment of the hematopoietic microenvironment by the addition of selected cellular elements. 30 63

We studied the effects of six cycles of repeated cyclophosphamide (CTX) therapy followed by restorative therapy with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF on the hematopoietic stem cell compartment. Stem cell function was assessed by serially transferring bone marrow cells from CTX-CSF-treated mice into lethally irradiated recipient mice. Bone marrow cells from mice that initially received either G-CSF or GM-CSF after CTX therapy more rapidly lost the ability to repopulate the recipient lymphoid organs, showed a dramatic loss of hematopoietic progenitors, a more rapid loss of CFU-S capacity, and a 40% to 50% reduction in marrow repopulating ability (MRA). Interleukin-1 (IL-1) appeared to have little effect on the CTX-treated mice when used alone. However, when administered before the CTX-CSF regimen, IL-1 prevented the stem cell depletion as determined by CFU-C, CFU-S, and MRA through the serial transplantation procedures. These results support the hypothesis that repeated treatments with myelosuppressive drugs followed by stimulation with the CSFs may induce damage to the host stem cell compartment, and further suggest that pretreatment with IL-1 before CTX therapy may prevent this stem cell damage.
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PMID:Hematopoietic stem cell depletion by restorative growth factor regimens during repeated high-dose cyclophosphamide therapy. 137 52

Three patients with breast cancer with poor prognosis were treated with high-dose chemotherapy (HD-CT) and peripheral blood stem cell transplantation (PBSCT) as adjuvant treatment. After radical mastectomy, the consolidation chemotherapy with Adriamycin 50 mg/m2, Cyclophosphamide 1,000 mg/m2, Vincristine 1.0 mg/m2 and Methotrexate 200 mg/m2 with Leucovorin rescue was started. Recombinant human granulocyte colony stimulating factor (rhG-CSF) was also added for early recovery from myelosuppression. This combination chemotherapy was given every 3 weeks for 3 courses, and after the 2nd and 3rd courses, peripheral blood stem cells (PBSC) were collected and cryopreserved. HD-CT with Cyclophosphamide 2,000 mg/m2/day, Thio-TEPA 200 mg/m2/day, and Etoposide 300 mg/m2/day, were administered for 3 consecutive days, and after 48 hours of last doses, frozen-thawed PBSC (6.4-8.9 x 10(4)/kg of CFU-GM) were administered. rhG-CSF was also added. HD-CT and PBSCT were well tolerated, recovery from myelosuppression of the HD-CT was very quick and no serious side effects were observed.
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PMID:[High-dose adjuvant chemotherapy with peripheral blood stem cell transplantation for breast cancer with poor prognosis--a pilot study]. 138 71

A 38-year-old male was admitted with edema of the neck and face. Chest X-ray revealed a mediastinal tumor. On chest CT and MRI, a tumor infiltrating the superior vena cava and bilateral brachiocephalic veins in the upper mediastinum was observed. Venography revealed obstruction of bilateral brachiocephalic veins. The tumor was diagnosed as thymoma by percutaneous biopsy, but since it was of stage III according to Masaoka's classification, complete extirpation was considered to be impossible. Preoperative chemotherapy with multiple drugs (CDDP, ADM, VCR, CPA) was administered. The superior vena cava syndrome resolved and the tumor diminished in size. Because of leukopenia, rhG-CSF was also used. The tumor infiltrated the left brachiocephalic vein; therefore, total resection and left brachiocephalic vein reconstruction were performed. Histopathological examination showed extensive, necrosis and fibrosis containing residual thymoma. Postoperatively, similar chemotherapy and cobalt irradiation (40 Gy) to the superior mediastinum were performed. We thus present a case of invasive thymoma which responded to preoperative chemotherapy.
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PMID:[A case of invasive thymoma responsive to preoperative chemotherapy]. 150 97

The effects on bone marrow (BM) cell proliferation and differentiation of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered after high-dose (7 g/m2/d) cyclophosphamide (HD-CTX) chemotherapy were studied in nine patients with malignancies without BM involvement and in three control patients. rhIL-3 at a dose of 1 to 5 micrograms/kg/day was administered for 14 to 18 days by continuous intravenous (i.v.) infusion and rhGM-CSF was administered at a dose of 5.5 micrograms/kg/day for 14 days. Changes induced by cytokine treatment were assessed by morphoimmunohistochemical analysis of BM biopsies. Comparison was made in the cytokine-treated groups and with control patients who received HD-CTX alone. BM cellularity and the myeloid/erythroid (ME) ratio were lower in rhIL-3-treated than in rhGM-CSF-treated patients, but in both groups it was significantly higher than in the controls. The proportion of BM cells stained by PC10, a monoclonal antibody (MoAb) recognizing a proliferation-associated nuclear protein (PCNA), increased from 6.78% to 21.18% (P less than .02) after rhIL-3, and from 5% to 35.33% (P less than .001) after rhGM-CSF; no increase was observed in the control group. The frequency of CD34+ BM cells was unchanged after rhIL-3 (P = NS) and decreased after rhGM-CSF (P less than .001). In both groups, most of the PC10+ cells were represented by promyelocytes and myelocytes with no increase in blast cell numbers. rhIL-3-treated BM showed an increased number of megakaryocytes and increased proliferative activity of erythroid cells as compared with rhGM-CSF cases. BM stroma changes observed in both treated groups included endothelial cell proliferation, increased BM macrophage concentration, and increase in BM fibroblasts as detected with an anti-nerve growth factor receptor antibody. In most rhIL-3-treated cases, BM fibrosis developed after treatment. The same effect was not observed in rhGM-CSF patients.
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PMID:Recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor administered in vivo after high-dose cyclophosphamide cancer chemotherapy: effect on hematopoiesis and microenvironment in human bone marrow. 158 13

This manuscript summarizes our experience with recombinant human granulocyte colony-stimulating factor (rhG-CSF) with high-dose Cytoxan, carmustine and etoposide (CBV in Hodgkin's disease). rhG-CSF regularly shortened the neutropenic phase following autologous bone marrow transplantation. However, this effect was more marked on the latter part of neutrophil recovery than the early part of granulocyte recovery to 100 granulocytes/microliters. The frequency of afebrile episodes was not reduced by rhG-CSF administration, but there was a tendency for the duration of fever to be shortened. Increasing doses and continuous infusion did not hasten the early part of neutrophil recovery needed to prevent the onset of infection, but was more effective than bolus infusion in increasing the rate of late neutrophil recovery. If fevers are to be prevented in this patient population, the duration of an absolute granulocyte count of less than 100/microliters will have to last only a few days. Recombinant hematopoietic growth factors alone do not hasten recovery fast enough to prevent the onset of afebrile episodes. Studies are described using both recombinant growth factor and peripheral blood and bone marrow cells to see if the neutropenic trough can be further shortened over that achievable with growth factor and autologous transplant alone.
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PMID:Use of recombinant human hematopoietic growth factors and autologous bone marrow transplantation to attenuate the neutropenic trough of high-dose therapy. 169 Dec 46

The results of several studies of chemotherapy in treatment of soft tissue sarcomas of adults (except embryonic rhabdomyosarcoma) are presented. Most of these studies have been performed and published by the EORTC Bone and Soft tissue sarcoma group. In advanced disease, a randomized trial including 551 evaluable patients and comparing doxorubicin alone (75 mg/m2 q. 3 weeks), and two combination regimens: DI (Doxorubicin (50 mg/m2) + Ifosfamide (5 g/m2 + mesnum q. 3 weeks), and Cyvadic (Doxorubicin 50 mg/m2 d1, DTIC 750 mg/m2 d1, VCR 1.5 mg/m2 d1 (maximum 2 mg/m2), Cyclophosphamide 500 mg/m2 d1 q. 3 weeks), failed to prove any significant difference between these 3 treatments for response rate (25%, 31%, 28%), quality of the response and survival. There is a dose/effect relationship doxorubicin, it is possible that if combination is not superior to a single agent, the reason could be that the dose of doxorubicin is too low when used in combination as compared with the dose when used alone. So, in a phase II trial including 48 evaluable patients, optimal dose of doxorubicin (75 mg/m2 and Ifosfamide (5 g/m2) was given in association with rhGM-CSF. The response rate observed with this combination was 50%. For localized disease, in a randomized trial of the EORTC including 374 evaluable patients with resectable tumors with a mean follow-up of 44 months, the interest of 8 Cyvadic as adjuvant chemotherapy after adequate locoregional treatment (surgery with or without radiotherapy) was demonstrated only for locoregional relapse free survival but no for metastatic disease free survival or overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Chemotherapy of soft tissue sarcoma in adults]. 180 96

Patients undergoing bone marrow transplantation (BMT) are subjected to the risk of pancytopenia in the immediate post-BMT period. Recipients of bone marrow (BM) autografts purged in vitro by chemical agents such as mafosfamide (ASTA-Z) are even more likely to develop a delayed engraftment. In a previous study in mice, we showed earlier immunohematopoietic reconstitution after syngeneic marrow grafting with BM cells precultured with single or combined cytokines. In this work we determined optimal culture conditions for the use of single and various cytokine combinations in order to activate progenitor cells following in vitro cultures of untreated, ASTA-Z purged or T cell-depleted human BM preparations prior to BMT. The best single cytokine for enhancing CFU-GM was found to be GM-CSF (0.1 mg/ml) which produced an increase of up to 8-fold over controls after 3 days' incubation. Addition of recombinant human interleukin 3 (rhIL3) (0.1 mg/ml) to rhGM-CSF had an additive effect. The same enhancing effect of in vitro CFU-GM by both cytokines was observed following ASTA-Z purging of BM cells obtained from patients undergoing autologous BMT. Similarly, depletion of lymphocytes from BM using the monoclonal rat anti-human lymphocyte antibody Campath-1M and human complement did not diminish the beneficial influence of rhIL3 and rhGM-CSF. When combined with rhGM-CSF and rhIL3, rhIL1 and rhIL2 had no appreciable enhancing effect on CFU-GM and occasionally even reduced it. We suggest that enhancement of differentiation of hematopoietic progenitor cells may be accomplished by in vitro incubation of BM cells without continuous administration of cytokines in vivo following BMT.
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PMID:The use of recombinant cytokines for enhancing immunohematopoietic reconstitution following bone marrow transplantation. II. The influence of lymphokines on CFU-GM colonies from human untreated, ASTA-Z or Campath-1M treated bone marrow. 218 7

Twenty-seven cancer patients underwent peripheral blood stem cell apheresis during hematopoietic regeneration following induction high-dose cyclophosphamide (7 g/sqm; HD-CTX). Among these patients, eleven were also treated with granulocyte-macrophage colony stimulating factor (rhGM-CSF) for 14 days after HD-CTX. We describe technique, peripheral blood cell yields and side effects of 76 leukaphereses performed using a continuous-flow blood cell separator COBE 2997. Leukaphereses, carried out through 2-5 consecutive days per patient, were started significantly earlier in rhGM-CSF treated patients. In comparison to patients receiving HD-CTX only, administration of rhGM-CSF resulted in a significantly higher yield per leukapheresis of mononuclear cells and granulocyte-macrophage colony forming units (CFU-GM) (two-fold and eight-fold, respectively). Procedures were completed and well tolerated in all cases. Minor side effects were unfrequent. Our results suggest that rhGM-CSF accelerates hematopoietic recovery after HD-CTX and facilitates large-scale collection of peripheral blood stem cells utilizable for autologous transplantation.
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PMID:Role of recombinant human granulocyte-macrophage colony stimulating factor for large scale collection of peripheral blood stem cells for autologous transplantation. 219 Aug 82

Antigen CD34+ cells represent 1-4% of adult bone marrow cells comprising virtually all hematopoietic colony-forming progenitors in-vitro and probably also stem cells capable of restoring hematopoiesis of lethally irradiated hosts. We report that sizable numbers of CD34+ cells transiently circulate in the peripheral blood (PB) of patients treated with high-dose (7 g/sqm) cyclophosphamide (HD-CTX) with or without recombinant human glycosylated granulocyte macrophage colony stimulating factor (rhGM-CSF). Evidence is presented demonstrating that CD34+ cells from PB possess qualitatively normal hematopoietic colony growth and high cloning efficiency similarly to marrow CD34+ cells. In addition, CD34+ cells from PB are shown to display heterogeneous flow cytometry characteristics and differentiation antigens analogous to those from bone marrow, i.e., CD34+/CD33-, CD34+/CD13-, CD34+/CD38-, CD34+/CD11b, CD34+/DRlow+ cells have light scatter properties of small lymphocytes while CD34+/CD33+, CD34+/CD13+, CD34+/CD38+, CD34+/CD11b+, CD34+/DRhigh+ cells have light scatter properties of blast-like cells. In HD-CTX treated patients, CD34+ cell circulation is 5-fold enhanced by rhGM-CSF 5.5 micrograms/kg/day by continuous iv infusion for 14 days. During the second-third week after HD-CTX, large-scale collection of PB leukocytes by 3-4 continuous-flow leukaphereses allows the yield of 2.19-2.73 x 10(9) or 0.45-0.56 x 10(9) CD34+ cells, depending on whether or not patients receive rhGM-CSF. The number of CD34+ cells retrieved from PB by leukaphereses exceeds the number that can be harvested by multiple bone marrow aspirations under general anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterogeneity of circulating hematopoietic progenitors in cancer patients treated with high-dose cyclophosphamide and recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF). 219 Aug 84


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