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)

In order to obtain more insight into the nature of the abnormal in vitro colony formation in myelodysplastic syndromes (MDS), we investigated the kinetics of the colony formation of 23 MDS cases in response to recombinant human interleukin-3 (IL-3), Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating Factor (G-CSF), and giant cell tumor cell line conditioned medium (GCT-CM). The kinetics of GCT-CM-induced colony formation were comparable to that of G-CSF-induced colony growth, both in MDS and in normal bone marrow cultures. Colony formation was found to be delayed in MDS. The delay in colony formation was most apparent in the GCT-CM (G-CSF) responsive progenitor cell compartment. In MDS cases with clinical features of high risk disease, this delay was more pronounced as compared with low risk cases (7 and 3 days, respectively, in response to GCT-CM). The delay in colony formation was found to be caused by an increase in the time interval before progenitor cells had begun to divide. These results suggest that a prolongation of the time spent in G0 of myeloid progenitor cells in MDS may be the cause of the indolent in vitro colony formation observed in this disease.
Leukemia 1990 Apr
PMID:The effects of interleukin-3, GM-CSF, and G-CSF on the growth kinetics of colony-forming cells in myelodysplastic syndromes. 169 40

In an ongoing phase-II trial we aimed to predict clinical responsiveness of Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML) to recombinant IFN-alpha-2C (rIFN-alpha-2C) by pretesting in vitro. From five normal controls and 14 CML patients in chronic phase, bone marrow samples were taken before treatment and tested for antiproliferative activity by rIFN-alpha-2C, using a microagar culture system for BFU-E, CFU-GM, and CFU-Meg. Light-density nucleated bone marrow cells were stimulated for BFU-E and CFU-Meg colony formation with Alpha medium containing 20% serum obtained from a patient with severe aplastic anaemia. CFU-GM growth was induced with conditioned medium from the cell line GCT. In normal controls BFU-E, CFU-GM and CFU-Meg colony formation was inhibited by rIFN-alpha-2C in a dose-dependent manner. BFU-E proved to be the most sensitive cell lineage (IC50: 65; range: 53-116 U/ml) whereas CFU-GM was about 20 times less sensitive (IC50: 643; range: 480-897 U/ml). The sensitivity of CFU-Meg ranged between these two colony types with 50% growth inhibition at an IFN concentration of 160 (range: 68-246 U/ml). A heterogeneous response to rIFN-alpha-2C in vitro was seen in CML patients. Three of the 14 patients were 'resistant' to rIFN-alpha-2C in vitro with IC50 values for BFU-E, CFU-GM and/or CFU-Meg colony formation greater than 10(4) U/ml. Patients were subsequently treated with a daily dose of rIFN-alpha-2C of 5 x 10(6) U. Four patients achieved a complete and six achieved a partial haematological response. Of the four non-responders three rapidly progressed into blastic crisis. Thus it was seen that treatment failure to interferon was accompanied by IFN-resistance in vitro of BFU-E, CFU-GM and/or CFU-Meg colony formation by bone marrow precursors (p less than 0.01). These results suggest a predictive value of IFN-sensitivity testing in vitro in Ph1 + CML.
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PMID:Recombinant interferon-alpha-2C in chronic myelogenous leukaemia: relationship of sensitivity of committed haematopoietic precursor cells in vitro (BFU-E, CFU-GM, CFU-Meg) and clinical response. 238 74

The response of human myeloid leukemia cells to various sources of colony-stimulating activity (CSA) and media conditioned by phytohemagglutinin-stimulated mononuclear cells (PHA-LCM) was investigated in liquid and colony culture. PHA-LCM, placenta-conditioned medium, GCT cell line-conditioned medium, leukocyte-conditioned medium, and partially purified CSA for human and murine cells were tested for ability to support growth of granulocyte-macrophage colonies from adherent cell-depleted human bone marrow. This activity was correlated with ability to support leukemia colony growth in methylcellulose, and [3H]thymidine incorporation in liquid culture by normal bone marrow cells, leukemia cells, and the KG-1 myeloid leukemia cell line. For normal cells, growth and liquid culture responses were highly correlated for various sources of CSA (r = 0.92), and addition of data using PHA-LCM changed results only slightly (r = 0.89). [3H]thymidine incorporation by leukemia cells from patients without a prior history of a myeloproliferative disorder was also highly correlated with normal CSA (r = 0.97) for sources other than PHA-LCM. Responses of leukemia blasts and KG-1 cells in liquid culture to PHA-LCM appeared in excess of its CSA for normal cells. Colony growth by leukemia cells was not clearly correlated with either liquid culture activity for leukemia cells or CSA for normal cells. PHA-LCM was also not statistically superior to placenta-conditioned medium as stimulus for leukemia colony growth, but was superior to placenta-conditioned medium for some patients. Differentiation in culture did not appear to depend on CSA source. We conclude that normal myeloid cells respond to CSA in a highly correlated fashion in both colony and liquid cultures. The majority of myeloid leukemia cells respond to either PHA-LCM or CSA, but the ability of PHA-LCM to support leukemia cell growth is greater than its CSA content. The possibility exists that overlapping populations responsive to CSA and to PHA-LCM are present simultaneously in patients with myeloid leukemia.
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PMID:Response of human myeloid leukemia cells to various sources of colony-stimulating activity and phytohemagglutinin-conditioned medium. 660 Sep 65

We have studied the effects of medium conditioned by the human progranulocytic leukemia cell line, HL-60, on the subsequent growth of new inocula of HL-60 cells. When HL-60 cells were cultured at high cell density, optimal growth rate occurred in liquid suspension and confluent colony growth was observed in viscous medium without the addition of conditioned medium. However, when cells were cultured at lower cell density, growth rate was reduced and colony growth was nil unless conditioned medium from HL-60 culture was added. All HL-60 populations studied, including the earliest available passage, 9, both elaborated and responded to HL-60 CM. HL-60 CM did not stimulate normal human or mouse granulocyte-monocyte colony-forming cell (CFU-GM) growth. Conditioned media from other human cell lines varied in the ability to stimulate HL-60 cell and CFU-GM proliferation. Some, such as GCT CM, stimulated both HL-60 cells and normal CFU-GM, whereas others, like HL-60 CM, stimulated only HL-60 growth. The majority of cell line CMs tested did not stimulate either HL-60 or CFU-GM. Chromatography of HL-60 CM on Ultrogel AcA54 showed a single peak of HL-60 stimulating activity of apparent molecular weight 13,000. The ability of HL-60 cells to elaborate this activity provides a possible explanation for their proliferation at higher cell densities. Autostimulation may prove to be important in the high growth potential of other cell populations that undergo unrepressed proliferation.
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PMID:Autostimulation of growth by human myelogenous leukemia cells (HL-60). 697 21

The recent identification of a leukemia-associated inhibitory activity (LIA) against granulocyte-macrophage progenitor cells (CFU-GM) as acidic isoferritins has now led to detection of this activity in normal bone marrow and blood cells. Detection of this activity depends on stimulation of CFU-GM by granulocyte-macrophage colony stimulatory factors (GM-CSF), and some conditioned media (CM) sources of GM-CSF (human placental and monocyte, mouse macrophage and WEHI-3) contained low levels of acidic isoferritin that lowered colony formation. Inactivation or removal of this activity increased the stimulatory capacity of the CM. CM depleted of acidic isoferritins or CM originally devoid of this activity (human GCT, 5637, Mo, lymphocytes: mouse L cells or pokeweed-mitogen-stimulated spleen cells) increased the sensitivity of the assay to detect acidic isoferritin inhibitory activity. This activity was selectively contained and released from normal monocytes and macrophages. Restriction of this activity to mononuclear phagocytes was substantiated, as only continuous cell lines of monocytes and macrophages or lines capable of induction to this lineage contained and released acidic isoferritin inhibitory activity. The cells of origin and target cells of action suggest that acidic isoferritin-inhibitory activity can be considered as a negative feedback regulator, at least in vitro.
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PMID:Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-macrophage progenitor cells in vitro. 698 Jun 76

Primary mediastinal non-seminomatous germ-cell tumors (PMNSGCTs) are rare neoplasms that occur in young male adults. Incidence is evaluated about half that of extra-gonadal GCT. Their treatment is generally based on protocols used for testicular cancer, but with poorer results. Based on our experience of 40 patients with PMNSGCTs and data from the literature, we review here the clinical and biological data of these neoplasms. PMNSGCTs seem to constitute a specific entity, distinct from other GCT by the following criteria: true extra-gonadal origin, high incidence in patients with the Klinefelter's syndrome, over-representation of the yolk-sac component, poorer chemosensitivity and survival compared to other GCT, frequent occurrence of non-treatment related hematological neoplasia. The finding of an isochromosome of the short arm of the chromosome 12 in the leukemic karyotype is one of the strongest argument for a common origin in the yolk-sac component of the PMNSGCTs and their associated leukemia. Treatment of PMNSGCTs is still a challenge and should be conducted by a well-trained medical team.
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PMID:[Primary mediastinal non-seminomatous germ-cell tumors: from clinics to biology]. 920 79

Cryotherapy, also called Cryoablation (CA), is a technique that provides a local treatment to various pathological conditions. In Musculoskeletal tumours management, Cryoablation is well accepted and validated as a treatment in palliative cures for metastatic patients. Recently, CA has been proposed also as an alternative to radiofrequency ablation in osteoid osteoma and other benign tumour treatment with promising results. Cryotherapy with argon ice-balls as local adjuvant in open surgery is a tool that can provide enlargement of surgical margins if used properly. There is still not enough evidence supporting use of cryotherapy as local adjuvant in Musculoskeletal open surgery as the series cited above are very small and there is no comparative RCT between local adjuvant therapies including CA. One-hundred-and-eighty-three patients were treated with Cryoablation from 2000 and 2018 in the Musculoskeletal Tumours Surgery Unit of Careggi (Florence) and the University 2nd Clinic of Pisa. In our study group, 38 patients (26.6%) were affected by bone metastasis, 16 patients (11.1%) by aneurismal bone cysts or angiomas, 22 patients (15.4%) by low-grade malignant musculoskeletal tumours, 2 patients (1,4%) by fibromatosis, 63 patients (44.1%) by benign musculoskeletal tumours (principally Giant Cell Tumours-GCT) and 2 patients (1.4%) by Osteosarcomas. In 125 cases (87.4%), CA has been used as an adjuvant therapy, in 12 cases (8.4%) as a percutaneous ablation therapy and in 6 cases (4.2%) as adjuvant to remove tumoral lesions 'en bloc' or as a 'poor technique' for its sterilizing effect on previously resected bones. Mean follow-up was 10 years. Twenty-three patients (16%) were classified as Alive with Disease (AWD) due to local recurrence or tumour progression (14 metastases, 5 low-grade malignant bone tumours, 4 Giant Cell Tumours). Eight patients died due to the disease (6 metastases, 2 osteosarcomas), while 1 died from leukaemia. One-hundred-and-eleven patients (78%) were classified as Continues Disease Free (CDF). All patients reported decrease in pain-related symptoms after surgery and all surgeons reported better control of blood loss. Three cases (2%) of local skin necrosis or wound dehiscence were reported. No local recurrences were reported after fibromatosis ablation. Our results confirm that CA could be considered as a safe and effective technique to treat various conditions as adjuvant and palliative therapy. In particular, in open surgery, cryotherapy as an adjuvant treatment could lead to very low rates of recurrence in locally aggressive tumours like Giant Cell Tumours. These results could be generalized but a better understanding about indications and outcomes can be reached studying CA in specific populations with comparation to other adjuvant techniques.
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PMID:Cryotherapy efficacy and safety as local therapy in surgical treatment of musculoskeletal tumours. A retrospective case series of 143 patients. 3064 84