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)

Serum ferritin was measured in a variety of hematologic malignancies at presentation, in remission following therapy, and in relapse. Ferritin was strikingly increased in all acute leukemias at presentation and in relapse, in the blastic crisis of CML, and in smouldering leukemia. Remission in both ALL and ANLL was associated with a reduction of serum ferritin, and this normalization was a function of remission duration. In the malignant lymphomas serum ferritin was related to tumor histology. Highest levels were found in Hodgkin disease and histiocytic lymphoma, normal levels in lymphocytic lymphoma, and intermediate levels in mixed histiocytic-lymphocytic lymphoma. In all cases, remission was associated with normalization of serum ferritin. These correlations suggest that serum ferritin measurements may be of clinical usefulness in the initial evaluation and in the assessment of response to therapy in patients with acute leukemia and malignant lymphoma.
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PMID:Serum ferritin in hematologic malignancies. 700 94

Retrospective analysis of childhood histiocytoses treated at the Department of Pediatrics, Ramathibodi Hospital from May 1970 till June 30, 1992 to verify the prevalence according to the recent classification, course and prognosis was conducted. Among 120 cases, 54 were Class I or Langerhan Cell Histiocytosis (LCH, previously called Histiocytosis-X). Nineteen cases were Class II: Infection-Associated Hemophagocytic Syndrome (IAHS) and Sinus Histiocytosis. Forty-seven cases were class III which included acute monocytic leukemia, juvenile CML; malignant histiocytosis, HMR, and histiocytic lymphoma. Excellent prognosis (cure) was seen in all cases of Hand-Schuller Christian Disease, eosinophilic granuloma, sinus histiocytosis with massive lymphadenopathy and many cases of Class II (except IAHS). The worse prognosis (100% mortality rate) was seen in HMR and juvenile CML. The intermediate prognosis (50%, 54%, 58.8% and 66.7% mortality rate) was seen in MH, HL, LSD and IAHS respectively. To differentiate between IAHS and MH/HMR, the prominent bone marrow findings in 12 cases of IAHS revealed that every case showed prominent hemophagocytosis by the promono-histiocytes/histiocytes, the maximal total erythroblasts (TE) were only 7.5 per cent except for 3 cases; in which one case with agranulocytosis from co-trimoxazole had 84 per cent erythroid cells, one case with prior co-trimoxazole treatment had 37 per cent TE, the last one had 40 per cent TE with massive GI bleeding while in the recovery stage of DHF. All 5 cases of HMR had prominent hemophagocytosis and increased TE (> 22%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Histiocytoses in children: analysis of 120 cases and the bone marrow findings in infection-induced hemophagocytic syndrome vs malignant histiocytosis. 782 9

Several new 4-diazopyrazole derivatives were synthesized by reaction of 1-(R-substituted)phenyl-3-methyl-5-benzamidopyrazoles with a sevenfold excess of nitrous acid in acetic media. The compounds were tested at 20 microM concentration for their antineoplastic activity in vitro against Raji (human Burkitt lymphoma), K562 (human chronic myelogenous leukemia) and U937 (human histiocytic lymphoma) cell lines. They showed a percent of growth inhibition in the range 23.4-100%.
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PMID:Synthesis and antineoplastic activity of new 4-diazopyrazole derivatives. 950 64

A 28-mer morpholino oligonucleotide analog was designed to hybridize to 8 bases of intron 1 and extend 2 bases beyond the translation initiation codon in exon 2 of the unspliced c-myc RNA transcript. Delivery of this compound into human chronic myeloid leukemia KYO1 cells, by streptolysin O permeabilization, resulted in almost total ablation of the 65 kDa c-MYC protein expression for at least 24 hours after treatment. An unexpected band with SDS-PAGE electrophoretic mobility indicating a protein of about 47 kDa was apparent on the 24-hour western blots that were developed using antibodies that recognize MYC protein C terminal epitopes. No inhibition of the approximately 2400 nt c-myc mRNA expression was observed by northern hybridization, a result of the inability of morpholino analogs to direct the activity of ribonuclease H. In fact, high molecular weight c-myc RNA species were found to have accumulated in antisense-treated KYO1 cells. Control sense and scrambled antisense morpholino analogs did not inhibit MYC protein expression or induce the appearance of the anomalous RNA and protein bands. Molecular analyses by RT-PCR and sequencing revealed that the morpholino antisense effector had (1) inhibited splicing of the c-myc pre-mRNA, (2) induced missplicing of the pre-mRNA, and (3) inhibited translation of normal spliced c-myc mRNA. Identical results were obtained with acute promyelocytic leukemia, acute lymphoblastic leukemia, and histiocytic lymphoma cell lines.
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PMID:Antisense morpholino oligonucleotide analog induces missplicing of C-myc mRNA. 1035 27

We demonstrated that arachidonic acid inhibits growth and induces apoptosis in the bcr-abl transformed leukemia cell line, H7.bcr-abl A54 and in human chronic myeloid leukemia hematopoietic cells. This investigation was undertaken to determine the cell-type specificity of this response. We compared the effect of arachidonic acid on H7.bcr-abl A54 cells to Jurkat (human acute T-cell leukemia), U937 (human histiocytic lymphoma) and RPMI 7666 (human normal B-lymphoblasts) cells. Arachidonic acid (100 microM, 72 h) inhibited growth of H7.bcr-abl A54, Jurkat and U937 cells by 82.2, 67.5 and 20%, respectively, but had no effect on RPMI 7666 cells. These effects were investigated in relationship to the activation of p38 mitogen activated protein kinase (p38 MAPK) and c-jun amino-terminal kinase (JNK) by arachidonic acid in these cell lines. Results from these studies suggest that signaling and proliferative responses to arachidonic acid are cell-type specific. Leukemia cells appear to be more sensitive to the antiproliferative effect of arachidonic acid than normal cells.
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PMID:Specificity of arachidonic acid-induced inhibition of growth and activation of c-jun kinases and p38 mitogen-activated protein kinase in hematopoietic cells. 1205 55

Cancer testis (CT) antigens have an expression pattern that is predominantly restricted to testis in normal tissues, yet they are expressed in many different histological types of cancers. One previously described member of the CT antigen family, XAGE-1, was shown to be expressed in Ewing's sarcomas and rhabdomyosarcomas. Here we show that XAGE-1 is also expressed in breast cancer, prostate cancer, and different types of lung cancers, including lung squamous cell carcinoma, adenocarcinoma, small cell lung carcinoma, and non-small cell lung carcinoma. In addition, XAGE-1 mRNA was present in ovarian cancer, melanoma, glioblastoma, T-cell lymphoma, chronic myelogenous leukemia, and histiocytic lymphoma cell lines. We also characterized the XAGE-1 transcript by primer extension analysis and found that transcription of the XAGE-1 gene is initiated from two distinct start sites, resulting in two overlapping transcripts, XAGE-1a and XAGE-1b. XAGE-1a contains two in-frame ATG translational start codons; whereas XAGE-1b initiates downstream of the first ATG start codon. Our results suggest that XAGE-1b is the dominant transcript, and that translation begins with the second ATG start codon, producing a 9 kDa protein. Because XAGE-1 is expressed in such a diverse range of cancers, it has potential to be used as a target for many cancer immunotherapies.
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PMID:Characterization of overlapping XAGE-1 transcripts encoding a cancer testis antigen expressed in lung, breast, and other types of cancers. 1247 62

In recent years, it has been reported that bisphosphonates inhibited the cell cycle of myeloma cells to inhibit cell proliferation directly, and it was also reported that bisphosphonates induced apoptosis of myeloma cells in vitro. Recently, YM529 was developed as a new third-generation bisphosphonate. In our experiment, we investigated whether YM529 showed an antitumor effect on hematopoietic tumor cell lines other than myeloma, and we compared YM529 with YM175, which had a relatively more potent antitumor effect than that of existing bisphosphonates. We found that YM529 inhibited cell proliferation in various hematopoietic tumor cell lines (acute promyelocytic leukemia cell line HL-60, chronic myeloid leukemia cell line K562, histiocytic lymphoma cell line U937, lymphoblastic leukemia T cell line Jurkat, acute lymphoblastic leukemia T cell line MOLT-4, lymphoblastic leukemia B cell line CCRF-SB) including myeloma (myeloma cell line HS-Sultan) dose-dependently and time-dependently to a degree equivalent or superior to that in myeloma, and induced apoptosis at a lower concentration as compared with YM175. We confirmed many dead cells as well as apoptosis based on the detection of the nuclei with separate globular structure, the activation of caspase-3, and the decrease in mitochondrial transmembrane potential. Therefore, it is concluded that further utilization of YM529 can be expected against hematopoietic tumor cells in the future.
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PMID:Apoptosis-inducing effect of a new bisphosphonate, YM529, on various hematopoietic tumor cell lines. 1252 Jan 82

The aim of the present study was to evaluate the antileukemic activity of six chemical classes of pure compounds present in commonly used medicinal plants in Taiwan--such as the genus Plantago. Studies were conducted on a series of human leukemia and lymphoma cell lines. Results showed that water soluble compounds (aucubin, caffeic acid, chlorogenic acid, ferulic acid, p-coumaric acid and vanillic acid) exhibited a weak antileukemic activity (IC50: 26-56 microg/ml, SI: 2-11). On the other hand, water insoluble compounds such as triterpenoids (oleanolic acid and ursolic acid), monoterpene (linalool) and flavonoid (luteolin) possessed strong activity against human leukemia and lymphoma cell lines. Among them, linalool showed the strongest activity against histiocytic lymphoma cells U937 (IC50: 3.51 microg/ml, SI: 592.6) and Burkitt lymphoma cells P3HR1 (IC50: 4.21 microg/ml, SI: 494.1). Ursolic acid was effective against P3HR1 cells (IC50: 2.5 microg/ml, SI: 262.6) and chronic myelogenous leukemia cells K562 (IC50: 17.79 microg/ml, SI: 36.91), whereas oleanolic acid inhibited the growth of P3HR1 cells (IC50: 26.74 microg/ml, SI: 11.37). Luteolin exhibited effective activity against K562 cells (IC50 18.96 microg/ml, SI: 5.14) and P3HR1 cells (IC50: 18.99 microg/ml, SI: 5.13). We conclude that terpenes and flavonoid in commonly used medicinal plants possess strong activity against lymphoma and leukemia cells, especially human lymphoma cells, suggesting the potential use of these compounds for treatment of lymphoma.
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PMID:Antileukemic activity of selected natural products in Taiwan. 1272 53

The recently discovered marine fatty acid (+/-)-2-methoxy-13-methyltetradecanoic acid was synthesized for the first time in six steps (26% overall yield) starting from commercially available methyl 12-methyltridecanoate. The synthetic approach provided enough material to corroborate the structure of the acid, which was recently identified in the sponge Amphimedon complanata from Aguadilla, Puerto Rico, and to test its cytotoxicity to three leukemia cell lines. The key step in the synthesis was the addition of trimethylsilyl cyanide to 12-methyltridecanal under triethylamine catalysis. Nuclear magnetic resonance data are provided for the first time for this methoxylated fatty acid and the synthetic approach utilized is of general applicability since it can be used in the synthesis of other methyl-branched 2-methoxylated fatty acids. We also report that the acid (+/-)-2-methoxy-13-methyltetradecanoic acid is cytotoxic to human chronic myelogenous leukemia K-562 (EC50=238 microM), histiocytic lymphoma U-937 (EC50=250 microM), and promielocytic leukemia HL-60 (EC50=476 microM) in RPMI 1640 medium.
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PMID:The first total synthesis of the marine fatty acid (+/-)-2-methoxy-13-methyltetradecanoic acid: a cytotoxic fatty acid to leukemia cells. 1462 50

The hitherto unknown 2-methylsulfanyldecanoic acid and 2-methylsulfanyldodecanoic acid were synthesized from methyl decanoate and methyl dodecanoate, respectively, through the reaction of lithium diisopropylamide and dimethyldisulfide in THF followed by saponification with potassium hydroxide in ethanol. Both alpha-methylsulfanylated FA were cytotoxic to the human chronic myelogenous leukemia K-562 and the human histiocytic lymphoma U-937 cell lines with EC50 values in the 200-300 microM range, which makes them more cytotoxic to these cell lines than decanoic and/or dodecanoic acid. The cytotoxicity of the studied FA toward K-562 followed the order 2-SCH3-12:0 > 2-SCH3-10:0 > 10:0 > 12:0 > 2-OCH3-12:0, whereas toward U-937 the cytotoxicity was 2-SCH3-10:0 > 2-SCH3-12:0 > 12:0 > 10:0 > 2-OCH3-12:0. These results indicate that the alpha-methylsulfanyl substitution increases the cytotoxicity of the C10 and C12 FA toward the studied leukemia cell lines.
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PMID:Synthesis of a novel series of 2-methylsulfanyl fatty acids and their toxicity on the human K-562 and U-937 leukemia cell lines. 1638 79


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