Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum samples from 340 pet cats presented to three inner city clinics in Sydney Australia, 68 feral cats from two separate colonies in Sydney, and 329 cattery-confined pedigree and domestic cats in eastern Australia, were collected over a 2-year period and tested for antibodies directed against feline immunodeficiency virus (FIV) using immunomigration (Agen FIV Rapid Immunomigration test) and enzyme-linked immunosorbent assay methods (Snap Combo feline leukaemia virus antigen/FIV antibody test kit, IDEXX Laboratories). Western blot analysis was performed on samples in which there was discrepancy between the results. Information regarding breed, age, gender, housing arrangement and health status were recorded for all pet and cattery-confined cats, while the estimated age and current physical condition were recorded for feral cats. The FIV prevalence in the two feral cat populations was 21% and 25%. The majority of FIV-positive cats were male (60-80%). The FIV prevalence in cattery-confined cats was nil. The prevalence of FIV in the pet cat sample population was 8% (27/340) with almost equal prevalence in 'healthy' (13/170) and 'systemically unwell' (14/170) cats. The age of FIV-positive pet cats ranged from 3 to 19 years; all FIV-positive cats were domestic shorthairs with outside access. The median age of FIV-positive pet cats (11 years) was significantly greater than the median age of FIV-negative pet cats (7.5 years: P<0.05). The prevalence of FIV infection in male pet cats (21/172; 12%) was three times that in female pet cats (6/168; 4%; P<0.05). With over 80% of this pet cat population given outside access and continued FIV infection present in the feral population, this study highlights the need to develop rapid, accurate and cost-effective diagnostic methods that are not subject to false positives created by concurrent vaccination against FIV. This is especially important in re-homing stray cats within animal shelters and monitoring the efficacy of the new vaccine, which has not been challenged against Australian strains. The absence of FIV within cattery-confined cats highlights the value in routine screening and indoor lifestyles. This study provides cogent baseline FIV prevalences in three cat subpopulations which can be used for appraising potential disease associations with FIV in Australia.
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PMID:Prevalence of feline immunodeficiency virus infection in domesticated and feral cats in eastern Australia. 1740 7

The aim of the present research was to investigate the possible in vitro stimulatory effect of substance P (SP) on blasts induction in childhood common acute lymphoblastic leukaemia (ALL). Bone marrow aspirates were incubated with SP receptor agonist or antagonist (spantide) and subsequently assayed for the presence of human interleukin (IL)-1b using ELISA kit. Blast cells incubated with SP receptor agonist were found to result in a significant increase of IL-1b concentration while incubated with spantide resulted in control levels of IL-1b. These findings suggest the novel possible role of SP in blasts proliferation in childhood ALL of common (CD10) origin.
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PMID:In vitro substance P-dependent induction of bone marrow cells in common (CD10) acute lymphoblastic leukaemia. 1761 85

The expression of wt1 and bcl-2 is considered to have a proliferating and survival supporting effect in leukemia blast cells. Here we describe the use of siRNA against wt1 and bcl-2 in leukemic cell lines for successful growth inhibition. We have used two different sequences designated as siRNA-A and siRNA-B corresponding to positions within the wt1 coding sequence to downregulate wt1 and a commercially available siRNA kit to downregulate bcl-2. WT1 and bcl-2 gene expression in transfected leukemic cell lines were evaluated with RT-PCR and western blot analyses. MTT assay was used to measure the cell viability and flow cytometry using annexin V/PI-staining for apoptosis. K562 and HL-60 cell lines transfected with siRNA-A targeted to wt1 had greatly decreased levels of both wt1 mRNA and protein expression. In contrast, siRNA-B and control siRNA led almost to no effect on wt1 mRNA and protein expression. siRNA-A-reduced wt1 mRNA expression was associated with a decreased cell proliferation and increased number of apoptotic cells in K562 and HL-60 cells by 24 and 48 h after transfection. Combined treatment with wt1 siRNA and bcl-2 siRNA simultaneously was not able to override the cell growth and apoptosis effects compared to single treatment with wt1 siRNA. siRNAs targeted against human wt1 might be a valuable tool as antiproliferative agent against wt1 expressing leukemic cells.
Leukemia 2007 Oct
PMID:Effective treatment of leukemic cell lines with wt1 siRNA. 1769 Jul 5

The objective of study was to investigate whether U937 cells-loaded dendritic cells (DCs) could induce anti-leukemic immune activity. The apoptosis of U937 cells was induced by artesunate (ART). DCs derived from peripheral blood mononuclear cells of health donors were loaded with apoptotic U937 cells, and induced to maturation in the presence of TNF-alpha. Matured DCs were cocultured with autologous T-lymphocytes, and combined with IL-2 in order to induce the leukemia-specific CTL. The phenotypes of DCs and T lymphocytes were tested by flow cytometry. The ability of DC capturing antigens was measured by Dextran-FITC endocytosis. The IL-12p70 level was assayed by ELISA kit. The proliferation of CTL and CTL activity were measured by MTT assay. The results showed that the apoptotic rate of the U937 cells was 51.2% when U937 cells were induced by 1 microg/ml ART for 48 hours in vitro. DCs had the most powerful ability of endocytosis in its immature phase. Apoptotic U937 cells could not induce the features of DC maturation, and apoptotic U937 cell-pulsed immature DCs could be matured with TNF-alpha. The IL-12p70 level secreded by apoptotic U937 cell-loaded mature DCs (mDC-(Apo)U937) was higher than that of non-loaded mDC. The proliferation of autologous T lymphocytes co-cultured with mDC-(Apo)U937 was significantly remarkable and the content of CD8(+) CTL was significantly higher in comparison with any other groups. CTL induced by mDC-(Apo)U937 had stronger killing effect on U937 cells than NB4 (p < 0.01). It is concluded that the mDC-(Apo)U937 can effectively generate T cell-mediated dendritic antileukemic responses in vitro.
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PMID:[Immune response of dendritic cells capturing antigens from apoptotic U937 cells induced by artesunate]. 1770 14

The aim of this study was to determine the prevalence and risk factors for Mycoplasma haemofelis (Mhf) and 'Candidatus Mycoplasma haemominutum' (Mhm) infections in domestic cats tested for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Based on serological testing, cats were grouped as i) FIV-positive (n=25); ii) FeLV-positive (n=39); iii) FIV/FeLV-positive (n=8); and iv) FIV/FeLV-negative (n=77). Complete blood counts were followed by DNA extraction, species-specific polymerase chain reaction (16S rRNA gene) for Mhf and Mhm and Southern blotting for all animals. Mhf DNA was found in 4.0, 2.6, 12.5 and 7.8% of the cats from groups i, ii, iii and iv, respectively, while 32, 5.1, 50 and 5.2% of these animals had an Mhm infection. Cats with FIV (OR=4.25, P=0.009) and both FIV and FeLV (OR=7.56, P=0.014) were at greater risk of being hemoplasma infected than retroviral-negative cats, mainly due to Mhm infection (OR=8.59, P=0.001 and OR=18.25, P=0.001, respectively). Among pure-breed cats, FIV-positive status was associated with hemoplasma infection (OR 45.0, P=0.001).
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PMID:Prevalence and risk factors for hemoplasmas in domestic cats naturally infected with feline immunodeficiency virus and/or feline leukemia virus in Rio de Janeiro--Brazil. 1790 24

The model of erythroleukemia caused by Spi-1/PU.1 transgenesis in mice is a multistage disease. A preleukemic step is characterized by an acute proliferation of proerythroblasts due to the arrest of differentiation provoked by Spi-1/PU.1. Later on, a blastic crisis occurs associated with somatic oncogenic mutations in the stem cell factor (SCF) receptor kit. To gain insights into the mechanisms of the leukemic progression, we performed proteomic profiling analyses of proerythroblasts isolated at the 2 stages of the disease. Our results indicate that the level of ezrin, a membrane cytoskeletal crosslinker, is increased in the leukemic cells. We show that Kit oncogenic forms are responsible for ezrin phosphorylation and that phosphorylation rather than overexpression is essential in the leukemic proerythroblasts. Using expression of dominant-negative forms of ezrin, we show that phosphorylation of ezrin on residue Y353 participates in apoptosis resistance, whereas phosphorylation on residue Y145 promotes proliferation of the leukemic cells in vitro and in vivo. Another recurrent oncogenic form of tyrosine kinases (Flt3) most frequently involved in human myeloid leukemia was also able to phosphorylate ezrin. These findings point to a new role for ezrin as signaling player in the development of leukemia, being a downstream effector of oncogenic tyrosine kinases in leukemic blasts.
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PMID:Ezrin is a target for oncogenic Kit mutants in murine erythroleukemia. 1818 70

HTLV-1 causes adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Recombinant envelope glycoprotein is used in production of diagnostic enzyme-linked immunosorbent assay (ELISA) kit. There are some reports that a significant percentage of Iranian HTLV-1 infected patients showed no seroreactivity with MTA-1 peptide, while HTLV-1 had been confirmed by PCR detection methods or ELISA kits containing a cocktail of HTLV-1 specific peptides. This report describes experiments designed to determine whether some discrepancies between ELISA and PCR results could be due to truncation of immunodominant epitopes using immunoassay method. We have cloned the MTA-1 epitope of env gene from HTLV-1 in NotI/NdeI sites of pET22b(+) expression vector. Sequencing analysis of recombinant plasmids revealed an insertion of a cytosine in position 271 causing a stop codon in the MTA-1 protein translation. SDS-PAGE analysis also failed to reveal the presence of the desired protein. Subjects with a mutant HTLV-1 env gene were shown to be seronegative using ELISA, but positive with PCR.
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PMID:Truncated MTA-1: a pitfall in ELISA-based immunoassay of HTLV-1 infection. 1856 80

A variety of 5-amino-6,8-dicyano-1H-[1,2,4]triazolo[1,5-a]pyridin-4-ium-2-thiolate containing compounds 3a-i, 5a-c were prepared via reaction of arylidenemalononitriles 1a-c, 4a and 4b with 2-[(substituted amino)thiocarbonyl]cyanoacetohydrazides 2a-d in refluxing ethanol in the presence of triethylamine. Anti-inflammatory activity screening of the synthesized compounds (at a dose of 50mg/kg body weight) utilizing in vivo acute carrageenan-induced paw oedema standard method in rats exhibited that the prepared heterocycles possess considerable pharmacological properties especially, 3f, 3h, 5b and 5c which reveal remarkable activities relative to indomethacin (which was used as a reference standard at a dose of 10mg/kg body weight). PGE(2) inhibitory properties of the highly promising synthesized anti-inflammatory active agents (3f, 3h, 5b and 5c) were determined by PGE(2) assay kit technique, which reveal remarkable activity coinciding greatly with the observed anti-inflammatory properties. Anti-tumor activity screening of 3b and 3e, as representative examples of the synthesized compounds, at a dose of 10 microM utilizing 59 different human tumor cell lines, representing leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate and kidney exhibited that the tested compounds reflect mild or no activity at all against most of the used human tumor cell lines. However, compound 3e reveals considerable anti-tumor properties against leukemia CCRF-CEM and HL-60(TB) cell line.
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PMID:Synthesis of [1,2,4]triazolo[1,5-a]pyridines of potential PGE2 inhibitory properties. 1902 98

The proto-oncogene c-kit plays an important role in the development and survival of mast cells. Gain-of-function mutations in c-kit are one of the most characteristic events in mast cell leukemia (MCL) but as yet there is no clinically approved treatment for the disease. Here we describe growth inhibition of human MCL cell lines by the use of RNAi against c-kit or its mutant form. Retroviral transduction of HMC1.1 and HMC1.2 cell lines with vectors carrying DNA to be transcribed to RNAi against the wild type or mutant c-kit messengers reduced Kit protein levels considerably, decreased cell proliferation, and increased the apoptotic levels five days after retroviral infection. Thus RNAi targeted against Kit or its mutant form could be considered as a new antiproliferative agent against human mast leukemia cell lines, especially HMC1.2 cells which are resistant to the Kit tyrosine kinase inhibitor, imatinib mesylate.
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PMID:Selective RNAi-mediated inhibition of mutated c-kit. 1977 Dec 31

Gain-of-function mutations of kit tyrosine kinase receptor are associated with mastocytosis. Two subclones of the HMC1 mast leukaemia cell line were used; both express an identical KIT allele-specific regulatory type mutation (V560G), but differ in that one also expresses an enzymatic site type mutation (D816V) that confers on them resistance to imatinib mesylate tyrosine kinase inhibitor. In both cell lines, proliferation was suppressed and apoptosis induced by the combination of KIT gene silencing and alpha-tocopherol succinate (alpha-TOS), a derivate of alpha-tocopherol, also known as vitamin E. Furthermore, HMC1 cells with decreased kit levels by KIT silencing, failed to form tumours when xenotransplanted into immunocompromised mice and the animals were treated systemically with alpha-TOS. Targeting kit in the presence of alpha-TOS represents a new approach against proliferation of human mast leukaemia cell lines.
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PMID:Combination of KIT gene silencing and tocopherol succinate may offer improved therapeutic approaches for human mastocytosis. 1980 54


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