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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The configuring of a radial basis function network (RBFN) consists of selecting the network parameters (centers and widths in RBF units and weights between the hidden and output layers) and network architecture. The issues of suboptimum and overfitting, however, often occur in RBFN configuring. This paper presented a hybrid particle swarm optimization (HPSO) algorithm to simultaneously search the optimal network structure and parameters involved in the RBFN (HPSORBFN) with an ellipsoidal Gaussian function as a basis function. The continuous version of PSO was used for parameter training, while the modified discrete PSO was employed to determine the appropriate network topology. The proposed HPSORBFN algorithm was applied to modeling the inhibitory activities of substituted bis[(acridine-4-carboxamide)propyl]methylamines to murine P388 leukemia cells and the bioactivities of COX-2 inhibitors. The results were compared with those obtained from RBFNs with the parameters optimized by continuous PSO and by conventionally RBFN training the algorithm for a fixed network topology, indicating that the HPSO was competent for RBFN configuring in that it converged quickly toward the optimal solution and avoided overfitting.
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PMID:Adaptive configuring of radial basis function network by hybrid particle swarm algorithm for QSAR studies of organic compounds. 1712 90

Constituents in rosemary have shown a variety of pharmacological activities for cancer chemoprevention and therapy in in vitro and in vivo models. In order to further explore the chemopreventive properties of crude extracts of rosemary (Rosmarinus officinalis L), we studied its anti-proliferative property on several human cancer cell lines and its antioxidant and anti-inflammatory properties in vitro in a mouse RAW 264.7 macrophage/monocyte cell line. Our study shows that crude ethanolic rosemary extract (RO) has differential anti-proliferative effects on human leukemia and breast carcinoma cells. The 50% inhibitory concentration (IC50) was estimated at 1/700, 1/400, 1/150 and 1/500 dilutions, for the HL60, K562, MCF7 and MDA-MB-468 cells, respectively. Non-cytotoxic concentrations of RO at 1/1000 dilution minimally induced HL60 cell differentiation into granulocyte lineage at 9.5+/-2.2% compared to 2.8+/-0.8% in the untreated control (p<0.001), and did not induce HL60 cell differentiation into monocyte/macrophage lineage. The 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid (Trolox) equivalent antioxidant capacity assay showed that RO has substantial antioxidant activity with RO at 1/10 and 1/5 dilutions having 8.1 and 12.6 microM Trolox equivalents, respectively. RO at non-cytotoxic 1/2000 and 1/1000 dilutions did not affect nitric oxide (NO) production by non-stimulated RAW 264.7 cells. However, at the same dilutions RO significantly reduced NO production by lipopolysaccharide (LPS)-activated cells in a dose-dependent manner from 32.6+/-2.3 microM in the LPS-activated cells to 19.2+/-2.2 microM (p<0.01), and 7.7+/-1.2 microM (p<0.001), respectively. RT-PCR analyses showed that RAW 264.7 cells treated with 1/1000 and 1/500 dilutions for 5 h did not affect TNFalpha, IL-1beta, iNOS and COX-2 mRNA expression in these cells when compared to the untreated controls, nor did the 1/1000 dilution of RO affect TNFalpha, IL-1beta, iNOS and COX-2 mRNA expression in the LPS-activated cells. At 1/500 dilution, RO significantly reduced IL-1beta (p<0.01) and COX-2 (p<0.05) mRNA expression and non-significantly reduced TNFalpha and iNOS mRNA expression in the LPS-activated cells. In view of the chemopreventive potentials, further studies are needed to explore other biological properties of this popular spice used by many cultures in the world.
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PMID:Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis. 1748 14

We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor alpha (ERalpha) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in MCF-7 and MCF-7R showed that curcumin or MR 39 produced early modifications in the amounts of relevant gene transcripts, which, however, were mostly diverse (i.e. represented by decreases in IAPs and COX-2 in MCF-7R versus reductions in Bcl-2 and Bcl-XL as well as increases in the Bcl-XS/Bcl-XL ratio in MCF-7) in the two cell lines. These results could not be explained by an involvement of NF-kappaB (p65 subunit) or STAT3, since the low nuclear levels of these transcription factors present in MCF-7 were only slightly, though significantly, elevated in MCF-7R; moreover, curcumin or MR 39 caused minor changes in NF-kappaB or STAT3 activation. Overall, these data underline that curcumin or MR 39 antitumor activities are not hampered by P-gp expression or lack of ERalpha in breast cancer cells. Remarkably, the agents appeared to modify their molecular effects according to the diverse gene expression patterns existing in the MDR and in the parental MCF-7. Clearly, the structure and properties of curcumin can form the basis for the development of antitumor compounds that are more effective against both chemosensitive and MDR cells.
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PMID:The antitumor activities of curcumin and of its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 breast cancer cell line: analysis of the possible molecular basis. 1767 37

Gambogic acid (GA), a xanthone derived from the resin of the Garcinia hanburyi, has been recently demonstrated to bind transferrin receptor and exhibit potential anticancer effects through a signaling mechanism that is not fully understood. Because of the critical role of NF-kappaB signaling pathway, we investigated the effects of GA on NF-kappaB-mediated cellular responses and NF-kappaB-regulated gene products in human leukemia cancer cells. Treatment of cells with GA enhanced apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents, inhibited the expression of gene products involved in antiapoptosis (IAP1 and IAP2, Bcl-2, Bcl-x(L), and TRAF1), proliferation (cyclin D1 and c-Myc), invasion (COX-2 and MMP-9), and angiogenesis (VEGF), all of which are known to be regulated by NF-kappaB. GA suppressed NF-kappaB activation induced by various inflammatory agents and carcinogens and this, accompanied by the inhibition of TAK1/TAB1-mediated IKK activation, inhibited IkappaBalpha phosphorylation and degradation, suppressed p65 phosphorylation and nuclear translocation, and finally abrogated NF-kappaB-dependent reporter gene expression. The NF-kappaB activation induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKbeta was also inhibited. The effect of GA mediated through transferrin receptor as down-regulation of the receptor by RNA interference reversed its effects on NF-kappaB and apoptosis. Overall our results demonstrate that GA inhibits NF-kappaB signaling pathway and potentiates apoptosis through its interaction with the transferrin receptor.
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PMID:Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-kappaB signaling pathway. 2364 Sep 97

In acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA) triggers cell differentiation, while arsenic trioxide (As(2)O(3)) generates partial differentiation and apoptosis. Animal and human studies suggest that newly diagnosed APL patients can be cured using As(2)O(3) combined with ATRA. Cyclooxygenases are involved in prostaglandins and thromboxane synthesis. We have recently demonstrated that ATRA induces cyclooxygenase-1 (COX-1) expression and prostaglandin synthesis in NB4 cells and in blasts from patients with APL. In the present study we investigated the effect of ATRA and As(2)O(3) co-treatment on COX-1 expression and prostaglandin formation and tested the effect of the COX-1/COX-2 nonselective inhibitor indomethacin on cell differentiation. Arsenic treatment of NB4 cells resulted in a partial but significant reduction of ATRA-dependent induction of COX-1 expression and activity. Pretreatment of NB4 cells with indomethacin significantly impaired ATRA/As(2)O(3)-induced differentiation, as assessed by cell morphology, nitroblue tetrazolium test or CD11c expression. PGE(2) reversed the negative effect of indomethacin on differentiation of ATRA/As(2)O(3)-treated NB4 cells. In conclusion, COX-1 contributes to ATRA-dependent maturation of NB4 cells and is affected by As(2)O(3). These results also suggest that nonsteroidal antiinflammatory drugs should be avoided in APL patients treated with the combination of ATRA and As(2)O(3).
Leukemia 2008 Jun
PMID:Arsenic trioxide inhibits ATRA-induced prostaglandin E2 and cyclooxygenase-1 in NB4 cells, a model of acute promyelocytic leukemia. 1835 91

Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called "curry powder") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an "old-age" disease such as cancer requires an "age-old" treatment.
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PMID:Curcumin and cancer: an "old-age" disease with an "age-old" solution. 1846 66

Sulforaphane (SFN) is a biologically active compound extracted from cruciferous vegetables, and possessing potent anti-cancer and anti-inflammatory activities. Here, we show that tumor necrosis factor-alpha (TNF-alpha), in combination with a sub-toxic dose of SFN, significantly triggered apoptosis in TNF-alpha-resistant leukemia cells (THP-1, HL60, U937, and K562), which was associated with caspase activity and poly (ADP-ribose)-polymerase cleavage. We also report that SFN non-specifically inhibited TNF-alpha-induced NF-kappaB activation through the inhibition of IkappaBalpha phosphorylation, IkappaBalpha degradation, and p65 nuclear translocation. This inhibition correlated with the suppression of NF-kappaB-dependent genes involved in anti-apoptosis (IAP-1, IAP-2, XIAP, Bcl-2, and Bcl-xL), cell proliferation (c-Myc, COX-2, and cyclin D1), and metastasis (VEGF and MMP-9). These effects suggest that SFN inhibits TNF-alpha-induced NF-kappaB activation through the suppression of IkappaBalpha degradation, leading to reduced expression of NF-kappaB-regulated gene products. Combined treatment with SFN and TNF-alpha was also accompanied by the generation of reactive oxygen species (ROS). Pre-treatment with N-acetyl-l-cysteine significantly attenuated the combined treatment-induced ROS generation and caspase-3-dependent apoptosis, implying the involvement of ROS in this type of cell death. In conclusion, the results of the present study indicate that SFN suppresses TNF-alpha-induced NF-kappaB activity and induces apoptosis through activation of ROS-dependent caspase-3.
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PMID:Sulforaphane suppresses TNF-alpha-mediated activation of NF-kappaB and induces apoptosis through activation of reactive oxygen species-dependent caspase-3. 1895 68

Despite its potential, use of trans-resveratrol as an anticancer drug is severely constrained because of its tendency to prolong gastric ulceration. We found that in addition to delaying ulcer healing, trans-resveratrol also aggravated acute gastric ulceration induced by the nonsteroidal anti-inflammatory drugs by reducing the synthesis of prostaglandin (PG) E(2) via a specific inhibition of cyclooxygenase (COX)-1 that also hampered angiogenesis. However, for the first time, we showed that the 3'-5'-hydroxylated congener [(E)-HST-1] of trans-resveratrol, synthesized in multigram scale, exerted potential chemotherapeutic property but was nonulcerogenic in nature, rather moderately accelerated healing of indomethacin-induced gastric ulceration. HST-1 did not suppress COX-1, COX-2 expression, and PGE(2) synthesis but reduced the level of inflammatory myeloperoxidase (MPO) activity. The healing was augmented primarily through the nitric oxide synthase (NOS)-dependent pathway. HST-1 treatment induced endothelial NOS (eNOS) expression and reduced inducible NOS (iNOS), resulting in increased eNOS/iNOS ratio. The selective iNOS inhibitor [L-N(6)-(1-iminoethyl) lysine hydrochloride] and nonselective NOS inhibitor (N(omega)-nitro-L-arginine methyl ester) treatment revealed that eNOS could be the probable molecular switch to accelerate the indomethacin-induced ulcer healing in HST-1-treated mice. Furthermore, the anticancer effect of HST-1 on U937 and K562 leukemia cell lines was found to be significantly better than that of trans-resveratrol. Overall, these established HST-1 as a potentially better anticancer compound than trans-resveratrol, considering it is devoid of any ulcerogenic side effects. In conclusion, for the first time, we showed that a novel analog of trans-resveratrol, HST-1, was devoid of ulcerogenic adversative effects of trans-resveratrol but retained potentially better anticancer property.
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PMID:Improved antiulcer and anticancer properties of a trans-resveratrol analog in mice. 1906 40

Polysaccharides of edible algae attracted extensive interest due to their numerous biological activities. Sargassum latifolium (Turner) C. Agardh, belongs to Sargassaceae, is a brown algae in red sea shores in Egypt. This work is a novel attempt to explore the cancer chemopreventive activity of different fractions of water-soluble polysaccharide extract derived from S. latifolium. Estimation of cancer chemopreventive activity, specifically anti-initiation, including the modulation of carcinogen metabolism and the antioxidant capacity, revealed that E1 and E4 were potent anti-initiators, where they lead not only to an inhibition in the carcinogen activator cytochrome P450 1A (IC50 2.54 and 10.30 microg/ml, respectively), but also to an induction in the carcinogen detoxification enzymes glutathione-S-transferases (144% and 225% of the control, respectively). E1 and E4 inhibited 59% and 63% of the induced-DNA damage, as measured by comet assay. Similarly both E1 and E4 possessed potential anti-promoting properties as indicated by their anti-inflammatory activity. E1 and E4 enhanced the macrophage proliferation; however they dramatically inhibited the stimulated NO (30.7% and 59.3%), TNF-alpha (38.2% and 54.9) and COX-2 (20% and 18%), respectively. E3 showed a selective cytotoxicity against lymphoblastic leukemia (1301 cells), while other fraction extracts had no cytotoxic effect against all tested cell lines. E3 led to a major disturbance in cell cycle including arrest in both S-phases in 1301 cells. This disturbance was associated with an induced-cell death due to apoptosis, but not necrosis. In conclusion, E1 and E4 are promising cancer chemopreventive fractions, since they had tumor anti- initiating activity via their protective modulation of carcinogen metabolism, and tumor anti-promoting activity via their anti-inflammatory activity, while E3 can be considered as a promising anti-cancer agent against leukemia.
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PMID:In vitro cancer chemopreventive properties of polysaccharide extract from the brown alga, Sargassum latifolium. 1930 10

NUP98 gene rearrangements occur in acute myeloid leukemia and result in the expression of fusion proteins. One of the most frequent is NUP98-DDX10 that fuses a portion of NUP98 to a portion of DDX10, a putative DEAD-box RNA helicase. Here, we show that NUP98-DDX10 dramatically increases proliferation and self-renewal of primary human CD34+ cells, and disrupts their erythroid and myeloid differentiation. It localizes to their nuclei and extensively deregulates gene expression. Comparison to another leukemogenic NUP98 fusion, NUP98-HOXA9, reveals a number of genes deregulated by both oncoproteins, including HOX genes, COX-2, MYCN, ANGPT1, REN, HEY1, SOX4 and others. These genes may account for the similar leukemogenic properties of NUP98 fusion oncogenes. The YIHRAGRTAR sequence in the DDX10 portion of NUP98-DDX10 represents a major motif shared by DEAD-box RNA helicases that is required for ATP binding, RNA-binding and helicase functions. Mutating this motif diminished the in vitro transforming ability of NUP98-DDX10, indicating that it has a role in leukemogenesis. These data show for the first time the in vitro transforming ability of NUP98-DDX10 and show that it is partially dependent on one of the consensus helicase motifs of DDX10. They also point to common pathways that may underlie leukemogenesis by different NUP98 fusions.
Leukemia 2010 May
PMID:Effects of the NUP98-DDX10 oncogene on primary human CD34+ cells: role of a conserved helicase motif. 2033 40


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