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)

Synthesis and characterization of new thiosemicarbazones derived from natural aldehydes (1-9) have been investigated in order to develop a research program aimed at the development of compounds with antiviral, antibacterial, and antitumor properties. These substances contain both a chain with N and S nucleophilic centers with tuberculostatic activity, and an alkyl or terpenic moiety. In addition, a few nickel(II) and copper(II) complexes (10-18), derived also from the previously studied ligands, were synthesized and characterized by means of NMR and IR techniques. The trans-2-octenal N(1)-phenylthiosemicarbazone and its nickel complex were also characterized by X-ray diffractometry. Biological studies, performed with some of these compounds, have involved both inhibition of cell proliferation and apoptosis tests in vitro on human leukemia cell line U937 to deepen our knowledge on the way these substances interfere with biological processes in leukemic cells.
 ...
PMID:Synthesis, characterization and X-ray structures of new antiproliferative and proapoptotic natural aldehyde thiosemicarbazones and their nickel(II) and copper(II) complexes. 1203 3

Copper-7 and Tatum-T (both manufactured by G.D. Searle and Co.) have similar dimensions: Tatum-T measures 31.5 mm by 36 mm, while Copper-7 measures 27 mm by 36 mm. Both are coated with about 200 sq. mm of copper. Expulsion rates; rates for pregnancies or removals for bleeding, pain or other complications were found to be similar for both in a comparative double-blind study conducted by the Population Council in conjunction with Searle. Tatum, the developer of the Tatum device, states that "the symmetry of the T is a major advantage since it matches the symmetry of the uterine cavity. The Copper-7 does not; it is off-center." Tatum further maintains that removal of the Tatum-T is easier than that of Copper 7 as the arms of the T can fold up so that the device can come straight down the cervical canal. In addition, the T is theoretically less likely to perforate the cervix during expulsion. The T-shape of the device also contributes to its flexibility in all directions and thus makes it easier to use by clinicians. The design of the tail makes insertion easier too. Disadvantages of Tatum-T is related to the folding capability of its arms, requiring a larger presenting diameter (5.96 mm) for the inserter tube than that of Copper-7 (3.07 mm). Contraindications to Tatum-T insertion are similar to those for Copper-7, and includes copper allergy; history of ectopic pregnancy; anemia or any condition which predisposes patients to infection, such as leukemia or steroid therapy.
 ...
PMID:New Tatum-T compared with Copper-7. 1227 58

The Population Council recently reworded the package labeling for the copper T380A IUD as follows: pelvic inflammatory disease (PID) is related to a woman's sexual behavior and not to the device itself. Formerly contraindicated, histories of PID or ectopic pregnancy are now merely precautions. The labeling now warns that the Copper T is contraindicated in the presence of PID or in women with a history of PID since the last pregnancy. If a woman has been free of infection, there is no need not to give her an IUD. The former contraindication about ectopic pregnancy has been deleted, while contraindications in the section of the label on conditions associated with increased susceptibility to infections with microorganisms now include only leukemia and AIDS. IV drug use and conditions requiring chronic corticosteroid therapy have been dropped from the section, along with diabetes. Finally, the former contraindication of genital actinomycosis has been changed to address symptomatic genital actinomycosis with organism confirmed by culture. This latter change is due to the high number of false-positives seen with Pap smears alone. These changes are logical given recent research findings about IUDs. A brief overview is given of recent findings about IUDs with regard to pelvic inflammatory disease, ectopic pregnancy, and diabetes.
 ...
PMID:New label broadens IUD candidacy profile. History of some diseases now just a precaution. 1231 42

Three new ligands, N-(8-quinolyl)pyridine-2-carboxamide (HL1), N-(8-quinolyl)glycine-N'-Boc-carboxamide (HL2), N-(8-quinolyl)-L-alanine-N'-Boc-carboxamide (HL3), and their Cu(II) complexes have been synthesized. Crystallographic data reveal that complex I, [Cu(L1)(Ac)(H2O)], is penta-coordinated with a square-pyramidal geometry while complexes V [Cu(L2')(H2O)] and VI [Cu(L3')(H2O)] are tetra-coordinated to give square planar geometry. In vitro tests showed that the Cu(II) complexes with L1 (I-IV) exhibited cytotoxicity at a concentration of 10(-8) M against murine leukemia P-388 and human leukemia HL-60 cell lines, which is more potent than cisplatin. However, ligands HL2 and HL3 and their corresponding copper complexes demonstrated very weak in vitro activities towards the cell lines examined. ESMS data shows that complex I binds rapidly with 5'-GMP to form 1:1 and 2:2 adduct.
 ...
PMID:Novel Cu(II)-quinoline carboxamide complexes: structural characterization, cytotoxicity and reactivity towards 5'-GMP. 1268 Jul 13

Homocysteine is considered to be an important risk factor for cancer as well as cardiovascular diseases. To clarify whether homocysteine has potential carcinogenicity, we investigated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is known to be correlated with the incidence of cancer, induced by homocysteine in human cultured cell lines. Homocysteine increased the amount of 8-oxodG in human leukemia cell line HL-60, whereas the amount of 8-oxodG in its hydrogen peroxide (H(2)O(2))-resistant clone HP100 was not increased. We investigated the mechanism for oxidative DNA damage by homocysteine using (32)P-labeled DNA fragments obtained from human tumor suppressor genes and a proto-oncogene. There were two mechanisms by which homocysteine caused DNA damage in the presence of Cu(II). A low concentration of homocysteine (20 microM) frequently induced piperidine-labile sites at thymine residues, whereas a high concentration of homocysteine (100 microM) resulted in damage principally to guanine residues. Catalase inhibited DNA damage by 20 microM homocysteine, indicating the participation of H(2)O(2), but was ineffective in preventing DNA damage by 100 microM homocysteine. Experiments using a singlet oxygen probe showed that 100 microM homocysteine enhanced chemiluminescence intensity in deuterium oxide more than that in H(2)O. These results indicated that the metal-dependent DNA damage through H(2)O(2) is likely to be a more relevant mechanism for homocysteine carcinogenicity.
 ...
PMID:Oxidative damage to cellular and isolated DNA by homocysteine: implications for carcinogenesis. 1278 61

Green tea catechins have antimutagenic and anticarcinogenic activities. On the other hand, several epidemiological studies have indicated significant positive relationship between green tea consumption and cancer. Catechins enhance colon carcinogenesis in rats initiated with chemical carcinogen. To clarify the mechanism underlying the potential carcinogenicity, we investigated the DNA-damaging ability of catechins in human cultured cells. Catechin increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60 but not in HP100, a hydrogen peroxide (H2O2)-resistant cell line derived from HL-60. The catechin-induced formation of 8-oxodG in HL-60 cells significantly decreased by bathocuproine. Furthermore, we investigated DNA damage and its site-specificity induced by catechins, using 32P-labeled DNA fragments. Catechin and epicatechin induced extensive DNA damage in the presence of Cu(II). Catechin caused piperidine-labile sites at thymine and cytosine residues in the presence of Cu(II). Catalase and bathocuproine inhibited the DNA damage, indicating the involvement of H2O2 and Cu(I). NADH enhanced catechins plus Cu(II)-induced 8-oxodG formation in calf thymus DNA, suggesting the redox cycle between catechins and their corresponding quinones, the oxidized forms of catechins. The DNA-damaging ability of epicatechin is stronger than that of catechin, possibly due to the greater turnover frequency of the redox cycle. The difference in their redox properties could be explained by their redox potentials estimated form an ab initio molecular orbital calculation. The present study demonstrated that catechins could induce metal-dependent H2O2 generation during the redox reactions and subsequently damage to cellular and isolated DNA. Therefore, it is reasonably considered that green tea catechins may have the dual function of anticarcinogenic and carcinogenic potentials.
 ...
PMID:Catechins induce oxidative damage to cellular and isolated DNA through the generation of reactive oxygen species. 1456 48

Soy isoflavones and other polyphenolics have a number of potentially important beneficial effects on the pro-oxidant aspects of chronic inflammation. The impact of inflammatory cell-specific metabolism of polyphenolics, which can include halogenation and nitration, on the properties of these compounds has not been examined. Using either human neutrophils or differentiated human leukemia cells (HL-60) stimulated with phorbol ester to elicit a respiratory burst, the hypothesis that local generation of reactive oxygen and nitrogen species may metabolize and modify the biological properties of the soy isoflavones was examined. Coincubation of the stimulated cells with genistein or daidzein had no effect on the respiratory burst. Medium from stimulated cells in the presence of the isoflavones and NO(2)(-) increased the inhibition of copper-induced LDL oxidation. Mass spectrometry analysis of this medium revealed that monochlorinated, dichlorinated, and nitrated isoflavones, formed through a myeloperoxidase-dependent mechanism, were present. The consumption of genistein in the presence of cells was both extensive and rapid with > 95% of the genistein converted to either the chlorinated or nitrated metabolites within 30 min. Chemically synthesized 3'-chlorogenistein and 3'-chlorodaidzein increased the inhibition of LDL oxidation by approximately 4-fold and 2-fold over genistein and daidzein, respectively. These results lead to the hypothesis that inflammatory cell-specific metabolism of polyphenolics can modify the properties of these compounds at the local site of inflammation.
 ...
PMID:Neutrophil myeloperoxidase chlorinates and nitrates soy isoflavones and enhances their antioxidant properties. 1464 89

Here we report that organic copper complexes can potently and selectively inhibit the chymotrypsin-like activity of the proteasome in vitro and in vivo. Several copper compounds, such as NCI-109268 and bis-8-hydroxyquinoline copper(II) [Cu(8-OHQ)(2)], can inhibit the chymotrypsin-like activity of purified 20S proteasome. In human leukemia cells, proteasome inhibition occurs within 15min after treatment, followed by apoptosis. Neither proteasome inhibition nor apoptosis occurs in non-transformed, immortalized human natural killer cells under the same treatment. Furthermore, proteasome inhibition and apoptosis induction were detected in prostate cancer cells treated with the ligand 8-OHQ alone following pre-treatment with copper(II) chloride. None of these events occurred in cells treated with copper(II) chloride alone, 8-OHQ alone (without growth in copper-enriched media), or nickel(II) chloride pre-treatment followed by 8-OHQ. Furthermore, we found that copper-mediated inhibition of purified 20S proteasome cannot be blocked by a reducing agent and that organic copper compounds do not generate hydrogen peroxide in the cells, suggesting that proteasome inhibition and apoptosis induction are not due to copper-mediated oxidative damage of proteins. Our results suggest that certain types of organic ligands could bind to tumor cellular copper, forming potent proteasome inhibitors and apoptosis inducers at copper concentrations found in tumor tissues.
 ...
PMID:Organic copper complexes as a new class of proteasome inhibitors and apoptosis inducers in human cancer cells. 1500 50

Propyl gallate (PG), widely used as an antioxidant in foods, is carcinogenic to mice and rats. PG increased the amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, but not in HP100, which is hydrogen peroxide (H2O2)-resistant cell line derived from HL-60. Although PG induced no or little damage to 32P-5'-end-labeled DNA fragments obtained from genes that are relevant to human cancer, DNA damage was observed with treatment of esterase. HPLC analysis of the products generated from PG incubated with esterase revealed that PG converted into gallic acid (GA). GA induced DNA damage in a dose-dependent manner in the presence of Fe(III)EDTA or Cu(II). In the presence of Fe(III) complex such as Fe(III)EDTA or Fe(III)ADP, GA caused DNA damage at every nucleotide. Fe(III) complex-mediated DNA damage by GA was inhibited by free hydroxy radical (*OH) scavengers, catalase and an iron chelating agent. These results suggested that the Fe(III) complex-mediated DNA damage caused by GA is mainly due to *OH generated via the Fenton reaction. In the presence of Cu(II), DNA damage induced by GA occurred at thymine and cytosine. Although *OH scavengers did not prevent the DNA damage, methional inhibited the DNA damage. Cu(II)-mediated DNA damage was inhibited by catalase and a Cu(I) chelator. These results indicated that reactive oxygen species formed by the interaction of Cu(I) and H2O2 participates in the DNA damage. GA increased 8-oxodG content in calf thymus DNA in the presence of Cu(II), Fe(III)EDTA or Fe(III)ADP. This study suggested that metal-mediated DNA damage caused by GA plays an important role in the carcinogenicity of PG.
 ...
PMID:Metal-mediated oxidative damage to cellular and isolated DNA by gallic acid, a metabolite of antioxidant propyl gallate. 1503 24

The trace element boron is essential for all higher plants and is beneficial or has been established as essential for several animal models of human nutrition. To help identify the biomolecules that require boron for function in humans, we determined whether intracellular boron is retained against a concentration gradient. Cells (Abelson leukemia virus BALB murine monocyte-macrophage RAW 264.7 [RAW] and HL60) and supplemented media (Dulbecco's modified essential media [+ 10% fetal calf serum] and Iscove's modified Dulbecco's medium [+ 5% fetal calf serum], respectively) were analyzed for mineral concentrations after culture and subculture. Special corrections were made for trapped extracellular media in cell pellets and endocytosed media. For RAW cells, the partitioning coefficients (PC; intracellular/extracellular ratios) were, in rank order, as follows: Mn, 110; Fe, 67; P, 65; Zn, 32; K, 15; Cu, 7.1; Mg, 4.3; B, 1.7; Ca, 0.4; Na, 0.3. For HL60 cells, the partitioning coefficients were, in rank order, as follows: Mn, 212; Zn, 211; P, 123; K, 21; Fe, 16; Mg, 11; B, 1.7; Ca, 0.8; Na, 0.3. Trapped extracellular media was estimated to be 6.7 +/- 0.8%; trapped extracellular and endocytosed media together was 24.8 +/- 0.3% of the mass within the isolated cell pellets. The partitioning coefficients indicate a positive gradient for intracellular accumulation of boron, zinc, phosphorus, manganese, magnesium, potassium, iron, and copper in RAW264.7 and HL60 cells. Specifically, the data indicate the existence of a selective boron-binding molecular species within the cell or the existence of a boron-specific membrane transporter.
 ...
PMID:Transmembrane partitioning of boron and other elements in RAW 264.7 and HL60 cell cultures. 1507 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>