Arabinonucleotides: Nucleotides containing arabinose as their sugar moiety.Myelodysplastic Syndromes: Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.Syndrome: A characteristic symptom complex.Anemia, Refractory: A severe sometimes chronic anemia, usually macrocytic in type, that does not respond to ordinary antianemic therapy.Anemia, Refractory, with Excess of Blasts: Chronic refractory anemia with granulocytopenia, and/or thrombocytopenia. Myeloblasts and progranulocytes constitute 5 to 40 percent of the nucleated marrow cells.Medical History Taking: Acquiring information from a patient on past medical conditions and treatments.Leukemia, Myelomonocytic, Chronic: A myelodysplastic-myeloproliferative disease characterized by monocytosis, increased monocytes in the bone marrow, variable degrees of dysplasia, but an absence of immature granulocytes in the blood.Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.Oligonucleotides: Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Oligonucleotides, Antisense: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.Ribonuclease H, Human Immunodeficiency Virus: A ribonuclease activity that is a component of the HIV REVERSE TRANSCRIPTASE. It removes the RNA strand of the RNA-DNA heteroduplex produced by reverse transcription. Once the RNA moiety is removed a double stranded DNA copy of the HIV RNA can be synthesized.Organothiophosphorus Compounds: Compounds containing carbon-phosphorus bonds in which the phosphorus component is also bonded to one or more sulfur atoms. Many of these compounds function as CHOLINERGIC AGENTS and as INSECTICIDES.RNA, Antisense: RNA molecules which hybridize to complementary sequences in either RNA or DNA altering the function of the latter. Endogenous antisense RNAs function as regulators of gene expression by a variety of mechanisms. Synthetic antisense RNAs are used to effect the functioning of specific genes for investigative or therapeutic purposes.Arabinofuranosylcytosine Triphosphate: A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis.Cytarabine: A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)ThymidineDNA Replication: The process by which a DNA molecule is duplicated.United States National Aeronautics and Space Administration: An independent Federal agency established in 1958. It conducts research for the solution of problems of flight within and outside the Earth's atmosphere and develops, constructs, tests, and operates aeronautical and space vehicles. (From U.S. Government Manual, 1993)National Library of Medicine (U.S.): An agency of the NATIONAL INSTITUTES OF HEALTH concerned with overall planning, promoting, and administering programs pertaining to advancement of medical and related sciences. Major activities of this institute include the collection, dissemination, and exchange of information important to the progress of medicine and health, research in medical informatics and support for medical library development.Surgical Mesh: Any woven or knit material of open texture used in surgery for the repair, reconstruction, or substitution of tissue. The mesh is usually a synthetic fabric made of various polymers. It is occasionally made of metal.United StatesNational Health Insurance, United StatesPolypropylenes: Propylene or propene polymers. Thermoplastics that can be extruded into fibers, films or solid forms. They are used as a copolymer in plastics, especially polyethylene. The fibers are used for fabrics, filters and surgical sutures.MEDLARS: A computerized biomedical bibliographic storage and retrieval system operated by the NATIONAL LIBRARY OF MEDICINE. MEDLARS stands for Medical Literature Analysis and Retrieval System, which was first introduced in 1964 and evolved into an online system in 1971 called MEDLINE (MEDLARS Online). As other online databases were developed, MEDLARS became the name of the entire NLM information system while MEDLINE became the name of the premier database. MEDLARS was used to produce the former printed Cumulated Index Medicus, and the printed monthly Index Medicus, until that publication ceased in December 2004.

A 3'-5' exonuclease in human leukemia cells: implications for resistance to 1-beta -D-arabinofuranosylcytosine and 9-beta -D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate. (1/101)

A 3'-5' exonuclease that excises the nucleotide analogs 1-beta-d-arabinofuranosylcytosine monophosphate and 9-beta-d-arabinofuranosyl-2-fluoroadenine 5'-monophosphate incorporated at 3' ends of DNA was purified from the nuclei of: 1) primary human chronic lymphocytic leukemia cells, 2) primary and established human acute myeloblastic leukemia cells, and 3) lymphocytes obtained from healthy individuals. The activity of this nuclear exonuclease (exoN) is elevated approximately 6-fold in 1-beta-d-arabinofuranosylcytosine-resistant leukemia cells as compared with drug-sensitive cells, and it differs between two healthy individuals and among three leukemia patients. exoN is a 46-kDa monomer, requires 50 mm KCl and 1 mm magnesium for optimal activity, and shows a preference for single-stranded over duplex DNA. Its physical and enzymatic properties indicate that exoN is a previously uncharacterized enzyme whose activity may confer resistance to clinical nucleoside analogs in leukemia cells.  (+info)

The role of c-Jun kinase in the apoptotic response to nucleoside analogue-induced DNA damage. (2/101)

Activation of the c-Jun NH2-terminal kinase type 1 (JNK1) signaling pathway is often associated with apoptosis. In this report, we elucidated the role of this kinase in the programmed cell death induced by the nucleoside analogue 9-beta-D-arabinosyl-2-fluoroadenine (F-ara-A). Treatment of ML-1 cells with 3 or 10 microM F-ara-A specifically killed cells in the S-phase of the population. Incorporation of F-ara-ATP, the nucleoside triphosphate of F-ara-A, into DNA resulted in the activation of JNK1 in a time- and dose-dependent fashion. Activation of JNK1 temporally preceded DNA fragmentation. When incorporation of F-ara-A into DNA was blocked by pretreatment of the cells with aphidicolin to inhibit DNA synthesis, neither JNK1 signaling nor apoptosis was evident. Furthermore, inhibition of JNK1 by treatment of the cells with forskolin or by pretreatment with an antisense oligonucleotide directed against JNK1 mRNA resulted in a decrease in F-ara-A-induced apoptosis. Finally, the JNK1 signaling pathway appeared to be upstream to that of the effector caspases in nucleoside analogue-induced apoptosis. Thus, our data strongly suggest that JNK1 is involved in transduction of F-ara-A-induced distress signals into an apoptotic response.  (+info)

Interactions between 2-fluoroadenine 9-beta-D-arabinofuranoside and the kinase inhibitor UCN-01 in human leukemia and lymphoma cells. (3/101)

Interactions between the purine analogue 2-fluoroadenine 9-beta-D-arabinofuranoside (F-ara-A) and the kinase inhibitor UCN-01 have been examined in human leukemia cells (U937 and HL-60) with respect to induction of mitochondrial damage, caspase activation, apoptosis, and loss of clonogenic survival. Simultaneous or subsequent exposure of F-ara-A-treated cells (2 microM) to UCN-01 (100 nM) resulted in a marked potentiation of apoptosis, manifested by loss of mitochondrial membrane potential (delta psi(m)), cleavage/activation of procaspase-9 and procaspase-3, DNA fragmentation, and degradation of poly-ADP(ribosyl) polymerase. Coadministration of UCN-01 with F-ara-A was also associated with diminished phosphorylation of the cdc25 phosphatase. In contrast, exposure of cells to the sequence UCN-01, followed by F-ara-A, resulted in only a modest increase in apoptotic cells. The ability of UCN-01 to potentiate F-ara-A-mediated lethality was not mimicked by the selective PKC inhibitor bisindolylmaleimide, nor did treatment of cells with UCN-01 enhance formation of F-ara-ATP or increase incorporation of [3H]F-ara-A into DNA. Enhanced apoptosis in cells exposed sequentially or simultaneously to F-ara-A and UCN-01 was accompanied by a substantial reduction in colony formation (e.g., to 0.01% of control values). Cotreatment with UCN-01 also increased F-ara-A-mediated apoptosis and loss of delta psi(m) in U937 cells ectopically expressing Bcl-2, although not to the same extent as that observed in empty-vector controls. Finally, simultaneous exposure (24 h) of malignant B lymphocytes from the pleural effusion of a patient with indolent non-Hodgkin's lymphoma to F-ara-A and UCN-01 ex vivo resulted in a striking increase in apoptosis, as determined by terminal deoxynucleotidyltransferase-mediated nick end labeling assay. These findings indicate that UCN-01 increases F-ara-A-induced mitochondrial damage and apoptosis in human leukemia cells in a sequence-dependent manner, and that these events occur in at least some primary human lymphoma cells.  (+info)

Evaluation of the combination of nelarabine and fludarabine in leukemias: clinical response, pharmacokinetics, and pharmacodynamics in leukemia cells. (4/101)

PURPOSE: A pilot protocol was designed to evaluate the efficacy of fludarabine with nelarabine (the prodrug of arabinosylguanine [ara-G]) in patients with hematologic malignancies. The cellular pharmacokinetics was investigated to seek a relationship between response and accumulation of ara-G triphosphate (ara-GTP) in circulating leukemia cells and to evaluate biochemical modulation of cellular ara-GTP metabolism by fludarabine triphosphate. PATIENTS AND METHODS: Nine of the 13 total patients had indolent leukemias, including six whose disease failed prior fludarabine therapy. Two patients had T-acute lymphoblastic leukemia, one had chronic myelogenous leukemia, and one had mycosis fungoides. Nelarabine (1.2 g/m(2)) was infused on days 1, 3, and 5. On days 3 and 5, fludarabine (30 mg/m(2)) was administered 4 hours before the nelarabine infusion. Plasma and cellular pharmacokinetic measurements were conducted during the first 5 days. RESULTS: Seven patients had a partial or complete response, six of whom had indolent leukemias. The disease in four responders had failed prior fludarabine therapy. The median peak intracellular concentrations of ara-GTP were significantly different (P =.001) in responders (890 micromol/L, n = 6) and nonresponders (30 micromol/L, n = 6). Also, there was a direct relationship between the peak fludarabine triphosphate and ara-GTP in each patient (r = 0.85). The cellular elimination of ara-GTP was slow (median, 35 hours; range, 18 to > 48 hours). The ratio of ara-GTP to its normal counterpart, deoxyguanosine triphosphate, was higher in each patient (median, 42; range, 14 to 1,092) than that of fludarabine triphosphate to its normal counterpart, deoxyadenosine triphosphate (median, 2.2; range, 0.2 to 27). CONCLUSION: Fludarabine plus nelarabine is an effective, well-tolerated regimen against leukemias. Clinical responses suggest the need for further exploration of nelarabine against fludarabine-refractory diseases. Determination of ara-GTP levels in the target tumor population may provide a prognostic test for the activity of nelarabine.  (+info)

Solution structure of an arabinonucleic acid (ANA)/RNA duplex in a chimeric hairpin: comparison with 2'-fluoro-ANA/RNA and DNA/RNA hybrids. (5/101)

Hybrids of RNA and arabinonucleic acid (ANA) as well as the 2'-fluoro-ANA analog (2'F-ANA) were recently shown to be substrates of the enzyme RNase H. Although RNase H binds to double-stranded RNA, no cleavage occurs with such duplexes. Therefore, knowledge of the structure of ANA/RNA hybrids may prove helpful in the design of future antisense oligonucleotide analogs. In this study, we have determined the NMR solution structures of ANA/RNA and DNA/RNA hairpin duplexes and compared them to the recently published structure of a 2'F-ANA/RNA hairpin duplex. We demonstrate here that the sugars of RNA nucleotides of the ANA/RNA hairpin stem adopt the C3'-endo (north, A-form) conformation, whereas those of the ANA strand adopt a 'rigid' O4'-endo (east) sugar pucker. The DNA strand of the DNA/RNA hairpin stem is flexible, but the average DNA/RNA hairpin structural parameters are close to the ANA/RNA and 2'F-ANA/RNA hairpin parameters. The minor groove width of ANA/RNA, 2'F-ANA/RNA and DNA/RNA helices is 9.0 +/- 0.5 A, a value that is intermediate between that of A- and B-form duplexes. These results rationalize the ability of ANA/RNA and 2'F-ANA/RNA hybrids to elicit RNase H activity.  (+info)

DNA repair initiated in chronic lymphocytic leukemia lymphocytes by 4-hydroperoxycyclophosphamide is inhibited by fludarabine and clofarabine. (6/101)

PURPOSE: Chronic lymphocytic leukemia (CLL) lymphocytes respond to DNA alkylation by excision repair, with the extent of repair increasing as the cells acquire resistance to alkylating agents. Because incorporation of nucleotide analogues into the repair patches elicits death signals in quiescent cells, the increased capacity for excision repair in alkylator-resistant cells could facilitate incorporation of nucleotide analogues. We hypothesized that the mechanism-based interaction of nucleoside analogues with alkylating agents could elicit greater than additive killing of CLL cells. EXPERIMENTAL DESIGN: Lymphocytes from 50 patients with CLL that were not refractory to alkylators were treated in vitro with 4-hydroperoxycyclophosphamide (4-HC) with or without prior incubation with fludarabine nucleoside (F-ara-A) or with clofarabine (Cl-F-ara-A). DNA damage repair kinetics were determined by the single-cell gel electrophoresis (comet) assay. Cytotoxicity was assessed by staining with annexin V. RESULTS: CLL lymphocytes promptly initiated and completed excision repair in response to 4-HC. A 2-h preincubation with 10 microM F-ara-A or 10 microM Cl-F-ara-A inhibited the repair initiated by 4-HC, with inhibition peaking at the intracellular concentrations of 50 microM F-ara-ATP or 5 microM Cl-F-ara-ATP. Combining 4-HC with either F-ara-A or Cl-F-ara-A produced more than additive apoptotic cell death than the sum of each alone. The increase in cytotoxicity was proportional to the initial magnitude of the DNA incision and to the extent of repair inhibition by the nucleoside analogues, suggesting close correlation between the repair inhibition and induction of cell death. CONCLUSIONS: DNA repair, which is active in CLL lymphocytes, may be a biological target for facilitating the incorporation of nucleoside analogues and increasing their cytotoxicity. Thus, the increased repair capacity associated with resistant disease may be manipulated to therapeutic advantage.  (+info)

Interferon alpha plus intermittent oral Ara-C ocfosfate (YNK-01) in chronic myeloid leukemia primarily resistant or with minimal cytogenetic response to interferon. (7/101)

BACKGROUND AND OBJECTIVES: Subcutaneous Ara-C plus interferon (IFN) produces more cytogenetic responses than IFN in chronic myeloid leukemia (CML) but a greater toxicity. The objective of this study was to determine the efficacy and tolerance of IFN plus oral Ara-C ocfosfate (YNK-01) in IFN-resistant CML patients. DESIGN AND METHODS: A phase II pilot study was conducted in 19 CML patients primarily resistant or with minimal cytogenetic response to IFN. Patients were scheduled to receive 6 monthly 14-day cycles of YNK-01 (500 mg/day), with progressive escalation if tolerated, in addition to IFN. Cytogenetic assessment was performed thereafter. RESULTS: Of the first 7 patients, 5 had severe hematologic and 5 moderate gastrointestinal toxicity; IFN was reduced in 6, YNK-01 in 5, and treatment discontinued in 2; hematologic response was achieved in 2 of the 5 evaluable patients. In the following 4 patients the Ara-C was reduced to 300 mg: 2 had severe hematologic and 2 moderate gastrointestinal toxicity; IFN and Ara-C were reduced in 2 patients and treatment discontinued in 2 due to progression or toxicity; the other 2 achieved a minor cytogenetic response, progressing in one to a major response after 6 more cycles. In 8 patients the starting Ara-C dose was 200 mg: 5 had moderate-severe hematologic and 5 mild gastrointestinal toxicity; IFN was reduced in 5, Ara-C in 1, and treatment discontinued in 1; Ara-C was increased in 7 cases; hematologic response was obtained in 4 patients, 2 of whom attained a minor and 1 a major cytogenetic response. INTERPRETATION AND CONCLUSIONS: These results provide background for future studies aimed at ascertaining the role of oral Ara-C combined with IFN or STI571 in newly diagnosed CML.  (+info)

Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01) and interferon alpha-2b for the treatment of chronic myelogenous leukemia patients in chronic phase. (8/101)

Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials.  (+info)

Gibson, M H. and Bertalanffy, F D., "In vivo synchrony of solid b16 melanoma by 1-beta-d-arabinofuranosyl- -cytosine (ara-c). Abstr." (1971). Subject Strain Bibliography 1971. 68 ...
1-beta-d-Arabinofuranosylcytosine (ara-C), an effective drug for acute leukemias, must be phosphorylated to its 5-triphosphate, ara-CTP, for activity. Our previous studies during therapy of acute myelogenous leukemia (AML) patients demonstrated that the accumulation of ara-CTP in circulating leukemia blasts was increased by a median of 2-fold when fludarabine (30 mg/m2/day over 30 min) was infused 4 h prior to intermediate dose ara-C. The augmentation was dependent on the cellular concentration of fludarabine triphosphate (F-ara-ATP). To determine the lowest dose of fludarabine needed for modulation of ara-C metabolism, the present study administered fludarabine at a test dose (15 mg/m2 over 30 min) followed by 2 g/m2 ara-C infused over 4 h. The next day, the fludarabine/ara-C couplet was repeated but with a standard dose (30 mg/m2) of fludarabine. There was a dose-dependent accumulation of F-ara-ATP in circulating leukemia blasts; the median peak concentrations were 33 and 41 microM with 15 ...
rezeki (8) sakit (5) hadiah (4) solat (4) ilmu (3) kek (3) muhasabah (3) segmen.. (3) .... (2) Malaikat (2) Neraka (2) aktiviti (2) hati.. (2) lelaki (2) makan (2) sumber dr buku 150 wasiat Rasulullah utk wanita (2) sumber.. (2) ............ (1) AKU... (1) Adab... (1) Alien (1) Azab (1) Azan (1) Begini (1) Celaru........ (1) Iblis . (1) Jangan-jangan (1) Kerana Allah. (1) MAMA (1) PROTON PREVE (1) SEGMEN (1) Speech (1) Tasbih.. (1) Yang terpuji.. (1) ajal (1) al-Quran (1) al-kisah (1) amal (1) anak (1) anakku (1) animation (1) approval.. (1) asal (1) aurat.. (1) bau (1) berkumpul dua thn sekali (1) berniaga. (1) berniaga.. (1) bila malam (1) binatang.. (1) bumi (1) bunga. (1) busuk.. (1) cahaya malam.. (1) cake (1) culture shock.. (1) cup cake (1) dakwah.. (1) dish (1) do (1) doktor (1) dosa (1) dr buku..-- (1) dunia sementara.. (1) dunia yg fana.. (1) exam..anak-anak. (1) familyku (1) fitnah dunia (1) gua (1) hasil.. (1) hati (1) hati... (1) hidup.. (1) human (1) ilmu. (1) indahnya (1) indahnya ...
Professional bodies and Institutes CPD schemes are either structured as Input or Output based. Input based schemes list a precise number of CPD hours that individuals must achieve within a given time period. These schemes can also use different currencies such as points, merits, units or credits, where an individual must accumulate the number required. These currencies are usually based on time i.e. 1 CPD point = 1 hour of learning. Output based schemes are learner centred. They require individuals to set learning goals that align to professional competencies, or personal development objectives. These schemes also list different ways to achieve the learning goals e.g. training courses, seminars or e:learning, which enables an individual to complete their CPD through their preferred mode of learning. The majority of Input and Output based schemes actively encourage individuals to seek appropriate CPD activities independently. As a formal provider of CPD certified activities, SMI Group ...
OKUMURA Hirokazu , YOSHIDA Takashi , TAKAMATSU Hideyuki , KATOH Tsutomu , MURASHIMA Makoto , WATANABE Akiharu , YAMAUCHI Hiromasa , MATANO Sadaya , CHUHJO Tatsuya , TAKESHIMA Minoru , KAYA Hiroyasu , OHTAKE Shigeki , NAKAMURA Shinobu , MATSUDA Tamotsu International journal of hematology 65(3), 263-268, 1997-04 医中誌Web 参考文献22件 被引用文献1件 ...
Fludarabine (NSC 118218) is a DNA synthesis inhibitor, which also inhibits phosphorylation of STAT1. Fludarabine, a pro-drug, is converted metabolically by dephosphorylation to the antimetabolite, F-ara-A. - Mechanism of Action & Protocol.
The PNP therapeutic approach derives its advantage from the fact that most conventional anti-cancer drugs achieve anti-tumor specificity as a result of their ability to kill rapidly dividing cells. In fact, these drugs are only suitable for systemic administration because they are most toxic to cells that are actively dividing, which includes a sub-population of cells within the growing tumor mass. This leads to an acceptable level of damage in other, rapidly proliferating tissues (cellular compartments such as the bone marrow, intestinal tract, and hair follicles are most commonly affected). However, many refractory tumors are intractable precisely because they have a very low growth fraction; that is, a relatively small percentage of the tumor mass (4 to 40%, typically) is made up of cells that are actively dividing at any particular point in time. The E. coli PNP Therapeutic System has been shown to be effective against these refractory tumors precisely because fluoroadenine, the active ...
Buna fetelor :) de cateva saptamanii bune caut acest parfum la noi in tara si nu il gasesc :, pe langa faptul ca sunt o fana Katy Perry ,ador pisicileee :X :)) De cand am vazut acest parfum la tv caut pe toate siteurile dar nu il gasesc...:, daca mai stiti siteuri de parfumuri lasati-mi si mie va rog ...
rezeki (8) sakit (5) hadiah (4) solat (4) ilmu (3) kek (3) muhasabah (3) segmen.. (3) .... (2) Malaikat (2) Neraka (2) aktiviti (2) hati.. (2) lelaki (2) makan (2) sumber dr buku 150 wasiat Rasulullah utk wanita (2) sumber.. (2) ............ (1) AKU... (1) Adab... (1) Alien (1) Azab (1) Azan (1) Begini (1) Celaru........ (1) Iblis . (1) Jangan-jangan (1) Kerana Allah. (1) MAMA (1) PROTON PREVE (1) SEGMEN (1) Speech (1) Tasbih.. (1) Yang terpuji.. (1) ajal (1) al-Quran (1) al-kisah (1) amal (1) anak (1) anakku (1) animation (1) approval.. (1) asal (1) aurat.. (1) bau (1) berkumpul dua thn sekali (1) berniaga. (1) berniaga.. (1) bila malam (1) binatang.. (1) bumi (1) bunga. (1) busuk.. (1) cahaya malam.. (1) cake (1) culture shock.. (1) cup cake (1) dakwah.. (1) dish (1) do (1) doktor (1) dosa (1) dr buku..-- (1) dunia sementara.. (1) dunia yg fana.. (1) exam..anak-anak. (1) familyku (1) fitnah dunia (1) gua (1) hasil.. (1) hati (1) hati... (1) hidup.. (1) human (1) ilmu. (1) indahnya (1) indahnya ...
|b|Malta 0-2 France|/b||br /|Karim Ait Fana scored with his first touch on his Under-21 debut as France won in Malta to go top of Group 8 on goal difference.
Bjerregaard-Andersen, Kaare; Johannesen, Hedda; Abdel-Rahman, Noha Mansour Hassan; Heggelund, Julie Elisabeth; Hoås, Helene Mykland; Abraha, Fana; Bousquet, Paula; Høydahl, Lene Støkken; Burschowsky, Daniel; Rojas, Gertrudis; Oscarson, Stefan; Løset, Geir Åge; Krengel, Ute (Journal article / Tidsskriftartikkel / PublishedVersion; Peer reviewed, 2018) ...
Nelarabine (Arranon) chemotherapy side effects, how its given, how it works, precautions and self care tips for treatment of leukemia and lymphoma
Okabayashi, T; Mihara, S; Repke, D B.; and Moffatt, J G., "A radioimmunoassay for 1-beta-d-arabinofuranosylcytosine." (1977). Subject Strain Bibliography 1977. 1646 ...
Adenosine-5-triphosphate - adenozynotrifosforan (ATP), nukleotyd adenionowy (składa się z adenozyny i trzech grup fosforanowych. ATP jest wielofunkcyjnym nu...
Cell-volume-normalized concentration of (a, d, g) monosaccharide and (b, e, h) polysaccharide excreted by the cells as well as (c, f, i) cellular concentration
Mūsu skaisto konkurences ritmiskā vingrošana leotard Romantika meitenes, jūs justies pārliecināti, un palikt koncentrējas tikai uz savu sniegumu!
The immunofluorescent antinuclear antibody (ANA or FANA) test is positive in almost all individuals with systemic lupus (97 percent), and is the most sensitive diagnostic test currently available for confirming the diagnosis of systemic lupus when accompanied by typical clinical findings. When three or more typical clinical features are present, such as skin, joint, kidney, pleural, pericardial, hematological, or central nervous system findings as described above, a positive ANA test confirms the diagnosis of systemic lupus ...
Since three is the number of innovation, its square stands for universality. It is significant that, in so many folktales drawn from all over the world, the supernumerary, infinity, is expressed by such repetitions of the number nine as the 999,999 Fravashis who, the Ancient Iranians believed, watched over the semen of Zoroaster, from which all prophets were to spring. The Ouroboros, the serpent which bites its own tail and the image of the return of the manifold to the one and hence of primeval and of final Oneness, is related graphically to the way the number nine is denoted in many alphabets such as the Tibetan, Persian, Egyptian hieratic, Armenian and so on. The mystical meaning of nine relates it, too, to what the Sufis term haqq, the final stage of the Way, bliss leading to fana, the annihilation of the individual in the rediscovery of the whole, or... the loss of personality in universal love. Indian tradition defines more clearly the redemptive meaning of the symbol nine through nine ...
The goal of this clinical research study is to learn the effectiveness of intensive chemotherapy given in combination with nelarabine (followed by maintenance therapy) in the treatment of patients with T cel ALL and T cell lymphoblastic lymphoma. The safety of this treatment will also be studied.
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ePub Version. Are you a diabetes beginner? If youve just been diagnosed with type 2 diabetes or have the warning signs of prediabetes, youre not alone. This revised and updated edition brings the latest in diabetes care while building ...
ADP-ribosyl cyclases catalyze the transformation of nicotinamide adenine dinucleotide (NAD+) into the calcium-mobilizing nucleotide second messenger cyclic adenosine diphosphoribose (cADP-ribose) by adenine N1-cyclization onto the C-1 position of NAD+. The invertebrate Aplysia californica ADP-ribosyl cyclase is unusual among this family of enzymes by acting exclusively as a cyclase, whereas the other members, such as CD38 and CD157, also act as NAD+ glycohydrolases, following a partitioning kinetic mechanism. To explore the intramolecular cyclization reaction, the novel nicotinamide 2-fluoroadenine dinucleotide (2-fluoro-NAD+) was designed as a sterically very close analogue to the natural substrate NAD+, with only an electronic perturbation at the critical N1 position of the adenine base designed to impede the cyclization reaction. 2-Fluoro-NAD+ was synthesized in high yield via Lewis acid catalyzed activation of the phosphoromorpholidate derivative of 2-fluoroadenosine 5-monophosphate and coupling
Has anyone else received their ANA results using the OD Ratio? My last lab showed ANA 2.24 OD Ratio. I have searched the internet and have found nothing regarding this. Any help is appreciated ...
Nowoczesna diagnostyka laboratoryjna. Dwuetapowa diagnostyka boreliozy. Molekularna diagnostyka alergii. Testy na alergię z krwi. Przeciwciała onkoneuronalne. IIFT. ELISA. Blot.
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For the main performance Masekela was joined on stage by Francis Manneh Fuster, percussion; Abednigo "Fana" Zulu, bass; Randall Skippers, keyboards; Lee-Roy Sauls, drums; and Cameron John Ward, guitar. Masekela performed a mix of old favorites and music from his most recent album Phola.. Two numbers that are no surprise, but always a highlight of a Masekela concert, were "Grazin in the Grass" and "Stimela," the coal train song."Stimela" is a tribute to the migrant workers of South Africa and the trains that take them away from their families and towards the dangerous work miles underground by which they must make their living. This song never ceases to send goose bumps down your arms when performed live. The song opens with a spoken introduction, cowbell and train-whistle crescendo, Cameron John Ward on guitar provided a bluesy sound to the opening instrumentations. Masekelas beautiful flugelhorn solo continued where the guitarist left off. The song escalated until all members of the band were ...
History has a sly sense of humor. It caused an epiphany regarding infrastructure projects - roads, harbors, airports, etc. - to occur on a bridge over Bostons Charles River, hard by Harvard Yard, where rarely is heard a discouraging word about government.Last spring, Larry Summers, former treasury secretary and Harvard president, was mired in congealed traffic on the bridge, which is being repaired, and he suddenly understood American sclerosis. Repairing the bridge, which was
GlaxoSmithKlines Atriance® (nelarabine solution for infusion) has received a positive opinion from the European Medicines Agency (EMEA) for the treatment of T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in patients whose disease has not responded to, or has relapsed following, treatment with at least two chemotherapy regimens.. Atriance® is now being considered for final marketing approval by the European Commission for these difficult to treat forms of acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL): T-ALL and T-LBL.. According to Paolo Paoletti, SVP and Global Head of Oncologylinks Research and Development, GSK:. "Nelarabine may offer some patients the chance to go on to have potentially curative treatment, such as a stem cell transplant, so we are delighted that nelarabine has been granted a positive opinion from the EMEA.. We are immensely proud of our involvement in the development of this orphan drug for such a rare disease, ...
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Arabinoside definition, a glycoside of arabinose, especially any of those used in antiviral therapy as structural analogs of ribonucleosides. See more.
... (RCC) is a subgroup of myelodysplastic syndrome (MDS), having been added to the World Health Organization classification in 2008. Before then, RCC cases were classified as childhood aplastic anemia. RCC is the most common form of MDS in children and adolescents, accounting for approximately half of all MDS cases. Symptoms result from underproduction of red blood cells (weakness, pallor, failure to thrive, pica), white blood cells (recurrent or overwhelming infection), and/or platelets (bleeding). Bone marrow transplant is the only known curative treatment. The bone marrow of patients with RCC contains islands of erythroid precursors and spare granulocytes. In some scenarios, multiple bone marrow biopsy examinations may be recommended before a diagnosis can be established. Niemeyer, C. M.; Baumann, I (2011). "Classification of childhood aplastic anemia and myelodysplastic syndrome". Hematology. 2011: 84-9. doi:10.1182/asheducation-2011.1.84. PMID 22160017. ...
The Myelodysplastic syndrome is a group of diseases and conditions that affect how blood is made. These diseases were formerly known as preleukemia, mostly because sometimes they can lead to leukemia. Often, its name is shortened to MDS.. Myelodysplastic syndromes affect the bone marrow stem cells. The production of blood does not rely on good stem cells, but ones that have been modified genetically. This means that the production of red blood cells, sometimes of white blood cells and blood platelets changed. The production becomes inefficient, or goes wrong altogether. Most of the time, this manifests in anemia - not having enough blood. Depending on the severity of the condition, it can also cause hemorrhages and infections with fever.. Most of the people who have these conditions are 60 years or older, but younger people can get it too, especially if they went through a form of chemotherapy. Most of the suffers die from the disease, usually after six to thirty months. The only known cure is a ...
The myeloproliferative neoplasms (MPNs), previously myeloproliferative diseases (MPDs), are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek.[1] In the most recent World Health Organization classification of hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms".[2] This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.. The increased numbers of blood cells may not cause any symptoms, but a number of medical problems or symptoms may occur. The risk of thrombosis is increased in some types of MPN.. ...
... or Di Guglielmo syndrome is a rare form of acute myeloid leukemia (less than 5% of AML cases) where the myeloproliferation is of erythroblastic precursors. It is defined as type "M6" under the FAB classification. The most common symptoms of AEL are related to pancytopenia (a shortage of all types of blood cells), including fatigue, infections, and mucocutaneous bleeding. Almost half of people with AEL exhibit weight loss, fever and night sweats at the time of diagnosis. Almost all people with AEL are anemic, and 77% have a hemoglobin level under 10.0 g/dl. Signs of thrombocytopenia are found in about half of people with AEL. The causes of AEL are unknown. Prior to a 2008 reclassification by the World Health Organization, cases that evolved from myelodysplastic syndromes, myeloproliferative neoplasms, chemotherapy for other cancers or exposure to toxins were defined as secondary AEL. These cases are now likely to instead be classified as acute myeloid leukemia with ...
... is a group of diseases that affect myelopoiesis, causing a congenital form of neutropenia (severe congenital neutropenia [SCN]), usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections. Most cases of SCN respond to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count and decreases the severity and frequency of infections. Although this treatment has significantly improved survival, people with SCN are at risk of long-term complications such as hematopoietic clonal disorders (myelodysplastic syndrome, acute myeloid leukemia). Kostmann disease (SCN3), the initial subtype recognized, was clinically described in 1956. This type has an autosomal recessive inheritance pattern, whereas the most common subtype of Kostmann syndrome, SCN1, shows autosomal dominant inheritance. Infants with SCN have frequent infections: 50% have a significant infection within 1 month, most others ...
2.5 x 109/L, >0% immature myeloid cells, >10% bone marrow blasts causes a reduced overall survival. This data allows cases of CMML to be stratified into low, intermediate-1, intermediate-2 and high risk groups. These groups have median survival times of 24, 15, 8 and 5 months respectively. The Düsseldorf score stratifies cases using four categories, giving one point for each; bone marrow blasts ≥5%, LDH >200U/L, haemoglobin ≤9g/dL and a platelet count ≤100,000/uL. A score of 0 indicates a low risk group' 1-2 indicates an intermediate risk group and 3-4 indicates a high risk group. The cumulative 2 year survival of scores 0, 1-2 and 3-4 is 91%, 52% and 9%; and risk of AML transformation is 0%, 19% and 54% respectively. The treatment of CMML remains challenging due to the lack of clinical trials investigating the disease as its own clinical entity. It is often grouped with MDS in clinical trials, and for this reason the treatment of CMML is very similar to that of MDS. Most cases are dealt ...
... is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets. If only two parameters from the full blood count are low, the term bicytopenia can be used. The diagnostic approach is the same as for pancytopenia. Iatrogenic causes of pancytopenia include chemotherapy for malignancies if the drug or drugs used cause bone marrow suppression. Rarely, drugs (antibiotics, blood pressure medication, heart medication) can cause pancytopenia. The antibiotics Linezolid and Chloramphenicol can cause pancytopenia in some individuals. Rarely, pancytopenia may have other causes, such as mononucleosis, or other viral diseases. Increasingly, HIV is itself a cause for pancytopenia. Familial hemophagocytic syndrome Aplastic anemia Gaucher's disease metastatic carcinoma of bone Multiple Myeloma overwhelming infections Lymphoma myelofibrosis Dyskeratosis congenita Myelodysplastic syndrome Leukemia Leishmaniasis Severe Folate or vitamin B12 ...
... (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cells. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated. Risk factors include smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes; for which treatments and outcomes may vary. AML is typically initially treated with ...
Splicing factor 3B subunit 1 is a protein that in humans is encoded by the SF3B1 gene. This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms. SF3B1 has been shown to interact with: CDC5L, DDX42, PPP1R8, SF3B2, SF3B3, SF3B14, Mutations in this gene have been recurrently seen in cases of advanced chronic lymphocytic leukemia, myelodysplastic syndromes and breast cancer. SF3B1 mutations are found in ...
... is carcinogenic and may increase the risk of developing lymphomas, leukemia, skin cancer, transitional cell carcinoma of the bladder or other malignancies.[29] Myeloproliferative neoplasms, including acute leukemia, non-Hodgkin lymphoma and multiple myeloma, occurred in 5 of 119 rheumatoid arthritis patients within the first decade after receiving cyclophosphamide, compared with one case of chronic lymphocytic leukemia in 119 rheumatoid arthritis patients with no history.[30] Secondary acute myeloid leukemia (therapy-related AML, or "t-AML") is thought to occur either by cyclophosphamide-inducing mutations or selecting for a high-risk myeloid clone.[31]. This risk may be dependent on dose and other factors, including the condition, other agents or treatment modalities (including radiotherapy), treatment length and intensity. For some regimens, it is rare. For instance, CMF-therapy for breast cancer (where the cumulative dose is typically less than 20 grams of cyclophosphamide) ...
A myelomonocyte is a type of cell observed in chronic myelomonocytic leukemia. It bears a resemblance to both a myelocyte and monocyte. It is derived from CFU-GM. "Definition of myelomonocyte - NCI Dictionary of Cancer Terms". Retrieved 2009-01-06 ...
... also known as Pashayan-Prozansky Syndrome, and blepharo-naso-facial syndrome is a rare syndrome. Facial abnormalities characterise this syndrome as well as malformation of extremities. Specific characteristics would be a bulky, flattened nose, where the face has a mask like appearance and the ears are also malformed. A subset of Pashayan syndrome has also been described, known as "cerebrofacioarticular syndrome", "Van Maldergem syndrome'" or "Van Maldergem-Wetzburger-Verloes syndrome". Similar symptoms are noted in these cases as in Pashayan syndrome. "OMIM Entry - 110050 - BLEPHARONASOFACIAL MALFORMATION SYNDROME". omim.org. Retrieved 4 August 2017. Bissonnette, Bruno; Luginbuehl, Igor; Dalens, Bernard J.; Marciniak, Bruno (2006). Bruno Bissonnette, ed. Syndromes: rapid recognition and perioperative management. McGraw-Hill. ISBN 978-0-07-135455-4. [page needed] Stoll (1999). "A three generations family with blepharo-naso-facial malformations suggestive of Pashayan syndrome". ...
mrvook submitted an item that might affect a lot of you 'Working with a laptop on one's lap for extended periods of time has been found to cause heat damage and skin discoloration in a handful of cases, prompting researchers examining the phenomenon to recommend thermal protection for laptop users a...
2-deoxy-2-fluoro-beta-D-arabinonucleic acid: PS-2F-ANA-DNA chimeras are efficient gene silencing molecules, and suggest that they could have significant therapeutic potential; structure in first source
Arabinonucleotides. 7. + +. 42. Receptors, Granulocyte Colony-Stimulating Factor. 7. + +. 43. Fluoxymesterone. 7. + +. ...
0066](a) one or more 2-substituted arabinonucleotides (ANA); and [0067](b) (i) one or more 2-substituted ribonucleotides (RNA ... DNA-like nucleotides include for example 2-deoxyribonucleotides, 2-deoxy-2-substituted arabinonucleotides such as 2-deoxy-2 ... arabinonucleotides (ANA); and(b) (i) one or more 2-substituted ribonucleotides (RNA), (ii) one or more locked nucleic acid ... arabinonucleotides (ANA); and (b) (i) one or more 2-substituted ribonucleotides (RNA), (ii) one or more locked nucleic acid ...
This invention also relates to the use of oligonucleotides based on arabinonucleotides or modified arabinonucleotides, ... β-D-arabinonucleotides (i.e., ANA oligomers) and 2-deoxy-2-fluoro-β-D-arabinonucleotides (i.e., 2F-ANA oligomers), can ... arabinonucleotides or modified arabinonucleotides in combination with RNaseH as laboratory reagents for the sequence specific ... The sugar-modified oligomers are composed of β-D-arabinonucleotides (i.e., ANA oligomers) and 2-deoxy-2-fluoro-β-D- ...
Arabinonucleotides: 1*Arabinofuranosylcytosine Triphosphate: 72*1-(2-deoxy-2-fluoro-beta-arabinofuranosyl)-5-methylcytosine ...
As this next arabinonucleotides especially 2 , 3-dideoxynucleotides are used, this method is also called dideoxy method. ...
The ribonucleoprotein enzyme telomerase is a specialized type of cellular reverse transcriptase which synthesizes one strand of telomeric DNA, using as the template a sequence in the RNA moiety of telomerase. We analyzed the effects of various nucleoside analogs, known to be chain-terminating inhibitors of retroviral reverse transcriptases, on Tetrahymena thermophila telomerase activity in vitro. We also analyzed the effects of such analogs on telomere length and maintenance in vivo, and on vegetative growth and mating of Tetrahymena cells ...
The RNA moiety of the ribonucleoprotein enzyme telomerase from the ciliate Euplotes crassus was identified and its gene was sequenced. Functional analysis, in which oligonucleotides complementary to portions of the telomerase RNA were tested for their ability to prime telomerase in vitro, showed that the sequence 5 CAAAACCCCAAA 3 in this RNA is the template for synthesis of telomeric TTTTGGGG repeats by the Euplotes telomerase. The data provide a direct demonstration of a template function for a telomerase RNA and demarcate the outer boundaries of the telomeric template ...
MeSH D13.695.065 --- arabinonucleotides. * MeSH D13.695.065.200 --- arabinofuranosylcytosine triphosphate * MeSH D13.695. ...
Arabinonucleotides ⌊. Dideoxynucleotides ⌊. Dinucleoside Phosphates ⌊. Nucleoside Diphosphate Sugars ⌊. Cyclic Nucleotides ⌊. ...

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