Pic Of The Day
Posted by rob on April 23, 2005 under Uncategorized | 
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The shadow of French tennis ace Amelie Mauresmo is cast of the clay surface as she trains in Portschach on the eve on the Fed Cup match vs Austria.
Pic Of The Day
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A Christie’s auction house employee stands next to an acrylic on fiberglass sculpture entitled ‘Romanticism and Realistic Study #4′ by Chinese Artist Yue Minjun in Hong Kong.
Gateways to clinical trials.
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Bayes M, Rabasseda X, Prous JR
Methods Find Exp Clin Pharmacol. 2005 Mar ; 27(2): 145-59
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole. (c) 2005 Prous Science. All rights reserved.
After imatinib: new hopes for chronic myeloid leukaemia.
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Bradbury J
Drug Discov Today. 2005 Apr 15; 10(8): 536-7
Imatinib (STI571) induces DNA damage in BCR/ABL-expressing leukemic cells but not in normal lymphocytes.
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Czechowska A, Poplawski T, Drzewoski J, Blasiak J
Chem Biol Interact. 2005 Apr 15; 152(2-3): 139-50
Imatinib (STI571) is a 2-phenylaminopyrimidine derivative used mostly in the treatment of chronic myeloid leukaemia. It targets the BCR/ABL oncogenic tyrosine kinase, inhibiting its activity. Using the alkaline comet assay we showed that STI571 at concentrations ranging from 0.2 to 2muM induced DNA damage in human leukemic K562 and BV173 cells expressing the BCR/ABL oncogene, whereas it had no effect in normal human lymphocytes and leukemic CCRF-CEM cells without the expression of BCR/ABL. Imatinib did not induce DNA strand breaks in the direct interaction with DNA as examined by the circular plasmid relaxation assay. Because the extent of DNA damage observed in the neutral and pH 12.1 versions of the comet assay was much lesser than in the alkaline version, we concluded that the drug induced DNA alkali-labile sites rather than strand breaks. K562 cells were unable to repair H(2)O(2)-induced DNA damage during a 120-min incubation, if they had been preincubated with STI571, whereas normal lymphocytes did so within 60min. Pre-treatment of K562 cells with Vitamins A, C and E reduced the extent of DNA damage evoked by STI571. Similar results brought experiments with the nitrone spin traps POBN and PBN, suggesting that free radicals may be involved in the formation of DNA lesions induced by STI571 in K562 cells. These cells exposed to imatinib and treated with endonuclease III, formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA glycosylase II, the enzymes recognizing oxidized and alkylated bases, displayed greater extent of DNA damage than those not treated with these enzymes. Therefore, the mechanism of the anti-leukemic action of STI571 may involve not only the inhibition of BCR/ABL, but also DNA damage in the cells expressing this fusion protein. DNA damage induced by STI571 may follow from oxidative and alkylative base modifications.
[Proteome analysis of nuclear matrix proteins during arsenic trioxide induced apoptosis in K562 cells.]
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Wang ZH, Yu D, Zheng J, Chen Y
Beijing Da Xue Xue Bao. 2005 Apr 18; 37(2): 163-6
OBJECTIVE: To investigate arsenic trioxide (As(2)O(3))-target interactions at the level of nuclear matrix (NM) in chronic myelogenous leukemia cell line K562 by proteomics. METHODS: DNA fragmentation analysis was used for As(2)O(3) induced apoptosis of K562 cells. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis. RESULTS: While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots were found characteristic of As(2)O(3) treated cells. Onset of mass mange apoptosis, and the profiling of nuclear matrix proteins had been alternated and it was a more sensitive indicator than nucleosomal DNA fragmentation against As(2)O(3) treatment. CONCLUSION: As(2)O(3) induced apoptosis in K562 cells in a dose-time-dependent manner. As(2)O(3) might be clinically useful in treatment of chronic myelogenous leukemia and the changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for the treatment.
A basic classification and a comprehensive examination of pediatric myeloproliferative syndromes.
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Gassas A, Doyle JJ, Weitzman S, Freedman MH, Hitzler JK, Sharathkumar A, Dror Y
J Pediatr Hematol Oncol. 2005 Apr ; 27(4): 192-6
Myeloproliferative syndromes (MPSs) are clonal stem cell disorders resulting in excessive proliferation of one or more cell lineages. Since MPSs in children occur much less commonly than adults, one can argue that the biology and the categories of the various pediatric MPSs seem to be different from adults. Furthermore, confusion exists between pediatric MPS and other overlapping conditions, such as myelodysplastic syndrome. The authors’ objectives were to develop a classification system with a list of disorders relevant to children and to characterize pediatric cases of MPS that were devised according to this classification. Based on the predominant proliferating cell lineage, the authors established a classification system for childhood MPS. Primary MPS was classified into granulocytic proliferation-chronic myelogenous leukemia (CML); monocytic-juvenile myelomonocytic leukemia (JMML); megakaryocytic-essential thrombocythemia (ET), familial thrombocytosis, transient myeloproliferative disorder of Down syndrome (TMD); erythrocytic-polycythemia vera, familial erythrocytosis; fibroblastic-idiopathic myelofibrosis (IMF); eosinophilic-idiopathic hypereosinophilic syndrome (IHES); and mast cells-mastocytosis. Secondary MPS was classified as non-clonal proliferation (eg, infections, drugs, toxins, autoimmune, non-hematologic neoplasm, and trauma), and these were excluded from the study. Next, the classification system was applied to the patient population at the authors’ institution. One hundred two cases with primary MPS were identified between 1970 and 2001. Patients were evaluated for clinical manifestations, blood and bone marrow parameters, cytogenetics, and survival following different treatment modalities. Significant proportions of cases of childhood MPS (60%) were unique to the pediatric population and not seen in adults. The most common disorders were JMML (n = 31), TMD of Down syndrome (n = 30), and CML (n = 30); the other disorders were rare: four cases of ET, two of IMF, two of IHES, two of mastocytosis, and one primary erythrocytosis. In contrast to adults, MPS in children is more frequently treated with hematopoietic stem cell transplantation (HSCT), the only available curative option for most of these diseases. HSCT was particularly successful in the more recent cases due to more advanced techniques for HSCT. The authors found that all the cases could be easily classified. MPS in children is different from adult-type MPS in terms of biology, categories, classification, and prognosis.
A basic classification and a comprehensive examination of pediatric myeloproliferative syndromes.
BCR-ABL induces the expression of Skp2 through the PI3K pathway to promote p27Kip1 degradation and proliferation of chronic myelogenous leukemia cells.
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Andreu EJ, Lledó E, Poch E, Ivorra C, Albero MP, Martínez-Climent JA, Montiel-Duarte C, Rifón J, Pérez-Calvo J, Arbona C, Prósper F, Pérez-Roger I
Cancer Res. 2005 Apr 15; 65(8): 3264-72
Chronic myelogenous leukemia (CML) is characterized by the expression of the BCR-ABL tyrosine kinase, which results in increased cell proliferation and inhibition of apoptosis. In this study, we show in both BCR-ABL cells (Mo7e-p210 and BaF/3-p210) and primary CML CD34+ cells that STI571 inhibition of BCR-ABL tyrosine kinase activity results in a G(1) cell cycle arrest mediated by the PI3K pathway. This arrest is associated with a nuclear accumulation of p27(Kip1) and down-regulation of cyclins D and E. As a result, there is a reduction of the cyclin E/Cdk2 kinase activity and of the retinoblastoma protein phosphorylation. By quantitative reverse transcription-PCR we show that BCR-ABL/PI3K regulates the expression of p27(Kip1) at the level of transcription. We further show that BCR-ABL also regulates p27(Kip1) protein levels by increasing its degradation by the proteasome. This degradation depends on the ubiquitinylation of p27(Kip1) by Skp2-containing SFC complexes: silencing the expression of Skp2 with a small interfering RNA results in the accumulation of p27(Kip1). We also demonstrate that BCR-ABL cells show transcriptional up-regulation of Skp2. Finally, expression of a p27(Kip1) mutant unable of being recognized by Skp2 results in inhibition of proliferation of BCR-ABL cells, indicating that the degradation of p27(Kip1) contributes to the pathogenesis of CML. In conclusion, these results suggest that BCR-ABL regulates cell cycle in CML cells at least in part by inducing proteasome-mediated degradation of the cell cycle inhibitor p27(Kip1) and provide a rationale for the use of inhibitors of the proteasome in patients with BCR-ABL leukemias.
Pic Of The Day
Posted by rob on April 21, 2005 under Uncategorized | Be the First to Comment
Thousands of tulips are seen in front of Berlin’s landmark Brandenburg Gate after Dutch Flower Park Keukenhof offered the German capital 55,000 of these flowers.
Pic Of The Day
Posted by rob on April 20, 2005 under Uncategorized | Be the First to Comment
The 5th-century BC temple of Poseidon at Cap Sounion, south of Athens, is seen in the setting sun and a small thunderstorm.
Next-era targeted therapy overcoming Gleevec’s shortcomings
Posted by rob on April 19, 2005 under Uncategorized | Be the First to Comment
Contact: Warren R. Froelich
froelich@aacr.org
215-440-9300
American Association for Cancer Research
Anaheim, Calif. — Though Gleevec has shown “wonder drug” capabilities for treating chronic myelogenous leukemia and other cancers, experience in treating patients has revealed some shortcomings. In some cases, patients have undergone relapse after building a resistance to the drug. For others with advanced disease, the drug has failed to produce durable remissions.
However, a molecular understanding of resistance has rapidly led to a new generation of drugs that might prove more effective than Gleevec.
Two studies presented here at the 96th Annual Meeting of the American Association for Cancer Research report that a new compound, known as AMN107, may one day offer a more potent alternative for treating patients with acquired Gleevec resistance and others with advanced CML.
As originally conceived, Gleevec works in CML patients by selectively deactivating Bcr-Abl, the abnormal tyrosine kinase protein that triggers rapid growth of leukemic cells. Gleevec was hailed as the first approved drug to directly inhibit the activity of an enzyme known to cause uncontrolled cell growth, and it has been highly successful for many patients.
Scientists soon recognized, however, that some patients develop mutations in the Bcr-Abl protein that drastically reduce Gleevec’s effectiveness.
AMN107 Holds Promise for Treating Gleevec-Resistant Leukemia According to Oregon Scientists: Abstract 5282
To overcome resistance to Gleevec, scientists are designing new compounds that bind tighter to the intended target, the Bcr-Abl protein. One such candidate drug is AMN107, created by investigators at the Dana-Farber Cancer Institute and Novartis Pharmaceuticals in Basel, Switzerland.
In essence, AMN107 retains half the chemical makeup of Gleevec, while the other half was engineered to assure a tighter link to Bcr-Abl, thus increasing potency and potentially overcoming resistance due to mutations in Bcr-Abl.
As a test, scientists at the Oregon Health and Science University in Portland compared the potency of the new compound against Gleevec using a panel of cell lines expressing 16 different Gleevec-resistant, mutant versions of Bcr-Abl.
Their results, reported during the AACR Annual Meeting, showed that AMN107 was at least 20 times more potent than Gleevec against most of the resistant mutants.
“Our findings show that 15 of the 16 mutants would be predicted to be sensitive to AMN107, while one mutant remains insensitive that would require a different, as yet undiscovered, inhibitor,” said Thomas O’Hare, a research specialist in Gleevec pioneer Brian Druker’s laboratory at the Oregon Health and Science University Cancer Institute.
“These data indicate that AMN107 is a highly active Bcr-Abl inhibitor that may have clinical utility in patients with Gleevec-refractory CML.
“In this study, we also investigated the other leading clinical candidate for treating Gleevec-refractory CML, a Bristol-Myers Squibb compound called BMS-354825. The results were equally impressive.
“This is great news for patients. We believe that having several safe and effective drugs available is the key to controlling acquired drug resistance in CML.”
AMN107 Rescues Gleevec-Resistant Patients in Clinical Trial Conducted by Researchers at UT M. D. Anderson: Abstract 3971
AMN107 appears to effectively rescue patients with chronic myeloid leukemia (CML) who did not respond to targeted therapy with Gleevec, according to researchers from The University of Texas M. D. Anderson Cancer Center.
The researchers report that more than 70 percent of advanced CML patients in an international study have shown a response to the drug, AMN107, and that patients with the early form of the disease have responded at a rate of more than 90 percent.
“If you can take a pill and rescue people who failed the current standard of care, that is remarkable,” says the study leader, Francis Giles, M.D., a professor of medicine in the Department of Leukemia at M. D. Anderson Cancer Center. The study, which includes researchers and patients at the University of Frankfurt in Germany, is still ongoing.
The researchers note that the response rate in over 100 patients enrolled in the clinical trial to date continues to improve, as doses are rapidly increased. The first patients began treatment at 50 milligrams, but now all are taking 400 milligrams twice a day “and we have certainly not reached a dose-limiting toxicity,” Giles say. “The drug is very safe, and we are seeing a response that improves daily.”
Giles stresses that the “vast majority” of CML patients do very well on Gleevec, and that AMN107 was designed to treat the 10 percent of patients who do not respond, either because of a known mutation that Gleevec does not treat, or because the cancer has advanced to the point where other mutations in the cancer arise.
He adds, however, that M. D. Anderson Cancer Center will soon launch a series of studies testing use of AMN107 as the first therapy used by CML patients, whether they have the early chronic stage, advanced “accelerated” and terminal “blast” stages of the disease.
“We are not looking to replace use of Gleevec, but to see how AMN107 can fit into the treatment picture,” says Giles. “My guess is that patients will benefit from both agents.” The study is being funded by Novartis, which manufacturers both AMN107 and Gleevec. Giles presented first results of the therapy in a fewer number of patients last December at the annual meeting of the American Society of Hematology.
AMN107 is a refinement of Gleevec because it binds more tightly on to the Bcr-Abl enzyme that pushes bone marrow stem cells to continually grow. The new agent also latches on to Gleevec-resistant, mutated versions of Bcr-Abl that cause resistance in some Gleevec users, Giles says. But the study also is demonstrating that not all patients, especially those in more advanced stages, benefit from AMN107, probably because they have developed new mutations, he says.
The high level of responses seen to date are classified as hematologic, which is defined as a return to normal blood counts, but increasing numbers of “cytogenetic” responses are also being seen, which is the elimination of cells with the so-called Philadelphia chromosome, which produces the cancer-causing Bcr-Abl kinase. Researchers also are monitoring the number of “molecular major responses,” defined as a complete absence of all molecular abnormalities and a return to a normal status. “We now are beginning to see the number of cytogenetic responses climb, as well as molecular major responses,” Giles says.
He added that the potential success of AMN107 represents a “phenomenal rate” of drug development since Gleevec was introduced in 1999. “We have been able to take the knowledge of how Gleevec works – where exactly it binds to Bcr-Abl – and tweak it to be as much as 30 to 100 times more potent.”
It also represents a new era of medical treatment “in which the integration between preclinical researchers and clinical oncologists is seamless,” Giles says. “I don’t work in a lab. I spend all my time with patients. But clinicians are now using molecular endpoints every day and in every way to direct our therapy and to design protocols. It is incredibly exciting.”
###
Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR’s mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR’s Annual Meetings attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.
http://www.eurekalert.org/pub_releases/2005-04/aafc-ntt040805.php
CML found to wield ‘death factor’ that kills normal blood marrow cells
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ANAHEIM – Based on surprising results from animal experiments, researchers at The University of Texas M. D. Anderson Cancer Center have revamped common beliefs about how chronic myeloid leukemia (CML) functions within bone marrow – a discovery they hope may some day lead to additional therapeutic strategies.
In a study presented at the annual meeting of the American Association for Cancer Research (AACR), they found that CML does not “crowd out” normal blood cells in the bone marrow, as has long been thought, but actually kills those healthy cells through use of a unique cell “death factor.”
Pic Of The Day
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The statue of Pope Leone IV sits in the foreground on St Peter’s Square at the Vatican City.
Pic Of The Day
Posted by rob on April 18, 2005 under Uncategorized | Be the First to Comment
A man holds a candle during prayer services at the Oklahoma City National Memorial, April 17, 2005.
Pic Of The Day
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In this photo, released by the Florida Keys News Bureau, ‘Love the Earth’, is spelled out in various sand sculptures, Saturday, April 16, 2005, during an Earth Day-oriented event at the Cheeca Lodge in Islamorada, Fla.
The t(8;21) translocation converts AML1 into a constitutive transcriptional repressor.
Posted by rob on April 16, 2005 under Uncategorized | Be the First to Comment
Wildonger J, Mann RS
Development. 2005 Apr 13;
The human translocation (t8;21) is associated with approximately 12% of the cases of acute myelogenous leukemia. Two genes, AML1 and ETO, are fused together at the translocation breakpoint, resulting in the expression of a chimeric protein called AML1-ETO. AML1-ETO is thought to interfere with normal AML1 function, although the mechanism by which it does so is unclear. Here, we have used Drosophila genetics to investigate two models of AML1-ETO function. In the first model, AML1-ETO is a constitutive transcriptional repressor of AML1 target genes, regardless of whether they are normally activated or repressed by AML1. In the second model, AML1-ETO dominantly interferes with AML1 activity by, for example, competing for a common co-factor. To discriminate between these models, the effects of expressing AML1-ETO were characterized and compared with loss-of-function phenotypes of lozenge (lz), an AML1 homolog expressed during Drosophila eye development. We also present results of genetic interaction experiments with AML1 co-factors that are not consistent with AML1-ETO behaving as a dominant-negative factor. Instead, our data suggest that AML1-ETO acts as a constitutive transcriptional repressor.
The t(8;21) translocation converts AML1 into a constitutive transcriptional repressor.
Bilateral recurrent calcareous degeneration of the cornea.
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Messmer EM, Hoops JP, Kampik A
Cornea. 2005 May ; 24(4): 498-502
PURPOSE:: To report clinical, histologic, and electron microscopic findings in several consecutive keratoplasties with recurrent pancorneal calcification in a patient with chronic graft versus host disease and severe keratoconjunctivitis sicca following bone marrow transplantation for chronic myelogenous leukemia. METHODS:: Altogether 5 penetrating keratoplasties were performed in both eyes for descemetocele formation and corneal perforation as well as pancorneal calcification associated with severe visual loss. Histologic examination and electron microscopy were performed on the corneal buttons obtained. RESULTS:: Histology and electron microscopy confirmed pancorneal extracellular calcium deposition with increasing severity in each consecutive keratoplasty. Calcification was associated with necrosis and inflammation of the corneal stroma. Clinically unsuspected fungal keratitis was observed in 1 specimen. CONCLUSIONS:: Keratoconjunctivitis sicca, epithelial defects, corneal inflammation, and infection are most probably responsible for the recurrent pancorneal calcification seen in our patient. The role of cytokines in this complication is discussed.
[Regulatory role of HTm4 gene in hematopoietic cell cycle.]
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Li J, Xie C, Xie XY, Wang DM, Pei XT
Sheng Li Xue Bao. 2005 Apr 25; 57(2): 188-92
Cell cycle progression is tightly regulated in hematopoietic stem cells. The cycle state decides cells’ fates, which includes self-renewal, proliferation and differentiation. Proper cell cycle regulation is a pivotal element for the maintenance of hematopoiesis homeostasis. HTm4 is a newly identified specific cell cycle regulator of the hematopoietic cell. Through interacting with KAP-CDK2 complex, it arrests cells in G(0)/G(1) phase. K562 is a human chronic myelogenous leukemia cell; it could be induced to megakaryoblast by phorbol 12-myristate 13-acetate (PMA). Such differentiation must be associated with cell cycle change. To further clarify HTm4’s function in hematopoietic cell cycle regulation, K562 cells were treated with PMA. Cell cycle change was analysed using flow cytometric system. And during the induction process gene expression of HTm4 as well as CycleE and CDK2, which are responsible for G(1) to S transition, were analysed using semi-quantitative RT-PCR. The C-terminal domain of HTm4 protein has been shown to be important for HTm4’s binding with KAP-CDK2 complex. To determine its impact on HTm4’s function, HTm4 and C-terminal truncated HTm4 (HTm4-ct) were transfected into K562 cells using Tet-Off regulation expression system. Their influence on cell cycle was observed. The results showed that PMA induced both expansion and differentiation of K562 cells as measured by cell number count and NBT staining respectively. During PMA treatment, G(0)/G(1) cell proportion and HTm4 expression displayed coordinated change, which suggested that HTm4 might drive K562 cells out of cell cycle but was not involved in the quiescence maintenance. Additionally, transfection of HTm4 caused G(0)/G(1) arrest in K562 cells, while transfection of HTm4-ct did not. It is therefore suggested that the C-terminal domain is important for the function of HTm4 in cell cycle regulation.
Role of cytochrome p450 activity in the fate of anticancer agents and in drug resistance : focus on tamoxifen, Paclitaxel and imatinib metabolism.
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Rochat B
Clin Pharmacokinet. 2005; 44(4): 349-66
Although activity of cytochrome P450 isoenzymes (CYPs) plays a major role in the fate of anticancer agents in patients, there are relatively few clinical studies that evaluate drug metabolism with therapeutic outcome. Nevertheless, many clinical reports in various non-oncology fields have shown the dramatic importance of CYP activity in therapeutic efficacy, safety and interindividual variability of drug pharmacokinetics. Moreover, variability of drug metabolism in the liver as well as in cancer cells must also be considered as a potential factor mediating cancer resistance.This review underlines the role of drug metabolism mediated by CYPs in pharmacokinetic variability, drug resistance and safety. As examples, biotransformation pathways of tamoxifen, paclitaxel and imatinib are reviewed.This review emphasises the key role of therapeutic drug monitoring as a complementary tool of investigation to in vitro data. For instance, pharmacokinetic data of anticancer agents have not often been published within subpopulations of patients who show ultra-rapid, extensive or poor metabolism (e.g. due to CYP2D6 and CYP2C19 genotypes).Besides kinetic variability in the systemic circulation, induction of CYP activity may participate in creating drug resistance by speeding up the cancer agent degradation specifically in the target cells. For one cancer agent, various mechanisms of resistance are usually identified within different cell clones. This review also tries to emphasise that drug resistance mediated by CYP activity in cancer cells should be taken into consideration to a greater degree.The unequivocal identification of the metabolising enzymes involved in clinical conditions will eventually allow improvement and individualisation of anticancer agent therapy, i.e. drug dosage and selection. In addition, a more complete understanding of the metabolism of anticancer agents will assist in the prediction of drug-drug interactions, as anticancer agent combinations are becoming more prevalent.
Survival benefit with imatinib mesylate therapy in patients with accelerated-phase chronic myelogenous leukemia-Comparison with historic experience.
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Kantarjian H, Talpaz M, O’brien S, Giles F, Faderl S, Verstovsek S, Garcia-Manero G, Shan J, Rios MB, Champlin R, de Lima M, Cortes J
Cancer. 2005 Apr 13;
BACKGROUND: The effect of imatinib mesylate on survival in the accelerated phase of chronic myelogenous leukemia (CML) is unknown. The objectives of this study were to update the long-term experience with imatinib in patients who had accelerated-phase CML and to compare outcomes with historic experience. METHODS: The outcomes of 176 patients who received treatment with imatinib were reviewed and compared with the outcomes of 213 historic control patients with accelerated-phase CML who received treatment with interferon-alpha or with other modalities. RESULTS: With imatinib, the complete hematologic response rate was 82% versus a rate
Survival benefit with imatinib mesylate therapy in patients with accelerated-phase chronic myelogenous leukemia-Comparison with historic experience.