This technique is based on the use of a solvent or combination of solvents to extract organic pollutants at elevated pressure and temperature from environmental samples, increasing the kinetics of the extraction process. As a result, the extraction time and solvent consumption are significantly decreased. In the last years, ASE has been applied for the extraction of pesticides from different matrices: soils, fish, fruits, vegetables, etc. and it is used in the U. S. Envir onmental Protection Agency method 3545 for the analysis of organic compounds in solid matrices. However, it has never been reported on the possibility of extending this approach to acetanilide herbicide residue analysis in cereal crops. In trace analysis of organic compounds in complex matrices like foods, the cleanup procedure is as important as the extraction step.

Moreover, the presence of inter ferences could impair the LOD or even damage the chro matographic LY294002 system. Therefore, when the great extracting power of the solvents and the analytical metho dology are employed, the extract contains numerous inter fering substance, which makes the purification of this extract mandatory. Several approaches have been developed for obtaining accurate results in pesticide residues deter mination, such as liquid liquid partitioning and size exclusion chromatography. However, these methods are usually time consuming or expensive. Over the last decades, solid phase extraction has become an important clean up technique and is commonly used in the process of acetanilide herbicides determination.

Daniele and Aramendia have applied Florisil tube for eliminating matrix MEK Inhibitors interference in the determination of acetanilide herbicide in wheat and olive oil, respectively. Now, in parallel with the development of new technologies, more and more adsorbents have been used in SPE tube, which largely expanded the application of SPE in pretreatment. The main objective of this work was to develop a simple method based on ASE and SPE purification for the simul taneous quantification of eight acetanilide herbicides, propyzamide, napropamide, acetochlor, alachlor, metola chlor, butachlor, pretiachlor and di ufenican, in cereal crops. During the ASE process, four factors, including temperature, static time, extraction solvent and the number of cycle, were considered.

In order to minimize the presence NF-kB signaling pathway of interfering compounds in the GC system, extraction was followed in both cases by a clean up step with SPE, graphitic carbon black/primary secondary amine, GCB, Florisil and alumina N SPE tubes and compared. Finally, the ASE GCB/PSA was used for the extraction and clean up procedure while gas chromatography electron capture detector was employed for the determination of acetanilide herbicides in the puri fied extracts due to the high sensitivity and selectivity of ECD, different samples from China were determined using the developed method. 2. 1 Materials and reagents Analytical standards of propyzamide, di ufenican and 2,4,5,6 tetrachloro m xylene as internal stan dard were purchased from Dr. Ehrenstofer. Alachlor, acetochlor, pretiachlor, butachlor, metola chlor, propanil were all supplied by Agro Environment Protection and Monitor Ministry.

The stock standard solution was prepared in n hexane at 100 mg/mL. The calibration solutions were prepared by diluting the stock solution using blank samples. Concentrations were NF-kB signaling pathway 0. 01, 0. 02, 0. 05, 0. 1 and 0. 5 mg/mL for each acetanilide herbicide. All stock solutions and working standard solutions were stored at _18 and 1 41C, respectively. Ethyl acetate, n hexane and acetonitrile were of chro matographic grade obtained from Tedia Company. Toluene, acetone and sodium sulfate were of analytical grade supplied by China National Medicine. Na 2SO 4 was heated at 6501C for 4 h, and then was stored in a desiccator before use. Deionized water was used throughout.

The SPE tubes investigated for the clean up NSCLC procedure were GCB/PSA SPE tube, 6 mL, carbon GCB SPE tube, 12 mL, Florisil SPE tube 6 mL and alumina N SPE tube 3 mL. The column oven temperature program was used as follows: initial temperature 1201C, held for 1 min and increased to 1401C at a rate of 101C/min, and held for 5 min, and increased to 1721C at 51C/min, and held for 10 min, and then increased to 2601C at 101C/min, and eventually held for 5 min. The injector temperature was set to 2601C in splitless mode and ECD tempera ture was 3401C. The carrier helium with a ow rate of 1. 5 mL/min and the make up gas nitrogen with a ow rate of 60 mL/min were selected based on the instrument optimization results provided by the manufac turers identification of peaks and compared with the retention times of each compound with the standard solution. 2. 4 Sample preparation The dried samples of cereals were collected from different areas of China. These samples were ground into powder and sieved through a 40 mesh sieve, and then stored at room temperature in glass recipients in the dark before their analysis.

Hows that in the presence of EDTA, Fe2 still can generate radicals, but is not at the GW3965 same speed as unchelated when Fe2. In the presence of baicalein, a radical Sch To a mediation observed, which is a free-radical Expected longer. Line in Figure 8B shows that when baicalein traded as a chelator, no Besch Ending mediated radical was observed. This shows that the iron chelator key baicalein, inhibition of induced radical Fenton chemistry is s damage. Baicalein may be a strong antioxidant by scavenging free radicals Fe2 chelator. Our data show that baicalein found k Can iron Promoted Fenton chemistry beyond the St Stoichiometry to inhibit the complexes formed. A Much the same Ph Phenomenon was also observed for quercetin.
The anti-Fenton can be d a combination of chelation and free-radical singer-activity Danoprevir of baicalein and its complexes Fe th Furthermore k Nnte baicalein Fe complex in the catalytic residues sysytem a mechanism similar to the capture of Zhao et al. Fe for the tannin. Show high iron chelation by baicalein by our results, seems general consensus with the observations that flavonoids with iron binding motif can iron in a number of other conditions, such as buffer be chelated, pH and L Solvents. Of the three m Aligned positions metal binding baicalein, contains Lt side of the two hydroxyl groups at positions 6 and 7 of the A ring appears to st His strongest point both Fe2 and Fe3. A recent study by NMR and DFT showed a strong intramolecular hydrogen bond between the carbonyl group of 4 or 5 files baicalein and baicalin is formed by both.
This H-bonding can prevent the metal carbonyl bond OH positions 4 and 5. Au Addition, baicalin, the 7-position is blocked by an OH group of glucose. This may be explained Ren, by the apparent interaction between baicalin and not Zn2 in our NMR study. However, this is not another link among alternatives. For example, Dong et al. reported that baicalin solid 2:01 Fe2 complex of baicalin and FeCl2 reflux 6 h at 65 in a basic L Solution of ascorbic Acid and ethanol was isolated. However, as discussed in this paper, avoids the instability t and rapid degradation of baicalin in w Ssrigem medium us. From conducting a detailed study of the L Solution baicalin interactions of iron in a buffer KBP The proportion of sugar baicalin m May receive the metal bound by the carbonyl or hydroxyl groups, however, this type of connection is not observed in our study by NMR.
This observation has been completed in general accordance with this Gyurcsik and Nagy sugar binding metal St Strength is so low, neutral or acidic w Ssrige L Solution of sugar molecules that replace not easy, the water molecules in the first coordination sphere re Ion metal. Recent in vivo and in vitro studies have shown that supplementation baicalin and baicalein their glycoside have multiple biological effects. Moreover, the protective layers on organs such as heart, liver and brain of their antioxidant activity Th brought together. Therefore, a number of conditions, confinement Lich been brought atherosclerosis, diabetes, cancer, Parkinson’s disease, Alzheimer’s disease and an increased FITTINGS production of radical connection

Patients with Ph positive leukemias, including CML CP, CML AP,

CML BP, and Phpositive ALL, and imatinib resistance or

intolerance were included in the trial. The definitions of

imatinib resistance and intolerance were as previously

20 23 Imatinib resistance was classified as either

hematologic or cytogenetic. Imatinib intolerance was defined as

the presence of any toxicity that prevented egfr review

patients from receiving therapy. Patients with resistance or

intolerance to other second line TKIs, such as dasatinib or

nilotinib, were also included. Definitions of CML phases were as

previously reported.20 23 To be enrolled in the study, patients

had to be 18 years of age or older, have an Eastern Cooperative

Oncology Group score of 0 2, and have normal cardiac, hepatic,

and renal functions.
Females enrolled in the study could Vismodegib not be

pregnant or lactating. Patients were not allowed to have

received chemotherapy within 1 week or imatinib within 3 days

before the start of the trial. Exceptions included hydroxyurea

administration, as clinically indicated before and during the

first 21 days of treatment, and corticosteroids up to 48 hours

before the first study dose. Patients with comorbid states, such

as opportunistic and/or uncontrolled systemic infections,

impaired gastrointestinal function, psychiatric disorders,

and/or sustained toxicity from prior therapies, were excluded

from the study, as were those with a history of another primary

malignancy of clinical significance requiring intervention. The

study protocol was reviewed and approved by institutional review

boards at each study site.
Patients were required to provide

written informed consent. Study Design and Therapy The primary

objective of this phase 1 study was to determine the maximum

tolerated dose and dose limiting toxicity of INNO 406. Secondary

objectives included evaluation of response, safety, and

pharmacokinetic parameters. The starting dose of INNO 406 was 30

mg administered orally once daily, equaling 10% of the 30 mg/kg

dose level used in a previous 4 week rat toxicity study, at

which no deaths occurred.24 In the absence of a CTCAE v3.0 grade

2 or higher drugrelated toxicity, the dose of INNO 406 was

escalated by 100% in cohorts of at least 3 patients. If grade 2

drug related toxicity occurred, INNO 406 dose was increased by

50% until the MTD was reached.
The INNO 406 doses evaluated

were: 30, 60, 120, 240, and 480 mg QD, and then 120, 240, and

480 mg administered orally twice daily. Because all of the

patients in the 480 mg BID cohort experienced toxicities, a BID

cohort between the 240 mg and 480 mg BID cohorts was evaluated,

this intermediate cohort received 360 mg BID. Once the MTD was

determined, up to 20 patients in each of the 3 CML phases and up

to 20 patients with Ph positive ALL were treated at that dose.

Intrapatient dose escalation of INNO 406 was permitted in

patients who had a suboptimal response to INNO 406 therapy only

after the next dose level had been documented to be safe. A

suboptimal response was defined as a failure to achieve either a

hematologic response after 1 month or a major cytogenetic

response after 6 months of therapy. This is based on

observations that failure to achieve early hematologic response

or major cytogenetic response after 6 12 month

CS Acid at codon 600 in exon 15 in 90% of melanoma tumors h Frequently. RAF mutant V600EB concerning gt 10.7 times more active than the wild-type protein ITMN-191 and ben Requires no membrane translocation by RAS mediated enzymatic activity T sentieren to pr. The activation takes place after a Change the conformation of the protein structure, which acts as glutamine Ure phosphomimetic between Thr598 and Ser601 phosphorylation. RAF mutant proteins V600EB bypasses the requirement for RAS GTP, N load in the region and 14 3 3 binding to S729 to th their activity Suspend. Also, resistance to negative feedback regulation by Sprouty proteins And S579A mutation. Thus, BRAF is an important therapeutic target in melanoma. 2.4.
Several r V600EB the RAF in melanoma cells as an inducer of proliferation V600EB RAF leads to hyperactivation of the MAPK pathway, JNJ-26481585 which in turn l St division and survival pathways rdern the development of tumors to f. However, it is only average levels of activation of the MAPK pathway for the transformation and immortalization melanocyte M Usen one Erh Increase of colony formation in vitro, and the elevation of ERK1 / 2 activity-t Ben CONFIRMS. V600EB RAF also induces the formation of new blood vessels E by the F Promotion of secretion Vaskul Ren endothelial growth factors and cytokines macrophage first Recent studies have shown that the expression of RAF V600EB IL-8, a proinflammatory chemokine and autocrine factor to the tumor growth and angiogenesis f Rdern regulates.
V600EB RAF embroidered the development of metastasis in invasive behavior of the cell as well as the F Promotion of IL-8-mediated anchoring of the melanoma cells to Vaskul Re endothelium with extravasation and the development of lung metastases foreign St. V600EB RAF can also induce senescence by activation of the MAPK pathway in concentrations that inhibit cell growth in a variety of normal cells and early melanocyte Ren L Emissions. V600EB RAF mutant has been shown to the proliferation of melanocytes anf Accessible indicating it Posts melanogenesis and development Gt stimulate nevi. It is followed by the subsequent growth inhibition associated with senescence, the t by the arrest of proliferation due to increased FITTINGS activity P16INK4a and Gal. The induction of senescence is increased due to the FITTINGS inhibitors of cyclin-dependent-Dependent kinases, such as p21Cip1, p16INK4a and p27Kip1 and acts as a putative defense mechanism of normal cells to oncogene activation overcome.
A recent study has also shown that the induction of apoptosis and senescence by V600EB RAF loan St by insulin growth factor binding protein secretion in 7 transformed melanocytes can be arranged. V600EB RAF k Nnte Developing N Vi, but the resulting high, intense activation of the MAPK l St senescence through inhibition of tumor progression and more. Therefore additionally USEFUL genetic changes Ver Like loss of p16INK4a is PTEN or elevation in AKT3 activity T by overexpression of quiescent cells melanocyte required Ren V600EB RAF-induced senescence overcome to return the cell cycle. In a study expressed zebrafish protein V600EB RAF pr Presents N Vi and fish were only if the zebrafish p53-deficient melanocyte Ren L Emissions, the increased rapidly grow into invasive melanomas Similar to those Developing hte expression occur in human tumors. This result provided direct evidence linkin

Ovide informations on combination strategies. In fact, these data by performing sequential biopsies from patients treated with AZD1480, to determine its in vivo effect on JAK2, ERK, p38 and Aurora A, and AS-604850 to correlate the phosphorylation status of these proteins with the response to AZD1480 therapy. Finally, these data provide a mechanistic rationale for combination strategies aiming at blocking the AZD1480 induced activation of ERK and p38. Hepatocellular carcinoma, the major form of primary liver cancer, is one of the most deadly human cancers. The pathogenesis of HCC is frequently linked with continuous hepatocyte death, inflammatory cell infiltration and compensatory liver regeneration.
Understanding the molecular signaling pathways driving or mediating these processes during liver tumorigenesis is important for the identification of novel therapeutic targets for this dreadful Baicalein disease. The classical IKK dependent NF ?B signaling pathway has been shown to promote hepatocyte survival in both developing and adult livers. In addition, it also plays a crucial role in liver inflammatory responses by controlling the expression of an array of growth factors and cytokines. One of these cytokines is IL 6, which is best known for its role in the liver acute phase response. IL 6 exerts many of its functions via activation of STAT3, a transcription factor found to be important for HCC development. This review will focus on recent studies on the roles of NF ?B and STAT3 in liver cancer. Interactions between the two pathways and their potential as therapeutic targets will also be discussed.
Introduction Nearly 25 years ago, Dvorak recognized that the composition of the tumor stroma is very similar to that of granulation tissue of healing skin wounds. He therefore suggests that tumors are wounds that do not heal. Careful examination of the many phases of wound healing and tumorigenesis reveals even more extensive similarities between these two processes. Importantly, the human body mounts inflammatory responses in both situations aiming to clear dead cells and restore the tissue integrity. However, unlike the normal wound healing process that is tightly regulated both in extent and in duration, the inflammatory response during cancer development is not self limited. It is estimated that about 15% of human cancers are associated with chronic infections and inflammation.
The best examples of inflammation and infection associated cancers include colon cancer and inflammatory bowel diseases, gastric cancer and chronic Helicobacter pylori infection, and hepatocellular carcinoma following chronic hepatitis virus infection. Persistent infections and inflammation in these organs lead to continuous cell death and long lasting local infiltration of inflammatory cells. Even those cancers, whose development is not associated with pre existing infection or inflammation, are accompanied by massive inflammatory cell recruitment into the tumor, a phenomenon which led Virchow to his original suggestion that inflammation and cancer are linked. This inflammatory response is likely caused by necrotic cell death in the core of rapidly growing tumor mass due to lack of oxygen and nutrients. Continuous cell death and inflammatory cell i

Multiple functional magnetic resonance imaging studies implicate the insula as a region of heightened neuronal activity in this condition. Since glutamate is a major cortical excitatory neurotransmitter Baicalein that functions in pain neurotransmission, we hypothesized that increased levels of insular Glu would be present in FM patients and that the concentration of this molecule would be correlated with pain report. Methods 19 FM patients and 14 age and sex matched pain free controls underwent pressure pain testing and a proton magnetic resonance spectroscopy session wherein the right anterior and right posterior insula were examined at rest. Results FM patients had significantly higher levels of Glu : FM 8. 09, HC 6. 86, p0. 009 and combined glutamate and glutamine : FM 12.38, HC 10. 59, p0. 001 within the right posterior insula as compared to controls. No differences were detected in any of the other major metabolites within this region and no group differences were detected for any metabolite within the right anterior insula. Within the right posterior insula, higher levels of Glu and Glx were associated with lower pressure BMS-707035 pain thresholds across both groups. Conclusion Enhanced glutamatergic neurotransmission resulting from higher concentrations of Glu within the posterior insula may play a role in the pathophysiology of FM and other central pain augmentation syndromes. Keywords fibromyalgia, glutamate, insula, pain, proton magnetic resonance spectroscopy Corresponding Author: Richard E.Harris, PhD Chronic Pain and Fatigue Research Center 24 Frank Lloyd Wright Drive PO Box 385, Lobby M Ann Arbor, MI 48106 Phone: 998 6996, Fax: 998 6900 Published in final edited form as: Arthritis Rheum. 2009 October, 60: 3146 3152. doi:10. 1002/art. 24849. Although acute pain can serve a beneficial function to alert an organism of immediate or imminent tissue damage, chronic pain can often occur in the absence of tissue damage or inflammation. Functional chronic pain syndromes are a subset of pain disorders wherein patients paradoxically report frequent pain symptoms in the absence of anatomical injury or objective pathological findings. As such these disorders are particularly troublesome for patients and clinicians alike. Although new treatment options exist, significant disability and dysfunction are prevalent.
Fibromyalgia is the prototypical functional chronic pain condition that afflicts approximately 2 4% of individuals. Although the etiology of this disorder remains largely unknown, emerging data suggests that FM arises through augmentation of central pain processing pathways. This hypothesis is based largely upon findings of previous functional neuroimaging studies showing that FM patients display augmented neuronal responses to both innocuous and painful stimuli, corroborating the allodynia and hyperalgesia seen in this condition. A growing body of literature suggests that glutamate, an excitatory neurotransmitter, within the central nervous system may play a role in FM pathology. A study by Peres et al. found that cerebrospinal fluid levels of Glu were elevated in FM patients possibly having consequences for glutamatergic neurotransmission. In a separate line of inquiry, the concentration of glutamine

 Materials and Methods. Beauveriolides I and III were purified from a culture broth of Beauveria sp. FO 6979 as reported. Ls Acid and cholesterol were purchased from DuPont NEN and oleoyl CoA was Pharmacia Amersham Biosciences. DMEM and Hanks balanced Salzl Solution were purchased from Nissui Seiyaku, is GIT medium Nippon SB-715992 CK0238273 Seiyaku, and penicillin, streptomycin and glutamine solutions were from GIBCO L. Phosphatidylcholine, phosphatidylserine, dicetylphosphate, cholesterol, 3-hydroxy-5 pregnene 20 a, Lrot O and free fatty Acid BSA were all from Sigma Aldrich. CL 283,546, an ACAT inhibitor was ? one large generous donation from J. Hess, Pfizer Diagnostics. Plastic microtiter plates were purchased from Corning. Animals.
Female ICR Mice were obtained from Japan SLC, Hamamatsu, BMS-707035 Japan. Low-density lipoprotein knockout M Usen receptor and apolipoprotein E knockout Mice On C57BL 6 background were purchased from The Jackson Laboratory. Mouse peritoneal macrophages. Mouse peritoneal macrophages of female ICR Mice were prepared as described. Peritoneal cells were obtained from unstimulated Mice with Hanks balanced Salzl Solution s, then at 2106 cells per ml in medium harvested GIT. Aliquots were dispensed into 48-well microtiter plates or plastic tissue culture chamber and incubated in a humidified CO 2 at 37 for 2 hours, after which each plate was washed three times with 0.25 ml of Hank’s balanced Salzl Solution to remove cells s only. The medium was subsequently End immediately with 0.
25 ml DMEM serum lipoprotein deficient 8%, penicillin and streptomycin replaced. Determination of Lebensf Ability of the cells. Lebensf Ability of macrophages was measured in the presence of inhibitors with Alamar Blue. Liposomenpr ready. Multilamellar liposomes were prepared as described. Briefly, a lipid mixture of phosphatidylcholine, phosphatidylserine, cholesterol and dicetyl dried in chloroform and then End in 1 ml of 0.3 M glucose. Erg preparation liposomes Complements cholesterol, cholesterol was added to the lipid mixture. Determining the lipid synthesis 14C-labeled neutral by macrophages. Determination of cholesterol esters and triacylglycerol synthesis from Ls Macrophages in acid was performed according to the method described. Briefly, macrophages in a 48 well plate plastic were cultured, then l 2.
5 l sample and 10 l of liposomes containing 5 Ls Acid were added to each culture. After incubation for 14 h, the medium was removed and the cells in each well was washed three times with PBS. The cells were lysed by addition of 0.25 ml of PBS containing 0.1% SDS and cellular Ren lipids were extracted by the method of Bligh and Dyer. The organic L Solvents was reduced by vacuum, were all separated lipids on a TLC plate and analyzed using a Bio-Imaging Analyzer as described. Zellanf coloring Neutral lipids. Macrophages were cultured in a tissue culture room with liposomes and inhibitors as described above. After an incubation of 14 h, the cells were washed three times with PBS and. By immersion in 10% formalin Nuclei and intracellular Re neutral lipid droplets were Tr Matoxylin then with H And L red O found Rbt, and the

Tests resonance energy transfer does not inhibit interaction with EGFR or HER2 HER3 trastuzumab. The use of a different model fusion protein truncated fragments they SB-715992 Ispinesib galactosidase complementation SES enzyme was reported that inhibit HER2 trastuzumab EGFR interaction, but not HER3 HER2 interactions. The truncated artificial receptors used in the latter study, it is less reliable SSIG SDAI, particularly in the light of evidence to the contrary FRET. Mechanism of inhibition of HER2 cleavage trastuzumab binding, the proteolytic cleavage of trastuzumab and HER2 ADAM protease degradation proteins. This may be partly the invasive properties of transformed cells inhibit truncated HER2 HER2 conversion invasive morphological and Kinaseaktivit t t FITTINGS erh, erh Associated hte process efficiency and is obtained in patients with metastatic disease Ht Ht.
Therefore, E7080 in this aspect, the Pr Prevention function of HER2 trastuzumab, although the transformation function of the HER2 protein is not for cutting of cancers overexpressing HER2 and many do not have a significant reduction known the HER2 protein. Mechanism of action of trastuzumab other conclusions Although the therapeutic effect of trastuzumab in HER2-define their direct objective function, have made numerous reports describing the effects of trastuzumab on the downstream signaling pathways. The antiproliferative mAb 4D5 or associated with trastuzumab in cell culture models for the induction of p27 and G1 block. Trastuzumab influences the expression of angiogenic factors and tumor exhibits some anti-angiogenic properties in mouse models.
Trastuzumab inhibits Akt signaling in certain types of tumor cells, but not others, recd Ht plasma PTEN localization and activity t of t in the cells, and their anti-proliferative and anti-tumor was mitigated by Cht PTEN knockdown. R are compatible with functional PTEN tumors in clinical antitumor activity with reduced or absent PTEN trastuzumabcontaining relatively resistant to chemotherapy. Although these records being tze by the concomitant use of cytotoxic chemotherapy are complicated, they are the only currently available evidence linking intracellular’re signaling with antitumor activity T t of trastuzumab. A correlation between the resistance of trastuzumab and loss of PTEN is zwangsl that trastuzumab inhibits tumor h Frequently Moasser page 6 direct Oncogene.
Author manuscript 6th, April 2011 PMC. Immunological mechanism of action of trastuzumab targeting indicating an increasing number of signs that the result in vivo effects of humanized anti-HER2 monoclonal antitumor 4D5 and trastuzumab, at least partially, if not completely Constantly through mechanisms immunological targeting. mAb 4D5 active ADCC in vitro. This activity T was strongly T ww During the design process and trastuzumab, the humanized version is indeed very effective in vitro activation Erh hter ADCC. Genetic mouse models experimentally manipulate Fc receptor function, positive or negative, clearly demonstrate the immunological mechanisms of the h Te r antitumor efficacy of these agents. The anti-tumor activity of T t of MAb 4D5 and trastuzumab completely almost two Constantly eliminated permanently lost

d . 2009, 114 abstr 3078. 96. Santo L, Hideshima T, Nelson EA, et al. AT9283, a small molecule multi targeted kinase inhibitor induces antimyeloma activity via potent aurora kinase and STAT3 inhibition. Blood . 2009, TGX-221 114 abstr 3833. 97. Ravandi F, Foran J, Verstovsek S, et al. A phase I trial of AT9283, a multitargeted kinase inhibitor, in patients with refractory hematological malignancies. Blood . 2007, 110 abstr 904. 98. Foran JM, Ravandi F, O,Brien SM, et al. Phase I and pharmacodynamic trial of AT9283, an aurora kinase inhibitor, in patients with refractory leukemia. J Clin Oncol. 2008, 26 abstr 2518. 99. Plummer ER, Calvert H, Arkenau H, et al. A dose escalation and pharmacodynamic study of AT9283 in patients with refractory solid tumours. J Clin Oncol. 2008, 26 abstr 2519. 100.
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nd ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts. Brivanib alaninate BMS-582664 Haematologica. 2008, 93:662 9. 78. Schellens JH, Boss D, Witteveen PO, et al. Phase I and pharmacological study of the novel aurora kinase inhibitor AZD1152. J Clin Oncol. 2006, 24 abstr 3008. 79. Lowenberg B, Rousselot P, Martinelli G, et al. Phase I/II study to assess the safety and efficacy of the aurora B kinase inhibitor, AZD1152, in patients with advanced acute myeloid leukemia. Blood . 2009, 114 abstr 2080. 80. Guo J, Anderson MG, Tapang P, et al. Identification of genes that confer tumor cell resistance to the aurora B kinase inhibitor, AZD 1152. Pharmacogenomics J. 2009, 9:90 102. 81. Anderson K, Lai Z, McDonald OB, et al.
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