BibSonomyburst/user/kanefendt/DrugBibSonomy RSS feed for /user/kanefendt/Drug2012-02-16T05:34:59+01:00http://www.bibsonomy.org/bibtex/2143cacfb64ea0a7986d0ab5e71479dba/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Angiogenesis Animals Blood Endothelial Factors Growth Humans Inhibitors Laboratories Neoplasms Neovascularization Pathologic Research Vascular Vessels antagonists blood cells drug inhibitors pathology supply therapeutic therapy use <span class="authorEditorList"><a href="/author/Fukumura">D. Fukumura</a>, and <a href="/author/Jain">R. K. Jain</a> </span><em>Microvasc.Res.</em> <em>74(2-3):72-84</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Microvasc.Res.2-372-84Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization742007& Angiogenesis Animals Blood Endothelial Factors Growth Humans Inhibitors Laboratories Neoplasms Neovascularization Pathologic Research Vascular Vessels antagonists blood cells drug inhibitors pathology supply therapeutic therapy use A solid tumor forms an organ-like entity comprised of neoplastic cells and non-transformed host stromal cells embedded in an extracellular matrix. Similar to normal tissues, blood vessels nourish cells residing in tumors. However, unlike normal blood vessels, tumor vasculature has abnormal organization, structure, and function. Tumor vessels are leaky and blood flow is heterogeneous and often compromised. Vascular hyperpermeability and the lack of functional lymphatic vessels inside tumors cause elevation of interstitial fluid pressure in solid tumors. Each of these abnormalities forms a physiological barrier to the delivery of therapeutic agents to tumors. Furthermore, elevated tumor interstitial fluid pressure increases fluid flow from the tumor margin into the peri-tumor area and may facilitate peri-tumor lymphatic hyperplasia and metastasis. Abnormal microcirculation in tumors also leads to a hostile microenvironment characterized by hypoxia and acidosis, which hinder the effectivehttp://www.bibsonomy.org/bibtex/230fd986fa9ab1ed24fcf59cfe32f7d3c/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Administration Adult Aged Agents Antineoplastic Carcinoma Cell Disease Disease-Free Female Follow-Up Humans Indoles Kidney Laboratories Male Method Middle Neoplasm Neoplasms Oral Outcome Progression Pyrroles Rate Renal Research Retrospective Single-Blind Staging States Studies Survival Treatment Tyrosine United administration dosage drug epidemiology methods mortality pathology response therapy <span class="authorEditorList"><a href="/author/Motzer">R. J. Motzer</a>, <a href="/author/Michaelson">M. D. Michaelson</a>, <a href="/author/Rosenberg">J. Rosenberg</a>, <a href="/author/Bukowski">R. M. Bukowski</a>, <a href="/author/Curti">B. D. Curti</a>, <a href="/author/George">D. J. George</a>, <a href="/author/Hudes">G. R. Hudes</a>, <a href="/author/Redman">B. G. Redman</a>, <a href="/author/Margolin">K. A. Margolin</a>, and <a href="/author/Wilding">G. Wilding</a> </span><em>J.Urol.</em> <em>178(5):1883-1887</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010J.Urol.51883-1887Sunitinib efficacy against advanced renal cell carcinoma1782007& Administration Adult Aged Agents Antineoplastic Carcinoma Cell Disease Disease-Free Female Follow-Up Humans Indoles Kidney Laboratories Male Method Middle Neoplasm Neoplasms Oral Outcome Progression Pyrroles Rate Renal Research Retrospective Single-Blind Staging States Studies Survival Treatment Tyrosine United administration dosage drug epidemiology methods mortality pathology response therapy PURPOSE: We assessed the efficacy of the oral multitargeted tyrosine kinase inhibitor sunitinib in patients with metastatic clear cell renal cell carcinoma. MATERIALS AND METHODS: Patients with metastatic clear cell renal cell carcinoma were enrolled in this multicenter, phase II clinical trial. Major eligibility requirements were clear cell renal cell carcinoma histology, prior nephrectomy, measurable metastases and failed prior cytokine therapy as a result of disease progression. Sunitinib was given orally as second line therapy in 6-week cycles of 50 mg daily for 4 weeks, followed by 2 weeks off drug per treatment cycle. Response to sunitinib was rigorously assessed by an independent third party core imaging laboratory (central review). RESULTS: Of 106 patients enrolled in the study 105 were evaluated for response. As determined by independent third party assessment, the objective response rate was 33% (95% CI 24%-43%) with a median response duration of 14.0 months. Median time to phttp://www.bibsonomy.org/bibtex/20aa419dc3c83957f2e585cc89e1b0de1/kanefendtkanefendt2010-02-05T11:28:39+01:00Animals Binding Biopharmaceutics Chemistry Control Drug Humans Pharmaceutical Pharmacokinetics Preparations Quality Reference Reproducibility Results Solutions Stability Standards analysis deficiency metabolism methods of standards <span class="authorEditorList"><a href="/author/Nowatzke">W. Nowatzke</a>, and <a href="/author/Woolf">E. Woolf</a> </span><em>AAPS.J.</em> <em>9(2):E117-E122</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010AAPS.J.2E117-E122Best practices during bioanalytical method validation for the characterization of assay reagents and the evaluation of analyte stability in assay standards, quality controls, and study samples92007Animals Binding Biopharmaceutics Chemistry Control Drug Humans Pharmaceutical Pharmacokinetics Preparations Quality Reference Reproducibility Results Solutions Stability Standards analysis deficiency metabolism methods of standards Characterization of the stability of analytes in biological samples collected during clinical studies together with that of critical assay reagents, including analyte stock solutions, is recognized as an important component of bioanalytical assay validation. Deficiencies in these areas often come to light during regulatory inspections. Best practices, based on current regulatory guidance, for the assessment of these issues as they pertain to ligand binding and chromatographic assays are covered in this review. Additionally, consensus recommendations reached during the recent AAPS/FDA Workshop on bioanalytical assay validation are highlightedhttp://www.bibsonomy.org/bibtex/2506ad4630500172729537a9ce24caf9c/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Aged Agents Animals Antineoplastic Arteries Artery Blood Carcinoma Coronary Disease Failure Female Gastrointestinal Heart Humans Hypertension Indoles Kinase Kinases Male Mice Middle Multicenter Pressure Protein-Tyrosine Pyrroles Rats Research Retrospective Safety Stroke Stromal Studies Topic Tumors Tyrosine Volume adverse antagonists as blood chemically drug effects induced inhibitors methods therapeutic therapy toxicity use <span class="authorEditorList"><a href="/author/Chu">T. F. Chu</a>, <a href="/author/Rupnick">M. A. Rupnick</a>, <a href="/author/Kerkela">R. Kerkela</a>, <a href="/author/Dallabrida">S. M. Dallabrida</a>, <a href="/author/Zurakowski">D. Zurakowski</a>, <a href="/author/Nguyen">L. Nguyen</a>, <a href="/author/Woulfe">K. Woulfe</a>, <a href="/author/Pravda">E. Pravda</a>, <a href="/author/Cassiola">F. Cassiola</a>, <a href="/author/Desai">J. Desai</a>, <a href="/author/George">S. George</a>, <a href="/author/Morgan">J. A. Morgan</a>, <a href="/author/Harris">D. M. Harris</a>, <a href="/author/Ismail">N. S. Ismail</a>, <a href="/author/Chen">J. H. Chen</a>, <a href="/author/Schoen">F. J. Schoen</a>, <a href="/author/van den Abbeele">A. D. van den Abbeele</a>, <a href="/author/Demetri">G. D. Demetri</a>, <a href="/author/Force">T. Force</a>, and <a href="/author/Chen">M. H. Chen</a> </span><em>Lancet</em> <em>370(9604):2011-2019</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Lancet96042011-2019Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib3702007& Aged Agents Animals Antineoplastic Arteries Artery Blood Carcinoma Coronary Disease Failure Female Gastrointestinal Heart Humans Hypertension Indoles Kinase Kinases Male Mice Middle Multicenter Pressure Protein-Tyrosine Pyrroles Rats Research Retrospective Safety Stroke Stromal Studies Topic Tumors Tyrosine Volume adverse antagonists as blood chemically drug effects induced inhibitors methods therapeutic therapy toxicity use BACKGROUND: Sunitinib, a multitargeted tyrosine-kinase inhibitor, which is approved by both US and European Commission regulatory agencies for clinical use, extends survival of patients with metastatic renal-cell carcinoma and gastrointestinal stromal tumours, but concerns have arisen about its cardiac safety. We therefore assessed the cardiovascular risk associated with sunitinib in patients with metastatic gastrointestinal stromal tumours. METHODS: We retrospectively reviewed all cardiovascular events in 75 patients with imatinib-resistant, metastatic, gastrointestinal stromal tumours who had been enrolled in a phase I/II trial investigating the efficacy of sunitinib. The composite cardiovascular endpoint was cardiac death, myocardial infarction, and congestive heart failure. We also examined sunitinib's effects on left ventricular ejection fraction (LVEF) and blood pressure. We investigated potential mechanisms of sunitinib-associated cardiac effects by studies in isolated rat cardihttp://www.bibsonomy.org/bibtex/286090cbc034bdaa48e8da2ccda1fc004/kanefendtkanefendt2010-02-05T11:28:39+01:00Antibodies Biological Epidermal Expression Factor Gene Growth Human Humans Immunohistochemistry Markers Monoclonal Neoplasms Neoplastic Prognosis Receptor Regulation Tyrosine analysis drug effects etiology identify pathology physiology response therapeutic therapy use <span class="authorEditorList"><a href="/author/Tos">A. P. Dei Tos</a> </span><em>Int.J.Biol.Markers</em> <em>22(1 Suppl 4):S3-S9</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Int.J.Biol.Markers1 Suppl 4S3-S9The biology of epidermal growth factor receptor and its value as a prognostic/predictive factor222007Antibodies Biological Epidermal Expression Factor Gene Growth Human Humans Immunohistochemistry Markers Monoclonal Neoplasms Neoplastic Prognosis Receptor Regulation Tyrosine analysis drug effects etiology identify pathology physiology response therapeutic therapy use Receptor tyrosine kinases play a major role in human carcinogenesis. Overexpression of the epidermal growth factor receptor (EGFR) has been associated with poor clinical outcome in several types of cancer. In principle, as with HER2, the EGFR status of a tumor should predict the likelihood of response to EGFR-targeted therapy. However, clinical data have failed to demonstrate a relationship between EGFR expression and response to the EGFR-targeted compounds cetuximab, gefitinib and erlotinib. Recently, patients reported to be EGFR negative have been shown to respond to cetuximab. Possible explanations include methodological failures or most likely heterogeneity and complexity of the mechanisms of EGFR-mediated molecular carcinogenesis. Immunohistochemistry is the most widely used method for measuring EGFR expression; however, its value is limited by lack of methodological standardization. Other approaches to measuring EGFR such as amplification assays are currently being introduced buthttp://www.bibsonomy.org/bibtex/2dae68b0a9f4d1cf86ed190a3ce1823df/kanefendtkanefendt2010-02-05T11:28:39+01:00Angiogenesis Biological Cells Endothelial Growth Humans Indoles Inhibitors Laboratories Markers Neoplasms Neovascularization Pathologic Proteins Pyrroles Research Tumor blood cells diagnosis drug effects metabolism methods pathology pharmacology protein response supply therapeutic therapy use <span class="authorEditorList"><a href="/author/Deprimo">S. E. Deprimo</a>, and <a href="/author/Bello">C. Bello</a> </span><em>Ann.Oncol</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Ann.Oncolx11-x19Surrogate biomarkers in evaluating response to anti-angiogenic agents: focus on sunitinib18 Suppl 102007Angiogenesis Biological Cells Endothelial Growth Humans Indoles Inhibitors Laboratories Markers Neoplasms Neovascularization Pathologic Proteins Pyrroles Research Tumor blood cells diagnosis drug effects metabolism methods pathology pharmacology protein response supply therapeutic therapy use Conventional methods to assess the clinical activity of new agents that target specific biological pathways involved in tumour pathology may not provide correlation with clinically relevant outcomes such as patient survival or progression-free disease, and new and alternative methods should be explored. Biomarkers can assist in evaluation, and once validated, serve as a surrogate for clinical activity. Angiogenesis, a process well known to be involved in tumour growth and metastasis, is the target of several agents available today in the treatment of cancer. Laboratory assays used to detect proteins involved in angiogenesis and emerging imaging approaches have provided the bulk of the biomarker data to date in this area, and have already corroborated aspects of the biochemical basis of anti-angiogenic strategy. This symposium article will provide a brief overview of biomarker data in several different tumour types and discuss the effect that sunitinib and other anti-angiogenic agents hhttp://www.bibsonomy.org/bibtex/23b5cf396d03997444d803a9b55701e09/kanefendtkanefendt2010-02-05T11:28:39+01:00Angiogenesis Antigens Biological Cells Endothelial Humans Inhibitors Markers Microcirculation Neoplasms Neovascularization Pathologic Research Tumor blood cells diagnosis drug metabolism pathology pharmacology supply therapeutic therapy use <span class="authorEditorList"><a href="/author/Bertolini">F. Bertolini</a>, <a href="/author/Mancuso">P. Mancuso</a>, <a href="/author/Shaked">Y. Shaked</a>, and <a href="/author/Kerbel">R. S. Kerbel</a> </span><em>Drug Discov.Today</em> <em>12(19-20):806-812</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Drug Discov.Today19-20806-812Molecular and cellular biomarkers for angiogenesis in clinical oncology122007Angiogenesis Antigens Biological Cells Endothelial Humans Inhibitors Markers Microcirculation Neoplasms Neovascularization Pathologic Research Tumor blood cells diagnosis drug metabolism pathology pharmacology supply therapeutic therapy use Medical oncologists are increasingly using anti-angiogenic drugs, but identifying the best-suited drug and the optimal dosage and schedule for treatment of patients remain challenging issues. Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) are modulated in a variety of diseases including cancer, and are promising surrogate biomarkers in oncology. Molecular surrogate markers, on the other hand, are more scanty at the present time, because the identification of truly endothelial cell-restricted genes and/or antigens is complex. Here, we discuss the biological and technical facets of the search and validation of new biomarkers for angiogenesishttp://www.bibsonomy.org/bibtex/277bee5565bfa32594d200c2c9fedca93/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Antibodies Biological Carcinoma Dosage Drug Epidermal Factor Gene Growth Human Humans Immunohistochemistry Inhibitors Kinase Kinases Lung Markers Monoclonal Mutation Neoplasm Neoplasms Non-Small-Cell Phosphoproteins Predictive Protein Protein-Tyrosine Proteins Proto-Oncogene Quinazolines Receptor Resistance Tests Tyrosine Value analysis antagonists c-akt drug effects erbB-2 erbB-3 genetics identify inhibitors of protein response therapeutic therapy use <span class="authorEditorList"><a href="/author/Cappuzzo">F. Cappuzzo</a>, <a href="/author/Toschi">L. Toschi</a>, <a href="/author/Finocchiaro">G. Finocchiaro</a>, <a href="/author/Ligorio">C. Ligorio</a>, and <a href="/author/Santoro">A. Santoro</a> </span><em>Int.J.Biol.Markers</em> <em>22(1 Suppl 4):S10-S23</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Int.J.Biol.Markers1 Suppl 4S10-S23Surrogate predictive biomarkers for response to anti-EGFR agents: state of the art and challenges222007& Antibodies Biological Carcinoma Dosage Drug Epidermal Factor Gene Growth Human Humans Immunohistochemistry Inhibitors Kinase Kinases Lung Markers Monoclonal Mutation Neoplasm Neoplasms Non-Small-Cell Phosphoproteins Predictive Protein Protein-Tyrosine Proteins Proto-Oncogene Quinazolines Receptor Resistance Tests Tyrosine Value analysis antagonists c-akt drug effects erbB-2 erbB-3 genetics identify inhibitors of protein response therapeutic therapy use The epidermal growth factor receptor (EGFR) plays a key role in cancer development and progression in several human malignancies including non-small cell lung cancer (NSCLC). Several strategies aimed at inhibiting the EGFR have been investigated in the last years, including the use of small tyrosine kinase inhibitors (TKIs) directed against the intracellular domain of the receptor and monoclonal antibodies targeting its extracellular portion. Subgroups of patients who are more likely to respond to TKIs have been identified based on both clinical and biological features. Never-smoking history has emerged as the most relevant clinical characteristic predictive of response to TKIs in NSCLC, while presence of drug-sensitive EGFR mutations and EGFR gene gain represent critical biological variables associated with an improved outcome for patients exposed to these agents. Recent studies have highlighted the existence of biological factors involved in intrinsic and acquired resistance to TKIs,http://www.bibsonomy.org/bibtex/2beabba54bd2d560c3e6e69f70f2777bd/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Aged Agents Angiogenesis Antineoplastic Carcinoma Cardiomyopathies Cell Dysfunction Echocardiography Female Humans Illness Index Indoles Inhibitors Kidney Kinase Kinases Left Neoplasms Protein-Tyrosine Pyrroles Renal Severity Tyrosine Ventricular adverse antagonists chemically contraindications drug effects induced inhibitors of therapy <span class="authorEditorList"><a href="/author/Chorianopoulos">E. Chorianopoulos</a>, <a href="/author/Jager">D. Jager</a>, <a href="/author/Katus">H. A. Katus</a>, and <a href="/author/Frey">N. Frey</a> </span><em>Clin.Res.Cardiol.</em> <em>96(11):829-830</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Clin.Res.Cardiol.11829-830Severe cardiomyopathy in a patient with renal cell carcinoma after treatment with the novel tyrosine kinase inhibitor sunitinib962007& Aged Agents Angiogenesis Antineoplastic Carcinoma Cardiomyopathies Cell Dysfunction Echocardiography Female Humans Illness Index Indoles Inhibitors Kidney Kinase Kinases Left Neoplasms Protein-Tyrosine Pyrroles Renal Severity Tyrosine Ventricular adverse antagonists chemically contraindications drug effects induced inhibitors of therapy http://www.bibsonomy.org/bibtex/2bc2ca7992c0575aea1a335cb36445dc3/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Algorithms Analytical Binding Calibration Chemistry Dose-Response Drug Ligands Models Pharmaceutical Pharmacokinetics Preparations Protein RANGE Relationship Reproducibility Research Results Sensitivity Specificity Statistical analysis and data metabolism methods numerical of response statistics <span class="authorEditorList"><a href="/author/Findlay">J. W. Findlay</a>, and <a href="/author/Dillard">R. F. Dillard</a> </span><em>AAPS.J.</em> <em>9(2):E260-E267</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010AAPS.J.2E260-E267Appropriate calibration curve fitting in ligand binding assays92007& Algorithms Analytical Binding Calibration Chemistry Dose-Response Drug Ligands Models Pharmaceutical Pharmacokinetics Preparations Protein RANGE Relationship Reproducibility Research Results Sensitivity Specificity Statistical analysis and data metabolism methods numerical of response statistics Calibration curves for ligand binding assays are generally characterized by a nonlinear relationship between the mean response and the analyte concentration. Typically, the response exhibits a sigmoidal relationship with concentration. The currently accepted reference model for these calibration curves is the 4-parameter logistic (4-PL) model, which optimizes accuracy and precision over the maximum usable calibration range. Incorporation of weighting into the model requires additional effort but generally results in improved calibration curve performance. For calibration curves with some asymmetry, introduction of a fifth parameter (5-PL) may further improve the goodness of fit of the experimental data to the algorithm. Alternative models should be used with caution and with knowledge of the accuracy and precision performance of the model across the entire calibration range, but particularly at upper and lower analyte concentration areas, where the 4- and 5-PL algorithms generally outphttp://www.bibsonomy.org/bibtex/224ae23315709946658083795ddc2c4f5/kanefendtkanefendt2010-02-05T11:28:39+01:00Agents Angiogenesis Animals Antineoplastic Blood Endothelium Humans Inhibitors Neoplasms Neovascularization Pathologic Physiologic Platelets RANGE Research drug effects genetics pathology pharmacology physiology therapeutic therapy use <span class="authorEditorList"><a href="/author/Folkman">J. Folkman</a> </span><em>Nat.Rev.Drug Discov.</em> <em>6(4):273-286</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Nat.Rev.Drug Discov.4273-286Angiogenesis: an organizing principle for drug discovery?62007Agents Angiogenesis Animals Antineoplastic Blood Endothelium Humans Inhibitors Neoplasms Neovascularization Pathologic Physiologic Platelets RANGE Research drug effects genetics pathology pharmacology physiology therapeutic therapy use Angiogenesis--the process of new blood-vessel growth--has an essential role in development, reproduction and repair. However, pathological angiogenesis occurs not only in tumour formation, but also in a range of non-neoplastic diseases that could be classed together as 'angiogenesis-dependent diseases'. By viewing the process of angiogenesis as an 'organizing principle' in biology, intriguing insights into the molecular mechanisms of seemingly unrelated phenomena might be gained. This has important consequences for the clinical use of angiogenesis inhibitors and for drug discovery, not only for optimizing the treatment of cancer, but possibly also for developing therapeutic approaches for various diseases that are otherwise unrelated to each otherhttp://www.bibsonomy.org/bibtex/2602435fc1730c5168f565863b795701d/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Adaptor Antibodies Benzenesulfonates Biological Delivery Diseases Drug Enzyme Heart Human Humans Indoles Inhibitors Kinase Kinases Models Monoclonal Mutation Neoplasms Protein Protein-Tyrosine Proteins Proto-Oncogene Pyridines Pyrroles Quinazolines Research Signal Systems Transducing Tyrosine adverse antagonists c-abl cells chemically development drug effects growth induced inhibitors physiology protein response therapy toxicity <span class="authorEditorList"><a href="/author/Force">T. Force</a>, <a href="/author/Krause">D. S. Krause</a>, and <a href="/author/van Etten">R. A. van Etten</a> </span><em>Nat.Rev.Cancer</em> <em>7(5):332-344</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Nat.Rev.Cancer5332-344Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition72007& Adaptor Antibodies Benzenesulfonates Biological Delivery Diseases Drug Enzyme Heart Human Humans Indoles Inhibitors Kinase Kinases Models Monoclonal Mutation Neoplasms Protein Protein-Tyrosine Proteins Proto-Oncogene Pyridines Pyrroles Quinazolines Research Signal Systems Transducing Tyrosine adverse antagonists c-abl cells chemically development drug effects growth induced inhibitors physiology protein response therapy toxicity Cancer therapy has progressed remarkably in recent years. In no area has this been more apparent than in the development of "targeted therapies", particularly those using drugs that inhibit the activity of certain tyrosine kinases, activating mutations or amplifications of which are causal, or strongly contributory, to tumorigenesis. However, some of these therapies have been associated with toxicity to the heart. Here we summarize what is known about the cardiotoxicity of cancer drugs that target tyrosine kinases. We focus on basic mechanisms through which interruption of specific signalling pathways leads to cardiomyocyte dysfunction and/or death, and contrast this with therapeutic responses in cancer cellshttp://www.bibsonomy.org/bibtex/2ef0f98aaa58251a4ab8b2c0be419ef9e/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; A Administration Agents Angiogenesis Animals Antineoplastic Antitumor Assays Blood Cell Dose-Response Drug Endothelial Factor Female Growth Humans Hypoxia Indoles Inducing Line Mice Model Neoplasms Organ Outcome Placenta Pregnancy Proteins Pyrroles RANGE Receptor-2 Relationship Research Schedule Scid Specificity Treatment Tumor Tyrosine Vascular Xenograft administration blood dosage drug effects metabolism pathology pharmacology protein response therapy toxicity <span class="authorEditorList"><a href="/author/Ebos">J. M. Ebos</a>, <a href="/author/Lee">C. R. Lee</a>, <a href="/author/Christensen">J. G. Christensen</a>, <a href="/author/Mutsaers">A. J. Mutsaers</a>, and <a href="/author/Kerbel">R. S. Kerbel</a> </span><em>Proc.Natl.Acad.Sci.U.S.A</em> <em>104(43):17069-17074</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Proc.Natl.Acad.Sci.U.S.A4317069-17074Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy1042007& A Administration Agents Angiogenesis Animals Antineoplastic Antitumor Assays Blood Cell Dose-Response Drug Endothelial Factor Female Growth Humans Hypoxia Indoles Inducing Line Mice Model Neoplasms Organ Outcome Placenta Pregnancy Proteins Pyrroles RANGE Receptor-2 Relationship Research Schedule Scid Specificity Treatment Tumor Tyrosine Vascular Xenograft administration blood dosage drug effects metabolism pathology pharmacology protein response therapy toxicity Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as surrogate biomarkers for pharmacodynamic drug activity/exposure and patient benefit. A postulated mechanism for these changes is that they are tumor-dependent, resulting from drug-induced decreases in vascular function, increases in tumor hypoxia, and changes in hypoxia-regulated genes. However, here we report that an identical pattern of change is observed in normal nontumor-bearing mice treated with SU11248/sunitinib, a small-molecule inhibitor of VEGF and PDGF RTKs. The changes were dose-dependent, plateaued after 4 days of consecutive treatment, reversed after discontinuation of therapy, and correlated with antitumor activity. Altered proteihttp://www.bibsonomy.org/bibtex/253e1171b8a15a9f6bacf8979fae3a8bb/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; A Angiogenesis Animals Carcinoma Clinical Design Drug Endothelial Factor France Growth Humans Indoles Inhibitors Kinase Kinases Neoplasm Neoplasms Protein-Tyrosine Pyrroles Receptors Resistance Topic Trials Tyrosine Vascular adverse antagonists as biosynthesis blood drug effects enzymology inhibitors metabolism pharmacology response supply therapeutic therapy use <span class="authorEditorList"><a href="/author/Faivre">S. Faivre</a>, <a href="/author/Demetri">G. Demetri</a>, <a href="/author/Sargent">W. Sargent</a>, and <a href="/author/Raymond">E. Raymond</a> </span><em>Nat.Rev.Drug Discov.</em> <em>6(9):734-745</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Nat.Rev.Drug Discov.9734-745Molecular basis for sunitinib efficacy and future clinical development62007& A Angiogenesis Animals Carcinoma Clinical Design Drug Endothelial Factor France Growth Humans Indoles Inhibitors Kinase Kinases Neoplasm Neoplasms Protein-Tyrosine Pyrroles Receptors Resistance Topic Trials Tyrosine Vascular adverse antagonists as biosynthesis blood drug effects enzymology inhibitors metabolism pharmacology response supply therapeutic therapy use Sunitinib malate (SU11248/Sutent; Pfizer) is a multitargeted tyrosine kinase inhibitor that has potent anti-angiogenic and antitumour activities. Definitive efficacy has been demonstrated in advanced renal cell carcinoma and in gastrointestinal stromal tumours that are refractory or intolerant to imatinib (Gleevec; Novartis), which has provided the basis for the recent regulatory approvals for these indications. This article summarizes the discovery and development of sunitinib, and discusses key issues for the multitargeted approach in cancer treatment, such as markers of response and development of resistance, and their significance for the future development of sunitinib and other multikinase inhibitorshttp://www.bibsonomy.org/bibtex/216cb496208ca695d0d314b31867b1929/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Angiogenesis Capillaries Human Humans Inhibitors Neoplasms Neovascularization Pathologic Research blood control drug metabolism pathology pharmacology prevention supply therapeutic therapy use <span class="authorEditorList"><a href="/author/Harper">J. Harper</a>, and <a href="/author/Moses">M. A. Moses</a> </span><em>EXS</em> (<em>2006</em>)Fri Feb 05 11:28:39 CET 2010EXS96223-268Molecular regulation of tumor angiogenesis: mechanisms and therapeutic implications2006& Angiogenesis Capillaries Human Humans Inhibitors Neoplasms Neovascularization Pathologic Research blood control drug metabolism pathology pharmacology prevention supply therapeutic therapy use Angiogenesis, the process of new capillary formation from a pre-existing vessel plays an essential role in both embryonic and postnatal development, in the remodeling of various organ systems, and in several pathologies, particularly cancer. In the last 20 years of angiogenesis research, a variety of angiogenic regulators, both positive and negative, have been identified. The discovery of several anti-angiogenic factors has led to the development of novel cancer therapies based on targeting a tumor's vascular supply. A number of these new therapies are currently being tested in clinical trials in the U.S.A. and elsewhere. A major advance in the field of anti-angiogenic therapy occurred recently when the FDA approved Avastin (bevacizumab), the first solely anti-angiogenesis therapy approved for treatment of human cancer. While it has long been appreciated that tumor growth and progression are dependent on angiogenesis, it is only recently that progress has been made in elucidating the mhttp://www.bibsonomy.org/bibtex/2514f8edfda6889057d6f46b8895ede87/kanefendtkanefendt2010-02-05T11:28:39+01:00Approval Biological Calibration Chemistry Control Data Design Drug Interpretation Markers Models Quality Reproducibility Research Results Statistical Terminology Topic analysis as of <span class="authorEditorList"><a href="/author/Lee">J. W. Lee</a>, <a href="/author/Devanarayan">V. Devanarayan</a>, <a href="/author/Barrett">Y. C. Barrett</a>, <a href="/author/Weiner">R. Weiner</a>, <a href="/author/Allinson">J. Allinson</a>, <a href="/author/Fountain">S. Fountain</a>, <a href="/author/Keller">S. Keller</a>, <a href="/author/Weinryb">I. Weinryb</a>, <a href="/author/Green">M. Green</a>, <a href="/author/Duan">L. Duan</a>, <a href="/author/Rogers">J. A. Rogers</a>, <a href="/author/Millham">R. Millham</a>, <a href="/author/O&#039;Brien">P. J. O&#039;Brien</a>, <a href="/author/Sailstad">J. Sailstad</a>, <a href="/author/Khan">M. Khan</a>, <a href="/author/Ray">C. Ray</a>, and <a href="/author/Wagner">J. A. Wagner</a> </span><em>Pharm.Res.</em> <em>23(2):312-328</em> (<em>2006</em>)Fri Feb 05 11:28:39 CET 2010Pharm.Res.2312-328Fit-for-purpose method development and validation for successful biomarker measurement232006Approval Biological Calibration Chemistry Control Data Design Drug Interpretation Markers Models Quality Reproducibility Research Results Statistical Terminology Topic analysis as of Despite major advances in modern drug discovery and development, the number of new drug approvals has not kept pace with the increased cost of their development. Increasingly, innovative uses of biomarkers are employed in an attempt to speed new drugs to market. Still, widespread adoption of biomarkers is impeded by limited experience interpreting biomarker data and an unclear regulatory climate. Key differences preclude the direct application of existing validation paradigms for drug analysis to biomarker research. Following the AAPS 2003 Biomarker Workshop (J. W. Lee, R. S. Weiner, J. M. Sailstad, et al. Method validation and measurement of biomarkers in nonclinical and clinical samples in drug development. A conference report. Pharm Res 22:499-511, 2005), these and other critical issues were addressed. A practical, iterative, "fit-for-purpose" approach to biomarker method development and validation is proposed, keeping in mind the intended use of the data and the attendant regulator