Obatoclax Mesylate in Samples From Young Patients With Acute Myeloid Leukemia
Summary
RATIONALE: Studying the effects of obatoclax mesylate in cell samples from patients with cancer in the laboratory may help doctors learn more about the effects of obatoclax mesylate on cancer cells. It may also help doctors identify biomarkers related to cancer.
PURPOSE: This research study is studying obatoclax mesylate in samples from young patients with acute myeloid leukemia.
Description
OBJECTIVES:
- Determine comprehensive gene and protein expression profiles of in vitro sensitivity and resistance to obatoclax mesylate in multiple-lineage leukemia (MLL)-rearranged cell lines and primary infant acute myeloid leukemia (AML) samples.
- Define optimum in vitro combinations of obatoclax mesylate targeting pro-survival BCL-2 family proteins with cytotoxic drugs in MLL-rearranged leukemia cell lines and primary infant AML samples.
- Identify synergistic combinations based on a pharmacodynamic modeling and simulation construct.
- Determine whether combinations of obatoclax mesylate targeting pro-survival BCL-2 family proteins with cytotoxic drugs improves survival in a xenograft model of MLL-rearranged infant AML.
OUTLINE: This is a multicenter study.
Obatoclax activity is assessed via the MTT assay. A priori features of AML blasts relating to the apoptosis and ATG cell death pathways and their execution are characterized using microarray analysis and Q-RT PCR. Gene and protein expression is described and quantified using Q-RT PCR and western blot analysis at specific time points after obatoclax exposure to identify pharmacodynamic biomarkers of activity and characterize the cell death mechanism in MLL+ AML. The MTT assay is performed using obatoclax-cytotoxic chemotherapy combinations to determine synergy focusing on common cytotoxic drugs employed in AML treatment regimens.
Obatoclax efficacy is tested in a therapeutic NOG xenograft model of primary MLL+ infant AML.
Study Design
N/A
Conditions
Leukemia
Intervention
gene expression analysis, microarray analysis, protein expression analysis, reverse transcriptase-polymerase chain reaction, western blotting, laboratory biomarker analysis, pharmacological study
Status
Not yet recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01150656
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-07-24T14:00:53-0400
Clinical Trials
Protein Expression in Tumor Tissue Samples From Patients With Cancer of the Oropharynx
RATIONALE: Studying the proteins expressed in samples of tumor tissue from patients with cancer may help doctors identify and learn more about biomarkers related to cancer. It may also hel...
Protein and RNA Expression Patterns in Predicting Response to Treatment in Patients With Lung Cancer
RATIONALE: Studying samples of tumor tissue and blood in the laboratory from patients with cancer may help doctors learn more about changes that occur in RNA and identify protein expressio...
RATIONALE: Studying the genes expressed in samples of tissue from patients with cancer may help doctors identify biomarkers related to cancer. PURPOSE: This laboratory study is using gene...
Studying Gene Expression and Location in Samples From Patients With Brain Tumors
RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to brain tumors. PURPOSE: This re...
RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cance...
PubMed Articles
Due to the high mortality of lung cancer, early diagnosis followed by early effective treatment is the key to prognosis improvement, which demands to identify the biological targets. Therefore, a mult...
Microarray analysis has been carried out in this pilot study to compare delineated gene expression profiles in the biopsies of skeletal muscle taken from patients with chronic critical limb ischaemia ...
Determination of miRNAs from Cancer Stem Cells Using a Low Density Array Platform.
A microarray approach has been extensively used for global gene expression profiles in many biological research fields such as understanding of pathological mechanism in malignancies and defining of m...
Colorectal cancer stages transcriptome analysis.
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differ...
Graves' disease (GD) is a common autoimmune thyroid disease characterized by positive thyroid stimulating hormone receptor antibody. To better understand its molecular pathogenesis, we adopted the wei...
Medical and Biotech [MESH] Definitions
Molecular Diagnostic Techniques
MOLECULAR BIOLOGY techniques used in the diagnosis of disease. Included are such techniques as IN SITU HYBRIDIZATION of chromosomes for CYTOGENETIC ANALYSIS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS of gene expression patterns in disease states; identification of pathogenic organisms by analysis of species specific DNA sequences; and detection of mutations with POLYMERASE CHAIN REACTION.
Microarray Analysis
The simultaneous analysis, on a microchip, of multiple samples or targets arranged in an array format.
Activation Analysis
A method of chemical analysis based on the detection of characteristic radionuclides following a nuclear bombardment. It is also known as radioactivity analysis. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Oligonucleotide Array Sequence Analysis
Hybridization of a nucleic acid sample to a very large set of oligonucleotide probes, which are attached to a solid support, to determine sequence or to detect variations in a gene sequence or expression or for gene mapping.
Network Meta-analysis
Meta-analysis of randomized trials in which estimates of comparative treatment effects are visualized and interpreted from a network of interventions that may or may not have been evaluated directly against each other. Common considerations in network meta-analysis include conceptual and statistical heterogeneity and incoherence.
