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Articles by Thomas Boulet in JoVE
JoVE Bioengineering
תהודה מגנטית elastography מתודולוגיה להערכת של רקמות מהונדסות צמיחה Construct
1Department of Biological Systems Engineering, University of Nebraska-Lincoln, 2Department of Engineering Mechanics, University of Nebraska-Lincoln
הליך מדגים את המתודולוגיה של elastography תהודה מגנטית לניטור התוצאה מהונדסים של השומן ואת בונה רקמות osteogenic מהונדסים באמצעות הערכה מקומית לא פולשנית של תכונות מכניות באמצעות תהודה מגנטית elastography מיקרוסקופיים (μMRE).
Other articles by Thomas Boulet on PubMed
Polymorphism Discovery in 62 DNA Repair Genes and Haplotype Associations with Risks for Lung and Head and Neck Cancers
DNA repair is essential for the maintenance of genetic stability. We undertook sequencing to determine common genetic variants in 70 genes involved in three major repair pathways (base excision repair, nucleotide excision repair and mismatch repair) and in DNA synthesis, and investigated their relationship to lung and head and neck (H-N) cancers. Of the 70 genes examined, 62 were successfully screened (exon coverage >20%) by sequencing exons, parts of introns and flanking regions in 32 DNA samples from healthy Caucasian individuals. The strategy used allowed the detection of almost all variants with a minor allele frequency >or=5% in the regions sequenced. During single-nucleotide polymorphism (SNP) discovery, 772 sequences were detected in introns or regions flanking the gene and 313 were found in exons (leading to 113 non-synonymous variations) during single-nucleotide polymorphism (SNP) discovery. In total, 695 variants were successfully genotyped in 151 lung cancer cases, 251 H-N cancer cases and 172 hospital controls. Score statistics were used to test differences in haplotype frequencies between cases and controls in an unconditional logistic regression model. To account for multiple testing, we associated to each P-value an estimated proportion of false discoveries. Haplotype analysis revealed potential associations (P < 0.05) between lung cancer and eight genes (MSH3, MLH3, POLK, LIG1, ERCC5, PMS1, POLG2 and RPA3) and between H-N cancer and four genes (PMS1, POLG2, POLR2B and RPA1) with false discovery proportions of 25 and 55%, respectively. The DNA synthesis pathway showed a tendency for more differential SNP allele frequencies between H-N cases and controls than expected by chance (P = 0.05). These results hint to a few potential candidates for further investigation in larger studies.
[Gene Expression Profiling in Cancer Research]
Gene expression profiling is increasingly used in cancer research. For each patient, the expression of thousands of genes in the tumour can be measured simultaneously on a microarray. Microarray studies aim at classifying patients based on two types of classification schemes: unsupervised classification, which uses clustering in order to identify homogeneous subtypes of a disease on the basis of gene expression, or supervised classification, which principally aims at the identification of genes or set of genes differentially expressed between tumours with different characteristics (molecular signature), for instance between a group of patients with bad and good prognosis. The data consists of a small number of patients and a large number of variables, raising serious methodological problems. We will use published results on breast cancer in order both to study the power of the experiments and to illustrate the problems in interpretation and validity of their results. We recommend rigorous evaluation of this new technology.
Variants in DNA Double-strand Break Repair and DNA Damage-response Genes and Susceptibility to Lung and Head and Neck Cancers
Cigarette smoking is the major risk factor for lung cancer, and together with alcohol for head and neck (H--N) cancer. These genotoxics produced DNA damage and particularly double-strand breaks (DSB) that are removed by various repair pathways. To understand the initiation of these cancers, we performed a genotype analysis to correlate some variants in specific genes in a case-control study of lung and H-N cancers. In a discovery phase, we sequenced DNA samples of 32 healthy Caucasians to describe genetic variants in 30 genes involved in the repair of DSB and in DNA damage response. 625 variants were detected on 29 out of the 30 genes successfully screened by sequencing exons, parts of introns and flanking regions. These included 470 non-exonic variants, from which 33 insertions/deletions, and 155 exonic alterations, corresponding to 59 non synonymous polymorphisms. 223 of these variants were not previously described. In total, 379 variants were successfully genotyped in a case-control study restricted to smokers including 151 lung cases, 251 H-N cases, and 172 controls. To account for multiple testing, we associated to each p-value a proportion of false positives (q-value). Haplotype-analysis suggested potential associations (p < 0.05) between lung cancer and 2 genes (RECQL4 and RAD52), which came with q-value of 8%, and between H-N cancer and 1 gene (DNA-PK) but with q-value of 56%. The 3 genes are key players for regulating the efficiency of DSB repair. Large-scale studies are needed to show if any of these 3 variants are truly associated with an increased risk of cancer.
Genetic Polymorphisms in 85 DNA Repair Genes and Bladder Cancer Risk
Several defense mechanisms have been developed and maintained during the evolution to protect human cells against damage produced from exogenous or endogenous sources. We examined the associations between bladder cancer and a panel of 652 polymorphisms from 85 genes involved in maintenance of genetic stability [base excision repair, nucleotide excision repair, double-strand break repair (DSBR) and mismatch repair, as well as DNA synthesis and cell cycle regulation pathways] in 201 incident bladder cancer cases and 326 hospital controls. Score statistics were used to test differences in haplotype frequencies between cases and controls in an unconditional logistic regression model. To account for multiple testing, we associated to each P-value the expected proportion of false discoveries (q-value). Haplotype analysis revealed significant associations (P < 0.01) between bladder cancer and two genes (POLB and FANCA) with an associated q-value of 24%. A permutation test was also used to determine whether, in each pathway analyzed, there are more variants whose allelic frequencies are different between cases and controls as compared with what would be expected by chance. Differences were found for cell cycle regulation (P = 0.02) and to a lesser extent for DSBR (P = 0.05) pathways. These results hint to a few potential candidate genes; however, our study was limited by the small sample size and therefore low statistical power to detect associations. It is anticipated that genome-wide association studies will open new perspectives for interpretation of the results of extensive candidate gene studies such as ours.
Interleukin-2 Before Antiretroviral Therapy in Patients with HIV Infection: a Randomized Trial (ANRS 119)
Interleukin (IL)-2 increases CD4 T cell counts when combined with antiretroviral therapy (ART). Whether IL-2 alone can increase CD4 cell counts is unknown.
CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence
Chemokine receptor 4 (CXCR4) has been demonstrated to have a critical role in the early metastatic process. The aim of this study was to evaluate the prognostic value of CXCR4 expression in primary breast tumors and describe correlations with the occurrence of metastasis in organs expressing the CXCR4 ligand stromal cell-derived factor 1 (i.e., liver, lung, brain, and bone).
Impact on Health-related Quality of Life of a Switch from Enfuvirtide to Raltegravir Among Multidrug-resistant HIV-1-infected Patients: a Randomized Open-label Trial (EASIER-ANRS 138)
among multidrug-resistant HIV-1-infected patients, enfuvirtide has demonstrated sustained efficacy, but long-term use is inconvenient due to twice-daily subcutaneous injections which often induce injection-site reactions. We investigated whether a switch from enfuvirtide to raltegravir, an orally available HIV-integrase inhibitor, may improve health-related quality of life (HRQoL).
Emerging Integrase Inhibitor Resistance Mutations in Raltegravir-treated HIV-1-infected Patients with Low-level Viremia
The emergence of integrase strand-transfer inhibitor (INSTI) resistance-associated mutations was examined in patients with low-level viremia after switching from enfuvirtide to raltegravir in the ANRS 138-Easier trial.
Microscopic Magnetic Resonance Elastography of Traumatic Brain Injury Model
Traumatic brain injury (TBI) is a major cause of death and disability for which there is no cure. One of the issues inhibiting clinical trial success is the lack of targeting specific patient populations due to inconsistencies between clinical diagnostic tools and underlying pathophysiology. The development of reliable, noninvasive markers of TBI severity and injury mechanisms may better identify these populations, thereby improving clinical trial design. Magnetic resonance elastography (MRE), by assessing tissue mechanical properties, can potentially provide such marker. MRE synchronizes mechanical excitations with a phase contrast imaging pulse sequence to noninvasively register shear wave propagation, from which local values of tissue viscoelastic properties can be deduced. The working hypothesis of this study is that TBI involves a compression of brain tissue large enough to bring the material out of its elastic range, sufficiently altering mechanical properties to generate contrast on MRE measurements. To test this hypothesis, we combined microscopic MRE with brain tissue collected from adult male rats subjected to a controlled cortical impact injury. Measurements were made in different regions of interest (somatosensory cortex, hippocampus, and thalamus), and at different time points following the injury (immediate, 24 h, 7 days, 28 days). Values of stiffness in the somatosensory cortex were found to be 23-32% lower in the injured hemisphere than in the healthy one, when no significant difference was observed in the case of sham brains. A preliminary in vivo experiment is also presented, as well as alternatives to improve the faithfulness of stiffness recovery.
