A5012407611- Virus-based gene therapy research
- Medical Imaging Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- bioluminescence and chemiluminescence research
- Radiopharmaceutical Chemistry and Applications
- Advanced MRI Techniques and Applications
- CAR-T cell therapy research
- Neuroblastoma Research and Treatments
- Drug Transport and Resistance Mechanisms
- Herpesvirus Infections and Treatments
- Lanthanide and Transition Metal Complexes
- Mitochondrial Function and Pathology
- MRI in cancer diagnosis
- Viral Infectious Diseases and Gene Expression in Insects
- Nanoplatforms for cancer theranostics
- Neuroscience and Neuropharmacology Research
- Amino Acid Enzymes and Metabolism
- Adrenal and Paraganglionic Tumors
- Brain Metastases and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Traumatic Brain Injury and Neurovascular Disturbances
- Barrier Structure and Function Studies
Memorial Sloan Kettering Cancer Center
2014-2023
Kettering University
2010-2023
Neurology, Inc
2008-2023
Memorial Hospital
2007-2019
Skolkovo Institute of Science and Technology
2019
Vanderbilt University Medical Center
2019
Cornell University
2013-2016
National Institutes of Health
1983-2015
National Cancer Institute
1975-2015
Laboratory of Molecular Genetics
2014
A theoretical model of blood-brain exchange is developed and a procedure derived that can be used for graphing multiple-time tissue uptake data determining whether unidirectional transfer process was dominant during part or all the experimental period. If graph indicates unidirectionality uptake, then an influx constant (Ki) calculated. The general, assumes linear kinetics, consists blood-plasma compartment, reversible region with arbitrary number compartments, one more irreversible regions....
The method of graphical analysis for the evaluation sequential data (e.g., tissue and blood concentrations over time) in which test substance is irreversibly trapped system has been expanded. A simpler derivation original presented. General equations are derived that can be used to analyze uptake when blood-plasma concentration cannot easily measured. In addition, general situations trapping incomplete a combination these two conditions. These derivations independent actual configuration...
Adoptive transfer of large numbers tumor-reactive CD8+ cytotoxic T lymphocytes (CTLs) expanded and differentiated in vitro has shown promising clinical activity against cancer. However, such protocols are complicated by extensive ex vivo manipulations cells have largely focused on CTLs, with much less emphasis the role contribution CD4+ cells. Using a mouse model advanced melanoma, we found that small naive into lymphopenic recipients induces substantial cell expansion, differentiation,...
We used bioluminescence imaging to reveal patterns of metastasis formation by human breast cancer cells in immunodeficient mice. Individual from a population established culture the pleural effusion patient showed distinct organ-specific metastasis. Single-cell progenies derived this exhibited markedly different abilities metastasize bone, lung, or adrenal medulla, which suggests that metastases organs have requirements. Transcriptomic profiling revealed these single-cell similarly express...
TGF-β can signal by means of Smad transcription factors, which are quintessential tumor suppressors that inhibit cell proliferation, and Smad-independent mechanisms, have been implicated in progression. Although mutations disable this tumor-suppressive pathway certain cancers, breast cancer cells frequently evade the cytostatic action while retaining function. Through immunohistochemical analysis human bone metastases functional imaging a mouse xenograft model, we provide evidence for active...
The transport of alpha-aminoisobutyric acid (AIB), N-methyl-AIB (MeAIB), and diethylenetriaminepentaacetic (DTPA) from blood to brain was measured over different experimental periods in eight regions the rat brain. Unidirectional transfer rate constants were determined multiple-time/graphical single-time analysis data; values 0.0018, 0.00057, 0.000021 ml g-1 min-1, respectively, obtained for thalamus by graphical analysis. initial distribution volume AIB MeAIB tissue several-fold greater...
Positron emission tomography studies with the opiate antagonist [18F]cyclofoxy ([18F]CF) were performed in baboons. Bolus injection demonstrated initial uptake dependent on blood flow. The late showed highest binding caudate nuclei, amygdala, thalamus, and brainstem least accumulation cerebellum. By 60 min postinjection, regional brain radioactivity cleared at same rate as metabolite-corrected plasma, i.e., transient equilibrium was achieved. Compartmental modeling methods applied to...
Ventriculocisternal perfusions with five isotopically labeled drugs were performed in the rhesus monkey and resultant tissue diffusion concentration profiles caudate nucleus analyzed. The periventricular distribution space respect to perfusate was measured expressed as microliters per 100 mg wet weight: hydroxyurea = 56; methotrexate 27; thiotepa 28; 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) 64 cytosine arabinoside greater than 170. apparent constants determined for (2.0 1.2 X 10(-6)...
Surface-enhanced resonance Raman scattering gold nanostars allow detection of macro- and microscopic foci premalignant cancerous lesions in vivo.
This report identifies evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients a persistent vegetative state (PVS) with different behavioural features, we employed [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET), MRI and magnetoencephalographic (MEG) responses to sensory stimulation. Each patient's brain expressed unique metabolic pattern. In three the patients, co-registered PET/MRI correlate islands relatively preserved...
A noninvasive method for molecular imaging of the activity different signal transduction pathways and expression genes in vivo would be considerable value. It aid understanding role specific have various diseases, could elucidate temporal dynamics regulation at stages disease during therapeutic interventions. We developed assessed a monitoring transcriptional activation endogenous by positron-emission tomography (PET) imaging. The HSV1-tk/GFP (TKGFP) dual reporter gene was used to monitor...
Tumor hypoxia is a spatially and temporally heterogeneous phenomenon, which results from several tumor host tissue-specific processes. To study the dynamics spatial heterogeneity of hypoxia-inducible factor-1 (HIF-1)-specific transcriptional activity in tumors, we used repetitive noninvasive positron emission tomography (PET) imaging hypoxia-induced HIF-1 tumors living mice. This approach uses novel retroviral vector bearing HIF-1-inducible "sensor" reporter gene (HSV1-tk/GFP fusion)...
Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer lines (highly metastatic 4T1; nonmetastatic 67NR) to identify differences in glucose and glutamine response metabolic environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 have higher glycolytic tricarboxylic acid (TCA) cycle flux than 67NR readily switch between glycolysis oxidative phosphorylation (OXPHOS) different extracellular environments. OXPHOS...
Abstract Purpose: To investigate the relationship between lactate dehydrogenase A (LDH-A) expression, concentration, cell metabolism, and metastases in murine 4T1 breast tumors. Experimental Design: Inhibition of LDH-A expression protein levels were achieved a metastatic cancer line (4T1) using short hairpin RNA (shRNA) technology. The tumor concentration (measured by magnetic resonance spectroscopic imaging, MRSI) was assessed. Results: knockdown cells (KD9) showed significant reduction LDH...
<sup>123</sup>I-meta-iodobenzylguanidine (<sup>123</sup>I-MIBG) imaging is currently a mainstay in the evaluation of many neuroendocrine tumors, especially neuroblastoma. <sup>123</sup>I-MIBG has several limitations that can be overcome by use PET agent. <sup>18</sup>F-meta-fluorobenzylguanidine (<sup>18</sup>F-MFBG) analog MIBG may allow for single-day, high-resolution quantitative imaging. We conducted first-in-human study <sup>18</sup>F-MFBG to evaluate safety, feasibility,...