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In JoVE (1)

Other Publications (18)

Articles by Edwin Chang in JoVE

 JoVE Clinical and Translational Medicine

Cerenkov Luminescence Imaging (CLI) for Cancer Therapy Monitoring

1Department of Radiology and Bio-X Program Canary Cancer at Stanford for Cancer Early Detection, Stanford University

JoVE 4341

Use of Cerenkov Luminescence Imaging (CLI) for monitoring preclinical cancer treatment is described here. This method takes advantage of Cerenkov Radiation (CR) and optical imaging (OI) to visualize radiolabeled probes and thus provides an alternative to PET in preclinical therapeutic monitoring and drug screening.

Other articles by Edwin Chang on PubMed

Aging and Survival of Cutaneous Microvasculature

The growth and turnover of blood vessels in the skin is fundamental in normal development, wound repair, hair follicle cycling, tumor cell metastasis, and in many different states of cutaneous pathology. Whereas many investigations are focused on mechanisms of angiogenesis in the skin, the influence of cellular aging and replicative senescence (i.e., the inability, after a critical number of population doublings, to replicate) on microvascular remodeling events has received relatively less attention. In this article, we review the clinical and pathologic relationships associated with cutaneous vascular aging and update current knowledge of endothelial cell survival characteristics. A hypothesis is presented in which endothelial cell aging and survival are linked to molecular mechanisms controlling cell proliferation, quiescence, apoptosis, and cellular senescence. We review recent results demonstrating how activation of telomerase in human dermal microvascular endothelial cells affects their durability both in vitro and in vivo and conclude by linking these studies with current concepts involving endothelial cell precursors, control of postnatal somatic cell telomerase activity, and murine model systems.

Endothelial Progenitor Cells Participate in Nicotine-mediated Angiogenesis

We aimed to determine the role of endothelial progenitor cells (EPCs) in cholinergic angiogenesis.

A Central Role for Nicotinic Cholinergic Regulation of Growth Factor-induced Endothelial Cell Migration

An endothelial nicotinic acetylcholine receptor (nAChR) participates in atherogenesis and tumorigenesis by promoting neovascularization. To date, the mechanisms of nAChR-mediated angiogenesis and their relationship to angiogenic factors, eg, VEGF and bFGF, are unknown.

"Priming" Endothelial Progenitor Cells: a New Strategy to Improve Cell Based Therapeutics

Diffusible Amyloid Oligomers Trigger Systemic Amyloidosis in Mice

AA (amyloid protein A) amyloidosis in mice is markedly accelerated when the animals are given, in addition to an inflammatory stimulus, an intravenous injection of protein extracted from AA-laden mouse tissue. Previous findings affirm that AA fibrils can enhance the in vivo amyloidogenic process by a nucleation seeding mechanism. Accumulating evidence suggests that globular aggregates rather than fibrils are the toxic entities responsible for cell death. In the present study we report on structural and morphological features of AEF (amyloid-enhancing factor), a compound extracted and partially purified from amyloid-laden spleen. Surprisingly, the chief amyloidogenic material identified in the active AEF was diffusible globular oligomers. This partially purified active extract triggered amyloid deposition in vital organs when injected intravenously into mice. This implies that such a phenomenon could have been inflicted through the nucleation seeding potential of toxic oligomers in association with altered cytokine induction. In the present study we report an apparent relationship between altered cytokine expression and AA accumulation in systemically inflamed tissues. The prevalence of serum AA monomers and proteolytic oligomers in spleen AEF is consistent to suggest that extrahepatic serum AA processing might lead to local accumulation of amyloidogenic proteins at the serum AA production site.

Outcomes of Trapeziectomy with a Modified Abductor Pollicis Longus Suspension Arthroplasty for the Treatment of Thumb Carpometacarpal Joint Osteoarthritis

Various arthroplasty procedures have been described for the treatment of thumb carpometacarpal joint osteoarthritis. The purpose of this study was to determine the outcomes of patients treated with trapeziectomy and a variation of abductor pollicis longus suspension arthroplasty.

IFATS Collection: Adipose Stromal Cells Adopt a Proangiogenic Phenotype Under the Influence of Hypoxia

Evolving evidence suggests a possible role for adipose stromal cells (ASCs) in adult neovascularization, although the specific cues that stimulate their angiogenic behavior are poorly understood. We evaluated the effect of hypoxia, a central mediator of new blood vessel development within ischemic tissue, on proneovascular ASC functions. Murine ASCs were exposed to normoxia (21% oxygen) or hypoxia (5%, 1% oxygen) for varying lengths of time. Vascular endothelial growth factor (VEGF) secretion by ASCs increased as an inverse function of oxygen tension, with progressively higher VEGF expression at 21%, 5%, and 1% oxygen, respectively. Greater VEGF levels were also associated with longer periods in culture. ASCs were able to migrate towards stromal cell-derived factor (SDF)-1, a chemokine expressed by ischemic tissue, with hypoxia augmenting ASC expression of the SDF-1 receptor (CXCR4) and potentiating ASC migration. In vivo, ASCs demonstrated the capacity to proliferate in response to a hypoxic insult remote from their resident niche, and this was supported by in vitro studies showing increasing ASC proliferation with greater degrees of hypoxia. Hypoxia did not significantly alter the expression of endothelial surface markers by ASCs. However, these cells did assume an endothelial phenotype as evidenced by their ability to tubularize when seeded with differentiated endothelial cells on Matrigel. Taken together, these data suggest that ASCs upregulate their proneovascular activity in response to hypoxia, and may harbor the capacity to home to ischemic tissue and function cooperatively with existing vasculature to promote angiogenesis.

Mesenchymal Stem Cells Can Participate in Ischemic Neovascularization

Cells from the bone marrow contribute to ischemic neovascularization, but the identity of these cells remains unclear. The authors identify mesenchymal stem cells as a bone marrow-derived progenitor population that is able to engraft into peripheral tissue in response to ischemia.

Quality of Clinical Studies in Aesthetic Surgery Journals: a 10-year Review

Evidence-based medicine (EBM) has earned increasing attention in all fields of medicine. However, the implementation of EBM is not yet universal, especially in surgery and its subspecialties. A critical assessment of the quality of scientific evidence in the aesthetic surgery literature is needed to promote the practice of EBM.

Venous Thromboembolic Disease in Autogenous Breast Reconstruction

Venous thromboembolic disease (VTE) is a cause of significant morbidity and mortality in patients with cancer. Large studies have estimated that VTE occurs in up to 1.1% of patients undergoing breast cancer tumor extirpation and in up to 1.5% of patients undergoing breast cancer reconstruction. This study sought to retrospectively review the experience of a large university practice with TRAM, DIEP, and latissimus flap reconstruction for mastectomy defects and evaluate our rate of VTE. In our series of 271 consecutive patients, 2 had deep venous thromboses, 2 had both deep venous thromboses and pulmonary emboli, and 2 had pulmonary embolus alone. VTE incidence was 2.2%, a relatively high rate compared with previously published, large population studies of VTE in breast reconstruction patients. Review of the literature suggests that physicians have poor compliance with established guidelines for prophylaxis and treatment of VTE in general and orthopedic surgery populations. Unfortunately, no specific guidelines are available for patients undergoing operative intervention for breast cancer or autogenous tissue based reconstruction. VTE is significantly under-diagnosed: clinical findings alone are unreliable, and the true prevalence may be greater than twice what is reported. Further research is needed in this largely unexplored field to determine appropriate means of VTE prophylaxis and treatment in the breast cancer population.

Cholinergic Activation of Hematopoietic Stem Cells: Role in Tobacco-related Disease?

Tobacco use is associated with an increase in the white blood cell (WBC) count. This association has been attributed to bronchopulmonary inflammation and/or infection. It is not known if nicotine itself may play a role. The objective of this study was to determine whether nicotine itself could affect the WBC count, and to determine whether this was due to a direct effect on hematopoietic stem cells (HSC). C57Bl6J mice received nicotine orally, and measurements of the WBC count, bone marrow and spleen cellularity, and HSC count were made. To determine the functionality of HSCs, irradiated animals received bone marrow transplants from vehicle or nicotine-treated mice. Nicotine increased leukocytes in the peripheral blood, bone marrow and spleen. The peripheral red cell and platelet count were unaffected. Nicotine increased the frequency of HSC in the bone marrow. Isolated long-term HSCs from nicotine-treated mice transplanted into irradiated mice regenerated all hematopoietic cell lineages, demonstrating the functional competence of those HSCs. HSCs expressed nicotinic acetylcholine receptors (nAChRs), as documented by FITC-conjugated alpha-bungarotoxin binding. Nicotine increased soluble Kit ligand, consistent with stem cell activation. In conclusion, the data suggest a new mechanism for the increased WBC associated with tobacco use. The effect of nicotine to activate hematopoiesis may contribute to tobacco-related diseases.

A Patient with Multiple Synchronous Gliomas of Distinctly Different Grades and Correlative Radiographic Findings

Multiple gliomas represent approximately 2 to 5% of all high-grade gliomas which are categorized as multifocal or multicentric depending on the timing, location and pattern of spread. We present a patient with bi-hemispheric, noncontiguous, low- and high-grade gliomas proven by biopsy. She underwent surgical excision and radiotherapy, but unfortunately succumbed to her disease shortly thereafter.

Reproducibility Study of [(18)F]FPP(RGD)2 Uptake in Murine Models of Human Tumor Xenografts

An (18)F-labeled PEGylated arginine-glycine-aspartic acid (RGD) dimer {[(18)F]FPP(RGD)(2)} has been used to image tumor α(v)β(3) integrin levels in preclinical and clinical studies. Serial positron emission tomography (PET) studies may be useful for monitoring antiangiogenic therapy response or for drug screening; however, the reproducibility of serial scans has not been determined for this PET probe. The purpose of this study was to determine the reproducibility of the integrin α(v)β(3)-targeted PET probe, [(18)F]FPP(RGD)(2,) using small animal PET.

Pilot Pharmacokinetic and Dosimetric Studies of (18)F-FPPRGD2: a PET Radiopharmaceutical Agent for Imaging α(v)β(3) Integrin Levels

To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 ((18)F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets α(v)β(3) integrin, in the first volunteers imaged with this tracer.

Adipose Tissue-derived Stem Cells Display a Proangiogenic Phenotype on 3D Scaffolds

Ischemic heart disease is the leading cause of death worldwide. Recent studies suggest that adipose tissue-derived stem cells (ASCs) can be used as a potential source for cardiovascular tissue engineering due to their ability to differentiate along the cardiovascular lineage and to adopt a proangiogenic phenotype. To understand better ASCs' biology, we used a novel 3D culture device. ASCs' and b.END-3 endothelial cell proliferation, migration, and vessel morphogenesis were significantly enhanced compared to 2D culturing techniques. ASCs were isolated from inguinal fat pads of 6-week-old GFP+/BLI+ mice. Early passage ASCs cells (P3-P4), PKH26-labeled murine b.END-3 cells or a co-culture of ASCs and b.END-3 cells were seeded at a density of 1 × 10(5) on three different surface configurations: (a) a 2D surface of tissue culture plastic, (b) Matrigel, and (c) a highly porous 3D scaffold fabricated from inert polystyrene. VEGF expression, cell proliferation, and tubulization, were assessed using optical microscopy, fluorescence microscopy, 3D confocal microscopy, and SEM imaging (n = 6). Increased VEGF levels were seen in conditioned media harvested from co-cultures of ASCs and b.END-3 on either Matrigel or a 3D matrix. Fluorescence, confocal, SEM, bioluminescence revealed improved cell, proliferation, and tubule formation for cells seeded on the 3D polystyrene matrix. Collectively, these data demonstrate that co-culturing ASCs with endothelial cells in a 3D matrix environment enable us to generate prevascularized tissue-engineered constructs. This can potentially help us to surpass the tissue thickness limitations faced by the tissue engineering community today.

Diffuse Idiopathic Skeletal Hyperostosis (DISH)-A Rare Etiology of Dysphagia

A 72-year-old gentleman presented to the hospital with progressively worsening dysphagia to soft foods and liquids. He was diagnosed with severe pharyngeal dysphagia by modified barium swallow. A CT scan of the neck with IV contrast showed anterior flowing of bridging osteophytes from C3-C6, indicative of DISH, resulting in esophageal impingement. He underwent resection of the DISH segments. Following the surgery, a PEG tube for nutrition supplementation was placed. However, the PEG tube was removed after five months when the speech and swallow evaluation showed no residual dysphagia. DISH is a rare non-inflammatory condition that results in pathological ossification and calcification of the anterolateral spinal ligaments.

First Experience with Clinical-grade ([¹⁸F]FPP(RGD₂): an Automated Multi-step Radiosynthesis for Clinical PET Studies

A reliable and routine process to introduce a new ¹⁸F-labeled dimeric RGD-peptide tracer ([¹⁸F]FPP(RGD₂) for noninvasive imaging of α(v)β₃ expression in tumors needed to be developed so the tracer could be evaluated for the first time in man. Clinical-grade [¹⁸F]FPP(RGD)₂ was screened in mouse prior to our first pilot study in human.

Proof-of-concept Study of Monitoring Cancer Drug Therapy with Cerenkov Luminescence Imaging

Cerenkov luminescence imaging (CLI) has emerged as a less expensive, easier-to-use, and higher-throughput alternative to other nuclear imaging modalities such as PET. It is expected that CLI will find many applications in biomedical research such as cancer detection, probe development, drug screening, and therapy monitoring. In this study, we explored the possibility of using CLI to monitor drug efficacy by comparisons against PET. To assess the performance of both modalities in therapy monitoring, 2 murine tumor models (large cell lung cancer cell line H460 and prostate cancer cell line PC3) were given bevacizumab versus vehicle treatments. Two common radiotracers, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) and (18)F-FDG, were used to monitor bevacizumab treatment efficacy.

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