Photoacoustic detection of metastatic melanoma in the human circulatory system

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Title from title screen of research.pdf file (viewed on August 29, 2007)Vita.Includes bibliographical references.Thesis (M.S.) University of Missouri-Columbia 2006.Dissertations, Academic -- University of Missouri--Columbia -- Biological engineering.Detection of disseminating tumor cells can function as an early warning system, alerting the metastatic spread or recurrence of the disease. Early detection of such cells can result in preventative treatment of the disease while late stage detection can serve as an indicator of the effectiveness of chemotherapeutics. We propose a system for the detection of metastatic circulating tumor cells based upon the thermo-elastic properties of melanoma. The method employs photoacoustic excitation coupled with a detection system capable of determining the presence of disseminating cells within the circulatory system in vitro. Detection trials consisting of a human melanoma cell line resulted in a detection threshold on the order of 10 individual cells. Melanoma cells were introduced into human blood in vitro to mimic a metastatic envrionment. Results imply the potential to assay simple blood draws from healthy and metastatic patients for the presence of cancerous melanoma providing an unprecedented method for routine cancer screening

International Society of Sports Nutrition Position Stand: Nutritional recommendations for single-stage ultra-marathon; training and racing

Background. In this Position Statement, the International Society of Sports Nutrition (ISSN) provides an objective and critical review of the literature pertinent to nutritional considerations for training and racing in single-stage ultra-marathon. Recommendations for Training. i) Ultra-marathon runners should aim to meet the caloric demands of training by following an individualized and periodized strategy, comprising a varied, food-first approach; ii) Athletes should plan and implement their nutrition strategy with sufficient time to permit adaptations that enhance fat oxidative capacity; iii) The evidence overwhelmingly supports the inclusion of a moderate-to-high carbohydrate diet (i.e., ~60% of energy intake, 5 – 8 g⸱kg−1·d−1) to mitigate the negative effects of chronic, training-induced glycogen depletion; iv) Limiting carbohydrate intake before selected low-intensity sessions, and/or moderating daily carbohydrate intake, may enhance mitochondrial function and fat oxidative capacity. Nevertheless, this approach may compromise performance during high-intensity efforts; v) Protein intakes of ~1.6 g·kg−1·d−1 are necessary to maintain lean mass and support recovery from training, but amounts up to 2.5 g⸱kg−1·d−1 may be warranted during demanding training when calorie requirements are greater; Recommendations for Racing. vi) To attenuate caloric deficits, runners should aim to consume 150 - 400 kcal⸱h−1 (carbohydrate, 30 – 50 g⸱h−1; protein, 5 – 10 g⸱h−1) from a variety of calorie-dense foods. Consideration must be given to food palatability, individual tolerance, and the increased preference for savory foods in longer races; vii) Fluid volumes of 450 – 750 mL⸱h−1 (~150 – 250 mL every 20 min) are recommended during racing. To minimize the likelihood of hyponatraemia, electrolytes (mainly sodium) may be needed in concentrations greater than that provided by most commercial products (i.e., >575 mg·L−1 sodium). Fluid and electrolyte requirements will be elevated when running in hot and/or humid conditions; viii) Evidence supports progressive gut-training and/or low-FODMAP diets (fermentable oligosaccharide, disaccharide, monosaccharide and polyol) to alleviate symptoms of gastrointestinal distress during racing; ix) The evidence in support of ketogenic diets and/or ketone esters to improve ultra-marathon performance is lacking, with further research warranted; x) Evidence supports the strategic use of caffeine to sustain performance in the latter stages of racing, particularly when sleep deprivation may compromise athlete safety

Detection of Circulating Tumor Cells in Uveal Melanoma by the Photoacoustic Method

Abstract Circulating tumor cells (CTCs) have been shown to be a prognostic marker in breast cancer1. We hypothesize that circulating melanoma cell (CMC) detection could be utilized in the management of uveal melanoma, including early intervention. Prior methodologies for circulating uveal melanoma cell (CUMC) detection have been fraught with poor sensitivity, limiting their clinical utility2. Development of an improved method is necessary to establish the clinical utility of CUMC monitoring. Photoacoustics, also referred to as laser-induced ultrasound, is a novel platform for the detection and capture of CMCs. Photoacoustics uses short duration pulsed light to create ultrasonic acoustic waves in an optically absorbing medium, in this case melanin within melanoma3. As light is absorbed by irradiated chromophores, the optical energy gets converted into kinetic thermal energy trapped within the chromophore and subsequent thermal expansion ensues. Transient thermoelastic expansion of the absorbent cell results in the propagation of ultrasonic acoustic waves which can be detected and analyzed using a piezoelectric response mechanism. In addition, detected CMCs can be isolated by a two-phase flow cell separation technique4. Due to the low cost and melanoma specific capabilities of photoacoustics, we evaluated this technology for the purpose of CUMC detection. Methods: Cells from uveal melanoma cell line UM002B, established at Thomas Jefferson, were titrated to various cell concentrations and analyzed in a neutral density solution utilizing the photoacoustic method. Uveal melanoma cells of differing concentrations were spiked into isolated healthy donor peripheral blood mononuclear cells (PBMCs) and healthy whole blood samples. PBMC isolates were analyzed for CUMCs. Results: CUMCs were successfully quantified by the photoacoustic method including single cell detection. Recovery rates of cultured cells in a neutral density solution approached 25%. Recovery rates for CUMCs in whole blood averaged 10% of expected cell yield (56/540 cells detected) with a higher detection rate at lower cell concentrations. Photoacoustics offers a viable method for the detection of CUMCs with an accuracy that meets or exceeds previously reported CUMC yields. Studies analyzing CUMCs from patients with metastatic disease are ongoing.https://jdc.jefferson.edu/medoncposters/1002/thumbnail.jp

Arterial Blood, Rather Than Venous Blood, is a Better Source for Circulating Melanoma Cells

ABSTRACTBackgroundCTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients.MethodsBlood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements.FindingCTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p=0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases.InterpretationOur data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs