OCT 05, 2016 7:30 AM PDT

Keynote Speaker: How to meet the challenge of counting and analyzing tumor cells circulating in the peripheral blood

Speakers
  • Donner Professor of Science and Professor of Chemistry, Emeritus
    Biography
      Giacinto Scoles (b. 1935, married to Lim Giok Lan since 1964) is Donner professor of Science, Emeritus at Princeton University, distinguished adjoint professor in the Departments of Physics and Biology at Temple University, and distinguished scientist at Synchrotron Elettra in Trieste. He is presently senior grantee of the ERC in the faculty of Medicine at the University of Udine (Italy). His career has spanned an unusually long length of time and an equally unusually broad range of subjects. He has developed instrumentation in mass spectroscopy, gas viscosimetry, crossed molecular beam scattering, clusters formation and spectroscopy, surface monolayer, grazing incidence X-ray scattering, super-fluid helium droplets; manipulation of bio-molecules, bio-molecular interaction at the nano scale and medical nano diagnostics. He and a group of collaborators have recently patented a method to count circulating tumor cells based on the measurement of the metabolism of every cell isolated into a droplet of blood of several picoliters. When the droplet results to become acid, that indicates the presence of the cancer cells. He has received several recognitions: the Herschbach prize (2013); the gold medal of honor of the Italian Chemical Society; the Ben Franklin Medal for Physics (2006) 2 Honorary doctorates (1997 and 2000) the Debye prize of the ACS, the Plyler prize of the APS and the Lippincott Award of the OSA. He is a Fellow of the APS, OSA and of the ROYAL Society of the UK and of the Royal Science Academy of the Netherlands (KNAW). He has published about 300 papers in peer reviewed journals, and has been quoted by his colleagues approximately 19.000 times, his H-index is 73, while the i10-index is 224. He has supervised about a hundred PhD students, an unusually high percentage of which now covers positions of responsibility in Academia and research.

    Abstract:

    The talk will first report on a new patented method of counting CTCs based on the metabolism of tumor cells, that favors acidification of their near environment. In order to maintain the acidity produced inside the cells and communicated to the near environment (Warburg effect), we isolate each cell in a liquid pico-droplet produced in a microfluidic emulsifier. The so-produced droplets pass through a light sheet produced by a laser and the ratio of fluorescence produced at two frequencies by the SNARF dye ratiometrically measures the acidity of droplets. The first preliminary results will be shown with very limited cohort of patients, and the nature of the tumor cell found will be discussed.
    As it is well known that the Veridex apparatus only counts epithelial cells, the presence in our machine of mesenchymal cells will also be discussed. In a parallel effort carried out with much more analysis precision but much less speed of execution, namely one analysis per day, we will dissect the population of cells present in patients of breast cancer carried out within a Deparray platform.
    Four CD45neg cell subpopulations were identified: cells expressing only epithelial markers (E CTC), cells co-expressing epithelial and mesenchymal markers (EM CTC), cells expressing only mesenchymal markers (MES) and cells negative for every tested marker (NEG). CTC subpopulations were quantified as both absolute cell count and relative frequency. We have been able to assess the presence of cells pertaining to the above-described classes in every Metastatic Breast Cancer (MBC) patient in a cohort of 56 patients. Importantly, the fraction of CD45neg cells co-expressing epithelial and mesenchymal markers (EM CTC) was significantly associated with poorer PFS and OS, computed, this latter, both from the diagnosis of a stage IV disease and from the initial CTC assessment. Our work suggests the importance of dissecting the heterogeneity of CTC in MBC. Precise characterization of CTC could help in estimating both metastatization pattern and outcome, driving clinical decision-making and surveillance strategies.
     


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