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Page 8 of 11                       Gasparello et al. J Cancer Metastasis Treat 2019;5:52  I  http://dx.doi.org/10.20517/2394-4722.2019.17

               the mouse xenograft model systems here presented are the differences between man and mouse with respect
               to ctDNA and microRNA dinamics in respect to their vasculature. Therefore we should carefully consider
               the sharply different ratios between the dimension of implanted tumors, the mouse body weight and the
               blood volume on one hand and those related the same parameters (i.e., tumor weight, body weight and blood
               total volume) in CRC patients. In this respect the analysis of the miRNome in liquid biopsy obtained when
               tumors of different dimensions are employed in mouse xenograft model systems might clarify whether the
               ratio between tumor size and mouse body weight or blood volume might affect the results. This might also
               be of interest for developing algorithms in human clinical settings.



               DECLARATIONS
               Authors’ contributions
               Revised and approved the final manuscript: Gasparello J, Allegretti M, Papi C, Giordani E, Giacomini P,
               Gambari R, Finotti A
               Wrote the manuscript: Allegretti M, Giacomini P, Gambari R, Finotti A
               Performed the literature search: Allegretti M, Giacomini P, Gambari R, Finotti A
               Critically analyzed the existing literature: Allegretti M, Giacomini P, Gambari R, Finotti A
               Designed the figures and created the tables: Gasparello J, Papi C, Giordani E, Gambari R, Finotti A

               Availability of data and materials
               Not applicable.

               Financial support and sponsorship
               This work was supported by the European Union (EU) Horizon 2020 Research and Innovation Programme:
               project ULTRAsensitive PLAsmonic devices for early CAncer Diagnosis (ULTRAPLACAD) (633937);
               Associazione Italiana per la Ricerca sul Cancro (AIRC) (13575) to Gambari R, (14204, 19052) to Giacomini
               P. Allegretti M is the recipient of a three-year AIRC fellowship (id. 19503). This study was also supported by
               the Interuniversity Consortium for the Biotechnology, Italy.

               Conflicts of interest
               The author declared that there are no conflicts of interest.

               Ethical approval and consent to participate
               Not applicable.

               Consent for publication
               Not applicable.

               Copyright
               © The Author(s) 2019.


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