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J Cancer Metastasis Treat 2019;5:31 I http://dx.doi.org/10.20517/2394-4722.2019.21 Page 22 of 36
3 Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa,
Pisa 56126, Italy.
4 Ortopedia Oncologica Pediatrica, AOU Careggi-AOU Meyer, Firenze 50139, Italy.
5 SOD Ortopedia Oncologica e Ricostruttiva, AOU Careggi, Firenze 50134, Italy.

In the last years, several studies have identified the presence inside many types of tumors of a subpopulation
of stem-like cells, a biologically unique subset of cells, which are probably involved in tumor progression
and in the resistance to the antineoplastic treatments. These cells are defined as cancer stem cells (CSCs)
and their uncomplete eradication represents a possible explanation as why many therapies seem to have an
initial effect, but the patient later relapses. On the other hand, there are a lot of researches about the role
of microRNAs (miRNAs) in several cancerous process (i.e., growth, invasion and metastases) and in the
maintenance of stemness. On the base of this, we have studied the presence of CSCs inside the primary and
aggressive bone malignancy which primarily affecting children and young adults, the osteosarcoma (OS).
In this study, we have shown not only the presence of the CSCs population inside different high grade types
of OS (i.e., telangiencatic OS, small cell OS and conventional OS), but also the preliminary results a about
the possibility to find a profile of miRNA expression, as “miRNA codes”, which can be analogue to all the
analyzed subtypes of OS. These results could be important to identify a common molecular code among the
three highly malignant forms of OS that could be used in the design of new and more effective treatments
against the highly aggressive types of OS.

Biography
2011 she has obtained her Master’s Degree in Biology at the University of Florence, Florence, Italy. 2016
she has completed her PhD from University of Florence, Florence, Italy, in the field on pathophysiology of
bone. 2016-present she is a Post-Doc researcher, at the Department of Surgery and Translational Medicine,
University of Florence, Florence, Italy. 2013-present she’s carrying on researches on primary bone cancers
(i.e., osteosarcoma, Ewing’s sarcoma and giant cell tumor). Her interest are focused on cancer stem cells
and on miRNAs involved in these bone diseases. She has published several papers in reputed journals and
she has attended national and international meetings on this topic.

28. Vitamin E d-tocotrienol induces apoptosis in prostate cancer cells through activation of the
ER stress-autophagy axis and rewiring of mitochondrial metabolism

Fabrizio Fontana, Marina Montagnani Marelli, Michela Raimondi, Roberta Manuela Moretti, Monica
Marzagalli, Raffaella Longo, Maurizio Crestani, Patrizia Limonta

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano 20133,
Italy.

Prostate cancer is androgen dependent in its early stage and responds to the androgen deprivation therapy;
however, it often progresses to the castration-resistant prostate cancer (CRPC) stage in which cancer cells
become resistant to therapies. Preliminary experiments performed in the authors’ laboratory demonstrate
that vitamin E-derivative d-tocotrienol (d-TT) exerts a proapoptotic activity in CRPC cells while sparing
normal prostate epithelial cells. These studies were performed to investigate the molecular mechanisms
underlying this activity: (1) in CRPC cells, d-TT induces endoplasmic reticulum (ER) stress (expression
of ER stress markers such as BiP, PERK, p-eIF2α, IRE1α, ATF4 and CHOP) and autophagy (expression
of autophagy markers such as LC3- II and p62). Using the ER stress inhibitors salubrinal and 4-PBA and
the autophagy flux inhibitors 3-methyladenine and chloroquine, we confirmed that the effect of d-TT is