Miha Koprivnikar Kranjc, Metka Novak, Richard G. Pestell and Tamara T. Lah
types in the GB stroma are affected: the tumour is able to stimulate angiogenesis and co-opt existing vasculature, suppress immune cell functions, disarm microglia and macrophages that should recognize and fight these “foreign elements” in the brain and coerce astrocytes into supporting tumour modification extracellular matrix (ECM) to facilitate invasion. GB cells recruit innate immune cells and change their phenotype to support tumour growth and suppress adaptive immune responses. 14 The increasing understanding of how T cells access the brain and how the tumour
Barbara Breznik, Clara Limback, Andrej Porcnik, Andrej Blejec, Miha Koprivnikar Krajnc, Roman Bosnjak, Janko Kos, Cornelis J.F. Van Noorden and Tamara T. Lah
therapeutic resistance 8 and apoptosis. 9 , 10 Besides the hydrolysis of selective proteins, cysteine cathepsins participate in proteolytic cascades, where one protease activates one or several others in sequences that finally regulate hydrolysis of peptide and protein substrates, which is called protease signaling. 10 For example, secreted cathepsins can be considered as initiators of extracellular matrix (ECM)-degrading cascades during cell invasion, by cleaving and activating serine proteases, and modifying the tumor microenvironment by cleaving ECM proteins, shedding
Felipe Maglietti, Matias Tellado, Nahuel Olaiz, Sebastian Michinski and Guillermo Marshall
separated by 8 mm. The pulse generator used was a BTX ECM 830 (Harvard Apparatus, Holliston, MA, USA). A train of 8 electric pulses (1000 V/cm, 100 microseconds, 10 Hz) was applied, covering the whole tumor 13 , beginning at the periphery of the tumor in a circular fashion in order to have maximum drug concentration at the margins and prevent the spreading of tumor cells. The superposition of electric fields was avoided in order to prevent overtreatment of the lesions.
The response to each treatment was evaluated according to the WHO criteria for tumor response 18 , 30
Felipe Maglietti, Matías Tellado, Nahuel Olaiz, Sebastian Michinski and Guillermo Marshall
the electric pulses eight minutes later to allow drug distribution according to the Standard Operating Procedures published by Mir et al. [ 14 ].
The SiNE was inserted deep into the nasal fossa and a train of pulses was delivered, see Figure 2 . For that purpose, a BTX ECM 830 Harvard Apparatus (Holliston, MA, USA) was used. The electric pulses consisted of thirty-two square pulses of 300V, 100 µs long at 1 Hz. The electrode was rotated 90 degrees clockwise and the pulses were repeated. After the rotation, the electrode was removed 2 cm and the whole procedure
Taja Lozar, Klara Gersak, Maja Cemazar, Cvetka Grasic Kuhar and Tanja Jesenko
the extracellular matrix (ECM) may also aid in metastatic colonization. Specific ECM components associated with colonization of the lung in breast cancer have been identified. 68 , 69 Hypoxia and fibrosis have also been linked to metastasis. 19 , 70 Interestingly, suitable microenvironment may start to develop prior to extravasation of tumor cells as a result of systemic effects of the primary tumor. 19 An observation by Costa-Silva et al . describes exosomes derived from tumor cells carrying DNA, mRNA, miRNA and proteins which prime the liver for metastasis