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For many years, cancer has been described as the accumulation of germinal and somatic mutations of the genome, impairing the function of tumor suppressor genes and stimulating oncogenes. Nowadays, it is commonly accepted that the tumor is not only a mass of malignant cells, rather than the result of a delicate network of interactions between tumor and stromal cells. Indeed, bidirectional communications between cancer cells and the surrounding microenvironment can strongly influence tumor development and progression. Stromal cells might support tumorigenesis, either via direct cell-cell contact mechanisms with tumor cells, or by releasing specific factors, including cytokines and growth factors in the surrounding extracellular matrix (ECM), with remodeling of the tumor microenvironment (TME) as a result.The aim of this thesis is to elucidate the delicate network of interactions between different TME components and tumor cells in prostate cancer (PCa) and oropharyngeal squamous cell carcinoma (OPSCC).

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Motor cortex stimulation (MCS) was proposed by Tsubokawa in 1991 for the treatment of post-stroke thalamic pain. Since that time, the indications have been increased and included trigeminal neuropathic pain and later other types of central and peripheral deafferentation pain. The results reported in the literature are quite good; the mean long-term success rate is 80% in facial pain and 53% in non-facial pain. Our own results are less impressive: 4 of 14 patients (28%) experienced a greater than 40% pain relief, but in 2 of them the effect faded with time. Only few minor complications have been reported. The accurate placement of the epidural electrode over the motor cortex that somatotopically corresponds to the painful area is believed to be essential for pain relief. Predictive factors included the response to pharmacological tests, the relative sparing from the disease process of the cortico-spinal tract and the sensory system, and the analgesic response achieved during the test period of MCS. A possible predictive factor might be a test of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. MCS may act by rebalancing the control of non-nociceptive sensory inputs over nociceptive afferents at cortical, thalamic, brainstem and spinal level. In addition, it may interfere with the emotional component of nociceptive perception. Biochemical processes involving endorphins and GABA may also be implicated in the mechanism of MCS. It is time for a large multicenter prospective randomized double blind study evaluating not only the effect of MCS on pain (based on the available guidelines for assessment of neuropathic pain), but also the optimal electrode placement and stimulation parameters, and the possible relationship with the response to rTMS. New electrode design and a new generation of stimulators may help in improving the results.

The technology of molecular imprinting permits recognition sites to be inserted into a polymeric material through the polymerisation of a monomer in the presence of a template, or through the dissolution of a preformed polymer in a solution containing the template and then crosslinking or phase inversion so as to obtain the matrix-template complex. This paper will focus on the application of both techniques in the realisation of polymeric membranes with molecular recognition properties in aqueous environments.

Spinal cord stimulation (SCS) has been shown to be effective in patients with refractory angina and coronary artery disease. No previous study assessed the clinical effects of SCS in patients with refractory angina who present angiographically normal coronary arteries.SCS was performed in 7 patients (4 men, 3 women, mean age 59.3 +/- 11 years) with refractory angina and normal coronary arteries. Clinical status was assessed 1 month after SCS device implantation and at a mean follow-up of 11 months (range 2-17 months) by: 1) an estimate of the number of anginal attacks and nitrate consumption in the 2 weeks prior to implantation and to follow-up visits; 2) a score of quality of life by a visual analogic scale; 3) a five-item questionnaire assessing effort angina and satisfaction with treatment; 4) treadmill exercise testing.At the last follow-up the number of anginal episodes (p0.001) and nitrate consumption (p0.004) were both reduced by SCS. Visual analogic scale score improved from 2.1 +/- 0.98 to 9.0 +/- 0.9 (p0.001) at 1 month and to 6.4 +/- 2.3 (p0.01) at the last follow-up. Questionnaire analysis showed that mild (p = 0.006) and moderate (p = 0.000) physical activity, as well as patient satisfaction with anginal status (p = 0.000) and with current treatment (p = 0.000) all improved by SCS. Finally, time to 1 mm ST segment depression, time to angina, and exercise duration were all prolonged by SCS.Our data point out that SCS may considerably improve anginal symptoms and exercise tolerance in a significant number of patients with refractory angina and normal coronary arteries and therefore it should be considered as a valuable treatment option in this group of patients.