Papers by Carlo Bellorofonte
European Urology Supplements, 2005

European Urology Open Science
Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dy... more Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α), and enhanced activating transcription factor 4 (ATF4) in an energy-dependent manner. In addition, GSK2656157-an inhibitor of PERK-effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF)1α or glial cell-derived neurotrophic factor (GDNF) in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy.

European Urology, 2005
Objectives: Malignant and normal tissues are known to have different electromagnetic properties, ... more Objectives: Malignant and normal tissues are known to have different electromagnetic properties, and various attempts have been made to use these information for diagnostic purposes. A nonlinear tuneable oscillator (Trimprob TM) generating extremely low energy multiple electromagnetic fields has been developed for noninvasive analysis of electromagnetic anisotropy in humans. Objective of this study was to evaluate the feasibility of prostate cancer detection using the TRIMprob TM and to evaluate its diagnostic accuracy. Methods: 757 men were evaluated with the TRIMprob TM between July 2002 and May 2003 in a prostate unit. The TRIMprob TM was moved over the surface of the patient's perineum while standing, normally dressed, in front of the system receiver. A single operator, blinded to the patient status, conducted the tests. Nonlinear resonance was analysed at 465, 930 and 1395 MHz. Results: Analysis of resonance values at 465 MHz showed a significant difference between controls, patients with benign prostatic hyperplasia and patients with prostate cancer. In our study population, a sensitivity of 95.5% and specificity of 42.7% for the diagnosis of prostate cancer with a positive and negative predictive value of 63.6% and 89.8% was found. Conclusions: The results of this study confirm the possibility of electromagnetic detection of cancer. An extracorporeal scan by the TRIMprob TM can identify patients at risk for prostate cancer, and recognise those in whom the risk is extremely low. The results of the present study represent a proof-of-concept, which may open a new field of medicine.
European Urology Supplements, 2016

European Urology, 2005
Objectives: Malignant and normal tissues are known to have different electromagnetic properties, ... more Objectives: Malignant and normal tissues are known to have different electromagnetic properties, and various attempts have been made to use these information for diagnostic purposes. A nonlinear tuneable oscillator (Trimprob TM) generating extremely low energy multiple electromagnetic fields has been developed for noninvasive analysis of electromagnetic anisotropy in humans. Objective of this study was to evaluate the feasibility of prostate cancer detection using the TRIMprob TM and to evaluate its diagnostic accuracy. Methods: 757 men were evaluated with the TRIMprob TM between July 2002 and May 2003 in a prostate unit. The TRIMprob TM was moved over the surface of the patient's perineum while standing, normally dressed, in front of the system receiver. A single operator, blinded to the patient status, conducted the tests. Nonlinear resonance was analysed at 465, 930 and 1395 MHz. Results: Analysis of resonance values at 465 MHz showed a significant difference between controls, patients with benign prostatic hyperplasia and patients with prostate cancer. In our study population, a sensitivity of 95.5% and specificity of 42.7% for the diagnosis of prostate cancer with a positive and negative predictive value of 63.6% and 89.8% was found. Conclusions: The results of this study confirm the possibility of electromagnetic detection of cancer. An extracorporeal scan by the TRIMprob TM can identify patients at risk for prostate cancer, and recognise those in whom the risk is extremely low. The results of the present study represent a proof-of-concept, which may open a new field of medicine.

Journal of Therapeutic Ultrasound, 2016
Objectives Thalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medi... more Objectives Thalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication resistant tremor in patients with essential tremor (ET) and Parkinson's disease (PD). MRI guided Focused Ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation. Methods Thirty eight ET and PD patients with severe medication resistant tremor underwent MRgFUS underwent unilateral VIM thalamotomy using MRgFUS. Effect was evaluated using clinical Rating Scale of Tremor (CRST) in ET patients and Unified PD Rating Scale motor part (UPDRS) in PD patients. Quality of life was assessed by Quality of life in ET Questionnaire (QUEST) and PD Questionaire (PDQ-39). Results Tremor stopped in the treated hand in 37 patients immediately following the treatment. In one patients tremor was modified but not abolished. At one month post-treatment, the ET patients' CRST score decreased from 38.6 ± 12.0 to 9.3 ± 7.7 (p < 0.001) and QUEST scores decreased from 44.8 ± 17.8 to 13.1 ± 15.9 (p < 0.001). In PD patients UPDRS-motor part decreased from 26.2 ± 8.7 to 16.3 ± 11.0 (p = 0.0087) and PDQ39 decreased from 40.8 ± 18.2 to 26.5 ± 15.1 (p = 0.027). During follow up of 1-24 months (mean 10.9 ± 8.1 months) tremor reappeared in seven of the patients, but in all but three, to a lesser degree than before the procedure. Adverse events that transiently occurred during sonication included: Headache (n = 11), short lasting vertigo (n = 17) and dizziness (n = 4), nausea (n = 4), burning scalp sensation (n = 3), vomiting (n = 3) and lip paresthesia (n = 2). Adverse events that lasted after the procedure included gait ataxia (n = 5), unsteady feeling when walking (n = 4,) unilateral taste disturbances (n = 3) and hand ataxia (n = 3). All adverse events were transient and none lasted beyond 3 months. Conclusions MRgFUS VIM thalamotomy to relieve medication resistant tremor was safe and effective in ET, and PD. Current results emphasize its low adverse events profile and high efficacy in treating tremor. Large randomized studies are needed to assess prolonged efficacy and safety. A2 Focused Ultrasound likely dominates deep brain stimulation and stereotactic radiosurgery for medically-refractory essential tremor: an initial decision and cost-effectiveness analysis

Technology in cancer research & treatment, 2014
The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients un... more The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53-85). The median Gleason score was 7 (range: 6-9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2-64.2). Seven of the 15 ...
Focal Therapy of Prostate Cancer, 2015
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Papers by Carlo Bellorofonte