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Orlando L.,University of Turin | Accomasso L.,University of Turin | Circosta P.,University of Turin | Turinetto V.,University of Turin | And 8 more authors.
Molecular Immunology | Year: 2011

Induction of the TCR signaling pathway terminates the expression of RAG genes, and a link between this pathway and their transcriptional control is evident from the recent demonstration of their re-expression if the TCR is subsequently lost or down-regulated. Since unstimulated T cells display a steady-state level of " tonic" TCR signaling, i.e. in the absence of any antigenic stimulus, it was uncertain whether this control was exerted through ligand-dependent or ligand-independent TCR signaling. Here we demonstrate for the first time that exogenous TCR α and β chains transferred into the human immature RAG+ T cell line Sup-T1 by lentiviral transduction inhibit RAG expression through tonic signaling, and that this inhibition could itself be reverted by pharmacological tonic pathway inhibitors. We also suggest that mature T cells already expressing an endogenous TCR on their surface maintain some levels of plasticity at the RAG locus when their basal TCR signaling is interfered with. Lastly, we show that the TCR constructs employed in TCR gene therapy do not possess the same basal signaling transduction capability, a feature that may have therapeutic implications. © 2011 Elsevier Ltd.


Russo F.,Candiolo Cancer Institute FPO | Regge D.,Candiolo Cancer Institute FPO | Armando E.,Candiolo Cancer Institute FPO | Giannini V.,Candiolo Cancer Institute FPO | And 6 more authors.
BJU International | Year: 2016

Objective: To evaluate the sensitivity of multiparametric magnetic resonance imaging (mp-MRI) for detecting prostate cancer foci, including the largest (index) lesions. Patients and Methods: In all, 115 patients with biopsy confirmed prostate cancer underwent mp-MRI before radical prostatectomy. A single expert radiologist recorded all prostate cancer foci including the index lesion ‘blinded’ to the pathologist's biopsy report. Stained whole-mount histological sections were used as the reference standard. All lesions were contoured by an experienced uropathologist who assessed their volume and pathological Gleason score. All lesions with a volume of >0.5 mL and/or pathological Gleason score of >6 were defined as clinically significant prostate cancer. Multivariate analysis was used to ascertain the characteristics of lesions identified by MRI. Results: In all, 104 of 115 index lesions were correctly diagnosed by mp-MRI (sensitivity 90.4%; 95% confidence interval [CI] 83.5–95.1%), including 98/105 clinically significant index lesions (93.3%; 95% CI 86.8–97.3%), among which three of three lesions had a volume of <0.5 mL and Gleason score of >6. Overall, mp-MRI detected 131/206 lesions including 13 of 68 ‘insignificant’ prostate cancers. The multivariate logistic regression modelling showed that pathological Gleason score (odds ratio [OR] 11.7, 95% CI 2.3–59.8; P = 0.003) and lesion volume (OR 4.24, 95% CI 1.3–14.7; P = 0.022) were independently associated with the detection of index lesions at MRI. Conclusions: This study shows that mp-MRI has a high sensitivity for detecting clinically significant prostate cancer index lesions, while having disappointing results for the detection of small-volume, low Gleason score prostate cancer foci. Thus, mp-MRI could be used to stratify patients according to risk, allowing better treatment selection. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd


Vercelli C.,University of Turin | Barbero R.,University of Turin | Cuniberti B.,University of Turin | Racca S.,Azienda Ospedaliero Universitaria San Luigi Gonzaga | And 3 more authors.
Journal of Breast Cancer | Year: 2014

Purpose: Transient receptor potential vanilloid 1 (TRPV1) is a non­selective cation channel belonging to the transient receptor po­tential family, and it is expressed in different neoplastic tissues. Its activation is associated with regulation of cancer growth and progression. The aim of this research was to study the expres­sion and pharmacological characteristics of TRPV1 in cells de­rived from human breast cancer MCF-7 cells.Methods: TRPV1 presence was assessed by binding studies and Western blotting. Receptor binding characteristics were evaluated through competition assays, while 3-(4,5-dimethylthiazol-2-yl)-2,5,-dipheyltetrazolium bromide reduction assays were performed to confirm an early hypothesis regarding the modulation of cancer cell pro­liferation. The functionality of TRPV1 was evaluated by measuring Ca2+ uptake in the presence of increasing concentrations of TRPV1 agonists and antagonists.Results: Binding studies identi­fied a single class of TRPV1 (Bmax 1,492±192 fmol/mg protein), and Western blot showed a signal at 100 kDa corresponding to the molecular weight of human TRPV1. Among the different tested agonists and antagonists, anandamide (Ki: 2.8×10-11 M) and 5-iodoresiniferatoxin (5-I-RTX) (Ki: 5.6×10-11 M) showed the highest degrees of affinity for TRPV1, respectively. All tested TRPV1 agonists and antagonists caused a significant (p<0.05) decrease in cell growth rate in MCF-7 cells. For agonists and antagonists, the efficacy of tested compounds displayed the following rank order: resiniferatoxin>anandamide>capsaicin and 5-I-RTX= capsazepine, respectively.Conclusion: These data indicate that both TRPV1 agonists and antagonists induce significant inhibition of MCF-7 cell growth. Even though the mechanisms involved in the antiproliferative effects of TRPV1 agonists and an­tagonists should be further investigated, it has been suggested that agonists cause desensitization of the receptor, leading to al­teration in Ca2+-influx regulation. By contrast, antagonists cause a functional block of the receptor with consequent fatal dysregulation of cell homeostasis. © 2014 Korean Breast Cancer Society. All rights reserved.


Saini A.,Medical Oncology | Berruti A.,Medical Oncology | Capogna S.,Nursing School | Negro M.,Azienda Ospedaliero Universitaria San Luigi Gonzaga | And 7 more authors.
Quality of Life Research | Year: 2011

Purpose: To explore the use of CAM (Complementary/Alternative Medicine) in a population of cancer patients undergoing antineoplastic therapy, and to compare differences in sociodemographics, quality of life, and psychological features between CAM users and non-users. Methods: The study population was consecutive cancer patients undergoing antineoplastic treatment in three Piedmont cancer centers. Data were collected from anonymous questionnaires investigating CAM use or not, and what type if used, and sociodemographics, and through validated psychometric instruments to assess psychological features: Functional Assessment of Cancer Therapy-General, the Hospital Anxiety and Depression Scale, and the Mini Mental Adjustment to Cancer Scale. Results: Of the 288 evaluable patients, 52 (18.1%) reported using one or more types of CAM; the most often cited were herbs, special diets and body-based practices, such as plantar reflexology, chiropractic application, and massage. On quality of life assessment, CAM users scored lower than CAM non-users for physical wellbeing (P = 0.006); no significant differences emerged for anxiety and depression and coping styles. Conclusions: CAM use is less prevalent in northern Italy than in most other European countries. CAM users were found to have a lower quality of life than CAM non-users. © 2010 Springer Science+Business Media B.V.


Porpiglia F.,Azienda Ospedaliero Universitaria San Luigi Gonzaga | Morra I.,Azienda Ospedaliero Universitaria San Luigi Gonzaga | Bertolo R.,Azienda Ospedaliero Universitaria San Luigi Gonzaga | Manfredi M.,Azienda Ospedaliero Universitaria San Luigi Gonzaga | And 2 more authors.
Urology | Year: 2012

Objective: To report the results of mini-laparoscopic pyeloplasty (mLP) in an adult population. The feasibility of pure mLP has been previously reported in children. Material and Methods: From April 2009 to February 2010, 10 patients with ureteropelvic junction obstruction (UPJO) were enrolled in this prospective study and underwent pure mLP (using only 3-mm instruments) according to the Anderson-Hynes technique. Inclusion criteria were: age >18 years, body mass index <25, primary UPJO, and no previous surgery on the affected kidney or a history of major abdominal surgery. Demographic and perioperative data, as well as 1-, 3-, 6-, and 12-month follow-up data were collected. Results: The mean operative time was 134 minutes, and blood loss was negligible. All procedures but one were completed using only 3.9-mm ports and 3-mm instruments. No perioperative complications occurred, and no patients had computed tomography evidence of hydronephrosis at 6 months after surgery. No functional obstructions were visualized with renal scintigraphy at 12 months after surgery. All patients were satisfied with the intervention and with their cosmetic results, as assessed by the Patient Scar Assessment Questionnaire and Scoring System. Conclusions: The results of our study suggest that pure mLP in an adult population is feasible and seems to be safe and effective in the treatment of UPJO. Furthermore, the patients tolerated the procedure well and appreciated its excellent cosmetic results. Further studies are required to determine the true advantages of mLP over standard laparoscopy. © 2012 Elsevier Inc.

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