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Gambara G.,University of Rome La Sapienza | De Cesaris P.,University of LAquila | De Nunzio C.,SantAndrea Hospital | Ziparo E.,University of Rome La Sapienza | And 3 more authors.
Journal of Cellular and Molecular Medicine | Year: 2013

Toll-Like receptors (TLRs) are a family of evolutionary conserved transmembrane proteins that recognize highly conserved molecules in pathogens. TLR-expressing cells represent the first line of defence sensing pathogen invasion, triggering innate immune responses and subsequently priming antigen-specific adaptive immunity. In vitro and in vivo studies on experimental cancer models have shown both anti- and pro-tumoural activity of different TLRs in prostate cancer, indicating these receptors as potential targets for cancer therapy. In this review, we highlight the intriguing duplicity of TLR stimulation by pathogens: their protective role in cases of acute infections, and conversely their negative role in favouring hyperplasia and/or cancer onset, in cases of chronic infections. This review focuses on the role of TLRs in the pathophysiology of prostate infection and cancer by exploring the biological bases of the strict relation between TLRs and prostate cancer. In particular, we highlight the debated question of how reliable mutations or deregulated expression of TLRs are as novel diagnostic or prognostic tools for prostate cancer. So far, the anticancer activity of numerous TLR ligands has been evaluated in clinical trials only in organs other than the prostate. Here we review recent clinical trials based on the most promising TLR agonists in oncology, envisaging a potential application also in prostate cancer therapy. © 2013 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. Source

Wirth M.,University Clinic Carl Gustav Carus | Tammela T.,University of Tampere | Cicalese V.,Azienda Ospedaliera S. Giuseppe Moscati | Gomez Veiga F.,University of La Coruna | And 9 more authors.
European Urology | Year: 2015

Background Patients with high-risk localised prostate cancer (PCa) are at risk of developing bone metastases (BMs). Zoledronic acid (ZA) significantly reduces the incidence of skeletal complications in castration-resistant metastatic PCa versus placebo. Objective To investigate ZA for the prevention of BMs in high-risk localised PCa. Design, setting, and participants Randomised open-label multinational study with patients having at least one of the following: prostate-specific antigen ≤20 ng/ml, node-positive disease, or Gleason score 8-10. Intervention Standard PCa therapy alone or combined with 4 mg ZA intravenously every 3 mo for ≤4 yr. Outcome measurements and statistical analysis BMs were assessed using locally evaluated bone-imaging procedures (BIPs), with subsequent blinded central review. Patients with BMs, time to BMs, overall survival, and adverse events were compared between treatment groups. Results and limitations A total of 1393 of 1433 randomised patients were used for intention-to-treat (ITT) efficacy analyses, with 1040 patients with BIP-BM outcome status at 4 0.5 yr. The local urologist/radiologist diagnosed BIP-BMs in 88 of 515 patients (17.1%) in the ZA group and 89 of 525 patients (17.0%) in the control group (chi-square test: p = 0.95), with a difference between proportions of 0.1% (95% confidence interval [CI], -4.4 to 4.7) in favour of the control group. In the ITT population (n = 1393), the Kaplan-Meier estimated proportion of BMs after a median follow-up of 4.8 yr was 14.7% in the ZA group versus 13.2% in the control group (log-rank: p = 0.65). Low hot spot numbers on bone scans were confirmed as metastases with additional imaging. Central reviews of BIPs were possible only on a subset of patients. Conclusions ZA administered every 3 mo was demonstrated to be ineffective for the prevention of BMs in high-risk localised PCa patients at 4 yr. Patient summary Zoledronic acid administered every 3 mo was demonstrated to be ineffective for the prevention of bone metastases in high-risk nonmetastatic PCa patients at 4 yr. © 2014 European Association of Urology. Source

Filippi L.,Santa Maria Goretti Hospital | Pelle G.,Santa Maria Goretti Hospital | Cianni R.,Santa Maria Goretti Hospital | Scopinaro F.,SantAndrea Hospital | Bagni O.,Santa Maria Goretti Hospital
Nuclear Medicine and Biology | Year: 2015

Introduction: Our aim was to assess the prognostic value of post-treatment decrease in total lesion glycolysis (δTLG) assessed by 2-[18F]-fluorodeoxyglucose ([18F] FDG) PET-CT performed 6weeks after 90Y radioembolization (90Y RE) in patients affected by intrahepatic cholangiocarcinoma (ICC). Methods: A total of 18 patients were accepted into our department for 90Y RE. Before the procedure, all patients underwent [18F] FDG PET-CT, and total lesion glycolysis was calculated. Six weeks after 90Y administration, PET scan was performed, and δTLG was determined. Patients underwent follow up by imaging and laboratory at quarterly intervals until death or for at least 24months from 90Y RE. Furthermore, subjects were divided in 2 groups (group 1: 6weeks δTLG>50%, group 2: δTLG<50%). Kaplan-Meier method was used to achieve time to progression (TTP) and overall survival (OS) curves for each group. TTP and OS curves were compared to demonstrate eventual relevant differences between the 2 groups. Results: Seventeen patients underwent 90Y RE, and one subject was considered ineligible. According to PET Response Criteria in Solid Tumors, partial response was found in 14 patients (82.4%), stable disease in 3 (17.6%). No patient showed complete metabolic response. The mean OS for all patients was 64.5±5.0weeks. Subjects with a δTLG>50% and δTLG<50% had a mean OS of 79.6±3.6 and 43.1±2.0weeks, respectively (p<0.001). TTP resulted of 28.9±3.8weeks for the whole cohort. Patients with δTLG>50% had a significantly longer TTP (mean 36.9±3.6weeks) than those with δTLG<50% (mean 13.7±1.7weeks, p=0.001). Conclusion: Our results indicate that 90Y RE can be an effective and safe therapy for ICC. δTLG calculated on post-treatment [18F] FDG PET-CT agrees with patients' final outcome. © 2014 Elsevier Inc. Source

Tonini G.,Biomedical University of Rome | D'Onofrio L.,Biomedical University of Rome | Dell'Aquila E.,Biomedical University of Rome | Pezzuto A.,SantAndrea Hospital
Future Oncology | Year: 2013

We know that cigarette smoking is a leading preventable cause of carcinogenesis in lung cancer. Cigarette smoke is a mixture of more than 5000 chemical compounds, among which more than 60 are recognized to have a specific carcinogenic potential. Carcinogens and their metabolites (i.e., N-nitrosamines and polycyclic aromatic hydrocarbons) can activate multiple pathways, contributing to lung cell transformation in different ways. Nicotine, originally thought only to be responsible for tobacco addiction, is also involved in tumor promotion and progression with antiapoptotic and indirect mitogenic properties. Lung nodules are frequent in smokers and can be transformed into malignant tumors depending on persistant smoking status. Even if detailed mechanisms underlying tobacco-induced cancerogenesis are not completely elucitated, this report collects the emergent body of knowledge in order to simplify the extremely complex framework that links smoking exposure to lung cancer. © 2013 Future Medicine Ltd. Source

Abdolrahimzadeh S.,Azienda Policlinico Umberto I | Recupero S.M.,SantAndrea Hospital
Drugs of Today | Year: 2014

Advanced biotechnological techniques and new polymers have led to the development of many innovative intravitreal drug delivery systems. Some designs are still in an experimental phase while others have gained widespread acceptance and are commercially available. Since steroids are a mainstay of therapy for uveitis and macular edema, new intravitreal implants have been developed to provide continuous release of corticosteroids over prolonged spans of time with reduced systemic adverse effects. Today, three long-acting corticosteroid implants are commercially available: the fluocinolone acetonide implants Retisert® and Iluvien® and the dexamethasone drug delivery system Ozurdex®. They offer an alternative route in the management of macular edema due to uveitis, retinal vein occlusion, diabetes and pseudophakia. Their advantage over treatment with steroid injections and the anti-vascular endothelial growth factor ranibizumab is the long-term control of inflammation and macular edema with a reduced frequency of administration. Their potential side effects are cataract and glaucoma, therefore, careful patient selection and monitoring is essential. Further studies are warranted to define the relative efficacy and indications for each treatment option. The development of new devices is a future challenge in the strive to improve drug delivery systems. © 2014 Prous Science, S.A.U. or its licensors. All rights reserved. Source

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