IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS

Italy

IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS

Italy

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Amadori D.,IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS | Aglietta M.,Institute for Cancer Research and Treatment | Alessi B.,University of Udine | Gianni L.,Infermi Hospital | And 8 more authors.
The Lancet Oncology | Year: 2013

Background: Zoledronic acid reduces skeletal-related events in patients with breast cancer, but concerns have been raised about prolonged monthly administration. We assessed the efficacy and safety of a reduced dosing frequency of zoledronic acid in women treated previously with monthly zoledronic acid. Methods: We did this non-inferiority, phase 3 trial in 62 centres in Italy. We enrolled patients with breast cancer who had one or more bone metastases and had completed 12-15 months of monthly treatment with zoledronic acid. Patients were randomly assigned with a permutated block (size four to eight) random list stratified by centre in a 1:1 ratio to zoledronic acid 4 mg once every 12 weeks or once every 4 weeks, and followed up for at least 1 year. Neither patients nor investigators were masked to treatment allocation. The primary outcome was skeletal morbidity rate (skeletal-related events per patient per year) in the intention-to-treat population. We used a non-inferiority margin of 0·19. The trial is registered with EudraCT, number 2005-004942-15. Findings: We screened 430 patients and enrolled 425, of whom 209 were assigned to the 12-week group and 216 to the 4-week group. The skeletal morbidity rate was 0·26 (95% CI 0·15-0·37) in the 12-week group versus 0·22 (0·14-0·29) in the 4-week group. The between-group difference was 0·04 and the upper limit of one-tailed 97·5% CI was 0·17, which is lower than the non-inferiority margin. The most common grade 3-4 adverse events were bone pain (56 [27%] patients in the 12-week group vs 65 [30%] in the 4-week group), nausea (24 [11%] vs 33 [15%]), and asthenia (18 [9%] vs 33 [15%]). Renal adverse events occurred in one patient (<1%) in the 12-week group versus two (1%) in the 4-week group. One patient (<1%) in the 4-week group had grade 1 acute renal failure. Osteonecrosis of the jaw occurred in four patients in the 12-week group versus three in the 4-week group. No treatment-related deaths were reported. Median N-terminal telopeptide concentration changed from baseline more in the 12-week group than in the 4-week group after 12 months (12·2% vs 0·0%; p=0·011). Interpretation: Our results raise the possibility of decreasing administration of zoledronic acid to a 12-weekly regimen to reduce exposure during the second year, while maintaining its therapeutic effects. However, the effects on N-terminal telopeptide should be investigated further before changing current practice. Funding: Novartis Farma. © 2013 Elsevier Ltd.


Ell B.,Princeton University | Qiu Q.,Princeton University | Wei Y.,Princeton University | Mercatali L.,IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS | And 4 more authors.
Journal of Biological Chemistry | Year: 2014

Background: The role of microRNA (miRNA)-23b/27b/24 in metastasis is controversial. Results: Ectopic expression of the miRNA-23b/27b/24 cluster enhances metastasis in vivo by direct inhibition of prosaposin (PSAP). Conclusion: PSAP is a metastasis suppressor that is targeted by miRNA-23b/27b/24 in breast cancer. Significance: This finding represents a novel miRNA-target interaction for therapeutic intervention of breast cancer metastasis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.


Ell B.,Princeton University | Mercatali L.,IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS | Ibrahim T.,IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS | Campbell N.,Rutgers Cancer Institute of New Jersey | And 5 more authors.
Cancer Cell | Year: 2013

Understanding the mechanism by which tumor cells influence osteoclast differentiation is crucial for improving treatment of osteolytic metastasis. Here, we report broad microRNA (miRNA) expression changes in differentiating osteoclasts after exposure to tumor-conditioned media, in part through activation of NFκB signaling by soluble intracellular adhesion molecule (sICAM1) secreted from bone-metastatic cancer cells. Ectopic expression of multiple miRNAs downregulated during osteoclastogenesis suppresses osteoclast differentiation by targeting important osteoclast genes. Intravenous delivery of these miRNAs invivo inhibits osteoclast activity and reduces osteolytic bone metastasis. Importantly, serum levels of sICAM1 and two osteoclast miRNAs, miR-16 and miR-378, which are elevated in osteoclast differentiation, correlate with bone metastasis burden. These findings establish miRNAs as potential therapeutic targets and clinical biomarkers of bone metastasis. © 2013 Elsevier Inc.


PubMed | Progression, IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS and Princeton University
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2014

MicroRNAs (miRNAs) have been shown to function as key regulators of tumor progression and metastasis. Recent studies have indicated that the miRNAs comprising the miR-23b/27b/24 cluster might influence tumor metastasis, although the precise nature of this regulation remains unclear. Here, expression of the miR-23b/27b/24 cluster is found to correlate with metastatic potential in mouse and human breast cancer cell lines and is elevated in metastatic lung lesions in human breast cancer patients. Ectopic expression of the miRNAs in the weakly metastatic mouse 4TO7 mammary tumor cell line had no effect on proliferation or morphology of tumor cells in vitro but was found to increase lung metastasis in a mouse model of breast cancer metastasis. Furthermore, gene expression profiling analysis of miRNA overexpressing 4TO7 cells revealed the direct targeting of prosaposin (PSAP), which encodes a secreted protein found to be inversely correlated with metastatic progression in human breast cancer patients. Importantly, ectopic expression of PSAP was able to suppress the metastatic phenotype in highly metastatic 4T1 and MDA-MB-231 SCP28 cells, as well as in cells ectopically expressing miR-23b/27b/24. These findings support a metastasis-promoting function of the miR-23b/27b/24 cluster of miRNAs, which functions in part through the direct inhibition of PSAP.


Marcon A.,Local Health Authority of Romagna | Bravi F.,Local Health Authority of Romagna | Foglino S.,University of Bologna | Angelastro A.,National Agency For Regional Health Services Agenas | And 4 more authors.
Annali di igiene : medicina preventiva e di comunità | Year: 2014

The Italian Ministry of Health declared oncology a priority and stressed the importance of ensuring continuity and integration in cancer care pathways. In order to monitor the quality of cancer care pathways, we need to explore patients' experience of the continuity of care, identifying the dimensions that define continuity. We found 886 relevant articles in the Pubmed database from 1987 to 5 November 2013. The search strategy for the electronic database was defined using the Population, Intervention, Comparison and Outcome(s) framework (PICO) to identify keywords. Two researchers independently reviewed records identified through the search strategy, analyzing continuity dimensions, specificity and/or transversal domains. We selected 20 articles that measure the patients' experience of continuity of care: 7 articles including 5 questionnaires [Questionnaire by King et al. 2008; Cancer care coordination Questionnaire (Cccq); Patient Continuity of Care Questionnaire (Pccq); Medical Care Questionnaire (Mcq); Continuity and Coordination of Care Questionnaire (CCCQ)]; 6 articles evaluating the relationship between patient and his/her physician (the same across the care pathway) in terms of frequency and/or dispersion; 6 articles considering one subscale of larger scales designed to evaluate the generic cancer care service patient experience; 1 revealing four organizational indicators of care pathway continuity / discontinuity. We traced 3 transversal dimensions across the individual analyses: informational, organizational, relational continuity. It follows that in order to cater to the needs of cancer patients, we need to simultaneously focus on these three dimensions along the cancer care pathway. In line with these results, we promoted the "R.In.Cu.ORAM.i" study (Networks for Integrated Treatment of colorectal and breast cancer), in Area Vasta Romagna Area (Italy), and developed a continuity of care patient-experience continuity tool.


PubMed | Local Health Authority of Romagna, Emilia Romagna Region Directorate General for Health and Social Policy, National Agency For Regional Health Services Agenas, University of Bologna and IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS
Type: Journal Article | Journal: Annali di igiene : medicina preventiva e di comunita | Year: 2014

The Italian Ministry of Health declared oncology a priority and stressed the importance of ensuring continuity and integration in cancer care pathways. In order to monitor the quality of cancer care pathways, we need to explore patients experience of the continuity of care, identifying the dimensions that define continuity.We found 886 relevant articles in the Pubmed database from 1987 to 5 November 2013. The search strategy for the electronic database was defined using the Population, Intervention, Comparison and Outcome(s) framework (PICO) to identify keywords. Two researchers independently reviewed records identified through the search strategy, analyzing continuity dimensions, specificity and/or transversal domains.We selected 20 articles that measure the patients experience of continuity of care: 7 articles including 5 questionnaires [Questionnaire by King et al. 2008; Cancer care coordination Questionnaire (Cccq); Patient Continuity of Care Questionnaire (Pccq); Medical Care Questionnaire (Mcq); Continuity and Coordination of Care Questionnaire (CCCQ)]; 6 articles evaluating the relationship between patient and his/her physician (the same across the care pathway) in terms of frequency and/or dispersion; 6 articles considering one subscale of larger scales designed to evaluate the generic cancer care service patient experience; 1 revealing four organizational indicators of care pathway continuity / discontinuity.We traced 3 transversal dimensions across the individual analyses: informational, organizational, relational continuity. It follows that in order to cater to the needs of cancer patients, we need to simultaneously focus on these three dimensions along the cancer care pathway. In line with these results, we promoted the R.In.Cu.ORAM.i study (Networks for Integrated Treatment of colorectal and breast cancer), in Area Vasta Romagna Area (Italy), and developed a continuity of care patient-experience continuity tool.

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