Browsing by Author "Scarpelli, Marina"
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Item Adjuvant therapy in renal cell carcinoma: is it the right strategy to inhibit VEGF?(AME Publishing, 2021-03) Mollica, Veronica; Rizzo, Alessandro; Di Nunno, Vincenzo; Santoni, Matteo; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Cimadamore, Alessia; Montironi, Rodolfo; Massari, Francesco; Pathology and Laboratory Medicine, School of MedicineDespite several clinical trials have assessed different agents in the adjuvant setting, renal cell carcinoma (RCC) still remains a disease orphan of an effective adjuvant treatment. In fact, systemic therapies targeting angiogenesis that have been observed to be effective in metastatic setting failed to show an improvement in terms of clinical outcomes when used ad adjuvant treatments. In this study, we performed a meta-analysis of 5 randomized clinical trials to assess the impact of tyrosine kinase inhibitors (TKIs) targeting angiogenesis after surgery: ASSURE, S-TRAC, PROTECT, ATLAS, SORCE. Among the 6,531 patients assessed, we confirmed the lack of efficacy of adjuvant treatments in terms of disease-free survival (DFS) (pooled-HR 0.93, 95% CI, 0.84–1.02, P=0.16) and overall survival (OS) (pooled-HR 0.98, 95% CI, 0.88–1.09, P=0.54). To the best of our knowledge, we still ignore why some treatments active in the metastatic setting do not show similar efficacy as adjuvant treatment. Exploring possible reasons of this apparently conflicting results is important as it may offer new insights that should be evaluated in next generation adjuvant trials. Immune checkpoint inhibitors (ICIs) have reported significant results—as monotherapy or in combinations with other anticancer agents—in metastatic setting, and the results of trials evaluating these agents in the adjuvant setting are awaited.Item Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications(MDPI, 2020-12) Aurilio, Gaetano; Cimadamore, Alessia; Mazzucchelli, Roberta; Lopez-Beltran, Antonio; Verri, Elena; Scarpelli, Marina; Massari, Francesco; Cheng, Liang; Santoni, Matteo; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineAround 80–90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient’s response to androgen ablation therapy is variable, and 20–30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs.Item Another one in the chamber: cabozantinib for patients with metastatic non clear cell renal cell carcinoma(AME Publishing Company, 2019-07) Di Nunno, Vincenzo; Massari, Francesco; Mollica, Veronica; Cimadamore, Alessia; Santoni, Matteo; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineItem Circulating Tumor Cells in Renal Cell Carcinoma: Recent Findings and Future Challenges(Frontiers, 2019-04-05) Santoni, Matteo; Cimadamore, Alessia; Cheng, Liang; Lopez-Beltran, Antonio; Battelli, Nicola; Massari, Francesco; Scarpelli, Marina; Galosi, Andrea Benedetto; Bracarda, Sergio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineItem Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter(Sage, 2019-01-08) Bianconi, Maristella; Cimadamore, Alessia; Faloppi, Luca; Scartozzi, Mario; Santoni, Matteo; Lopez-Beltran, Antonio; Cheng, Liang; Scarpelli, Marina; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineUpper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1-2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic UCs. Although initial response rates are high, the median survival with combination chemotherapy is about 15 months. In first-line chemotherapy several cisplatin-based regimens have been proposed. For patients with advanced UC who progress to first-line treatment, the only product licensed in Europe is vinflunine, a third-generation, semisynthetic, vinca alkaloid. Better response rates (15-60%), with higher toxicity rates and no overall survival (OS) benefit, are generally achieved in multidrug combinations, which often include taxanes and gemcitabine. The US FDA has recently approved five agents targeting the programmed death-1 and programmed death ligand-1 pathway as a second-line therapy in patients with locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy. Potential therapeutic targets are present in 69% of tumours analyzed. Specific molecular alterations include those involved in the RTK/Ras/PI(3)K, cell-cycle regulation and chromatin-remodeling pathways, many of them have either targeted therapies approved or under investigation. Angiogenic agents, anti-epidermal growth factor receptor therapy, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathway inhibitors and immunotherapeutic drugs are being successfully investigated.Item Contemporary grading of prostate cancer: 2017 update for pathologists and clinicians(Wolters Kluwer, 2017-08-04) Gasparrini, Silvia; Cimadamore, Alessia; Scarpelli, Marina; Massari, Francesco; Doria, Andrea; Mazzucchelli, Roberta; Cheng, Liang; Lopez-Beltran, Antonio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineThe Gleason grading system for prostate cancer (PCa) was developed in the 1960s by DF Gleason. Due to changes in PCa detection and treatment, the application of the Gleason grading system has changed considerably in pathology routine practice. Two consensus conferences were held in 2005 and in 2014 to update PCa Gleason grading. This review provides a summary of the changes in the grading of PCa from the original Gleason grading system to the prognostic grade grouping, as well as a discussion of the clinical significance of the percentage of Gleason patterns 4 and 5.Item Digital diagnostics and artificial intelligence in prostate cancer treatment in 5 years from now(AME, 2021-03) Cimadamore, Alessia; Cheng, Liang; Scarpelli, Marina; Lopez-Beltran, Antonio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineItem Digital pathology and COVID-19 and future crises: pathologists can safely diagnose cases from home using a consumer monitor and a mini PC(BMJ Publishing Group, 2020-07-30) Cimadamore, Alessia; Lopez-Beltran, Antonio; Scarpelli, Marina; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of MedicineCOVID-19 pandemic has a profound impact on routine pathology services.1 Digital pathology can play a role ‘to safeguarding clinical services and pathology-based research in the current climate and in the future’.1 This digital-based approach to diagnosis represents a new way in the evaluation of surgical pathology slides from formalin-fixed paraffin-embedded tissue (FFPE). It makes the pathologist free from the constraints of using an optical microscope in his/her office. At the same time, it can have an effect on ‘social interaction’ among pathologists, including their interplay with clinicians and even patients. A recent contribution from our group briefly dealt with the changing aspects of such a relationship at the peak of the COVID-19 pandemic.2 The aim was to try to foresee how the kind of experience acquired during the pandemic could have influenced the approach to histopathology in the digital and postdigital eras. Our laboratories as well as many others worldwide, even though not yet ready for substituting and replacing the optical microscope with a scanner for digital pathology image creation, already have digital cameras and scanners for ‘sharing images and consulting, teaching and communicating with clinicians and patients’.Item Does prostate acinar adenocarcinoma with Gleason Score 3 + 3 = 6 have the potential to metastasize?(BioMed Central, 2014-10-18) Montironi, Rodolfo; Scarpelli, Marina; Mazzucchelli, Roberta; Lopez-Beltran, Antonio; Santoni, Matteo; Briganti, Alberto; Montorsi, Francesco; Cheng, Liang; Department of Pathology & Laboratory Medicine, School of MedicineBackground: There is a worldwide debate involving clinicians, uropathologists as well as patients and their families on whether Gleason score 6 adenocarcinoma should be labelled as cancer. Case description: We report a case of man diagnosed with biopsy Gleason score 6 acinar adenocarcinoma and classified as low risk (based on a PSA of 5 ng/mL and stage cT2a) whose radical prostatectomy specimen initially showed organ confined Gleason score 3 + 3 = 6, WHO nuclear grade 3, acinar adenocarcinoma with lymphovascular invasion and secondary deposit in a periprostatic lymph node. When deeper sections were cut to the point that almost all the slice present in the paraffin block was sectioned, a small tumor area (<5% of the whole tumor) of Gleason pattern 4 (poorly formed glands) was found in an extraprostatic position. Conclusion: The epilogue was that the additional finding changed the final Gleason score to 3 + 3 = 6 with tertiary pattern 4 and the stage to pT3a. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/13000_2014_190Item Emerging immunotherapeutic strategies targeting telomerases in genitourinary tumors(Elsevier, 2018) Carrozza, Francesco; Santoni, Matteo; Piva, Francesco; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Montironi, Rodolfo; Battelli, Nicola; Tamberi, Stefano; Pathology and Laboratory Medicine, School of MedicineTelomerase activity and telomere length are essential for the pathogenesis of several human diseases, including genitourinary tumors. Telomerase constitutes a complex system that includes human telomerase reverse transcriptase (hTERT), human telomerase RNA component (hTR) and telomerase associated protein 1 (TEP1), which are overexpressed in tumor cells compared to normal cells and are involved in the carcinogenesis and progression of renal cell carcinoma (RCC), bladder (BC) and prostate cancer (PCa). In addition, telomerase degraded peptide fragments expressed on the surface of tumor cells lead to their recognition by immune cells. On this scenario, in vitro and in vivo studies have shown effective anti-tumor activity of hTERT-tailored strategies in genitourinary tumors, including active immunotherapy with hTERT-peptide vaccines and passive immunotherapy with hTERT-transduced T cell infusion. This review emphasizes the role of telomerase in the carcinogenesis and progression of genitourinary tumors, thus underlying the potential of emerging telomerase-tailored immunotherapies in these patients.