Publications by authors named "Steno Sentinelli"

Our study explored frozen section reliability in prostate cancer (PCa) diagnoses and described surgical steps of a 3D magnetic resonance imaging (MRI)-ultrasound (US)-guided prostate biopsy (PB) and focal cryoablation of the index lesion (IL) in a single-setting procedure. Patients with a suspicious prostatic specific antigen (PSA) value, with a PIRADS 4 or 5 single lesion, were enrolled for trans perineal 3D MRI-US-guided PB and TRUS-guided focal cryoablation. Three cores were taken from the IL, three cores from the surrounding area, while systematic sampling was performed for the rest of the gland.

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The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry.

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Introduction: The optimal length for clinical follow-up of renal cell carcinoma (RCC) patients is unclear. We evaluated the impact of ISUP/WHO tumor grade and histological subtype on short- and long-term survival and risk of recurrence/metastasis in a large cohort of RCC patients.

Patients And Methods: We studied 1679 RCC patients from a single referral center in Italy.

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Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.

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Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the analysis of shared molecular alterations could provide new insights into the understanding of this rare disease and also therapeutic options.

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Article Synopsis
  • The study investigates intratumor heterogeneity (ITH) and clonal evolution in papillary renal cell carcinoma (pRCC) and other rare kidney cancer types, using whole-genome sequencing and DNA methylation data from 29 tumors.
  • Findings reveal that in pRCC, most driver gene mutations and somatic copy number alterations (SCNAs) are clonal, suggesting that a single biopsy is adequate for identifying key genetic drivers.
  • Additionally, type 1 pRCC lacks structural variants (SVs), while aggressive type 2 pRCC and rarer subtypes have many SVs, indicating potential prognostic implications.
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Recently cabozantinib, a tyrosine kinase inhibitor with activity against VEGF, MET, AXL, and downregulating cathepsin K in vitro, has been proposed for the treatment of advanced clear and non-clear renal cell carcinomas. Since it is well known that cathepsin K is expressed in the majority of MiT family translocation renal cell carcinomas, we investigated cathepsin K, MET, AXL, and VEGF in a large series of those tumours, looking for possible predictive markers. We collected the clinicopathological features of 34 genetically confirmed MiT family translocation renal cell carcinomas [26 Xp11 and 8 t(6;11) renal cell carcinomas] and studied them using an immunohistochemical panel including PAX8, cathepsin K, HMB45, Melan-A, CD68 (PG-M1), CK7, CA9, MET, AXL and by FISH for VEGFA and MET.

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The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients' life and aggressive forms still remain difficult to treat.

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Splenic metastasis is uncommon and is usually associated with widespread disease. Isolated splenic metastases from renal cancer are also rarer and are often an incidental finding. This eventuality may turn into a dangerous scenario due to a spontaneous splenic rupture leading to sudden death.

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Background: Clear cell RCC (ccRCC) accounts for approximately 75% of the renal cancer cases. Surgery treatment seems to be the best efficacious approach for the majority of patients. However, a consistent fraction (30%) of cases progress after surgery with curative intent.

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The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma).

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Purpose: To compare the oncologic outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) for cT1-2/N0 renal tumors and pathologically confirmed pT1-pT3a-pNx clear cell (cc)-renal cell carcinoma (RCC). Few studies compared the oncologic outcomes of PN and RN for renal tumors >7 cm.

Methods: A prospective "renal cancer" database was queried for cT<3-cN0-cM0 and pT1a-pT3a-pNx cc-RCC.

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The genetic landscape and molecular features of collecting duct carcinoma (CDC) of the kidney remain largely unknown. Herein, we performed whole exome sequencing (WES) and transcriptome sequencing (RNASeq) on 7 CDC samples (CDC1 -7). Among the 7 samples, 4 samples with matched non-tumor tissue were used for copy number analysis by SNP array data.

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A 34-year-old man was admitted in our department with a 3 months history of epigastric pain, abdominal distension and tenderness. Helical computed tomography scan and magnetic resonance imaging showed a 10 cm low-density fluid-filled polilobate cystic lesion with internal septations and calcifications located between the left lobe of the liver, shorter gastric curvature, pancreas and mesocolon. Laparoscopic exploration was performed.

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LINE-1 (L1) retrotransposons are a source of endogenous reverse transcriptase (RT) activity, which is expressed as part of the L1-encoded ORF2 protein (L1-ORF2p). L1 elements are highly expressed in many cancer types, while being silenced in most differentiated somatic tissues. We previously found that RT inhibition reduces cell proliferation and promotes differentiation in neoplastic cells, indicating that high endogenous RT activity promotes cancer growth.

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Prostate cancer is among the most commonly diagnosed male diseases and a leading cause of cancer mortality in men. There is emerging evidence that autophagy plays an important role in malignant cell survival and offers protection from the anti-cancer drugs in prostate cancer cells. AMBRA1 and the autophagic protein sequestosome-1 (SQSTM1; p62) expression were evaluated by immunohistochemistry and western blot on tissue samples from both benign and malignant prostatic lesions.

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Background: Prostate cancer (PCa) is the most common male cancer in Europe and the US. The early diagnosis relies on prostate specific antigen (PSA) serum test, even if it showed clear limits. Among the new tests currently under study, one of the most promising is the prostate cancer gene 3 (PCA3), a non-coding mRNA whose level increases up to 100 times in PCa tissues when compared to normal tissues.

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Purpose: To develop two nomograms predicting disease-free survival (DFS) and cancer-specific survival (CSS) and to externally validate them in multiple series.

Methods: Prospectively collected data from a single-centre series of 818 consecutive patients who underwent RC and PLND were used to build the nomogram. External validation was performed in 3,173 patients from 7 centres worldwide.

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Background: The involvement of the testis by metastatic medullary thyroid carcinoma has never been described before. We describe the first case of metastatic medullary thyroid carcinoma affecting testis and inguinal lymph nodes.

Case Presentation: A 73-year-old Caucasian man was referred to undergo urologic surgery due to a painless nodule in the right testis and an homolateral inguinal lymphoadenomegaly.

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Background: HPV is one of the most common sexually transmitted infections. However little is known about its prevalence in the male population and concordance with female partners.

Objectives: This cross-sectional study aimed to: (a) investigate HPV prevalence and genotype distribution among a series of stable male sexual partners of CIN/HPV positive women and (b) assess HPV infection and type-specific concordance between partners.

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Background: The urokinase plasminogen activating system (uPAS) is implicated in neoplastic progression and high tissue levels of uPAS components correlate with a poor prognosis in different human cancers. Despite that, relative few studies are available on the expression and function of the uPAS components in human seminomas. In the present study we characterized the expression of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR) and the uPA inhibitors PAI-1 and PAI-2 in normal human testis and seminomas.

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Purpose: To compare the toxicity and efficacy of hypofractionated (62 Gy/20 fractions/5 weeks, 4 fractions per week) vs. conventional fractionation radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate cancer.

Methods And Materials: From January 2003 to December 2007, 168 patients were randomized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles.

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Background: Recent studies have underlined the role of tumor cells in the endogenous synthesis of pro-inflammatory molecules. We tested whether malignant progression in prostate cancer was associated with the activation of a phenotype typical of the innate immune system.

Methods: The expression of a set of molecules involved in tissue inflammation and repair was measured by real-time PCR and Western blot analysis in prostate samples in the absence or slight presence of a detectable leukocyte infiltrate.

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The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor beta (ERbeta). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production.

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Purpose: The aim was to correlate the color Doppler flow activity pre- and postradiotherapy, using transrectal color Doppler ultrasonography (CDUS) and the 2 year positive biopsy rate after radiotherapy in patients with prostate cancer.

Methods And Materials: Analysis was carried out in 69 out of 160 patients who had undergone treatment with 3D-conformal radiotherapy (3D-CRT) to prostate and seminal vesicles. Patients were randomized to receive 80 Gy in 40 fractions in 8 weeks (arm A) and 62 Gy in 20 fractions in 5 weeks, 4 fractions per week (arm B).

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