EXPRESSION OF CONCERN: Metformin inhibits growth and sensitizes osteosarcoma cell lines to cisplatin through cell cycle modulation (Oncology Reports (2014) 31 (370-375) DOI: 10.3892/or.2013.2862) Irene Quattrini, Amalia Conti, Laura Pazzaglia, Chiara Novello, Stefano Ferrari, Piero Picci, Maria Benassi Oncology Reports, 2026 Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the flow cytometric plots shown in Fig. 3 on p. 372, the C/U2OS and 48 h/U2OS, C/143B and 48 h/143B, and C/MG63 and 72 h/143B data panels, respectively, were strikingly similar, suggesting that this figure has been assembled incorrectly, and that these data were derived from a smaller number of original sources. The authors have been contacted by the Editorial Office to offer an explanation for the apparent duplication of these data panels within this figure, and we are waiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 31: 370‑375, 2014; DOI: 10.3892/or.2013.2862].
The need for clinical, genetic and radiological characterization of atypical polycystic kidney disease Matteo Righini, Cristiana Corsi, Nicola Sciascia, Valeria Aiello, Francesca Ciurli, Sarah Lerario, Gian Marco Berti, Francesca Montanari, Amalia Conti, Carlotta Pia Cristalli, Soara Menabò, Luca Caramanna, Francesco Tondolo, Daniela Turchetti, Gaetano La Manna, Irene Capelli Journal of Nephrology, 2025 Background Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a monogenic disease having a prevalence of 1:400–1000 live births. Depending on kidney imaging, patients can be subdivided into Class 1 (typical) and Class 2 (atypical). The present study aims to provide better assessment of Class 2 patients to help define their family history, together with their clinical and radiological characteristics. Methods One hundred twenty-four PKD patients with abdominal Magnetic Resonance Imaging (MRI) for the staging of ADPKD, were retrospectively analyzed, aiming to focus on Class 2 ADPKD patients. Total kidney volume and total cyst volume were evaluated, while also assessing their clinical and genetic characteristics. Results Twelve patients fulfilled the Mayo criteria for Class 2 ADPKD (two Class 2B and ten Class 2A). Extrarenal involvement was observed in 66.7% of cases, but only two subjects presented an estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73 m2. A positive family history for cystic disease was more frequent compared to other published cohorts. Only 8.3% tested positive for a likely pathogenic mutation in the PKD1 gene. Class 2B patients showed a lower height-adjusted total kidney volume, with a lower percentage of total cyst volume. Conclusion Based on our results, atypical ADPKD does not represent an uncommon condition, being present in about 10% of MRI-evaluated patients diagnosed with ADPKD. Genetic tests are frequently negative for PKD1/PKD2, and total cyst volume and residual tissue volume do not increase the prognostic value of MRI in patients with these radiological characteristics. Other tools are needed to better characterize their kidney prognosis. Graphical abstract
Integrated Use of Autosomal Dominant Polycystic Kidney Disease Prediction Tools for Risk Prognostication Constantin A. Wolff, Valeria Aiello, Elhussein A. E. Elhassan, Carlotta Cristalli, Sarah Lerario, Alexandro Paccapelo, Francesca Ciurli, Francesca Montanari, Amalia Conti, Katherine Benson, Marco Seri, Carolin B. Brigl, Julia S. Münster, Nicola Sciascia, Sebastian Kursch, Jonathan de Fallois, Gaetano La Manna, Kai-Uwe Eckardt, Nina Rank, Bernt Popp, Ria Schönauer, Peter J. Conlon, Irene Capelli, Jan Halbritter Clinical Journal of the American Society of Nephrology, 2025 Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure. Specific treatment is indicated upon observed or predicted rapid progression. For the latter, risk stratification tools have been developed independently based on either total kidney volume or genotyping as well as clinical variables. This study aimed to improve risk prediction by combining both imaging and clinical-genetic scores. Methods: We conducted a retrospective multi-center cohort study of 468 patients diagnosed with ADPKD. Clinical, imaging, and genetic data were analyzed for risk prediction. We defined rapid disease progression as an estimated glomerular filtration rate (eGFR) slope ≥3 ml/min/1.73m2/year over two years, Mayo imaging classification (MIC) 1D-1E, or a Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score of ≥7 points. Using MIC, PROPKD, and Rare Exome Variant Ensemble Learner (REVEL) scores, several combined models were designed to develop a new classification with improved risk stratification. Primary endpoints were the development of advanced chronic kidney disease (aCKD) stages G4-G5, longitudinal changes in eGFR, and clinical variables such as hypertension or urological events. Statistically, logistic regression, survival, Receiver Operating Characteristic (ROC) analyses, linear mixed models, and Cox proportional hazards models were used. Results: PKD1-genotype (p <0.001), MIC class 1E (p <0.001), early-onset hypertension (p <0.001) and early-onset urological events (p =0.003) correlated best with rapid progression in multivariable analysis. While the MIC showed satisfactory specificity (77%), the PROPKD was more sensitive (59%). Among individuals with an intermediate risk in one of the scores, integration of the other score (combined scoring) allowed for more accurate stratification. Conclusions: The combined use of both risk scores was associated with higher ability to identify rapid progressors and resulted in a better stratification, notably among intermediate risk patients.
DNAJB11 Mutation in ADPKD Patients: Clinical Characteristics in a Monocentric Cohort Valeria Aiello, Francesca Ciurli, Amalia Conti, Carlotta Pia Cristalli, Sarah Lerario, Francesca Montanari, Nicola Sciascia, Gisella Vischini, Benedetta Fabbrizio, Roberta Di Costanzo, Giulia Olivucci, Andrea Pietra, Antonia Lopez, Loretta Zambianchi, Gaetano La Manna, Irene Capelli Genes, 2024 Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a late-onset cilia-related disorder, characterized by progressive cystic enlargement of the kidneys. It is genetically heterogeneous with PKD1 and PKD2 pathogenic variants identified in approximately 78% and 15% of families, respectively. More recently, additional ADPKD genes, such as DNAJB11, have been identified and included in the diagnostic routine test for renal cystic diseases. However, despite recent progress in ADPKD molecular approach, approximately ~7% of ADPKD-affected families remain genetically unresolved. We collected a cohort of 4 families from our center, harboring heterozygous variants in the DNAJB11 gene along with clinical and imaging findings consistent with previously reported features in DNAJB11 mutated patients. Mutations were identified as likely pathogenetic (LP) in three families and as variants of uncertain significance (VUS) in the remaining one. One patient underwent to kidney biopsy and showed a prevalence of interstitial fibrosis that could be observed in ~60% of the sample. The presence in the four families from our cohort of ADPKD characteristics together with ADTKD features, such as hyperuricemia, diabetes, and chronic interstitial fibrosis, supports the definition of DNAJB11 phenotype as an overlap disease between these two entities, as originally suggested by the literature.
Molecular and Clinical Links between Drug-Induced Cholestasis and Familial Intrahepatic Cholestasis Giovanni Vitale, Alessandro Mattiaccio, Amalia Conti, Sonia Berardi, Vittoria Vero, Laura Turco, Marco Seri, Maria Cristina Morelli International Journal of Molecular Sciences, 2023 Idiosyncratic Drug-Induced Liver Injury (iDILI) represents an actual health challenge, accounting for more than 40% of hepatitis cases in adults over 50 years and more than 50% of acute fulminant hepatic failure cases. In addition, approximately 30% of iDILI are cholestatic (drug-induced cholestasis (DIC)). The liver’s metabolism and clearance of lipophilic drugs depend on their emission into the bile. Therefore, many medications cause cholestasis through their interaction with hepatic transporters. The main canalicular efflux transport proteins include: 1. the bile salt export pump (BSEP) protein (ABCB11); 2. the multidrug resistance protein-2 (MRP2, ABCC2) regulating the bile salts’ independent flow by excretion of glutathione; 3. the multidrug resistance-1 protein (MDR1, ABCB1) that transports organic cations; 4. the multidrug resistance-3 protein (MDR3, ABCB4). Two of the most known proteins involved in bile acids’ (BAs) metabolism and transport are BSEP and MDR3. BSEP inhibition by drugs leads to reduced BAs’ secretion and their retention within hepatocytes, exiting in cholestasis, while mutations in the ABCB4 gene expose the biliary epithelium to the injurious detergent actions of BAs, thus increasing susceptibility to DIC. Herein, we review the leading molecular pathways behind the DIC, the links with the other clinical forms of familial intrahepatic cholestasis, and, finally, the main cholestasis-inducing drugs.
Genetics in Familial Intrahepatic Cholestasis: Clinical Patterns and Development of Liver and Biliary Cancers: A Review of the Literature Giovanni Vitale, Alessandro Mattiaccio, Amalia Conti, Laura Turco, Marco Seri, Fabio Piscaglia, Maria Cristina Morelli Cancers, 2022 The family of inherited intrahepatic cholestasis includes autosomal recessive cholestatic rare diseases of childhood involved in bile acids secretion or bile transport defects. Specific genetic pathways potentially cause many otherwise unexplained cholestasis or hepatobiliary tumours in a healthy liver. Lately, next-generation sequencing and whole-exome sequencing have improved the diagnostic procedures of familial intrahepatic cholestasis (FIC), as well as the discovery of several genes responsible for FIC. Moreover, mutations in these genes, even in the heterozygous status, may be responsible for cryptogenic cholestasis in both young and adults. Mutations in FIC genes can influence serum and hepatic levels of bile acids. Experimental studies on the NR1H4 gene have shown that high bile acids concentrations cause excessive production of inflammatory cytokines, resistance to apoptosis, and increased cell regeneration, all risk conditions for developing hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). NR1H4 gene encodes farnesoid X-activated receptor having a pivotal role in bile salts synthesis. Moreover, HCC and CCA can emerge in patients with several FIC genes such as ABCB11, ABCB4 and TJP2. Herein, we reviewed the available data on FIC-related hepatobiliary cancers, reporting on genetics to the pathophysiology, the risk factors and the clinical presentation.
Circulating Candidate Biomarkers in Giant Cell Tumors of Bone Amalia Conti, Alessandra Luchini, Maria Serena Benassi, Giovanna Magagnoli, Michela Pierini, Martina Piccinni-Leopardi, Irene Quattrini, Serena Pollino, Piero Picci, Lance A. Liotta, Laura Pazzaglia Proteomics Clinical Applications, 2018 Approximately 5% of giant cell tumors (GCT) of bone develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict malignant progression.
Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas S. Pollino, M. Benassi, L. Pazzaglia, A. Conti, N. Bertani, A. Righi, Martina Piccinni-Leopardi, P. Picci, R. Perris Histology and Histopathology, 2018 BACKGROUND The outcome of patients with metastatic soft tissue sarcoma (STS) remains unfavourable and new therapeutic strategies are needed. The aim of this study was to determine the role of RhoGAP, XTP1/DEPDC1B and SDP35/DEPDC1A, as possible prognostic markers, to be used to identify candidate patients for more effective and personalized therapies. MATERIALS-METHODS SDP35/DEPDC1A and XTP1/DEPDC1B transcriptional levels were evaluated by Real-Time PCR in 86 primary STS and 22 paired lung metastasis. 17 normal tissues were used as control. Protein expression was evaluated by tissue microarray, including 152 paraffin-embedded STS samples and by western blot in 22 lung metastases and paired primary STS. Non-parametric and parametric analysis were used to establish the differences in gene and protein expression and prognostic factors were tested with Kaplan Meier and Cox's regression analyses. RESULTS SDP35/DEPDC1A and XTP1/DEPDC1B gene were down-regulated in adjacent normal tissues while sarcoma specimens presented high mRNA levels, significantly related to metastasis-free survival. Gene expression further increased in paired metastatic lesions. Immunohistochemical staining showed a variable expression in intensity and distribution, with a significantly higher probability of metastatic disease in patients up-regulating SDP35/DEPDC1A. Western blotting assessed high levels of proteins in STS specimens and indicated a stronger expression of SDP35/DEPDC1A in metastases when compared to primary tumours. Multivariate analyses highlighted that SDP35/DEPDC1A abundance, grade III and no history of radiation therapy were significant independent risk factors. CONCLUSIONS Our results demonstrated that increased expression of SDP35/DEPDC1A and XPT1/DEPDC1B correlates with metastatic progression and identified SDP35/DEPDC1A as an independent marker for prediction of poor prognosis.
MiR-196a expression in human and canine osteosarcomas: A comparative study Laura Pazzaglia, Leonardo Leonardi, Amalia Conti, Chiara Novello, Irene Quattrini, Luisa Montanini, Franco Roperto, Fabio Del Piero, Giovanni Di Guardo, Federica Piro, Piero Picci, Maria Serena Benassi Research in Veterinary Science, 2015
Tissue and serum IGFBP7 protein as biomarker in high-grade soft tissue sarcoma American Journal of Cancer Research, 2015
Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas Histology and Histopathology, 2007
