30 results on '"Elena Maldi"'
Search Results
2. The neuronal protein Neuroligin 1 promotes colorectal cancer progression by modulating the APC/β-catenin pathway
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Margherita Pergolizzi, Laura Bizzozero, Federica Maione, Elena Maldi, Claudio Isella, Marco Macagno, Elisa Mariella, Alberto Bardelli, Enzo Medico, Caterina Marchiò, Guido Serini, Federica Di Nicolantonio, Federico Bussolino, and Marco Arese
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Gene Expression Regulation, Neoplastic ,Mice ,Cancer Research ,Oncology ,Cell Adhesion Molecules, Neuronal ,Cell Line, Tumor ,Adenomatous Polyposis Coli Protein ,Animals ,Humans ,Colorectal Neoplasms ,Wnt Signaling Pathway ,beta Catenin - Abstract
Background Colorectal cancer (CRC) remains largely incurable when diagnosed at the metastatic stage. Despite some advances in precision medicine for this disease in recent years, new molecular targets, as well as prognostic/predictive markers, are highly needed. Neuroligin 1 (NLGN1) is a transmembrane protein that interacts at the synapse with the tumor suppressor adenomatous polyposis Coli (APC), which is heavily involved in the pathogenesis of CRC and is a key player in the WNT/β-catenin pathway. Methods After performing expression studies of NLGN1 on human CRC samples, in this paper we used in vitro and in vivo approaches to study CRC cells extravasation and metastasis formation capabilities. At the molecular level, the functional link between APC and NLGN1 in the cancer context was studied. Results Here we show that NLGN1 is expressed in human colorectal tumors, including clusters of aggressive migrating (budding) single tumor cells and vascular emboli. We found that NLGN1 promotes CRC cells crossing of an endothelial monolayer (i.e. Trans-Endothelial Migration or TEM) in vitro, as well as cell extravasation/lung invasion and differential organ metastatization in two mouse models. Mechanistically, NLGN1 promotes APC localization to the cell membrane and co-immunoprecipitates with some isoforms of this protein stimulates β-catenin translocation to the nucleus, upregulates mesenchymal markers and WNT target genes and induces an “EMT phenotype” in CRC cell lines Conclusions In conclusion, we have uncovered a novel modulator of CRC aggressiveness which impacts on a critical pathogenetic pathway of this disease, and may represent a novel therapeutic target, with the added benefit of carrying over substantial knowledge from the neurobiology field.
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- 2022
3. Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study
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Valentina Tuninetti, Eleonora Ghisoni, Sandro Pignata, Elisa Picardo, Francesco Raspagliesi, Claudia Andreetta, Elena Maldi, Grazia Artioli, Serafina Mammoliti, Lucia Zanchi, Angelica Sikokis, Nicoletta Biglia, Alessandro Parisi, Vincenzo Dario Mandato, Claudia Carella, Gennaro Cormio, Marco Marinaccio, Andrea Puppo, Biagio Paolini, Lucia Borsotti, Giulia Scotto, Margherita Turinetto, Dario Sangiolo, Massimo Di Maio, and Giorgio Valabrega
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Cancer Research ,ovarian cancer ,PARP inhibitor ,Oncology ,Ki67 ,niraparib ,rucaparib - Abstract
Background: There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC). Methods: MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010–2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off. Results: A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0–99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials. Conclusions: Ki67 at diagnosis did not discriminate responders to PARPi.
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- 2023
4. A pancreatic metastasis from a colon carcinoma mimicking a primary tumor diagnosed by EUS-guided fine-needle biopsy
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Stefano Rizza, Elena Maldi, Cristiana Laudi, Alfredo Mellano, Alberto Pisacane, and Teresa Staiano
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Hepatology ,Gastroenterology ,Radiology, Nuclear Medicine and imaging - Published
- 2022
5. A non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine
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Carlos Sebastian, Christina Ferrer, Maria Serra, Jee-Eun Choi, Nadia Ducano, Alessia Mira, Manasvi S. Shah, Sylwia A. Stopka, Andrew J. Perciaccante, Claudio Isella, Daniel Moya-Rull, Marianela Vara-Messler, Silvia Giordano, Elena Maldi, Niyati Desai, Diane E. Capen, Enzo Medico, Murat Cetinbas, Ruslan I. Sadreyev, Dennis Brown, Miguel N. Rivera, Anna Sapino, David T. Breault, Nathalie Y. R. Agar, and Raul Mostoslavsky
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Animals ,Cell Transformation, Neoplastic ,Glycolysis ,Intestines ,Mice ,Pyruvate Dehydrogenase Acetyl-Transferring Kinase ,Neoplasms ,Sirtuins ,Neoplastic ,Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,Cell Transformation ,General Biochemistry, Genetics and Molecular Biology - Abstract
Although reprogramming of cellular metabolism is a hallmark of cancer, little is known about how metabolic reprogramming contributes to early stages of transformation. Here, we show that the histone deacetylase SIRT6 regulates tumor initiation during intestinal cancer by controlling glucose metabolism. Loss of SIRT6 results in an increase in the number of intestinal stem cells (ISCs), which translates into enhanced tumor initiating potential in APCmin mice. By tracking down the connection between glucose metabolism and tumor initiation, we find a metabolic compartmentalization within the intestinal epithelium and adenomas, where a rare population of cells exhibit features of Warburg-like metabolism characterized by high pyruvate dehydrogenase kinase (PDK) activity. Our results show that these cells are quiescent cells expressing +4 ISCs and enteroendocrine markers. Active glycolysis in these cells suppresses ROS accumulation and enhances their stem cell and tumorigenic potential. Our studies reveal that aerobic glycolysis represents a heterogeneous feature of cancer, and indicate that this metabolic adaptation can occur in non-dividing cells, suggesting a role for the Warburg effect beyond biomass production in tumors.
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- 2021
6. How Risk Factors Affect Head and Neck Squamous Cell Carcinoma (HNSCC) Tumor Immune Microenvironment (TIME): Their Influence on Immune Escape Mechanisms and Immunotherapy Strategy
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Danilo Galizia, Silvia Minei, Elena Maldi, Giovanna Chilà, Alessio Polidori, and Marco Carlo Merlano
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Medicine (miscellaneous) ,General Biochemistry, Genetics and Molecular Biology - Abstract
Most head and neck squamous cell carcinomas (HNSCCs) are caused by lifestyle, such as cigarette smoking, or by viruses, such as human papillomavirus (HPV) and Epstein–Barr virus (EBV). HNSCC remains a clinical challenge, notwithstanding the improvements observed in the past years, involving surgery, radiotherapy, and chemotherapy. Recurrent/metastatic (R/M) disease represents an unmet clinical need. Immunotherapy has improved the prognosis of a small proportion of these patients, but most still do not benefit. In the last decade, several preclinical and clinical studies have explored the HNSCC tumor immune microenvironment (TIME), identifying important differences between smoking-associated and virus-associated HNSCCs. This review aims to present how different etiologies affect the HNSCC TIME, affecting immune escape mechanisms and sensitivity to immunotherapy.
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- 2022
7. A Rare Nasopharyngeal Presentation of Amyloidosis
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Erika Crosetti, Giovanni Succo, Elena Maldi, and Andrea Manca
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Larynx ,Pathology ,medicine.medical_specialty ,Amyloid ,Disease ,Pathogenesis ,03 medical and health sciences ,head and neck diseases ,0302 clinical medicine ,Nasopharynx ,Medical Illustration ,medicine ,Humans ,amyloidosis ,localized ,nasopharynx ,030223 otorhinolaryngology ,Multiple myeloma ,Aged, 80 and over ,business.industry ,Amyloidosis ,Standard treatment ,medicine.disease ,medicine.anatomical_structure ,Nasopharyngeal Diseases ,Otorhinolaryngology ,Female ,Presentation (obstetrics) ,business ,030217 neurology & neurosurgery - Abstract
Amyloidosis is a heterogeneous group of diseases characterized by the extracellular deposition of insoluble proteins whose pathogenesis is not yet fully understood. The deposition of amyloid proteins can be systemic or localized, idiopathic or related to systemic diseases, mostly multiple myeloma or chronic inflammatory diseases. Localized head and neck amyloidosis is a rare entity, mainly involving the larynx. Given the rarity of the disease and the absence of a lasting follow-up protocol, there is no standard treatment defined for localized amyloidosis. We report a rare case of localized nasopharyngeal amyloidosis, treated with complete transoral resection and confirmed by histological examination.
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- 2020
8. Endoscopic submucosal dissection for chronically bleeding gastric metastasis from undifferentiated liposarcoma
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Endrit Shahini, Giovanni Grignani, T. Staiano, and Elena Maldi
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Male ,medicine.medical_specialty ,Hepatology ,Endoscopic Mucosal Resection ,business.industry ,Gastric metastasis ,Stomach ,Gastroenterology ,Endoscopic submucosal dissection ,Liposarcoma ,medicine.disease ,Gastric Mucosa ,Stomach Neoplasms ,medicine ,Humans ,Radiology ,business ,Gastrointestinal Hemorrhage ,Aged - Published
- 2020
9. A Strange Association Between A Rectum- Infiltrating / Metastatic Dedifferentiated Chordoma And Schmidt’s Syndrome
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T. Staiano, Elena Maldi, and Endrit Shahini
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Dedifferentiated chordoma ,Tumor microenvironment ,medicine.anatomical_structure ,S syndrome ,Antitumor immunity ,business.industry ,medicine.medical_treatment ,T cell ,Cancer research ,medicine ,Rectum ,Immunotherapy ,business - Published
- 2019
10. Growth rate and site of pulmonary metastasis to predict lung relapse and overall survival in patients affected by bone and soft tissue sarcomas (B-STS)
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Giulia Manessi, Alberto Pisacane, Claudio Mossetti, Andrea Mogavero, Bruno Vincenzi, Enrico Ruffini, Delia Campanella, Sandra Aliberti, Alessandro Minelli, Alessandra Merlini, Raimondo Piana, Elena Maldi, Giovanni Grignani, Lorenzo D'Ambrosio, Maria Cristina Bruna, Tiziana Robba, and Francesco Tolomeo
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Oncology ,Cancer Research ,medicine.medical_specialty ,Lung ,business.industry ,Soft tissue ,medicine.anatomical_structure ,Internal medicine ,medicine ,Overall survival ,Pulmonary metastasis ,In patient ,business - Abstract
11571 Background: Despite surgically resectable pulmonary metastases may lead to cure patients with B-STS (Chudgar NP 2017), a substantial proportion of patients will eventually relapse. Presently, patient selection is based on unique organ involvement, number of metastases, interval between previous surgery and pulmonary progression or relapse. We assessed the impact of anatomical site of metastasis into the lung (as if the pleural site might ease further tumor spreading) and nodule growth rate as additional predictive/prognostic factors of lung progression-free survival (L-PFS) and overall survival (OS). Methods: In our prospectively collected database, we retrospectively evaluated patients operated for B-STS pulmonary progression at 3 different centers from 2005 to 2019. Beyond patients’ clinical features at both baseline and disease progression in the lungs, we focused on whether the relapse occurred into the parenchyma or nearby the pleura (Welter S 2012); secondly, we estimated lung metastasis growth rate, defined as tumor doubling time (TDT) (Nakamura T 2011). Statistical analyses were carried out with IBM SPSS (v. 20.0). Survival outcomes were estimated by Kaplan-Meier method. Hazard ratios (HR) were estimated by Cox regression. Multivariate analysis was performed for both L-PFS and OS according to Cox proportional hazard model. All tests were 2-sided with their corresponding 95% confidence intervals (CI95%). Results: We identified 138 patients who underwent lung metastasectomy [(F=66 (48%); median age at surgery 50 (14-78)]. Median PFS and L-PFS were 8.7 months (CI95% 6.6-10.9) and 8.6 months (CI95% 6.2-11.0), respectively. Median OS was 40.6 months (CI 95% 32.8-48.5). Univariate analysis showed a statistically significant impact of the following variables for both L-PFS and OS: ECOG 0, nodule number 40 days. Disease-free interval ≤ 24 months and absence of metastases at diagnosis showed significant correlation with L-PFS and OS, respectively. At multivariate analyses the following variables retained statistical significance for L-PFS: TDT >40 days (HR 0.53, CI95% 0.31-0.93, p=0.028); nodule number 40 days (HR 0.36, CI95% 0.18-0.72, p=0.004), nodule number
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- 2021
11. T02.01.16 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR CHRONICALLY BLEEDING GASTRIC METASTASIS OF DEDIFFERENTIATED LIPOSARCOMA: A CASE REPORT AND LITERATURE REVIEW
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C. Laudi, G. Galatola, Endrit Shahini, Elena Maldi, T. Staiano, and G. Grignani
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medicine.medical_specialty ,Dedifferentiated liposarcoma ,Hepatology ,business.industry ,Gastric metastasis ,Gastroenterology ,medicine ,Endoscopic submucosal dissection ,Radiology ,business - Published
- 2020
12. Fibroadenoma
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Elena Maldi and Anna Sapino
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- 2019
13. Open partial horizontal laryngectomy using CO
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Erika, Crosetti, Marco, Fantini, Elena, Maldi, Davide, Balmativola, and Giovanni, Succo
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Lasers, Gas ,Humans ,Laryngectomy ,Carbon Dioxide ,Larynx ,Laryngeal Neoplasms - Abstract
The application of COThe current video shows three examples of open partial horizontal laryngectomies (OPHLs) performed using COCOIn our experience, the application of CO
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- 2019
14. Fibroadenoma
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Elena Maldi and Anna Sapino
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- 2018
15. T06.02.18 A STRANGE ASSOCIATION BETWEEN A RECTUM-INFILTRATING/METASTATIC DEDIFFERENTIATED CHORDOMA AND SCHMIDT'S SYNDROME
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T. Staiano, G. Galatola, Elena Maldi, C. Laudi, and Endrit Shahini
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Pathology ,medicine.medical_specialty ,Dedifferentiated chordoma ,medicine.anatomical_structure ,S syndrome ,Hepatology ,business.industry ,Gastroenterology ,medicine ,Rectum ,business - Published
- 2020
16. Abstract 1677: Assays of conventional chemotherapeutics and targeted drugs for ovarian cancer using patient derived models
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Mercedes Jimenez-Linan, Douglas Hall, Giorgio Valabrega, Mariaflavia Di Renzo, Fulvio Borella, Gloria Mittica, Raffaele A. Calogero, Sonia Capellero, Martina Olivero, Maddalena Arigoni, Dionyssios Katsaros, Jessica Erriquez, Anna L. Paterson, Marisa Ribotta, Enrico Berrino, Elena Maldi, Riccardo Ponzone, Eleonora Ghisoni, Marco Vaira, James D. Brenton, Giovanna Di Nardo, Silvana Privitera, Concetta D'Ambrosio, and Tiziana Venesio
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Cancer Research ,Stromal cell ,business.industry ,Buparlisib ,Cancer ,medicine.disease ,Carboplatin ,chemistry.chemical_compound ,Oncology ,chemistry ,medicine ,Cancer research ,Immunohistochemistry ,Ovarian cancer ,business ,PI3K/AKT/mTOR pathway ,Exome sequencing - Abstract
Patients with advanced ovarian cancers have experienced little improvement in overall survival with standard treatments. We used patient derived models to accelerate the discovery of treatment options. We developed a platform of Patient Derived Xenografts (PDX), by implanting and propagating patient's tumor samples collected at surgery in severely immunocompromised mice. From each PDX line we derived short term cultures of PDX Derived Tumor Cells (PDTCs). We envisioned that the weakness of PDXs and PDTCs, i.e. lack of human stromal and immune cells, might be instrumental to link tumor biomarkers to treatments. We have successfully propagated 49 PDX lines from metastatic EOC, which were fully characterized as far as histology, immunohistochemistry of epithelial and tissue specific markers and presence of TP53 and BRCA1/2 mutations. On PDTCs cultures we first assessed sensitivity to Carboplatin, currently used as first-line drug in ovarian cancer treatment. Of PDX lines derived from naïve metastatic HGS-EOC copy number variations and whole exome sequencing analyses were carried out, in order to identify putative and actionable cancer genes. Thus, on PDTCs we assayed also approved or experimental targeted drugs as monotherapy or in combinations. In one PDX line we identified a possibly loss-of-function mutation (W624R) of the PIK3R1 gene (encoding the p85alpha regulatory subunit of PI3K) with an allele frequency of 0.9, which could result in activation of the PI3K pathway. Several PI3K inhibitors were assayed on PDTCs of this PDX line harboring the PIK3R1W624R. Buparlisib (a Pan Class I PI3Ki) showed the ability to block proliferation of the PDTCs and the growth of the relevant PDXs in vivo. Altogether these data show that Patient Derived models are invaluable tools to unveil actionable pathways for the treatment of advanced/metastatic HGS-EOC. Citation Format: Concetta D'Ambrosio, Jessica Erriquez, Maddalena Arigoni, Sonia Capellero, Gloria Mittica, Eleonora Ghisoni, Fulvio Borella, Dionyssios Katsaros, Silvana Privitera, Marisa Ribotta, Elena Maldi, Giovanna Di Nardo, Enrico Berrino, Tiziana Venesio, Riccardo Ponzone, Marco Vaira, Douglas Hall, Mercedes Jimenez-Linan, Anna Paterson, Giorgio Valabrega, Raffaele Calogero, James Brenton, Mariaflavia Di Renzo, Martina Olivero. Assays of conventional chemotherapeutics and targeted drugs for ovarian cancer using patient derived models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1677.
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- 2020
17. Fimbrial Cells Exposure to Catalytic Iron Mimics Carcinogenic Changes
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Diletta Francesca Squarzanti, Debora Lattuada, Renzo Boldorini, Giorgio Bolis, Alessandro Bulfoni, Paola Colombo, Barbara Colciaghi, Vera Morsanuto, Francesca Uberti, Elena Maldi, and Claudio Molinari
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MAPK/ERK pathway ,Cell Survival ,Iron ,Immunocytochemistry ,Biology ,Nitric Oxide ,Models, Biological ,Proto-Oncogene Proteins c-myc ,Phosphatidylinositol 3-Kinases ,Western blot ,medicine ,Humans ,Viability assay ,Extracellular Signal-Regulated MAP Kinases ,Protein kinase B ,Cells, Cultured ,Fallopian Tubes ,PI3K/AKT/mTOR pathway ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,Obstetrics and Gynecology ,Epithelial Cells ,medicine.disease ,Cell biology ,Oxidative Stress ,Cell Transformation, Neoplastic ,Ki-67 Antigen ,medicine.anatomical_structure ,Oncology ,ras Proteins ,Cancer research ,Female ,Tumor Suppressor Protein p53 ,Ovarian cancer ,Proto-Oncogene Proteins c-akt ,Fallopian tube - Abstract
Recent evidence strongly suggests that the fallopian tube is a site of origin of ovarian cancer. Although histological data show iron deposition in the fallopian tubes, its role remains unclear. To establish whether catalytic iron has a possible role in ovarian carcinogenesis, we isolated human fimbrial secretory epithelial cells (FSECs).Fimbrial secretory epithelial cells, isolated from women undergoing isteroannessiectomy, were treated with different doses of catalytic iron (0.05-100 mM) to study cell viability; NO production; p53, Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc protein expressions through Western blot analysis; and immunocytochemistry or immunofluorescence.In FSECs treated with catalytic iron for up to 6 days, we observed an increase in cell viability, NO production, and p53, pan-Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc activations (P0.05) in a dose-dependent and time-dependent manner. These same results were also observed in FSECs maintained for respectively 2 and 4 weeks in the absence of catalytic iron after 6 days of stimulation.Our model aimed at studying the main nongenetic risk factor for ovarian cancer, providing an alternative interpretation for the role of menstruation in increasing risk of this pathology. This in vitro model mimics several features of the precursor lesions and opens new scenarios for further investigations regarding the correlation between damages produced by repeated retrograde menstruation carcinogenic stimuli.
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- 2015
18. Antitumor activity of pazopanib (P) and trametinib (T) in preclinical models of osteosarcoma (OS)
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Dario Sangiolo, Maria Laura Centomo, Alessandra Merlini, Giulia Chiabotto, Umberto Miglio, Federica Capozzi, Lorenzo D'Ambrosio, Enrico Berrino, Ymera Pignochino, Elena Maldi, Maja Todorovic, Anna Sapino, Giovanni Grignani, Tiziana Venesio, Massimo Aglietta, and Lucia Napione
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Trametinib ,Antitumor activity ,Cancer Research ,biology ,business.industry ,medicine.disease ,Receptor tyrosine kinase ,Pazopanib ,Oncology ,biology.protein ,Cancer research ,Medicine ,Osteosarcoma ,business ,medicine.drug - Abstract
e22509 Background: Receptor tyrosine kinases (RTKs) and their signal transducers are suitable targets for the treatment of advanced OS. We evaluated the antitumor activity of the RTK inhibitor P and the MEK inhibitor T and deeply investigated molecular mechanisms behind their activity and potential escape. Methods: Flow cytometry and western blot analyses were carried out in 7 OS cell lines to study the expression of RTK P targets and the activation of their pathways, respectively. Cell viability and colony growth were evaluated after 72h and 7-day treatment respectively, with scalar doses of both single agents and their constant combination. Cell cycle distribution and apoptosis were evaluated by flow cytometry after 72h. In vivo antitumor activity was studied in NOD/SCID mice bearing MNNG-HOS xenografts after 3 weeks of treatment. Cell migration was studied by scratch assays. The involvement of MAPK-PI3K pathway key transducers was explored by Vantage 3D RNA Panel and Nanostring technology, validated by western blot and confirmed by silencing experiments. Results: P targets are expressed on OS cell lines and their pathways are activated. P+T have synergistic antitumor activity (combination index < 1) in OS cell lines by inducing apoptosis (6/7) and inhibiting both ERK1/2(7/7) and AKT (7/7). Furthermore, in vivo antitumor activity was shown in OS bearing mice (tumor volume: P+T/untreated = 0.036, p = 0.002). P+T significantly down-modulated RTK EphaA2 (mean log2 fold change RNA P+T/untreated = -2.02±0.50) and induced Janus kinase MEK6 (mean log2 fold change RNA P+T/untreated = 2.9±0.51). EphA2 silencing reduced cellular proliferation and migration of OS cells. Impeding MEK6-up-regulation in P+T treated cells significantly increased the antitumor effect (51.5±14.3%) of the studied drugs. Conclusions: P+T exert antitumor activity in OS preclinical models through ERK and AKT inhibition and EphA2 downmodulation. MEK6-upregulation after P+T is likely implied in escape mechanism.
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- 2019
19. Stewart-Treves Syndrome of the Breast after Quadrantectomy for Breast Carcinoma
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Roberto Franchini, Enrico Colombo, Elisa Zavattaro, Benedetta Miglino, Renzo Boldorini, Paolo Boggio, Elena Maldi, Rossana Tiberio, and Stefano Astolfi
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Hemangiosarcoma ,Treatment outcome ,Breast Neoplasms ,Breast cancer ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Lymphangiosarcoma ,Mastectomy ,Stewart–Treves syndrome ,Aged ,business.industry ,medicine.disease ,Treatment Outcome ,Female ,Surgery ,business ,Breast carcinoma ,Quadrantectomy - Published
- 2015
20. Reciprocal Potentiation of the Antitumoral Activities of FK866, an Inhibitor of Nicotinamide Phosphoribosyltransferase, and Etoposide or Cisplatin in Neuroblastoma Cells
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Cristina Travelli, Fabio Di Lisa, Gian Cesare Tron, Pier Luigi Canonico, Nina Kaludercic, Armando A. Genazzani, Valentina Drago, Ubaldina Galli, Elena Maldi, and Renzo Boldorini
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Programmed cell death ,Adenosine ,Cell Survival ,Nicotinamide phosphoribosyltransferase ,Down-Regulation ,Antineoplastic Agents ,Ubiquitin-Activating Enzymes ,Pharmacology ,Biology ,Autophagy-Related Protein 7 ,Neuroblastoma ,chemistry.chemical_compound ,Adenosine Triphosphate ,Piperidines ,Cell Line, Tumor ,Autophagy ,medicine ,Humans ,Annexin A5 ,Nicotinamide Phosphoribosyltransferase ,Etoposide ,Cell Nucleus ,Cisplatin ,Acrylamides ,Cell Death ,L-Lactate Dehydrogenase ,Nicotinamide ,Chloroquine ,Drug Synergism ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Immunohistochemistry ,chemistry ,Molecular Medicine ,Comet Assay ,NAD+ kinase ,DNA Damage ,medicine.drug - Abstract
NAD is an essential coenzyme involved in numerous metabolic pathways. Its principal role is in redox reactions, and as such it is not heavily "consumed" by cells. Yet a number of signaling pathways that bring about its consumption have recently emerged. This has brought about the hypothesis that the enzymes that lead to its biosynthesis may be targets for anticancer therapy. In particular, inhibition of the enzyme nicotinamide phosphoribosyl transferase has been shown to be an effective treatment in a number of preclinical studies, and two lead molecules [N-[4-(1-benzoyl-4-piperidinyl)butyl]-3-(3-pyridinyl)-2E-propenamide (FK866) and (E)-1-[6-(4-chlorophenoxy)hexyl]-2-cyano-3-(pyridin-4-yl)guanidine (CHS 828)] have now entered preclinical trials. Yet, the full potential of these drugs is still unclear. In the present study we have investigated the role of FK866 in neuroblastoma cell lines. We now confirm that FK866 alone in neuroblastoma cells induces autophagy, and its effects are potentiated by chloroquine and antagonized by 3-methyladenine or by down-regulating autophagy-related protein 7. Autophagy, in this model, seems to be crucial for FK866-induced cell death. On the other hand, a striking potentiation of the effects of cisplatin and etoposide is given by cotreatment of cells with ineffective concentrations of FK866 (1 nM). The effect of etoposide on DNA damage is potentiated by FK866 treatment, whereas the effect of FK866 on cytosolic NAD depletion is potentiated by etoposide. Even more strikingly, cotreatment with etoposide/cisplatin and FK866 unmasks an effect on mitochondrial NAD depletion.
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- 2011
21. Nicotinamide phosphoribosyltransferase (NAMPT) is over-expressed in melanoma lesions
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Elena Maldi, Renzo Boldorini, Ubaldina Galli, Nicolò Agazzone, Benedetta Miglino, Cristina Travelli, Antonio Caldarelli, Giovanna Chiorino, Sara Cintura, Paola Ostano, Armando A. Genazzani, and Maria Scatolini
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Regulation of gene expression ,Acrylamides ,Skin Neoplasms ,Cell Death ,business.industry ,Melanoma ,Nicotinamide phosphoribosyltransferase ,Dermatology ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Gene Expression Regulation, Neoplastic ,chemistry.chemical_compound ,Oncology ,chemistry ,Piperidines ,Cell culture ,Cell Line, Tumor ,Cancer research ,medicine ,Humans ,Enzyme Inhibitors ,business ,Nicotinamide Phosphoribosyltransferase - Published
- 2012
22. Diagnostic yield of EUS-FNA in the diagnosis of subepithelial lesions of the gastrointestinal tract
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F Brizzi, M. Goss, Donatella Pacchioni, Paola Cassoni, P. Francia Di Celle, Patrizia Carucci, C. De Angelis, Elena Maldi, P. Allegranza, G. Accinelli, D. Reggio, Mauro Bruno, and M. Rizzetto
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Gastrointestinal tract ,medicine.medical_specialty ,Yield (engineering) ,business.industry ,Internal medicine ,Gastroenterology ,Medicine ,Radiology ,business - Published
- 2011
23. Extra-osseous Ewing sarcoma of the thyroid gland mimicking lymphoma recurrence: a case report
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Rosanna Mezzapelle, Davide Rossi, Guido Monga, Elena Maldi, Renzo Boldorini, and Antonella Tosoni
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Male ,Pathology ,medicine.medical_specialty ,Sarcoma, Ewing ,Biology ,Translocation, Genetic ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Biopsy ,medicine ,Biomarkers, Tumor ,Humans ,Neuroectodermal Tumors, Primitive, Peripheral ,Thyroid Neoplasms ,B-cell lymphoma ,In Situ Hybridization, Fluorescence ,Aged ,Incidental Findings ,medicine.diagnostic_test ,Peripheral Primitive Neuroectodermal Tumor ,Secretory Vesicles ,Thyroid ,Biopsy, Needle ,RNA-Binding Proteins ,Nodule (medicine) ,Cell Biology ,DNA, Neoplasm ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Immunohistochemistry ,Calmodulin-Binding Proteins ,Sarcoma ,Lymph Nodes ,Lymphoma, Large B-Cell, Diffuse ,medicine.symptom ,Neoplasm Recurrence, Local ,RNA-Binding Protein EWS ,Glycogen - Abstract
Extra-osseous Ewing sarcomas/peripheral primitive neuroectodermal tumors (EOES/pPNETs) are high-grade malignant tumors found in various organs, such as the lung, skin, intestine, kidney and female genital tract; however, to the best of our knowledge, only two cases have previously been identified in the thyroid gland. We describe a case of primary EOES/PNET of the thyroid gland in a 66-year-old man with a previous history of large B cell lymphoma. During a routine follow-up examination, the patient underwent an ultrasound cervical scan showing a solid nodule of the left thyroid lobe. The fine-needle aspiration biopsy of the nodule suggested a neuroendocrine tumor. Histological and immunohistochemical examination of the surgical specimen supported a diagnosis of EOES/PNET, which was further confirmed by the demonstration of EWSR1 gene translocation by means of fluorescent in situ hybridization and by the detection of glycogen particles and neurosecretory granules by means of electron microscopy. Total body computed tomography and magnetic resonance imaging excluded the involvement of other sites, and therefore a diagnosis of primary EOES/PNET of the thyroid gland was made.This paper also discusses the main differential diagnoses, including lymphoma recurrence, other small round cell tumors (primary or metastatic), and a thyroid localization of an EWS/PNET from another organ.
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- 2011
24. Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases
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Paola Cassoni, Veronica Tavaglione, Lorenzo Daniele, Marco Volante, Luisella Righi, Giorgio V. Scagliotti, Mauro Papotti, Silvia Novello, and Elena Maldi
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Pathology ,medicine.medical_specialty ,Histology ,Lung Neoplasms ,Caveolin 1 ,Adrenal Gland Neoplasms ,Adenocarcinoma ,Pathology and Forensic Medicine ,medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,Epidermal growth factor receptor ,Lung cancer ,biology ,medicine.diagnostic_test ,business.industry ,Brain Neoplasms ,Large cell ,Respiratory disease ,Gene Amplification ,Cancer ,General Medicine ,DNA, Neoplasm ,medicine.disease ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,cardiovascular system ,biology.protein ,Carcinoma, Squamous Cell ,Disease Progression ,Carcinoma, Large Cell ,business ,Brain metastasis ,Fluorescence in situ hybridization - Abstract
Aims: To study caveolin-1 (Cav-1) expression in metastatic lung carcinomas. Methods and results: Cav-1 expression was investigated in a series of 121 lung carcinomas and it was shown that 18/121 tumours (14.9%) were Cav-1+. None of the pure bronchioloalveolar carcinomas proved to be positive, vs. 42.8% of the large cell carcinomas (neuroendocrine subtype excluded). Adenocarcinomas (8.5%), large cell neuroendocrine carcinomas (20%) and squamous cell carcinomas (29.6%) displayed an intermediate percentage of positive cases, suggesting a gradient of Cav-1 expression according to tumour histotype-related aggressiveness. Moreover, the percentage of Cav-1+ tumours with distant metastases was almost double that of non-metastatic tumours (17.8% vs. 8.1%), irrespective of the histotype. In 34 tumours metastatic to the brain, primary and secondary lesions were compared and 53% of brain metastases were Cav-1+ vs. 20.6% of primaries, indicating a de novo acquisition of Cav-1 expression. This pattern was exclusive to the brain, as it was not acquired in adrenal metastases. In our series, the presence of epidermal growth factor receptor amplification, determined by fluorescence in situ hybridization, was not related to Cav-1 reactivity. Conclusions: Cav-1 immunoreactivity in lung carcinoma is histotype-dependent and acquired de novo in brain metastases, suggesting a site-specific phenotypic shift in secondary lesions.
- Published
- 2009
25. TfR2 expression in human colon carcinomas
- Author
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Ugo Testa, Fabio Malavasi, Paola Cassoni, Elena Maldi, Alessia Calzolari, and Silvia Deaglio
- Subjects
Transferrin receptor ,Colorectal cancer ,Iron ,Biology ,Membrane Microdomains ,Cell Line, Tumor ,Receptors, Transferrin ,medicine ,Humans ,Receptor ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Lipid raft ,Regulation of gene expression ,Carcinoma ,Cell Cycle ,Cell Biology ,Hematology ,Cell cycle ,medicine.disease ,Iron metabolism ,Colon cancer ,Gene Expression Regulation, Neoplastic ,Biochemistry ,Cell culture ,Colonic Neoplasms ,Cancer research ,Molecular Medicine ,Phosphorylation - Abstract
Different proteins regulate iron metabolism at the level of various tissues. Among these is a second transferrin receptor (TfR2) that seems to play a key role in the regulation of iron homeostasis. Although TfR2 expression in normal tissues is restricted at the level of the liver, we observed that TfR2 is frequently expressed in cancer cell lines. Taking advantage of this observation we investigated TfR2 expression in primary colon cancers, and showed that this receptor is expressed in about 26% of cases. TfR2 expression in colon cancer is not related to histological grade, but is preferentially associated with mucinous tumors. In colon cancer cell lines, TfR2 is localized in membrane lipid rafts, induces ERK1/ERK2 phosphorylation, when activated by its ligand transferring, and is preferentially expressed during S-M phases of the cell cycle. The presence of TfR2 on the membrane of colon cancer cells may contribute the growth advantage to these cells.
- Published
- 2009
26. Pattern of relapse in limb/girdle low-grade liposarcoma/atypical lipomatous tumor (ALT) during guidelines-suggested follow up (FU)
- Author
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Antonella Boglione, R. Piana, Alessandra Linari, Erica Palesandro, Michele Boffano, Danilo Galizia, U. Albertini, Enrico Bellato, P. Bergnolo, Paola Boccone, Alessandro Comandone, Lorenzo D'Ambrosio, and Elena Maldi
- Subjects
Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Soft tissue ,Limb girdle ,Radiology ,Liposarcoma ,business ,medicine.disease ,Atypical Lipomatous Tumor - Abstract
10570 Background: In soft tissue sarcomas (STS) after complete (marginal/wide/radical margins) surgery, surveillance should be tailored to individual patient’s (pts) risk that depends on histotype,...
- Published
- 2015
27. Mo1403 Definite Diagnosis of Subepithelial Lesions of the Gastrointestinal Tract by Means of Endoscopic Ultrasound-Fine Needle Aspiration (EUS-FNA)
- Author
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Paola Cassoni, Paola Francia di Celle, Patrizia Carucci, Mauro Bruno, Donatella Pacchioni, Claudio De Angelis, Milena Marietti, M. Goss, Elena Maldi, and Selene Manfrè
- Subjects
Endoscopic ultrasound ,Gastrointestinal tract ,medicine.medical_specialty ,Fine-needle aspiration ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business - Published
- 2014
28. P.03.3 SUBEPITHELIAL LESIONS OF THE GASTROINTESTINAL TRACT: DIAGNOSTIC YIELD OF ENDOSCOPIC ULTRASOUND-FINE NEEDLE ASPIRATION
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Patrizia Carucci, C. De Angelis, Marco Bruno, G. Accinelli, Paola Cassoni, Selene Manfrè, P. Francia Di Celle, Milena Marietti, Donatella Pacchioni, and Elena Maldi
- Subjects
Endoscopic ultrasound ,medicine.medical_specialty ,Gastrointestinal tract ,Yield (engineering) ,Fine-needle aspiration ,Hepatology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,medicine ,Radiology ,business - Published
- 2014
29. Abstract 5146: Nicotinamide phosphoribosyl transferase (NAMPT) is over-expressed in Melanoma
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GianCesare Tron, Ubaldina Galli, Renzo Boldorini, Cristina Travelli, Elena Maldi, and Armando A. Genazzani
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Cancer Research ,Nicotinamide ,Angiogenesis ,Chemistry ,Melanoma ,medicine.medical_treatment ,Cancer ,medicine.disease ,medicine.disease_cause ,chemistry.chemical_compound ,Cytokine ,Oncology ,medicine ,Cancer research ,NAD+ kinase ,Carcinogenesis ,neoplasms ,Nicotinamide mononucleotide - Abstract
NAD is an essential coenzyme involved in numerous metabolic pathways and it has been demonstrated that a number of signalling pathways bring about its consumption. Different pathways leading to the formation of NAD are present in cells. Nicotinamide phosphoribosyl transferase (NAMPT), which forms nicotinamide mononucleotide (NMN) from nicotinamide (NM) and PRPP, plays a crucial role in cells to re-use nicotinamide released by NAD-metabolizing enzymes. Moreover, NAMPT has also been described as a cytokine released by immune cells and adipocytes, however the role of NAMPT in the extracellular space is still unclear. The link between NAMPT and cancer is rapidly strengthening. NAMPT has been shown to be involved in angiogenesis and to be up-regulated in a number of solid tumours. Moreover, an important role in tumorigenesis has been postulated for a number of NAD-utilizing enzymes and inhibitors of NAMPT, named FK866 and CHS 828 have entered clinical trails for cancer treatment. In particular, FK866 has entered phase II trial for metastatic melanoma. The aim of our work was to determine the role of NAMPT in melanoma progression and the possibility to use NAMPT inhibitors as anti-cancer agents in melanoma. We investigated the expression of NAMPT in normal nevi, dysplastic nevi and melanoma human samples. Surprisingly, in all melanoma samples and in dysplastic nevi NAMPT is over-expressed, suggesting a possible contribution of this enzyme in melanoma progression. To confirm this data, we investigated the expression of NAMPT in six different melanoma cell lines. All melanoma cells show high levels of NAMPT expression compared to melanocytes. To test if the inhibition of NAMPT was able to decrease melanoma cells viability, we capitalize the action of FK866. However, only one to six melanoma cell line is sensitive to FK866 treatment. To understand why melanoma cells are insensitive to NAMPT inhibition, we investigate MDR expression and the possibility that NAMPT is mutated. Unfortunately, verapamil was not able to increase the sensitivity to FK866 and NAMPT is not mutated in all melanoma cell lines tested, moreover the treatment with FK866 is able to decrease the intracellular NAD level, suggesting that this agent is able to enter cells but not to induce cell death. As NAMPT was described also as a cytokine, we speculate the possibility that melanoma cells are able to release NAMPT in the extracellular space. Indeed, in starvation condition NAMPT is released by melanoma cells in a time-dependent manner. In conclusion, we have demonstrated that NAMPT is over-expressed in human melanoma samples and in melanoma cells, however NAMPT inhibition is not able to affect melanoma cells growth and viability, suggesting that NAMPT up-regulation does not correlate with a pharmacological response. Moreover, NAMPT is released by melanoma cells as a cytokine, we can speculate that NAMPT has a role in the angiogenic process of melanoma progression Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5146. doi:1538-7445.AM2012-5146
- Published
- 2012
30. P.1.211: DIAGNOSTIC YIELD OF EUS-FNA IN THE DIAGNOSIS OF SUBEPITHELIAL LESIONS OF THE GASTROINTESTINAL TRACT
- Author
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D. Reggio, C. De Angelis, Mauro Bruno, Patrizia Carucci, Donatella Pacchioni, P. Francia Di Celle, Paola Cassoni, Elena Maldi, V. Valente, M. Rizzetto, F Brizzi, and P. Allegranza
- Subjects
medicine.medical_specialty ,Gastrointestinal tract ,Yield (engineering) ,Hepatology ,business.industry ,Gastroenterology ,Medicine ,Radiology ,business - Published
- 2011
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