Review
Oncology
Shigeki Kusamura, Dario Baratti, Michele De Simone, Enrico Maria Pasqual, Luca Ansaloni, Daniele Marrelli, Manuela Robella, Fabio Accarpio, Mario Valle, Stefano Scaringi, Daniele Biacchi, Carmen Palopoli, Sergio Gazzanelli, Marcello Guaglio, Marcello Deraco
Summary: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare cancer that originates in the peritoneum and has a poor prognosis. Cytoreductive surgery and HIPEC are currently the standard treatments, but selecting suitable patients and managing the perioperative period is challenging.
Review
Surgery
Luanbiao Sun, Chenguang Li, Shuohui Gao
Summary: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and life-threatening tumor that invades the abdominal cavity. CT is commonly used for diagnosis and immunohistochemical markers such as WT 1, D2-40, and calmodulin can help identify the disease. The standard treatment involves cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but DMPM is resistant to conventional chemotherapies. Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway shows promise, and inhibiting multiple RTKs could be effective, though further research is needed. Discovering novel targeted therapies is crucial for improving the prognosis of DMPM patients.
FRONTIERS IN SURGERY
(2023)
Article
Oncology
Vahan Kepenekian, Olivia Sgarbura, Frederic Marchal, Laurent Villeneuve, Shigeki Kusamura, Marcello Deraco
Summary: Through an international consensus, it was confirmed that hyperthermic intraperitoneal chemotherapy (HIPEC) following complete cytoreductive surgery (CRS) is the first-line treatment for diffuse malignant peritoneal mesothelioma (DMPM), and the combination of cisplatin and doxorubicin is recommended as the preferred HIPEC regimen.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Louis Gros, Petr Szturz, Antonella Diciolla, Volker Kirchner, Solange Peters, Niklaus Schaefer, Martin Hubner, Antonia Digklia
Summary: Mesothelioma is a malignancy of serosal membranes, with parietal pleura being the most common site and peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is rare and aggressive, with a poor prognosis.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Melina E. Marmarelis, Xiao Wang, Leonid Roshkovan, Connor B. Grady, John T. Miura, Michelle S. Ginsberg, Christine A. Ciunci, Jacklynn Egger, Suzanne Walker, Andrea Cercek, Michael B. Foote, Leslie A. Litzky, Garrett Nash, Andrew R. Haas, Giorgos C. Karakousis, Keith A. Cengel, Sharyn I. Katz, Marjorie G. Zauderer, Corey J. Langer, Michael Offin
Summary: This retrospective cohort study aimed to evaluate the outcomes of Pembrolizumab monotherapy in the treatment of DMPM patients. The results of the study suggest that Pembrolizumab has clinical activity in DMPM patients, regardless of PD-L1 status or histology, although patients with nonepithelioid histology may have additional clinical benefit.
Article
Medicine, General & Internal
Cai-Pu Chun, Lin-Xie Song, Hong-Pan Zhang, Dan -Dan Guo, Gui-Xuan Xu, Ya Li, Xin Xin, Jiachen Cao, Feng Li
Summary: This article presents a rare case of malignant peritoneal mesothelioma (MPM) in a 67-year-old male patient, with severe abdominal pain, bloating, and bloody ascites. The diagnosis was confirmed through cytology and laparoscopic exploratory biopsy. The characteristics of signs and clinical manifestations in this case are less common.
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Xiao Wang, Sharyn Katz, John Miura, Giorgos Karakousis, Leonid Roshkovan, Suzanne Walker, Sally McNulty, Christine Ciunci, Keith Cengel, Corey J. Langer, Melina E. Marmarelis
Summary: Using neoadjuvant chemotherapy in the treatment of diffuse malignant peritoneal mesothelioma (DMPM) did not result in worse outcomes compared to adjuvant chemotherapy. It was well-tolerated and helped stabilize the disease during the preoperative period.
Article
Medicine, General & Internal
Claire Y. Li, Timothy Kennedy, Henry Richard Alexander
Summary: Malignant peritoneal mesothelioma is a rare malignancy that is diagnosed through cross sectional imaging and tissue biopsy. Surgical cytoreduction and chemotherapy are the preferred treatments, providing prolonged benefits to many patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Respiratory System
Marie Shamseddin, Joanna Obacz, Mathew J. Garnett, Robert Campbell Rintoul, Hayley Elizabeth Francies, Stefan John Marciniak
Summary: Malignant pleural mesothelioma is an aggressive cancer with a median survival of 12-18 months and existing models have limitations, so new technologies are being developed to study effective treatments.
Article
Oncology
Zhi-Ran Yang, Yan-Dong Su, Ru Ma, He-Liang Wu, Yan Li
Summary: Apatinib shows promising efficacy and acceptable safety in treating refractory diffuse malignant peritoneal mesothelioma (DMPM) based on the study of 27 patients, with a certain treatment effect observed in the majority of patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Manuela Labbozzetta, Marilia Barreca, Virginia Spano, Maria Valeria Raimondi, Paola Poma, Monica Notarbartolo, Paola Barraja, Alessandra Montalbano
Summary: A series of newly synthesized [1,2]oxazolo[5,4-e]isoindole derivatives showed antiproliferative activities against HL-60 and HL-60R cells, with compound 4k exhibiting synergistic effects in combination with Vinblastine and Paclitaxel. All compounds demonstrated antimitotic activity through inhibition of tubulin polymerization.
DRUG DEVELOPMENT RESEARCH
(2022)
Article
Oncology
Ambarish Chatterjee, Shigeki Kusamura, Dario Baratti, Marcello Guaglio, Luigi Battaglia, Marcello Deraco
Summary: This study evaluated the impact of perioperative systemic chemotherapy (SC) on the survival outcomes of diffuse malignant peritoneal mesothelioma (DMPM) patients undergoing CRS-HIPEC and identified prognostic factors that affect the decision to administer SC. The results showed that adjuvant chemotherapy (ACT) significantly improved overall survival (OS) for high-risk patients, while neoadjuvant chemotherapy (NACT) did not have a significant association with progression-free survival (PFS).
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Takuya Kohama, Toshihiko Sakamoto, Takeshi Okino
Summary: This is a rare case of a parahiatal hernia sac tumor, which was successfully treated with radical resection via thoracoscopic surgery. No recurrence was observed in the patient 10 months after surgery.
ANNALS OF THORACIC SURGERY
(2021)
Article
Pathology
Federica Pezzuto, Luigi Vimercati, Francesco Fortarezza, Andrea Marzullo, Antonio Pennella, Domenica Cavone, Alessandra Punzi, Concetta Caporusso, Antonio d'Amati, Teresa Lettini, Gabriella Serio
Summary: The study investigated the pathology and prognostic factors of diffuse malignant peritoneal mesothelioma (DMPM). High-grade epithelioid mesothelioma, high Ki67, and p16/CDKN2A deletion were significantly associated with shorter survival. The nuclear grading system and p16 deletion were found to be significantly correlated with survival.
DIAGNOSTIC PATHOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Rihan El Bezawy, Stefano Percio, Chiara Maura Ciniselli, Michelandrea De Cesare, Gennaro Colella, Matteo Dugo, Silvia Veneroni, Valentina Doldi, Silvia Martini, Dario Baratti, Shigeki Kusamura, Paolo Verderio, Marcello Deraco, Paolo Gandellini, Nadia Zaffaroni, Valentina Zuco
Summary: In this study, miR-550a-3p was found to be downregulated in DMPM patients and its expression levels were associated with patient outcome. Functional experiments showed that miR-550a-3p inhibited proliferation and invasiveness, enhanced apoptosis, and reduced tumor growth in DMPM cell lines and xenograft models. Similar antitumor effects were observed in prostate and ovarian cancer cell lines. The effects of miR-550a-3p were mediated, at least in part, by the inhibition of HSP90AA1 and its target proteins.
CANCER GENE THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Camilla Pecoraro, Barbara Parrino, Stella Cascioferro, Adrian Puerta, Amir Avan, Godefridus J. Peters, Patrizia Diana, Elisa Giovannetti, Daniela Carbone
Summary: CDK1 plays a crucial role in pancreatic ductal adenocarcinoma and is one of the main causes of chemoresistance. A new compound that inhibits cell growth and induces apoptosis while targeting CDK1 has been discovered in this study.
Article
Oncology
Irene Alessandrini, Stefano Percio, Eisa Naghshineh, Valentina Zuco, Silvia Stacchiotti, Alessandro Gronchi, Sandro Pasquali, Nadia Zaffaroni, Marco Folini
Summary: This study found an up-regulation of telomere maintenance pathways in DDLPS, suggesting telomeres as a potential therapeutic target. Further experiments showed that a telomeric G-quadruplex binder (RHPS4) can alter telomeric c-circle levels, induce DNA damage, and induce apoptosis/autophagy in DDLPS cells, leading to a reduction in cell migration.
Review
Cell Biology
Giovanni Luca Beretta, Nadia Zaffaroni
Summary: Necroptosis is a cell death mechanism characterized by inflammatory reactions and is involved in viral defense, inflammatory diseases, and drug response of tumors such as prostate cancer.
Article
Pharmacology & Pharmacy
Lorenzo Monteleone, Barbara Marengo, Francesca Musumeci, Giancarlo Grossi, Anna Carbone, Giulia E. Valenti, Cinzia Domenicotti, Silvia Schenone
Summary: This study demonstrates that Src inhibitors such as SI306 and its prodrug show promising anti-tumor effects on GBM cells and are associated with a reduction in the expression of epidermal growth factor receptor.
Article
Biochemistry & Molecular Biology
Salvatore Di Maria, Francesca Picarazzi, Mattia Mori, Annarita Cianciusi, Anna Carbone, Emmanuele Crespan, Cecilia Perini, Samantha Sabetta, Serenella Deplano, Federica Poggialini, Alessio Molinari, Rossella Aronne, Elias Maccioni, Giovanni Maga, Adriano Angelucci, Silvia Schenone, Francesca Musumeci, Elena Dreassi
Summary: This study identified a family of pyrazolo[3,4-d]pyrimidines as dual Src/Bcr-Abl inhibitors through a target-oriented approach. These compounds showed potential anti-leukemic activity and could be promising candidates for chronic myeloid leukemia (CML) therapy.
BIOORGANIC CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Nadia Zaffaroni, Giovanni L. L. Beretta
Summary: Pyroptosis is a programmed cell death characterized by the rupture of the plasma membranes and release of cellular content leading to inflammatory reaction. Four cellular mechanisms inducing pyroptosis have been reported thus far. Pyroptosis plays roles in tumor initiation, progression, metastasis, treatment response, and patient outcome. Induction of pyroptosis has been reported in several tumor types following antitumor therapies, including melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Valentina Zuco, Sandro Pasquali, Monica Tortoreto, Stefano Percio, Valentina Doldi, Marta Barisella, Paola Collini, Gian Paolo Dagrada, Silvia Brich, Patrizia Gasparini, Marco Fiore, Michela Casanova, Anna Maria Frezza, Alessandro Gronchi, Silvia Stacchiotti, Andrea Ferrari, Nadia Zaffaroni
Summary: This study used a patient-derived xenograft (PDX) model to evaluate the effectiveness of different drugs against desmoplastic small round cell tumor (DSRCT). It was found that doxorubicin, pazopanib, and larotrectenib had moderate antitumor effects, while trabectedin had higher activity. Vinorelbine, irinotecan, and eribulin achieved nearly complete tumor growth inhibition. The combination of irinotecan with either eribulin or trabectedin resulted in complete responses. This study highlights the importance of patient-derived preclinical models in exploring new treatments for DSRCT.
DISEASE MODELS & MECHANISMS
(2023)
Article
Biochemistry & Molecular Biology
Daniela Carbone, Michele De Franco, Camilla Pecoraro, Davide Bassani, Matteo Pavan, Stella Cascioferro, Barbara Parrino, Girolamo Cirrincione, Stefano Dall'Acqua, Stefano Moro, Valentina Gandin, Patrizia Diana
Summary: A library of 3-amino-1,2,4-triazine derivatives was designed and synthesized, which showed potent and selective inhibition of PDK. These compounds proved to be effective in inducing cancer cell death, especially in human pancreatic KRAS mutated cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marika A. Franczak, Oliwia Krol, Gabriela Harasim, Agata Jedrzejewska, Nadia Zaffaroni, Carlotta Granchi, Filippo Minutolo, Amir Avan, Elisa Giovannetti, Ryszard T. Smolenski, Godefridus J. Peters
Summary: Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. In this study, the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP/NAD+ metabolism, glycolysis and mitochondrial respiration was investigated. The inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were most effective in cells with the highest metabolic modulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Camilla Pecoraro, Daniela Carbone, Barbara Parrino, Stella Cascioferro, Patrizia Diana
Summary: Infectious diseases caused by antimicrobial-resistant strains have become a serious threat to global health, with a high social and economic impact. Strategies to fight antibiotic resistance, such as inhibiting bacterial adhesion to host surfaces, can effectively hamper bacterial virulence without affecting cell viability. Targeting structures and biomolecules involved in the adhesion of Gram-positive and Gram-negative pathogens can lead to the development of promising tools against pathogens.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Daniela Carbone, Michele De Franco, Camilla Pecoraro, Davide Bassani, Matteo Pavan, Stella Cascioferro, Barbara Parrino, Girolamo Cirrincione, Stefano Dall'Acqua, Stefania Sut, Stefano Moro, Valentina Gandin, Patrizia Diana
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type with poor prognosis and drug resistance. Cell metabolism alteration plays a key role in PDAC progression, leading to cell proliferation, invasion, and chemotherapy resistance. In this study, a new series of indolyl-7-azaindolyl triazine compounds were synthesized, inspired by marine bis-indolyl alkaloids. These compounds were found to inhibit the enzymatic activity of pyruvate dehydrogenase kinases (PDKs), with a high selectivity against KRAS-mutant PDAC. Molecular docking analysis and cell growth inhibition assays demonstrated the potential of these derivatives as therapeutic options for PDAC.
Article
Biochemistry & Molecular Biology
Silvia Gobbi, Silvia Martini, Riccardo Rozza, Angelo Spinello, Jessica Caciolla, Angela Rampa, Federica Belluti, Nadia Zaffaroni, Alessandra Magistrato, Alessandra Bisi
Summary: In this study, novel compounds with dual AR and ER activity were designed by modifying flavonoid-related compounds. Compounds 3b and 4a showed promising submicromolar activity against both targets. Computational studies confirmed the feasibility of using multi-target approaches for ER+ BC treatment. The homoisoflavone core emerged as a valuable scaffold for the design of multifunctional compounds.
Article
Chemistry, Medicinal
Daniela Carbone, Camilla Pecoraro, Giovanna Panzeca, Geng Xu, Margot S. F. Roeten, Stella Cascioferro, Elisa Giovannetti, Patrizia Diana, Barbara Parrino
Summary: A series of new nortopsentin analogs were successfully synthesized by replacing the central imidazole ring with a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety. The antiproliferative activity of these derivatives was evaluated against pancreatic cancer cell lines, showing significant reduction in cell migration. Cell cycle analysis indicated cell cycle arrest and inhibition of CDK1 activity, a crucial regulator of cell cycle progression and cancer cell proliferation.
Article
Chemistry, Organic
Camilla Pecoraro, Daniela Carbone, Daniele Aiello, Anna Carbone
Summary: A series of thiazole nortopsentin analogues with a 5-azaindole moiety were synthesized conveniently and showed cytotoxic activity against different human tumor cell lines.