Review
Chemistry, Medicinal
Rita Rebelo, Barbara Polonia, Lucio Lara Santos, M. Helena Vasconcelos, Cristina P. R. Xavier
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly tumor with limited diagnostic and treatment options. Drug repurposing may offer a time-efficient and cost-effective approach for PDAC treatment. Multiple drugs have been studied for repurposing in PDAC treatment, but further research is needed to support their clinical applications.
Article
Pharmacology & Pharmacy
Ningna Weng, Siyuan Qin, Jiayang Liu, Xing Huang, Jingwen Jiang, Li Zhou, Zhe Zhang, Na Xie, Kui Wang, Ping Jin, Maochao Luo, Liyuan Peng, Edouard C. Nice, Ajay Goel, Suxia Han, Canhua Huang, Qing Zhu
Summary: Econazole (ECON), an antifungal compound, has been found to inhibit the growth of pancreatic ductal adenocarcinoma (PDAC) by promoting autophagy initiation and blocking lysosome biogenesis. It also exhibits synergistic effects with trametinib on PDAC.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Charlotte Dubois, Kateryna Kondratska, Artem Kondratskyi, Angela Morabito, Lina Mesilmany, Valerio Farfariello, Robert-Alain Toillon, Nathalie Ziental Gelus, Emilie Laurenge, Fabien Vanden Abeele, Loic Lemonnier, Natalia Prevarskaya
Summary: Changes in cytosolic free Ca2+ concentration play a central role in cellular processes. ORAI3 channels are expressed in both normal and pancreatic ductal adenocarcinoma cell lines, affecting store-operated calcium entry (SOCE). Silencing ORAI3 increases SOCE in PDAC cell lines and decreases SOCE in normal pancreatic cell line, impacting proliferation, cell cycle, viability, mitotic catastrophe, and cell death.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Oncology
Katharina M. Ewers, Shilpa Patil, Waltraut Kopp, Juergen Thomale, Tabea Quilitz, Anna Magerhans, Xin Wang, Elisabeth Hessmann, Matthias Dobbelstein
Summary: Pancreatic cancer cells show varied sensitivities to cisplatin, with some being sensitive due to high expression of GATA6 and microRNA 200, while others can be sensitized by inhibiting HSP90. The combination of cisplatin and HSP90 inhibitors has shown promise in improving treatment outcomes for PDAC.
Article
Biochemistry & Molecular Biology
Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, T. Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Weiming Yang, Jianbo Pan, Bo Wen, Yongchao Dou, Wen Jiang, Yuxing Liao, Zhiao Shi, Nadezhda Terekhanova, Song Cao, Rita Jui-Hsien Lu, Yize Li, Ruiyang Liu, Houxiang Zhu, Peter Ronning, Yige Wu, Matthew A. Wyczalkowski, Hariharan Easwaran, Ludmila Danilova, Arvind Singh Mer, Seungyeul Yoo, Joshua M. Wang, Wenke Liu, Benjamin Haibe-Kains, Mathangi Thiagarajan, Scott D. Jewell, Galen Hostetter, Chelsea J. Newton, Qing Kay Li, Michael H. Roehr, David Fenyo, Pei Wang, Alexey Nesvizhskii, D. R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang
Summary: This study conducted comprehensive proteogenomic analysis of PDAC to understand the molecular alterations that drive oncogenesis. Multiple analyses were performed on tissues from patients, providing valuable resources for early detection and identification of therapeutic targets.
Review
Biochemistry & Molecular Biology
Nausika Betriu, Juan Bertran-Mas, Anna Andreeva, Carlos E. Semino
Summary: Syndecans, a subfamily of proteoglycans, play critical roles in various physiological processes and have implications in disease progression. Their interactions with other macromolecules contribute to normal cellular functions and disease pathogenesis.
Review
Oncology
Eleonora Lai, Pina Ziranu, Dario Spanu, Marco Dubois, Andrea Pretta, Simona Tolu, Silvia Camera, Nicole Liscia, Stefano Mariani, Mara Persano, Marco Migliari, Clelia Donisi, Laura Demurtas, Valeria Pusceddu, Marco Puzzoni, Mario Scartozzi
Summary: Despite ongoing research, there is still insufficient data on BRCA1/2-mutant PDAC, and more understanding is needed on the specific landscape of PDAC with BRCA mutations.
BRITISH JOURNAL OF CANCER
(2021)
Review
Medicine, General & Internal
Alessandro Coppola, Tommaso Farolfi, Vincenzo La Vaccara, Immacolata Iannone, Francesco Giovinazzo, Elena Panettieri, Mariarita Tarallo, Roberto Cammarata, Roberto Coppola, Damiano Caputo
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease for healthcare professionals. Neoadjuvant treatment (NAD) has shown promising results in improving overall survival (OS) for PDAC patients. However, more randomized trials are needed to compare upfront surgery with NAD. CA 19-9 may be a valuable tool for decision-making in the presence of lymph-node metastases. The future challenge is to identify patients who will truly benefit from upfront surgery combined with NAD.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Cell Biology
Tianyi Zhang, Yanxian Ren, Pengfei Yang, Jufang Wang, Heng Zhou
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with a high deposition of extracellular matrix (ECM) and poor prognosis. ECM proteins derived from tumor cells reduce the effectiveness of conventional cancer treatment and contribute to tumor progression and metastasis. Cancer-associated fibroblasts (CAFs) in the ECM are promising targets for novel anti-tumor interventions.
CELL DEATH & DISEASE
(2022)
Editorial Material
Biology
Jessica Castrillon Lal
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a low survival rate. Understanding the complexity of tumor architecture and identifying targetable cellular phenotypes are major challenges in PDAC. Recent research has found recurrent gene expression patterns in malignant and fibroblast cellular neighborhoods in PDAC tumors that are correlated with treatment outcomes.
COMMUNICATIONS BIOLOGY
(2022)
Review
Oncology
Kongyuan Wei, Thilo Hackert
Summary: Surgery is the main potential cure for pancreatic ductal adenocarcinoma, with advancements in surgical techniques and multimodal approaches. Despite low survival rates, combining surgery with adjuvant therapy can increase five-year survival to around 20%. However, pancreatic resection is complex and high-risk, with ongoing developments in minimally-invasive and robotic approaches.
Review
Oncology
Eric M. Anderson, Shant Thomassian, Jun Gong, Andrew Hendifar, Arsen Osipov
Summary: Pancreatic cancer, with its highly immunosuppressive tumor microenvironment and dense stroma, presents challenges for traditional treatment approaches. Emerging treatment strategies have the potential to significantly improve outcomes for pancreatic cancer patients.
Review
Oncology
Vida Karimnia, Frank J. Slack, Jonathan P. Celli
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with current clinical trials showing limited improvements in patient survival. Photodynamic therapy (PDT) has emerged as a potential approach for treating pancreatic tumors based on studies indicating its effectiveness in activating photosensitizing agents in target tissues.
Review
Pharmacology & Pharmacy
Delphine Quatannens, Yannick Verhoeven, Peter Van Dam, Filip Lardon, Hans Prenen, Geert Roeyen, Marc Peeters, Evelien L. J. Smits, Jonas Van Audenaerde
Summary: PDAC is a leading cause of cancer related death, with urgent need for effective therapies. Aberrant activation of the Hh signaling pathway in PDAC prompts it as a possible target for treatment, despite ongoing debate on its clinical benefits.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Roman Bubin, Romans Uljanovs, Ilze Strumfa
Summary: The discovery of cancer stem cells (CSCs) in leukemia has led to active research on stemness in neoplastic tissues. CSCs are a subpopulation of malignant cells with unique properties, including a dedifferentiated state, self-renewal, pluripotency, resistance to therapy, epigenetic alterations, and higher tumorigenicity. CSCs have been confirmed in various malignancies, including pancreatic ductal adenocarcinoma, which has a poor prognosis. This review aims to summarize the current knowledge on the markers and molecular features of CSCs in pancreatic ductal adenocarcinoma and the therapeutic options for their elimination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rosalba Florio, Barbara De Filippis, Serena Veschi, Viviana di Giacomo, Paola Lanuti, Giulia Catitti, Davide Brocco, Annalisa di Rienzo, Amelia Cataldi, Ivana Cacciatore, Rosa Amoroso, Alessandro Cama, Laura De Lellis
Summary: Pancreatic cancer has limited response to current therapeutic options, so there is a need for more effective and low-toxic agents. In this study, the antiproliferative activities of newly synthetized resveratrol analogues in pancreatic cancer cell lines were explored. The most active compound exhibited marked antiproliferative effects through mechanisms involving DNA damage, apoptosis induction, and interference in cell cycle progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marialucia Gallorini, Valentina Di Valerio, Isabella Bruno, Simone Carradori, Rosa Amoroso, Amelia Cataldi, Alessandra Ammazzalorso
Summary: The NF-E2-related factor 2 transcription factor (Nrf2) plays a crucial role in regulating the activation of antioxidant genes. Increased Nrf2 activity has been linked to enhanced metastatic potential in breast cancer. The interaction between peroxisome proliferator-activated receptors (PPARs) and Nrf2 pathways has also been observed in cancer. A study investigated the effects of PPAR alpha antagonists on breast cancer cells and found that IB66 showed promising results by inhibiting cell proliferation and inducing programmed cell death through oxidative stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Infectious Diseases
Adriano Casulli, Bernadette Abela-Ridder, Daniele Petrone, Massimo Fabiani, Branko Bobic, David Carmena, Barbara Soba, Enver Zerem, Maria Joao Gargate, Gordana Kuzmanovska, Cristian Calomfirescu, Iskra Rainova, Smaragda Sotiraki, Vera Lungu, Balazs Dezsenyi, Zaida Herrador, Jacek Karamon, Pavlo Maksimov, Antti Oksanen, Laurence Millon, Mario Sviben, Renata Shkjezi, Valbona Gjoni, Ilir Akshija, Urmas Saarma, Paul Torgerson, Viliam Snabel, Daniela Antolova, Damir Muhovic, Hasan Besim, Fanny Chereau, Moncef Belhassen Garcia, Francois Chappuis, Severin Gloor, Marcel Stoeckle, Beat Muellhaupt, Valerio Manno, Azzurra Santoro, Federica Santolamazza
Summary: Cystic echinococcosis, a neglected zoonosis, is prevalent in pastoral and rural communities in low-income and upper-middle-income countries. In Europe, it is considered an orphan and rare disease, but its under-reporting by national health systems is a practical issue. This study extracted data on human cystic echinococcosis cases in Europe from 1997 to 2021, revealing a total of 64,745 cases from 40 European countries. The highest incidence rates were found in southeastern European countries, while historical endemic Mediterranean countries showed a decrease in cases over time.
LANCET INFECTIOUS DISEASES
(2023)
Review
Pharmacology & Pharmacy
Francesco Melfi, Simone Carradori, Andrea Angeli, Ilaria D'Agostino
Summary: In the past 5 years, extensive research has been conducted on the biological potential of natural products as human monoamine oxidase B (hMAO-B) inhibitors. However, natural compounds often face pharmacokinetic issues, such as poor solubility, extensive metabolism, and low bioavailability.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Review
Chemistry, Medicinal
Francesco Melfi, Simone Carradori, Cristina Campestre, Entela Haloci, Alessandra Ammazzalorso, Rossella Grande, Ilaria D'Agostino
Summary: This review provides an overview of the recent advances in the discovery of new inhibitors and biological targets for the treatment of Human African Trypanosomiasis. It also discusses the development of new vaccines and formulations. The findings of this study are valuable for the search of new therapeutic options for this neglected disease.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Biochemistry & Molecular Biology
Emira D'Amico, Tania Vanessa Pierfelice, Rosa Amoroso, Ivana Cacciatore, Camillo D'Arcangelo, Stefania Lepore, Simonetta D'Ercole, Natalia Di Pietro, Annalisa Di Rienzo, Morena Petrini, Adriano Piattelli, Alessia Ricci, Susi Zara, Antonio Di Stefano, Giovanna Iezzi, Barbara De Filippis
Summary: Recently, research has focused on finding new approaches to manage oral wound healing. The use of resveratrol (RSV) as a drug is limited due to its poor bioavailability. This study aimed to investigate a series of RSV derivatives (1a-j) with better pharmacokinetic profiles. Among them, derivatives 1d and 1h showed increased cell viability compared to RSV. Further studies demonstrated that both 1d and 1h exhibited positive effects on cell viability, proliferation, and gene expression in various cells involved in oral wound healing. Additionally, 1d and 1h showed promising physicochemical properties and stability, indicating their potential as RSV-based agents for oral tissue repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Valentina Puca, Gabriele Turacchio, Beatrice Marinacci, Claudiu T. Supuran, Clemente Capasso, Pamela Di Giovanni, Ilaria D'Agostino, Simone Carradori, Rossella Grande
Summary: The World Health Organization has identified Helicobacter pylori as a high-priority pathogen requiring updated antibacterial treatments. This study investigated the potential of combining a CA inhibitor, carvacrol (CAR), amoxicillin (AMX), and a urease inhibitor (SHA) to develop a multiple-targeted anti-H. pylori therapy. The combinations of these compounds showed strong inhibition of H. pylori growth and biofilm formation, with CAR-AMX and CAR-SHA combinations demonstrating additive effects and AMX-SHA combination showing indifferent effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Simone Carradori, Andrea Angeli, Patrick S. Sfragano, Xheila Yzeiri, Massimo Calamante, Damiano Tanini, Antonella Capperucci, Hannah Kunstek, Mihayl Varbanov, Clemente Capasso, Claudiu T. Supuran
Summary: In this study, new heptamethine-based compounds decorated with a sulfonamide moiety were synthesized for selectively inhibiting bacterial carbonic anhydrases (CAs) and being photoactivated by specific wavelengths. The compounds showed potent CA inhibition and a slight preference for bacterial isoforms. They also exhibited promising effects against S. epidermidis under irradiation, while being non-cytotoxic to human red blood cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marialuigia Fantacuzzi, Ilaria D'Agostino, Simone Carradori, Francesco Liguori, Fabrizio Carta, Mariangela Agamennone, Andrea Angeli, Filomena Sannio, Jean-Denis Docquier, Clemente Capasso, Claudiu T. Supuran
Summary: Vibrio cholerae, a pathogen responsible for life-threatening infections in low-income countries, has developed resistance to antibacterial drugs. Researchers have identified carbonic anhydrases (CAs) encoded by V. cholerae as potential pharmacological targets. They have developed a large library of CAs inhibitors with different flexibility degrees and found compounds with strong inhibition against Vch alpha CA. Computational studies have provided insights into the inhibitory activity and isoform selectivity of these compounds.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Sara Pagotto, Pasquale Simeone, Davide Brocco, Giulia Catitti, Domenico De Bellis, Simone Vespa, Natalia Di Pietro, Lisa Marinelli, Antonio Di Stefano, Serena Veschi, Laura De Lellis, Fabio Verginelli, Francesco Kaitsas, Manuela Iezzi, Assunta Pandolfi, Rosa Visone, Nicola Tinari, Ignazio Caruana, Mauro Di Ianni, Alessandro Cama, Paola Lanuti, Rosalba Florio
Summary: This review highlights the potential of CAR-T-derived extracellular vesicles (EVs) as therapeutic agents in tumors. CAR-T lymphocytes have shown potential effectiveness in immunotherapy against refractory neoplastic diseases. However, physical barriers, hostile microenvironment, and tumor heterogeneity limit their efficacy against solid tumors. The use of CAR-T-derived EVs as therapeutic agents may enhance CAR-T homing and overcome some adverse effects.
Review
Chemistry, Medicinal
Francesco Melfi, Simone Carradori, Noemi Mencarelli, Cristina Campestre, Marialucia Gallorini, Silvia Di Giacomo, Antonella Di Sotto
Summary: This article provides a brief description of the anticancer potential of natural compounds, followed by a search for patents published from 2019 onwards according to the PRISMA guidelines. Additionally, relevant publications from the overall scientific literature were discussed.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Chemistry, Medicinal
German Benito, Ilaria D'Agostino, Simone Carradori, Marialuigia Fantacuzzi, Mariangela Agamennone, Valentina Puca, Rossella Grande, Clemente Capasso, Fabrizio Carta, Claudiu T. Supuran
Summary: In this study, dual-acting antibacterial agents containing Erlotinib were synthesized and evaluated. Some of the compounds showed strong inhibitory activity against Helicobacter pylori carbonic anhydrase and good antibacterial activity against H. pylori. Computational studies provided insights into the binding mode of these compounds.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Daniele Sadutto, Paolo Guglielmi, Simone Carradori, Daniela Secci, Roberto Cirilli
Summary: The study investigates the tautomerization process of the imine moiety of the isoxazoline ring in the presence of a basic catalyst. The results can be used to control the stereointegrity of pharmacologically active compounds and guide the synthesis towards the desired tautomer.