Article
Biochemistry & Molecular Biology
Masato Mashimo, Akane Morozumi, Akari Nobeyama, Misato Kanzaki, Shigeru Negi, Jiro Kato, Joel Moss, Atsuo Nomura, Takeshi Fujii
Summary: Parthanatos is a programmed cell death process mediated by PARP1, which inhibits endocytosis by binding to Rab5, leading to cell starvation and death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Vanishree Rao, Sri Pragnya Cheruku, Suman Manandhar, R. J. A. Vibhavari, Krishnadas Nandakumar, C. Mallikarjuna Rao, V Ravichandiran, Nitesh Kumar
Summary: The study evaluated the potential of naringin in inhibiting PARP-1 and found that the combination of naringin and TMZ increased cytotoxicity to C6 cells and successfully reversed the resistance to TMZ.
Article
Oncology
Yves Pommier, Anish Thomas
Summary: ADCs are effective in delivering cytotoxic agents to tumors, and two ADCs delivering TOP1 poisons have been FDA-approved. A recent study introduced a TOP1-anti B7-H4 ADC that showed synergistic effect with a PARP1-selective inhibitor.
CLINICAL CANCER RESEARCH
(2023)
Article
Biology
Sridevi Challa, Keun W. Ryu, Amy L. Whitaker, Jonathan C. Abshier, Cristel Camacho, W. Lee Kraus
Summary: In this study, PAR Trackers were developed and characterized as highly sensitive tools for detecting ADPR in various experimental and biological systems, providing greater temporal and spatial precision.
Article
Oncology
William P. Tew, Christina Lacchetti, Elise C. Kohn
Summary: ASCO Rapid Recommendations Updates provide revisions to select ASCO guideline recommendations based on new and practice-changing data. The goal is to disseminate updated recommendations in a timely manner to inform health practitioners and the public on the best available cancer care options.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Michael S. Cohen
Summary: ADP-ribosylation is a crucial post-translational modification, involving MAR and PAR. Researchers have identified distinct MAR and PAR readers using a chemical biology approach.
Article
Oncology
Emad Matanes, Vanessa M. Lopez-Ozuna, David Octeau, Tahira Baloch, Florentin Racovitan, Amandeep Kaur Dhillon, Roy Kessous, Oded Raban, Liron Kogan, Shannon Salvador, Susie Lau, Walter H. Gotlieb, Amber Yasmeen
Summary: The study showed that PARG inhibition can complement PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects. PARG inhibitor alone or in combination with PARPi or Cisplatin can reduce cell migration and induce cell death.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Yuyan Zhang, Jiusui Huang, Yapeng Huang, Shike Zhang, Weizhou Wu, Hui Long, Xiaolu Duan, Yongchang Lai, Wenqi Wu
Summary: This study explored the impact of PARP inhibitors and PARP1 expression on melanoma progression, revealing that sunitinib reduced PARP1 expression and proliferation of melanoma cells, while the PARPi veliparib reversed this effect. Additionally, simvastatin and tanshinone I were found to inhibit melanoma cell proliferation by regulating PARP1 expression, with their combination showing synergistic effects in vivo. These results highlight the potential role of PARP1 expression in tumour progression and suggest that targeting PARP1 may offer a novel therapeutic approach for melanoma.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
David Hutin, Karoline Alvik Hagen, Peng Shao, Kim Sugamori, Denis M. Grant, Jason Matthews
Summary: PARP7 is an important regulator of the immune system, and is involved in intestinal inflammation. Loss of PARP7 impairs immune response to colon inflammation, possibly due to its role in IFN-I signaling rather than AHR signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Cassandra L. R. van Doorn, Sanne A. M. Steenbergen, Kimberley V. Walburg, Tom H. M. Ottenhoff
Summary: The inhibition of PARP has been shown to reduce the levels of Mycobacterium tuberculosis (Mtb) in human macrophages, indicating that PARP could be a potential target for developing innovative host-directed therapies against Mtb.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Oncology
Keun-Yeong Jeong, Haejun Lee
Summary: Chemotherapeutic regimens for pancreatic cancer are limited as it is typically diagnosed in advanced stages and hard to detect early symptoms. Mutations in BRCA leading to reduced susceptibility to conventional chemotherapies offer a new perspective, emphasizing the key role of PARP-1 in genomic instability.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2021)
Article
Chemistry, Physical
Iqbal Azad, Jawahar L. Jat, Ajay K. Yadav, Sudipta Saha, Yusuf Akhter
Summary: This study reveals that compound 3a is a potential anticancer candidate targeting PARP1. Through computation and simulation, the stable binding of compound 3a to PARP1 and its good binding free energy were determined.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Divakar Vishwanath, Swamy S. Girimanchanaika, Dukanya Dukanya, Shobith Rangappa, Ji-Rui Yang, Vijay Pandey, Peter E. Lobie, Basappa Basappa
Summary: In this study, a series of oxadiazole-based compounds were synthesized and found to exhibit potential PARP-1 targeting activity in mammary carcinoma cells. These compounds demonstrated comparable anti-tumor and anti-proliferation activities to Olaparib.
Review
Pharmacology & Pharmacy
Ruihong Dong, Ting Ding, Zhengyu Li
Summary: Ovarian cancer is a common reproductive system tumor with increasing incidence in China. Poly(ADP-ribose) polymerase inhibitor (PARPi) targets DNA repair enzyme PARP to kill tumor cells, particularly those with HR dysfunction. PARPi has been widely used in clinical practice for maintenance therapy of advanced ovarian epithelial cancer. However, the development of intrinsic or acquired drug resistance to PARPi has become a significant clinical problem. This review summarizes the mechanisms of PARPi resistance and current progress on PARPi-based combination strategies.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Lingchao Liu, Bahetiyaer Huwatibieke, Xiaoqing Lu, Dexin Li, Haiyan Dong, Jingyan Han, Weizhen Zhang, Yi Zhang, Yin Li
Summary: TiPARP plays a crucial role in regulating adipogenesis in both white and brown adipocytes, influencing lipid accumulation and cell maturity, providing a potential strategy for combating obesity.
JOURNAL OF TRANSLATIONAL INTERNAL MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Lucia Lisi, Pedro Miguel Lacal, Maria Martire, Pierluigi Navarra, Grazia Graziani
Summary: Immune checkpoint inhibitors have been investigated as an important approach for cancer immunotherapy, but combination therapy may lead to increased immune-related adverse events. The recent development of anti-CTLA-4 probodies and bispecific molecules targeting both CTLA-4 and PD-1 is considered a potential solution to overcome this drawback.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Grazia Raffaella Tundo, Diego Sbardella, Francesco Oddone, Giuseppe Grasso, Stefano Marini, Maria Grazia Atzori, Anna Maria Santoro, Danilo Milardi, Francesco Bellia, Gabriele Macari, Grazia Graziani, Fabio Polticelli, Paolo Cascio, Mariacristina Parravano, Massimo Coletta
Summary: Carfilzomib has been found to target Insulin-Degrading Enzyme (IDE) in vitro, which has interactions with proteasomes in cells. The inhibitory effect of Carfilzomib on IDE is 10-fold lower than on 20S proteasomes. Additionally, the interaction of IDE with 20S enhances the inhibitory power of Carfilzomib on proteasomes. Silencing the IDE gene significantly reduces the cytotoxicity of Carfilzomib in rMC1 cells.
Article
Biochemistry & Molecular Biology
Andrea Mammoli, Elisa Bianconi, Luana Ruta, Alessandra Riccio, Carlo Bigiotti, Maria Souma, Andrea Carotti, Sofia Rossini, Chiara Suvieri, Maria Teresa Pallotta, Ursula Grohmann, Emidio Camaioni, Antonio Macchiarulo
Summary: Over the last two decades, IDO1 has been recognized as a crucial player in immune regulation. This study presents a screening campaign of a compound fragment library and discusses the impact of IDO1's structural plasticity on drug design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Claudia Ceci, Pedro Miguel Lacal, Grazia Graziani
Summary: Antibody-drug conjugates (ADCs) are a new group of anticancer agents that combine the selectivity of monoclonal antibodies with the cell killing properties of chemotherapeutic agents. However, the development of ADCs faces challenges such as low tumor selectivity, premature release of drugs, and tumor resistance mechanisms. The design of inert antibodies and the discovery of innovative targets and drugs have led to the development of next-generation ADCs with improved therapeutic properties.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Diego Sbardella, Grazia Raffaella Tundo, Alice Mecchia, Camilla Palumbo, Maria Grazia Atzori, Lauretta Levati, Alessandra Boccaccini, Anna Maria Caccuri, Paolo Cascio, Pedro Miguel Lacal, Grazia Graziani, Monica Varano, Massimiliano Coletta, Mariacristina Parravano
Summary: This study uncovers a novel pathway of Muller glia (MG) activation by high glucose, which is regulated by a calcium-dependent calmodulin kinase II (CamKII)-proteasome axis. Inhibition of CamKII and proteasome prevents the pro-inflammatory program induced by high glucose.
CELL AND BIOSCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Luigi Aurisicchio, Nadia Brambilla, Marina E. Cazzaniga, Paolo Bonfanti, Stefano Milleri, Paolo A. Ascierto, Serena Capici, Cristina Vitalini, Federica Girolami, Giampaolo Giacovelli, Gianfranco Caselli, Michela Visintin, Francesca Fanti, Matteo Ghirri, Antonella Conforti, Mirco Compagnone, Lucia Lione, Erika Salvatori, Eleonora Pinto, Alessia Muzi, Emanuele Marra, Fabio Palombo, Giuseppe Roscilli, Alessandro Manenti, Emanuele Montomoli, Matteo Cadossi, Lucio C. Rovati
Summary: COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, was well tolerated and induced an immune response in up to 90% of volunteers, but did not induce neutralizing antibodies. The T cell-mediated immune response is significant and should be further studied for its protective capacity.
Review
Pharmacology & Pharmacy
Grazia R. Tundo, Paolo Cascio, Danilo Milardi, Anna Maria Santoro, Grazia Graziani, Pedro Miguel Lacal, Alessio Bocedi, Francesco Oddone, Mariacristina Parravano, Andrea Coletta, Massimo Coletta, Diego Sbardella
Summary: The immunoproteasome, initially discovered for its role in MHC class I antigen processing and immune system modulation, has been found to have additional functions unrelated to antigen presentation. Its expression and activity alterations are important in understanding neuroinflammation dynamics and the pathogenesis of neurological disorders. Furthermore, these new functions suggest the potential of immunoproteasome as a therapeutic target for neurodegeneration. This review provides an overview of the structure-function relationships of immunoproteasome and its observed neuro-modulatory functions.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Maria Grazia Atzori, Claudia Ceci, Federica Ruffini, Manuel Scimeca, Rosella Cicconi, Maurizio Mattei, Pedro Miguel Lacal, Grazia Graziani
Summary: The study indicates that inhibiting the activation of VEGFR-1 by PlGF can effectively restrain the metastatic potential of melanoma, reducing tumor invasiveness and tropism toward bone tissue.
Review
Oncology
Celia Garcia-Chico, Susana Lopez-Ortiz, Saul Penin-Grandes, Jose Pinto-Fraga, Pedro L. Valenzuela, Enzo Emanuele, Claudia Ceci, Grazia Graziani, Carmen Fiuza-Luces, Simone Lista, Alejandro Lucia, Alejandro Santos-Lozano
Summary: The prevalence of breast cancer is increasing and there is a need to investigate the molecular pathways that influence its progression. This review aims to describe the effects of physical exercise on breast cancer hallmarks, which are associated with the development of the disease. Regular physical exercise has positive effects on all major hallmarks of breast cancer and may help counteract its progression.
Review
Oncology
Ornella Franzese, Grazia Graziani
Summary: This review analyzes the potential combined use of PARP inhibitors and immune checkpoint inhibitors in the treatment of tumors. Preclinical studies have shown that PARP inhibitors can enhance the immune response and sensitivity to immunotherapies through DNA damage-related mechanisms. In-depth analysis of individual patients and clinical trials can contribute to the development of more effective and personalized treatments.
Article
Pharmacology & Pharmacy
Federica Ruffini, Claudia Ceci, Maria Grazia Atzori, Simona Caporali, Lauretta Levati, Laura Bonmassar, Gian Carlo Antonini Cappellini, Stefania D'Atri, Grazia Graziani, Pedro Miguel Lacal
Summary: The overexpression of PDGF-C and NRP-1 in resistant melanoma cells contributes to their invasive properties. Inhibition of PDGF-C and NRP-1 activation can reduce drug resistance and invasiveness of tumor cells. Furthermore, PDGF-C expression is differentially modulated by BRAFi treatment in responsive and non-responsive melanoma patients, indicating its potential as a therapeutic target for resistant melanoma.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Antonella Conforti, Elisa Sanchez, Erika Salvatori, Lucia Lione, Mirco Compagnone, Eleonora Pinto, Fabio Palombo, Emanuela D'Acunto, Alessia Muzi, Giuseppe Roscilli, Yuhua Sun, Brian Viscount, James Hayward, Clay Shorrock, Diego G. Diel, Joseph A. Impellizeri, Luigi Aurisicchio
Summary: SARS-CoV-2 can infect a wide range of animal species, including cats, and it is important to find mechanisms to prevent transmission and reduce the risk of infection. A genetic vaccine targeting COVID-19 has been shown to be safe and effective in cats, generating specific antibodies and T cells that can block the spread of the virus.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Plant Sciences
Sara Francesconi, Riccardo Ronchetti, Emidio Camaioni, Stefano Giovagnoli, Francesco Sestili, Samuela Palombieri, Giorgio Mariano Balestra
Summary: According to the European Green Deal, the application of imidazole fungicides for managing Fusarium head blight (FHB) and Fusarium crown rot (FCR) will be restricted by 2030. Therefore, a novel and eco-sustainable nanostructured particle formulation (NPF) was developed using cellulose nanocrystals (CNC) and resistant starch as carrier and excipient, chitosan and gallic acid as antifungal and elicitor active principles. The NPF effectively inhibited conidia germination and mycelium growth, reducing FHB and FCR symptoms in susceptible bread wheat genotypes while being biocompatible. Furthermore, the genome of Cadenza SBEIIa showed potential responsiveness to elicitor-like molecules and resistance to FCR fungal spread.
Article
Plant Sciences
Daniele Schiavi, Riccardo Ronchetti, Veronica Di Lorenzo, Riccardo Vivani, Stefano Giovagnoli, Emidio Camaioni, Giorgio M. Balestra
Summary: Nanotechnology is being used in crop protection with a focus on sustainable nanopesticides and nanocarriers for plant pathogen management. Cellulose nanocrystals (CNC) derived from agrofood waste are emerging as innovative antimicrobial materials. This study evaluated new chemical and enzymatic extraction methods for CNC from tomato harvest residues. Both methods were efficient, with the enzymatic method being greener and producing purer CNC at a slightly lower yield. The obtained CNC showed promising antimicrobial activity against plant bacterial pathogens, suggesting their potential in sustainable crop protection strategies.
Article
Biology
C. Maresca, A. Dello Stritto, C. D'Angelo, E. Petti, A. Rizzo, E. Vertecchi, F. Berardinelli, L. Bonanni, A. Sgura, A. Antoccia, G. Graziani, A. Biroccio, E. Salvati
Summary: PARP1 interacts with TRF1 and modifies its DNA affinity, influencing telomere replication and helicase recruitment. This study uncovers a new role for PARP1 as a surveillant of telomere replication, orchestrating protein dynamics at the replication fork.
COMMUNICATIONS BIOLOGY
(2023)