Article
Chemistry, Organic
Kelly Bugatti, Andrea Sartori, Lucia Battistini, Jessica Ruzzolini, Chiara Nediani, Claudio Curti, Francesca Bianchini, Franca Zanardi
Summary: Melanoma, the deadliest form of skin cancer, is increasing in incidence. New studies have shown the potential of combining nintedanib with immuno- and/or targeted therapy drugs in melanoma treatment.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Yongjie Li, Qian Gao, Xin Shu, Lamei Xiao, Yan Yang, Ningbo Pang, Yulin Luo, Jing He, Liping Zhang, Jianbo Wu
Summary: The study demonstrated that inhibition of alpha V beta 3 integrin improves blood flow perfusion and angiogenesis in a mouse hindlimb ischemia model, possibly through modulation of macrophage infiltration and polarization. This suggests that alpha V beta 3 integrin inhibition may be a promising therapeutic strategy for peripheral artery disease.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Jian Zhou, Rui Li, Jinhang Zhang, Qinhui Liu, Tong Wu, Qin Tang, Cuiyuan Huang, Zijing Zhang, Ya Huang, Hui Huang, Guorong Zhang, Yingnan Zhao, Ting Zhang, Li Mo, Yanping Li, Jinhan He
Summary: Renal fibrosis is the end result of various chronic kidney diseases and current therapies do not effectively target interstitial myofibroblasts. PEGylated liposomes modified with cRGDfC show promise in specifically delivering drugs to these cells, leading to reduced fibroblast uptake and decreased proliferation and activation. The system has potential for renal fibrosis treatment with minimal side effects.
MOLECULAR PHARMACEUTICS
(2021)
Review
Cell Biology
Tsai-Mu Cheng, Wong-Jin Chang, Hsiu-Yi Chu, Roberto De Luca, Jens Z. Pedersen, Sandra Incerpi, Zi-Lin Li, Ya-Jung Shih, Hung-Yun Lin, Kuan Wang, Jacqueline Whang-Peng
Summary: Integrin alpha v beta 3 plays a crucial role in cancer cell proliferation and metastasis, with its ligands and crosstalk with other signaling pathways regulating cancer growth. Inhibition of signals related to integrin alpha v beta 3 has shown promise as a target for cancer therapies. Nanotechnologies, such as the use of nanomaterial carriers, are being increasingly explored for their potential potentiation in cancer treatments targeting integrin alpha v beta 3.
Article
Food Science & Technology
Meihong Guo, Lei Yang, Xiaonan Zhao, Pinru Yan, Mengjiao Zhu, Weidong Ding, Dongmei Li, Xiaodong Han, Jiang Wu
Summary: This study found that Microcystin-leucine-arginine (MC-LR) reduces the fertility of female mice by affecting the construction of the vascular network in the corpus luteum and inhibiting hormone synthesis, which in turn affects embryo implantation and maintenance of early pregnancy.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Pharmacology & Pharmacy
Elham Seidkhani, Fatemeh Moradi, Auob Rustamzadeh, Sara Simorgh, Sakine Shirvalilou, Mehdi Mehdizadeh, Hamed Dehghani, Zeinab Akbarnejad, Manijeh Motevalian, Enam Alhagh Charkhat Gorgich
Summary: This study aimed to evaluate the effects of sunitinib on GBM-bearing rats and compare the effects of different delivery methods on angiogenesis inhibition and hepatotoxicity. The results showed that intra-nasal delivery of sunitinib may be a potential non-hepatotoxic alternative for the treatment of GBM.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Oncology
Fangfang Liu, Qiong Wu, Wei Han, Kyle Laster, Yamei Hu, Fayang Ma, Hanyong Chen, Xueli Tian, Yan Qiao, Hui Liu, Dong Joon Kim, Zigang Dong, Kangdong Liu
Summary: High ITGAV levels are associated with poor prognosis in ESCC patients. Targeting ITGAV may be a rational approach for preventing ESCC recurrence. Indomethacin can attenuate ESCC growth and enhance anti-tumour immune responses by binding to ITGAV.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Biology
Ravi Chakra Turaga, Ganesh Satyanarayana, Malvika Sharma, Jenny J. Yang, Shiyuan Wang, Chunfeng Liu, Sun Li, Hua Yang, Hans Grossniklaus, Alton Brad Farris, Jordi Gracia-Sancho, Zhi-Ren Liu
Summary: Turaga et al. present a strategy for treatment of chronic liver disease using their rationally designed protein (ProAgio) which targets integrin alpha(v)beta(3). They find that ProAgio-mediated apoptosis of these disease-associated cells reverses liver fibrosis and ameliorates intrahepatic vascular resistance in a mouse model. This study demonstrates an effective approach for CLD treatment.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Zhan Xie, Xin-Jing Wu, Rui-Wen Cheng, Jia-Hua Cui, Song-Tao Yuan, Jian-Wei Zhou, Qing-Huai Liu
Summary: JP1, a polypeptide targeting integrin alpha V beta 3, demonstrates efficacy in inhibiting CNV by targeting integrins, counteracting oxidative stress and inflammation, and modulating signal transduction pathways in vascular endothelial cells.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Cell Biology
Yingzhuo Xu, Jian Wang, Xu Wang, Xiaoshu Zhou, Jing Tang, Xiaohua Jie, Xijie Yang, Xinrui Rao, Yunhong Xu, Biyuan Xing, Zhenyu Li, Gang Wu
Summary: Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) tyrosine kinase inhibitors (TKIs) have achieved significant progress in the treatment of non-small-cell lung cancer, but resistance limits their efficacy. The study found that the use of ADRB2 antagonist propranolol can enhance the therapeutic effect of VEGFR2-TKIs by inhibiting ADRB2 signaling pathway. This research contributes to the understanding of VEGF-TKI and ICI resistance mechanisms and provides a new direction for developing effective treatment strategies.
CELL DEATH DISCOVERY
(2022)
Review
Chemistry, Organic
Lucia Battistini, Kelly Bugatti, Andrea Sartori, Claudio Curti, Franca Zanardi
Summary: Targeted therapies have gained increasing interest in recent years as effective strategies to improve therapeutic efficiency, especially in the field of cancer chemotherapeutics. RGD peptide-drug conjugates offer new possibilities for targeted drug delivery systems.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Gastroenterology & Hepatology
Ravi Chakra Turaga, Malvika Sharma, Falguni Mishra, Alyssa Krasinskas, Yi Yuan, Jenny J. Yang, Shiyuan Wang, Chunfeng Liu, Sun Li, Zhi-Ren Liu
Summary: ProAgio specifically induces apoptosis in CAPaSC and extends survival in PDAC tumor models, reducing intratumoral insulin-like growth factor 1 levels and enhancing Gem efficacy.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Chemistry, Medicinal
Bruce A. Hay, Kavitha Godugu, Noureldien H. E. Darwish, Kazutoshi Fujioka, Thangirala Sudha, Ozlem Ozen Karakus, Shaker A. Mousa
Summary: The newly discovered fb-PMT can significantly reduce GBM tumor growth and viability by up to 98%, is suitable for large-scale synthesis, and can be analyzed using mass spectrometry-based detection.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Susanne Kossatz, Ambros Johannes Beer, Johannes Notni
Summary: The article summarizes recent research on integrins and suggests that some approaches may ultimately improve the clinical management of the most lethal cancers, such as pancreatic carcinoma. Research on integrin-targeting radiopharmaceuticals has been shifting towards other integrin subtypes which are involved in various tumorigenic pathways, with a focus on alpha v beta 6-integrin due to its expression by cancers with poor prognosis and its potential as a biomarker for malignancy and invasiveness. This shift may lead to a paradigm change in the field of theranostics.
Article
Radiology, Nuclear Medicine & Medical Imaging
Marcus R. Makowski, Christoph Rischpler, Ullrich Ebersberger, Alexandra Keithahn, Markus Kasel, Ellen Hoffmann, Tienush Rassaf, Horst Kessler, Hans-Juergen Wester, Stephan G. Nekolla, Markus Schwaiger, Ambros J. Beer
Summary: Increased αvβ3 expression was observed in some patients after myocardial infarction, showing correlation with infarct size and restricted blood flow, but not solely dependent on perfusion effects.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Review
Pharmacology & Pharmacy
Giulia Assoni, Valeria La Pietra, Rosangela Digilio, Caterina Ciani, Nausicaa Valentina Licata, Mariachiara Micaelli, Elisa Facen, Weronika Tomaszewska, Linda Cerofolini, Anna Perez-Rafols, Marta Varela Rey, Marco Fragai, Ashwin Woodhoo, Luciana Marinelli, Daniela Arosio, Isabelle Bonomo, Alessandro Provenzani, Pierfausto Seneci
Summary: The article provides an overview of the role and mechanisms of the Human antigen R (HuR) protein in RNA maturation and processing, as well as its significance and clinical applications in oncology and inflammation.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Oncology
Luigi Ippolito, Giuseppina Comito, Matteo Parri, Marta Iozzo, Assia Duatti, Francesca Virgilio, Nicla Lorito, Marina Bacci, Elisa Pardella, Giada Sandrini, Francesca Bianchini, Roberta Damiano, Lavinia Ferrone, Giancarlo la Marca, Sergio Serni, Pietro Spatafora, Carlo V. Catapano, Andrea Morandi, Elisa Giannoni, Paola Chiarugi
Summary: This research reveals that lactate can promote lipid metabolism in prostate cancer cells through the regulation of gene expression, thus contributing to cancer progression and metastasis.
Article
Chemistry, Medicinal
Theodora Chatzisideri, George Leonidis, Theodoros Karampelas, Eleni Skavatsou, Angeliki Velentza-Almpani, Francesca Bianchini, Constantin Tamvakopoulos, Vasiliki Sarli
Summary: In this study, c(RGDyK)-based conjugates of gemcitabine (GEM) with the carbonate and carbamate linkages in the 6-OH group of GEM were synthesized for targeted delivery to integrin alpha(v)beta(3) overexpressing cancer cells. Among the synthesized conjugates, TC113 bearing the carbamate linker showed stability in human plasma and potent antiproliferative properties against WM266.4 and A549 cells, making it a promising candidate for further clinical applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lorenzo Baldini, Elena Lenci, Francesca Bianchini, Andrea Trabocchi
Summary: Molecular targets in tumor angiogenesis include VEGF, integrin receptors, and MMPs. Inhibiting these targets can help block tumor cell invasion and metastasis. Combining the inhibition of alpha(v)beta(3) and MMP2 as a multitarget approach can deliver a synergistic blockade of tumor cell migration, invasion, and metastasis.
Article
Pharmacology & Pharmacy
Giulia Frapporti, Eleonora Colombo, Hazem Ahmed, Giulia Assoni, Laura Polito, Pietro Randazzo, Daniela Arosio, Pierfausto Seneci, Giovanni Piccoli
Summary: This study focuses on the rational design and synthesis of nano-lipid-trehalose conjugates for enhanced therapeutic application. The nanoassemblies, characterized by small diameter and high stability, exhibit improved pharmacokinetic profile.
Article
Chemistry, Multidisciplinary
Kelly Bugatti, Elena Andreucci, Noemi Monaco, Lucia Battistini, Silvia Peppicelli, Jessica Ruzzolini, Claudio Curti, Franca Zanardi, Francesca Bianchini, Andrea Sartori
Summary: This study reports the synthesis and in vitro biological evaluation of three new covalent conjugates, consisting of an alpha(V)beta(6) integrin-recognizing small cyclopeptide and nintedanib, for the treatment of fibrotic diseases. One of these conjugates demonstrates optimal antifibrotic properties in vitro. The integrin ligand within the conjugate plays a role in inhibiting fibrotic stimuli and enhancing the effect of nintedanib, while selectively targeting cells overexpressing alpha(V)beta(6) integrin.
Article
Oncology
Elena Andreucci, Jessica Ruzzolini, Francesca Bianchini, Giampaolo Versienti, Alessio Biagioni, Matteo Lulli, Daniele Guasti, Patrizia Nardini, Simona Serrati, Francesca Margheri, Anna Laurenzana, Chiara Nediani, Silvia Peppicelli, Lido Calorini
Summary: Cutaneous melanoma is a highly metastatic form of skin cancer, and current treatments have limited effectiveness. This study focuses on the role of extracellular vesicles (EV) in melanoma metastasis. The researchers found that melanoma cells release more EV enriched with miR-214 in an acidic environment, which activates macrophages and promotes the trans-endothelial migration of melanoma cells. This discovery suggests that targeting miR-214 could be a potential therapeutic strategy for preventing melanoma intravasation.
Article
Biochemistry & Molecular Biology
Sara Peri, Jessica Ruzzolini, Silvia Urciuoli, Giampaolo Versienti, Alessio Biagioni, Elena Andreucci, Silvia Peppicelli, Francesca Bianchini, Andrea Bottari, Lido Calorini, Chiara Nediani, Lucia Magnelli, Laura Papucci
Summary: Oleocanthal, a compound found in extra-virgin olive oil, has been found to exhibit anticancer properties and can inhibit the growth of gastric cancer cells. In addition, an extract enriched with oleocanthal has a synergistic effect when used in combination with chemotherapy drugs, potentially overcoming drug resistance in gastric cancer cells.
Article
Chemistry, Multidisciplinary
Giovanni Sacco, Daniela Arosio, Mayra Paolillo, Andreas Gloger, Jorg Scheuermann, Luca Pignataro, Laura Belvisi, Alberto Dal Corso, Cesare Gennari
Summary: By installing salicylaldehyde derivatives at the C terminus of an integrin-binding cyclopeptide, the ligand affinity for the receptor is enhanced and stronger biological activity is observed in cultured glioblastoma cells.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Elena Andreucci, Kelly Bugatti, Silvia Peppicelli, Jessica Ruzzolini, Matteo Lulli, Lido Calorini, Lucia Battistini, Franca Zanardi, Andrea Sartori, Francesca Bianchini
Summary: Growth factors and cytokines in the lung cancer microenvironment induce EMT and promote tumor progression. A novel conjugate targeting the α v β 6 integrin receptor, linked to the kinase inhibitor nintedanib, inhibits cancer cell adhesion and growth through selective delivery. The conjugate also suppresses clonogenic ability and other aspects associated with EMT transition, offering a precise strategy against non-small cell lung cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Enrico Marcantonio, Debora Guazzetti, Kelly Bugatti, Lucia Battistini, Andrea Sartori, Giorgio Pelosi, Claudio Curti, Franca Zanardi
Summary: Organocatalytic asymmetric transformation of aromatic heterocycles via in situ formation of reactive diene species and subsequent cycloaddition has become a powerful tool. This study reveals the efficient and direct preparation of 6,7-dihydrobenzo[d]imidazoles with optimal enantio- and regioselectivities using previously intractable aromatic imidazole rings as cycloaddends. Post-cycloaddition chemical editing allows the modification of imidazole-based ring systems.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Cell Biology
Isabelle Bonomo, Giulia Assoni, Valeria La Pietra, Giulia Canarutto, Elisa Facen, Greta Donati, Chiara Zucal, Silvia Genovese, Mariachiara Micaelli, Anna Perez-Rafols, Sergio Robbiati, Dimitris L. Kontoyannis, Marilenia De Matteo, Marco Fragai, Pierfausto Seneci, Luciana Marinelli, Daniela Arosio, Silvano Piazza, Alessandro Provenzani
Summary: The study found that small-molecule tanshinone mimics can inhibit the inflammatory response in macrophages stimulated by LPS by reducing the interaction between HuR and genes involved in chemotaxis and immune response. These findings suggest that HuR could be a potential therapeutic target for inflammation-related diseases.
DISEASE MODELS & MECHANISMS
(2023)
Article
Biochemistry & Molecular Biology
Greta Donati, Vincenzo Maria D'Amore, Pasquale Russomanno, Linda Cerofolini, Jussara Amato, Simona Marzano, Maria Salobehaj, Domenico Rizzo, Giulia Assoni, Alfonso Carotenuto, Valeria La Pietra, Daniela Arosio, Pierfausto Seneci, Marco Fragai, Diego Brancaccio, Francesco Saverio Di Leva, Luciana Marinelli
Summary: The PD-1/PD-L1 axis is crucial in evading the immune system in cancers, and anti-PD-1/PD-L1 antibodies have been extensively studied in clinical trials. However, the development of small molecules as anti-PD-L1 drugs faces certain limitations. This study utilized theoretical and experimental approaches to gain insights into the molecular interactions between biphenyl-based compounds and human and murine PD-L1, providing valuable information for the design of next-generation anti-PD-L1 molecules.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)