Article
Cell Biology
I-Lun Hsin, Huang-Pin Shen, Hui-Yi Chang, Jiunn-Liang Ko, Po-Hui Wang
Summary: The study revealed a novel mechanism of the PI3K/mTOR dual inhibitor, PQR309, in lowering cell viability in endometrial cancer cells by disrupting the PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop.
Article
Biochemistry & Molecular Biology
Xin Sun, Yang Yang, Lulu Xia, Shiyu Wang, Yuxing Fu, Yuxuan Zhu, Shan Xu, Wufu Zhu, Wufu Zhu
Summary: The study investigates the effect of XIN-10, a dual PI3K/mTOR inhibitor, on the growth and antiproliferation of tumor cells. It demonstrates that XIN-10 has a potent inhibitory effect on breast cancer cells and can block the activation of the downstream mTOR pathway. These findings suggest that XIN-10 has strong potential as a novel PI3K/mTOR dual inhibitor for the treatment of breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maria Zapevalova, Ekaterina S. Shchegravina, Irina P. Fonareva, Diana Salnikova, Danila Sorokin, Alexander M. Scherbakov, Alexander A. Maleev, Stanislav K. Ignatov, Ivan D. Grishin, Alexander N. Kuimov, Maryia Konovalova, Elena Svirshchevskaya, Alexey Yu Fedorov
Summary: A series of potential inhibitors targeting the PI3K/Akt/mTOR cascade were synthesized, demonstrating cytotoxicity against cancer cell lines. Compound 7c exhibited the highest activity and selective inhibition towards specific cells expressing mutant PI3K. The compound inhibited key molecules in the signaling pathway and showed inhibition of tumor growth in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Krisida Cerma, Federico Piacentini, Luca Moscetti, Monica Barbolini, Fabio Canino, Antonio Tornincasa, Federica Caggia, Sara Cerri, Alessia Molinaro, Massimo Dominici, Claudia Omarini
Summary: Breast cancer is the most common and deadliest cancer in women, and new drugs often have limited clinical benefits. Mutations in the PI3K/AKT/mTOR pathway are frequent in breast cancer and contribute to aggressive tumor behavior and treatment resistance. Understanding the role of PI3K-mTORC1/C2 mutations in different breast cancer subtypes is crucial for improving clinical outcomes and treatment efficacy. A broad knowledge of tumor biology will be essential for personalized breast cancer therapy in the era of precision medicine.
Article
Chemistry, Medicinal
Ruoyu He, Bingyong Xu, Li Ping, Xiaoqing Lv
Summary: Structural modification of the PI3K/mTOR dual inhibitor 4 was conducted to enhance oral exposure, resulting in the discovery of 14d with potent anti-tumor activity and selectivity towards the PI3K family. 14d can strongly down-regulate the PI3K/Akt/mTOR pathway in U87MG cells by blocking both PI3K and mTOR signaling.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Carla L. Alves, Henrik J. Ditzel
Summary: The PI3K/AKT/mTOR pathway plays a crucial role in estrogen receptor-positive breast cancer tumorigenesis and drug resistance, making it a highly attractive therapeutic target. Several inhibitors targeting this pathway are currently under clinical development. The recent approval of the PIK3CA isoform-specific inhibitor alpelisib and the pan-AKT inhibitor capivasertib, in combination with fulvestrant, has provided new treatment options for advanced estrogen receptor-positive breast cancer patients. However, the clinical development of multiple inhibitors and incorporating CDK4/6 inhibitors into the standard treatment has complicated the personalization of therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Huayi Li, Lorenzo Prever, Emilio Hirsch, Federico Gulluni
Summary: The PI3K signaling pathway is crucial in breast cancer and inhibitors targeting this pathway show promising activity, but resistance and adverse reactions limit their efficacy. Combination therapies and identifying suitable patient subpopulations are needed to enhance therapeutic benefit.
Article
Biochemistry & Molecular Biology
Chi Yan, Jinming Yang, Nabil Saleh, Sheau-Chiann Chen, Gregory D. Ayers, Vandana G. Abramson, Ingrid A. Mayer, Ann Richmond
Summary: The study identified that combining PI3K/mTOR inhibitors with paclitaxel can enhance response to immune checkpoint inhibitors, leading to a positive impact on breast cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Alireza Mardanshahi, Nasrin Abbasi Gharibkandi, Samaneh Vaseghi, Seyed Mohammad Abedi, Sajjad Molavipordanjani
Summary: Radiotherapy is a common cancer treatment modality that can activate the PI3K and AKT signaling pathway to enhance tumor cell radiosensitivity. By inhibiting downstream mediators like mTOR, combined with radiation, can increase malignant cell radiosensitivity through autophagy activation.
MOLECULAR BIOLOGY REPORTS
(2021)
Review
Pharmacology & Pharmacy
Xianbo Wu, Yihua Xu, Qi Liang, Xinwei Yang, Jianli Huang, Jie Wang, Hong Zhang, Jianyou Shi
Summary: Studies have shown that PI3K/mTOR inhibitors are effective in cancer treatment, as they can inhibit cell proliferation and promote apoptosis. These inhibitors exhibit high potency and low drug resistance, indicating they have great potential as anticancer drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Wei Wang, Dong Han, Qinbo Cai, Tao Shen, Bingning Dong, Michael T. Lewis, Runsheng Wang, Yanling Meng, Wolong Zhou, Ping Yi, Chad J. Creighton, David D. Moore, Feng Yang
Summary: This study demonstrates that in a subset of TNBC, MAPK4 activation can occur independently of PI3K and promote tumor growth, and that inhibiting MAPK4 can increase the sensitivity of these tumors to PI3K blockade.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ming-Chun Hung, Wan-Ping Wang, Ya-Hui Chi
Summary: Constitutive activation of PI3K signaling has therapeutic potential in small cell lung cancer, with correlation between protein expression levels and cell survival in the pathway. Evaluation of efficacy should consider the use of PI3K/mTOR dual inhibition in conjunction with p-AKT levels.
CELL AND BIOSCIENCE
(2022)
Article
Biology
Zijie Cai, Jingru Wang, Yudong Li, Qianfeng Shi, Liang Jin, Shunying Li, Mengdi Zhu, Qi Wang, Lok Lam Wong, Wang Yang, Hongna Lai, Chang Gong, Yandan Yao, Yujie Liu, Jun Zhang, Herui Yao, Qiang Liu
Summary: CDK4/6 inhibitors are standard treatment for advanced HR+/HER2- breast cancer, but resistance is inevitable. This study found that overexpression of Cyclin D1 and CDK4 proteins leads to resistance, and targeting the PI3K/mTOR pathway can restore sensitivity.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Ayda Baghery Saghchy Khorasani, Atieh Pourbagheri-Sigaroodi, Ali Pirsalehi, Ava Safaroghli-azar, Mohammad Reza Zali, Davood Bashash
Summary: Genetic and epigenetic alterations have long been the focus of cancer pathogenesis research, with dysregulated genes and protein products potentially affecting cancer cell growth through signaling cascades regulating cell survival and metabolism. The activation of the phosphatidylinositol-3-kinase (PI3K) axis in about one-third of human cancers, including gastric cancer, plays a significant role in the development of malignancies. This indicates the potential importance of targeting this axis in therapeutic strategies for such cancers.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Oncology
Parham Jabbarzadeh Kaboli, Saber Imani, Masume Jomhori, King-Hwa Ling
Summary: Breast cancer displays poor response to conventional chemotherapy due to the activation of Akt signaling, which is considered a key factor in intrinsic and acquired drug resistance. Akt signaling not only enhances multi-drug resistance, but also plays crucial roles in cellular metabolism, apoptosis, and other processes.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Review
Veterinary Sciences
N. C. Galinelli, S. R. Bailey, N. J. Bamford, P. A. Harris
Summary: This article proposes a stepwise approach to developing an individual nutritional plan for equines with PPID. It emphasizes the importance of providing appropriate amounts and forms of energy, carbohydrate, and protein, and discusses practical considerations for feeding aged animals and those with clinical sequelae to PPID. The article also stresses the significance of determining the degree of insulin dysregulation.
EQUINE VETERINARY EDUCATION
(2023)
Article
Oncology
Subramaniam Ramanathan, Rebecca M. Hill, Jade Ryles, Gail Halliday, Dipayan Mitra, Simon Bailey
Summary: Central nervous system germ cell tumors (CNS-GCTs) account for 4% of all pediatric CNS tumors, with one third being nongerminomatous GCT (CNS-NG-GCT) type. This case presents a rare occurrence of a 2-year-old boy with an intradural-extramedullary NG-GCT arising from the lumbosacral spine, accompanied by unfavorable features including young age, alpha-feto protein >1000 ng/mL, and disseminated disease within the cranium. The patient was treated with chemotherapy alone and achieved remission.
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
(2023)
Article
Oncology
Katherine Green, Paraskevi Panagopoulou, Felice D'Arco, Patricia O'Hare, Richard Bowman, Bronwen Walters, Christine Dahl, Mette Jorgensen, Pritesh Patel, Olga Slater, Rehana Ahmed, Simon Bailey, Fernando Carceller, Rhiannon Collins, Elizabeth Corley, Martin English, Lisa Howells, Ahmed Kamal, John-Paul J. P. Kilday, Stephen Lowis, Blanche Lumb, Erika Pace, Susan Picton, Barry Pizer, Ayad Shafiq, Lena Uzunova, Harriet Wayman, Shaun Wilson, Darren Hargrave, Enrico Opocher
Summary: A nationwide UK service evaluation on the use of bevacizumab in children with pediatric low-grade glioma (PLGG) showed that it can effectively control short-term progression of PLGG and significantly improve visual outcomes. However, there are potential toxicities and risks of further progression, highlighting the need for further research to optimize the treatment strategy of bevacizumab.
Article
Veterinary Sciences
Fang I. Li, Robert J. Spence, Melody A. de Laat, Patricia A. Harris, Johanna Sonntag, Nicola J. Menzies-Gow, Andy E. Durham, Simon R. Bailey, Martin N. Sillence
Summary: High insulin levels may be associated with high ACTH levels in aged animals without clinical signs of PPID. Further research is needed to understand this interaction and its implications for ACTH diagnostic reference ranges.
EQUINE VETERINARY JOURNAL
(2023)
Article
Veterinary Sciences
Erica Lyn Macon, Patricia Harris, Simon Bailey, Ashley Caldwell Barker, Amanda Adams
Summary: This study found that insulin dysregulated horses seem to have an apparent threshold for NSC of around 0.1 g/kg bwt/meal, above which significantly increased insulin responses are seen compared with noninsulin dysregulated horses.
EQUINE VETERINARY JOURNAL
(2023)
Article
Oncology
Craig Erker, Martin Mynarek, Simon Bailey, Claire M. Mazewski, Lorena Baroni, Maura Massimino, Juliette Hukin, Dolly Aguilera, Andrea M. Cappellano, Vijay Ramaswamy, Alvaro Lassaletta, Sebastien Perreault, Cassie N. Kline, Revathi Rajagopal, George Michaiel, Michal Zapotocky, Vicente Santa-Maria Lopez, Andres Morales La Madrid, Chantel Cacciotti, Eric S. Sandler, Lindsey M. Hoffman, Darren Klawinski, Sara Khan, Ralph Salloum, Anna L. Hoppmann, Valerie Larouche, Kathleen Dorris, Helen Toledano, Stephen W. Gilheeney, Mohamed S. Abdelbaki, Beverly Wilson, Derek S. Tsang, Jeffrey Knipstein, Michal Yalon Oren, Shafqat Shah, Jeffrey C. Murray, Kevin F. Ginn, Zhihong J. Wang, Gudrun Fleischhack, Denise Obrecht, Svenja Tonn, Virginia L. Harrod, Kara Matheson, Bruce Crooks, Douglas R. Strother, Kenneth J. Cohen, Jordan R. Hansford, Sabine Mueller, Ashley Margol, Amar Gajjar, Girish Dhall, Jonathan L. Finlay, Paul A. Northcott, Stefan Rutkowski, Steven C. Clifford, Giles Robinson, Eric Bouffet, Lucie Lafay-Cousin
Summary: The purpose of this study was to assess salvage strategies and prognostic features of patients with infant and young childhood medulloblastoma (iMB) who relapse after craniospinal irradiation (CSI)-sparing therapy. The results showed that the 3-year postrelapse survival rate for patients treated with curative intent was 52.4%. Salvage radiotherapy and chemotherapy might be beneficial for a subset of patients. Therefore, CSI-sparing therapy can be effective in a substantial proportion of relapsed iMB patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Meeting Abstract
Oncology
Maria Trissal, Lisa Mayr, Kallen Schwark, Jenna LaBelle, Seongbae Kong, Julia Furtner, Liesa Weiler-Wichtl, Jeffrey Supko, Jacob Rozowsky, Olivia Hack, Andrew Groves, Joana Marques, Ulrike Leiss, Verena Rosenmayr, Frank Dubois, Noah F. Greenwald, Sibylle Madlener, Armin Sebastian Guntner, Hana Palova, Natalia Stepien, Daniela Lotsch-Gojo, Christian Dorfer, Karen Dieckmann, Andreas Peyrl, Amadeo A. Azizi, Alicia Baumgartner, Ondrej Slaby, Petra Pokorna, Pratiti Bandopadhayay, Rameen Beroukhim, Keith L. Ligon, Christof M. Kramm, Annika Bronsema, Simon Bailey, Ana Guerreiro Stucklin, Sabine Mueller Mueller, David T. W. Jones, Natalie Jager, Leonhard Mullauer, Christine Haberler, Chandan Kumar-Sinha, Arul Chinnaiyan, Rajen Mody, Jaroslav Sterba, Mary Skrypek, Nina Martinez, Daniel C. Bowers, Carl Koschmann Koschmann, Johannes Gojo, Mariella Filbin
Meeting Abstract
Oncology
Lindsay Kilburn, Dong-Anh Khuong-Quang, Karsten Nysom, Daniel Landi, David Ziegler, Pablo Hernaiz Driever, Sarah Leary, Simon Bailey, Jasper Van der Lugt, Sebastien Perreault, Angela Waanders, Patricia Baxter, Olaf Witt, Darren Hargrave, Geoffrey McCowage, Xin Zhao, Daniel Da Costa, Michael Cox, Peter Manley, Jordan Hansford
Review
Clinical Neurology
Daniel Williamson, Edward C. Schwalbe, Simon Bailey, Steven C. Clifford
Summary: Childhood brain tumour medulloblastoma can be classified into multiple molecular subgroups based on DNA methylation and expression patterns. Recent studies have shown a continuous association between survival outcome, the transcriptional profile of a Group3/Group4 medulloblastoma, and the specific point during early fetal cerebellar development at which initial pathogenic disruption occurred. This finding suggests that using expression biomarkers for continuous risk prediction may offer a more effective stratification of patients with Group3/Group4 medulloblastoma, instead of relying on discrete DNA methylation subgroups.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Letter
Oncology
Frederik W. van Delft, Simon Bailey, Roderick Skinner, Geoff Shenton, Peter Carey, Quentin Campbell-Hewson, Juliet Hale, Leigh McDonald, Kate Pearce, Richard Martin, Katrina Robinson, Gavin Cuthbert
PEDIATRIC BLOOD & CANCER
(2023)
Article
Oncology
Sarah M. Kelly, Andrada Turcas, Coreen Corning, Simon Bailey, Adela Canete, Enrico Clementel, Andrea di Cataldo, Karin Dieckmann, Mark N. Gaze, Gail Horan, Meriel Jenney, Ruth Ladenstein, Laetitia Padovani, Dominique Valteau-Couanet, Tom Boterberg, Henry Mandeville
Summary: SIOP Europe's QUARTET project aims to improve access to high-quality radiotherapy for children and adolescents in clinical trials in Europe. This report presents the profile of institutions participating in QUARTET trials and the outcomes of individual case reviews. A total of 103 institutions commenced QUARTET site approval procedures, with 66 sites across 20 countries approved. The most common reason for rejection in the individual case reviews was target delineation. The QUARTET facility questionnaire proves to be a valuable tool for assessing resources and technology available for pediatric radiotherapy.
RADIOTHERAPY AND ONCOLOGY
(2023)
Article
Veterinary Sciences
N. J. Bamford, A. J. Stewart, C. M. El-Hage, F. R. Bertin, S. R. Bailey
Summary: The objective of this study was to compare plasma ACTH concentrations among different breeds of mature horses and ponies. In autumn, non-Shetland pony breeds and Shetland ponies had higher ACTH concentrations compared to Thoroughbreds. However, no differences were identified among breed groups in spring.
VETERINARY JOURNAL
(2023)
Article
Physiology
Ashenafi H. Betrie, Shuai Ma, Connie P. C. Ow, Rachel M. Peiris, Roger G. Evans, Scott Ayton, Darius J. R. Lane, Adam Southon, Simon R. Bailey, Rinaldo Bellomo, Clive N. May, Yugeesh R. Lankadeva
Summary: In ovine sepsis, renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI). Tempol, an antioxidant and anti-inflammatory drug, can protect renal medullary perfusion and oxygenation, decrease the occurrence of AKI, and reduce the expression of tumor necrosis factor alpha (TNF-α) and uncoupling of endothelial nitric oxide synthase (eNOS). However, it does not affect markers of oxidative/nitrosative stress, which are significantly decreased during Gram-negative sepsis.
Meeting Abstract
Oncology
Gunther Nussbaumer, Martin Benesch, Yura Grabovska, Alan Mackay, David Castel, Jacques Grill, Marta M. Alonso Roldan, Manila Antonelli, Simon Bailey, Joshua N. Baugh, Alberto Broniscer, Shauna Crampsie, Natacha Entz-Werle, Matthias Eyrich, Maria L. Garre, Nicolas U. Gerber, Felice Giangaspero, Maria J. Gil-da-Costa, Darren Hargrave, Peter Hauser, Ulrich Herrlinger, Marion Hoffmann, Sandra Jacobs, Michael Karremann, Antonis Kattamis, Rejin Kebudi, Robert Kwiecien, Maura Massimino, Angela Mastronuzzi, Virve Pentikainen, Thomas Perwein, Stefan M. Pfister, Torsten Pietsch, Dominik Sturm, David Sumerauer, Dannis van Vuurden, Andre O. von Bueren, Pascale Varlet, Sophie E. M. Veldhuijzen van Zanten, Maria Vinci, Monika Warmuth-Metz, Pieter Wesseling, Maria Wiese, Josef Zamecnik, Andres Morales La Madrid, Brigitte Bison, Gerrit H. Gielen, David T. W. Jones, Chris Jones, Christof M. Kramm
Meeting Abstract
Pharmacology & Pharmacy
S. R. Bailey, G. Forbes
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
