Article
Biochemical Research Methods
Ketaki Bachal, Shital Yadav, Prasanna Gandhi, Abhijit Majumder
Summary: This study introduces a user-friendly and portable static drug testing platform that can generate stable concentration gradients. By utilizing nonconventional techniques in the fabrication process, the device successfully validated the efficacy of two drugs.
Article
Biotechnology & Applied Microbiology
Kai Yang, Zhi Wang
Summary: The interaction between Rab18 and VSIG4 plays a role in the proliferation, apoptosis, and temozolomide sensitivity of glioma cells. Silencing Rab18 led to decreased proliferation, increased apoptosis, and enhanced TMZ sensitivity in U87-MG and U251-MG cells. Additionally, VSIG4 overexpression reversed the biological effects and TMZ sensitivity caused by Rab18 silencing.
Article
Cell Biology
Baiwei Zhang, Cheng Xu, Junfeng Liu, Jinsheng Yang, Qinglei Gao, Fei Ye
Summary: The study revealed that NID1 is overexpressed in glioma tissues, and high NID1 expression is associated with overall survival and temozolomide sensitivity in low-grade glioma patients. NID1 could serve as a potential prognostic biomarker and therapeutic target in this patient population.
Article
Oncology
Bodo Haas, Janine Ciftcioglu, Sanja Jermar, Sandra Weickhardt, Niels Eckstein, Bernd Kaina
Summary: MET showed cytotoxic effects at high, clinically irrelevant concentrations in all GBM cell lines and primary GBM cells, inducing apoptosis and necrosis. Sensitizing effects were only observed when combined with doxorubicin, not with TMZ. Therefore, the use of MET in combination with TMZ for the treatment of GBM is not supported.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
S. Daisy Precilla, Shreyas S. Kuduvalli, E. Angeline Praveena, Saravanabhavan Thangavel, T. S. Anitha
Summary: This study found that the combination of chloroquine, naringenin, and phloroglucinol enhances the anti-tumor effects of temozolomide on glioma by inducing apoptosis and cell cycle arrest.
Article
Oncology
Denise Casey, Suzanne Demko, Arup Sinha, Pallavi S. Mishra-Kalyani, Yuan-Li Shen, Sachia Khasar, M. Anwar Goheer, Whitney S. Helms, Lili Pan, Yuan Xu, Jianghong Fan, Ruby Leong, Jiang Liu, Yuching Yang, Katherine Windsor, Mei Ou, Olen Stephens, Byeongtaek Oh, Gregory H. Reaman, Abhilasha Nair, Stacy S. Shord, Vishal Bhatnagar, Selena R. Daniels, Sharon Sickafuse, Kirsten B. Goldberg, Marc R. Theoret, Richard Pazdur, Harpreet Singh
Summary: The FDA approved selumetinib for pediatric patients with neurofibromatosis type 1 who have inoperable plexiform neurofibromas. The approval was based on a single-arm multicenter trial showing clinical improvements and a durable overall response rate. The risks of selumetinib are consistent with MEK inhibitor class effects, with favorable benefit-risk assessment for patients with inoperable plexiform neurofibromas.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Hong-Chieh Tsai, Kuo-Chen Wei, Pin-Yuan Chen, Chiung-Yin Huang, Ko-Ting Chen, Ya-Jui Lin, Hsiao-Wei Cheng, Yi-Rou Chen, Hsiang-Tsui Wang
Summary: Combination treatment of TMZ and VPA in GBM patients can be beneficial for survival, depending on the p53 gene status. In cellular experiments, VPA enhances the antineoplastic effect of TMZ by promoting p53 activation.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Malihe Mohamadian, Seyed Sajad Ahmadi, Afsane Bahrami, Gordon A. Ferns
Summary: Gliomas, aggressive brain tumors with poor prognosis, are often resistant to current treatment options. Curcumin, a natural compound with anti-tumor effects, has been shown to inhibit glioma cell viability and enhance the effectiveness of chemotherapy and radiation. Studying the effects and mechanisms of curcumin in treating gliomas is of great significance.
NEUROCHEMICAL RESEARCH
(2022)
Article
Oncology
Huikai Zhang, Yang Xu, Gang Deng, Fanen Yuan, Yinqiu Tan, Lun Gao, Qian Sun, Yangzhi Qi, Kun Yang, Rongxin Geng, Hongxiang Jiang, Baohui Liu, Qianxue Chen
Summary: The study demonstrates that SAA1 is up-regulated in GBM and its high expression indicates poor prognosis, promoting GBM cell death by regulating apoptosis. Gliomas with low SAA1 expression show increased sensitivity to TMZ, suggesting SAA1 as a regulator of cell apoptosis and a novel biomarker for glioma sensitivity to TMZ.
Article
Oncology
Lea Beltzig, Christian Schwarzenbach, Petra Leukel, Katrin B. M. Frauenknecht, Clemens Sommer, Alessandro Tancredi, Monika E. Hegi, Markus Christmann, Bernd Kaina
Summary: In the treatment of glioblastoma, cellular senescence induced by DNA damage is found to be more important than apoptosis. The primary trigger of cellular senescence is DNA damage, rather than apoptosis. Cells that acquire resistance to treatment also become resistant to the induction of senescence. Induction of cellular senescence during treatment may play a significant role in therapy resistance.
Article
Oncology
Lea Beltzig, Bjoern Stratenwerth, Bernd Kaina
Summary: The study suggests that even low doses can accumulate therapeutic effects in glioblastoma therapy, supporting the effectiveness of metronomic dose schedule. Temozolomide, as a first-line therapy targeting tumor DNA at various sites, primarily induces genotoxic and cytotoxic effects through O-6-methylguanine.
Article
Biochemistry & Molecular Biology
Moumita Kundu, Subhayan Das, Suvendu Nandi, Dibakar Dhara, Mahitosh Mandal
Summary: The study found that magnolol (MGN) enhances the therapeutic effect of temozolomide (TMZ) on glioma. MGN promotes glioma cell apoptosis induced by TMZ by inhibiting NF-xB pathway-mediated MGMT activation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Editorial Material
Biochemistry & Molecular Biology
Kirit Singh, Kelly M. Hotchkiss, Ian F. Parney, John De Groot, Solmaz Sahebjam, Nader Sanai, Michael Platten, Evanthia Galanis, Michael Lim, Patrick Y. Wen, Giuseppe Minniti, Howard Colman, Timothy F. Cloughesy, Minesh P. Mehta, Marjolein Geurts, Isabel Arrillaga-Romany, Annick Desjardins, Kirk Tanner, Susan Short, David Arons, Elizabeth Duke, Wolfgang Wick, Stephen J. Bagley, David M. Ashley, Priya Kumthekar, Roel Verhaak, Anthony J. Chalmers, Anoop P. Patel, Colin Watts, Peter E. Fecci, Tracy T. Batchelor, Michael Weller, Michael A. Vogelbaum, Matthias Preusser, Mitchel S. Berger, Mustafa Khasraw
Summary: A breakthrough in drug discovery for glioblastoma necessitates the consecutive collection of central nervous system tissue through window of opportunity trials.
Article
Multidisciplinary Sciences
Hui-Ju Huang, Hsiang-Tsui Wang, Ting-Yu Yeh, Bo-Wei Lin, Young-Ji Shiao, Yu-Li Lo, Anya Maan-Yuh Lin
Summary: Selumetinib exhibits neuroprotective effects against acrolein-induced neurotoxicity by inhibiting the Nrf-2-HO-1 pathway, reducing protein conjugation and aggregation, attenuating damage in neurite outgrowth, and preventing cell death, suggesting its potential as a therapeutic agent for CNS neurodegenerative diseases.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Tahar Sif eddine Bouchema, Maxime Annereau, Victoire Vieillard, Raphael Boquet, Gisele Abreu Coelho, Florence Castelli, Audrey Solgadi, Muriel Paul, Najet Yagoubi, Philippe-Henri Secretan, Bernard Do
Summary: Selumetinib, an orally administered drug for treating neurofibromatosis, requires development of liquid formulations for dosage adjustment. The study found that selumetinib is sensitive to oxidation and photodegradation in solution, leading to the formation of amide and ester derivatives. Investigating these degradation mechanisms allows for targeted stabilization of the active molecule.
Article
Cell Biology
Juliana B. Candido, Jennifer P. Morton, Peter Bailey, Andrew D. Campbell, Saadia A. Karim, Thomas Jamieson, Laura Lapienyte, Aarthi Gopinathan, William Clark, Ewan J. McGhee, Jun Wang, Monica Escorcio-Correia, Raphael Zollinger, Rozita Roshani, Lisa Drew, Loveena Rishi, Rebecca Arkell, T. R. Jeffry Evans, Colin Nixon, Duncan I. Jodrell, Robert W. Wilkinson, Andrew V. Biankin, Simon T. Barry, Frances R. Balkwill, Owen J. Sansom
Article
Oncology
Nadine Nelson, Marta Lopez-Pelaez, Asis Palazon, Edmund Poon, Maike De La Roche, Simon Barry, Viia Valge-Archer, Robert W. Wilkinson, Simon J. Dovedi, Paul D. Smith
Article
Oncology
Stefanie R. Mullins, John P. Vasilakos, Katharina Deschler, Iwen Grigsby, Pete Gillis, Julius John, Matthew J. Elder, John Swales, Elina Timosenko, Zachary Cooper, Simon J. Dovedi, Andrew J. Leishman, Nadia Luheshi, James Elvecrog, Ashenafi Tilahun, Richard Goodwin, Ronald Herbst, Mark A. Tomai, Robert W. Wilkinson
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2019)
Article
Oncology
Shannon Burke, Amy Shergold, Matthew J. Elder, Justine Whitworth, Xing Cheng, Hong Jin, Robert W. Wilkinson, James Harper, Danielle K. Carroll
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2020)
Article
Multidisciplinary Sciences
Denice T. Y. Chan, Lesley Jenkinson, Stuart W. Haynes, Mark Austin, Agata Diamandakis, Daniel Burschowsky, Chitra Seewooruthun, Alexandra Addyman, Sebastian Fiedler, Stephanie Ryman, Jessica Whitehouse, Louise H. Slater, Ellen Gowans, Yoko Shibata, Michelle Barnard, Robert W. Wilkinson, Tristan J. Vaughan, Sarah Holt, Vincenzo Cerundolo, Mark D. Carr, Maria A. T. Groves
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Oncology
Susannah L. Hewitt, Dyane Bailey, John Zielinski, Ameya Apte, Faith Musenge, Russell Karp, Shannon Burke, Fabien Garcon, Ankita Mishra, Sushma Gurumurthy, Amanda Watkins, Kristen Arnold, James Moynihan, Eleanor Clancy-Thompson, Kathy Mulgrew, Grace Adjei, Katharina Deschler, Darren Potz, Gordon Moody, David A. Leinster, Steve Novick, Michal Sulikowski, Chris Bagnall, Philip Martin, Jean-Martin Lapointe, Han Si, Chris Morehouse, Maja Sedic, Robert W. Wilkinson, Ronald Herbst, Joshua P. Frederick, Nadia Luheshi
CLINICAL CANCER RESEARCH
(2020)
Article
Medicine, Research & Experimental
Darren J. Schofield, Jennifer Percival-Alwyn, Mateusz Rytelewski, John Hood, Raymond Rothstein, Leslie Wetzel, Kelly McGlinchey, Grace Adjei, Amanda Watkins, LeeAnn Machiesky, Weimin Chen, John Andrews, Maria Groves, Michelle Morrow, Ross A. Stewart, Andrew Leinster, Robert W. Wilkinson, Scott A. Hammond, Nadia Luheshi, Claire Dobson, Michael Oberst
Summary: Development of murine surrogate antibodies with pharmacologic properties similar to those of durvalumab and tremelimumab showed anti-tumor activity in select mouse syngeneic tumor models. This activity was not solely dependent on antibody-dependent cellular cytotoxicity, cellular phagocytosis effector function, or regulatory T-cell depletion, as antibodies engineered to lack these features also demonstrated activity, though at a lower level.
Article
Oncology
Simon J. Dovedi, Matthew J. Elder, Chunning Yang, Suzanne Sitnikova, Lorraine Irving, Anna Hansen, James Hair, Des C. Jones, Sumati Hasani, Bo Wang, Seock-Ah Im, Ben Tran, Deepa S. Subramaniam, Shelby D. Gainer, Kapil Vashisht, Arthur Lewis, Xiaofang Jin, Stacy Kentner, Kathy Mulgrew, Yaya Wang, Michael G. Overstreet, James Dodgson, Yanli Wu, Asis Palazon, Michelle Morrow, Godfrey J. Rainey, Gareth J. Browne, Frances Neal, Thomas Murray, Aleksandra D. Toloczko, William Dall'Acqua, Ikbel Achour, Daniel J. Freeman, Robert W. Wilkinson, Yariv Mazor
Summary: MEDI5752 is a novel monovalent bispecific antibody that enhances the clinical benefits of PD-1 blockade while reducing immune-related adverse events, leading to improved therapeutic outcomes. It represents a significant advancement in the rational design of cancer immunotherapy and shows promising potential in targeting PD-1(+) T cells with enhanced activity compared to conventional mAb combination strategies.
Article
Oncology
James Harper, Shannon Burke, Jon Travers, Nicola Rath, Andrew Leinster, Christel Navarro, Ruth Franks, Rebecca Leyland, Kathy Mulgrew, Kelly McGlinchey, Lee Brown, Simon J. Dovedi, Jens-Oliver Koopmann, Nicholas M. Durham, Xing Cheng, Hong Jin, Jim Eyles, Robert W. Wilkinson, Danielle Carroll
Summary: The recombinant NDVmuGM-CSF showed oncolytic activity and immune modulation in human tumor cells. In vivo experiments demonstrated antitumor effects with intratumoral injection, enhanced by co-treatment with immunomodulatory agents. Ex vivo profiling revealed changes in immune contexture and tumor microenvironment towards an immune-permissive state, supporting the utility of MEDI5395 in combination with other cancer treatments.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Oncology
Suzanne Isabelle Sitnikova, Sophie Munnings-Tomes, Elena Galvani, Stacy Kentner, Kathy Mulgrew, Chris Rands, Judit Espana Agusti, Tianhui Zhang, Kristina M. Ilieva, Guglielmo Rosignoli, Hormas Ghadially, Matthew J. Robinson, Tim Slidel, Robert W. Wilkinson, Simon J. Dovedi
Summary: A novel non-terminal tumor sampling method was developed and validated for biopsy of TME in mouse models, enabling repeated in-life sampling of subcutaneous flank tumors and linking TME biomarkers to treatment responses, which is not possible with current terminal sampling methods.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemical Research Methods
James Hair, Matthew J. Robinson, Robert W. Wilkinson, Simon J. Dovedi
Summary: This study provides a comprehensive understanding of the SICR profile of T and NK cells in solid tumors, guiding the design and application of future IO molecules.
Article
Oncology
Marta Lopez-Pelaez, Lucy Young, Mercedes Vazquez-Chantada, Nadine Nelson, Steve Durant, Robert W. Wilkinson, Edmund Poon, Miguel Gaspar, Viia Valge-Archer, Paul Smith, Simon J. Dovedi
Summary: This study demonstrates that targeting compensatory DNA repair pathways enhances the sensitivity of tumor cells to ATR inhibitor and DNA crosslinker, and activates dendritic cells (DCs) to increase tumor cell immunogenicity through the innate immune system activation. This provides a potential strategy to combat tumors.
Article
Multidisciplinary Sciences
Remi Samain, Oscar Maiques, Joanne Monger, Hoyin Lam, Juliana Candido, Samantha George, Nicola Ferrari, Leonie Kohihammer, Sophia Lunetto, Adrian Varela, Jose L. Orgaz, Felip Vilardell, Jorge Juan Olsina, Xavier Matias-Guiu, Debashis Sarker, Adrian Biddle, Frances R. Balkwill, Jim Eyles, Robert W. Wilkinson, Hemant M. Kocher, Fernando Calvo, Claire M. Wells, Victoria Sanz-Moreno
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to its high metastasis tendency and immunosuppressive microenvironment. The ROCK-Myosin II activity in PDAC cells supports an amoeboid invasive and immunosuppressive program, leading to in vivo metastasis. CD73, an immune checkpoint, is highly expressed in amoeboid PDAC cells and contributes to their invasive, metastatic, and immunomodulatory traits.
Article
Immunology
Damien J. Zanker, Alex J. Spurling, Natasha K. Brockwell, Katie L. Owen, Jasmine M. Zakhour, Tina Robinson, Hendrika M. Duivenvoorden, Paul J. Hertzog, Stefanie R. Mullins, Robert W. Wilkinson, Belinda S. Parker
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2020)
Article
Medicine, Research & Experimental
Mark Austin, Daniel Burschowsky, Denice T. Y. Chan, Lesley Jenkinson, Stuart Haynes, Agata Diamandakis, Chitra Seewooruthun, Alexandra Addyman, Sebastian Fiedler, Stephanie Ryman, Jessica Whitehouse, Louise H. Slater, Andreas V. Hadjinicolaou, Uzi Gileadi, Ellen Gowans, Yoko Shibata, Michelle Barnard, Teresa Kaserer, Pooja Sharma, Nadia M. Luheshi, Robert W. Wilkinson, Tristan J. Vaughan, Sarah V. Holt, Vincenzo Cerundolo, Mark D. Carr, Maria A. T. Groves