Article
Multidisciplinary Sciences
Jian Zhong, Xujia Wu, Yixin Gao, Junju Chen, Maolei Zhang, Huangkai Zhou, Jia Yang, Feizhe Xiao, Xuesong Yang, Nunu Huang, Haoyue Qi, Xiuxing Wang, Fan Bai, Yu Shi, Nu Zhang
Summary: The MET signalling pathway is crucial for maintaining glioblastoma (GBM) stem cells. Researchers have discovered a circular RNA from the MET gene (circMET) that produces a MET variant protein (MET404), which directly activates the MET receptor and promotes GBM tumorigenesis. This study uncovers hidden mechanisms of MET signalling in GBM and provides a potential therapeutic strategy for GBM patients.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Chaofan Wang, Jie Li, Lingzhi Qu, Xia Tang, Xiaojuan Song, Fang Yang, Xiaojuan Chen, Qianmeng Lin, Weibin Lin, Yang Zhou, ZhengChao Tu, Yongheng Chen, Zhang Zhang, Xiaoyun Lu
Summary: MET alterations are crucial in NSCLC and gastric cancers. We designed and optimized a series of new c-Met inhibitors using molecular hybridization and macrocyclization strategy, among which D6808 exhibited potent inhibitory activity, extraordinary target specificity, and promise for further anticancer drug development.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Yu-Ra Choi, Eun Hye Kang, Sunshin Kim, Seog-Yun Park, Ji-Youn Han, Youngjoo Lee
Summary: This study evaluated the efficacy of single MET inhibition in EGFR-mutant and MET-amplified lung cancer and found that it produced a short-lived response. Further research on novel combination therapy schedules is needed to achieve long-lasting efficacy with less toxicity.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Jianbing Hou, Minghao Xu, Hongyu Gu, Dakun Pei, Yudong Liu, Pan Huang, Hongbo Chang, Hongjuan Cui
Summary: ZC3H15, an overexpressed protein in GBM, promotes the proliferation, migration, invasion, and tumorigenesis of GBM cells by activating the EGFR signaling pathway. High expression of ZC3H15 is associated with poor patient survival.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Ryan J. Hartmaier, Aleksandra A. Markovets, Myung Ju Ahn, Lecia Sequist, Ji-Youn Han, Byoung Chul Cho, Helena A. Yu, Sang-We Kim, James Chih-Hsin Yang, Jong-Seok Lee, Wu-Chou Su, Dariusz M. Kowalski, Sergey Orlov, Song Ren, Paul Frewer, Xiaoling Ou, Darren A. E. Cross, Nisha Kurian, Mireille Cantarini, Pasi A. Jaenne
Summary: Combining MET inhibitor and EGFR tyrosine kinase inhibitor can overcome acquired osimertinib resistance mediated by MET. In this study, savolitinib and osimertinib combination therapy showed promising results in advanced non-small cell lung cancer patients with MET amplification and EGFR mutation who had progressed on prior EGFR-TKI treatment. The combination therapy demonstrated acceptable safety profile and improved antitumor activity.
Article
Cell Biology
Pinar Ozden Eser, Raymond M. Paranal, Jieun Son, Elena Ivanova, Yanan Kuang, Heidi M. Haikala, Ciric To, Jeffrey J. Okoro, Kshiti H. Dholakia, Jihyun Choi, Yoonji Eum, Atsuko Ogino, Pavlos Missios, Dalia Ercan, Man Xu, Michael J. Poitras, Stephen Wang, Kenneth Ngo, Michael Dills, Masahiko Yanagita, Timothy Lopez, Mika Lin, Jeanelle Tsai, Nicolas Floch, Emily S. Chambers, Jennifer Heng, Rana Anjum, Alison D. Santucci, Kesi Michael, Alwin G. Schuller, Darren Cross, Paul D. Smith, Geoffrey R. Oxnard, David A. Barbie, Lynette M. Sholl, Magda Bahcall, Sangeetha Palakurthi, Prafulla C. Gokhale, Cloud P. Paweletz, George Q. Daley, Pasi A. Janne
Summary: Some EGFR-mutant, MET-amplified lung cancers may develop dependence on MET activation alone, suggesting that these patients could be treated with a single-agent MET TKI instead of the current standard-of-care EGFR and MET inhibitor combination regimens.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Medicinal
Zhenhao Liu, Kuan Liang, Wenlang Liu, Tao Jiang, Rui Zhou, Mojie Duan, Zheng Zheng
Summary: The tyrosine-protein kinase Met (c-Met) is a crucial signaling molecule involved in cellular growth and division. Dysregulation of c-Met can lead to various fatal diseases. Understanding the mechanisms of ligand binding and regulation of c-Met is important for developing effective drugs against drug tolerance.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Pharmacology & Pharmacy
Ying Jiang, Chunhui Huang, Yaqi Huang, Lifan Long, Guowu Wu, Fengqiu Guo, Chuan Huang, Siming Liu, Zhengguang Zhu, Shaoyu Wu, Zhonghuang Li, Jiajie Zhang, Shanhe Wan
Summary: Targeting EGFR with the inhibitor SMUZ106 has shown promising anti-tumor effects for glioblastoma (GBM). In this study, SMUZ106 was found to inhibit the growth and proliferation of GBM cells through various experiments, including MTT, clone formation, and flow cytometry. The selectivity and inhibitory activity of SMUZ106 to EGFR were confirmed using Western blotting, molecular docking, and kinase spectrum screening methods. In vivo experiments demonstrated that SMUZ106 hydrochloride has a high bioavailability and low toxicity, and it significantly inhibited GBM growth.
Article
Cell Biology
Xuan Wang, Shuyong Wang, Baolin Guo, Yuxin Su, Zuolong Tan, Mingyang Chang, Jinmei Diao, Yi Zhao, Yunfang Wang
Summary: The study presents a method for establishing and expanding human primary epidermal organoids under a chemically defined condition, which show tolerance to dermatophyte infections caused by Trichophyton Rubrum. This experimental model provides new insights into the pathogenesis of T. rubrum infections and serves as a potential tool for studying and testing antifungal drugs.
CELL DEATH & DISEASE
(2021)
Article
Medicine, Research & Experimental
Masahiro Hitomi, Anastasia P. Chumakova, Daniel J. Silver, Arnon M. Knudsen, W. Dean Pontius, Stephanie Murphy, Neha Anand, Bjarne W. Kristensen, Justin D. Lathia
Summary: ACD generates progeny cells with enhanced therapeutic resistance and increased growth factor receptors, contributing to the therapeutic resistance of cancer stem cells.
Article
Biochemistry & Molecular Biology
Tamara Reyes-Robles, Aleksandra K. Olow, Tyler J. Bechtel, Scott A. Lesley, Olugbeminiyi O. Fadeyi, Rob C. Oslund
Summary: Receptor tyrosine kinases play essential roles in cell signaling, with mutations or overexpression potentially leading to diseases such as cancer. Strategies targeting multiple RTKs, like EGFR and c-MET, have emerged to overcome therapeutic resistance.
ACS CHEMICAL BIOLOGY
(2022)
Article
Oncology
Toshio Fujino, Kenichi Suda, Takamasa Koga, Akira Hamada, Shuta Ohara, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Junichi Soh, Tetsuya Mitsudomi
Summary: The study identified that the type II MET-TKI foretinib could be a suitable second-line treatment option for NSCLCs carrying METex14 after capmatinib/tepotinib treatment failure due to secondary mutations at residue D1228 or Y1230.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joost Neijssen, Rosa M. F. Cardoso, Kristen M. Chevalier, Luus Wiegman, Thomas Valerius, G. Mark Anderson, Sheri L. Moores, Janine Schuurman, Paul W. H. Parren, William R. Strohl, Mark L. Chiu
Summary: This study focused on developing a bispecific antibody targeting EGFR and MET pathways to overcome resistance to targeted therapies in nonsmall cell lung cancer patients. By sequentially screening a panel of BsAbs and selecting the optimal bispecific molecule, amivantamab was generated and demonstrated superior antitumor activity in preclinical models. The unique mode of action of amivantamab may provide benefits to patients with malignancies associated with aberrant EGFR and MET signaling.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Immunology
Fenge Li, Huancheng Wu, Xueming Du, Yimo Sun, Barbara Nassif Rausseo, Amjad Talukder, Arjun Katailiha, Lama Elzohary, Yupeng Wang, Zhiyu Wang, Gregory Lizee
Summary: The EGFR gene is frequently overexpressed and mutated in various solid tumors, and peptide vaccines targeting mutated EGFR have shown promising clinical efficacy and safety profiles.
Article
Oncology
Helene Babey, Philippe Jamme, Hubert Curcio, Jean Baptiste Assie, Remi Veillon, Helene Doubre, Maurice Perol, Florian Guisier, Eric Huchot, Chantal Decroisette, Lionel Falchero, Romain Corre, Alexis Cortot, Christos Chouaid, Renaud Descourt
Summary: This study aimed to describe the management of METexon14 aNSCLC patients. The study found no significant benefit in median overall survival with the use of MET targeted tyrosine kinase inhibitors in METexon14 aNSCLC patients.
Article
Oncology
Ding Ma, Senquan Liu, Bachchu Lal, Shuang Wei, Shuyan Wang, Daqian Zhan, Hao Zhang, Richard S. Lee, Peisong Gao, Hernando Lopez-Bertoni, Mingyao Ying, Jian Jian Li, John Laterra, Mary Ann Wilson, Shuli Xia
Article
Oncology
Hernando Lopez-Bertoni, Ivan S. Kotchetkov, Nicole Mihelson, Bachchu Lal, Yuan Rui, Heather Ames, Maria Lugo-Fagundo, Hugo Guerrero-Cazares, Alfredo Quinones-Hinojosa, Jordan J. Green, John Laterra
Article
Oncology
Daqian Zhan, Ding Ma, Shuang Wei, Bachchu Lal, Yi Fu, Charles Eberhart, John Laterra, Mingyao Ying, Yunqing Li, Alan Meeker, Hernando Lopez-Bertoni, Shuli Xia
Summary: The presence of heterozygous isocitrate dehydrogenase (IDH) R132H mutation (IDH1(R132H/WT)) in glioma cells contributes to improved therapeutic responses by inducing senescence. Additionally, IDH1(R132H/WT) in conjunction with ATRX knockout and p53/RB loss can transform nonneoplastic human astroglial cells to form tumors in mouse brains, with a subset of these cells undergoing senescence-like changes. These findings suggest that targeting senescent cells could aid in eliminating precancerous cells and reducing tumor growth following antitumor therapies.
MOLECULAR CANCER RESEARCH
(2021)
Article
Oncology
Hernando Lopez-Bertoni, John Laterra
Summary: Cutting-edge developments in nanomedicine and the recent FDA approval of two siRNA-based therapeutics have reignited interest in RNA interference (RNAi) as potential novel cancer treatments. MiRNAs are emerging as the next-generation RNAi therapeutics, advancements in delivery vehicles for in vivo miRNA delivery are progressing, and the clinical translation of miRNA technology is being explored.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Oncology
Ding Ma, Daqian Zhan, Yi Fu, Shuang Wei, Bachchu Lal, Jie Wang, Yunqing Li, Hernando Lopez-Bertoni, Fatih Yalcin, Omar Dzaye, Charles G. Eberhart, John Laterra, Mary Ann Wilson, Mingyao Ying, Shuli Xia
Summary: The study demonstrates that IDH1 mutations impact TAM phenotypes, promoting anti-tumor functions in macrophages while inhibiting tumor growth. Decreased ICAM-1 expression plays a critical role in mediating the immunomodulatory function of IDH1 mutations.
Review
Oncology
Amanda L. Johnson, John Laterra, Hernando Lopez-Bertoni
Summary: Immunotherapy has not been effective in clinical trials for gliomas due to the cold tumor immune microenvironment and the role of glioma stem cells in promoting immunosuppression. Recent studies have identified intrinsic mechanisms in glioma stem cells that contribute to immune escape and modulation of the tumor immune microenvironment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Daqian Zhan, Fatih Yalcin, Ding Ma, Yi Fu, Shuang Wei, Bachchu Lal, Yunqing Li, Omar Dzaye, John Laterra, Mingyao Ying, Hernando Lopez-Bertoni, Shuli Xia
Summary: This study reveals that UGDH in glioblastoma (GBM) plays a role in promoting tumor growth through multiple mechanisms and is involved in the development of tumor-associated microglia/macrophages (TAMs) and T cells. Targeting UGDH can reduce tumor growth and promote the activation and infiltration of TAMs and T cells.
Article
Multidisciplinary Sciences
Myungjun Ko, Monish R. Makena, Paula Schiapparelli, Paola Suarez-Meade, Allatah X. Mekile, Bachchu Lal, Hernando Lopez-Bertoni, Kristen L. Kozielski, Jordan J. Green, John Laterra, Alfredo Quinones-Hinojosa, Rajini Rao
Summary: Self-renewing stem cells play a crucial role in tumor initiation and therapeutic resistance in glioblastoma. The endosomal pH regulator NHE9 promotes cell surface expression and phosphorylation of multiple receptor tyrosine kinases (RTKs), leading to the activation of oncogenic signaling pathways and induction of pluripotency genes. Alkalization of the endosomal lumen through the use of chemical agents can bypass NHE9 and induce similar effects.
Article
Biochemistry & Molecular Biology
Hernando Lopez-Bertoni, Amanda Johnson, Yuan Rui, Bachchu Lal, Sophie Sall, Maureen Malloy, Jonathan B. Coulter, Maria Lugo-Fagundo, Sweta Shudir, Harmon Khela, Christopher Caputo, Jordan J. Green, John Laterra
Summary: DNA methylation is a reversible process that plays an important role in cancer development. The loss of TET2, an enzyme involved in DNA methylation, is associated with glioblastoma stem cells and poor patient survival. The study also uncovers a mechanism involving SOX2:miR-10b-5p:TET2 axis that leads to the repression of TET2 expression and the loss of 5-hydroxymethylcytosine (5hmC), resulting in increased levels of 5-methylcytosine (5mC) and the promotion of tumor stemness and growth. Restoring TET2 expression and 5hmC levels using a miR-10b-5p inhibitor inhibits tumor growth and improves survival in a mouse model of glioblastoma.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Meeting Abstract
Oncology
Hernando M. Lopez-Bertoni
Meeting Abstract
Oncology
Hernando Lopez-Bertoni
Meeting Abstract
Oncology
Hernando Lopez-Bertoni
Meeting Abstract
Oncology
Harmon Khela, Sweta Sudhir, Maria Lugo-Fagundo, Bachchu Lal, Hernando Lopez-Bertoni, John Laterra
Meeting Abstract
Oncology
Hernando Lopez-Bertoni
Meeting Abstract
Oncology
Hernando Lopez
Article
Clinical Neurology
Hyunjung Kim, Jhii-Hyun Ahn, Sung Min Ko, Jin Woo Kim
Summary: The pre-navigation balloon technique significantly reduces the occurrence of distal embolism and increases the first-pass effect (FPE) during stent retriever thrombectomy. This technique is particularly effective for patients with ICA occlusion, improving clinical outcomes.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2024)
Review
Clinical Neurology
Mehdi Khaleghi, Joshua Vignolles-Jeong, Bradley Otto, Ricardo Carrau, Daniel Prevedello
Summary: This study presented a rare case of symptomatic ectopic Rathke's cleft cyst (RCC), which was located posterior to the pituitary gland and caused extensive clival erosion. The surgical technique of wide marsupialization of the cyst using intraoperative ultrasound-assisted endoscopic endonasal transclival approach was described, and a systematic literature review of intracranial ectopic RCCs was conducted.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2024)
Article
Clinical Neurology
Oscar H. Del Brutto, Denisse A. Rumbea, Aldo F. Costa, Maitri Patel, Mark J. Sedler, Robertino M. Mera
Summary: This study found an association between cognitive impairment and mortality risk in adults of Amerindian ancestry living in rural Ecuador.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2024)
Article
Clinical Neurology
Yangjingyi Xia, Li Li, Yunze Li, Manyan Hu, Tianrui Zhang, Qinghua Feng, Wenlei Li, Yuan Zhu, Minghua Wu
Summary: This study shows that fasting blood glucose (FBG) level is significantly associated with unfavorable outcome after acute ischemic stroke (AIS) in patients. The risk of unfavorable outcome increases significantly when FBG is above 5.5 mmol/L.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2024)