Article
Chemistry, Analytical
Nana Wang, Jiejun Wang, Pu Wang, Nan Ji, Shuhua Yue
Summary: Temozolomide (TMZ) is a first line chemotherapy drug for glioblastoma (GBM). However, GBMs without methylation of O-6-methylguanine-DNA methyltransferase (MGMT) show resistance to TMZ treatment. This study found that MGMT methylation affects lipid accumulation in GBM, and the amount and composition of lipid droplets (LDs) are significantly reduced in GBMs without MGMT methylation.
ANALYTICAL CHEMISTRY
(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
Edikan A. Ogunnaike, Alain Valdivia, Mostafa Yazdimamaghani, Ernesto Leon, Seema Nandi, Hannah Hudson, Hongwei Du, Simon Khagi, Zhen Gu, Barbara Savoldo, Frances S. Ligler, Shawn Hingtgen, Gianpietro Dotti
Summary: The delivery of CAR-T cells within the surgical cavity using a fibrin-based gel demonstrates superior antitumor activity compared to direct inoculation into the tumor resection cavity in a model of subtotal glioblastoma resection.
Article
Oncology
Youri Hoogstrate, Kaspar Draaisma, Santoesha A. Ghisai, Levi van Hijfte, Nastaran Barin, Iris de Heer, Wouter Coppieters, Thierry P. P. van den Bosch, Anne Bolleboom, Zhenyu Gao, Arnaud J. P. E. Vincent, Latifa Karim, Manon Deckers, Martin J. B. Taphoorn, Melissa Kerkhof, Astrid Weyerbrock, Marc Sanson, Ann Hoeben, Slavka Lukacova, Giuseppe Lombardi, Sieger Leenstra, Monique Hanse, Ruth E. M. Fleischeuer, Colin Watts, Nicos Angelopoulos, Thierry Gorlia, Vassilis Golfinopoulos, Vincent Bours, Martin J. van den Bent, Pierre A. Robe, Pim J. French
Summary: A better understanding of the transcriptional evolution of IDH-wild-type glioblastoma is crucial for optimizing treatment. Through RNA sequencing, this study demonstrates that glioblastomas mainly evolve through microenvironmental reorganization rather than molecular evolution of tumor cells. The changes in tumor composition over time, including alterations in neuron and oligodendrocyte marker genes and an increase in tumor-associated macrophages, are confirmed by single-cell RNA-seq and immunohistochemistry.
Review
Biochemistry & Molecular Biology
Karoline Almeida Lima, Isabeli Yumi Araujo Osawa, Maria Carolina Clares Ramalho, Izadora de Souza, Camila Banca Guedes, Claudio Henrique Dahne de Souza Filho, Linda Karolynne Seregni Monteiro, Marcela Teatin Latancia, Clarissa Ribeiro Reily Rocha
Summary: This article highlights the constitutive activation of NRF2 in glioblastoma and its role in promoting survival and protecting against TMZ resistance through various molecular pathways. It also discusses potential strategies for targeting NRF2 as an adjuvant therapy and the importance of identifying NRF2 modulators for therapeutic intervention.
Article
Biochemistry & Molecular Biology
Rodolfo Bortolozo Serafim, Cibele Cardoso, Vanessa Cristina Arfelli, Valeria Valente, Leticia Frohlich Archangelo
Summary: PIMREG expression is strongly related to cellular proliferation in malignant and normal cells. It is highly expressed in the central nervous system during embryo development and has been found to be elevated in various types of tumors. The expression level of PIMREG can serve as a biomarker for glioma progression and patient outcome. Additionally, it plays a role in DNA damage response and temozolomide resistance in glioblastoma cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Review
Cell Biology
Chia-Hung Chien, Wei-Ting Hsueh, Jian-Ying Chuang, Kwang-Yu Chang
Summary: Glioblastoma is considered fatal due to its development of resistance, with temozolomide being effective in disease control but recurrence eventually occurring. The main factor determining drug susceptibility is aberrations in O-6-methylguanine-DNA methyltransferase, while alterations in other DNA repair genes also impact drug effect. Recent identification of specific cellular subsets with features of stem-like cells may play a role in evading cancer treatment.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Alexandra M. Amen, Christof Fellmann, Katarzyna M. Soczek, Shawn M. Ren, Rachel J. Lew, Gavin J. Knott, Jesslyn E. Park, Andrew M. McKinney, Andrew Mancini, Jennifer A. Doudna, Joseph F. Costello
Summary: Mutations in the TERT promoter of glioblastomas create binding sites for GABP transcription factor complexes, leading to reactivation of TERT and maintenance of telomeres. GBM cells with TERT promoter mutations display a dependence on GABPB1L for proliferation, which can be rescued by upregulation of the protein paralogue GABPB2. Inhibition of GABPB1L in combination with chemotherapy results in reduced growth of intracranial GBM tumors by impairing DNA damage response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Christian T. Stackhouse, Joshua C. Anderson, Zongliang Yue, Thanh Nguyen, Nicholas J. Eustace, Catherine P. Langford, Jelai Wang, James R. Rowland, Chuan Xing, Fady M. Mikhail, Xiangqin Cui, Hasan Alrefai, Ryan E. Bash, Kevin J. Lee, Eddy S. Yang, Anita B. Hjelmeland, C. Ryan Miller, Jake Y. Chen, Yancey Gillespie, Christopher D. Willey
Summary: The key molecular regulators of acquired radiation resistance in recurrent glioblastoma (GBM) are largely unknown. In this study, patient-derived xenograft (PDX) models were generated to mimic the longitudinal evolution of patient recurrent tumors following radiation therapy. Whole-exome sequencing and bioinformatics analysis identified genomic alterations and kinomic alterations associated with acquired radiation resistance. The study also found multiple molecular routes to acquired radiation resistance and identified targetable kinases for potential therapeutic interventions. This research provides important insights into overcoming treatment resistance in GBM patients.
Review
Biochemistry & Molecular Biology
Zhang Qiang, Xu Can, Tang Chao-Ke
Summary: The balance of intracellular cholesterol level is crucial for cellular function. Imbalances are associated with increased risk of cardiovascular and metabolic diseases. Key factors involved in the regulation of cholesterol biosynthesis, uptake, efflux, and esterification have been identified.
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Chemistry, Medicinal
Meng-Meng Zhang, Yan Jia, Peng Li, Yan Qiao, Ke-Li Han
Summary: The study found that lysosomal sulfatase expression is closely related to the prognosis of glioblastoma. A new probe, MNG, was developed to detect lysosomal sulfatase, and the first reported lysosomal sulfatase inhibitor, sulbactam, was found to inhibit tumor growth in GBM.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Mohammad Hazaymeh, Ronja Loeber-Handwerker, Katja Doering, Tammam Abboud, Dorothee Mielke, Veit Rohde, Vesna Malinova
Summary: Approximately 25% of glioblastomas show corpus callosum infiltration at diagnosis, which is associated with poor prognosis. The extent of corpus callosum involvement ranges from partial unilateral to complete bilateral infiltration. The role of surgery in glioblastoma with corpus callosum involvement is controversial.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Katharina Otte, Kai Zhao, Madita Braun, Andreas Neubauer, Hartmann Raifer, Frederik Helmprobst, Felipe Ovalle Barrera, Christopher Nimsky, Joerg W. Bartsch, Tillmann Rusch
Summary: This study found that Eltanexor, a second-generation XPO1 inhibitor, has effective monotherapy effects on GBM cells and can be combined with current adjuvant therapies to provide a more effective treatment for GBM. The mechanism of Eltanexor-induced apoptosis in GBM cells may be related to increased expression of TP53-dependent genes.
Article
Multidisciplinary Sciences
Silvia Chiesa, Antonella Mangraviti, Maurizio Martini, Tonia Cenci, Ciro Mazzarella, Simona Gaudino, Serena Bracci, Antonella Martino, Giuseppe M. Della Pepa, Martina Offi, Marco Gessi, Rosellina Russo, Matia Martucci, Francesco Beghella Bartoli, Luigi M. Larocca, Liverana Lauretti, Alessandro Olivi, Roberto Pallini, Mario Balducci, Quintino Giorgio D'Alessandris
Summary: This study aimed to identify molecular predictive factors for response to regorafenib in recurrent IDH-wildtype glioblastoma patients and found that mutations in the MAPK pathway may predict poor response and shorter survival in patients treated with regorafenib.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Fanchen Wang, Lixia Xu, Binli Wen, Sirong Song, Yan Zhou, Haiyang Wu, Qiaoli Wu, Yinsong Wang, Xiaoguang Tong, Hua Yan
Summary: In this study, we found that temozolomide (TMZ) can produce reactive oxygen species (ROS) under the influence of ultrasound (US), enhancing its therapeutic effect on glioblastoma (GBM). Our findings will facilitate the development of TMZ-associated therapies for GBM, considering the increasing use of US in central nervous system (CNS) diseases and the significance of TMZ in GBM therapy. Furthermore, we also discovered the potential of other chemotherapeutic drugs to generate ROS under US excitation, suggesting broader implications in drug research.
Article
Clinical Neurology
Kentaro Mori, Kojiro Wada, Naoki Otani, Arata Tomiyama, Terushige Toyooka, Satoru Takeuchi, Takuji Yamamoto, Yasuaki Nakao, Hajime Arai
JOURNAL OF NEUROSURGERY
(2019)
Article
Oncology
Yoshiko Nakano, Arata Tomiyama, Takashi Kohno, Akihiko Yoshida, Kai Yamasaki, Tatsuya Ozawa, Kohei Fukuoka, Hiroko Fukushima, Takeshi Inoue, Junichi Hara, Hiroaki Sakamoto, Koichi Ichimura
BRAIN TUMOR PATHOLOGY
(2019)
Article
Oncology
Arata Tomiyama, Koichi Ichimura
SEMINARS IN CANCER BIOLOGY
(2019)
Article
Clinical Neurology
Kosuke Kumagai, Arata Tomiyama, Satoru Takeuchi, Naoki Otani, Masanori Fujita, Kazuya Fujii, Kojiro Wada, Kentaro Mori
Summary: The new SAH + UCCAO model successfully simulated EBI with aggravation of reactive astrogliosis, cerebral vasospasm, and DBI without high mortality.
JOURNAL OF NEUROSURGERY
(2021)
Article
Clinical Neurology
Naoki Otani, Kentaro Mori, Kojiro Wada, Arata Tomiyama, Terushige Toyooka, Satoru Takeuchi, Yasuaki Nakao, Takuji Yamamoto, Hajime Arai
WORLD NEUROSURGERY
(2020)
Article
Multidisciplinary Sciences
Kosuke Kumagai, Terushige Toyooka, Satoru Takeuchi, Naoki Otani, Kojiro Wada, Arata Tomiyama, Kentaro Mori
SCIENTIFIC REPORTS
(2020)
Article
Oncology
Tatsuya Kobayashi, Makoto Miyazaki, Nobuyoshi Sasaki, Shun Yamamuro, Eita Uchida, Daisuke Kawauchi, Masamichi Takahashi, Yohei Otsuka, Kosuke Kumagai, Satoru Takeuchi, Terushige Toyooka, Naoki Otani, Kojiro Wada, Yoshitaka Narita, Hideki Yamaguchi, Yoshihiro Muragaki, Takakazu Kawamata, Kentaro Mori, Koichi Ichimura, Arata Tomiyama
Article
Peripheral Vascular Disease
Kosuke Kumagai, Terushige Toyooka, Yohei Otsuka, Masahiro Horikawa, Kentaro Yamada, Arata Tomiyama, Satoru Takeuchi, Koichi Kurihara, Kojiro Wada
Summary: In rat models, repeated VCA cannulations on different days were found to be superior to repeated femoral artery cannulations in terms of surgical time, postsurgical weight loss, and ischemic complications. The lateral caudal arteries and the segmental anastomosing vessels were identified as important factors for resistance to ischemic complications after VCA occlusion.
BLOOD PRESSURE MONITORING
(2021)
Article
Oncology
Daisuke Kawauchi, Masamichi Takahashi, Kaishi Satomi, Shun Yamamuro, Tatsuya Kobayashi, Eita Uchida, Mai Honda-Kitahara, Yoshitaka Narita, Yasuo Iwadate, Koichi Ichimura, Arata Tomiyama
Summary: The study found that second-generation ALK inhibitors, alectinib and ceritinib, effectively induced GBM cell death in human GBM cell lines expressing low ALK levels and showed antitumor activity, suggesting that they could serve as potent therapeutic strategies against GBM.
Article
Oncology
Shun Yamamuro, Masamichi Takahashi, Kaishi Satomi, Nobuyoshi Sasaki, Tatsuya Kobayashi, Eita Uchida, Daisuke Kawauchi, Tomoyuki Nakano, Takashi Fujii, Yoshitaka Narita, Akihide Kondo, Kojiro Wada, Atsuo Yoshino, Koichi Ichimura, Arata Tomiyama
Summary: The study demonstrated that CCNU and ACNU have significant antitumor effects against TMZ-resistant GBM, suggesting their potential as effective therapeutic agents in salvage treatment against TMZ-R-GBM.
Article
Oncology
Yuko Nagamura, Makoto Miyazaki, Yoshiko Nagano, Arata Tomiyama, Rieko Ohki, Kazuyoshi Yanagihara, Ryuichi Sakai, Hideki Yamaguchi
Summary: Diffuse-type gastric carcinoma (DGC) is characterized by aggressive progression associated with rapid infiltrative growth, massive fibrosis, and peritoneal dissemination. In this study, SHP2 was identified as a critical regulator downstream of the amplified Met and FGFR2 receptor tyrosine kinases (RTKs) in DGC cell lines. Targeting SHP2 selectively suppressed the growth and malignant phenotypes of RTK-addicted DGC, highlighting its potential as a therapeutic target for DGC treatment.
Article
Oncology
Jo Sasame, Naoki Ikegaya, Masahito Kawazu, Manabu Natsumeda, Takahiro Hayashi, Masataka Isoda, Kaishi Satomi, Arata Tomiyama, Akito Oshima, Hirokuni Honma, Yohei Miyake, Katsuhiro Takabayashi, Taishi Nakamura, Toshihide Ueno, Yuko Matsushita, Hiromichi Iwashita, Yu Kanemaru, Hidetoshi Murata, Akihide Ryo, Keita Terashima, Shoji Yamanaka, Yukihiko Fujii, Hiroyuki Mano, Takashi Komori, Koichi Ichimura, Daniel P. Cahill, Hiroaki Wakimoto, Tetsuya Yamamoto, Kensuke Tateishi
Summary: The study reveals that the treatment of BRAFV600E-mutant high-grade gliomas can lead to drug resistance due to the deregulation of negative feedback mechanisms, causing the reactivation of the MAPK pathway. However, combination therapy using an HSP90 inhibitor with BRAF or MEK inhibitors can overcome this resistance mechanism and improve the therapeutic effect.
CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Kyuto Sonehara, Yui Kimura, Yoshiko Nakano, Tatsuya Ozawa, Meiko Takahashi, Ken Suzuki, Takashi Fujii, Yuko Matsushita, Arata Tomiyama, Toshihiro Kishikawa, Kenichi Yamamoto, Tatsuhiko Naito, Tomonari Suzuki, Shigeru Yamaguchi, Tomoru Miwa, Hikaru Sasaki, Masashi Kitagawa, Naoyuki Ohe, Junya Fukai, Hideki Ogiwara, Atsufumi Kawamura, Satoru Miyawaki, Fumihiko Matsuda, Nobutaka Kiyokawa, Koichi Ichimura, Ryo Nishikawa, Yukinori Okada, Keita Terashima
Summary: In this study, a genome-wide association study was conducted to identify a risk locus at BAK1 gene for intracranial germ cell tumors (IGCTs). Functional characterization of this risk locus revealed its role in altering BAK1 expression and contributing to the susceptibility of IGCTs. Additionally, the study found shared genetic susceptibility of GCTs between Japanese and European populations.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Terushige Toyooka, Satoru Takeuchi, Naoki Otani, Kosuke Kumagai, Arata Tomiyama, Kojiro Wada, Kentaro Mori
Summary: This study developed a novel intraoperative method of prophylactic intraventricular piping (PIP) to prevent entrapped temporal horn (ETH) after tumor removal. By inserting catheters into the tumor cavity, pressure balance between each compartment of the lateral ventricle was maintained, thus preventing the occurrence of ETH.
WORLD NEUROSURGERY
(2022)
Article
Oncology
Motoo Nagane, Koichi Ichimura, Ritsuko Onuki, Daichi Narushima, Mai Honda-Kitahara, Kaishi Satomi, Arata Tomiyama, Yasuhito Arai, Tatsuhiro Shibata, Yoshitaka Narita, Takeo Uzuka, Hideo Nakamura, Mitsutoshi Nakada, Yoshiki Arakawa, Takanori Ohnishi, Akitake Mukasa, Shota Tanaka, Toshihiko Wakabayashi, Tomokazu Aoki, Shigeki Aoki, Soichiro Shibui, Masao Matsutani, Keisuke Ishizawa, Hideaki Yokoo, Hiroyoshi Suzuki, Satoshi Morita, Mamoru Kato, Ryo Nishikawa
Summary: This study evaluated the efficacy and safety of bevacizumab in Japanese patients with newly diagnosed glioblastoma and identified an expression classifier that may predict patient prognosis.
