Article
Oncology
Anja Kathrin Wege, Eva-Maria Rom-Jurek, Paul Jank, Carsten Denkert, Peter Ugocsai, Christine Solbach, Jens-Uwe Blohmer, Bruno Sinn, Marion Mackelenbergh, Volker Moebus, Andreas Trumpp, Elisabetta Marangoni, Nicole Pfarr, Christoph Irlbeck, Jens Warfsmann, Bernhard Polzer, Florian Weber, Olaf Ortmann, Sibylle Loibl, Valentina Vladimirova, Gero Brockhoff
Summary: The study aimed to discover and validate biomarkers associated with tumor progression and clinical outcome in Luminal breast cancer, with findings showing that an elevated mdm2 gene was linked to tumor growth and metastasis in mice, as well as correlated with prognosis and treatment response in patients.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Review
Oncology
Anna Chen, Ines Neuwirth, Dietmar Herndler-Brandstetter
Summary: Cancer immunotherapy has benefited many patients with malignant disease, but only a small fraction of patients respond completely and durably. More effective immunotherapies, combination treatments, and predictive biomarkers are needed. The molecular properties of a tumor, intratumor heterogeneity, and the tumor immune microenvironment play important roles in tumor evolution, metastasis, and therapy resistance. Humanized mouse models that replicate the human tumor immune microenvironment are promising for studying precision immuno-oncology and testing immunotherapeutic approaches.
Article
Oncology
Sandra D. Scherer, Alessandra Riggio, Fadi Haroun, Yoko S. DeRose, H. Atakan Ekiz, Maihi Fujita, Jennifer Toner, Ling Zhao, Zheqi Li, Steffi Oesterreich, Ahmed A. Samatar, Alana L. Welm
Summary: This study developed an immune-humanized PDX model for studying endocrine-resistant ER+ breast cancer, which contains a naturally occurring ESR1 mutation and recapitulates the lymphocyte-excluded and myeloid-rich tumor microenvironment of human ER+ breast tumors. The model provides a platform for studying mechanisms of endocrine resistance and tumor-immune interactions in a clinically relevant in vivo setting.
BREAST CANCER RESEARCH
(2021)
Review
Immunology
Nina B. Horowitz, Imran Mohammad, Uriel Y. Moreno-Nieves, Ievgen Koliesnik, Quan Tran, John B. Sunwoo
Summary: Innate lymphoid cells (ILCs) play an important role in antitumor immunity, but their behavior in the context of cancer is not fully understood. Humanized mouse models serve as excellent tools for studying these pathways and interactions between ILCs and tumors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Katrin Kleinmanns, Stein-Erik Gullaksen, Geir Bredholt, Ben Davidson, Cecilie Fredvik Torkildsen, Sindre Grindheim, Line Bjorge, Emmet McCormack
Summary: Epithelial ovarian cancer (EOC) is a heterogenous disease and new combination therapies are employed to improve treatment. Immunotherapy has the potential to improve the prognosis of EOC patients, but there is a lack of reliable biomarkers and personalized treatment methods. This study aims to develop and characterize humanized patient-derived xenograft models to understand the interaction between the tumor microenvironment and the immune system in EOC.
Article
Oncology
Morten F. F. Gjerstorff, Sofie Traynor, Odd L. L. Gammelgaard, Simone Johansen, Christina B. B. Pedersen, Henrik J. J. Ditzel, Mikkel G. G. Terp
Summary: Breast cancer patient-derived xenograft (PDX) models have been shown to be excellent tools for studying and targeting myeloid-derived suppressive cells (MDSCs) in tumors. These models demonstrate active recruitment of MDSCs to the tumors and reflect clinical complexity seen in breast cancer patients, providing valuable insights for the development of novel therapeutic strategies.
Article
Immunology
Ji Hye Jeong, Sujin Park, Sangyeon Lee, Yeounhee Kim, In Kyong Shim, Seong-Yun Jeong, Eun Kyung Choi, Jinju Kim, Eunsung Jun
Summary: A pancreatic cancer model using humanized mice was constructed to monitor tumor growth and investigate the correlation between immune cell count and tumor ECM density. Tumor-derived cells and organoids with continuous passage capacity were isolated from the model for testing the efficacy of targeted immunotherapeutic agents.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Oncology
Yongxian Zhuang, Jordan M. Grainger, Peter T. Vedell, Jia Yu, Ann M. Moyer, Huanyao Gao, Xiao-Yang Fan, Sisi Qin, Duan Liu, Krishna R. Kalari, Matthew P. Goetz, Judy C. Boughey, Richard M. Weinshilboum, Liewei Wang
Summary: The study successfully established two breast cancer cell lines with unique genomic characteristics derived from patient-derived xenografts. These cell lines retained the genetic and drug response information of the patients, providing a valuable tool for understanding the molecular mechanisms of drug resistance and exploring new treatment strategies.
Article
Oncology
Nicolas Aubert, Simon Brunel, Daniel Olive, Gilles Marodon
Summary: HVEM/BTLA immune checkpoint is associated with disease progression in patients with prostate cancer. Targeting HVEM through immunotherapy can reduce tumor growth by twofold, dependent on CD8(+) T cells, improving T cell activation and reducing exhaustion.
Article
Multidisciplinary Sciences
Yingjue Li, Yiwen Li, Yu Yang, Yuwei Deng, Xiangdong Ni, Bochen Zhao, Zhaoqi Yan, Wen He, Yixin Li, Shuhui Li, Linbo Liu, Dan Lu
Summary: This study found that PI3K8 inhibitor could enhance the sensitivity of endocrine resistance hormone receptor-positive (HR+) advanced breast cancer (ABC) to immunecheckpoint inhibitors (ICIs) by reducing immune evasion. Patient-derived xenografts were used to evaluate the treatment response, tumor progression, and immune changes. The combination of YY20394 and camrelizumab showed strong inhibitory effects on HR+ BC in vivo by suppressing Treg activity and increasing CD8+ T cells.
Article
Biotechnology & Applied Microbiology
Qiong Wu, Yongnian Yu, Xiaorui Yu, Qijun Du, Li Gou, Longfei Tan, Changhui Fu, Xiangling Ren, Jun Ren, Kai Xiao, Xianwei Meng
Summary: The study presents a liquid metal-based nanozyme that addresses the issues of poor delivery of microwave sensitizers and tumor hypoxic microenvironment in microwave dynamic therapy (MDT). The nanozyme effectively targets tumor cells, catalyzes oxygen production, and achieves excellent MDT effect in both in vitro and PDX model experiments.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Review
Oncology
Morgane M. Cogels, Redouane Rouas, Ghanem E. Ghanem, Philippe Martinive, Ahmad Awada, Dirk Van Gestel, Mohammad Krayem
Summary: Immunotherapy with checkpoint inhibitors has revolutionized cancer treatment, but clinical trials face challenges, leading to the importance of humanized mouse models for preclinical research to better understand treatment mechanisms and select optimal regimens. These models also hold potential for advancing research on radiation therapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Geriatrics & Gerontology
Joel H. L. Tan, You Yi Hwang, Hui Xian Chin, Min Liu, Sue Yee Tan, Qingfeng Chen
Summary: This study establishes a humanized mouse model of immune aging and investigates its impact on liver tumor dynamics. The findings show that aging is associated with increased senescent-like cells and decreased immune responses and cytokine production in T cell subsets. Additionally, aged humanized mice exhibit faster liver tumor growth compared to younger mice.
Review
Oncology
Sharad S. S. Singhal, Rachana Garg, Atish Mohanty, Pankaj Garg, Sravani Keerthi Ramisetty, Tamara Mirzapoiazova, Raffaella Soldi, Sunil Sharma, Prakash Kulkarni, Ravi Salgia
Summary: Animal models, especially genetically engineered mouse models and xenograft transplantation technologies, have greatly advanced our understanding of disease mechanisms, including cancer. These models have been used to evaluate specific genetic changes in carcinogenesis and provide insights into tumor biomarkers. The patient-derived xenograft model has revolutionized drug discovery and therapeutics.
Article
Oncology
Patrick N. Song, Ameer Mansur, Yun Lu, Deborah Della Manna, Andrew Burns, Sharon Samuel, Katherine Heinzman, Suzanne E. Lapi, Eddy S. Yang, Anna G. Sorace
Summary: This study investigates the synergistic effect of trastuzumab and radiation therapy in treating HER2-overexpressing breast cancer. It is found that a subtherapeutic dose of trastuzumab sensitizes the tumor microenvironment to fractionated radiation, resulting in a sustained response through innate immune activation, reduced DNA damage repair, and increased tumor oxygenation. The findings suggest that combination therapies can enhance the effectiveness of radiation therapy in HER2-positive breast cancer by modulating the tumor microenvironment.
Article
Oncology
Takahiko Murayama, Takashi Nakaoku, Masato Enari, Tatsunori Nishimura, Kana Tominaga, Asuka Nakata, Arinobu Tojo, Sumio Sugano, Takashi Kohno, Noriko Gotoh
Article
Gastroenterology & Hepatology
Shuji Hibiya, Kiichiro Tsuchiya, Ryohei Hayashi, Keita Fukushima, Nobukatsu Horita, Sho Watanabe, Tomoaki Shirasaki, Ryu Nishimura, Natsuko Kimura, Tatsunori Nishimura, Noriko Gotoh, Shigeru Oshima, Ryuichi Okamoto, Tetsuya Nakamura, Mamoru Watanabe
JOURNAL OF CROHNS & COLITIS
(2017)
Article
Biochemistry & Molecular Biology
K. Tominaga, T. Shimamura, N. Kimura, T. Murayama, D. Matsubara, H. Kanauchi, A. Niida, S. Shimizu, K. Nishioka, E-I Tsuji, M. Yano, S. Sugano, Y. Shimono, H. Ishii, H. Saya, M. Mori, K. Akashi, K-I Tada, T. Ogawa, A. Tojo, S. Miyano, N. Gotoh
Article
Biochemistry & Molecular Biology
S. Kitajima, A. Yoshida, S. Kohno, F. Li, S. Suzuki, N. Nagatani, Y. Nishimoto, N. Sasaki, H. Muranaka, Y. Wan, T. C. Thai, N. Okahashi, F. Matsuda, H. Shimizu, T. Nishiuchi, Y. Suzuki, K. Tominaga, N. Gotoh, M. Suzuki, M. E. Ewen, D. A. Barbie, O. Hirose, T. Tanaka, C. Takahashi
Article
Genetics & Heredity
Ankur Garg, Mukesh Bansal, Noriko Gotoh, Gen-Sheng Feng, Jian Zhong, Fen Wang, Ariana Kariminejad, Steven Brooks, Xin Zhang
Article
Biochemistry & Molecular Biology
Tatsunori Nishimura, Asuka Nakata, Xiaoxi Chen, Kurumi Nishi, Makiko Meguro-Horike, Soichiro Sasaki, Kenji Kita, Shin-ichi Horike, Kaori Saitoh, Keiko Kato, Kaori Igarashi, Takahiko Murayama, Susumu Kohno, Chiaki Takahashi, Naofumi Mukaida, Seiji Yano, Tomoyoshi Soga, Arinobu Tojo, Noriko Gotoh
Article
Multidisciplinary Sciences
Kana Tominaga, Hiroshi Minato, Takahiko Murayama, Asako Sasahara, Tatsunori Nishimura, Etsuko Kiyokawa, Hajime Kanauchi, Seiichiro Shimizu, Ayaka Sato, Kotoe Nishioka, Ei-ichi Tsuji, Masao Yano, Toshihisa Ogawa, Hideshi Ishii, Masaki Mori, Koichi Akashi, Koji Okamoto, Masahiko Tanabe, Kei-ichiro Tada, Arinobu Tojo, Noriko Gotoh
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Oncology
Takahiko Murayama, Yasuto Takeuchi, Kaoru Yamawaki, Toyoaki Natsume, Mengjiao Li, Rojas-Chaverra N. Marcela, Tatsunori Nishimura, Yuta Kogure, Asuka Nakata, Kana Tominaga, Asako Sasahara, Masao Yano, Satoko Ishikawa, Tetsuo Ohta, Kazuhiro Ikeda, Kuniko Horie-Inoue, Satoshi Inoue, Masahide Seki, Yutaka Suzuki, Sumio Sugano, Takayuki Enomoto, Masahiko Tanabe, Kei-ichiro Tada, Masato T. Kanemaki, Koji Okamoto, Arinobu Tojo, Noriko Gotoh
Summary: The study reveals that c-Myc expression induces stronger DNA replication stress in patient-derived breast CSCs, with MCM10 playing a critical role in compensating for this stress. The expression of MCM10 is upregulated in CSCs and maintained by c-Myc, leading to the activation of dormant replication origins to ensure replication progress in the presence of c-Myc-mediated collisions between RNA transcription and DNA replication machinery in the nuclei. Additionally, patient-derived breast CSCs are found to be dependent on MCM10 for their maintenance, even after enrichment for CSCs resistant to paclitaxel, suggesting a potential target for preventing drug resistance and tumor recurrence.
Article
Oncology
Navin R. Mahadevan, Erik H. Knelson, Jacquelyn O. Wolff, Amir Vajdi, Maria Saigi, Marco Campisi, Deli Hong, Tran C. Thai, Brandon Piel, Saemi Han, Bruce B. Reinhold, Jonathan S. Duke-Cohan, Michael J. Poitras, Luke J. Taus, Patrick H. Lizotte, Andrew Portell, Victor Quadros, Alison D. Santucci, Takahiko Murayama, Israel Canadas, Shunsuke Kitajima, Aoi Akitsu, Maya Fridrikh, Hideo Watanabe, Brendan Reardon, Prafulla C. Gokhale, Cloud P. Paweletz, Mark M. Awad, Eliezer M. Van Allen, Ana Lako, Xi-Tao Wang, Benjamin Chen, Fangxin Hong, Lynette M. Sholl, Michael Y. Tolstorukov, Kathleen Pfaff, Pasi A. Janne, Evisa Gjini, Robin Edwards, Scott Rodig, Ellis L. Reinherz, Matthew G. Oser, David A. Barbie
Summary: A subset of SCLC patients exhibit durable response to immune checkpoint blockade by upregulating MHC I after losing neuroendocrine differentiation, which can be enhanced through EZH2 inhibition and STING agonism, leading to immune rejection of SCLC in preclinical models.
Article
Oncology
Mitsuhito Hirano, Yoichi Imai, Yuta Kaito, Takahiko Murayama, Kota Sato, Tadao Ishida, Junichi Yamamoto, Takumi Ito, Muneyoshi Futami, Masaki Ri, Hiroshi Yasui, Tamami Denda, Yukihisa Tanaka, Yasunori Ota, Masanori Nojima, Yasuhiko Kamikubo, Noriko Gotoh, Shinsuke Iida, Hiroshi Handa, Arinobu Tojo
Summary: The study found that the combination of HDAC inhibitor and Akt inhibitor holds promise for the treatment of relapsed/refractory MM, as HDAC inhibitors suppressed drug-resistant MM cell growth and enhanced antibody-dependent cellular cytotoxicity, while also downregulating c-Myc through GSK-3 phosphorylation blockage.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Yasuto Takeuchi, Natsuko Kimura, Takahiko Murayama, Yukino Machida, Daisuke Iejima, Tatsunori Nishimura, Minoru Terashima, Yuming Wang, Mengjiao Li, Reiko Sakamoto, Mizuki Yamamoto, Naoki Itano, Yusuke Inoue, Masataka Ito, Nobuaki Yoshida, Jun-ichiro Inoue, Koichi Akashi, Hideyuki Saya, Koji Fujita, Masahiko Kuroda, Issay Kitabayashi, Dominic Voon, Takeshi Suzuki, Arinobu Tojo, Noriko Gotoh
Summary: Adaptor protein FRS20 induces proinflammatory changes in premalignant mammary tissues and is responsible for disease onset, while the FRS2 beta-NF-kappa B axis reveals the molecular link between inflammation changes and tumorigenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Mizuki Yamamoto, Kota Sakane, Kana Tominaga, Noriko Gotoh, Takayoshi Niwa, Yasuko Kikuchi, Keiichiro Tada, Naoki Goshima, Kentaro Semba, Jun-ichiro Inoue