Review
Immunology
Syed A. Mian, Fernando Anjos-Afonso, Dominique Bonnet
Summary: Immunotherapy shows promise in cancer treatment, yet challenges remain, including the lack of suitable mouse models. Improved immunodeficient mice offer opportunities for comprehensive evaluation of therapeutic strategies and advancement in human hematopoietic research.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Yixin Wang, Lei Wang, Cong Fu, Xue Wang, Siyao Zuo, Chang Shu, Yanhong Shan, Jin He, Qi Zhou, Wei Li, Yong-Guang Yang, Zheng Hu, Shucheng Hua
Summary: This study utilized a humanized mouse model with human lung tissue xenografts to investigate the immunopathogenesis and therapeutic interventions of viral respiratory diseases. The findings highlight the importance of tissue-resident memory T cells and viral Ag-specific T cells in the immune response against respiratory viruses.
JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Yinxi Zhou, Jinghua Xia, Shuonan Xu, Tao She, Yanning Zhang, Ying Sun, Miaomiao Wen, Tao Jiang, Yanlu Xiong, Jie Lei
Summary: The development and growth of tumors pose a significant and ongoing threat to human life globally. Despite the remarkable progress achieved by advanced therapeutic strategies such as immune checkpoint therapy and CAR-T in treating solid and hematological malignancies, the malignant initiation and progression of cancer remains controversial and requires further research. Experimental animal models not only have great advantages in simulating tumor occurrence, development, and malignant transformation mechanisms, but also can be used to evaluate the therapeutic effects of diverse clinical interventions, gradually becoming indispensable in cancer research. This paper reviews recent research progress in mouse and rat models, focusing on spontaneous, induced, transgenic, and transplantable tumor models, aiming to provide guidance for future studies on malignant mechanisms and tumor prevention.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Geriatrics & Gerontology
Wouter R. P. H. van de Worp, Jan Theys, Alba Sanz Gonzalez, Brent van der Heyden, Frank Verhaegen, Duncan Hauser, Florian Caiment, Hubertus J. M. Smeets, Annemie M. W. J. Schols, Ardy van Helvoort, Ramon C. J. Langen
Summary: A syngeneic, orthotopic lung cancer mouse model was evaluated to see if it replicates the systemic and muscle-specific alterations associated with human lung cancer cachexia.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Endocrinology & Metabolism
Inka Rapoehn, Ivet Elias, Juliane Weiner, Anna Pujol, Stephanie Kehr, Alexandra Chadt, Hadi Al-Hasani, Ralph Burkhardt, Nora Kloeting, Michael Stumvoll, Fatima Bosch, Peter Kovacs, John T. Heiker, Jana Breitfeld
Summary: Adipose tissue inflammation and insulin resistance are important factors in the development of metabolic diseases resulting from overweight and obesity. The serpin vaspin has compensatory roles in inflammation and insulin resistance. A new transgenic mouse line with human vaspin expression in adipose tissue has been developed, which showed improved metabolic parameters and increased energy expenditure under high-fat diet conditions.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
J. Jason Morton, Nathaniel Alzofon, Stephen B. Keysar, Tugs-Saikhan Chimed, Julie Reisinger, Loni Perrenoud, Phuong N. Le, Cera Nieto, Karina Gomez, Bettina Miller, Randi Yeager, Dexiang Gao, Aik-Choon Tan, Hilary Somerset, Theresa Medina, Xiao-Jing Wang, Jing H. Wang, William Robinson, Dennis R. Roop, Rene Gonzalez, Antonio Jimeno
Summary: The research team constructed an autologous humanized mouse model that successfully replicated the patient-specific tumor microenvironment, showing that tumors in this model grew faster, possibly due to enhanced immune cell activity. By mimicking the immunotherapies received by the original patients, the study found that accelerated tumor growth was associated with decreased immune cell infiltration and reduced interferon gamma-related gene expression.
MOLECULAR CANCER RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Chuangen Li, Harry Cheuk-Hay Lau, Xiang Zhang, Jun Yu
Summary: This review explores the overall features and mechanisms of carcinogen-induced and transgenic mouse models for colon tumorigenesis, as well as their limitations and applications in evaluating and studying drugs and treatment regimens against CRC. These mouse models provide a better understanding of the mechanisms of colon tumorigenesis and facilitate the discovery of novel therapeutic strategies against CRC.
Article
Oncology
Yukako Ito, Shinji Kobuchi, Amiri Kawakita, Kazuki Tosaka, Yume Matsunaga, Shoma Yoshioka, Shizuka Jonan, Kikuko Amagase, Katsunori Hashimoto, Mitsuro Kanda, Takuya Saito, Hayao Nakanishi
Summary: There is no definite experimental evidence for the significance of circulating tumor cells (CTCs) in estimating the chemotherapeutic effect in cancer patients. This study found a transient increase in CTC number 1-2 weeks after chemotherapy in human pancreatic cancer xenograft models, and proposed a hypothesis about the mechanism of CTC mobilization after chemotherapy.
Article
Cell Biology
Eva-Marie Bichlmayer, Lina Mahl, Leo Hesse, Eric Pion, Victoria Haller, Andreas Moehwald, Christina Hackl, Jens M. Werner, Hans J. Schlitt, Siegfried Schwarz, Philipp Kainz, Christoph Brochhausen, Christian Groeger, Felix Steger, Oliver Koelbl, Christoph Daniel, Kerstin Amann, Andre Kraus, Bjorn Buchholz, Thiha Aung, Silke Haerteis
Summary: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that leads to the progressive enlargement of kidney cysts and renal failure. Current models for studying human cyst growth and drug trials are limited. In this study, a chorioallantoic membrane (CAM) model was used to culture renal tissue from ADPKD patients and mouse kidney slices, and successfully evaluated cystic tissue growth. The CAM model may provide a valuable platform for bridging the gap between animal studies and clinical trials of human cyst growth.
Article
Multidisciplinary Sciences
Celine Bonnet, Panhong Gou, Simon Girel, Vincent Bansaye, Catherine Lacout, Karine Bailly, Marie-Helene Schlagetter, Evelyne Lauret, Sylvie Meleard, Stephane Giraudier
Summary: This study reconciled steady-state and stress hematopoiesis by analyzing the effects of a stress condition on mouse hematopoietic stem and progenitor cells. A mathematical model incorporating time-dependent regulation was developed and successfully replicated biological data under different stress conditions. The findings provide new insights into both normal and pathological hematopoiesis.
Article
Biochemistry & Molecular Biology
Evan Y. Wu, Laura Landry
Summary: This study developed a bioinformatics pipeline to effectively quantify highly expressed tRNAs in RNA-Seq data and examined their expression patterns in different tissues and developmental stages in humans and mice. The results revealed that heart had the highest overall tRNA expression and that tRNA expression peaked during development before steadily decreasing. Furthermore, certain tRNAs were associated with various human diseases, suggesting their important roles in disease pathogenesis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Oncology
Reihaneh Alsadat Mahmoudian, Moein Farshchian, Mohammad Reza Abbaszadegan
Summary: Esophageal cancer is a leading cause of cancer-related deaths worldwide, and understanding the mechanisms of its development is crucial for improving patient outcomes. Genetically engineered mouse models provide valuable insights into cancer pathogenesis and treatment strategies, despite the differences between mice and humans. By addressing challenges in modeling and utilizing advanced technologies, researchers can maximize the value of studying esophageal cancer in GEMMs.
EXPERIMENTAL CELL RESEARCH
(2021)
Review
Oncology
Bo-Tao Zhang, Jia-Ying Xu, Wei Wang, Yang Zeng, Jun Jiang
Summary: There is increasing evidence suggesting a link between obesity and the occurrence and development of malignant tumors. However, choosing an appropriate animal model is crucial when studying this relationship. Currently used models such as BALB/c nude mice are difficult to induce obesity, while models commonly used for obesity research, such as C57BL/6 mice, are not suitable for tumor xenograft transplantation. This review summarizes several experimental animal models and protocols that can simultaneously induce obesity and tumor xenografts.
FRONTIERS IN ONCOLOGY
(2023)
Article
Veterinary Sciences
Natalia M. Del Rio, Liupei Huang, Lydia Murphy, Jayalaxmi Suresh Babu, Cross Matthew Daffada, William John Haynes, James G. Keck, Michael. A. Brehm, Leonard D. Shultz, Matthew E. Brown
Summary: Humanized mouse models created by transplanting human hematopoietic tissues into immune-deficient mice have various research applications. The NeoThy mouse model, using nonfetal tissue sources, incorporates stem and progenitor cells from umbilical cord blood and discarded thymus tissue. The protocol for creating NeoThy mice and evaluating human immune cell reconstitution takes approximately 19 hours to complete and can be divided into multiple sessions.
Article
Biochemistry & Molecular Biology
Haruki Inoue, Eriko Aimono, Akiyoshi Kasuga, Haruto Tanaka, Aika Iwasaki, Hideyuki Saya, Yoshimi Arima
Summary: Our mouse BTC models are suitable for studying BTC carcinogenesis and may contribute to the development of new therapeutic strategies. Analysis of images of mouse and human tumor tissues reveals similarities in tissue structure between the two, suggesting similarities in tumor characteristics independent of animal species. Additionally, our pixel-level clustering model can serve as a new diagnostic tool for BTC.
Review
Biochemistry & Molecular Biology
Deepavali Chakravarti, Kyle A. LaBella, Ronald A. DePinho
Summary: The escalating social and economic burden of an aging world population has brought aging research into the spotlight. Through the lens of telomere biology, we can better understand the mechanisms of aging and the development of age-related diseases, providing insights for prevention and treatment.
Review
Cell Biology
Peiwen Chen, Wen-Hao Hsu, Jincheng Han, Yan Xia, Ronald A. DePinho
Summary: This review explores the symbiotic interactions between cancer stem cells and immune cells, highlighting the importance of tumor-associated macrophages, myeloid-derived suppressor cells, and T cells in maintaining CSC stemness and survival niche. It also discusses therapeutic strategies targeting this co-dependency to disrupt tumor-promoting ecosystems.
Article
Cardiac & Cardiovascular Systems
Kate L. Weeks, Yow Keat Tham, Suzan G. Yildiz, Yonali Alexander, Daniel G. Donner, Helen Kiriazis, Claudia A. Harmawan, Amy Hsu, Bianca C. Bernardo, Aya Matsumoto, Ronald A. DePinho, E. Dale Abel, Elizabeth A. Woodcock, Julie R. McMullen
Summary: This study found that the transcription factor FoxO1 is a critical mediator of exercise-induced cardiac hypertrophy, which has important implications when considering FoxO1 as a target for treating the diseased heart. Given that exercise-induced hypertrophy is protective, this finding is significant in the context of treating heart disease.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Review
Oncology
Prasenjit Dey, Alec C. Kimmelman, Ronald A. DePinho
Summary: Cancer cell metabolic reprogramming is driven by signals from both intrinsic and extrinsic factors. Intrinsic signaling maintains the baseline metabolic state, while extrinsic signals fine-tune metabolic processes based on metabolite availability and cellular requirements. Therefore, successful targeting of metabolic pathways will require a nuanced approach based on cancer genotype, tumor microenvironment composition, and tissue location.
Review
Cell Biology
Jiexi Li, Xingdi Ma, Deepavali Chakravarti, Shabnam Shalapour, Ronald A. DePinho
Summary: Colorectal cancer ranks as the third most common cancer in women, the fourth most common in men, and the fourth leading cause of cancer death globally. Incidence and mortality rates vary by race and ethnicity, with non-Hispanic blacks having the highest rates. In recent years, there has been a decline in the incidence of colorectal cancer in individuals over 50 years old.
GENES & DEVELOPMENT
(2021)
Article
Cell Biology
Pingping Hou, Xingdi Ma, Zecheng Yang, Qiang Zhang, Chang-Jiun Wu, Jun Li, Lin Tan, Wantong Yao, Liang Yan, Xin Zhou, Alec C. Kimmelman, Philip L. Lorenzi, Jianhua Zhang, Shan Jiang, Denise Spring, Y. Alan Wang, Ronald A. DePinho
Summary: The study uncovers USP21 as a driver of KRAS*-independent PDAC growth by inducing macropinocytosis, which maintains intracellular amino acid levels. USP21 may play a role in affecting responsiveness to emergent anti-KRAS* therapy.
GENES & DEVELOPMENT
(2021)
Editorial Material
Gastroenterology & Hepatology
Jincheng Han, Ronald A. DePinho, Anirban Maitra
Summary: The application of single-cell RNA sequencing platforms has provided significant insights into the heterogeneity of PDAC, covering both the neoplastic compartment and tumor microenvironment. This Comment discusses key findings from mouse models and human PDAC samples, as well as future opportunities.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Oncology
Aftab Alam, Eric Levanduski, Parker Denz, Helena Solleiro Villavicencio, Maulasri Bhatta, Lamees Alhorebi, Yali Zhang, Eduardo Cortes Gomez, Brian Morreale, Sharon Senchanthisai, Jun Li, Steven G. Turowski, Sandra Sexton, Sheila Jani Sait, Prashant K. Singh, Jianmin Wang, Anirban Maitra, Pawel Kalinski, Ronald A. DePinho, Huamin Wang, Wenting Liao, Scott I. Abrams, Brahm H. Segal, Prasenjit Dey
Summary: TH2 cells and ILC2 cells stimulate tumor growth by secreting pro-tumorigenic cytokines. Oncogenic Kras(G12D) increases IL-33 expression in PDAC cells, recruiting and activating TH2 and ILC2 cells. Cancer-cell-specific deletion of IL-33 reduces TH2 and ILC2 recruitment and promotes tumor regression.
Article
Oncology
Shawn M. Davidson, Daniel R. Schmidt, Julia E. Heyman, James P. O. 'Brien, Amy C. Liu, William J. Israelsen, Talya L. Dayton, Raghav Sehgal, Roderick T. Bronson, Elizaveta Freinkman, Howard H. Mak, Giuseppe Nicolo Fanelli, Scott Malstrom, Gary Bellinger, Arkaitz Carracedo, Pier Paolo Pandolfi, Kevin D. Courtney, Abhishek Jha, Ronald A. DePinho, James W. Horner, Craig J. Thomas, Lewis C. Cantley, Massimo Loda, Matthew G. Vander Heiden
Summary: This study reveals the impact of differential expression of pyruvate kinase isoforms on cancer initiation and progression. The M2 splice isoform of pyruvate kinase (PKM2) supports cancer cell proliferation and survival in prostate cancer, while the M1 isoform (PKM1) has a suppressive effect on tumor development. Alterations in nucleotide levels are observed in tumors with high PKM1 expression, leading to DNA replication stress and senescence which inhibits tumor progression. A small molecule pyruvate kinase activator that mimics the high activity PKM1-like state can suppress the progression of established prostate tumors.
Article
Oncology
Rumi Lee, Jiexi Li, Jun Li, Chang-Jiun Wu, Shan Jiang, Wen-Hao Hsu, Deepavali Chakravarti, Peiwen Chen, Kyle A. LaBella, Jing Li, Denise J. Spring, Di Zhao, Y. Alan Wang, Ronald A. DePinho
Summary: This study identifies critical effectors in the maintenance of APC-deficient colorectal cancer and demonstrates the relationship between APC/WNT pathway and kynurenine pathway signaling. It further determines the tumor-associated macrophage biology in APC-deficient colorectal cancer, informing genotype-specific therapeutic targets and the use of TDO2 inhibitors.
Article
Immunology
Rodney Cheng-En Hsieh, Sunil Krishnan, Ren-Chin Wu, Akash R. Boda, Arthur Liu, Michelle Winkler, Wen-Hao Hsu, Steven Hsesheng Lin, Mien-Chie Hung, Li-Chuan Chan, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Ricardo Alexandre De Azevedo, Yung-Chih Chou, Ronald A. DePinho, Matthew Gubin, Eduardo Vilar, Chao Hsien Chen, Ravaen Slay, Priyamvada Jayaprakash, Shweta Mahendra Hegde, Genevieve Hartley, Spencer T. Lea, Rishika Prasad, Brittany Morrow, Coline Agnes Couillault, Madeline Steiner, Chun-Chieh Wang, Bhanu Prasad Venkatesulu, Cullen Taniguchi, Yon Son Betty Kim, Junjie Chen, Nils-Petter Rudqvist, Michael A. Curran
Summary: Radiation therapy induces up-regulation of CD47 and PD-L1 through the ATR-mediated DNA repair signaling pathway in CRC cells, which limits TAA cross-presentation and immune activation. Combination therapy with anti-SIRP alpha and anti-PD-1 reverses immune resistance, promotes TAA cross-presentation and robust antitumor immune priming.
SCIENCE IMMUNOLOGY
(2022)
Article
Oncology
Pat Gulhati, Aislyn Schalck, Shan Jiang, Xiaoying Shang, Chang-Jiun Wu, Pingping Hou, Sharia Hernandez Ruiz, Luisa Solis Soto, Edwin Parra, Haoqiang Ying, Jincheng Han, Prasenjit Dey, Jun Li, Pingna Deng, Emi Sei, Dean Y. Maeda, John A. Zebala, Denise J. Spring, Michael Kim, Huamin Wang, Anirban Maitra, Dirk Moore, Karen Clise-Dwyer, Y. Alan Wang, Nicholas E. Navin, Ronald A. DePinho
Summary: Pancreatic ductal adenocarcinoma (PDAC) is resistant to PD1 and CTLA4 immune checkpoint therapies. This study characterized the mechanisms of ICT resistance and identified effective therapeutic options. The combination of agonist 41BB and antagonist LAG3 ICT increased survival and antitumor immunity. Triple therapy with T cell-activating ICTs and a CXCR1/2 inhibitor resulted in durable complete responses. This provides a testable hypothesis for clinical testing in human PDAC.
Article
Multidisciplinary Sciences
Jiexi Li, Zhengdao Lan, Wenting Liao, James W. W. Horner, Xueping Xu, Jielin Liu, Yohei Yoshihama, Shan Jiang, Hong Seok Shim, Max Slotnik, Kyle A. A. LaBella, Chang-Jiun Wu, Kenneth Dunner Jr, Wen-Hao Hsu, Rumi Lee, Isha Khanduri, Christopher Terranova, Kadir Akdemir, Deepavali Chakravarti, Xiaoying Shang, Denise J. J. Spring, Y. Alan Wang, Ronald A. A. DePinho
Summary: Sex plays an important role in cancer incidence, spectrum, and outcomes, particularly in colorectal cancer (CRC) where men have higher metastases and mortality rates. A study using a murine CRC model revealed that oncogenic mutant KRAS (KRAS*) CRC in males showed higher metastases and worse outcomes. Further analysis found that the Y-chromosome gene histone demethylase KDM5D, driven by KRAS*-mediated activation of the STAT4 transcription factor, contributed to the sex differences in KRAS* CRC. Deletion of Kdm5d in cancer cells improved tight junction integrity, reduced invasiveness, and enhanced cancer cell killing by CD8(+) T cells. On the contrary, mice with a Kdm5d transgene had a higher propensity for invasive tumors. Therefore, the upregulation of Y chromosome KDM5D via KRAS*-STAT4 pathway disrupts cancer cell adhesion properties and tumor immunity, providing a potential therapeutic strategy for reducing metastasis risk in men with KRAS* CRC.
Article
Medicine, Research & Experimental
Ya'an Kang, Jenying Deng, Jianhua Ling, Xinqun Li, Yi-Ju Chiang, Eugene J. Koay, Huamin Wang, Jared K. Burks, Paul J. Chiao, Mark W. Hurd, Manoop S. Bhutani, Jeffrey H. Lee, Brian R. Weston, Anirban Maitra, Naruhiko Ikoma, Ching-Wei D. Tzeng, Jeffrey E. Lee, Ronald A. DePinho, Robert A. Wolff, Shubham Pant, Florencia McAllister, Matthew H. G. Katz, Jason B. Fleming, Michael P. Kim
Summary: An organoid-based platform was developed to personalize PDAC therapy by quantifying PDO responses to drug treatments and evaluating tumor-stroma modulation.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cell Biology
Hong Seok Shim, James W. Horner, Chang-Jiun Wu, Jiexi Li, Zheng D. Lan, Shan Jiang, Xueping Xu, Wen-Hao Hsu, Tomasz Zal, Ivonne I. Flores, Pingna Deng, Yuan-Ta Lin, Li-Huei Tsai, Y. Alan Wang, Ronald A. DePinho
Summary: The research found that deficiency of telomerase reverse transcriptase (TERT) affects neuronal expression and accumulation of amyloid-beta in the brain, while maintaining normal levels of TERT helps reduce amyloid-beta accumulation and preserve cognitive function. Furthermore, the interaction between TERT, beta-catenin, and RNA polymerase II at gene promoters leads to the upregulation of gene networks governing synaptic signaling and learning processes.
