Article
Multidisciplinary Sciences
Frida Ek, Kristin Blom, Tove Selvin, Jakob Rudfeldt, Claes Andersson, Wojciech Senkowski, Christian Brechot, Peter Nygren, Rolf Larsson, Malin Jarvius, Marten Fryknas
Summary: Quiescent cancer cells can resist cell-cycle active treatment, leading to cancer spread and recurrence. Using three-dimensional cancer cell models, oxidative phosphorylation (OXPHOS) has been identified as a context-dependent vulnerability. The limited treatment options for advanced hepatocellular carcinoma and colorectal carcinoma metastatic to the liver include sorafenib and regorafenib, which exhibit off-target effects related to OXPHOS inhibition. This study demonstrates that the OXPHOS inhibition caused by sorafenib and regorafenib parallels 3D activity and can be further investigated for new combination strategies.
SCIENTIFIC REPORTS
(2022)
Review
Biotechnology & Applied Microbiology
Yaqian Sun, Haiyang Ma
Summary: The drug development process involves evaluating drug activity, analyzing biological indicators, and using them as preclinical drug evaluation criteria. Currently, traditional 2D cell culture is the main method for screening preclinical anticancer drugs. However, this method lacks the ability to simulate the tumor microenvironment and accurately predict drug activity. 3D cell culture, as a technology between 2D cell culture and animal experiments, can better reflect the biological state and predict drug activity and resistance.
BIOTECHNOLOGY LETTERS
(2023)
Article
Cell Biology
Siobhan Crilly, Adrian Parry-Jones, Xia Wang, Julian N. Selley, James Cook, Victor S. Tapia, Craig S. Anderson, Stuart M. Allan, Paul R. Kasher
Summary: Zebrafish larvae provide a unique platform for screening neuroprotective compounds after intracerebral hemorrhage (ICH). Through this screening, six compounds, including ACE-Is, were identified as potential therapeutics for reducing brain cell death. Clinical trial data further supported the effectiveness of ACE-I in reducing unfavorable outcomes after ICH.
DISEASE MODELS & MECHANISMS
(2022)
Article
Oncology
Ioannis Ntafoulis, Anne Kleijn, Jie Ju, Kevin Jimenez-Cowell, Federica Fabro, Michelle Klein, Romain Tching Chi Yen, Rutger K. Balvers, Yunlei Li, Andrew P. Stubbs, Trisha V. Kers, Johan M. Kros, Sean E. Lawler, Laurens V. Beerepoot, Andreas Kremer, Ahmed Idbaih, Maite Verreault, Annette T. Byrne, Alice C. O'Farrell, Kate Connor, Archita Biswas, Manuela Salvucci, Jochen H. M. Prehn, Diether Lambrechts, Gonca Dilcan, Francesca Lodi, Ingrid Arijs, Martin J. van den Bent, Clemens M. F. Dirven, Sieger Leenstra, Martine L. M. Lamfers
Summary: This study found that patient-derived glioma stem-like cells (GSCs) retain patient-unique gene expressions despite the loss of their natural environment. Drug screening using GSCs predicted patient response to temozolomide (TMZ) more specifically than the MGMT status alone. Transcriptome analysis identified potential biomarkers for TMZ sensitivity.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Ioannis Ntafoulis, Anne Kleijn, Jie Ju, Kevin Jimenez-Cowell, Federica Fabro, Michelle Klein, Romain Tching Chi Yen, Rutger K. Balvers, Yunlei Li, Andrew P. Stubbs, Trisha V. Kers, Johan M. Kros, Sean E. Lawler, Laurens V. Beerepoot, Andreas Kremer, Ahmed Idbaih, Maite Verreault, Annette T. Byrne, Alice C. O'Farrell, Kate Connor, Archita Biswas, Manuela Salvucci, Jochen H. M. Prehn, Diether Lambrechts, Gonca Dilcan, Francesca Lodi, Ingrid Arijs, Martin J. van den Bent, Clemens M. F. Dirven, Sieger Leenstra, Martine L. M. GLIOTRAIN Consortium, Martine L. M. Lamfers
Summary: The study revealed that patient-derived glioma stem-like cells (GSCs) retain gene expressions similar to their corresponding DNA and RNA sequences despite the loss of their natural environment. GSCs were found to predict patient response to treatment more accurately and transcriptome analysis identified potential biomarkers for this response. This study demonstrates that GSCs provide a tool to improve glioblastoma drug development and precision medicine.
BRITISH JOURNAL OF CANCER
(2023)
Article
Obstetrics & Gynecology
Jungho Ahn, Min-Ji Yoon, Seon-Hwa Hong, Hwijae Cha, Danbi Lee, Hwa Seon Koo, Ji-Eun Ko, Jungseub Lee, Soojung Oh, Noo Li Jeon, Youn-Jung Kang
Summary: A microengineered vascularized endometrium-on-a-chip model has been successfully developed to mimic the complex behaviors of the human endometrium, providing a new in-vitro approach for drug screening and discovery. The model could be a valuable tool for studying female diseases and addressing critical challenges in a personalized manner.
HUMAN REPRODUCTION
(2021)
Article
Pharmacology & Pharmacy
Kyoung Jin Choi, Joon Ho Lee, Sung Bum Park, Yoon-Ju Na, Won Hoon Jung, Hyuk Lee, Ki Young Kim
Summary: Macrophages in adipose tissue contribute to metabolic disorders, and a 3D culture system was developed to study drug screening for anti-obesity effects.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Hui Niu, Jiarui Xiao, Xiaoli Lou, Lingling Guo, Yongsheng Zhang, Runhuai Yang, Hao Yang, Shouli Wang, Fuzhou Niu
Summary: This study utilized natural silk fibroin and chitosan to fabricate 3D microscaffolds with good biocompatibility for cancer cell culture and drug sensitivity testing. The scaffolds were characterized using various testing methods and showed promising results in facilitating cell growth and drug sensitivity screening.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Oncology
Kolluri Poornima, Arul Prakash Francis, Muddasarul Hoda, Mohamed Ahmed Eladl, Srividya Subramanian, Vishnu Priya Veeraraghavan, Mohamed El-Sherbiny, Saad Mohamed Asseri, Abdulrahman Bashir Ahmed Hussamuldin, Krishna Mohan Surapaneni, Ullas Mony, Rukkumani Rajagopalan
Summary: Replicating the natural biomechanical environment of cells is crucial for understanding fundamental life processes. Traditional 2D cell cultures do not replicate the native environment, while 3D cell cultures provide a better replication of extracellular matrix properties and offer insights into tumorigenesis mechanisms. 3D cell culture is a valuable platform for studying the biological characteristics of tumor cells.
FRONTIERS IN ONCOLOGY
(2022)
Review
Instruments & Instrumentation
Tina Sara Biju, Veeraraghavan Vishnu Priya, Arul Prakash Francis
Summary: Drug development and testing are time-consuming and expensive, with uncertainties in clinical success and preclinical validation. Currently, most therapeutic drug manufacturers use 2D cell culture models, but they have limitations in mimicking cellular mechanisms and environmental interactions. To overcome these limitations, newer in vivo drug testing models, such as 3D cell culture models, are required. This review article outlines the advancements, types, significance, limitations, and applications of cell culture models in drug toxicity screening and preclinical testing.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Review
Oncology
Asmaa F. Khafaga, Shaker A. Mousa, Lotfi Aleya, Mohamed M. Abdel-Daim
Summary: This review focuses on various established 3D culture models of hepatocellular carcinoma (HCC) and their role in investigating tumor-tumor microenvironment interactions and HCC-related therapeutic resistance.
CANCER CELL INTERNATIONAL
(2022)
Article
Engineering, Biomedical
Peipei Wang, Lejia Sun, Changcan Li, Bao Jin, Huayu Yang, Bin Wu, Yilei Mao
Summary: The existing in vitro models for antitumor drug screening have limitations in predicting in vivo pharmacological effects. 3D bioprinting technology offers advantages in constructing human tissues compared to other methods. We used this technology to construct a 3D multicellular model and found improved expression of tumor-related genes compared to a 3D bioprinted single-cell model. The multicellular model also showed resistance to chemotherapy drugs, highlighting its potential in drug screening.
INTERNATIONAL JOURNAL OF BIOPRINTING
(2023)
Article
Oncology
Yun Haeng Lee, Minkyeong Kim, Hyon Jin Park, Ji Yun Park, Eun Seon Song, Haneur Lee, Gahyun Ko, Soonkil Ahn, Hyung Wook Kwon, Youngjoo Byun, Changmu Kim, Jaehyuk Choi, Joon Tae Park
Summary: A study identified that the mycelium culture extract of Polyporus mushrooms has potential anticancer properties by inducing apoptosis and S-phase arrest. The active ingredient 3,4-dihydroxybenzaldehyde was found to inhibit cancer cell proliferation similar to the mycelium extract, but without increasing the proportion of chemoresistant side population. These findings have clinical applications for treating chemo-resistant cancer.
Article
Oncology
Eun Seon Song, Moon Kyoung So, Hyon Jin Park, Haneur Lee, Yun Haeng Lee, Myeong Uk Kuk, Jiho Park, Hyung Wook Kwon, Jaehyuk Choi, Joon Tae Park
Summary: Most conventional anticancer drugs cause resistance to chemotherapy, posing a major obstacle in cancer treatment. In this study, novel anticancer compounds were identified from mycelial culture extracts of Polyporus tuberaster (P. tuberaster). These extracts effectively inhibited cancer cell growth through apoptosis induction and S-phase arrest, with efficacy not limited to a specific type of cancer. Furthermore, unlike traditional medications, these extracts did not increase the proportion of side population (SP) cells, which contribute to chemoresistance. This discovery offers a promising new drug candidate for the treatment of chemoresistant malignancies.
Article
Virology
Hailin Tang, Yang Liu, Ruiwen Ren, Yan Liu, Yanhua He, Zhongtian Qi, Haoran Peng, Ping Zhao
Summary: This study identified four compounds from approved drugs that can effectively inhibit WNV infection and also demonstrated broad-spectrum antiviral activity. These compounds may be promising therapeutics for WNV infection.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Oncology
Ellin-Kristina Hillert, Slavica Brnjic, Xiaonan Zhang, Magdalena Mazurkiewicz, Amir Ata Saei, Arjan Mofers, Karthik Selvaraj, Roman Zubarev, Stig Linder, Padraig D'Arcy
Article
Oncology
Juri Habicht, Ashley Mooneyham, Mihir Shetty, Xiaonan Zhang, Vijayalakshmi Shridhar, Boris Winterhoff, Ying Zhang, Jason Cepela, Timothy Starr, Emil Lou, Martina Bazzaro
CANCER BIOLOGY & THERAPY
(2019)
Article
Cell Biology
Xiaonan Zhang, Bela Espinosa, Amir Ata Saei, Padraig D'Arcy, Roman A. Zubarev, Stig Linder
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2019)
Review
Oncology
Xiaonan Zhang, Stig Linder, Martina Bazzaro
Article
Chemistry, Multidisciplinary
Julia Steinmetz, Wojciech Senkowski, Johan Lengqvist, Jenny Rubin, Elena Ossipova, Stephanie Herman, Rolf Larsson, Per-Johan Jakobsson, Marten Fryknas, Kim Kultima
Article
Cell Biology
Juri Habicht, Ashley Mooneyham, Asumi Hoshino, Mihir Shetty, Xiaonan Zhang, Edith Emmings, Qing Yang, Courtney Coombes, Melissa K. Gardner, Martina Bazzaro
Summary: UNC-45A is identified as a novel type of microtubule-severing protein, which can disrupt microtubule stability and also be involved in regulating the activity of non-muscle myosin II. This finding has significant implications in the biology of microtubules and human diseases.
JOURNAL OF CELL SCIENCE
(2021)
Review
Chemistry, Medicinal
Xiaonan Zhang, Tobias Sjoblom
Summary: Loss of heterozygosity (LOH) is a common genetic event in cancer development, creating genetic differences between tumor and normal cells that provide opportunities for novel cancer therapies.
Article
Biochemistry & Molecular Biology
Xiaonan Zhang, Mihir Shetty, Valentino Clemente, Stig Linder, Martina Bazzaro
Summary: Ovarian clear cell carcinoma (OCCC) is a rare and chemorefractory tumor with about 50% of patients having inactivating mutations in the ARID1A gene. Loss of ARID1A leads to increased mitochondrial metabolism in OCCC cells, making them more dependent on mitochondrial activity. Preclinical testing has shown that targeting mitochondrial activity can extend overall survival in ARID1A-mutated OCCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Henning Karlsson, Marten Fryknas, Wojciech Senkowski, Rolf Larsson, Peter Nygren
Summary: Nitazoxanide selectively targets quiescent glucose-deprived tumor cells and sensitizes these cells to radiation in vitro. It also inhibits tumor growth in vivo. Therefore, nitazoxanide has potential as an anticancer drug, including its use as a radiosensitizer.
Article
Multidisciplinary Sciences
Niklas Handin, Evgeniya Mickols, Magnus Olander, Jakob Rudfeldt, Kristin Blom, Frida Nyberg, Wojciech Senkowski, Jozef Urdzik, Varun Maturi, Marten Fryknas, Per Artursson
Summary: This study investigated the influence of various culture conditions on spheroid cultures of primary human hepatocytes (PHH) to find optimal conditions for maintaining an in vivo-like phenotype. The medium composition was found to affect spheroid histology, global proteome profile, drug metabolism, and drug-induced toxicity. Maintaining healthy PHH with functional features is crucial for more reproducible hepatocyte research.
Article
Oncology
Amanda Westergren Jakobsson, Snehangshu Kundu, Jing Guo, Azazul Chowdhury, Miao Zhao, Emma Lindell, Peter Bergsten, Fredrik J. Swartling, Tobias Sjoblom, Xiaonan Zhang
Summary: This study demonstrates for the first time that the iron chelator VLX600 inhibits mitochondrial activity and induces cell death regardless of MYCN status in neuroblastoma cells. Blocking glucose uptake enhances the effect of VLX600, suggesting potential therapeutic strategies for neuroblastoma targeting energy supply/metabolism pathways.
Article
Pharmacology & Pharmacy
Xiaonan Zhang, Ece Akcan, Mario Correia, Natallia Rameika, Snehangshu Kundu, Ivaylo Stoimenov, Veronica Rendo, Anna U. Eriksson, Martin Haraldsson, Daniel Globisch, Tobias Sjoblom
Summary: This study reports a novel compound CBK034026C that exhibits specific toxicity towards CRC cells with high NAT2 activity. Through analysis of its response pattern and metabolomic profiling, it was found that CBK034026C affects pathways associated with antioxidant defense and mitochondrial metabolism, thereby weakening the response of CRC cells to oxidative stress induced by CBK034026C.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
Xuerun Peng, Jianyou Shi, Zhipeng Zhao, Rongsheng Tong, Xiaonan Zhang, Lei Zhong
Summary: This study aimed to evaluate the efficacy of emetine against gastric cancer (GC) and explore its molecular mechanisms. The results demonstrated that emetine effectively inhibited GC cell growth, induced apoptosis, blocked migration and invasion, and regulated multiple signaling pathways. Emetine could be a potential drug candidate for GC treatment.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Emma Lindell, Lei Zhong, Xiaonan Zhang
Summary: Quiescent cancer cells (QCCs) are nonproliferating cells that avoid most chemotherapies and are associated with cancer recurrence. Understanding the characteristics, mechanisms, and developing strategies to eliminate QCCs is important for effective treatment of solid tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lei Zhong, Zhipeng Zhao, Xiaonan Zhang
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)