Article
Chemistry, Multidisciplinary
Chengzhi Huang, Yue Zhou, Xingyu Feng, Junjiang Wang, Yong Li, Xueqing Yao
Summary: This study reports a noncoding RNA delivery system using exosomes derived from primary patient cells to target liver metastasis and chemoresistance in colorectal cancer (CRC). The coiled-coil domain-containing protein 80 (CCDC80) was identified as strongly associated with CRC liver metastasis and chemoresistance. Silencing CCDC80 increased sensitivity to chemotherapy agents in OXA-resistant cell lines and mouse models. The delivery system successfully delivered siRNAs targeting CCDC80 and increased chemotherapy sensitivity in CRC liver metastasis mouse models and patient-derived xenograft models. The results offer a therapeutic target and a potential alternative treatment for CRC patients with distant metastasis and chemoresistant cases.
Review
Oncology
Antonio Barbachano, Asuncion Fernandez-Barral, Pilar Bustamante-Madrid, Isabel Prieto, Nuria Rodriguez-Salas, Maria Jesus Larriba, Alberto Munoz
Summary: Colorectal cancer is a common and deadly disease, and organoids have emerged as a valuable tool to study its molecular and genetic mechanisms. These organoids allow for in-depth research on tumorigenesis features, including immunotherapy and personalized drug treatments, thus advancing our understanding and treatment of colorectal cancer.
Review
Oncology
Sau Yee Kok, Mizuho Nakayama, Atsuya Morita, Hiroko Oshima, Masanobu Oshima
Summary: The stepwise accumulation of key driver mutations is responsible for the development and malignant progression of colorectal cancer in primary sites. Non-genetic mechanisms such as negative selection and polyclonal metastasis also play a role in cancer evolution. Studies using genetic mouse models and organoid transplantation experiments have provided insights into these mechanisms.
Review
Genetics & Heredity
Haruna Takeda
Summary: This review discusses the platform for functionally validating colorectal cancer driver genes using CRISPR-Cas9 in mouse intestinal tumor organoids. It highlights the application of mouse organoids in CRC research and the validation of CRC genes.
FRONTIERS IN GENETICS
(2021)
Article
Engineering, Biomedical
Yong Hun Jung, Dong-Hee Choi, Kyungwon Park, Sat-Byol Lee, Jonghun Kim, Hyunho Kim, Hyun-Woo Jeong, Ji Hun Yang, Jin-A Kim, Seok Chung, Byung Soh Min
Summary: This study demonstrates a scalable organoid production platform that can produce functionally complex and uniform organoids. Hydro-organoids produced on the new platform show better consistency in drug screening and have the potential to be used in high-throughput assays and predicting clinical outcomes.
Article
Medicine, Research & Experimental
Kushtrim Kryeziu, Seyed H. Moosavi, Christian H. Bergsland, Marianne G. Guren, Peter W. Eide, Max Z. Totland, Kristoffer Lassen, Andreas Abildgaard, Arild Nesbakken, Anita Sveen, Ragnhild A. Lothe
Summary: Tumor heterogeneity and changes in drug sensitivity play crucial roles in treatment failure. Using patient-derived organoids (PDOs) to predict clinical drug responses ex vivo is a promising approach for evaluating novel treatment strategies.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Alyna Katti, Adrian Vega-Perez, Miguel Foronda, Jill Zimmerman, Maria Paz Zafra, Elizabeth Granowsky, Sukanya Goswami, Eric E. Gardner, Bianca J. Diaz, Janelle M. Simon, Alexandra Wuest, Wei Luan, Maria Teresa Calvo Fernandez, Anastasia P. Kadina, John A. Walker II, Kevin Holden, Scott W. Lowe, Francisco J. Sanchez Rivera, Lukas E. Dow
Summary: To study the impact of single-nucleotide variants (SNVs) on tumor initiation and progression, researchers developed an inducible base editing (iBE) mouse model that allows for temporal and regulatable in vivo gene editing. This model efficiently edits SNVs in intestinal, lung, and pancreatic organoids using plasmid-based or synthetic guide RNAs. Temporal regulation of base editor activity allows for controlled sequential genome editing both ex vivo and in vivo, while delivery of sgRNAs directly to target tissues facilitates the generation of in situ preclinical cancer models. The iBE mouse model enables the testing of the function of SNVs.
NATURE BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Shaobo Mo, Peiyuan Tang, Wenqin Luo, Long Zhang, Yaqi Li, Xiang Hu, Xiaoji Ma, Yikuan Chen, Yichao Bao, Xingfeng He, Guoxiang Fu, Xiaoya Xu, Xinxin Rao, Xiaomeng Li, Ruoyu Guan, Shengzhi Chen, Yun Deng, Tao Lv, Peiyuan Mu, Qiang Zheng, Simin Wang, Fangqi Liu, Yiwei Li, Weiqi Sheng, Dan Huang, Chen Hu, Jianjun Gao, Zhen Zhang, Sanjun Cai, Hans Clevers, Junjie Peng, Guoqiang Hua
Summary: A living biobank with 50 patient-derived organoids (PDOs) derived from colorectal cancer liver metastasis (CRLM) has been successfully constructed. Comprehensive analysis at the multiomics levels confirmed that this organoid platform could capture intra- and interpatient heterogeneity. In vitro chemosensitivity data have revealed the potential clinical application for PDOs to predict chemotherapy response and clinical prognosis for CRLM patients.
Review
Oncology
Carolin Kastner, Anne Hendricks, Hanna Deinlein, Mohammed Hankir, Christoph-Thomas Germer, Stefanie Schmidt, Armin Wiegering
Summary: Despite advancements in multimodal therapy, cancer remains a leading cause of death in industrial nations. Organoids, a 3D ex vivo culture system, have been developed and show great potential in personalized drug investigations. They retain genetic, functional, and phenotypic characteristics of original tissue, making them valuable tools in studying a wide range of physiological and pathophysiological processes.
Review
Pharmacology & Pharmacy
Amanda Catalina Ramirez-Phillips, Dexi Liu
Summary: Advancements in understanding human genetics have fueled interest in therapeutic genome editing using engineered nucleases, with CRISPR/Cas9 emerging as a cost-effective and efficient system. Clinical applications of CRISPR/Cas9 include treatments for genetic diseases and cancer, highlighting its potential for targeted genetic modifications and viral infection eradication. Future progress in therapeutic genome editing will rely on improved delivery methods and repair efficiency for site-specific gene modification.
Article
Biochemistry & Molecular Biology
Kohta Toshimitsu, Ai Takano, Masayuki Fujii, Kazuhiro Togasaki, Mami Matano, Sirirat Takahashi, Takanori Kanai, Toshiro Sato
Summary: This study establishes a drug screening platform for patient-derived colorectal cancer organoids and identifies the bromodomain and extra-terminal bromodomain protein inhibitor as a cancer-selective growth suppressor. It also discovers an association between checkpoint with forkhead and ring finger domaines silencing and paclitaxel sensitivity.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andrea Kelemen, Idan Carmi, Adam Oszvald, Peter Lorincz, Gabor Petovari, Tamas Tolgyes, Kristof Dede, Attila Bursics, Edit Buzas, Zoltan Wiener
Summary: The study identified functional differences in EV uptake ability among CRC cells, which must be considered when using EVs as therapeutic tools for targeting cancer cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Chemistry, Physical
Juhee Lee, Yoo Kyung Kang, Eonju Oh, Juhee Jeong, San Hae Im, Duk Ki Kim, Haeshin Lee, Sang-Gyu Kim, Keehoon Jung, Hyun Jung Chung
Summary: The study presents a cancer gene therapy strategy based on NanoRNP that efficiently blocks the PD-L1 immune checkpoint and induces an antitumor effect in vivo without the need for combination therapy. In vivo results demonstrate that NanoRNP can induce indels in target cells at high frequencies, significantly suppressing tumor growth.
CHEMISTRY OF MATERIALS
(2022)
Article
Oncology
Josep Tarrago-Celada, Carles Foguet, Miriam Tarrado-Castellarnau, Silvia Marin, Xavier Hernandez-Alias, Jordi Perarnau, Fionnuala Morrish, David Hockenbery, Roger R. Gomis, Eytan Ruppin, Mariia Yuneva, Pedro de Atauri, Marta Cascante
Summary: This study identified cystine uptake and folate metabolism as potential therapeutic targets against metastatic colorectal cancer, highlighting the importance of redox homeostasis in the metastatic cell lines.
Review
Immunology
Cai-Ping Sun, Huan-Rong Lan, Xing-Liang Fang, Xiao-Yun Yang, Ke-Tao Jin
Summary: Cancer immunotherapy modulates the immune system to treat diseases, but conventional animal and in vitro models fail to accurately simulate the tumor immune microenvironment. More physiomimetic cancer models, such as patient-derived organoids, are needed to evaluate the efficacy of immunotherapy agents. The dynamic interactions between neoplastic cells and non-neoplastic host components in the tumor immune microenvironment play a crucial role in carcinogenesis, tumor metastasis, cancer progression, and drug resistance. Tumor organoids can effectively recapitulate the tumor immune microenvironment and be used for testing immunotherapy agents and personalized cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, Research & Experimental
Calvin D. De Louche, Ali Roghanian
Summary: In recent decades, immunotherapeutic strategies have been used to treat a wide range of previously incurable pathologies, but a considerable number of patients do not respond or develop resistance to current immunotherapies. Therefore, developing the next generation of immune-targeted therapies is urgently needed. Human LILRBs play important roles in regulating immune functions, and blocking these inhibitory receptors can enhance immune responses.
Article
Oncology
Yadira M. Soto-Feliciano, Francisco J. Sanchez-Rivera, Florian Perner, Douglas W. Barrows, Edward R. Kastenhuber, Yu-Jui Ho, Thomas Carroll, Yijun Xiong, Disha Anand, Alexey A. Soshnev, Leah Gates, Mary Clare Beytagh, David Cheon, Shengqing Gu, X. Shirley Liu, Andrei Krivtsov, Maximiliano Meneses, Elisa de Stanchina, Richard M. Stone, Scott A. Armstrong, Scott W. Lowe, C. David Allis
Summary: Menin interacts with oncogenic MLL1-fusion proteins, and disrupting these interactions can be a potential treatment for leukemia. The study found a molecular switch that determines the response to Menin-MLL inhibitors, involving MLL3/4-UTX chromatin-modifying complexes. By disrupting the Menin-MLL1 interaction, a tumor-suppressive program can be activated, and treatment resistance in leukemia cells can be overcome by using CDK4/6 inhibitors.
Article
Cell Biology
Kristen J. Tomaszewski, Azfar Neyaz, Kenan Sauder, Steffen Rickelt, M. Lisa Zhang, Omer Yilmaz, Rory Crotty, Stuti Shroff, Robert Odze, Anthony Mattia, Deepa T. Patil, Vikram Deshpande
Summary: Aimsp53 is an independent risk stratification marker in Barrett's esophagus (BE), but there is no universally accepted definition for abnormal p53 staining. This study assessed p53 staining in two cohorts to define abnormal p53 staining in BE-related dysplasia and evaluate the sensitivity and specificity of this cut-point for diagnosing dysplasia. The results showed that a single strongly positive p53 gland is highly sensitive and specific for dysplasia.
Article
Chemistry, Multidisciplinary
Christian C. Schreib, Maria I. Jarvis, Tanguy Terlier, Jacob Goell, Sudip Mukherjee, Michael D. Doerfert, Taylor Anne Wilson, Michael Beauregard, Kevin N. Martins, Jared Lee, Leonardo Sanchez D. Solis, Esperanza Vazquez, Matthias A. Oberli, Brian W. Hanak, Michael Diehl, Isaac Hilton, Omid Veiseh
Summary: Lipids on implant surfaces can affect the foreign body response (FBR) and fibrosis. Time-of-flight secondary ion mass spectroscopy (ToF-SIMS) is used to characterize lipid deposition on implants and it is found that multiple immunosuppressive phospholipids deposit preferentially on implants with anti-FBR surface modifications. Phospholipid deposition upregulates the transcription of anti-inflammatory genes in murine macrophages, while fatty acid deposition stimulates the expression of pro-inflammatory genes.
ADVANCED MATERIALS
(2023)
Article
Oncology
Noor Jailkhani, Karl R. Clauser, Howard H. Mak, Steffen Rickelt, Chenxi Tian, Charles A. Whittaker, Kenneth K. Tanabe, Stephen R. Purdy, Steven A. Carr, Richard O. Hynes
Summary: Metastases, which are difficult to detect and treat, are the leading cause of cancer-related deaths. There is a clinical need for therapies specifically targeting metastases. This study focuses on developing nanobodies against extracellular matrix (ECM) proteins expressed in human metastases as potential vehicles for targeted delivery of imaging and therapeutic agents. By using phage-display libraries and proteomics, the researchers identified a conserved set of ECM proteins that are abundantly expressed in metastases from TNBC and colorectal cancer. They successfully isolated nanobodies against one of these proteins, tenascin-C (TNC), and demonstrated their specificity in binding TNBC tumors and metastases. The study suggests that generic nanobodies against tumors and metastases have great potential as cancer-agnostic tools for delivering therapeutics to the tumor microenvironment.
Review
Immunology
Alex Look, Daniel Burns, Ivo Tews, Ali Roghanian, Salah Mansour
Summary: Invariant natural killer T (iNKT) cells are a unique type of T lymphocyte that can recognize lipid antigens presented by CD1d. They have potent anti-tumour activity through direct killing and indirect activation of other anti-tumour immune cells. Despite their potential, the translation of iNKT cell immunotherapy into human cancer patients has been challenging.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Aiman Obed, Saqr Alsakarneh, Mohammad Abuassi, Abdalla Bashir, Bashar Ali Ahmad, Anwar Jarrad, Thomas Lorf, Mohammad Almeqdadi
Summary: This case report series highlights an unusual clinical course in which complete recovery can occur following severe hepatic IRI post-transplantation, without the need for retransplantation or definitive therapeutic intervention. Three cases of severe IRI following liver transplantation are presented, with all patients recovering without significant complications.
GASTROENTEROLOGY RESEARCH
(2023)
Review
Gastroenterology & Hepatology
Fouad Jaber, Azizullah Beran, Saqr Alsakarneh, Khalid Ahmed, Mohamed Abdallah, Khaled Elfert, Mohammad Almeqdadi, Mohammed Jaber, Wael T. Mohamed, Mohamd Ahmed, Laith Al Momani, Laith Numan, Thomas Bierman, John H. Helzberg, Hassan Ghoz, Wendell K. Clarkston
Summary: A meta-analysis showed that combined variceal embolization (VE) and transjugular intrahepatic portosystemic shunt (TIPS) can reduce the incidence of variceal rebleeding in patients with cirrhosis, especially when covered stents are used.
GASTROENTEROLOGY RESEARCH
(2023)
Letter
Gastroenterology & Hepatology
Minyi Lee, George Eng, Anna Handte-reinecker, Vikram S. Deshpande, Omer H. Yilmaz, Manish K. Gala
Article
Cell Biology
Azfar Neyaz, Rory Crotty, Steffen Rickelt, Amaya Pankaj, Marija Stojanova, Theodoros P. Michelakos, Yurie Sekigami, Filippos Kontos, Paige H. Parrack, Deepa T. Patil, Christopher M. Heaphy, Cristina R. Ferrone, Vikram Deshpande
Summary: Immunohistochemistry for ARX and ALT FISH status can predict the aggressive behavior of nonfunctional PanNETs. This information can help identify patients who may benefit from surgical intervention.
Review
Oncology
Mijin Kim, Magdalini Panagiotakopoulou, Chen Chen, Stephen B. B. Ruiz, Karuna Ganesh, Tuomas Tammela, Daniel A. A. Heller
Summary: This review summarizes the use of micro-engineering approaches and nanosensors in establishing multicomponent tumour models and assessing tumour plasticity. These methods are being explored to model the interactions among tumour cells, the tumour microenvironment, and non-tumour tissues, and to measure them in situ and in vivo. The potential of nanosensors for transmitting information about changes in chemical gradients, enzymatic activities, and immune profiles of the tumour microenvironment and circulating analytes is also discussed.
NATURE REVIEWS CANCER
(2023)
Meeting Abstract
Oncology
Jun Ho Lee, Harihar Basnet, Francisco Sanchez-Rivera, Zhenghan Wang, Liangji Li, Joan Massague
Review
Immunology
Silvia Redondo-Garcia, Christopher Barritt, Charys Papagregoriou, Muchaala Yeboah, Bjorn Frendeus, Mark S. Cragg, Ali Roghanian
Summary: Human leukocyte immunoglobulin-like receptors (LILRs) are an important family of immunomodulatory receptors associated with various pathologies. These receptors play a crucial role in immune activation and inhibition, making them potential targets for immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Sanya Goswami, Mohammad Almeqdadi, Qi Yu
Meeting Abstract
Gastroenterology & Hepatology
Mohammad Almeqdadi, Brian S. Yueh, Charlie Chung, Marzia Spagnardi, Jianying Zeng, Jenny Paredes, Mubarak Akadri, Laura Martello-Rooney, Semir Beyaz