Article
Immunology
Silvia Ghione, Cindy Racoeur, Nesrine Mabrouk, Jingxuan Shan, Emma Groetz, Elise Ballot, Caroline Truntzer, Lotfi Chouchane, Frederique Vegran, Catherine Paul, Stephanie Plenchette, Ali Bettaieb
Summary: Immunotherapy has made limited clinical benefits in the treatment of colorectal cancer (CRC), but the multikinase inhibitor H89 has shown promise in delaying colon oncogenesis and inhibiting tumor growth. H89 appears to activate NK cells and promote differentiation of CD4(+) T cells into Th1 cells, while inhibiting the differentiation of T-reg cells. H89 also increases CD8(+) T cell activation and cytotoxicity. Overexpression of genes involved in antitumor immune response, such as IL-15RA, is induced by H89. These findings suggest that H89 could be a potential strategy for immune system activation in the prevention and treatment of CRC.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Adnan Deronic, Anneli Nilsson, Mia Thagesson, Doreen Werchau, Karin Enell Smith, Peter Ellmark
Summary: Mitazalimab, a human anti-CD40 agonist antibody, was found to activate antigen-presenting cells, leading to expansion and activation of antigen-specific T cells, ultimately enhancing the anti-tumor efficacy of a model cancer vaccine.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Medicine, Research & Experimental
Yajun Zhang, Pei Wang, Tengjiao Wang, Yuan Fang, Yongmei Ding, Qijun Qian
Summary: This study demonstrates that CAR-T cells engineered to secrete anti-CD40 antibodies using a nonviral vector system have enhanced antitumor efficacy against solid tumors, showing increased cytokine secretion, higher proportion of central memory T cells, and improved cytotoxicity. In a human ovarian cancer xenograft model, these anti-CD40-secreting CAR-T cells showed enhanced antitumor activity, suggesting their potential as a clinical strategy to improve CAR-T cell therapy efficacy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Hannah I. Ghasemi, Julien Bacal, Amanda C. Yoon, Katherine U. Tavasoli, Carmen Cruz, Jonathan T. Vu, Brooke M. Gardner, Chris D. Richardson
Summary: The efficiency of gene editing via homology-directed repair (HDR) can be enhanced by covalently modifying the template DNA to form interstrand crosslinks. These crosslinked templates (xHDRTs) significantly increase Cas9-mediated editing efficiencies in various cell types. The increased editing from xHDRTs is dependent on events occurring on the template molecule and requires the ATR kinase and components of the Fanconi anemia pathway.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Douglas R. Wassarman, Kondalarao Bankapalli, Leo J. Pallanck, Kevan M. Shokat
Summary: Mammalian target of rapamycin (mTOR) is a crucial factor in cell growth and metabolism, and its signaling in different tissues affects whole-organism processes. Researchers have developed selecTOR, a chemical-genetic system that restricts the activity of rapamycin analog in specific cell populations, achieving selective mTOR inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Rattanaporn Jaidee, Veerapol Kukongviriyapan, Laddawan Senggunprai, Auemduan Prawan, Apinya Jusakul, Phatthamon Laphanuwat, Sarinya Kongpetch
Summary: Knockdown of FGFR2 suppressed cell growth and colony formation in CCA cells through G2/M cell cycle arrest and downregulation of STAT3, cyclin A, and cyclin B1. Silencing FGFR2 enhanced the suppressive effect of gemcitabine on cell migration and invasion.
Article
Medicine, Research & Experimental
Kathryn M. Pflug, Dong W. Lee, Ashutosh Tripathi, Vytas A. Bankaitis, Kevin Burgess, Raquel Sitcheran
Summary: The study suggests that Crizotinib holds potential as a treatment for GBM, although its effectiveness is limited due to poor penetration of the blood brain barrier. Additionally, conjugation of Crizotinib with a dye showed improved inhibition of glioma cell proliferation and survival. Furthermore, IR-Crizotinib demonstrated effective tumor localization and growth inhibition in mice.
MOLECULAR PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Da Mao, Meihong Xu, Qiyu Jiang, Huiwei Sun, Fang Sun, Ruichuang Yang, Yantao Chai, Xiaojuan Li, Boan Li, Yong Li
Summary: This study explored the role of a single nucleotide mixture (SNM) in the anti-tumor therapy of hepatocellular carcinoma (HCC) and investigated its importance as adjuvant therapy. The results showed that compared to a commonly used nutritional supplement, the SNM did not induce metabolic abnormalities in HCC cells and could attenuate lymphocyte injury induced by antitumor drugs, promoting lymphocyte recruitment and survival in HCC tissues. Additionally, the SNM enhanced the anti-tumor activity of molecular-targeted drugs against HCC.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Sile Liu, Weiyuan Wang, Yue Ning, Hongmei Zheng, Yuting Zhan, Haihua Wang, Yang Yang, Jiadi Luo, Qiuyuan Wen, Hongjing Zang, Jinwu Peng, Jian Ma, Songqing Fan
Summary: Everolimus decreases intracellular miR-7-5p levels by promoting the release of miR-7-5p-loaded exosomes from NSCLC cells, and enhances anticancer efficacy by targeting the MNK/eIF4E axis and mTOR. Low expression of miR-7-5p and upregulation of MNK1 are associated with poor prognosis in NSCLC.
CELL DEATH & DISEASE
(2022)
Review
Chemistry, Medicinal
Patrik Oleksak, Eugenie Nepovimova, Zofia Chrienova, Kamil Musilek, Jiri Patocka, Kamil Kuca
Summary: Mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cell functions. Dysregulation of mTOR activity is associated with various pathological conditions. Inhibition of overactivated mTOR is a rational approach for treating human diseases. Rapamycin is a natural inhibitor of mTOR with antitumor and immunosuppressive activity. Different generations of mTOR inhibitors have been developed, including rapalogs, mTOR kinase inhibitors, and dual PI3K/mTOR inhibitors. Novel inhibitors are still being developed to better understand the role of mTOR in signaling pathways and human diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Chanjuan Shi, Michael A. Morse
Summary: This article summarizes the treatment methods for advanced neuroendocrine tumors in the intestinal tract and pancreas, as well as the limitations in therapeutic resistance. Although the mechanisms of resistance are poorly understood, early studies suggest that combination therapy or the use of novel targeted drugs may be promising.
Article
Medicine, General & Internal
Daisuke Obinata, Daigo Funakoshi, Fuminori Sakurai, Tsuyoshi Yoshizawa, Junichi Mochida, Kenya Yamaguchi, Satoru Takahashi
Summary: This study aimed to investigate the efficacy of sequential nivolumab treatment for metastatic renal cancer. The results showed that the overall survival was significantly longer in the 2017-2020 group compared to the 2014-2016 group. Nivolumab treatment as second-line therapy and prompt switching to nivolumab were identified as important factors for improved survival. These findings suggest the importance of sequential nivolumab treatment in patients who have received first-line molecular targeted therapy.
Article
Multidisciplinary Sciences
Yi An, Jun Jeon, Lillian Sun, Adeeb Derakhshan, Jianhong Chen, Sophie Carlson, Hui Cheng, Christopher Silvin, Xinping Yang, Carter Van Waes, Zhong Chen
Summary: This study identified distinct alterations in cell death-related genes in HPV(+) HNSCC cells, which were associated with HPV status, tumor staging, and anatomic locations. Combination therapies, especially involving TRAIL and birinapant, showed increased drug sensitivity in these cells, highlighting the importance of targeting death pathways in HPV(+) HNSCC. Further research in this area may lead to improved treatment strategies for HNSCC and other squamous cancer types.
SCIENTIFIC REPORTS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Sadaf Aghevlian, Bo Wu, Marina Nura Raie, Spencer K. Tumbale, Aris J. Kare, Jai W. Seo, Katherine W. Ferrara
Summary: A novel [Cu-64]Cu-NOTA-aCD40 immunoPET tracer showed high specificity in imaging a CD40(+) pancreatic tumor model in mice. Co-injection with cold aCD40 mAb or with PD-1 and CTLA-4 mAbs reduced spleen and tumor uptake but increased liver uptake. Liver to spleen accumulation ratio was greater with a smaller injected dose in a dosimetry study, indicating the potential safety of human patient imaging with [Cu-64]Cu.
NUCLEAR MEDICINE AND BIOLOGY
(2021)
Article
Oncology
Hiroo Imai, Ken Saijo, Sonoko Chikamatsu, Yoshifumi Kawamura, Chikashi Ishioka
Summary: A novel HDAC/PI3K dual inhibitor FK-A11 was developed and found to have enhanced cytotoxicity with LPIN1 gene. Downregulation of LPIN1 can enhance the cytotoxicity of FK-A11, while co-treatment with LPIN1 inhibitor propranolol can enhance the antitumor effect of FK-A11.
Article
Biochemistry & Molecular Biology
Walter A. Baseler, Luke C. Davies, Laura Quigley, Lisa A. Ridnour, Jonathan M. Weiss, S. Perwez Hussain, David A. Wink, Daniel W. McVicar
Article
Multidisciplinary Sciences
Debashree Basudhar, Sharon A. Glynn, Madison Greer, Veena Somasundaram, Jae Hong No, David A. Scheiblin, Pablo Garrido, William F. Heinz, Aideen E. Ryan, Jonathan M. Weiss, Robert Y. S. Cheng, Lisa A. Ridnour, Stephen J. Lockett, Daniel W. McVicar, Stefan Ambs, David A. Wink
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Immunology
Jonathan M. Weiss, W. Gregory Alvord, Octavio A. Quinones, Jimmy K. Stauffer, Robert H. Wiltrout
Article
Medicine, Research & Experimental
Jonathan M. Weiss, Luke C. Davies, Megan Karwan, Lilia Ileva, Michelle K. Ozaki, Robert Y. S. Cheng, Lisa A. Ridnour, Christina M. Annunziata, David A. Wink, Daniel W. McVicar
JOURNAL OF CLINICAL INVESTIGATION
(2018)
Article
Immunology
Jonathan M. Weiss, Lisa A. Ridnour, Tim Back, S. Perwez Hussain, Peijun He, Anna E. Maciag, Larry K. Keefer, William J. Murphy, Curtis C. Harris, David A. Wink, Robert H. Wiltrout
JOURNAL OF EXPERIMENTAL MEDICINE
(2010)
Article
Immunology
Jonathan M. Weiss, Jeff J. Subleski, Tim Back, Xin Chen, Stephanie K. Watkins, Hideo Yagita, Thomas J. Sayers, William J. Murphy, Robert H. Wiltrout
JOURNAL OF IMMUNOLOGY
(2014)
Review
Cell Biology
Luke C. Davies, Christopher M. Rice, Daniel W. McVicar, Jonathan M. Weiss
JOURNAL OF LEUKOCYTE BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Jonathan M. Weiss, Timothy C. Back, Anthony J. Scarzello, Jeff J. Subleski, Veronica L. Hall, Jimmy K. Stauffer, Xin Chen, Dejan Micic, Kory Alderson, William J. Murphy, Robert H. Wiltrout
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2009)
Article
Multidisciplinary Sciences
Christopher M. Rice, Luke C. Davies, Jeff J. Subleski, Nunziata Maio, Marieli Gonzalez-Cotto, Caroline Andrews, Nimit L. Patel, Erika M. Palmieri, Jonathan M. Weiss, Jung-Min Lee, Christina M. Annunziata, Tracey A. Rouault, Scott K. Durum, Daniel W. McVicar
NATURE COMMUNICATIONS
(2018)
Review
Oncology
Jonathan M. Weiss
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2020)
Article
Endocrinology & Metabolism
Jonathan M. M. Weiss, Erika M. M. Palmieri, Marieli Gonzalez-Cotto, Ian A. A. Bettencourt, Emily L. L. Megill, Nathaniel W. W. Snyder, Daniel W. W. McVicar
Summary: In this study, the authors demonstrate that itaconate derived from macrophages impacts hepatocyte lipid metabolism, which is involved in the crosstalk between the immune system and hepatocytes during non-alcoholic fatty liver disease development. Itaconate regulates various biological processes, including fatty acid beta-oxidation and metabolic interaction between macrophages and tumors. The study shows upregulation of itaconic acid in human non-alcoholic steatohepatitis and a mouse model of non-alcoholic fatty liver disease. Deficiency in the gene responsible for itaconate production exacerbates lipid accumulation, glucose and insulin intolerance, and fat deposition in the liver. Treatment with a derivative of itaconate reverses dyslipidemia associated with high-fat diet feeding. Mechanistically, itaconate treatment reduces lipid accumulation and increases oxidative phosphorylation in hepatocytes through fatty acid oxidation.