Article
Chemistry, Medicinal
Wei Wang, Jiacheng He, Junjie Yang, Chan Zhang, Zhiyuan Cheng, Yao Zhang, Qiansen Zhang, Peili Wang, Shuowen Tang, Xin Wang, Mingyao Liu, Weiqiang Lu, Han-Kun Zhang
Summary: The EP4 receptor plays a crucial role in the immunosuppressive activity in the tumor microenvironment. Compound 47, a newly synthesized compound, exhibits good EP4 antagonistic activity and effectively suppresses the expression of immunosuppression-related genes. Oral administration of compound 47, alone or in combination with anti-PD-1 antibody, enhances the antitumor immune response and inhibits tumor growth in a mouse colon carcinoma model.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Ward Vleeshouwers, Koen van den Dries, Sandra de Keijzer, Ben Joosten, Diane S. Lidke, Alessandra Cambi
Summary: This study highlights the modulation of myeloid immune cell function by Prostaglandin E2 (PGE2) through the activation of EP2 and EP4 receptors. EP4 plays a key role in podosome loss in DCs, while both EP2 and EP4 signaling lead to different cAMP production profiles and reciprocal control of signaling pathways. Efficient signaling of both EP2 and EP4 relies on an intact microtubule network, enhancing our understanding of early signaling events in myeloid cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Kun Liu, Wei Mao, Bo Liu, Tingting Li, Xinfei Wang, Le Pei, Jinshan Cao, Fenglong Wang
Summary: The study found that PGE2 enhances Staphylococcus aureus infection in bovine endometrium through the EP4 receptor. This result is essential for the development of new approaches to treating S. aureus infection, such as the application of EP4 antagonist as an adjunct drug treatment.
MICROBIAL PATHOGENESIS
(2021)
Article
Pharmacology & Pharmacy
Philipp Gercke, Nikoleta Lautenschlager, Nora Vedder, Chiel van Geffen, Harald Renz, Saeed Kolahian
Summary: Research findings suggest that myeloid-derived suppressor cells (MDSCs) play a crucial role in chronic lung diseases like asthma, and modulating MDSCs locally or systemically may be a potential therapeutic option.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Marie Goepp, Siobhan Crittenden, You Zhou, Adriano G. Rossi, Shuh Narumiya, Chengcan Yao
Summary: Research suggests that PGE(2) negatively regulates iTreg cell differentiation through a direct action on T cells, indicating the potential importance of targeting the PGE(2)-EP2/EP4 pathway to control T cell-mediated inflammation.
Article
Oncology
Yoshihiko Manabe, Yutaka Takahashi, Chikao Sugie, Zhen Wang, Shohei Katsuki, Takuhito Kondo, Taro Murai, Masahiro Nakashima, Taiki Takaoka, Kazuhiko Ogawa, Yuta Shibamoto
Summary: A newly developed antagonist of PGE2-EP4, AAT-008, enhances the radiosensitivity of colon cancer cells by stimulating the immune system against the cancer cells, as revealed by flow cytometry.
TRANSLATIONAL CANCER RESEARCH
(2023)
Article
Immunology
Miho Tokumasu, Mikako Nishida, Takamasa Kawaguchi, Ikuru Kudo, Tohru Kotani, Kazuhiko Takeda, Takao Yoshida, Heiichiro Udono
Summary: In this study, it was found that EP4i, an inhibitor of the PGE2 receptor EP4, suppressed tumor metabolism, stimulated IFN gamma production by NK cells, polarized macrophages, and reduced tumor hypoxia through normalization of the tumor vasculature.
INTERNATIONAL IMMUNOLOGY
(2022)
Article
Cell Biology
Mingjie Liang, Lexun Wang, Weixuan Wang
Summary: SW033291, a small molecule inhibitor of 15-hydroxyprostaglandin dehydrogenase, increases PGE2 levels and exerts a protective effect against T2DM by promoting glycogen synthesis and inhibiting gluconeogenesis.
CELLULAR SIGNALLING
(2023)
Article
Pathology
Benedicte Oules, Lydia Deschamps, Pierre Sohier, Matthieu Tihy, Anais Chassac, Anais Couvelard, Eric Frouin, Maxime Battistella
Summary: GATA6 immunostaining has been identified as a new diagnostic tool for sebaceous tumors, showing higher accuracy compared to other markers and being able to differentiate from non-sebaceous tumors. It also shows similar sensitivity to adipophilin and higher specificity, especially in clear-cell histology. Furthermore, GATA6 expression is found in skin metastases of gastrointestinal origin but not in metastases from breast or lung cancers.
Review
Immunology
Monica Parodi, Simonetta Astigiano, Paolo Carrega, Gabriella Pietra, Chiara Vitale, Laura Damele, Melania Grottoli, Maria de la Luz Guevara Lopez, Riccardo Ferracini, Giulia Bertolini, Ilaria Roato, Massimo Vitale, Paola Orecchia
Summary: Since the first studies, mouse models have played a crucial role in understanding NK cells, their development, function, and behavior in normal and tumor tissues. Initially used to study murine NK cells, more sophisticated human-in-mice models have been developed to investigate human NK cells and minimize murine interference. This review provides an overview of the different models used to study NK cells, with a focus on the popular NOG and NSG models, which are used for human-in-mice tumor models, studying transferred human NK cells, and evaluating enhancers of human NK cell function.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Alice Mac Donald, Delphine Guipouy, William Lemieux, Mario Harvey, Louis-Jean Bordeleau, David Guay, Hugo Romero, Yuanyi Li, Renaud Dion, Kathie Beland, Elie Haddad
Summary: NK cell therapy has the potential to be a universal off-the-shelf option for cancer treatment. However, the limited efficacy of NK cell-based immunotherapies against solid tumors is a major challenge. In this study, targeting the NKG2A/HLA-E immune checkpoint by using CRISPR-mediated KLRC1 gene editing significantly improved NK cell cytotoxicity against HLA-E+ tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Sanja Nabergoj, Tijana Markovic, Damjan Avsec, Martina Gobec, Helena Podgornik, Ziga Jakopin, Irena Mlinaric-Rascan
Summary: The EP4 receptor agonist L-902688 shows selective cytotoxicity against various B-cell malignancies, including CLL, by inhibiting the NF-kappa B pathway, cell proliferation, and inducing apoptosis. When used in combination with ibrutinib, idelalisib, or venetoclax, L-902688 demonstrates synergistic cytotoxic activity against patient derived CLL cells, presenting a promising adjunct to existing therapies for CLL patients.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Oncology
Martin Benej, Jinghai Wu, McKenzie Kreamer, Martin Kery, Sergio Corrales-Guerrero, Ioanna Papandreou, Terence M. Williams, Zihai Li, Edward E. Graves, Laura E. Selmic, Nicholas C. Denko
Summary: This study demonstrates that pharmacological regulation of mitochondrial metabolism can directly impact tumor hypoxia levels in murine tumor models and spontaneous canine soft tissue sarcomas. Reducing mitochondrial metabolism can potentially decrease tumor hypoxia and offer therapeutic benefits.
Article
Cell & Tissue Engineering
Wenhao Jiang, Yunyun Jin, Shiwei Zhang, Yi Ding, Konglin Huo, Junjie Yang, Lei Zhao, Baoning Nian, Tao P. Zhong, Weiqiang Lu, Hankun Zhang, Xu Cao, Karan Mehul Shah, Ning Wang, Mingyao Liu, Jian Luo
Summary: The study reveals the important role of PGE2/EP4 signaling in osteoclasts in promoting the progression of OA and related pain. Inhibition of EP4 with the novel antagonist HL-43 shows therapeutic potential in alleviating disease progression and pain in OA.
Article
Peripheral Vascular Disease
Aikaterini Kourpa, Angela Schulz, Eva Mangelsen, Debora Kaiser-Graf, Nils Koppers, Monika Stoll, Michael Rothe, Michael Bader, Bettina Purfuerst, Severine Kunz, Thomas Gladytz, Thoralf Niendorf, Sebastian Bachmann, Kerim Mutig, Juliane Bolbrinker, Daniela Panakova, Reinhold Kreutz
Summary: This study explored the renoprotective effects of pharmacological blockade of EP2 and EP4 receptors in the development of albuminuria. The results showed that separate and combined blockade of EP2 and EP4 receptors reduced albuminuria. This finding provides a basis for further research on the therapeutic potential of this treatment option and the possible role of circadian clock genes.
Article
Medicine, General & Internal
Carole Lunny, Areti Angeliki Veroniki, Brian Hutton, Ian White, Jpt Higgins, James M. Wright, Ji Yoon Kim, Sai Surabi Thirugnanasampanthar, Shazia Siddiqui, Jennifer Watt, Lorenzo Moja, Nichole Taske, Robert C. Lorenz, Savannah Gerrish, Sharon Straus, Virginia Minogue, Franklin Hu, Kevin Lin, Ayah Kapani, Samin Nagi, Lillian Chen, Mona Akbar-nejad, Andrea C. Tricco
Summary: This study aimed to develop a risk of bias (RoB) tool for assessing network meta-analysis (NMA) and gather opinions from knowledge users. The Delphi process and knowledge user survey identified the content of the RoB NMA tool and revealed a preference for assessing both individual NMA results and authors' conclusions.
BMJ EVIDENCE-BASED MEDICINE
(2023)
Article
Oncology
Joseph W. Kim, Rana R. McKay, Marc R. Radke, Shilin Zhao, Mary-Ellen Taplin, Nancy B. Davis, Paul Monk, Leonard J. Appleman, Primo N. Lara, Ulka N. Vaishampayan, Jingsong Zhang, Asit K. Paul, Glenn Bubley, Eliezer M. Van Allen, Serhan Unlu, Ying Huang, Massimo Loda, Geoffrey I. Shapiro, Peter M. Glazer, Patricia M. LoRusso, S. Percy Ivy, Yu Shyr, Elizabeth M. Swisher, Daniel P. Petrylak
Summary: The study investigated the clinical outcomes of combining Cediranib with olaparib in patients with prostate cancer. The results showed that the combination improved radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer compared to olaparib alone. However, it was also associated with a higher incidence of adverse events.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Bradley J. Monk, Keiichi Fujiwara, David M. O'Malley, Robert L. Coleman, Iain A. McNeish, Kevin K. Lin, Stephanie Hume, Rebecca S. Kristeleit
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Kevin Lin, Heather R. MacDonald, Merry L. Tetef, Colleen L. Coleman
ADVANCES IN RADIATION ONCOLOGY
(2023)
Article
Oncology
Eve Rodler, Priyanka Sharma, William E. Barlow, Julie R. Gralow, Shannon L. Puhalla, Carey K. Anders, Lori Goldstein, Debu Tripathy, Ursa A. Brown-Glaberman, Thu-Tam Huynh, Christopher S. Szyarto, Andrew K. Godwin, Harsh B. Pathak, Elizabeth M. Swisher, Marc R. Radke, Kirsten M. Timms, Danika L. Lew, Jieling Miao, Lajos Pusztai, Daniel F. Hayes, Gabriel N. Hortobagyi
Summary: PARP inhibitors are effective in germline BRCA1/2-mutated metastatic breast cancer. This study demonstrates that adding veliparib to cisplatin improves progression-free survival in patients with BRCA-like metastatic triple-negative breast cancer.
Article
Oncology
Ann Oluloro, Sarah M. Temkin, Jonathan Jackson, Elizabeth M. Swisher, Liz Sage, Kemi Doll
Summary: This study comprehensively assessed gynecologic cancer clinical trial protocols and found that they lack design elements that provide high value to Black individuals, such as lifestyle risk factors, ancestry, and remuneration. Inclusion of these valued items should be considered in efforts to improve diversity in clinical trial enrollment among Black individuals.
GYNECOLOGIC ONCOLOGY
(2023)
Article
Oncology
Miranda P. Steenbeek, Majke H. D. van Bommel, Joanna intHout, Christine B. Peterson, Michiel Simons, Kit C. B. Roes, Marleen Kets, Barbara M. Norquist, Elizabeth M. Swisher, Rosella P. M. G. Hermens, Karen H. Lu, Joanne A. de Hullu
Summary: This study aims to investigate whether delayed oophorectomy is non-inferior to standard salpingo-oophorectomy for the prevention of tubo-ovarian cancer among individuals at high inherited risk. It is an international prospective preference trial, where participants can choose between delayed oophorectomy and standard salpingo-oophorectomy. Recruitment is expected to be completed by the end of 2026, and the primary outcome will be available in 2036.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Medicine, General & Internal
Olivier Colomban, Elizabeth M. Swisher, Rebecca Kristeleit, Iain McNeish, Ronnie Shapira-Frommer, Sandra Goble, Kevin K. Lin, Lara Maloney, Gilles Freyer, Benoit You
Summary: Mathematical modeling of early CA-125 kinetics can be used as an indicator of rucaparib efficacy in recurrent ovarian carcinoma patients. The KELIM-PARP score is associated with treatment response and progression-free survival. This study suggests the potential use of this strategy in selecting patients for PARPi-based treatment regimens.
Review
Oncology
Ru Li, Mousumi Beto Mukherjee, Zhaosheng Jin, Hengrui Liu, Kevin Lin, Qiuyue Liu, James P. Dilger, Jun Lin
Summary: This meta-analysis examined the effect of general anesthetics on metastasis and recurrence after cancer surgery. It showed that propofol-based total intravenous anesthesia is associated with a lower risk of metastasis/recurrence and lower IL-6 level compared to inhalational anesthesia. Pre-clinical studies confirmed these findings and explored potential mechanisms.
Article
Oncology
Heidi J. Gray, Payel Chatterjee, Rachele Rosati, Lauren R. Appleyard, Grace J. Durenberger, Robert L. Diaz, Hallie A. Swan, Danielle Peretti, Maddy Pollastro, Trevor Ainge, Katannya Kapeli, Shalini Pereira, Astrid L. Margossian, Kalyan Banda, Barbara A. Goff, Elizabeth M. Swisher, Brady Bernard, Christopher J. Kemp, Carla Grandori
Summary: This article describes a remarkable response to targeted therapy in a patient with platinum-resistant, advanced low-grade serous ovarian cancer. Genomic analysis did not provide obvious therapeutic options, but a drug sensitivity assay identified several potential therapies. This case highlights the clinical utility of ex vivo drug testing of patient-derived tumor organoids as a new approach to identify personalized therapies.
NPJ PRECISION ONCOLOGY
(2023)
Editorial Material
Oncology
Melvin J. Silverstein, Brian Kim, Shane Lloyd, Peter Chen, Kevin Lin
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Obstetrics & Gynecology
Joyce Y. Wang, Kimberly K. Ma, Daniel J. Reiter, Ana Torvie, Elizabeth M. Swisher
GYNECOLOGIC ONCOLOGY REPORTS
(2023)
Meeting Abstract
Clinical Neurology
David Glickenstein, Avinash Karamchandani, Camille Korbut, Michelle Bang, Alexa Aucoin, Leah Callovini, Kevin Lin, Patricia Haynes
Meeting Abstract
Oncology
Katherine Kramme, Emily Welker, Oana Andreea Raicu, Melvin Silverstein, Sadia Khan, Peter Chen, Kevin Lin, Brian Kim, Shane Lloyd
ANNALS OF SURGICAL ONCOLOGY
(2023)
Meeting Abstract
Oncology
Emily Welker, Peter Chen, Sadia Khan, Brian Kim, Katherine Kramme, Kevin Lin, Shane Lloyd, Oana Andreea Raicu, Melvin Silverstein
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Andra S. Martinikova, Miroslav Stoyanov, Anna Oravetzova, Yannick P. Kok, Shibo Yu, Jana Dobrovolna, Pavel Janscak, Marcel van Vugt, Libor Macurek
Summary: Oncogene-induced replication stress is a major cause of genome instability in cancer cells. This study reveals that increased activity of PPM1D exacerbates replication stress caused by cyclin E1 overexpression, leading to abnormal cell cycle progression and accumulation of DNA copy number alterations. Pharmacological inhibition of PPM1D can alleviate replication stress-induced genome instability.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Alamelu G. Bharadwaj, Meghan E. McLean, Margaret L. Dahn, Hannah F. Cahill, Marie-Claire D. Wasson, Raj Pranap Arun, Olivia L. Walker, Brianne M. Cruickshank, Wasundara Fernando, Jaganathan Venkatesh, Penelope J. Barnes, Gillian Bethune, Gregory Knapp, Lucy K. Helyer, Carman A. Giacomantonio, David M. Waisman, Paola Marcato
Summary: ALDH1A3 regulates the plasminogen activation pathway to promote breast cancer metastasis. Co-expression of ALDH1A3 and tPA is associated with TNBC subtype, high tumor grade, and recurrent metastatic disease.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Nayela N. Chowdhury, Yi Yang, Ananya Dutta, Michelle Luo, Zimu Wei, Sara R. Abrahams, Alexey S. Revenko, Fenil Shah, Lindsey A. Miles, Robert J. Parmer, Bas de Laat, Alisa S. Wolberg, James P. Luyendyk, Melissa L. Fishel, Matthew J. Flick
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. Primary fibrinolytic protease plasminogen promotes PDAC tumor growth and metastatic potential through engaging plasminogen receptors on tumor cells.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Nuria Gendrau-Sanclemente, Agnes Figueras, Kristina Gracova, Alvaro Lahiguera, Elisenda Alsina-Sanchis, Juan A. Marin-Jimenez, August Vidal, Xavier Matias-Guiu, Sergi Fernandez-Gonzalez, Marc Barahona, Lola Marti, Jordi Ponce, Francesc Vinals
Summary: High-grade serous ovarian cancer (HGSOC), the deadliest gynecological malignancy, spreads through transcoelomic dissemination. This study reveals that platelet-derived growth factor receptor beta (PDGFRβ) is essential for the formation of tumorspheres in HGSOC. Inhibition of PDGFRβ blocks the clustering of ovarian cancer cells and prevents peritoneal dissemination.
MOLECULAR ONCOLOGY
(2024)
