Article
Immunology
Roberto Gallus, Tarik Gheit, Dana Holzinger, Marco Petrillo, Davide Rizzo, Gianluigi Petrone, Francesco Micciche, Gian Carlo Mattiucci, Damiano Arciuolo, Giampiero Capobianco, Giovanni Delogu, Vincenzo Valentini, Massimo Tommasino, Francesco Bussu
Summary: This study evaluated the prevalence of high-risk human papillomavirus (HPV) infection and the clinico-biological significance of p16 overexpression in laryngeal squamous cell carcinoma (LSCC) from different subsites. The results showed that high-risk HPV infection appears to have a marginal role in LSCC, but p16 overexpression has a prognostic role in patients undergoing primary surgery.
Editorial Material
Chemistry, Medicinal
Mark Klein
Summary: Cyclin-dependent kinases (CDKs) have important roles in normal cells and can be targeted for cancer therapy. CDK4 inhibitors have been approved for advanced breast cancer treatment. However, the development of selective inhibitors for individual CDKs is challenging due to the highly conserved ATP-binding site.
Article
Oncology
Elena Garralda, Alison M. Schram, Philippe L. Bedard, Gary K. Schwartz, Eunice Yuen, Samuel C. McNeely, Silvia Ribeiro, Jason Cunningham, Yi Wang, Arantxa Urunuela, Xiaojian Xu, Patricia LoRusso
Summary: LY3405105 is a promising CDK7 inhibitor with good bioavailability and selectivity. However, the clinical trial showed limited efficacy and no plans for further development. The MTD of LY3405105 monotherapy was determined to be 20 mg QD.
Article
Plant Sciences
Rui-Yi Yang, Jia-Yi Tan, Zhe Liu, Xiao-Ling Shen, Ying-Jie Hu
Summary: The natural lignan LAF from Arctium lappa Linne has been found to inhibit tumor cell growth in vitro and in vivo. However, its role in cell cycle regulation remains unknown.
PHARMACEUTICAL BIOLOGY
(2023)
Article
Immunology
Tianyi Cheng, Yingyi Wu, Zhiyu Liu, Yi Yu, Shixue Sun, Min Guo, Baoqing Sun, Chen Huang
Summary: Breast cancer is the most common cancer worldwide, with triple-negative breast cancer having the worst prognosis. This study identified the role of the CDKN2A gene in breast cancer and developed a prognostic model based on CDKN2A, providing new insights for the treatment of triple-negative breast cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Yanting Zhou, Xiandeng Li, Peifang Luo, Huiting Chen, Yan Zhou, Xueting Zheng, Yuan Yin, Haoche Wei, Hongji Liu, Wen Xia, Mingsong Shi, Xiaoan Li
Summary: CDK4/6 is a crucial player in various cancers and a potential target for anticancer drugs. The interaction between abemaciclib and human CDK6 was studied, and C2231-A was identified as a promising candidate compound with significant inhibitory effects on human breast cancer cell lines.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Yi Zeng, Gang Ma, Fenglin Cai, Pengliang Wang, Han Liang, Rupeng Zhang, Jingyu Deng, Yong Liu
Summary: SMYD3 is highly expressed in gastric cancer tissues and is associated with aggressive clinical characteristics and poor prognosis. Inhibition of SMYD3 expression significantly reduces the proliferation of gastric cancer cells and Akt signaling pathway activity. SMYD3 epigenetically represses the expression of EMP1 through H4K20me3-dependent mechanisms.
CELL DEATH & DISEASE
(2023)
Article
Chemistry, Multidisciplinary
Lanlan Fu, Jiajia Mou, Yanru Deng, Xiaoliang Ren, Shuang Qiu
Summary: CDK1 plays an essential role in the cell cycle and has emerged as a new target for cancer therapy. A new series of flavone derivatives, including compound 2a, were discovered as potent CDK1 inhibitors. Compound 2a exhibited strong inhibitory activity against CDK1 and showed potential as a lead compound for CDK1 inhibitor development.
FRONTIERS IN CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Marketa Kovalova, Joseph Peter Baraka, Vaclav Mik, Radek Jorda, Lei Luo, Hao Shao, Vladimir Krystof
Summary: CDK7 is a protein kinase that regulates the cell cycle and mRNA transcription, and it has emerged as a potential drug target in oncology. Six promising drug candidates have been evaluated in early clinical trials. This review analyzes patents published from 2018 to 2022 and provides an overview of CDK7 inhibitors as anticancer drugs, including their chemical structures, biochemical profiles, and developmental stages.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Review
Biochemistry & Molecular Biology
Marika A. V. Reinius, Elizabeth Smyth
Summary: The introduction of CKI inhibitors has been a major development in the treatment of advanced breast cancer, with potential applications beyond metastatic breast cancer treatment. Evidence suggests that these agents have impacts on cancer immunology and metabolism, expanding our understanding of their therapeutic effects. Challenges and opportunities in the 2020s, including treatment resistance and biomarker development, are anticipated in the continued research and application of CKIs.
EXPERT REVIEWS IN MOLECULAR MEDICINE
(2021)
Article
Microbiology
Fanfan Shu, Yu Li, Wenlun Chu, Xuehua Chen, Ziding Zhang, Yaqiong Guo, Yaoyu Feng, Lihua Xiao, Na Li
Summary: Calcium-dependent protein kinases (CDPKs) play important roles in Cryptosporidium spp., triggering various biological processes. This study characterized CpCDPK2A and its expression pattern in different stages of Cryptosporidium. Although the specific role of CpCDPK2A remains unclear, it has the potential to be a drug target for treating cryptosporidiosis.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Cell Biology
Brian J. McHugh, Jillian Stephen, Calum T. Robb, Sarah Fox, Tiina Kipari, Jennifer A. Cartwright, Christopher Haslett, Rodger Duffin, Christopher D. Lucas, Adriano G. Rossi
Summary: Cyclin-dependent kinase inhibitor drugs can induce neutrophil apoptosis and enhance inflammation resolution. In this study, CDKi showed significant effects on macrophage pro-inflammatory mediator production and viability. Targeting CDK9 inhibited an inflammatory phenotype in human MDMs, suggesting its importance in therapeutically targeting pro-inflammatory macrophage functions during chronic inflammation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Laura Abaandou, Ashish K. Sharma, Joseph Shiloach
Summary: Knocking out the CASP8AP2 gene in HEK293 cells using CRISPR/Cas9 significantly increases the specific expression of recombinant proteins without affecting cell growth and viability. Transcriptome analysis indicated that the upregulation of the CDKN2A gene, which regulates the cell cycle, contributes to the improved recombinant protein expression in CASP8AP2 deficient cells. This validates CASP8AP2 as a viable engineering target for enhancing recombinant protein expression in HEK293 cells.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Cell Biology
Kanta Yamazoe, Yoshihiro H. Inoue
Summary: The Cdk1-CycB complex is crucial for cell-cycle regulation. Import and export processes are important for the localization and activation of Cdk1. Interaction between Cdc25C and Cdk-activating kinase with Cdk1 in the nucleus is necessary for centrosome separation.
Article
Biochemistry & Molecular Biology
Jiajia Mou, Shuang Qiu, Danghui Chen, Yanru Deng, Teka Tekleab
Summary: The study reported a series of baicalein derivatives that significantly inhibited the proliferation of MCF-7 tumor cells and the activity of CDK1/cyclin B kinase. Among them, compound 4a showed better inhibition against MCF-7 proliferation, while compound 3o exhibited the best activity against CDK1/cyclin B kinase. These findings demonstrate that baicalein derivatives can be used as CDK1 inhibitors fighting against cancer.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Immunology
Alexandra Maximiliane Hierweger, Jan Broder Engler, Manuel A. Friese, Holger M. Reichardt, John Lydon, Francesco DeMayo, Hans-Willi Mittruecker, Petra Clara Arck
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2019)
Article
Multidisciplinary Sciences
Dmitri Lodygin, Moritz Hermann, Nils Schweingruber, Cassandra Fluegel-Koch, Takashi Watanabe, Corinna Schlosser, Arianna Merlini, Henrike Korner, Hsin-Fang Chang, Henrike J. Fischer, Holger M. Reichardt, Marta Zagrebelsky, Brit Mollenhauer, Sebastian Kuegler, Dirk Fitzner, Jens Frahm, Christine Stadelmann, Michael Haberl, Francesca Odoardi, Alexander Fluegel
Correction
Multidisciplinary Sciences
Dmitri Lodygin, Moritz Hermann, Nils Schweingruber, Cassandra Flugel-Koch, Takashi Watanabe, Corinna Schlosser, Arianna Merlini, Henrike Korner, Hsin-Fang Chang, Henrike J. Fischer, Holger M. Reichardt, Marta Zagrebelsky, Brit Mollenhauer, Sebastian Kugler, Dirk Fitzner, Jens Frahm, Christine Stadelmann, Michael Haberl, Francesca Odoardi, Alexander Flugel
Article
Clinical Neurology
Robert Hoepner, Maud Bagnoud, Maximilian Pistor, Anke Salmen, Myriam Briner, Helen Synn, Lisa Schrewe, Kirsten Guse, Farhad Ahmadi, Seray Demir, Louis Laverick, Melissa Gresle, Paul Worley, Holger Michael Reichardt, Helmut Butzkueven, Ralf Gold, Imke Metz, Fred Luehder, Andrew Chan
ACTA NEUROPATHOLOGICA
(2019)
Article
Immunology
Henrike J. Fischer, Tobias L. K. Finck, Hannah L. Pellkofer, Holger M. Reichardt, Fred Luehder
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Immunology
Tina K. Kaiser, Hu Li, Laura Rossmann, Sybille D. Reichardt, Hanibal Bohnenberger, Claus Feldmann, Holger M. Reichardt
EUROPEAN JOURNAL OF IMMUNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Hu Li, Tina K. Kaiser, Marina Borschiwer, Hanibal Bohnenberger, Sybille D. Reichardt, Fred Luehder, Lutz Walter, Ralf Dressel, Sebastiaan H. Meijsing, Holger M. Reichardt
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2019)
Review
Cell Biology
Sybille D. Reichardt, Agathe Amouret, Chiara Muzzi, Sabine Vettorazzi, Jan P. Tuckermann, Fred Luehder, Holger M. Reichardt
Summary: Glucocorticoids have been a powerful and affordable treatment option for inflammatory diseases for over 70 years, but their benefits come with side effects. Efforts are being made to improve their therapeutic index through novel approaches such as chemical modifications and nanoformulations. Despite being one of the oldest class of drugs in medical use, GCs remain a topic of highly active scientific research.
Article
Immunology
Fabian A. Gayer, Sybille D. Reichardt, Hanibal Bohnenberger, Michael Engelke, Holger M. Reichardt
Summary: The testis is an immune privileged site, and testicular macrophages play a crucial role in maintaining immune tolerance. This study characterized the features of testicular macrophages in mice, including surface markers, localization, morphology, and function. It was found that testicular macrophages consist of distinct subsets with different features, and the polarization of the immune system and the presence of glucocorticoid receptors affect their phenotype.
IMMUNOLOGY LETTERS
(2022)
Article
Cell Biology
Fabian A. Gayer, Alexander Fichtner, Tobias J. Legler, Holger M. Reichardt
Summary: Research has found that the interaction between seminoma cells and immune cells plays an important role in the progression of testicular germ cell cancer (TGCC). Seminoma cells can induce immune cell activation and generate a pro-inflammatory environment, while T cells can increase the proliferation, metastatic potential, and stemness of tumor cells.
Article
Cell Biology
Leonie Meyer-Heemsoth, Katja Mitschke, Jasmina Bier, Konstantin Schuetz, Andreas Villunger, Tobias J. Legler, Martin S. Weber, Fred Luehder, Holger M. Reichardt
Summary: Glucocorticoids (GCs) have immunomodulatory effects by inducing apoptosis and suppressing cytokine production in T cells. However, their impact on energy metabolism is not well understood. This study found that dexamethasone (Dex) can repress energy metabolism in murine and human primary T cells, mediated by the GC receptor and unrelated to apoptosis induction and Stat1 activity. Moreover, rapamycin treatment can abolish the repression of metabolic gene expression by Dex, implicating mTOR as a critical target. Similar findings were observed in multiple sclerosis (MS) patients after intravenous methylprednisolone (IVMP) pulse therapy. The expression of metabolic genes was reduced in the peripheral blood T cells of most patients, correlating with disease activity. These findings establish the regulation of T cell energy metabolism by GCs as a new immunomodulatory principle.
Article
Oncology
Fabian A. Gayer, Miriam Henkel, Juliane Luft, Sybille D. Reichardt, Alexander Fichtner, Tobias J. Legler, Holger M. Reichardt
Summary: Testicular germ cell cancer (TGCC) can be divided into different subtypes, with seminomatous germ cell tumors (SGCT) and non-seminomatous germ cell tumors (NSGCT) being distinct. This study found that immune cells cocultured with TCam-2 cells, a seminomatous cell line, produced pro-inflammatory cytokines and upregulated expression of pro-inflammatory genes, while immune cells cocultured with NTERA-2 cells, a non-seminomatous cell line, showed reduced activation and downregulated expression of activation markers and effector molecules.
Meeting Abstract
Immunology
T. Kaiser, C. Feldmann, H. M. Reichardt
EUROPEAN JOURNAL OF IMMUNOLOGY
(2019)
Meeting Abstract
Immunology
H. Li, S. H. Meijsing, H. M. Reichardt
EUROPEAN JOURNAL OF IMMUNOLOGY
(2019)
Meeting Abstract
Clinical Neurology
Robert Hoepner, Maud Bagnoud, Maximilian Pistor, Anke Salmen, Myriam Briner, Lisa Schrewe, Kirsten Guse, Farhad Ahmadi, Seray Demir, Louise Laverick, Melissa Gresle, Paul Worley, Holger Reichardt, Helmut Butzkueven, Ralf Gold, Fred Luehder, Andrew Chan