Article
Chemistry, Multidisciplinary
Sarah A. Badawy, Ahmed R. Hassan, Rawah H. Elkousy, Salwa Abu A. El Wafa, Abd-El Salam I. Mohammad
Summary: The n-hexane fraction of Silene succulenta Forssk. aerial parts showed high anticancer activity against breast carcinoma cell lines (MCF-7). Two new cyclic glucolipids were isolated from the fraction and showed potential suppression of MCF-7 cells. Molecular docking analysis revealed that these compounds have high binding affinity to Mps1 kinase.
Article
Chemistry, Medicinal
Ricardo A. M. Serafim, Andre da Silva Santiago, Martin P. Schwalm, Zexi Hu, Caio dos Reis, Jessica E. Takarada, Priscila Mezzomo, Katlin B. Massirer, Mark Kudolo, Stefan Gerstenecker, Apirat Chaikuad, Lars Zender, Stefan Knapp, Stefan Laufer, Rafael M. Counago, Matthias Gehringer
Summary: This study presents the design and characterization of the first irreversible covalent MPS1 inhibitor, RMS-07, which shows potent inhibitory activity against MPS1 and exhibits selectivity and cellular target engagement.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Noureen Ashraf, Asnuzilawati Asari, Numan Yousaf, Matloob Ahmad, Mahmood Ahmed, Amir Faisal, Muhammad Saleem, Muhammad Muddassar
Summary: In this study, 3D-QSAR modeling was used to design TTK protein inhibitors, and validation and simulation studies provided insights for the optimization of new compounds.
FRONTIERS IN CHEMISTRY
(2022)
Article
Cell Biology
Gonghua Qi, Hanlin Ma, Yingwei Li, Jiali Peng, Jingying Chen, Beihua Kong
Summary: This study reveals the important role of TTK in high-grade serous ovarian cancer (HGSOC) and suggests that TTK inhibitors in combination with cisplatin may lead to improved therapeutic responses in patients with HGSOC presenting high TTK expression.
CELL DEATH & DISEASE
(2021)
Article
Pathology
Geetika Suyal, Prerna Pandey, Anoop Saraya, Rinu Sharma
Summary: The research revealed that miR-335-5p plays a tumor suppressive role in esophageal cancer by inhibiting cell proliferation, migration, and invasion. Through RNA-seq and Insilico analysis, TTK was identified as a newly discovered direct target of miR-335-5p, providing insights into its potential role in esophageal tumorigenesis.
EXPERIMENTAL AND MOLECULAR PATHOLOGY
(2022)
Article
Microbiology
Stuart Cannon, William Kay, Sreedhar Kilaru, Martin Schuster, Sarah Jane Gurr, Gero Steinberg
Summary: Global banana production is facing challenges from Panama disease, but there are currently no effective fungicide-based strategies to control it. Research found that the pathogen causing Panama disease, FocTR4, has innate resistance to all single-site fungicides but little resistance to multi-site fungicides. Only a few fungicides have been shown to effectively suppress the disease in soil-grown bananas.
Article
Oncology
Jian Yu, Ge Gao, Xiangpin Wei, Yang Wang
Summary: This study revealed that TTK protein kinase promotes TMZ resistance in GBM cells by inducing autophagy both in vitro and in vivo. TTK inhibitors significantly inhibited GBM cell proliferation and enhanced the growth-suppressive effect of TMZ. Furthermore, blocking TTK could suppress the autophagy process in GBM cells.
Review
Chemistry, Multidisciplinary
Kristen A. Munoz, Paul J. Hergenrother
Summary: It has been over 50 years since the FDA approved a new class of antibiotics targeting problematic Gram-negative bacteria, with the main challenge being the inability of most small molecules to penetrate the gram-negative membrane and accumulate in the cell. A successful strategy has been developed to enhance the accumulation of Gram-positive antibiotics, resulting in broad-spectrum activity.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Zhao Wang, Waleed A. Zalloum, Wenbo Wang, Xiangyi Jiang, Erik De Clercq, Christophe Pannecouque, Dongwei Kang, Peng Zhan, Xinyong Liu
Summary: Compound 20a, designed based on structural biology information, shows remarkable antiviral activity against HIV-1, low toxicity, high safety index, improved solubility, and promising drug-like properties. It has the potential to be a valuable drug candidate.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Zachariah P. Schuurs, John P. McDonald, Laura V. Croft, Derek J. Richard, Roger Woodgate, Neha S. Gandhi
Summary: This study focuses on the issue of antibiotic resistance and explores the structure and function of LexA protein to find small molecule inhibitors that can inhibit its degradation. The research reveals that a specific covalent inhibitor can react with the Ser-119 residue in LexA protein, thus inhibiting the SOS response. This study provides a starting point for future research on preventing antibiotic resistance.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Zepeng Xu, Xinrui Kang, Pu Han, Pei Du, Linjie Li, Anqi Zheng, Chuxia Deng, Jianxun Qi, Xin Zhao, Qihui Wang, Kefang Liu, George Fu Gao
Summary: This study reveals the binding mechanism between equine ACE2 and SARS-CoV-2 and related coronaviruses, highlighting the importance of continuous surveillance on these viruses and their potential spillover events. Horses are identified as potential targets for SARS-CoV-2.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Maria Gabriella Chiariello, Mercedes Alfonso-Prieto, Emiliano Ippoliti, Christoph Fahlke, Paolo Carloni
Summary: The research demonstrates how glutamate E318 in CLCF-eca binds to F-, facilitating the release of H+ as HF to the cytosol and achieving a net 1:1 F-/H+ stoichiometry.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Review
Medicine, Research & Experimental
Nasreddine El Omari, Learn-Han Lee, Saad Bakrim, Hafiz A. Makeen, Hassan A. Alhazmi, Syam Mohan, Asaad Khalid, Long Chiau Ming, Abdelhakim Bouyahya
Summary: Romidepsin, a natural molecule produced by Chromobacterium violaceum bacterium, has been approved for its anti-cancer effect. It is a selective histone deacetylase (HDAC) inhibitor that modifies histones and epigenetic pathways. This review aims to highlight the specific molecular mechanisms responsible for HDAC inhibition by romidepsin, which can significantly improve the understanding of cancer cell disorders and pave the way for new therapeutic approaches using targeted therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Reproductive Biology
Yixuan Liu, Keyu Zhu, Xiaolin Guan, Suhong Xie, Yanchun Wang, Ying Tong, Lin Guo, Hui Zheng, Renquan Lu
Summary: TTK is up-regulated in cisplatin-resistant ovarian cancer, and down-regulation of TTK can restore sensitivity to cisplatin, with the PI3K/AKT signaling pathway affected by TTK expression.
JOURNAL OF OVARIAN RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Lauren Pugh, Alisha Pancholi, Priscila Celeste Purat, Sandra Agudo-Alvarez, Raul Benito-Arenas, Agatha Bastida, Victor M. Bolanos-Garcia
Summary: This study investigated the interaction dynamics between human Mps1 kinase and isoflavones using computational biology approach and compared it with the crystal structure of Mps1 in complex with reversine. The findings suggest that isoflavones can serve as a chemical scaffold for developing new Mps1 inhibitors for cancer treatment associated with Mps1 amplification and aberrant chromosome segregation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anna G. Manjon, Simon Linder, Hans Teunissen, Anoek Friskes, Wilbert Zwart, Elzo de Wit, Rene H. Medema
Summary: CRISPR has revolutionized molecular biology as a genome editing tool. However, lentiviral-based sgRNA vectors may integrate into the endogenous genomic target location, leading to undesired activation of the target gene and potential drug resistance. Further research is needed to understand and address this unreported CRISPR/Cas9 on-target effect.
Article
Oncology
Lea Volmer, Andre Koch, Sabine Matovina, Dominik Dannehl, Martin Weiss, Ganna Welker, Markus Hahn, Tobias Engler, Markus Wallwiener, Christina Barbara Walter, Ernst Oberlechner, Sara Yvonne Brucker, Klaus Pantel, Andreas Hartkopf
Summary: This study found that disseminated tumor cells (DTCs) in the bone marrow are an indicator of minimal residual disease and micrometastatic spread in breast cancer patients and can be detected at early stages of the disease. Neoadjuvant chemotherapy may promote the spread of DTCs and lead to poorer outcomes. The study also found that DTC-positive patients with >= 2 DTCs per 1.5 x 10(6) mononuclear cells in the bone marrow had impaired disease-free survival and overall survival.
Article
Biochemistry & Molecular Biology
Mary E. Carter, Andreas D. Hartkopf, Anna Wagner, Lea L. Volmer, Sara Y. Brucker, Susanne Berchtold, Ulrich M. Lauer, Andre Koch
Summary: This study developed a protocol to evaluate the effects of two different types of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue. The greatest oncolytic effects were observed when the oncolytic viruses were engineered to express a suicide gene.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Mila Ilic, Irene C. Zaalberg, Jonne A. Raaijmakers, Rene H. Medema
Summary: Advances in genome sequencing have revealed the presence of double minutes, a type of extrachromosomal DNA, in various types of cancer. These circular DNA molecules contain amplified oncogenes or drug resistance genes and contribute to tumor aggressiveness. Unequal distribution of double minutes increases intratumoral heterogeneity. This review discusses the generation, maintenance, evolution, and potential mechanisms of elimination of double minutes.
Article
Cell Biology
Sara Y. Brucker, Thomas Hentrich, Julia M. Schulze-Hentrich, Martin Pietzsch, Noel Wajngarten, Anjali Ralhan Singh, Katharina Rall, Andre Koch
Summary: MRKH syndrome is a condition characterized by the underdevelopment of the uterus and upper part of the vagina in females with normal ovarian function. The cause of the disease is still unknown and current research has been focused on DNA sequencing efforts. However, the development of long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients has provided insights into potential disease-causing pathways and treatment opportunities.
DISEASE MODELS & MECHANISMS
(2022)
Correction
Oncology
Maud Kamal, Sonia Lameiras, Marc Deloger, Adeline Morel, Sophie Vacher, Charlotte Lecerf, Celia Dupain, Emmanuelle Jeannot, Elodie Girard, Sylvain Baulande, Coraline Dubot, Gemma Kenter, Ekaterina Jordanova, Els M. J. J. Berns, Guillaume Bataillon, Marina Popovic, Roman Rouzier, Wulfran Cacheux, Christophe Le Tourneau, Alain Nicolas, Nicolas Servant, Suzy Scholl, Ivan Bieche, RAIDs Consortium
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Claire Vennin, Chiara M. Cattaneo, Leontien Bosch, Serena Vegna, Xuhui Ma, Hugo G. J. Damstra, Moreno Martinovic, Efi Tsouri, Mila Ilic, Leyla Azarang, Jan R. T. van Weering, Emilia Pulver, Amber L. Zeeman, Tim Schelfhorst, Jeroen O. Lohuis, Anne C. Rios, Johanna F. Dekkers, Leila Akkari, Renee Menezes, Rene Medema, Serena R. Baglio, Anna Akhmanova, Sabine C. Linn, Simone Lemeer, Dirk M. Pegtel, Emile E. Voest, Jacco van Rheenen
Summary: Although treatment with taxanes may not always be effective, it carries the risk of side effects like peripheral neuropathy. A study found that taxanes can directly stimulate T cells to selectively kill cancer cells, independent of the T cell receptor. This mechanism involves the release of cytotoxic extracellular vesicles by T cells, inducing apoptosis specifically in tumor cells. These findings were utilized to develop a therapeutic approach using pre-treated T cells, avoiding systemic toxicity.
Article
Oncology
Lisa Koob, Anoek Friskes, Louise van Bergen, Femke M. Feringa, Bram van den Broek, Emma S. Koeleman, Ellis van Beek, Michael Schubert, Vincent A. Blomen, Thijn R. Brummelkamp, Lenno Krenning, Rene H. Medema
Summary: This study demonstrates that the meiotic recombination co-factor MND1 plays a role in the repair of DNA double-strand breaks (DSBs) in somatic cells. MND1 localizes to DSBs and stimulates DNA repair through homologous recombination (HR). Importantly, MND1 specifically functions in the repair response to two-ended DSBs induced by irradiation (IR) or chemotherapeutic drugs, and its activity is primarily observed in the G2 phase.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gyuntae Bae, Georgy Berezhnoy, Andre Koch, Claire Cannet, Hartmut Schaefer, Stefan Kommoss, Sara Brucker, Nicolas Beziere, Christoph Trautwein
Summary: This study identified metabolic and inflammatory differences between high-grade serous ovarian cancer (HGSOC) and borderline ovarian tumor (BOT) through analysis of metabolites, lipoproteins, and inflammation parameters. These differences could serve as potential serum markers for the diagnosis and prognosis of ovarian cancer in the future.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Polina Kaidun, Samuel J. Holzmayer, Sarah M. Greiner, Anna Seller, Christian M. Tegeler, Ilona Hagelstein, Jonas Mauermann, Tobias Engler, Andre Koch, Andreas D. Hartkopf, Helmut R. Salih, Melanie Maerklin
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options. The development of bispecific fusion proteins (BFPs) targeting NKG2DLs has shown promising results in activating NK and T cells against TNBC cells, leading to efficient eradication of tumors. This approach could be a valuable addition to the current treatment options for TNBC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Nicole Anderle, Felix Schaefer-Ruoff, Annette Staebler, Nicolas Kersten, Andre Koch, Cansu Oender, Anna-Lena Keller, Simone Liebscher, Andreas Hartkopf, Markus Hahn, Markus Templin, Sara Y. Brucker, Katja Schenke-Layland, Christian Schmees
Summary: Despite progress in deciphering breast cancer at the genomic level, the heterogeneity remains an obstacle to effective treatment. Patient-derived tumor models reflect individual tumors and allow comprehensive analyses of vulnerabilities. 3D microtumors (BC-PDMs) generated from breast cancer patients may provide valuable insights for personalized treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Anna G. Manjon, Stefano Giustino Manzo, Stefan Prekovic, Leon Potgeter, Tom van Schaik, Ning Qing Liu, Koen Flach, Daniel Peric-Hupkes, Stacey Joosten, Hans Teunissen, Anoek Friskes, Mila Ilic, Dorine Hintzen, Vinicius H. Franceschini-Santos, Wilbert Zwart, Elzo de Wit, Bas van Steensel, Rene H. Medema
Summary: Acquired drug resistance is a major problem in cancer treatment. The study reveals that dissociation of the nuclear lamina can lead to derepression of the ABCB1 gene, resulting in drug resistance. This finding suggests that disruption of 3D genome topology plays an important role in tumor evolution and the acquisition of drug resistance.
Article
Oncology
Cansu E. Oender, Teresa J. Ziegler, Ronja Becker, Sara Y. Brucker, Andreas D. Hartkopf, Tobias Engler, Andre Koch
Summary: The development of ascites and pleural effusion in metastasized breast cancer often leads to disability and poor outcomes. Malignant cells in these fluids indicate cancer spreading and can be used as a model for metastatic breast cancer. In this study, we cultured metastatic cells from patients with ascites or pleural effusion in a three-dimensional manner to obtain organoids. The organoids showed characteristics similar to metastatic samples and were used for personalized drug assays. These metastatic organoids provide an accurate model for studying breast cancer progression and predicting therapy outcomes.
Article
Genetics & Heredity
Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M. Grochowski, Ruizhi Duan, Jawid M. Fatih, Moez Dawood, Sejal Salvi, Shalini N. Jhangiani, Donna M. Muzny, Andre Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A. Wise, Jennifer E. Dietrich, Ignatia B. Van den Veyver, Antigone S. Dimas, Sara Brucker, V. Reid Sutton, Richard A. Gibbs, Stylianos E. Antonarakis, Na Wu, Zeynep H. Coban-Akdemir, Lan Zhu, Jennifer E. Posey, James R. Lupski
Summary: MRKH syndrome is a condition characterized by underdeveloped female reproductive tract, along with renal and skeletal anomalies. This study identified 18 novel GREB1L gene variants, strengthening the association between GREB1L and MRKH.
HUMAN GENETICS AND GENOMICS ADVANCES
(2023)
Article
Genetics & Heredity
Marit A. E. van Bueren, Aniek Janssen
Summary: Eukaryotic nuclei rely on multiple repair pathways to accurately repair DNA damage, particularly in chromatin domains enriched for repetitive DNA sequences. Tailored repair mechanisms are necessary to maintain genome stability in these domains.