Article
Biotechnology & Applied Microbiology
Martina Fiumara, Samuele Ferrari, Attya Omer-Javed, Stefano Beretta, Luisa Albano, Daniele Canarutto, Angelica Varesi, Chiara Gaddoni, Chiara Brombin, Federica Cugnata, Erika Zonari, Matteo Maria Naldini, Matteo Barcella, Bernhard Gentner, Ivan Merelli, Luigi Naldini
Summary: Base and prime editors have shown potential for precise genetic engineering, but their cellular responses and genotoxicity are not well understood. This study compared the efficiency, toxicity, and genotoxicity between base and prime editors and Cas9 in human hematopoietic cells. The findings suggest that these editors can induce harmful effects and genotoxicity, raising concerns for their clinical applications.
NATURE BIOTECHNOLOGY
(2023)
Article
Environmental Sciences
Ghada Tagorti, Bulent Kaya
Summary: This review further explores the genotoxic potential of microplastics, particularly their impact on aquatic organisms and human cells, revealing their association with reactive oxygen production, inflammatory responses, and DNA repair interference. Additionally, with lifestyle changes during the COVID-19 pandemic, the outbreak may enhance the genotoxic risk of MPs through increased human exposure and disruption of defense systems.
Article
Cell Biology
Elena Navarro-Carrasco, Pedro A. Lazo
Summary: Depletion of the chromatin kinase VRK1 using RNA interference reduces glioblastoma cell dependence on temozolomide and olaparib, promoting tumor cell death.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, General & Internal
Andrew N. J. Tutt, Judy E. Garber, Bella Kaufman, Giuseppe Viale, Debora Fumagalli, Priya Rastogi, Richard D. Gelber, Evandro de Azambuja, Anitra Fielding, Judith Balmana, Susan M. Domchek, Karen A. Gelmon, Simon J. Hollingsworth, Larissa A. Korde, Barbro Linderholm, Hanna Bandos, E. Senkus, Jennifer M. Suga, Z. Shao, Andrew W. Pippas, Zbigniew Nowecki, Tomasz Huzarski, Patricia A. Ganz, Peter C. Lucas, Nigel Baker, Sibylle Loibl, Robin McConnell, Martine Piccart, Rita Schmutzler, Guenther G. Steger, Joseph P. Costantino, Amal Arahmani, Norman Wolmark, Eleanor McFadden, Vassiliki Karantza, Sunil R. Lakhani, Greg Yothers, Christine Campbell, Charles E. Geyer
Summary: In patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than placebo. Olaparib had limited effects on global patient-reported quality of life.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Oncology
Karrie Mei-Yee Kiang, Wanjun Tang, Qingchun Song, Jiaxin Liu, Ning Li, Tsz-Lung Lam, Ho Cheung Shum, Zhiyuan Zhu, Gilberto Ka-Kit Leung
Summary: This study investigates the therapeutic potential of targeting PDI to overcome chemoresistance. The inhibition of PDI significantly enhances the cytotoxic effect of TMZ on glioblastoma cells and sensitizes previously resistant cells. The nanoformulation of CCF642 loaded in albumin effectively suppresses tumor growth and induces cell death-triggering ER perturbations. Combination treatment of TMZ with CCF642 reduces tumor growth compared to monotherapy.
BRITISH JOURNAL OF CANCER
(2023)
Review
Genetics & Heredity
Ritesh K. Shukla, Ashish Badiye, Kamayani Vajpayee, Neeti Kapoor
Summary: The rapid development of nanotechnology has led to enhanced production of nanoparticles, which poses potential threats to human health. Interaction between nanoparticles and DNA can result in structural and functional modifications, impacting the cellular system negatively.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Yuli Thamires Magalhaes, Fabio Luis Forti
Summary: Resistance to radio and chemotherapy in Glioblastoma is correlated with its malignancy, invasiveness, and aggressiveness. The involvement of the Rho GTPase pathway in GBM response to genotoxic treatments remains unresolved. Inhibition of this pathway using ROCK inhibitors shows potential in CNS therapies and may improve the efficiency of antitumor treatments based on ROCK inhibitors.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)
Article
Oncology
Maxime Cahuzac, Benjamin Peant, Anne-Marie Mes-Masson, Fred Saad
Summary: This study established new models of resistance in prostate cancer cells and identified potential targets, such as DNA repair, autophagy, and ROCK2, to reverse acquired olaparib-resistance.
Article
Multidisciplinary Sciences
Jeremy Sandoz, Max Cigrang, Amelie Zachayus, Philippe Catez, Lise-Marie Donnio, Clemence Elly, Jadwiga Nieminuszczy, Pietro Berico, Cathy Braun, Sergey Alekseev, Jean-Marc Egly, Wojciech Niedzwiedz, Giuseppina Giglia-Mari, Emmanuel Compe, Frederic Coin
Summary: The exonuclease EXD2 plays a role in the recovery of class II gene transcription after UV irradiation. It moves from mitochondria to the nucleus where it interacts with RNA Pol II and degrades newly synthesized mRNA, allowing transcription to resume after DNA repair. Lack of EXD2 impairs mRNA synthesis recovery and reduces cell survival after UV irradiation, but does not affect DNA repair. Overexpression of wild-type EXD2 restores mRNA synthesis recovery and cell survival. EXD2 is relocated from mitochondria to the nucleus upon UV irradiation, where it interacts transiently with chromatin-bound RNA Pol II to promote the degradation of nascent mRNAs. In vitro experiments show that EXD2 primarily interacts with elongation-blocked RNA Pol II and efficiently degrades mRNA. Overall, this study highlights the crucial role of EXD2 in the transcriptional response to genotoxic attack, where it interacts with elongation-stalled RNA Pol II on chromatin to potentially degrade the associated nascent mRNA, allowing transcription restart after DNA repair.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
C. Fritsch, J-F Gout, S. Haroon, A. Towheed, C. Chung, J. LaGosh, E. McGann, X. Zhang, Y. Song, S. Simpson, P. S. Danthi, B. A. Benayoun, D. Wallace, K. Thomas, M. Lynch, M. Vermulst
Summary: Research shows that mutagenic compounds not only cause genetic mutations, but are also a powerful source of transcription errors. These errors occur in both dividing and nondividing cells, and sometimes greatly exceed the number of mutations in the genome. Additionally, DNA repair is crucial in mitigating transcriptional mutagenesis after exposure to mutagens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Environmental Sciences
Ivana Durovcova, Stanislav Kyzek, Jana Fabova, Jana Makukova, Eliska Galova, Andrea Sevcovicova
Summary: This review aims to summarize the genotoxic effects of BPA on organisms across all taxa. BPA can induce DNA damage through multiple mechanisms and has adverse effects on organisms in various ecosystems.
ENVIRONMENTAL POLLUTION
(2022)
Article
Biology
Maxime Cahuzac, Patricia Langlois, Benjamin Peant, Hubert Fleury, Anne-Marie Mes-Masson, Fred Saad
Summary: Autophagy has a differential effect on the response of prostate cancer (PC) cell lines to olaparib, with pre-activation leading to resistance and post-treatment activation or inhibition increasing sensitivity. The resistance mechanism involves SQSTM1/p62 nuclear localization, filamin A expression, and BRCA1/Rad51 recruitment in the homologous recombination (HR) pathway.
COMMUNICATIONS BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Shi-Qi Wu, Shi-Hui Huang, Qian-Wen Lin, Yi-Xuan Tang, Lei Huang, Yun-Gen Xu, Shu-Ping Wang
Summary: Inducing HR deficiency is a promising strategy for expanding the indication of PARP1/2 inhibitors in pancreatic cancer treatment. In this study, the FOXM1 inhibitor FDI-6 and PARP1/2 inhibitor Olaparib showed synergy in inhibiting malignant growth of pancreatic cancer cells in vitro and in vivo. The mechanism involves repression of gene expression related to cell cycle progression and DNA damage repair.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Maria Ines Costa, Beatriz Santos Lapa, Joana Jorge, Raquel Alves, Isabel Marques Carreira, Ana Bela Sarmento-Ribeiro, Ana Cristina Goncalves
Summary: Zinc plays a dual role in modulating the DNA damage response in acute myeloid leukemia (AML), increasing genotoxicity and cytotoxicity in leukemia cells while preventing damage accumulation in normal cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Somayeh Shahmoradi Ghahe, Konrad Kosicki, Maria Wojewodzka, Bartosz A. Majchrzak, Anna Fogtman, Roksana Iwanicka-Nowicka, Agata Ciuba, Marta Koblowska, Marcin Kruszewski, Barbara Tudek, Elzbieta Speina
Summary: Resistance to photodynamic therapy in cancer cells may be caused by various mechanisms, including efficient repair of oxidative DNA damage and DNA breaks. Higher activity of APE1 endonuclease and increased expression and activation of DNA damage kinase ATM in the U-87 MGR cell line suggest that they are potential targets for sensitizing resistant cells to PDT.
Article
Cell & Tissue Engineering
Xiuxing Wang, Briana C. Prager, Qiulian Wu, Leo J. Y. Kim, Ryan C. Gimple, Yu Shi, Kailin Yang, Andrew R. Morton, Wenchao Zhou, Zhe Zhu, Elisabeth Anne Adanma Obara, Tyler E. Miller, Anne Song, Sisi Lai, Christopher G. Hubert, Xun Jin, Zhi Huang, Xiaoguang Fang, Deobrat Dixit, Weiwei Tao, Kui Zhai, Cong Chen, Zhen Dong, Guoxin Zhang, Stephen M. Dombrowski, Petra Hamerlik, Stephen C. Mack, Shideng Bao, Jeremy N. Rich
Article
Oncology
Mikkel Staberg, Rikke Darling Rasmussen, Signe Regner Michaelsen, Henriette Pedersen, Kamilla Ellermann Jensen, Mette Villingshoj, Jane Skjoth-Rasmussen, Jannick Brennum, Kristoffer Vitting-Seerup, Hans Skovgaard Poulsen, Petra Hamerlik
MOLECULAR ONCOLOGY
(2018)
Article
Oncology
Yi Chieh Lim, Kathleen S. Ensbey, Carolin Offenhauser, Rochelle C. J. D'souza, Jason K. Cullen, Brett W. Stringer, Hazel Quek, Zara C. Bruce, Amanda Kijas, Valentina Cianfanelli, Bijan Mahboubi, Fiona Smith, Rosalind L. Jeffree, Lisa Wiesmueeller, Adrian P. Wiegmans, Amanda Bain, Fanny J. Lombard, Tara L. Roberts, Kum Kum Khanna, Martin F. Lavin, Baek Kim, Petra Hamerlik, Terrance G. Johns, Mark J. Coster, Andrew W. Boyd, Bryan W. Day
Article
Cell Biology
Sara R. Bang-Christensen, Rasmus S. Pedersen, Marina A. Pereira, Thomas M. Clausen, Caroline Loppke, Nicolai T. Sand, Theresa D. Ahrens, Amalie M. Jorgensen, Yi Chieh Lim, Louise Goksoyr, Swati Choudhary, Tobias Gustavsson, Robert Dagil, Mads Daugaard, Adam F. Sander, Mathias H. Torp, Max Sogaard, Thor G. Theander, Olga Ostrup, Ulrik Lassen, Petra Hamerlik, Ali Salanti, Mette O. Agerbaek
Article
Biochemistry & Molecular Biology
Henriette Pedersen, Elisabeth Anne Adanma Obara, Kirstine Juul Elbaek, Kristoffer Vitting-Serup, Petra Hamerlik
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Oncology
Camilla Bjornbak Holst, Ib Jarle Christensen, Jane Skjoth-Rasmussen, Petra Hamerlik, Hans Skovgaard Poulsen, Julia Sidenius Johansen
FRONTIERS IN ONCOLOGY
(2020)
Review
Oncology
Casper Hempel, Kasper B. Johnsen, Serhii Kostrikov, Petra Hamerlik, Thomas L. Andresen
CANCER AND METASTASIS REVIEWS
(2020)
Article
Clinical Neurology
M. Marku, B. K. Rasmussen, S. O. Dalton, C. Johansen, P. Hamerlik, K. K. Andersen, S. M. Meier, P. E. Bidstrup
Summary: Individuals with neurological diseases and mental disorders have an increased risk of developing primary brain tumors up to 10 years before diagnosis. Specific conditions such as inflammatory neurological diseases, epilepsy, and use of antiepileptic medications were associated with higher odds of primary brain tumors, while antidementia medications had a protective effect. Further research is needed to uncover potential shared pathogenic pathways among these conditions.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Oncology
Dorte S. Noroxe, Christina W. Yde, Olga Ostrup, Signe R. Michaelsen, Ane Y. Schmidt, Savvas Kinalis, Mathias H. Torp, Jane Skjoth-Rasmussen, Jannick Brennum, Petra Hamerlik, Hans S. Poulsen, Finn C. Nielsen, Ulrik Lassen
MOLECULAR ONCOLOGY
(2020)
Article
Multidisciplinary Sciences
Elisabeth Anne Adanma Obara, Diana Aguilar-Morante, Rikke Darling Rasmussen, Alex Frias, Kristoffer Vitting-Serup, Yi Chieh Lim, Kirstine Juul Elbaek, Henriette Pedersen, Lina Vardouli, Kamilla Ellermann Jensen, Jane Skjoth-Rasmussen, Jannick Brennum, Lucie Tuckova, Robert Strauss, Christoffel Dinant, Jiri Bartek, Petra Hamerlik
NATURE COMMUNICATIONS
(2020)
Article
Oncology
Deobrat Dixit, Briana C. Prager, Ryan C. Gimple, Hui Xian Poh, Yang Wang, Qiulian Wu, Zhixin Qiu, Reilly L. Kidwell, Leo J. Y. Kim, Qi Xie, Kristoffer Vitting-Seerup, Shruti Bhargava, Zhen Dong, Li Jiang, Zhe Zhu, Petra Hamerlik, Samie R. Jaffrey, Jing Crystal Zhao, Xiuxing Wang, Jeremy N. Rich
Summary: Research reveals that m6A mRNA modifications are upregulated in glioblastoma stem cells, with the key m6A reader YTHDF2 stabilizing important transcripts such as MYC. Targeting the YTHDF2-MYC-IGFBP3 axis could potentially be a novel therapeutic approach for glioblastoma. Epitranscriptomics have the potential to reveal specific vulnerabilities in cancer cells that can be targeted for treatment.
Review
Oncology
Henriette Pedersen, Kjeld Schmiegelow, Petra Hamerlik
Article
Biochemistry & Molecular Biology
Diana Aguilar-Morante, Daniel Gomez-Cabello, Hazel Quek, Tianqing Liu, Petra Hamerlik, Yi Chieh Lim
Summary: This article discusses the treatment challenges of adult diffuse glioma, particularly glioblastoma, and the role of DNA repair in treatment failure. Research shows that different DNA repair pathways can influence treatment response, providing potential for the use of specific inhibitors for clinical benefit.
Article
Oncology
Yi Chieh Lim, Kamilla E. Jensen, Diana Aguilar-Morante, Lina Vardouli, Kristoffer Vitting-Seerup, Ryan C. Gimple, Qiulian Wu, Henriette Pedersen, Kirstine J. Elbaek, Irina Gromova, Robert Ihnatko, Bjarne W. Kristensen, Jeanette K. Petersen, Jane Skjoth-Rasmussen, William Flavahan, Jeremy N. Rich, Petra Hamerlik
Summary: In this study, we identified PFKM as a driver of bevacizumab resistance in GBM. Cytosolic PFKM interacted with KIF11 to promote tumor invasion, while nuclear PFKM safeguarded genomic stability of tumor cells through interaction with NBS1. Based on these findings, we explored the potential of the drug bupivacaine to target PFKM and found that it enhanced the efficacy of bevacizumab in preclinical GBM models in vivo.
Article
Medicine, Research & Experimental
Guoxin Zhang, Zhen Bong, Briana C. Prager, Leo J. K. Kim, Qiulian Wu, Ryan C. Gimple, Xiuxing Wang, Shideng Bao, Petra Hamerlik, Jeremy N. Rich
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)