Article
Oncology
Andrew J. Massey
Summary: The study revealed that treatment with the Chk1 inhibitor led to a significant upregulation of BCL2A1 in U2OS cells, but not in HT29 cells.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Vladimir Baran, Alexandra Mayer
Summary: After fertilization, the remodeling of the oocyte and sperm genome is crucial for the successful initiation of mitotic activity in the fertilized oocyte and subsequent proliferation of the early embryo. The specific nature of gene totipotency in early cleavage embryos leads to differences in cell cycle control mechanisms compared to somatic cells. This review focuses on the Chk1 kinase as an important factor in monitoring DNA integrity during early embryogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Tom Egger, Benoit Bordignon, Arnaud Coquelle
Summary: Colorectal cancer is a common malignancy and its therapy often causes replication stress. The ATR-CHK1 pathway is responsible for managing this stress, and mutations in the ATR gene can increase sensitivity to drugs and enhance their synergy. These mutations lead to DNA damage, but targeting RPA and DNA-PK can optimize inhibition of the ATR-CHK1 pathway.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Xiaomei Zhu, Qunshu Su, Haiyuan Xie, Lizhi Song, Fan Yang, Dandan Zhang, Binghong Wang, Shixian Lin, Jun Huang, Mengjie Wu, Ting Liu
Summary: The cell-cycle checkpoint kinase WEE1 is a potential therapeutic target for cancer treatment, but the regulation of its catalytic activity and the identification of reliable biomarkers for predicting response to WEE1 inhibitor remain unclear. This study identifies a conserved segment surrounding its Lys177 residue that inhibits WEE1 activity through an interaction with the catalytic kinase domain. Phosphorylation and acetylation modifications of WEE1 regulate its activation status, and the expression level of SIRT1 and WEE1 Lys177 acetylation in tumor cells could serve as useful biomarkers for predicting WEE1 inhibitor sensitivity or resistance.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Oncology
Fiifi Neizer-Ashun, Resham Bhattacharya
Summary: The DNA damage response relies on CHK1 kinase for maintaining genomic integrity, involving in processes such as DNA replication and mitotic progression. While CHK1 has potential in cancer therapy, it has yet to be fully realized clinically.
Review
Oncology
Federica Martorana, Leandro Apolinario Da Silva, Cristiana Sessa, Ilaria Colombo
Summary: DNA damage leads to genome instability and increases cancer susceptibility. Targeted drugs against DNA repair, such as PARP inhibitors, have shown efficacy in various tumor types but also come with potential toxicities. Therefore, it is crucial to identify and manage adverse events of these drugs, especially in combination therapies.
Article
Multidisciplinary Sciences
Junjun Wang, Xiaofei Tian, Chuanlin Feng, Chao Song, Biao Yu, Ying Wang, Xinmiao Ji, Xin Zhang
Summary: KimH3 is a kinase that can phosphorylate H3Ser10 in both interphase and mitosis, and it is upregulated in various human cancers. Its high expression is associated with reduced median survival time in cancer patients. CDK1 phosphorylates KimH3 in mitosis, while EGF activates it in interphase, and both processes regulate the phosphorylation of H3Ser10.
Review
Biochemistry & Molecular Biology
David A. Gillespie
Summary: Two recent reports demonstrate that heritable, gain-of-function mutations within the Chk1 C-terminal regulatory domain can cause female infertility. Treatment with selective Chk1 inhibitor drugs can rescue this mutation and allow embryos to develop normally.
Article
Genetics & Heredity
Teresa Brooks, Joanne Wayne, Andrew J. Massey
Summary: Chk1 inhibitors have significant biological effects on cancer cells, inducing a bystander effect that increases DNA damage or replication stress in cells not directly exposed to the inhibitor. However, this bystander effect may also contribute to toxicity in non-tumor cells by increasing DNA damage.
Article
Medicine, Research & Experimental
Minhao Yu, Hao Wang, Wei Zhao, Xiaoxiao Ge, Wei Huang, Fengjuan Lin, Wenbo Tang, Ang Li, Sailiang Liu, Rong-Kun Li, Shu-Heng Jiang, Junli Xue
Summary: This study reveals the significant role of PIPKI?? in oxaliplatin resistance and provides a key mechanism of exosomal PD-L1 in colorectal cancer with potential therapeutic implications.
Article
Medicine, Research & Experimental
Le Zhang, Matthias Wirth, Upayan Patra, Jacob Stroh, Konstandina Isaakidis, Leonie Rieger, Susanne Kossatz, Maja Milanovic, Chuanbing Zang, Uta Demel, Jan Keiten-Schmitz, Kristina Wagner, Katja Steiger, Roland Rad, Florian Bassermann, Stefan Mueller, Ulrich Keller, Markus Schick
Summary: The DNA damage response (DDR) acts as a barrier to malignant transformation and is often impaired during tumorigenesis. We identified SLF2 as a regulator of the DDR and a biomarker for adverse prognosis in B-cell lymphoma (BCL) patients. SLF2 deficiency leads to loss of DDR factors and impairs CHK1 activation, and its genetic deletion drives lymphomagenesis in vivo. Tumor cells lacking SLF2 have high DNA damage levels and alterations in the post-translational SUMOylation pathway, making them sensitive to a clinically applicable SUMOylation inhibitor (SUMOi) and synergistic with DDR pathway inhibitors.
EMBO MOLECULAR MEDICINE
(2023)
Review
Oncology
Congqi Shi, Kaiyu Qin, Anqi Lin, Aimin Jiang, Quan Cheng, Zaoqu Liu, Jian Zhang, Peng Luo
Summary: This study summarizes currently identified and promising biomarkers for predicting the response of oncology patients to immune checkpoint inhibitors, and explores the mechanism of combination therapy with immune checkpoint inhibitors and DNA damage repair inhibitors.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Cell Biology
Luisa Maresca, Barbara Stecca, Laura Carrassa
Summary: Targeted therapies and immunotherapies have shown clinical benefits in melanoma patients, but resistance and relapse are common. This review discusses the potential of exploiting DNA damage response (DDR) as a therapeutic approach in melanoma. The use of DDR inhibitors, both as single agents and in combination with other therapies, shows promise in preclinical studies and ongoing clinical trials.
Article
Multidisciplinary Sciences
Devashish Dwivedi, Daniela Harry, Patrick Meraldi
Summary: This study reveals that mild replication stress leads to premature centriole disengagement while delaying mitotic onset. This is caused by sub-critical Plk1 kinase activity, enabling centrosome cycling but impeding rapid mitotic entry.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Alexandros Georgiou, Adam Stewart, Georgios Vlachogiannis, Lisa Pickard, Nicola Valeri, David Cunningham, Steven R. Whittaker, Udai Banerji
Summary: This study found that activation of the PI3K pathway is a potential mechanism of cetuximab resistance in KRAS/NRAS/BRAF(V600) wild-type CRC. The results suggest that the combination of PI3K pathway inhibitors with cetuximab can significantly reduce colony formation capacity in resistant cell lines.
Article
Gastroenterology & Hepatology
Laura Rosa Mangiapane, Annalisa Nicotra, Alice Turdo, Miriam Gaggianesi, Paola Bianca, Simone Di Franco, Davide Stefano Sardina, Veronica Veschi, Michele Signore, Sven Beyes, Luca Fagnocchi, Micol Eleonora Fiori, Maria Rita Bongiorno, Melania Lo Iacono, Irene Pillitteri, Gloria Ganduscio, Gaspare Gulotta, Jan Paul Medema, Alessio Zippo, Matilde Todaro, Ruggero De Maria, Giorgio Stassi
Summary: In colorectal cancer stem cells, high HER2 expression levels are associated with activation of the PI3K/AKT pathway. The targeting of HER2 in combination with PI3K and MEK inhibitors induces CR-CSC death and regression of tumor xenografts, including those with specific mutations. Triple targeting of PI3K, HER2, and MEK is necessary to overcome resistance to anti-EGFR therapies.
Article
Oncology
Livia Ronchetti, Irene Terrenato, Margherita Ferretti, Giacomo Corrado, Frauke Goeman, Sara Donzelli, Chiara Mandoj, Roberta Merola, Ashanti Zampa, Mariantonia Carosi, Giovanni Blandino, Laura Conti, Anna Maria Lobascio, Marcello Iacobelli, Enrico Vizza, Giulia Piaggio, Aymone Gurtner
Summary: The study demonstrated the presence of NETosis features in tissues from all EC grades. Serum levels of cfDNA and cfmtDNA were found to differentiate between ECs and HSs, with direct correlation between citH3 and cfDNA content, and inverse correlation between cfmtDNA and citH3 in EC sera. MCA indicated associations of cfDNA, cfmtDNA, and citH3 with G1 and G2 grades, as well as correlations between increased levels of cfDNA, citH3, and inflammation features. Serum nucleosomal cfDNA fragmentation pattern varied in EC sera and correlated with higher levels of cfDNA, citH3, lymphocytes, and fibrinogen.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Maria Laura De Angelis, Federica Francescangeli, Chiara Nicolazzo, Michele Signore, Alessandro Giuliani, Lidia Colace, Alessandra Boe, Valentina Magri, Marta Baiocchi, Antonio Ciardi, Francesco Scarola, Massimo Spada, Filippo La Torre, Paola Gazzaniga, Mauro Biffoni, Ruggero De Maria, Ann Zeuner
Summary: This study successfully isolated CTCs from a colorectal cancer xenograft model and investigated their biological features and drug sensitivity through organoid generation. The results showed that CTC-derived organoids exhibited a hybrid epithelial-mesenchymal transition state and increased expression of stemness-associated markers. Additionally, CTC-derived organoids were more sensitive to drugs affecting the Survivin pathway. These findings contribute to a better understanding and prevention of colorectal cancer metastasis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Polymer Science
Cristina De Monte, Marina Locritani, Silvia Merlino, Lucia Ricci, Agnese Pistolesi, Simona Bronco
Summary: This paper presents two novel experimental setups for in situ long-term monitoring of the aging behavior of commercial plastic granules in marine environments. The effects of environmental conditions on the physical-chemical modifications of the granules were studied through chemical spectroscopic and thermal analyses before and after exposure to seawater and sandy coastal conditions for six months.
Article
Oncology
Giorgia Castellani, Mariachiara Buccarelli, Valentina Lulli, Ramona Ilari, Gabriele De Luca, Francesca Pedini, Alessandra Boe, Nadia Felli, Mauro Biffoni, Emanuela Pilozzi, Giovanna Marziali, Lucia Ricci-Vitiani
Summary: MiR-378a-3p plays a critical role in CRC carcinogenesis as a tumor suppressor by establishing a finely tuned crosstalk with lncRNAs MALAT1 and NEAT1, restraining tumorigenic properties of CRC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sveva Grande, Alessandra Palma, Anna Maria Luciani, Pasqualino Anello, Lucia Ricci-Vitiani, Mariachiara Buccarelli, Quintino Giorgio D'Alessandris, Roberto Pallini, Laura Guidoni, Vincenza Viti, Antonella Rosi
Summary: Glioblastoma stem cells (GSCs) play a crucial role in promoting tumor heterogeneity and therapy resistance in glioblastoma. This study used magnetic resonance spectroscopy (MRS) to analyze the lipid unsaturation behavior of GSCs in response to different treatments. The results showed metabolic heterogeneity among GSCs, but also revealed unusual robustness of unsaturation levels in certain cell lines after stressful treatments.
Article
Immunology
Martina Musella, Andrea Guarracino, Nicoletta Manduca, Claudia Galassi, Eliana Ruggiero, Alessia Potenza, Ester Maccafeo, Gwenola Manic, Luca Mattiello, Sara Soliman Abdel Rehim, Michele Signore, Marco Pietrosanto, Manuela Helmer-Citterich, Matteo Pallocca, Maurizio Fanciulli, Tiziana Bruno, Francesca De Nicola, Giacomo Corleone, Anna Di Benedetto, Cristiana Ercolani, Edoardo Pescarmona, Laura Pizzuti, Francesco Guidi, Francesca Sperati, Sara Vitale, Daniele Macchia, Massimo Spada, Giovanna Schiavoni, Fabrizio Mattei, Adele De Ninno, Luca Businaro, Valeria Lucarini, Laura Bracci, Eleonora Arico, Giovanna Ziccheddu, Francesco Facchiano, Stefania Rossi, Massimo Sanchez, Alessandra Boe, Mauro Biffoni, Ruggero De Maria, Ilio Vitale, Antonella Sistigu
Summary: The study demonstrates that type I interferons can promote the formation of cancer stem cells by upregulating the chromatin remodeling factor KDM1B. Inhibition of KDM1B could potentially prevent stem cell expansion and increase the long-term benefit of therapy.
Article
Cell Biology
Giorgia Pedini, Mariachiara Buccarelli, Fabrizio Bianchi, Laura Pacini, Giulia Cencelli, Quintino Giorgio D'Alessandris, Maurizio Martini, Stefano Giannetti, Franceschina Sasso, Valentina Melocchi, Maria Giulia Farace, Tilmann Achsel, Luigi M. Larocca, Lucia Ricci-Vitiani, Roberto Pallini, Claudia Bagni
Summary: Converging evidence suggests that FMRP, which is absent or mutated in Fragile X Syndrome, plays a role in various types of cancers. This study demonstrates that increased expression of FMRP is correlated with worse prognosis in human glioblastoma patients. Additionally, reductions in FMRP lead to decreased tumor growth and proliferation of glioblastoma stem-like cells. The study also reveals that FMRP regulates GSC proliferation through the WNT signaling pathway.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Tommaso Ceruti, Quintino Giorgio D'Alessandris, Roberta Frapolli, Jay Gopalakrishnan, Mariachiara Buccarelli, Marina Meroni, Liverana Lauretti, Lucia Ricci-Vitiani, Roberto Pallini, Massimo Zucchetti
Summary: In this study, the pharmacokinetic profile of Nifuroxazide (NAZ) in mice was investigated using a newly developed high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. The study found that NAZ has the ability to cross the injured blood-brain barrier and reaches systemic levels suitable for testing its efficacy in preclinical models of glioblastoma. These findings provide robust evidence supporting the repositioning of NAZ as an antitumor drug.
Article
Biochemistry & Molecular Biology
Valentina Dini, Giuseppe Esposito, Andrea Sacconi, Marco D'Andrea, Maria Antonella Tabocchini, Pasquale Anello, Lucia Ricci-Vitiani, Mariachiara Buccarelli, Roberto Pallini, Lidia Strigari
Summary: Literature data on the administration of conventional high-dose beams show conflicting results on biological effects at the cellular level. To contribute to this field, the authors irradiated different cell lines using a clinical accelerator with and without flattening filters and studied cell survival, DNA damage induction, and gene expression. The results showed no significant differences in cell survival based on dose rates and type of beams, but a trend of reduction in late survival was observed at the highest dose rate with the FFF beam. Gene expression analysis of the two cell lines indicated gene signatures resembling the prognosis of glioblastoma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Valeria Coppola, Ilaria Marino, Uwe Warnken, Mario Falchi, Luca Pasquini, Mauro Biffoni, Ruggero De Maria, Tobias Longin Haas
Summary: We have identified FYCO1 as a protein that promotes the transport of autophagic and endosomal vesicles. It interacts with activated CASP8 and its loss leads to increased sensitivity of cells to apoptosis and impaired transport of TNFRSF10B/TRAIL-R2/DR5.
Article
Chemistry, Medicinal
Pegi Pavletic, Ana Semeano, Hideaki Yano, Alessandro Bonifazi, Gianfabio Giorgioni, Alessandro Piergentili, Wilma Quaglia, Maria Giovanna Sabbieti, Dimitrios Agas, Giorgio Santoni, Roberto Pallini, Lucia Ricci-Vitiani, Emanuela Sabato, Giulio Vistoli, Fabio Del Bello
Summary: In this paper, new ligands with high affinity and selectivity for D4R were discovered to better understand its role in GBM. The D4R antagonist 24 and biased ligand 29 showed the most potential and induced a decreased viability of GBM cells. Interestingly, these compounds had a greater effect in reducing cell viability compared to temozolomide, the first-choice chemotherapeutic drug in GBM.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
