Article
Medicine, Research & Experimental
Damian Carvajal Ibanez, Maxim Skabkin, Jooa Hooli, Santiago Cerrizuela, Manuel Goepferich, Adrien Jolly, Katrin Volk, Marc Zumwinkel, Matilde Bertolini, Gianluca Figlia, Thomas Hoefer, Guenter Kramer, Simon Anders, Aurelio A. Teleman, Anna Marciniak-Czochra, Ana Martin-Villalba
Summary: Stem cells have intrinsic interferon signalling that protects them from viral infections. However, interferon signalling in the ageing brain reduces stem cell activation. The relationship between interferons and stem cell functioning, as well as their timing, are still unknown.
EMBO MOLECULAR MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Linhua Wei, Weiwei Chen, Linke Huang, Hui Wang, Yuangang Su, Jiamin Liang, Haoyu Lian, Jiake Xu, Jinmin Zhao, Qian Liu
Summary: This study explored the effects and mechanism of Alpinetin (Alp) on inflammatory osteolysis. The results showed that Alp suppressed the differentiation and function of osteoclasts, reduced reactive oxygen species production, and inhibited the expression of inflammatory genes. Moreover, Alp inhibited the phosphorylation of specific pathways and minimized LPS-induced osteolysis in mice.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Engineering, Biomedical
Jie Xie, Yihe Hu, Hui Li, Yinan Wang, Xiaolei Fan, Wei Lu, Runzhi Liao, Haoyi Wang, Yurui Cheng, Yute Yang, Jiahao Wang, Shuailong Liang, Tianliang Ma, Weiping Su
Summary: In this study, exosomes from urine-derived stem cells were encapsulated with macrophage membrane to achieve targeted delivery to the osteolysis zone and enhance therapeutic effectiveness. The macrophage membrane encapsulated exosomes could avoid phagocytosis by macrophages and promote cellular uptake by BMSCs.
ACTA BIOMATERIALIA
(2023)
Editorial Material
Hematology
Noemie Karabacz, Nina Cabezas-Wallscheid
Summary: In this study, Greenberg et al. demonstrate that hematopoietic stem cells (HSCs) utilize a novel mechanism involving the CD53-mediated dimerization partner, Rb-like, E2F and multi-vulval class B (DREAM) complex to revert to a quiescent state after exposure to inflammatory and proliferative stress, thus safeguarding their functional integrity.
Article
Cell Biology
Fan Yang, Eoin C. Whelan, Xuebing Guan, Bingquan Deng, Shu Wang, Jiachen Sun, Mary R. Avarbock, Xin Wu, Ralph L. Brinster
Summary: Overexpression of Fgf9 in vivo results in arrested spermatogenesis and accumulation of undifferentiated spermatogonia; exposure of germ cell cultures to FGF9 leads to increased numbers of SSCs over time; inhibition of p38 MAPK phosphorylation negates the growth advantage provided by FGF9.
CELL PROLIFERATION
(2021)
Article
Multidisciplinary Sciences
Brian DeVeale, Leqian Liu, Ryan Boileau, Jennifer Swindlehurst-Chan, Bryan Marsh, Jacob W. Freimer, Adam Abate, Robert Blelloch
Summary: This study reveals the cell cycle structure of pluripotent embryonic stem cells and the relationship between G1/S restriction point, gene expression, and cellular differentiation. By genetically manipulating G1/S restriction point regulators miR-302 and P27, the researchers found that they can accelerate or delay the onset of phasic gene expression in mouse embryos. Additionally, loss of miR-302-mediated p21 or p27 suppression expedites embryonic stem cell differentiation, while a mutated Cyclin E blocks it. These findings provide new insights into our understanding of cellular differentiation.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Xiaofan Jiang, Lu Liang, Guanglei Chen, Caigang Liu
Summary: Cancer stem cells (CSCs) and dormant cancer cells play significant roles in tumor progression and treatment, but the precise relationship between them is still unclear. Understanding how immune components interact with CSCs and dormant cancer cells is essential for preventing cancer relapse and metastasis.
Article
Biochemistry & Molecular Biology
Rosemary Lane, Chiara Cilibrasi, Jianing Chen, Kalpit Shah, Eleonora Messuti, Nektarios K. Mazarakis, Justin Stebbing, Giles Critchley, Erwei Song, Thomas Simon, Georgios Giamas
Summary: This study identifies PDGF-R alpha/beta inhibitor CP-673451 as a potential differentiation agent for GBM. In vitro experiments showed that CP-673451 promotes differentiation of GBM cells and GBM stem cells into neural-like cells, while reducing proliferation and invasion. In vivo experiments demonstrated that CP-673451 enhances the anti-tumor effects of temozolomide. Mechanistically, upregulation of phosphatase DUSP1 and downregulation of phosphorylated-p38(MAPK) may underlie the pro-differentiation effect of CP-673451 on GBM cells.
Article
Multidisciplinary Sciences
Qihong Yu, Jin-Xin Liu, Xichuan Zheng, Xueke Yan, Peng Zhao, Chuanzheng Yin, Wei Li, Zifang Song
Summary: This study reveals the significant role of Sox9 in mediating autophagy-dependent vSMC phenotypic modulation and the development of TA. Inhibition of Sox9 expression can attenuate neointimal formation, providing a potential therapeutic approach for vascular pathologies.
Article
Orthopedics
Andre Lunz, Moritz Von Falkenhayn, Sebastian Jaeger, Tobias Reiner, Christian Merle, Marcus R. Streit, Tobias Renkawitz, Moritz M. Innmann
Summary: This study aimed to determine the minimum 20-year survival rates of a cementless press-fit cup in young patients. The results showed that the 22-year survival rate for aseptic cup or inlay revision was 94%, and the survival rate for aseptic cup loosening was 99%.
Article
Cell Biology
Takeshi Utsunomiya, Ning Zhang, Tzuhua Lin, Yusuke Kohno, Masaya Ueno, Masahiro Maruyama, Claire Rhee, Ejun Huang, Zhenyu Yao, Stuart B. Goodman
Summary: The local injection of MSCs or pMSCs during the chronic inflammatory phase can reverse decreased bone mineral density and increased osteoclast-like cells, while immediate injection of pMSCs during the acute inflammatory phase may impair bone healing. Timing of interventions to modulate inflammation is critical for bone healing outcomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Bashar A. Alhasan, Sergei A. Gordeev, Aleksandra R. Knyazeva, Kseniia V. Aleksandrova, Boris A. Margulis, Irina V. Guzhova, Irina I. Suvorova
Summary: Cancer cell dormancy may not only be a privilege of cancer cells, but also a reproductive survival strategy shared with embryonic stem cells. Recent research has found that high autophagy and reduction of the mTOR pathway are key mechanisms contributing to dormancy and diapause.
Article
Cell & Tissue Engineering
Ruzhica Bogeska, Ana-Matea Mikecin, Paul Kaschutnig, Malak Fawaz, Marleen Buechler-Schaeff, Duy Le, Miguel Ganuza, Angelika Vollmer, Stella Paffenholz, Noboru Asada, Esther Rodriguez-Correa, Felix Frauhammer, Florian Buettner, Melanie Ball, Julia Knoch, Sina Staeble, Dagmar Walter, Amelie Petri, Martha J. Carreno-Gonzalez, Vinona Wagner, Benedikt Brors, Simon Haas, Daniel B. Lipka, Marieke A. G. Essers, Vivienn Weru, Tim Holland-Letz, Jan-Philipp Mallm, Karsten Rippe, Stephan Kraemer, Matthias Schlesner, Shannon McKinney Freeman, Maria Carolina Florian, Katherine Y. King, Paul S. Frenette, Michael A. Rieger, Michael D. Milsom
Summary: Infection or inflammation may lead to irreversible depletion of functional hematopoietic stem cells, resulting in long-term effects on tissue maintenance and regeneration.
Article
Cell Biology
Orlando Arguello-Miranda, Ashley J. Marchand, Taylor Kennedy, Marielle A. X. Russo, Jungsik Noh
Summary: Cellular quiescence is a nonproliferative state that allows cell survival under stress and during development. This study investigates the stress pathways associated with high-Cdk1 quiescent states triggered by starvation in Saccharomyces cerevisiae. It is found that both low- and high-Cdk1 quiescent states involve stress-associated processes, but differ in the nuclear accumulation of stress transcription factors. The decision between low- or high-Cdk1 quiescence is controlled by cell cycle-independent accumulation of Xbp1.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Oncology
Antonio Maurizi, Michela Ciocca, Cristiano Giuliani, Ilaria Di Carlo, Anna Teti
Summary: This study identified the role of N-Cadherin in breast cancer cell dormancy and stemness. Breast cancer cells that interact with spindle-shaped N-Cadherin(+) Osteoblasts (SNOs) become dormant, and N-Cadherin mediates the adhesion of breast cancer cells to SNOs. The study also revealed differences in the role of N-Cadherin between human and mouse breast cancer cell lines.
Article
Cell Biology
Karmele Valencia, Cristina Sainz, Cristina Bertolo, Gabriel de Biurrun, Jackeline Agorreta, Arantza Azpilikueta, Marta Larrayoz, Graziella Bosco, Carolina Zandueta, Miriam Redrado, Esther Redin, Francisco Exposito, Diego Serrano, Mirari Echepare, Daniel Ajona, Ignacio Melero, Ruben Pio, Roman Thomas, Alfonso Calvo, Luis M. Montuenga
Summary: There is a lack of adequate mouse models and cell lines for studying lung squamous cell carcinoma (LUSC). In this study, two models of transplantable LUSC cell lines were generated and characterized, revealing similar genetic and transcriptomic patterns. The immune landscape and response to immune checkpoint inhibition were also compared. Furthermore, the metastatic potential of these models showed organotropism similar to LUSC in humans. Overall, these valuable cell line tools recapitulate the complexity of the human disease.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biochemistry & Molecular Biology
Catia Monteiro, Lauritz Miarka, Maria Perea-Garcia, Neibla Priego, Pedro Garcia-Gomez, Laura Alvaro-Espinosa, Ana de Pablos-Aragoneses, Natalia Yebra, Diana Retana, Patricia Baena, Coral Fustero-Torre, Osvaldo Grana-Castro, Kevin Troule, Eduardo Caleiras, Patricia Tezanos, Pablo Muela, Elisa Cintado, Jose Luis Trejo, Juan Manuel Sepulveda, Pedro Gonzalez-Leon, Luis Jimenez-Roldan, Luis Miguel Moreno, Olga Esteban, Angel Perez-Nunez, Aurelio Hernandez-Lain, Jose Mazarico Gallego, Irene Ferrer, Rocio Suarez, Eva M. Garrido-Martin, Luis Paz-Ares, Celine Dalmasso, Elizabeth Cohen-Jonathan Moyal, Aurore Siegfried, Aisling Hegarty, Stephen Keelan, Damir Vareslija, Leonie S. Young, Malte Mohme, Yvonne Goy, Harriet Wikman, Jose Fernandez-Alen, Guillermo Blasco, Lucia Alcazar, Clara Cabanuz, Sergei Grivennikov, Andrada Ianus, Noam Shemesh, Claudia C. Faria, Rebecca Lee, Paul Lorigan, Emilie Le Rhun, Michael Weller, Riccardo Soffietti, Luca Bertero, Umberto Ricardi, Joaquim Bosch-Barrera, Elia Sais, Eduard Teixidor, Alejandro Hernandez-Martinez, Alfonso Calvo, Javier Aristu, Santiago M. Martin, Alvaro Gonzalez, Omer Adler, Neta Erez, Manuel Valiente
Summary: This study identifies a molecular mechanism underlying resistance to whole-brain radiotherapy and suggests potential targets and biomarkers for personalized radiotherapy. The findings have important implications for improving the efficacy of treatment for patients with brain metastasis.
Review
Oncology
Irati Garmendia, Esther Redin, Luis M. Montuenga, Alfonso Calvo
Summary: YES1, a nonreceptor tyrosine kinase, is considered as an emerging target in solid tumors. It is overexpressed in many tumor types, promoting cell proliferation and invasiveness. Novel specific inhibitors of YES1 have shown impressive antitumor effects in pre-clinical models. Inhibiting YES1 in tumors with high expression of this protein is a promising strategy against cancer.
MOLECULAR CANCER THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Fernando Torres Andon, Sergio Leon, Aldo Ummarino, Esther Redin, Paola Allavena, Diego Serrano, Clement Anfray, Alfonso Calvo
Summary: TLRs serve as natural initial triggers of immune responses and hold potential in cancer immunotherapy. Intratumoral injection of TLR agonists achieves high local drug exposure and strong antitumor response, potentially leading to cure and antitumor immunological memory.
Article
Immunology
Karmele Valencia, Mirari Echepare, Alvaro Teijeira, Andrea Pasquier, Cristina Bertolo, Cristina Sainz, Ibon Tamayo, Benat Picabea, Graziella Bosco, Roman Thomas, Jackeline Agorreta, Jose Maria Lopez-Picazo, Joan Frigola, Ramon Amat, Alfonso Calvo, Enriqueta Felip, Ignacio Melero, Luis M. Montuenga
Summary: Valencia et al. have identified DSTYK as a novel therapeutic target in lung cancer. Inhibition of DSTYK sensitizes lung cancer cells to T cell-mediated killing and impairs mitochondrial fitness and cytoprotective autophagy. DSTYK copy number gain predicts lack of response to immunotherapy in lung cancer patients.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Oncology
Esther Redin, Eva M. Garrido-Martin, Karmele Valencia, Miriam Redrado, Jose Luis Solorzano, Rafael Carias, Mirari Echepare, Francisco Exposito, Diego Serrano, Irene Ferrer, Angel Nunez-Buiza, Irati Garmendia, Juana M. Garcia-Pedrero, Alfonso Gurpide, Luis Paz-Ares, Katerina Politi, Luis M. Montuenga, Alfonso Calvo
Summary: YES1 was identified as a novel targetable oncogene driving SCLC maintenance and metastasis, and its overexpression was associated with poor prognosis.
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Oncology
Cora Palanca-Ballester, David Hervas, Maria Villalba, Teresa Valdes-Sanchez, Diana Garcia, Maria Isabel Alcoriza-Balaguer, Marta Benet, Raquel Martinez-Tomas, Andres Briones-Gomez, Jose Galbis-Caravajal, Alfonso Calvo, Oscar Juan, Agustin Lahoz, Enrique Cases, Juan Sandoval
Summary: This study validates a noninvasive detection method using a 4-gene signature of DNA methylation levels for efficient diagnosis of lung cancer in plasma.
CLINICAL EPIGENETICS
(2022)
Article
Oncology
Francisco Exposito, Miriam Redrado, Maeva Houry, Katherine Hastings, Magdalena Molero-Abraham, Teresa Lozano, Jose Luis Solorzano, Julian Sanz-Ortega, Vera Adradas, Ramon Amat, Esther Redin, Sergio Leon, Naroa Legarra, Javier Garcia, Diego Serrano, Karmele Valencia, Camila Robles-Oteiza, Giorgia Foggetti, Nerea Otegui, Enriqueta Felip, Juan J. Lasarte, Luis Paz-Ares, Jon Zugazagoitia, Katerina Politi, Luis Montuenga, Alfonso Calvo
Summary: Immunotherapy resistance in non-small cell lung cancer (NSCLC) can be attributed to an immunosuppressive microenvironment created by genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression. PTEN-low tumors are associated with higher levels of immune checkpoint proteins and poorer response to immunotherapy. Preclinical models demonstrate that PTEN loss promotes metastasis and fibrosis, and facilitates the conversion of immune cells into immunosuppressive regulatory T cells (Treg). However, targeting PTEN loss-mediated immunosuppression can reverse immunotherapy resistance in NSCLC.
Review
Oncology
Nerea Otegui, Maeva Houry, Imanol Arozarena, Diego Serrano, Esther Redin, Francisco Exposito, Sergio Leon, Karmele Valencia, Luis Montuenga, Alfonso Calvo
Summary: Immunotherapy for NSCLC is effective for some patients, but less than half of them will benefit from it. Detection of PD-L1 in tumors is currently the only validated predictive biomarker. Genetic and metabolic alterations in tumor cells can affect the tumor microenvironment and the response to immunotherapy. Novel strategies based on these alterations may improve the efficacy of immunotherapy for lung cancer patients.
Editorial Material
Oncology
Karmele Valencia, Luis M. Montuenga, Alfonso Calvo
Summary: The influence of sex on immunotherapy response in patients with non-small cell lung cancer (NSCLC) is inconclusive. However, a recent study suggests that the existence of a 17 beta-estradiol/ER alpha/PDL1 signaling loop in NSCLC is a key factor determining the response to immunotherapy, opening up new therapeutic options.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Paola Anna Jablonska, Nuria Galan, Jennifer Barranco, Sergio Leon, Ramon Robledano, Jose Ignacio Echeveste, Alfonso Calvo, Javier Aristu, Diego Serrano
Summary: This study investigates the role of STAT3 and other inflammatory markers in the development of brain radiation necrosis (RN). The results suggest that STAT3 plays an important role in RN development, and targeting STAT3 may be a promising strategy for ameliorating symptomatic RN in brain metastases patients undergoing stereotactic radiosurgery (SRS).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)