EMBO Molecular MedicinePub Date : 2024-07-01Epub Date: 2024-06-19DOI: 10.1038/s44321-024-00082-6
Mark Sementsov, Leonie Ott, Julian Kött, Alexander Sartori, Amelie Lusque, Sarah Degenhardt, Bertille Segier, Isabel Heidrich, Beate Volkmer, Rüdiger Greinert, Peter Mohr, Ronald Simon, Julia-Christina Stadler, Darryl Irwin, Claudia Koch, Antje Andreas, Benjamin Deitert, Verena Thewes, Andreas Trumpp, Andreas Schneeweiss, Yassine Belloum, Sven Peine, Harriett Wikman, Sabine Riethdorf, Stefan W Schneider, Christoffer Gebhardt, Klaus Pantel, Laura Keller
{"title":"Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma.","authors":"Mark Sementsov, Leonie Ott, Julian Kött, Alexander Sartori, Amelie Lusque, Sarah Degenhardt, Bertille Segier, Isabel Heidrich, Beate Volkmer, Rüdiger Greinert, Peter Mohr, Ronald Simon, Julia-Christina Stadler, Darryl Irwin, Claudia Koch, Antje Andreas, Benjamin Deitert, Verena Thewes, Andreas Trumpp, Andreas Schneeweiss, Yassine Belloum, Sven Peine, Harriett Wikman, Sabine Riethdorf, Stefan W Schneider, Christoffer Gebhardt, Klaus Pantel, Laura Keller","doi":"10.1038/s44321-024-00082-6","DOIUrl":"10.1038/s44321-024-00082-6","url":null,"abstract":"<p><p>Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1560-1578"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO Molecular MedicinePub Date : 2024-07-01Epub Date: 2024-05-15DOI: 10.1038/s44321-024-00074-6
Shene Chiou, Aysha H Al-Ani, Yi Pan, Komal M Patel, Isabella Y Kong, Lachlan W Whitehead, Amanda Light, Samuel N Young, Marilou Barrios, Callum Sargeant, Pradeep Rajasekhar, Leah Zhu, Anne Hempel, Ann Lin, James A Rickard, Cathrine Hall, Pradnya Gangatirkar, Raymond Kh Yip, Wayne Cawthorne, Annette V Jacobsen, Christopher R Horne, Katherine R Martin, Lisa J Ioannidis, Diana S Hansen, Jessica Day, Ian P Wicks, Charity Law, Matthew E Ritchie, Rory Bowden, Joanne M Hildebrand, Lorraine A O'Reilly, John Silke, Lisa Giulino-Roth, Ellen Tsui, Kelly L Rogers, Edwin D Hawkins, Britt Christensen, James M Murphy, André L Samson
{"title":"An immunohistochemical atlas of necroptotic pathway expression.","authors":"Shene Chiou, Aysha H Al-Ani, Yi Pan, Komal M Patel, Isabella Y Kong, Lachlan W Whitehead, Amanda Light, Samuel N Young, Marilou Barrios, Callum Sargeant, Pradeep Rajasekhar, Leah Zhu, Anne Hempel, Ann Lin, James A Rickard, Cathrine Hall, Pradnya Gangatirkar, Raymond Kh Yip, Wayne Cawthorne, Annette V Jacobsen, Christopher R Horne, Katherine R Martin, Lisa J Ioannidis, Diana S Hansen, Jessica Day, Ian P Wicks, Charity Law, Matthew E Ritchie, Rory Bowden, Joanne M Hildebrand, Lorraine A O'Reilly, John Silke, Lisa Giulino-Roth, Ellen Tsui, Kelly L Rogers, Edwin D Hawkins, Britt Christensen, James M Murphy, André L Samson","doi":"10.1038/s44321-024-00074-6","DOIUrl":"10.1038/s44321-024-00074-6","url":null,"abstract":"<p><p>Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators - Caspase-8, RIPK1, RIPK3 and MLKL - in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1717-1749"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO Molecular MedicinePub Date : 2024-07-01Epub Date: 2024-06-14DOI: 10.1038/s44321-024-00085-3
Partho Protim Adhikary, Temilolu Idowu, Zheng Tan, Christopher Hoang, Selina Shanta, Malti Dumbani, Leah Mappalakayil, Bhuwan Awasthi, Marcel Bermudez, January Weiner, Dieter Beule, Gerhard Wolber, Brent Dg Page, Sarah Hedtrich
{"title":"Disrupting TSLP-TSLP receptor interactions via putative small molecule inhibitors yields a novel and efficient treatment option for atopic diseases.","authors":"Partho Protim Adhikary, Temilolu Idowu, Zheng Tan, Christopher Hoang, Selina Shanta, Malti Dumbani, Leah Mappalakayil, Bhuwan Awasthi, Marcel Bermudez, January Weiner, Dieter Beule, Gerhard Wolber, Brent Dg Page, Sarah Hedtrich","doi":"10.1038/s44321-024-00085-3","DOIUrl":"10.1038/s44321-024-00085-3","url":null,"abstract":"<p><p>Thymic stromal lymphopoietin (TSLP) is a key player in atopic diseases, which has sparked great interest in therapeutically targeting TSLP. Yet, no small-molecule TSLP inhibitors exist due to the challenges of disrupting the protein-protein interaction between TSLP and its receptor. Here, we report the development of small-molecule TSLP receptor inhibitors using virtual screening and docking of >1,000,000 compounds followed by iterative chemical synthesis. BP79 emerged as our lead compound that effectively abrogates TSLP-triggered cytokines at low micromolar concentrations. For in-depth analysis, we developed a human atopic disease drug discovery platform using multi-organ chips. Here, topical application of BP79 onto atopic skin models that were co-cultivated with lung models and Th2 cells effectively suppressed immune cell infiltration and IL-13, IL-4, TSLP, and periostin secretion, while upregulating skin barrier proteins. RNA-Seq analysis corroborate these findings and indicate protective downstream effects on the lungs. To the best of our knowledge, this represents the first report of a potent putative small molecule TSLPR inhibitor which has the potential to expand the therapeutic and preventive options in atopic diseases.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1630-1656"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO Molecular MedicinePub Date : 2024-07-01Epub Date: 2024-06-05DOI: 10.1038/s44321-024-00083-5
Laura de Boni, Amber Wallis, Aurelia Hays Watson, Alejandro Ruiz-Riquelme, Louise-Ann Leyland, Thomas Bourinaris, Naomi Hannaway, Ullrich Wüllner, Oliver Peters, Josef Priller, Björn H Falkenburger, Jens Wiltfang, Mathias Bähr, Inga Zerr, Katharina Bürger, Robert Perneczky, Stefan Teipel, Matthias Löhle, Wiebke Hermann, Björn-Hendrik Schott, Kathrin Brockmann, Annika Spottke, Katrin Haustein, Peter Breuer, Henry Houlden, Rimona S Weil, Tim Bartels
{"title":"Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.","authors":"Laura de Boni, Amber Wallis, Aurelia Hays Watson, Alejandro Ruiz-Riquelme, Louise-Ann Leyland, Thomas Bourinaris, Naomi Hannaway, Ullrich Wüllner, Oliver Peters, Josef Priller, Björn H Falkenburger, Jens Wiltfang, Mathias Bähr, Inga Zerr, Katharina Bürger, Robert Perneczky, Stefan Teipel, Matthias Löhle, Wiebke Hermann, Björn-Hendrik Schott, Kathrin Brockmann, Annika Spottke, Katrin Haustein, Peter Breuer, Henry Houlden, Rimona S Weil, Tim Bartels","doi":"10.1038/s44321-024-00083-5","DOIUrl":"10.1038/s44321-024-00083-5","url":null,"abstract":"<p><p>Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1657-1674"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO Molecular MedicinePub Date : 2024-07-01Epub Date: 2024-06-26DOI: 10.1038/s44321-024-00090-6
Nicla Lorito, Angela Subbiani, Alfredo Smiriglia, Marina Bacci, Francesca Bonechi, Laura Tronci, Elisabetta Romano, Alessia Corrado, Dario Livio Longo, Marta Iozzo, Luigi Ippolito, Giuseppina Comito, Elisa Giannoni, Icro Meattini, Alexandra Avgustinova, Paola Chiarugi, Angela Bachi, Andrea Morandi
{"title":"FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer.","authors":"Nicla Lorito, Angela Subbiani, Alfredo Smiriglia, Marina Bacci, Francesca Bonechi, Laura Tronci, Elisabetta Romano, Alessia Corrado, Dario Livio Longo, Marta Iozzo, Luigi Ippolito, Giuseppina Comito, Elisa Giannoni, Icro Meattini, Alexandra Avgustinova, Paola Chiarugi, Angela Bachi, Andrea Morandi","doi":"10.1038/s44321-024-00090-6","DOIUrl":"10.1038/s44321-024-00090-6","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA). Here we identify fatty acid desaturases 1 and 2 (FADS1/2), which are responsible for PUFA biosynthesis, to be highly expressed in a subset of TNBC with a poorer prognosis. Lipidomic analysis, coupled with functional metabolic assays, showed that FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents and that targeting FADS1/2 by both genetic interference and pharmacological approach renders those tumors ferroptosis-resistant while unbalancing PUFA/MUFA ratio by the supplementation of exogenous PUFA sensitizes resistant tumors to ferroptosis induction. Last, inhibiting lipid droplet (LD) formation and turnover suppresses the buffering capacity of LD and potentiates iron-dependent cell death. These findings have been validated in vitro and in vivo in mouse- and human-derived clinically relevant models and in a retrospective cohort of TNBC patients.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1533-1559"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO Molecular MedicinePub Date : 2024-07-01Epub Date: 2024-06-17DOI: 10.1038/s44321-024-00088-0
Majid Momeny, Mari Tienhaara, Mukund Sharma, Deepankar Chakroborty, Roosa Varjus, Iina Takala, Joni Merisaari, Artur Padzik, Andreas Vogt, Ilkka Paatero, Klaus Elenius, Teemu D Laajala, Kari J Kurppa, Jukka Westermarck
{"title":"DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer.","authors":"Majid Momeny, Mari Tienhaara, Mukund Sharma, Deepankar Chakroborty, Roosa Varjus, Iina Takala, Joni Merisaari, Artur Padzik, Andreas Vogt, Ilkka Paatero, Klaus Elenius, Teemu D Laajala, Kari J Kurppa, Jukka Westermarck","doi":"10.1038/s44321-024-00088-0","DOIUrl":"10.1038/s44321-024-00088-0","url":null,"abstract":"<p><p>Despite clinical benefits of tyrosine kinase inhibitors (TKIs) in cancer, most tumors can reactivate proliferation under TKI therapy. Here we present transcriptional profiling of HER2+ breast cancer cells transitioning from dormant drug tolerant cells to re-proliferating cells under continuous HER2 inhibitor (HER2i) therapy. Focusing on phosphatases, expression of dual-specificity phosphatase DUSP6 was found inhibited in dormant cells, but strongly induced upon regrowth. DUSP6 expression also selectively associated with poor patient survival in HER2+ breast cancers. DUSP6 overexpression conferred apoptosis resistance, whereas its pharmacological blockade prevented therapy tolerance development under HER2i therapy. DUSP6 targeting also synergized with clinically used HER2i combination therapies. Mechanistically DUSP6 is a positive regulator of HER3 expression, and its impact on HER2i tolerance was mediated by neuregulin-HER3 axis. In vivo, genetic targeting of DUSP6 reduced tumor growth in brain metastasis model, whereas its pharmacological targeting induced synthetic lethal therapeutic effect in combination with HER2i. Collectively this work demonstrates that DUSP6 drives escape from HER2i-induced dormancy, and that DUSP6 is a druggable target to overcome HER3-driven TKI resistance.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1603-1629"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christine T Styles, Jie Zhou, Katie E Flight, Jonathan C Brown, Charlotte Lewis, Xinyu Wang, Michael Vanden Oever, Thomas P Peacock, Ziyin Wang, Rosie Millns, John S O'Neill, Alexander Borodavka, Joe Grove, Wendy S Barclay, John S Tregoning, Rachel S Edgar
{"title":"Author Correction: Propylene glycol inactivates respiratory viruses and prevents airborne transmission.","authors":"Christine T Styles, Jie Zhou, Katie E Flight, Jonathan C Brown, Charlotte Lewis, Xinyu Wang, Michael Vanden Oever, Thomas P Peacock, Ziyin Wang, Rosie Millns, John S O'Neill, Alexander Borodavka, Joe Grove, Wendy S Barclay, John S Tregoning, Rachel S Edgar","doi":"10.1038/s44321-024-00078-2","DOIUrl":"10.1038/s44321-024-00078-2","url":null,"abstract":"","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1751"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO Molecular MedicinePub Date : 2024-07-01Epub Date: 2024-06-11DOI: 10.1038/s44321-024-00087-1
Merryn Fraser, Blake Curtis, Patrick Phillips, Patrick A Yates, Kwong Sum Lam, Otto Netzel, Giel G van Dooren, Alyssa Ingmundson, Kai Matuschewski, Malcolm D McLeod, Alexander G Maier
{"title":"Harnessing cholesterol uptake of malaria parasites for therapeutic applications.","authors":"Merryn Fraser, Blake Curtis, Patrick Phillips, Patrick A Yates, Kwong Sum Lam, Otto Netzel, Giel G van Dooren, Alyssa Ingmundson, Kai Matuschewski, Malcolm D McLeod, Alexander G Maier","doi":"10.1038/s44321-024-00087-1","DOIUrl":"10.1038/s44321-024-00087-1","url":null,"abstract":"<p><p>Parasites, such as the malaria parasite P. falciparum, are critically dependent on host nutrients. Interference with nutrient uptake can lead to parasite death and, therefore, serve as a successful treatment strategy. P. falciparum parasites cannot synthesise cholesterol, and instead source this lipid from the host. Here, we tested whether cholesterol uptake pathways could be 'hijacked' for optimal drug delivery to the intracellular parasite. We found that fluorescent cholesterol analogues were delivered from the extracellular environment to the intracellular parasite. We investigated the uptake and inhibitory effects of conjugate compounds, where proven antimalarial drugs (primaquine and artesunate) were attached to steroids that mimic the structure of cholesterol. These conjugated antimalarial drugs improved the inhibitory effects against multiple parasite lifecycle stages, multiple parasite species, and drug-resistant parasites, whilst also lowering the toxicity to human host cells. Steroids with introduced peroxides also displayed antimalarial activity. These results provide a proof-of-concept that cholesterol mimics can be developed as a drug delivery system against apicomplexan parasites with the potential to improve drug efficacy, increase therapeutic index, and defeat drug resistance.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1515-1532"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Minimally-invasive implantable device enhances brain cancer suppression.","authors":"Xiaona Cao, Jie Li, Jinliang Ren, Jiajin Peng, Ruyue Zhong, Jiahao He, Ting Xu, Zhenhua Yu, Huawei Jin, Siqi Hao, Ruiwei Liu, Bingzhe Xu","doi":"10.1038/s44321-024-00091-5","DOIUrl":"10.1038/s44321-024-00091-5","url":null,"abstract":"<p><p>Current brain tumor treatments are limited by the skull and BBB, leading to poor prognosis and short survival for glioma patients. We introduce a novel minimally-invasive brain tumor suppression (MIBTS) device combining personalized intracranial electric field therapy with in-situ chemotherapeutic coating. The core of our MIBTS technique is a wireless-ultrasound-powered, chip-sized, lightweight device with all functional circuits encapsulated in a small but efficient \"Swiss-roll\" structure, guaranteeing enhanced energy conversion while requiring tiny implantation windows ( ~ 3 × 5 mm), which favors broad consumers acceptance and easy-to-use of the device. Compared with existing technologies, competitive advantages in terms of tumor suppressive efficacy and therapeutic resolution were noticed, with maximum <sup>~</sup>80% higher suppression effect than first-line chemotherapy and 50-70% higher than the most advanced tumor treating field technology. In addition, patient-personalized therapy strategies could be tuned from the MIBTS without increasing size or adding circuits on the integrated chip, ensuring the optimal therapeutic effect and avoid tumor resistance. These groundbreaking achievements of MIBTS offer new hope for controlling tumor recurrence and extending patient survival.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1704-1716"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO Molecular MedicinePub Date : 2024-07-01Epub Date: 2024-06-10DOI: 10.1038/s44321-024-00086-2
Chongbo Yang, J Magarian Blander
{"title":"Seeing is believing: a breakthrough to visualize necrosomes in the tissue.","authors":"Chongbo Yang, J Magarian Blander","doi":"10.1038/s44321-024-00086-2","DOIUrl":"10.1038/s44321-024-00086-2","url":null,"abstract":"","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"1487-1489"},"PeriodicalIF":9.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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