Oral Hydrogel Microbeads-Mediated In Situ Synthesis of Selenoproteins for Regulating Intestinal Immunity and Microbiota

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(22), С. 12193 - 12205

Опубликована: Май 19, 2023

Selenoprotein plays a crucial role in immune cells and inflammatory regulation. However, as protein drug that is easily denatured or degraded the acidic environment of stomach, efficient oral delivery selenoprotein great challenge. Herein, we innovated an hydrogel microbeads-based biochemical strategy can situ synthesize selenoproteins, therefore bypassing necessity harsh conditions for while effectively generating selenoproteins therapeutic applications. The microbeads were synthesized by coating hyaluronic acid-modified selenium nanoparticles with protective shell calcium alginate (SA) hydrogel. We tested this mice bowel disease (IBD), one most representative diseases related to intestinal immunity microbiota. Our results revealed microbeads-mediated synthesis could prominently reduce proinflammatory cytokines secretion mediate (e.g., neutrophils monocytes increase regulatory T cells) relieve colitis-associated symptoms. This was also able regulate gut microbiota composition (increase probiotics abundance suppress detrimental communities) maintain homeostasis. Considering widely associated cancers, infections, inflammations, etc., might be possibly applied broadly tackle various diseases.

Язык: Английский

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Microfluidics-free single-cell genomics with templated emulsification

Nature Biotechnology, Год журнала: 2023, Номер 41(11), С. 1557 - 1566

Опубликована: Март 6, 2023

Current single-cell RNA-sequencing approaches have limitations that stem from the microfluidic devices or fluid handling steps required for sample processing. We develop a method does not require specialized devices, expertise hardware. Our approach is based on particle-templated emulsification, which allows encapsulation and barcoding of cDNA in uniform droplet emulsions with only vortexer. Particle-templated instant partition sequencing (PIP-seq) accommodates wide range emulsification formats, including microwell plates large-volume conical tubes, enabling thousands samples millions cells to be processed minutes. demonstrate PIP-seq produces high-purity transcriptomes mouse-human mixing studies, compatible multiomics measurements can accurately characterize cell types human breast tissue compared commercial platform. Single-cell transcriptional profiling mixed phenotype acute leukemia using reveals emergence heterogeneity within chemotherapy-resistant subsets were hidden by standard immunophenotyping. simple, flexible scalable next-generation workflow extends new applications.

Язык: Английский

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The Potential Revolution of Cancer Treatment with CRISPR Technology

Cancers, Год журнала: 2023, Номер 15(6), С. 1813 - 1813

Опубликована: Март 17, 2023

Immuno-oncology (IO) and targeted therapies, such as small molecule inhibitors, have changed the landscape of cancer treatment prognosis; however, durable responses been difficult to achieve due tumor heterogeneity, development drug resistance, adverse effects that limit dosing prolonged use. To improve upon current medicinal armamentarium, there is an urgent need for new ways understand, reverse, treat carcinogenesis. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 a powerful efficient tool genome editing has shown significant promise developing therapeutics. While CRISPR/Cas9 successfully used pre-clinical research, its use in clinical setting still early stage development. The purpose this review describe CRISPR technology provide overview applications future potential therapies.

Язык: Английский

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Circulating tumor cells: from new biological insights to clinical practice

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 2, 2024

Abstract The primary reason for high mortality rates among cancer patients is metastasis, where tumor cells migrate through the bloodstream from original site to other parts of body. Recent advancements in technology have significantly enhanced our comprehension mechanisms behind bloodborne spread circulating (CTCs). One critical process, DNA methylation, regulates gene expression and chromosome stability, thus maintaining dynamic equilibrium Global hypomethylation locus-specific hypermethylation are examples changes methylation patterns that pivotal carcinogenesis. This comprehensive review first provides an overview various processes contribute formation CTCs, including epithelial-mesenchymal transition (EMT), immune surveillance, colonization. We then conduct in-depth analysis how modifications within CTCs impact each these stages during CTC dissemination. Furthermore, we explored potential clinical implications with cancer. By understanding epigenetic modifications, can gain insights into metastatic process identify new biomarkers early detection, prognosis, targeted therapies. aims bridge gap between basic research application, highlighting significance context metastasis offering avenues improving patient outcomes.

Язык: Английский

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Advances and applications of nanoparticles in cancer therapy

MedComm – Oncology, Год журнала: 2024, Номер 3(1)

Опубликована: Март 1, 2024

Abstract Rapid growth in nanoparticles (NPs) as delivery systems holds vast promise to promote therapeutic approaches for cancer treatment. Presently, a diverse array of NPs with unique properties have been developed overcome different challenges and achieve sophisticated routes enhancement series therapies. Inspiring advances achieved the field therapy using NPs. In this review, we aim summarize up‐to‐date progression addressing various challenges, expect elicit novel potential opportunities alternatively. We first introduce sorts NP technologies, illustrate their mechanisms, present applications. Then, achievements made by break obstacles delivering cargoes specific sites through particular are highlighted, including long‐circulation, tumor targeting, responsive release, subcellular localization. subsequently retrospect recent research treatments from single therapy, like chemotherapy, combination chemoradiotherapy, integrative therapy. Finally, perspectives impact on oncology discussed. believe review can offer deeper understanding

Язык: Английский

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Protein translation: biological processes and therapeutic strategies for human diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 23, 2024

Abstract Protein translation is a tightly regulated cellular process that essential for gene expression and protein synthesis. The deregulation of this increasingly recognized as critical factor in the pathogenesis various human diseases. In review, we discuss how deregulated can lead to aberrant synthesis, altered functions, disease progression. We explore key mechanisms contributing translation, including functional alterations factors, tRNA, mRNA, ribosome function. Deregulated leads abnormal expression, disrupted signaling, perturbed functions- all which contribute pathogenesis. development profiling techniques along with mass spectrometry-based proteomics, mRNA sequencing single-cell approaches have opened new avenues detecting diseases related errors. Importantly, highlight recent advances therapies targeting translation-related disorders their potential applications neurodegenerative diseases, cancer, infectious cardiovascular Moreover, growing interest lies targeted aimed at restoring precise control over diseased cells discussed. conclusion, comprehensive review underscores role its therapeutic target. Advancements understanding molecular deregulation, coupled therapies, offer promising improving outcomes Additionally, it will unlock doors possibility precision medicine by offering personalized deeper underpinnings future.

Язык: Английский

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Cell-intrinsic and microenvironmental determinants of metastatic colonization

Nature Cell Biology, Год журнала: 2024, Номер 26(5), С. 687 - 697

Опубликована: Май 1, 2024

Язык: Английский

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Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Ноя. 6, 2020

Abstract Therapeutic efficacy against cancer relies heavily on the ability of therapeutic agents to reach their final targets. The optimal targets most are usually biological macromolecules at subcellular level, which play a key role in carcinogenesis. Therefore, improve efficiency drugs, researchers need focus delivering not only target tissues and cells but also drugs relevant structures. In this review, we discuss recent construction strategies release patterns various cell subcellular-targeting nanoformulations, aiming providing guidance overall design precise nanomedicine. Additionally, future challenges potential perspectives illustrated hope enhancing anticancer accelerating translational progress

Язык: Английский

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Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity

EMBO Molecular Medicine, Год журнала: 2020, Номер 12(9)

Опубликована: Июль 15, 2020

Article15 July 2020Open Access Source DataTransparent process Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity Claudia Koch Department Tumor Biology, Center Experimental Medicine, University Medical Hamburg-Eppendorf, Hamburg, Germany Search for more papers by this author Andra Kuske Simon A Joosse orcid.org/0000-0002-4296-5615 Gökhan Yigit Institute Human Genetics, Göttingen, George Sflomos orcid.org/0000-0003-2972-0549 ISREC – Swiss Cancer Research, School Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland Sonja Thaler European Centre Angioscience (ECAS), Faculty Mannheim, Heidelberg, Daniel J Smit orcid.org/0000-0002-3190-9511 Biochemistry Signal Transduction, Stefan Werner Kerstin Borgmann Radiobiology& Radiooncology, Sebastian Gärtner Parinaz Mossahebi Mohammadi Laura Battista Laure Cayrefourcq Laboratory Rare Circulating Cells (LCCRH), Centre, Montpellier, France Montpellier University, Janine Altmüller Cologne Genomics, Cologne, Gabriela Salinas-Riester NGS Integrative Genomics Core Unit, Kaamini Raithatha Arne Zibat Yvonne Goy Leonie Ott Kai Bartkowiak Tuan Zea Tan orcid.org/0000-0001-6624-1593 Science Singapore, National Singapore City, Qing Zhou orcid.org/0000-0001-7737-9643 Diagnostic Research Molecular BioMedicine, Graz, Austria Michael R Speicher orcid.org/0000-0003-0105-955X Volkmar Müller Gynecology, Tobias M Gorges Manfred Jücker Jean-Paul Thiery orcid.org/0000-0003-0478-5020 INSERM Unit 1186, Comprehensive Center, Institut Gustave Roussy, Villejuif, Cathrin Brisken Breast Now London, UK Sabine Riethdorf orcid.org/0000-0003-0028-5643 Catherine Alix-Panabières orcid.org/0000-0002-6401-2903 Klaus Pantel Corresponding Author [email protected] orcid.org/0000-0001-5736-2772 Information Koch1,†, Kuske1,†, Joosse1, Yigit2, Sflomos3, Thaler4, Smit5, Werner1, Borgmann6, Gärtner1, Mohammadi1, Battista3, Cayrefourcq7,8, Altmüller9, Salinas-Riester10, Raithatha10, Zibat2, Goy6, Ott1, Bartkowiak1, Tan11, Zhou12, Speicher12, Müller13, Gorges1, Jücker5, Thiery14, Brisken3,15,‡, Riethdorf1,‡, Alix-Panabières7,8,‡ *,1 1Department 2Institute 3ISREC 4European 5Institute 6Radiobiology& 7Laboratory 8Montpellier 9Cologne 10NGS 11Cancer 12Institute 13Department 14INSERM 15Breast † These authors contributed equally to work as first ‡ senior *Corresponding author. Tel: +49 40 741053503; Fax: 49 7410-55379; E-mail: EMBO Mol Med (2020)12:e11908https://doi.org/10.15252/emmm.201911908 PDFDownload PDF article text main figures. Peer ReviewDownload a summary the editorial decision including letters, reviewer comments responses feedback. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Functional studies giving insight into biology tumor (CTCs) remain scarce due low frequency CTCs lack appropriate models. Here, we describe characterization novel CTC-derived cell line, designated CTC-ITB-01, established from patient estrogen receptor-positive (ER+) cancer, resistant endocrine therapy. CTC-ITB-01 remained ER+ in culture, copy number alteration (CNA) profiling showed high concordance between originally present at time point blood draw. RNA-sequencing data indicate that has predominantly epithelial expression signature. Primary metastasis formation an intraductal PDX mouse model mirrored clinical progression cancer. Downstream ER signaling was constitutively active independent ligand availability, CDK4/6 inhibitor Palbociclib strongly inhibited growth. Thus, functional opens new avenue study CTC biology. Synopsis Blood-born dissemination subsequent outgrowth - called is leading cause cancer-related death. Cell lines derived patients provide excellent models largely unknown CTCs. The line receptor (ER)-positive situ provided therefore realistic investigate Xenograft experiments demonstrated pattern similar ER-positive involving bone, liver lung secondary organs. Growth protein analyses revealed subtle signs epithelial-mesenchymal transition (EMT) falling on end EMT spectrum. carried mutations druggable genes relevant therapy (e.g., PIK3CA mutations). In vitro drug screening indicated cytostatic activity paper explained Problem Metastases developing upon primary tumor, access circulation distant organs are most frequent causes vast majority cases driven hormone receptors enabling treatment promising therapeutic strategy. However, can develop resistance therapy, which constitutes significant problem, especially stage disease. Analyzing might be helpful identify targets, but limited their Results This describes establishment CTC-ITB-01. availability. therapy; however, inhibits Genomic reflected Impact Our characterized allows in-depth insights properties common subtype enables further experimental steps uncover mechanisms targets. Introduction Detection have prognostic value various entities several large studies, e.g., prostate (Bidard et al, 2014; Goldkorn Scher 2015; Alix-Panabieres Pantel, 2016). Moreover, these potential exploited monitoring markers function blood-based biopsy guiding personalized decisions (Keller 2019; Alix-Panabieres, 2019). perspective accompany or even replace invasive tissue biopsies order gain important diagnostically therapeutically information makes essential contribution non-invasive "real-time liquid biopsies" (Pantel 2010; Bardelli 2017). spite enormous progress development approaches detection molecular up single level (Joosse 2012; 2014a,b; 2019), still very concentrations peripheral (Alix-Panabieres 2014a). Not all possess extravasate sites grow out form lesion (Wicha Hayes, 2011). plethora different factors play survival stream metastasize (Strilic Offermanns, 2017; Giuliano 2018), hemodynamic forces within (Follain 2018) genomic make-up 2016; Gkountela only few viable, survive shear flow, evade immune system well systemic therapies, reach organs, eventually overt (Chambers 2002, Y. Kang 2013). Adaptation microenvironment proliferation cluster site requires highly specialized traits, unknown. understand underlying cascade, viable capable forming required. prerequisite were recent advances ability culture (Zhang 2013; Yu 2015) expand pool vivo using xenografts (Baccelli Hodgkinson Carter our knowledge, none compared characteristics original captured directly line. Besides unraveling allow testing drugs against context, presently available disturbing, since 70–80% harbor tumors target therapies (Pan report unique properties. Comparison before indicates it mirrors situation provides response patient-derived subtype. Patient MBC presented bilateral mammary carcinoma, lymph node (LN) metastases, bone metastases (BM) age 75, 2 years prior collection analysis begin cultivation (Fig 1A). Histopathological performed both well-differentiated (G1) lobular carcinoma (ILC) left ductal (IDC) right (Table EV1). E-cadherin re-staining described sub-fraction E-cadherin+ EV1A) besides E-cadherin− EV1B). could toward ducto-lobular histopathology. Both EV1C) vaginal EV1D) contained cells. Figure 1. mBCa A. Scheme patient's status therapies. Course disease (blue) scheme (green) rise indicated. Timeline months (mo). Drugs administered standard dosage according pattern. red star represents sample collection. More detailed Appendix Supplementary Methods. B. Representative pictures initial CellSearch® who gave detected display clear keratin DAPI staining, CD45 negativity of, weak (4, 8), ERBB2 expression. small (about 5 μm diameter, 1, 2) size (larger than 10 3) detected. While some displayed dot-like perinuclear signals (1, 2), diffuse staining. Additionally, clusters 4 (5, 6). Some multiple/lobed nuclei (7, 8). C. Bright field images growing adherently. D. non-adherently (relation adherent non-adherent cells: 80/20%). Data information: White scale bars represent μm. Black online figure. 1 [emmm201911908-sup-0007-SDataFig1.pdf] Download figure PowerPoint Click here EV1. re-immunostaining taken metastasisFormalin-fixed paraffin-embedded (FFPE) analyzed immunohistochemistry (brown). Nuclear visualization Mayer's hemalum solution. show exemplary IHC correspond 20 Area (primarily diagnosed carcinoma) E-cadherin-positive (red arrow). negative weakly black arrow shows strong staining normal epithelium. Strongly arrow) (right) tumor. metastasis. vulvar squamous epithelium shown arrow. classified (ER+ ≥ 80% nuclei), progesterone positive (PR+ (ERBB2−), Ki67+ fraction 5%. At collection, additional spleen, liver, vagina had been diagnosed. An overview found Fig 1A Establishment (MBC) screened System, resulting count 1,547 per ml (total 7.5 ml). parallel, same processed culture. led permanent draw comprised shapes diameters 1B, panels 1–3), approximately 700 5–6). 8) immunostaining ERBB2. now successfully cultured mixed epithelial–mesenchymal morphology 1C) fractions 1D). Remarkably, considerable multiple lobed nuclei, probably abnormal cytokinesis EV2A). Those also detectable CellSearch 7–8), indicating not artificial effect originating Giant carrying recently associated relapse (Mirzayans 2018). Karyotyping broad range chromosomes (32–110), mean 70.7 (s = 17.66) EV2B C). EV2. karyotype ICC containing nuclei. stained pan-keratin (orange). (blue). Gray Histogram showing chromosome distribution across 66 measured 73.7 (SD 12.9) calculated, representing triploidy. bright Giemsa used karyotyping (purple). Examples 32 (upper image) 75 (lower image). Whole-genome next-generation sequencing

Язык: Английский

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Cancer and stem cells

Experimental Biology and Medicine, Год журнала: 2021, Номер 246(16), С. 1791 - 1801

Опубликована: Апрель 5, 2021

Being the second leading cause of death globally, cancer has been a long-standing and rapidly evolving focus biomedical research practice in world. A tremendous effort made to understand origin cells, formation cancerous tissues, mechanism by which they spread relapse, but disease still remains mysterious. Here, we an attempt scrutinize evidences that indicate role stem cells tumorigenesis metastasis, relapse. We also looked into influence cancers on turn represent major constituent tumor microenvironment. Based current understandings properties (cancer) their relation cancers, can foresee novel therapeutic approaches would become next wave treatment.

Язык: Английский

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