Precise Capture and Direct Quantification of Tumor Exosomes via a Highly Efficient Dual-Aptamer Recognition-Assisted Ratiometric Immobilization-Free Electrochemical Strategy

Analytical Chemistry, Journal Year: 2020, Volume and Issue: 93(3), P. 1709 - 1716

Published: Dec. 28, 2020

Tumor exosomes are promising biomarkers for early cancer diagnosis in a noninvasive manner. However, precise capture and direct analysis of tumor-specific complex biological samples still challenging. Herein, we present highly efficient dual-aptamer recognition system precisely isolating quantifying tumor from the environment based on hyperbranched DNA superstructure-facilitated signal amplification ratiometric dual-signal strategies. When were captured by system, cholesterol-modified probe was anchored surface exosomes, activating tetrahedron-based hybridization chain reaction to generate sandwich complex. Then, could bind large number Ru(NH3)63+ (Ru(III)), leading small amount unbound Ru(III) left supernatant after magnetic separation. Hence, redox between Ru(II) [Fe(CN)6]3– (Fe(III)) significantly prevented, causing an obviously enhanced IFe(III)/IRu(III) value. Consequently, sensitive detection achieved. The developed approach successfully realized isolation sample media human serum as well. More significantly, this mode immobilization-free strategy effectively circumvented systematic errors caused external factors tedious immobilization processes, thus displaying excellent performances high reliability, improved accuracy, easy manipulation. Overall, is expected offer novel ways nondestructive diagnosis.

Language: Английский

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Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling

Science, Journal Year: 2022, Volume and Issue: 377(6611), P. 1180 - 1191

Published: Aug. 18, 2022

Drug resistance in cancer is often linked to changes tumor cell state or lineage, but the molecular mechanisms driving this plasticity remain unclear. Using murine organoid and genetically engineered mouse models, we investigated causes of lineage prostate its relationship antiandrogen resistance. We found that initiates an epithelial population defined by mixed luminal-basal phenotype it depends on increased Janus kinase (JAK) fibroblast growth factor receptor (FGFR) activity. Organoid cultures from patients with castration-resistant disease harboring mixed-lineage cells reproduce dependency observed mice up-regulating luminal gene expression upon JAK FGFR inhibitor treatment. Single-cell analysis confirms presence JAK/STAT (signal transducer activator transcription) signaling a subset metastatic disease, implications for stratifying clinical trials.

Language: Английский

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Immunomodulation by targeted anticancer agents

Cancer Cell, Journal Year: 2020, Volume and Issue: 39(3), P. 310 - 345

Published: Dec. 18, 2020

At odds with conventional chemotherapeutics, targeted anticancer agents are designed to inhibit precise molecular alterations that support oncogenesis or tumor progression. Despite such an elevated degree of specificity, many clinically employed and experimental also mediate immunostimulatory immunosuppressive effects (at least in some settings) influence therapeutic efficacy. Here, we discuss the main immunomodulatory explore potential avenues harness them superior clinical

Language: Английский

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CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1651 - 1651

Published: July 9, 2020

Radiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% all cancer patients either alone or in combination with other modalities such as surgery, chemotherapy, immunotherapy, and therapeutic targeting. Despite the technological advances RT, which allow more precise delivery radiation while progressively minimizing impact on normal tissues, issues like radioresistance tumor recurrence remain important challenges. Tumor heterogeneity responsible for variation response different subpopulations. A main factor related presence stem cells (CSC) inside tumors, are metastases, relapses, RT failure, poor prognosis patients. The plasticity CSCs, process highly dependent epithelial–mesenchymal transition (EMT) associated cell dedifferentiation, complicates identification eradication CSCs it might involved disease relapse progression after irradiation. microenvironment interactions their niches also play an role RT. This review provides deep insight into characteristics mechanisms both primary metastasis radiation, radiobiological principles CSC Finally, we summarize major clinical trials development CSC-based therapies combined overcome radioresistance. better understanding potential targets radiosensitization will provide safer efficient strategies, turn improve live expectancy curability

Language: Английский

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Epigenetics as a mediator of plasticity in cancer

Science, Journal Year: 2023, Volume and Issue: 379(6632)

Published: Feb. 10, 2023

The concept of an epigenetic landscape describing potential cellular fates arising from pluripotent cells, first advanced by Conrad Waddington, has evolved in light experiments showing nondeterministic outcomes regulatory processes and mathematical methods for quantifying stochasticity. In this Review, we discuss modern approaches to gene regulation landscapes the associated ideas entropy attractor states, illustrating how their definitions are both more precise relevant understanding cancer etiology plasticity cancerous states. We address interplay between different types changes underlie progression. also consider roles aging intrinsic extrinsic stimuli modulating states alterations can be quantitatively mapped onto phenotypic thereby used therapy development.

Language: Английский

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Breast cancer heterogeneity and its implication in personalized precision therapy

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Jan. 9, 2023

Abstract Breast cancer heterogeneity determines progression, treatment effects, and prognosis. However, the precise mechanism for this remains unknown owing to its complexity. Here, we summarize origins of breast influence on disease recurrence, therapeutic resistance. We review possible mechanisms research methods used analyze it. also highlight importance cell interactions heterogeneity, which can be further categorized into cooperative competitive interactions. Finally, provide new insights individual treatments based heterogeneity.

Language: Английский

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The hallmarks of cancer immune evasion

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1825 - 1863

Published: Oct. 10, 2024

Language: Английский

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Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 18, 2023

Abstract Cancer stem cells (CSCs), initially identified in leukemia 1994, constitute a distinct subset of tumor characterized by surface markers such as CD133, CD44, and ALDH. Their behavior is regulated through complex interplay networks, including transcriptional, post-transcriptional, epigenetic, microenvironment (TME), epithelial-mesenchymal transition (EMT) factors. Numerous signaling pathways were found to be involved the regulatory network CSCs. The maintenance CSC characteristics plays pivotal role driving CSC-associated metastasis conferring resistance therapy. Consequently, CSCs have emerged promising targets cancer treatment. To date, researchers developed several anticancer agents tailored specifically target CSCs, with some these treatment strategies currently undergoing preclinical or clinical trials. In this review, we outline origin biological explore networks governing discuss implicated investigate influential factors contributing therapy Finally, offer insights into designed eliminate

Language: Английский

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Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(4), P. 607 - 618

Published: March 16, 2023

Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated transcriptomic epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% interpatient molecular differences. Instead, MESOMICS project paves way morphomolecular MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response CpG island methylator profile. We show these dimensions are complementary, capture major differences delimited by extreme phenotypes that—in case interdependent morphology adapted response—reflect specialization. These findings unearth interplay between functional biology its genomic history, provide insights into variations observed in behavior patients MPM.

Language: Английский

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Hybrid Graphene‐Gold Nanoparticle‐Based Nucleic Acid Conjugates for Cancer‐Specific Multimodal Imaging and Combined Therapeutics

Advanced Functional Materials, Journal Year: 2020, Volume and Issue: 31(5)

Published: Oct. 23, 2020

Nanoparticle-based nucleic acid conjugates (NP-NACs) hold great promise for theragnostic (diagnostic and therapeutic) applications. However, several limitations have hindered the realization of their full potential in clinical treatment cancer other diseases. In diagnosis, NP-NACs, combined with conventional optical sensing systems, been applied detection

Language: Английский

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