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- Hoshino, Ayuko, et al.
(author)
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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
- 2020
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In: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
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Journal article (peer-reviewed)abstract
- There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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- Vickman, R. E., et al.
(author)
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Deconstructing tumor heterogeneity : The stromal perspective
- 2020
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In: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 11:40, s. 3621-3632
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Journal article (peer-reviewed)abstract
- Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive versus suppressive stroma and how cellular composition and function may be altered during disease progression. It also highlighted microenvironment-centered mechanisms dictating indolence or aggressiveness of early lesions and how spatial geography impacts stromal attributes and function. The prognostic and therapeutic implications as well as potential vulnerabilities within the heterogeneous tumor microenvironment were also discussed. These broad topics were included in this workshop as an effort to identify current challenges and knowledge gaps in the field. Copyright:
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- Ilyakov, I., et al.
(author)
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Terahertz-wave decoding of femtosecond extreme-ultraviolet light pulses
- 2022
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In: Optica. - : Optica Publishing Group. - 2334-2536. ; 9:5, s. 545-550
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Journal article (peer-reviewed)abstract
- In recent years, femtosecond extreme-ultraviolet (XUV) and x-ray pulses from free-electron lasers have developed into important probes to monitor processes and dynamics in matter on femtosecond-time and angstrom-length scales. With the rapid progress of versatile ultrafast x-ray spectroscopy techniques and more sophisticated data analysis tools, accurate single-pulse information on the arrival time, duration, and shape of the probing x-ray and XUV pulses becomes essential. Here, we demonstrate that XUV pulses can be converted into terahertz electromagnetic pulses using a spintronic terahertz emitter. We observe that the duration, arrival time, and energy of each individual XUV pulse is encoded in the waveform of the associated terahertz pulses, and thus can be readily deduced from single-shot terahertz time-domain detection.
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- J.Lindner, A.Scherz, P.Poulopoulos, C.Rudt, A.N.Anisimov, H.Wende, K.Baberschke, P.Blomquist, R.Wäppling, F.Wilhelm, N.B.Brookes
(author)
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Ultrathin Fe-limit in Fe/V(001) superlattices
- 2003
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In: Journal of Magnetism and Magnetic Materials. ; 256:1-3, s. 404-411
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Journal article (peer-reviewed)
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- Menushenkov, A. P., et al.
(author)
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Direct evidence of real-space pairing in BaBiO3
- 2024
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In: Physical Review Research. - : American Physical Society. - 2643-1564. ; 6:2
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Journal article (peer-reviewed)abstract
- The parent compound BaBiO3 of bismuthate high-temperature superconductors (HTSCs) BaBi(Pb)O3 and Ba(K)BiO3 with perovskitelike structure exhibits unusual electronic and structural properties, which can be satisfactorily explained if we assume that all charge carriers are in the paired state. However, the prior experiments and the first-principle calculations only indirectly indicate the existence of paired charge carriers in BaBiO3. In this work, we report the direct evidence of initially paired electrons and holes in the upper antibonding Bi 6s-O 2p sigma* orbital of the neighboring octahedral complexes in the ground state of BaBiO3 using the time-resolved x-ray absorption spectroscopy (XAS) to monitor the electron dynamics after the femtosecond resonant 633 nm laser excitation. We observe strong changes in the oxygen K-edge XAS preedge region, defined by the Bi 6s-O 2p sigma* orbitals. We interpret them as a fast (<= 0.3 ps) breaking of charge carrier pairs and slower (0.3-0.8 ps) lattice rearrangement from the distorted monoclinic structure into the new metastable state with a cubic lattice, which persists at least up to 60 ps after the excitation. Analysis of the intermediate state at the fast excitation shows that the bond disproportionation and monoclinic distortion of BaBiO3 structure are energetically favorable due to the charge carrier pairing. Thus the compound BaBiO3 forms a new quantum state that we define as a local pair density wave. Taking into account a large number of similarities between bismuthate and cuprate high-temperature superconductors, we believe that our work will give a new impetus to understanding the nature of superconductivity in perovskite HTSCs.
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- Shaashua, Lee, et al.
(author)
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BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling
- 2022
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In: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Tumors initiate by mutations in cancer cells, and progress through interactions of the cancer cells with non-malignant cells of the tumor microenvironment. Major players in the tumor microenvironment are cancer-associated fibroblasts (CAFs), which support tumor malignancy, and comprise up to 90% of the tumor mass in pancreatic cancer. CAFs are transcriptionally rewired by cancer cells. Whether this rewiring is differentially affected by different mutations in cancer cells is largely unknown. Here we address this question by dissecting the stromal landscape of BRCA-mutated and BRCA Wild-type pancreatic ductal adenocarcinoma. We comprehensively analyze pancreatic cancer samples from 42 patients, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA Wild-type tumors. In particular, we detect an increase in a subset of immune-regulatory clusterin-positive CAFs in BRCA-mutated tumors. Using cancer organoids and mouse models we show that this process is mediated through activation of heat-shock factor 1, the transcriptional regulator of clusterin. Our findings unravel a dimension of stromal heterogeneity influenced by germline mutations in cancer cells, with direct implications for clinical research. Cancer-associated fibroblasts are transcriptionally rewired by signals from the cancer cells, resulting in heterogeneous populations. Here the authors show that loss of BRCA function in pancreatic cancer cells leads to HSF1-dependent accumulation of immune-regulatory clusterin-positive cancer associated fibroblasts.
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