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  • 1
    Online Resource
    Online Resource
    XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary
    Springer Science and Business Media LLC ; 2020
    In:  Oncogene Vol. 39, No. 17 ( 2020-04-23), p. 3541-3554
    Details
    In: Oncogene, Springer Science and Business Media LLC, Vol. 39, No. 17 ( 2020-04-23), p. 3541-3554
    Abstract: Molecular characteristics of carcinoma arising from mature cystic teratoma of the ovary (MCT) remain unclear due to its rarity. We analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. By epidermis-associated pathways activity based on gene set enrichment analysis, 1030 SCCs were divided into two groups: epidermis-signature high (head and neck, esophagus, and skin) and low (cervix, lung, and MCT). In addition to pan-SCC transcriptome analysis, cytokeratin profiling based on immunohistochemistry in the independent samples of 21 MCT-SCCs clarified that MCT-SCC dominantly expressed CK18, suggesting the origin of MCT-SCC was columnar epithelium. Subsequently, we investigated differentially expressed genes in MCT-SCCs compared with different SCCs and identified XCL1 was specifically overexpressed in MCT-SCCs. Through immunohistochemistry analysis, we identified XCL1 expression on tumor cells in 13/24 (54%) of MCT-SCCs but not in MCTs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 produced by tumor cells may induce PD1/PD-L1 interaction and dysfunction of CD8-positive T cells in tumor microenvironment. XCL1 expression may be a novel biomarker for malignant transformation of MCT into SCC and a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.
    Type of Medium: Online Resource
    ISSN: 0950-9232 , 1476-5594
    URL: Article
    DOI: 10.1038/s41388-020-1237-0
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2008404-3
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  • 2
    Online Resource
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    Statistical Evaluation of Total Expiratory Breath Samples Collected throughout a Year: Reproducibility and Applicability toward Olfactory Sensor-Based Breath Diagnostics
    MDPI AG ; 2021
    In:  Sensors Vol. 21, No. 14 ( 2021-07-11), p. 4742-
    Details
    In: Sensors, MDPI AG, Vol. 21, No. 14 ( 2021-07-11), p. 4742-
    Abstract: The endogenous volatile organic compounds (VOCs) in exhaled breath can be promising biomarkers for various diseases including cancers. An olfactory sensor has a possibility for extracting a specific feature from collective variations of the related VOCs with a certain health condition. For this approach, it is important to establish a feasible protocol for sampling exhaled breath in practical conditions to provide reproducible signal features. Here we report a robust protocol for the breath analysis, focusing on total expiratory breath measured by a Membrane-type Surface stress Sensor (MSS), which possesses practical characteristics for artificial olfactory systems. To assess its reproducibility, 83 exhaled breath samples were collected from one subject throughout more than a year. It has been confirmed that the reduction of humidity effects on the sensing signals either by controlling the humidity of purging room air or by normalizing the signal intensities leads to reasonable reproducibility verified by statistical analyses. We have also demonstrated the applicability of the protocol for detecting a target material by discriminating exhaled breaths collected from different subjects with pre- and post-alcohol ingestion on different occasions. This simple yet reproducible protocol based on the total expiratory breath measured by the MSS olfactory sensors will contribute to exploring the possibilities of clinical applications of breath diagnostics.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    URL: Article
    DOI: 10.3390/s21144742
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2052857-7
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  • 3
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    Online Resource
    Biological significance of KRAS mutant allele expression in ovarian endometriosis
    Wiley ; 2021
    In:  Cancer Science Vol. 112, No. 5 ( 2021-05), p. 2020-2032
    Details
    In: Cancer Science, Wiley, Vol. 112, No. 5 ( 2021-05), p. 2020-2032
    Abstract: KRAS is the most frequently mutated in ovarian endometriosis. However, it is unclear whether the KRAS mutant allele's mRNA is expressed and plays a biological role in ovarian endometriosis. Here, we performed mutation‐specific RNA in situ hybridization to evaluate mutant allele expression of KRAS p.G12V, the most frequently detected mutation in ovarian endometriosis in our previous study, in formalin‐fixed paraffin‐embedded tissue (FFPE) samples of ovarian endometriosis, cancer cell lines, and ovarian cancers. First, we verified that mutant or wild‐type allele of KRAS were expressed in all 5 cancer cell lines and 9 ovarian cancer cases corresponding to the mutation status. Next, we applied this assay to 26 ovarian endometriosis cases, and observed mutant allele expression of KRAS p.G12V in 10 cases. Mutant or wild‐type allele of KRAS were expressed in line with mutation status in 12 available endometriosis cases for which KRAS gene sequence was determined. Comparison of clinical features between ovarian endometriosis with KRAS p.G12V mutant allele expression and with KRAS wild‐type showed that KRAS p.G12V mutant allele expression was significantly associated with inflammation in ovarian endometriosis. Finally, we assessed the spatial distribution of KRAS mutant allele expression in 5 endometriosis cases by performing multiregional sampling. Intratumor heterogeneity of KRAS mutant allele expression was observed in two endometriosis cases, whereas the spatial distribution of KRAS p.G12V mutation signals were diffuse and homogenous in ovarian cancer. In conclusion, evaluation of oncogene mutant expression will be useful for clarifying the biological significance of oncogene mutations in benign tumors.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    URL: Article
    DOI: 10.1111/cas.v112.5
    DOI: 10.1111/cas.14871
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2115647-5
    detail.hit.zdb_id: 2111204-6
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  • 4
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    Spatial genomic diversity associated with APOBEC mutagenesis in squamous cell carcinoma arising from ovarian teratoma
    Wiley ; 2023
    In:  Cancer Science Vol. 114, No. 5 ( 2023-05), p. 2145-2157
    Details
    In: Cancer Science, Wiley, Vol. 114, No. 5 ( 2023-05), p. 2145-2157
    Abstract: Although the gross and microscopic features of squamous cell carcinoma arising from ovarian mature cystic teratoma (MCT‐SCC) vary from case to case, the spatial spreading of genomic alterations within the tumor remains unclear. To clarify the spatial genomic diversity in MCT‐SCCs, we performed whole‐exome sequencing by collecting 16 samples from histologically different parts of two MCT‐SCCs. Both cases showed histological diversity within the tumors (case 1: nonkeratinizing and keratinizing SCC and case 2: nonkeratinizing SCC and anaplastic carcinoma) and had different somatic mutation profiles by histological findings. Mutation signature analysis revealed a significantly enriched apolipoprotein B mRNA editing enzyme catalytic subunit (APOBEC) signature at all sites. Intriguingly, the spread of genomic alterations within the tumor and the clonal evolution patterns from nonmalignant epithelium to cancer sites differed between cases. TP53 mutation and copy number alterations were widespread at all sites, including the nonmalignant epithelium, in case 1. Keratinizing and nonkeratinizing SCCs were differentiated by the occurrence of unique somatic mutations from a common ancestral clone. In contrast, the nonmalignant epithelium showed almost no somatic mutations in case 2. TP53 mutation and the copy number alteration similarities were observed only in nonkeratinizing SCC samples. Nonkeratinizing SCC and anaplastic carcinoma shared almost no somatic mutations, suggesting that each locally and independently arose in the MCT. We demonstrated that two MCT‐SCCs with different histologic findings were highly heterogeneous tumors with clearly different clones associated with APOBEC‐mediated mutagenesis, suggesting the importance of evaluating intratumor histological and genetic heterogeneity among multiple sites of MCT‐SCC.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    URL: Article
    DOI: 10.1111/cas.v114.5
    DOI: 10.1111/cas.15754
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2115647-5
    detail.hit.zdb_id: 2111204-6
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  • 5
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    The New Era of Three-Dimensional Histoarchitecture of the Human Endometrium
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 8 ( 2021-07-25), p. 713-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 8 ( 2021-07-25), p. 713-
    Abstract: The histology of the endometrium has traditionally been established by observation of two-dimensional (2D) pathological sections. However, because human endometrial glands exhibit coiling and branching morphology, it is extremely difficult to obtain an entire image of the glands by 2D observation. In recent years, the development of three-dimensional (3D) reconstruction of serial pathological sections by computer and whole-mount imaging technology using tissue clearing methods with high-resolution fluorescence microscopy has enabled us to observe the 3D histoarchitecture of tissues. As a result, 3D imaging has revealed that human endometrial glands form a plexus network in the basalis, similar to the rhizome of grass, whereas mouse uterine glands are single branched tubular glands. This review summarizes the relevant literature on the 3D structure of mouse and human endometrium and discusses the significance of the rhizome structure in the human endometrium and the expected role of understanding the 3D tissue structure in future applications to systems biology.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11080713
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 6
    Online Resource
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    Therapeutic Strategies Focused on Cancer-Associated Hypercoagulation for Ovarian Clear Cell Carcinoma
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 9 ( 2022-04-24), p. 2125-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 9 ( 2022-04-24), p. 2125-
    Abstract: Ovarian clear cell carcinoma (OCCC) is associated with chemotherapy resistance and poor prognosis, especially in advanced cases. Although comprehensive genomic analyses have clarified the significance of genomic alterations such as ARID1A and PIK3CA mutations in OCCC, therapeutic strategies based on genomic alterations have not been confirmed. On the other hand, OCCC is clinically characterized by a high incidence of thromboembolism. Moreover, OCCC specifically shows high expression of tissue factor and interleukin-6, which play a critical role in cancer-associated hypercoagulation and may be induced by OCCC-specific genetic alterations or the endometriosis-related tumor microenvironment. In this review, we focused on the association between cancer-associated hypercoagulation and molecular biology in OCCC. Moreover, we reviewed the effectiveness of candidate drugs targeting hypercoagulation, such as tissue factor- or interleukin-6-targeting drugs, anti-inflammatory drugs, anti-hypoxia signaling drugs, anticoagulants, and combined immunotherapy with these drugs for OCCC. This review is expected to contribute to novel basic research and clinical trials for the prevention, early detection, and treatment of OCCC focused on hypercoagulation.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14092125
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Three-dimensional understanding of the morphological complexity of the human uterine endometrium
    Elsevier BV ; 2021
    In:  iScience Vol. 24, No. 4 ( 2021-04), p. 102258-
    Details
    In: iScience, Elsevier BV, Vol. 24, No. 4 ( 2021-04), p. 102258-
    Type of Medium: Online Resource
    ISSN: 2589-0042
    URL: Article
    DOI: 10.1016/j.isci.2021.102258
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2927064-9
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  • 8
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    Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-02-17)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-02-17)
    Abstract: It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we sequence 1311 endometrial glands from 37 women. By collecting endometrial glands from different parts of the endometrium, we show that multiple glands with the same somatic mutations occupy substantial areas of the endometrium. We demonstrate that “rhizome structures”, in which the basal glands run horizontally along the muscular layer and multiple vertical glands rise from the basal gland, originate from the same ancestral clone. Moreover, mutant clones detected in the vertical glands diversify by acquiring additional mutations. These results suggest that clonal expansions through the rhizome structures are involved in the mechanism by which mutant clones extend their territories. Furthermore, we show clonal expansions and copy neutral loss-of-heterozygosity events occur early in life, suggesting such events can be tolerated many years in the normal endometrium. Our results of the evolutionary dynamics of mutant clones in the human endometrium will lead to a better understanding of the mechanisms of endometrial regeneration during the menstrual cycle and the development of therapies for the prevention and treatment of endometrium-related diseases.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-28568-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 9
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    How Does Endometriosis Lead to Ovarian Cancer? The Molecular Mechanism of Endometriosis-Associated Ovarian Cancer Development
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 6 ( 2021-03-22), p. 1439-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 6 ( 2021-03-22), p. 1439-
    Abstract: Numerous epidemiological and histopathological studies support the notion that clear cell and endometrioid carcinomas derive from ovarian endometriosis. Accordingly, these histologic types are referred to as “endometriosis-associated ovarian cancer” (EAOC). Although the uterine endometrium is also considered an origin of endometriosis, the molecular mechanism involved in transformation of the uterine endometrium to EAOC via ovarian endometriosis has not yet been clarified. Recent studies based on high-throughput sequencing technology have revealed that cancer-associated gene mutations frequently identified in EAOC may exist in the normal uterine endometrial epithelium and ovarian endometriotic epithelium. The continuum of genomic alterations from the uterine endometrium to endometriosis and EAOC has been described, though the significance of cancer-associated gene mutations in the uterine endometrium or endometriosis remains unclear. In this review, we summarize current knowledge regarding the molecular characteristics of the uterine endometrium, endometriosis, and EAOC and discuss the molecular mechanism of cancer development from the normal endometrium through endometriosis in an effort to prevent EAOC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13061439
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Visualization of Flow‐Induced Strain Using Structural Color in Channel‐Free Polydimethylsiloxane Devices
    Wiley ; 2023
    In:  Advanced Science Vol. 10, No. 1 ( 2023-01)
    Details
    In: Advanced Science, Wiley, Vol. 10, No. 1 ( 2023-01)
    Abstract: Measuring flow of gases is of fundamental importance yet is typically done with complex equipment. There is, therefore, a longstanding need for a simple and inexpensive means of flow measurement. Here, gas flow is measured using an extremely simple device that consists of an Ar plasma‐treated polydimethylsiloxane (PDMS) slab adhered on a glass substrate with a tight seal. This device does not even have a channel, instead, gas can flow between the PDMS and the glass by deforming the PDMS wall, in other words, by making an interstice as a temporary path for the flow. The formation of the temporary path results in a compressive bending stress at the inner wall of the path, which leads to the formation of well‐ordered wrinkles, and hence, the emergence of structural color that changes the optical transmittance of the device. Although it is very simple, this setup works sufficiently well to measure arbitrary gases and analyzes their flow rates, densities, and viscosities based on the change in color. It is also demonstrated that this technique is applicable to the flow‐induced display of a pattern such as a logo for advanced applications.
    Type of Medium: Online Resource
    ISSN: 2198-3844 , 2198-3844
    URL: Issue
    URL: Article
    DOI: 10.1002/advs.v10.1
    DOI: 10.1002/advs.202204310
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2808093-2
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