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  • 1
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    Online Resource
    A new calibration method for charm jet identification validated with proton-proton collision events at √s = 13 TeV
    IOP Publishing ; 2022
    In:  Journal of Instrumentation Vol. 17, No. 03 ( 2022-03-01), p. P03014-
    Details
    In: Journal of Instrumentation, IOP Publishing, Vol. 17, No. 03 ( 2022-03-01), p. P03014-
    Abstract: Many measurements at the LHC require efficient identification of heavy-flavour jets, i.e. jets originating from bottom (b) or charm (c) quarks. An overview of the algorithms used to identify c jets is described and a novel method to calibrate them is presented. This new method adjusts the entire distributions of the outputs obtained when the algorithms are applied to jets of different flavours. It is based on an iterative approach exploiting three distinct control regions that are enriched with either b jets, c jets, or light-flavour and gluon jets. Results are presented in the form of correction factors evaluated using proton-proton collision data with an integrated luminosity of 41.5 fb -1 at  √s = 13 TeV, collected by the CMS experiment in 2017. The closure of the method is tested by applying the measured correction factors on simulated data sets and checking the agreement between the adjusted simulation and collision data. Furthermore, a validation is performed by testing the method on pseudodata, which emulate various mismodelling conditions. The calibrated results enable the use of the full distributions of heavy-flavour identification algorithm outputs, e.g. as inputs to machine-learning models. Thus, they are expected to increase the sensitivity of future physics analyses.
    Type of Medium: Online Resource
    ISSN: 1748-0221
    URL: Article
    DOI: 10.1088/1748-0221/17/03/P03014
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2022
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  • 2
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    Classification of molecular subtypes of high-grade serous ovarian cancer by MALDI-Imaging.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e17544-e17544
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e17544-e17544
    Abstract: e17544 Background: High-grade serous ovarian cancer (HGSOC) can be separated by gene expression profiling into four molecular subtypes with clear correlation of the clinical outcome. However, these gene signatures have not been implemented in clinical practice to stratify patients for targeted therapy. This is mainly due to a lack of easy, cost-effective and reproducible methods, as well as the high heterogeneity of HGSOC. Hence, we aimed to examine the potential of unsupervised matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to stratify patients, which might benefit from targeted therapeutic strategies. Methods: Molecular subtyping of paraffin-embedded tissue samples from 279 HGSOC patients was performed by NanoString analysis (ground truth labeling). Next, we applied MALDI-IMS, a novel technology to identify distinct mass profiles on the same paraffin-embedded tissue sections paired with machine learning algorithms to identify HGSOC subtypes by proteomic signature. Finally, we devised a novel strategy to annotate spectra of stromal origin. Results: We elucidated a MALDI-derived proteomic signature (135 peptides) able to classify HGSOC subtypes. Random forest classifiers achieved an area under the curve (AUC) of 0.983. Furthermore, we demonstrated that the exclusion of stroma associated spectra provides tangible improvements to classification quality (AUC = 0.988). False discovery rates (FDR) were reduced from 10.2% to 8.0%. Finally, novel MALDI-based stroma annotation achieved near-perfect classifications (AUC = 0.999, FDR 〈 1.0%). Conclusions: Here, we present a concept integrating MALDI-IMS with machine learning algorithms to classify patients according to distinct molecular subtypes of HGSOC. This has great potential to assign patients for targeted therapies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e17544
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 3
    Online Resource
    Online Resource
    Classification of Molecular Subtypes of High-Grade Serous Ovarian Cancer by MALDI-Imaging
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 7 ( 2021-03-25), p. 1512-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 7 ( 2021-03-25), p. 1512-
    Abstract: Despite the correlation of clinical outcome and molecular subtypes of high-grade serous ovarian cancer (HGSOC), contemporary gene expression signatures have not been implemented in clinical practice to stratify patients for targeted therapy. Hence, we aimed to examine the potential of unsupervised matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to stratify patients who might benefit from targeted therapeutic strategies. Molecular subtyping of paraffin-embedded tissue samples from 279 HGSOC patients was performed by NanoString analysis (ground truth labeling). Next, we applied MALDI-IMS paired with machine-learning algorithms to identify distinct mass profiles on the same paraffin-embedded tissue sections and distinguish HGSOC subtypes by proteomic signature. Finally, we devised a novel approach to annotate spectra of stromal origin. We elucidated a MALDI-derived proteomic signature (135 peptides) able to classify HGSOC subtypes. Random forest classifiers achieved an area under the curve (AUC) of 0.983. Furthermore, we demonstrated that the exclusion of stroma-associated spectra provides tangible improvements to classification quality (AUC = 0.988). Moreover, novel MALDI-based stroma annotation achieved near-perfect classifications (AUC = 0.999). Here, we present a concept integrating MALDI-IMS with machine-learning algorithms to classify patients according to distinct molecular subtypes of HGSOC. This has great potential to assign patients for personalized treatment.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13071512
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 4
    Online Resource
    Online Resource
    Short term outcome in infants with birth weights lt; 1750 g born to mothers with HELLP syndrome
    Walter de Gruyter GmbH ; 1992
    In:  jpme Vol. 20, No. 1 ( 1992), p. 25-28
    Details
    In: jpme, Walter de Gruyter GmbH, Vol. 20, No. 1 ( 1992), p. 25-28
    Type of Medium: Online Resource
    ISSN: 0300-5577 , 1619-3997
    URL: Article
    DOI: 10.1515/jpme.1992.20.1.25
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1992
    detail.hit.zdb_id: 1467968-1
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  • 5
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    Online Resource
    Fully Immersible Subcortical Neural Probes With Modular Architecture and a Delta-Sigma ADC Integrated Under Each Electrode for Parallel Readout of 144 Recording Sites
    Institute of Electrical and Electronics Engineers (IEEE) ; 2018
    In:  IEEE Journal of Solid-State Circuits Vol. 53, No. 11 ( 2018-11), p. 3111-3125
    Details
    In: IEEE Journal of Solid-State Circuits, Institute of Electrical and Electronics Engineers (IEEE), Vol. 53, No. 11 ( 2018-11), p. 3111-3125
    Type of Medium: Online Resource
    ISSN: 0018-9200 , 1558-173X
    URL: Article
    DOI: 10.1109/JSSC.2018.2873180
    Language: Unknown
    Publisher: Institute of Electrical and Electronics Engineers (IEEE)
    Publication Date: 2018
    detail.hit.zdb_id: 240580-5
    detail.hit.zdb_id: 2040287-9
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  • 6
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    Online Resource
    The role of tumor associated macrophages in ovarian cancer
    Elsevier BV ; 2014
    In:  Gynecologic Oncology Vol. 135, No. 2 ( 2014-11), p. 385-
    Details
    In: Gynecologic Oncology, Elsevier BV, Vol. 135, No. 2 ( 2014-11), p. 385-
    Type of Medium: Online Resource
    ISSN: 0090-8258
    URL: Article
    DOI: 10.1016/j.ygyno.2014.07.016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 1467974-7
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  • 7
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    Imaging of Tumor-Associated Macrophages in a Transgenic Mouse Model of Orthotopic Ovarian Cancer
    Springer Science and Business Media LLC ; 2017
    In:  Molecular Imaging and Biology Vol. 19, No. 5 ( 2017-10), p. 694-702
    Details
    In: Molecular Imaging and Biology, Springer Science and Business Media LLC, Vol. 19, No. 5 ( 2017-10), p. 694-702
    Type of Medium: Online Resource
    ISSN: 1536-1632 , 1860-2002
    URL: Article
    DOI: 10.1007/s11307-017-1061-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2079211-6
    SSG: 12
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  • 8
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    Abstract 3202: Single cell analysis of ascites macrophages in ovarian cancer
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 3202-3202
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 3202-3202
    Abstract: Macrophages compose a major part of the tumor microenvironment (TME) in several types of cancer, including ovarian cancer [1]. Studies have shown that a high percentage of tumor associated macrophages (TAMs) correlates with a poor prognosis in ovarian cancer [2] , due to the crucial role of TAMs in promoting tumor growth and angiogenesis [3,4]. Yet not much investigation has been executed to reveal the function of macrophages in ovarian cancer ascites, a hallmark of ovarian cancer. Previous gene expression analysis in TAMs often used bulk samples [5,6]. However, due to the complexity of the peritoneal environment, this approach had the effect of “dampening” rare and potentially informative signals from a heterogeneous population such as ascites macrophages. Therefore, we resorted to single-cell expression analysis to dissect the heterogeneity of ascites macrophages. Recent breakthroughs in single cell RNA-seq techniques have made it more cost effective to process a large number of samples at single cell resolutions. Here we used Fluidigm's Single-Cell Auto Prep System, a state-of-art technology for automate single cell cDNA synthesis [7]. We sequenced single ascites macrophages from ID8 murine ovarian cancer model and single alternatively activated bone marrow derived macrophages (BMDM-M2). When comparing the single cell expression profiles of ascites macrophages to BMDM using principle component analysis (PCA), we observed that the ascites macrophages scattered broadly and could be further divided into two groups, whereas BMDM were tightly clustered into one group. Furthermore, gene oncology (GO) analysis of highly expressed genes in each group revealed that ascites macrophages had a distinct gene expression profile from BMDM, highlighting the metabolic pathways, especially catabolic process. We are currently working on validating these findings in human patients with ovarian carcinoma. In summary, this work sheds light on the understanding of the role of ascites macrophages in ovarian cancer. 1. Qian BZ, Pollard JW. Cell. 2010;141:39-51. 2. He YF, Zhang MY, Wu X, et al. PLoS One. 2013;8:e79769. 3. Mantovani A, Germano G, Marchesi F, et al. Eur J Immunol 2011;41:2522-25. 4. Murray PJ, Wynn TA. Nat Rev Immunol, 2011;11:723-37. 5. The Cancer Genome Atlas Research Network. Nature. 2014;511:543-50. 6. The Cancer Genome Atlas Research Network. Nature. 2014;513:202-9. 7. Wu AR, Neff NF, Kalisky T, et al. Nat Methods. 2014;11:41-6. Citation Format: Huanhuan Mahsa He, Feiqiao Brian Yu, Stephen R. Quake, Oliver Dorigo. Single cell analysis of ascites macrophages in ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3202. doi:10.1158/1538-7445.AM2015-3202
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-3202
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 9
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    Abstract 5351: FLASH irradiation enhances the therapeutic index of abdominal radiotherapy in mice
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5351-5351
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5351-5351
    Abstract: Radiation therapy is the most effective cytotoxic cancer therapy available for the treatment of localized tumors. However, radiation-induced toxicity to normal tissues limits the radiation dose and therefore the curative potential of radiotherapy. In particular, the highly radiosensitive intestine greatly limits the use of radiation for patients with intra-abdominal tumor diseases including women with ovarian cancer. Here we sought to investigate the safety and efficacy of FLASH radiation therapy in the treatment of widespread ovarian cancer peritoneal metastases. We performed abdominal irradiation on healthy and ovarian tumor-bearing mice at conventional (CONV, (0.07 Gy/sec)) or FLASH (200 Gy/sec) dose rates and examined gut function by stool counts, DNA damage in crypt cells by γ-H2AX staining, cell death and proliferation by TUNEL/ caspase-3 staining and BrdU immunohistochemistry respectively. We report that ultrahigh dose rate FLASH irradiation causes significantly less radiation-induced intestinal injury in both healthy and tumor-bearing mice compared to CONV dose rate irradiation. Abdominal FLASH reduced the mortality from gastrointestinal syndrome, preserved gut function and epithelial integrity as reflected by their stool counts and FITC-Dextran analysis. In addition, we found decreased cell death and enhanced proliferation of crypt base columnar cells (CBCs) following FLASH irradiation in comparison to CONV irradiation. We also detected reduced number of γ-H2AX foci in crypt cells indicating less DNA damage and/or increased DNA repair after FLASH compared to CONV irradiation. Importantly, FLASH and CONV irradiation have similar efficacy in the reduction of ovarian cancer peritoneal metastases. These findings suggest that FLASH irradiation has biological advantages compared to conventional dose rate irradiation in reducing radiation-induced intestinal injury within the irradiation field and therefore may be an effective strategy to enhance the therapeutic index of radiotherapy for the treatment of abdominal and pelvic tumor disease. Citation Format: Suchitra Natarajan, Karen Levy, Jinghui Wang, Stephanie Chow, Joshua Eggold, Phoebe Loo, Rakesh Manjappa, Frederick M. Lartey, Emil Schüler, Lawrie Skinner, Marjan Rafat, Ryan Ko, Anna Kim, Duaa Al Rawi, Rie von Eyben, Oliver Dorigo, Kerriann M. Casey, Edward E. Graves, Karl Bush, Amy S. Yu, Albert C. Koong, Peter G. Maxim, Billy W. Loo, Erinn B. Rankin. FLASH irradiation enhances the therapeutic index of abdominal radiotherapy in mice [abstract] . In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5351.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-5351
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 10
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    Online Resource
    Abstract LB-364: Mesothelial cells promote ovarian cancer stemness and chemoresistance through osteopontin paracrine signaling
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. LB-364-LB-364
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. LB-364-LB-364
    Abstract: Aims: As mesothelial cells are a major stromal component of the ovarian cancer metastatic microenvironment, in this study we investigated the role of ovarian cancer-associated mesothelial cells (CAMs) on cancer responsiveness to chemotherapy and intrinsic-related cancer stemness properties. Methods: Indirect co-culture system that enables medium exchange between human primary serous-type ovarian cancer cells and primary CAMs isolated from patient ascites was employed, and these co-cultured cancer cells were subsequently grafted subcutaneously to NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice and received serial cisplatin challenges, or checked by Annexin V apoptosis assays and cell viability assays to determine chemosensitivity. In addition, patient derived tumor organoid cultures were compared between the addition of control and its paired primary CAM conditioned medium. In vivo limiting dilution assays and sphere formation assays were utilized to evaluate CAM regulated cancer stemness properties. Finally, a cytokine array on CAM conditioned medium was performed to identify the secreted factors mediating phenotypical changes, and RNA-sequencing analysis of co-cultured cancer cells was conducted to uncover the major events that underlie changed chemo-responsiveness. Results: Cancer cell response to platium-based chemotherapy was inhibited after indirect CAM co-culture or CAM conditioned medium priming, as evidenced both in vivo and in vitro. Organoid formation was drastically enhanced with the supplement of paired CAM conditioned medium, while no tumor organoid was well formed in control medium. These organoids in CAM conditioned medium group are positive for cancer stem cell markers. Correspondingly, CAMs induced a cancer stemness phenotype, as shown by increased tumor formation rate in limiting dilution assays and by strengthened sphere formation abilities in sphere formation assays. Through a cytokine array and functional validations, we pinpointed soluble osteopontin as a key mediator of CAM-responsive cancer stemness and chemoresistance, and it initiates paracrine signaling through the CD44 receptor on cancer cells. RNA-sequencing of ovarian cancer cells primed with CAMs revealed overexpression of multi-drug resistance-related ABC-binding cassette transporters (ABC transporters). Lastly, genetic inhibition of osteopontin in CAMs with shRNA constructs and therapeutic targeting with an anti-osteopontin neutralizing antibody reduced cancer stemness and chemoresistance. Conclusions: We demonstrated that CAMs promote ovarian cancer chemoresistance and tumor formation by establishing a cancer stem cell niche. Importantly, our study identified paracrine osteopontin signaling as a critical mediator of chemoresistance and stemness, and targeting osteopontin from CAMs holds the potential to restore ovarian cancer chemosensitivity. Citation Format: Jin Qian, Bauer LeSavage, Chenkai Ma, Suchitra Natarajan, Joshua Eggold, Kelsea Hubka, Yiren Xiao, Katherine Fuh, Venkatesh Krishnan, Annika Enejder, Sarah Heilshorn, Oliver Dorigo, Erinn Rankin. Mesothelial cells promote ovarian cancer stemness and chemoresistance through osteopontin paracrine signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-364.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-LB-364
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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