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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-10-15)
    Abstract: Spatially-resolved molecular profiling by immunostaining tissue sections is a key feature in cancer diagnosis, subtyping, and treatment, where it complements routine histopathological evaluation by clarifying tumor phenotypes. In this work, we present a deep learning-based method called speedy histological-to-immunofluorescent translation (SHIFT) which takes histologic images of hematoxylin and eosin (H & E)-stained tissue as input, then in near-real time returns inferred virtual immunofluorescence (IF) images that estimate the underlying distribution of the tumor cell marker pan-cytokeratin (panCK). To build a dataset suitable for learning this task, we developed a serial staining protocol which allows IF and H & E images from the same tissue to be spatially registered. We show that deep learning-extracted morphological feature representations of histological images can guide representative sample selection, which improved SHIFT generalizability in a small but heterogenous set of human pancreatic cancer samples. With validation in larger cohorts, SHIFT could serve as an efficient preliminary, auxiliary, or substitute for panCK IF by delivering virtual panCK IF images for a fraction of the cost and in a fraction of the time required by traditional IF.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 2
    Online Resource
    Online Resource
    British Institute of Radiology ; 2015
    In:  BJR|case reports ( 2015-06-08), p. 20150100-
    In: BJR|case reports, British Institute of Radiology, ( 2015-06-08), p. 20150100-
    Type of Medium: Online Resource
    ISSN: 2055-7159
    Language: English
    Publisher: British Institute of Radiology
    Publication Date: 2015
    detail.hit.zdb_id: 2912937-0
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  • 3
    Online Resource
    Online Resource
    Archives of Pathology and Laboratory Medicine ; 2016
    In:  Archives of Pathology & Laboratory Medicine Vol. 140, No. 9 ( 2016-09-01), p. 910-925
    In: Archives of Pathology & Laboratory Medicine, Archives of Pathology and Laboratory Medicine, Vol. 140, No. 9 ( 2016-09-01), p. 910-925
    Abstract: Context.—Immunohistochemical analysis of tissue biopsy specimens is a crucial tool in diagnosis of both rejection and infection in patients with solid organ transplants. In the past 15 years, the concept of antibody-mediated rejection has been refined, and diagnostic criteria have been codified in renal, heart, pancreas, and lung allografts (with studies ongoing in liver, small intestine, and composite grafts), all of which include immunoanalysis for the complement split product C4d. Objectives.—To review the general concepts of C4d biology and immunoanalysis, followed by organ-allograft–specific data, and interpretative nuances for kidney, pancreas, and heart, with discussion of early literature for lung and liver biopsies. Additionally, practical applications and limitations of immunostains for infectious organisms (Polyomavirus, Adenoviridae [adenovirus], and the herpes virus family, including Herpes simplex virus, Cytomegalovirus, Human herpes virus 8, and Epstein-Barr virus) are reviewed in the context of transplant recipients. Data Sources.—Our experience and published primary and review literature. Conclusions.—Immunohistochemistry continues to have an important role in transplant pathology, most notably C4d staining in assessment of antibody-mediated rejection and assessment of viral pathogens in tissue. In all facets of transplant pathology, correlation of morphology with special studies and clinical data is critical, as is close communication with the transplant team.
    Type of Medium: Online Resource
    ISSN: 1543-2165 , 0003-9985
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    Language: English
    Publisher: Archives of Pathology and Laboratory Medicine
    Publication Date: 2016
    detail.hit.zdb_id: 2028916-9
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  • 4
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 7, No. 12 ( 1997-12-01), p. 1169-1173
    Abstract: Nearly all of the open reading frames (ORFs) of the yeast Saccharomyces cerevisiae have been synthesized by PCR using a set of ∼6000 primer pairs. Each of the forward primers has a common 22-base sequence at its 5′ end, and each of the back primers has a common 20-base sequence at its 5′ end. These common termini allow reamplification of the entire set of original PCR products using a single pair of longer primers—in our case, 70 bases. The resulting 70-base elements that flank each ORF can be used for rapid and efficient cloning into a linearized yeast vector that contains these same elements at its termini. This cloning by genetic recombination obviates the need for ligations or bacterial manipulations and should permit convenient global approaches to gene function that require the assay of each putative yeast gene.
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
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    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 1997
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 5
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-12-01)
    Abstract: Mechanistic disease progression studies using animal models require objective and quantifiable assessment of tissue pathology. Currently quantification relies heavily on staining methods which can be expensive, labor/time-intensive, inconsistent across laboratories and batch, and produce uneven staining that is prone to misinterpretation and investigator bias. We developed an automated semantic segmentation tool utilizing deep learning for rapid and objective quantification of histologic features relying solely on hematoxylin and eosin stained pancreatic tissue sections. The tool segments normal acinar structures, the ductal phenotype of acinar-to-ductal metaplasia (ADM), and dysplasia with Dice coefficients of 0.79, 0.70, and 0.79, respectively. To deal with inaccurate pixelwise manual annotations, prediction accuracy was also evaluated against biological truth using immunostaining mean structural similarity indexes (SSIM) of 0.925 and 0.920 for amylase and pan-keratin respectively. Our tool’s disease area quantifications were correlated to the quantifications of immunostaining markers (DAPI, amylase, and cytokeratins; Spearman correlation score = 0.86, 0.97, and 0.92) in unseen dataset (n = 25). Moreover, our tool distinguishes ADM from dysplasia, which are not reliably distinguished with immunostaining, and demonstrates generalizability across murine cohorts with pancreatic disease. We quantified the changes in histologic feature abundance for murine cohorts with oncogenic Kras-driven disease, and the predictions fit biological expectations, showing stromal expansion, a reduction of normal acinar tissue, and an increase in both ADM and dysplasia as disease progresses. Our tool promises to accelerate and improve the quantification of pancreatic disease in animal studies and become a unifying quantification tool across laboratories.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 22_Supplement ( 2021-11-15), p. PO-014-PO-014
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 22_Supplement ( 2021-11-15), p. PO-014-PO-014
    Abstract: Objective and quantifiable assessment of tissue pathology is necessary to study mechanistic disease progression; however, current quantification methods based on tissue staining have many drawbacks including cost, time, labor, batch effects, as well as uneven staining which can result in misinterpretation and investigator bias. Here we present VISTA, an automated deep learning tool for semantic segmentation and quantification of histologic features from hematoxylin and eosin (H & E) stained pancreatic tissue sections. VISTA is trained to identify four key tissue types in developing murine PDAC samples: normal acinar, acinar-to-ductal metaplasia (ADM), dysplasia, and other normal tissue. Predicted segmentations were quantitatively evaluated against pathologist annotation with Dice Coefficients, achieving scores of 0.79, 0.70, 0.79 for normal acinar, ADM, and dysplasia, respectively. Predictions were evaluated against biological ground truth using the mean structural similarity index to immunostainings amylase and pan-keratin (0.925 and 0.920, respectively). The total area of feature prediction was also correlated to the area of immunostaining in whole tissue sections using spearman correlation (0.86, 0.97, and 0.92 for DAPI, amylase, and cytokeratins, respectively). Importantly, our tool is not only able to predict staining information, but it is able to distinguish between ADM and dysplasia, which are not reliably distinguished with common immunostaining methods, showing VISTA’s potential to expand research beyond what is capable with current standards. As a use case example of VISTA, we quantified abundance of histologic features in murine cohorts with oncogenic Kras-driven disease. We observed stromal expansion, a reduction in normal acinar, and an increase in both ADM and dysplasia as the disease progresses, which matches known biology. Since VISTA is an automated algorithm, it can accelerate histological analysis and improve the consistency of quantification between laboratories and investigators. This work has been published in Nature Scientific Reports, and the code is available on github at https://github.com/GelatinFrogs/MicePan-Segmentation. Citation Format: Luke Ternes, Ge Huang, Christian Lanciault, Guillaume Thibault, Rachelle Riggers, Joe Gray, John Muschler, Young Hwan Chang. VISTA: VIsual Semantic Tissue Analysis for pancreatic disease quantification in murine cohorts [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-014.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 24_Supplement ( 2019-12-15), p. A34-A34
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 24_Supplement ( 2019-12-15), p. A34-A34
    Abstract: The basement membrane (BM) is a predominant microenvironmental factor of the precancerous exocrine pancreas, and evidence suggests that the BM functions not only as a barrier to tumor cell invasion but also as an active tumor-suppressing signaling substrate. However, the molecular underpinnings of such a mechanism have not been resolved. Here we explore the expression and function of the prominent BM receptor dystroglycan (DG) in the normal pancreas and pancreatic disease. We show that DG is highly expressed in the acinar compartment of the normal pancreas; however, there is a strong suppression of DG expression with acinar-to-ductal metaplasia (ADM) in chronic pancreatitis and in all stages of pancreatic cancer evolution, from ADM to neoplasias to adenocarcinoma. The conditional knockout of DG in the murine pancreas produced no evidence of developmental or functional deficiency. However, deletion of DG expression in the context of oncogenic Kras expression (p48-Cre;KrasG12D) led to a clear acceleration of disease, including accelerated PanIN formation and an increased incidence of adenocarcinoma and metastases. Disease acceleration was accompanied by neoplasias with a strongly cystic morphology. These data establish DG as a potent suppressor of pancreatic neoplasias and cancers, and one that is muted in chronic pancreatitis and at the earliest stages of oncogenic transformation. We conclude that DG is a key mediator of the tumor-suppressing functions of the normal BM, and that maintenance or restoration of DG function is a potential target for the delay or prevention of pancreatic cancer evolution. Citation Format: Ge Huang, Christian Lanciault, Rosalie Sears, John Muschler. Suppression of dystroglycan function is a hallmark of acinar-to-ductal metaplasia and favors the development of neoplasias and PDAC [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A34.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    In: Molecular Therapy, Elsevier BV, Vol. 29, No. 2 ( 2021-02), p. 680-690
    Type of Medium: Online Resource
    ISSN: 1525-0016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2001818-6
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  • 9
    In: Annals of Pancreatic Cancer, AME Publishing Company, Vol. 1, No. 1 ( 2018-4), p. AB024-AB024
    Type of Medium: Online Resource
    ISSN: 2616-2741
    Language: Unknown
    Publisher: AME Publishing Company
    Publication Date: 2018
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  • 10
    In: Hepatology Research, Wiley, Vol. 47, No. 13 ( 2017-12), p. 1469-1483
    Abstract: Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis (NASH) are not well understood. Aims To understand the molecular basis of NASH, we evaluated reversible phosphorylation events in hepatic tissue derived from Class III obese subjects by phosphoproteomic means with the aim of highlighting key regulatory pathways that distinguish NASH from non‐alcoholic fatty liver disease (also known as simple steatosis; SS). Materials & Methods Class III obese subjects undergoing bariatric surgery underwent liver biopsy (eight normal patients, eight with simple steatosis, and eight NASH patients). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects. Results Of the 3078 phosphorylation sites assigned (2465 phosphoserine, 445 phosphothreonine, 165 phosphotyrosine), 53 were altered by a factor of 2 among cohorts, and of those, 12 were significantly increased or decreased by ANOVA ( P 〈 0.05). Discussion Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post‐transcriptional modification among the most over‐represented networks. Conclusion Collectively, these results raise the possibility of abnormalities in carbohydrate metabolism as an important trigger for the development of NASH, in parallel with already established abnormalities in lipid metabolism.
    Type of Medium: Online Resource
    ISSN: 1386-6346 , 1872-034X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2006439-1
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