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Onozato, Maristela Lika

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Onozato

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Maristela Lika

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Onozato, Maristela Lika
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    HER2 expression identifies dynamic functional states within circulating breast cancer cells
    (2016) Jordan, Nicole Vincent; Bardia, Aditya; Wittner, Ben; Benes, Cyril; Ligorio, Matteo; Zheng, Yu; Yu, Min; Sundaresan, Tilak K.; Licausi, Joseph A.; Desai, Rushil; O’Keefe, Ryan M.; Ebright, Richard; Boukhali, Myriam; Sil, Srinjoy; Onozato, Maristela Lika; Iafrate, Anthony; Kapur, Ravi; Sgroi, Dennis; Ting, David; Toner, Mehmet; Ramaswamy, Sridhar; Haas, Wilhelm; Maheswaran, Shyamala; Haber, Daniel
    Circulating tumor cells (CTCs) in women with advanced estrogen receptor-positive/HER2-negative breast cancer acquire a HER2-positive subpopulation following multiple courses of therapy1,2. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here, we analyzed CTCs from 19 ER+/HER2− patients, 84% of whom had acquired CTCs expressing HER2. Cultured CTCs maintain discrete HER2+ and HER2− subpopulations: HER2+ CTCs are more proliferative but not addicted to HER2, consistent with activation of multiple signaling pathways. HER2− CTCs show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2+ and HER2− CTCs interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. While HER2+ and HER2− CTCs have comparable tumor initiating potential, differential proliferation favors the HER2+ state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2− phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic CTC-derived tumor models. Together, these results point to distinct yet interconverting phenotypes within patient-derived CTCs, contributing to progression of breast cancer and acquisition of drug resistance.
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    A Role of Three-Dimensional (3D)-Reconstruction in the Classification of Lung Adenocarcinoma
    (IOS Press, 2012) Onozato, Maristela Lika; Klepeis, Veronica; Yagi, Yukako; Mino-Kenudson, Mari
    Background:: Three-dimensional (3D)-reconstruction from paraffin embedded sections has been considered laborious and time-consuming. However, the high-resolution images of large object areas and different fields of view obtained by 3D-reconstruction make one wonder whether it can add a new insight into lung adenocarcinoma, the most frequent histology type of lung cancer characterized by its morphological heterogeneity. Objective:: In this work, we tested whether an automated tissue sectioning machine and slide scanning system could generate precise 3D-reconstruction of microanatomy of the lung and help us better understand and define histologic subtypes of lung adenocarcinoma. Methods:: Four formalin-fixed human lung adenocarcinoma resections were studied. Paraffin embedded tissues were sectioned with Kurabo-Automated tissue sectioning machine and serial sections were automatically stained and scanned with a Whole Slide Imaging system. The resulting stacks of images were 3D reconstructed by Pannoramic Viewer software. Results:: Two of the four specimens contained islands of tumor cells detached in alveolar spaces that had not been described in any of the existing adenocarcinoma classifications. 3D-reconstruction revealed the details of spatial distribution and structural interaction of the tumor that could hardly be observed by 2D light microscopy studies. The islands of tumor cells extended into a deeper aspect of the tissue, and were interconnected with each other and with the main tumor with a solid pattern that was surrounded by the islands. The finding raises the question whether the islands of tumor cells should be classified into a solid pattern in the current classification. Conclusion:: The combination of new technologies enabled us to build an effective 3D-reconstruction of resected lung adenocarcinomas. 3D-reconstruction may help us refine the classification of lung adenocarcinoma by adding detailed spatial/structural information to 2D light microscopy evaluation.
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    An Ultra-High Speed Whole Slide Image Viewing System
    (IOS Press, 2012) Yagi, Yukako; Yoshioka, Shigeatsu; Kyusojin, Hiroshi; Onozato, Maristela Lika; Mizutani, Yoichi; Osato, Kiyoshi; Yada, Hiroaki; Mark, Eugene; Frosch, Matthew; Louis, David
    Background:: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed. Method: A prototype WSI viewer based on PlayStation®3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course. Results:: Pathologists were being able to use the system comfortably after 0–15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out. Conclusion:: The preliminary results of adapting the Sony PlayStation®3 (PS3®) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice.
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    Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq
    (American Association for the Advancement of Science (AAAS), 2017) Venteicher, Andrew S; Tirosh, Itay; Hebert, Christine; Yizhak, Keren; Neftel, Cyril Ralf Alexander; Filbin, Mariella; Hovestadt, Volker; Escalante, Leah; Shaw, McKenzie; Rodman, Christopher Jiahn-Leh; Gillespie, Shawn; Dionne, Danielle; Luo, Christina; Ravichandran, Hiranmayi; Mylvaganam, Ravindra; Mount, Christopher; Onozato, Maristela Lika; Nahed, Brian; Wakimoto, Hiroaki; Curry, William; Iafrate, Anthony; Rivera, Miguel; Frosch, Matthew; Golub, Todd; Brastianos, Priscilla; Getz, Gad; Patel, Anoop Premswaroop; Monje, Michelle; Cahill, Daniel; Rozenblatt-Rosen, Orit; Louis, David; Bernstein, Bradley; Regev, Aviv; Suva, Mario