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Castro, Cesar

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Castro

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Cesar

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Castro, Cesar
Author's Publications: search.filters.isAuthorOfPublication.2ab84e4a-41df-47ca-86ef-dd8ba8f4ceed

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    Rapid identification of health care–associated infections with an integrated fluorescence anisotropy system
    (American Association for the Advancement of Science, 2016) Park, Ki Soo; Huang, Chen-Han; Lee, Kyungheon; Yoo, Yeong-Eun; Castro, Cesar; Weissleder, Ralph; Lee, Hakho
    Health care–associated infections (HAIs) and drug-resistant pathogens have become a major health care issue with millions of reported cases every year. Advanced diagnostics would allow clinicians to more quickly determine the most effective treatment, reduce the nonspecific use of broad-spectrum antimicrobials, and facilitate enrollment in new antibiotic treatments. We present a new integrated system, polarization anisotropy diagnostics (PAD), for rapid detection of HAI pathogens. The PAD uses changes of fluorescence anisotropy when detection probes recognize target bacterial nucleic acids. The technology is inherently robust against environmental noise and economically scalable for parallel measurements. The assay is fast (2 hours) and performed on-site in a single-tube format. When applied to clinical samples obtained from interventional procedures, the PAD determined the overall bacterial burden, differentiated HAI bacterial species, and identified drug resistance and virulence status. The PAD system holds promise as a powerful tool for near-patient, rapid HAI testing.
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    Holographic Assessment of Lymphoma Tissue (HALT) for Global Oncology Field Applications
    (Ivyspring International Publisher, 2016) Pathania, Divya; Im, Hyungsoon; Kilcoyne, Aoife; Sohani, Aliyah R.; Fexon, Lioubov; Pivovarov, Misha; Abramson, Jeremy; Randall, Thomas; Chabner, Bruce; Weissleder, Ralph; Lee, Hakho; Castro, Cesar
    Low-cost, rapid and accurate detection technologies are key requisites to cope with the growing global cancer challenges. The need is particularly pronounced in resource-limited settings where treatment opportunities are often missed due to the absence of timely diagnoses. We herein describe a Holographic Assessment of Lymphoma Tissue (HALT) system that adopts a smartphone as the basis for molecular cancer diagnostics. The system detects malignant lymphoma cells labeled with marker-specific microbeads that produce unique holographic signatures. Importantly, we optimized HALT to detect lymphomas in fine-needle aspirates from superficial lymph nodes, procedures that align with the minimally invasive biopsy needs of resource-constrained regions. We equipped the platform to directly address the practical needs of employing novel technologies for “real world” use. The HALT assay generated readouts in <1.5 h and demonstrated good agreement with standard cytology and surgical pathology.
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    On Chip Analysis of CNS Lymphoma in Cerebrospinal Fluid
    (Ivyspring International Publisher, 2015) Turetsky, Anna; Lee, Kyungheon; Song, Jun; Giedt, Randy; Kim, Eunha; Kovach, Alexandra E.; Hochberg, Ephraim; Castro, Cesar; Lee, Hakho; Weissleder, Ralph
    Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples. Presented herein is a microfluidic platform for complete CSF lymphoid cell analysis, including single cell capture in sub-nanoliter traps, and molecular and chemotherapeutic response profiling via on-chip imaging, all in less than one hour. The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns. The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs.
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    CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis
    (Public Library of Science, 2016) Sosulski, Amanda; Horn, Heiko; Zhang, Lihua; Coletti, Caroline; Vathipadiekal, Vinod; Castro, Cesar; Birrer, Michael J.; Nagano, Osamu; Saya, Hideyuki; Lage, Kasper; Donahoe, Patricia; Pepin, David
    CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be indicative of a more metastatic disease and worse prognosis.
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    A High-Throughput Magneto-Electrochemical Array for the Integrated Isolation and Profiling of Extracellular Vesicles From Plasma
    (2021-06-28) Park, Jongmin; Park, Jun Seok; Huang, Chen-han; Jo, Ala; Cook, Kaitlyn; Wang, Rui; Lin, Hsing-Ying; Van Deun, Jan; Li, Huiyan; Min, Jouha; Wang, Lan; Yoon, Ghilsuk; Carter, Bob; Balaj, Leonora; Choi, Gyu-Seog; Castro, Cesar; Weissleder, Ralph; Lee, Hakho