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  1. AU="Sunitha Nagrath"
  2. AU="Kevin A. Bybee, MD"
  3. AU="Carty, Lucy"
  4. AU="Milosević, Milan"
  5. AU="Garcini, Jackelin"
  6. AU="Mohamad, Imran Syakir"
  7. AU="Ștefănescu, Roxana"
  8. AU="De Jong, Ymke"
  9. AU="Balajthy, J"
  10. AU="David B. Volkin"
  11. AU="Hancock, Brandon"
  12. AU="Gatesy, Samuel W M"
  13. AU="Chénard, Caroline"
  14. AU="Krishna Chinthapalli"
  15. AU="Eneyda Secada Cárdenas"
  16. AU="Talbot, Nick"
  17. AU="Perez-Shibayama, Christian"
  18. AU="Melissa M. Mills"
  19. AU="Goli, Haneesha"
  20. AU="Viviana Falcón-Cama"
  21. AU="Januschek, Friederike"
  22. AU="Bonilla-Aldana, D. Katterine"
  23. AU="Stix, Michael S"
  24. AU="Xiao, Bing"
  25. AU="Algattas, Hanna N"
  26. AU="Ihm, M"
  27. AU="Nivelo, Luis A"
  28. AU="Nirja Kaka"
  29. AU="Bahnă, Adriana Florina"
  30. AU="Wen, Changchun"
  31. AU="Nizami, Sarea Islam Nuha"
  32. AU="Douglas J Kelly"
  33. AU=Kingston Elizabeth V
  34. AU="Jyoti Nepal"
  35. AU="González, Ana M Martín"

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  1. Artikel ; Online: Synergistic Analysis of Circulating Tumor Cells Reveals Prognostic Signatures in Pilot Study of Treatment-Naïve Metastatic Pancreatic Cancer Patients

    Sarah Owen / Emily Prantzalos / Valerie Gunchick / Vaibhav Sahai / Sunitha Nagrath

    Biomedicines, Vol 10, Iss 146, p

    2022  Band 146

    Abstract: Pancreatic ductal adenocarcinoma is typically diagnosed at late stages and has one of the lowest five-year survival rates of all malignancies. In this pilot study, we identify signatures related to survival and treatment response found in circulating ... ...

    Abstract Pancreatic ductal adenocarcinoma is typically diagnosed at late stages and has one of the lowest five-year survival rates of all malignancies. In this pilot study, we identify signatures related to survival and treatment response found in circulating tumor cells (CTCs). Patients with poor survival had increased mutant KRAS expression and deregulation of connected pathways such as PI3K-AKT and MAPK signaling. Further, in a subset of these patients, expression patterns of gemcitabine resistance mechanisms were observed, even prior to initiating treatment. This work highlights the need for identifying patients with these resistance profiles and designing treatment regimens to circumvent these mechanisms.
    Schlagwörter CTC ; liquid biopsy ; pancreatic cancer ; mutant KRAS ; gene expression profiling ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2022-01-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Integrated Workflow for the Label-Free Isolation and Genomic Analysis of Single Circulating Tumor Cells in Pancreatic Cancer

    Brittany Rupp / Sarah Owen / Harrison Ball / Kaylee Judith Smith / Valerie Gunchick / Evan T. Keller / Vaibhav Sahai / Sunitha Nagrath

    International Journal of Molecular Sciences, Vol 23, Iss 14, p

    2022  Band 7852

    Abstract: As pancreatic cancer is the third deadliest cancer in the U.S., the ability to study genetic alterations is necessary to provide further insight into potentially targetable regions for cancer treatment. Circulating tumor cells (CTCs) represent an ... ...

    Abstract As pancreatic cancer is the third deadliest cancer in the U.S., the ability to study genetic alterations is necessary to provide further insight into potentially targetable regions for cancer treatment. Circulating tumor cells (CTCs) represent an especially aggressive subset of cancer cells, capable of causing metastasis and progressing the disease. Here, we present the Labyrinth–DEPArray pipeline for the isolation and analysis of single CTCs. Established cell lines, patient-derived CTC cell lines and freshly isolated CTCs were recovered and sequenced to reveal single-cell copy number variations (CNVs). The resulting CNV profiles of established cell lines showed concordance with previously reported data and highlight several gains and losses of cancer-related genes such as FGFR3 and GNAS. The novel sequencing of patient-derived CTC cell lines showed gains in chromosome 8q, 10q and 17q across both CTC cell lines. The pipeline was used to process and isolate single cells from a metastatic pancreatic cancer patient revealing a gain of chromosome 1q and a loss of chromosome 5q. Overall, the Labyrinth-DEPArray pipeline offers a validated workflow combining the benefits of antigen-free CTC isolation with single cell genomic analysis.
    Schlagwörter circulating tumor cells ; pancreatic cancer ; copy number variation ; single-cell analysis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2022-07-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Optimizing the Detection of Circulating Markers to Aid in Early Lung Cancer Detection

    Vasudha Murlidhar / Nithya Ramnath / Sunitha Nagrath / Rishindra M. Reddy

    Cancers, Vol 8, Iss 7, p

    2016  Band 61

    Abstract: Improving early detection of lung cancer is critical to improving lung cancer survival. Studies have shown that computerized tomography (CT) screening can reduce mortality from lung cancer, but this involves risks of radiation exposure and can identify ... ...

    Abstract Improving early detection of lung cancer is critical to improving lung cancer survival. Studies have shown that computerized tomography (CT) screening can reduce mortality from lung cancer, but this involves risks of radiation exposure and can identify non-cancer lung nodules that lead to unnecessary interventions for some. There is a critical need to develop alternative, less invasive methods to identify patients who have early-stage lung cancer. The detection of circulating tumor cells (CTCs) are a promising area of research, but current technology is limited by a low yield of CTCs. Alternate studies are investigating circulating nucleic acids and proteins as possible tumor markers. It is critical to develop innovative methods for early lung cancer detection that may include CTCs or other markers that are low-risk and low-cost, yet specific and sensitive, to facilitate improved survival by diagnosing the disease when it is surgically curable.
    Schlagwörter biomarkers ; circulating tumor cells ; microRNA ; lung cancer ; proteomics ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2016-06-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity

    Yoon‐Tae Kang / Zeqi Niu / Thomas Hadlock / Emma Purcell / Ting‐Wen Lo / Mina Zeinali / Sarah Owen / Venkateshwar G. Keshamouni / Rishindra Reddy / Nithya Ramnath / Sunitha Nagrath

    Advanced Science, Vol 8, Iss 6, Pp n/a-n/a (2021)

    2021  

    Abstract: Abstract As the recognition between natural killer (NK) cells and cancer cells does not require antigen presentation, NK cells are being actively studied for use in adoptive cell therapies in the rapidly evolving armamentarium of cancer immunotherapy. In ...

    Abstract Abstract As the recognition between natural killer (NK) cells and cancer cells does not require antigen presentation, NK cells are being actively studied for use in adoptive cell therapies in the rapidly evolving armamentarium of cancer immunotherapy. In addition to utilizing NK cells, recent studies have shown that exosomes derived from NK cells also exhibit antitumor properties. Furthermore, these NK cell‐derived exosomes exhibit higher stability, greater modification potentials and less immunogenicity compared to NK cells. Therefore, technologies that allow highly sensitive and specific isolation of NK cells and NK cell‐derived exosomes can enable personalized NK‐mediated cancer therapeutics in the future. Here, a novel microfluidic system to collect patient‐specific NK cells and on‐chip biogenesis of NK‐exosomes is proposed. In a small cohort of non‐small cell lung cancer (NSCLC) patients, both NK cells and circulating tumor cells (CTCs) were isolated, and it is found NSCLC patients have high numbers of NK and NK‐exosomes compared with healthy donors, and these concentrations show a trend of positive and negative correlations with bloodborne CTC numbers, respectively. It is further demonstrated that the NK‐exosomes harvested from NK‐graphene oxide chip exhibit cytotoxic effect on CTCs. This versatile system is expected to be used for patient‐specific NK‐based immunotherapies along with CTCs for potential prognostic/diagnostic applications.
    Schlagwörter cancer immunotherapy ; circulating tumor cells ; exosome biogenesis ; microfluidics ; natural killer cells ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-03-01T00:00:00Z
    Verlag Wiley
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Epidermal Growth Factor Receptor Mutations Carried in Extracellular Vesicle-Derived Cargo Mirror Disease Status in Metastatic Non-small Cell Lung Cancer

    Emma Purcell / Sarah Owen / Emily Prantzalos / Abigail Radomski / Nayri Carman / Ting-Wen Lo / Mina Zeinali / Chitra Subramanian / Nithya Ramnath / Sunitha Nagrath

    Frontiers in Cell and Developmental Biology, Vol

    2021  Band 9

    Abstract: In non-small cell lung cancer (NSCLC), identifying the presence of sensitizing and resistance epidermal growth factor receptor (EGFR) mutations dictates treatment plans. Extracellular vesicles (EVs) are emerging as abundant, stable potential liquid ... ...

    Abstract In non-small cell lung cancer (NSCLC), identifying the presence of sensitizing and resistance epidermal growth factor receptor (EGFR) mutations dictates treatment plans. Extracellular vesicles (EVs) are emerging as abundant, stable potential liquid biopsy targets that offer the potential to quantify EGFR mutations in NSCLC patients at the RNA and protein level at multiple points through treatment. In this study, we present a systematic approach for serial mutation profiling of 34 EV samples from 10 metastatic NSCLC patients with known EGFR mutations through treatment. Using western blot and droplet digital PCR (ddPCR), sensitizing (exon 19 deletion, L858R) mutations were detected in EV-Protein, and both sensitizing and resistance (T790M) mutations were quantified in EV-RNA. EGFR mutations were detected in EV-Protein from four patients at multiple time points through treatment. Using EV-RNA, tumor biopsy matched sensitizing mutations were detected in 90% of patients and resistance mutations in 100% of patients. Finally, mutation burden in EV-RNA at each time point was compared to disease status, described as either stable or progressing. For 6/7 patients who were longitudinally monitored through treatment, EV mutation burden mirrored clinical trajectory. When comparing mutation detection between EV-RNA and ctDNA using ddPCR, EVs had a better detection rate for exon 19 deletions and the L858R point mutation. In conclusion, this study demonstrates that integrating EV analysis into liquid biopsy mutation screening has the potential to advance beyond the current standard of care “rule in” test. The multi-analyte testing allows future integration of EGFR mutation monitoring with additional EV-markers for a comprehensive patient monitoring biomarker.
    Schlagwörter extracellular vesicle (EV) ; EGFR mutation ; longitudinal monitoring ; resistance mutation ; non-small cell lung cancer ; EV-protein ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 616 ; 610
    Sprache Englisch
    Erscheinungsdatum 2021-10-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Dual‐Isolation and Profiling of Circulating Tumor Cells and Cancer Exosomes from Blood Samples with Melanoma Using Immunoaffinity‐Based Microfluidic Interfaces

    Yoon‐Tae Kang / Thomas Hadlock / Ting‐Wen Lo / Emma Purcell / Anusha Mutukuri / Shamileh Fouladdel / Monica De Silva Raguera / Heather Fairbairn / Vasudha Murlidhar / Alison Durham / Scott A. McLean / Sunitha Nagrath

    Advanced Science, Vol 7, Iss 19, Pp n/a-n/a (2020)

    2020  

    Abstract: Abstract Melanoma is among the most aggressive cancers, and its rate of incidence continues to grow. Early detection of melanoma has been hampered due to the lack of promising markers for testing. Recent advances in liquid biopsy have proposed ... ...

    Abstract Abstract Melanoma is among the most aggressive cancers, and its rate of incidence continues to grow. Early detection of melanoma has been hampered due to the lack of promising markers for testing. Recent advances in liquid biopsy have proposed noninvasive alternatives for cancer diagnosis and monitoring. Circulating tumor cells (CTCs) and cancer‐exosomes are gaining influence as promising biomarkers because of their cancer‐associated molecular markers and signatures. However, technologies that offer the dual‐isolation of CTCs and exosomes using a single sample have not been thoroughly developed. The dual‐utilization OncoBean (DUO) device is conjugated with melanoma specific antibodies, MCAM and MCSP, enabling simultaneous CTC and exosome isolations. Using blood samples from patients, CTCs and exosomes are specifically isolated from a single sample and then undergo molecular profiling for comprehensive study. Melanoma patients have 0–17CTCs mL−1 and 299 µg exosomal protein mL−1 while healthy donors display fewer than 2CTCs and 75.6 µg of exosomes mL−1, respectively. It is also demonstrated that both markers express melanoma‐associated genes using multiplex qRT‐PCR to test for expression pattern of a 96 gene panel. The dual isolation and molecular characterization will allow for further research into melanoma to identify viable markers for disease progression and treatment efficacy.
    Schlagwörter circulating tumor cells ; dual isolation and profiling ; melanoma ; microfluidics ; tumor exosomes ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2020-10-01T00:00:00Z
    Verlag Wiley
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: PD-L1 Expression in Circulating Tumor Cells Increases during Radio(chemo)therapy and Indicates Poor Prognosis in Non-small Cell Lung Cancer

    Yang Wang / Tae Hyun Kim / Shamileh Fouladdel / Zhuo Zhang / Payal Soni / Angel Qin / Lili Zhao / Ebrahim Azizi / Theodore S. Lawrence / Nithya Ramnath / Kyle C. Cuneo / Sunitha Nagrath

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Band 9

    Abstract: Abstract Preclinical studies demonstrated that radiation up-regulates PD-L1 expression in tumor cells, providing a rationale for combining PD-1/PD-L1 inhibitors with radiation. However this has not been validated in patients with non-small cell lung ... ...

    Abstract Abstract Preclinical studies demonstrated that radiation up-regulates PD-L1 expression in tumor cells, providing a rationale for combining PD-1/PD-L1 inhibitors with radiation. However this has not been validated in patients with non-small cell lung cancer due to the difficulty to obtain serial biopsies. Measuring PD-L1 expression in circulating tumor cells (CTCs), may allow real-time monitoring of immune activation in tumor. In this study, whole blood from non-metastatic NSCLC patients was collected before, during, and after radiation or chemoradiation using a microfluidic chip. PD-L1 expression in CTCs was assessed by immunofluorescence and qPCR and monitored through the course of treatment. Overall, PD-L1(+) CTCs were detected in 25 out of 38 samples (69.4%) with an average of 4.5 cells/ml. After initiation of radiation therapy, the proportion of PD-L1(+) CTCs increased significantly (median 0.7% vs. 24.7%, P < 0.01), indicating up-regulation of PD-L1 in tumor cells in response to radiation. In addition, patients positive for PD-L1 (≥5% of CTCs positive for PD-L1) at baseline had shorter PFS. Gene expression analysis revealed that higher levels of PD-L1 were associated with poor prognosis. Therefore, CTCs can be used to monitor dynamic changes of PD-L1 during radiation therapy which is potentially prognostic of response to treatment.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610 ; 616
    Sprache Englisch
    Erscheinungsdatum 2019-01-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells

    Tae Hyun Kim / Yang Wang / C. Ryan Oliver / Douglas H. Thamm / Laura Cooling / Costanza Paoletti / Kaylee J. Smith / Sunitha Nagrath / Daniel F. Hayes

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Band 8

    Abstract: Ex vivo methods of circulating tumor cell (CTC) isolation use small blood volumes, limiting sensitivity and introducing analytical inaccuracies. The authors describe a proof-of-concept study of an in vivo aphaeresis system that continuously collects CTCs ...

    Abstract Ex vivo methods of circulating tumor cell (CTC) isolation use small blood volumes, limiting sensitivity and introducing analytical inaccuracies. The authors describe a proof-of-concept study of an in vivo aphaeresis system that continuously collects CTCs from a peripheral vein over several hours.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2019-04-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells

    Tae Hyun Kim / Yang Wang / C. Ryan Oliver / Douglas H. Thamm / Laura Cooling / Costanza Paoletti / Kaylee J. Smith / Sunitha Nagrath / Daniel F. Hayes

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Band 8

    Abstract: Ex vivo methods of circulating tumor cell (CTC) isolation use small blood volumes, limiting sensitivity and introducing analytical inaccuracies. The authors describe a proof-of-concept study of an in vivo aphaeresis system that continuously collects CTCs ...

    Abstract Ex vivo methods of circulating tumor cell (CTC) isolation use small blood volumes, limiting sensitivity and introducing analytical inaccuracies. The authors describe a proof-of-concept study of an in vivo aphaeresis system that continuously collects CTCs from a peripheral vein over several hours.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2019-04-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells

    Yu-Heng Cheng / Yu-Chih Chen / Eric Lin / Riley Brien / Seungwon Jung / Yu-Ting Chen / Woncheol Lee / Zhijian Hao / Saswat Sahoo / Hyun Min Kang / Jason Cong / Monika Burness / Sunitha Nagrath / Max S. Wicha / Euisik Yoon

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Band 11

    Abstract: Transcriptome analysis of circulating tumor cells (CTCs) provides insights into monitoring target therapeutics and underlying tumor metastasis. Here the authors present Hydro-Seq, a contamination-free high-throughput hydrodynamic scRNA-seq barcoding ... ...

    Abstract Transcriptome analysis of circulating tumor cells (CTCs) provides insights into monitoring target therapeutics and underlying tumor metastasis. Here the authors present Hydro-Seq, a contamination-free high-throughput hydrodynamic scRNA-seq barcoding technique for rare CTCs.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2019-05-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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