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Article: Light-induced Extracellular Vesicle Adsorption.

Hisey, Colin L / Rima, Xilal Y / Doon-Ralls, Jacob / Nagaraj, Chiranth K / Mayone, Sophia / Nguyen, Kim T / Wiggins, Sydney / Dorayappan, Kalpana D P / Selvendiran, Karuppaiyah / Wood, David / Hu, Chunyu / Patel, Divya / Palmer, Andre / Hansford, Derek / Reategui, Eduardo

bioRxiv : the preprint server for biology

2024

Abstract: The role of extracellular vesicles (EVs) in human health and disease has garnered considerable attention over the past two decades. However, while several types of EVs are known to interact dynamically with the extracellular matrix and there is great ... ...

Abstract	The role of extracellular vesicles (EVs) in human health and disease has garnered considerable attention over the past two decades. However, while several types of EVs are known to interact dynamically with the extracellular matrix and there is great potential value in producing high-fidelity EV micropatterns, there are currently no label-free, high-resolution, and tunable platform technologies with this capability. We introduce Light-induced Extracellular Vesicle Adsorption (LEVA) as a powerful solution to rapidly advance the study of matrix- and surface-bound EVs and other particles. The versatility of LEVA is demonstrated using commercial GFP-EV standards, EVs from glioblastoma bioreactors, and E. coli outer membrane vesicles (OMVs), with the resulting patterns used for single EV characterization, single cell migration on migrasome-mimetic trails, and OMV-mediated neutrophil swarming. LEVA will enable rapid advancements in the study of matrix- and surface-bound EVs and other particles, and should encourage researchers from many disciplines to create novel diagnostic, biomimetic, immunoengineering, and therapeutic screening assays.
Language	English
Publishing date	2024-04-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.24.590318
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Article ; Online: Correction: Targeting TMEM205 mediated drug resistance in ovarian clear cell carcinoma using oncolytic virus.

Saini, Uksha / Smith, Brentley Q / Dorayappan, Kalpana Deepa Priya / Yoo, Ji Young / Maxwell, G Larry / Kaur, Balveen / Konishi, Ikuo / O'Malley, David / Cohn, David E / Selvendiran, Karuppaiyah

Journal of ovarian research

2023 Volume 16, Issue 1, Page(s) 38

Language	English
Publishing date	2023-02-13
Publishing country	England
Document type	Published Erratum
ZDB-ID	2455679-8
ISSN	1757-2215 ; 1757-2215
ISSN (online)	1757-2215
ISSN	1757-2215
DOI	10.1186/s13048-023-01111-7
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Article ; Online: Tissue factor as a novel diagnostic target for early detection of ovarian cancer using ultrasound microbubbles.

Newcomer, Meghan M / Dorayappan, Kalpana Deepa Priya / Wagner, Vincent / Suarez, Adrian A / Calo, Corinne A / Kalmar, Eileen L / Maxwell, G Larry / O'Malley, David / Cohn, David E / Tweedle, Michael F / Selvendiran, Karuppaiyah

Gynecologic oncology

2023 Volume 173, Page(s) 138–150

Abstract: Introduction: Ovarian cancer (OC) is the deadliest gynecologic malignancy, with an overall 5-year survival rate of less than 30%. The existing paradigm for OC detection involves a serum marker, CA125, and ultrasound examination, neither of which is ... ...

Abstract	Introduction: Ovarian cancer (OC) is the deadliest gynecologic malignancy, with an overall 5-year survival rate of less than 30%. The existing paradigm for OC detection involves a serum marker, CA125, and ultrasound examination, neither of which is sufficiently specific for OC. This study addresses this deficiency through the use of a targeted ultrasound microbubble directed against tissue factor (TF). Methods: TF expression was examined in both OC cell lines and patient-derived tumor samples via western blotting and IHC. In vivo microbubble ultrasound imaging was analyzed using high grade serous ovarian carcinoma orthotopic mouse models. Results: While TF expression has previously been described on angiogenic, tumor-associated vascular endothelial cells (VECs) of several tumor types, this is first study to show TF expression on both murine and patient-derived ovarian tumor-associated VECs. Biotinylated anti-TF antibody was conjugated to streptavidin-coated microbubbles and in vitro binding assays were performed to assess the binding efficacy of these agents. TF-targeted microbubbles successfully bound to TF-expressing OC cells, as well as an in vitro model of angiogenic endothelium. In vivo, these microbubbles bound to the tumor-associated VECs of a clinically relevant orthotopic OC mouse model. Conclusion: Development of a TF-targeted microbubble capable of successfully detecting ovarian tumor neovasculature could have significant implications towards increasing the number of early-stage OC diagnoses. This preclinical study shows potential for translation to clinical use, which could ultimately help increase the number of early OC detections and decrease the mortality associated with this disease.
MeSH term(s)	Humans ; Mice ; Female ; Animals ; Microbubbles ; Thromboplastin ; Endothelial Cells/metabolism ; Early Detection of Cancer ; Ultrasonography/methods ; Ovarian Neoplasms/diagnostic imaging ; Ovarian Neoplasms/metabolism
Chemical Substances	Thromboplastin (9035-58-9)
Language	English
Publishing date	2023-05-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2023.04.008
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Article ; Online: Targeting TMEM205 mediated drug resistance in ovarian clear cell carcinoma using oncolytic virus.

Saini, Uksha / Smith, Brentley Q / Dorayappan, Kalpana Deepa Priya / Yoo, Ji Young / Maxwell, G Larry / Kaur, Balveen / Konishi, Ikuo / O'Malley, David / Cohn, David E / Selvendiran, Karuppaiyah

Journal of ovarian research

2022 Volume 15, Issue 1, Page(s) 130

Abstract: Background: Ovarian clear cell carcinoma (OCCC) accounts for approximately 8-10% of epithelial ovarian cancers in the United States. Although it is rare, OCCC usually presents with treatment challenges and the overall prognosis is far worse than high ... ...

Abstract	Background: Ovarian clear cell carcinoma (OCCC) accounts for approximately 8-10% of epithelial ovarian cancers in the United States. Although it is rare, OCCC usually presents with treatment challenges and the overall prognosis is far worse than high grade serous ovarian cancer HGSOC. The objective of this study was to examine the therapeutic relevance of combining oncolytic virus with cisplatin for ovarian cancer clear cell carcinoma (OCCC). Results: We identified that TMEM205, a recently discovered transmembrane protein, contributes to chemoresistance in OCCC cells via the exosomal pathway. Mechanistically, TMEM205 undergoes ligand-independent constitutive endocytosis and co-localizes with Rab11 to contribute to the late recycling endosomes in a clathrin-independent manner. Further, we observed that oncolytic virus (oHSV) pretreatment followed by treatment with cisplatin decreases TMEM205 expression and sensitizes cells to cisplatin in a synergistic manner in OCCC cells. TMEM205 interacts with glycoprotein-C of oHSV post-infection; both of these proteins undergo ubiquitination and ultimately get shuttled outside the cell via exosomes. Thus, we demonstrate the mechanotransduction pathway of TMEM205-mediated chemoresistance along with targeting this pathway using oHSV and cisplatin as a powerful therapeutic strategy for OCCC. oHSV combination with cisplatin inhibits OCCC tumor growth in vivo in immunodeficient and immunocompetent mice models. Conclusion: Our results suggest that the combination of oHSV and cisplatin in immunocompetent as well as immune deficient OCCC tumor bearing mice reduces overall tumor burden as well as metastatic disease thereby providing survival benefit. Additionally, the detection of TMEM205 in exosomal cargo early in OCCC development has potential to be exploited as a biomarker.
MeSH term(s)	Animals ; Mice ; Humans ; Female ; Oncolytic Viruses/genetics ; Mechanotransduction, Cellular ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Drug Resistance ; Carcinoma ; Membrane Proteins/genetics
Chemical Substances	TMEM205 protein, human ; Membrane Proteins
Language	English
Publishing date	2022-12-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2455679-8
ISSN	1757-2215 ; 1757-2215
ISSN (online)	1757-2215
ISSN	1757-2215
DOI	10.1186/s13048-022-01054-5
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Article ; Online: Microfluidic affinity separation chip for selective capture and release of label-free ovarian cancer exosomes.

Hisey, Colin L / Dorayappan, Kalpana Deepa Priya / Cohn, David E / Selvendiran, Karuppaiyah / Hansford, Derek J

Lab on a chip

2018 Volume 18, Issue 20, Page(s) 3144–3153

Abstract: Exosomes are nanoscale vesicles found in many bodily fluids which play a significant role in cell-to-cell signaling and contain biomolecules indicative of their cells of origin. Recently, microfluidic devices have provided the ability to efficiently ... ...

Abstract	Exosomes are nanoscale vesicles found in many bodily fluids which play a significant role in cell-to-cell signaling and contain biomolecules indicative of their cells of origin. Recently, microfluidic devices have provided the ability to efficiently capture exosomes based on specific membrane biomarkers, but releasing the captured exosomes intact and label-free for downstream characterization and experimentation remains a challenge. We present a herringbone-grooved microfluidic device which is covalently functionalized with antibodies against general and cancer exosome membrane biomarkers (CD9 and EpCAM) to isolate exosomes from small volumes of high-grade serous ovarian cancer (HGSOC) serum. Following capture, intact exosomes are released label-free using a low pH buffer and immediately neutralized downstream to ensure their stability. Characterization of captured and released exosomes was performed using fluorescence microscopy, nanoparticle tracking analysis, flow-cytometry, and SEM. Our results demonstrate the successful isolation of intact and label-free exosomes, indicate that the amount of both total and EpCAM+ exosomes increases with HGSOC disease progression, and demonstrate the downstream internalization of isolated exosomes by OVCAR8 cells. This device and approach can be utilized for a nearly limitless range of downstream exosome analytical and experimental techniques, both on and off-chip.
MeSH term(s)	Cell Fractionation/instrumentation ; Equipment Design ; Exosomes/pathology ; Female ; Humans ; Lab-On-A-Chip Devices ; Ovarian Neoplasms/pathology
Language	English
Publishing date	2018-08-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2056646-3
ISSN	1473-0189 ; 1473-0197
ISSN (online)	1473-0189
ISSN	1473-0197
DOI	10.1039/c8lc00834e
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Article ; Online: The biological significance and clinical applications of exosomes in ovarian cancer.

Dorayappan, Kalpana Deepa Priya / Wallbillich, John J / Cohn, David E / Selvendiran, Karuppaiyah

Gynecologic oncology

2016 Volume 142, Issue 1, Page(s) 199–205

Abstract: Exosomes are nano-sized (20-100nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and ... ...

Abstract	Exosomes are nano-sized (20-100nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and other cancers. The protein and microRNA content of exosomes has been implicated in various intracellular processes that mediate oncogenesis, tumor spread, and drug resistance. Exosomes may prime distant tissue sites for reception of future metastases and their release can be mediated by the tumor microenvironment (e.g., hypoxia). Ovarian cancer-derived exosomes have unique features that could be leveraged for use as biomarkers to facilitate improved detection and treatment of the disease. Further, exosomes have the potential to serve as targets and/or drug delivery vehicles in the treatment of ovarian cancer. In this review we discuss the biological and clinical significance of exosomes relevant to the progression, detection, and treatment of ovarian cancer.
MeSH term(s)	Animals ; Biomarkers, Tumor/genetics ; Drug Resistance, Neoplasm ; Exosomes ; Female ; Humans ; MicroRNAs/genetics ; Neoplasm Metastasis ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology
Chemical Substances	Biomarkers, Tumor ; MicroRNAs
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2016.03.036
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Aberrant expression of TMEM205 signaling promotes platinum resistance in ovarian cancer: An implication for the antitumor potential of DAP compound.

Calo, Corinne A / Smith, Brentley Q / Dorayappan, Kalpana Deepa Priya / Saini, Uksha / Lightfoot, Michelle / Wagner, Vincent / Kalaiyarasan, Deepika / Cosgrove, Casey / Wang, Qi-En / Maxwell, G Larry / Kálai, Tamás / Kuppusamy, Periannan / Cohn, David E / Selvendiran, Karuppaiyah

Gynecologic oncology

2021 Volume 164, Issue 1, Page(s) 136–145

Abstract: Introduction: TMEM205 is a novel transmembrane protein associated with platinum resistance (PR) in epithelial ovarian carcinoma (OC), however, the specific mechanisms associated with this resistance remain to be elucidated.: Methods: TMEM205 ... ...

Abstract	Introduction: TMEM205 is a novel transmembrane protein associated with platinum resistance (PR) in epithelial ovarian carcinoma (OC), however, the specific mechanisms associated with this resistance remain to be elucidated. Methods: TMEM205 expression was evaluated in platinum-sensitive (PS) versus platinum resistant (PR) ovarian cancer cell lines and patient serum/tissues. Exosomal efflux of platinum was evaluated with inductively coupled plasma mass spectrometry (ICP-MS) after pre-treatment with small molecule inhibitors (L-2663/L-2797) of TMEM205 prior to treatment with platinum. Cytotoxicity of combination treatment was confirmed in vitro and in an in vivo model. Results: TMEM205 expression was 10-20 fold higher in PR compared to PS ovarian cancer cell lines, serum samples, and tissues. Co-localization with CD1B was confirmed by in-situ proximity ligation assay suggesting that TMEM205 may mediate PR via the exosomal pathway. Exosomal secretion was significantly increased 5-10 fold in PR cell lines after treatment with carboplatin compared to PS cell lines. Pre-treatment with L-2663 prior to carboplatin resulted in significantly increased intracellular concentration of fluorescently-labeled cisplatin and decreased exosomal efflux of platinum. Decreased cell survival and tumor growth in vitro and in vivo was observed when PR cells were treated with a combination of L-2663 with carboplatin compared to carboplatin alone. Conclusion: TMEM205 appears to be involved in the development of PR in ovarian cancer through the exosomal efflux of platinum agents. This study provides pre-clinical evidence that TMEM205 could serve as a possible biomarker for PR as well as a therapeutic target in combination with platinum agents.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Carboplatin/pharmacology ; Carboplatin/therapeutic use ; Cell Line, Tumor/drug effects ; Cell Line, Tumor/metabolism ; Disease Models, Animal ; Drug Resistance, Neoplasm/drug effects ; Membrane Proteins/antagonists & inhibitors ; Membrane Proteins/drug effects ; Membrane Proteins/metabolism ; Mice, Nude ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/metabolism
Chemical Substances	Antineoplastic Agents ; Carboplatin (BG3F62OND5) ; Membrane Proteins ; TMEM205 protein, human ; L-2663
Language	English
Publishing date	2021-10-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2021.10.076
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Article ; Online: Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype: a novel mechanism linking STAT3/Rab proteins.

Dorayappan, Kalpana Deepa Priya / Wanner, Ross / Wallbillich, John J / Saini, Uksha / Zingarelli, Roman / Suarez, Adrian A / Cohn, David E / Selvendiran, Karuppaiyah

Oncogene

2018 Volume 37, Issue 28, Page(s) 3806–3821

Abstract: Hypoxia-mediated tumor progression, metastasis, and drug resistance are major clinical challenges in ovarian cancer. Exosomes released in the hypoxic tumor microenvironment may contribute to these challenges by transferring signaling proteins between ... ...

Abstract	Hypoxia-mediated tumor progression, metastasis, and drug resistance are major clinical challenges in ovarian cancer. Exosomes released in the hypoxic tumor microenvironment may contribute to these challenges by transferring signaling proteins between cancer cells and normal cells. We observed that ovarian cancer cells exposed to hypoxia significantly increased their exosome release by upregulating Rab27a, downregulating Rab7, LAMP1/2, NEU-1, and also by promoting a more secretory lysosomal phenotype. STAT3 knockdown in ovarian cancer cells reduced exosome release by altering the Rab family proteins Rab7 and Rab27a under hypoxic conditions. We also found that exosomes from patient-derived ascites ovarian cancer cell lines cultured under hypoxic conditions carried more potent oncogenic proteins-STAT3 and FAS that are capable of significantly increasing cell migration/invasion and chemo-resistance in vitro and tumor progression/metastasis in vivo. Hypoxic ovarian cancer cells derived exosomes (HEx) are proficient in re-programming the immortalized fallopian tube secretory epithelial cells (FT) to become pro-tumorigenic in mouse fallopian tubes. In addition, cisplatin efflux via exosomes was significantly increased in ovarian cancer cells under hypoxic conditions. Co-culture of HEx with tumor cells led to significantly decreased dsDNA damage and increased cell survival in response to cisplatin treatment. Blocking exosome release by known inhibitor Amiloride or STAT3 inhibitor and treating with cisplatin resulted in a significant increase in apoptosis, decreased colony formation, and proliferation. Our results demonstrate that HEx are more potent in augmenting metastasis/chemotherapy resistance in ovarian cancer and may serve as a novel mechanism for tumor metastasis, chemo-resistance, and a point of intervention for improving clinical outcomes.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis/physiology ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Movement/physiology ; Cell Proliferation/drug effects ; Cell Proliferation/physiology ; Cell Survival/drug effects ; Cell Survival/physiology ; Cisplatin/pharmacology ; Disease Progression ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/physiology ; Exosomes/drug effects ; Exosomes/metabolism ; Exosomes/pathology ; Female ; Humans ; Hypoxia/drug therapy ; Hypoxia/metabolism ; Hypoxia/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis/pathology ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Phenotype ; STAT3 Transcription Factor/metabolism ; rab GTP-Binding Proteins/metabolism
Chemical Substances	STAT3 Transcription Factor ; STAT3 protein, human ; rab GTP-Binding Proteins (EC 3.6.5.2) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2018-04-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-018-0189-0
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Article ; Online: Oncolytic HSV Therapy Modulates Vesicular Trafficking Inducing Cisplatin Sensitivity and Antitumor Immunity.

Hong, Bangxing / Chapa, Valerie / Saini, Uksha / Modgil, Puneet / Cohn, David E / He, Guangan / Siddik, Zahid H / Sood, Anil K / Yan, Yuanqing / Selvendiran, Karuppaiyah / Pei, Guangsheng / Zhao, Zhongming / Yoo, Ji Young / Kaur, Balveen

Clinical cancer research : an official journal of the American Association for Cancer Research

2020 Volume 27, Issue 2, Page(s) 542–553

Abstract: Purpose: Here we investigated the impact of oncolytic herpes simplex virus (HSV) treatment on cisplatin sensitivity of platinum-resistant ovarian cancer, and the impact of the combination on immunotherapy.: Experimental design: Therapeutic efficacy ... ...

Abstract	Purpose: Here we investigated the impact of oncolytic herpes simplex virus (HSV) treatment on cisplatin sensitivity of platinum-resistant ovarian cancer, and the impact of the combination on immunotherapy. Experimental design: Therapeutic efficacy of the combination was assessed in platinum-resistant human and murine ovarian cancer peritoneal metastatic mouse models ( Results: Gene Ontology pathway analysis uncovered disruption of cellular extracellular vesicle (EV)-related pathways in infected cells (FDR = 2.97E-57). Mechanistically, we identified reduced expression of transporters expressed on EV implicated in cisplatin efflux. The increased cisplatin retention led to increased cisplatin-DNA adducts, which resulted in micronuclei and the subsequent activation of cGAS-STING pathway with a significant activation of innate immune cells and translated to an increase in antitumor immunity and efficacy. In mice bearing platinum-resistant ovarian cancer, we also observed a feedback induction of PD-L1 on tumor cells, which sensitized combination-treated mice to anti-PD-1 immune checkpoint therapy. Conclusions: To our knowledge, this is the first report to show HSV-induced cisplatin retention in infected cells. The consequential increased damaged DNA was then expelled from cells as micronuclei which resulted in induction of inflammatory responses and education of antitumor immunity. The combination therapy also created an environment that sensitized tumors to immune checkpoint therapy.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cells, Cultured ; Cisplatin/therapeutic use ; Combined Modality Therapy ; DNA Adducts/genetics ; DNA Adducts/immunology ; Disease Models, Animal ; Female ; Herpesvirus 1, Human/physiology ; Humans ; Immunotherapy/methods ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Oncolytic Virotherapy/methods ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/therapy ; Ovarian Neoplasms/virology ; Signal Transduction/genetics ; Signal Transduction/immunology ; Treatment Outcome ; Xenograft Model Antitumor Assays/methods ; Mice
Chemical Substances	Antineoplastic Agents ; DNA Adducts ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2020-10-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-20-2210
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Article ; Online: Microfluidic affinity separation chip for selective capture and release of label-free ovarian cancer exosomes

Hisey, Colin L. / Dorayappan, Kalpana Deepa Priya / Cohn, David E. / Selvendiran, Karuppaiyah / Hansford, Derek J.

2018

Abstract	Exosomes are nanoscale vesicles found in many bodily fluids which play a significant role in cell-to-cell signaling and contain biomolecules indicative of their cells of origin. Recently, microfluidic devices have provided the ability to efficiently capture exosomes based on specific membrane biomarkers, but releasing the captured exosomes intact and label-free for downstream characterization and experimentation remains a challenge. We present a herringbone-grooved microfluidic device which is covalently functionalized with antibodies against general and cancer exosome membrane biomarkers (CD9 and EpCAM) to isolate exosomes from small volumes of high-grade serous ovarian cancer (HGSOC) serum. Following capture, intact exosomes are released label-free using a low pH buffer and immediately neutralized downstream to ensure their stability. Characterization of captured and released exosomes was performed using fluorescence microscopy, nanoparticle tracking analysis, flow-cytometry, and SEM. Our results demonstrate the successful isolation of intact and label-free exosomes, indicate that the amount of both total and EpCAM+ exosomes increases with HGSOC disease progression, and demonstrate the downstream internalization of isolated exosomes by OVCAR8 cells. This device and approach can be utilized for a nearly limitless range of downstream exosome analytical and experimental techniques, both on and off-chip.
Language	English
Publisher	RSC (Royal Society of Chemistry)
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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