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  1. Article ; Online: Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

    Ekaterina I. Galanzha / Vladimir P. Zharov

    Cancers, Vol 5, Iss 4, Pp 1691-

    2013  Volume 1738

    Abstract: Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 103–104 CTCs, resulting in the development of ... ...

    Abstract Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 103–104 CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 102–103 times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-rsesolution PAFC beyond the diffraction and spectral limits.
    Keywords in vivo flow cytometry ; metastasis ; circulating tumor cells ; photoacoustic method ; photothermal imaging ; CTC assay ex vivo/in vitro ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2013-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Photoswitchable Spasers with a Plasmonic Core and Photoswitchable Fluorescent Proteins

    Walter N. Harrington / Marina V. Novoselova / Daniil N. Bratashov / Boris N. Khlebtsov / Dmitry A. Gorin / Ekaterina I. Galanzha / Vladimir P. Zharov

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

    2019  Volume 7

    Abstract: Abstract Photoswitchable fluorescent proteins (PFPs) that can change fluorescence color upon excitation have revolutionized many applications of light such as tracking protein movement, super-resolution imaging, identification of circulating cells, and ... ...

    Abstract Abstract Photoswitchable fluorescent proteins (PFPs) that can change fluorescence color upon excitation have revolutionized many applications of light such as tracking protein movement, super-resolution imaging, identification of circulating cells, and optical data storage. Nevertheless, the relatively weak fluorescence of PFPs limits their applications in biomedical imaging due to strong tissue autofluorecence background. Conversely, plasmonic nanolasers, also called spasers, have demonstrated potential to generate super-bright stimulated emissions even inside single cells. Nevertheless, the development of photoswitchable spasers that can shift their stimulated emission color in response to light is challenging. Here, we introduce the novel concept of spasers using a PFP layer as the active medium surrounding a plasmonic core. The proof of principle was demonstrated by synthesizing a multilayer nanostructure on the surface of a spherical gold core, with a non-absorbing thin polymer shell and the PFP Dendra2 dispersed in the matrix of a biodegradable polymer. We have demonstrated photoswitching of spontaneous and stimulated emission in these spasers below and above the spasing threshold, respectively, at different spectral ranges. The plasmonic core of the spasers serves also as a photothermal (and potentially photoacoustic) contrast agent, allowing for photothermal imaging of the spasers. These results suggest that multimodal photoswitchable spasers could extend the traditional applications of spasers and PFPs in laser spectroscopy, multicolor cytometry, and theranostics with the potential to track, identify, and kill abnormal cells in circulation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 535
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: New Frontiers in Diagnosis and Therapy of Circulating Tumor Markers in Cerebrospinal Fluid In Vitro and In Vivo

    Olga A. Sindeeva / Roman A. Verkhovskii / Mustafa Sarimollaoglu / Galina A. Afanaseva / Alexander S. Fedonnikov / Evgeny Yu. Osintsev / Elena N. Kurochkina / Dmitry A. Gorin / Sergey M. Deyev / Vladimir P. Zharov / Ekaterina I. Galanzha

    Cells, Vol 8, Iss 10, p

    2019  Volume 1195

    Abstract: One of the greatest challenges in neuro-oncology is diagnosis and therapy (theranostics) of leptomeningeal metastasis (LM), brain metastasis (BM) and brain tumors (BT), which are associated with poor prognosis in patients. Retrospective analyses suggest ... ...

    Abstract One of the greatest challenges in neuro-oncology is diagnosis and therapy (theranostics) of leptomeningeal metastasis (LM), brain metastasis (BM) and brain tumors (BT), which are associated with poor prognosis in patients. Retrospective analyses suggest that cerebrospinal fluid (CSF) is one of the promising diagnostic targets because CSF passes through central nervous system, harvests tumor-related markers from brain tissue and, then, delivers them into peripheral parts of the human body where CSF can be sampled using minimally invasive and routine clinical procedure. However, limited sensitivity of the established clinical diagnostic cytology in vitro and MRI in vivo together with minimal therapeutic options do not provide patient care at early, potentially treatable, stages of LM, BM and BT. Novel technologies are in demand. This review outlines the advantages, limitations and clinical utility of emerging liquid biopsy in vitro and photoacoustic flow cytometry (PAFC) in vivo for assessment of CSF markers including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA (miRNA), proteins, exosomes and emboli. The integration of in vitro and in vivo methods, PAFC-guided theranostics of single CTCs and targeted drug delivery are discussed as future perspectives.
    Keywords cerebrospinal liquid biopsy ; in vivo flow cytometry ; tumor biomarkers ; circulating tumor cells ; ctdna ; mirna ; exosomes ; emboli ; targeted therapy ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    Mazen A. Juratli / Mustafa Sarimollaoglu / Dmitry A. Nedosekin / Alexander V. Melerzanov / Vladimir P. Zharov / Ekaterina I. Galanzha

    Cancers, Vol 6, Iss 1, Pp 128-

    2014  Volume 142

    Abstract: Circulating tumor cells (CTCs) are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of ... ...

    Abstract Circulating tumor cells (CTCs) are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min). These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients.
    Keywords circulating tumor cells (CTCs) ; CTC dynamics ; quantitative heterogeneity ; in vivo flow cytometry ; photoacoustics ; personalized diagnosis and therapy ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  5. Article ; Online: Real-Time Label-Free Embolus Detection Using In Vivo Photoacoustic Flow Cytometry.

    Mazen A Juratli / Yulian A Menyaev / Mustafa Sarimollaoglu / Eric R Siegel / Dmitry A Nedosekin / James Y Suen / Alexander V Melerzanov / Tareq A Juratli / Ekaterina I Galanzha / Vladimir P Zharov

    PLoS ONE, Vol 11, Iss 5, p e

    2016  Volume 0156269

    Abstract: Thromboembolic events are one of the world's leading causes of death among patients. Embolus or clot formations have several etiologies including paraneoplastic, post-surgery, cauterization, transplantation, or extracorporeal circuits. Despite its ... ...

    Abstract Thromboembolic events are one of the world's leading causes of death among patients. Embolus or clot formations have several etiologies including paraneoplastic, post-surgery, cauterization, transplantation, or extracorporeal circuits. Despite its medical significance, little progress has been made in early embolus detection, screening and control. The aim of our study is to test the utility of the in vivo photoacoustic (PA) flow cytometry (PAFC) technique for non-invasive embolus detection in real-time. Using in vivo PAFC, emboli were non-invasively monitored in the bloodstream of two different mouse models. The tumor-free mouse model consisted of two groups, one in which the limbs were clamped to produce vessel stasis (7 procedures), and one where the mice underwent surgery (7 procedures). The melanoma-bearing mouse model also consisted of two groups, one in which the implanted tumor underwent compression (8 procedures), and one where a surgical excision of the implanted tumor was performed (8 procedures). We demonstrated that the PAFC can detect a single embolus, and has the ability to distinguish between erythrocyte-rich (red) and leukocyte/platelet-rich (white) emboli in small vessels. We show that, in tumor-bearing mice, the level of circulating emboli was increased compared to tumor-free mice (p = 0.0013). The number of circulating emboli temporarily increased in the tumor-free control mice during vessel stasis (p = 0.033) and after surgical excisions (signed-rank p = 0.031). Similar observations were noted during tumor compression (p = 0.013) and after tumor excisions (p = 0.012). For the first time, it was possible to detect unlabeled emboli in vivo non-invasively, and to confirm the presence of pigmented tumor cells within circulating emboli. The insight on embolus dynamics during cancer progression and medical procedures highlight the clinical potential of PAFC for early detection of cancer and surgery-induced emboli to prevent the fatal thromboembolic complications by well-timed therapy.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Spaser as a biological probe

    Ekaterina I. Galanzha / Robert Weingold / Dmitry A. Nedosekin / Mustafa Sarimollaoglu / Jacqueline Nolan / Walter Harrington / Alexander S. Kuchyanov / Roman G. Parkhomenko / Fumiya Watanabe / Zeid Nima / Alexandru S. Biris / Alexander I. Plekhanov / Mark I. Stockman / Vladimir P. Zharov

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 7

    Abstract: Advanced diagnostic probes are required for monitoring disease progression. Here Galanzhaet al. demonstrate a 22 nm plasmonic nanolaser to serve as a super-bright, biocompatible probe capable of generating stimulated emission directly inside living cells ...

    Abstract Advanced diagnostic probes are required for monitoring disease progression. Here Galanzhaet al. demonstrate a 22 nm plasmonic nanolaser to serve as a super-bright, biocompatible probe capable of generating stimulated emission directly inside living cells and animal tissue, while targeting cancer cells.
    Keywords Science ; Q
    Language English
    Publishing date 2017-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: In Vivo Long-Term Monitoring of Circulating Tumor Cells Fluctuation during Medical Interventions.

    Mazen A Juratli / Eric R Siegel / Dmitry A Nedosekin / Mustafa Sarimollaoglu / Azemat Jamshidi-Parsian / Chengzhong Cai / Yulian A Menyaev / James Y Suen / Ekaterina I Galanzha / Vladimir P Zharov

    PLoS ONE, Vol 10, Iss 9, p e

    2015  Volume 0137613

    Abstract: The goal of this research was to study the long-term impact of medical interventions on circulating tumor cell (CTC) dynamics. We have explored whether tumor compression, punch biopsy or tumor resection cause dissemination of CTCs into peripheral blood ... ...

    Abstract The goal of this research was to study the long-term impact of medical interventions on circulating tumor cell (CTC) dynamics. We have explored whether tumor compression, punch biopsy or tumor resection cause dissemination of CTCs into peripheral blood circulation using in vivo fluorescent flow cytometry and breast cancer-bearing mouse model inoculated with MDA-MB-231-Luc2-GFP cells in the mammary gland. Two weeks after tumor inoculation, three groups of mice were the subject of the following interventions: (1) tumor compression for 15 minutes using 400 g weight to approximate the pressure during mammography; (2) punch biopsy; or (3) surgery. The CTC dynamics were determined before, during and six weeks after these interventions. An additional group of tumor-bearing mice was used as control and did not receive an intervention. The CTC dynamics in all mice were monitored weekly for eight weeks after tumor inoculation. We determined that tumor compression did not significantly affect CTC dynamics, either during the procedure itself (P = 0.28), or during the 6-week follow-up. In the punch biopsy group, we observed a significant increase in CTC immediately after the biopsy (P = 0.02), and the rate stayed elevated up to six weeks after the procedure in comparison to the tumor control group. The CTCs in the group of mice that received a tumor resection disappeared immediately after the surgery (P = 0.03). However, CTC recurrence in small numbers was detected during six weeks after the surgery. In the future, to prevent these side effects of medical interventions, the defined dynamics of intervention-induced CTCs may be used as a basis for initiation of aggressive anti-CTC therapy at time-points of increasing CTC number.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: In vivo magnetic enrichment, photoacoustic diagnosis, and photothermal purging of infected blood using multifunctional gold and magnetic nanoparticles.

    Ekaterina I Galanzha / Evgeny Shashkov / Mustafa Sarimollaoglu / Karen E Beenken / Alexei G Basnakian / Mark E Shirtliff / Jin-Woo Kim / Mark S Smeltzer / Vladimir P Zharov

    PLoS ONE, Vol 7, Iss 9, p e

    2012  Volume 45557

    Abstract: Bacterial infections are a primary cause of morbidity and mortality worldwide. Bacteremia is a particular concern owing to the possibility of septic shock and the development of metastatic infections. Treatment of bacteremia is increasingly compromised ... ...

    Abstract Bacterial infections are a primary cause of morbidity and mortality worldwide. Bacteremia is a particular concern owing to the possibility of septic shock and the development of metastatic infections. Treatment of bacteremia is increasingly compromised by the emergence of antibiotic resistant strains, creating an urgent need for alternative therapy. Here, we introduce a method for in vivo photoacoustic (PA) detection and photothermal (PT) eradication of Staphylococcus aureus in tissue and blood. We show that this method could be applicable for label-free diagnosis and treatment of in the bloodstream using intrinsic near-infrared absorption of endogenous carotenoids with nonlinear PA and PT contrast enhancement. To improve sensitivity and specificity for detection of circulating bacteria cells (CBCs), two-color gold and multilayer magnetic nanoparticles with giant amplifications of PA and PT contrasts were functionalized with an antibody cocktail for molecular targeting of S. aureus surface-associated markers such as protein A and lipoprotein. With a murine model, the utility of this approach was demonstrated for ultrasensitive detection of CBCs with threshold sensitivity as low as 0.5 CBCs/mL, in vivo magnetic enrichment of CBCs, PT eradication of CBCs, and real-time monitoring of therapeutic efficacy by CBC counting. Our PA-PT nano-theranostic platform, which integrates in vivo multiplex targeting, magnetic enrichment, signal amplification, multicolor recognition, and feedback control, could be used as a biological tool to gain insights on dissemination pathways of CBCs, infection progression by bacteria re-seeding, and sepsis development and treatment, and could potentially be feasible in humans, especially using bypass schematic.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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