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  1. Article ; Online: Indocyanine green fluorescence in second near-infrared (NIR-II) window.

    Zbigniew Starosolski / Rohan Bhavane / Ketan B Ghaghada / Sanjeev A Vasudevan / Alexander Kaay / Ananth Annapragada

    PLoS ONE, Vol 12, Iss 11, p e

    2017  Volume 0187563

    Abstract: Indocyanine green (ICG), a FDA approved near infrared (NIR) fluorescent agent, is used in the clinic for a variety of applications including lymphangiography, intra-operative lymph node identification, tumor imaging, superficial vascular imaging, and ... ...

    Abstract Indocyanine green (ICG), a FDA approved near infrared (NIR) fluorescent agent, is used in the clinic for a variety of applications including lymphangiography, intra-operative lymph node identification, tumor imaging, superficial vascular imaging, and marking ischemic tissues. These applications operate in the so-called "NIR-I" window (700-900 nm). Recently, imaging in the "NIR-II" window (1000-1700 nm) has attracted attention since, at longer wavelengths, photon absorption, and scattering effects by tissue components are reduced, making it possible to image deeper into the underlying tissue. Agents for NIR-II imaging are, however, still in pre-clinical development. In this study, we investigated ICG as a NIR-II dye. The absorbance and NIR-II fluorescence emission of ICG were measured in different media (PBS, plasma and ethanol) for a range of ICG concentrations. In vitro and in vivo testing were performed using a custom-built spectral NIR assembly to facilitate simultaneous imaging in NIR-I and NIR-II window. In vitro studies using ICG were performed using capillary tubes (as a simulation of blood vessels) embedded in Intralipid solution and tissue phantoms to evaluate depth of tissue penetration in NIR-I and NIR-II window. In vivo imaging using ICG was performed in nude mice to evaluate vascular visualization in the hind limb in the NIR-I and II windows. Contrast-to-noise ratios (CNR) were calculated for comparison of image quality in NIR-I and NIR-II window. ICG exhibited significant fluorescence emission in the NIR-II window and this emission (similar to the absorption profile) is substantially affected by the environment of the ICG molecules. In vivo imaging further confirmed the utility of ICG as a fluorescent dye in the NIR-II domain, with the CNR values being ~2 times those in the NIR-I window. The availability of an FDA approved imaging agent could accelerate the clinical translation of NIR-II imaging technology.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: MDM4 inhibition

    Sarah E. Woodfield / Yan Shi / Roma H. Patel / Zhenghu Chen / Aayushi P. Shah / Richard S. Whitlock / Aryana M. Ibarra / Samuel R. Larson / Stephen F. Sarabia / Andrew Badachhape / Zbigniew Starosolski / Ketan B. Ghaghada / Pavel Sumazin / D. Allen Annis / Dolores López-Terrada / Sanjeev A. Vasudevan

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    a novel therapeutic strategy to reactivate p53 in hepatoblastoma

    2021  Volume 17

    Abstract: Abstract Hepatoblastoma (HB) is the most common pediatric liver malignancy. High-risk patients have poor survival, and current chemotherapies are associated with significant toxicities. Targeted therapies are needed to improve outcomes and patient ... ...

    Abstract Abstract Hepatoblastoma (HB) is the most common pediatric liver malignancy. High-risk patients have poor survival, and current chemotherapies are associated with significant toxicities. Targeted therapies are needed to improve outcomes and patient quality of life. Most HB cases are TP53 wild-type; therefore, we hypothesized that targeting the p53 regulator Murine double minute 4 (MDM4) to reactivate p53 signaling may show efficacy. MDM4 expression was elevated in HB patient samples, and increased expression was strongly correlated with decreased expression of p53 target genes. Treatment with NSC207895 (XI-006), which inhibits MDM4 expression, or ATSP-7041, a stapled peptide dual inhibitor of MDM2 and MDM4, showed significant cytotoxic and antiproliferative effects in HB cells. Similar phenotypes were seen with short hairpin RNA (shRNA)-mediated inhibition of MDM4. Both NSC207895 and ATSP-7041 caused significant upregulation of p53 targets in HB cells. Knocking-down TP53 with shRNA or overexpressing MDM4 led to resistance to NSC207895-mediated cytotoxicity, suggesting that this phenotype is dependent on the MDM4-p53 axis. MDM4 inhibition also showed efficacy in a murine model of HB with significantly decreased tumor weight and increased apoptosis observed in the treatment group. This study demonstrates that inhibition of MDM4 is efficacious in HB by upregulating p53 tumor suppressor signaling.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

    Ling Tao / Myrthala Moreno‐Smith / Rodrigo Ibarra‐García‐Padilla / Giorgio Milazzo / Nathan A. Drolet / Blanca E. Hernandez / Young S. Oh / Ivanshi Patel / Jean J. Kim / Barry Zorman / Tajhal Patel / Abu Hena Mostafa Kamal / Yanling Zhao / John Hicks / Sanjeev A. Vasudevan / Nagireddy Putluri / Cristian Coarfa / Pavel Sumazin / Giovanni Perini /
    Ronald J. Parchem / Rosa A. Uribe / Eveline Barbieri

    Advanced Science, Vol 8, Iss 19, Pp n/a-n/a (2021)

    2021  

    Abstract: Abstract Neuroblastoma (NB) arises from oncogenic disruption of neural crest (NC) differentiation. Treatment with retinoic acid (RA) to induce differentiation has improved survival in some NB patients, but not all patients respond, and most NBs ... ...

    Abstract Abstract Neuroblastoma (NB) arises from oncogenic disruption of neural crest (NC) differentiation. Treatment with retinoic acid (RA) to induce differentiation has improved survival in some NB patients, but not all patients respond, and most NBs eventually develop resistance to RA. Loss of the chromatin modifier chromatin assembly factor 1 subunit p150 (CHAF1A) promotes NB cell differentiation; however, the mechanism by which CHAF1A drives NB oncogenesis has remained unexplored. This study shows that CHAF1A gain‐of‐function supports cell malignancy, blocks neuronal differentiation in three models (zebrafish NC, human NC, and human NB), and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression. Targeting polyamine synthesis promotes NB differentiation and enhances the anti‐tumor activity of RA. The authors' results provide insight into the mechanisms that drive NB oncogenesis and suggest a rapidly translatable therapeutic approach (DFMO plus RA) to enhance the clinical efficacy of differentiation therapy in NB patients.
    Keywords CHAF1A ; metabolism ; neural crest differentiation ; neuroblastoma ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Restoration of the molecular clock is tumor suppressive in neuroblastoma

    Myrthala Moreno-Smith / Giorgio Milazzo / Ling Tao / Baharan Fekry / Bokai Zhu / Mahmoud A. Mohammad / Simone Di Giacomo / Roshan Borkar / Karthik Reddy Kami Reddy / Mario Capasso / Sanjeev A. Vasudevan / Pavel Sumazin / John Hicks / Nagireddy Putluri / Giovanni Perini / Kristin Eckel-Mahan / Thomas P. Burris / Eveline Barbieri

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 16

    Abstract: MYCN is frequently amplified in neuroblastomas. Here, the authors show that MYCN disrupts the molecular clock by downregulating clock activator RORα and that the reactivation of RORα restores BMAL1 activity, and inhibits lipid metabolism and ... ...

    Abstract MYCN is frequently amplified in neuroblastomas. Here, the authors show that MYCN disrupts the molecular clock by downregulating clock activator RORα and that the reactivation of RORα restores BMAL1 activity, and inhibits lipid metabolism and neuroblastoma growth
    Keywords Science ; Q
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Author Correction

    Sarah E. Woodfield / Yan Shi / Roma H. Patel / Zhenghu Chen / Aayushi P. Shah / Rohit K. Srivastava / Richard S. Whitlock / Aryana M. Ibarra / Samuel R. Larson / Stephen F. Sarabia / Andrew Badachhape / Zbigniew Starosolski / Ketan B. Ghaghada / Pavel Sumazin / D. Allen Annis / Dolores López-Terrada / Sanjeev A. Vasudevan

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    MDM4 inhibition: a novel therapeutic strategy to reactivate p53 in hepatoblastoma

    2021  Volume 1

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma

    Sarah E. Woodfield / Yan Shi / Roma H. Patel / Jingling Jin / Angela Major / Stephen F. Sarabia / Zbigniew Starosolski / Barry Zorman / Siddharth S. Gupta / Zhenghu Chen / Aryana M. Ibarra / Karl-Dimiter Bissig / Ketan B. Ghaghada / Pavel Sumazin / Dolores López-Terrada / Sanjeev A. Vasudevan

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 11

    Abstract: Abstract Currently, preclinical testing of therapies for hepatoblastoma (HB) is limited to subcutaneous and intrasplenic xenograft models that do not recapitulate the hepatic tumors seen in patients. We hypothesized that injection of HB cell lines into ... ...

    Abstract Abstract Currently, preclinical testing of therapies for hepatoblastoma (HB) is limited to subcutaneous and intrasplenic xenograft models that do not recapitulate the hepatic tumors seen in patients. We hypothesized that injection of HB cell lines into the livers of mice would result in liver tumors that resemble their clinical counterparts. HepG2 and Huh-6 HB cell lines were injected, and tumor growth was monitored with bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). Levels of human α-fetoprotein (AFP) were monitored in the serum of animals. Immunohistochemical and gene expression analyses were also completed on xenograft tumor samples. BLI signal indicative of tumor growth was seen in 55% of HepG2- and Huh-6-injected animals after a period of four to seven weeks. Increased AFP levels correlated with tumor growth. MRI showed large intrahepatic tumors with active neovascularization. HepG2 and Huh-6 xenografts showed expression of β-catenin, AFP, and Glypican-3 (GPC3). HepG2 samples displayed a consistent gene expression profile most similar to human HB tumors. Intrahepatic injection of HB cell lines leads to liver tumors in mice with growth patterns and biologic, histologic, and genetic features similar to human HB tumors. This orthotopic xenograft mouse model will enable clinically relevant testing of novel agents for HB.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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