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      1. Author :
        Owen, John Henry; Komarck, Christine M.; Wang, Anthony C.; Abuzeid, Waleed M.; Keep, Richard F.; McKean, Erin L.; Sullivan, Stephen; Fan, Xing; Prince, Mark E. P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Journal of Neurosurgery
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        chordoma; cell line; clivus; oncology; IVIS; IVIS BLI in vivo
      12. Abstract :
        OBJECTIVE Chordomas are rare malignant tumors thought to arise from remnants of the notochord. They can be located anywhere along the axial skeleton but are most commonly found in the clival and sacrococcygeal regions, where the notochord regresses during fetal development. Chordomas are resistant to many current therapies, leaving surgery as the primary method of treatment. Cancer cell lines have been useful for developing new cancer treatments in a laboratory setting that can then be transferred to the clinic, but there are only 4 validated chordoma cell lines available. The objective of this work was to establish chordoma cell lines from surgical tissue in order to expand the library of lines available for laboratory research. METHODS Chordoma tissue from the clivus was processed and sorted by flow cytometry to obtain an isolated population of chordoma cells. These cells were grown in culture and expanded until enough doublings to consider the line established. Identification of a chordoma cell line was made with known markers for chordoma, and the line was observed for ALDH (aldehyde dehydrogenase) subpopulations and tested in serum-free growth conditions as well as in vivo. RESULTS A fifth chordoma cell line, UM-Chor1, was successfully established. This is the first chordoma cell line originating from the clivus. Validation was confirmed by phenotype and positivity for the chordoma markers CD24 and brachyury. The authors also attempted to identify an ALDHhigh cell population in UM-Chor1, UCH1, and UCH2 but did not detect a distinct population. UM-Chor1 cells were able to form spheroids in serum-free culture, were successfully transduced with luciferase, and could be injected parasacrally and grown in NOD/SCID mice. CONCLUSIONS The availability of this novel clival chordoma cell line for in vitro and in vivo research provides an opportunity for developments in treatment against the disease.
      13. URL :
        http://thejns.org/doi/abs/10.3171/2016.10.JNS16877
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13750
      15. Serial :
        13830
      1. Author :
        Iwami, K.; Momota, H.; Natsume, A.; Kinjo, S.; Nagatani, T.; Wakabayashi, T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Journal of neurosurgery
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        N/A
      12. Abstract :
        Object Mouse models have been widely used in developing therapies for human brain tumors. However, surgical techniques such as bone drilling and skin suturing to create brain tumors in adult mice are still complicated. The aim of this study was to establish a simple and accurate method for intracranial injection of cells or other materials into mice. Methods anatomical characteristics of the mouse postglenoid foramen. They then used xenograft and genetically engineered mouse models to evaluate a novel technique of percutaneous intracranial injection via the postglenoid foramen. They injected green fluorescent protein-labeled U87MG cells or virus-producing cells into adult mouse brains via the postglenoid foramen and identified the location of the created tumors by using bioluminescence imaging and histological analysis. Results The postglenoid foramen was found to be a well-conserved anatomical structure that allows percutaneous injection into the cerebrum, cerebellum, brainstem, and basal cistern in mice. The mean (+/- SD) time for the postglenoid foramen injection technique was 88 +/- 15 seconds. The incidence of in-target tumor formation in the xenograft model ranged from 80% to 100%, depending on the target site. High-grade gliomas were successfully developed by postglenoid foramen injection in the adult genetically engineered mouse using virus-mediated platelet-derived growth factor B gene transfer. There were no procedure-related complications. Conclusions The postglenoid foramen can be used as a needle entry site into the brain of the adult mouse. Postglenoid foramen injection is a less invasive, safe, precise, and rapid method of implanting cells into the adult mouse brain. This method can be applied to both orthotopic xenograft and genetically engineered mouse models and may have further applications in mice for the development of therapies for human brain tumors.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22149378
      14. Call Number :
        PKI @ catherine.lautenschlager @ 6350
      15. Serial :
        8834
      1. Author :
        XB Liu
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Artificial Cells, Nanomedicine, and Biotechnology
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        Objective : Hypoxic tumor cells are more resistant to standard chemotherapies. A number of studies indicated that improving oxygenation inside the tumor could serve as a potential strategy to target hypoxia-induced chemoresistance. In this study, we examined whether a hemoglobin-based oxygen carrier (OC89) could increase tumor oxygenation and thus enhance the effi ciency of transarterial chemoembolization (TACE) in an orthotopic rat HCC model. Methods : Effi ciency of the hemoglobin-based oxygen carrier (OC89) in improving tumor oxygenation was examined by OxyLab pO 2 . Sensitization of chemotherapy (cisplatin) in TACE by OC89 was evaluated in four diff erent therapeutic regimens including cisplatin (1 mg/kg) OC89 (0.2 g/kg), cisplatin (1 mg/kg) OC89 (0.4 g/kg), cisplatin (3 mg/kg) OC89 (0.2 g/kg), cisplatin (3 mg/kg) OC89 (0.4 g/kg). For all the therapeutic regimens, a single delivery of OC89 via the tail vein was performed 1 h before TACE. Results : Compared with Ringer ’ s buff er, systemic delivery of OC89 (0.4 g/kg) attenuated tumor hypoxia ( p 0.05). Additionally, partial pressure of oxygen (pO 2 ) fraction of low readings (0 – 10 mmHg) inside the tumor decreased from 74.1% to 24.6% after OC89 delivery, while pO 2 fraction of high readings (15 – 25 mmHg) increased from 22.2% to 41.5%. When cisplatin was combined with OC89, regimen cisplatin (3 mg/kg) OC89 (0.4 g/kg) resulted in a signifi cant inhibition of tumor growth at Day 21 after therapy ( p 0.05). Further investigation indicated that OC89 delivery infl uenced anti-apoptotic and pro-apoptotic balance of the UPR pathway in the tumor. Conclusions : Our data suggest that targeting tumor hypoxia with the hemoglobinbased O 2 carrier serves as a promising approach to enhance the effi cacy of cisplatin-based chemotherapy in HCC.
      13. URL :
        http://dx.doi.org/10.3109/21691401.2013.808647
      14. Call Number :
        PKI @ catherine.lautenschlager @ 5093
      15. Serial :
        14750
      1. Author :
        Jiang, Linlin; Yang, Ming; Zhang, Xiaoyun; Bao, Shiqi; Ma, Li; Fan, Dongmei; Zhou, Yuan; Xiong, Dongsheng; Zhen, Yongsu
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Journal of Drug Targeting
      6. Products :
      7. Volume :
        24
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Anti-CD19(Fab)-LDM; B-lymphoma; DNA damage; internalization; targeted therapy; Maestro
      12. Abstract :
        Background: Rituximab is widely used in clinical setting for the treatment of B malignant lymphoma and has achieved remarkable success. However, in most patients, the disease ultimately relapses and become resistant to rituximab. To overcome the limitation, there is still a need to find novel strategy for improving therapeutic efficacy. Objective: To construct genetically engineered antibody anti-CD19(Fab)-LDM, and verify the anticancer activity targeted toward B-lymphoma. Methods: The anticancer activity of anti-CD19(Fab)-LDM in vitro and in vivo was examined. In vitro, the binding activity and internalization of anti-CD19(Fab)-LDP were measured. Using comet assay and apoptosis, the cytotoxicity of energized fusion proteins was observed. From in vivo experiments, targeting of therapeutic effect and anticancer efficacy bythe fusion protein was verified. Results: Data showed that anti-CD19(Fab)-LDM does not only binding the cell surface but is also internalized into the cell. The energized fusion proteins anti-CD19(Fab)-LDM can induce DNA damage. Furthermore, significant in vivo therapeutic efficacy was observed. Conclusion: The present study demonstrated that the genetically engineered antibody anti-CD19(Fab)-LDM exhibited enhanced cytotoxicity compared to LDM alone. One of the most powerful advantages of anti-CD19(Fab)-LDM, however, is that it can be internalized within the cells and carry out cytotoxic effects. Therefore, anti-CD19(Fab)-LDM may be as a useful targeted therapy for B-cell lymphoma.
      13. URL :
        http://informahealthcare.com/doi/abs/10.3109/1061186X.2015.1055568
      14. Call Number :
        PKI @ catherine.lautenschlager @ 9872
      15. Serial :
        13082
      1. Author :
        Zheng, Nan; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Wang, Kun; Li, Jian; Zhang, Qiang
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2014
      5. Publication :
        Journal of Drug Targeting
      6. Products :
      7. Volume :
        23
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Antitumor,; lanreotide,; paclitaxel,; PEG-DSPE micelles,; receptor-mediated delivery,; somatostatin receptor 2
      12. Abstract :
        Lanreotide is an octapeptide analog of endogenous somatostatin, specifically binding with tumors over-express somatostatin receptor 2 (SSTR2). In this study, we conjugated lanreotide to 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (poly-(ethylene glycol))-2000] (PEG-DSPE), constructed active targeted micelles (lanreotide-PM), characterized their in vitro and in vivo targeting effect, and explored the receptor mediated transportion. The uptake of lanreotide-PM was found to be related to the expression level of SSTR2 in different cell lines and the competitive inhibition phenomenon indicated that the cellular uptake of lanreotide-PM was via a receptor meditated mechanism. In vivo, more lanreotide-PM accumulated in SSTR2 high expression tumor xenografts, endocytosed by the tumor cells, induced more apoptosis of tumor cells, and suppressed tumor growth efficiently. In conclusion, lanreotide–modified micelles containing antitumor drugs provide a promising strategy for the treatment of SSTR-expressing tumors. Read More: http://informahealthcare.com/doi/abs/10.3109/1061186X.2014.954118
      13. URL :
        http://informahealthcare.com/doi/abs/10.3109/1061186X.2014.954118
      14. Call Number :
        PKI @ catherine.lautenschlager @ 8533
      15. Serial :
        13119
      1. Author :
        Grinberg, I.; Dukhovny, A.; Goldstein, R. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Leukemia & lymphoma
      6. Products :
      7. Volume :
        53
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Maestro; IVIS Imaging
      12. Abstract :
        Abstract Detection of grafted human cells in mice using fluorescence is a rapid and simple technique whose use is continually expanding. Robust engraftment of human hematological malignancy (HHM) lines and patient cells into the naturally immunodeficient turkey embryo has recently been demonstrated by polymerase chain reaction (PCR), fluorescence activated cell sorting (FACS) and histology. We demonstrate here that fluorescence imaging is a rapid and simple technique for detecting engraftment and homing of cells derived from HHM in turkey embryos. Raji lymphoma cells expressing a far-red fluorescent protein were injected intravascularly into turkey embryos and fluorescence was detected 8 days later in their limbs and skulls. Much stronger signals were obtained after removal of the bones from the limbs. Unlabeled Raji cells did not give a fluorescent signal. Treatment with doxorubicin dramatically reduced the fluorescent signal. Intravenously injected HL-60 leukemia cells labeled with infrared-fluorescing dye were detected in the bone marrow after 16 h. Homing was active, although some non-specific fluorescence was present. Use of fluorescence imaging of HHM in turkey embryos is therefore feasible and reduces the time, effort and expense for detecting engraftment. This technique has potential to become a high-throughput xenograft system for hematological chemotherapy development and testing, and for study of hematological cell homing.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21895546
      14. Call Number :
        PKI @ catherine.lautenschlager @ 385
      15. Serial :
        8899
      1. Author :
        Akudugu, J. M.; Azzam, E. I.; Howell, R. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Int J Radiat Biol
      6. Products :
      7. Volume :
        88
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H1, MDA-MB-231-luc-D3H1, IVIS, Bioware, Breast Cancer
      12. Abstract :
        Abstract Purpose: This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with (125)I-labeled 5-iodo-2 -deoxyuridine ((125)IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. Materials and methods: In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix carbon scaffold. Cultures were pulse-labeled for 3 h with (125)IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2'-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT((R)) EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with (125)IdU/EdU. Additional aliquots were used to determine the mean (125)I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Results: Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. Conclusions: These studies demonstrate the capacity of (125)IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22489958
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10514
      1. Author :
        Fendler, Wolfgang P.; Stuparu, Andreea D.; Evans-Axelsson, Susan; Lückerath, Katharina; Wei, Liu; Kim, Woosuk; Poddar, Soumya; Said, Jonathan; Radu, Caius G.; Eiber, Matthias; Czernin, Johannes; Slavik, Roger; Herrmann, Ken
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
      6. Products :
      7. Volume :
        58
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        177Lu; prostate cancer; Psma; specific activity; syngeneic; Pet; G8 Pet/Ct; PET imaging; Ct
      12. Abstract :
        Clinical (177)Lu-PSMA-617 radioligand therapy (RLT) is applied in advanced-stage prostate cancer. However, to the best of our knowledge murine models to study the biologic effects of various activity levels have not been established. The aim of this study was to optimize specific and total activity for (177)Lu-PSMA-617 RLT in a syngeneic model of murine prostate cancer. Methods: Murine-reconstituted, oncogene-driven prostate cancer cells (0.1 × 10(6)) (RM1), transduced to express human prostate-specific membrane antigen (PSMA), were injected into the left flank of C57Bl6 immunocompetent mice. RLT was performed by administering a single tail vein injection of (177)Lu-PSMA-617 at different formulations for specific (60 MBq at high, 62 MBq/nmol; intermediate, 31 MBq/nmol; or low 15 MBq/nmol specific activity) or total activity (30, 60, or 120 MBq). Organ distribution was determined by ex vivo γ-counter measurement. DNA double-strand breaks were measured using anti-gamma-H2A.X (phospho S139) immunohistochemistry. Efficacy was assessed by serial CT tumor volumetry and (18)F-FDG PET metabolic volume. Toxicity was evaluated 4 wk after the start of RLT. Results: Mean tumor-to-kidney ratios ± SEM were 19 ± 5, 10 ± 5, and 2 ± 0 for high, intermediate, and low (each n = 3) specific activity, respectively. Four of 6 (67%) mice treated with intermediate or high specific activity and none of 6 (0%) mice treated with low specific activity or formulation demonstrated significant DNA double-strand breaks (≥5% γ-H2A.X-positive cells). High when compared with intermediate or low specific activity resulted in a lower mean ± SEM tumor load by histopathology (vital tissue, 4 ± 2 vs. 8 ± 3 mm(2); n = 3 vs. 6), day-4 (18)F-FDG PET (metabolic volume, 87 ± 23 vs. 118 ± 14 mm(3); n = 6 vs. 12), and day-7 CT (volume, 323 ± 122 vs. 590 ± 46 mm(3); n = 3 vs. 6; P = 0.039). (177)Lu-PSMA-617 (120 MBq) with high specific activity induced superior tumor growth inhibition (P = 0.021, n = 5/group) without subacute hematologic toxicity (n = 3/group). Conclusion:(177)Lu-PSMA-617 (120 MBq) and high specific activity resulted in the highest efficacy in a syngeneic model of murine prostate cancer. The model will be useful for studying the effects of PSMA-directed RLT combined with potentially synergistic pharmacologic approaches.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/28546332
      14. Call Number :
        PKI @ user @
      15. Serial :
        17155
      1. Author :
        Gowrishankar, Gayatri; Hardy, Jonathan; Wardak, Mirwais; Namavari, Mohammad; Reeves, Robert; Neofytou, Evgenios; Srinivasan, Ananth; Wu, Joseph; Contag, Christopher; Gambhir, Sanjiv
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Journal of Nuclear Medicine
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Infectious Disease; Molecular Imaging; PET/CT; 6-18F-Fluoromaltotriose; Bacteria Infection imaging; PET/CT imaging; IVIS; IVIS BLI in vivo
      12. Abstract :
        Purpose: 6”-18F-fluoromaltotriose is a novel positron emission tomography (PET) tracer that can potentially be used to image and localize most bacterial infections, much like 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) has been used to image and localize many cancers. However, unlike 18F-FDG, 6”-18F-fluoromaltotriose is not taken up by inflammatory lesions and appears to be specific to bacterial infections by targeting the maltodextrin transporter that is expressed in most Gram-positive and Gram-negative strains of bacteria. Materials and Methods: 6”-18F-fluoromaltotriose was synthesized with high radiochemical purity and evaluated in several clinically relevant bacterial strains incultures in vitro and in living mice. Results: 6”-18F-fluoromaltotriose was taken up in both Gram-positive and Gram-negative bacterial strains. 6”-[18F]-fluoromaltotriose was also able to detect Pseudomonas aeruginosa in a clinically relevant mouse model of wound infection. The utility of 6”-18F-fluoromaltotriose to help monitor antibiotic therapies was also evaluated in rats. Conclusion: 6”-18F-fluoromaltotriose is a promising new tracer that has significant diagnostic utility, with the potential to change the clinical management of patients suffering from infectious diseases of bacterial origin.
      13. URL :
        http://jnm.snmjournals.org/content/early/2017/05/10/jnumed.117.191452.abstract http://jnm.snmjournals.org/content/early/2017/05/10/jnumed.117.191452
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13812
      15. Serial :
        14070
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