Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging
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{"title"=>"Development of a preclinical orthotopic xenograft model of ewing sarcoma and other human malignant bone disease using advanced in vivo imaging", "type"=>"journal", "authors"=>[{"first_name"=>"Britta", "last_name"=>"Vormoor", "scopus_author_id"=>"56085144400"}, {"first_name"=>"Henrike K.", "last_name"=>"Knizia", "scopus_author_id"=>"56085283800"}, {"first_name"=>"Michael A.", "last_name"=>"Batey", "scopus_author_id"=>"7004360651"}, {"first_name"=>"Gilberto S.", "last_name"=>"Almeida", "scopus_author_id"=>"56596321300"}, {"first_name"=>"Ian", "last_name"=>"Wilson", "scopus_author_id"=>"22999257500"}, {"first_name"=>"Petra", "last_name"=>"Dildey", "scopus_author_id"=>"17345488700"}, {"first_name"=>"Abhishek", "last_name"=>"Sharma", "scopus_author_id"=>"56085813500"}, {"first_name"=>"Helen", "last_name"=>"Blair", "scopus_author_id"=>"7102730907"}, {"first_name"=>"I. Geoff", "last_name"=>"Hide", "scopus_author_id"=>"35618020000"}, {"first_name"=>"Olaf", "last_name"=>"Heidenreich", "scopus_author_id"=>"7005213313"}, {"first_name"=>"Josef", "last_name"=>"Vormoor", "scopus_author_id"=>"56186608600"}, {"first_name"=>"Ross J.", "last_name"=>"Maxwell", "scopus_author_id"=>"15051955100"}, {"first_name"=>"Chris M.", "last_name"=>"Bacon", "scopus_author_id"=>"7103109677"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372701524", "sgr"=>"84896907722", "issn"=>"19326203", "pmid"=>"24409320", "scopus"=>"2-s2.0-84896907722", "doi"=>"10.1371/journal.pone.0085128"}, "id"=>"999b440b-8294-3575-b573-72d2f2043829", "abstract"=>"Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2(-/-/)γc(-/-) mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000-5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised \"malignant\" bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which resemble the human disease. We have shown the utility of small animal bioimaging for tracking disease progression, making this model a useful assay for preclinical drug testing.", "link"=>"http://www.mendeley.com/research/development-preclinical-orthotopic-xenograft-model-ewing-sarcoma-other-human-malignant-bone-disease-2", "reader_count"=>36, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Doctoral Student"=>3, "Student > Ph. D. 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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1340490"], "description"=>"<p>Representative FDG-PET images of mice anaesthetized with isofluorane (right mouse) versus ketamine/medetomidine (left mouse) showing a marked reduction in cardiac FDG uptake in the latter.</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "anaesthetic"], "article_id"=>895616, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g005", "stats"=>{"downloads"=>0, "page_views"=>40, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_different_anaesthetic_techniques_/895616", "title"=>"Comparison of different anaesthetic techniques.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340488"], "description"=>"<p><b>A</b>, Representative CT image 29 days after transplantation of PC3M cells, showing lytic destruction of the femur (arrow) (sagittal section). <b>B</b>, Lytic destruction of the femoral cortex associated with numerous osteoclasts (short arrow) and focal reactive bone formation (long arrow) (H&E, original magnification 200×). <b>C</b>, Lysis and virtual destruction of the bone by numerous osteoclasts on the periosteal surface (long arrows), with osteoblastic reaction on the medullary surface (short arrow) (H&E, original magnification 200×). <b>D</b>, Lysis of bone by osteoclasts in resorption pits on the medullary surface (arrows), clearly distinct from intrafemoral tumour (H&E, original magnification 400×).</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "lesions", "caused", "injection"], "article_id"=>895614, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g003", "stats"=>{"downloads"=>1, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Osteolytic_lesions_caused_by_injection_of_PC3M_/895614", "title"=>"Osteolytic lesions caused by injection of PC3M.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340499", "https://ndownloader.figshare.com/files/1340500"], "description"=>"<div><p>Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing <i>in vivo</i> monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2<sup>−/−/</sup>γc<sup>−/−</sup> mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic <i>in vivo</i> model for Ewing sarcoma and other primary and secondary human bone malignancies, which resemble the human disease. We have shown the utility of small animal bioimaging for tracking disease progression, making this model a useful assay for preclinical drug testing.</p></div>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "preclinical", "orthotopic", "xenograft", "ewing", "sarcoma", "malignant", "imaging"], "article_id"=>895625, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085128.s001", "https://dx.doi.org/10.1371/journal.pone.0085128.s002"], "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Development_of_a_Preclinical_Orthotopic_Xenograft_Model_of_Ewing_Sarcoma_and_Other_Human_Malignant_Bone_Disease_Using_Advanced_In_Vivo_Imaging/895625", "title"=>"Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced <i>In Vivo</i> Imaging", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340497"], "description"=>"<p>VH-64 and TC-71: Ewing sarcoma cell lines; SaOS-2: osteosarcoma cell line; PC3M: prostatic adenocarcinoma cell line; Medium: mice were injected with medium alone. N.A.: not applicable. All mice were NSG mice unless stated otherwise.</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "mice", "orthotopic"], "article_id"=>895623, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.t001", "stats"=>{"downloads"=>0, "page_views"=>31, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experimental_mice_for_the_development_of_an_orthotopic_model_of_bone_malignancies_/895623", "title"=>"Experimental mice for the development of an orthotopic model of bone malignancies.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340498"], "description"=>"<p>One mouse with an IVIS-positive femoral tumour was culled on day 4 and could not be assessed for metastatic spread. Post mortem bioluminescence imaging of dissected organs was performed on 5 animals. The involved leg of one of these had been removed before imaging.</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "tc-71", "bioluminescent", "detection", "mice", "post-mortem"], "article_id"=>895624, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.t002", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_TC_71_bioluminescent_signal_detection_in_live_mice_and_post_mortem_after_dissection_/895624", "title"=>"Summary of TC-71 bioluminescent signal detection in live mice and post-mortem (after dissection).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340496"], "description"=>"<p><b>A,</b> Example of a mouse transplanted with 1×10<sup>5</sup> 25% EGFP positive TC-71 cells with metastatic spread to the jaw, and post mortem IVIS imaging of individual organs (dissected head, lungs and liver) demonstrating the signal from the jaw and additional weak signals from both lungs, all of which were confirmed by histology. <b>B,</b> TC-71 tumour deposit contained completely within liver parenchyma as an example of visceral tumour spread (H&E, original magnification 40×). <b>C,</b> TC-71 tumour deposit (T) within the mandible as an example of spread to distant osseus sites. Tng: tongue; arrowheads: teeth (H&E, original magnification 40×). <b>D,</b> Cluster of TC-71 tumour cells within a small arterial vessel adjacent to a bronchiole as an example of haematogenous spread (H&E, original magnification 400×). <b>E,</b> Cluster of TC-71 tumour cells within a lymphatic vessel adjacent to an arterial vessel and bronchiole as an example of intralymphatic spread (H&E, original magnification 400×).</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "bioluminescent", "imaging", "tumour", "mortem", "histology"], "article_id"=>895622, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g011", "stats"=>{"downloads"=>2, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Examples_of_bioluminescent_imaging_of_tumour_spread_to_bone_post_mortem_imaging_of_organs_and_the_histology_of_tumour_spread_/895622", "title"=>"Examples of bioluminescent imaging of tumour spread to bone, post mortem imaging of organs, and.the histology of tumour spread.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340493"], "description"=>"<p>Weekly bioluminescent imaging of two Rag2<sup>−/−</sup> γc<sup>−/−</sup> mice transplanted with 5×10<sup>5</sup> transduced TC-71 cells in a volume of 30 µl (25% EGFP positive cells, top row and sorted 100% EGFP positive cells, bottom row).</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "imaging", "mice", "intrafemorally", "transplanted", "transduced", "tc-71"], "article_id"=>895619, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g008", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bioluminescent_imaging_of_Rag2_8722_8722_947_c_8722_8722_mice_intrafemorally_transplanted_with_transduced_TC_71_cells_/895619", "title"=>"Bioluminescent imaging of Rag2<sup>−/−</sup> γc<sup>−/−</sup> mice intrafemorally transplanted with transduced TC-71 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340492"], "description"=>"<p>MRI imaging performed 47 days after injection of a mouse with VH-64 cells, providing an example of respiratory gating to obtain good quality images. 2 out of 25 adjacent 2 mm slices (selected slices 12 mm apart) are presented showing upper abdomen (left panel), revealing a large liver tumour, and lungs (right panel). Despite slight movement artifacts on the thoracic images there is good visualisation of the lung fields. L: liver; K: kidney; S: stomach.</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "images", "deposits", "lungs", "respiratory"], "article_id"=>895618, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g007", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MR_images_of_liver_deposits_and_lungs_using_respiratory_gating_/895618", "title"=>"MR images of liver deposits and lungs using respiratory gating.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340487"], "description"=>"<p><b>A</b>, Representative CT image 70 days after intrafemoral transplantation of SaOS-2 cells showing “malignant” bone formation within the extraosseous tumour mass (arrow). <b>B</b>, Representative Maximum Intensity Projection CT image of a mouse bearing a SaOS tumour 70 days after transplantation, showing “malignant” bone formation within the extraosseous tumour mass (arrow). <b>C</b>, “Malignant” bone forming amongst tumour cells in the medullary cavity, showing appositional deposition (scaffolding) on existing bone trabeculae (“T”) (H&E, original magnification 200×). <b>D</b>, Left panel: malignant tumour cells amongst pale eosinophilic osteoid which is partially mineralised (arrow) (H&E, original magnification 400×). Right panel: fine, randomly arborising strands of mineralised osteoid (“malignant” bone) amongst SaOS-2 tumour cells (H&E, original magnification 400×).</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "tumour", "saos-2"], "article_id"=>895613, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g002", "stats"=>{"downloads"=>2, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_8220_Malignant_8221_bone_formation_within_the_tumour_mass_after_SaOS_2_transplantation_/895613", "title"=>"“Malignant” bone formation within the tumour mass after SaOS-2 transplantation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340486"], "description"=>"<p><b>A</b>, Representative CT image of a VH-64 transplanted femur 42 days after transplantation showing a “sunburst” pattern of reactive bone formation. <b>B</b>, Representative Maximum Intensity Projection CT image of a mouse with a VH-64 tumour 52 days after transplantation showing a “sunburst” pattern of reactive bone formation on the transplanted femur (between arrows, and extending proximally along the femur). <b>C</b>, Extensive reactive bone (arrows) arcing through a VH-64 tumour accompanied by foci of cartilage (arrowheads). Tumour is partly necrotic (N) (H&E, original magnification 20×). <b>D</b>, Reactive bone emanating from femoral cortex (top) within a VH-64 tumour (H&E, original magnification 100×). <b>E</b>, Reactive new bone formation partially lined by osteoblasts (arrows) amongst VH-64 tumour cells. A single multinucleate osteoclast (arrowhead) is also present (H&E, original magnification 400×). <b>F</b>, Reactive bone and a focus of cartilage (arrow) amongst VH-64 tumour cells (H&E, original magnification 200×) <b>G</b>, Representative CT image of a TC-71 transplanted femur 15 days after transplantation showing cortical destruction (arrow) and possible reactive new bone formation (arrowhead). <b>H</b>, Marked reactive new bone formation within a TC-71 tumour, beneath the raised periosteum (arrow). Cortical destruction is seen distally (arrowhead) (H&E, original magnification 40×). <b>I</b>, Reactive new bone in a TC-71 transplanted mouse, lined by osteoblasts (arrow) clearly distinct from infiltrating tumour cells (arrowhead) (H&E, original magnification 400×).</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "reactive", "transplantation", "ewing", "sarcoma", "lines", "vh-64", "tc-71"], "article_id"=>895612, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g001", "stats"=>{"downloads"=>5, "page_views"=>53, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Prominent_reactive_bone_formation_following_transplantation_of_Ewing_sarcoma_cell_lines_VH_64_A_8211_E_and_TC_71_F_8211_I_/895612", "title"=>"Prominent reactive bone formation following transplantation of Ewing sarcoma cell lines VH-64 (A–E) and TC-71 (F–I).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340495"], "description"=>"<p>Depicted is the development of signal intensity for 5 animals injected with either 1×10<sup>3</sup>, 5×10<sup>3</sup> or 1×10<sup>4</sup> cells in a volume of 10 µl. The experiment was performed with EGFP sorted cells one week prior to injection.</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "bioluminescent", "mice", "injected", "numbers", "transduced", "tc-71"], "article_id"=>895621, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g010", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Timecourse_of_bioluminescent_signal_in_mice_injected_with_low_numbers_of_transduced_TC_71_cells_/895621", "title"=>"Timecourse of bioluminescent signal in mice injected with low numbers of transduced TC-71 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340494"], "description"=>"<p>Weekly bioluminescent imaging of 3 Rag2<sup>−/−</sup> γc<sup>−/−</sup> mice transplanted with 1×10<sup>3</sup> (top row), 5×10<sup>3</sup> (middle row) or 1×10<sup>4</sup> (bottom row) transduced TC-71 cells (EGFP sorted 1 week prior to injection). Injected cells were suspended in a volume of 10 µl. The images obtained on day 7 did show a low signal over the right femur for all of the mice, but due to the chosen radiance settings to enable comparison with subsequent iamges, they do not appear on this panel. On some images of mice who were not imaged individually towards the end of the experiment (i.e. middle row day 27 and 41), the reflection of a signal emitted from a neighbouring mouse is unfortunately projected onto the left femur (day 27) or left side (day 41) of that mouse. All mice developed distant disease, either in lungs (top row), liver/abdomen (middle and bottom row) or contralateral leg (middle row).</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "imaging", "mice", "intrafemorally", "transplanted", "numbers", "transduced", "tc-71"], "article_id"=>895620, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g009", "stats"=>{"downloads"=>7, "page_views"=>72, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bioluminescent_imaging_of_of_Rag2_8722_8722_947_c_8722_8722_mice_intrafemorally_transplanted_with_low_numbers_of_transduced_TC_71_cells_/895620", "title"=>"Bioluminescent imaging of of Rag2<sup>−/−</sup> γc<sup>−/−</sup> mice intrafemorally transplanted with low numbers of transduced TC-71 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340491"], "description"=>"<p>Measurement of a VH-64 Ewing sarcoma of the injected femur with a large extra-osseous tumour component. The regions of interest (within red markings) were measured in sequential 2 mm thick slices that showed tumour, and by adding the volumes of individual slices the total tumour volume was calculated. In the depicted case the estimated total volume was 492 mm<sup>3</sup> (tumour in 6 slices; region of interest per slice: 22 mm<sup>2</sup>, 42 mm<sup>2</sup>, 57 mm<sup>2</sup>, 59 mm<sup>2</sup>, 52 mm<sup>2</sup>, 14 mm<sup>2</sup>; total area = 246 mm<sup>2</sup>; slice thickness = 2 mm; estimated total volume = 492 mm<sup>3</sup>).</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "imaging", "tumour"], "article_id"=>895617, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g006", "stats"=>{"downloads"=>9, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MR_imaging_of_primary_tumour_with_measurement_of_tumour_volume_/895617", "title"=>"MR imaging of primary tumour with measurement of tumour volume.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1340489"], "description"=>"<p><b>A</b>, PET/CT image of a mouse with a VH-64 tumour following intrafemoral transplantation. Image taken 52 days after transplantation, tumour marked with a white arrow (Maximum Intensity Projection CT image overlaid with FDG-PET image, dorsal view, ketamine/medetomodine anaeshesia). <b>B</b>, PET/CT image of a mouse injected with medium alone, also 52 days after i.f. injection, no tumour visible (Maximum Intensity Projection CT image overlaid with FDG-PET image, dorsal view, ketamine/medetomodine anaeshesia).</p>", "links"=>[], "tags"=>["Clinical research design", "Animal models of disease", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Bone and soft tissue sarcomas", "Ewing sarcoma", "osteosarcoma", "Genitourinary tract tumors", "Prostate cancer", "Pediatric oncology", "radiology", "Diagnostic radiology", "Computed tomography", "Magnetic resonance imaging", "Nuclear medicine", "PET imaging", "imaging"], "article_id"=>895615, "categories"=>["Medicine"], "users"=>["Britta Vormoor", "Henrike K. Knizia", "Michael A. Batey", "Gilberto S. Almeida", "Ian Wilson", "Petra Dildey", "Abhishek Sharma", "Helen Blair", "I. Geoff Hide", "Olaf Heidenreich", "Josef Vormoor", "Ross J. Maxwell", "Chris M. Bacon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085128.g004", "stats"=>{"downloads"=>8, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PET_CT_imaging_of_primary_tumour_/895615", "title"=>"PET-CT imaging of primary tumour.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-07 03:35:56"}

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Relative Metric

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