Theranostic Protein Targeting ErbB2 for Bioluminescence Imaging and Therapy for Cancer
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Mendeley | Further Information

{"title"=>"Theranostic Protein Targeting ErbB2 for Bioluminescence Imaging and Therapy for Cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Xiao-Jian", "last_name"=>"Han"}, {"first_name"=>"Ling-Fei", "last_name"=>"Sun"}, {"first_name"=>"Yuki", "last_name"=>"Nishiyama"}, {"first_name"=>"Bin", "last_name"=>"Feng"}, {"first_name"=>"Hiroyuki", "last_name"=>"Michiue"}, {"first_name"=>"Masaharu", "last_name"=>"Seno"}, {"first_name"=>"Hideki", "last_name"=>"Matsui"}, {"first_name"=>"Kazuhito", "last_name"=>"Tomizawa"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0075288", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24069396"}, "id"=>"a0ebfd84-38c5-3858-a978-5be444028639", "abstract"=>"A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from E. coli BL21. In vitro experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy.", "link"=>"http://www.mendeley.com/research/theranostic-protein-targeting-erbb2-bioluminescence-imaging-therapy-cancer", "reader_count"=>9, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Argentina"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1206965"], "description"=>"<p>At indicated time points after intratumoral injection of EC1-GLuc-p53C, mice were killed and tumors were excised. Tumors were then immediately fixed with 4% PFA. Paraffin-embedded slices of tumors were prepared at a thickness of 10 µm. Immunofluorescence staining with rabbit anti-<i>Gaussia</i> Luciferase serum was used to detect the retention of EC1-GLuc-p53C in tumors. Scale bars = 100 µm. n = 3 in each group.</p>", "links"=>[], "tags"=>["retention", "ec1-gluc-p53c"], "article_id"=>801376, "categories"=>["Biological Sciences"], "users"=>["Xiao-Jian Han", "Ling-Fei Sun", "Yuki Nishiyama", "Bin Feng", "Hiroyuki Michiue", "Masaharu Seno", "Hideki Matsui", "Kazuhito Tomizawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075288.g005", "stats"=>{"downloads"=>5, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumor_site_retention_of_EC1_GLuc_p53C_after_injection_/801376", "title"=>"Tumor site retention of EC1-GLuc-p53C after injection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:42:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206960"], "description"=>"<p>a) Time-dependent changes in proliferation of MCF7 (top panel) and BT474 (bottom panel) cells. Cells were supplemented with 1 µM of each recombinant protein or PBS (control) on day 0 and further cultured 96 h (day 4). Cellular proliferation was assessed by the WST-1 assay every 24 h. ♦, PBS (control); ■, GLuc; ▲, EC1-GLuc; ×, EC1-GLuc-p53C. n = 6 each. *p<0.05 and **p<0.01 vs control. b) Dose-dependent effect of EC1-GLuc-p53C on the proliferation of BT474 cells. BT474 cells were treated with EC1-GLuc-p53C at various concentrations or PBS (Cont.), and WST-1 assay was performed on day 4. n = 6 each. *, p < 0.05; **, p < 0.01. c) p53-driven transcriptional activity with the p21<sup><i>WAF1</i></sup> luciferace reporter assay. BT474 transfected with the luciferase reporter vector were incubated with 1µM of GLuc, EC1-GLuc, EC1-GLuc-p53C or PBS for 24h. p21<sup><i>WAF1</i></sup> luciferase reporter activities in cells were measured with Luciferase Assay System. Data are presented as the mean±S.E.M. <i>n</i> = 5 in each group; **P < 0.01.</p>", "links"=>[], "tags"=>["ec1-gluc-p53c", "proliferation", "mcf7", "bt474"], "article_id"=>801371, "categories"=>["Biological Sciences"], "users"=>["Xiao-Jian Han", "Ling-Fei Sun", "Yuki Nishiyama", "Bin Feng", "Hiroyuki Michiue", "Masaharu Seno", "Hideki Matsui", "Kazuhito Tomizawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075288.g004", "stats"=>{"downloads"=>1, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_EC1_GLuc_p53C_on_proliferation_of_MCF7_and_BT474_cells_/801371", "title"=>"Effect of EC1-GLuc-p53C on proliferation of MCF7 and BT474 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:42:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206959"], "description"=>"<p>a) Expression of ErbB2 in MCF7 and BT474 cells. Cell lysate of the two cell lines was subjected to 6% SDS-PAGE and immunoblotted with anti-ErbB2 antibody. β-actin was used as an endogenous control. b) Bioluminescence imaging <i>in </i><i>vitro</i>. Cells incubated with 1 µM of EC-GLuc-p53C were washed with culture medium without serum. Images were acquired with a bioluminescence microscope immediately after the addition of 1 µg/mL CTZ. I and III, bioluminescence images; II and IV, phase-contrast images. Bar = 100 µm. c) Internalization of EC1-fused proteins into ErbB2-overexpressing BT474 cells. Cells were incubated with 1 µM of protein for 24 h, lane 1: GLuc; lane 2: EC-GLuc-p53C; lane 3: EC-GLuc; lane 4: anti-ErbB2+EC1-GLuc-p53C; lane 5: anti-ErbB2+EC-GLuc. The internalization of fusion protein was immunoblotted with rabbit anti-<i>Gaussia</i> Luciferase serum. β-actin was used as an endogenous control.</p>", "links"=>[], "tags"=>["bioluminescence", "imaging", "ec1-gluc-p53c"], "article_id"=>801370, "categories"=>["Biological Sciences"], "users"=>["Xiao-Jian Han", "Ling-Fei Sun", "Yuki Nishiyama", "Bin Feng", "Hiroyuki Michiue", "Masaharu Seno", "Hideki Matsui", "Kazuhito Tomizawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075288.g003", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ErbB2_targeted_bioluminescence_imaging_of_EC1_GLuc_p53C_in_vitro_/801370", "title"=>"ErbB2-targeted bioluminescence imaging of EC1-GLuc-p53C <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:42:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206968"], "description"=>"<p>MCF7 and BT474 tumors were established on the left and right flank of nude mice, respectively. At 6, 8, 12 and 24 h after the application of EC1-GLuc-p53C, the mice were imaged immediately after the intravenous injection of CTZ solution (3mg/Kg). The color scale represents p/sec/cm<sup>2</sup>/steradian. n = 3 in each group.</p>", "links"=>[], "tags"=>["imaging", "nude", "mice", "bearing", "mcf7", "bt474"], "article_id"=>801379, "categories"=>["Biological Sciences"], "users"=>["Xiao-Jian Han", "Ling-Fei Sun", "Yuki Nishiyama", "Bin Feng", "Hiroyuki Michiue", "Masaharu Seno", "Hideki Matsui", "Kazuhito Tomizawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075288.g006", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bioluminescence_imaging_in_living_nude_mice_bearing_MCF7_and_BT474_tumors_/801379", "title"=>"Bioluminescence imaging in living nude mice bearing MCF7 and BT474 tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:42:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206980", "https://ndownloader.figshare.com/files/1206981", "https://ndownloader.figshare.com/files/1206982"], "description"=>"<div><p>A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with <i>Gaussia</i> luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from <i>E. coli</i> BL21. <i>In vitro</i> experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy.</p> </div>", "links"=>[], "tags"=>["targeting", "erbb2", "bioluminescence", "imaging"], "article_id"=>801391, "categories"=>["Biological Sciences"], "users"=>["Xiao-Jian Han", "Ling-Fei Sun", "Yuki Nishiyama", "Bin Feng", "Hiroyuki Michiue", "Masaharu Seno", "Hideki Matsui", "Kazuhito Tomizawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0075288.s001", "https://dx.doi.org/10.1371/journal.pone.0075288.s002", "https://dx.doi.org/10.1371/journal.pone.0075288.s003"], "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Theranostic_Protein_Targeting_ErbB2_for_Bioluminescence_Imaging_and_Therapy_for_Cancer_/801391", "title"=>"Theranostic Protein Targeting ErbB2 for Bioluminescence Imaging and Therapy for Cancer", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-09-17 01:42:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206956"], "description"=>"<p>a) Schema of the purification of EC1-GLuc-p53C with the GST expression system. The GST tag was cleaved by PreScission protease after purification. b) Coomassie brilliant blue staining of purified proteins after 15% SDS-PAGE. Lane 1~4 are marker, GLuc, EC1-GLuc and EC1-GLuc-p53C, respectively. c) The purified proteins after 15% SDS-PAGE were detected using Western blotting with rabbit anti-<i>Gaussia</i> Luciferase serum. Lanes 1~3 are GLuc, EC1-GLuc and EC1-GLuc-p53C, respectively. d) Bioluminescent activities of the purified proteins. Each protein (2 µg) was evaluated using a plate luminometer. The bioluminescent values of EC1-GLuc and EC1-GLuc-p53C were normalized with GLuc. n=6 each, * p<0.01.</p>", "links"=>[], "tags"=>["recombinant"], "article_id"=>801367, "categories"=>["Biological Sciences"], "users"=>["Xiao-Jian Han", "Ling-Fei Sun", "Yuki Nishiyama", "Bin Feng", "Hiroyuki Michiue", "Masaharu Seno", "Hideki Matsui", "Kazuhito Tomizawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075288.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Purification_and_activity_of_the_recombinant_proteins_/801367", "title"=>"Purification and activity of the recombinant proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:42:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206957"], "description"=>"<p>Proteins incubated with an equal volume of mouse serum at 37°C were withdrawn at the indicated time points for bioluminescent activity evaluation (a) and Western blotting (c). b) The bioluminescent activity of EC1-GLuc-p53C and GLuc was examined 3 h after incubation in serum. The bioluminescent values of EC1-GLuc-p53C were normalized with GLuc. n = 6 each.</p>", "links"=>[], "tags"=>["bioluminescent", "recombinant", "proteins"], "article_id"=>801368, "categories"=>["Biological Sciences"], "users"=>["Xiao-Jian Han", "Ling-Fei Sun", "Yuki Nishiyama", "Bin Feng", "Hiroyuki Michiue", "Masaharu Seno", "Hideki Matsui", "Kazuhito Tomizawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075288.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stability_and_bioluminescent_activity_of_the_recombinant_proteins_in_serum_/801368", "title"=>"Stability and bioluminescent activity of the recombinant proteins in serum.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:42:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206969"], "description"=>"<p>30 µL of EC1-GLuc-p53C (0.5 µg/µL) or the same volume of PBS (control) were injected into MCF7 and BT474 tumors every day for 5 days. The mice were monitored daily and their tumor volume was measured twice a week to evaluate the effect of EC1-GLuc-p53C on tumor growth. n = 9 in each group.</p>", "links"=>[], "tags"=>["ec1-gluc-p53c"], "article_id"=>801380, "categories"=>["Biological Sciences"], "users"=>["Xiao-Jian Han", "Ling-Fei Sun", "Yuki Nishiyama", "Bin Feng", "Hiroyuki Michiue", "Masaharu Seno", "Hideki Matsui", "Kazuhito Tomizawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075288.g007", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_EC1_GLuc_p53C_on_tumor_growth_/801380", "title"=>"Effect of EC1-GLuc-p53C on tumor growth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:42:21"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"3", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[272, 472, 600, 713, 815, 911, 1004, 1094, 1185, 1273, 1358, 1441]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Oncology", "average_usage"=>[249, 468, 599, 718, 820, 920, 1008, 1093, 1181, 1281, 1357, 1444, 1517]}, {"subject_area"=>"/Medicine and health sciences/Pharmaceutics", "average_usage"=>[254, 457, 591, 700, 808, 906, 1001, 1093, 1185, 1276, 1373, 1457, 1535]}, {"subject_area"=>"/Physical sciences/Physics", "average_usage"=>[254, 421, 527, 626, 720, 813, 900, 983, 1063, 1136, 1210, 1283, 1342]}]}
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