Furin Overexpression Suppresses Tumor Growth and Predicts a Better Postoperative Disease-Free Survival in Hepatocellular Carcinoma
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{"title"=>"Furin overexpression suppresses tumor growth and predicts a better postoperative disease-free survival in hepatocellular carcinoma", "type"=>"journal", "authors"=>[{"first_name"=>"Ya Hui", "last_name"=>"Huang", "scopus_author_id"=>"7501575076"}, {"first_name"=>"Kwang Huei", "last_name"=>"Lin", "scopus_author_id"=>"7403967446"}, {"first_name"=>"Chen Hsin", "last_name"=>"Liao", "scopus_author_id"=>"23980443400"}, {"first_name"=>"Ming Wei", "last_name"=>"Lai", "scopus_author_id"=>"9233300800"}, {"first_name"=>"Yi Hsin", "last_name"=>"Tseng", "scopus_author_id"=>"55148122700"}, {"first_name"=>"Chau Ting", "last_name"=>"Yeh", "scopus_author_id"=>"25935661400"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84863677003", "pmid"=>"22808247", "sgr"=>"84863677003", "doi"=>"10.1371/journal.pone.0040738", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"365221602"}, "id"=>"2921d009-a88c-3314-b83a-541ca832bbc3", "abstract"=>"Furin is a member of the pro-protein convertase family. It processes several growth regulatory proteins into their active forms, which are critical to tumor progression, metastasis, and angiogenesis. Furin over-expression could occur in liver cancer and a previous study showed that over-expression of furin promoted HepG2 cell invasion in tail vein xenograft models. However, the clinical relevance of furin expression in hepatocellular carcinoma (HCC) remained unknown. Surprisingly, in a postoperative survival analysis for HCC patients, it was found that the tumor/non-tumor (T/N) ratio of furin expression ≥ 3.5 in HCC tissues predicted a better postoperative disease-free survival (DFS) (P = 0.010; log-rank test). Furthermore, subcutaneous xenograft experiments demonstrated a significant suppression effect of tumor growth in the furin-overexpressed xenografts (Huh7-Furin) compared to the mock control. Administration of a synthetic furin inhibitor for inhibition of the pro-protein convertase activity, decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decRVKR-CMK), to the Huh7-Furin xenograft bearing mice restored the repression effect of tumor growth. In contrast, administration of decRVKR-CMK to the mock Huh7 xenograft bearing mice showed no change in growth rate. In conclusion, furin overexpression inhibited HCC tumor growth in a subcutaneous xenograft model and predicted a better postoperative DFS in clinical analysis.", "link"=>"http://www.mendeley.com/research/furin-overexpression-suppresses-tumor-growth-predicts-better-postoperative-diseasefree-survival-hepa", "reader_count"=>19, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>6, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/611893"], "description"=>"<p>(A) Expression levels of furin, pro-TGFβ1 and TGFβ1 in Huh7-Neo and Huh7-Fruin cells were showed by immunoblot. Gelatin zymography was performed to detect the MMP2 activities. (B) Immunoblot was performed to determine the pro-TGFβ1 and TGFβ1 expression levels and gelatin zymography was performed to determine the MMP2 activities in the absence (-) and presence (+) of decRVKR-CMK.</p>", "links"=>[], "tags"=>["furin", "decrvkr-cmk", "huh7-fruin"], "article_id"=>282369, "categories"=>["Cancer", "Molecular Biology", "Genetics"], "users"=>["Ya-Hui Huang", "Kwang-Huei Lin", "Chen-Hsin Liao", "Ming-Wei Lai", "Yi-Hsin Tseng", "Chau-Ting Yeh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0040738.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_furin_activity_by_decRVKR_CMK_in_Huh7_Fruin_cells_/282369", "title"=>"Inhibition of furin activity by decRVKR-CMK in Huh7-Fruin cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-10 00:39:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/611763"], "description"=>"<p>(A) Furin overexpression in 20 pairs of representative cancerous (T) and adjacent noncancerous (N) tissues demonstrated by immunoblot analysis. (B) Furin underexpressed in the 8 representative paired HCC tissues. (C) Expression of furin assessed by IHC staining in noncancerous and cancerous liver tissue (i and ii). Specificity of the IHC staining was verified by blocking of the primary antibody with recombinant furin protein (iii and iv). (D) Disease-free survivals in HCC patients expressing different levels of furin (Kaplan-Meier survival analysis).</p>", "links"=>[], "tags"=>["dual", "contradictory", "furin"], "article_id"=>282246, "categories"=>["Cancer", "Molecular Biology", "Genetics"], "users"=>["Ya-Hui Huang", "Kwang-Huei Lin", "Chen-Hsin Liao", "Ming-Wei Lai", "Yi-Hsin Tseng", "Chau-Ting Yeh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0040738.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_dual_and_contradictory_role_of_furin_in_HCC_/282246", "title"=>"A dual and contradictory role of furin in HCC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-10 00:37:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/612241"], "description"=>"<p>The expression level of furin, pro-TGFβ1, and several cell proliferation and cell death regulatory molecules between Huh7-Neo and Huh7-Furin xenograft tumors after administration with or without decRVKR-CMK was analyzed by immunoblot.</p>", "links"=>[], "tags"=>["proliferation"], "article_id"=>282727, "categories"=>["Cancer", "Molecular Biology", "Genetics"], "users"=>["Ya-Hui Huang", "Kwang-Huei Lin", "Chen-Hsin Liao", "Ming-Wei Lai", "Yi-Hsin Tseng", "Chau-Ting Yeh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0040738.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_expression_of_cell_proliferation_and_cell_death_regulatory_molecules_/282727", "title"=>"Differential expression of cell proliferation and cell death regulatory molecules.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-10 00:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/612545"], "description"=>"a<p>Comparison between patients with tumor number  = 1 and those with tumor number >1.</p>b<p>Median (range).</p>c<p>Mann-Whitney test.</p>", "links"=>[], "tags"=>["characterization", "patients"], "article_id"=>283033, "categories"=>["Cancer", "Molecular Biology", "Genetics"], "users"=>["Ya-Hui Huang", "Kwang-Huei Lin", "Chen-Hsin Liao", "Ming-Wei Lai", "Yi-Hsin Tseng", "Chau-Ting Yeh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0040738.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Basic_clinical_characterization_of_patients_included_/283033", "title"=>"Basic clinical characterization of patients included.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-10 00:50:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/318820"], "description"=>"<div><p>Furin is a member of the pro-protein convertase family. It processes several growth regulatory proteins into their active forms, which are critical to tumor progression, metastasis, and angiogenesis. Furin over-expression could occur in liver cancer and a previous study showed that over-expression of furin promoted HepG2 cell invasion in tail vein xenograft models. However, the clinical relevance of furin expression in hepatocellular carcinoma (HCC) remained unknown. Surprisingly, in a postoperative survival analysis for HCC patients, it was found that the tumor/non-tumor (T/N) ratio of furin expression ≥ 3.5 in HCC tissues predicted a better postoperative disease-free survival (DFS) (<em>P</em> = 0.010; log-rank test). Furthermore, subcutaneous xenograft experiments demonstrated a significant suppression effect of tumor growth in the furin-overexpressed xenografts (Huh7-Furin) compared to the mock control. Administration of a synthetic furin inhibitor for inhibition of the pro-protein convertase activity, decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decRVKR-CMK), to the Huh7-Furin xenograft bearing mice restored the repression effect of tumor growth. In contrast, administration of decRVKR-CMK to the mock Huh7 xenograft bearing mice showed no change in growth rate. In conclusion, furin overexpression inhibited HCC tumor growth in a subcutaneous xenograft model and predicted a better postoperative DFS in clinical analysis.</p> </div>", "links"=>[], "tags"=>["furin", "overexpression", "suppresses", "postoperative", "disease-free", "hepatocellular", "carcinoma"], "article_id"=>122922, "categories"=>["Cancer", "Molecular Biology", "Genetics"], "users"=>["Ya-Hui Huang", "Kwang-Huei Lin", "Chen-Hsin Liao", "Ming-Wei Lai", "Yi-Hsin Tseng", "Chau-Ting Yeh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0040738", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Furin_Overexpression_Suppresses_Tumor_Growth_and_Predicts_a_Better_Postoperative_Disease_Free_Survival_in_Hepatocellular_Carcinoma/122922", "title"=>"Furin Overexpression Suppresses Tumor Growth and Predicts a Better Postoperative Disease-Free Survival in Hepatocellular Carcinoma", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-10 00:48:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/612435"], "description"=>"<p>(A to C) Comparisons of the tumor volumes between Huh7-Neo xenografts with or without decRVKR-CMK. (D) Immunohistochemistry analysis for xenograft tumor section. Immunostain for furin (i and ii) and Ki-67 (v and vi); TUNEL assay (iii and iv) (200X).</p>", "links"=>[], "tags"=>["viability", "decrvkr-cmk", "huh7-neo", "xenograft"], "article_id"=>282919, "categories"=>["Cancer", "Molecular Biology", "Genetics"], "users"=>["Ya-Hui Huang", "Kwang-Huei Lin", "Chen-Hsin Liao", "Ming-Wei Lai", "Yi-Hsin Tseng", "Chau-Ting Yeh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0040738.g005", "stats"=>{"downloads"=>2, "page_views"=>36, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_No_effects_of_cell_viability_by_treatment_with_decRVKR_CMK_in_Huh7_Neo_xenograft_tumor_/282919", "title"=>"No effects of cell viability by treatment with decRVKR-CMK in Huh7-Neo xenograft tumor.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-10 00:48:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/612076"], "description"=>"<p>(A) Animal experimental protocol was shown. (B to D) Comparisons of the tumor volumes between Huh7-Furin xenografts with or without decRVKR-CMK. (E) Gelatin zymography was performed to detect the MMP2 activities. (F) Immunohistochemistry analysis for xenograft tumor section. Immunostain for furin (i and ii) and Ki-67 (vii and viii); H&E stain (iii and iv); TUNEL assay (v and vi) (200X). The areas marked by yellow dashed lines in (iii) and (iv) were necrosis areas.</p>", "links"=>[], "tags"=>["decrvkr-cmk", "promoted", "viability", "huh7-furin", "xenograft"], "article_id"=>282557, "categories"=>["Cancer", "Molecular Biology", "Genetics"], "users"=>["Ya-Hui Huang", "Kwang-Huei Lin", "Chen-Hsin Liao", "Ming-Wei Lai", "Yi-Hsin Tseng", "Chau-Ting Yeh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0040738.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Treatment_with_decRVKR_CMK_promoted_cell_viability_in_Huh7_Furin_xenograft_tumor_/282557", "title"=>"Treatment with decRVKR-CMK promoted cell viability in Huh7-Furin xenograft tumor.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-10 00:42:37"}

PMC Usage Stats | Further Information

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Relative Metric

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