SERPINB3 in the Chicken Model of Ovarian Cancer: A Prognostic Factor for Platinum Resistance and Survival in Patients with Epithelial Ovarian Cancer
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{"title"=>"SERPINB3 in the Chicken Model of Ovarian Cancer: A Prognostic Factor for Platinum Resistance and Survival in Patients with Epithelial Ovarian Cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Whasun", "last_name"=>"Lim", "scopus_author_id"=>"36465454300"}, {"first_name"=>"Hee Seung", "last_name"=>"Kim", "scopus_author_id"=>"56981494200"}, {"first_name"=>"Wooyoung", "last_name"=>"Jeong", "scopus_author_id"=>"53879639600"}, {"first_name"=>"Suzie E.", "last_name"=>"Ahn", "scopus_author_id"=>"36464810700"}, {"first_name"=>"Jinyoung", "last_name"=>"Kim", "scopus_author_id"=>"36013189400"}, {"first_name"=>"Yong Beom", "last_name"=>"Kim", "scopus_author_id"=>"26424665100"}, {"first_name"=>"Min A.", "last_name"=>"Kim", "scopus_author_id"=>"55660885600"}, {"first_name"=>"Mi Kyung", "last_name"=>"Kim", "scopus_author_id"=>"26029895800"}, {"first_name"=>"Hyun Hoon", "last_name"=>"Chung", "scopus_author_id"=>"7404006497"}, {"first_name"=>"Yong Sang", "last_name"=>"Song", "scopus_author_id"=>"13310265600"}, {"first_name"=>"Fuller W.", "last_name"=>"Bazer", "scopus_author_id"=>"7101737931"}, {"first_name"=>"Jae Yong", "last_name"=>"Han", "scopus_author_id"=>"7406440402"}, {"first_name"=>"Gwonhwa", "last_name"=>"Song", "scopus_author_id"=>"8837198200"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84869851878", "sgr"=>"84869851878", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0049869", "pmid"=>"23185467", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"366113419"}, "id"=>"c642a348-a2ab-3711-99a3-d59fa725e5f9", "abstract"=>"Serine protease inhibitors (SERPINs) appear to be ubiquitously expressed in a variety of species and play important roles in pivotal physiological processes such as angiogenesis, immune responses, blood coagulation and fibronolysis. Of these, squamous cell carcinoma antigen 1 (SCCA1), also known as a SERPINB3, was first identified in squamous cell carcinoma tissue from the cervix of women. However, there is little known about the SERPINB3 expression in human epithelial ovarian cancer (EOC). Therefore, in the present study, we investigated the functional role of SERPINB3 gene in human EOC using chickens, the most relevant animal model. In 136 chickens, EOC was found in 10 (7.4%). SERPINB3 mRNA was induced in cancerous, but not normal ovaries of chickens (P<0.01), and it was abundant only in the glandular epithelium of cancerous ovaries of chickens. Further, several microRNAs, specifically miR-101, miR-1668 and miR-1681 were discovered to influence SERPINB3 expression via its 3'-UTR which suggests that post-transcriptional regulation influences SERPINB3 expression in chickens. SERPINB3 protein was localized predominantly to the glandular epithelium in cancerous ovaries of chickens, and it was abundant in the nucleus of both chicken and human ovarian cancer cell lines. In 109 human patients with EOC, 15 (13.8%), 66 (60.6%) and 28 (25.7%) patients showed weak, moderate and strong expression of SERPINB3 protein, respectively. Strong expression of SERPINB3 protein was a prognostic factor for platinum resistance (adjusted OR; odds ratio, 5.94; 95% Confidence Limits, 1.21-29.15), and for poor progression-free survival (PFS; adjusted HR; hazard ratio, 2.07; 95% CI; confidence interval, 1.03-4.41). Therefore, SERPINB3 may play an important role in ovarian carcinogenesis and be a novel biomarker for predicting platinum resistance and a poor prognosis for survival in patients with EOC.", "link"=>"http://www.mendeley.com/research/serpinb3-chicken-model-ovarian-cancer-prognostic-factor-platinum-resistance-survival-patients-epithe", "reader_count"=>10, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Other"=>1, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Other"=>1, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"France"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/538618"], "description"=>"<p>RT-PCR analysis was performed using cDNA templates from chicken <i>SERPINB3</i> and <i>GAPDH</i>-specific primers. [A] Lanes 1 to 4 show four different normal ovaries and N is negative control. [B] Lanes 1–10 show 10 different cancerous ovaries. [C] Quantitative RT-PCR analysis was performed using cDNA templates from normal and cancerous ovaries of laying hens (mean ± SEM; P<0.01).</p>", "links"=>[], "tags"=>["quantitation", "mrna", "cancerous", "ovaries", "laying"], "article_id"=>209086, "categories"=>["Physiology", "Cancer", "Cell Biology"], "users"=>["Whasun Lim", "Hee Seung Kim", "Wooyoung Jeong", "Suzie E. Ahn", "Jinyoung Kim", "Yong Beom Kim", "Min A. Kim", "Mi-Kyung Kim", "Hyun Hoon Chung", "Yong Sang Song", "Fuller W. Bazer", "Jae Yong Han", "Gwonhwa Song"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049869.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_and_quantitation_of_SERPINB3_mRNA_in_normal_and_cancerous_ovaries_of_laying_hens_/209086", "title"=>"Expression and quantitation of <i>SERPINB3</i> mRNA in normal and cancerous ovaries of laying hens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:54:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/539236"], "description"=>"<p>(a and a′) Weak, (b and b′) moderate and (c and c′) strong expression of SERPINB3 protein was detected in women with epithelial ovarian cancer. There was either no expression of very weak expression of SERPINB3 in normal ovaries, whereas SERPINB3 protine was easily detectable in cancerous ovaries from women. The negative control used was mouse IgG instead of primary antibody. <i>Scale bar</i> represents 200 μm (the first horizontal panels and IgG) or 50 μm (the second horizontal panels).</p>", "links"=>[], "tags"=>["was", "serpinb3", "cancerous", "ovaries"], "article_id"=>209717, "categories"=>["Physiology", "Cancer", "Cell Biology"], "users"=>["Whasun Lim", "Hee Seung Kim", "Wooyoung Jeong", "Suzie E. Ahn", "Jinyoung Kim", "Yong Beom Kim", "Min A. Kim", "Mi-Kyung Kim", "Hyun Hoon Chung", "Yong Sang Song", "Fuller W. Bazer", "Jae Yong Han", "Gwonhwa Song"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049869.g005", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemistry_was_used_to_demonstrate_expression_of_SERPINB3_protein_in_cancerous_ovaries_but_not_in_normal_ovaries_from_women_/209717", "title"=>"Immunohistochemistry was used to demonstrate expression of SERPINB3 protein in cancerous ovaries, but not in normal ovaries from women.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:58:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/539391"], "description"=>"<p>Abbreviation: FIGO, International Federation of Gynecology and Obstetrics; HR, hazard ratio; CI, confidence interval.</p>", "links"=>[], "tags"=>["proportional", "prognostic", "factors", "affecting", "progression-free"], "article_id"=>209871, "categories"=>["Physiology", "Cancer", "Cell Biology"], "users"=>["Whasun Lim", "Hee Seung Kim", "Wooyoung Jeong", "Suzie E. Ahn", "Jinyoung Kim", "Yong Beom Kim", "Min A. Kim", "Mi-Kyung Kim", "Hyun Hoon Chung", "Yong Sang Song", "Fuller W. Bazer", "Jae Yong Han", "Gwonhwa Song"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049869.t002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multivariate_Cox_8217_s_proportional_hazard_analysis_for_poor_prognostic_factors_affecting_progression_free_survival_/209871", "title"=>"Multivariate Cox’s proportional hazard analysis for poor prognostic factors affecting progression-free survival.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 19:58:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/539116"], "description"=>"<p>[A] SERPINB3 protein was rarely detected in normal cells, but abundant in the nuclei of chicken ovarian cancer cells. [B] SERPINB3 protein was expressed in nuclei of human OVCAR-3, SKOV-3 and PA-1 cells. Cell nuclei were stained with DAPI (blue). All images were captured at 40X objective magnification.</p>", "links"=>[], "tags"=>["microscopy", "serpinb3", "ovarian", "cancer", "lines", "women", "laying"], "article_id"=>209597, "categories"=>["Physiology", "Cancer", "Cell Biology"], "users"=>["Whasun Lim", "Hee Seung Kim", "Wooyoung Jeong", "Suzie E. Ahn", "Jinyoung Kim", "Yong Beom Kim", "Min A. Kim", "Mi-Kyung Kim", "Hyun Hoon Chung", "Yong Sang Song", "Fuller W. Bazer", "Jae Yong Han", "Gwonhwa Song"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049869.g004", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunofluorescence_microscopy_detected_SERPINB3_protein_in_ovarian_cancer_cell_lines_of_both_women_and_laying_hens_/209597", "title"=>"Immunofluorescence microscopy detected SERPINB3 protein in ovarian cancer cell lines of both women and laying hens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:57:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/538777"], "description"=>"<p>[A] <i>In situ</i> hybridization analyses of <i>SERPINB3</i> mRNA. Cross-sections of normal and cancerous ovaries from laying hens were hybridized with sense or anti-sense chicken <i>SERPINB3</i> cRNA probes. [B] Immunohistochemical expression of SERPINB3 protein: For negative control, the primary antibody was substituted with purified non-immune mouse IgG. F, follicle; GE, glandular epithelium; S, stroma; <i>Scale bar</i> represents 200 μm (the first columnar panels and sense) or 50 μm (the second columnar panels).</p>", "links"=>[], "tags"=>["mrna", "glandular", "epithelium", "cancerous", "ovaries", "laying"], "article_id"=>209253, "categories"=>["Physiology", "Cancer", "Cell Biology"], "users"=>["Whasun Lim", "Hee Seung Kim", "Wooyoung Jeong", "Suzie E. Ahn", "Jinyoung Kim", "Yong Beom Kim", "Min A. Kim", "Mi-Kyung Kim", "Hyun Hoon Chung", "Yong Sang Song", "Fuller W. Bazer", "Jae Yong Han", "Gwonhwa Song"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049869.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_SERPINB3_mRNA_and_protein_is_unique_to_glandular_epithelium_of_cancerous_ovaries_from_laying_hens_/209253", "title"=>"Expression of <i>SERPINB3</i> mRNA and protein is unique to glandular epithelium of cancerous ovaries from laying hens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:55:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/539340"], "description"=>"<p>Abbreviation: FIGO, International Federation of Gynecology and Obstetrics; OR, odd ratio; CI, confidence interval.</p>", "links"=>[], "tags"=>["linear", "logistic", "regression", "factors", "affecting", "platinum"], "article_id"=>209814, "categories"=>["Physiology", "Cancer", "Cell Biology"], "users"=>["Whasun Lim", "Hee Seung Kim", "Wooyoung Jeong", "Suzie E. Ahn", "Jinyoung Kim", "Yong Beom Kim", "Min A. Kim", "Mi-Kyung Kim", "Hyun Hoon Chung", "Yong Sang Song", "Fuller W. Bazer", "Jae Yong Han", "Gwonhwa Song"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049869.t001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multivariate_linear_logistic_regression_analysis_for_factors_affecting_platinum_resistance_/209814", "title"=>"Multivariate linear logistic regression analysis for factors affecting platinum resistance.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 19:58:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/538959"], "description"=>"<p>[A] Diagram of <i>miR-101, miR-1668</i> and <i>miR-1681</i> binding sites in <i>SERPINB3</i> 3′-UTR. [B] Expression vector maps for eGFP with <i>SERPINB3</i> 3′-UTR and mutated <i>SERPINB3</i> 3′-UTR and Ds-Red with each miRNA. The wild-type (WT) and mutants of 3′-UTR of the <i>SERPINB3</i> transcript were subcloned between the eGFP gene and the polyA tail to generate the fusion construct of the GFP transcript following the miRNA target 3′-UTR (pcDNA-eGFP-3′UTR) (top and middle panel) and the miRNA expression vector was designed to co-express DsRed and each miRNA (pcDNA-DsRed-miRNA) (bottom panel). [C] After co-transfection of pcDNA-eGFP-3′UTR for the <i>SERPINB3</i> transcript and pcDNA-DsRed-miRNA for the <i>miR-101, miR-1668</i> and <i>miR-1681</i>, the fluorescence signals of GFP and DsRed were detected using fluorescent microscopy. [D] The rate of inhibition of eGFP expression from miRNA modulation was calculated by fluorescence-activated cell sorting (FACS). Solid bars represent WT of <i>SERPINB3</i> 3′-UTR and empty bars show the mutant of <i>SERPINB3</i> 3′-UTR for each miRNA. Error bars indicate the standard error of triplicate analyses. The asterisks denote statistically significant differences between WT vs. mutants (***P<0.001).</p>", "links"=>[], "tags"=>["assay", "micrornas", "serpinb3"], "article_id"=>209441, "categories"=>["Physiology", "Cancer", "Cell Biology"], "users"=>["Whasun Lim", "Hee Seung Kim", "Wooyoung Jeong", "Suzie E. Ahn", "Jinyoung Kim", "Yong Beom Kim", "Min A. Kim", "Mi-Kyung Kim", "Hyun Hoon Chung", "Yong Sang Song", "Fuller W. Bazer", "Jae Yong Han", "Gwonhwa Song"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049869.g003", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_target_assay_of_microRNAs_on_the_SERPINB3_transcript_/209441", "title"=>"<i>In vitro</i> target assay of microRNAs on the SERPINB3 transcript.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:56:29"}

PMC Usage Stats | Further Information

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Relative Metric

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