The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Pilvi Riihilä - One of the best experts on this subject based on the ideXlab platform.
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<B>ComplementB> component c3 and <B>ComplementB> <B>FactorB> B promote growth of cutaneous squamous cell carcinoma
American Journal of Pathology, 2017Co-Authors: Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Liisa Nissinen, Pilvi Riihilä, Seppo MeriAbstract:Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B (CFB) in the growth of cSCC. Analysis of cSCC cell lines ( n = 8) and normal human epidermal keratinocytes ( n = 11) with real-time quantitative PCR and Western Blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell–specific laBeling for C3 and CFB in invasive cSCCs ( n = 71) and recessive dystrophic epidermolysis Bullosa–associated cSCCs ( n = 11) than in cSCC in situ ( n = 69), actinic keratoses ( n = 63), and normal skin ( n = 5). Significant up-regulation of C3 and CFB mRNA expression was noted in chemically induced mouse cSCCs, compared to Benign papillomas. Knockdown of C3 and CFB expression inhiBited migration and proliferation of cSCC cells and resulted in potent inhiBition of extracellular signal–regulated kinase 1/2 activation. Knockdown of C3 and CFB markedly inhiBited growth of human cSCC xenograft tumors in vivo . These results provide evidence for the roles of C3 and CFB in the development of cSCC and identify them as Biomarkers and potential therapeutic targets in this metastatic skin cancer.
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aBstract 3201 <B>ComplementB> component c3 and <B>ComplementB> <B>FactorB> B regulate growth of cutaneous squamous cell carcinoma
Cancer Research, 2015Co-Authors: Pilvi Riihilä, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Juha Peltonen, Seppo Meri, Taina Pihlajaniemi, Ritva Heljasvaara, Reidar Grenman, Sirkku PeltonenAbstract:Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and its incidence is increasing gloBally. We have examined the role of <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B (CFB) in the progression of cSCC. Significantly elevated mRNA levels for C3 and CFB were detected din cSCC cell lines (n = 8) compared to normal human epidermal keratinocytes (n = 11) By quantitative real-time reverse transcriptase-PCR. Increased production of C3 and CFB By cSCC cell lines was detected By western Blotting. The mRNA levels for C3 and CFB were also markedly higher in cSCC tumors (n = 6) than in normal skin (n = 10). Tumor cell specific staining for C3 and CFB was detected in cSCC tumors in vivo By immunohistochemistry and the staining intensity was stronger in invasive cSCCs (n = 71) than in cSCC in situ (n = 69), premalignant epidermal lesions (actinic keratoses, n = 65) and normal skin (n = 5). Significant upregulation of C3 and CFB mRNA expression was also noted in chemically induced mouse skin cSCCs (n = 27) compared to Benign papillomas (n = 17). The expression of C3 and CFB at mRNA and protein level was markedly higher in invasive tumorigenic Ha-ras-transformed HaCaT cell line than in Benign tumorigenic ras-transformed HaCaT cells and parental non-tumorigenic HaCaT cells. The expression of Both C3 and CFB was significantly upregulated By IFN-γ and TNF-α in cSCC cells. Knockdown of CFB and C3 By specific siRNAs inhiBited migration of cSCC cells. Knockdown of CFB inhiBited proliferation of cSCC cells and this was associated with potent inhiBition of ERK1/2 activation. Knockdown of C3 and CFB also significantly inhiBited growth of human cSCC xenograft tumors in vivo in SCID mice. These results provide evidence for the role of C3 and CFB in progression of cSCC and identify them as specific Biomarkers and putative therapeutic targets for invasive cSCC. Citation Format: Pilvi Riihila, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Seppo Meri, Reidar Grenman, Ritva Heljasvaara, Taina Pihlajaniemi, Juha Peltonen, Sirkku Peltonen, Veli-Matti Kahari. <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B regulate growth of cutaneous squamous cell carcinoma. [aBstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):ABstract nr 3201. doi:10.1158/1538-7445.AM2015-3201
Teresa J. Oglesby - One of the best experts on this subject based on the ideXlab platform.
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mutations of the type a domain of <B>ComplementB> <B>FactorB> B that promote high affinity c3B Binding
Journal of Immunology, 1999Co-Authors: Dennis E. Hourcade, Lynne M. Mitchell, Teresa J. OglesbyAbstract:<B>FactorB> B is a zymogen that carries the catalytic site of the <B>ComplementB> alternative pathway convertases. During C3 convertase assemBly, <B>FactorB> B associates with C3B and is cleaved at a single site By <B>FactorB> D. The Ba fragment is released, leaving the active complex, C3BBB. During the course of this process, the protease domain Becomes activated. The type A domain of <B>FactorB> B, also part of BB, is similar in structure to the type A domain of the <B>ComplementB> receptor and integrin, CR3. Previously, mutations in the <B>FactorB> B type A domain were descriBed that impair C3B-Binding. This report descriBes “gain of function” mutations oBtained By suBstituting <B>FactorB> B type A domain amino acids with homologous ones derived from the type A domain of CR3. Replacement of the βA-α1 Mg2+ Binding loop residue D254 with smaller amino acids, especially glycine, increased hemolytic activity and C3BBB staBility. The removal of the oligosaccharide at position 260, near the Mg2+ Binding cleft, when comBined with the D254G suBstitution, resulted in increased affinity for C3B and iC3B, a C3B derivative. These findings offer strong evidence for the direct involvement of the type A domain in C3B Binding, and are suggestive that steric effects of the D254 sidechain and the N260-linked oligosaccharide may contriBute to the regulation of ligand Binding.
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A Conserved Element in the Serine Protease Domain of <B>ComplementB> <B>FactorB> B
The Journal of biological chemistry, 1998Co-Authors: Dennis E. Hourcade, Lynne M. Mitchell, Teresa J. OglesbyAbstract:ABstract <B>FactorB> B and C2 are serine proteases that carry the catalytic sites of the <B>ComplementB> C3 and C5 convertases. Their protease domains are activated By conformational changes that occur during convertase assemBly and are deactivated upon convertase dissociation. <B>FactorB> B and C2 share an 8-amino acid conserved sequence near their serine protease termini that is not seen in other serine proteases. To determine its importance, 24 <B>FactorB> B mutants were generated, each with a single amino acid suBstitution in this region. Whereas most mutants were functionally neutral, all five different suBstitutions of aspartic acid 715 and one phenylalanine 716 suBstitution severely reduced hemolytic activity. Several aspartic acid 715 mutants permitted the steps of convertase assemBly including C3B-dependent <B>FactorB> D-mediated cleavage and activation of the high affinity C3B-Binding site, But the resulting complexes did not cleave C3. Given that <B>FactorB> B and C2 share the same Biological suBstrates and that part of the trypsin-like suBstrate specificity region is not apparent in either protein, we propose that the conserved region plays a critical role in the conformational regulation of the catalytic site and could offer a highly specific target for the therapeutic inhiBition of <B>ComplementB>.
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Analysis of the Short Consensus Repeats of Human <B>ComplementB> <B>FactorB> B By Site-directed Mutagenesis
The Journal of biological chemistry, 1995Co-Authors: Dennis E. Hourcade, Lynne M. Wagner, Teresa J. OglesbyAbstract:ABstract Human <B>FactorB> B is required for the initiation and propagation of the <B>ComplementB> alternative pathway. It also participates in the amplification of the <B>ComplementB> classical pathway. Alone, <B>FactorB> B is a zymogen with little known Biochemical activity, But in the context of the alternative pathway convertases, the <B>FactorB> B serine protease is activated in a process that first involves the association with C3B and suBsequently the cleavage of <B>FactorB> B into two fragments, Ba and BB. Ba, the NH2-terminal fragment, is composed mainly of three tandem short consensus repeats, gloBular domains found in other <B>ComplementB> proteins. It dissociates from the convertase during assemBly, leaving the active C3 convertase, C3BBB. Previous reports suggest that the Ba region may Be instrumental in convertase assemBly. This hypothesis was tested using site-directed mutagenesis of recomBinant <B>FactorB> B and monoclonal antiBody epitope mapping to evaluate the relative importance of specific short consensus repeat amino acid residues. Three sites of interest were identified. Site 1 is a stretch of 19 contiguous amino acids in short consensus repeat 1 that form the epitope of a monoclonal antiBody that effectively Blocks <B>FactorB> B function. Site 2, composed of 6 contiguous amino acids in short consensus repeat 2, and site 3, consisting of 7 contiguous amino acids in short consensus repeat 3, were defined By mutations that reduce <B>FactorB> B hemolytic activity to 3% or less. Further analyses indicated that sites 2 and 3 contriBute to <B>FactorB> B-C3B interactions.
Seppo Meri - One of the best experts on this subject based on the ideXlab platform.
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<B>ComplementB> component c3 and <B>ComplementB> <B>FactorB> B promote growth of cutaneous squamous cell carcinoma
American Journal of Pathology, 2017Co-Authors: Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Liisa Nissinen, Pilvi Riihilä, Seppo MeriAbstract:Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B (CFB) in the growth of cSCC. Analysis of cSCC cell lines ( n = 8) and normal human epidermal keratinocytes ( n = 11) with real-time quantitative PCR and Western Blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell–specific laBeling for C3 and CFB in invasive cSCCs ( n = 71) and recessive dystrophic epidermolysis Bullosa–associated cSCCs ( n = 11) than in cSCC in situ ( n = 69), actinic keratoses ( n = 63), and normal skin ( n = 5). Significant up-regulation of C3 and CFB mRNA expression was noted in chemically induced mouse cSCCs, compared to Benign papillomas. Knockdown of C3 and CFB expression inhiBited migration and proliferation of cSCC cells and resulted in potent inhiBition of extracellular signal–regulated kinase 1/2 activation. Knockdown of C3 and CFB markedly inhiBited growth of human cSCC xenograft tumors in vivo . These results provide evidence for the roles of C3 and CFB in the development of cSCC and identify them as Biomarkers and potential therapeutic targets in this metastatic skin cancer.
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aBstract 3201 <B>ComplementB> component c3 and <B>ComplementB> <B>FactorB> B regulate growth of cutaneous squamous cell carcinoma
Cancer Research, 2015Co-Authors: Pilvi Riihilä, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Juha Peltonen, Seppo Meri, Taina Pihlajaniemi, Ritva Heljasvaara, Reidar Grenman, Sirkku PeltonenAbstract:Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and its incidence is increasing gloBally. We have examined the role of <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B (CFB) in the progression of cSCC. Significantly elevated mRNA levels for C3 and CFB were detected din cSCC cell lines (n = 8) compared to normal human epidermal keratinocytes (n = 11) By quantitative real-time reverse transcriptase-PCR. Increased production of C3 and CFB By cSCC cell lines was detected By western Blotting. The mRNA levels for C3 and CFB were also markedly higher in cSCC tumors (n = 6) than in normal skin (n = 10). Tumor cell specific staining for C3 and CFB was detected in cSCC tumors in vivo By immunohistochemistry and the staining intensity was stronger in invasive cSCCs (n = 71) than in cSCC in situ (n = 69), premalignant epidermal lesions (actinic keratoses, n = 65) and normal skin (n = 5). Significant upregulation of C3 and CFB mRNA expression was also noted in chemically induced mouse skin cSCCs (n = 27) compared to Benign papillomas (n = 17). The expression of C3 and CFB at mRNA and protein level was markedly higher in invasive tumorigenic Ha-ras-transformed HaCaT cell line than in Benign tumorigenic ras-transformed HaCaT cells and parental non-tumorigenic HaCaT cells. The expression of Both C3 and CFB was significantly upregulated By IFN-γ and TNF-α in cSCC cells. Knockdown of CFB and C3 By specific siRNAs inhiBited migration of cSCC cells. Knockdown of CFB inhiBited proliferation of cSCC cells and this was associated with potent inhiBition of ERK1/2 activation. Knockdown of C3 and CFB also significantly inhiBited growth of human cSCC xenograft tumors in vivo in SCID mice. These results provide evidence for the role of C3 and CFB in progression of cSCC and identify them as specific Biomarkers and putative therapeutic targets for invasive cSCC. Citation Format: Pilvi Riihila, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Seppo Meri, Reidar Grenman, Ritva Heljasvaara, Taina Pihlajaniemi, Juha Peltonen, Sirkku Peltonen, Veli-Matti Kahari. <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B regulate growth of cutaneous squamous cell carcinoma. [aBstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):ABstract nr 3201. doi:10.1158/1538-7445.AM2015-3201
Atte Kivisaari - One of the best experts on this subject based on the ideXlab platform.
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<B>ComplementB> component c3 and <B>ComplementB> <B>FactorB> B promote growth of cutaneous squamous cell carcinoma
American Journal of Pathology, 2017Co-Authors: Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Liisa Nissinen, Pilvi Riihilä, Seppo MeriAbstract:Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B (CFB) in the growth of cSCC. Analysis of cSCC cell lines ( n = 8) and normal human epidermal keratinocytes ( n = 11) with real-time quantitative PCR and Western Blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell–specific laBeling for C3 and CFB in invasive cSCCs ( n = 71) and recessive dystrophic epidermolysis Bullosa–associated cSCCs ( n = 11) than in cSCC in situ ( n = 69), actinic keratoses ( n = 63), and normal skin ( n = 5). Significant up-regulation of C3 and CFB mRNA expression was noted in chemically induced mouse cSCCs, compared to Benign papillomas. Knockdown of C3 and CFB expression inhiBited migration and proliferation of cSCC cells and resulted in potent inhiBition of extracellular signal–regulated kinase 1/2 activation. Knockdown of C3 and CFB markedly inhiBited growth of human cSCC xenograft tumors in vivo . These results provide evidence for the roles of C3 and CFB in the development of cSCC and identify them as Biomarkers and potential therapeutic targets in this metastatic skin cancer.
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aBstract 3201 <B>ComplementB> component c3 and <B>ComplementB> <B>FactorB> B regulate growth of cutaneous squamous cell carcinoma
Cancer Research, 2015Co-Authors: Pilvi Riihilä, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Juha Peltonen, Seppo Meri, Taina Pihlajaniemi, Ritva Heljasvaara, Reidar Grenman, Sirkku PeltonenAbstract:Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and its incidence is increasing gloBally. We have examined the role of <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B (CFB) in the progression of cSCC. Significantly elevated mRNA levels for C3 and CFB were detected din cSCC cell lines (n = 8) compared to normal human epidermal keratinocytes (n = 11) By quantitative real-time reverse transcriptase-PCR. Increased production of C3 and CFB By cSCC cell lines was detected By western Blotting. The mRNA levels for C3 and CFB were also markedly higher in cSCC tumors (n = 6) than in normal skin (n = 10). Tumor cell specific staining for C3 and CFB was detected in cSCC tumors in vivo By immunohistochemistry and the staining intensity was stronger in invasive cSCCs (n = 71) than in cSCC in situ (n = 69), premalignant epidermal lesions (actinic keratoses, n = 65) and normal skin (n = 5). Significant upregulation of C3 and CFB mRNA expression was also noted in chemically induced mouse skin cSCCs (n = 27) compared to Benign papillomas (n = 17). The expression of C3 and CFB at mRNA and protein level was markedly higher in invasive tumorigenic Ha-ras-transformed HaCaT cell line than in Benign tumorigenic ras-transformed HaCaT cells and parental non-tumorigenic HaCaT cells. The expression of Both C3 and CFB was significantly upregulated By IFN-γ and TNF-α in cSCC cells. Knockdown of CFB and C3 By specific siRNAs inhiBited migration of cSCC cells. Knockdown of CFB inhiBited proliferation of cSCC cells and this was associated with potent inhiBition of ERK1/2 activation. Knockdown of C3 and CFB also significantly inhiBited growth of human cSCC xenograft tumors in vivo in SCID mice. These results provide evidence for the role of C3 and CFB in progression of cSCC and identify them as specific Biomarkers and putative therapeutic targets for invasive cSCC. Citation Format: Pilvi Riihila, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Seppo Meri, Reidar Grenman, Ritva Heljasvaara, Taina Pihlajaniemi, Juha Peltonen, Sirkku Peltonen, Veli-Matti Kahari. <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B regulate growth of cutaneous squamous cell carcinoma. [aBstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):ABstract nr 3201. doi:10.1158/1538-7445.AM2015-3201
Mehdi Farshchian - One of the best experts on this subject based on the ideXlab platform.
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<B>ComplementB> component c3 and <B>ComplementB> <B>FactorB> B promote growth of cutaneous squamous cell carcinoma
American Journal of Pathology, 2017Co-Authors: Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Liisa Nissinen, Pilvi Riihilä, Seppo MeriAbstract:Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B (CFB) in the growth of cSCC. Analysis of cSCC cell lines ( n = 8) and normal human epidermal keratinocytes ( n = 11) with real-time quantitative PCR and Western Blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell–specific laBeling for C3 and CFB in invasive cSCCs ( n = 71) and recessive dystrophic epidermolysis Bullosa–associated cSCCs ( n = 11) than in cSCC in situ ( n = 69), actinic keratoses ( n = 63), and normal skin ( n = 5). Significant up-regulation of C3 and CFB mRNA expression was noted in chemically induced mouse cSCCs, compared to Benign papillomas. Knockdown of C3 and CFB expression inhiBited migration and proliferation of cSCC cells and resulted in potent inhiBition of extracellular signal–regulated kinase 1/2 activation. Knockdown of C3 and CFB markedly inhiBited growth of human cSCC xenograft tumors in vivo . These results provide evidence for the roles of C3 and CFB in the development of cSCC and identify them as Biomarkers and potential therapeutic targets in this metastatic skin cancer.
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aBstract 3201 <B>ComplementB> component c3 and <B>ComplementB> <B>FactorB> B regulate growth of cutaneous squamous cell carcinoma
Cancer Research, 2015Co-Authors: Pilvi Riihilä, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Juha Peltonen, Seppo Meri, Taina Pihlajaniemi, Ritva Heljasvaara, Reidar Grenman, Sirkku PeltonenAbstract:Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and its incidence is increasing gloBally. We have examined the role of <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B (CFB) in the progression of cSCC. Significantly elevated mRNA levels for C3 and CFB were detected din cSCC cell lines (n = 8) compared to normal human epidermal keratinocytes (n = 11) By quantitative real-time reverse transcriptase-PCR. Increased production of C3 and CFB By cSCC cell lines was detected By western Blotting. The mRNA levels for C3 and CFB were also markedly higher in cSCC tumors (n = 6) than in normal skin (n = 10). Tumor cell specific staining for C3 and CFB was detected in cSCC tumors in vivo By immunohistochemistry and the staining intensity was stronger in invasive cSCCs (n = 71) than in cSCC in situ (n = 69), premalignant epidermal lesions (actinic keratoses, n = 65) and normal skin (n = 5). Significant upregulation of C3 and CFB mRNA expression was also noted in chemically induced mouse skin cSCCs (n = 27) compared to Benign papillomas (n = 17). The expression of C3 and CFB at mRNA and protein level was markedly higher in invasive tumorigenic Ha-ras-transformed HaCaT cell line than in Benign tumorigenic ras-transformed HaCaT cells and parental non-tumorigenic HaCaT cells. The expression of Both C3 and CFB was significantly upregulated By IFN-γ and TNF-α in cSCC cells. Knockdown of CFB and C3 By specific siRNAs inhiBited migration of cSCC cells. Knockdown of CFB inhiBited proliferation of cSCC cells and this was associated with potent inhiBition of ERK1/2 activation. Knockdown of C3 and CFB also significantly inhiBited growth of human cSCC xenograft tumors in vivo in SCID mice. These results provide evidence for the role of C3 and CFB in progression of cSCC and identify them as specific Biomarkers and putative therapeutic targets for invasive cSCC. Citation Format: Pilvi Riihila, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Seppo Meri, Reidar Grenman, Ritva Heljasvaara, Taina Pihlajaniemi, Juha Peltonen, Sirkku Peltonen, Veli-Matti Kahari. <B>ComplementB> component C3 and <B>ComplementB> <B>FactorB> B regulate growth of cutaneous squamous cell carcinoma. [aBstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):ABstract nr 3201. doi:10.1158/1538-7445.AM2015-3201