bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B19: Rapid in vivo screen of pancreatic ductal adenocarcinoma therapeutics
Authors: Ocal Ozhan , Heath Blake , Rivera Lee B. , Pashkov Victor , Swift Galvin H. , Brekken Rolf A. , Wilkie Tom M. 
Published: May 2015

Abstract
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer related deaths. Limited progress has been made in developing effective therapy for PDA. Compounding this challenge has been the lack of a systematic and robust in vivo screen for effective drug combinations. Kras mutations (e.g. KrasG12D) are found in over 90% of human PDA and occur early in tumor progression. Protein kinase and G-Protein Coupled Receptor (GPCR) signaling can initiate Ras activation. Regulators of G-protein Signaling (RGS) proteins are coincidence detectors that can be induced by and integrate multiple inputs to feedback regulate GPCR signaling. We previously described Rgs16 expression during embryonic and postnatal pancreas development in pancreatic progenitors, endocrine cells and ductal-associated cells. Here, we show that the Rgs16::GFP transgene is a KrasG12D dependent marker of all stages of neoplasia in the p48Cre; LSL-KrasG12D; Cdkn2af/f PDA mice. Although KrasG12D is expressed in embryonic pancreas progenitor cells and in all mature acinar cells, Rgs16::GFP expression in tumors first emerges in ductal pancreatic intraepithelial neoplasms as early as 12 days post birth. The distribution and intensity of expression is proportional to and coincident with tumor burden. Rgs16::GFP expression in acinar cells of distal lobes initiates only after tumor occlusion of proximal ducts. The gene expression signature of primary PDA cells in culture obtained via RNA-seq is closely related to embryonic progenitors of pancreatic ducts and endocrine cells. PDA cells in culture are highly sensitive to the chemotherapic drug gemcitabine mediated cell death. In a proof-of-principle for drug screens, we find PDA weanling mice treated with gemcitabine and Nab-paclitaxel for two weeks have significantly lower Rgs16::GFP expression and reduced tumor size and occurrence. Rgs16::GFP is a novel in vivo reporter of PDA progression and sensitivity to new drug regimens that inhibit KrasG12D mediated oncogenesis.
Supported by NCI-CA161624
Citation Format: Ozhan Ocal, Blake Heath, Lee B. Rivera, Victor Pashkov, Galvin H. Swift, Rolf A. Brekken, Tom M. Wilkie. Rapid in vivo screen of pancreatic ductal adenocarcinoma therapeutics. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B19. doi: 10.1158/1557-3125.RASONC14-B19
Abstract B23: CD4+ T lymphocytes promote pancreatic cancer progression by suppressing anti-tumor immune responses
Authors: Zhang Yaqing , Yan Wei , Yan Wei , Mathew Esha , Bednar Filip , Wan Shanshan , Collins Meredith A. , Evans Rebecca A. , Welling Theodore H. , Vonderheide Robert H. , Magliano Marina Pasca di , Magliano Marina Pasca di 
Published: May 2015

Abstract
Pancreatic cancer, one of the deadliest human malignancies, is associated with oncogenic Kras and is most commonly preceded by precursor lesions known as Pancreatic Intraepithelial Neoplasias (PanINs). PanIN formation is accompanied by the establishment of an immune-tolerant microenvironment. However, the immune contribution to the initiation of pancreatic cancer is currently poorly understood. Here, we show that oncogenic Kras-expressing epithelial cells drive the establishment of an immunosuppressive microenvironment through the recruitment and activity of CD4+ T cells. We further show that CD4+ T cells functionally repress the activity of CD8+ T cells. Elimination of CD4+ T cells uncovers CD8+ T cells anti-neoplastic function, and blocks the onset of pancreatic carcinogenesis. Thus, our studies uncover essential and opposing roles of immune cells during PanIN formation, and provide rationale to explore immune-modulatory approaches in pancreatic cancer.
Citation Format: Yaqing Zhang, Wei Yan, Wei Yan, Esha Mathew, Filip Bednar, Shanshan Wan, Meredith A. Collins, Rebecca A. Evans, Theodore H. Welling, Robert H. Vonderheide, Marina Pasca di Magliano, Marina Pasca di Magliano. CD4+ T lymphocytes promote pancreatic cancer progression by suppressing anti-tumor immune responses. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B23. doi: 10.1158/1557-3125.RASONC14-B23
Abstract B28: Multiplexed mass spectrometry analysis of KRAS-associated metabolic reprogramming in colorectal tumors and cell lines
Authors: Hutton Josiah E. , Zimmerman Lisa J. , Slebos Robbert J. , Li Ming , Liebler Daniel C. 
Published: May 2015

Abstract
Mutational activation of KRAS is associated with increased cellular proliferation and tumorigenicity, and metabolic reprogramming. We have used a mass spectrometry analysis by multiple reaction monitoring (MRM) to quantify the expression of 62 proteins encompassing glycolysis (21 proteins), TCA cycle (14 proteins), pentose phosphate pathway (10 proteins), serine biosynthesis (4 proteins), and 13 other proteins involved in metabolism. We applied this MRM panel to the colon tumor cell line DLD-1 (one mutant (G13D) KRAS allele and one WT allele) and the isogenic derivative cell lines DKO-1 (G13D, -) and DKs-8 (+,-). DLD-1 and DKO-1 cells produce lactate at a significantly higher rate than the Dks-8 cells, indicating metabolic reprogramming reflecting a “Warburg” phenotype. MRM panel comparisons of these cell lines revealed that KRAS mutation was associated with the increased expression of glucose and glutamine transporters, glycolytic enzymes, enzymes involved in serine biosynthesis, and a few TCA cycle enzymes. Comparison of the isogenic KRAS mutant/WT pair to each other and to the DLD-1 parental cell line revealed distinct expression changes for the three different KRAS mutant/WT combinations, which suggests that mutant and WT KRAS play distinct roles in metabolic reprogramming. The MRM panel was also used to analyze 16 human formalin-fixed, paraffin-embedded (FFPE) Stage II colorectal tumors. Although the expression of the metabolic proteins varied from patient to patient, a consensus group of 7 metabolic proteins, including enzymes of glycolysis, were significantly increased in KRAS mutant tumors. These results demonstrate that mutational activation of KRAS induces metabolic reprogramming via signaling through both BRAF and PI3K signaling pathways in colorectal cancer cells by the altered expression of metabolic proteins. (Supported by NIH Grant U24CA159988)
Citation Format: Josiah E. Hutton, III, Lisa J. Zimmerman, Robbert J. Slebos, Ming Li, Daniel C. Liebler. Multiplexed mass spectrometry analysis of KRAS-associated metabolic reprogramming in colorectal tumors and cell lines. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B28. doi: 10.1158/1557-3125.RASONC14-B28
Abstract B31: The RhoGEF GEF-H1 is required for RAS oncogene-driven pancreatic cancer
Authors: Cullis Jane , Meiri Dedi , Jose-Sandi Maria , Kent Oliver , Medrano Mauricio , Mokady Daphna , Tsao Ming , Gingras Anne-Claude , Rottapel Robert 
Published: May 2015

Abstract
Cellular transformation by oncogenic RAS engages the MAPK pathway under strict spatiotemporal regulation by the scaffold protein KSR-1. Here, we find using a whole genome functional shRNA-based screen, that the guanine nucleotide exchange factor GEF-H1 plays a critical role in a positive feedback loop for the RAS/MAPK pathway independently of its RhoGEF activity. GEF-H1 acts as an adaptor protein, linking the PP2A B' subunits to KSR-1, required for the dephosphorylation of KSR-1 S392 and activation of MAPK signaling. GEF-H1 is required for the growth and survival of RASV12-transformed cells and pancreatic xenografts. GEF-H1 expression is induced by oncogenic RAS and is correlated with pancreatic neoplastic progression. Our results therefore identify GEF-H1 as an amplifier of MAPK signaling required for cell transformation and provide mechanistic insight into the progression of RAS-mutant tumors.
Citation Format: Jane Cullis, Dedi Meiri, Maria Jose-Sandi, Oliver Kent, Mauricio Medrano, Daphna Mokady, Ming Tsao, Anne-Claude Gingras, Robert Rottapel. The RhoGEF GEF-H1 is required for RAS oncogene-driven pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B31. doi: 10.1158/1557-3125.RASONC14-B31
Abstract B34: A systems biology approach to elucidate novel drug targets in KRAS mutant tumors
Authors: Wah David A. , Giorgi Federico M. , Petrey Donald , Alvarez Mariano J. , Silkov Tonya , Broyde Josh , Rieckhof Gabrielle E. , Honig Barry , Califano Andrea 
Published: May 2015

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR09) of the Conference Proceedings.
Citation Format: David A. Wah, Federico M. Giorgi, Donald Petrey, Mariano J. Alvarez, Tonya Silkov, Josh Broyde, Gabrielle E. Rieckhof, Barry Honig, Andrea Califano. A systems biology approach to elucidate novel drug targets in KRAS mutant tumors. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B34. doi: 10.1158/1557-3125.RASONC14-B34
Abstract B37: Prenylation inhibition induces cell death in NRAS mutant melanoma cells
Authors: Garay Tamas , Kenessey Istvan , Laszlo Viktoria , Tovari Jozsef , Berger Walter , Kovacs Laszlo , Timar Jozsef , Hegedus Balazs 
Published: May 2015

Abstract
While targeted therapeutic approaches are now available for the treatment of BRAF mutant melanomas, non-BRAF mutant melanoma still lacks this modality. In order to explore the potential of prenylation inhibition we investigated the response of NRAS or BRAF mutant and double wild-type melanoma to zoledronic acid treatment. Effect of zoledronic acid on proliferation, apoptosis and migration of melanoma cells as well as the activation of downstream elements of the RAS/RAF pathway were characterized in vitro. In vivo subcutaneous xenograft and spleen to liver colonization models were used to evaluate the influence of zoledronic acid treatment on primary tumor growth and metastatic potential of melanoma cells. Zoledronic acid significantly decreased proliferation in NRAS mutant cells as compared to BRAF mutant and double wild-type cells, in vitro. Similarly, TUNEL assay revealed apoptosis induction in an oncogenic mutation specific manner. In line with this finding, activation of ribosomal protein S6 was decreased. Unexpected activation of the downstream effector Erk1/2 and increase in migration was found in BRAF mutant cells. Zoledronic acid failed to show significant synergism with cytotoxic cisplatin or DTIC treatment in vitro. In vivo zoledronic acid did not inhibit the subcutaneous growth of melanoma cells irrespective of oncogenic mutations. In contrast, the lower dose of zoledronic acid resulted in significantly higher liver metastasis in double wild-type cells. Altogether our data demonstrates that prenylation inhibition may be a novel therapeutic approach in NRAS mutant melanoma. However, further investigations are needed to identify drugs that have appropriate pharmacological properties to efficiently target melanoma cells.
Citation Format: Tamas Garay, Istvan Kenessey, Viktoria Laszlo, Jozsef Tovari, Walter Berger, Laszlo Kovacs, Jozsef Timar, Balazs Hegedus. Prenylation inhibition induces cell death in NRAS mutant melanoma cells. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B37. doi: 10.1158/1557-3125.RASONC14-B37
Abstract B46: Stabilized helices targeting the RAS-SOS interaction as inhibitors of RAS-dependent cancer cell growth
Authors: Nickerson Seth , Joy Stephen T. , Arora Paramjit S. , Bar-Sagi Dafna 
Published: May 2015

Abstract
Accumulating evidence supports an essential role for wild-type RAS isoforms in oncogenic RAS-driven tumorigenesis. Recently, we demonstrated that allosteric stimulation of SOS by oncogenic RAS facilitates cross-activation of wild-type RAS and is required for malignancy. To inhibit SOS-mediated activation of RAS we generated stabilized peptide α-helices derived from the catalytic helix of SOS using the hydrogen bond surrogate approach (HBSSOS). Treatment of RAS-mutant cancer cells with HBSSOS inhibits cell proliferation and induces a G2/M phase checkpoint arrest. Importantly, HBSSOS is taken up into cells by macropinocytosis, an endocytic mechanism that is elevated in RAS-mutant cancer cells, and the levels of macropinocytosis for a given cell line correlate inversely with the half maximum effective concentration (EC50) of HBSSOS, indicating preferential uptake of HBSSOS by RAS-mutant cells. Our results identify macropinocytic uptake of stabilized helices as a potential strategy for inhibiting RAS-dependent cancer cell growth.
Citation Format: Seth Nickerson, Stephen T. Joy, Paramjit S. Arora, Dafna Bar-Sagi. Stabilized helices targeting the RAS-SOS interaction as inhibitors of RAS-dependent cancer cell growth. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B46. doi: 10.1158/1557-3125.RASONC14-B46
Abstract B48: Regulation of mutant KRAS protein stability via SMURF2:UBCH5 complex mediated degradation of beta-TrCP1
Authors: Shukla Shirish , Allam Uday Shankar , Ahsan Aarif , Chen Guoan , Beer David G. , Lawrence Theodore S. , Nyati Mukesh K. , Ray Dipankar 
Published: May 2015

Abstract
Attempts to target mutant KRAS have been unsuccessful. Most of the current therapeutic approaches are indirect, mainly via inhibiting KRAS down-stream signaling, which have been marginally successful. Here we report the identification of Smad ubiquitination regulatory factor 2 (SMURF2), a HECT-type ubiquitin ligase (E3) as a critical regulator of mutant KRAS protein stability. We show that the loss of SMURF2 either by si-/sh-RNA mediated gene silencing or by overexpression of a catalytically inactive SMURF2 Cys716Ala (CA) mutant, can cause lysosome-mediated KRAS degradation; whereas, overexpression of wild type SMURF2 enhances KRAS protein stability. Most importantly, we found that mutant KRAS protein is more susceptible to SMURF2 alterations in that mutant protein half-life decreased from &gt;12h in control siRNA-treated cells to &lt;3h with Smurf2 siRNA treatment, whereas only marginal differences were noted for wild-type KRAS protein upon similar treatments. Importantly, this loss of mutant KRAS protein could be rescued by overexpressing a siRNA-resistant (si-R) wild type SMURF2. Our data further show that SMURF2 along with an ubiquitin conjugating enzyme (E2), UBCH5, poly-ubiquitinates and degrades a Ras family E3, beta-Transducing Repeat Containing Protein 1 (beta-TrCP1). Conversely, beta-TrCP1 is accumulated upon the loss of SMURF2, leading to its increased binding and degradation of KRAS. Therefore, as expected, beta-TrCP1 knockdown following Smurf2 siRNA treatment rescues Smurf2 siRNA-mediated mutant KRAS loss. Functionally, we found a positive correlation between SMURF2 and KRAS protein levels among different cancer cell lines and demonstrated that a loss of SMURF2 reduces the clonogenic survival in vitro and prolongs tumor latency of mutant KRAS-dependent cells in vivo. Taken together, we show that SMURF2 catalytic activity is critical in maintaining mutant KRAS protein stability and propose that targeting of SMURF2 may be a unique strategy to degrade mutant KRAS and thus kill mutant KRAS-addicted cancer cells.
Citation Format: Shirish Shukla, Uday Shankar Allam, Aarif Ahsan, Guoan Chen, David G. Beer, Theodore S. Lawrence, Mukesh K. Nyati, Dipankar Ray. Regulation of mutant KRAS protein stability via SMURF2:UBCH5 complex mediated degradation of beta-TrCP1. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B48. doi: 10.1158/1557-3125.RASONC14-B48
Abstract B55: Hypoxanthine wobble base multimutant KRAS2 mRNA PET imaging agent in G12D mice
Authors: Wickstrom Eric , Chen Chang-Po , Wampole Matthew E. , Zhang Kaijun , Paudyal Bishnuhari , Wang Antican , Tripathi Sushil , Kumar Pardeep , Mitchell Edith P. , Lu Bo , Thakur Mathew L. , Gray Brian D. , Mattis Jeffrey A. 
Published: May 2015

Abstract
Activating mutations in KRAS2 oncogene lead to constitutive K-Ras-GTP signals regardless of EGFR signaling, enabling resistance to EGFR-targeted therapies. Some cancers are activated by mutation of the KRAS2 12th codon from the wild type GGU that encodes glycine (G) to a mutant GAU that encodes aspartate (D) or a mutant GUU that encodes valine (V). For this reason, we hypothesize that determining multiple KRAS2 mutations in vivo by external mRNA PET imaging will enable physicians to decide on alternatives to EGFR-directed therapy. We previously pioneered tumor mRNA PET imaging in pancreatic cancer and breast cancer xenografts [Paudyal, et al. (2013) Nuclear Medicine and Biology 40(8):994-9] with peptide nucleic acid (PNA) 12-mers coupled to receptor-targeting peptides and imaging reporter moieties, showing single mismatch specificity. Thus, we designed and synthesized a 12-mer PNA hybridization agent with a hypoxanthine wobble base opposite the middle base of the KRAS2 mRNA 12th codon. At the C-terminus, we included a cyclized tetrapeptide based on insulin-like growth factor 1 (IGF1) to enable IGF1R-mediated cellular uptake. We included an N-terminal N2S2 chelator in order to bind 64Cu. Molecular dynamics and circular dichroism analysis of the wobble base PNA H-bonded to KRAS2 RNA showed preference for mutant A or U over wild type G [Sanders, et al. (2013) Journal of Physical Chemistry B 117(39):11584-95]. We then administered 200 μCi of the [64Cu]PNA wobble base agent, or the complementary G12D agent, or the wild type agent, by tail vein into 3-month-old G12D transgenic mice that developed spontaneous lung tumors. 4 hr and 24 hr later, mice were imaged in a Siemens Inveon microPET/CT scanner. The PET standard uptake value (SUV) with the G12D agent was 1.4, while SUV was 1.3 with the G12DVA wobble base agent, vs. 0.04 with the G12 wild type sequence. The wobble base approach enables detection of three different KRAS2 mutations, G12D, G12V, or G12A, with a single agent. mRNA PET imaging also enables external monitoring of therapeutic efficacy. Supported by NIH CA148565; IP owned by EW/MLT, licensed to MTTI.
Citation Format: Eric Wickstrom, Chang-Po Chen, Matthew E. Wampole, Kaijun Zhang, Bishnuhari Paudyal, Antican Wang, Sushil Tripathi, Pardeep Kumar, Edith P. Mitchell, Bo Lu, Mathew L. Thakur, Brian D. Gray, Jeffrey A. Mattis. Hypoxanthine wobble base multimutant KRAS2 mRNA PET imaging agent in G12D mice. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B55. doi: 10.1158/1557-3125.RASONC14-B55
Abstract IA08: Systematic functional genomics and KRAS
Authors: Hahn William C. 
Published: May 2015

Abstract
Large scale characterization of cancer genomes has led to information regarding the identify, number, and types of alterations found in human tumors. However, the large number of mutations identified to date require complementary approaches to understand the function of these mutated genes and to elucidate pathways involved in cancer initiation and progression. Over the past several years, we have developed genome scale RNAi libraries and open reading frame expression libraries that permit a systematic evaluation of genes involved in cancer initiation and maintenance. We have used these tools to dissect known and novel pathways involved in malignant transformation. In particular, we have dissected the signaling pathways related to one of the most frequently mutated oncogenes KRAS, that has proven to be difficult to target therapeutically. We have identified new components of KRAS effector pathways that are essential for the survival of KRAS driven cancers. We have also developed signatures that allow us to dissect KRAS-driven gene programs that correspond to KRAS-dependence. We have used this information to develop inhibitors of components of KRAS signaling that show promise in KRAS-driven cancer models.
Citation Format: William C. Hahn. Systematic functional genomics and KRAS. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr IA08. doi: 10.1158/1557-3125.RASONC14-IA08
Abstract IA09: Copper is required for oncogenic BRAF signaling and tumorigenesis
Authors: Brady Donita , Crowe Matt , Turski Michelle , Hobbs Aaron , Yao Xiaojie , Chaikuad Apirat , Knapp Stefan , Xiao Kunhong , Campbell Sharon , Thiele Dennis , Counter Chris 
Published: May 2015

Abstract
The BRAF serine/threonine kinase is mutated, typically at V600, to induce an active oncogenic state in a large fraction of melanoma, thyroid, hairy cell leukemia, and to a lesser extent, a wide spectrum of other cancers. BRAFV600E activates the kinases MEK1 and MEK2, which stimulate the MAPK pathway to promote cancer. ATP inhibitors of oncogenic BRAF and MEK1/2 provide a survival advantage in metastatic melanoma, an effect enhanced by co-administering two such inhibitors. Thus, combining multiple approaches to inhibit MAPK signaling is a promising strategy to treat BRAF mutation-positive cancers. We previously found that copper (Cu) influx enhances MEK1 phosphorylation of its substrates ERK1 and ERK2 through a Cu-MEK1 interaction. We now show here that genetic loss of the high affinity Cu transporter Ctr1 or mutations in MEK1 that disrupt Cu binding reduced MAPK signaling and oncogenic BRAFV600E-mediated tumorigenesis. Loss of tumor growth was rescued by expressing a MEK1/5 chimera that phosphorylates ERK1/2 independent of Cu or an activated ERK2. Importantly, Cu chelators used in the treatment of Wilson disease reduced tumor growth of not only BRAFV600E-transformed cells, but also cells resistant to BRAF inhibition. Taken together, these results suggest that Cu-chelation therapy could be repurposed to treat BRAFV600E mutation-positive cancers.
Citation Format: Donita Brady, Matt Crowe, Michelle Turski, Aaron Hobbs, Xiaojie Yao, Apirat Chaikuad, Stefan Knapp, Kunhong Xiao, Sharon Campbell, Dennis Thiele, Chris Counter. Copper is required for oncogenic BRAF signaling and tumorigenesis. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr IA09. doi: 10.1158/1557-3125.RASONC14-IA09