bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4180: Rewiring the cytokine network in melanoma
Authors: Nagaraju Raghavendar , Dee Christopher , Young Helen , Barriuso Jorge , Secombes Christopher , Hurlstone Adam 
Published: July 2016

Abstract
Malignant melanoma is one of the most aggressive types of malignancies in humans resulting in 50,000 deaths worldwide annually. Fortuitously, malignant melanoma is highly immunogenic and it is now well established that the host immune system can detect and kill melanoma. T helper type-1 lymphocytes (TH1) play a pivotal role in inducing and maintaining anti-tumour immune responses. In melanoma patients, it has been observed that higher number of TH1 cells in the tumour micro-environment lead to better prognosis. In this study, using an autochthonous zebrafish melanoma model, when we forced the expression of interferon gamma (IFNg) locally in the tumour microenvironment, thereby potentially enhancing TH1 differentiation, we observed an inflammatory response against melanoma that eventually lead to complete tumour regression.
Using transposon mediated BAC transgenesis, we have generated a Tg(cd4:mcherry) reporter line labelling CD4+ cells in zebrafish. By driving Human NRASQ61L in zebrafish melanocytes we have modelled melanoma in zebrafish and later when these fish developed tumours we forced the expression of IFNg in melanoma cells using a tamoxifen inducible LSL/CreERT2 system driven by mitfa minimal promoter. Experiments were performed using animals with and without CreERT2. Following tamoxifen administration, we observed a loss of pigmentation in all the IFNg induced tumours (n = 12) by 2 weeks post induction which gradually increased over the study period. Whereas no loss of pigmentation was observed in control tumours (n = 12) throughout the study period. At 9 weeks post induction, the study was terminated and tumours were analysed using histology. In tumours were IFNg was induced, we observed that the tumour tissue was now replaced with fibrotic tissue accompanied by a marked lymphocyte infiltration and patches of necrosis. However, new tumour nodules were also observed to develop in the vicinity of regressing nodules which are unpigmented and potentially hypo-immunogenic. We observed no signs of tumour regression in control tumours.
Although preliminary, our data is very exciting and promising as it will open new avenues for developing combinatorial therapies in melanoma. Using a high throughput in-vivo model system such as zebrafish, it is an exciting proposition to test the impact of combining anti-PD1/PDL1 inhibitors with various cytokines/chemokines in inducing effective and sustained tumour regression in melanoma.
Citation Format: Raghavendar Nagaraju, Christopher Dee, Helen Young, Jorge Barriuso, Christopher Secombes, Adam Hurlstone. Rewiring the cytokine network in melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4180.
Abstract 4188: RNAi and CRISPR/Cas9 based in vivo models for drug discovery
Authors: Premsrirut Prem K. , Martin Gregory , Dow Lukas , Kim Sang Yong , Zuber Johannes , Lowe Scott , Hannon Greg 
Published: July 2016

Abstract
With the advent of CRISPR-Cas9 technology, the speed and precision in which genetically engineered mouse models can be created is unprecedented. We now have at our disposal a genetic toolbox that will enable the rapid generation of sophisticated mouse models of cancer. Recently, an inducible CRISPR-Cas9 (iCRISPR) system was described that enables doxycycline-regulated Cas9 induction of widespread gene mutagenesis in multiple tissues. Previously, we also demonstrated how inducible RNA interference (RNAi) can be exploited experimentally to effectively and reversibly silence nearly any gene target not only in vitro but also in live mice. Here, we take advantage of these powerful technologies and combine both tet-inducible CRISPR-Cas9 and inducible RNAi-mediated gene silencing to develop animal models in which both de novo tumorigenesis can be induced by Cas9-mediated genome editing and therapeutic strategies assessed downstream via RNA interference-mediated gene silencing. By using this combination of CRISPR/Cas9 and RNAi technologies, we are able to not only model disease pathogenesis, but also mimic drug therapy in the same mice, giving us exceptional capabilities to perform preclinical studies in vivo. Using our robust flexible system, we have created a cost-effective and scalable platform for the production of complex genetically engineered mouse models of cancer with RNAi silencing of nearly any gene - mice with enormous predictive power that will shape our development of better tolerated therapies.
Citation Format: Prem K. Premsrirut, Gregory Martin, Lukas Dow, Sang Yong Kim, Johannes Zuber, Scott Lowe, Greg Hannon. RNAi and CRISPR/Cas9 based in vivo models for drug discovery. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4188.
Abstract 4193: Reporter systems to measure dynamics and specificity of targeted cancer therapy
Authors: Marquez Rebecca T. , Xu Liang ,   Experimental and Preclinical Imaging Core
Published: July 2016

Abstract
The Precision Medicine Initiative has driven the need for targeted therapy development to increase cancer patient survival. Due to this initiative, developing enhanced methods for measuring the accuracy and specificity of lead compound delivery is critical for moving these compounds through preclinical studies at a more efficient rate. The Experimental and Preclinical Imaging Core at the University of Kansas (epicore.ku.edu) is developing reporter constructs to assist in validating lead compound inhibition of oncogenic targets. Our lentiviral reporter constructs are used to establish stable cell lines that can be used either in vitro or in vivo to ensure optimal target inhibition. Our constructs include promoter reporters as well as 3’ untranslated-region (UTR) reporters to measure either changes in mRNA stabilization or translation by RNA-binding proteins or microRNA target validation. Our goal is to provide reporter constructs that will enable industry and academic institutions to ensure optimal inhibition of signaling pathways targeted by their lead compounds or microRNA-based therapies. Currently, we are constructing stable cancer cell lines that express near-infrared proteins, such as iRFP670, for measuring primary tumor and metastatic growth in vivo. In comparison to luciferase-expressing cell lines, we have found that cells expressing iRFP670 provided a more robust signal and were easier to image without the need for injecting a substrate. New promoter and 3’UTR reporters are being developed using iRFP670 and will be tested in vivo.
Citation Format: Rebecca T. Marquez, Liang Xu, Experimental and Preclinical Imaging Core. Reporter systems to measure dynamics and specificity of targeted cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4193.
Abstract 4209: Targeting GPNMB with 89Zr-CR011 for PET imaging of triple negative breast cancer
Authors: Marquez Bernadette V. , Lee Supum , Keler Tibor , Hawthorne Thomas , Hoog Jeremy , Li Shunqiang , Ma Cynthia , Lapi Suzanne E. 
Published: July 2016

Abstract
Glycoprotein non-metastatic melanoma B (GPNMB) is a transmembrane protein overexpressed in 30 - 40% of triple negative breast cancer (TNBC) and has shown to be associated with metastasis and disease recurrence. An anti-GPNMB antibody drug conjugate, Glembatumumab Vedotin (CDX-011), is currently in Phase II clinical trials for the treatment of metastatic TNBC patients, with promising outcomes. Positron Emission Tomography using radiolabeled antibodies could be advantageous in stratifying patients who may benefit from CDX-011, tracking the biodistribution of CDX-011, and assessing GPNMB expression in vivo. To this end, we radiolabeled the naked antibody, Glembatumumab (CR011), with the positron-emitting 89Zr (half life = 3.3 days). We characterized the stability, affinity, rate of cellular internalization, and specificity of 89Zr-CR011 using various cell-binding assays in human TNBC cell lines. We determined that 89Zr-CR011 is stable in serum solution for up to 5 days, binds specifically to GPNMB+ TNBC cells with high affinity (KD = 16 nM), and internalizes rapidly (50% within 30 - 60 min). We conducted a biodistribution study from 1 - 12 days post administration via tail vein in GPNMB+ MDA-MB-468 xenografts to determine the time point at which we achieve the optimal tumor-to-nontarget ratios. A subset of mice was administered a blocking dose of unlabeled CR011 (100-fold excess, 1 mg/mouse), where we observed a 2.5-fold reduction in 89Zr-CR011 tumor uptake, confirming the specificity of 89Zr-CR011 for GPNMB+ TNBC tumors. PET imaging studies and dosimetry calculations are currently in progress. This preliminary study demonstrates that 89Zr-CR011 may be an excellent companion diagnostic agent for CDX-011 therapy and an essential tool to assess the function of GPNMB in vivo.
Citation Format: Bernadette V. Marquez, Supum Lee, Tibor Keler, Thomas Hawthorne, Jeremy Hoog, Shunqiang Li, Cynthia Ma, Suzanne E. Lapi. Targeting GPNMB with 89Zr-CR011 for PET imaging of triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4209.
Abstract 421: Non reportable results - maternal neoplasm can alter results from non-invasive prenatal testing (NIPT)
Authors: Grosu Daniel , Dharajiya Nilesh G. , McCullough Ron M. , Sun Youting , Saldivar Juan-Sebastian , van den Boom Dirk , Ehrich Mathias 
Published: July 2016

Abstract
Cell free DNA is a powerful new analyte for the detection of chromosomal abnormalities of fetuses from the plasma of pregnant women. In non-invasive prenatal testing (NIPT), cfDNA is contributed into the plasma by the placenta. In rare cases, these results are distorted by additional sources of cfDNA in the maternal bloodstream. For example, organ transplantation can severely affect the cfDNA levels and lead to uninterpretable results. Another source of cfDNA that can lead to similar difficulties and ultimately to a non-reportable NIPT results, can be a maternal neoplasm. In our clinical laboratory, we have processed samples from over 450,000 pregnant patients. In cases of uninterpretable findings due to aberrant genomic profiles, potential reasons for non-reportable results were discussed with the caregiving physician. When feedback about these cases was available, it was collected in a database. In summary, we observed non-reportable NIPT results with aberrant genomic profile for 55 cases. A set of 43 had sufficient information available to allow inclusion in this summary. In 40 cases, a maternal neoplasm was confirmed (18 malignant, 20 benign, and two with imaging but without pathological confirmation). These observational results support further investigation by prospective controlled trials.
Citation Format: Daniel Grosu, Nilesh G. Dharajiya, Ron M. McCullough, Youting Sun, Juan-Sebastian Saldivar, Dirk van den Boom, Mathias Ehrich. Non reportable results - maternal neoplasm can alter results from non-invasive prenatal testing (NIPT). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 421.
Abstract 4211: Discovery of a novel peptide for improvement of radiotherapeutic efficacy and development of prognotic diagnosis
Authors: Lee Kyoung Jin , Lee Jae Hee , Song Si Yeol , Jeong Seong-Yun , Choi Eun Kyung 
Published: July 2016

Abstract
Cancer can be treated by the various modalities including surgery, chemotherapy, radiotherapy, among which the radiotherapy is the most important therapeutics in the cancer treatment. Despite the progression of modalities, cancer therapy has been constrained by impasse of prediction of treatment outcome and direction of cancer therapeutics because of diagnosis date, metastasis and genetic diversity of the individual patients.
In this study, we discovered specific tumor targeting peptides and radiotherapy-responding peptides suitable to apply to cancer therapy and monitoring of radiotherapy response. For a non-invasive imaging for potential cancer diagnosis system, we screened peptides using the phage display technique. Phage display is used in various pharmaceutical biotechnologies, and the one of the most powerful technologies to identify novel peptides regulating carcinogenesis. To emphasize the function of peptide ligands in a living body and consider the tumoral microenvironment, we used the patient-derived xenograft (PDX) tumor models for in vivo peptide displayed phage screening. It is warranted that the peptides specifically targeting in vivo human cancer xenografts with radiation treatment or not in colorectal cancer PDXs. We performed in vivo peptide screening in the two different cases of colorectal cancer PDX mouse models, and selected peptides were confirmed to radiation responding peptides and radiation resistant peptides. The results suggested that selected peptides were a promising diagnostic lead molecule for rapid and accurate detection for the radiotherapy response.
Taken together, we described a strategy to identify the peptides by in vivo phage display, and peptides possessed the specific targeting ability which would be potentially feasible for the development of personalized precision treatment. Its might be potential IR-guided probe and prognostic diagnosis in radiotherapy for colorectal cancer.
Keywords: Peptide, Colorectal cancer, Patient-derived xenograft (PDX), Radiation, In vivo peptide screening
Citation Format: Kyoung Jin Lee, Jae Hee Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi. Discovery of a novel peptide for improvement of radiotherapeutic efficacy and development of prognotic diagnosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4211.
Abstract 4217: First pre-clinical validation of radiogenomics in glioblastoma
Authors: Zinn Pascal , Singh Sanjay , Luedi Markus M. , Zandi Faramak , Kotrotsou Aikaterini , Hatami Masumeh , Thomas Ginu , Elakkad Ahmed , Gumin Joy , Sulman Erik P. , Lang Frederick , Piwnica-Worms David , Colen Rivka R. 
Published: July 2016

Abstract
A plethora of Magnetic Resonance Imaging (MRI) features have been correlated to cancer genomics to date, however, none have established causality. Here, we present an in vivo xenograft RNA interference validated, potentially clinically applicable test method termed “Magnetic Resonance Radiomic Sequencing” (MRRS) for the noninvasive detection of cancer genomics in Glioblastoma. MRRS comprehensively assesses the entire tumor mass using imaging texture-based algorithms that generate thousands of variables (features) inherent to the tumor. Two independent glioblastoma stem cells (GSC1 and GSC3) harboring doxycycline inducible short hairpin RNA against Periostin (POSTN), a gene previously identified in our radiogenomic screen, were implanted at orthotopic location in nude mouse brain. In vivo knockdown of &gt;90% and ∼40% POSTN gene was achieved in GSC3 and GSC1 respectively. The T2 and T1 post MRI texture features, in edema and contrast enhancement phenotype features were compared between doxycycline (POSTN knockdown) and sucrose (control) group of mice using T test statistics. The significant features were included in a Stepwise Forward Logistic Regression analysis to build the final predictive model. The accuracy of the model was tested using ROC cure analysis. Among 3600 features in GSC3 mice cohort, 117 features were significantly (p value&lt;0.05) different between the two groups. The significant features were included in a Stepwise Forward Logistic Regression analysis, 2 textures features (feature 234 of edema T1 and feature 251 of edema T2) were selected to be included in the final predictive model. The AUC of the model with leave one out cross validation method was 100%. The similar analyses were done in the GSC1 mice. The final predictive model in the GSC1 group was statistically insignificant (p value = 0.15) with AUC (95% CI) = 73% (46%-98%), suggesting that MRRS is reflective of underlying gene expression levels. Our results therefore describe the ‘first mouse model derived MRRS signature to describe a causal link of gene alteration to MRRS. This novel test method may open an avenue for human-mouse matched co-clinical trials and noninvasive Radiogenomic diagnostics.
Citation Format: Pascal Zinn, Sanjay Singh, Markus M. Luedi, Faramak Zandi, Aikaterini Kotrotsou, Masumeh Hatami, Ginu Thomas, Ahmed Elakkad, Joy Gumin, Erik P. Sulman, Frederick Lang, David Piwnica-Worms, Rivka R. Colen. First pre-clinical validation of radiogenomics in glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4217.
Abstract 4219: Surface-displayed RGD enhanced the targeting and therapeutic efficacy of attenuated Salmonella typhimurium
Authors: Park Seung-Hwan , Zheng Jin Hai , Yun Hee-Seung , Park In-Kyu , Hong Yeongjin , Choy Hyun E. , Min Jung-Joon 
Published: July 2016

Abstract
Anticancer therapy using engineered bacteria aims to overcome limitations of current cancer therapy by actively targeting and efficiently removing cancer. In order to achieve this goal, new approaches are essential to target therapeutically resistant regions of tumors, to maintain enough number of bacteria in tumor and to deliver drugs at sufficient concentrations during the period of therapeutic process. Therefore, it is necessary to enhance the bacterial targeting efficiency through bacterial surface engineering. Here, we demonstrate that Salmonella tumor tropism can be strengthened significantly via surface displaying of RGD peptide sequence (ACDCRGDCFCG; RGD sequence) in the external loop of outer membrane protein A (OmpA) of attenuated Salmonella typhimurium. RGD-displaying Salmonella strongly bound to αvβ3 over-expressing cancer cells while showed weak binding to non-expressing cancer cells, indicating the feasibility of surface display with preferential homing peptide. In vivo bioluminescence imaging showed strong targeting efficiency of RGD-displayed Salmonella in αvβ3 over-expressing cancer xenografts (MDA-MB-231, MDA-MB-435, M21, and U87MG). The surface engineered bacteria significantly suppressed both human breast tumor (MDA-MB-231) and human melanoma (MDA-MB-435), and prolonged survival in mice. In conclusion, engineered bacteria displaying RGD peptides on the surface could advance both targeting efficiency and therapeutic effects.
Citation Format: Seung-Hwan Park, Jin Hai Zheng, Hee-Seung Yun, In-Kyu Park, Yeongjin Hong, Hyun E. Choy, Jung-Joon Min. Surface-displayed RGD enhanced the targeting and therapeutic efficacy of attenuated Salmonella typhimurium. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4219.
Abstract 4220: Tumor-targeting Salmonella typhimurium A1-R efficacy on colon cancer liver metastasis alone and in combination with fluorescence-guided surgery
Authors: Murakami Takashi , Hiroshima Yukihiko , Zhang Yong , Zhao Ming , Matsuyama Ryusei , Chishima Takashi , Tanaka Kuniya , Bouvet MIchael , Endo Itaru , Hoffman Robert M. 
Published: July 2016

Abstract
Liver metastasis is the most frequent cause of death from colon and other cancers. Surgical treatment of liver metastasis has had limited success. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R alone and in combination with fluorescence-guided surgery on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) developed liver metastasis after orthotopic implantation. In the orthotopic nude-mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth (p &lt; 0.01) after i.v. administration. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase overall survival (p = 0.01) and disease-free survival (p &lt; 0.01) after bright-light surgery (BLS) of liver metastasis. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R treatment of liver metastasis.
Citation Format: Takashi Murakami, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, MIchael Bouvet, Itaru Endo, Robert M. Hoffman. Tumor-targeting Salmonella typhimurium A1-R efficacy on colon cancer liver metastasis alone and in combination with fluorescence-guided surgery. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4220.
Abstract 4221: Imaging formation of the tumor microenvironment in orthotopic liver tumors in red fluorescent protein (RFP) transgenic nude mice
Authors: Suetsugu Atsushi , Hiroshima Yukihiko , Matsumoto Takuro , Hasegawa Kosuke , Nakamura Miki , Shimizu Masahito , Saji Shigetoyo , Moriwaki Hisataka , Bouvet Michael , Hoffman Robert M. 
Published: July 2016

Abstract
We report here dual-color imaging of the formation of the TME in orthotopic liver cancer in transgenic red fluorescent protein (RFP) nude mice, which express RFP in all organs. Non-colored HUH-7 human hepatoma cells were injected in the spleen of RFP nude mice to establish an orthotopic liver cancer model. TME formation in the liver tumor was observed using the Olympus OV100 small animal fluorescence imaging system. Non-colored liver cancer cells formed colonies in the liver 28 days after cell transplantation to the spleen. In the liver, RFP host-mouse cells accumulated around and in the liver tumor as visualized by fluorescence imaging. A desmin and sirus-red positive area increased around and within the liver tumor over time. These results indicate cancer-associated fibroblasts (CAFs) were recruited by the liver metastasis suggesting that CAFs, along with the angiogenic tumor blood vessels, could serve as visible therapeutic targets.
Citation Format: Atsushi Suetsugu, Yukihiko Hiroshima, Takuro Matsumoto, Kosuke Hasegawa, Miki Nakamura, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Michael Bouvet, Robert M. Hoffman. Imaging formation of the tumor microenvironment in orthotopic liver tumors in red fluorescent protein (RFP) transgenic nude mice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4221.