bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3099: Radiation-induced angiogenesis is associated with MMP-9-miR-494-Syndecan-1 regulatory loop in medulloblastoma cells.
Authors: Asuthkar Swapna , Velpula Kiran Kumar , Gondi Christopher , Nalla Arun Kumar , Gogineni Venkateswara Rao , Rao Jasti S. 
Published: August 2014

Abstract
Matrix metalloproteinase-9 (MMP-9) is one of the most prominent proteins associated with tumorigenesis and is a modulator of the tumor microenvironment during angiogenesis. Recently, it has been speculated that Syndecan-1, a transmembrane heparan sulfate-bearing proteoglycan, has a critical role in contributing to angiogenesis when associated with MMP-9. However, the mechanism behind their synergistic regulation is not fully understood. In the current study, we report that ionizing radiation (IR)-induced MMP-9 enhances Syndecan-1 shedding and tube-inducing ability of medulloblastoma cells. Furthermore, tumor angiogenesis is associated with higher MMP-9-Syndecan-1 interactions on both the cell surface and extracellular medium. Our results also revealed the existence of a novel regulatory mechanism where MMP-9 drives the suppression of miR-494, thereby resulting in enhanced Syndecan-1 shedding and angiogenesis. By employing bioinformatics and functional luciferase experiments, we demonstrated that 3’-UTR of Syndecan-1 mRNA is a direct target of miR-494. Moreover, from the in situ hybridization analysis, we found that MMP-9-specific shRNA (pM) treatment of mouse intracranial tumors resulted in elevated expression of miR-494. This negative correlation between MMP-9 and miR-494 levels was found to be dependent on the methylation status of the miR-494 promoter-associated CpG island region (-186 to -20), which was confirmed by bisulfite-sequencing and methylation-specific-PCR (MSP) analysis. Overall, our results demonstrate a previously unrecognized mechanism of angiogenesis regulation in medulloblastoma through which miR-494 modulates the transcription of radiation-induced angiogenesis promoting molecules and that MMP-9-Syndecan-1 activity creates a negative feedback loop by regulating the expression of miR-494.
Citation Format: Swapna Asuthkar, Kiran Kumar Velpula, Christopher Gondi, Arun Kumar Nalla, Venkateswara Rao Gogineni, Jasti S. Rao. Radiation-induced angiogenesis is associated with MMP-9-miR-494-Syndecan-1 regulatory loop in medulloblastoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3099. doi:10.1158/1538-7445.AM2013-3099
Abstract 3104: HOXB7 promotes tumor progression via activation of the transformation growth factor-β signaling pathway.
Authors: Liu Shou , Zhang Hongmei , Chen Hexin 
Published: August 2014

Abstract
Our previous studies have shown that overexpression of Hoxb7 delays tumors onset, but promotes tumor progression and metastasis in oncogene Her2/neu-induced mammary tumorigenesis, which is reminiscent of the dual role of TGF-β in breast cancer. To investigate whether HOXB7 directly or indirectly regulates the TGF-β signaling, we examined the phosphorylation levels of SMAD3, an important mediator of TGF-beta signaling, in primary mammary tumors derived from the Hoxb7 and Her2/neu double-transgenic mice and the Her2/neu mono-transgenic mice. Phosphorylation of SMAD3 is detected in a higher percentage of primary tumor tissues from double transgenic mice than that from Her2/neu mono-transgenic mice (69.2% versus 15.4%, p &lt; 0.05), suggesting that Hoxb7 may activate TGF-β/Smad signaling in breast tumor tissues. In line with this finding, overexpression of HOXB7 induces expression of TGF-β ligands in both mouse and human breast cancer cell lines, leading to increased cell motility and invasiveness. The acquainted phenotypes in HOXB7-overepressing cells can be reversed by pharmacologic inhibition of TGF-β signaling. Promoter deletion analysis and Chromotin-immunprocipiration assay further demonstrated that HOXB7 can directly bind to and activate the promoter of TGFβ2. More importantly, expression of HOXB7 and TGFβ2 is strongly correlated in primary breast cancer tissues and associated with advanced stages of tumor progression and reduced survival rate. Taken together, our results suggest that HOXB7 may promote tumor migration, invasion and possibly metastasis through activation of the TGF-β signaling pathway.
Citation Format: Shou Liu, Hongmei Zhang, Hexin Chen. HOXB7 promotes tumor progression via activation of the transformation growth factor-β signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3104. doi:10.1158/1538-7445.AM2013-3104
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 3147: Cancer-specific mutations in adult soft tissue sarcomas.
Authors: Abaan Ogan D. , Francis Princy , Pineda Marbin , Walker Robert L. , Zhu Yuelin J. , Bilke Sven , Davis Sean R. , Meltzer Paul S. 
Published: August 2014

Abstract
Understanding of how cancer initiates and progresses is a fundamental goal of cancer research. Identification of cancer mutations is of profound importance for both understanding of the disease and for developing novel therapies. Soft-tissue sarcomas include multiple uncommon histotypes with features of diverse connective tissue lineages. Although some of their underlying genetic changes have been elucidated, for example in those types which contain etiologic chromosome translocations, in general, the genetic basis of these tumors is incompletely described. To investigate mutations in 8 subtypes of adult soft tissue sarcomas, we resequenced coding exons from about 1300 cancer relevant genes in 66 tumor samples. Data was analyzed for somatic variants in samples with matched normals while samples without normal were analyzed individually. The most frequent events were TP53 mutations (26%) followed by RB1 (9%) and APC (8%) mutations. Even though, well-defined oncogene activating mutations were present, they were very rare. Given the prevalence of tumor suppressor mutations in these samples we are currently integrating CGH results to look for chromosomal deletions to support loss of tumor suppressor genes. In addition, we are investigating low-frequency mutations in lesser-known genes that may be of potential interest. Our preliminary results suggest that these subtypes of soft-tissue sarcomas depend on tumor-suppressor loss predominantly, and may have gained multiple complex sets of mutations in a number of other pathways. In conclusion, our work will be important in cataloging novel cancer mutations in rare types of adult sarcomas, with potential implications for understanding their biology and the development of new therapies.
Citation Format: Ogan D. Abaan, Princy Francis, Marbin Pineda, Robert L. Walker, Yuelin J. Zhu, Sven Bilke, Sean R. Davis, Paul S. Meltzer. Cancer-specific mutations in adult soft tissue sarcomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3147. doi:10.1158/1538-7445.AM2013-3147
Abstract 3192: Lin28 promotes growth of prostate cancer cells and activates the androgen receptor.
Authors: Tummala Ramakumar , Nadiminty Nagalakshmi , Zhu Yezi , Lou Wei , Evans Christopher P. , Gao Allen C. 
Published: August 2014

Abstract
Purpose: Lin28 is essential for stem cell viability and pluripotency. Recently Lin28 expression has been linked to several malignancies and its mechanisms of action proposed to be both let-7-dependent and -independent. It is a master regulator of let-7 miRNA biogenesis as well as a regulator of translation of a multitude of eukaryotic proteins. This study tested the hypothesis that Lin28 is overexpressed in prostate cancer (CaP) and that it activates the androgen receptor (AR) and promotes growth of CaP cells. Experimental Design: Human clinical CaP samples were analyzed for the expression of Lin28 by qRT-PCR, Western blotting and immunohistochemistry. Lin28 was transfected into a panel of CaP cell lines and growth was monitored. LNCaP cells stably expressing Lin28 were generated and growth was examined. Clonogenic ability of CaP cells expressing Lin28 was determined by colony formation and soft agar assays. Increase in expression of the AR and subsequent increase in transcription of AR-target genes were analyzed by qRT-PCR, luciferase assays and ELISA. LNCaP cells stably expressing Lin28 were injected into nude mice and tumorigenesis was monitored. Results: Lin28 was found to be overexpressed in clinical CaP compared to the benign tissues. Overexpression of Lin28 enhanced while downregulation of Lin28 reduced growth of CaP cells. Lin28 enhanced the ability of CaP cells to form colonies in anchorage-dependent and -independent manners. LNCaP cells stably expressing Lin28 exhibited significantly higher tumorigenic ability in vivo. Furthermore, Lin28 induces expression of the AR and its target genes such as PSA and NKX3.1. Conclusions: Lin28 promotes growth of CaP cells in vitro and in vivo. Lin28 induces expression and activation of the AR. Our findings suggest an important role of Lin28 in CaP development and activation of the AR axis.
Citation Format: Ramakumar Tummala, Nagalakshmi Nadiminty, Yezi Zhu, Wei Lou, Christopher P. Evans, Allen C. Gao. Lin28 promotes growth of prostate cancer cells and activates the androgen receptor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3192. doi:10.1158/1538-7445.AM2013-3192
Abstract 3216: Using protein microarray technology to develop mono-specific anti-ERCC1 mAbs for anatomic pathology applications.
Authors: Ma Donghui , Shu Youmin , Yuan Kehu , He Wei-Wu 
Published: August 2014

Abstract
Antibody with cross-reactivity can create unexpected side effects or false diagnostic reports if used for clinical purposes. ERCC1 is a predictive biomarker for cisplatin based chemotherapy. High ERCC1 expression is linked to drug resistance to cisplatin-based chemotherapy. 8F1 is one of the most commonly used monoclonal antibodies for evaluating ERCC1 expression levels in lung cancer patient tissue samples. By using high density protein microarray chip, we discovered that 8F1 not only reacts with its authentic target ERCC1, but also cross-reacts with an unrelated nuclear membrane protein, PCYT1A. The cross-reactivity to PCYT1A was further confirmed by other immunoassays, including Western blot, antigen absorption test, and immunohistochemistry (IHC) analyses. In this study, we also discovered that PCYT1A gene expression level is even significantly higher than ERCC1 gene expression level in a certain population of lung cancer patient tissue samples. In summary, 8F1 clone is not suitable for ERCC1 IHC assay due to its cross-reactivity with PCYT1A protein. To develop the best monoclonal antibody for ERCC1 IHC analysis, 18 monoclonal antibodies were generated and 6 of them were screened against our protein microarray chip. Two clones showed high mono-specificity on protein microarray chip test and both worked in IHC application.
Citation Format: Donghui Ma, Youmin Shu, Kehu Yuan, Wei-Wu He. Using protein microarray technology to develop mono-specific anti-ERCC1 mAbs for anatomic pathology applications. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3216. doi:10.1158/1538-7445.AM2013-3216
Abstract 3218: Interrogating the role of NOX4 in colon cancer metastasis.
Authors: Bauer Kerry M. , Buechler Steven , Hummon Amanda B. 
Published: August 2014

Abstract
Colon cancer is a major cause of cancer-related deaths worldwide. Adjuvant chemotherapy significantly reduces mortality in stage III colon cancer; however, it is only marginally effective in stage II patients. Molecular biomarkers are used to partition tumors into a poor prognosis group that is likely to metastasize and a good prognosis group that has a higher probability to be relapse-free. These biomarkers for relapse risk are of clinical interest, and lead to insight into how a tumor progresses to metastasis.
There is increasing evidence that cancer of the ascending (right-side) colon is different from the descending (left-side) colon. There are site-specific differences in histological and molecular characteristics and different signaling pathways have been shown to dominate progression to relapse in right and left-side colon cancer. We have observed that the genes altered in expression between the poor prognosis and good prognosis tumors vary significantly depending on whether the malignancy originates on the right or left side of the colon. We have identified NADPH oxidase 4 (NOX4) to be highly predictive of relapse in stage II and stage III left-side colon cancer where elevated expression of NOX4 is correlated with relapse. Furthermore, NOX4 expression is greatly elevated in the human colon cancer derived metastatic cell line SW620 compared to human cell lines derived from primary adenoma or carcinoma colon tumors. NOX4 silencing using RNA interference results in decreased levels of reactive oxygen species (ROS). The NOX family of genes has been implicated in cancer development in several types of cancer while overproduction of ROS has been implicated in tumor metastasis.
We are exploring the newly identified role of NOX4-mediated ROS generation in metastatic colon cancer. To investigate the underlying molecular mechanism we are analyzing the effect of NOX4 silencing via RNA interference and NOX4 inhibition using pharmacological NOX inhibitors on global protein expression patterns in metastatic-derived SW620 cells. Proteomic changes are being assessed by iTRAQ labeling and mass spectrometry. Bioinformatics and cluster analysis will be used to identify the functional role of redox responsive and ROS regulative proteins in colon cancer metastasis. The role of NOX4 as a prognostic biomarker in colon cancer makes it an important target for research in cancer biology and therapeutics.
Citation Format: Kerry M. Bauer, Steven Buechler, Amanda B. Hummon. Interrogating the role of NOX4 in colon cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3218. doi:10.1158/1538-7445.AM2013-3218
Abstract 3219: DrIMS-3DCC: Drug imaging mass spectrometry of 3D cell culture systems.
Authors: Liu Xin , Weaver Eric , Hummon Amanda B. 
Published: August 2014

Abstract
3D cell cultures have increased complexity compared to simple monolayer and suspension cultures, recapitulating the cellular architecture in the body. For example, many colon cancer cell lines form rounded heterogeneous spheroid structures that mimic the pathophysiological properties of tumors when grown under appropriate cell culture conditions. Classical imaging methodologies, like immunohistochemistry, are commonly used to examine the distribution of specific species within the spheroids. However, there is a need for an unbiased discovery-based methodology that would allow examination of protein/peptide distributions in 3D culture systems, without a need for prior knowledge of the analytes. We have developed a MALDI imaging mass spectrometry approach to examine protein distributions in 3D culture models (MALDI IMS-3DCC), allowing us to map the spatiotemporal dynamics of proteins in these valuable model systems.
We are currently expanding our approach to image the distribution of drugs within 3D cell cultures. We are using our MALDI IMS-3DCC to analyze the penetration of drugs within 3D cell cultures. With our mass-spectrometric based approach, we have the ability to map the distribution of the 1) the drug, 2) the metabolites produced from the drug, and 3) the spatiotemporal changes in proteins following treatment. Thus far, we have successfully evaluated the effects of two clinically relevant species, oxaliplatin and Irinotecan, on spheroids. In the future, we will expand our approach to evaluate new therapeutic compounds. We believe that our novel imaging strategy will drastically alter how new therapeutic compounds are evaluated, reducing the need for animal models in the early stages of drug development, thereby speeding up the drug evaluation process.
Citation Format: Xin Liu, Eric Weaver, Amanda B. Hummon. DrIMS-3DCC: Drug imaging mass spectrometry of 3D cell culture systems. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3219. doi:10.1158/1538-7445.AM2013-3219
Abstract 3230: Targeted sequencing of 16 archived ovary cancers.
Authors: Li Shihong , Jongkam Narisra , Xia Wei , Tran Hong , Suh K. Stephen 
Published: August 2014

Abstract
We developed a method to extract up to 22 μg DNA from a single 10 μm FFPE slide. Although FFPE DNA is notoriously fragmented, our extraction method enabled us to consistently generate 150-250 bp amplicons. This DNA enables whole genome sequencing and targeted sequencing using various platforms. This poster will present targeted amplicon sequencing on the Ion Torrent PGM™ .
Single FFPE pathology slides from 16 ovary cancer specimens (5 cured with first line chemotherapy and 11 relapsed within 5 years), archived from 1999-2005, were processed. Amplicons targeting selected exons and hotspots of 54 cancer genes were sequenced using both traditional Sanger sequencing (28 amplicons covering 8 genes) and by Next Generation sequencing (190 amplicons covering 46 genes using Ion AmpliSeq™ Cancer Panel).
5 ng FFPE DNA (based on Qubit measurement) from each patient was subjected to 190-plex PCR. The resulting amplicon libraries were ligated with indexed adaptors. Each eight libraries were pooled and sequenced on one 318 Chip. Average read depth ranged from 1521 to 3138, with 87.3% to 99.6% targets covered at least 20 times. Quality scores were above 30 for the first 80 bps, above 25 for 100 bps, and above 19 for 200 bps.
12 to 76 genetic variants were detected from each patient at frequency ranges from 0.7% to 100%. Both the genomic variation that occurred only in cured or relapsed group, and the genetic variations that were common to both groups will be presented.
Citation Format: Shihong Li, Narisra Jongkam, Wei Xia, Hong Tran, K. Stephen Suh. Targeted sequencing of 16 archived ovary cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3230. doi:10.1158/1538-7445.AM2013-3230
Abstract 3231: Comprehensive profiling of actionab.
Authors: Wang Yulei , Bourgon Richard , Lu Shan , Yan Yibing , Guan Yinghui , Ryner Lisa , Partel Rajesh , Lackner Mark , Amler Lukas 
Published: August 2014

Abstract
Comprehensive characterization of genetic profiles in clinically actionable genes in each tumor promises to facilitate personalized approaches to cancer treatment. However, development of systematic genetic profiling of cancers in the clinical setting is facing unique technical challenges. More than 90% of tumor samples available for clinical sequencing are formalin-fixed and paraffin-embedded (FFPE). These samples are not only limited by quantities, the DNA quality in these samples is often compromised due to different degree of degradation, cross-links and chemical modifications. Targeted sequencing, in which genomic regions of interests are selectively enriched before sequencing to achieve high coverage and sensitivity, can potentially provide a cost-effective and efficient solution for clinical sequencing. However, very few studies have been reported on the development of methodology that is applicable and robust in analyzing “real-world” clinical FFPE samples. Here we report the development of a novel methodology that integrates microfluidic multiplex PCR-based target enrichment with massively parallel sequencing for high-throughput, high-content targeted sequencing of clinically actionable cancer genes in FFPE tumor tissues. This method enables amplifying 963 regions from 88 common cancer genes in 48 samples and simultaneously sequencing 48 pooled barcoded samples in a single sequencing reaction. Using this method, we sequenced 40 cancer cell lines and a well-defined Latin square study with dilution series of 8 known somatic mutations, to comprehensively assess the sensitivity, specificity, reproducibility in both target enrichment and variant detection. Furthermore, using paired fresh frozen/FFPE tissues obtained from 16 cancer patients, we developed and optimized a FFPE protocol that yields high-quality genetic profiles highly concordant to those derived from parallel fresh frozen samples. To demonstrate the clinical utility of this method, we sequenced a cohort of 73 FFPE tumor samples from endometrial cancer patients. Many clinically actionable mutations were identified in these patients’ samples and confirmed using orthogonal validations. Our results demonstrated the feasibility and clinical utility of our method in clinical sequencing, setting the stage for ultimately translating this method in clinical setting to inform and guide cancer treatment.
Citation Format: Yulei Wang, Richard Bourgon, Shan Lu, Yibing Yan, Yinghui Guan, Lisa Ryner, Rajesh Partel, Mark Lackner, Lukas Amler. Comprehensive profiling of actionab. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3231. doi:10.1158/1538-7445.AM2013-3231