bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1499: SUPR peptides as novel targeted molecular imaging agents for Her2
Authors: Kelderhouse Lindsay , Hardy Amanda , Takahashi Terry T. , Ornelas Argentina , Gammon Seth , Howell Shannon , Yang Peiying , Wang Pin , Roberts Richard W. , Fiacco Steve , Millward Steven W. 
Published: August 2015

Abstract
Ideal molecular imaging agents would combine the affinity and selectivity of monoclonal antibodies with the rapid clearance and pharmacokinetics of small molecules Here we describe the use of directed evolution to design Scanning Unnatural Protease Resistant (SUPR) peptides as novel molecular scaffolds for in vivo optical and PET imaging of the Her2 receptor. SUPR peptides were obtained through selection against Her2-expressing breast cancer cells in culture using focused biological display peptide libraries pre-selected for protease resistance. SUPR peptide libraries were programmed with unnatural amino acids for enhanced stability and chemically cyclized after translation to enhance affinity. Peptides isolated from selection selectively bind the Her2 receptor in vitro with low nanomolar affinity and do not compete with Trastuzumab or Pertuzumab. Cy5-labeled SUPR peptides show rapid and Her2-specific tumor uptake in vivo and minimal retention in non-tumor tissues after 24 hours of washout. SUPR peptides can be efficiently labeled with 18F via the copper-catalyzed azide-alkyne cycloaddtion and the resulting radiotracers used for nuclear imaging of Her2-postive tumors by PET/CT. Unlike antibodies and their derivatives, SUPR peptides are synthesized chemically and show rapid clearance from systemic circulation. SUPR peptides also show dramatically enhanced stability relative to linear peptides obtained from phage display or combinatorial chemistry while still retaining affinities compatible with molecular imaging applications. While SUPR peptides are selected from biological display libraries, they share similar chemical composition and structure with peptides derived from non-ribosomal peptide synthesis. We believe that this combination of affinity, stability, evolvability, and synthetic accessibility make SUPR peptide technology a general approach for generating highly potent compounds for targeted molecular imaging of cancer biomarkers.
Citation Format: Lindsay Kelderhouse, Amanda Hardy, Terry T. Takahashi, Argentina Ornelas, Seth Gammon, Shannon Howell, Peiying Yang, Pin Wang, Richard W. Roberts, Steve Fiacco, Steven W. Millward. SUPR peptides as novel targeted molecular imaging agents for Her2. [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 1499. doi:10.1158/1538-7445.AM2015-1499
Abstract 1501: Evaluation of tumor vascularity in colorectal cancer using contrast enhanced ultrasonograpy in comparison with microvessel density
Authors: Okawa Takaomi , Nogami Hiromi , Takaoka Munenori 
Published: August 2015

Abstract
Background : The relationship between tumor vascularity and malignant potential in colorectal cancer a(CRC) is reported by many authors. Therefore, to assess the tumor vascularity before surgical treatment is thought to be one of very important factors in CRC patients. Contrast enhanced ultrasonography (CEUS) can visualize the tumor vascularity vividly. We aim to determine the reliability of CEUS for the assessment of vascularity of CRC and to analyze the relationship between tumor vascularity and clinicopathological characteristics. In addition, to find the clinical application, we assessed the efficacy of chemotherapy in unresectable advanced CRC patients by CEUS.
Methods : 56 patients undergoing surgical resection of CRC were studied. An ultrasound system (GE health care, LOGIC 7) is used and visualized the colo-rectal tumor using a 4.5MHZ probe. The 2nd generated ultrasonic contrast medium (Belfulbuttan, Sonazoid) is injected intravenously. Approximately 20 s after injection, microbubbles were obtained to enhance the B-mode image. Using the tumor image showing the strongest vascularity, region of interest were determined to measure mean echo intensity in the tumor. Their images were analyzed with NIH image program (developed by the US National Institutes of health) and calculated tumor vascularity as Vascular Index (VI). The clinicopathological features are based on the TNM classification from UICC. Using surgical specimens, tumor vascularity was assessed by immunohistochemistry as microvessel density in order to do statistical analysis for the correlation between VI, clinicopathologic features and microvessel density.
Results : CEUS could visualize the tumor vascularity in all patients. In advanced CRC patients, we observed that the tumor invaded into other organ, such as prostate gland, small intestine and so on. The VI correlated significantly with depth of tumor invasion, liver metastasis and microvessel density. Furthermore, in patients with abundant vascularity in tumor before treatment, chemotherapy led to the reduction of VI prior to the radiographically visible difference in tumor size.
Conclusion : CEUS can evaluate the tumor vascularity non-invasively and is very useful for the evaluation of their pathological diagnosis and the efficacy of chemotherapy in CRC.
Citation Format: Takaomi Okawa, Hiromi Nogami, Munenori Takaoka. Evaluation of tumor vascularity in colorectal cancer using contrast enhanced ultrasonograpy in comparison with microvessel density. [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 1501. doi:10.1158/1538-7445.AM2015-1501
Abstract 151: Transcriptome-wide expression profiling of long noncoding and small nucleolar RNAs in head and neck squamous cell carcinomas identifies novel transcripts associated with survival
Authors: Honda Thomas K. , Zou Angela , Yu Vicky , Zheng Hao , Kuo Selena , Saad Maarouf , Xuan Yinan , Singh Pranav , Wang-Rodriguez Jessica , Ongkeko Weg M. 
Published: August 2015

Abstract
Head and neck squamous cell carcinoma (HNSCC) persists as one of the most common and deadly malignancies, with early detection and effective treatment still posing formidable challenges. To expand our currently sparse knowledge of the epigenetic alterations involved in this disease and identify potential biomarkers and therapeutic targets, we globally profiled the dysregulation of small nucleolar (snoRNA) and long non-coding RNAs (lncRNA) in head and neck tumors. Using next-generation RNA-sequencing data from 40 pairs of tumor and matched normal tissues, we profiled lncRNA expression by mapping each RNA-seq library to a reference annotation containing 32,108 lncRNAs. Using edgeR, we found 19,681 lncRNA transcripts significantly differentially expressed by a fold change magnitude ≥ 4 with a false discovery rate &lt;10-4. We selected the 10 most dysregulated lncRNAs and further confirmed the dysregulation of these lncRNAs in-vitro by performing quantitative reverse transcriptase PCR (RT-qPCR) on two normal oral epithelial cell lines and five HNSCC cell lines. Using Kaplan-Meier analysis, we demonstrated a correlation between high expression of several lncRNAs, including JPH1-7, upregulated by 40-fold in HNSCC, with overall poor survival in a cohort of over 400 HNSCC patients (HR = 1.62, p &lt; 0.01). Meanwhile, RNA-sequencing analysis of 31 tumor-normal pairs yielded 33 significantly dysregulated snoRNA. We identified one snoRNA, SNORD116-20, downregulated by 4-fold in HNSCC, whose expression levels correlated significantly with overall patient survival (HR = 1.64, p &lt; 0.05), suggesting its functional significance and clinical relevance in head and neck cancer pathogenesis. Similarly, in in-vitro experiments, we found reduced expression of this snoRNA in HNSCC cell lines compared to normal oral epithelial cell lines. The precise molecular roles of these transcripts identified warrants further characterization, but our data suggest that they are likely to play substantial roles in head and neck cancer pathogenesis and are significantly associated with patient survival.
Note: This abstract was not presented at the meeting.
Citation Format: Thomas K. Honda, Angela Zou, Vicky Yu, Hao Zheng, Selena Kuo, Maarouf Saad, Yinan Xuan, Pranav Singh, Jessica Wang-Rodriguez, Weg M. Ongkeko. Transcriptome-wide expression profiling of long noncoding and small nucleolar RNAs in head and neck squamous cell carcinomas identifies novel transcripts associated with survival. [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 151. doi:10.1158/1538-7445.AM2015-151
Abstract 1526: HOXA5 inhibits cell plasticity and stemness in breast cancer cells by reinforcing epithelial traits
Authors: Teo Wei Wen , Merino Vanessa , Cho Sean , Korangath Preethi , Neumann Neil M. , Ewald Andrew J. , Sukumar Saraswati 
Published: August 2015

Abstract
Members of the Retinoic acid receptor (RAR) and HOX gene families are known to be associated with cellular differentiation. Nonetheless, how HOX genes drive differentiation in mammalian cells is poorly understood. HOX genes are transcription factors that orchestrate body segmentation during embryogenesis. But the continued expression of several members in adulthood indicates the necessity of their biological functions in specifying cell fate in adulthood. The mammary gland is an organ that continues to go through multiple cycles of development during life. Here, loss of specific HOX genes could be detrimental to normal development.
We have previously shown that expression of HOXA5, a downstream target of the retinoic acid signaling pathway, is often lost in breast cancer. Loss of HOXA5 expression correlates with increasing pathological grades of breast cancer. Expression array analysis of HOXA5-depleted MCF10A (immortalized line of human breast epithelium) revealed its potential role in regulating several traits of the epithelial lineage, including expression of E-cadherin and CD24. Depleting HOXA5 in MCF10A enhanced cell motility, invasiveness and increased stem-cell population (CD24lo/CD44hi). Using an inducible HOXA5-depletion system, differentiation of the stem cells in MCF10A was shown to be mediated by HOXA5. Conversely, ectopic expression of HOXA5 in SUM149 breast cancer cells significantly reduced plasticity and stem cell population, confirmed by in vivo limiting dilution assays in mice. MCF10A-KRAS-HOXA5 depleted cells formed invasive structures in 3D matrigel cultures, and formed larger tumors, implanted orthotopically in mice. MCF10A-KRAS-tumors were histologically dedifferentiated and lost expression of luminal cell markers such as E-cadherin and cytokeratin 18. Collectively, our findings demonstrate the role of HOXA5 in retinoid-induced cell differentiation by regulating cell fate specific surface adhesion molecules.
Citation Format: Wei Wen Teo, Vanessa Merino, Sean Cho, Preethi Korangath, Neil M. Neumann, Andrew J. Ewald, Saraswati Sukumar. HOXA5 inhibits cell plasticity and stemness in breast cancer cells by reinforcing epithelial traits. [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 1526. doi:10.1158/1538-7445.AM2015-1526
Abstract 1548: Baseline serum levels of osteopontin and thrombospondin-1 predict shorter overall survival in primary resected non-small cell lung cancer
Authors: Rouanne Mathieu , Adam Julien , Goubar Aïcha , Robin Angélique , Ohana Caroline , Louvet Emilie , Cormier Jiemin , Mercier Olaf , Dorfmüller Peter , Fattal Soly , Thomas de Montpreville Vincent , Fadel Elie , Besse Benjamin , Olaussen Ken André , Auclair Christian , Soria Jean-Charles 
Published: August 2015

Abstract
Background: Osteopontin and thrombospondin-1 are extracellular matrix proteins secreted by both stromal and tumor cells. These proteins may play a key role in the tumor microenvironment for cancer development and metastasis. This study focused on the prognostic value of circulating osteopontin and thrombospondin-1 in primary resected NSCLC patients.
Methods: Between January and December of 2012, serums were collected from 171 patients prior to primary surgery and from age-matched cancer-free individuals (n = 20). At baseline, circulating osteopontin and thrombospondin-1 levels were measured by ELISA. Tissue protein expression in primary tumor samples was determined by immunohistochemical analysis.
Results: High levels of serum osteopontin and thrombospondin-1 levels were found in the cohort study. The difference between patients and healthy individuals was statistically significant (p&lt;0.0001). Serum levels of osteopontin and thrombospondin-1 were independent prognostic factors of overall survival in multivariate analysis (HR 1.71, 95% CI 1.04-2.82, p = 0.04 for an increase in osteopontin of 50 ng/mL; HR 0.18, 95% CI 0.04-0.87, p = 0.03 for an increase in thrombospondin-1 of 10 ng/mL) similarly to their combination (HR is 1.31, 95% CI 1.03-1.67, p = 0.03 for an increase in osteopontin/thrombospondin-1 ratio of 6 ng/mL). Osteopontin and thrombospondin-1 levels were inversely correlated to survival rates.
Conclusions: Baseline osteopontin and thrombospondin-1 serum levels, and even more importantly their combination, can serve as strong independent prognostic factors to predict overall survival in primary resected NSCLC patients, and therefore reflect the aggressiveness of the tumor.
Citation Format: Mathieu Rouanne, Julien Adam, Aïcha Goubar, Angélique Robin, Caroline Ohana, Emilie Louvet, Jiemin Cormier, Olaf Mercier, Peter Dorfmüller, Soly Fattal, Vincent Thomas de Montpreville, Elie Fadel, Benjamin Besse, Ken André Olaussen, Christian Auclair, Jean-Charles Soria. Baseline serum levels of osteopontin and thrombospondin-1 predict shorter overall survival in primary resected non-small cell lung cancer. [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 1548. doi:10.1158/1538-7445.AM2015-1548
Abstract 155: LncRNA AK023948 promotes breast tumorigenesis by enhancing AKT phosphorylation
Authors: Koirala Pratirodh , MO Yin Yuan 
Published: August 2015

Abstract
The human genome expresses a large number of long non-coding RNAs (lncRNAs), however, little is known about their physiological functions or their role in cancer for the vast majority of these lncRNAs. In the present study, we identified a set of lncRNAs that were differentially expressed in breast cancer tissues as compared to normal tissue. Among them is AK023948 which is up-regulated in breast cancer tissue and in breast cancer cell lines. Ectopic expression of AK023948 in breast cancer MCF-7 cells promotes proliferation and anchorage independent cell growth along with activation of AKT phosphorylation. On the other hand, knockdown or knockout of AK023948 in MCF-7 cells reduces the proliferation of cells and phosphorylation of AKT. Furthermore, there is a positive correlation between AK023948 and pAKT expression in breast cancer tissue microarray. To determine the underlying mechanism of AK023948-mediated activation of AKT, we performed RNA precipitation assays using biotin-labeled AK023948 RNA probe, followed by PAGE analysis, and detected a unique protein band by silver staining. Mass spectrometry analysis identified it as ATP dependent RNA helicase A (RHA/DHX9) which was confirmed by Western blot and RNA immunoprecipitation (IP), respectively. Co-IP indicated that DHX9 interacts with p85PI3K regulatory subunit. Further characterization revealed that p85-DHX9 interaction is essential for stability of p85α and AKT phosphorylation. Together, these results suggest that AK023948 may function as an oncogenic lncRNA in breast cancer and thus, it may serve as a novel target for breast cancer therapy.
Citation Format: Pratirodh Koirala, Yin Yuan MO. LncRNA AK023948 promotes breast tumorigenesis by enhancing AKT phosphorylation. [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 155. doi:10.1158/1538-7445.AM2015-155
Abstract 1561: Detection of colorectal cancer-associated genetic and epigenetic alterations in urine of patients with CRC
Authors: Clemens Adam Winfield , Lin Selena , Jain Surbhi , Su Ying-Hsiu , Song Wei 
Published: August 2015

Abstract
Colorectal cancer (CRC) has been the second leading cause of cancer-related deaths due in part to a low compliance rate (&lt;50%) of the current screening method, an invasive colonoscopy, resulting in failure of detecting cancer early in its curative stages. 20% of CRC cases are only detected once the cancer has spread to a distant site, drastically reducing the 5-year survival rate from 90% to 12%. In order to improve the success of early detection methods of CRC, we have focused on developing non-invasive, multi-biomarker detection assays designed to identify CRC-associated genetic alterations. We have previously demonstrated that urine contains circulation-derived low molecular weight (LMW) DNA (&lt;300 bp), which suggests that LMW urine DNA could be used to detect CRC-associated genetic alterations. Using previously identified stool and serum-based biomarkers for CRC, we have developed a panel of potential CRC markers for early detection for use in a non-invasive urine DNA test. Our panel contains genetic mutations and epigenetic alterations of nine genes: mutations of KRAS codons 12/13 and BRAF V600E and aberrant hypermethylation of VIM, SEPT9, BMP3, NDRG4, CDKN2A, TFPI2, and MGMT. The proof-of-concept of a CRC urine DNA test was demonstrated in a small pilot study investigating mVIM as a biomarker for CRC in matched tissue-urine samples. This led to the development of a PCR-based approach to quantify these markers in a prevalidation study with blinded CRC samples to identify the specificity and sensitivity of these genetic mutations and epigenetic alterations. In a concordant study using this blinded CRC sample set, our panel of markers was used in an amplicon NGS-based study. Results from these two studies will be used to confirm the sensitivity and specificity of each marker for early detection of CRC.
Citation Format: Adam Winfield Clemens, Selena Lin, Surbhi Jain, Ying-Hsiu Su, Wei Song. Detection of colorectal cancer-associated genetic and epigenetic alterations in urine of patients with CRC. [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 1561. doi:10.1158/1538-7445.AM2015-1561
Abstract 157: LncRNA ANRIL indicates a potential prognostic biomarker in gastric cancer and promotes tumor growth by silencing of miR-99a/miR-449a
Authors: Xu Zhi , Chen Jinfei , Luk John M. , De Wei 
Published: August 2015

Abstract
Long noncoding RNAs are involved in several kinds of cancers. Here, we reported that ANRIL (CDKN2B-AS1), a 3.8-kb long noncoding RNA, recruiting and binding to PRC2, was generally upregulated in human gastric cancer (GC) tissues. In a cohort of 120 GC patients, the higher expression of ANRIL was significantly correlated with higher TNM stages (P = 0.041) and larger tumor sizes (P = 0.001). Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (OS) (P = 0.036). Further experiments revealed that the knockdown of ANRIL significantly repressed the proliferation of GC cell lines both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is partly due to epigenetic repression of miR-99a/miR-449a in Trans (controlling the targets_mTOR and CDK6/E2F1 pathway) by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation. To our knowledge, this is the first report which showed that the role of ANRIL in the progression of GC and ANRIL could crosstalk with microRNAs in epigenetic level. Our results suggest that ANRIL, as a growth regulator, may serve as a potential prognostic biomarker and target for new therapies in human GC.
Citation Format: Zhi Xu, Jinfei Chen, John M. Luk, Wei De. LncRNA ANRIL indicates a potential prognostic biomarker in gastric cancer and promotes tumor growth by silencing of miR-99a/miR-449a. [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 157. doi:10.1158/1538-7445.AM2015-157
Abstract 1604: IMI CANCER-ID: Validation of novel blood-based biomarker technologies in clinical settings
Authors: Schlange Thomas , Krahn Thomas , Pleier Sabrina , Pantel Klaus , Terstappen Leon WMM , Baggiani Barbara 
Published: August 2015

Abstract
The Innovative Medicines Initiative (IMI) was launched in 2008 as a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). IMI aims to facilitate the collaboration of healthcare stakeholders such as academic and clinical researchers, pharmaceutical industry and small and medium-sized enterprises (SMEs) in Europe, in order to address key issues in drug development and patient access to innovative medicines.
Tumor heterogeneity and the dynamic changes at the molecular level during disease progression make longitudinal monitoring of malignant disease highly desirable in order to choose the best treatment options and to monitor treatment efficacy. As access to tumor tissue is often the limiting factor and historic samples are not predictive for the current state of the disease, liquid biopsies are explored to support personalized treatment of cancer patients. The CANCER-ID consortium was established in 2014 and aims to validate technologies for blood-based biomarkers such as Circulating Tumor Cells (CTCs), circulating tumor DNA (ctDNA) and microRNAs (miRNAs) to determine the absence/presence of drug targets and to assess the response to treatment. To prove broader applicability and clinical utility of the consortium's technologies and protocols, the validated assays will be deployed in controlled clinical studies (TRACERx, NCT01888601; NVALT17, NTR4410; SPECTAlung, NCT02214134; patients under SoC treatment) in 1) Non-Small Cell Lung Cancer (NSCLC) and 2) anti-Her2-resistant metastatic breast cancer (Her2RMBC). CANCER-ID is a unique network of experts in the fields of tumor biology, biomarker development, clinical sciences and bioinformatics with a total indicative budget of 14 Mio €. The consortium joins forces of 16 academic groups (ten large clinical trial sites), 6 EFPIA companies, 1 multi-national diagnostics company, 5 SMEs with advanced technologies for CTC isolation or for complex data analysis and big data handling, and two non-profit organizations. In order to fully exploit the synergies created by CANCER-ID, regulatory agencies and patient advocacy groups are involved and invited to participate in the IMI project.
Citation Format: Thomas Schlange, Thomas Krahn, Sabrina Pleier, Klaus Pantel, Leon WMM Terstappen, Barbara Baggiani. IMI CANCER-ID: Validation of novel blood-based biomarker technologies in clinical settings. [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 1604. doi:10.1158/1538-7445.AM2015-1604