bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4773: Dysregulated expression of pentraxin-3 in glioblastoma (GBM) stem cells: Implications for GBM invasion and progression
Authors: Wesley Umadevi V. , Clark Paul , Kuo John S. , Dempsey Robert J. 
Published: July 2017

Abstract
Glioblastoma multiforme (GBM) is highly invasive and resistant to current therapies. The aggressiveness of brain tumor is attributed to GBM stem cells (GSC) that release inflammatory cytokines, and exacerbate inflammation in tumor microenvironment, critically affecting GBM survival and invasiveness. The glycoprotein pentraxin-3 (PTX3), a modulator of tumor-associated inflammation, is known to be correlated with tumor grade and severity of malignancies of some cancers. However, little is known about the role of PTX3 in GBM growth and invasion. In this study, we examined the role of PTX3 in GSCs exhibiting various degree of invasiveness. From patient brain tumors, our team has isolated the small subsets of glioblastoma stem cells (GSCs) and are validated for their self-renewal and multi-lineage potential. Our studies have shown that these GSCs efficiently form orthotopic brain tumors in immune-deficient mice. Our results show that conditioned media from GSCs promote pro-angiogenic tube formation from endothelial cells. GSCs that are grown in the absence of growth factors EGF and bFGF, formed efficient xenografts in immune-deficient mice and showed increased dispersal in the mice brain. Interestingly, polymerase chain reaction (RT-PCR) and immunofluorescence staining showed upregulated expression of PTX3 in these GSCs, and correlated with the degree of invasiveness. Differentiation of GSC into astrocytes in vitro, lead to decreased expression of PTX3. In support of this, recent histochemical study has shown that PTX3 levels correlate with GBM grade and is a candidate biomarker for cancer progression. Thus, PTX3 may represent a new target and marker of inflammation for glioma malignancy.
Citation Format: Umadevi V. Wesley, Paul Clark, John S. Kuo, Robert J. Dempsey. Dysregulated expression of pentraxin-3 in glioblastoma (GBM) stem cells: Implications for GBM invasion and progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4773. doi:10.1158/1538-7445.AM2017-4773
Abstract 4776: Circulating clusters in breast cancer express cancer stem cell phenotypes
Authors: Harouaka Ramdane , Hodges Gabrielle , David Allison , Polasani Rishika , Freeman Spencer , Sanchez Katherine , Harvey Kaitlin , Wicha Max S. 
Published: July 2017

Abstract
Breast cancer is a leading cause of death in women and its metastatic spread to distant organs is responsible for over 90% of these deaths. Circulating tumor cells (CTCs) implicated in the metastatic process occur when cancer cells undergo cytoskeletal and phenotypic transitions that enhance motility, then penetrate into the blood circulation. While CTC dissemination has typically been considered as the spread of single cells, recent evidence suggests that collective migration results in polyclonal circulating clusters that are the main drivers of metastasis. To study circulating clusters we have developed a dual microfiltration system employing two stages of antigen-independent mechanical cell isolation. As whole blood is passed through the system, circulating clusters are trapped by the first stage while single CTCs are retained by the second stage. Characterization experiments using cell lines demonstrated a capture efficiency of 87.1% for clusters and 85.7% for single cells on their respective microfilters. This system was used to investigate circulating cells in the metastatic MMTV-PyMT syngeneic mouse breast cancer model. Both clusters and single CTCs were detected in mice with histological evidence of lung metastases (14-16 weeks old), but not in mice that had not yet developed metastatic tumors (&lt;12 weeks old). Immunofluorescence assays were established to determine expression of CD24, CD90, cytokeratins, CD45 and DAPI. Tumor cells were identified as nucleated cells that expressed epithelial cytokeratins, but not the leukocyte antigen CD45. While PyMT cells with a CD90+/CD24+ stem cell phenotype comprise only ~1.5% of tumors, they were observed in &gt; 50% of circulating clusters. The presence of cancer stem cells was correlated to cluster size, with smaller clusters containing a greater percentage of CD90+/CD24+ cells. Isolated clusters will be further analyzed to quantify expression levels of cancer stem cell markers in each individual constituent cell. The analysis of circulating clusters may provide crucial insight into the mechanisms of metastatic disease and provide the means to discover novel targets for therapeutic intervention.
Citation Format: Ramdane Harouaka, Gabrielle Hodges, Allison David, Rishika Polasani, Spencer Freeman, Katherine Sanchez, Kaitlin Harvey, Max S. Wicha. Circulating clusters in breast cancer express cancer stem cell phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4776. doi:10.1158/1538-7445.AM2017-4776
Abstract 4814: Testing personalized therapies for ovarian cancer using mate pair genomic analysis and patient-derived xenografts
Authors: Leventakos Konstantinos , Harris Faye R. , Yang Lin , Hou Xiaonan , Weroha Saravut , Kovtun Irina V. 
Published: July 2017

Abstract
Purpose: The treatment of ovarian cancer poses a challenge since 70% of patients will relapse with incurable platinum resistant disease. Although ovarian cancers lack frequently-occurring driver mutations or amplifications, the study presented herein examines the concept of individualized therapy based on mate pair sequencing and protein expression in ovarian cancer patient-derived xenografts.
Experimental Procedure: Macrodissection of patient tumor was followed by genomic DNA isolation and next-generation sequencing using an Illumina Mate Pair protocol to identify structural genomic changes and copy number variations. Secondary analyses were carried out to select potential therapeutic targets among those. The tumors were also propagated intraperitoneally in immunocompromised mice and treated with standard chemotherapy or/and targeted therapy chosen based on genomic analyses.
Results: Mate pair analysis revealed that, in general, copy number changes (amplifications, gains and losses) were common in ovarian tumors and included genes potentially targetable. Tumors from early generation patient- derived xenografts showed a landscape of genomic aberrations identical to that of original patient tumor. One PDX model in which high expression of HER2 and copy number gains at RICTOR and AKT genetic loci were revealed, was treated with either chemotherapy and Pertuzumab/trastuzumab (HER2 inhibitors), MK-8669 (mTOR inhibitor) or MK-2206 (AKT inhibitor) or chemotherapy alone. Tumor size was measured by serial abdominal ultrasound and after 28 days, the final tumor size ratio compared to baseline was 0.23, 0.36, 0.55 and 0.56, respectively, indicating that the best response was seen in the combined chemotherapy and Pertuzumab/trastuzumab cohort and that was better than in the chemotherapy only cohort.
Conclusions: Patient-derived xenografts models in conjunction with genomic and protein analyses of patient tumors are valuable for testing of combination therapies including specific targeting drugs. This approach also provides actionable information for more tailored treatment of ovarian cancer patients.
Citation Format: Konstantinos Leventakos, Faye R. Harris, Lin Yang, Xiaonan Hou, Saravut Weroha, Irina V. Kovtun. Testing personalized therapies for ovarian cancer using mate pair genomic analysis and patient-derived xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4814. doi:10.1158/1538-7445.AM2017-4814
Abstract 4826: Maternal high butter fat intake heightens mammary cancer risk in offsprings gestationally exposed to bisphenol A at environmentally relevant dose
Authors: Leung Yuet-Kin , Govindarajah Vinothini , Cheong Ana , Song Dan , Zhu Xuegong , Ying Jun , Kendler Ady , Medvedovic Mario , Belcher Scott , Ho Shuk-Mei 
Published: July 2017

Abstract
In utero exposure to bisphenol A (BPA) at 250ug/kg BW was shown to augment mammary cancer risk in rodent models. High fat diet is widely believed to be a major risk of breast cancer (BCa). It is therefore important to investigate whether maternal high fat intake could potentially heighten mammary cancer risk associated to gestational BPA exposure. In this study, we exposed Sprague Dawley rats with different doses of BPA (2.5-2500ug/kg BW) mixed with high butter-based diet (HBF) in the period from preconception to birth. DMBA-PND50 protocol was followed. In the presence of HBF, we observed non-monotonic effects of BPA in cancer incidence as well as in the number of terminal end buds of PND21 mammary glands. Both results were peaked at a dosage of 25ug/kg BW BPA and the effects were significant when compared with HBF alone group. We further analyzed transcriptomic data of microdissected epithelia of PND21 mammary glands from BPA (25ug/kg BW) group as well as HBF group and revealed that two specific cancer networks involving ERK and androgen receptor signaling were dysregulated. DNA methylation is one of the key mechanisms to dysregulate and impair the transcription of two selected top genes, Car7 and Kcnv2, as supported by our bisulfite-sequencing data. These data suggest that in utero BPA exposure could epigenetically modify gene expression and predispose cancer risk during early development. More importantly, some BPA genes are of high human relevance because seven selected BPA genes could dichotomize patients into two groups with significant difference in overall survival in a TCGA cancer cohort. The prognostic power of the genes was further enhanced in the survival analysis of Caucasian with ER positive patients. In conclusion, our data strongly suggest that BPA predisposes higher cancer risk by dysregulating gene expression during early mammary gland development in the presence of HBF, which could facilitate cancer development later in life.
Citation Format: Yuet-Kin Leung, Vinothini Govindarajah, Ana Cheong, Dan Song, Xuegong Zhu, Jun Ying, Ady Kendler, Mario Medvedovic, Scott Belcher, Shuk-Mei Ho. Maternal high butter fat intake heightens mammary cancer risk in offsprings gestationally exposed to bisphenol A at environmentally relevant dose [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4826. doi:10.1158/1538-7445.AM2017-4826
Abstract 4832: Establishment of lung cancer organoid lines as a new preclinical model for lung cancer
Authors: Kim Minsuh , Chun Sung-Min , Mun Hyemin , Suh Young-Ah , Jang Se jin 
Published: July 2017

Abstract
Human cancers are composed of genetically and phenotypically heterogeneous subpopulations organized into a hierarchy of tumor initiating stem cells and various differentiated tumor cell. Cancer organoids seem to be more suitable in vitro models for targeting tumor heterogeneity than cell lines. We established cancer organoid lines from lung cancer patient tissues, recapitulating histology of human cancers in three dimensional culture conditions. Thirteen organoid lines from various lung cancer subtypes including adenocarcinoma, squamous cell carcinoma and small cell carcinoma were compared with their original human tumors in histologic features and genetic profiles. In the IHC staining, it revealed that organoids of adenocarcinomas have typical glandulo-papillary structures or mucin-containing tumor cells. Organoids of squamous cell carcinomas showed keratinization and intercellular bridges. Organoids of small cell carcinoma displayed typical neuroendocrine morphology. Using NGS cancer panel sequencing, the organoid lines maintained genetic characteristics of the original human tumors in major driver genes including EGFR, TP53, and RB mutation. In xenograft experiments, the organoid lines revealed stronger tumorigenesity than direct graft of human tumor tissues. Cancer organoids showed resistance to various anticancer drug treatments. In conclusion, our lung cancer organoid lines are alternative cancer model for preclinical researches recapitulating genotypic and phenotypic heterogeneity of original human tumors.
Note: This abstract was not presented at the meeting.
Citation Format: Minsuh Kim, Sung-Min Chun, Hyemin Mun, Young-Ah Suh, Se jin Jang. Establishment of lung cancer organoid lines as a new preclinical model for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4832. doi:10.1158/1538-7445.AM2017-4832
Abstract 4841: Suppression of metastasis by KP54 and non-KP54 kisspeptins
Authors: Hampton Kelsey Rebecca , Pounds Keke M. , Trembath Andrew P. , Welch Danny R. 
Published: July 2017

Abstract
KISS1 is a secreted neuropeptide which can act as a metastasis suppressor protein. Expression of KISS1 inhibits metastatic colonization at secondary sites, rendering disseminated cells dormant. In order for KISS1 to suppress metastasis, it must be secreted outside of the cell, where furin cleaves KISS1 into kisspeptins. This cleavage liberates an internal kisspeptin, Kisspeptin-54 (KP54, K67 to F121), which is amidated and has the ability to bind a Gq/11-coupled protein receptor KISS1R. The mechanism of action for KISS1 metastasis suppression has long been assumed to be KP54 interacting with KISS1R. However, expression of KISS1R is not necessary for KISS1 metastasis suppression, and the extracellular processing of KISS1 hints at an alternative hypothesis: a different kisspeptin may be responsible for suppressing metastasis. To test this hypothesis, all possible kisspeptins were generated based on known dibasic cleavage sites (M1-Q145; M1-R56; M1-R67; M1-R124; R56-R66; R67-F121; R56-F121; R56-Q145; R67-Q145; R124-Q145) and were cloned to include the same secretion sequence as nascent KISS1. These kisspeptins (KISS1 Manufactured Peptides, or KMP) were independently expressed in B16-F10 murine melanoma cells. To test for experimental metastasis, B16-F10 cells expressing KMP were injected intravenously into the lateral tail vein of syngeneic mice and the lungs were examined for metastatic load. While KP54 suppressed metastasis, additional KMP lacking the KISS1R binding site (LRF-NH2) were able to completely suppress metastasis (p&lt;0.05). When assessing metastasis-associated traits in vitro, suppressor KMP suppressed motility, increased mitochondrial biomass, and increased oxidative phosphorylation (phenotypes previously reported with KISS1 expression). In particular, one kisspeptin (KMP2, M1 - R56) suppressed metastatic traits in vitro as well as completely suppressing metastasis in vivo. As a whole, these data suggest that metastasis suppression by KISS1 is not necessarily contingent on KISS1R activation, and also supports investigation into additional receptors.
Citation Format: Kelsey Rebecca Hampton, Keke M. Pounds, Andrew P. Trembath, Danny R. Welch. Suppression of metastasis by KP54 and non-KP54 kisspeptins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4841. doi:10.1158/1538-7445.AM2017-4841
Abstract 486: Production of an unbiased, highly reproducible small RNA library for NGS using a novel circularization technology
Authors: Gonzalez-Plasky Marta , McNulty Amanda , Charizanis Konstantinos , Ning Jing , Jan Edward , Carroll Matthew , Kamberov Emmanuel , Hecker Karl 
Published: July 2017

Abstract
MicroRNA sequencing (miRNA-Seq) is a useful tool for aiding researchers in the examination of miRNA expression patterns, the characterization of novel miRNAs, and for uncovering miRNA-disease associations. Since miRNAs are also unusually well-preserved in a range of samples (e.g. urine, FFPE tissue, plasma), profiling their expression is becoming a powerful diagnostic tool. However, current methods for sequencing miRNA require large amounts of total RNA, are not very reproducible and, more importantly, have considerable systematic bias resulting in loss of many prospective biomarkers. This bias severely affects the trustworthiness of results as libraries are not a true representation of the biological state of the sample.
We have recently developed a technology that efficiently captures miRNA species with extremely low bias. Through a circularization approach, Illumina P5 and P7 adapters are ligated to miRNA, resulting in sequenceable libraries in under 5 hours in a single tube. These libraries are then purified and size-selected prior to sequencing.
Analysis of read distributions of libraries prepared from an equimolar mixture of 963 miRNAs demonstrated the technology is able to efficiently capture all species with high reproducibility between replicates and input amounts (correlation coefficient of ≥0.97). Furthermore, 80-86% of these captured miRNA read numbers fall within a +/- 2-fold variation of the expected read number demonstrating unbiased representation. In contrast, frequency distribution analyses for other technologies reveal that 47-56% of miRNAs are greatly under-represented (i.e. less than 2X fewer reads than expected), 29-38% of miRNAs are represented within a +/- 2-fold variation of the expected read number, and around 15% are over-represented by more than 2X.
These findings highlight the fact that the current technical state of library preparation for miRNA sequencing fails to accurately represent miRNA expression patterns. This in turn leads researchers to perform more costly validation experiments than necessary. Our product is designed and developed for more accurately reflecting the true biological state of a sample. This will provide researchers with a tool that can aid in advancing miRNA sequencing in translational research.
Note: This abstract was not presented at the meeting.
Citation Format: Marta Gonzalez-Plasky, Amanda McNulty, Konstantinos Charizanis, Jing Ning, Edward Jan, Matthew Carroll, Emmanuel Kamberov, Karl Hecker. Production of an unbiased, highly reproducible small RNA library for NGS using a novel circularization technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 486. doi:10.1158/1538-7445.AM2017-486
Abstract 4865: The functional and clinicopathological analysis of hypoxia inducible factor-1α (HIF1-α) in head and neck squamous cell carcinoma
Authors: Ikari Yuichi , Ozawa Hiroyuki , Imanishi Yorihisa , Tomita Toshiki , Sekimizu Mariko , Watanabe Yoshihiro , Ito Fumihiro , Saito Shin , Ogawa Kaoru 
Published: July 2017

Abstract
Introduction: Tumor hypoxia is considered to be associated with progression in various cancers. Hypoxia inducible factor-1α (HIF-1α) is one of the molecules which play a key role in tumor hypoxia. High HIF-1α expression is reported to have an impact on poor prognosis and resistance to chemotherapy or radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the effect and mechanism of HIF-1α on tumor metastasis in HNSCC is still unclear. The aim of the present study was to investigate the molecular targets of HIF1-α relevant to metastasis, and to reveal the impact of HIF1-α on HNSCC metastasis by using clinicopathological assays. Methods: The cell proliferation rate with or without HIF-1 inhibitor (KC7F2) in HNSCC cell lines (FaDu, Detroit512) was evaluated by MTS assay. Gene expression levels related to epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) and HIF-1α in each HNSCC cell lines were measured by quantitative real-time PCR. Immunohistochemical expressions of HIF-1α and clinicopathological factors were analyzed using surgical specimens from 33 patients with hypopharyngeal carcinoma who had undergone trans-oral tumor resection without previous chemotherapy nor radiotherapy.
Results: HIF-1 inhibitor suppressed the cell growth of HNSCC cell lines in a dose dependent manner. HIF-1 inhibitor downregulated the expression of HIF-1α, twist, Oct3/4 and Nanog. In immunohistochemical study, the HIF-1α expression was higher in cancer cells than in normal cells of the adjacent normal mucosa. Univariate analysis revealed that high expression of HIF-1α was significantly correlated with T-classification (P=0.012), lymph node metastasis (P=0.002) and lymphatic invasion (P=0.03).
Conclusion: These results suggest that HIF-1α plays a key role in tumor progression of HNSCC through EMT and CSC properties. From the present study, HIF-1α inhibition may have the possibility to suppress tumor metastasis, making HIF-1α an attractive target for the treatment of HNSCC.
Citation Format: Yuichi Ikari, Hiroyuki Ozawa, Yorihisa Imanishi, Toshiki Tomita, Mariko Sekimizu, Yoshihiro Watanabe, Fumihiro Ito, Shin Saito, Kaoru Ogawa. The functional and clinicopathological analysis of hypoxia inducible factor-1α (HIF1-α) in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4865. doi:10.1158/1538-7445.AM2017-4865