bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2289: A novel mouse model of endometrial cancer: epithelial specific Pten deletion with lactoferrin-iCre
Authors: Daikoku Takiko , Terakawa Jumpei , Dey Sudhansu K. 
Published: August 2015

Abstract
Endometrial cancer is a common gynecological malignancy, causing approximately 8,000 deaths each year in the United States. Underlying causes of endometrial cancer are not clearly understood, and treatment options for patients with advanced stages are limited. Animal models that spontaneously develop cancer are powerful tools for studying the mechanism of cancer initiation and progression and for developing treatment strategies. We previously created a mouse model of endometrial cancer in which the floxed phosphatase and tensin homologue (Pten) gene was deleted by Cre expression under the control of a progesterone receptor (PR) promoter. Pten is a tumor suppressor with the highest frequency of mutation in human endometrial cancer. In the PtenloxP/loxP/PR-Cre mouse model, uterine deletion of Pten resulted in complex atypical hyperplasia of the uterine epithelium by three weeks of age with cancer occurring by one month. As PR is expressed in the epithelium, stroma, and myometrium compartments, the question remains whether Pten deletion in the uterine epithelium alone contributes to endometrial cancer since human endometrial cancer is derived from epithelial cells. To address this question, we used lactoferrin-iCre (Ltf-Cre) mice to specifically delete Pten in the uterine epithelium, since lactoferrin is restricted to the epithelium of adult mice. We found that PtenloxP/loxP/Ltf-Cre mice develop complex atypical hyperplasia in uterine epithelium by three months of age, whereas uteri from immature mice are normal. These results demonstrate that Pten deletion specifically in the uterine epithelium can contribute to toward endometrial cancer in mice. This mouse model will help us to study in detail the initiation and progression of endometrial cancer. This study was supported in parts by grants from NIH-P01-CA-77839 (S. K. D).
Citation Format: Takiko Daikoku, Jumpei Terakawa, Sudhansu K. Dey. A novel mouse model of endometrial cancer: epithelial specific Pten deletion with lactoferrin-iCre. [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 2289. doi:10.1158/1538-7445.AM2015-2289
Abstract 230: Do-It-Yourself expression microdissection (DIY xMD): A low-cost, high-throughput cell and organelle isolation system
Authors: Tangrea Michael A. , Rosenberg Avi Z. , Fetsch Patricia A. , Armani Michael D. , Xi Liqiang , Raffeld Mark , Pham Tina Thu , Chen Yun , O'Flaherty Neil , Stussman Rebecca , Blackler Adele R. , Du Qiang , Hanson Jeffrey C. , Roth Mark J. , Filie Armando C. , Roh Michael H. , Hipp Jason D. , Emmert-Buck Michael R. 
Published: August 2015

Abstract
Laser-based microdissection technologies precisely recover histological regions or cells from cytology preparations and tissue sections. Yet, due to the high-cost and time-intensiveness of these methods, coarse manual microdissection is the most commonly used tool for laboratory-based studies and clinical applications, enabling rapid procurement but at the expense of reduced cell purity. We present a low-cost, do-it-yourself expression microdissection (DIY xMD) kit that combines the speed and ease-of-use of manual methods with the precision of laser-based instruments. Using DIY xMD, we isolated cell targets including ER+ nuclei and GMS-stained aspergillis fungi from clinical specimens. We also demonstrate the advantage of cellular enrichment in a cytology-based study where BRAF and KRAS mutations were masked by background cells in a manual dissection, yet identifiable after cells were recovered by DIY xMD. The new system makes high-throughput, efficient microdissection accessible to investigators and clinicians throughout the world.
Citation Format: Michael A. Tangrea, Avi Z. Rosenberg, Patricia A. Fetsch, Michael D. Armani, Liqiang Xi, Mark Raffeld, Tina Thu Pham, Yun Chen, Neil O'Flaherty, Rebecca Stussman, Adele R. Blackler, Qiang Du, Jeffrey C. Hanson, Mark J. Roth, Armando C. Filie, Michael H. Roh, Jason D. Hipp, Michael R. Emmert-Buck. Do-It-Yourself expression microdissection (DIY xMD): A low-cost, high-throughput cell and organelle isolation system. [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 230. doi:10.1158/1538-7445.AM2015-230
Abstract 2306: Quantitative assessment of one-side directed in vivo angiogenesis
Authors: Prager Gerald , Unseld Matthias , Breuss Johannes , Pausz Clemens , Schabbauer Gernot , Zielinski Christoph , Uhrin Pavel 
Published: August 2015

Abstract
Angiogenesis, the sprouting of new blood vessels from pre-existing vasculature, is an essential process under physiologic and pathological conditions, and is in focus of therapeutic intervention. Reliable in vivo models to study angiogenesis are a pre-requisite for the characterization of novel therapeutic targets. Several methods like the matrigel plug assay, the chick chorioallantoic membrane assay or the cornea assay have addressed the objective to analyse angiogenesis in vivo, but a precise method to quantify one side-directed angiogenesis is lacking so far. Here, we describe an assay, which is based on the use of small matrigel-filled silicone cylinders that are implanted subcutaneously into mice for a period of up to 15 days. In C57BL/6J mice, the effect of the incubation period as well as the dose of the growth factors VEGF and FGF on angiogenic ingrowth was investigated. We describe the appropriate explantation procedure of the silicon tubes, ensuring the complete recovery of the in-grown vessels. The subsequent ex vivo assessment of neo-angiogenesis was then achieved by anti-CD31 as well as anti-endomucin immuno-histochemical staining of ingrown endothelial cells. Additionally, we show that vessel perfusion can be assessed by intravenous injection of a cell staining dye. Altogether, the elaborated protocol offers an effective and reliable assay which facilitates in vivo research on angiogenesis thus might support the development of novel therapeutic agents.
Citation Format: Gerald Prager, Matthias Unseld, Johannes Breuss, Clemens Pausz, Gernot Schabbauer, Christoph Zielinski, Pavel Uhrin. Quantitative assessment of one-side directed in vivo angiogenesis. [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 2306. doi:10.1158/1538-7445.AM2015-2306
Abstract 2313: Characterizing intratumoral cellular heterogeneity in human glioblastoma xenografts by 30+ parameter single-cell mass cytometry
Authors: Simonds Erin F. , Nolan Garry P. , Weiss William A. 
Published: August 2015

Abstract
Introduction: Glioblastoma tumors contain dramatic intratumoral heterogeneity at the level of cellular phenotypes. High-parameter single-cell platforms such as mass cytometry offer an opportunity to simultaneously measure tumor subpopulations with unexpected combinations of differentiation markers, as well as stromal cells, vasculature, and infiltrating immune cells.
Methods: A subcutaneous patient-derived xenograft from an adult with glioblastoma was enzymatically digested into a single-cell suspension. Half of the cells were treated with epidermal growth factor (EGF) at 20 ng/mL for 15 minutes. Both samples were then stained with a 32-marker antibody panel and measured by single-cell mass cytometry. The antibody panel included surface-expressed markers of stemness and differentiation, as well as intracellular markers to monitor cell cycle, apoptosis, and growth factor signaling. Unsupervised spectral clustering was used to segregate &gt;200,000 tumor cells into 13 tumor cell subsets. Inducible signaling phenotypes were quantified in these subsets by comparing binding of phospho-specific antibodies in the stimulated sample, relative to the unstimulated control.
Results: Many previously reported markers of cancer stem cells were detectable, but they did not agree on a single population of cells. Although the CD133+ fraction was rare (&lt;5% of cells), it contained three distinct subpopulations of phenotypically distinct cells. The most informative markers for discriminating the tumor subsets were markers of stemness (i.e. CD133, CD44, Sox2) or integrin expression (i.e. CD49e, CD49f, CD51). The primitive cells (i.e. Sox2+) exhibited higher basal kinase activity across multiple pathways, including markers of cell division (i.e. Histone H3 pSer28). Short-term stimulation with EGF induced distinct responses in each of the different CD133+ subsets.
Conclusions: Single-cell phenotyping by mass cytometry produced rich developmental and functional profiles of glioblastoma cell subsets. Subpopulations of primitive (CD133+) cells can exist in a single glioblastoma tumor and exhibit distinct signaling responses to external stimulation. Altogether, these results validate the use of this platform for investigation of the intratumoral cellular heterogeneity of solid neural tumors with this platform. Work is underway to identify correlations between intratumoral cellular phenotypes and upstream driver mutations in a larger cohort.
Citation Format: Erin F. Simonds, Garry P. Nolan, William A. Weiss. Characterizing intratumoral cellular heterogeneity in human glioblastoma xenografts by 30+ parameter single-cell mass cytometry. [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 2313. doi:10.1158/1538-7445.AM2015-2313
Abstract 2327: Placenta-derived mesenchymal stem cells and their secreted exosomes inhibit the self-renewal and stemness of glioma stem cells in vitro and in vivo
Authors: Brodie Chaya , Buchris Edrat , Finniss Susan , Cazacu Simona , Xiang Cunli , Lee Hae Kyung , Poisson Laila 
Published: August 2015

Abstract
Mesenchymal stromal cells (MSCs) are multipotent stem cells that can be obtained from bone marrow and adipose tissues or from other sources such as placenta and umbilical cord. The latter allow the potential use of universal, allogeneic cell therapy because to reduced antigenicity due to low expression of MHC class II molecules. MSCs can be easily expanded in vitro for therapeutic applications and their safety and therapeutic impact have been demonstrated in various pre-clinical and clinical studies. MSCs have been shown to cross the blood brain barrier and migrate to sites of experimental GBM and can deliver cytotoxic compounds that exert anti-tumor effects. In this study we examined the effects of placenta-derived MSCs and their secreted exosomes on GSCs in vitro and in vivo. Conditioned medium of placenta MSCs or their derived exosomes decreased the self-renewal, stemness markers, Sox2 and Oct4 and the migration of these cells. Similarly, intracranial administration of the MSCs decreased the tumor volume of GSC-derived xenografts and prolonged animal survival. miRNA sequencing analysis of placenta MSC-derived exosomes revealed a set of specific miRNAs that were downregulated in GSCs and that acted as tumor suppressor in these cells. We demonstrated delivery of some of these miRNAs to GSCs following treatments with MSC-derived exosomes. We further demonstrated that MSCs or exosomes that were loaded with exogenous miR-124 delivered high levels of this miRNA into glioma cells as detected by a novel quantitative miRNA reporter. Moreover, administration of placenta MSCs loaded with exogenous miR-124 exerted a strong inhibitory effect on GSC-derived xenograft growth. These results demonstrate that placenta-derived MSCs may have important clinical applications in stem cell-based glioma therapeutics. Moreover, these studies provide a novel approach for the targeted delivery of endogenous and exogenous anti-tumor miRNAs to glioma cells as a miRNA replacement therapy for GBM.
Citation Format: Chaya Brodie, Edrat Buchris, Susan Finniss, Simona Cazacu, Cunli Xiang, Hae Kyung Lee, Laila Poisson. Placenta-derived mesenchymal stem cells and their secreted exosomes inhibit the self-renewal and stemness of glioma stem cells in vitro and in vivo. [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 2327. doi:10.1158/1538-7445.AM2015-2327
Abstract 2331: CD271 defines a cancer-initiating cell population in hypopharyngeal cancer
Authors: Tanaka Nobuyuki , Imai Takayuki , Mochizuki Mai , Tamai Keiichi , Yamaguchi Kazunori , Satoh Kennichi , Matsuura Kazuto , Sato Ikuro , Saijo Shigeru , Sugamura Kazuo 
Published: August 2015

Abstract
Cancer stem cells (CSCs) or Cancer initiating cells (CICs) contribute to the malignant phenotypes of a variety of cancers, but markers to identify human hypopharyngeal cancer (HPC) stem cells remain poorly understood. We found that the CD271+ but not CD271- cell population sorted from xenotransplanted HPCs possesses tumor-initiating capability in immunodeficient mice. Tumors generated from the CD271+ cells contained both CD271+ and CD271- cells, indicating that the population could undergo differentiation. Immunohistological analyses of the tumors revealed that the CD271+ cells localized to a perivascular niche near CD34+ vasculature, to invasive fronts, and to the basal layer. In accordance with these characteristics, a stemness marker, Nanog, and matrix metaloproteinases (MMPs), which are implicated in cancer invasion, were significantly up-regulated in the CD271+ compared to the CD271- cell population. Furthermore, using primary HPC specimens, we demonstrated that high CD271 expression was correlated with a poor prognosis for patients. Furthermore, RNA interference of CD271 in CD271+ cells decreased efficiency of tumor initiation and migration phenotypes, suggesting that CD271 is indeed functional. Taken together, our findings indicate that CD271 is a novel marker for cancer initiating cells and for HPC prognosis.
Citation Format: Nobuyuki Tanaka, Takayuki Imai, Mai Mochizuki, Keiichi Tamai, Kazunori Yamaguchi, Kennichi Satoh, Kazuto Matsuura, Ikuro Sato, Shigeru Saijo, Kazuo Sugamura. CD271 defines a cancer-initiating cell population in hypopharyngeal 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 2331. doi:10.1158/1538-7445.AM2015-2331
Abstract 2333: The tumor suppressive role of PRMT6 in regulating the pathogenesis of hepatocellular carcinoma
Authors: Chan Lok Hei , Ng Kai Yu , Ma Stephanie 
Published: August 2015

Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. The overall 5-year survival rate of HCC patients remains at a dismal 15% due to late diagnosis, metastasis and frequent tumor relapse. The presence of cancer stem cells (CSCs) has been proposed to account partly for the challenge of treating HCC. Our group has previously identified CD133 as a functional CSC marker of HCC. By adopting a PCR array encompassing diverse human chromatin modifiers, protein arginine methyltransferase 6 (PRMT6) was found to be differentially down-regulated in CD133+ human HCC cells. 55.8% (43/77) of clinical HCC tumor tissues showed down-regulated PRMT6 expression and patients with reduced PRMT6 expression were at significant risk of disrupted tumor encapsulation and manifested vascular invasion. An antagonistic relationship between PRMT6 and CD133 was observed in HCC cells, while modulation of PRMT6 led to an inversely altered CD133 expression. PRMT6 knockdown in liver cancer cells induced morphological alterations, where extensive cytoplasmic stretching and filopodia-like projections were observed. Moreover, PRMT6 regulated cancer and stem cell-like properties in vitro and in vivo including proliferation, colony formation, invasion, migration, angiogenesis, self-renewal, chemo-sensitivity and tumor initiation. In addition, stable knockdown of CD133 in HCC cells did not alter PRMT6 expression levels, which suggested that PRMT6 is potentially functioning upstream of CD133. Ongoing studies are in progress to delineate the underlying mechanisms by which PRMT6 suppress HCC.
Citation Format: Lok Hei Chan, Kai Yu Ng, Stephanie Ma. The tumor suppressive role of PRMT6 in regulating the pathogenesis of hepatocellular carcinoma. [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 2333. doi:10.1158/1538-7445.AM2015-2333
Abstract 235: SNORD76, a box C/D snoRNA, acts as a tumor suppressor in glioblastoma
Authors: chen Luyue , Han Lei , zhang kailiang , wei jianwei , pu peiyu , zhang jianning , kang chunsheng 
Published: August 2015

Abstract
Background
Gliomblastoma (GBM) is associated with disproportionately high morbidity and mortality, reflecting the need to develop new diagnostic and therapeutic targets for this disease. Recently, accumulating evidence has suggested that small nucleolar RNAs (snoRNAs) are gaining prominence and are more actively involved in tumorigenesis than previously thought. However, no report concerning the implication of snoRNAs in glioma has been published to date.
Methods
The expression of SNORD76 and its host gene, GAS5, in glioma patients were evaluated by quantitative PCR. Flow cytometry was used to analyze to cell cycle distribution after SNORD76 over-expression. After SNORD76 over-expression in GBM cell lines, cell growth and anti-tumor effect were investigated in vitro and in vivo.
Results
SNORD76 expression was selectively decreased in glioblastoma (WHO grade IV) compared with low grades glioma (WHO grade II and III). Forcibly expressed SNORD76 inhibited proliferation and anchorage-independent growth of glioma cells. Flow cytometry demonstrated that enforced SNORD76 expression arrested the cells at S phase of the cell cycle. Western blot Cell cycle-associated proteins cyclin A1, cyclin B1 and p107 were down-regulated after SNORD76 over-expression, while the expression of Rb and pRb increased. The growth of orthotopic tumors was significantly inhibited by forced expression of SNORD76.
Conclusion
In summary, engineered restoration of SNORD76 caused marked repression of glioma growth in vitro and in vivo. The tumor suppression could be achieved at least partially through inducing S phase arrest in an Rb-associated manner. Thus, SNORD76 may act as a potential tumor suppressive gene in the development and progression of glioblastoma and may be a potential specific glioblastoma biomarker.
Citation Format: Luyue chen, Lei Han, kailiang zhang, jianwei wei, peiyu pu, jianning zhang, chunsheng kang. SNORD76, a box C/D snoRNA, acts as a tumor suppressor in glioblastoma. [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 235. doi:10.1158/1538-7445.AM2015-235
Abstract 2388: Interaction between connective tissue growth factor and a disintegrin and metalloproteinase with thrombospondin type I repeats 7 during cancer development
Authors: Pi Liya , Petersen Bryon E. 
Published: August 2015

Abstract
Introduction: Connective tissue growth factor (CTGF) is a secreted pro-angiogenic protein within the CCN (Cyr61/CTGF/Nov) family and modulates multiple angiogenic pathways through its broad binding ability to cysteine knot motifs presents in key angiogenic factors including vascular endothelial growth factor (VEGF)-A. Overexpression of CTGF has been found in many cancers such as Lewis lung carcinoma (LLC), cholangiocarcinoma (CC), and hepatocellular carcinoma (HCC). In an effort to understand the molecular action of CTGF, we identified a disintegrin and metalloproteinase with thrombospondin type I repeat 7 (ADAMTS7) as a CTGF binding protein in yeast two-hybrid analysis. This enzyme belongs to the ADAMTS family capable of cleaving extracellular matrix (ECM) components and extracellular regulatory molecules. Here, we show that ADAMTS7 binds to and degrades CTGF during cancer development.
Methods: Adamts7 knockout mice were used to investigate the importance of ADAMTS7 in CTGF interaction and cleavage during LLC development. Adamts7+/+ and Adamts7−/− mice were subcutaneously implanted with LLC cells. Tumor growth was quantitatively measured within two weeks after implantation. Tumor angiogenesis was assessed utilizing a microvascular density assay. In addition, Adamts7 expression was tracked via X-gal staining of LLC tumors grown in Adamts7−/− mice that contained a LacZ trap-in cassette in the targeted Adamts7 allele. VEGF-A, CTGF, and ADAMTS7 were determined at both the mRNA and protein levels.
Results: Adamts7 induction as indicated by the β-galactosidase activity in X-gal staining was found in intra-tumor stromal cells of LLC tumors grown in Adamts7−/− mice. The association of CTGF and ADAMTS7 proteins in protein lysates of LLC tumors grown in Adamts7+/+ mice was confirmed in immunoprecipitation assays. Higher levels of VEGF-A, CTGF and ADAMTS7 mRNAs were found in LLC tumors from Adamts7−/− animals as compared to Adamts7+/+ controls. Slower rate of CTGF turnover, faster growth of LLC tumors, and higher microvascular density were also found in Adamts7−/− animals than controls.
Conclusion: These observations confirmed the binding and processing of CTGF by ADAMTS7 during LLC growth. The host-derived ADAMTS7 appears to regulate CTGF turnover and provides a protective effect towards aberrant LLC tumorigenesis and angiogenesis.
Citation Format: Liya Pi, Bryon E. Petersen. Interaction between connective tissue growth factor and a disintegrin and metalloproteinase with thrombospondin type I repeats 7 during cancer development. [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 2388. doi:10.1158/1538-7445.AM2015-2388