bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1495: Quantification of blood perfusion in rhabdomyosarcoma xenograft in 3D using contrast-enhanced ultrasound imaging
Authors: Shirinifard Abbas , Thiagarajan Suresh , Sablauer András 
Published: August 2015

Abstract
This study aims to estimate individual 3D perfusion maps using nonlinear contrast-enhanced ultrasound imaging (CEUS) over the volume of individual rhabdomyosarcoma xenograft tumors in CD1 nude mice. We implanted the tumors subcutaneously close to the right kidney. We administered MicroMarker® microbubbles via tail vein catheter and acquired images using VisualSonics VEVO 2100 imaging system. We used the burst-replenishment technique to image tumor perfusion. To maintain a steady concentration of microbubbles, we used a programmable pump to inject a small bolus followed by constant infusion, achieving a steady state in less than 1 min, significantly shorter than the commonly used constant infusion without an initial bolus. Our preliminary analysis showed that the nonlinear CEUS signal intensities of kidney cortex have less than 20% variation between mice. We used a custom program to acquire the CEUS perfusion images over a 3D volume that included the tumor and the right kidney. We used the kidney as a reference organ to normalize whole tumor perfusion data. We applied temporal clustering methods to identify regions with similar perfusion profiles. We fitted three perfusion models to each region: a) mono-exponential, b) lognormal, c) beam-specific. We compared the performance of the models based on their overall quality of fit (across all the regions) and their error in estimated pre-burst signal level. Our preliminary analysis showed that log-normal and multi-vessel beam-specific models provide better performance than the mono-exponential model. We estimated individual 3D perfusion maps based on the model fits. These perfusion maps over the entire tumor volume represent tumor perfusion more accurately than the commonly used methods based on a single 2D plane over a region of interest and without including a reference organ. Our approach quantifies intratumoral blood perfusion heterogeneity and enables comparison of perfusion across individuals. Our method is extensible to other animal models and cancer types provided they can be imaged using ultrasound and a reference tissue can be imaged reliably in tandem on a subset of planes containing the tumor.
Citation Format: Abbas Shirinifard, Suresh Thiagarajan, András Sablauer. Quantification of blood perfusion in rhabdomyosarcoma xenograft in 3D using contrast-enhanced ultrasound imaging. [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 1495. doi:10.1158/1538-7445.AM2015-1495
Abstract 1496: Quantification of tumor blood perfusion of an orthotopic mouse model of neuroblastoma using nonlinear contrast-enhanced ultrasound imaging
Authors: Thiagarajan Suresh , Shirinifard Abbas , Jacus Megan O. , Davis Abigail D. , Patel Yogesh T. , Throm Stacy L. , Daryani Vinay , Stewart Clinton F. , Sablauer András 
Published: August 2015

Abstract
This study quantifies tumor perfusion in individual tumors to estimate blood flow and blood volume parameters of an individualized tumor compartment of a comprehensive physiologically-based pharmacokinetic model of topotecan using an orthotopic xenograft model of pediatric neuroblastoma. We non-invasively imaged perfusion in orthotopic neuroblastoma (NB5) xenograft tumors (n = 3 CD1 nude mice/time point) using nonlinear contrast enhanced ultrasound technique (CEUS). Tumor tissue and organs from the mice were harvested at predefined time-points. We used a programmable syringe pump to inject MicroMarker® microbubbles via tail vein catheter and acquired images using VisualSonics VEVO 2100 imaging system. We used the burst-replenishment technique to image tumor perfusion, which requires a constant concentration of microbubbles in blood during acquisition. To maintain a steady concentration of microbubbles, we programmed the pump to inject a small bolus followed by constant infusion. Our preliminary analysis showed that healthy kidneys rapidly reach a steady state in less than 1 min, significantly shorter than the commonly used constant infusion without an initial bolus. The nonlinear CEUS signal intensities of kidney cortex showed less than 20% variation between mice. We used a custom program to acquire the CEUS perfusion images over a 3D volume that included the tumor and a kidney. We used the kidney as a reference organ to normalize whole tumor perfusion data. We fitted the log-normal perfusion model to estimate perfusion parameters for individual tumors. Our perfusion quantification over the entire tumor volume represents tumor perfusion more accurately than the commonly used methods based on a single 2D plane without a reference organ. Our approach provides population estimates of blood perfusion based on properly normalized estimates of individual blood perfusion parameters.
Citation Format: Suresh Thiagarajan, Abbas Shirinifard, Megan O. Jacus, Abigail D. Davis, Yogesh T. Patel, Stacy L. Throm, Vinay Daryani, Clinton F. Stewart, András Sablauer. Quantification of tumor blood perfusion of an orthotopic mouse model of neuroblastoma using nonlinear contrast-enhanced ultrasound imaging. [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 1496. doi:10.1158/1538-7445.AM2015-1496
Abstract 1504: Quantification of dedifferentiation rates in breast cancer using fluorescent reporter constructs and lineage tracing
Authors: Brooks Michael D. , Wicha Max S. 
Published: August 2015

Abstract
Breast cancer is the second most common cancer in women and despite significant advances in treatment, once metastatic it is almost universally fatal. One explanation for this is that current treatments don't target the true driver of tumor growth, cancer stem cells (CSCs). It has been shown that many cancers, including breast cancer, are hierarchically organized with CSCs driving tumor growth. It is also well known that a hallmark of tumor biology is an increased phenotypic plasticity, which helps tumor cells to evade treatment. It has been hypothesized that one consequence of this is an increased rate of dedifferentiation of bulk tumor cells back to CSCs. While a good deal of research has shown that this can sometimes occur, recent work showing the existence of multiple CSC states in breast cancer combined with a lack of direct lineage tracing experiments merits further investigation into the rate, and biological significance, of dedifferentiation in breast cancer. In order to monitor movement between cell states, we have developed a number of fluorescent reporter constructs for genes important in breast cancer including stemness genes (CD44, ALDH1A1, ALDH1A3, Sox2, Oct4), luminal genes (ESR1, Gata3, KRT19, E-Cadherin), myoepithelial/basal genes (CD10, p63, KRT7, Vimentin), and proliferation genes (Ki67, PCNA). These genes will be used in combination with each other in Cre-Recombinase mediated LoxP-STOP-LoxP lineage tracing constructs to track movement between luminal or basal bulk tumor cells and cancer stem cells. Validation of ALDH1A1 and ALDH1A3 reporters by immunofluorescent staining and the AldeFluor Assay has shown good concordance between the reporters and native expression of the genes. These reporters will help to quantify the rate of dedifferentiation and cell state flux in breast cancer.
Citation Format: Michael D. Brooks, Max S. Wicha. Quantification of dedifferentiation rates in breast cancer using fluorescent reporter constructs and lineage tracing. [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 1504. doi:10.1158/1538-7445.AM2015-1504
Abstract 1509: Leptin drives mammary stem cell self-renewal via the mTOR pathway
Authors: Esper Ray , Dame Michael , McClintock Shannon , Simon Becky , Wicha Max , Brenner Dean 
Published: August 2015

Abstract
Normal tissue stem cells exist in either a quiescent or proliferating/self-renewing phenotypic state with different patterns of gene expression. In the breast, the CD44+/CD24− cells are retained in a quiescent state, while the ALDH+ stem cells are actively self-renewing cells; the quiescent CD44+/CD24− cells must transition through a self-renewing ALDH+ state in order to differentiate into mature mammary cells. The adipose-rich stroma that makes up the stem cell niche in the human breast is a source of leptin that may alter stem cell phenotype in a paracrine manner. A larger population of proliferating breast stem cells could, in turn, increase the risk of breast cancer. We previously demonstrated that the increased local leptin/adiponectin ratio that commonly occurs in breast tissue of obese women promotes increased breast stem cell self-renewal leading to a larger population of stem cells in vivo, and that the mTOR pathway is activated in normal human mammary stem cells by physiologic concentrations of adipokines, including leptin. There was a physiologic dose response, with a measurable increase in mTOR activity over baseline with 31.25 ng/ml leptin, and a near maximal effect with 125 ng/ml. Here, we isolated the quiescent and proliferating stem cell fractions from human reduction mammoplasty samples and measured basal mTOR activity by ELISA for phosphorylated S6 ribosomal protein (pS6/tS6 ratio), which was greater in the proliferating ALDH+ cells. The quiescent stem cell fraction was treated with physiologic concentrations of leptin prior to resorting with FACS to measure a transition from a CD44+/CD24− to an ALDH+ proliferating phenotype. Parallel quiescent stem cells treated with the mTOR inhibitor everolimus simultaneously with leptin demonstrated that mTOR activity is necessary for this phenotypic switch. If inflammatory adipokines promote stem cell symmetric self-renewal by activating mTOR, targeted interventions may maintain potential tumor-initiating cells in a quiescent state and reduce cancer incidence.
Citation Format: Ray Esper, Michael Dame, Shannon McClintock, Becky Simon, Max Wicha, Dean Brenner. Leptin drives mammary stem cell self-renewal via the mTOR pathway. [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 1509. doi:10.1158/1538-7445.AM2015-1509
Abstract 1511: Identification of metastatic subsets of pancreatic cancer stem cells possessing metabolic features of pluripotent stem cells
Authors: Hsieh Chi-Che , Liao Wen-Ying , Chen Chih-Lung , Lin Pei-Yu , Shen Chia-Ning 
Published: August 2015

Abstract
The current cancer chemotherapy can mainly cause pancreatic cancer remission but often fails to cure cancer due to the existence of cancer stem cells in pancreatic ductal adenocarcinomas (PDACs). Therefore, development of methods targeting pancreatic cancer stem cells could lead to improvement in PDAC therapeutic. However, the key characteristics of pancreatic cancer stem cells remain to be determined. Accumulating evidences revealed the similar features shared by pluripotent stem cells and cancer stem cells, we therefore hypothesize acquisition of pluripotent characteristics during the reprogramming process is superficially reminiscent of the dysplastic transformation proposed in cancers. In the current work, comparative genome-wide profiling analysis was conducted on embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and different subpopulation of pancreatic cancer cells. We initially revealed expression of pluripotent transcriptional factors and surface markers such as Oct4, Sox2, Lin28, CD133, ABCG2 and CD44 was significantly higher in ABCG2+ CD44+ pancreatic CSC subpopulation which was correlated with their drug resistance and high metastatic potentials. Metabolic pathway analysis was further performed and identified that, very similar to ESCs/iPSCs, the metastatic ABCG2+CD44+ subpopulations had evaluated levels of of GLUT5 and KHK and expressed higher levels of ST6Gal1. Utilizing tumor-engraft mice and spontaneous pancreatic cancer mice, we actually revealed fructose diet enhanced cancer drug resistance and CSC-mediated cancer metastasis possibly via up-regulating ST6Gal1 as knockdown of ST6Gal can affect self-renewal, invasion potential and ABCG2 efflux ability of ABCG2+CD44+ CSC subpopulations. In summary, the current work elucidated that pancreatic ABCG2+CD44+ CSC subpopulations possess metabolic features of pluripotent stem cells including the capability to efficiently to utilize fructose and to perform 2,6 sialylation via sialyltransferase ST6Gal1 which critically mediated cancer drug resistance and metastasis. Hopefully, the findings can lead to developing efficient treatments for patients of PDAC in the near future.
Citation Format: Chi-Che Hsieh, Wen-Ying Liao, Chih-Lung Chen, Pei-Yu Lin, Chia-Ning Shen. Identification of metastatic subsets of pancreatic cancer stem cells possessing metabolic features of pluripotent stem cells. [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 1511. doi:10.1158/1538-7445.AM2015-1511
Abstract 1517: G0-like cells support an oral cancer stem cell pool by transitioning to a JARID1B-high state
Authors: Facompre Nicole , Belden Zachary , Gimotty Phyllis , Rustgi Anil , Herlyn Meenhard , Nakagawa Hiroshi , Basu Devraj 
Published: August 2015

Abstract
Oral squamous cell carcinomas (OSCCs) likely contain a subset of tumor cells whose stem cell-like molecular and functional properties help sustain tumor growth. There is growing evidence that this cancer stem cell (CSC) pool exists in dynamic equilibrium with other subpopulations with tumorigenic potential. To characterize this plasticity in OSCC, we examined the developmental potential of tumor cells in a “G0-like” cell state previously shown to have high growth capacity and innate drug resistance in other tumor types. G0-like cells in OSCC exhibited hallmark molecular traits of low reactive oxygen species (ROS), high Hes1, and low total Akt levels. However, despite lacking high levels of CD44 and other stem cell markers, they prominently displayed stem cell-like functional properties of in vitro sphere formation and in vivo tumorigenicity. To evaluate the contribution of G0-like cells to the oral CSC pool, a GFP reporter system was used to isolate CSCs based on high expression of JARID1B, an H3K4me3 demethylase associated with multiple normal and malignant stem cell phenotypes. JARID1B-high OSCC cells were distinct from the G0-like subset, highly expressed CD44 and ALDH1, and possessed both molecular and functional CSC traits. Silencing JARID1B expanded the G0-like subset but abrogated its functional CSC properties, suggesting these cells mediate such functions by returning to a JARID1B-high CSC state. The G0-like and JARID1B-high subsets were further distinguished by widely disparate levels of PI3-kinase pathway activation, which corresponded to distinct responses to cytotoxic and targeted therapies. These findings reveal a JARID1B-mediated mechanism underlying a contribution of G0-like cells to a CSC pool. Further they may provide a novel basis for OSCC therapy by simultaneously targeting the CSCs and a subset G0-like cells that appear uniquely primed to return to a CSC state.
Citation Format: Nicole Facompre, Zachary Belden, Phyllis Gimotty, Anil Rustgi, Meenhard Herlyn, Hiroshi Nakagawa, Devraj Basu. G0-like cells support an oral cancer stem cell pool by transitioning to a JARID1B-high state. [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 1517. doi:10.1158/1538-7445.AM2015-1517
Abstract 1532: A Microbiomic analysis in African American with colonic lesions reveals bacterial markers with potential diagnostic value
Authors: Brim Hassan , Varma Sudhir , Laiyemo Adeinko , Sharif Zaki , Lee Edward L. , Ashktorab Hassan 
Published: August 2015

Abstract
Background: Increasing evidence suggests a role of the gut microbiota in colorectal carcinogenesis. However, no specific bacteria have been unequivocally linked to either initiation or progression of colorectal cancer (CRC).
Aim: To analyze the taxonomic composition and functional potential of the gut microbiome in African Americans with colorectal lesions with the goal of detecting markers of diagnostic value.
Materials & Methods: DNA extracts from 10 stool samples of colon adenoma patients, 10 healthy subjects’ stool samples and from 10 CRC tumors and their matched normal tissues were analyzed for their microbiota composition and genomic content using Illumina MiSeq. Metagenomic Linkage Groups (MLGs) were established and those with high discriminative power between healthy and neoplastic specimens were analyzed for their genetic content. Metagenomic reads from stool samples were mapped against bacterial genes from tissues and vice-versa to identify common markers with discriminative power.
Results: The microbiota in both cancer vs. normal tissues and adenoma vs. normal stool samples were different at the 16S rRNA gene level. The metagenomic analysis led to 5 statistically significant MLGs in each set of samples. There was little overlap between the stool-based and tissue-based significant MLGs. Mapping stools reads to annotated tissue genes and vice-versa revealed a panel of 9 bacterial markers with statistically significant discriminative power between normal and adenoma in the stool dataset and visually striking (though non-significant) discriminative power between normal and tumor samples in the tissue dataset.
Conclusion: We defined MLGs with discriminative power among cancers vs. normal and adenomas vs. normals and identified 9 bacterial markers that can potentially be used as a panel for non-invasive colorectal cancer screening tests. These findings will need to be validated in a larger population of patients at different stages of the carcinogenic process and from different ethnic/racial backgrounds.
Citation Format: Hassan Brim, Sudhir Varma, Adeinko Laiyemo, Zaki Sharif, Edward L. Lee, Hassan Ashktorab. A Microbiomic analysis in African American with colonic lesions reveals bacterial markers with potential diagnostic value. [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 1532. doi:10.1158/1538-7445.AM2015-1532
Abstract 1536: Effect of ascites on tumor response in advanced stage ovarian cancer
Authors: Kim Soochi , Kim Anna , Kim Hee Seung , Gwak HyeRan , Jo UnTek , Song Yong Sang 
Published: August 2015

Abstract
Background: Ascites can create a progressive microenvironment for tumor cells, whereas there is few evidence on the role of ascites on tumor response in ovarian cancer. Thus, we investigated cellular response by ascites in ovarian cancer cell line, and evaluated the effect of ascites on clinical outcomes in patients with advanced-stage ovarian cancer.
Methods: Moreover, we collected clinico-pathologic database of 277 patients with stage IIIC-IV ovarian cancer, and investigated factors affecting overall response (OR) and survival. Furthermore, we collected ascites from four patients with stage IIIC-IV serous adenocarcinoma of the ovary, and cell migration, invasiveness and proliferation by adding ascites were evaluated in SKOV-3.
Results: OR rates were not different between patients with ascites and those without ascites (77.8% vs. 89.1%; P = 0.094), and no ascites was associated with better progression-free survival with marginal significance (37.4 vs. 27.1 mons; P = 0.056) in spite of no effect of ascites on overall survival. In multivariate analyses, no ascites was a favorable factor for reducing the risk of non-OR with marginal significance (adjusted OR, 0.286; 95% CI, 0.080-1.018; P = 0.053), whereas ascites was not an independent factor affecting survival. Moreover, ascites increased migration and invasiveness of SKOV-3 (Figs. 1A and 1B). Although proliferation of SKOV-3 was decreased for the first 24 h, it increased in time-dependent manner till 72h (Fig. 1C).
Conclusions: Ascites may contribute to invasion, migration and proliferation of ovarian cancer cells. Our clinical findings also support that ascites may affect overall response after primary treatment, suggesting the possibility that ascites can act as a tumor microenvironment related with tumor cell survival.
Citation Format: Soochi Kim, Anna Kim, Hee Seung Kim, HyeRan Gwak, UnTek Jo, Yong Sang Song. Effect of ascites on tumor response in advanced stage ovarian 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 1536. doi:10.1158/1538-7445.AM2015-1536
Abstract 1538: Levels and enzyme activity of CD73 in primary samples from cancer patients
Authors: Huang Qihui , Durham Nicholas M. , Sult Erin , Wu Yuling , Liu Jenny , Holoweckyj Nicholas , Iciek Laurie , Hollingsworth Robert , Hall Brett , Herbst Ronald , Leow Ching Ching , Sachsenmeier Kris 
Published: August 2015

Abstract
CD73 is an ectonucleotidase that converts extracellular AMP to Adenosine. Within the tumor microenvironment, adenosine produced by CD73 is believed to have an immunosuppressive effect upon anti-tumor immunity. CD73 is found on lymphoid and myeloid cells, and blockade of this enzyme has been shown to alter the suppressive capacity of cells. Expression of surface CD73 as well as soluble CD73(sCD73) levels were measured in serum, peripheral blood mononuclear cells, and tumor samples from healthy and cancer patient donors. Enzymatic activity of both surface CD73 and sCD73 was determined and differences in levels across varying tumor types and disease status were quantified. In addition, CD73 levels and activity were measured after incubation or treatment with anti-CD73 antibody, MEDI9447. These studies suggest a potential role of surface and sCD73 as a pharmacodynamic and/ or predictive biomarker of anti-CD73 immunotherapy.
Citation Format: Qihui Huang, Nicholas M. Durham, Erin Sult, Yuling Wu, Jenny Liu, Nicholas Holoweckyj, Laurie Iciek, Robert Hollingsworth, Brett Hall, Ronald Herbst, Ching Ching Leow, Kris Sachsenmeier. Levels and enzyme activity of CD73 in primary samples from cancer patients. [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 1538. doi:10.1158/1538-7445.AM2015-1538