bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2071: The utility of FDG uptake as a surrogate biomarker to monitor tumor cell metabolism in response to anticancer therapy
Authors: Huser Nanni , Li Wenlin , Lira Maruja , Lappin Patrick , Kindt Erick , Fantin Valeria , Li Gary , Zhang Cathy C. 
Published: May 2015

Abstract
[18F]FDG-PET imaging has been emerging as a powerful clinical tool for tumor diagnosis, staging and monitoring anticancer therapy. Due to some physiologic variants and technical artifacts, one of the limitations for [18F]FDG-PET imaging is the potential to show negative scans despite the presence of malignant tumors. In this report, we aimed to gain insights into the FDG tracer biology in different tumor models and subsequently to validate the use of FDG tracer uptake for monitoring targeted therapy. To measure the FDG tracer uptake in tumor cells, a LC/MS method was established to monitor the FDG monophosphate; these results were compared with the outcome of [18F]FDG-PET imaging. In a subset tumor models including patient derived xenografts, not all growing tumors showed high FDG tracer avidity. RT-PCR and IHC assays were performed to understand the potential physiological factors that could impact the FDG tracer avidity including the intrinsic glucose level, the exposure and distribution of FDG, as well as the expressions of glucose transporters and hexokinase. The results indicated that LC/MS analysis of FDG monophosphate served as a cost-effective tool to provide a surrogate measure of [18F]FDG-PET imaging. By using FDG tracer avid tumor models, several anticancer agents including the PI3K/mTOR dual inhibitor PF-04691502, crizotinib and the γ-Secretase inhibitor PF-03084014 demonstrated suppression in FDG tracer uptake after treatment, which predicted their antitumor efficacies in the corresponding models. This work provides insights into the FDG tracer biology and the utility of [18F]FDG-PET imaging as a non-invasive biomarker for anticancer drug discovery.
Citation Format: Nanni Huser, Wenlin Li, Maruja Lira, Patrick Lappin, Erick Kindt, Valeria Fantin, Gary Li, Cathy C. Zhang. The utility of FDG uptake as a surrogate biomarker to monitor tumor cell metabolism in response to anticancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2071. doi:10.1158/1538-7445.AM2014-2071
Abstract 2072: Chitinase-3-like-1 protein expression associated with pulmonary inflammation accelerates metastasis to the lung
Authors: Libreros Stephania , Garcia-Areas Ramon , Iragavarapu-Charyulu Vijaya 
Published: May 2015

Abstract
Disseminated metastasis accounts for majority of breast cancer deaths. Recently, elevated serum levels of a glycoprotein known as chitinase-3-like-1 protein (CHI3L1) has been correlated with poor prognosis and shorter survival of patients with metastatic breast cancer. We found that there are elevated levels of CHI3L1 in plasma of mammary tumor-bearing mice. However, the biological and physiological functions of CHI3L1 are still unclear. We previously found that CHI3L1 has an inhibitory role on the expression of interferon-gamma, and in up-regulation of pro-inflammatory mediators such MCP-1, IL-8 and MMP-9 all of which contribute towards tumor growth and metastasis. In determining the cause of high levels of CHI3L1 in plasma, we found that in addition to tumor cells, splenic macrophages and more interestingly pulmonary macrophages from mammary tumor bearers secrete high levels of CHI3L1. Additionally, allergic mice also expressed higher levels of CHI3L1 in circulation and lung tissue. More specifically, CD11b+Ly6C+ cells from the lungs of allergic mice produced higher amounts of CHI3L1 compared to control mice. We have previously established that pulmonary myeloid cells through their production of CHI3L1 set up the proper microenvironment for growth of incoming mammary tumor cells. Thus, we hyphothesize that CHI3L1 levels in the lungs of mice with allergic pulmonary inflammation could accelerate metatstasis. To understand the role of CHI3L1 in accelerating pulmonary metastasis, pulmonary inflammation was induced by sensitization with ragweed allergen. Allergic mice implanted with either 4T1 or 67NR mammary tumors had a 5-fold increase in tumor volume, and formation of metastatic foci in their lungs compared to control mammary tumor bearers. Further, allergic mice showed accelerated tumor growth and shorter survival. In contrast, CHI3L1 null mice showed decreased tumor volume and metastasis, and increased survival compared to control mice. In vivo administration of chitin (β-(1-4)-poly-N-acetyl D-glucosamine) microparticles, the ligand for CHI3L1, to control and allergic mammary tumor bearers resulted in a significant reduction in pulmonary metastasis and tumor growth. These studies suggest that CHI3L1 plays a role in tumor progression and that chitin microparticles can inhibit the pleiotropic effects of CHI3L1 giving support to the idea that CHI3L1 is a useful target for treatment of breast cancer.
Citation Format: Stephania Libreros, Ramon Garcia-Areas, Vijaya Iragavarapu-Charyulu. Chitinase-3-like-1 protein expression associated with pulmonary inflammation accelerates metastasis to the lung. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2072. doi:10.1158/1538-7445.AM2014-2072
Abstract 2074: Metastasis prevention using fibroblast activation protein-targeting prodrugs at the pre-metastatic niche
Authors: Murgai Meera , Giles Amber , Kasai Miki , Vicioso Yorleny , Mackall Crystal , Kaplan Rosandra 
Published: May 2015

Abstract
Metastasis is the major cause of cancer death, and therapies that effectively target this process are required in order to improve patient survival. Previous work by Kaplan et al demonstrated that activated resident stromal cells and recruited bone marrow derived cells (BMDCs) form an altered microenvironment at distant sites in response to the primary tumor, termed the pre-metastatic niche, that promotes metastatic progression. Current on-going studies in the laboratory focus on in-depth investigations of the role, composition and mechanism of action by which each cell population including the bone marrow-derived hematopoietic cells and the activated stromal cells within the pre-metastatic niche contribute to metastatic progression. Fibroblast activation protein (FAP) is a serine protease that is overexpressed by tumor associated stromal cells, including cancer-associated fibroblasts (CAFs) and is implicated in the suppression of tumor immunity. Using a mouse model that expresses FAP promoter-driven mCherry and luciferase, we demonstrate that FAP gene expression is up-regulated in both tumor-bearing mice in pre-metastatic tissue at pre-metastatic time-points and in non-tumor-bearing mice injected with tumor-conditioned media, suggesting that metastatic tumors secrete factors that increases the number of FAP-expressing cells at the pre-metastatic niche. The studies described herein investigate the hypothesis that FAP-expressing cells at the pre-metastatic niche promote metastasis, and FAP-targeted cytotoxic drug delivery will aid in targeting tumor colonization and inhibiting metastatic progression.
Citation Format: Meera Murgai, Amber Giles, Miki Kasai, Yorleny Vicioso, Crystal Mackall, Rosandra Kaplan. Metastasis prevention using fibroblast activation protein-targeting prodrugs at the pre-metastatic niche. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2074. doi:10.1158/1538-7445.AM2014-2074
Abstract 2093: LPP promotes ErbB2 overexpressing breast cancer cell migration, invasion and metastasis
Authors: Ngan Elaine , Siegel Peter M. 
Published: May 2015

Abstract
Metastatic breast cancer remains a major hurdle to the successful treatment of this disease. Overexpression of the HER2/ErbB2 receptor tyrosine kinase in breast cancer is associated with metastatic disease and correlates with poor patient prognosis. Growing evidence demonstrates that TGFβ can potentiate ErbB2 signaling to enhance the invasive and metastatic behavior of breast cancer cells. Nonetheless, the mechanisms underlying the synergy between TGFβ and ErbB2 signaling pathways remain to be elucidated.
We previously identified Lipoma Preferred Partner (LPP) as an indispensable mediator of TGFβ-induced migration, invasion and focal adhesion turnover of ErbB2-expressing breast cancer cells. Furthermore, we established domains within LPP that are required for its localization to focal adhesions and for its interaction with α-Actinin, an actin cross-linking protein, to promote cell migration and invasion.
Herein, we examine the requirement of LPP in tumorigenesis and metastasis formation. We observe that LPP is dispensable for primary tumor growth. Nonetheless, the loss of LPP leads to decrease in spontaneous lung metastasis formation of ErbB2-expressing breast cancer cells injected into the mammary fat pads of mice. Furthermore, we observe that LPP is a critical determinant for efficient dissemination of breast cancer cells. We show that shRNA-mediated reduction of LPP significantly impairs pulmonary metastasis formation in experimental metastasis tail vein assay.
Overall, we have identified LPP as a novel mediator that integrates TGFβ and ErbB2 signaling to promote the migration, invasion and metastasis of breast cancer cells. We identify LPP as a pro-metastatic mediator of ErbB2 overexpressing breast cancer cells and a potential new biomarker of metastatic breast cancer.
Citation Format: Elaine Ngan, Peter M. Siegel. LPP promotes ErbB2 overexpressing breast cancer cell migration, invasion and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2093. doi:10.1158/1538-7445.AM2014-2093
Abstract 2479: Nuclear promyelocytic leukemia bodies tether to early endosomes during mitosis
Authors: Palibrk Vuk , Lång Emma , Lång Anna , Rowe Alexander , Bøe Stig Ove 
Published: May 2015

Abstract
During mitosis, the nuclear envelope breaks down, leading to potential interactions between cytoplasmic and nuclear components. PML bodies are nuclear structures with tumor suppressor functions. However, the protein responsible for generating these bodies, the promyelocytic leukemia protein (PML), has been shown to support both nuclear and cytoplasmic activities. Here we demonstrate that PML bodies form stable interactions with the cytoplasmic transport vesicles early endosomes immediately following entry into mitosis. The two compartments remain stably associated throughout the mitotic phase and dissociate in the cytoplasm of newly divided daughter cells. We also show that PML promotes ligand-induced endosome-mediated degradation of the epidermal growth factor receptor, and that a minor subset of PML bodies become anchored to the mitotic spindle during cell division. The study demonstrates a stable mitosis-specific interaction between a cytoplasmic and a nuclear compartment. The implications of these findings will be discussed in relation to PMLs role in tumor suppression and as a target for cancer therapy.
Citation Format: Vuk Palibrk, Emma Lång, Anna Lång, Alexander Rowe, Stig Ove Bøe. Nuclear promyelocytic leukemia bodies tether to early endosomes during mitosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2479. doi:10.1158/1538-7445.AM2014-2479
Abstract 2488: Analysis of the salivary proteome of the prolactin-inducible-protein knockout mouse
Authors: Blanchard Anne , Ezzati Peyman , Ma Xiuli , Wilkins John , Myal Yvonne 
Published: May 2015

Abstract
The human Prolactin-Inducible-Protein (PIP)/Gross Cystic Disease Fluid Protein 15 (GCDFP-15) gene is abnormally expressed in human invasive breast cancer and gross cystic disease of the breast. In healthy individuals PIP is highly expressed in salivary, sweat and lacrimal glands, and the secreted protein abundantly found in saliva as well as other bodily fluids which bathe various ports of entry. PIP has been shown to bind numerous bacterial strains as well as a number of immunoregulatory molecules including the CD4-T cell receptor and IgG and is therefore implicated to play an immune role in host defense. In the present study we interrogated the salivary proteome of the PIP knockout (Pip KO) mouse by mass spectrometry to determine protein changes that occur in saliva in the absence of PIP. Proteomic analysis identified 165 proteins in the mouse saliva which had a minimum of 2 unique peptides at the 99% confidence level. Nineteen proteins, including 2 proposed markers of disease, S100A9 and adenosine deaminase, were significantly differentially expressed in the saliva of the Pip KO mouse, compared to the saliva of the wild type counterparts. Functional and biological determinations revealed that the differentially expressed proteins were associated with processes that include inflammatory responses, immunity and cell death. This study provides evidence that a number of proteins associated with host defense are affected by the loss of PIP, and lends support for an immunomodulatory role for PIP.
Citation Format: Anne Blanchard, Peyman Ezzati, Xiuli Ma, John Wilkins, Yvonne Myal. Analysis of the salivary proteome of the prolactin-inducible-protein knockout mouse. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2488. doi:10.1158/1538-7445.AM2014-2488
Abstract 2495: Quantitative screening of protein biomarkers of hepatocellular carcinoma by antibody array
Authors: Luo Shuhong , Huang Ruochun , Wang Zhongsheng , Chen Yun-Ru , Lin Jinfei , Huang Ruo-Pan 
Published: May 2015

Abstract
Protein biomarkers can be key indicators for evaluating the presence or progression of a human disease or therapeutic response to treatment. We recently carried out a biomarker screening in hepatocellular carcinoma (HCC) using our antibody array platform. Using 25 pairs of HCC and adjacent control tissue samples, the expression levels of 274 proteins including growth factors, inflammation factors, angiogenesis, apoptosis factors and adhesion molecules, were examined using an antibody arrays. A panel of proteins demonstrating significant differences in expression levels between HCC and adjacent control samples was identified by significance analysis of microarrays (SAM) and Wilcoxon signed-rank test, combined with fold-change determination. Additionally, proteomic analysis algorithms were used to capture GO annotations and to construct signaling pathways and protein-protein interaction networks for these proteins. Proteins selected through these comprehensive analyses were designated as potential biomarkers and were well able to distinguish hepatocellular carcinoma tissue samples from paired, adjacent controls with cluster tools. The expression levels of several proteins were further evaluated by enzyme-linked immunosorbent assay (ELISA). Finally, we performed follow-up verification studies on selected proteins (Nidogen-1 and CEACAM-1) for detection of HCC in 164 pairs of serum samples from HCC patients and normal subjects with reverse phase protein array (RPPA). Our work reveals promising protein biomarkers for detection of HCC.
Citation Format: Shuhong Luo, Ruochun Huang, Zhongsheng Wang, Yun-Ru Chen, Jinfei Lin, Ruo-Pan Huang. Quantitative screening of protein biomarkers of hepatocellular carcinoma by antibody array. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2495. doi:10.1158/1538-7445.AM2014-2495
Abstract 2496: Defining the cell surface landscape in cancer: Comprehensive profiling of surface antigens for biomarker discovery and immune monitoring
Authors: O'Donnell Erika A. , Alvendia Erica L. , Osetek Benjamin E. , Wehrman Tom S. , Krutzik Peter O. 
Published: May 2015

Abstract
Flow cytometric analysis of surface marker expression is a fundamental component of diagnosis, classification, and monitoring for many hematologic malignancies. However, most clinical implementations of surface immunophenotyping focus on only a handful of markers. A comprehensive survey of CD markers and cell-surface receptors could provide a higher resolution and more accurate characterization of cancer lineages, as well as a better understanding of the immune response to disease progression or therapeutic intervention. To this end, we collated and validated 400 antibodies to known markers and receptors. Antibodies were validated for their performance on live and formaldehyde-stabilized samples to ensure compatibility with standard processing procedures. To establish the baseline and variability of each marker in the normal human population, a protocol was established to co-stain each sample for CD3, CD19, CD16, CD56, and CD14 simultaneously with each of the 400 markers. Differences in antigen abundance and expression frequency were calculated to establish the variation inherent in each marker across the population. To further validate the application of this panel for cancer immunophenotyping, eight commonly studied leukemia and lymphoma cell lines were selected for comprehensive surface characterization. Prior to staining, each cell line was fixed and barcoded with a combination of fluorescent dyes to generate a unique fluorescent signature. This approach allowed multiple cell lines to be combined into a single well for staining and analysis, enabling the rapid evaluation of hundreds of surface antigens using less than five million cells from each line. These studies have resulted in the optimization of a protocol and antibody panel for use in profiling surface protein expression on fixed human blood cells and cell lines. Application of this procedure to clinical samples may provide information useful for biomarker discovery, improved stratification of hematologic malignancies, and the identification of new drug targets.
Citation Format: Erika A. O'Donnell, Erica L. Alvendia, Benjamin E. Osetek, Tom S. Wehrman, Peter O. Krutzik. Defining the cell surface landscape in cancer: Comprehensive profiling of surface antigens for biomarker discovery and immune monitoring. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2496. doi:10.1158/1538-7445.AM2014-2496
Abstract 2497: Extracellular vesicle-mediated reversal of the prostate cancer phenotype
Authors: Panagopoulos Kiriaki , Cross-Knorr Sam , Renzulli Joseph F. , Quesenberry Peter J. , Chatterjee Devasis 
Published: May 2015

Abstract
Extracellular vesicle (EV) trafficking is a fundamental cellular process that occurs in cells and is required for different aspects of pathophysiology. EV trafficking leads to changes in cellular function including apoptosis, angiogenesis and proliferation required for increased tumor formation.
In our current study we report several phenotypic changes mediated by EVs isolated from non-malignant and malignant prostate cells as well as patient biopsied prostate tumor samples. EVs can reverse the resistance of prostate cancer cells to camptothecin EVs isolated from non-malignant PrECs (Prostate Epithelial Cells) can reverse soft agar colony formation of malignant DU145 cells, with the reciprocal effect observed. Isolation of EVs from 2 Gleason grade 8 prostate cancer patients significantly induced soft agar colony formation of non-malignant PrECs. We have identified proteins via antibody and Mass spectrometry analysis that may be responsible for the phenotypic changes. Mass spectrometry analysis of protein lysates using ProteoIQ revealed protein candidates associated with gene ontology annotations that may be responsible for this phenotypic change. Ingenuity Pathway Analysis was used to identify statistically relevant canonical pathways and functions associated the protein IDs and expression values obtained using ProteoIQ. Western blot analysis confirmed the increase of 14-3-3 zeta, pRKIP and prohibitin protein levels in PrEC cells co-cultured with patient EVs. 14-3-3 proteins were also found as common proteins of 3 other Gleason grade 8 patients.
Our results provides a rational basis to further investigate putative proteins, such as 14-3-3 and prohibitin and genetic factors that may be responsible for phenotypic changes that are associated with prostate cancer progression.
Citation Format: Kiriaki Panagopoulos, Sam Cross-Knorr, Joseph F. Renzulli, Peter J. Quesenberry, Devasis Chatterjee. Extracellular vesicle-mediated reversal of the prostate cancer phenotype. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2497. doi:10.1158/1538-7445.AM2014-2497