bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3933: To image or not to image by bioluminescence? A question of validation for live animal imaging.
Authors: Zhang Yong , Tang Suni , Zhang Jinhui , Jiang Cheng , Lu Junxuan 
Published: August 2014

Abstract
Bioluminescent imaging (BLI) is an optical approach that enables rapid, non-invasive and real-time analysis of various cellular and molecular events in live animals. For over a decade, BLI has been widely used to monitor tumor take, growth, metastasis and treatment efficacy in preclinical cancer research. The technique is based on the light-emitting enzyme luciferase expressed in the live cells as internal light sources that can go through the tissue and be detected externally as the biological readout. Numerous studies have reported BLI applications for internal organ cancers and metastases, however few, in our opinion, underwent careful and rigorous validation to assess reliability and establish best-practice protocols. Our recent applications of BLI to detect xenograft tumors of human cancers and metastases highlight many practical challenges. In a subcutaneous model with LNCaP-AR-luc prostate cancer cells, we observed a linear regression R2 = 0.062 (n = 32; p = 0.056) for BLI readout (15 minute post i.p. D-luciferin for all mice imaged) vs. tumor weight at necropsy. In addition, subcutaneous xenograft tumors inoculated on two flanks within the same mice could vary as much as 10-fold in BLI per gram. In an intraprostatically-inoculated human PC-3-luc prostate cancer model, we observed a linear regression R2 = 0.080 (n = 16; p = 0.229) for BLI readout vs. tumor weight at necropsy. In a subcutaneous model of MDA-MB-231-luc breast cancer cells, correlation between tumor volume and BLI was less linear than that between tumor weight and tumor volume. Preliminary histology examination suggested that extent of central necrosis could not completely account for the poor correlation between tumor weight (all smaller than 1 g) and BLI. Examination of BLI readout kinetics showed considerable individual variability of peak intensity time, confirming findings of others (e.g., Keyaerts et. al, Eur J Nucl Med Mol Imaging, 2008; 35:999 -1007; Sim et. al, Cancer Res 2011;71:686 - 692). We are currently examining differences in cellular expression of luciferase and tumor vascularity as potential contributors to the discordance between BLI readout and tumor weight. In summary, positive BLI readout can be a reliable predictor of the presence of tumor, but careful validation is required to improve its predictive power of tumor burden for specific BLI applications. Grant supports: R21AT005383; R01AT007395.
Citation Format: Yong Zhang, Suni Tang, Jinhui Zhang, Cheng Jiang, Junxuan Lu. To image or not to image by bioluminescence? A question of validation for live animal imaging. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3933. doi:10.1158/1538-7445.AM2013-3933
Abstract 3936: The role of megakaryocytes in breast cancer metastasis to bone.
Authors: Jackson Walter , Mastro Andrea M. 
Published: August 2014

Abstract
Breast cancer cells frequently metastasize to bone. Despite the clinical ramifications, very little is understood about the fundamental mechanisms responsible for this phenomenon. While analyzing femur sections from mice that had been inoculated in the left ventricle of the heart with human metastatic MDA-MB-231 breast cancer cells, we saw a several fold increase in the number of megakaryocytes (MKs) in the bone marrow. We hypothesized that either MKs aid in the growth of cancer cells in the bone by preparing a niche for the metastases or that the increase resulted from the altered microenvironment of the marrow due to the presence of the cancer. MKs are the pre-cursors to platelets and normally represent a small portion of all bone marrow cells. However, they can increase exponentially under stressful conditions such as primary thrombocythemia and in chronic myelogenous leukemia. Platelets are known to interact with tumor cells to contribute to hematogenous metastasis and angiogenesis. Thrombocytosis, high platelet count, is a poor prognostic factor for breast cancer metastasis; and moreover, many cancer patients die from thromboembolisms. MKs also play a crucial role in bone metabolism and skeletal homeostasis.
Objectives: to determine (1) if the increase in MKs precedes the growth of cancer cells in the bone; (2) the role that cancer cell-osteoblast/stromal interactions play in the increase in megakaryopoiesis. For aim 1, MK numbers in the femurs of athymic mice inoculated with MDA-MB-231-luc intracardially (metastasis) were compared with those inoculated in the mammary gland (no metastasis). Serum was assayed for key MK maturation factors thrombopoietin (TPO) and stromal-derived factor-1(SDF-1). There was on average a two-fold increase in MK numbers in the femurs of mice with metastasic disease. However, this increase was not found in mice with localized growth but no metastasis. The increase correlated with the increase in metastatic tumor burden. There was no increase in platelet count, SDF-1, or TPO even when MK numbers were high. We concluded that the cancer cells preceded the increase of MKs in the bone marrow in a xenograft model. A syngeneic model of Balb/c mice with 4T1.2 cancer cells that metastasize from the mammary gland and 67NR cells that do not are also being compared. Thus far we have found that femurs of mice carrying 4t1.2 cells for 30 days also showed an increase in the numbers of MKs. Finally, Balb/c mice lacking TPO and thus having low MKs will be tested for metastasis.
This work was supported by the U.S. Army Medical Research and Materiel Command under W81XWH-10-1-0253.
Citation Format: Walter Jackson, Andrea M. Mastro. The role of megakaryocytes in breast cancer metastasis to bone. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3936. doi:10.1158/1538-7445.AM2013-3936
Abstract 3957: Cardiac metastasis in mice with primary breast carcinoma.
Authors: Zhang Yong , Zhang Nan , Hoffman Robert M. , Zhao Ming 
Published: August 2014

Abstract
The incidence of cardiac metastases reported in the literature ranges from 2.3% to 18.3%. Cancer cells invade the heart either directly or through the blood stream or lymphatics. This report describes cardiac metastasis from primary breast carcinoma in an orthotopic nude mouse model. 4T1 mammary carcinoma cells expressing FP were orthotopically implanted into the right second mammary fat pad of BALB/c mice. When the average tumor volume reached approximate 500-600 mm3, the 4T1 primary tumors were removed at approximately day-18 after tumor implantation. At autopsy, 2 of 12 mice were found to have metastasized to the heart, as brightly visualized by RFP fluorescence, when the mice were sacrificed 6-8 weeks after cell implantation. Post-mortem histological and frozen sample sections showed extensive tumor infiltration into the pericardium, epicardium, and myocardium. The novel mouse model of cardiac metastasis can be used to screen for effective agents.
Citation Format: Yong Zhang, Nan Zhang, Robert M. Hoffman, Ming Zhao. Cardiac metastasis in mice with primary breast carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3957. doi:10.1158/1538-7445.AM2013-3957
Abstract 3962: SGN-LIV1A: a development stage antibody drug-conjugate targeting LIV-1 for the treatment of metastatic breast cancer.
Authors: Sussman Django , Smith Leia M. , Anderson Martha E. , Duniho Steve , Hunter Joshua H. , Kostner Heather , Miyamoto Jamie B. , Nesterova Albina , Westendorf Lori , Van Epps Heather A. , Whiting Nancy , Benjamin Dennis R. 
Published: August 2014

Abstract
LIV-1, also known as SLC39A6 or ZIP6, is a member of the zinc transporter family and was first identified as an estrogen-inducible gene in breast cancer derived cell lines. LIV-1, as a downstream target of STAT3, promotes the epithelial to mesenchymal transition that is important in the malignant progression to metastasis. Consistent with its role in cancer, we determined by immunohistochemical (IHC) analysis that LIV-1 is expressed in subtypes of metastatic breast cancers (ER+/HER2-, HER2+ and triple negative). In healthy human tissues, LIV-1 expression is limited to four hormonally-regulated organs. The broad expression of LIV-1 in metastatic breast cancer in combination with the limited expression in vital organs makes LIV-1 an excellent target for an antibody-drug conjugate (ADC). SGN-LIV1A is an ADC consisting of a humanized anti-LIV-1 mAb conjugated to the microtubule-disrupting agent, monomethyl auristatin E, via a protease-cleavable linker. In vitro, SGN-LIV1A shows target specific internalization and cytotoxic activity against a breast cancer cell line. In vivo studies also demonstrate antitumor activity of SGN-LIV1A in preclinical xenograft models with significant delay of tumor growth compared to control groups. These findings support further evaluation and development of SGN-LIVA as a therapeutic for the treatment of metastatic breast cancer.
Citation Format: Django Sussman, Leia M. Smith, Martha E. Anderson, Steve Duniho, Joshua H. Hunter, Heather Kostner, Jamie B. Miyamoto, Albina Nesterova, Lori Westendorf, Heather A. Van Epps, Nancy Whiting, Dennis R. Benjamin. SGN-LIV1A: a development stage antibody drug-conjugate targeting LIV-1 for the treatment of metastatic breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3962. doi:10.1158/1538-7445.AM2013-3962
Abstract 401: Gene expression signatures differentiate primary and metastatic uterine leiomyosarcoma.
Authors: Davidson Ben , Abeler Vera Maria , Førsund Mette , Holth Arild , Shih Ie-Ming , Kristensen Gunnar B. , Chen Li , Yang Yanqin , Wang Tian-Li 
Published: August 2014

Abstract
Leiomyosarcoma (LMS) is the most common uterine sarcoma, but is a rare cancer. The genetic events related to LMS metastasis are unknown to date. The aim of the present study was to compare the global gene expression patterns of primary uterine LMS and LMS metastases in order to identify potential biological targets. Gene expression profiles of 13 primary uterine LMS and 15 LMS metastases were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated primary from metastatic LMS samples. We identified 203 unique probes that were significantly differentially expressed in the two tumor groups by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini-Hochberg correction, of which 94 and 109 were overexpressed in primary and metastatic LMS, respectively. Genes overexpressed in primary uterine LMS included OSTN, NLGN4X, NLGN1, SLITRK4, MASP1, XRN2, ASS1, RORB, HRASLS and TSPAN7. Genes overexpressed in LMS metastases included FOLR3, TDO2, CRYM, GJA1, TSPAN10, THBS1, SGK1, SHMT1, EGR2 and AGT. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry. We present the first study in which gene expression profiling was shown to distinguish between primary uterine LMS and LMS metastases. The molecular signatures unique to primary and metastatic LMS may aid in understanding tumor progression in this cancer and in providing a molecular basis for prognostic studies and therapeutic target discovery.
Citation Format: Ben Davidson, Vera Maria Abeler, Mette Førsund, Arild Holth, Ie-Ming Shih, Gunnar B. Kristensen, Li Chen, Yanqin Yang, Tian-Li Wang. Gene expression signatures differentiate primary and metastatic uterine leiomyosarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 401. doi:10.1158/1538-7445.AM2013-401
Abstract 4032: Transcriptomics analyses of normal and transformed keratinocyte lines generated novel biomarkers for prognosticating outcome in head and neck cancer.
Authors: Grafstrom Roland C. , Merne Marina , Kohonen Pekka , Jerhammar Fredrik , Nees Matthias , Roberg Karin , Ceder Rebecca 
Published: August 2014

Abstract
We tested the hypothesis that characterization of differentiation-related features in human cell lines might reveal prognosticating genes undetected in cancer tissue analyses. Serum-driven changes in transcripts were assessed in otherwise serum-free models of oral epithelium, including normal oral keratinocytes and the transformed keratinocyte lines SVpgC2a, SqCC/Y1 and LK0412. Bioinformatics-driven analyses implicated altered expression of many differentation-related functions, including unique sets of gene ontologies, molecular networks and key regulator genes for each line. Analysis of the complete in vitro/serum exposure-derived gene set relative an information-rich tumor data set identified 17 survival-associated genes, several of which had no previous association to head and neck squamous cell carcinoma (HNSCC). Multi-step validation of these genes relative to independent clinical microarray data sets, including the Human Gene Expression Map and Human Protein Atlas databases, confirmed novel association or predictive correlation with poor outcome in HNSCC for a subset of the genes. The results agreed with the hypothesis under testing, pointing to that cell line studies under a systems biology concept might couple new and prognosis-relevant genes to diverse cancers.
Citation Format: Roland C. Grafstrom, Marina Merne, Pekka Kohonen, Fredrik Jerhammar, Matthias Nees, Karin Roberg, Rebecca Ceder. Transcriptomics analyses of normal and transformed keratinocyte lines generated novel biomarkers for prognosticating outcome in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4032. doi:10.1158/1538-7445.AM2013-4032
Abstract 4038: Investigating the effect of glucose-regulated protein 78 (GRP78) inhibition in pancreatic cancer chemoresistance.
Authors: Richards Katherine , Gunn Ellen , Hill Reginald 
Published: August 2014

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related deaths in the United States with a 5-year survival rate of 6%. Current therapeutic regimens have done little to halt the progression of this disease. This demonstrates an urgent need for novel therapeutic strategies which address the mechanisms underlying the tumor cells’ ability to develop resistance to drug treatment. Increased expression of GRP78, a member of the Hsp70 protein family, is associated with poor prognosis in a number of human cancers. This prompted us to explore the role of GRP78 expression in pancreatic tumorigenesis.
Our data show that while no GRP78 expression was observed in the ducts of wild-type pancreata, GRP78 expression is significantly increased in the ductal cells of PDACs in our murine models. Moreover, this upregulated GRP78 expression, especially its membrane-associated form, corresponded to P-AKT activation. Our previous results showed that increased P-AKT signaling is significantly associated with distinct pancreatic cancer patient subgroups with more aggressive disease progression. Taken together, these data raised the question of whether GRP78 is essential for pancreatic chemoresistance.
GRP78 expression was inhibited in several gemcitabine resistant PDAC cell lines using siRNA. GRP78 knockdown produced no measurable levels of cell death in any cell lines tested. Likewise, treatment with gemcitabine alone produced very little cell death. However, gemcitabine treatment in cells with GRP78 knockdown showed significantly increased cell death. Examination of cells treated with GRP78 siRNA showed decreased P-AKT activation. These data suggest GRP78 could serve as a potential therapeutic target for chemoresistant pancreatic cancers which show PI3K/AKT pathway activation.
Citation Format: Katherine Richards, Ellen Gunn, Reginald Hill. Investigating the effect of glucose-regulated protein 78 (GRP78) inhibition in pancreatic cancer chemoresistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4038. doi:10.1158/1538-7445.AM2013-4038
Abstract 4040: Age-related effects following exposure of bone marrow-derived mesenchymal stem cells to etoposide .
Authors: Hare Ian , Gencheva Marieta , Gibson Laura 
Published: August 2014

Abstract
Mesenchymal stem cells (MSCs) have been shown to be one of the populations that support hematopoietic stem cell (HSC) development within the bone marrow microenvironment. High dose myelosuppressive or ablative chemotherapy regimens that are utilized prior to bone marrow transplantation have the potential to damage MSCs, consistent with damage which we have previously reported for more differentiated stromal and osteoblast cells. As with more differentiated progenitor cells, interactions between MSCs and HSCs are vital to hematopoietic homeostasis with alterations of these interactions having the potential to hamper hematopoietic reconstitution following treatment. In the current study we begin to investigate age associated differences in the vulnerability of the microenvironment to stress utilizing primary human MSCs from passages 6 to 10, characterized functionally by adipocytic and osteogenic differentiation and surface expression profiling (CD105+CD44+CD166+CD45−). We have shown that treatment of MSCs with 25μM etoposide for 24 hours in-vitro causes the occurrence of dsDNA breaks that recover within 48 hours following treatment. In addition, chemotherapy induced stress was followed by an induction of p21. Homologous recombination associated transcripts (XRCC2, XRCC3, Rad51) were reduced following etoposide treatment relative to non-homologous end joining associated transcripts (Ku70, Ku80, DNA-PK), and the magnitude of these differences was augmented with age in-vitro. Pro-apoptotic transcripts Puma and Noxa and the anti-apoptosis associated Bcl-XL showed induction with treatment while Bcl-2 decreased, suggesting the wide range of genes that are responsive to chemotherapy exposure. These results provide insight into the damage responses of MSCs to etoposide and how DNA repair capabilities following chemotherapy could be influenced by patient age. A more mechanistic understanding of the recovery pathways that are altered with age may be valuable for innovative approaches to the treatment of elderly patients for whom escalated chemotherapy is required in an effort to optimize microenvironment supported immune system recovery.
Citation Format: Ian Hare, Marieta Gencheva, Laura Gibson. Age-related effects following exposure of bone marrow-derived mesenchymal stem cells to etoposide . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4040. doi:10.1158/1538-7445.AM2013-4040
Abstract 4091: RapidCap: A new generation of mouse models for prostate cancer.
Authors: Cho Hyejin , Herzka Tali , Zheng Wu , Castillo-Martin Mireia , Cordon-Cardo Carlos , Trotman Lloyd C. 
Published: August 2014

Abstract
Genetically Engineered Mouse Models are the gold standard for functional cancer research. However, the associated time and cost requirements severely limit their application. As a consequence, projects carry typically a high risk, are lengthy, and scientists become ‘locked in’ with a few chosen candidate alterations. To realize the full potential of mouse modeling technology we have developed RapidCaP, a system that relies on surgical gene transfer. Through prostate speciﬁc delivery of transgenic virus we can 1) reduce model generation times from several years to a few weeks, 2) test various genetic alterations such as loss or gain of function, alone or in combination, and 3) use non-invasive imaging to monitor disease progression. Using RapidCaP, we show that focal loss of Pten and Trp53 genes triggers prostate lesions within 2 months. Furthermore, we ﬁnd that this disease responds to castration by strong regression within several weeks, but it later relapses to produce lethal hormone refractory disease. Taken together, our approach establishes a novel platform for basic prostate cancer research and it realizes the goal of carrying out pre-clinical studies in genetically engineered mice.
Citation Format: Hyejin Cho, Tali Herzka, Wu Zheng, Mireia Castillo-Martin, Carlos Cordon-Cardo, Lloyd C. Trotman. RapidCap: A new generation of mouse models for prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4091. doi:10.1158/1538-7445.AM2013-4091
Abstract 4131: Alternative splicing changes during the acquisition of anoikis resistance.
Authors: Huynh Quoc , Chalfant Charles E. , Park Margaret A. 
Published: August 2014

Abstract
Breast cancer is the most common cancer in women and the second leading cause of cancer-related death among women in the U.S. Metastases from the primary tumor are common and are the main cause of mortality in this population. Therefore, it is imperative to identify therapeutic molecules that target mechanisms specific to metastatic cells. One such mechanism to target is anoikis, a specialized form of programmed cell death that prevents epithelial cells shed from basement membranes from colonizing distant organs. Circulating tumor cells (CTCs) become anoikis-resistant, which is an essential early step in the development of distant metastases in many types of cancer including breast cancer. Recent studies have implicated RNA splicing dysregulation in a number of cancer phenotypes (e.g. oncogenesis).
In these studies, we have developed anoikis-resistant (AnR) breast cancer cell lines, which grow unattached to hydrophilic surfaces. We then performed a preliminary intron / exon array screen comparing parental and AnR breast cancer cell lines. This approach identified a novel splice variant of Non-catalytic region of tyrosine kinase associated protein 1 (NckAP1), in which the 15-18 cassette is deleted. This splice variant is dysregulated in both AnR cells and in relevant samples from breast cancer patients. NckAP1, along with Nck and Ras-related C3 botulinum toxin substrate (Rac), are found in a complex with the actin-polymerization protein Wiskott Aldrich syndrome protein verprolin homologous 1 (WAVE1). After dissociation from this complex, WAVE1 is able to induce polymerization of actin during lamellipodia formation, and is thus a mediator of migration. Hence, splicing of NckAP1 may help mediate migratory capacity of breast cancer cells. These studies also suggest a major role for splicing regulation in metastasis.
Citation Format: Quoc Huynh, Charles E. Chalfant, Margaret A. Park. Alternative splicing changes during the acquisition of anoikis resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4131. doi:10.1158/1538-7445.AM2013-4131