bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3203: Multiple myeloma microenvironment and obesity
Authors: Bullwinkle Erica 
Published: August 2015

Abstract
Multiple myeloma accounts for roughly 1% of all cancers diagnosed in the United States each year. Risk factors include environmental exposure, age, ancestry, gender, and obesity. Rates of obesity are on the rise in the United States and around the world; in the United States alone, 69% of adults are either overweight (BMI 25-30) or obese (BMI 30-35) and 6.3% of adults are extremely obese (BMI &gt; 35). Although there is a strong epidemiological correlation between obesity and multiple myeloma, the mechanism by which adipocytes contribute to the development and progression of the cancer has yet to be identified. In this study, we isolated stem cells from patients undergoing elective liposuction surgery, differentiated the stem cells into adipocytes, and co-cultured the adipocytes with RPMI 8226 or NCI-H929 multiple myeloma (MM) cell lines. MM cells proliferated faster when co-cultured with adipocytes versus growing alone. MM growth rate was significantly higher in response to adipocytes from obese patients in comparison to adipocytes from normal weight individuals. Further, conditioned media from adipocytes from obese patients significantly increased pro-angiogenic signaling within a tube formation assay, induced an increase in MM cell adhesion, and increased expression of matrix metalloproteinases. In summary, our data suggests that adipocytes in the MM microenvironment contribute to MM progression and should be further evaluated as a possible therapeutic target.
Citation Format: Erica Bullwinkle. Multiple myeloma microenvironment and obesity. [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 3203. doi:10.1158/1538-7445.AM2015-3203
Abstract 3216: Immunogenicity and genomic profiling reveal sub-clonal diversity of a murine acute myeloid leukemia (AML) cell line
Authors: Brinster Carine , DRISS Virginie , Quesnel Bruno , Figeac Martin , Leprêtre Frédéric , Villenet Céline , Briche Isabelle 
Published: August 2015

Abstract
In acute myeloid leukemia (AML), clonal heterogeneity at diagnosis and the presence of minor sub-clones were shown to be responsible for minimal residual disease and relapses in patients. Several studies have proposed that their persistence could be due to their dormant state (i.e. quiescence and/or control of their growth by immune cells). As contribution of immunity to clonal persistence could not be evaluated in xenografts models, we assessed for the clonal diversity of a murine AML cell line. Genomic analyses revealed heterogeneity among the parental cell line and its derived clones. Injected individually into immune-deficient mice, all clones induced AML with different kinetics. However, when administered into immune-competent animals, some clones triggered AML with no mice survival, whereas others elicited reduced lethality rates. The leukemia-surviving mice presented an efficient anti-tumoral CTL activity and reduced lymphopenia. Investigating for residual leukemic cells in the organs of these mice, elimination rather than persistence was observed. Thus, we showed that genetic heterogeneity among the clones led to differential immunogenicity resulting either in their immune escape or elimination. Such findings could have potent implications for new immunotherapeutic strategies in patients.
Citation Format: Carine Brinster, Virginie DRISS, Bruno Quesnel, Martin Figeac, Frédéric Leprêtre, Céline Villenet, Isabelle Briche. Immunogenicity and genomic profiling reveal sub-clonal diversity of a murine acute myeloid leukemia (AML) cell line. [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 3216. doi:10.1158/1538-7445.AM2015-3216
Abstract 3219: A patient-centric repository of PDX models for translational oncology research
Authors: Khor Tin O. , Ben Zvi Ido , Katz Amanda , Vasquez-Dunddel David , Sloma Ido , Ciznadija Daniel , Sidransky David , Paz Keren 
Published: August 2015

Abstract
Patient-derived xenograft (PDX) models maintain the complex intra-tumoral biology and heterogeneity of an intact malignancy, as well as the interplay with stromal components and other cells fluxing into the tumor environment. This intrinsic cross-talk between different elements of the tumor makes PDX models a superior tool for translational drug discovery research and personalized oncology studies. Champions PDX models were originally developed for personalizing cancer treatments through the different Champions clinical programs. These models accurately reflect the population of patients enrolling in clinical trials. We describe herein our extensive TumorBank of PDX models, a valuable resource for translational oncology research to predetermine target populations for intervention with novel therapeutics in specific cancer subtypes.
Tumor tissue from over 950 patients with a variety of primary and metastatic solid malignancies, across all ages and ethnicities and encompassing both treatment-naïve and heavily-pretreated individuals, has been implanted into immunodeficient mice with successful engraftment observed in ∼72% of cases. Comprehensive and translational-relevant clinical annotations have been maintained for these PDX models, including patient demographics, disease stage, anatomic location, tumor grade and histology, and treatment history. Importantly, whole exome and RNA sequencing, tissue histopathology, and protein immunohistochemistry have all been applied to 297 of these models. Finally, 70 of the models were screened against the corresponding patient's treatment used in the clinic, demonstrating a sensitivity of 98%, specificity of 76%, positive predictive value of 89% and negative predictive value of 96%. This wealth of information can be accessed through the Champions TumorGraft Database. The combination of extensive molecular and clinical annotation, together with opportunities for unlimited prospective preclinical testing, makes Champions TumorBank a pioneering resource for pharmaceutical companies seeking to identify target populations for therapeutic intervention.
Citation Format: Tin O. Khor, Ido Ben Zvi, Amanda Katz, David Vasquez-Dunddel, Ido Sloma, Daniel Ciznadija, David Sidransky, Keren Paz. A patient-centric repository of PDX models for translational oncology research. [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 3219. doi:10.1158/1538-7445.AM2015-3219
Abstract 3224: Molecular Response LLC tumor bank and patient-derived tumor xenograft models: a powerful translational engine for discovery and development of novel oncology therapeutics
Authors: Broudy Thomas , Ricono Jill , Scott Colleen , Nair Praveen , Thatte Jayant , Mirsaidi Cyrus 
Published: August 2015

Abstract
Patient-derived xenograft (PDX) models have been established from the world's largest living tumor bank at Molecular Response and used to mimic clinical trial settings with patients with heterogeneous populations and heterogeneous disease within oncology indications for a faster and less expensive path to test novel compounds in a more predictive preclinical setting. Overall, the collection is comprised of 144 000 tumor samples corresponding to 70 000 unique patients and continues to grow with new patient samples added routinely. For several patients, multiple samples were collected at different times (before and after treatment) or at different locations (primary/ metastatic). This allows evaluation of drug efficiency in pre and post treatment application which mimics a clinical setting as well the ability to monitor the effect of drug on the primary tumor and a matched metastatic tumor. For banked tumors, we have histo-pathological and molecular data as well as FFPE slides, DNA, RNA and chemosensitivity data from the original patient. MRL currently has over 350 PDX models in progress and has established &gt;300 unique PDX models in multiple indications. Many established PDX models have confirmed histology and mutational profiling (Next-Gen sequencing) to demonstrate preservation of the biological characteristics of these models to the original patient sample as well as between passages within the model. MRL's vast collection of patient samples allows clients the ability to focus on unique subsets of patients for a custom model build or the ability to choose from our extensive list of established PDX models to further drug discovery of novel compounds.
Citation Format: Thomas Broudy, Jill Ricono, Colleen Scott, Praveen Nair, Jayant Thatte, Cyrus Mirsaidi. Molecular Response LLC tumor bank and patient-derived tumor xenograft models: a powerful translational engine for discovery and development of novel oncology therapeutics. [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 3224. doi:10.1158/1538-7445.AM2015-3224
Abstract 3226: Patient-derived xenograft (PDX) models for triple negative breast cancer (TNBC): A pre-clinical platform for drug discovery
Authors: Thatte Jayant , Meza Miguel , Ricono Jill , Mirsaidi Cyrus , Broudy Thomas 
Published: August 2015

Abstract
In the United States, TNBC comprises 15-20% of breast cancers and are characterized by the lack of expression of estrogen receptor, progesterone receptor and receptor tyrosine protein kinase ERBB2 or Her-2/neu oncogene amplification. As a result, this type of breast cancer is difficult to treat as most of the chemotherapies target these 3 receptors. TNBC is highly aggressive and is associated with high morbidity, mortality and shorter disease-free survival. Given its heterogeneous clinical presentation, histology and response to therapy, prognosis and management of TNBC is complicated. In this study, we report development and characterization of the TNBC PDX model. We used patient derived TNBC tissues to generate 5 new TNBC models in NOD-SCID mice. Patient tumors were pre-screened for their ER, PR and Her-2/Neu expression by IHC, prior to inoculation in mice. Efficacy of two standard of care drugs, Cisplatin and Vinorelbine in the TNBC PDX model demonstrates the potential utility of the TNBC model in drug discovery effort in oncology for treatment of TNBC.
Citation Format: Jayant Thatte, Miguel Meza, Jill Ricono, Cyrus Mirsaidi, Thomas Broudy. Patient-derived xenograft (PDX) models for triple negative breast cancer (TNBC): A pre-clinical platform for drug discovery. [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 3226. doi:10.1158/1538-7445.AM2015-3226
Abstract 3232: CEP-37440, a highly selective and potent dual inhibitor of ALK and FAK1 inhibits the proliferation of inflammatory breast cancer cells
Authors: Salem Israa , Aburto Lucy , Addya Sankar , Chervoneva Inna , Mu Zhaomei , Ruggeri Bruce , Cristofanilli Massimo , Fernandez Sandra V. 
Published: August 2015

Abstract
Inflammatory breast cancer (IBC) is a very aggressive type of advanced breast cancer with a poor prognosis. Due to its propensity to rapidly metastasize, IBC is responsible for a disproportionate number of breast cancer-related deaths; 15% of all breast cancer deaths result from this disease. Approximately 30% of IBC patients have distant metastases at time of diagnosis, in contrast to 5% of patients with non-IBC breast cancers. Currently, there is no adequate adjuvant therapy to reduce the risk of recurrence and mortality in IBC patients. We recently found that FAK1, also known as PTK2, is amplified, up-regulated and phosphorylated (active) in some inflammatory breast cancer cells [1]. The focal adhesion kinase FAK1 is a cytoplasmic tyrosine kinase that localizes to focal adhesions, and controls a number of cell pathways including proliferation, viability and survival. Activated FAK1 is absent or low in normal tissue and benign neoplasms and up-regulated in invasive and metastatic tumors. In this study, we investigated a new dual FAK1/ALK inhibitor, CEP-37440, in vitro and in vivo using preclinical models of IBC. We found that 300 nM CEP-37440 was able to decrease the proliferation of the triple negative FC-IBC02 cell line and, 1000 nM CEP-37440 was able to complete inhibit the proliferation of these cells. SUM190 showed a 50% decreased in proliferation when these cells were treated with 1000 nM CEP-37440. Genes involved in functions such as cellular growth and proliferation, cell cycle, cell death and survival and cellular movement and cell-to cell signaling and interaction were differentially regulated by CEP-37440 in sensitive IBC cell lines. Among them, TGFβ1 and MMP3 were down-regulated and DKK3, CAV1 and TFPI2 were up-regulated by CEP-37440. In FC-IBC02 orthotopic breast cancer xenograft models, CEP-37440 was able to reduce the growth of the primary tumor and inhibit the development of spontaneous metastases in brain. In conclusion, CEP-37440 was highly effective in reducing the proliferation in vitro and in vivo of IBC cells that expressed high levels of phospho-FAK (Tyr397).
References
1. Fernandez S, Robertson F, Pei J, Aburto-Chumpitaz L, Mu Z, Chu K, Alpaugh K, Huang Y, Cao Y, Ye Z et al: Inflammatory breast cancer (IBC): clues for targeted therapies. Breast Cancer Res Treat 2013, 140:23-33.
Citation Format: Israa Salem, Lucy Aburto, Sankar Addya, Inna Chervoneva, Zhaomei Mu, Bruce Ruggeri, Massimo Cristofanilli, Sandra V. Fernandez. CEP-37440, a highly selective and potent dual inhibitor of ALK and FAK1 inhibits the proliferation of inflammatory breast cancer 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 3232. doi:10.1158/1538-7445.AM2015-3232
Abstract 3233: Contribution of cell types and genetic alterations in breast cancer progression
Authors: Bhagirath Divya , Zhao Xiangshan , West William W. , Band Hamid , Band Vimla 
Published: August 2015

Abstract
Breast cancer is classified in to different subtypes based on gene expression profiling. Significantly distinct subtypes present different outcome for patient survival, thus underscoring importance of understanding the role of precursor cell and genetic alterations in breast cancer subtypes. In the present study we are evaluating the role of defined combination of oncogenes in two distinct cell types in regulating the oncogenesis and metastatic behavior. We have earlier developed two hTERT-immortalized human stem/progenitor cell lines that are designated as K5+/K19- or K5+/K19+. We introduced different oncogenes in these cell lines and then examined their oncogenic potential, tumor formation and metastasis, using both in vitro and in vivo assays. We found that combinations of mutant H-Ras(mRas) and mutant p53(mp53), together with either wild type ErbB2(wtErbB2) or wild type EGFR(wtEGFR) efficiently transformed both cell types. Tumors formed by these cells were histologically heterogeneous, with variable proportions of luminal, basal-like and claudin-low type components dependent on cell types and oncogene combinations. Notably, K5+/K19- cells transformed with mRas/mp53/wtEGFR combination had significantly longer latency for primary tumor development than those expressing mRas/mp53/wtErbB2. Despite the longer latency, overall oncogene combination mRas/mp53/wtEGFR give early lung metastasis onset in both K5+/K19- and K5+/K19+ cells as compared to mRas/mp53/wtErbB2 indicating higher metastatic potential of this combination. Besides the effect of different oncogene combinations, we also found that K5+/K19+ cells overall had shorter primary tumor latency, and high metastatic potential than K5+/K19- cells. Histological and biochemical characterization of metastatic tumors is underway and will be discussed at the time of presentation. Our results suggest that both the genetic alteration and cell type contribute to oncogenicity of breast tumors.
Citation Format: Divya Bhagirath, Xiangshan Zhao, William W. West, Hamid Band, Vimla Band. Contribution of cell types and genetic alterations in breast cancer progression. [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 3233. doi:10.1158/1538-7445.AM2015-3233
Abstract 3238: Taiwanin A targets against nonsteroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma
Authors: Chuang Hong-Meng , Harn Horng-Jyh 
Published: August 2015

Abstract
Taiwanin A (α,β-bis(piperonylidene)-γ-butyrolactone) is isolated from Taiwania cryptomerioides. Similar to paclitaxel, Taiwanin A also extracted from tree barks and have anti-tumor activity in breast, liver, and lung cancer cell lines. The objective of this study is to demonstrate the cytotoxicity of Taiwanin A against tumor cells by increasing the expression of Non-steroidal anti-inflammatory drug-activated gene (NAG-1). NAG-1 has been reported to have antitumor and pro-apoptotic activity, suggesting potential target for cancer therapy. Silencing NAG-1 mRNA expression in A549 reduces the cytotoxicity caused by Taiwanin A. Furthermore, the c-Jun-N-terminal kinase/Ste20-related protein proline/alanine-rich kinase (JNK/SPAK) pathway played a key role in the action of NAG-1 on cell viability, whereas the addition of the JNK pathway inhibitor, SP600125, resulted in the inhibitory effect of NAG-1 and recovery of Taiwanin A treated cells. Xenograft tumor model showed that Taiwanin A dose-dependently significantly decreases tumor mediated growth in nude mice by increasing NAG-1 expression accompanied tumor apoptosis. These data support the conclusion that Taiwanin A inhibits lung carcinoma growth by increasing NAG-1 expression via the JNK pathway both in vivo and in vitro. This result might be contributed to compound design for increasing cytotoxicity activity in the future.
Citation Format: Hong-Meng Chuang, Horng-Jyh Harn. Taiwanin A targets against nonsteroidal anti-inflammatory drug-activated gene-1 in human lung 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 3238. doi:10.1158/1538-7445.AM2015-3238
Abstract 3247: Primary tumor cell lines generated from patient-derived-xenograft models are useful tools for study tumor biology, drug efficacy
Authors: Hu Gang , Huang Yong , Xie Fubo , Tang Xuzhen , Yang Xueyan , Liu Kunyan , Zhang Yixin , Tao Weikang , Zhou He 
Published: August 2015

Abstract
Patient-derived-xenograft (PDX) models have been widely used in the biomedical research. They recapitulate the genomic diversity/heterogeneity of patient tumors, maintain a lot of the characteristics of the original tumors and showed much better correlation with clinical outcome comparing to traditional cell line derived xenograft models. However, the relatively low throughput and time-consuming nature of PDX studies prevent them from being used in large scale screening or mechanistic studies. To address this, different cancer cell lines have been developed in our laboratory from the PDX tumors. We performed STR analyses to validate their identity. Whole exome sequencing, RNA-seq, SNP array 6.0 were performed on selected cell lines. When we compared 5 of these cell lines with their parental PDX tumors, over 93% of the CNVs identified in the cell lines were also found in the corresponding PDX models. Copy number analyses also revealed similar focal amplifications both on the cell lines and the original PDX models. More importantly, efficacy studies using different compounds showed similar drug responses using in vitro cell culture, xenografts using these cell lines and original PDX models. Our data demonstrated the high fidelity of these cell lines to their parental PDX models. In addition, we generated cell lines from progressed tumors upon exposure to long term drug treatment. The pair of treatment sensitive and resistant tumor cell lines facilitated the research on development of drug resistance. Overall, while maintaining the genetic background and phenotypic characteristics of the PDX models, these primary tumor cell lines serve as a bridge between the high-throughput drug screening and highly clinical relevant PDX models. They represent useful tools in biomedical research.
Citation Format: Gang Hu, Yong Huang, Fubo Xie, Xuzhen Tang, Xueyan Yang, Kunyan Liu, Yixin Zhang, Weikang Tao, He Zhou. Primary tumor cell lines generated from patient-derived-xenograft models are useful tools for study tumor biology, drug efficacy. [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 3247. doi:10.1158/1538-7445.AM2015-3247
Abstract 3249: Recurrent 3p21 deletion in head and neck squamous cell carcinoma identifies SEMA3F as an anti-lymphangiogenic metastasis suppressor gene
Authors: Doçi Colleen L. , Mikelis Constantinos M. , Lionakis Michail S. , Molinolo Alfredo A. , Gutkind J Silvio 
Published: August 2015

Abstract
Head and neck squamous cell carcinomas (HNSCC) often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. HNSCC are remarkably lymphangiogenic and represent a clear example of a cancer that utilizes the lymphatic vasculature for malignant dissemination; however, the molecular mechanisms underlying lymphangiogenesis in HNSCC is still poorly understood. Of interest, we found that an axon guidance molecule, Semaphorin 3F (SEMA3F), is among the top 1% underexpressed genes in HNSCC, and that genomic loss of SEMA3F correlates with increased metastasis and decreased survival. SEMA3F acts on its co-receptors, plexins and neuropilins, among which neuropilin-2 (NRP2) is highly expressed in lymphatic endothelial cells (LECs) but not in oral epithelium and most HNSCCs. We show that recombinant SEMA3F promotes LEC collapse and potently inhibits lymphangiogenesis in vivo. By reconstituting all possible plexin and neuropilin combinations, we found that SEMA3F acts through multiple receptors, but predominantly requires NRP2 to signal in LECs. Using orthotopic HNSCC metastasis mouse models, we provide direct evidence that SEMA3F re-expression diminishes lymphangiogenesis and lymph node metastasis. Furthermore, analysis of a large tissue collection revealed that SEMA3F is progressively lost during HNSCC progression, concomitant with increased tumor lymphangiogenesis. SEMA3F is localized to 3p21, an early and frequently deleted locus in HNSCC and many other prevalent human malignancies. Thus, SEMA3F may represent an antilymphangiogenic metastasis suppressor gene widely lost during cancer progression, hence serving as a prognostic biomarker and an attractive target for therapeutic intervention to halt metastasis.
Citation Format: Colleen L. Doçi, Constantinos M. Mikelis, Michail S. Lionakis, Alfredo A. Molinolo, J Silvio Gutkind. Recurrent 3p21 deletion in head and neck squamous cell carcinoma identifies SEMA3F as an anti-lymphangiogenic metastasis suppressor gene. [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 3249. doi:10.1158/1538-7445.AM2015-3249