bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2207: Elucidating mechanisms employed by NFIL3 to impact cancer cell survival
Authors: Keniry Megan , Caballero Omar , Flores Itzel , Salinas Andrea 
Published: August 2015

Abstract
NFIL3 was recently identified as a novel modulator of FOXO1 output on the PI3K pathway. NFIL3 bound to DNA to physically block FOXO1 recruitment to genes that induce apoptosis. The diminishment in NFIL3 expression via RNA interference led to FOXO recruitment to cell death genes, an increase in Histone H3 acetylation on these genes, and increased expression of these genes. However, a number of observations suggest that FOXO1 is not the main target of NFIL3 in these cells. First, the NFIL3 and FOXO1 DNA consensus sites have almost no similarity. Second, the loss of FOXO1 or all three FOXO factors failed to suppress the cell death phenotype upon the diminishment of NFIL3 in MEFs. The goal of this project is to identify the factor(s) that NFIL3 directly blocks from DNA recruitment to promote cellular survival. In previous work, the NFIL3 and FOXO1 sites were mapped as being adjacent on the DNA. The mapped NFIL3 site was required for NFIL3 to associate with the DNA in biochemical experiments and for NFIL3 to regulate the promoter sequence in reporter assays. The mapped NFIL3 site is a perfect match for the bZIP transcription factor CCAAT/enhancer binding protein beta (CEBPB) consensus sequence. NFIL3 has been shown to block the ability of CEBPB to activate transcription by competing for access to the same DNA consensus site in numerous contexts including neuronal regeneration, PKA pathway transcriptional programs and the regulation of hepatitis C viral genes. Aside from DBP in circadian rhythm, CEBPB is the most commonly antagonized factor by NFIL3 in the literature. We are investigating if NFIL3 hinders FOXO1 recruitment to cell death genes by directly antagonizing CEBPB recruitment to these genes using cell biological and bioinformatics approaches. We have found that CEBPB is required for efficient induction of a subset of NFIL3 repressed genes.
Citation Format: Megan Keniry, Omar Caballero, Itzel Flores, Andrea Salinas. Elucidating mechanisms employed by NFIL3 to impact cancer cell survival. [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 2207. doi:10.1158/1538-7445.AM2015-2207
Abstract 2208: Interferon Consensus Sequence-Binding Protein (ICSBP) regulates the transforming growth factor-beta type I receptor expression in osteosarcoma cells
Authors: Sung Jee Young , Kim Hyeryeong , Yoon Kyung-Sil , Kim Yong-Nyun , Park Byung-Kiu 
Published: August 2015

Abstract
Transforming growth factor-beta (TGF-β), known as a tumor suppressor, may exert tumor promoting activity in the advanced stage of cancer. Previously, we reported that interferon consensus sequence-binding protein (ICSBP), also known as interferon regulatory factor-8, up-regulates TGF-β type I receptor (TGF-βR I), and augments growth in HL-60 leukemic cells. In the current study, we demonstrate that ICSBP expression up-regulates TGF-βR I and increase in cell growth in U2OS human osteosarcoma cells. To further investigate the mechanism of TGF-βR I up-regulation by ICSBP, we tested the possibility that ICSBP regulates promoter activity of TGF-βR I gene. We analyzed the promoter region of the human TGF-βR I gene in U2OS cells to find putative transcription elements regulated by ICSBP. Luciferase reporter gene assays indicated that ICSBP expression could enhance TGF-βR I gene expression, and by promoter deletion analysis we identified a functional ICSBP-dependent region located at nucleotides -220 to +5 in the TGF-βR I promoter. We also performed EMSA (Electro Mobility Shift Assay) using probe and found that there are putative ICSBP binding sites between -222 to -204 regions.
In conclusion, ICSBP increased TGF-βR I expression by binding to TGF-βR I promoter (-220/218) regions in U2OS cells.
Note: This abstract was not presented at the meeting.
Citation Format: Jee Young Sung, Hyeryeong Kim, Kyung-Sil Yoon, Yong-Nyun Kim, Byung-Kiu Park. Interferon Consensus Sequence-Binding Protein (ICSBP) regulates the transforming growth factor-beta type I receptor expression in osteosarcoma 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 2208. doi:10.1158/1538-7445.AM2015-2208
Abstract 2210: DNA methylation to identify non-coding gene regulatory regions in tumor samples
Authors: Berman Benjamin P. 
Published: August 2015

Abstract
Altered control of transcriptional regulation via mutations to transcription factors and chromatin modifiers is a hallmark of cancer. Many popular methods for studying transcriptional regulation, such as ChIP-seq, DNase-I hypersensitivity, and Chromatin Conformation Capture, can be challenging to apply to clinical samples. DNA methylation has long been the chromatin biomarker of choice in disease studies because of its stability under clinical collection conditions. We have used DNA methylation profiles of thousands of tumors within the TCGA to reconstruct cancer-specific transcription factor regulatory networks, including non-coding transcription factor binding sites in enhancer regions. We use methyl-expression QTL (M-&gt;E QTL) analysis to associate changes at individual binding sites with their gene targets, often hundreds of thousands of base pairs away. This new approach allows for the first time the identification of in vivo enhancer changes in thousands of individuals, and provides a technology platform to identify key regulatory events in cancer progression.
Note: This abstract was not presented at the meeting.
Citation Format: Benjamin P. Berman. DNA methylation to identify non-coding gene regulatory regions in tumor samples. [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 2210. doi:10.1158/1538-7445.AM2015-2210
Abstract 2211: A comparative analysis of the cis-regulatory landscape between human and mouse
Authors: Yue Feng , Shen Yin , Ye Zhen , Ren Bing 
Published: August 2015

Abstract
As the premier model organism in biomedical research, the laboratory mouse shares the vast majority of protein-coding genes with humans, but significant differences exist between the two mammals, posing considerable challenges in the study and modeling of human diseases. The mouse ENCODE consortium applied the same high throughput approaches as the human ENCODE studies and produced more than1000 coordinated datasets in over 100 mouse cell types and tissues and greatly expanded the annotation of the mouse genome. By comparative analysis with the human genome, we found that although the majority of gene expression and cis-regulatory elements are conserved between the two species, a large degree of gene regulatory elements appear to be species-specific and these species-specific elements are enriched for genes involved in immune system and metabolic process, suggesting that different gene pathways evolve at distinct rates. Moreover, we found that species-specific elements are also enriched for repetitive DNA elements such LTR and SINE, which we hypothesize to be responsible generating the species-specific elements. Finally, we developed a novel computational method to study the functional conservation between two species without requiring perfectly matched cell lines or tissues. The result confirms that cis-elements with different evolutionary rates are associated distinct biological pathways and reveals the complex driving forces in the evolution of cis-regulatory landscape in mammals.
Note: This abstract was not presented at the meeting.
Citation Format: Feng Yue, Yin Shen, Zhen Ye, Bing Ren. A comparative analysis of the cis-regulatory landscape between human and mouse. [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 2211. doi:10.1158/1538-7445.AM2015-2211
Abstract 2217: Prognostic and predictive values of CD68+ macrophage and aberrant expression of cathepsin L, IL-12, CTL4A genes in classic Hodgkin's lymphoma
Authors: Zekri Abdel-Rahman N. , Bahnassy Abeer A. , El-Bastawisi Ahmad E-S , Hammad Osama , Ali Nasr M. , Diks John E. , Yousif Hend F. 
Published: August 2015

Abstract
Background: Despite advances in the treatment of classic Hodgkin lymphoma (CHL), current therapies fail to cure 10%-15% of patients, and a similar proportion of patients may be over treated, resulting in both short-term and long-term treatment-related complications. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on international prognostic score.
Patients and Methods: CD 68 protein and RNA expression were assessed in 81 classic Hodgkin's lymphoma patients from Egypt by immunohistochemistry and Quantitative real time PCR (Q-RTP) respectively. Then CD 68 positive and CD 68 negative cases where profiled using the SABioscience array (Qiagen). Genetic aberrations were correlated to standard prognostic factors, patients response to the treatment, progression free and overall survival (PFS, OS) rates.
Results: Increased CD68 protein and RNA expression were detected in 70.3% and 53.1% of the cases, respectively. Increased CD68 protein associated significantly with old age &gt;40 (p = 0.035), advanced stage (p = 0.007), and poor response to treatment (DP/SD, p = 0.001). CD68 RNA expression significantly associated with age (p = 0.035), and poor response to treatment (DP/SD, p = 0.001). CD68+ positive patients, showed high expression of cathepsin L, IL-12, ATXN2L, CTL4A and MMP11. The 5 years OS correlated significantly with CD68, IL-12, MMP11 and CTL4A-RNA expression (p&lt; 0.001) as well as with age (p&lt;0.001) and stage (p&lt;0.001). The 5 years PFS correlated significantly with age (p = 0.003), stage (p = 0.012), CD68 protein and RNA expression (p&lt; 0.001) as well as with cathepsin L, IL-12, CTL4A and MMP11 (p&lt;0.01). CD68 protein expression significantly correlated with 2 years OS (p&lt; 0.001).
Conclusions: in classic Hodgkin's lymphoma, CD68+ macrophage and aberrant expression of cathepsin L, IL-12, CTL4A and MMP11 provide sensitive biomarkers that can accurately predict patients response to treatment and survival with high accuracy.
Citation Format: Abdel-Rahman N. Zekri, Abeer A. Bahnassy, Ahmad E-S El-Bastawisi, Osama Hammad, Nasr M. Ali, John E. Diks, Hend F. Yousif. Prognostic and predictive values of CD68+ macrophage and aberrant expression of cathepsin L, IL-12, CTL4A genes in classic Hodgkin's lymphoma. [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 2217. doi:10.1158/1538-7445.AM2015-2217
Abstract 2268: Tenascin C as an effector of prostate cancer derived bone metastasis
Authors: San Martin Rebeca , Rowley David R. , Pienta Kenneth J. 
Published: August 2015

Abstract
The stroma plays a key role in maintenance of tissue homeostasis. A reactive stroma evolves early in the progression of prostate cancer. One way reactive stroma remodels the microenvironment is by deposition of tenascin-C. Tenascin-C is an extracellular matrix protein that is expressed during development and is critical for neuronal patterning and osteogenesis. In contrast, expression of tenascin C in adult tissues is limited and is restricted to regions of wound repair, tissue remodeling and pathological conditions, such as cancer.
To assess whether the bone exhibits a reactive tissue phenotype in the context of metastasis, human prostate cancer metastasis tissue arrays were evaluated using immunohistochemistry and spectral deconvolution. This work identified a tenascin-C expression pattern at trabeculae-associated metastatic sites, suggesting the evolution of a reactive endosteum.
In order to evaluate the mechanisms involved, we developed an in vitro 3D osteogenic organoid, using human mesenchymal stem cells induced to osteoblastic differentiation, which exhibits a reactive endosteum phenotype. Co-culture with the metastatic prostate cancer cell line VCaP showed preferential binding at sites high in tenascin C deposition. Also, metastatic cells were capable of adherence to purified tenascin C in vitro, forming 3D colonies. We have identified α9β1 integrin as a mediator of prostate cancer cell adhesion to tenascin C-rich surfaces. Preliminary data has also identified signaling through WNK1 and STAT6 as additional candidate mechanisms that mediate tenascin-C induced biology in prostate cancer cells that are metastatic to bone surfaces.
These studies characterize a reactive endosteum phenotype at sites of metastatic prostate cancer foci and suggest that elevated tenascin-C at these sites mediates the adhesive and other biological properties of cancer cells. This study will help provide data from which to develop novel therapeutic approaches to treat metastatic disease.
Citation Format: Rebeca San Martin, David R. Rowley, Kenneth J. Pienta. Tenascin C as an effector of prostate cancer derived bone metastasis. [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 2268. doi:10.1158/1538-7445.AM2015-2268
Abstract 2271: Peptidylarginine deiminase 2 as a novel therapeutic target for breast cancer
Authors: Horibata Sachi , McElwee John L. , Sadegh David , Rogers Katherine , McLean Dalton , Coonrod Scott A. 
Published: August 2015

Abstract
Peptidylarginine deiminases (PADIs) enzymes are calcium-dependent enzymes that post-translationally convert positively charged protein arginine residues to a neutrally charged citrulline in a process known as citrullination or deimination. This loss of charge can alter the tertiary structure of proteins and affect protein-protein and protein-DNA interactions. We, and others, have found that PADI-mediated histone tail citrullination alters chromatin structure and regulates gene expression. For example, we found that PADI2 interacts with estrogen receptor (ERα) and that PADI2-mediated citrullination of histone H3 arginine 26 residues at ERα binding sites regulates target gene expression. In addition, we also found that PADI2 is often co-expressed with HER2 in both breast cancer cell lines and in tumor tissue. Our molecular studies suggest that PADI2 activates HER2 expression via histone citrullination at the HER2 gene locus and that HER2 signaling appears to induce PADI2 expression, thus potentially forming an oncogenic positive feedback loop with HER2. These findings suggest an important role for PADI2 in breast cancer progression. This prediction is supported by our finding that PADI2 expression is upregulated in cancer cells and that depletion of PADI2 from breast cancer cells results in reduced tumorigenicity. In addition, we found that transgenic overexpression of PADI2 promotes carcinogenesis and that the PADI inhibitor, Cl-Amidine, slows tumor growth in mouse models of breast cancer. Furthermore, we found that Cl-Amidine also maintains basement membrane integrity in xenograft tumors, preventing initiation of metastasis. Together, these findings suggest that PADI2 represents a novel therapeutic target and biomarker for early stage breast cancer.
Citation Format: Sachi Horibata, John L. McElwee, David Sadegh, Katherine Rogers, Dalton McLean, Scott A. Coonrod. Peptidylarginine deiminase 2 as a novel therapeutic target for breast 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 2271. doi:10.1158/1538-7445.AM2015-2271
Abstract 2274: The dual role of fibronectin in lung cancer progression
Authors: Cheng Hung-Chi , Chang Ming-Min , Tseng Yau-Lin 
Published: August 2015

Abstract
Tumor cells chronically progress, involving a series of aberrant activities within distinct organs, to accomplish final metastasis. The role of fibronectin (FN) in tumor progression has been controversial, being either tumor-suppressive or metastatic-promoting. Nevertheless, little effort has been made to reconcile these discrepancies in a systemic manner. Here, we deprived metastatic tumor cells of pericellular FN (periFN) in the spontaneous metastasis assay and demonstrated a dual role of FN. We found that, while knocking down FN expression of Lewis lung carcinoma cells (FNKD-LLC) increased the tumor sizes and migratory activities, it significantly decreased the tumor metastasis in the lungs. Histological examination revealed that subcutaneous tumors of mice bearing FNKD LLC invaded the surrounding tissues to a higher extent than those of mice bearing control scramble-LLC. Immunohistochemical staining with antibodies against CD31, FN, and casepase 3, revealed that FNKD-LLC rendered more angiogenesis, tumor intravasation, and fibrous FN deposited in the surrounding inflammatory tissues, without altering the tumor apoptosis, suggesting that the FN expression in tumor cells indeed plays a role in suppressing the tumor progression in the primary tumor tissues. Conversely, the metastatic tumor nodule numbers in the lungs were significantly reduced for the FNKD-LLC cells, clearly indicative of a metastatic-promoting role of periFN. We reasoned these seemingly conflicting phenomena by hypothesizing that the FN expression of neoplastic lung carcinoma cells is initially downregulated to trigger fibrotic microenvironments (FN deposition in extracellular matrices) to which pro-inflammatory leukocytes are recruited, leading to the enhanced angiogenesis and tumor intravasation. However, the early circulating lung cancer cells fail to colonize distant organs (including lungs) until periFN is re-assembled in the later progression stages, thus facilitating the tumor cell adhesion to CD26 on endothelial cells and consequently extravasation and metastasis. This hypothesis of temporal-spatial regulations was clinically supported by comparing and statistically analyzing the FN expression levels in lung cancer tissues collected from patients hospitalized by the NCKU hospital for surgery within 2003 through 2006 with low and high survivals. This study was supported by Grant # MOST 102-2320-B-006 -031- and MOST 103-2325-B-006 -009 -.
Citation Format: Hung-Chi Cheng, Ming-Min Chang, Yau-Lin Tseng. The dual role of fibronectin in lung 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 2274. doi:10.1158/1538-7445.AM2015-2274
Abstract 2278: The hypusine cascade promotes cancer progression and metastasis through the regulation of RhoA in squamous cell carcinoma
Authors: Muramatsu Tomoki , Kozaki Ken-ichi , Imoto Seiya , Yamaguchi Rui , Tsuda Hitoshi , Kawano Tatsuyuki , Morishita Maki , Miyano Satoru , Inazawa Johji 
Published: August 2015

Abstract
Metastasis is one of the critical factors contributing to poor prognosis in cancer, but the mechanisms are poorly understood. We established a highly metastatic subline (HOC313-LM) derived from an oral squamous cell carcinoma cell line (HOC313) for uncovering the metastatic mechanisms. We identified deoxyhypusine synthase (DHPS) as a metastasis-related gene through the specific amplification at 19p13.2-p13.13 in the HOC313-LM. Overexpression of DHPS promoted cell motility, invasion and metastasis through activation of the RhoA signaling pathway, and increased the tumor formation in vivo. We also demonstrated that eukaryotic translation factor 5A (eIF5A) bound to RhoA mRNA and regulated its translation. Moreover, GC7, a DHPS inhibitor, showed significant decrease in the tumor formation in vivo. In patients with esophageal squamous cell carcinoma (ESCC), overexpression of DHPS in ESCC tumors was significantly associated with worse recurrence-free survival, and correlated with distant metastasis. Our elucidation of these molecular mechanisms within the hypusine cascade suggests opportunities for novel therapeutic targets in SCC.
Citation Format: Tomoki Muramatsu, Ken-ichi Kozaki, Seiya Imoto, Rui Yamaguchi, Hitoshi Tsuda, Tatsuyuki Kawano, Maki Morishita, Satoru Miyano, Johji Inazawa. The hypusine cascade promotes cancer progression and metastasis through the regulation of RhoA in squamous cell 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 2278. doi:10.1158/1538-7445.AM2015-2278
Abstract 2282: K-RasV12 bone marrow cell reconstitution causes lung cancer in wild type mice
Authors: Belloni Elena , Martin-Padura Ines , Gerbino Elvira , Orecchioni Stefania , Fusar-Imperatore Fulvia , Marighetti Paola , Bertalot Giovanni , Pelicci Pier Giuseppe , Bertolini Francesco 
Published: August 2015

Abstract
The potential of recruited bone-marrow-derived cells (BMDCs) to act as a source of malignancy was disputed for a long time. A role for BMDCs in tissue repair has also been proposed, since these cells are capable of homing to the lung and differentiating into multiple epithelial cell lineages so thus contributing in lung tissue repair and regeneration. We tested the ability of bone marrow cells containing an inducible oncogene to initiate lung adenocarcinoma. Since the role of the K-Ras gene in lung cancer is well known, for our experimental strategy, we used a mouse model expressing oncogenic K-RasV12 (K-Ras+/V12RERTert/ert). This model generates a specific neoplastic phenotype induced by the K-RasV12 mutation. Mice usually develop lung tumors with complete penetrance evolving from hyperplasia, through adenoma, to adenocarcinoma, when the oncogene expression is induced by 4-hydroxitamoxifen (4-OHT) administration. Following lethal irradiation, wild-type mice were transplanted with donor bone marrow cells derived from K-RasV12 mice and, once the bone marrow was reconstituted, treated with 4-OHT. Mice were monitored and sacrificed at subsequent post-induction time points (0, 3.5, 5.5, 8.5, 11, 13.5, 15, and 16 months) and lungs and peripheral blood were collected. Analysis of the H&E-stained lung sections from both reconstituted K-RasV12 and control mice revealed diffuse hyperplasia, possibly due to irradiation. Epithelial lesions, adenomas and/or adenocarcinomas, were detected in 4 out of 8 K-RasV12-reconstituted animals at 3.5, 5.5, 13.5 and 15 months post oncogene induction while no lesions were detected in the control group (transplanted but not induced mice). In addition, the K-Ras implication on the origin of the tumor was confirmed by X-Gal staining of lung lesions in reconstituted mice. In our model, -geo is indeed a marker protein coexpressed along with the same K-RasV12 transcript by a bicistronic strategy. Our results suggest a direct implication of BMDCs in lung epithelial tumor development and emphasize the need of further studies to dissect the mechanisms regulating BMDCs’ recruitment to injured tissues and their role in tumor initiation and/or progression.
Citation Format: Elena Belloni, Ines Martin-Padura, Elvira Gerbino, Stefania Orecchioni, Fulvia Fusar-Imperatore, Paola Marighetti, Giovanni Bertalot, Pier Giuseppe Pelicci, Francesco Bertolini. K-RasV12 bone marrow cell reconstitution causes lung cancer in wild type mice. [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 2282. doi:10.1158/1538-7445.AM2015-2282