bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4206: Identification of transcriptional regulatory motifs that control gene expression in premenopausal women with previous history of breast cancer
Authors: Cano Oscar D. , Gökmen-Polar Yesim , Chirayu Goswami , Li Lang , Sirimalle Usha , Gu Xiaoping , Nakshatri Harikrishna , Badve Sunil 
Published: August 2012

Abstract
Background: Age is an important risk factor for Breast Cancer. Older women have a 50 times greater risk for breast cancer as compared to younger women (under the age of 30 years). Aging is associated with activation of specific transcription factor networks. We hypothesized that premature activation of these programs may predispose to cancer. The aims of this study were 1) to identify active transcription factor networks controlling the expression of specific cancer-related genes in the normal breast and 2) to analyze whether premature activation of this network is associated with neoplastic transformation. Methods: Fresh frozen normal breast tissue of women, under the age of 50 years, with and without history of breast cancer was obtained (ncancer=8, nnon cancer=4). Total RNA was extracted, cDNA annealed and Whole-genome DASL assay (Illumina Corp) was conducted to identify genes that correlated with cancer outcome in premenopausal women. Differential expression analysis was performed using Partek® software program to identify the up or down regulated genes in women with cancer compared to those without. Transcription factors affecting the regulation of genes in patients with cancer were predicted using MotifModeler program (Liu et al). The resulting data was confirmed using qPCR analysis. Results: Whole genome DASL analysis showed differential expression of 34 genes (p-value &lt;0.01). MotifModeler analysis predicted 18 transcription factors as major regulators of gene expression in premenopausal women with previous history of breast cancer. JUNB and FOS were the most significantly altered in this comparison. qPCR pre-validated the over expression of JUNB and FOS in association with cancer development. Further validation studies in an independent cohort are ongoing using Formalin-fixed Paraffin-embedded (FFPE) samples. Conclusion: Gene expression analysis identified transcriptional features of cancer outcome. Differential expression of the JUNB and FOS family of proteins, which are part of AP-1 transcription factor complex, may be correlated with neoplastic transformation in premenopausal women. Breast Cancer Program of the IU Simon Cancer Center funded this project.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4206. doi:1538-7445.AM2012-4206
Abstract 4210: Association of the 15q25 and 5p15 lung cancer susceptibility regions with gene expression in lung tumor tissue
Authors: Fehringer Gordon , Liu Geoffrey , Pintilie Melania , Sykes Jenna , Liu Ni , Cheng Dangxiao , Chen Zhuo , Seymour Lesley , Der Sandy D. , Shepherd Frances A. , Tsao Ming-Sound , Hung Rayjean J. 
Published: August 2012

Abstract
Lung cancer is one of the most commonly diagnosed cancers worldwide, with 1.6 million new cases reported each year and ranks first in annual global cancer deaths. Genome-wide association studies have identified two independent lung cancer susceptibility loci at chromosome 15q25 and one locus at 5p15. We examined the association of genetic variants in these lung cancer susceptibility regions with gene expression in lung tumor tissue in an effort to elucidate carcinogenic mechanisms by which these variants influence lung cancer risk. We used data from two independent studies: the JBR.10 clinical trial (131 NSCLC patients) and a patient sample from the University Health Network (UHN) in Toronto (181 NSCLC patients). We genotyped seven 15q25 and five 5p15 variants and examined their association with the expression profiles of genes in the corresponding regions measured by Affymetrix HG-U133A. The minor allele (C) of a variant representing one of the two loci at 15q25 (rs2036534) was associated with increased expression of the IREB2 (iron-responsive element binding protein 2) gene in both studies (JBR.10 P=0.042; UHN P=0.002). An FDRα0.05 in the UHN sample increased our confidence in this association. The association appears to be more prominent among patients with lung adenocarcinoma. We did not detect an association between the genotype and expression profile for the other 15q25 locus (represented by rs16969968 and rs1051730). Previous studies suggest that 15q25 variants are associated with risk through an effect on smoking behaviour, indicating risk is modulated through activity of nicotinic acetylcholine receptor genes present in this region. Our results indicate there is a second mechanism through which variants at 15q25 influence risk, operating through modulation of IREB2 gene expression. This finding may have implications for future research on lung cancer chemoprevention strategies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4210. doi:1538-7445.AM2012-4210
Abstract 4215: Integrin-dependent mechanisms for sensitizing melanomas to chemotherapy
Authors: Bays Jennifer L. , Palma Melissa , DeMali Kris A. 
Published: August 2012

Abstract
BRAF is mutated in 50-70% of human melanomas, resulting constitutive activation of the MEK-ERK1/2 signal transduction pathway and resistance to apoptosis. Agents that target the oncogenic BRAF signaling pathway are revolutionizing the treatment of metastatic melanoma. However, it is already evident that there is both intrinsic and acquired resistance to this class of compounds suggesting that combinatorial therapies may be needed to combat melanoma resistance. We recently described a novel compound, denoted vinculin activating peptide (VAP) that engages defective integrins with the extracellular matrix and consequently sensitizes melanomas to chemotherapy. VAP is relatively large and the minimal sequences required for the sensitization of melanomas to chemotherapy are not known. In this study, we investigated the smallest domains of VAP that are required for its chemosensitizing effects. Here, we report that VAP contains three small domains, termed vinculin binding sites (VBSs) which are sufficient to bind the integrin-associated protein, vinculin and sensitize melanoma cells to chemotherapeutics. Out of the three VBSs within VAP, VBS3 exhibits stronger binding to vinculin and increases cell-matrix adhesion and focal adhesion number to a greater extent. Furthermore, VBS3 enhances melanoma sensitivity to chemotherapy more than VBS1 or VBS2. The residues of VBS3 required for the sensitization of melanomas have been investigated and suggest that divergent residues are important for chemosensitization. Collectively these data suggest that small molecule mimetics of VBS3 would be an ideal therapy to overcome the resistance of metastatic melanomas to chemotherapeutic agents.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4215. doi:1538-7445.AM2012-4215
Abstract 4217: Engaging CD151 inhibits cell migration and metastasis through a novel mechanism involving the cell adhesion molecule ALCAM/CD166
Authors: Palmer Trenis D. , Mazzocca Antonio , Hansen Amanda , Arnold Shanna , Jones-Paris Celestial , Yamada Masashi , Sekiguchi Kiyotoshi , Zijlstra Andries 
Published: August 2012

Abstract
We recently demonstrated that actively promoting the formation of cell surface complexes by engaging the tetraspanin CD151 with a monoclonal antibody (mAb 1A5) inhibits metastasis by immobilizing the tumor cells. Tetraspanins influence cellular behavior via the regulation of associated partner molecules such as integrins, cell adhesion molecules, and members of the immunoglobulin superfamily. Although CD151 is able to associate with and regulate the activity of laminin-binding integrins we demonstrate that CD151 does not associate with α3α1 in the presence of mAb 1A5. Using a 2-color flow cytometric approach we mapped the domains of CD151 required for antigen recognition by mAb 1A5 and determined that 1A5 maps to the integrin 194QRD196 motif of CD151, using this information we further performed CD151 co-immunoprecipitations and demonstrated that 1A5 recognizes CD151 not associated with α3α1.To determine the identity of the protein(s) associated with the antibody-engaged CD151 and also possibly responsible for the anti-migratory, anti-metastatic phenotype we used a proteomic approach. Using tandem mass spectrometry on CD151-associated proteins co-immunoprecipitated by mAb 1A5, we detected in excess of 200 proteins. This strategy identified several putative partners of CD151. Further analysis of the CD151 associated proteins led to our discovery of the novel CD151-associated protein ALCAM/CD166, a member of the immunoglobulin superfamily. Using an RNAi-mediated knockdown approach we demonstrate that ALCAM/CD166 is required for the CD151 complex to regulate tumor cell mobility in vitro. Conversely, CD151 is required for ALCAM to control motility. Spontaneous metastasis assays using the avian chorioallantoic membrane and subcutaneous murine xenografts demonstrate thatALCAM/CD166 is indeed required for the engaged tetraspanin to inhibit tumor cell dissemination in vivo. Further mechanistic analysis of this complex revealed that the CD151/ALCAM protein complex promotes activation of the small GTPase Rap1 via activated protein kinase C. Collectively, we present data, which demonstrate that, the ALCAM-containing CD151 complex can control metastasis. This novel complex reveals how cell-cell interactions can control migration through the regulation of cell-matrix adhesions. These results also demonstrate mechanistically that tetraspanins can integrate signaling between physically distinct molecular functions and therefore behave as a molecular clutch that controls matrix adhesion in response to cell-cell interactions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4217. doi:1538-7445.AM2012-4217
Abstract 4225: Annexin A4 induces chemoresistance for multiple drugs in ovarian clear cell carcinoma
Authors: Morimoto Akiko , Enomoto Takayuki , Serada Satoshi , Matsuzaki Shinya , Yokoyama Takuhei , Kimura Toshihiro , Ueda Yutaka , Yoshino Kiyoshi , Fujita Masami , Fujimoto Minoru , Kimura Tadashi , Naka Tetsuji 
Published: August 2012

Abstract
BACKGROUND: Platinum drugs play the key role for postoperative adjuvant therapy and treatment in progress and recurrent ovarian cancer. We have previously reported that ovarian clear cell carcinoma (CCC) has increased expression of Annexin A4 (Anx A4) in comparison with other subtypes of ovarian cancer. Enhanced expression of Anx A4 has been shown to induce chemoresistance via extracellular efflux of carboplatin. However, it remains unclear whether targeting Anx A4 is effective for improving the sensitization against chemotherapy, like platinum drugs. The aim of this study was to evaluate the role of Anx A4 in chemoresistance in ovarian CCC. MATERIAL AND METHODS: RMG-I cell lines were used to establish the stable knockdown of Anx A4. Plasmids encoding short hairpin RNAs (shRNAs) targeting Anx A4 were transfected. Chemoresistance was assessed by IC50 value in various drugs. RESULTS: Compared with control cells, knockdown of Anx A4 gene expression in RMG-I cells induced chemosentisitzation around 2-fold to cisplatin (IC50: 11.2 μM to 5.8 μM, P&lt;0.01) and Carboplatin (IC50: 130.4 μM to 63.3 μM, P&lt;0.01). Unexpectedly, knockdown of Anx A4 also improved the chemosentisitzation of epirubicin (IC50: 256.7 nM to 180.3 nM, P&lt;0.01) and Paclitaxel (IC50: 5.5 nM to 2.9 nM, P&lt;0.01). In consistent with the improved chemosensitivity, drugs induced p53 was markedly increased by knockdown of Anx A4 in RMG-I cells. In xenograft models, significant chemosensitization toward cisplatin was demonstrated by knockdown of Anx A4 in RMG-I cells. CONCLUSIONS: Inhibition of Anx A4 induced chemosensitization in ovarian CCC cells. Anx A4 blockade might be a novel therapeutic target of chemoresistance in patients with ovarian CCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4225. doi:1538-7445.AM2012-4225
Abstract 4228: Aryl hydrocarbon receptor nuclear translocator is associated with cisplatin resistance in cancer cells
Authors: Chen Ben-Kuen , Kalpana Sriram , Chang Wen-Chang 
Published: August 2012

Abstract
The (ARNT) belongs to the basic-helix-loop-helix (bHLH) transcription factors containing Per-Arnt-Sim (PAS) domain. In addition to forming heterodimers with many other bHLH-PAS proteins, including the aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α, ARNT can also form homodimers. Our previous study had shown that ARNT is a new factor involved in EGF regulated COX-2 gene expression under normoxia involving tumorigenesis in cervical cancer tissues. Resistence to cisplatin is often observed in cervical cancer therapy. Here we showed that ARNT expression is critical for cisplatin resistance. Specifically, we showed that in HeLa cervical cancer lines, cisplatin decreased ARNT expression level. Over-expression of ARNT rendered HeLa cells resistant to cisplatin. In addition, inhibition of ARNT by small interfering RNA silencing increased cisplatin induced cell death by activation of caspase 3 and sensitized drug resistant cells to cisplatin. Using ARNT deficient and ARNT fully expressed cell lines showed that induction of apoptosis by cisplatin correlates with ARNT. Importantly down regulation of ARNT decreased drug efflux pump protein MDR1 expression, suggesting that MDR1 gene expression depends on ARNT activity. In conclusion, ARNT mediates the efflux of cisplatin and has a functional role in cervical cancer cell sensitivity to cisplatin. In a xenograft analysis of SCID mice, cisplatin also efficiently inhibited ARNT-deficient tumor formation. These results suggest that targeting ARNT could overcome cisplatin resistance in human cervical cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4228. doi:1538-7445.AM2012-4228
Abstract 4231: Immunohistochemical analysis of claudins expression in penile squamous cell carcinoma
Authors: Bulgarelli Adriana , Lourenço Silvia Vanessa , Coutinho-Camillo Cláudia Malheiros , Guimarães Gustavo Cardoso , Soares Fernando Augusto , Vassallo José 
Published: August 2012

Abstract
Background: Claudins are tight junction proteins that are critical for the sealing of cellular sheets and controlling paracellular ion flux. Members of the claudin family have been demonstrated to play an important role in carcinogenesis and tumor progression. Penile squamous cell carcinoma (SCC) is a major health problem in Brazil, corresponding to 2,1% of all brazilian men tumors and 5-year survival rate drops dramatically in patients with lymph node metastasis. Objective: The aim of this study was to determine the protein expression pattern of claudins in penile SCC and correlate it with the clinicopathological features of penile cancer. Method: Tissue microarray (TMA) comprising 101 cases of penile SCC were immunohistochemically stained for claudin-1, -3, -4, -5 and -7, with which TMA core showing more than 10% of positive membranous staining cells. Results: Claudin-1, -3, -5 and -7 were downregulated in 55%, 68%, 62% and 88% of penile SCC samples, respectively. Claudin-4 was overexpressed in 58% of the tumor samples. Strong correlation was found between downregulation of claudin-1 and -3 (p&lt; 0.001). Absence of claudin-1, -3 and -5 was associated with urethral infiltration (p=0.03 and p=0.02 and p=0.019, respectively). Loss of claudin -1 and -3 was also associated with perineural invasion (p=0.05 and p=0.02, respectively). Conclusion: Our data provides the first evidence that claudins expression was decreased in areas of invasion and infiltration and could be related to evolution and prognosis of these tumours.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4231. doi:1538-7445.AM2012-4231
Abstract 4234: A genome-wide RNAi screen implicates histone deacetylases as a therapeutic target for osteosarcoma
Authors: Perry Jennifer A. , Orkin Stuart 
Published: August 2012

Abstract
Osteosarcoma, the most common primary malignancy of bone, is an aggressive cancer occurring predominantly in children and adolescents. Studies of familial cancer syndromes and sporadic cases have strongly implicated both p53 and pRb in osteosarcoma tumorigenesis. Thus, our lab created a fully penetrant mouse model of osteosarcoma based on the osteoblast-specific deletion of p53 and pRb. This model faithfully recapitulates the defining features of human OS, including pathology, metastatic behavior, and cytogenetic complexity and shares a transcriptional profile with the human disease. Using a genome-wide shRNA screen, we have identified gene products whose inhibition synergizes with p53 and pRb deletion to kill osteosarcoma cells. This screen identified genes that are required for proliferation and survival of osteosarcoma cell lines in an unbiased fashion. The screen identified a number of druggable gene products and pathways, including members of the HDAC family of histone deacetylases. Follow-up studies with selective chemical HDAC inhibitors and shRNAs against individual HDACs demonstrate that osteosarcoma cells are vulnerable to HDAC1, 2, 3, 5 and 7 inhibition. Selective inhibition of HDACs has emerged as a promising avenue toward cancer therapy, therefore we look to understand if and how HDAC inhibition can be used as a therapeutic approach to treating osteosarcoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4234. doi:1538-7445.AM2012-4234
Abstract 4236: Comparison of optical imaging approaches in 2D and 3D in disseminated mouse tumor models
Authors: Baugher Meridith , Castorena Jeremy , Baranski Jeni , Shaw Darren , Leopold Dick , Trachet Erin , Lister Deanne , McConville Patrick 
Published: August 2012

Abstract
Introduction: Optical imaging allows staging and tracking of multiple tumors in disseminated tumor models and to this end, bioluminescence (BLI) imaging has been the most common approach. While BLI is cost effective and quantitative, it requires luciferase-engineered tumor lines, which have the disadvantages of time and uncertainty associated with transfection, as well as potential phenotype change in the engineered line, compared with the parent. Exogenous fluorescence probes preferentially activated by tumors provide a similar efficient optical imaging means to tumor burden tracking in these models, directly in any tumor lines of interest. This methods also allows 3D imaging through new tomographic optical imaging technologies. In this work, BLI and activated fluorescent probe imaging were used in a luciferase-expressing Raji-luc human Burkitt's lymphoma model and an M-NFS-60 mouse leukemia model. 2D fluorescence reflectance imaging was also compared to 3D tomographic imaging to determine additional utility of the 3D imaging approach. Methods: Raji-luc lymphoma cells were transfected to express luciferase using a lentiviral vector transfection method. Raji-luc cells (1x107 cells in 100µl PBS) were injected IV in CB-17 mice on Day 0. In CD-1 mice, M-NFS-60 leukemia cells (1x107 cells in 100µl PBS) were injected IP. Bioluminescence scans were used to determine the distribution of light throughout the body immediately following implantation. In vivo and ex vivo bioluminescence imaging was used to localize tumor signals and determine incidence and tumor growth. Both cathepsin- (ProSense) and MMP- (MMPSense) activated fluorescent probes were injected IV 24h prior to fluorescence reflectance and fluorescence molecular tomographic imaging. Results and Discussion: Bioluminescence imaging of intravenously injected of Raji-luc cells from one to four weeks after inoculation showed a high incidence of tumor growth at sites including hind limbs, spine, and brain in addition to lung and to a lesser extent, the axillary lymph nodes and sternum. Fluorescence imaging with tumor activated probes provided a measure of disseminated tumor burden, but had the disadvantage of normal tissue background, compared with BLI where there was inherently no normal tissue background. Fluorescence molecular tomographic imaging provided a quantitative advantage over 2D fluorescence reflectance. Activated fluorescent probe imaging provides a viable means for imaging in disseminated tumor models without the need for engineered cell lines.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4236. doi:1538-7445.AM2012-4236