bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1114: IGF-II regulates the expression of estrogen receptor beta 5: Role in the survival disparity between African-American and Caucasian women with breast cancer
Authors: O'Bannon Chane’ , Hamilton Nalo , De Leon Daisy 
Published: June 2012

Abstract
African American (AA) women with breast cancer are more likely to be diagnosed at a more advanced stage of the disease, have a higher recurrence rate and a poorer prognosis than Caucasian (CA) women. African American women are more often diagnosed with high-grade breast tumors at an earlier age most of which are negative for the estrogen and progesterone receptors. These factors result in a higher mortality rate among AA patients. This survival disparity can be attributed to socieconomic status and other related factors, however there are biological factors that may also be involved. The insulin-like growth factor II (IGF-II) plays a crucial role in fetal and cancer development by signaling through the IGF-I receptor (IGF-IR), the insulin receptor (InsR) and crosstalk with the estrogen receptor alpha (ER-α). Compared to CA women, AA women have an increased level of proIGF-II expression in breast tissues and higher signaling activation through the IGF-1 and InsRs. Since the estrogen receptor beta (ER-β) is also expressed in a majority of breast cancers we propose that IGF-II may also activate the ER-β signaling pathway. ER-β has 5 isoforms of which ER-β5 is the most abundantly expressed among AA women with breast cancer and it is associated with a poor prognosis and decreased survival. Thus, our hypothesis is that IGF-II activation of the ER-β5 contributes to the survival disparity between AA women and CA women. To test this hypothesis we analyzed the expression of ER-β5 in AA and CA breast cancer cell lines by western blot, siRNA analysis and IGF-II stimulation. IGF-II not only modulated the phosphorylation of ER-β5, but it also promoted the translocation of ER-β5 to different organelles. Thus, we conclude that ER-β5 may contribute to the survival disparity among AA breast cancer patients since ER-β5 impairs the inhibitory effect of other ER-β isoforms.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1114. doi:10.1158/1538-7445.AM2011-1114
Abstract 1121: A novel KIF5B-ALK fusion gene variant with transforming potentials in non-small cell lung cancer
Authors: Wong Daisy Wing-Sze , Leung Elaine Lai-Han , Wong Sunny Kit-Man , Tin Vicky Pui-Chi , Wong Maria Pik 
Published: June 2012

Abstract
BACKGROUND: The anaplastic lymphoma kinase (ALK) gene is frequently involved in chromosomal translocations resulting in fusion genes with different partners found in various lympho-proliferative conditions. In non-small cell lung cancers (NSCLC), the fusion protein encoded by echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene was recently reported to confer oncogenic properties. This study aimed to identify other possible ALK fusion genes and analyze their oncogenic potentials. METHODS: Immunohistochemical analysis was used to screen for aberrant ALK expression in primary NSCLC. 5’ rapid amplification of cDNA ends was used to screen for potential novel 5’ fusion partners of ALK other than EML4-ALK. Reverse transcription polymerase chain reaction and fluorescence in situ hybridization were used to confirm the identity of 5’fusion partner. The genomic breakpoint was verified using genomic sequencing. Overexpression of the novel ALK fusion gene and variants 3a and 3b of EML4-ALK was performed to assess downstream signaling and functional effects. RESULTS: We identified a novel gene resulting from fusion of kinesin family member 5B (KIF5B) exon 15 to ALK exon 20 in a primary lung adenocarcinoma. Western blot of the clinical tumor tissues showed expression of a protein whose size correlated with that of the predicted KIF5B-ALK. Overexpression of KIF5B-ALK in mammalian cells led to STAT3 and AKT activation, enhanced cell proliferation, migration and invasion. These oncogenic properties were comparable to those of EML4-ALK variants. CONCLUSIONS: The discovery of the novel KIF5B-ALK variant with transforming functions further consolidates the role of aberrant ALK signaling in lung carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1121. doi:10.1158/1538-7445.AM2011-1121
Abstract 1127: Lack of MAPK activation in significant number of uveal melanomas with somatic mutation in GNAQ and GNA11
Authors: Abdel-Rahman Mohamed H. , Boru Getachew , Cebulla Colleen M. , Christopher Benjamin , Massengill James B. , Frederick Davidorf H. 
Published: June 2012

Abstract
Purpose: The aims of this study were to investigate the correlation between MAPK activation and somatic mutation in GNAQ and GNA11 genes in uveal melanoma (UM) and to investigate the potential utility of MEK inhibition as a target for therapy of UM in tumors with GNAQ and GNA11 mutations.
Methods: Sequencing and restriction fragment length polymorphism (RFLP) were utilized for detection of activating mutations in codon 209 of the GNAQ and GNA11 genes in 44 primary UMs. The expression of phospho p44/42 MAPK (pERK1/2) was assessed by immunohistochemistry in 44 UMs. In addition, the expression of pERK1/2 and pMEK 1/2 were studied using Western blot analysis in 17 primary UMs (14 with GNAQ or GNA11 mutations) and five UM cell lines (C918, 92.1, OCM3, MEL202, MEL270). Three of the UM cell lines (92.1, MEL202 and MEL270) have GNAQ codon 209 mutations. The effect of three different selective MEK inhibitors (U126, PD98059 and PD184352) on UM cell proliferation and apoptosis were studied.
Results: The majority (30/44, 68.2%) of the primary UM tumors showed somatic mutation in codon 209 of either the GNAQ or the GNA11 genes. With the exception of one tumor, the mutations in either gene were mutually exclusive. Of the 30 UM primary tumors with GNAQ and/or GNA11 mutation, pERK1/2 expression was absent in 26.7%, weak in 33.3%, moderate in 23.3%, and high in only 16.7%. Western blot showed no pMEK1/2 expression in 6/14 (42.9%) of UM with either GNAQ or GNA11 mutations. Two of the UM cell lines with GNAQ mutation showed weak pERK1/2 expression. In addition one showed no pMEK1/2 expression while the other one showed very weak pMEK1/2 expression. Selective MEK inhibitors slowed UM cell proliferation but didn't induce significant apoptosis in UM cell lines regardless of GNAQ status.
Conclusions: Our results indicate that a significant number of UM with somatic mutations in GNAQ or GNA11 showed no MAPK pathway activation. In UM, MEK inhibition is mostly cytostatic suggesting that selective MEK inhibitors alone may not be sufficient to control UM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1127. doi:10.1158/1538-7445.AM2011-1127
Abstract 1142: A specific miRNA signature characterizes metastasis in renal cell carcinoma
Authors: Heinzelmann Joana , Unrein Andre , Sanjmyatav Jimsgene , Wunderlich Heiko , Grimm Marc-Oliver , Junker Kerstin 
Published: June 2012

Abstract
Background: MicroRNAs (miRNAs) as small non-coding RNAs are regulators of gene expression in tumor development and progression. However, its specific role in metastasis of clear cell renal cell carcinoma (ccRCC) is almost unknown. Therefore, we aimed in defining specific miRNA expression pattern of metastatic ccRCC and identifying cellular functions of specific miRNAs deregulated in metastatic process.
Methods: We isolated total RNA of 29 ccRCC samples (including 13 non-metastatic and 16 metastatic tumors) and from 16 metastases using snap frozen tissue. Single channel microarray analysis was performed for a global miRNA expression profiling in 22 ccRCC samples. The validation of the differentially expressed miRNAs in metastatic ccRCC compared to non-metastatic tumor samples and furthermore in metastases of ccRCC was performed by using qRT-PCR.
Results: We identified a miRNA expression pattern that distinguishes between metastatic and non-metastatic ccRCC. Furthermore, we found a group of miRNAs with altered expression in early-metastatic compared to late metastatic and non-metastatic tumors. These microarray results were verified by qRT-PCR. By analyzing the expression of four of these differentially expressed miRNAs (26a, 30c, 126, 451) in metastases tissue by qRT-PCR we detected the same expression behavior as in the primary metastatic tumor counterparts.
Conclusion: Our findings indicate that miRNAs are involved in the metastatic process. Thus, we were able to identify a specific miRNA expression pattern in metastatic ccRCC. Metastases of ccRCC are characterized by the same expression value of specific miRNAs as the primary metastatic tumor tissue. These investigations showed that specific miRNAs are possible prognostic markers for metastatic disease in RCC patients. Further studies have to define the functional role of the miRNAs in the metastatic process.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1142. doi:10.1158/1538-7445.AM2011-1142
Abstract 1147: microRNA expression profiling in cisplatin resistant human non-small cell lung cancer cell lines
Authors: Suzuki Toshihiro , Irisawa Ai , Nishio Kazuto , Togawa Tadayasu , Sakuraba Hitoshi 
Published: June 2012

Abstract
Cisplatin combination chemotherapy is one of the important treatments for many cancers including lung cancer. Despite impressive initial clinical responses, the majority of patients eventually develop some degree of resistance to cisplatin-based therapy. To understand the clinically relevant mechanisms of resistance, many studies have been aimed at clarifying the biochemical/molecular alterations of cisplatin-resistant cells. However, cellular resistance mechanisms of cisplatin are still unclear. MicroRNA (miRNA) is small noncoding RNA that function to control gene expression. These small RNAs have been shown to contribute to the control of cell growth, differentiation and apoptosis, important features related to cancer development progression and sensitivity of chemotherapy. However, the interaction between the development of cisplatin resistance and miRNA has not been previously explored.
In this study we utilized a miRNA array to compare the differentially expressed miRNAs in cisplatin-resistant cell lines, PC-9/CPr and PC-14/CPr and their parental cell lines, PC-9 and PC-14. We verified that miR-7, miR-106 and miR-181 were up-regulated in cisplatin-resistant non-small cell lung cancer cells by means of real-time PCR and discusses the potential of these miRNAs as biomarkers for cisplatin sensitivity in combination chemotherapy. We further investigated the role and mechanisms of miR-181 in cisplatin resistance. We found that specific miR-181 precursor (Pre-miR-181) transfection significantly acquired cisplatin resistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1147. doi:10.1158/1538-7445.AM2011-1147
Abstract 1148: Development and validation of a second generation microRNA-based assay for diagnosing tumor tissue origin
Authors: Rosenwald Shai , Edmonston Tina , Barshack Iris , Feinmesser Meora , Huszar Monica , Mueller Wolf , Fogt Franz , Spector Yael , Aharonov Ranit , Meiri Eti 
Published: June 2012

Abstract
Background: Cancer of unknown primary (CUP) constitutes 3%-5% of all newly diagnosed cancer cases. It presents a major diagnostic challenge due to the therapeutic implications of the tissue origin of the cancer. MicroRNAs are a family of non-coding, regulatory RNA genes that are involved in development, differentiation and cell cycle and were shown to be involved in oncogenesis. MicroRNAs are highly tissue-specific and therefore ideal candidates for CUP diagnosis. We have previously presented a biologically-motivated classification assay to identify the tissue of origin using a set of 48 microRNAs measured on a qRT-PCR platform. This assay can differentiate 25 different tumor types from 17 origins. We present here the development and validation of a second generation assay that can identify 42 different tumor types using a custom array platform.
Methods: Over 1200 primary and metastatic tumor FFPE samples were used for the training and development of the assay. High-quality RNA, including the well-preserved microRNA fraction, was extracted from the FFPE blocks using proprietary protocols. Expression levels of all known and additional Rosetta's proprietary microRNAs were profiled using a custom array platform. A combination of a decision tree classifier with a KNN classifier was developed to identify the tissue of origin based on the microRNA expression patterns. A validation set of more than 500 independent FFPE samples of primary tumors and metastases was analyzed blindly and classified using the developed assay.
Results: The assay is able to identify 42 tumor types based on the expression of only several dozens microRNAs with very high accuracy. Based on the validation set, the sensitivity (positive agreement) for identifying the tumor origin is 85%. In more than 80% of the cases, a single answer was reported, and for these cases, the sensitivity is 90%.
Conclusions: Previous studies have highlighted the tissue-specificity of microRNA expression, and have demonstrated their potential use for classification of human malignancies. An assay utilizing microRNA expression in paraffin-embedded tissue for identification of the tissue of origin was previously developed. Here we present the development and the performance of a second generation assay, designed to identify 42 tumor types. This assay will provide an important new tool for diagnosing tumor tissue origin.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1148. doi:10.1158/1538-7445.AM2011-1148
Abstract 1153: Nanoparticle delivery of microRNA-107 reduces the tumorigenicity of head and neck squamous carcinoma (HNSCC)
Authors: Piao Longzhu , Zhang Manchao , Su Tizhi , Bhave Sanjay , Li Hong , Teknos Theodoros N. , Pan Quintin 
Published: June 2012

Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The 5-year survival rate of HNSCC has remained stagnant despite advances in the clinical management of this disease. Understanding the molecular pathways that lead to aggressive HNSCC is crucial to identify new “druggable” targets for anti-cancer drug development. Recently, our laboratory showed that miR-107 is significantly reduced in primary HNSCC tumors and HNSCC cell lines. Ectopic expression of miR-107 in CAL-27 HNSCC cells significantly inhibited cell proliferation, DNA replication, clonogenic survival, and tumor growth in nude mice. Our data demonstrate the potential application of miR-107 as a novel anti-cancer therapeutic for HNSCC. In this study, we determine the efficacy of miR-107 encapsulated nanoparticles (NP-miR-107) in a xenograft model of HNSCC. NP-miR-107 was successfully formulated by ethanol injection method. The particle size of NP-miR-107 was 47.8 ± 3.5 nm and zeta potential was +12.1 mV. NP-miR-107 significantly retarded (57.6% inhibition, p&lt;0.02) tumor growth of CAL27 HNSCC tumors compared to NP-miR-control; tumor volume of 340.6 ± 51.6 mm3 and 804.1 ± 181.6 mm3 for the NP-miR-107 group and the NP-miR-control group, respectively. Moreover, Kaplan-Meir analysis showed a survival advantage for the NP-miR-107 treatment group (p=0.039). Our results demonstrate that our nanoparticles are an effective carrier approach to deliver therapeutic miRs to tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1153. doi:10.1158/1538-7445.AM2011-1153
Abstract 1165: PKC epsilon modulated miRNAs profiling during development of prostate cancer in transgenic adenocarcinoma of mouse prostate model
Authors: Hafeez Bilal B. , Zhong Weixiong , Verma Ajit K. 
Published: June 2012

Abstract
MicroRNAs (miRNAs) are small nucleotides endogenously expressed non-coding RNAs that have been implicated in a wide range of cellular processes. Dysregulation of miRNA expression has been identified in a number of cancers including prostate. Evidence indicates that miRNAs are involved in prostate cancer (PCa) development and metastasis via activating several oncogenes and inhibiting tumor suppressor genes. However, the molecules’ targeting these microRNAs is poorly understood. Protein kinase C epsilon (PKC∈), a novel PKC isoforms, is over-expressed in both human and mouse PCa. We have previously shown that PKC∈ expression correlates with the aggressiveness of PCa. We generated PKC∈-deleted TRAMP mice by crossbreeding transgenic adenocarcinoma of mouse prostate (TRAMP) (TG//WT) mice with PKC∈ knock out (TG//KO) mice. Sixteen weeks old TG Wild-type (TG//WT), TG//PKC∈ Heterozygous (TG//Het) and TG//PKC∈ KO (TG//KO) mice were evaluated for PCa development and metastasis. We observed that deletion of PKC∈ in TRAMP mice inhibited PCa development and metastasis as observed by CT-PET scanning, tumor weight and histopathology of livers, lungs, kidneys and lymph nodes. To determine the clues about the miRNAs, which are modulated by PKC∈, we performed global miRNA profiling in prostate tissues of TG//WT and TG//KO mice by using miRNA Microarray chip containing transcripts of 750 miRNAs (Listed in Sanger miRBase Release 15.0). We observed a significant down-regulation of 7 miRNAs (miRNA762, miR125b-5p, miR-16, miR-467a-1, miR-574-3p, miRNA-451 and miR-669f) and up-regulation of 6 miRNAs (miR-1187, miR-1195, miR-2133, miR-574-5p, miR-690 and miR-709) in prostate tissues of TG//KO mice compared to TG//WT mice. It has been reported that miRNA-451 plays a role in the induction of mTOR signaling, which is well documented for its role in human PCa progression. Importantly, we observed 20-fold decreased expression of miRNA-451 in prostate tissues of TG//KO mice compared to TG//WT mice. It has been reported that up-regulation of miRNA-709 inhibits expression of BORIS, a tumor promoting transcription factor. We observed two fold induction of miRNA-709 in TG//KO mice. Taken together these finding suggest that PKC∈ plays an important role in PCa development and metastasis via up-regulating oncogenic miRNA and down regulating tumor suppressing miRNA. We suggest that these miRNAs modulated by PKC∈ have role in PCa development and metastasis. However further studies warranted to understand the functional implication of these miRNAs in human PCa. (Support: NIH Grant, CA35368).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1165. doi:10.1158/1538-7445.AM2011-1165
Abstract 1179: Global increase in ultraconserved non-coding RNA expression in pancreatic adenocarcinoma
Authors: Azevedo Ana Clara P. , Jiang Jinmai , Lee Eun Joo , Gusev Yuriy , Allard David , Tuveson David A. , Calin George A. , Schmittgen Thomas D. 
Published: June 2012

Abstract
Transcribed ultraconserved regions (T-UCRs) are a class of 482 non-coding RNAs with 100% sequence conservation among human, rat and mouse genomes. T-UCRs are differentially expressed in colorectal cancer, leukemia and neuroblastoma, however their expression in pancreatic adenocarcinoma (PDAC) has not been studied. We used qPCR to profile all 482 T-UCRs in a variety of pancreatic cancer specimens including pancreatic adenocarcinoma, chronic pancreatitis and benign/normal pancreas and in the pancreas of genetically engineered mice (P48+/Cre;LSL-KRASG12D and PDX-1-Cre;LSL-KRASG12D). Of the 257 expressed T-UCRs in the human pancreas tissues, 166 were differentially expressed in the PDAC compared to normal and adjacent benign pancreas (≥ 1.5 fold; p &lt; 0.05). In the genetically engineered mice, 29% of the expressed T-UCRs were differentially expressed in the pancreas of old P48+/Cre;LSL-KRASG12D mice (mean age, 231 days) compared to control. In both the patient and mouse data, the vast majority of the differentially expressed T-UCRs increased with disease progression. Interestingly, the expression pattern among groups of two T-UCRs closely correlated with each other. This was to be expected for T-UCRs directly adjacent to one another in the genome, but surprisingly we found strong correlations among T-UCRs that are located on different chromosomes. This suggests that large groups of T-UCRs are co-expressed in PDAC. In vitro models that simulate the desmoplastic reaction have been shown it to alter gene expression in PDAC. In an effort to understand the mechanism responsible for this global increase in expression in PDAC, the T-UCRs were profiled in normal pancreas (HPDE) cells that were cultured on the extracellular matrix deposited by Panc-1 cells. Ninety-one T-UCRs were increased in the HPDE co-cultures (fold-change &gt; 1.5, p&lt; 0.05). We report a global increase in the T-UCR expression in PDAC tissues, the pancreas of genetically engineered mice and in HPDE cells co-cultured with Panc-1 cells. The ability of the MAP kinase and TGF-β signaling pathways to regulate T-UCR expression will be investigated in the future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1179. doi:10.1158/1538-7445.AM2011-1179