bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3041: Differential expression of microRNAs between sporadic and hereditary nonmedullary thyroid cancer
Authors: Xiong Yin , Kebebew Electron 
Published: February 2011

Abstract
Background: MicroRNAs (miRNAs) are small noncoding RNAs, which regulate gene expression and play a significant role in many biological processes, including tumorigenesis. Approximately 5% of all non-medullary thyroid cancers are hereditary and may have more aggressive tumor biology than sporadic cases. The susceptibility gene for hereditary non-medullary thyroid cancer has not been identified. We hypothesized that miRNA expression profile between sporadic and hereditary non-medullary thyroid cancer are different and could help identify candidate suspceptibility genes.
Methods: Twenty nine tumor tissue samples were analyzed using miRNA microarrays for 1190 miRNAs with genotyping for common somatic mutations (BRAF V600E, NRAS, KRAS, RET/PTC1, RET/PTC3) present in non-medullary thyroid cancer. The samples were matched for age, gender and stage of cancer. Differences in miRNA expression profile were validated by quantitative RT-PCR and correlated with clinicopathologic data.
Results: We found 5 miRNAs significantly differentially expressed between sporadic and hereditary non-medullary thyroid cancer cases; two miRNAs were upregulated and three miRNAs were downregulated in hereditary non-medullary thyroid cancer. Two miRNAs were validated by quantitative RT-PCR; miR-20a (p=0.025) and miR-886-3p (p=0.028) were upregulated in hereditary non-medullary thyroid cancer samples. Higher expression level of miR-886-3p was significantly associated with higher TNM stage (p&lt;0.05). There was no significant difference in somatic mutation rates between sporadic and hereditary cases (9 BRAF V600E, 1 RET/PTC1), and there was no significant difference in miR-20a and miR-886-3p expression by mutation status.
Conclusions: To our knowledge, this is the first study to show different expression profile of miRNAs between sporadic and hereditary cancer using non-medullary thyroid cancer as a model. These differences in miRNAs may have an important role in tumor cell biology and clinical manifestation of non-medullary thyroid cancer in sporadic versus hereditary cases.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3041.
Abstract 3044: Enzymatic bioluminescence assay for microRNA quantification
Authors: Sun Ye , Golovlev Val 
Published: February 2011

Abstract
A quantitative bioluminescence assay (qBLA) for rapid and sensitive microRNA expression analysis was developed. The qBLA detects the release of inorganic pyrophosphate (PPi) when target microRNA hybridizes with its complementary oligonucleotide template and is extended by DNA polymerization reaction. The luminescence detection of PPi is performed by converting PPi to ATP by ATP-sulfurylase that provides energy for luciferase to oxidize luciferin and produce light. This approach is faster, simpler, and less expensive than microarrays and real-time PCR for microRNA detection. It requires less reagents and can be performed at a constant temperature without thermal cycling. The experimental results indicate a broad dynamic range for microRNA quantification. Strategies for isothermal amplification of microRNA targets with different oligonucleotide template designs were studied, which illustrate the improved sensitivity and specificity. In this report, the real-time and end-point microRNA detection by qBLA is presented and discussed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3044.
Abstract 3045: Identification of specific microRNA signatures in VHL-functional and VHL-silenced renal cell carcinoma cell lines
Authors: Kurisetty Vittal , JeBailey Lellean , Luongo Tony , Merchan Jaime R. 
Published: February 2011

Abstract
Objective& Background: Renal cell carcinoma is the most common renal malignancy in adults. Up to 70% of clear cell renal cancers have VHL silencing either because of gene mutation or methylation. MicroRNAs are a class of small non-coding RNAs that control gene expression by targeting mRNAs and trigger either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases including cancer. This study set out to investigate the influences of VHL status and the ensuing differences in miRNA profiles and biological/phenotypic effects in renal carcinoma cell lines. Methods: Normal cell line, HREC, and renal cancer cell lines that are VHL-ve cell lines, A498, A704, 786.O, and 786.O. Vec, VHL+ve cell line,786.O.VHL, VHL-WT cell line, ACHN and Caki.1 and VHL-CH3 cell line, KV6 were used for the VHL-specific genome wide miRNA profiling. miRNAs were extracted, in triplicate, from the above cell lines at 48 hrs time point by using miRVana miRNA isolation kit (Ambion). The extracted miRNAs were subjected to analysis by MEGAPlex RT primers and MEGAPlex Pre-Amp primers, followed by loading them to TaqMan Human miRNA microarrays v2.0 (Human Array A/B (Applied Biosystems). Resulting miRNAs were analysed further by using the RealTimeStatMiner v3.0 software (Integromics) followed by GeneGO pathways analysis. Results: We show that approximately 577 miRNAs were altered in human kidney cancer. 270 miRNAs and 180 miRNAs were upregulated and down-regulated in cancer cell lines when compared against normal HREC cell line, respectively. Upon analysis of differentially expressed miRNAs in RCC cell lines based on VHL status, we found that 7 miRNAs were differentially upregulated in VHL wild type RCC cells. In VHL mutant cell lines, 5 miRNAs and 6 miRNAs were differentially up and down regulated, respectively, while in RCC cell lines with wild type, but silenced (methylated) VHL, 7 and 10 miRNAs were differentially up and down regulated, respectively. Target prediction and microRNA enrichment analysis suggested that the differentially expressed miRNAs are involved in regulation of HIF, angiogenesis, invasion & metastasis, extracellular matrix degradation, EMT phenomenon, metabolism and apoptosis pathways. Conclusion: This MicroRNome analysis reveals a specific spectrum of hypoxia, angiogenesis, tumor metabolism, metastasis, cell cycle and apoptotic specific miRNAs. In vitro experiments to characterize the biological significance differential miRNA expression profiles on different steps of tumorigenesis and tumor progression are underway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3045.
Abstract 305: Frequent PIK3R1 somatic mutations promote oncogenic signaling
Authors: Jaiswal Bijay S. , Janakiraman Vasantharajan , Chaudhuri Subhra , Stern Howard M. , Kljavin Noelyn M. , Wang Weiru , Kan Zhengyan , Bowman Krista , Wu Jiansheng , Kaminker Joshua , Yue Peng , de Sauvage Frederic J. , Backer Jonathan , Seshagiri Somasekar 
Published: February 2011

Abstract
We performed a systematic analysis of human fresh frozen tumors for somatic mutations in the RAS-effector pathways and have identified frequent mutations (&gt;8%) in PIK3R1 (p85α) regulatory subunit of PI3K (p110) enzyme complex. Mutations in other members of the PI3K regulatory subunits, along with mutations in additional components of the pathway were also identified in this study. An integrated analysis of somatic mutations and genomic copy number variations identified by comparative genome hybridization revealed distinct mutation patterns across tumor types. In order to understand the functional consequence of p85α mutations, we generated mutant p85α constructs and tested them for activity in biochemical and cellular assays. In this studies, we found that all the mutants that contain an intact p110-binding domain were able to interact with p110α, p110β and p110δ. Also, all these mutants stabilized expression of p110 class IA members when tested in pan-p85 null fibroblasts, indicating that the p110-stabilizing activity of p85 mutants was still intact. However, in un-stimulated cells, some of the p85α mutants were not as effective as wild-type p85α in inhibiting the activity of p110. Furthermore, these p85α somatic mutants activated AKT signaling leading to cell survival. Additionally, cells expressing the p85α mutants when transplanted in vivo promote a leukemia-like disease leading to decreased overall survival of the mice compared to wild-type p85α. These data demonstrate an alternate mechanism for activation of class IA PI3Ks in tumors through somatic mutations in p85α that abrogates its p110 regulatory activity while maintaining its p110-stabilizing activity. The frequent occurrence of p85α mutations and its ability to promote survival signaling suggest that tumors with such mutations are likely candidates for inhibitors that target the components of the PI3K pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 305.
Abstract 3054: MicroRNA expression profile in cutaneous melanoma: miR-17-92 cluster is a progression and prognostic marker
Authors: Kim Donghwa , Zhao Jianjun , Kong William , Smalley Keiran S. , Messina Jane L. , Weber Jeffrey S. , Cheng Jin Q. 
Published: February 2011

Abstract
MicroRNAs (miRNA) represent a novel class of RNAs that play important roles in cell survival, proliferation, differentiation and angiogenesis through negative regulation of protein-coding genes. Deregulation of miRNAs has been detected in various types of human malignancies. Some miRNAs are implicated in diagnosis, prognosis, treatment response and pathogenesis. However, aberrant miRNA expression and its pathologic significance in human melanoma have not been well documented. Here, we report on the miRNA expression profile of human cutaneous melanoma as well as melanoma cell lines. Of 650 miRNAs examined, at least 28 miRNAs were significantly deregulated in melanoma compared to normal skin and primary melanocytes, with the most common aberrantly expressed miRNAs being miR-17-92 cluster, miR-21, miR-146a/b. miR-148a/b, miR-126, miR-606, and miR-655. Notably, miRNA expression signatures could stratify patients into 2 groups (e.g., good and poor prognosis). Further analysis revealed that elevated levels of the miR17-92 cluster are associated with tumor progression and shorter overall survival. Our results suggest that miRNAs may be a useful new biomarker for and be a therapeutic target in cutaneous melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3054.
Abstract 3055: Wnt inhibitory factor 1 inhibits cervical cancer cell growth in vitro
Authors: Ramachandran Ilangovan , Ramalingam Satish , Natarajan Gopalan , Mills Wilbur K. , Anant Shrikant , Reis Antonio M.C. , Queimado Lurdes 
Published: February 2011

Abstract
Background and Purpose: Cervical cancer is one of the most common malignancies and major causes of death in women worldwide. Aberrant activation of Wnt/β-catenin pathway is associated with various cancers including cervical cancer. Mutations within intracellular components of the Wnt pathway are rare in cervical cancer. We hypothesize that alterations in secreted Wnt antagonists might play a major role in Wnt activation. Here we characterize the status of the Wnt inhibitory factor 1 (WIF1) in cervical cancer cell lines and determined the in vitro effects of WIF1 on cervical cancer cells. Methods: Three cervical cancer cell lines (HeLa, C33A and CC1) were treated with the demethylating agent 5-aza-2′-deoxycytidine (DAC) for 4 days, total RNA was isolated and real-time RT-PCR was performed to determine WIF1 mRNA expression. HeLa cells were transfected simultaneously with either pCI blast (empty vector) or pCI blast-WIF1 using LipoD293 transfection reagent and assessed for cell proliferation and apoptosis. Cell proliferation was determined at different time intervals (24, 48, 72 and 96 h) by hexosaminidase assay. Cell cycle analysis was performed after 72 h by flow cytometry using FACSCalibur analyzer. Caspase 3/7 activity was measured using the Apo-one Homogeneous Caspase-3/7 Assay kit. Results: We demonstrated that WIF1 is down-regulated in cervical cancer cells. Treatment with DAC caused a significant increase in WIF1 mRNA expression in all the cell lines tested compared with vehicle treatment. Furthermore, transfection with a plasmid expressing WIF1 significantly inhibited cervical cancer cell proliferation at all time points studied. To probe the possible mechanisms involved in WIF1 cell growth inhibition, we performed cell cycle analysis and caspase 3/7 assay. Interestingly, cell cycle analysis demonstrated that transfection with WIF1 significantly increased the G2-M cell population and the number of apoptotic cells. In addition, WIF1 significantly induced caspase 3/7 activity suggesting that WIF1 induced apoptosis is mediated through caspase 3/7 activation. Conclusions: Our data suggests that WIF1 is silenced in cervical cancer cells and WIF1 restoration inhibits cervical cancer cell growth by inducing G2-M arrest and apoptosis. This study emphasizes the importance of WIF1 as a potential therapeutic strategy in the treatment of cervical cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3055.
Abstract 3058: ADAMTS9 inhibits angiogenesis and induces apoptosis in nasopharyngeal carcinoma
Authors: Lung Hong Lok , Lo Paulisally Hau Yi , Cheung Arthur Kwok Leung , Apte Suneel S. , Lung Maria Li 
Published: February 2011

Abstract
Background and aims: A disintegrin-like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9), a gene mapping to 3p14.2, has been shown to be silenced by promoter hypermethylation in nasopharyngeal carcinoma (NPC). The ADAMTS family consists of 19 secretion protein members consisting of a disintegrin domain, metalloproteinase domain, and different numbers of thrombospondin type 1 motifs. ADAMTS9 encodes a member of a large family of 19 metalloproteases involved in maturation of precursor proteins, extracellular matrix remodeling, cell migration, and inhibition of angiogenesis. Although the related matrix metalloproteases and ADAM proteases have been clearly implicated in tumor progression and angiogenesis, the role of ADAMTS proteases in cancer is less clearly defined. In the present study, we investigated the in vivo and in vitro functional roles of ADAMTS9 in angiogenesis of NPC.
Methods: To examine the antigiogenic activity of ADAMTS9 in NPC, the in vivo gel plug and in vitro tube formation assays were performed using a tetracycline-regulated expression vector in the present study.
Results: Here we show that when incubated with conditional media from the ADAMTS9 stable transfectant, the human umbilical vein endothelial cells (HUVEC) showed a dramatic decrease of tube formation ability. When the gel plugs used for the in vivo angiogenesis in the above section were stained with H&E, we observed that the numbers of apoptotic cells in the ADAMTS9 stable transfectant were dramatically increased. The numbers of apoptotic cells were also increased when growing in the absence of serum. Conclusions: Taken together, these studies indicate that ADAMTS9 is an important candidate tumor suppressor gene in NPC, which might mediate its tumor suppressive effects through the anti-angiogenic and pro-apoptotic mechanisms.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3058.
Abstract 3061: Tumor suppressive and angiogenic role of THSD1 in esophageal squamous cell carcinoma and nasopharyngeal carcinoma
Authors: Ko Josephine Mun Yee , Cheung Arthur KL , Lung Maria Li 
Published: February 2011

Abstract
Background and aims: Loss of chromosome 13q regions is a frequent event in both esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). By microcell-mediated chromosome transfer, chromosome 13 was demonstrated to play a significant tumor suppressive role in both ESCC and NPC in our laboratory. THSD1 is a novel candidate tumor suppressor gene (TSG) previously identified by microarray differential gene expression profiling. It encodes a transmembrane molecule containing a thrombospondin type 1 repeat (TSR), which may be involved in cell adhesion and angiogenesis. Proteins possessing the TSR, such as thrombospondin-1 (Tsp1), ADAM metallopeptidase with thrombospondin type 1 motif, 1 (ADAMTS1) and ADAMTS8, regulate angiogenesis. We previously showed that the mechanisms for THSD1 silencing in ESCC involved loss of heterozygosity and promoter hypermethylation. Our preliminary data indicated transfection of wild type THSD1 into an ESCC cell line, SLMT-1, resulted in significant reduction of colony-forming ability, hence providing functional evidence for its growth suppressive activity. The current study aims to examine if THSD1 plays a significant tumor suppressive role in the nude mouse tumorigenicity assay and to elucidate the mechanism(s) involved in tumor suppression. Methods: Transfection by lipofection of both variants of THSD1 into the ESCC SLMT-1 and NPC HONE1-2 cell lines was used to study the effect of THSD1 in tumor suppression and anti-angiogenesis. Results: Quantitative RT-PCR detected down-regulation of THSD1 expression in 36.4% (16/44) primary ESCC and 54.5% (12/22) NPC tissues. Nude mouse tumorigenicity assays showed tumor suppression in THSD1 over-expressing clones in both ESCC and NPC. Flow cytometry analysis showed over-expression of THSD1 resulted in endoreplication. Tube formation assay with HUVEC is underway to examine the angiogenic role of THSD1. Conclusions: THSD1 is a promising candidate TSG in both ESCC and NPC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3061.
Abstract 3065: Loss of ARL11 function promotes growth of in situ neoplasia by activating the ras pathway
Authors: Lee Sooyong , Lee Sangkyou , Bondaruk Jolanta , Wang Hua , Zhang Shizhen , Bar-Eli Menashe , Black Peter , Dinney Colin , Grossman H. Barton , Knowles Margaret , Baggerley Keith , Czerniak Bogdan 
Published: February 2011

Abstract
Our previously reported whole-organ genome-wide mapping studies of bladder cancer provided evidence that a new class of genes, referred to as forerunner (FR) genes (ITM2B, P2RY5, GPR38 and ARL11), located near known tumor suppressors such as RB1, may drive early clonal expansion of neoplasia. (S Lee, et al. PNAS 104: 13732-13737, 2007; T Majewski et al. Lab Inv 88: 694-712, 2008) These studies suggested three major steps for the involvement of the RB1 locus in tumor development. In the first step, one allele of FR gene and RB1 is inactivated by large deletions. In the second step, homozygous inactivation of the FR genes is accomplished by hypermethylation or less frequently by missence mutations. Homozygous inactivation of FR genes is associated with the clonal expansion of in situ lesions referred to as low-grade intraurothelial neoplasia. In the final, third step, the contiguous tumor suppressor, such as RB1, is inactivated most commonly by a mutation. This step is associated with clonal evolution into a transformed phenotype with microscopic features of carcinoma in situ progressing to invasive cancer. Recently, we concentrated our efforts on the ARL11 candidate FR gene, which encodes ADP-ribosylation factor-like 11 protein, a ras-related member of the small GTPases, that functions as GDP/GTP nucleotide interswitch for signal transduction. We have shown that it has been silenced by hypermethylation in approximately 40% of urothelial carcinomas of the bladder and the silencing was associated with in situ expansion of intraurothelial neoplasia. Moreover, loss of ARL11 expression was almost mutually exclusive with the FGFR3 mutations (&lt;5% of bladder tumors showed a co-existence of mutant FGFR3 and methylated ARL11). Functional studies conducted on immortalized normal urothelial cells grown in vitro showed that ARL11 reduced cell proliferation, which was mediated by the inhibition of the ras pathway. This effect was associated with the down-regulation of the active ras and ERK1/2 phosphorylation as well as with the up-regulation of negative cell cycle regulator proteins such as p27kip1 and parallel down-regulation of cyclins D1 and E. Conversely, the silencing of ARL11 conferred a tumor suppressor effect promoting cell proliferation via the activation of the ras signaling pathway. In summary, our studies show that recessive events in the RB1 locus associated with the loss of ARL11 function promote clonal expansion of intraurothelial precursor lesions by activating the ras pathway in early occult phases of human bladder carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3065.
Abstract 3070: CHFR, a potential tumor suppressor, downregulates interleukin-8 via inhibition of NF-κB
Authors: Tokino Takashi , Kashima Lisa , Toyota Minoru , Sasaki Yasushi 
Published: February 2011

Abstract
The mitoic checkpoint gene CHFR is silenced in various human cancers, suggesting that CHFR is a tumor suppressor. Here, we reveal that CHFR functions as a negative regulator of the NF-kB pathway. Expression of CHFR inhibited NF-kB reporter activity, while knockdown of CHFR activated reporter activity. These activities are independent of its RING finger domain. Further we found that CHFR interacts with p65 and negatively regulates transcriptional activity of p65. Moreover, our data demonstrate that IL-8 is significantly downregulated by CHFR and that the migration of human endothelial cells is suppressed in culture medium conditioned from CHFR-expressing cancer cells. Using a xenograft model, we show that angiogenesis is suppressed by adenovirus-mediated transfer of CHFR. These results indicate that expression of CHFR markedly reduces expression of IL-8 via the inhibition of NF-kB. Because the NF-kB plays a critical role in the development and progression of cancer, our finding demonstrate the functional relationship between epigenetic alteration and inflammation/antiogenesis in human cancer cells, thereby revealing several potential target for therapeutic intervention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3070.