bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5023: CpG pethylator phenotype (CIMP) methylation pattern in Puerto Ricans Hispanics colorectal cancer patients
Authors: Lacourt Mercedes Y. , Reyes Jeyshka , Lozada María E. , Rodriguez Heriberto M. , Castillo Xiomara , Cardona Alberto , Bernabe Raúl D. , Cruz-Correa Marcia 
Published: August 2012

Abstract
Introduction: The CpG island methylator phenotype (CIMP), characterized by extensive promoter methylation, seems to be a distinct epigenotype of colorectal cancer (CRC). CIMP hypermethylation blocks transcriptional activation of several genes associated with tumor suppression, cell cycle, DNA repair, differentiation and apoptosis. Moreover, CIMP hypermethylation is an important epigenetic change associated with gene silencing, poor prognosis and lower response to chemotherapy in CRC patients. However, prevalence of CIMP status and specific clinicopathological features has not been examined in Puerto Rican Hispanic CRC patients. In this study, we determined the CIMP status in PR Hispanics with CRC and examined its association with phenotypical characteristics. Methods: Methylation-specific PCR (MSP) was used to evaluate DNA methylation in eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, hMLH 1, CRABP1 and p16) gene in eighty-nine CRC cases. No-CIMP status was defined as the absence of methylation, CIMP-Low status as one to four methylated loci, and CIMP-High status as five or more methylated loci. Clinicopathological characteristics were correlated with CIMP status using Wilcoxon rank tests, Chi square and Fisher exact t-tests, as appropriate using STATA 10.0. Results: Eighty-nine CRC cases (mean age at diagnosis 60.5 ± 10.3 years; 49 males) were evaluated. Tumors were mostly located in the distal colon (71.0%). The 5.6 percent (5/89) of CRC cases were CIMP-High, 88% (87.6/89) were CIMP-Low, and 6.7% (6/89) were No-CIMP. CRABP1 (69.7%), IGF2 (48.3%) and p16 (43.8%) were the three most commonly methylated genes. CIMP-High/Low tumors were more common among women and among individuals ≥ 60 y/o (borderline statistical significance). There were no significant statistical associations between CIMP status and tumor staging, differentiation, tumor location or survival. Discussion: We report the CIMP status in Puerto Rican Hispanics with CRC. CIMP-hypermethylation may be less frequent among Hispanics than previously reported in other racial and/or ethnic groups, with a discrete clinicopathological phenotype and gene methylation pattern. A comprehensive understanding of the differences in epigenetic silencing of promoter regions by hypermethylation will shed light on the mechanisms resulting in colorectal tumorigenesis in Hispanic patients. Current efforts are underway to characterize a large number of Puerto Rican Hispanics CRC patients which may help tailor screening and therapeutic strategies for this population.
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 5023. doi:1538-7445.AM2012-5023
Abstract 5025: Regulation of miR-145 expression by Foxo3a, C/EBP-β and p53 in cancer cells
Authors: Zhou Nanjiang , Mo Yin-Yuan 
Published: August 2012

Abstract
Background: MicroRNAs are master gene regulators that control gene expression through the posttranscriptional repression mechanism. Accumulating evidence indicates that microRNAs are often dysregulated in human cancers, and they may function as oncogenes or tumor suppressors. Our laboratory and other groups have previously shown that miR-145 is a tumor suppressor that is downregulated in a variety of tumors. However, it is not fully understood about the underlying mechanism of miR-145 regulation. In this study, we characterized miR-145 regulation involving transcription factors FoxO3a, C/EBP-β and p53 in cancer cells. Methods: We previously constructed the miR-145 promoter luciferase reporter in pGL3-basic, which was used in this study to determine the effect of FoxO3a, C/EBP-β or p53 on miR-145 promoter activity. p53 expression vector was constructed in pEGFP; C/EBP-β and FoxO3a were cloned into pCDH lentiviral vector carrying copGFP. Western blot and fluorescence microscope were used to determine expression of exogenous genes. Endogenous miR-145 levels were determined by TaqMan real time PCR after reverse transcription as well as by in situ hybridization. The expression vectors or luciferase reporter were introduced into cells by either transfection or infection. Results: We showed that miR-145 functions a downstream effector of Akt, and impacts tumor growth and invasion. For example, suppression of Akt by serum starvation or PI3K inhibitor LY29 significantly activates p53, which in turn binds to the miR-145 promoter and induces miR-145 expression. Furthermore, we showed that in addition to p53, FoxO3a also functions a positive regulator of miR-145. Of considerable interest, FoxO3a induces miR-145 expression in the mutant p53 background; however, in the wild type p53 background, p53 suppresses the ability of FoxO3a to induce miR-145. On the other hand, C/EBP-β serves as a negative regulator of miR-145 in both wild type p53 and mutant p53 backgrounds, which is likely in part through regulation of Akt activity. Experiments are underway to further dissect the regulation of miR-145. Conclusion: Together, these results suggest a sophisticated regulatory system controlling miR-145 expression in cancer cells. Thus, a better understanding of this regulatory network will aid in the identification of novel cancer biomarkers and therapeutic targets, and improve cancer diagnosis and treatment.
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 5025. doi:1538-7445.AM2012-5025
Abstract 5028: MicroRNA-212 targets multiple signaling pathways in prostate cancer
Authors: Ramalinga Malathi , Srivastava Anvesha , Dimtchev Alexander , Soldin Offie , Li James , Marian Catalin , Suy Simeng , Collins Sean P. , Kumar Deepak 
Published: August 2012

Abstract
Prostate cancer (PCa) is the most common type of cancer in men in the United States. While metastasis is the most common cause of death among PCa patients, no specific markers have been assigned to the severity of the disease. Identification of molecular factors could improve diagnosis and therapeutic intervention of PCa. MicroRNAs represent a promising new class of circulating biomarkers owing to their inherent stability and resilience. Studies in our lab have demonstrated that miR-212 is a differentially modulated circulatory microRNA in prostate cancer patients. Identification and validation of miRNA targets provides functional insights in mechanisms of prostate carcinogenesis and strategies for therapy. The present study was aimed to investigate and validate the targets for miR-212 to elucidate its role in prostate cancer and identify potential biomarkers and/or therapeutic targets for prostate cancer. Common mRNA targets of miR-212 were extracted from four web-based databases: TargetScan, miRanda, RNAhybrid, and PicTar. Some of the important common targets for miR-212 included DEDD, E2F5, GRM3, G2L1, SPRED1, SIRT1, SOS1, RASA1, PEA15, MYC, MAPK3, MAPK1 and HMGA2. Out of these SIRT1, SOS1, SPRED1, RASA1 were picked for further validation based on their documented role in carcinogenesis and tumor progression. Transfection studies with miR-212 mimics were performed in PC3 and LnCap prostate cancer cell lines. Western blotting was used to see the initial expression of various targets. 3′UTR-Luciferase reporter assay was performed for validating the target inhibition by miR-212. In addition, Cell proliferation assay and wound-healing assay were performed to evaluate the effects of miR-212 on PCa cell proliferation and migration. In summary the present study identifies and validates miR-212 targets and examines the functional significance of miR-212 in prostate cancer (PCa) cells lines. *Contributed equally.
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 5028. doi:1538-7445.AM2012-5028
Abstract 5029: Upregulation of miRNA27, miRNA125a and 125b in ERalpha-negative breast cancers
Authors: Lehmann Tomasz P. , Korski Konstanty , Ibbs Matthew , Breborowicz Jan , Grodecka-Gazdecka Sylwia , Gryczka Robert , Jagodzinski Pawel 
Published: August 2012

Abstract
MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that post-transcriptionally inhibit gene expression. Many miRNAs have been implicated in the human breast cancer. We show here the correlation between breast cancer types characterized upon histological and immunohistochemical analysis and miRNA expression in 22 Polish patients. The group was divided into three categories: ERalpha-negative / ERalpha-positive, HER2-negative / HER2-positive and lymph node -negative / lymph node -positive (N-/N+) cases. Surgically removed tumors were congealed in liquid nitrogen and subsequently small RNA was extracted. We investigated the level of miR-17-5p, miR-27, miR-125a, miR-125b and miR-206 using real-time PCR TaqMan probes. Let-7 miRNA and U6 RNA were used as reference genes. We observed upregulation of the subsequent suppressor miRNAs miR-27, miR-125a and 125b in ERalpha-negative tumors (p&lt;0.05). Comparison of expression of miR-17-5p, miR-27, miR-125a, miR-125b and miR-206 in N- and N+ samples did not reveal any significant differences. We also observed a tendency to lower level of expression of all investigated miRNAs in HER2-positive patients in comparison with HER2-negative. We concluded that miR-27, miR-125a and miR-125b may play an important role in the regulation of ER-alpha expression in breast cancer cells. They could also be regarded as surrogate markers of ER-alpha -negativity. However, the small number of patients included to the study warrants further investigation in the larger cohort of breast cancer patients.
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 5029. doi:1538-7445.AM2012-5029
Abstract 5030: Identification of the Her-2 expression-regulating miRNAs by microdissection and RT-PCR in breast cancer tissue
Authors: Hao Yubin , Xing Hangying , He Chunnian 
Published: August 2012

Abstract
Her-2/neu oncogene is overexpressed in human breast cancer and is correlated with the tumor cell proliferation, metastasis, and resistance against chemo- and hormonotherapy. The expression levels of both Her-2/neu gene and HER-2 protein are recommended for evaluation of treatment efficacy as well as for selection of treatments. However, clinical studies have shown that the Her-2/neu gene and the HER-2 protein are differently expreesed in 10-15% of human breast cancers and we hypothesized that the expression difference might be related to the post-transcriptional regulation of the Her-2/neu gene by microRNAs (miRNAs). To identify the specific miRNAs, we first analyzed 120 human breast cancer samples for the Her-2/neu gene amplification and protein expression with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Fourty-four cancer samples (36.7%, 44/120) showed overexpression of HER-2 protein with IHC (IHC+) and 26 samples (26.5%, 26/98) exhibited Her-2/neu gene amplification with FISH (FISH+). Interestingly, five samples exhibited amplification of the Her-2/neu gene, but absence of the HER-2 protein expression (FISH+/IHC-). We then dissected the FISH+/IHC- tumor cells using laser capture microdissection from the five samples. Tumor cells with FISH+/IHC+ from another set of five samples were also dissected and analyzed as the control. Based on TargetScanHuman and literature search, five candidate miRNAs including miR-125b, -1224-3p, -1296, -193a-5, and -331-3p were screened with quantitative real-time RT-PCR and their expression levels in the FISH+/IHC- cells were 3.1-, 2.7-, 1.7-, 1.7-, and 1.3-fold higher than in the FISH+/IHC+ cells, respectively, with a significant difference for miR-1224-3p and miR-1296 (both P &lt; 0.01). These results indicate that miR-1224-3p and miR-1296 may be responsible for the different expressions of Her-2/neu gene and its protein by regulating the Her-2/neu gene posttranscription, thus down-regulating the HER-2 protein expression in FISH+/IHC- breast cancer cells.
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 5030. doi:1538-7445.AM2012-5030
Abstract 5031: miR-21 targets TGF-β Pathway in breast cancer
Authors: Chen Liang , Wang Meng , Peng Jin , Teal Christine , Stamatakos Michael , McCaffrey Timothy , Fu Sidney W. 
Published: August 2012

Abstract
MicroRNAs (miRNAs) are endogenous non-coding RNAs (∼22 nt), which regulate the stability and translation of coding mRNAs. miRNA dysregulation is observed in a variety of cancers, including breast cancer. Our previous studies, by miRNA expression profiling using archived FFPE tissues, identified a set of miRNAs that are differentially expressed during breast cancer progression. Using ANOVA test, we identified 8 clusters of miRNAs, which discrete the normal and disease lesions, such as ADH, DCIS and IDC. miR-21 has been well documented as an oncogene, while miR-200c/b are reported as biomarkers for primary hepatocellular carcinoma, and miR-200c as an independent prognostic factor in pancreatic cancer. Our study shows that miR-21 consistently expresses high level in pre-cancerous lesions, i.e. ADH and DCIS, which indicates that miR-21 plays an important role in breast cancer initiation and progression. However, the exact mechanism is not clear. To test the effects of miR-21 inhibition in both ER+ and ER- breast cancer cells, we transfected anti-miR-21 oligos and scrambled oligo mocks into human breast cancer cells, MCF-7 (ER+) and Hs578T (ER-). We observed a significantly increased expression of MSH2 and SMAD7, when miR-21 was knocked down by 60%-80%. Both MSH2 and SMAD7 are key players in TGF-β signaling pathway, which is well known for its anti-mitogenic function during tumor initiation. These findings help establish miR-21 as an important oncogene that targets a network of TGF-β in breast 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 5031. doi:1538-7445.AM2012-5031
Abstract 5032: New insights of miR-221 and miR-222 cluster functions in Burkitt lymphoma.
Authors: Consiglio Jessica , Luca Luciana De , Acunzo Mario , Galasso Marco , Rocci Alberto , Sapienza Maria-Rosaria , Piccaluga Pier Paolo , Vecchione Andrea , Zanesi Nicola , Volinia Stefano , Croce Carlo Maria , Pichiorri Flavia 
Published: August 2012

Abstract
Burkitt lymphoma (BL) is a mature aggressive B-cell neoplasm, with a characteristic clinical presentation, morphology and immunophenotype. Several studies have indicated the importance of miRNAs in B cell maturation and in the development of B cell lymphomas. MicroRNAs (miRNA) are a class of naturally occurring, small, non-coding RNA that can control gene expression by targeting mRNA molecules for translational repression or cleavage. They are usually expressed in a tissue-specific manner and play important roles in apoptosis, differentiation and cell proliferation; therefore their deregulation may be involved in carcinogenesis or tumor progression by altering normal gene expression patterns. Over the past years microRNAs signatures have been described to characterize and classify different types of BL or to investigate the expression of miRNAs possibly regulated by c-Myc in BL cases positive or negative for Myc traslocation. Howhever, it remained unclear the functional role of miRNAs that have been found differentially expressed and no further studies have been conducted. We performed miRNA expression profile to gain further insights into the molecular pathology of BL. We conducted array analysis on a set of 5 sporadic BL patients, 3 endemic BL patients, 9 reactive tissues and 11 cases of mononucleosis. A common trend of miRNAs altered expression was also observed by NanoString analysis in 10 BL cell lines compared to 5 normal CD-19+ B cells. Among several miRNAs previously described be deregulated in BL we identified a severe down-regulation of miR-221, miR-222 in all classes of comparisons we analyzed. The down-regulation of miR-221 and miR-222 associated to BL has been also confirmed by q-RT-PCR method in a different cohort of BL patients (20) compared to the healthy controls (6). When miR-221 and miR-222 expressions have been restored in BL cancer cell lines, lacking of their expression, by gene expression profile we identified the differentially expression of several genes involved in ncRNAs processing, ncRNA metabolic process and also in the regulation of cell differentiation and cell cycle. Furthermore, functional experiments identified many of these genes as new direct targets of miR-221 and miR-222. In conclusion, our study reveals new insights into the functional significance in loss of miR-221 and miR-222 expression in BL pathogenesis.
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 5032. doi:1538-7445.AM2012-5032
Abstract 5033: Relationship between microRNA expression and Gleason grading system in prostate cancer
Authors: Tsuchiyama Katsuki , Ito Hideaki , Taga Minekatsu , Oshinoya Konosuke , Nagano Kenichi , Yokoyama Osamu , Itoh Hiroshi 
Published: August 2012

Abstract
Background: Recent studies have shown that some microRNA (miRNA) expression profiles are associated with clinicopathological findings, including “Gleason score (GS)” in human prostate cancer (PC). However, the direct relationship between “Gleason pattern (GP)” and miRNA expression remains unclear. In this study, we investigated the miRNA expression profile in each GP (GP 3, GP 4, and GP 5). Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from radical prostatectomy (patient set 1, n = 43, including [GP 3] n = 22, [GP 4] n = 35, and [GP 5] n = 12) and prostate needle biopsy (patient set 2, n = 9, [GP 4] n = 9) were used. Cancer tissues and adjacent normal counterparts were collected separately using laser-captured microdissection with subsequent isolation of total RNA. Real time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the relative expression of miRNAs, including miR-31, -34c, -96, -182, -183, -205, -221, and miR-222, which are currently reported to be involved in the progression of PC. Results: In the radical prostatectomy samples (patient set 1), relative expression (mean ± SE) of miR-31, miR-34c, and miR-205 in every GP was significantly decreased (miR-31: [GP 3] 0.028 ± 0.007, [GP 4] 0.047 ± 0.017, and [GP 5] 0.071 ± 0.022; miR-34c: 0.208 ± 0.066, 0.419 ± 0.219, and 0.210 ± 0.054; and miR-205: 0.021 ± 0.008, 0.015 ± 0.003, and 0.050 ± 0.023, all p-values &lt; 0.01) compared to normal counterparts. However, there was no significant difference between GP 3, GP 4, and GP 5. Meanwhile, in GP4, expression of miR-31, miR-182, and miR-205 in tissues obtained from high-grade cancer (GS 8 or GS 9) were significantly higher than those in tissues obtained from intermediate-grade cancer (GS 7) (miR-31: [high grade] 0.071 ± 0.027, [intermediate grade] 0.011 ± 0.003, p = 0.040; miR-182: 1.745 ± 0.278, 0.864 ± 0.136, p = 0.021; and miR-205: 0.022 ± 0.005, 0.005 ± 0.002, p = 0.002, respectively). Validation testing of biopsy samples (patient set 2) revealed that the relative expression of miR-182 was similarly and significantly higher in high-grade cancer tissue (high grade: 1.863 ± 0.381, intermediate grade: 0.717 ± 0.196, p = 0.043). Conclusion: The expression of miR-182 differed by cancer grade even in the same GP 4, and this difference was detected in both biopsy and radical prostatectomy samples. Our findings suggest that evaluations of miRNA expression with respect to Gleason grading in biopsy samples may contribute to more accurate preoperative cancer risk evaluation.
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 5033. doi:1538-7445.AM2012-5033
Abstract 5036: MicroRNA expression profiling potential for human breast cancer diagnosis using a bead-based microRNA-specific capturing method
Authors: Tran Kathy , Xu Tom , Stevens Junko 
Published: August 2012

Abstract
MicroRNAs (miRNAs), a family of small, endogenous, non-coding (∼17-24 nucleotides) nucleic acids, were initially discovered in 1993, but the discovery of a second miRNA led to their use as molecular markers of disease and potential therapeutic targets. MiRNAs regulate RNA translation, play a role in cell proliferation, control timing of organism development, and are associated with carcinogenesis. Because of their regulatory function in cell differentiation and renewal during physiologic and malignant conditions, miRNAs are emerging as a new class of effective biomarkers for cancer research. The miRNA expression profiling of tumor cells will allow for the identification of prognostic markers to indicate potential targets for patient- or disease-specific therapies. Three criteria important for profiling miRNAs are ease of use, simplicity and sensitivity. We have designed and developed a new method to quickly extract and purify specific miRNAs for detection using our current reverse transcription and real-time quantitative PCR workflows. The method involved 1μm-diameter magnetic beads conjugated with anti-miRNA oligoncleotides to capture these select miRNA targets from blood, plasma, and other tissues. The miRNAs were then transcribed into cDNA and subsequently used as templates for TaqMan® qRT-PCR analysis. We used this method to evaluate the miRNA signatures from normal and cancerous human breast modeled by cell lines and represented by formalin-fixed, paraffin-embedded tissues.
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 5036. doi:1538-7445.AM2012-5036