bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4037: Higher Expressions of miR-21, miR-106a, miR-181b, and miR-203 are Associated with Poor Prognosis in Colorectal Cancer Patients
Authors: Bovell Liselle , Katkoori Venkat R. , Shanmugam Chandrakumar , Lee Choo H. , Meleth Sreelatha , Bumpers Harvey L. , Grizzle William E. , Manne Upender 
Published: February 2011

Abstract
Background: MicroRNAs (miRNAs) are a family of small (20- to 24-nucleotide) non-coding RNAs that regulate gene expression at the post-transcriptional level. Although miRNAs are potential prognostic biomarkers in colorectal cancers (CRCs), their value based on the patient race/ethnicity has not been examined. Thus, this study evaluated the prognostic value of miRNAs for CRCs in African-Americans (Blacks) and non-Hispanic Caucasians (Whites).
Methods: TaqMan® microRNA assays and qRT-PCR were used to quantify the expression profiles of a panel of miRNAs (miR-20a, miR-21, miR-106a, miR-181b, and miR-203) in CRCs and corresponding benign tissues collected from 104 Blacks and 114 Whites. The expression profiles were correlated with patient overall survival, and p values were calculated by the log-rank test.
Results: For both racial groups, all five miRNAs had higher expression in CRCs (&gt;1.0 fold; range, 1.23 to 7.52) compared to their corresponding controls. Univariate Kaplan-Meier analyses demonstrated that increased expression of miR-106a was associated with decreased overall survival of both Blacks and Whites (p=0.040 and p=0.049, respectively). Increased expressions of miR-181b and miR-203 were each significantly associated with short patient survival of Blacks (p=0.009 and 0.003, respectively), but not Whites (p=0.117 and p=0.071, respectively). When Blacks and Whites were combined, over-expression of miR-21 was associated with poor patient survival (p=0.049), but statistical significance was not reached when the values were analyzed based on race. In contrast, increased expression of miR-20a was not associated with survival of either Blacks (p=0.193), Whites (p=0.242), or the combined patient population (p=0.072).
Conclusions: These findings suggest that, for all CRC patients, over-expression of miR-21 and miR-106a are associated with poor prognosis, whereas over-expression of miR-181b and miR-203 are associated with poor outcomes for Blacks. These findings suggest that, in prognostic assessment of miRNAs in CRC, patient race/ethnicity should be considered. These studies were supported by NCI/NIH grants, U54-CA118948 and R01-CA098932-01.
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 4037.
Abstract 4042: MiR-200c sensitizes colorectal cancer cells to 5-FU through Bcl-2-involved apoptotic pathway
Authors: Qian Xuemin , Howell Paul , Li Xiaobo , Qin Xin , Gao Lin , Xi Yaguang 
Published: February 2011

Abstract
Effective clinical management of colorectal cancer is still a major challenge in cancer care. MicroRNA is a set of newly-discovered, non-coding small RNA molecules that significantly contribute to a number of critical biological events including cell proliferation, apoptosis development, as well as tumorigenesis. Our group has previously identified a number of microRNA candidates associated with potential prognostic value in colorectal cancer patients. In this study, we investigated miR-200c and validated its impact on 5-FU chemosensitivity in colorectal cancer. Human colorectal cancer cell lines HCT116 and HCT15 were employed in this study. Pre-miR-200c precursor molecules and negative control (Ambion, Inc.) were transiently transfected into these cell lines and cell viability was examined using WST-1 assay (Roche, Inc.) after 5-FU treatment for 24 hours. The results indicate that miR-200c can potentially sensitize colorectal cancer cells to 5-FU up to 25% compared to controls. Also, cells over-expressing miR-200c have an approximately 50% higher apoptotic rate than controls based on flow cytometry results. Bioinformatics predicts Bcl-2 is a putative mRNA target of miR200c. Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria. Overexpression of Bcl-2 has been demonstrated to prevent cells from undergoing apoptosis in response to a variety of stimuli. In this study, we further experimentally validated the repressive abilities of miR-200c on Bcl-2 expression using Western Blot and Luciferase reporter assay. Our results demonstrates that miR-200c is a potential biomarker for predicting chemotherapeutic response in colorectal cancer and functions by repressing Bcl-2 expression and inducing apoptotic susceptibility to 5-FU. These results hold great promise for moving miRNAs toward future clinical application and contribute to the ultimate goal of developing or improving therapeutic intervention for patients with colorectal 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 4042.
Abstract 4044: microRNA mimics as cancer therapeutics
Authors: Daige Chritopher L. , Fields Robert B. , Li ChuanYu , Cantley Will , Akinc Akin , Bhat Balkrishen , Marcusson Eric G. , Linsley Peter S. 
Published: February 2011

Abstract
microRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally. The mRNA targets of microRNAs are usually determined based on complementarily to the 5′ end of the microRNA; the area termed the seed sequence. One microRNA can have more than 100 mRNA targets that are usually inhibited by ∼50%. The expression of microRNAs has been shown to be dysregulated in numerous cancer types. These dysregulated microRNAs can act to either positively or negatively regulate initiation, proliferation and metastasis of cancer cells. Some of the most important pathways in cancer biology (e.g. the Ras and p53 pathways) have been shown to interact with microRNAs. Therefore, both inhibiting and replacing microRNAs have therapeutic potential in oncology. We are using technology similar to that used for antisense oligonucleotides and lipid nanoparticle formulated siRNAs, both of which are currently in clinical trials for cancer, to determine the best potential microRNA based therapeutics to develop as drugs. In this report we will focus on our attempts to introduce mimics of microRNAs known to be down-regulated in tumors (e.g. miR-34a). Initial experiments were performed in wild-type mice and demonstrated the ability to deliver microRNA mimics to the liver and to affect gene expression in a seed sequence-dependent manner. These results, along with effects of successful microRNA introduction into an orthotopic xenograft model of hepatocellular carcinoma will be presented.
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 4044.
Abstract 4054: Prognostic value of microRNAs expression in diffuse large B cell lymphoma
Authors: Kushnir Michal , Lahav Meir , Ram Ron , Gilad Shlomit , Zepeniuk Meirav , Cohen Lahav , Ezagouri Meital , Baery Osnat , Spilberg Ofer , Feinmesser Meora , Aharonov Ranit , Yanai Gila Lithwick 
Published: February 2011

Abstract
Background: Diffuse large cell lymphoma (DLBCL) is heterogeneous in its clinical sequel. Approximately 50% of patients relapse after treatment and many succumb to the disease. Risk stratification of these patients is based mainly on the International Prognostic Index (IPI), while molecular profiling is not widely used for prognostication. Thus, there exists a need for identification of additional biomarkers that can be used as prognostic indicators for patients with DLBCL. Here we propose microRNAs, a family of small non-coding regulatory RNAs involved in cancer development, as an emerging class of potential biomarkers for risk stratification of DLBCL.
Methods: Expression profiling of microRNAs was performed on RNA extracted from biopsy specimens of 83 DLBCL patients diagnosed and treated at Rabin Medical Center, using custom microRNAs microarrays. All patients were treated with CHOP or CHOP like therapy and were dichotomized into a “good prognosis” group (patients that achieved complete remission and no relapse within 5 years) and a “bad prognosis” group (patients that were either resistant to treatment or relapsed within 9 months). Expression levels were compared between the two groups of samples and statistically analyzed. The expression of differential microRNAs was verified using a microRNA qRT-PCR platform.
Results: We found that several microRNAs are significantly differentially expressed in tumors from patients with bad prognosis compared with patients with good prognosis. Proprietary microRNA qRT-PCR showed a high correlation to microarrays and similar separation into prognosis groups based on miR expression.
Conclusion: In summary, according to the results of this study, miRNA expression can serve as a novel tool for risk stratification and prognosis prediction of DLBCL patients. This approach can potentially be used to tailor treatment and further management to specific patient needs.
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 4054.
Abstract 4055: Real-time quantitation of primary transcripts of microRNA genes
Authors: Liang Yu , Hu Fangqi , Langit Emanuel , Lu Julia , Brzoska Pius , Chen Caifu 
Published: February 2011

Abstract
Regulation of mature microRNA (miRNA) expression has been shown during the course of biogenesis under different contexts: from transcription, processing of pri-miRNA to pre-miRNA by Drosha, to processing of pre-miRNA to mature miRNA by Dicer. A mature miRNA can be processed from two or more stem-loop precursor loci, which are denoted with numeric suffixes such as −1, −2, etc. As of the 14th Release of the miRBase, there are 154 genes among the 750 miRNA genes that belong to this category. To interrogate regulation of miRNA expression at the transcriptional level for those that can be processed from multiple genomic locations, it requires assays to specifically quantitate the precise locus of interest. We have developed a pipeline to design and select real-time RT-PCR assays to quantitate primary transcripts of miRNA genes. These assays are designed against genomic DNA sequence so the genomic DNA needs to be removed by prior enzyme treatment. We showed that the TaqMan® Pri-miRNA Assays have minimally detectable or no background using either cell lysates or commercial tissue total RNA. Excellent linearity was seen using cDNA synthesized from total RNA, or using 1ng/ul or greater of genomic DNA. The specificity of the assays to distinguish loci that are processed into identical mature miRNA was demonstrated using subcloned plasmids, as well as using breast cancer cell lines that showed concordant expression patterns among such loci with published data in human breast cancer. The TaqMan® Pri-miRNA Assays will be a useful tool to identify the precise loci that contribute to the mature miRNA expression of interest at the transcription level, so as to further investigate the regulatory mechanisms for the differential expression.
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 4055.
Abstract 4060: Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma
Authors: Gogineni Venkateswara Rao , Nalla Arun Kumar , Gupta Reshu , Gorantla Bharathi , Gujrati Meena , Dinh Dzung H. , Fassett Daniel , Klopfenstein Jeffrey D. , Rao Jasti S. 
Published: February 2011

Abstract
Stereospecific radiation treatment offers a distinct opportunity for temporal and spatial regulation of gene expression at tumor sites by means of inducible promoters. To achieve this, a plasmid, pCArG-U2, was constructed by incorporating nine CArG elements (in tandem) of EGR1 gene upstream to uPA and uPAR siRNA oligonucleotides in a pCi-Neo vector. Radiation-induced siRNA expression was detected in a meningioma cell line (IOMM-Lee). Immunoblotting and RT-PCR analyses confirmed downregulation of uPA and uPAR. A similar effect was observed in transfected cells followed by H2O2 treatment. Moreover, pre-treatment of transfected cells with N-Acetyl L-Cysteine blocked the silencing of uPA and uPAR, which further confirmed the oxidative damage-mediated downregulation. Cell proliferation assays and western blot analysis for apoptotic molecules confirmed cell death in a radiation-inducible fashion. Migration and Matrigel invasion assays also revealed a marked decrease in the migration and invasive behavior. Immunocytochemistry showed a marked decrease in uPA and uPAR levels in the transfected and irradiated cells. H&E staining revealed a decrease in the pre-established tumor volume among the animals treated with pCArG-U2 and radiation. Immunohistochemistry of the brain sections established with intracranial tumors also revealed a marked decrease in uPA and uPAR in a radiation-inducible fashion. Altogether, our data suggest pCArG-U2 as a suitable candidate for radiation-inducible gene therapy.
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 4060.
Abstract 4065: Suppression of mannosylphospho dolichol synthase (DPMS) expression by vector-based siRNA technology reduces angiogenesis and inhibits tumor growth
Authors: Zhang Zhenbo , Banerjee Aditi , Santiago Jesus , Baksi Krishna , Banerjee Dipak K. 
Published: February 2011

Abstract
Suppression of mannosylphospho dolichol synthase (DPMS) expression by vector-based siRNA technology reduces angiogenesis and inhibits tumor growth
Zhenbo Zhang1, Aditi Banerjee1, Jesus Santiago1, Krishna Baksi2 and Dipak K. Banerjee1. 1Dept Biochem, Sch Med, Univ Puerto Rico, San Juan, PR and Dept Anatomy and Cell Biol, Sch Med, Universidad Central del Caribe, Bayamon, PR, USA.
Mannosylphospho dolichol synthase (DPMS), a 31kDa phosphoprotein is essential for the synthesis of lipid-linked oligosaccharide (LLO; Glc3Man9GlcNAc2-PP-Dol), a pre-requisite for asparagine-linked (N-linked) protein glycosylation. Earlier observations from our laboratory have suggested that up-regulation of DPMS activity plays an important role in capillary endothelial cell proliferation and consequently in angiogenesis. Our recent study suggests that blockade of N-linked glycosylation by tunicamycin may provide a novel therapeutic approach for the treatment of cancers. However, the roles of suppressing DPMS expression by genetic manipulation and its impact on angiogenesis and tumor cell proliferation have not been investigated. We report here that knocking down DPMS expression by vector-based short interfering RNA technique dramatically reduced the N-linked glycosylation of protein in endothelial cells and inhibited angiogenesis and cell proliferation. After isolating DPMS overexpression and siRNA stable cell lines, DPMS expression in these cells has been confirmed by fluorescence microscopy, western blotting, QRT-PCR and measuring the catalytic activity. All detected elevated DPMS level in overexpressing clone but is down-regulated in cells silenced with siRNA. Fluorescence microscopy with WGA supported high expression of complex glycans on the cell surface overexpressing DPMS and is considerably reduced in cells DPMS silenced with siRNA. Two-dimension gel combined fluorescence with FITC-labeled Con A and Texas-Labeled WGA also support this observation. Overexpressing DPMS clone proliferates faster compared to the cells whose DPMS has been silenced with siRNA. This is corroborated with the cell proliferative antigens Bcl-2 and PCNA expression monitored by western blotting and/or by QRT-PCR. In wound healing assay DPMS overexpression facilitated faster cell migration than its siRNA clone. Thus, DPMS exerts influence on capillary endothelial cell proliferation and may serve as a modulator of angiogenesis. We, therefore, conclude that DPMS may serve as a potential target for developing anti-angiogenic therapeutics treating cancer. Supported by Susan G. Komen for the Cure BCTR 056206 (DKB) and NIH/NCRR/RCMI G12-RR0303 (KB) grants.
1
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 4065.
Abstract 4066: Benzyl isothiocyanate causes degradation of the aryl hydrocarbon receptor in hepa1c1c7 cells
Authors: Kioko Stephen M. , Kirlin Ward G. 
Published: February 2011

Abstract
The biotransformation and detoxification of many carcinogens, including 2,3,7,8-tetrachlorodibenzodioxin, benzo [a] pyrene and 3-methylchloranthrene is dependent upon the activity of phase I and II enzymes, particularly CYP1A1 and NQO1. The transcriptional activation of these enzymes is regulated by the aryl hydrocarbon receptor (AhR) and Nuclear Factor-Erythroid 2-Related Factor. These transcription factors reside in the cytoplasm and when activated, shed their respective chaperones and translocate into the nucleus where they interact with nuclear proteins involved with transcription of genes possessing xenobiotic (XRE) and antioxidant (ARE) response elements. We have previously observed that the phytochemical benzyl isothiocyanate (BITC) induces nuclear translocation of the AhR independently of traditional ligands in Hepa1c1c7 cells and also induces AhR heterodimerization with ARNT. These observations suggest that BITC might bind the AhR and affect activity of these enzymes as well as the transcriptional regulation of XRE-responsive genes. In the current study we investigated whether BITC causes degradation of the AhR. This is important because it provides insight into potential mechanisms by which BITC affects AhR transcriptional regulation and the activity of phase I and II enzymes. Hepa1c1c7 cells were treated for 4 hours with DMSO alone, 10 μM BITC, 10 μM BNF or a combination of both 10 μM BITC and 10 μM BNF. Whole cell lysates were prepared and AhR immunoprecipitated and analyzed by western blot. Results showed that AhR was rapidly degraded in cells treated with BITC alone compared to controls. Furthermore, BITC enhanced degradation of the receptor in cells treated with a combination of both BITC and BNF compared to cells treated with BNF alone. In other experiments, Hepa1 cells were treated for 16 hours with BNF alone or a combination of 1, 2, 5, 10 and 20 μM BITC. Isolated proteins analyzed by western blot indicated that BITC enhanced degradation of the AhR in a dose dependent manner in cells treated with both BITC and BNF compared to BNF-only treated cells. Cumulatively, these data show that BITC degrades the AhR, which might decrease its function in transcription of XRE responsive genes. The results also suggest that increased degradation of the AhR might affect the activity of CYP1A1 and NQO1 thus affecting biotransformation and detoxification of carcinogens. They also provide preliminary evidence into one of the potential mechanisms by which BITC is chemopreventive. (Support: NIH MBRS/GM028248; RCMI RR033032).
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 4066.
Abstract 4068: Reciprocal regulation of RNase-L and tristetraproline modulates the induction of proinflammatory cytokines
Authors: Hassel Bret A. , Li Xiao-Ling 
Published: February 2011

Abstract
The endoribonuclease RNase-L is the terminal component of an interferon-regulated RNA decay pathway that functions in antiviral and antiproliferative/tumor suppressor activities. We recently identified a novel role for RNase-L in the induction of tumor necrosis factor-a (TNFa). The induction of TNFa is an important mediator of inflammation, therefore the RNase-L-dependent regulation of TNFa may contribute to its tumor suppressor activity. In the current study, we sought to investigate the mechanism of this regulation. The induction of TNFa mRNA was diminished in the absence of RNase-L suggesting that RNase-L targeted a negative regulator of TNFa expression. The RNA binding protein tristetraproline (TTP) is a critical regulator of TNFa that enhances the degradation of its mRNA; thus TTP represented a viable target mRNA by which RNase-L may indirectly modulate TNFa expression. Consistent with this model, inhibition of RNase-L expression using knockdown or knockout strategies enhanced TTP induction by interferon and Toll-Like Receptor agonists and reduced levels of TTP target mRNAs (e.g. TNFa). In contrast, ectopic RNase-L expression diminished TTP expression. Importantly, the stability of TTP mRNA inversely correlated with RNase-L expression, suggesting that the TTP transcript is a direct target of RNase-L. Interestingly, analysis of RNase-L expression in lipopolysaccharide-stimulated macrophages demonstrated a downregulation of RNase-L that corresponded with TTP induction, suggesting that TTP may regulate RNase-L. Indeed, TTP overexpression decreased the half-life of RNase-L mRNA, and pharmacologic MAP kinase inhibitors that block TTP activity stabilized RNase-L mRNA. Taken together, these findings suggest that RNase-L and TTP represent reciprocally regulated components of a post-transcriptional network that functions to tightly control the expression of proinflammatory cytokines, and may influence the antitumor immune response.
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 4068.