bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2982: Activation of checkpoint kinase Chk2 by cisplatin and its role in cisplatin resistance
Authors: Liang Xiaobing , Mueller Michael D. , Yu Jing Jie 
Published: February 2011

Abstract
One of the mechanisms of platinum resistance in cancer chemotherapy is the activation of DNA damage checkpoint pathways. Chk2 is a multifunctional key component of the DNA replication-monitoring S/G2 checkpoint system, which mediates DNA damage signaling following genotoxic stress and leads to DNA repair or apoptosis. Developing checkpoint kinase inhibitors for better treatment of cancer has been a major target in drug discovery over the past decade. In our study, flow cytometric experiments show that cisplatin induces an initial accumulation of cells at S phase of cell cycle followed by an increase of cell fraction at G2 phase, suggesting cisplatin-induced cell cycle arrest. Treatment of cisplatin in human ovarian carcinoma cells resulted in Chk2 phosphorylation at Thr-68 and p53 phosphorylation at Ser-15. The observed cisplatin-induced increase in p53 phosphorylation preceded (by about 12 hours) the observed increase in Chk2 phosphorylation. Elevated protein levels of ATM, p53 and P21 by cisplatin in these cells appear in a dose-dependent manner. In addition, overexpression of p53 by cDNA transfection in cells with wild type p53-function doubled the amount of Chk2 phosphorylation 48 hours after cisplatin treatment, whereas p53 knock-down by specific siRNA greatly reduced Chk2 phosphorylation. Furthermore, selective Chk2 Inhibitor (C3742) potentiated the cell-killing effect of cisplatin in both sensitive and resistant ovarian cancer cells. In conclusion, our results suggest that after cisplatin exposure the DNA damage response pathway is activated with greatly increased Chk2 phosphorylation which is modulated by p53. Inhibition of Chk2 with a small-molecule inhibitor may overcome cisplatin resistance in cancer chemotherapy.
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 2982.
Abstract 2987: Oncogenic Wip1 is activated and negatively regulates DNA-damage induced apoptosis in p53-null cancer cells
Authors: PARK JIYOUNG , Jang Se Jin , Seol Hyang sook , Choi Jene 
Published: February 2011

Abstract
Wip1 (wild-type p53-induced phosphatase, or PPM1D) belongs to the protein phosphatase type 2C family and its expression is induced by p53 in response to various stresses. Wip1 is known to dephosphorylate cellular target proteins such as p38 MAPK, p53, and uracil DNA glycosylase that are involved in DNA-repair and cell-cycle-checkpoint pathways. Here, we show that after methylmethane sulfonate (MMS) treatment Wip1 is induced in various breast-cancer cell lines in the absence of wild-type p53 and p38 MAPK activity. Wip1 expression in response to MMS was not blocked by the p38 MAPK inhibitor SB202190 or in p38-silenced MCF-7 cells using p38 MAPK small-interfering RNA (siRNA). The Wip1 promoter displayed great induction in breast cancer cell lines, which have DNA-binding deficient p53 mutants, and p53-null cancer cells such as Saos-2, A549-E6 and HCT116(p53−/−), whereas a control promoter, p53-Luc, showed the least promoter activity after MMS treatment. The mutation of p53 response element in the Wip1 promoter decreased its activity in both unstressed and stressed cells, but the overall level of fold-induction was similar. In addition, cell death was greatly increased in Wip1-siRNA and MMS treated cells in comparison with scrambled siRNA and MMS treated cells in the both cell lines of HCT116 (p53 +/+) and HCT116 (p53−/−). Our data indicate that Wip1 induction in response to various stimuli is not solely controlled by p53, and other damage response signaling appears to compensate for p53. Furthermore, Wip1 negatively regulates DNA-damage induced cell death regardless of the presence wild-type p53.
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 2987.
Abstract 2995: MicroRNA expression and outcome of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer: International Adjuvant Lung Cancer Trial Biologic Program (IALT-Bio)
Authors: Voortman Johannes , Goto Akiteru , Mendiboure Jean , Sohn Jane J. , Schetter Aaron J. , Dunant Ariane , Khan Mohamed , Pham Trung C. , Petrini Iacopo , Lee Alan , Hainaut Pierre , Pignon Jean-Pierre , Brambilla Elisabeth , Popper Helmut H. , Filipits Martin , Harris Curtis C. , Giaccone Giuseppe 
Published: February 2011

Abstract
The aim of our study was to assess whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic and/or predictive biomarkers in patients who participated in the International Adjuvant Lung Cancer Trial (IALT), the largest randomized study conducted so far of adjuvant chemotherapy in patients with radically resected NSCLC stage I-III.
Expression of miR-21, miR-29b, miR-34a/b/c, miR-155 and Let-7a was determined by quantitative real-time PCR in paraffin embedded formalin fixed tumor specimens from 639 IALT patients, using small nuclear RNA U66 as the endogenous normalization control. From 79 patients sufficient tumor adjacent normal tissue was available as well. The prognostic and predictive value of microRNA expression and chemotherapy for survival were studied using a Cox model, which included every factor used in the stratified randomization plus clinical and histological prognostic factors as well as other factors statistically related to microRNA expression. Association of p53 mutation status and miR-34a/b/c expression was analyzed, as well as association of EGFR and K-Ras mutation status with miR-21 and Let-7a expression, respectively. Finally association of p16 and miR-29b expression was assessed. In situ hybridization was performed for validation and to determine histological expression patterns.
Overall, we found that there was no significant association between the expression profile of any of the tested microRNAs and survival. However, for miR-21, miR-34b and miR-34c, there is a suggested deleterious prognostic effect of lower values on survival. No single microRNA expression profile or a combination of microRNA expression profiles, as determined by cluster analysis, predicted response to adjuvant cisplatin-based chemotherapy.
Concluding, expression levels of the tested microRNAs were neither predictive nor prognostic in this patient cohort.
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 2995.
Abstract 3006: Alterations of the microRNA genes targeting MYCC are frequent in medulloblastomas with MYCC overexpression
Authors: Lv Sheng-Qing , Kim Young-Ho , Nobusawa Sumihito , Grotzer Michael , Ohgaki Hiroko 
Published: February 2011

Abstract
MicroRNAs (miRNAs) regulate a variety of cellular processes (including differentiation, proliferation and apoptosis) via the regulation of multiple target genes, including oncogenes and tumor suppressors. Abnormal miRNA expression may therefore play a significant role in tumor development. Medulloblastoma is a common malignant brain tumor in children. Several studies have shown abnormal miRNA-expression profiles in medulloblastomas, but little is known as to whether such profiles are caused by alterations in miRNA genes. In the present study, we screened 48 medulloblastomas for mutation, deletion, and amplification of nine miRNA genes (miR-33b, miR-135a-1, miR-135a-2, miR-135b, miR-186, miR-200b, miR-512-2, miR-548d-1, and miR-548d-2). These miRNAs were selected on the basis of the presence of potential target sequences within the 3’-untranslated region of the MYCC messenger RNA, since MYCC is frequently overexpressed without MYCC gene amplification in medulloblastoma. Differential PCR revealed deletions in miR-186 (15%), miR-135a-1 (33%), miR-548d-1 (42%), miR-548d-2 (21%) and miR-512-2 (33%) genes, whereas deletion or amplification was detected in miR-135b (23%) and miR-135a-2 (15%). In miR-33b, deletion, amplification or a mutation at the precursor miRNA were detected in 10% of medulloblastomas. Overall, 35 out of 48 (73%) medulloblastomas had at least one alteration in the miRNA genes analyzed. Real-time RT-PCR revealed MYCC overexpression in 11 out of 37 medulloblastomas analyzed (30%), and there was a significant correlation between MYCC overexpression and miR-512-2 gene deletion (P = 0.0084). These results suggest that deletion or amplification in miRNA genes is frequent, and may play a role in the pathogenesis of medulloblastomas.
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 3006.
Abstract 3008: PNA based microarray for cancer & stem cell related miRNAs profiling from low total RNA with on-chip labeling
Authors: Hyunsun Kim , Choi Jae-Jin , cho Minhye , Park Heekyung 
Published: February 2011

Abstract
MicroRNAs(miRNAs) are short non-coding RNAs that play a critical role in many important biological processes. MiRNA expression profiling is important to understand the biological mechanisms, develop drugs, and diagnose. However, analyzed method of expression profiling is limited for short base of miRNA. Microarray which is hybridization based technique is the best for detection tool on miRNA characteristic. So, we have developed a PNA-based microarray that is highly sensitive, specific and reproducible to analyze miRNA expression profiles with direct miRNA labeling on chip after hybridization. PNA probes are well known to have stronger binding affinity, specificity to its complementary DNA or RNA strand and stability to biological enzymes. Unlabeled total RNA is hybridized to the PNA-based microarray for 4 hours and then only hybridized miRNA labeling is performed by using enzymatic ligation with pCp-Cy3. Labeling method of only hybridized miRNAs is an important technique for reproducibility and reliable results of microarray. Our data showed very low cross hybridization for miRNAs differing by single nucleotide such as human let7 family and miR-181 family. We used this microarray to determine the profile of microRNAs expressed in the developing cancer cell lines and Tissue. Array results have been validated by subsequent confirmation of miRNA expression using TaqMan qRT-PCR analysis. The results from the TaqMan qRT-PCR and PNA based microarray are shown that the range of correlation were 0.904-0.989. PNA-based microarray platform can detect small amounts of individual miRNAs from &lt;400ng of total RNA with above 99% correlation between independent replicates in 6hrs. Therefore, PANArrayTM miRNA can be a powerful tool to analyze miRNA expression profiling in cancer diagnosis and prognosis for high throughput screening with high accuracy.
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 3008.
Abstract 3015: The miR-21:miR-221 ratio as a serum-based diagnostic for non-small cell lung cancer
Authors: Karkera Jayaprakash , Gaffney Dana S. , Londhe Puja , Wu Xiaoying , Fan Hongtao , Raponi Mitch 
Published: February 2011

Abstract
MicroRNAs (miRNA) are small (21-25 nucleotides) non-coding regulatory RNAs that control protein expression at the transcriptional level through various mechanisms. Previous studies have shown that circulating miRNA can be utilized as a tool to gain a better understanding of both benign and malignant tumor conditions. Their altered expression has been linked with several cancers including lung cancer. Lung cancer is the leading cause of death worldwide with approximately 85% of diagnoses being attributed to non-small cell lung cancer (NSCLC). The goal of this study was to determine if the presence of circulating miRNAs from NSCLC patients can serve as non-invasive diagnostic biomarkers of disease and therapy monitoring. We initially evaluated the expression of 16 NSCLC-specific miRNAs (miR-146b, miR-155, miR-205, miR-21, miR-221, miR-199a-5p, miR-222, miR-320, miR-223, miR-25, miR-16, miR-191, miR-20a, miR-24, miR-145, and miR-152) in 46 NSCLC serum samples ranging from stage I to IV, including 20 adenocarcinoma and 26 squamous cell carcinoma samples. Eighteen healthy controls were used for comparison. RNA was extracted from serum using the single-step Trizol method and real-time PCR (Taqman). Of the 16 miRNAs tested, six miRNAs were significantly upregulated in the NSCLC when compared to the normals (p&lt;0.0001 with AUROCs of 0.80 to 0.93). Top Scoring Pair analyses identified the ratio of miR-21 to miR-221 as the most robust predictor of NSCLC status compared to healthy subjects with an AUROC of 0.95 (95% CI; 0.91-0.99, p &lt; 0.001) and 17% error rate (leave-one-out cross validation). This miRNA pair was then validated in an independent set of 19 NSCLC and 26 normal serum samples with overall accuracy of 80% (89% and 73% for NSCLC and normal, respectively) and AUC of 0.88 (95%CI: 0.78-0.98). These findings demonstrate the potential of using miR-21 and miR-221 in detecting NSCLC from the serum. Furthermore, these miRNAs could lead to the development of non-invasive biomarkers for early diagnosis, prognosis, and therapy monitoring in NSCLC.
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 3015.
Abstract 3019: MicroRNAs as a powerful diagnostic tools for the differential diagnosis of kidney tumors
Authors: Spector Yael , Fridman Eddie , Barshack Iris , Dotan Zohar , Ramon Jacob , Rosenwald Nitzan , Aharonov Ranit , Tabak Sarit , Banjamin Sima , Dov Avital , David Miriam Ben , Zion Orit , Banjamin Hila , Faerman Alexander 
Published: February 2011

Abstract
Background: Renal cell tumors are a group of tumors which differ both in morphologic appearance and biological behavior. In some cases, despite morphologic and immunohistochemical assessment, the pathological differential diagnosis might be difficult. Since accurate diagnosis might change the management of the patient, additional tools for exact diagnosis are required. In this work we propose microRNAs, a family of small non-coding regulatory RNAs involved in human development and pathology, as an emerging class of effective biomarkers for Renal cell tumors.
Patients and Methods: Two independent sets of kidney tumors FFPE samples were collected and reviewed by a pathologist with special experience in uropathology. Historically, renal cell tumors includes: clear cell RCC, chromophobe RCC, papillary RCC (both subtypes) and oncocytoma and are classified histologically using H&E stained slides. High-quality totalRNA was extracted from the FFPE samples using a proprietary protocol developed to preserve the fraction of small RNAs and the expression levels of microRNAs were measured on a microarray and verified on qRT-PCR platforms both developed at Rosetta Genomics.
Results: Expression levels of about 800 microRNAs in a training set of more than 70 kidney tumors identified differentially expressed microRNAs between the different histological types of renal cell tumors. We defined a simple algorithm for classification based on a set of only 6 microRNAs to classify clear cell, chromophobe, papillary and oncocytoma tumors. The classifier was then tested on an independent validation set including samples from the same histological types, and the classifier diagnosed correctly 91% of the tumors. Technical validation was performed using qRT-PCR showing a high correlation to the results obtained by the microarrays.
Conclusions: Expression levels of certain microRNAs are highly specific to subtypes of kidney tumors. A combination of 6 microRNAs can successfully answer specific differential diagnosis of morphologically similar renal cell tumors. The results we present provide a basis for the development of microRNA based diagnostic assay for renal neoplasia.
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 3019.
Abstract 303: Developing predictive biomarkers of PI3K/AKT pathway activation
Authors: Savage Heidi M. , Mullappally Berny , Mohan Sankar , Pandita Ajay , Shames David , Lackner Mark , Punnoose Elizabeth 
Published: February 2011

Abstract
The PI3K/AKT pathway is frequently up-regulated in cancer. This occurs through activation of growth factor receptors, PI3K (p110α) mutations and amplifications, PTEN loss, and more rarely mutations and amplifications of the AKT genes. These pathway alterations could be useful as predictive biomarkers to identify the tumors that are dependent on the PI3K/AKT pathway and therefore, most likely to respond to PI3K/AKT targeted agents. PTEN is frequently inactivated in tumors from various tissues especially brain, endometrium, prostate, ovary, and breast. Developing a predictive biomarker assay PTEN status is challenging because PTEN is lost in cancer by multiple mechanisms including gene deletion, mutations, and DNA methylation. Here we evaluate multiple assays to detect PTEN loss in breast, ovarian, and prostate cancer cell lines as well as tumors to assess the prevalence by which loss occurs by these different 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 303.
Abstract 3032: MicroRNA profiling in head and neck cancer
Authors: Lu Ya-Ching , Cheng Ann-Joy 
Published: February 2011

Abstract
Endogenous small non-coding RNA molecules, such as micorRNAs (miRNAs) are thought to play an important role in human carcinogenesis. These 21-23 nucleotides of miRNAs will silence gene expressions through binding to the 3’UTR of their target mRNAs. Previous evidence with differential expression of microRNA in cancer and normal samples suggests that they are involved in the development of cancer. To identify the miRNA expression specific for head-neck cancer (HNC), the miRNA profiling of 6 cancer cell lines, 2 immortalized normal cell lines and 3 lines of primary normal cell were performed by miRNA microarray. Total of 470 human miRNA were screened for the differential expressions between cancer and normal cell lines. There were 23 miRNAs expressed significantly between two groups (P &lt; 0.05), with 19 elevated and 4 decreased in HNC cell lines. Of which, 9 miRNAs were further validated using RT-qPCR analysis, including miR-10b. The biological function of miR-10b was investigated. Suppression of miR-10b expression by anti-sense oligonucleotide led to repression of cell migration and invasion phenotype. However, there is no significant effect on cell growth, apoptosis or chemo/radio-sensitivity. In conclusion, we have identified at least 9 miRNAs which associated with HNC. miR-10b plays role in the carcinogenesis through promoting cancer cell migrating and invasive, while no effect on cell viability or stress responses.
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 3032.
Abstract 3046: Differential microRNA patterns in prostate carcinoma cells after single and fractionated radiation
Authors: Aryankalayil Molykutty J. , Palayoor Sanjeewani T. , Cerna David , Coleman C. Norman 
Published: February 2011

Abstract
Our previous mRNA microarray analysis showed that fractionated radiation induced more differentially expressed genes compared to single dose radiation in PC3 and DU145 cells. MicroRNAs (miRNAs) are an important class of non-coding small RNAs capable of regulating gene expression at the translational level. To understand the role of miRNAs in regulation of radiation-induced gene expression patterns, we studied the expression levels of miRNAs by microarray analysis in prostate cancer cells. Methods: PC3 and DU145 cells were exposed to 5 Gy and 10Gy either as a single dose radiation or multi-fractionated (0.5Gyx10 and 1Gyx10) radiation. RNA was extracted at 24h after the final dose of radiation and miRNA microarray analysis was done using Agilent human miRNA Microarray Kit (V2). The chip contains probes for 723 human and 76 human viral microRNAs from the Sanger database v.10.1. Data were analyzed using GeneSpring software (Agilent technologies). Results: Of the total 723 miRNAs represented in the array, 141 miRNAs were differentially expressed (&gt; 1.5 fold change) by the 4 radiation protocols. Significant difference in the miRNA expression pattern was noted between the two cell lines. The number of radiation - induced miRNAs was higher in PC3 cells than in DU145 cells. In PC3 cells fractionated radiation resulted in more down regulated miRNAs compared to single dose radiation. In our previous study immune response genes were significantly up regulated by fractionated radiation in PC3 cells but not in DU145 cells. In the present study Mir-146a was significantly up regulated in DU145 cells after fractionated radiation but not in PC3 cells suggesting an inverse correlation between the differential expression of mir-146a and immune response genes in both cell lines. This study also demonstrated significant differences in let-7 family of miRNAs in the two cell lines and also between single and fractionated radiation. In PC3 cells, 8 of the let-7 miRNAs were upregulated after fractionated radiation whereas in DU145 cells they were either downregulated or not changed. Conclusion: Fractionated radiation resulted in expression of more number of miRNAs compared to single dose radiation. We are currently in the process of evaluating radiation-induced differential gene expression changes by a combined approach of mRNA, miRNA and protein array analysis to identify radiation induced molecular targets for cancer therapy.
This work was supported by the Intramural Research Program of Center for Cancer Research, National Cancer Institute, National Institutes of Health.
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 3046.