bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3012: Development of a microRNA signature for risk of progression in renal cell carcinoma
Authors: Banumathy Gowrishankar , Ibragimova Ilsiya , Al-Saleem Tahseen , Uzzo Robert G. , Cairns Paul 
Published: February 2011

Abstract
The incidence of asymptomatic pathologically localized renal cell carcinoma (RCC) has shown the greatest increase in recent decades. Despite the finding of organ-confined (pT1 or T2) disease at the time of nephrectomy, a subset of patients will have local recurrence or distant metastasis after nephrectomy. Most solid neoplasms are now thought to accumulate a series of genetic and epigenetic changes as they progress through well-defined clinical and histopathological changes. The association of particular molecular markers with progression and outcome of disease means that the status of certain markers can be used to identify the presence of disease and its likelihood for progression. To identify an epigenetic signature that may predict recurrence in patients with organ-confined RCC, we examined RNA hybridized to the Agilent microRNA (miRNA) array from a large number (&gt;100) of RCC patients with extensive clinicopathological annotation. The potential of miRNAs as biomarkers for risk of progression and early detection of recurrent RCC has not yet been studied. Since approximately 90% of metastatic RCC is of clear cell histology, we examined only this histological cell type. The cell type and grade of the RCC was re-reviewed blind by a single pathologist. miRNA expression signatures were established from a series of low grade (I-II), low stage (pT1-2) clear cell RCC with no evidence of disease after nephrectomy for at least 5 years; a series of high grade, high stage (pT3-4), clear cell RCC; and a series of low grade and low stage clear cell RCC that progressed. The expression of particular miRNAs was validated by qRT-PCR. In the growing number of patients who have undergone surgical resection for organ-confined RCC, the near term goal would be to identify those that should be followed more closely and a future goal, depending upon results of ongoing therapeutic trials, to be directed to adjuvant therapy. There would also be cost benefits in potentially following those RCC patients with lowest risk of progression less frequently. MiRNA signatures obtained by our study will address the clinical question whether risk of progression could be defined in patients with organ-confined RCC at initial surgery.
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 3012.
Abstract 3020: Identification of a subgroup with good prognosis of small-cell lung cancer by miRNA expression profiling
Authors: Oba Takehiko , Ninomiya Hironori , Okumura Sakae , Nishio Makoto , Fujiwara Mutsunori , Ishikawa Yuichi 
Published: February 2011

Abstract
Background: Long-term outcomes of patients suffering from small-cell lung cancer (SCLC), a neuroendocrine carcinoma, are usually poor, but a few patients achieve long-term survival. Prognostic factors in SCLC have not been fully elucidated. Previously we successfully identified a neuroendocrine carcinoma subgroup with good prognosis by mRNA profiling (Jones et al. Lancet 2004). Here we attempted to identify the subgroup by microRNA (miRNA) profiling. miRNAs are known to negatively regulate gene expression and to be relevant to tumorigenesis, tumor classification and prognosis.
Methods 63 samples (46 neuroendocrine tumors including 35 SCLC and 11 large cell neuroendocrine carcinomas (LCNEC), 5 squamous cell carcinoma (Sq), 4 adenocarcinoma and 8 normal lungs) were obtained through surgical resection. miRNA expression profiling was performed using miRNA microarray (Agilent). Hierarchical clustering was performed after selection of about 600 miRNA by choosing those with signal strength more than five.
Results: Unsupervised hierarchical clustering using the 600 miRNA classified the tumors into two subgroups. Group 1 contained 20 SCLC (8 females and 12 males) and 3 LCNEC, and was associated with unfavorable prognosis. Group 2 contained 15 SCLC (1 female and 14 males), 8 LCNEC and 4 Sq, and was with good prognosis. 5-year survival of the two groups was 0% and 79%, respectively (p=0.007). As compared with our former study by mRNA, all 5 cases in the poor prognosis group fell into Group 1, and 6 out of 7 cases in the good prognosis group were included by Group 2, indicating good agreement between mRNA and miRNA profiling. Clinically, tumors of Group 1 tended to be smaller (29mm) than Group 2 (40mm), and cumulative smoking of Group 1 was lower (41 pack-years) than Group 2 (67 p-y) (p=0.03). Serum proGRP levels were significantly higher in Group 1 (50.9 pg/ml) than in Group 2 (26.4) (p&lt;0.01). Among cases treated by preoperative chemotherapy (n=12), PR:NC ratio was 6:3 in Group 1 and 2:1 in Group 2, suggesting no apparent difference of chemosensitivity. A few miRNA were differentially expressed in the two groups.
Conclusion: A distinct subgroup with favorable prognosis existed in SCLC. The subgroup was identified by both miRNA profiling as well as mRNA profiling. Detailed characterization of the subgroup 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 3020.
Abstract 3023: MicroRNA expression profile in pancreatic cancer stem cells
Authors: Jung Dawoon E. , Wen Jing , Oh Tae Yun , Song Si Young 
Published: February 2011

Abstract
MicroRNA(or miRNA) regulates various biological process including development, differentiation, proliferation, maintenance and apoptosis. Recently, existence of cancer stem cells was reported in some solid malignancies, including breast, brain, prostate, liver and pancreas cancers. Pancreatic ductal adenocarcinoma remains an extremely aggressive malignancy that is virtually therapy-resistant. Thus better understanding on cancer stem cell biology will not only help us to develop diagnostic marker for early diagnosis but also to treat against chemoresistant pancreatic cancer. Lately, evidences of miRNA involvement in cancer stem cells have been reported. Several miRNAs including let-7, mir-200, and mir-181 shows regulatory functions in cancer stem cells of different organs, however, miRNAs in other cancers including pancreas has not yet been reported. In this present study, we analyzed pancreatic cancer stem cell specific miRNAs and further investigated their functional role in cancer stem cells.
To analyze the differentially expressed miRNAs, we used sphere cultivation methods to enrich stem cell population and analyzed overall miRNA expression with miRNA microarray. Then correlation of miRNA expression and mRNA expression was analyzed by using linear model Yijkg=µ+Ai+Dj+Vk+Gg+AGig+VGkg+εijkg where A, D, V, and G represent the additive effect of the ith array, jth dye, kth biological group, and gth gene, respectively; AG represents the combinatorial effect of the ith array with the gth gene; εijkg describes the random error associated with each measurement; and VG for the combinatorial effect of the kth biological group with the gth gene. All additive effects were estimated via least squares and an F-test was performed on the modeled data to select differentially expressed genes. The candidate miRNA expression was confirmed by qRT-PCR.
As a result, number of miRNAs showed differential expression in sphere and are considered to have functional role in cancer stem cells by directly or indirectly targeting mRNAs. Further, correlation analysis suggested possible linkage between miRNA clusters with stem cell associated mRNAs.
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 3023.
Abstract 3026: miR-203 and miR-205 expression profiles are predictive of high grade non-invasive urothelial carcinoma progression
Authors: Rieger-Christ Kimberly M. , Tsai Sheaumei , Lenherr Sara M. , Cimmino Cara B. , Gee Jason R. , Libertino John A. , Summerhayes Ian C. 
Published: February 2011

Abstract
Introduction: MicroRNA (miRNA) has been shown to play a role in regulating the expression of genes involved in tumor suppression and oncogenesis. High-grade, non-muscle-invasive urothelial carcinoma of the bladder (UCB) harbors a significant risk of progression to muscle invasion. In this study, we sought to identify miRNAs differentially expressed in non-progressive high-grade non-muscle-invasive UCB as compared to pathologically identical lesions that progress to muscle invasion.
Methods: Total RNA was extracted from formalin fixed paraffin-embedded tissue (FFPE) of high-grade non-muscle-invasive (TaG3/T1G3) UCB lesions. Patients were categorized into two groups: non-progressors with at least 3 years follow-up or progressors advancing to ≥T2. Exclusion criteria were previous tumors of the upper tract, prior systemic chemotherapy or previous pelvic irradiation. Total RNA was pooled for microarray analysis from a subset of the non-progressor and progressor groups. Data was analyzed using the LOWESS normalization method. Expression profiles of miRNAs were verified with qRT-PCR on 89 high-grade non-muscle-invasive UCB (68 non-progressors and 21 progressors). Logistic regression analysis was performed to identify miRNAs predictive of tumor progression.
Results: MicroRNA microarray data identified a panel of miRNAs (25) with potential involvement in the progression to invasion of high-grade non-muscle-invasive UCB. 36% of these miRNAs were upregulated and 64% were downregulated in the progressor samples. To validate differential expression of these miRNAs, qRT-PCR was performed on the 89 FFPE tissue samples. Logistic regression analysis of qRT-PCR data revealed decreased expression of miR-203 and miR-205 as predictive of progression (p = 0.031 and p = 0.045, respectively). Subsequent qRT-PCR with miR-203 and miR-205 on 31 muscle-invasive tumor samples (≥T2) showed expression profiles that were similar to those of the non-invasive progressors.
Conclusions: In this study, we have shown that miR-203 and miR-205 can identify patients with non-muscle- invasive UCB at high risk to progress to muscle-invasive disease. Our findings also suggest that such tumors have a biomolecular profile similar to muscle-invasive lesions. Further validation studies are underway to investigate additional miRNAs and determine the mechanism by which these miRNAs promote tumor invasion and progression. These results provide an important tool that can be used to prognosticate the clinical behavior of a very challenging subset of tumors.
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 3026.
Abstract 3035: MicroRNA expression in early stage endometrial cancers
Authors: Chandramouli Gadisetti VR , Shoji Yutaka , Casablanca Yovanni , Maxwell G Larry , Risinger John I. 
Published: February 2011

Abstract
The molecular signatures of endometrial cancers from whole genome gene expression studies are now available setting a stage to explore the key regulators involved in these cancers. Non-coding micro-RNAs (miRNAs) are functionally important regulators of numerous cellular processes affecting growth and dissemination and possibly possess prognostic significance for several cancer types. In a first step toward understanding the miRNA biology of endometrial cancers, we performed an unbiased characterization of about 667 unique human miRNAs in stage-1 endometrial cancers including 51 endometrioid (16 grade-1, 23 grade-2 and 12 grade-3) and 7 serous (grade-3) cancer types and 17 endometrial epithelial samples from healthy individuals. In total, there were 8 stage IA, 32 stage IB and 18 stage IC cancers. RNA was extracted from samples prepared by laser capture micro-dissection which contained minimal non-epithelial cells. TaqMan Low Density Arrays (TLDA) were used to quantitatively determine the expression levels of miRNAs (TaqMan® MicroRNA Arrays A and B from Applied Biosystems). Isolated RNA was transcribed into cDNA and used to quantitatively assess the expression of 768 miRNAs arrayed within the TLDA. The Ct-values were initially normalized by subtracting a reference Ct-value derived from multiple positive controls on the array. These ΔCt values were filtered to exclude the miRNAs that were not expressed in any of the arrays. Statistical calculations were performed on -ΔCt values. In summary, about 158 miRNAs were up or down regulated in cancers at least by four-fold (p&lt;0.001) including many novel candidates for this cancer type. Notably, miR-183* was on average the most differentially over-expressed in both endometrioid and serous cancers compared to normal endometrium. The numbers of miRNAs and their statistical significance to distinguish the histological type, grade, and stage among cancers were found to be in decreasing order respectively. The putative mRNA targets of miRNAs were predicted using Targetscan v. 5.1. These predicted targets were further examined using gene expression data (Affymetrix Human Genome Plus 2.0) of the same RNAs. In conclusion, we identified numerous miRNAs that are disregulated in endometrial cancer. The potential of these miRNAs to define the biology of endometrial cancer is further 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 3035.
Abstract 3036: Comparison of miRNA expression between human osteoblasts and osteosarcoma cells
Authors: Duan Zhenfeng , Choy Edwin , Harmon David , Liu Xianzhe , Susa Michiro , Schwab Joe , Mankin Henry , Hornicek Francis 
Published: February 2011

Abstract
Osteosarcoma is the most common primary malignant bone tumor that most frequently affects young adults. There is increasing evidence that miRNAs (miRs) are important modulators of gene expression and their deregulation has been reported in various human tumors. This study investigated differences in miR expression in normal human osteoblast cells versus malignant human osteosarcoma cells differ in their miR expression. Analysis of miRNA expression in normal osteoblast cell lines (hOBc, NHOST, hFOB) and osteosarcoma cell lines (KHOS, Saos, U-2OS) were completed using miR microarray technology with unsupervised hierarchical clustering analysis. The relative expression levels of these miRs were confirmed by real-time quantitative RT-PCR. A number of miRs were found to have different expression in the osteosarcoma cells when compared to normal human osteoblasts. Three miRs, miR-199a-3p, miR-127-3p and miR-376c were significantly decreased in osteosarcoma cell lines while miR-151-3p and miR-191 were increased in osteosarcoma cell lines in comparison to osteoblasts. Because miR-199a-3p has been suggested to play a vital role in lung and liver cancer, we further characterized its biological functional role in osteosarcomas. The precursor (miR-199a-1) of miR-199a-3p was stably transfected into osteosarcoma cell lines KHOS and U-2OS, resulting in a decrease of cellular proliferation. The expression of miR-199a-3p targeted genes in transfected cells was evaluated by Western blot. These targets included MET and mTOR, two genes that were observed to be overexpressed in osteosarcoma tissues and various cell lines. Following miR-199a-3p transfection, a decrease in MET and mTOR expression was observed in KHOS and U-2OS cells. This study demonstrates that various miRs are differentially expressed in osteosarcomas, and miR-199a-3p, in particular may play a functional role in osteosarcoma cell growth and proliferation.
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 3036.
Abstract 304: Comparison of commercially available phospho-AKT [Ser473] antibodies for immunohistochemical biomarker analysis
Authors: Jeffers Michael , Dauffenbach Lisa M. , Bhargava Ajay , Lathia Chetan , Kerfoot Christopher A. 
Published: February 2011

Abstract
Immunohistochemical (IHC) analysis of AKT phosphorylation on Ser473 is commonly performed on pre- and post-treatment cancer biopsies as part of pharmacodynamic biomarker assessment for targeted oncology therapeutics. The current study was performed to assess the specificity and sensitivity of four pAKT Ser473 monoclonal antibodies for IHC analysis (clones D9E, 736E11, 587F11 and 14-5). To facilitate this analysis, cancer cell lines with constitutive activation of the PI3K pathway due to mutations in PIK3CA (MCF-7 and MKN-1) or PTEN (MDA-MB-468) were grown in the presence or absence of inhibitors of the PI3K pathway (wortmannin and LY294002). Cell lysates were prepared for analysis via Western blotting and formalin-fixed, paraffin-embedded cell pellets were prepared for analysis via IHC. All antibodies produced a band at 65 kDa, the expected molecular weight for pAKT, when used for Western blot analysis of untreated cell lines and demonstrated a reduction or ablation of this band following treatment of the cell lines with inhibitors of the PI3K pathway. When examined via IHC, antibodies 736E11 and 587F11 demonstrated nuclear and cytoplasmic staining in MCF-7 and MKN-1 cells and membrane staining in MDA-MB-468 cells. These antibodies demonstrated a reduction of staining in all three cell lines treated with PI3K inhibitors, but the reduction was modest in MCF-7 and MKN-1 cells. Clone 587F11 was the least sensitive for IHC. Staining with antibodies 14-5 and D9E was predominantly cytoplasmic or membrane associated, while clone14-5 produced a more punctate appearance. Strong staining was achieved with clone 14-5 and prominent reduction or ablation of staining was observed in all three cell lines treated with PI3K pathway inhibitors. Staining with clone D9E was a little less sensitive than with clone 14-5, but significant reduction or ablation of staining in cell lines treated with PI3K inhibitors was also observed. In summary, clones 14-5 and D9E appear to demonstrate adequate specificity and sensitivity for use in IHC assays.
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 304.
Abstract 3042: Investigating microRNA expression profiles in colon cancer cells in response to cyclooxygenase 2 signaling
Authors: Harpster Kelsey L. , Bean Ronald R. , Jakobi Rolf , Chang Yu-Wen E. 
Published: February 2011

Abstract
MicroRNAs (miRNAs) are emerging as central players in cancer progression. Aberrant expression of miRNAs leads to malignant transformation and correlates with staging, progression and prognosis of cancers. Unfortunately, signaling pathways leading to altered expression of miRNAs are largely unknown. During early development of colon cancer, the expression of cyclooxygenase 2 (COX-2) is constitutively induced. We and others have shown that constitutive expression of COX-2 promotes colon carcinogenesis. However, the underlying mechanisms are not completely understood. To determine if COX-2 signaling alters expression of miRNAs, we used the Human Cancer RT2-miRNA PCR arrays to profile miRNA expression in HCA-7 human colon cancer cells treated with or without the COX-2 selective inhibitor NS-398. HCA-7 cells constitutively express endogenous COX-2. We found that expression levels of 39 miRNAs are different in HCA-7 cells as compared to HCA-7 cells treated with NS-398; 8 miRNAs were up-regulated and 31 miRNAs were down-regulated. To confirm the data from the PCR array, we used quantitative RT-PCR to quantify expression of 8 miRNAs in HCA-7 cells with or without NS-398 treatment. These 8 miRNAs were selected due to their relevance to cancer invasion and metastasis. We also compared the expression of these miRNAs in HCT-15 human colon cancer cells that were engineered to stably express COX-2 (HCT-15-COX-2) to the parental HCT-15 cells. Expression levels of 6 of the 8 examined miRNAs (miR-23b, 124, 146b-5p, 155, 183, 184) were significantly lower in HCT-15-COX-2 or HCA-7 cells than in parental HCT-15 or HCA-7 cells that were treated with NS-398. Therefore, we identified 6 miRNAs that are modulated by COX-2 and may play a role in mediating COX-2 signaling to promote colon 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 3042.
Abstract 3047: 2-Methoxyestradiol inhibits proliferation and induces apoptosis through modulation of miR-7/FLIP signaling in prostate cancer cells
Authors: Kumar Saikartik , Ghosh Rita , Kumar Addanki P. 
Published: February 2011

Abstract
Prostate cancer is the second most common cause of death related to cancer in Western societies. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of 17-β estradiol inhibits tumor cell proliferation in various cancer cells, including in the prostate. Previous studies from our laboratory showed that 2-ME2 (i) inhibits proliferation of both androgen responsive and independent cells through induction of apoptosis involving G2/M check point block; (ii) prevents the development of prostate tumors in transgenic adenocarcinoma of mouse prostate (TRAMP) model. Although various molecular targets have been proposed, the mechanism of action behind its antiproliferative activity is still uncertain. Here we investigated the hypothesis that 2-ME2 may induce apoptosis in prostate cancer cells through modulation of microRNA (miRNAs). MicroRNAs are small non-coding RNAs that down regulate gene expression during cellular processes including proliferation and apoptosis. These studies led to the identification of miR-7 and −10 as predominantly up-regulated in response to 2-ME2 treatment in prostate cancer cell lines. Knock-down of miR-7 and −10 using mercury LNA probes showed resistance to 2-ME2-induced proliferation of prostate cancer cells. Additional studies to assess the effect of miR-7 knock-down to regulate apoptosis gene expression identified FLIP (FLICE -inhibitory protein) as one of the downstream targets of miR-7. We have shown that high grade prostate tumors express FLIP at higher levels compared to low grade and inhibition of prostate tumor development by 2-ME2 in preclinical animal model is associated with down regulation of FLIP. In addition overexpression of FLIP has been shown to contribute to resistance to apoptosis. We interpret our findings to suggest that up regulation of miR-7 following treatment with 2-ME2 inhibits FLIP leading to reduced proliferation and induction of apoptosis. Therefore our results may provide a molecular basis for the ability of 2-ME2 to suppress proliferation and to induce apoptosis in prostate cancer cells through modulation of miR-7 mediated inhibition of antiapoptotic genes including FLIP. Supported by ACS RSG-04-169 and NIH CA 135451 (APK).
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 3047.