bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1927: Polyploidy across breast cancer subtypes.
Authors: Fothergill Amy , Burkard Mark 
Published: August 2014

Abstract
Introduction: Breast cancer remains the most common cancer in women. Although treatment advances have improved the prognosis for many women, many existing therapies have significant associated toxicities. A major goal of current research is to develop targeted therapies based on characteristics of each individual's cancer.
Polyploidy can provide a potential difference between cancer and normal cells that can be harnessed to selectively destroy cancer cells. We hypothesize that polyploidy is common in aggressive triple negative breast cancer. If this is the case, polyploidy could provide a target for therapy in triple negative cancers.
Methods:We conducted a retrospective review of data collected by the University of Wisconsin Tumor Registry and HER2 testing by the state lab of hygiene between 2003 and 2011. Patients from the two data sets were matched by name and/or medical record number. Tumors were considered polyploid if ≥3 CEP17 signals were detected. Chi square testing and student T-tests were used to identify statistical correlations.
Results: A total of 1211 were identified meeting eligibility criteria and 170 women had polyploid tumors. Of these, 72 had unknown or equivocal results for ER/PR or HER2 and were excluded from analyses. Polyploid tumors correlated with TNBC (p=0.028) and hormone receptor negative cancer (p=0.02). Subgroup analysis showed a positive correlation between HER2 positive tumors and polyploid tumors (p=0.0005). Polyploidy tumors were more likely to be either stage I or stage IV (p=0.0019). Vital status at last contact and age at diagnosis were not significantly different between the two groups (p=0.2875 and 0.7826, respectively).
Discussion:We conclude that polyploid tumors cross all known subtypes of breast cancer, but are enriched among triple negative cancers. This may represent a viable group of cancers that can be targeted with specialized therapy.
Table 1 Polyploid Euploid P HER2- 122 857 0.0005 Hormone- 38 164 0.02 Triple negative cancers 29 121 0.028 Stage I 80 612 0.002 Stage II 54 275 Stage III 29 99 Stage IV 4 49 Unknown stage 3 6 Mortality 33 168 0.29 Mean Age 59 58 0.78
Citation Format: Amy Fothergill, Mark Burkard. Polyploidy across breast cancer subtypes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1927. doi:10.1158/1538-7445.AM2013-1927
Abstract 1936: The increased frequency of ERG oncoprotein expression in high grade prostate cancers in Caucasian American in comparison to African American men.
Authors: Young Denise , Farrell James , Chen Yongmei , Cullen Jennifer , Petrovics Gyorgy , Rosner Inger , McLeod David G. , Srivastava Shiv , Sesterhenn Isabell A. 
Published: August 2014

Abstract
Introduction & Objectives: ERG is one of the most commonly over expressed oncogene (50-70%) in prostate cancer (CaP) due to TMPRSS2-ERG gene fusion. Prior studies suggested that the fusion is more common in Caucasian American (CA) than in African Americans (AA) men with CaP. Previous studies from our laboratory have also shown that in AA patients the higher grade index tumors were predominantly ERG negative. We sought to quantify the association between race and ERG expression in a cohort of high grade CaP patients. We then examined whether the prevalence of ERG has prognostic significance for CaP disease-specific outcomes.
Materials & Methods: The CPDR multi-center national database was queried to identify patients with high grade CaP who underwent radical prostatectomy between 1994 and 2011. Sixty-three AA patients were age-matched with 63 CA patients (n=126). Immunohistochemistry was performed to detect fusion status in representative whole mount prostate specimens using an ERG monoclonal antibody (9FY). Tumors were classified as ERG positive or negative and compared by race. Multivariate analysis and Kaplan-Meier curves were used to evaluate the clinical significance of ERG oncoprotein positivity.
Results: The frequency of ERG-positive index tumors in high grade CaP was significantly greater among CA patients compared to AA patients (49% vs.16%, P &lt; .0001) by chi-squared analysis. This observation persisted when all ERG-positive tumor foci were assessed between CA and AA patients (59% vs. 33%, P = .0042). Neither ERG prevalence nor race was predictive of biochemical recurrence in this cohort.
Conclusions: This study examined the prevalence of ERG oncoprotein expression in high grade CaP patients stratified by race. ERG expression (predominantly due to TMPRSS2-ERG gene fusion) is significantly more common in high grade CaP of CA compared with AA patients. Genetic alterations in high grade CaP in the AA population need to be further determined. This study underscores that typing of prostate tumors for ERG may enhance our understanding of biological differences between ethnic groups.
Citation Format: Denise Young, James Farrell, Yongmei Chen, Jennifer Cullen, Gyorgy Petrovics, Inger Rosner, David G. McLeod, Shiv Srivastava, Isabell A. Sesterhenn. The increased frequency of ERG oncoprotein expression in high grade prostate cancers in Caucasian American in comparison to African American men. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1936. doi:10.1158/1538-7445.AM2013-1936
Abstract 1941: Identification of microRNA(miRNA) signature genes for chemoresistance through high throughput profiling of cancer related miRNAs (OncomiRs) in ovarian cancer cell lines and formalin fixed, paraffin embedded (FFPE) ovarian tissues.
Authors: Guan Yinghui , Lu Shan , Ryner Lisa , Wang Yulei 
Published: August 2014

Abstract
The standard treatment for ovarian cancer after cytoreductive surgery is platinum combined with taxane based chemotherapy. However, most patients quickly develop resistance to these therapies. Many miRNA have been implicated to play critical roles in regulating genes involved in chemoresistance.
In order to understand mechanism of potential drug resistance to small molecule agents used in our pipeline antibody drug conjugates, we first optimized and developed a gene expression panel for detecting 96 OncomiRs that have previously been identified as either oncogenic or tumor suppressive genes in multiple cancer types using the Fluidigm 96.96 dynamic array platform. A synthetic miRNA pool and a 22-tissue total
RNA pool were first titrated and tested against these 96 OncomiRs to determine the feasibility of multiplexing of 96 genes in the reverse transcription and pre-PCR amplification steps and the dynamic range of the assay. The slopes of Ct vs. RNA input in most assays showed over 90% amplification efficiency and more than 1000 fold detection range. We then profiled 53 ovarian cancer cell lines using this 96-OncomiR panel.
Unsupervised hierarchical clustering showed that expression of 96 genes in these cell lines could separate them into two distinctive clusters with overexpression of either markers for epithelial or for mesenchymal subtypes, indicating the OncomiR panel could represent both molecular subtypes. By correlating miRNA expression levels of these cell lines with their responses to several chemotherapeutic compounds, we have identified distinctive miRNA signatures of sensitivity or resistance to each compound. The overexpression of some miRNAs is consistently correlated with resistance to multiple compounds implying their target mRNA genes might confer multidrug resistance. We have also profiled 130 FFPE samples from ovarian cancer patients who were either platinum treatment sensitive or resistant using the OncomiR panel. miRNA expression markers for predicting platinum sensitivity and resistance will be also presented. In conclusion, our OncomiR
Fluidigm panel can provide an important tool for predicting clinical outcome and drug response.
Citation Format: Yinghui Guan, Shan Lu, Lisa Ryner, Yulei Wang. Identification of microRNA(miRNA) signature genes for chemoresistance through high throughput profiling of cancer related miRNAs (OncomiRs) in ovarian cancer cell lines and formalin fixed, paraffin embedded (FFPE) ovarian tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1941. doi:10.1158/1538-7445.AM2013-1941
Abstract 1946: Downregulated microRNAs in salivary rinse from patients with head and neck squamous cells carcinoma.
Authors: Pelarin Maria Fernanda A. , Horst Maria Aderuza , Carvalho Ana Carolina , Kowalski Luiz Paulo , Vettore André Luiz , Karia Bruno 
Published: August 2014

Abstract
Head and neck Squamous cell carcinoma (HNSCC) is a disease with high incidence and mortality, and the sixth most common cancer worldwide. The diagnosis is usually made late, after the appearance of visible lesions. The discovery of altered epigenetic profiles in cancer awakened to new paradigms by which molecular mechanisms contribute significantly to carcinogenesis. To date, approximately 1000 miRNAs have been described and it is estimated that they may influence the expression of up to one third of human genes. The deregulation of the expression of miRNAs can directly influence cell proliferation and differentiation and therefore, they can act as oncogenes or tumor suppressors. The aim of this study is to compare the miRNAs expression profiles in saliva samples from patients with HNSCC and normal controls in order to identify potential diagnostic markers for this cancer. Comprehensive miRNA profile was done in 4 salivary rinse samples from HNSCC patients and 3 samples from healthy donors using a Megaplex TaqMan Low Density miRNA Arrays (TLDA) to assess the expression status of miRNAs. 101 miRNAs differentialy expressed were identified. From that, 21 were upregulated in the HNSCC samples while 80 were downregulated in these samples. After a deep revision of the information available from them, we selected candidates to be validated in an independent group of 100 salivary rinses collected from HNSCC patient at diagnoses. A preliminary result indicated that four selected miRNA were down regulated with 90-91% of specificity and 53-64% of sensibility. Our hypothesis is based on the fact that the down regulation confirmed in our results may be related to the potential of tumor suppressor activity of these miRNAs; Besides the validation obtained by our tests, important studies in the literature show agreement with this hypothesis and may add relevant data in developing this study.
Supported by Fapesp (Grant 2011/15122-9).
Citation Format: Maria Fernanda A. Pelarin, Maria Aderuza Horst, Ana Carolina Carvalho, Luiz Paulo Kowalski, André Luiz Vettore, Bruno Karia. Downregulated microRNAs in salivary rinse from patients with head and neck squamous cells carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1946. doi:10.1158/1538-7445.AM2013-1946
Abstract 1954: Circulating microRNA-21 predicts the response to hypomethylating agents in patients with myelodysplastic syndromes.
Authors: Min Yoo Hong , Cho Jae Yong , Kim Yundeok , Kim Yeo-Kyeoung , Kim Soo Jeong , Kim Jin Seok , Cheong June-Won , Kim Hyeuong Joon 
Published: August 2014

Abstract
Background: Although hypomethylating agents therapy have considerably improved the outcomes of patients with myelodysplastic syndromes (MDS), the discovery of sensitive non-invasive biomarkers that can facilitate the prediction of response to hypomethylating agents (HMA) and therapeutic outcomes are highly desirable to determine optimized strategies of epigenetic therapy for MDS. Circulating microRNAs have been evaluated as potential biomarkers for cancer diagnosis and prognosis prediction.
Purpose: We evaluated the significance of miR-21 expression in serum as a biomarker for predicting response in MDS patients treated with HMA.
Patients and methods: Serum miR-21 level was measured by quantitative real-time PCR in 58 MDS patients at diagnosis and 14 healthy controls. We analyzed the correlation between serum miR-21 level and clinical characteristics and response to HMA and survival.
Results: We found that serum miR-21 level was significantly downregulated in patients with MDS than those in healthy controls (P&lt;0.001). Moreover, miR-21 level was significantly lower in patients with response (CR, mCR, PR and SD with HI) to HMA compared to those without response (median, 0.9414±0.6349 vs. 1.1443±0.7707; P=0.041). Receiver-operator characteristic curve analysis indicated that serum miR-21 was useful in differentiating responder from non-responder with AUC of 0.648. At a cut-off value of 1.2613 for serum miR-21 level, the optimal sensitivity and specificity were 83.3% (95% CI: 68.6-93.3%) and 45.8% (95%CI: 25.5-67.1%), respectively. Patients, whose miR-21 level at diagnosis was higher than cutoff level, were defined as high miR-21 group (n=17) and the low miR-21 group representing the remaining 41 patients. We found that patients in high miR-21 grooup, compared with those in low miR-21 group, had a shorter median PFS (P=0.001). On multivariate analysis, Serum miR-21 level remained as a significant prognostic factor for response to HMA and PFS.
Conclusion: In this study, we evaluated the levels of serum miR-21 in patients with MDS, and found that serum miR-21 level predicts response to HMA and PFS in MDS. Although this prognostic significance should be validated in an independent set of patients receiving HMA, serum miR-21 level is a promising biochemical marker for response prediction to HMT.
Citation Format: Yoo Hong Min, Jae Yong Cho, Yundeok Kim, Yeo-Kyeoung Kim, Soo Jeong Kim, Jin Seok Kim, June-Won Cheong, Hyeuong Joon Kim. Circulating microRNA-21 predicts the response to hypomethylating agents in patients with myelodysplastic syndromes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1954. doi:10.1158/1538-7445.AM2013-1954
Abstract 1960: Implication of miR-34a in radioresistance of bladder cancer .
Authors: Mansure Jose J. , Nassim Roland , Kassouf Wassim 
Published: August 2014

Abstract
Purpose : Investigate resistance of radiation via miR-34a expression in human urothelial carcinoma
Methods : Human urothelial carcinoma cell lines derived from well-differentiated superficial bladder tumors as well as from high-grade invasive tumors were screened for their sensitivity to radiation. Growth inhibition was monitored by clonogenic assays. qRT-PCR analysis was used to evaluate expression of miR-34a among the human urothelial carcinoma cell lines. Methylation-specific polymerase chain reaction (MSP) was performed to determine CpG methylation status of miR-34a gene promoter among the cell lines. Association between miR-34a and sensitivity to radiation was also investigated by ectopic expression of miR-34a. Western blot was performed to evaluate protein expression.
Results: Remarkable differences in sensitivity to radiation have been shown among those cell lines in vitro. Of interest, miR-34a expression correlates with human bladder cancer cell response to radiation, with resistant cell lines showing lower expression of miR-34a and that is due to CpG methylation of its promoter. Additionally, an inverse correlation was observed between miR-34a and expression of sirtuin1 (SIRT1). Ectopic expression of miR-34a in cell lines resistant to radiation showed a positive effect of miR-34a to the response therapy. Growth inhibition observed after treatment could be explained, in part, by the increased expression of the cell cycle inhibitor p21.
Conclusion: Preliminary results suggest that detection of miR-34a expression may potentially be used as a predictor of therapeutic efficacy, and its regulation represent an attractive mechanism for the management of bladder cancer therapy.
Citation Format: Jose J. Mansure, Roland Nassim, Wassim Kassouf. Implication of miR-34a in radioresistance of bladder cancer . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1960. doi:10.1158/1538-7445.AM2013-1960
Abstract 1975: AICAR induces cell death in LKB1-deficient NSCLC.
Authors: Liu Fakeng , Zhou Wei , Liu Xiuju , Sun Shi-yong , Khuri Fadlo , He Yu-long , Zhong Diansheng 
Published: August 2014

Abstract
AICAR is a well known AMPK activator, and AICAR-induced AMPK activation has been shown to inhibit cell proliferation or induce apoptosis through various mechanisms, such as the inactivation of metabolic enzyme involved ATP consumption, the inhibition of the of fatty acid synthesisPI3K/AKT pathway, the activation of cell cycle regulators, or the activation of the JNK pathway. LKB1 is an upstream AMPK kinase, and energetic stress-induced AMPK activation usually requires LKB1. Interestingly, AICAR has also been shown to induce caspase-3 cleavage in LKB1- null MEF and ovarian cancer cells, indicating AICAR can induce cell killing through an AMPK- independent mechanism. Because LKB1 is most frequently inactivated in non-small cell lung cancer, we evaluated the effect of AICAR in lung cancer cell lines. AICAR preferentially induced caspase-3 cleavage in LKB1- mutant NSCLC cell lines H157, A549, H460 and H1944, but not in LKB1- wild type cell lines H1299, H358, H1650 and H1792. Transient depletion of LKB1 by RNAi in H1299 and H1792 cells promoted AICAR-induced caaspase-3 cleavage in the absence of AMPK activation, supporting the notion that AICAR induces cell killing in LKB1-depleted cells through an AMPK- independent mechanism. In LKB1-null H460 cells, AICAR treatment led to a significant increase in S phase cell populations, and G1 cell cycle arrest by serum starvation is was sufficient to prevent AICAR-induced cell death. These data indicated that AICAR-induced cell killing in LKB1- deficient cells is cell cycle dependent. In summary, the ability of AICAR to preferentially induce cell death in LKB1- deficient NSCLC suggestsed that LKB1 deficiency may be a therapeutic target for the treatment of NSCLC.
Citation Format: Fakeng Liu, Wei Zhou, Xiuju Liu, Shi-yong Sun, Fadlo Khuri, Yu-long He, Diansheng Zhong. AICAR induces cell death in LKB1-deficient NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1975. doi:10.1158/1538-7445.AM2013-1975
Abstract 1982: TCEB3C (Elongin A3) on chromosome 18 presents a putative tumor suppressor gene of small intestine neuroendocrine tumors.
Authors: Edfeldt Katarina , Ahmad Tanvver , Åkerström Göran , Tiensuu Janson Eva , Hellman Per , Stålberg Peter , Björklund Peyman , Westin Gunnar 
Published: August 2014

Abstract
Small intestine neuroendocrine tumors (SI-NETs) arise from the enterochromaffin cells and produce hormones which can cause the carcinoid syndrome. The incidence is increasing and the five-year survival rate is 60-80 %. Loss of one copy of chromosome 18 is a very frequent event in these tumors, supporting the presence of a crucial tumor suppressor gene. This study investigated whether TCEB3C, encoding Elongin A3, presents a putative tumor suppressor gene in SI-NETs. This gene is currently the only known imprinted gene on chromosome 18, requiring only one gene copy inactivation event to fulfill the Knudson hypothesis.
Elongin A3 expression in SI-NETs (n=47) was heterogeneous and negative in most cells. 5-Aza-2’-deoxycytidine induced expression of Elongin A3 in a carcinoid tumor cell line and in tumor derived primary cell cultures, but not in a control cell line. Also the general histone methyltransferase inhibitor 3-deazaneplanocin A induced TCEB3C expression in the carcinoid tumor cell line, but not in control cells suggesting further that the TCEB3C gene was epigenetically suppressed in neuroendocrine tumor cells. The TCEB3C gene encompasses an CpG island and quantitative cytosine CpG methylation analysis will be presented. Furthermore, overexpression of Elongin A3 led to a decrease in clonogenic survival of carcinoid tumor cells, but not of control cells strongly supporting a growth-regulatory role. These results support a putative tumor suppressor role of TCEB3C in neuroendocrine cells of the small intestine.
Citation Format: Katarina Edfeldt, Tanvver Ahmad, Göran Åkerström, Eva Tiensuu Janson, Per Hellman, Peter Stålberg, Peyman Björklund, Gunnar Westin. TCEB3C (Elongin A3) on chromosome 18 presents a putative tumor suppressor gene of small intestine neuroendocrine tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1982. doi:10.1158/1538-7445.AM2013-1982
Abstract 1992: Is the ubiquitin ligase WWP2 playing a role in PTEN degradation in endometrial cancer.
Authors: Clements Aine , McElroy Joseph , Suarez Adrian , Majumder Sarmila , Cohn David , Leone Gustavo 
Published: August 2014

Abstract
Objective: The ubiquitin ligase WWP2 has recently been described to directly interact with PTEN, the major tumor suppressor gene in the PI3K pathway commonly altered in endometrial cancer. Whether alterations of WWP2 contribute to post-translational modifications of the PTEN protein in endometrial cancer are unknown. We sought to determine if WWP2 gene expression levels differ in human endometrial cancer tissues with evidence of post-translational PTEN degradation. We also wished to determine if elevated WWP2 gene expression was associated with clinical prognostic variables.
Methods: Twenty-four endometrial cancer specimens collected at hysterectomy were available for analysis. These tumors were stained for PTEN by immunohistochemistry (IHC) and scored using a scale of 0-6. Frozen tissue was then used to determine PTEN and WWP2 expression by Real time PCR (RT PCR). Gene expression was then compared with findings on immunohistochemistry. Patient clinical characteristics including stage, grade, lymph node metastases, recurrence or 2 year disease status were then compared with PTEN and WWP2 expression.
Results: Three tumors had elevated PTEN gene expression (at least 2 fold) but low (score of less than 4) PTEN protein on IHC, indicating post-translational modification of PTEN. In these tumors, however, WWP2 expression was not elevated (range 0.004-0.09). There were three tumors with elevation in WWP2 expression (1.9-4.7). PTEN was low in these tumors on IHC, but was also low by RT-PCR indicating genomic, epigenetic or post-transcriptional modification of PTEN. Neither PTEN nor WWP2 expression on RT PCR was associated with stage, grade, lymph node metastases, recurrence or 2 year disease status.
Conclusions: In this cohort of tumors, WWP2 did not contribute to post-translational degradation of PTEN. WWP2 expression was not associated with stage, grade, lymph node metastases, recurrence, or 2 year disease status.
Citation Format: Aine Clements, Joseph McElroy, Adrian Suarez, Sarmila Majumder, David Cohn, Gustavo Leone. Is the ubiquitin ligase WWP2 playing a role in PTEN degradation in endometrial cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1992. doi:10.1158/1538-7445.AM2013-1992