bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4581: Implementation of a new cancer protein biomarker development pipeline - NCI's clinical proteomic technologies for cancer
Authors: Kinsinger Chris , Mesri Mehdi , Boja Emily , Hiltke Tara , Rahbar Amir , Rivers Robert , Rodriguez Henry 
Published: February 2011

Abstract
Proteomic technologies have revolutionized the area of protein biomarker discovery by providing powerful new tools such as protein arrays and mass spectrometry to characterize complex proteomes, multi-protein complexes and post-translational modifications. However, attempts to use proteomic approaches to discover cancer biomarkers in biofluids and tissues have been largely unsuccessful in the past. This indicates issues present in the biomarker candidate pipeline mainly due to variability within biomarker discovery and the lack of verification (or pre-validation) of biomarkers prior to costly clinical validation studies using immunosorbent assay (ELISA). Clinical Proteomic Technologies for Cancer (CPTC) initiative established by NCI in 2006 sought to develop a more refined, efficient, and reliable biomarker development pipeline anticipated to produce better-credentialed candidate leads, ultimately accelerating the translation of new cancer biomarkers into diagnostic tests. CPTC is a team science based five-year initiative composed of three components with an emphasis on the optimization of technology platforms, standards development, involvement with the U.S. Food and Drug Administration, and community reagents and resources development to address the challenges of clinical proteomics and to enhance technical abilities to identify and measure proteins accurately, quantitatively and reproducibly in biological systems. This presentation highlights the significant milestones of this initiative in building a more reliable and efficient protein biomarker development pipeline - one that consists of three development stages that we believe places the field of proteomics as a key component in initiatives for personalized medicine - Discovery, Verification, and Validation.
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 4581.
Abstract 4592: ER-beta inhibits cell proliferation in normal mammary epithelial cells
Authors: Pan Zhongzong , Zhong Yili , Song Xiaozheng 
Published: February 2011

Abstract
ER-beta is the second subtype of estrogen receptor and its role in mammary epithelial cell proliferation remains obscure. Studies using human breast cancer cell lines suggest that ER-beta may function as a tumor suppressor to inhibit cell proliferation. In the in vivo mouse studies, however, activation of ER-beta was shown to promote cell proliferation of normal mammary epithelial cells. It is not clear whether the difference is caused by the different experimental models, such as in vitro versus in vivo or breast cells versus normal cells. In our studies, we evaluated the effect of ER-beta on cell proliferation using immortalized normal mammary epithelial cell lines. We found that cell proliferation was significantly inhibited by ER-beta. FACS analysis on cell cycle showed that more cells were in the G2/M phase, suggesting that ER-beta may induce G2 arrest. The inhibitory function of ER-beta is independent of estrogen binding. In summary, our data support that ER-beta is a negative regulator of mammary epithelial cell 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 4592.
Abstract 46: Interdependence of choline kinase and phospholipase D in human breast cancer cells
Authors: Krishnamachary Balaji , Gadiya Mayur , Mori Noriko , Mironchik Yelena , Glunde Kristine , Bhujwalla Zaver M. 
Published: February 2011

Abstract
One hallmark of cancer is an increase of cellular phosphocholine (PC) and total choline-containing compounds (tCho), which are closely related to malignant transformation, invasion and metastasis. Enzymes in choline metabolism present attractive targets that can be exploited for treatment. Choline kinase (Chk) is a cytosolic enzyme that catalyzes the phosphorylation of choline (Cho) to phosphocholine (PC) by using ATP in the presence of magnesium. Over-expression of Chk-α has been observed in breast, prostate and lung cancers, making it an obvious choice for targeting. Down-regulation of Chk-α results in a significant reduction of cell proliferation and increased differentiation in highly invasive MDA-MB-231 human breast cancer cells after siRNA-Chk transfection. Another potential target is phosphatidylcholine-specific phospholipase D (PC-PLD). Two mammalian isoforms of PLD, PLD1 and PLD2 have currently been identified. PLD1 is activated by G proteins such as ARF, Rho and Rac. Elevated PLD1 has been reported in gastric, renal, colon and breast carcinoma.
We characterized the expression of PLD1 in metastatic MDA-MB-231 cells, poorly metastatic MCF-7 cells, and nonmalignant MCF-12A cells and used siRNA to transiently down-regulate PLD1 and Chk-α in MDA-MB-231 and MCF-7 cells. Forty-eight hours post-transfection cells were harvested for protein and RNA. To determine the effective knock-down of Chk-α or PLD1, about 30µg of protein was resolved on 7.5% acrylamide gel, transferred to nitrocellulose membrane and probed with antibody specific to either Chk-α or PLD1. The effects of Chk-α downregulation on PLD1 expression and the effects of PLD1 downregulation on Chk-α expression were determined by western blots, and the message was quantified with q-RT-PCR. Downregulation of Chk resulted in an increase of PLD1 in MDA-MB-231 cells stably expressing shRNA against Chk or transiently transfected with Chk siRNA. Similar data were obtained for MCF-7 cells. PLD1 levels were highest in the metastatic MDA-MB-231 cells. Effective downregulation of PLD1 was achieved with transient PLD1 siRNA transfection, which resulted in an increase of Chk-α in these cells. These data demonstrate the adaptability of cancer cells, the interdependence of Chk-α and PLD1, and the importance of multiple targeting to eliminate any adaptive compensatory effects that would allow cancer cells to survive. This work was supported by NIH P50 CA103175.
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 46.
Abstract 4630: Seminal AMACR protein: a non-invasive test in the detection of prostate cancer
Authors: Huang Wei , Jarrard David , Ritter Mark , Waknitz Michelle , Straus Jane , Wilding George 
Published: February 2011

Abstract
Introduction: Current prostate cancer screening relies on the PSA test and the digital rectum rectal examination (DRE), which have relatively low specificity. A more specific marker is in need for prostate cancer screening and risk stratification could reduce the burden of unnecessary biopsies. AMACR, has been proven to be an excellent tissue marker for prostate caner, could be an attractive candidate, but. Soso far, serum the detection of AMACR detection in serum has been unsuccessfuldifficult. This study explored the detection of AMACR protein in semen ejaculate and its potential as a non-invasive test in the diagnosis and management of prostate cancer.
Methods: Semen ejaculates were analyzed from 23 prostate cancer (biopsy proven) patients, 21 of which had prostatectomy, as well as 15 age-comparable controls (&gt;50y, PSA&lt;2 ng/mL, assumed prostate cancer free). An indirect sandwich ELISA chemiluminescence assay was used to test semen AMACR protein. Tissue AMACR protein was also quantified in 13 corresponding prostatectomy specimens using automated quantitative analysis (AQUATM).
Results: AMACR was detected in 19 of 23 (83%) semen ejaculates of prostate cancer patients. Among the other 4 patients with undetectable semen AMACR, one had no residual tumor in the prostatectomy specimen (#40), one had Gleason score of 9 cancer (#37) with no detectable tissue AMACR either, while the other two remaining patients (#31 and #33) had a very small volume of cancer on two separate sextant biopsies biopsy sets and are on watchful waiting list. AMACR was also detected in 7 of 15 (47%) control group. Using 100 ng/mL as a cutoff value, semen AMACR protein was positive in 16 of 23 (70%) cancer patients who had underwent prostatectomy and in 5 of 15 (33%) age-comparable controls.
Conclusions: This has been the first study first to demonstrated that AMACR protein is detectable in semen ejaculate. A high semen AMACR detection rate in cancer patients suggested suggests that semen AMACR may be useful, supplemental, as a non-invasive test in addition toto the PSA test for detecting prostate cancer, especially cancer of significant volume. Questions regarding specificity of AMACR are, however, raised. Given the lack of prostate biopsy confirmation, The the age-comparable controls in this study may not be an entirely representative sample of men free of prostate cancer without confirmation by prostate biopsy. This Our study's findings will form the basis for the design of a larger finding need to be further validated in a larger prospective screening trial of AMACR.
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 4630.
Abstract 4636: Increased expression of CSE1L/hCAS in colorectal cancer: Correlation with tumor progression
Authors: Shivers Steven C. , Coppola Domenico , Eschrich Steven A. , Chen Dung-Tsa , Shibata David , Yeatman Timothy J. , Malafa Mokenge P. 
Published: February 2011

Abstract
Introduction. The chromosome segregation and human cellular apoptosis susceptibility gene (CSE1L/hCAS) has been implicated in cancer and has been shown to be amplified in several human maligancies, including colorectal cancer. In this work, we sought to evaluate the gene expression of CSE1L/hCAS in colorectal cancer cell lines and tumor tissue and to examine CSE1L/hCAS expression in colorectal cancer progression.
Methods. In order to examine CSE1L/hCAS at the gene expression level, we surveyed three different datasets from studies in which Affymetrix U133+ gene chips had been performed on tissue samples from patients with colorectal cancer, as well as patients with adenomas and normal individuals. We examined relative gene expression levels for 3 probe sets on the U133+ gene chip that closely align to the RefSeq for the CSE1L/hCAS gene. In order to examine CSE1L/hCAS at the level of protein expression, we utilized a tissue microarray (TMA) that had been previously created at the Moffitt Cancer Center from primary colorectal tumors of various stages, adenomas and normal tissues and performed immunohistochemical (IHC) staining for the CSE1L/hCAS protein.
Results. CSE1L/hCAS showed increased gene expression in all of the adenoma and colorectal cancer patient samples tested by microarray, compared to tissue samples from normal individuals. However, there was not a significant difference in CSE1L/hCAS mRNA levels between patients with adenoma and those with invasive cancer, nor between patients compared by cancer stage, grade, vascular invasion, sex or age. IHC staining also demonstrated intense nuclear and/or cytoplasmic staining for the CSE1L/hCAS gene product in adenomas and invasive colorectal cancers. Furthermore, later stage specimens showed more intense nuclear staining, while early stage lesions, and even fibroblasts in nearby normal tissue, showed predominately cytoplasmic staining for CSE1L/hCAS.
Conclusions. These results demonstrate that increased expression of the CSE1L/hCAS gene, while not specific for invasive cancer cells, might be a good marker for early detection of colorectal cancer. This gene appears to be expressed early and across all stages of cancer development. Because of its early expression and potential involvement in a variety of important cellular processes, we believe that this gene product might represent a potential target for prevention and/or treatment of early 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 4636.
Abstract 4645: CIP2A is a marker of reduced survival in serous ovarian cancer patients
Authors: Böckelman Camilla , Lassus Heini , Hemmes Annabrita , Leminen Arto , Westermarck Jukka , Haglund Caj , Bützow Ralf , Ristimäki Ari 
Published: February 2011

Abstract
Cancerous inhibitor of PP2A (CIP2A) is a recently identified oncoprotein, but its role in ovarian cancer is not known. We analyzed CIP2A protein expression in 562 consecutive serous ovarian cancer patients, of which 524 were scored successfully and analyzed for presence of CIP2A immunopositivity using tissue microarrays. The association of CIP2A expression with survival was evaluated according to the Kaplan-Meier method. We found strong CIP2A positive immunostaining in 212 (40.4%) specimens, 222 (42.4%) were weakly positive, while the rest (n = 90, 17.2%) were immunonegative for CIP2A protein. Our results demonstrate that CIP2A immunopositivity is a marker of reduced overall survival in ovarian cancer patients (P &lt; 0.0001). In addition, positive CIP2A expression was significantly more frequent in specimens with high grade (P &lt; 0.0001), advanced stage (P = 0.0005), aberrant p53 immunoreactivity (P &lt; 0.0001), high proliferation index (P &lt; 0.0001), and aneuploidy (P = 0.001). Interestingly, in subgroups of patients with favorable clinical factors (i.e. low stage and optimal debulking surgery) CIP2A expression was strongly associated with reduced survival (P &lt; 0.0001 for both parameters). This shows that CIP2A could be used to predict biological behavior in the group of patients with otherwise favorable prognosis. In conclusion, our results show that CIP2A protein expression is a novel marker of reduced survival in patients with serous ovarian carcinoma. Furthermore, these results suggest that CIP2A characterizes the aggressive type of this disease even within subgroups with initially favorable prognosis.
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 4645.
Abstract 4649: Comprehensive isoform expression analysis reveals that EGFR and sEGFR are prognostic determinants of cancer
Authors: Wilken Jason A. , Baron Andre T. , McCormick Daniel J. , Singh Meenakshi , Maihle Nita J. 
Published: February 2011

Abstract
In July, 2009 the United States’ Food and Drug Agency (FDA) approved the use of a new biologically-targeted drug called ‘cetuximab’ (Erbitux) for the treatment of patients with advanced colorectal cancer (CRC). Cetuximab is a chimeric antibody directed against the extracellular domain of the epidermal growth factor receptor (EGFR). Paradoxically, EGFR expression, as it is currently measured by commercially available assays, has not been useful for predicting who will respond to cetuximab. We propose that one problem with these assays is their inability to measure EGFR and soluble EGFR (sEGFR) isoforms independently. We previously have documented the expression of an sEGFR isoform in human tissues (1), and have generated antibodies directed against a 31-mer peptide (residues 604-634) located within the unique 78 amino acid carboxy-terminal sequence of sEGFR (2). Interestingly, this anti-sEGFR antibody recognizes a second protein of ∼140-kDa (p140), which we have identified as human α5-integrin. Biochemical and mass spectrometry analyses show that a short region in the calf domain of α5-integrin shares sequence identity with the 31-mer sEGFR peptide. We have used this 31-mer antibody with an antibody directed against the intracellular domain of full-length EGFR to develop a novel EGFR vs. sEGFR/α5-integrin expression assay. This assay demonstrates that sEGFR/α5-integrin is co-expressed with EGFR in normal as well as malignant tissues, including in a number of carcinoma-derived cell lines. We also observe that high expression of EGFR and sEGFR/α5-integrin in a large cohort of ovarian cancer patients defines a strong adverse prognostic determinant of survival. These results implicate EGFR, sEGFR, and integrins as cancer biomarkers and demonstrate the critical importance of independently assessing both full-length and soluble EGFR isoforms in prognostic EGFR expression assays.
*–JAW and ATB contributed equally to this study
(1). Reiter et al. (2001) Genomics. 71(1):1-20
(2). Christensen et al. (2002) Hybrid Hybridomics. 21(3):183-9
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 4649.
Abstract 465: Human enhancer of filamentation 1 is a mediator of hypoxia-inducible factor-1 alpha-mediated migration in colorectal carcinoma cells
Authors: Kim Sun-Hee , Xia Dianren , Kim Sang-Wook , Holla Vijaykumar , Menter David G. , DuBois Raymond N. 
Published: February 2011

Abstract
Human enhancer of filamentation 1 (HEF1, also known as NEDD9 or Cas-L) is a scaffolding protein that is implicated in regulating diverse cellular processes, including cellular attachment, motility, cell cycle progression, apoptosis and inflammation. Here, we identify HEF1 as a novel hypoxia-inducible factor-1α (HIF-1α) regulating gene and reveal that HEF1 mediates hypoxia-induced migration of colorectal cancer (CRC) cells. Moreover, we found that HIF-1α binds to a hypoxia-responsive element (HRE) of the HEF1 promoter to activate its transcription under hypoxic conditions. We further demonstrate that inhibition of HIF-1α expression abolished hypoxia-induced HEF1 expression and promoter activity in CRC cells. Importantly, silencing of HEF1 significantly inhibited hypoxia-stimulated HIF-1α transcriptional activity by preventing the interaction between HIF-1α and the transcriptional coactivator p300. HEF1 silencing also reduced the expression of hypoxia-inducible genes including those regulating cell motility and inhibited cell migration under hypoxic conditions. Thus, the positive feedback loop may contribute to adaptive responses by CRC cells that encounter hypoxia during CRC progression.
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 465.
Abstract 4672: Tumor dihydropyrimide dehydrogenase (DPYD) expression is associated with survival in patients with metastatic colorectal cancer treated with gefitinib, 5-fluorouracil, leucovorin, and oxaliplatin (IFOX)
Authors: Francisco Edgar B. , Link James T. , Ramsey Meghan , Beck Andy H. , Schwartz Erich , Rouse Robert , Fisher George A. , Sikic Branimir I. 
Published: February 2011

Abstract
New drugs that target the EGFR signaling pathways suggest that EGFR inhibition exerts a chemosensitizing effect in colorectal cancer. We have previously reported that the combination of gefitinib, leucovorin, 5-flourouracil, and oxaliplatin (IFOX) resulted in higher response rates than those reported with FOLFOX-4 alone in patients with metastatic colorectal cancer. The aim of the present study was to examine genomic factors that might be associated with response or survival in the IFOX regimen.
Patients and Methods: Seventy-two patients had stage IV colorectal adenocarcinoma and were either untreated or previously treated prior to receiving the IFOX regimen. Formalin-fixed, paraffin-embedded tissues (FFPE; n=63) were obtained, and 4-um sections were cut, placed on slides, and deparaffinized in xylene, followed by laser capture microdissection (LCM; n=42) to enrich for tumor cells. Using real-time quantitative RT-PCR, thirty-five samples had good-quality actin RNA readings following LCM, and the expression levels of dihydropyrimidine dehydrogenase (DPYD), epidermal growth factor receptor (EGFR), excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), thymidylate synthase (TYMS), and thymidine phosphorylase (TYMP) were separately quantified. To detect mutations in KRAS, DNA was extracted from fifty-eight patient samples and analyzed using the KRAS Mutector II kit (TrimGen, Sparks, MD).
Results: For the 33 patients available for RT-PCR analysis, expression levels of DPYD, EGFR, ERCC1, TYMP, or TYMS did not correlate significantly with response. However, in terms of survival, the overall survival rate was significantly worse in patients with a high DPYD expression level compared to patients with a low DPYD expression level (p&lt;0.05), and in a multivariate analysis, patients with both a high DPYD expression and a low EGFR expression had the worst survival compared to all other patients with differing expression levels of these two genes (p&lt;0.01). KRAS mutations were identified in 24 out of 58 patients (41%), but KRAS mutational status did not correlate with either response or survival.
Conclusion: Dihydropyrimidine dehydrogenase mRNA expression was a significant independent prognostic factor for overall survival in colorectal cancer patients treated with FOLFOX-4 along with EGFR inhibition by gefitinib.
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 4672.