bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2708: E-cadherin expression might be a predictive marker for chemosensitivity in triple-negative breast cancer
Authors: Shinichiro Kashiwagi , Yashiro Masakazu , Takashima Tsutomu , Noda Satoru , Kawajiri Hidemi , Matsuoka Junko , Fuyuhiro Yuhiko , Kato Yukihiro , Doi Yosuke , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Inoue Toru , Sawada Tetsuji , Onoda Naoyoshi , Nakata Bunzo , Ohira Masaichi , Ishikawa Tetsuro , Hirakawa Kosei 
Published: February 2011

Abstract
Introduction: Triple-negative breast cancer (TNBC), a subtype of breast tumor with ER negative, PR negative, and HER2 negative, shows a poor prognosis because of a frequent recurrence. Chemotherapy is important for the treatment of recurrent TNBC, however no reliable parameter has been identified for chemo-sensitivity in TNBC. Although E-cadherin is one of markers for chemo-sensitivity in several types of carcinomas, not much of the correlation between E-cadherin expression and chemo-sensitivity is known in TNBC. The aim of this study was to evaluate the significance of E-cadherin in TNBC.
Material and Methods: The subjects of this study were 574 patients with primary infiltrating breast ductal cancer. Adjuvant therapy was performed according to the guidelines of breast cancer by NCCN. ER and PR status were assessed by immunohistochemistry. HER2 status was assessed by either immunohistochemistry or fluorescent in situ hybridization. E-cadherin expression was immunohistochemically analyzed by ABC method. E-cadherin expression was semi-quantitatively analyzed according to the percentage of cells showing membrane positivity: 0-10%; 0, 10-30%; 1+, 30-70%; 2+, &gt;70%; 3+. E-cadherin expression was considered positive when scores were ≥2+.
Results: Among the 574 breast cancer cases, 123 (21.4%) revealed a triple-negative phenotype. Reduced levels of E-cadherin were observed in 238 (41.5%) of the 574 breast cancer cases. The cases with E-cadherin loss was frequent (90 of 123 cases) in TNBC. Eighty-nine cases of 123 TNBC cases were performed chemotherapy. In 89 TNBC cases with chemotherapy, the prognosis of E-cadherin-negative patients is significantly poor (p&lt;0.01), in comparison with that of E-cadherin-positive patients, while a multiple analysis demonstrated that reduction of E-cadherin expression was not an independent prognostic factor. In contrast, no significant difference of prognosis between E-cadherin positive patients and negative patients was found in 34 TNBC cases without chemotherapy. Conclusion: E-cadherin might be a useful predictive marker for chemo-sensitivity in TNBC.
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 2708.
Abstract 271: Heregulin internalization to the nucleus is mediated via binding to nucleolin
Authors: Yang Lin , Lupu Ruth 
Published: February 2011

Abstract
Heregulin internalization to the nucleus is mediated via binding to Nucleolin
Lin Yang, and Ruth Lupu. Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, Minnesota 55902
Heregulin (HRG) is known as a soluble secreted growth factor of EGF-like family, which binds and activates HER3 and HER4 and transactivates HER2 and HER1 receptors. It has been shown that HRG translocates to the nucleus in triple negative breast cancer cells that express high level of HRG. The mechanism by which HRG translocates to the nucleus is still unknown. We have recently uncovered that Nucleolin binds to Heregulin and allows HRG to translocate to the nucleus. Mass spectrometry analysis revealed that multifunctional protein Nucleolin is a major HRG-associated protein. Using co-immunoprecipitation we confirmed HRG interacts with Nucleolin in both endogenous and ectopic levels. Then, we made deleted mutants of HRG to map the Nucleolin binding domain on HRG and we found that Nucleolin binds to HRG on its N-terminus which contains a putative nuclear localization signal (NLS). Remarkably, in these cells we found a striking peri-nuclear accumulation when Nucleolin was knocked down. These results show for the first time that HRG translocate to the nucleus mediated by Nucleolin binding in breast cancer cells. Importantly, the nuclear function of HRG remains as a positive regulator of chemosensitization.
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 271.
Abstract 2712: Heterogeneous nuclear ribonucleoprotein H1 confers transcription and transactivation of androgen receptor: Implications for prostate cancer progression in African American men
Authors: Yang Yijun , Jia Dingwu , Davis Rodney , Moparty Krishnarao , Thomas Raju , Moroz Krzysztof , Agrawal Krishna C. , Abdel-Mageed Asim B. 
Published: February 2011

Abstract
Caucasian American (CA) and other ethnic minority groups. The causes of this ethnic disparity in clinical manifestation and outcome of the disease are not well understood. Here we identified, by employing a combined approach of laser capture microdissected (LCM), suppressive subtractive hybridization (SSH), and custom race-based CaP cDNA microarray on fresh specimens, selective expression of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) in prostate tumor cells of AA men in comparison to CA men. An ethnicity-based tissue microarray (TMA) analysis revealed selective nuclear accumulation of hnRNPH1 in tumor cells compared to adjacent normal epithelium and benign prostatic hyperplasia (BPH). We also show that hnRNPH1 up-regulates transcription, physically interact with, and confers hormone-dependent (HD) and independent (HI) transactivation of androgen receptor (AR) in CaP cells. Further, our reporter, ChIP, and EMSA analyses demonstrate hnRNPH1 binds to androgen response elements (AREs) on promoter and enhancer element of PSA gene and the ligand binding domain-encoding exons D, E and H of the AR gene, suggesting it acts as a coactivator of AR in CaP cells. Interestingly, siRNA silencing of hnRNPH1caused growth arrest and enhanced cytotoxicty of Bicalutamide in AR-expressing CaP cells. These findings support a model in which hnRNP H1 is an exclusive auxiliary factor for AR to elicit androgen-specific transcriptional regulation of androgen-regulated genes and drug resistance. Given heterogeneity of CaP and that AR is implicated in androgen independent progression of CaP, the results demonstrate a previously uncharacterized mechanism for AR-hnRNPH1 axis in disease progression and hormone refractory via enhancing HD and HI mediated transcription and transactivation of AR in a subset of prostate tumor cells in AA men. The results not only reveal racial differences in the biology of CaP, but also provide, for the first time, a new frontier for the development of diagnostic, preventive, and/or targeted therapeutic strategies to circumvent disease progression in AA men.
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 2712.
Abstract 2714: Colorectal Cancer in young (&lt;50 years old) African Americans, Could race be a risk factor? A 20 years experience in an inner city teaching hospital
Authors: Ashktorab Hassan , Mohammed Roshila , Nouraie Mehdi , Brim Hassan , Lee Edward , Ghadyari Firoozeh , Moon Tara , Yepuri Aparna D. , Zahaf Marwah , Smoot Duane T. 
Published: February 2011

Abstract
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer, and survival in African Americans (AAs) is worse than Caucasians. Some studies suggest that the incidence of CRC is higher in AA patients below the age of 50 when compared to Caucasians. This study aims to confirm the higher prevalence of CRC in an AA population less than 50, and its implications to the screening guidelines.
METHOD: In a retrospective study demographic data, indication and outcome of colonoscopy, and biopsy data were collected at Howard University Hospital (HUH) over a period of 21 years (1989-2008). All of the study patients were (AA), and cases were classified either symptomatic average risk (91%); or high risk (family history, IBD) (9%). Distribution of variables was studied by median (inter-quartile range) or number (%).
RESULTS: Seventy five CRC cases younger than 50 years old were recorded from 1989 to 2008 at HUH. Median age (inter-quartile range) of these patients were 43 (40-46) years and 35 (47%) were female. Among them 55 (73%) were adenocarcinoma and 43 (57%) were located at left colon. In the same period a total of 671 CRC was recorded in HUH. We compared this data with 4591 CRC cases who were registered at District of Colombia (DC) from 1996 to 2007. While in HUH 11% of all CRC cases were under 50, this ratio for DC area was 9% (P=0.1). Among HUH patients 4%, 16% and 80% were 20-29, 30-39 and 40-49 years old, respectively. In DC area these ratios were 3%, 26% and 70% (P = 0.2). Among HUH tumors with available data 49%, 40%, 11% were local, regional, distant and unknown extension, while these proportions in DC area were 40%, 37%, 23% (P=0.018), respectively.
CONCLUSION: Our data showed a high burden of colorectal CRC in young AAs (&lt;50). CRC rate of 80% (60/75) was seen for the age group of 40-49, which indicates cancer in AAs may starts at younger age than predicted (&lt;45). The American College of Gastroenterology recommends to start screening of AAs at age of 45, but this may not cover many high risk people who are younger than 45. Further study is needed on AAs to confirm these findings.
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 2714.
Abstract 2731: Serum prostate health index and biopsy tissue DNA content at the time of diagnosis predicts the need for treatment in men enrolled in an active surveillance program
Authors: Isharwal Sumit , Makarov Danil , Sokoll Lori J. , Landis Patricia , Marlow Cameron , Epstein Jonathan I. , Partin Alan W. , Carter H. Ballentine , Veltri Robert W. 
Published: February 2011

Abstract
Introduction and Objective: We assessed a novel application of the Prostate Health Index [Phi = (proPSA / free PSA) × (square root of PSA)] developed by Beckman-Coulter Inc. and DNA content measurements in benign-adjacent and cancer tissue areas to predict which patients would eventually require treatment for prostate cancer (PCa) in an active surveillance (AS) cohort.
Methods: We identified 71 men at the Johns Hopkins Hospital AS program which had banked serum from the time of diagnosis available for the study. 39 developed an unfavorable biopsy (Gleason score &gt;6, Gleason pattern 4/5, &gt;2 cores positive for cancer, &gt;50% of any core involved with cancer), while 32 have maintained favorable biopsies (median follow-up: 3.7 years). Serum total PSA, free PSA and [−2] proPSA were measured by the Beckman Coulter immunoassay. DNA content measurements of Feulgen-stained biopsy sections were performed with the AutoCyteTM imaging system. Cox proportional hazard regression and Kaplan-Meier plots were used to identify significant prognosticators for unfavorable biopsy conversion-free survival.
Results: The ratio of Phi in serum was significantly higher (37.23 ± 15.76 vs. 30.60 ± 12.70 p=0.03) in men ultimately developing unfavorable biopsies. Serum Phi [HR(95%CI): 2.39 (1.26-4.52), p=0.007], BA excess of optical density (OD) [HR (95%CI): 2.58 (1.17-5.68), p=0.019] and CA standard deviation of OD [HR (95%CI): 5.36 (1.89-15.24), p=0.002] were significant predictors of an unfavorable biopsy conversion in both Kaplan-Meier and Cox regression analysis. Patients with Phi &gt;34.2 and CA standard deviation of OD &gt;4.0 showed the highest risk for unfavorable biopsy conversion (p&lt;0.0001).
Conclusions: Measurement of the serum Phi and tissue DNA content at the time of diagnosis are able to predict which men enrolled in an AS cohort will ultimately require treatment for PCa.
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 2731.
Abstract 2734: Tumor-associated antigen c-terminal binding protein-2 is overexpressed in epithelial ovarian tumors
Authors: Barroilhet Lisa M. , Yang Junzheng , Welch William R. , Berkowitz Ross S. , Ng Shu-Wing 
Published: February 2011

Abstract
OBJECTIVES: Investigation of the expression pattern and functional roles of tumor antigen CtBP-2 in ovarian cancer. BACKGROUND: Tumor-associated antigens may have mechanistic function in cancer development and serum antibodies that target the tumor-associated antigens may have value in early detection. Antibodies to C-terminal binding protein 2 (CtBP-2), a component of the Wnt signaling pathway and a transcriptional corepressor via interaction with histone deacetylases (HDACs), were identified in patient serum using an innovative reverse capture antibody array method. We investigated the expression and function of CtBP-2 in human ovarian cancer tissue and ovarian cancer cell lines. METHODS: CtBP-2 expression was studied in 105 paraffin-embedded ovarian tumors by standard immunohistochemistry (IHC). ANOVA was used to compare the mean IHC staining scores (area stained x intensity) between healthy and tumor samples. Functional assays were performed with human ovarian cancer cell lines SKOV3 and MCAS that stably integrated a CtBP2-targeting short-hairpin RNA (shRNA) construct via a Lentivirus vector. Protein expression was examined by western blotting. Cell proliferation in culture was evaluated by cell counting. Cell adhesion assays were performed using a CytoMatrix Screen kit from Millipore. Cell migration assays were performed using a Boyden chamber-based cell migration assay. B-catenin activity was measured using a TOPFLASH luciferase reporter assay. Cellular sensitivity to trichostatin A, a HDAC inhibitor, was measured using MTT assay. RESULTS: 83% of ovarian epithelial tumors stained positive with a mean score of 4.77 (borderline tumors) and 5.49 (invasive tumors) and showed a significant difference (p-value 50% and showed reduced proliferation rates. The knock-down cell lines also showed 40-80% reduction in adhesion to extracellular matrix proteins collagen I and collagen IV, 50-70% reduction in migration, suppressed B-catenin activity and enhanced sensitivity to trichostatin A. CONCLUSIONS: CtBP-2 is overexpressed in ovarian epithelial tumors and cancer cell lines. Ovarian cancer cell lines with suppressed CtBP-2 expression show a reduction in proliferation rate, cell adhesion and cell migration. The phenotype may be related to suppressed B-catenin activity. The knockdown cell lines are also more sensitive to HDAC inhibitor trichostatin A, suggesting that the expression of CtBP-2 might modulate cellular response to HDAC inhibitor in the clinical setting.
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 2734.
Abstract 2743: Accelerating the exploration of novel gene fusion events in prostate cancer
Authors: Pflueger Dorothee , Terry Stephane , Sboner Andrea , Habegger Lukas , Esgueva Raquel , Svensson Maria A. , Lin Pei-Chun , Kitabayashi Naoki , Moss Benjamin J. , Tewari Ashutosh K. , Chee Mark S. , Demichelis Francesca , Gerstein Mark B. , Rubin Mark A. 
Published: February 2011

Abstract
Gene fusions are regarded as cancer defining and often proven causative for cancer development. Up to 50% of prostate cancers harbor recurrent gene fusions, most often the TMPRSS2-ERG fusion. Other ETS gene fusions have been described involving ETV1, ETV4, and ETV5. The remaining prostate cancers are considered gene fusion negative based on fluorescence in-situ hybridization (FISH) or RT-PCR for known fusion specific transcripts. Paired-end RNA-sequencing is a novel approach to systematically interrogate for fusion transcripts in a global and un-biased manner. Herein, we exploit FusionSeq, a computational tool specifically developed to nominate chimeric transcripts from paired-end RNA-seq data, with the goal of identifying new gene fusions. Using FusionSeq we identified the androgen-induced genes FKBP5 and KLK2 as two novel 5′ fusion partners for the ETS genes ERG and ETV1, respectively. General transcriptional chimerism (e.g. read-through transcripts) without evidence of underlying genomic rearrangements is not restricted to prostate cancer but also occurs in the patient's matched benign prostate tissue, providing evidence for an extended complexity of the cellular transcriptome and supporting the notion that a gene's definition might have to be considered flexible. Finally, we report the identification and the validation of two novel gene fusions: i) the tumor suppressor and cell cycle regulator CDKN1A (p21WAF, CIP1) is fused to CD9; besides down-regulating p21 gene expression, the CDKN1A-CD9 fusion also alters the CD9 protein. ii) by fusing IKBKB (IKK2, IκB kinase beta subunit) to TNPO1 (transportin 1), IKBKB gene expression increases over other prostate cancers, suggesting a pronounced activation of the NFκB complex. Our results show that a small subset of prostate cancers may harbor private gene fusions involving tumor suppressors and regulators of pathways implicated in cancer development.
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 2743.
Abstract 2744: Loss of VAV3 expression as a novel biomarker and indicator of chemosensitivity in basal-like breast cancer
Authors: Getz Julie E. , Anderson Eric M. , Black Michael A. , Hedenfalk Ingrid A. , Balagurunathan Yoganand , Willis Amanda L. , Mancini Catherine M. , Ramos Pilar , Cunliffe Heather E. 
Published: February 2011

Abstract
Microarray-based technologies have revealed at least five molecularly distinct subtypes of breast cancer that share similarities in their underlying disease biology and have more predictable responses to therapy: Luminal A, Luminal B, Basal-like, ERBB2 positive, and Normal Breast-like. The ability to objectively subclassify breast tumors adds significant prognostic information that is independent of standard clinical parameters and provides insight for clinical decision-making. Basal-like breast (BLB) cancer, accounts for approximately 16% of breast tumors diagnosed. The majority of BLB tumors do not express estrogen and progesterone receptors (ER/PR) and HER2/neu, and they commonly have mutations in the TP53 or BRCA1 genes. Patients diagnosed with BLB tumors have a relatively poor prognosis, and the molecular basis for disease progression in this subtype remains unclear.
Due to proposed differences in etiology and mesenchymal characteristics of BLB tumors, we hypothesized that regulators of cell morphology, contractility and motility may be distinctly deregulated in this subtype and may provide insight into molecular pathology operating in BLB tumors. We therefore investigated genes associated with the Rho/Rac/Cdc42 superfamily, a key regulator of cell morphology. Using unsupervised hierarchical clustering, we confirmed diverse regulation of this gene superfamily in publicly available breast tumor gene expression microarray datasets. Very low expression of VAV3 was observed in BLB tumors compared to all other intrinsic subtypes across six breast cancer cohorts.
Analysis of VAV3 transcript and protein expression in cell lines and tumor samples indicated low VAV3 expression correlates with BLB subtypes. We have confirmed that loss of VAV3 expression in BLB cell lines is not due to gene copy number loss by Fluorescence In Situ Hybridization and array Comparative Genomic Hybridization (aCGH). Kaplan Meyer analysis from publicly available breast tumor data suggested that elevated VAV3 expression in BLB tumors is predictive of response to chemotherapy. We are currently investigating whether exogenous VAV3 overexpression in BLB cancer cell lines increases their chemosensitivity. In conclusion, our findings support a hypothesis that VAV3 is a potential biomarker of BLB cancer, and VAV3 expression in BLB tumors may be a predictor of response to 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 2744.
Abstract 2762: An open-label phase 1 study to evaluate the pharmacokinetics of axitinib (AG-013736) in healthy Chinese volunteers
Authors: Chen Ying , Jiang Ji , Zhang Jianyan , Tortorici Michael , Pithavala Yazdi K. , Lu Lei , Ni Grace , Hu Pei 
Published: February 2011

Abstract
Introduction: Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. It is mainly metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP1A2, CYP2C19, and uridine glucuronyltransferase (UGT1A1). Axitinib currently is in Phase 3 development for renal cell carcinoma. As part of the global clinical development program for axitinib, studies are ongoing in cancer patients in China. A clinical assessment of axitinib pharmacokinetics in healthy Chinese subjects, including dose-proportionality, was conducted to support the regulatory submission in China.
Methods: This was an open-label, fixed-sequence study conducted in mainland China in 14 healthy volunteers. All subjects received a single axitinib dose of 5 mg, 7 mg, and 10 mg under fed conditions in study periods 1, 2, and 3, respectively, followed by safety and pharmacokinetic monitoring. Each study period was separated by a washout period of at least 7 days between successive axitinib doses. Serial blood sampling for axitinib pharmacokinetics was performed up to 32 hours postdose in each period. Plasma concentrations of axitinib were measured using a validated LC/MS/MS (liquid chromatography coupled with mass spectrometry) method. Axitinib plasma pharmacokinetic parameters were estimated using standard noncompartmental methods.
Results: Axitinib AUC0-∞ (area under the curve from time zero to infinity) and Cmax (maximal plasma concentration) estimates in healthy Chinese volunteers in this study are reported here. The geometric mean estimate of AUC0-∞ was 150, 251, and 321 ng[[Unable to Display Character: &#8729;]]h/mL for doses of 5 mg, 7 mg, and 10 mg, respectively. This represented AUC0-∞ increments of 1:1.7:2.1 for dose increments of 1:1.4:2, respectively (ie, a proportional increase in AUC0-∞ per dose increment). Similarly, the geometric mean estimate of Cmax was 33.5, 51.1, and 69.4 ng/mL for 5 mg, 7 mg, and 10 mg, respectively, representing Cmax increments of 1:1.5:2.1 for dose increments of 1:1.4:2, respectively (a proportional increase in Cmax per dose increment). Axitinib was well tolerated with no serious adverse events (AEs) or discontinuations; the only observed AE was mild abdominal distension in 1 subject.
Conclusions:. Dose-proportional linear pharmacokinetics for axitinib were observed for the 5 mg to 10 mg dose range in this study.
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 2762.