bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2208: Overexpression of NDRG1 inhibits cell migration of breast cancer cells via reactive oxygen species during reoxygenation
Authors: Lai Liang-Chuan , Su Yi-Yu , Chen Kuo-Chih , Tsai Mong-Hsun , Sher Yuh-Pyng , Lu Tzu-Pin , Chuang Eric Y. 
Published: June 2012

Abstract
One characteristic of tumor microenvironment is oxygen fluctuation, which results from hyper-proliferation and abnormal metabolism of tumor cells as well as disorganized neo-vasculature. Reoxygenation in tumor microenvironment can induce oxidative stress, which further leads to DNA damage and genomic instability. Although multiple cellular responses are activated in order to survive under this microenvironment, little is known about the dynamic response upon reoxygenation. Therefore, in order to investigate the transcriptional response of tumor adaptation to reoxygenation, breast cancer cells MCF-7 was cultured under 0.5% of hypoxia for 24h followed by 24h of reoxygenation in normoxia. Cells were harvested respectively at 0, 1, 4, 8, 12, and 24h during reoxygenation. The genomic profiling of MCF-7 upon reoxygenation was examined using Illumina Human-6 v3 BeadChips. We identified 127 differentially expressed genes in which 53.1% were up-regulated and 46.9% were down-regulated upon reoxygenation. Pathway analysis revealed that HIF-1-alpha transcription factor network was most significantly (P=2.02×10-3) enriched in these differentially expressed genes. Among these genes, a group of selected genes of interest were further validated by quantitative real-time PCR. In particular, NDRG1 was highly suppressed upon reoxygenation. NDRG1 (human N-myc down-regulated gene 1) is associated with a variety of stress and cell growth-regulatory conditions. To characterize whether NDRG1 play a role in reoxygenation, NDRG1 protein was overexpressed in MCF-7 cells. Upon reoxygenation, overexpression of NDRG1 inhibited cell migration, and this inhibition could be reversed by adding reactive oxygen species scavengers. Our results revealed dynamic expression profiling of MCF-7 upon reoxygenation, and demonstrated that NDRG1 is involved in tumor adaptation to reoxygenation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2208. doi:10.1158/1538-7445.AM2011-2208
Abstract 222: Differential p73 isoform expression profile in non-Hodgkin's lymphoma with 1p36 chromosomal abnormality modulates angiogenic phenotype
Authors: Hassan Hesham M. , Varney Michelle L. , Jain Smrati , Joshi Shantaram S. , Singh Rakesh K. , Dave Bhavana J. 
Published: June 2012

Abstract
Alteration of tumor suppressor gene function often leads to imbalance in expression of angiogenic and angiostatic factors facilitating disease progression. TP73, a member of the p53 tumor suppressor gene family, regulates many important cellular pathways and has been shown to be abnormally expressed in non-Hodgkin's lymphoma (NHL). TP73 gene function is controlled by harmony between two isoforms with opposing functions, the full length TAp73 protein (pro-apoptotic) and the NH2-terminally truncated ΔNp73 protein (anti-apoptotic through antagonizing both TAp73 and p53). We have observed differential ΔNp73 up-regulation and increase in ΔNp73:TAp73 expression ratio among NHL cases with 1p36 chromosomal disruption as compared to NHL cases without 1p36 disruption, which is associated with aggressiveness. To decipher whether deregulated p73 isoforms expression modulates the angiogenic potential in NHL we examined the mRNA expression of angiogenic factors (VEGF-A, FGF-2, and angiogenic chemokine CXCL-8) and angiostatic factors (TSP-1 and Endostatin) in NHL cases with and without chromosome 1p36 abnormality by real-time PCR. We observed higher levels of expression of angiogenic factors (VEGF-A, FGF-2, and CXCL-8) and lower levels of angiostatic factors (TSP-1 and Endostatin) in NHL cases with 1p36 abnormality as compared to NHL cases without 1p36 abnormality. Next, we performed a non-parametric bivariate correlation analysis (Kendall's tau_b and Spearman's rho) to examine whether ΔNp73:TAp73 expression ratio correlates with the expression of angiogenic and angiostatic factors. We observed a significant correlation between ΔNp73:TAp73 expression ratio with the expression of VEGF-A (r=0.900, p&lt;0.001), FGF-2 (r=0.620, p&lt;0.05) and TSP-1 (r=−0.873, p&lt;0.001). To further elucidate the relationship between differential p73 isoforms expression and the expression pattern of angiogenic and angiostatic factors, we stably transfected an NHL cell line with 1p36 disruption, Granta-519 (TAp73 non expressor) with a wild type TAp73 mammalian expression vector. We observed an up-regulation of TSP-1 and Endostatin expression among Granta-519 cells transfected with TAp73 vectors compared to isogenic control vector transfected cells. Our data highlights the molecular and functional consequences of the differential p73 isoforms expression pattern caused by 1p36 chromosomal disruption on angiogenic phenotype in NHL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 222. doi:10.1158/1538-7445.AM2011-222
Abstract 223: ΔNp63α, a p53 family member protein, promotes tumor progression in pancreatic cancer
Authors: Danilov Alexey , Neupane Divas , DiRenzo James , Korc Murray 
Published: June 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in both men and women. Targeted therapies thus far have failed to demonstrate survival advantage in PDAC and novel therapies are needed. Mutations in Ras and p53 are frequently found in PDAC and promote cancer cell survival, invasiveness and chemoresistance. In contrast, p63, an ancestral member of p53 family, is rarely mutated in cancer. ΔNp63α was shown to be overexpressed in squamous cell tumors of the lung and head and neck and thus has been implicated in carcinogenesis. We tested expression of p63 isoforms in five PDAC cell lines and investigated its role in tumor progression.
Expression of p63 was determined by immunoblotting, real-time quantitative and semi-quantitative PCR in 5 PDAC cell lines. PANC-1 cells, with low levels of p63, were transfected with ΔNp63α cDNA-expressing vector. Conversely, high endogenous p63 levels in T3M4 and BxPC3 cell lines were suppressed by specific shRNA. We studied cell proliferation in a doubling assay, motility in wound assay and invasiveness in Matrigel chambers.
We found that pancreatic cancer cell lines predominantly expressed ΔN isoform of p63, and specifically ΔNp63α variant. ΔNp63α protein and transcript levels were high in T3M4, BxPC3 and Colo-357 cell lines and low in ASPC-1 and PANC-1 cell lines. Interestingly, transcript levels of TAp63, a p63 variant implicated in cellular senescence and suppression of metastases, were near the detection threshold in all cell lines. Overexpression of ΔNp63α in PANC-1 cells resulted in increased proliferation and enhanced migration of those cells but had no effect on invasiveness in serum-free conditions. Incubation of ΔNp63α-expressing PANC-1 cells in presence of epidermal growth factor increased both migration and invasiveness. By contrast, shRNA knockdown of endogenous p63 in BxPC3 cells led to decreased proliferation. Silencing p63 in T3M4 cells resulted in attenuated migration in serum-free conditions and decreased migration and invasiveness in response to epidermal growth factor.
Thus, ΔNp63α is a predominantly expressed isoform of p63 in PDAC cell lines. ΔNp63α plays an important role in PDAC progression and thus its associated pathways may potentially be therapeutically targeted in this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 223. doi:10.1158/1538-7445.AM2011-223
Abstract 2265: Clinical significance of HER3 expression in curatively resected pancreatic cancer
Authors: Hirakawa Toshiki , Nakata Bunzo , Kashiwagi Shinichiro , Kato Yukihiro , Fuyuhiro Yuhiko , Iwauchi Takehiko , Matsusoka Junko , Itoh Gentaro , Aomatsu Naoki , Yoshii Mami , Hasegawa Tsuyoshi , Amano Ryosuke , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Yamada Nobuya , Yashiro Masakazu , Sawada Tetsuji , Ohira Masaichi , Hirakawa Kosei 
Published: June 2012

Abstract
Introduction: HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated.HER2/HER3 heterodimer is likely to be the most effective complex for activating downstream pathways.Because of special importance of HER2/HER3 heterodimer in tumorgenesis, the signaling pathways and downstream effectors of the HER family become key molecules in the strategy of cancer therapy.HER3 is overexpressed in diverse human cancers, and has been associated with poor prognosis in breast, lung, and ovarian cancer.The objective of this study was to evaluate the significance of HER3 expression in pancreatic cancer cells.
Material and Methods: A total 86 patients were enrolled.The pancreatic cancers were stained with antibodies against HER3 by immunohistochemistry. HER3 expression was evaluated by intensity of staining.Intensity was given scores 0-3 (score 0:no staining, score1+:barely perceptible staining, score2+:moderate staining, score3+:strong staining). Scores of 0 and 1+ were considered to be negative for HER3 expression, while 2+ and 3+ were considered to be positive (overexpression).We examined the association between HER3 expression and other clinicopathologic variables.
Results: HER3 expression was positive in 36 (41.9%) cases.There were no significant correlation between HER3 expression and other clinicopathological factors. The prognosis of HER3 positive patients was significantly poorer than that of HER3-negative patients (p=0.002). A univariate survival analysis revealed that HER3 overexpression, intrapancreatic nerve invasion and T category were significantly correlated with patient survival. A multivariate analysis showed HER3 overexpression was an independent predictor of worse prognosis in resectable pancreatic cancer.
Conclusion: The expression of HER3 might be a novel predictive prognostic marker for patients with pancreatic cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2265. doi:10.1158/1538-7445.AM2011-2265
Abstract 2273: Validation of putative stem cell factor SOX2 as predictive marker in breast cancer – with overall poor prognosis
Authors: Pradel Leon Paul , Swierczynski Stefan , Greil Richard , Dietze Otto , Hauser-Kronberger Cornelia 
Published: June 2012

Abstract
As member of the high-mobility-group (HMG)-domain containing proteins – SOX2 (Sex determining Region Y – box 2) transcriptional activator is known for its pivotal role in maintaining self-renewal, pluripotency and cellular identity in embryonic stem cells. While its status in adult tissue, e.g. in homeostasis – is still less understood and controversy – SOX2 has shown recently to be up regulated in a huge variety of human tumors like oesophagus, lung, brain and breast.
Within this study whole sections – provided as formalin-fixed paraffin-embedded tumor samples, derived from 86 patients with advanced breast cancer disease were stained via immunohistochemistry (IHC) for SOX2 positivity. Further on – six breast cancer cell lines (MCF-7, MDA-MB231, MDA-MB453, SK-BR3, SUM-159, T47-D) as well as an individual based tissue micro array (TMA) containing 1080 fine needle biopsies were additionally analyzed using IHC and qRT-PCR. Initially – all samples have been evaluated for their particular molecular subtype (Luminal A, Luminal B, Normal-like, HER2 Overexpressing, Basal-like) and their histopathological parameters (histological subtype, grade, size, lymph node metastasis).
For further proof of principle the applied SOX2 polyclonal antibody (SOX2 PAb AF2018, R&D SystemsTM) was validated for its marker capacity via Surface Plasmon Resonance (SPR) Spectroscopy and Western Blot to determine the kinetic profile, limit of detection, epitope variety and specificity of this antibody. With the so called ‘fishing’ opportunity for analyte recovery in SPR, native putative antigen bound by the SOX2 PAb can be enriched and further characterized from whole cell lysates.
In conclusion – SOX2 showed association to overall bad prognosis due to high grade (p&lt;0.001), huge size (p=0.003), lymph node metastasis (p&lt;0.001) as well as histological and molecular subtypes with poor overall-survival (p&lt;0.001). Further on it is independent (p=0.6) of oestrogen receptor (ER) presence but correlated to EGFR expression (p=0.007). During antibody-based validation – SOX2 PAb revealed to possess high specificity, sensitivity and affinity to native and recombinant SOX2 full length protein finally. In this way SOX2 – as marker, can be applied to predict overall poor prognosis in breast cancer in an ER- and subtype-independent fashion.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2273. doi:10.1158/1538-7445.AM2011-2273
Abstract 2276: Serum endoglin and uPA change predicts PFS and overall survival in first line trastuzumab-treated breast cancer
Authors: Evans Matthew S. , Hou Hui Ying , Anyanwu Uchechi , Leitzel Kim , Ali Suhail M. , Koestler Wolfgang , Fuchs Eva-Maria , Brown-Shimer Sheryl , Hamer Peter , Carney Walter , Lipton Allan 
Published: June 2012

Abstract
Background: About half of HER2-positive breast cancer patients will respond to first-line trastuzumab-containing therapy, but of these most will progress within a year with acquired resistance. Since trastuzumab treatment is now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a recurring clinical problem, and better predictive and prognostic biomarkers are urgently needed.
Methods: Serum TIMP-1, uPA, carbonic anhydrase 9 (CA9), and endoglin (co-receptor for TGF- β) were measured using ELISA in 60 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy, and at the closest 1 month post-trastuzumab blood draw. The TIMP-1, uPA and CA9 ELISAs were from Oncogene Science/Siemens Healthcare Diagnostics, and the endoglin ELISA was from R&D Systems. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling.
Results: When serum biomarker change (pretreatment to 1 month post-trastuzumab treatment) was analyzed on a continuous basis, change in serum TIMP-1 and CA 9 were not significant for PFS or OS. However the change in serum endoglin (HR = 1.017, p = 0.013) and serum uPA (HR 1.018, p = 0.006) were significant predictive factors for PFS to first-line trastuzumab treatment. The change in serum endoglin (HR = 1.021, p = 0.004) and serum uPA (HR 1.016, p = 0.03) were also significant prognostic factors for OS: declining serum endoglin or uPA predicted for increased PFS and OS. Changes in serum endoglin and uPA were positively correlated (r = 0.7, p &lt;0.0001). Due to the significant correlation between the change in serum endoglin and uPA levels, these 2 serum biomarkers were analyzed separately along with the change in serum TIMP-1 and CA9 in multivariate analysis. In these analyses, only the change in serum endoglin or uPA was significant.
Conclusions: The change in serum endoglin and uPA level from pretreatment to 1 month post-trastuzumab treatment predicted PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Endoglin (CD105) is a co-receptor for TGF-β, is expressed by human vascular endothelial cells, and plays a major role in angiogenesis. These angiogenesis-related serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment.
Supported by a grant from Komen for the Cure.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2276. doi:10.1158/1538-7445.AM2011-2276
Abstract 229: A cross-species approach to identifying genetic modifiers of BRCA1-associated breast cancer risk
Authors: Hu Hsien-Ming , Voytovich Uliana , Paulovich Amanda G. 
Published: June 2012

Abstract
Background: Although carriers of germline mutations of BRCA1 have a high risk of developing breast and ovarian cancers, penetrance is not complete, and it is likely that unidentified genes modify the risk for individual mutation carriers. We hypothesize that genes that modify the penetrance of cancer in BRCA1 carriers interact with BRCA1 mutations to confer increased sensitivity to DNA damage at the cellular level, and that cellular sensitivity to DNA damage can be used as an intermediate phenotype to predict breast cancer susceptibility in humans.
Objective: Our goal is to test a cross-species systems biology approach to predict gene-gene interactions underlying breast cancer susceptibility, using sensitivity to DNA damage as an intermediate phenotype.
Experiment Procedure: The yeast RAD9 gene is one putative homolog of the human breast tumor suppressor gene BRCA1. We conducted a genome-wide screen to identify genes that interact with a rad9 mutation to confer enhanced sensitivity to DNA damage. The yeast screen identified 25 interactions, from which we selected 10 candidate gene-gene interactions to be tested in human breast epithelial cells. To determine if the gene-gene interactions discovered in yeast are conserved in human mammary epithelial cells, we built stable human mammary epithelial cells (MCF10A) capable of single- or double-gene knockdown via lentivirus-mediated RNA interference. Cells confirmed for intended gene knockdown were subject to a clonogenic assay to determine if increased sensitivity to DNA damage can be observed in double gene vs. single gene knockdowns.
Results: Among the 10 pairs of interactions tested in MCF10A cells, two genes, HLTF and MGMT, were found to interact with BRCA1 to confer enhanced DNA damage sensitivity, based on a clonogenic assay. Cells with combined knockdown of BRCA1 and HLTF show increased sensitivity to a chronic low dose of MMS treatment compared with those with only single knockdown of BRCA1 or HLTF. In addition, distinct morphological features were observed in double knockdown cells with MMS treatment. Cells became enlarged and showed a flat, senescence-like morphology. Even a low concentration of 0.001% MMS induced a strong and irreversible growth arrest in cells with combined knockdown of BRCA1 and HLTF, but not in the single knockdown cells.
Conclusion: Our results suggest that it is feasible to use a cross-species (yeast-to-human) comparative systems genetics strategy to identify gene-gene and pathway-pathway interactions. Ongoing studies are aimed at determining whether any of the observed gene-gene interactions contribute to breast cancer penetrance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 229. doi:10.1158/1538-7445.AM2011-229
Abstract 2298: ck2-Dependent phosphorylation of progesterone receptors (PR) on Ser81 regulates PR-B-isoform-specific target gene expression in breast cancer cells
Authors: Hagan Christy R. , Regan Tarah , Dressing Gwen , Lange Carol 
Published: June 2012

Abstract
Progesterone receptors (PR) are critical mediators of mammary gland development and contribute to breast cancer progression. Progestin-induced rapid activation of cytoplasmic protein kinases leads to selective regulation of growth-promoting genes by phospho-PR species. Herein, we show that phosphorylation of PR Ser81 is ck2-dependent and progestin-regulated in intact cells, but also occurs in the absence of PR ligands, when cells enter the G1/S phase of the cell cycle. T47D breast cancer cells stably expressing a PR-B mutant that cannot be phosphorylated at Ser81 (S81A) formed fewer soft agar colonies. Regulation of selected genes by PR-B, but not PR-A, also required Ser81 phosphorylation for basal and/or progestin-regulated (BIRC3, HSD11β2, and HbEGF) expression. Additionally, wt PR-B, but not S81A mutant PR, was robustly recruited to a PRE-containing transcriptional enhancer region of BIRC3; abundant ck2 also associated with this region in cells expressing wt but not S81A PR. We conclude that phospho-Ser81 PR provides a platform for ck2 recruitment and regulation of selected PR-B target genes. Understanding how PR functions in the context of high kinase activities characteristic of breast cancer is critical to understanding the basis of tumor-specific changes in gene expression and will speed the development of highly selective treatments.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2298. doi:10.1158/1538-7445.AM2011-2298