bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3729: Prognostication using Hif-1 alpha may require simultaneous nicotine assessment
Authors: Warren Graham W. , Singh Anurag , Randall Marcus , McGarry Ronald , Kudrimoti Mahesh , Rangnekar Vivek 
Published: February 2011

Abstract
Background: Current cancer diagnosis and treatment increasingly incorporates biomarker expression in the prognostication and therapeutic stratification of cancer patients; however, there is no accurate assessment of exposure to environmental agents such as nicotine that may significantly impact biomarker expression patterns.
Methods: Athymic nude mice with human H460 lung cancer cell xenografts were stratified into three treatment groups (n=5 per group) beginning when tumors reached 5 mm in maximal dimension: control (CON), short term nicotine (STN, 60 ug subcutaneously every other day x 6 days), or long term nicotine (LTN, 60 ug SC every other day until tumor explant). All tumors were explanted at endpoint defined when tumors reached 15 mm in maximal dimension. Tumors were analyzed immunohistochemically for hypoxia (using CA-IX expression) and hypoxia-inducible factor 1-alpha (Hif-1) expression. This protocol was approved by the Institutional Animal Care and Use Committee at the University of Kentucky.
Results: Nicotine administration had no effect on tumor growth rate and all tumors reached endpoint within a median of 9 days following treatment initiation (range 8-11 days). Areas of hypoxia were defined using CA-IX expression. Tumor hypoxia was not significantly affected by nicotine administration. Moreover, Hif-1 expression was only minimally increased in areas of hypoxia in CON animals. In STN animals, Hif-1 expression was very similar to CON animals. In contrast, LTN animals demonstrated widespread marked increases in Hif-1 expression at the viable: necrotic tumor interface. Separately, xenografts removed at day 6 demonstrated similar widespread Hif-1 expression confirming that Hif-1 expression is significantly increased after 6 days of nicotine administration.
Conclusions: This study demonstrates that widespread Hif-1 expression may be dominated by the presence of nicotine rather than hypoxia. Furthermore, acute removal of nicotine results in the restoration of basal low-level Hif-1 expression within 3 days of nicotine removal. This data may significantly limit the prognostic utility of clinical Hif-1 expression in the absence of simultaneous nicotine assessment.
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 3729.
Abstract 3734: TLE3 expression is predictive of response to chemotherapy in NSCLC
Authors: Ross Douglas T. , Seitz Robert S. , Ring Brian Z. , Wang Yanling , Beck Rodney A. , Soltermann Alex 
Published: February 2011

Abstract
Purpose: Previously we have shown that the wnt pathway marker TLE3 is associated with outcome in taxane-treated breast cancer but not in patients treated with anthracycline-only supporting TLE3 as a taxane predictive marker. The purpose of this study was to assess the association between TLE3 expression and outcome in NSCLC patients treated with chemotherapy as opposed to those treated with a surgical resection and or radiation alone.
Experimental Design: We performed TLE3 immunohistochemistry staining on NSCLC cancer specimens from the University of Zurich, Switzerland. Most advanced stage chemotherapy treated patients at this institute receive a taxane containing regimen. Local and distant recurrences within the first five years of follow-up were analyzed using Kaplan Meier, Cox proportional hazard, and multivariate analysis to assess an interaction between TLE3 expression and response to chemotherapy.
Results: TLE3 staining with a monoclonal antibody was associated with outcome only when patients received chemotherapy (HR=0.42 p=0.0047 n=68) while no association was identified in untreated patients (p=0.83 n=300). Multivariate analysis showed that TLE3 was independent of stage, grade and age. An interaction test between TLE3 expression and chemotherapy response was significant (p=0.036).
Conclusion: High TLE3 expression is associated with response to chemotherapy in NSCLC. This is consistent with data in breast cancer where TLE3 is associated with response to taxane therapy. Further study in randomized cohorts is warranted to confirm TLE3 as a predictive marker for response the taxane therapy in NSCLC.
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 3734.
Abstract 3739: Clinicopathologic significance of ERCC1, Thymidylate Synthase and Glutathione S-Transferase P1 expression for advanced gastric cancer patients receiving adjuvant 5-FU and cisplatin chemotherapy
Authors: OH SUNG YONG , Kim Ki Han , Kim Sung Hyun , Lee Suee , Kwon Kyung-A , Jang Jin Seok , Kim Min Chan , Kim Su-Jin , Kim Hyo-Jin , Kwon Hyuk-Chan 
Published: February 2011

Abstract
Background: The aim of this study was to determine whether expressions of the excision cross-complementing (ERCC1), thymidylate synthase (TS) and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric cancer treated with adjuvant 5-fluorouracil (5-FU) and cisplatin (FP) chemotherapy.
Patients and methods: The study population consisted of 149 advanced gastric cancer patients. After curative resection, if the patients had stage II or higher disease, we administered adjuvant FP combination chemotherapy. The FP regimen was as follows. Cisplatin 60 mg/m2 was administered intravenously on day 1, and 5-FU 1,000 mg/m2 was administered intravenously on days 1 to 5. This regimen was repeated every three weeks. The expressions of ERCC1, TS and GSTP1 of primary tumors were examined by immunohistochemistry. Clinicopathologic information, including tumor size, histological grade, Lauren's classification, Borrmann type, vascular invasion, ratio of involved lymph nodes to dissected nodes, stage, carcinoembryonic antigen (CEA), and disease-free survival (DFS) and overall survival (OS) were evaluated with respect to the expressions of ERCC1, TS and GSTP1.
Results: Median follow-up duration was 65.2 months, and median patient age was 51 ± 11 years (range 24-75). The positive rates of ERCC1, TS, and GSTP1 were 63.1%, 76.5%, and 40.3%, respectively. ERCC1 and GSTP1 expression was significantly correlated with size (p = 0.040, p = 0.018, respectively). Positive relationships were found between the expression of TS and Borrmann type (p = 0.030) and stage (p = 0.041). Univariate analysis showed that Lauren classification, stage, positive lymph node ratio, and type of operation were associated with both DFS and OS. ERCC1 and GTP1 were significant variables affecting OS (p = 0.005, p = 0.024, respectively). Patients who were both ERCC1 and GSTP1 positive had longer survival (p = 0.003). Multivariate analysis revealed that stage and positive lymph node ratio were independently associated with DFS and OS. Expression of both ERCC1 and GSTP1significantly impacted on OS (hazard ratio = 0.069, p = 0.021).
Conclusion: Immunohistochemical studies for ERCC1 and GSTP1 were useful in prediction of the clinical outcome in advanced gastric cancer patients treated with adjuvant FP.
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 3739.
Abstract 3742: FOXC1 is a potential prognostic marker with functional significance in basal-like breast cancer
Authors: Wang Jinhua , Ray Partha , Qu Ying , Sim Myung-Shin , Shamonki Jaime , Bagaria Sanjay , Ye Xing , Liu Bingya , Walter Michael , Hoon Dave , Giuliano Armando , Cui Xiaojiang 
Published: February 2011

Abstract
Although basal-like breast cancer (BLBC) is a distinct molecular subtype, it has no defining gene or protein marker that can be used as the basis for therapy. Estrogen receptor (ER) and HER2 receptor guide treatment of luminal and HER2 breast cancer subtypes, respectively, but chemotherapy is still the only systemic treatment available for BLBC. In view of its poor clinical outcomes, high proliferation rates and preferential metastasis to the brain, there is an urgent need for effective targeted therapy of BLBC.
In a previous study using cDNA microarray analyses and immunohistochemistry of archival breast cancer tissue specimens, we showed consistent and exclusive overexpression of FOXC1 in BLBC versus other molecular subtypes. FOXC1 overexpression was significantly associated with poor overall survival and brain metastasis. In the present study, we show that overexpression of FOXC1 in breast cancer cells with low endogenous FOXC1 levels increased cellular proliferation, migration, and invasion, and induced epithelial-mesenchymal transition. Knockdown of FOXC1 by shRNA in breast cancer cells with high endogenous FOXC1 expression had the opposite effect. Cell signaling studies showed that FOXC1 activated the NF-κB pathway by upregulating the peptidyl-prolyl isomerase Pin1 and downregulating the ubiquitin ligase SOCS-1. Pin1 binds to p65, inhibits the p65 interaction with IκBα, and thus enhances p65 nuclear localization and protein stability. SOCS-1 directly interacts with p65 and promotes its degradation. FOXC1 knockdown reduced p65 protein levels and NF-κB activity. The importance of the NF-κB pathway for FOXC1 function was confirmed by the increased sensitivity to NF-κB inhibitors in cells that overexpressed FOXC1. Because BLBC under-expresses ER, FOXC1 was inversely associated with ER, as expected. Interestingly, FOXC1 repressed ER transcription and activity via NF-κB signaling, and FOXC1 overexpression switched MCF-7 breast cancer cell growth from estrogen-dependent to estrogen-independent. This may explain why ER is not normally detected in BLBC.
These results suggest that FOXC1 may be a specific diagnostic and prognostic biomarker for BLBC and may play an important role in regulating aggressive traits associated with BLBC. It might also serve as a potential molecular therapeutic target for BLBC.
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 3742.
Abstract 375: Targeting pericytes in ovarian carcinoma
Authors: Lu Chunhua , Shahzad Mian M.K , Moreno-Smith Myrthala , Lin Yvonne G. , Jennings Nicholas B. , Allen Julie K. , Hu Wei , stone Rebecca L. , Matsuo Koji , Landen Charles N. , Coleman Robert L. , Sood Anil K. 
Published: February 2011

Abstract
Purpose: Pericytes interact with and closely regulate endothelial cell function. Platelet-derived growth factor (PDGF)-BB/PDGF receptor (PDGFR) β plays a critical role in pericyte regulation, therefore highly specific inhibitors of this target are needed. We hypothesize that dual targeting of endothelial cells and pericytes provide a more efficacious antiangiogenic approach for ovarian cancer therapy. Experimental Design: The therapeutic efficacy of targeting endothelial cells (bevacizumab) and/or pericytes (PDGF-aptamer, AX102) was examined using SKOV3ip1 and HeyA8 orthotopic ovarian cancer models. The biomarkers, such as microvessel density (MVD), vascular maturation (pericyte coverage), and proliferative index (proliferating cell nuclear antigen, PCNA) were examined. Results: Bevacizumab inhibited tumor growth by 48% and 45% in the SKOV3ip1 and HeyA8 models, respectively. AX102 had minimal effect on the HeyA8 model, but increased tumor growth in the SKOV3ip1 model. However, bevacizumab plus AX102 was more effective than bevacizumab alone, and reduced 76 - 88% of tumor growth in both models. A longitudinal study using bioluminescence imaging in the HeyA8 model showed that a combination of bevacizumab, AX102 and paclitaxel caused tumor reduction by 65% (based on bioluminescence imaging). MVD and proliferative index counts were significantly reduced in the bevacizumab treatment groups, and pericyte coverage was significantly decreased in the AX102 treatment groups. Conclusions: Dual targeting of endothelial cells and pericytes demonstrates therapeutic potential as a unique anti-vascular approach in treating ovarian carcinoma.
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 375.
Abstract 3751: Clinical correlation between Cyclin D1, pAKT, and FOXO1A in African American and Latino Breast Cancer Patients
Authors: Lee Jane , Wu Yanyuan , Sarkissyan Marianna , Elshimali Yayha , Vadgama Jaydutt V. 
Published: February 2011

Abstract
Breast cancer is the most common cause of cancer amongst women and is the seventh highest cause of death in this population in the United States. Statistics indicate that minority and underserved populations have worse overall survival from breast cancer. Clinical data from our laboratory have shown that African American and Latino breast cancer patients with HER2/neu overexpression and high pAKT have poor outcomes. In vitro data on breast cancer cells have shown that Cyclin D1 is up-regulated by the PI3K/AKT pathway, while the FOXO1A transcription factor is down-regulated. Hence, the purpose of our current study was to evaluate clinical correlation between pAKT, Cyclin D1, and FOXO1A in tissues from the same patient. We used the same cohort of patients from our previous study. Immunohistochemistry was performed on paraffin tissues from African American and Latino women with breast cancer. Results indicate that patients with HER2/neu overexpression were likely to be Cyclin D1 positive. In addition, those with high pAKT were also Cyclin D1 positive, thus indicating that HER2/neu overexpression might be associated with increase in Cyclin D1 and pAKT. Interestingly, breast tumors with high pAKT and low FOXO1A were also Cyclin D1 positive. In summary, immunohistochemical analysis and subsequent correlation of biomarkers associated with the HER2-PI3/AKT pathway, that include pAKT, Cyclin D1 and FOXO1 may provide better assessment of clinical outcome of breast cancer patients and therefore better target therapies.
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 3751.
Abstract 3752: Folate receptor expression prevalence across multiple tumor types and concordance between matched primary and metastatic tumor pairs
Authors: Li Hewei , Wu Qiuyan , Xing Guan , Teslenko Vic , Tornout Jan Van , Ahlers Christoph M. , Huang Fei 
Published: February 2011

Abstract
Background: The human folate receptor (FR) is selectively overexpressed in a number of human epithelial malignancies, including ovarian, renal, and prostate cancers. Folate-conjugated therapies provide a strategy for targeting patients with FR expressing tumors. Identification of patients with FR expressing tumors is important to increase the opportunity for clinical benefit from folate conjugated therapies. The goals of this study are to determine the prevalence of FRα expression in various solid tumors, and to determine the concordance of FRα expression between primary and matched metastatic tumors. This concordance could help to determine if primary tumor samples would be suitable for assessing FR expression in metastatic tumors. Little information on this is currently available.
Methods: FRα expression was analyzed by immunohistochemistry (IHC) in 339 primary tumors covering a wide range of human tumor types. Concordance of FRα status in 86 archived primary and matched metastatic breast, renal, endometrial and ovarian tumors was assessed by IHC.
Results: FRα expression prevalence was moderate to high in primary tumors of lung (13/29; 45%), renal (66/115; 57%), colon (17/27; 63%), prostate (8/12; 67%) and ovarian (22/29; 76%). FRα expression frequency was found relatively low in breast tumor (26/127; 20%) which is consistent with previous reports. Furthermore, for the first time, we showed a good concordance (81.4%) of FRα expression between paired primary and metastatic ovarian, endometrial, renal and breast malignancies.
Conclusions: FRα is frequently overexpressed in ovarian, prostate, colon and renal tumors, suggesting these tumor patients might benefit more from folate conjugated therapies. New findings from this study show that FRα expression is maintained in metastatic tumors, indicating the utility of archived primary tumor samples for determining the FR positivity of metastatic tumors in patients receiving a folate conjugated agent.
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 3752.
Abstract 3755: Phosphorylated STAT3 in polymorphonucleur cells (PMNs) as a potential surrogate marker to evaluate the efficiency of sorafenib therapy
Authors: Wu Jun , Wang Yan , Yen Yun , Reckamp Karen L. 
Published: February 2011

Abstract
Sorafenib tosylate (BAY43-9006) is an oral multi-kinase inhibitor which targets c-Raf and b-Raf, and thus interrupts this critical oncogenic pathway. Sorafenib has been successfully applied in the clinic to treat patients with certain types of renal cell carcinoma and hepatocellular carcinoma. Signal transducer and activator of transcription 3 (STAT3) plays an important role in the pathogenesis and progression of cancer. Furthermore, the inhibition of STAT3 by sorafenib has been previously described. In order to evaluate STAT3 within polymorphonucleur cells (PMNs) as a potential surrogate marker of phosphorylated STAT3 (p-STAT3) in tumor tissue, we proposed a preclinical animal model to examine the relationship of p-STAT3 as in tumors and PMNs during treatment with sorafenib.
Both normal balb/c mice (female and male, 10 weeks old) and immunodeficient NOD/SCID/IL2Rgamma null (NSG) mice (female at 10 weeks old) were used in the animal studies. Human ovarian cancer cells OV-90 were inoculated subcutaneously into the dorsal area of NSG mice to create a xenograft model. Sorafenib was given at 50 or 100 mg/kg in balb/c mice and 60 mg/kg in NSG mice via oral gavage for three doses before tissue sampling. Two hours after the last drug treatment, the mice were euthanized and the blood and tumor tissues were harvested for pSTAT3 level assays. Phosphorylated STAT3 expression levels were analyzed by flow cytometry and western blot.
Suppression of pSTAT3 levels in PMNs from balb/c mice was observed in 1/3 of mice at 50 mg/kg and 2/3 of mice at 100 mg/kg by both western blot and flow cytometry, however the difference between the vehicle control and sorafenib group was not significant. Suppression of pSTAT3 levels in OV-90 tumor tissue from sorafenib-treated NSG mice was significant by western blot analysis. However the suppression of pSTAT3 on the PMNs from the corresponding NSG mice was minor by flow cytometry analysis. In conclusion, in this murine model, pSTAT3 in PMNs was not a consistent surrogate marker for the evaluation of sorafenib activity. Based on the emerging data linking escalating doses of sorafenib to STAT3 inhibition in cancer cells, and the tumor responses seen with increasing doses, evaluation of surrogate biomarkers to predict clinical efficacy will be useful.
Supported by NCI K12 CA 01727 and the Phase One Foundation.
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 3755.
Abstract 3758: Global expression profiling of highly degraded RNA by DASL assay from formalin-fixed paraffin-embedded lung tissue
Authors: Su Li 
Published: February 2011

Abstract
Microarray-based genome-wide gene expression analysis on fresh frozen tissue is widely used in cancer studies. Compared to fresh frozen tissues, formalin-fixed paraffin-embedded (FFPE) tissues are more accessible in clinical setting for genomic analysis, but its use has been hampered by technical difficulty. Recently, cDNA-medi¬ated annealing, selection, extension, and ligation (DASL) assay was developed by Illumina (San Diego, CA) to investigate the global gene expression profiling of highly degraded RNA from FFPE samples. In this study, we tested the potential of the Whole-Genome DASL Assay for Expression Profiling in FFPE Samples (covering up to 24,000 annotated probes) in biomarker discovery for lung disease research. We obtained biopsy tissue from two lung cancer patients and six acute respiratory distress syndrome (ARDS) patients. Five 5 μm-thick slides from each specimen were evaluated by a pathologist for tumor cellularity (lung cancer) or diffuse alveolar damage (ARDS), and RNA was extracted using commercially available (Roche High Pure RNA Paraffin) kits. The DASL expression profiles on 2 ARDS FFPE-extracted RNA samples had poor quality as determined by low detection rate (&lt;25%) and low array-wide average signals. The other 6 (75%) of the RNA samples had a median detection of 8,442 genes with a range between 7,306 and 10,616 genes. These array data also had strong array-wide average signals and low noise. Our study demonstrated that DASL expression profiling technology, genome-wide expression profiles can be successfully generated from FFPE lung tissues.
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 3758.