bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1751: The influence of sex on prognostic markers for non-small cell lung cancer
Authors: Paul Boutros C. 
Published: February 2011

Abstract
There are significant differences between the sexes in the incidence, presentation, and response to therapy of non-small cell lung cancer (NSCLC). This study evaluated the effects of these differences on mRNA-based prognostic markers.
Several prognostic markers have been developed over the past decade by various groups, generally from microarray datasets. These markers look at the mRNA levels of specific genes and use these to determine whether a patient is likely to good or poor outcome. If such markers were successful at complementing traditional staging criteria (i.e. molecular sub-staging) then patients predicted to have poor outcome could receive additional or more intensive therapies. Surprisingly, to date, the effect of sex on such markers has not been evaluated, despite major differences in disease between males and females.
To evaluate this issue, I compiled the data from nine transcriptomic studies of primary NSCLC. These studies were integrated using a novel normalization approach and then subject to meta-analysis. For each gene present in the analysis (16,391 in total), the univariate prognostic capacity was calculated separately for men and women using median dichotomization and Cox proportional hazards modeling. Of the top 100 genes in each sex, only 12 were overlapping. Novel sex-specific prognostic signatures were then derived, and shown to out-perform sex-independent signatures by a statistically significant (p &lt; 0.01) margin.
In summary, sex plays a major role in NSCLC etiology and response to therapy. I have demonstrate here that it also greatly effects the efficacy of transcriptomic prognostic markers.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 1751.
Abstract 1752: Prognostic significance of Aquaporin(AQP) expression in gastric and colorectal cancer
Authors: Osawa Soshi , Shimada Yutaka , Sekine Shinichi , Shigeaki Sawada , Kashima Shiro , Fukuoka Jyunya , Okumura Tomoyuki , Tsukada Kazuhiro 
Published: February 2011

Abstract
Introduction :
Aquaporins (AQPs) are a membrane proteins involved in water transport and have been found to be expressed in several cancers. We have already reported that AQP 5 expression is associated with differentiation for gastric cancer (J Physiol Science 2009). However, the role of AQP family expression has not been well evaluated yet. In this study, we examined the expression of AQP 1, 4, 5 and 8 in gastric cancer and colorectal cancer, and compared them with the clinico-pathological characteristics of the patients.
Method :
The expression of AQP1, 4, 5, and 8 was comprehensively examined by tissue microarray (TMA1150) that has been established in our hospital. The specimens of gastric cancer and colorectal cancer were obtained from the patients who receive an operation between 1993 to 2004. Clinico-pathological data were obtained from the patients’ medical records. After careful examination of two independent pathologists, the results were scored according to the intensity and the distribution. Finally, AQP expressions were compared to the clinical pathologic finding of the patients.
Result :
In stomach cancer, positivity of AQP1, 4, 5, and 8 expressions were 40.7% (22/54), 43.2% (19/44), 97.6% (41/42) and 18.2% (8/44) respectively. AQP4 positive patients have a significant better prognosis than that of negative patients (p=0.004) and low expression of AQP4 tended to relate to poorly differentiated adenocarcinoma (p=0.07). However there was no significant difference between the prognosis, histological type, disease stage (TNM classification) and AQP1, 5, and 8 expressions.
With regard to colorectal cancer, positivity of AQP1, 4, 5, and 8 expressions were 27.4% (20/73), 45.9% (34/74), 98.4% (61/62), and 76.4% (55/72) respectively. AQP4 positive patients tended to have a favorable prognosis (p=0.12), on the other hand AQP1 positive group tended to have a worse prognosis (p=0.06). There was the other relationship between low expression of AQP4 and N factor (p=0.04).
Conclusion :
AQP 1 and 4 expression have some roles in the progression of gastric cancer and colorectal cancer, however the role of AQP 5 and 8 are still unknown. Our findings suggested that AQP 1 and 4 may be a molecular target of gastric cancer and 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 1752.
Abstract 1753: High expression of the microtubule destabilizing protein stathmin is prognostic for worse outcome in breast cancer
Authors: Baquero Maria , Hanna Jason , Agarwal Seema , Killiam Elizabeth , Camp Robert L. , Rimm David L. 
Published: February 2011

Abstract
INTRODUCTION: Taxanes are microtubule targeting agents (MTAs) and potent cytotoxic molecules recognized as highly effective chemotherapeutic agents. In large randomized clinical trials, taxane-based chemotherapies provided benefits in overall and disease-free survival, but they are accompanied by significant adverse effects. Thus the clinical utility of taxane therapy would be enhanced if there were companion diagnostic tests so that only the taxane-sensitive patients (about half of breast cancers) could be treated with this drug. Accumulating evidence indicates that microtubule associated proteins (MAPs) may be responsible for tumor cell resistance to taxanes. Here we use a large retrospective cohort to measure expression levels of stathmin, a microtubule destabilizing protein, and to determine prognostic value, as a first step toward development of a companion diagnostic.
METHODS: Stathmin expression was measured in a large retrospective breast cancer cohort (n= 645) with 20 year follow-up using tissue microarray technology (TMA) in two-fold redundancy and quantitative immunofluorescence (AQUA). Patient stathmin expression levels were correlated with clinical, pathological, and disease free survival variables.
RESULTS: Stathmin expression exhibited nonparametric distribution with high correlation (R= 0.70) between redundant TMA cores. Prognostic evaluation of the cohort using univariate analysis indicated an inverse correlation between high stathmin expression and overall survival (HR = 1.30, 95% confidence interval [CI] = 1.02-1.65; p&lt; 0.028). Kaplan Meier survival analysis showed 10-year survival of 54% for patients with high stathmin expression versus a 65% survival rate for low expressers (log rank, P&lt;.0058). Multivariate analysis indicated that high stathmin expression, nodal status, HER2 expression, and tumor size are independent predictors of survival.
CONCLUSIONS: Stathmin expression in breast tumor tissue functions as a prognostic factor where high expression is associated with worse outcome. Since stathmin expression is useful in predicting survival, it may serve as marker to accurately select patients for current taxane-based or other anti-microtubule 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 1753.
Abstract 1756: Automated digital analysis of interleukin-6 (IL-6) expression in a prostate cancer (PCa) matched case-control outcome based tissue microarray (TMA) design set
Authors: Shah Jarna , Macias Virgilia , del Mundo-Galicia Marisa , Xue Mark , Kajdacsy-Balla Andre A. 
Published: February 2011

Abstract
IL-6 is a multifunctional cytokine that has been involved in modulation of growth and differentiation in several malignant tumors. Studies have shown its role as an important autocrine growth factor for androgen-dependent human prostate cancer in vivo. Serum IL-6 has also been associated with poor prognosis in prostate cancer. We performed a digital analysis of IL-6 immunoreactivity in prostate cancer epithelial cells to determine differences in IL-6 expression between recurrence and non-recurrence groups in a PCa nested case-control cohort.
We analyzed an outcome-based TMA obtained from the Cooperative Prostate Cancer Tissue Resource (CPCTR) containing quadruplicate cores (0.6mm core diameter) from 200 pairs of PCa tumor samples (n=400). Cases with PSA recurrence were matched 1:1 with cases without recurrence by race, age, year of surgery, Gleason grade, and pathological stage. All cases had at least five-years follow up. TMA slides were incubated with rabbit polyclonal IL-6 antibody (Abcam) in a 1:600 dilution. Expression levels of IL-6 were assessed by Colocalization Algorithm (ScanScope®, Aperio Corp). Differences in IL-6 intensity between case-control pairs were calculated by Wilcoxon signed rank paired test.
Automated data was available for analysis in 149 pairs (n=298). The Wilcoxon signed rank test showed no statistically significant differences in IL-6 intensity between the two groups (p = 0.7).
To the best of our knowledge, this is the first study to examine the expression of IL-6 in a large PCa TMA set. Our results revealed IL-6 expression in cancer tissue; however, after statistical analysis, no significant differences were obtained to indicate that IL-6 may be considered as prognostic marker of prostate cancer with biochemical recurrence if cases were first matched by race, age, date of prostatectomy, Gleason score, and stage. In our study we excluded stromal and inflammatory cells IL-6 expression.
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 1756.
Abstract 1767: Gene expression signatures as predictors of chemotherapeutic response in breast cancer
Authors: Fournier Marcia V. , Martin Katherine J. 
Published: February 2011

Abstract
The purpose of this study is to evaluate a novel 22-gene signature as a predictor of response to chemotherapy in breast cancer. The extent of residual viable tumor following chemotherapy is the most important predictor of long-term outcome in breast cancer. It is essential to identify patients who will not respond to chemotherapy to avoid ineffective therapies as well as unnecessary side effects. The rate of complete pathologic response to chemotherapy is relatively low, ranging from 3% to 27% of patients. Much work has been performed to predict chemotherapy responsiveness, but, as of yet, no test is effective and widely used in the clinic. Gene expression signatures are a multifaceted approach to characterizing disease states. They offer the potential to tailor a chemotherapy regimen to an individual patient. Here we compare the ability of multiple gene signatures, including the 70-gene prognostic signature (MammaPrint) and the 22-gene signature among others, to accurately predict response to multiple different regimens of primary chemotherapy in breast cancer. Predictive ability is compared in independent microarray datasets totaling approximately 157 breast cancer patients treated with primary chemotherapy. Sensitivity, specificity, and overall accuracy were evaluated by receiver operating characteristics (ROC) graphs, a technique for visualizing, organizing, and selecting classifiers based on their performance. Results show that the 22-gene signature accurately predicts response to multiple primary chemotherapies (p&lt;0.05). Importantly, the 22-gene signature outperformed other signatures with highly significant p-values in all datasets tested. This signature potentially represents a clinically useful method to select a personalized chemotherapy regimen for breast cancer patients.
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 1767.
Abstract 1768: Comprehensive mass spectrometry based metabolomic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer
Authors: Urayama Shiro , Zou Wei , Tolstikov Vladimir 
Published: February 2011

Abstract
Background: Poor outcome of pancreatic cancer (PDAC) necessitates development of early diagnostic method to reduce mortality. In current study, metabolic profiling of plasma samples from selected cancer patients and noncancerous controls was performed to seek novel metabolic biomarkers of PDAC. Comprehensive mass spectrometry based analytical platform were applied for detection of compounds in the plasma from early stage PDAC patients.
Methods: Plasma available from the patients involved in the IRB-approved UC Davis Pancreas Registry was utilized. Five histologically proven cases of early stage pancreatic cancer without clinical evidence of distant metastasis [AJCC TNM stages: IB (2) and IIB (3)] and 5 noncancerous cases [3 chronic pancreatitis, 2 normal-based on clinical and follow-up evidences] were chosen from the Registry. Combination mass spectrometry (MS) methods, GC-TOF-, HILIC-LC-ESI-, and RP-LC-ESI-MS were applied for the plasma analysis. Data values obtained were evaluated for principle component analysis (PCA). Further feature selection and ANOVA were conducted after the PCA. Statistical significance was defined as p-value less than 0.05. Feature components with statistically significant classifiers of the PDAC were analyzed further with LTQ-Orbitrap MS for accurate mass measurement. Mass spectra of potential biomarkers thus obtained were spectrally corrected and unique elemental formula was searched against CAS database using the strategy of Explore Substances-Chemical Structure for known compounds. Mass Frontier 5.0 was used for MS/MS fragmentation modeling analysis; with parent compounds that had the best match of MS/MS fragmentation pattern were considered as the molecular structure of the potential biomarkers.
Results: The candidate biomarkers included amino acids (N-methylalanine, lysine, glutamine, phenylalanine), fatty acids (arachidonic acid), lipids (lysoPC (18:2), PC (34:2), PE (26:0)), and bile acids (tauroursodeoxycholic and taurocholic acids, deoxycholylglycine, cholylglycine).
Conclusion: We have demonstrated that combination of the comprehensive mass spectrometry based metabolic profiling techniques, data mining, and data analysis successfully find potent classifiers for pancreatic cancer in plasma. These metabolites upon validation, selectivity study, and broader cohort study could become clinical biomarkers for early diagnosis of pancreatic 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 1768.
Abstract 178: RASSF10 is frequently methylated in epithelial cancers
Authors: Hill Victoria , Krex Dietmar , Bieche Ivan , Minna John , Morton Dion , Yao Msahiro , Maher Eammon R. , Latif Farida 
Published: February 2011

Abstract
The classical Ras-association domain family (RASSF1-6) are a group of Ras effector molecules that contain a C-terminal Ras-association (RA) domain of the RalGDS/AF-6 variety and a protein interaction domain known as the Sav/RASSF/Hippo (SARAH) domain. Several members of the classical RASSF family are involved in tumorigenesis since epigenetic inactivation of many isoforms is a frequent event across many tumor types and their functions are consistent with roles as tumor suppressor proteins. Recently several additional RA-domain containing family members have been identified and designated N-terminal RASSF proteins (RASSF7-10). These comprise RASSF7 (also known as HRC1 located 11p15.5), RASSF8 (also known as HOJ-1 or C12ORF2 located 12p12.1), RASSF9 (also known as P-CIP1 or PAMCI located 12q21.31) and RASSF10 (located 11p15.2). These proteins are divergent and structurally distinct from RASSF1-6, containing an RA domain within their extreme N-termini and lacking the SARAH protein interaction domain. Little is known about the N-terminal RASSF7-10 proteins although they represent an evolutionarily conserved group of proteins with orthologues of all four in the lower vertebrate Xenopus laevis and a RASSF7/8 homologue in Drosophila melanogaster distinct from the RASSF1-6 Drosophila homologue.
We have recently characterized the N-terminal RASSF10 gene and demonstrated frequent methylation of the associated 5’ CpG island in acute lymphoblastic leukemia. In this report we analysed the methylation status of the CpG island in a range of common epithelial cancers. RASSF10 was frequently methylated in grade II-IV gliomas (grade II, 50%; grade III, 80%, grade IV 57%) but was unmethylated in grade I astrocytomas and in DNA from age matched control brain samples. In other common epithelial cancers RASSF10 was also methylated but at a lesser frequency compared to grade II-IV gliomas. RASSF10 was methylated in 25% breast tumors, 31% of colorectal cancers, 20% lung tumors and 28% of renal cell carcinomas. RASSF10 was unmethylated in DNA from corresponding normal tissues or control tissue samples.
This work demonstrates that RASSF10 is a frequent target of epigenetic inactivation in a range of epithelial cancers as well as haematological cancers. We are now undertaking biological characterization of this novel protein.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 178.
Abstract 1783: Activated c-MET; a prognostic factor and potential therapeutic target for malignant peripheral nerve sheath tumors (MPNST)
Authors: Torres Keila E. , Ghadimi Markus , Wang Suizhao , Liu Jun , Lazar Alexander , Pollock Raphael E. , Lev Dina 
Published: February 2011

Abstract
There is a crucial need for sensitive prognosticators and novel therapeutic approaches for better management of MPNST. These tumors harbor a dismal prognosis due to their chemoresistant nature and enhanced metastatic propensity. A large body of evidence suggests a role for the tyrosine kinase receptor c-Met in cancer and its utility as a target for cancer therapy is currently being investigated. Here we aimed to evaluate the role of the c-Met signaling pathway in human MPNST. Expression level of c-Met, its ligand HGF and phosphorylated c-Met was determined immunohistochemically in a tissue microarray of human MPNSTs (n = 96) and benign neurofibromas (n = 31). All three markers were found to be over-expressed in MPNST as compared to their pre-malignant precursors (neurofibroma; p&lt;0.05). Furthermore, univariable and multivariable analyses identified a statistically significant correlation between activated-c-Met expression and poor patient outcome (HR=2.32, p=0.012 and HR=1.48, p&lt;0.001, respectively). Human MPNST cell lines expressed c-Met, HGF, and activated c-Met to varying levels. An activating c-Met mutation (Exon 2: N375S) was identified in one cell line (T265); all cells evaluated (n=3) harbored c-Met and HGF amplification based on aCGH. c-Met activation resulted in significantly increased MPNST cell motility and invasion. Furthermore, c-Met activation enhanced the pro-angiogenic effects of MPNST. c-Met blockade (via siRNA or a small molecule inhibitor) abrogated the HGF-induced downstream signaling and MPNST cell migration/invasion. Dual blockade of c-Met and VEGFR significantly abrogated MPNST local and metastatic growth in vivo. In conclusion, Human MPNST tumors and cell lines express the c-Met receptor which, upon activation, results in increased MPNST migration, invasion, and angiogenesis. Inhibition of c-Met-mediated signaling could impair MPNST metastatic capacity, and therefore merits further consideration as a potential MPNST therapeutic target.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 1783.
Abstract 1788: Preclinical development of a selective, potent small molecule ALK inhibitor
Authors: Lovly Christine M. , de Stanchina Elisa , Liang Chris , Pao William 
Published: February 2011

Abstract
A chromosomal inversion [inv (2)(p21p23)] resulting in the expression of an oncogenic kinase fusion protein known as EML4-ALK [echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase] has been implicated in the pathogenesis of a subset of lung adenocarcinomas. An agent (PF-02341066), originally described as a MET tyrosine kinase inhibitor (TKI) but with “off-target” ALK activity, has demonstrated significant activity in ALK-fusion positive lung cancer patients and is currently in phase II/III clinical trials. In this study, we describe the development and characterization of a novel and highly selective ALK TKI. X-276 (racemic mixture) is an orally bioavailable ATP mimetic that has high selectivity for ALK as assessed by Ambit assays (binding constant 2nM). Treatment of H3122 lung adenocarcinoma cells, which harbor the EML4-ALK E13;A20 fusion product, resulted in potent inhibition of cell growth with an IC50 of 10nM, approximately 10 fold less than the IC50 of H3122 cells treated with a racemic mixture of PF-02341066. Immunoblot analysis confirmed that X-276 inhibited ALK phosphorylation in H3122 cells. Importantly, the IC50 of X-276 in H1993 lung cancer cells, known to be MET-dependent, was &gt;100 fold higher. In addition, the selectivity index of H3122 cells vs. hepatocyte HepG2 cells was &gt;135. Finally, compared to vehicle controls, X-276 delayed the growth of H3122 xenografts in established nude mice by &gt;60%. Collectively, these data show that TKIs can be developed with greater specificity against ALK. Such compounds may lead to the development of ‘second-generation’ ALK TKIs with more potency against ALK-mutant cancers. Future studies will focus on determining the mechanism of acquired resistance to ALK TKIs using these more potent ALK inhibitors.
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 1788.