bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1695: Imaging of the interaction of pancreatic cancer and stellate cells during liver metastasis
Authors: Suetsugu Atsushi , Snyder Cynthia , Moriwaki Hisataka , Saji Shigetoyo , Bouvet Michael , Hoffman Robert M. 
Published: August 2012

Abstract
Pancreatic stellate cells are involved in fibrosis of pancreatic cancer. An understanding of pancreatic cancer-cell interactions with stellate cells is critical to our ability to develop effective anti-tumor therapeutics for pancreatic cancer. We report here imaging of the interaction of pancreatic cancer cells and pancreatic stellate cells in liver metastasis. Human pancreatic cancer cell lines (XPA1 and MiaPaCa-2) were engineered to express green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm. Pancreatic stellate cells, engineered to express RFP, were co-injected with the cancer cells into the spleen of transgenic cyan fluorescent protein (CFP) nude mice. Three hours after splenic injection dual-color pancreatic cancer cells and pancreatic stellate cells were found distributed in the host liver. Seven days after cancer cell-stellate cell co-injection, most pancreatic cancer cells and stellate cells were dead. However, by 28 days after injection, liver metastases were observed in the host CFP nude mice. With the high-resolution intravital imaging afforded by the Olympus FV1000 confocal microscope, the interaction of the dual-colored pancreatic cancer cells and the RFP-expressing pancreatic stellate cells could be clearly imaged in the liver metastasis, suggesting that stellate cells participate in metastasis formation. Our hypothesis is that pancreatic stellate cells form a niche for liver metastasis of pancreatic cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1695. doi:1538-7445.AM2012-1695
Abstract 1699: Breast cancer protein markers in African Americans
Authors: Broome Carolyn W. , Beyene Desta , Esnakula Ashwini K. , Smith Rachel , Abdel-Hameed Enass , Naab Tammey J. 
Published: August 2012

Abstract
The purpose of this study is to characterize protein markers in African American breast tumors that correspond to different tumor subtypes, recurrence, and survival. Tissue microarrays (TMA) have been used because they have the advantage of analyzing numerous samples on a single slide and can be used in clinical pathology laboratories. Protein markers that have been used are estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), cyclin A2, cytokeratin 5, vimentin, Bcl2, and Ki67. TMA have been prepared and stained for proteins that will distinguish 5 tumor subtypes: luminal A (ER+ and/or PR+ Her2-); luminal B (ER+ and/or PR+ Her2- Cyclin A2+ and/or Ki67+); luminal B Her2+ (ER+ and/or PR+ Her2+); Her2+ (ER- PR- Her2+), and triple negative (ER- PR- Her2-). These subtypes are known to be associated with different relapse-free survival and overall survival. Luminal B tumors have the same ER+PR+HER2- profile as luminal A tumors; however, luminal B tumors have a poor prognosis, whereas luminal A tumors have the best prognosis of all 5 subtypes. Luminal B tumors can be distinguished from luminal A tumors by staining for cell cycle proteins Cyclin A2 or Ki67, which promote cell proliferation. Cyclin A2 was more frequently expressed than Ki67 in tumors with poor prognosis such as luminal B (ER+PR+HER-) and ER-PR-HER2- (triple negative) tumors. Therefore, Cyclin A2+ may better serve to identify luminal B and triple negative tumors with a poor prognosis and thus aid physicians in treatment decisions. The RASSF1A protein has been reported to inhibit the transcription of Cyclin A2. Methylation of the RASSF1A promoter is expected to decrease RASSF1A transcription and thereby increase Cyclin A2 transcription and protein levels. Significantly increased levels of RASSF1A methylation have been observed in this laboratory with AA ER-PR-HER- breast cancer patients compared to mammoplasty samples. Thus, increased Cyclin A2 protein staining correlated with increased RASSF1A methylation. This is one molecular explanation for elevated cyclin A2 protein levels in triple negative tumors. Discovery of molecular markers and subtypes that are most prevalent in African Americans could lead to a better treatment, targets for therapy, and understanding of the factors contributing to higher mortality in this group compared to other groups.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1699. doi:1538-7445.AM2012-1699
Abstract 1707: A real-time PCR assay for detecting EGFR mutations in formalin-fixed paraffin-embedded tissue (FFPET) specimens of non-small cell lung cancer (NSCLC)
Authors: O'Donnell Patrick , Ferguson Jane , Shyu Johnny , Current Robert , Rehage Taraneh , Tsai Julie , Christensen Mari , Tran Ha Bich , Chien Shih-Chang , Wei Wen , Lawrence H.Jeffrey , Soviero Stephen 
Published: August 2012

Abstract
EGFR mutations identify patients with NSCLC who have a high likelihood of benefiting from first-line treatment with anti-EGFR tyrosine kinase inhibitors. Sanger sequencing is widely used for mutation detection but can be time-consuming, and has limited sensitivity for low levels of mutations. We describe the analytic performance of the cobas EGFR Mutation Test, a multiplex, 3-reaction real-time PCR assay designed to detect 41 mutations in exons 18, 19, 20 and 21. The mutations detected and the mutation report calls are listed below: The amount of DNA required for the assay (150 ng) can typically be isolated from a single 5-micron FFPET section, and the test can be performed in &lt; 8 hours. Analytic sensitivity was assessed using DNA blends from NSCLC FFPET tumor sections. A &gt;95% hit rate was obtained in blends with &gt;5% mutant alleles for L858R and exon 19 deletions as determined by 454 sequencing (quantitative massively parallel pyrosequencing) at a total DNA input of 150ng, or 50 ng per PCR amplification. The cobas test was compared to 2x bidirectional Sanger sequencing using a set of 152 NSCLC FFPET specimens. The overall percent agreement (OPA) between the 2 methods was 96.7% (negative agreement - NPA 97.5%; positive agreement - PPA 95.8%). Specimens with discordant cobas EGFR Test and Sanger results were analyzed by 454 and a revised agreement analysis was performed based on the composite results of the 3 assays. The revised OPA was 98.7% (NPA 98.8%; PPA 98.6%). The call repeatability of a panel of NSCLC FFPET specimens was 98% when tested with two operators, instruments, and reagent lots. Necrotic tissue, hemoglobin, triglycerides, and common respiratory organisms did not interfere with the assay. The test showed no cross reactivity with the corresponding exon sequences from the HER2, HER3, and HER4 genes. These analytic studies demonstrate that the cobas EGFR Mutation Test is a sensitive, accurate and reproducible assay.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1707. doi:1538-7445.AM2012-1707
Abstract 1728: Genetic variations in epidermal growth factor receptor pathway predict recurrence and response to chemotherapy in early stage non-small cell lung cancer
Authors: Kim Eric S. , Ye Yuanqing , Vaporciyan Ara A. , Xing Jinliang , Huang Maosheng , Gu Jian , Roth Jack A. , Lippman Scott M. , Wu Xifeng 
Published: August 2012

Abstract
Purpose: We hypothesized that genetic variants within EGFR pathway would have significant predictive value for recurrence and response to chemotherapy after curative resection in early-stage NSCLC. Methods: This study included 467 patients with histologically confirmed NSCLC who were enrolled from 1995 to 2008 in an ongoing, prospective epidemiologic lung cancer study at MD Anderson Cancer Center. A total of 387 single nucleotide polymorphisms (SNPs) within 26 genes from EGFR pathway were genotyped in patients who were treated with surgery only (N=340) or surgery plus chemotherapy (N=127). The risk of recurrence was estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) using a multivariate Cox proportional hazard regression model. Results: We identified 5 top SNPs that significantly (P&lt;0.05) predicted risk of recurrence in both surgery only and surgery plus chemotherapy groups. To identify a subgroup of patients who may benefit from adjuvant chemotherapy, we divided these 5 SNPs into two different groups according to varying hazard ratios for the analysis performed in surgery only or surgery plus chemotherapy group; A (2 SNPs)=should receive surgery only (HR&lt;1 in surgery only and HR&gt;1 in surgery+chemotherapy); B (3 SNPs)=should receive chemotherapy in addition to surgery (HR&gt;1 in surgery only and HR&lt;1 in surgery+chemotherapy). Cumulative genotype analysis reveals that patients with 1 or 2 SNPs from Group A had risk of recurrence that was 0.57-fold that of the reference group without any of these two SNPs (HR=0.57; 95% CI=0.34-0.96; P=0.035). However, if patients with the same 1 or 2 SNPs undergo chemotherapy, the risk of recurrence increases to 3.3-fold that of the reference group (HR=3.28; 95% CI=1.51-7.12; P=0.003). On the other hand, patients with one or greater number of SNPs from Group B after surgery only had 2.3-fold increased risk of recurrence compared to the reference group without any of these SNPs (HR=2.30; 95% CI=1.36-3.88; P=0.002). However, with addition of chemotherapy the risk of recurrence in patients with the same SNPs decreased significantly to 0.24-fold that of the reference group (HR=0.24; 95% CI=0.12-0.51; P=0.001). Conclusions: Our proposed SNPs from EGFR pathway may help identify a subgroup of patients at high risk of recurrence after resection and guide decision for adjuvant chemotherapy in early-stage NSCLC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1728. doi:1538-7445.AM2012-1728
Abstract 1763: A novel synthetic alkylating agent inducing DNA damages is associated with distinct DNA repair pathways
Authors: Wang Hui-Chun , Kuo Ching-Ying 
Published: August 2012

Abstract
Alkylating agents are a commonly used category of chemotherapy drugs for a verity type of malignancy. They kill cells by forming DNA adducts and interfering DNA processes if not to being removed. In respect to the types of mono- or bi-functional DNA alkylation, different classes of DNA repair processes are involved. In this study, a new DNA-directed alkylating agent BO738 was investigated. We emphasized to confirming its ability of DNA damage, and revealing which kinds of DNA repair mechanisms to be involved in BO738-induced damage. Our results proved BO738 is a bi-functional alkylating DNA damage agent, evidences including BO738 was able to induce phosphorylation of Chk1, Chk2 and p53, and elevated more potent of FANCD2 monoubiquitination, a hallmark of DNA-crosslink damage, than induced by BCNU. Followed with the finding of DNA damage response, as expected, cells that abolish in removal of BO738-induced DNA damage are link to at least base excision repair, double strand break repair and MGMT-mediate direct repair machineries. In conclusion, we provide a foundation to understand the molecular action of BO738 in subcellular environment, and according that BO738 displays comparable ability in tumor cytotoxicity than BCNU, our study highlighting a therapeutic potential in cancer chemosensitization.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1763. doi:1538-7445.AM2012-1763
Abstract 1789: Preclinical profile of novel and potent c-Met kinase inhibitors
Authors: Vakkalanka Swaroop , Muthuppalaniappan Meyyappan , Govindarajulu Babu , Varanasi Kanthikiran , Veeraraghavan Sridhar , Kuppireddi Sumalatha , Viswanadha Srikant , Dhanapalan Nagarathnam , Bhavar Prashant 
Published: August 2012

Abstract
Background: c-Met is a proto-oncogene that encodes the protein Met with intrinsic tyrosine kinase activity. Aberrant Met kinase activity triggers a series of unwarranted phosphorylation events and signalling processes that ultimately lead to the development of cancer. Alteration of the Met kinase signalling cascade represents an attractive approach aimed at blocking invasion and metastasis of cancer cells. Herein, we describe the biological and pharmacokinetic properties of representative molecules from a series of novel and small molecule inhibitors with scope to be further developed as clinical candidates for cancers mediated by dysregulated Met kinase activity. Methods: Met Kinase activity of test compounds was determined using an HTRF® KinEASE assay kit (Cisbio, Bedford, MA) with modifications. Met-dependent anti-proliferative effect was determined in MKN-45 cells. Inhibition of constitutive Met kinase phosphorylation in MKN-45 and NCI-H441 cells was measured in an ELISA assay. Subsequently, effect of the compounds on Akt phosphorylation, a downstream marker in the Met signalling cascade, was determined. Metabolic stability of the compounds was evaluated in microsomes obtained from mouse, rat, dog, monkey, and human. Results: Among the compounds evaluated, RP1269 and RP1316 demonstrated remarkable potency against the purified Met kinase enzyme (20.17 & 40.5 nM) as well as in an MKN-45 cell proliferation assay (18.0 & 2.3 nM). In addition, the compounds caused a significant reduction in constitutive Met kinase phosphorylation in MKN-45 (11.5 & 33.3 nM) and NCI-H441 (2.2 & 4.1 nM) cells. As a consequence, Akt phosphorylation was inhibited at half-maximally in MKN-45 and NCI-H441 cells at &lt;100 nM and &lt;50 nM respectively. Further, the compounds exhibited a favourable ADME profile across the species studied. Conclusions: Our findings demonstrate that RP1269 and RP1316 are potent Met kinase inhibitors with efficacy values comparable to existing Met kinase inhibitors in development. On lines with selective inhibitors, the compounds display anti-proliferative effect only in cells with amplification of the Met kinase gene. The compounds are currently being tested for efficacy and target inhibition in various xenograft models. Clinical candidate shall be nominated by 2012.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1789. doi:1538-7445.AM2012-1789
Abstract 1800: Targeted therapy using saracatinib adjunctive to castration inhibits progression to castration-resistant prostate cancer in a murine model
Authors: Yang Joy C. , Hu Brian , Durbin-Johnson Blythe , Gao Allen C. , Kung Hsing-Jien , Evans Christopher P. 
Published: August 2012

Abstract
Introduction: Prostate cancer treatment with androgen deprivation is typically efficacious for two years prior to the development of castration resistant disease (CRPC). The Src family kinases (SFK) are upregulated with androgen deprivation and have been implicated in the progression to CRPC. Saracatinib is a specific SFK inhibitor that inhibits castration resistant growth and metastases in an animal model using LNCaP cells overexpressing the neuropeptide gastrin-releasing peptide. We test the hypothesis that saracatinib given immediately after androgen deprivation inhibits castration resistant tumor recurrence using a CWR22 xenograft model. Materials and Methods: CWR22 prostate cancer xenografts were injected subcutaneously into nude mice primed with testosterone pellets (21-day release). Twenty-six mice were castrated after adequate tumor development (day 0). Mice in the treatment arm were administered saracatinib from day 7 to day 150. Mice were sacrificed at days 0, 3, 30 and 150. Tumors and sera were collected for analysis including tumor weight, serum testosterone, serum PSA and gene-profile studies. The data was analyzed using the t-test and analysis of variance. Results: CRPC recurrence was significantly inhibited with the administration of saracatinib. The mean weight of tumor recurrence was 0.18 grams with saracatinib compared to 3.20 grams in the control group (p=0.015). Saracatinib was associated with a reduction in serum PSA (1.6 versus 14.7 ng/dl) and testosterone (21.1 versus 24.1 pg/ml) compared to controls, though statistical significance was not reached (p=0.08 and p=0.63, respectively). Gene expression of signaling kinases and their downstream olecules including Src, Etk, FAK, JAK, Stat3, c-myc, β-catenin, NF-κB, Akt, and mTOR is being compared between time points. Conclusions: Saracatinib significantly inhibits castration resistant tumor recurrence when started with androgen deprivation. Additional investigation into the genetic and molecular changes induced by saracatinib with gene microarray and polymerase chain reaction is ongoing. Saracatinib may have a role in combination with androgen deprivation to delay the onset of castration resistant disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1800. doi:1538-7445.AM2012-1800
Abstract 2411: The epithelial-mesenchymal transition of gastric cancer cells was stimulated by TGFβR signaling in hypoxia
Authors: Matsuoka Junko , Yashiro Masakazu , Aomatsu Naoki , Hirakawa Toshiki , Hasegawa Tsuyoshi , Fukuoka Tatsunari , Morisaki Tamami , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Yamada Nobuya , Ohira Masaichi , Ishikawa Tetsuro , Hirakawa Kosei 
Published: August 2012

Abstract
Introduction: Epithelial mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal properties while losing cell-cell interactions and apicobasal polarity. EMT is considered to be correlated with malignancy of cancer cells and responsible for cancer invasion and metastasis. Patients with gastric cancer show a poor prognosis because of frequent metastasis. We previously reported that distant metastasis was associated with hypoxia in gastric cancer. Therefore, we investigated the effect of hypoxic condition on EMT of gastric cancer cells. Materials and Methods:Seven gastric cancer cell lines derived from gastric cancer were used. Cells were cultured in normoxia (21% O2) or hypoxia (1% O2) for 24h. EMT rate was evaluated as the percentage of spindle-shaped cells of total cells. The expression level of TGFβ and TGFβ receptor was evaluated by real time RT-PCR. Effect of several inhibitors on the EMT was evaluated by cell morphology. The TGFβ1 level of the cell culture supernate was measured by a quantitative sandwich enzyme immunoassay technique. Results: Hypoxia stimulated EMT of OCUM-2MD3 and OCUM-12 cells, but not that of other cell lines. The level of TGFβ expression was increased significantly (p&lt;0.01) under hypoxia in comparison with normoxia. The level of TGFβ receptor expression was increased in OCUM-2MD3 cells, but not OCUM-2M cells. TGFβR inhibitor, SB431542, significantly suppressed EMT of OCUM-2MD3 (p=0.03) and OCUM-12 (p&lt;0.01). In OCUM-2MD3 and OCUM-12, the quantity of TGFβ1 in cell culture supernatant significantly increased under hypoxia compared to normoxia, but not OCUM-2Mcells. Conclusion: Hypoxia stimulates the EMT of gastric cancer cells via TGFβ/ TGFβ receptor signaling. TGFβ receptor inhibitor might be promising for the treatment of metastasis of gastric cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2411. doi:1538-7445.AM2012-2411
Abstract 2417: Oncogenic properties shared by all Snail family members
Authors: Gras Baptiste , Chassot Christelle , Puisieux Alain , Ansieau Stéphane 
Published: August 2012

Abstract
The epithelial to mesenchymal transition (EMT) is a latent embryonic process promoting cell migration by transiently affording epithelial cells a mesenchymal phenotype, motility and a survival advantage. The inappropriate activation of this program in adult cells is associated with several pathologies including tumor development where EMT promotes cancer cell dissemination and multidrug resistance development. We have recently demonstrated that EMT-inducers, beyond their prometastatic potential, facilitate the malignant transformation of human mammary epithelial cells in vitro and promote breast carcinogenesis in vivo. Although their ability to alleviate senescence and apoptosis failsafe program induction unquestionably contributes to their oncogenic potentials, we sought to investigate whether EMT inducers share additional properties. To this end, the activities of all three Snail members were examined. Likewise SNAI1 and SNAI2, SNAI3 expression is aberrantly activated in cancers, especially in mammary carcinomas. Ectopic expression of all three proteins in mammary epithelial cells induces their commitment into EMT, provides cells with a survival advantage in low adherent conditions and promotes their neoplastic transformation, with a similar gradient of efficiencies. Interestingly, this efficiency parallels with their ability to upregulate intracellular signaling pathways. We will update on the progress of our work aimed at understanding how these dysregulations impact on their oncogenic and prometastatic potential.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2417. doi:1538-7445.AM2012-2417