bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3541: Significance of osteopontin in the sensitivity of malignant pleural mesothelioma cells to pemetrexed.
Authors: Seike Masahiro , Takeuchi Susumu , Soeno Chie , Noro Rintaro , Minegishi Yuji , Gemma Akihiko 
Published: August 2014

Abstract
Introduction: Malignant pleural mesothelioma (MPM) is one of the fatal cancers associated with asbestos exposure.Pemetrexed (PEM) is currently recommended as one of the antitumor drugs consisted of standard therapies for MPM.However, the mechanism of the sensitivity of MPM to PEM remains unclear. Methods: We analyzed the antitumor effects of PEM in six MPM cell lines by MTS assay. To identify genes associated with drug sensitivity,we conducted gene expression profiling on the same set of cell lines using Affymetrix HG-U133A GeneChips. Pathway analysis was performed to provide a viewpoint of the biological function of the genes. Results: Three cell lines were sensitive to PEM. Eighteen transcripts and fourteen genes identified by Gene-chips were significantly correlated with sensitivity to PEM. Pathway analysis revealed that SPP1/OPN was an important target in PEM sensitivity. Overexpression of SPP1 was observed in the sensitive cells by Western blotting. Introduction of SPP1 by lentiviral vector significantly enhanced the invasion activities of MPM cells. Expression of SPP1/OPN and AKT phosphorylation were significantly decreased after PEM treatment of the PEM-sensitive cells. PEM treatment with SPP1/OPN knockdown inhibited the PEM-induced cell growth inhibitory effect in PEM-sensitive cells. Conclusions: Our results suggest that SPP1 may be used as a single predictive biomarker of the effectiveness of PEM treatment in MPM. Patient selection based on SPP1/OPN expression may be useful for future clinical development of PEM therapy for MPM.
Citation Format: Masahiro Seike, Susumu Takeuchi, Chie Soeno, Rintaro Noro, Yuji Minegishi, Akihiko Gemma. Significance of osteopontin in the sensitivity of malignant pleural mesothelioma cells to pemetrexed. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3541. doi:10.1158/1538-7445.AM2013-3541
Abstract 3547: The BIM deletion polymorphism not associated with treatment efficacy of sorafenib for advanced hepatocellular carcinoma.
Authors: Shao Yu-Yun , Chang Yung-Lin , Huang Chung-Yi , Hsu Chih-Hung , Cheng Ann-Lii 
Published: August 2014

Abstract
Background: A germline BIM deletion polymorphism was recently proposed to predict poor treatment efficacy of certain kinase inhibitors, including imatinib and gefitinib. Sorafenib, a multi-kinase inhibitor, is the current standard treatment for advanced hepatocellular carcinoma (HCC). We aimed to explore whether BIM deletion predicted the treatment efficacy of sorafenib for advanced HCC.
Methods: All patients who were enrolled in clinical trials to receive sorafenib-containing regimens as first-line therapy for advanced HCC and consented to provide peripheral blood samples were included in the study. Genomic DNA was extracted from the mononuclear cells of peripheral blood. We performed PCR and agarose gel electrophoresis to detect the genotypes with and without the BIM deletion polymorphism, and then analyzed the associations between BIM genotypes and treatment outcomes.
Results: A total of 90 patients were enrolled. Among them, 64 patients received sorafenib plus metronomic tegafur/uracil, and 26 patients received sorafenib alone; 69 (77%) patients had chronic hepatitis B infection, and 18 (20%) had chronic hepatitis C infection. Most (90%) patients had BCLC stage C disease. The heterozygous BIM deletion polymorphism was identified in 9 (10%) patients. Patients with and without the BIM deletion polymorphism had similar objective response rates (12.5 % vs. 6.2%, p = 0.479) and disease control rates (55.6% vs. 60.5%, p = 0.774). Time to progression, progression-free survival, and overall survival were also similar between patients with and without BIM deletion (Table), regardless the treatment regimens. Besides, the BIM polymorphism had no associations with gender, age, hepatitis etiology, and disease stage.
Conclusions: The BIM deletion polymorphism was not associated with the treatment efficacy of sorafenib for advanced HCC. (This work was supported by grants NSC98-3112-B-002-038, NSC101-2314-B-002-141, 100CAP1020-2 & NTUH.101-N1965.)
BIM deletion & treatment outcomes BIM deletion polymorphism Yes (n = 10) No (n = 80) p value Time to progression 4.2 (0–10.5) 4.1 (3.6–4.7) 0.978 Progression-free survival 4.2 (0–10.5) 3.7 (2.7–4.8) 0.871 Overall survival 8.1 (0–187.1) 7.4 (5.6–9.1) 0.742 Data presented as median (95% confidence interval), in months
Citation Format: Yu-Yun Shao, Yung-Lin Chang, Chung-Yi Huang, Chih-Hung Hsu, Ann-Lii Cheng. The BIM deletion polymorphism not associated with treatment efficacy of sorafenib for advanced hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3547. doi:10.1158/1538-7445.AM2013-3547
Abstract 356: Role of the LMO1 oncogene in neuroblastoma pathogenesis.
Authors: Zhu Shizhen , Wood Andrew , He Shuning , Stanton Rebecca , Guo Feng , Maris John , Look A. Thomas 
Published: August 2014

Abstract
Neuroblastoma, an embryonic tumor of the peripheral sympathetic nervous system (PSNS), accounts for 10% of all childhood cancer deaths. We recently developed a robust zebrafish model of neuroblastoma and demonstrated that activated ALK synergizes with MYCN by inhibiting a developmentally-timed apoptotic response that is otherwise induced by MYCN (Zhu et.al. Cancer Cell, 2012). We have now used this model to provide evidence in support of the results of a neuroblastoma genome-wide association study (GWAS) showing that common variation within the LIM domain-only 1 (LMO1) gene locus is highly associated with the development of advanced neuroblastoma and may function as an oncogene in established disease (Wang K et.al. Nature, 2011). We are collaborating because our zebrafish system provides a robust in vivo tumor model to investigate the underlying mechanisms through which LMO1 overexpression contributes to malignant transformation. Here we developed transgenic lines in which LMO1 is overexpressed in the PSNS under control of the dopamine-beta-hydroxylase (dβh) promoter. We observed that overexpression of LMO1 in three individual transgenic lines synergized with MYCN to accelerate the onset of neuroblastoma in the interrenal gland (IRG), the zebrafish analogue of the adrenal medulla. Tumors began to appear at 13 weeks in transgenic fish overexpressing MYCN alone and this latency was shortened dramatically to 5 weeks (p=0.02) and the penetrance was increased more than three-fold in the transgenic fish coexpressing both MYCN and LMO1. In addition, we found that coexpression of LMO1 with activated ALK induced neuroblastoma, which is the first time in our model system that neuroblastoma has been induced without MYCN overexpression. Thus, the zebrafish model system appears to be robust for “functional genomics analysis” to provide in vivo evidence and investigate mechanisms and pathways underlying new associations emerging from GWAS, tumor genome resequencing and other genome-wide technologies that are currently under intense investigation in human cancers.
Citation Format: Shizhen Zhu, Andrew Wood, Shuning He, Rebecca Stanton, Feng Guo, John Maris, A. Thomas Look. Role of the LMO1 oncogene in neuroblastoma pathogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 356. doi:10.1158/1538-7445.AM2013-356
Abstract 3568: Induction of aberrant breast acinar morphogenesis by deregulation of an estrogen receptor alpha circadian circuit.
Authors: Rossetti Stefano , Corlazzoli Francesca , Gregorski Alex , Sacchi Nicoletta 
Published: August 2014

Abstract
Altered estrogen receptor alpha (ERA) signaling and altered circadian rhythms are both features of breast cancer. ERA mRNA oscillates in a circadian fashion in ERA-positive breast epithelial cells, but not in ERA-positive breast cancer cells (Rossetti et al., 2012a). Interestingly, we identified a circuit consisting of ERA and an estrogen-regulated loop consisting of PER2 and BMAL1, two circadian clock genes, in entrained ERA-positive breast epithelial cells. This estrogen-regulated circuit is apparently necessary for breast epithelial acinar morphogenesis, and its disruption by ERA knock down negatively affects both the estrogen-sustained circadian PER2-BMAL1mechanism and the formation of acini in three-dimensional (3D) culture on basement membrane. Conversely, knock down of either PER2 or BMAL1, by hampering the PER2-BMAL1 loop of the circadian clock, negatively affects both ERA circadian oscillations and 3D breast acinar morphogenesis (Rossetti et al., 2012b). This is the first evidence that a circuit comprising ERA and key circadian clock components is implicated in the acinar developmental processes of breast epithelial cells.
Acknowledgments: this work was supported by the Department of Defense (DOD) Concept Award W81XWH0610657 (NS), the Breast Cancer Coalition of Rochester (NS), and the Friends for an Earlier Test for Breast Cancer Foundation (NS).
Rossetti, S, Esposito, J, Corlazzoli, F, Gregorski, A, and Sacchi, N. (2012a). Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes. Cell Cycle 11, 350-360.
Rossetti, S, Corlazzoli, F, Gregorski, A, Azmi, NH, and Sacchi, N. (2012b). Identification of an estrogen-regulated circadian mechanism necessary for breast acinar morphogenesis. Cell Cycle 11, 3691-3700.
Citation Format: Stefano Rossetti, Francesca Corlazzoli, Alex Gregorski, Nicoletta Sacchi. Induction of aberrant breast acinar morphogenesis by deregulation of an estrogen receptor alpha circadian circuit. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3568. doi:10.1158/1538-7445.AM2013-3568
Abstract 3594: Mutations and DNA adducts induced by diesel exhaust particles.
Authors: Ross Jeffrey A. , Mutlu Esra , King Charly , Warren Sarah H. , DeMarini David M. , Gilmour M. Ian , Linak William P. , Nelson Garret B. 
Published: August 2014

Abstract
We performed bioassay-directed fractionation and analyzed the polycyclic aromatic hydrocarbon (PAH) levels of a composite sample of diesel-exhaust particles (C-DEP) generated on site from petroleum diesel with a 30-kW 4-cylinder Deutz BF4M1008 diesel engine connected to an air compressor. C-DEP was generated to be representative of contemporary DEP. We extracted particles with dichloromethane (DCM) and determined the percentage of extractable organic material (EOM), solvent-exchanged extracts into dimethyl sulfoxide, and evaluated them for mutagenicity in Salmonella strains TA100 and TA98 +/- S9. More than 50% of the C-DEP EOM mass eluted in fraction 1, but this fraction was not mutagenic. Fraction 2 contained 6% of the mass of OEM, and had 60% of the TA100+S9 activity, suggestive of PAHs. The 3rd fraction contained 14% of the OEM mass and contributed 60% of the TA98-S9 activity, suggestive of nitroarenes. S9 mediated binding of C-DEP extracts was assessed by 32P-postlabeling analysis. Unfractionated C-DEP EOM was incubated with S9 in the presence of calf thymus DNA. The modified DNA was enzymatically hydrolyzed and then subjected to postlabeling analysis using either butanol extraction or nuclease P1 pre-enrichment. Multiple DNA adducts were produced with chromatographic mobilities consistent with PAH and nitro-PAH adducts. Although previous studies of the mutagenicity and adduct-forming potential of diesel exhaust have been reported, most of those utilized exhaust particles that were generated by older diesel engines that were not representative of contemporary diesel exhaust. Data derived from the C-DEP particles are more relevant to understanding the risks posed by contemporary diesel engines. This study provides further characterization of the biochemical potential for these particles to induce DNA damage and gene mutations, key events in the process of chemical carcinogenesis by diesel exhausts. [This is an abstract of a proposed presentation and does not necessarily reflect the views of the U.S. EPA.]
Citation Format: Jeffrey A. Ross, Esra Mutlu, Charly King, Sarah H. Warren, David M. DeMarini, M. Ian Gilmour, William P. Linak, Garret B. Nelson. Mutations and DNA adducts induced by diesel exhaust particles. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3594. doi:10.1158/1538-7445.AM2013-3594
Abstract 3608: The effect of tobacco on prostate cancer cell aggressiveness.
Authors: Bodmer Natalie , Gokuldass Aishwarya , Kucynda Theresa , Macias Virgilia , Munirathinam Gnasekar , Kajdacsy-Balla Andre 
Published: August 2014

Abstract
Studies have shown that smoking is associated with both greater incidence and worse outcomes of prostate cancer. The mechanism involved in this adverse effect of cigarette smoke on prostate cancer cells is not known. We hypothesized that cigarette smoke condensate (CSC) would have an effect on in vitro cell proliferation and motility. CSC is the tar phase of smoke particulate. We submitted PC-3 cells for proliferation assays after 4 and 24 hours exposure to varying concentrations of CSC. We also performed motility assays and probed for epithelial to mesenchymal transition (EMT) using immunohistochemistry on cells exposed to CSC to investigate how the action of cigarette smoke induces more aggressive behavior in cells. Results showed that CSC caused up to 83% increase in cell proliferation depending on dose and time of exposure. The antioxidant Ebselen, a scavenger of H2O2 and hydroperoxides, decreased but did not abrogate the proliferation caused by CSC. There was no effect of CSC on cell motility in Boyden chamber assays. There was also no effect of CSC on EMT, which was demonstrated by testing the immunohistochemical expression of vimentin, E-cadherin, and beta-catenin after cell exposure to CSC. In conclusion, CSC increases cell proliferation, but has no effect on motility. This action of CSC is at least in part mediated by H2O2, as shown by Ebselen inhibition of cell proliferation. The increase in proliferation could in part explain the worse prognosis of patients who smoke.
Citation Format: Natalie Bodmer, Aishwarya Gokuldass, Theresa Kucynda, Virgilia Macias, Gnasekar Munirathinam, Andre Kajdacsy-Balla. The effect of tobacco on prostate cancer cell aggressiveness. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3608. doi:10.1158/1538-7445.AM2013-3608
Abstract 3696: Resveratrol inhibits oxidative stress and prevents estrogen-induced breast carcinogenesis via activation of NRF2-mediated protective pathways.
Authors: Singh Bhupendra , Ronghe Amruta , Chatterjee Anwesha , Bhat Hari K. 
Published: August 2014

Abstract
The importance of estrogens in the etiology of breast cancer is widely recognized. Estrogen-induced oxidative stress has been implicated in this carcinogenic process. Resveratrol, a natural antioxidant phytoestrogen has chemopreventive effects against a variety of illnesses including cancer. The objective of the present study was to characterize the mechanism of resveratrol-mediated protection against estrogen-induced breast carcinogenesis. Female ACI rats were treated with 17β-estradiol (E2), resveratrol, and resveratrol + E2 for 8 months. Co-treatment of rats with resveratrol + E2 significantly increased tumor latency and reduced E2-induced breast tumor development. Resveratrol treatment upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression and inhibited E2-mediated changes in activities of antioxidant enzymes in the mammary tissues. Resveratrol upregulated NRF2-regulated antioxidant genes NQO1, SOD3, and OGG1 a gene involved in protection against oxidative DNA damage. Resveratrol also prevented E2-mediated inhibition of detoxification genes flavin monooxygenase 1, aldehyde oxidase 1 and monoamine oxidase b1. Resveratrol treatment upregulated NRF2 expression by inhibiting E2-mediated alterations in NRF2 promoter methylation pattern and by reverting E2-mediated increased expression of NRF2 targeting micoRNA miR-93. Resveratrol treatment induced apoptosis and inhibited E2-mediated increase in 8-OHdG levels, a marker of oxidative DNA damage. Decreased colony formation, mammosphere formation and cell migration in resveratrol-treated MCF-10A cells further suggest protective role of resveratrol against E2-induced mammary carcinogenesis. Taken together, these results suggest that resveratrol inhibits E2-induced breast carcinogenesis through inhibition of oxidative stress and activation of NRF2-mediated protective pathways.
Citation Format: Bhupendra Singh, Amruta Ronghe, Anwesha Chatterjee, Hari K. Bhat. Resveratrol inhibits oxidative stress and prevents estrogen-induced breast carcinogenesis via activation of NRF2-mediated protective pathways. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3696. doi:10.1158/1538-7445.AM2013-3696
Abstract 3700: Prepubertal dietary genistein intake reduces ovarian cancer risk in BRCA+/- mice.
Authors: Carney E , Hilakivi-Clarke L. , Warri A. , de Assis S. 
Published: August 2014

Abstract
Genistein, a soy-derived isoflavone, is thought to play a key role in the cancer-preventive activity of soy consumption. Germline mutations in BRCA1 and BRCA2 genes are known risk factors for both ovarian and breast cancers. Previously, our lab has discovered that prepubertal dietary exposure to genistein reduced 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary incidence (P = 0.029) and aggressiveness of the tumors (P &lt; 0.001) in the WT mice, and upregulated the expression of BRCA1 in their mammary glands (P = 0.04). In this study, we investigated whether prepubertal dietary exposure to genistein reduces ovarian tumors in heterozygous BRCA+/- mice and their wild type littermates. Mice were fed a control diet AIN93G or 500 ppm genistein-supplemented diet from postnatal day (PND) 15 to PND 30, and thereafter mice received the control AIN93G diet. On PND42, control and genistein mice were primed with medroxyprogesterone acetate and, starting at PND50, administered 7,12-dimethylbenz(a)anthracene (DMBA) once a week for four weeks. Ovarian tissues were harvested at 5 months of age. Histopathology assessment shows that mice developed granulosa cell tumors. Ovarian tumor incidence in control diet fed wildtype mice was 80% and in the BRCA+/- mice 100%. The incidence dropped to 33% in the wildtype and to 50% in the BRCA+/- mice following prepubertal genistein intake. Thus, the exposure to prepubertal genistein in both BRCA+/- and WT mice significantly reduced ovarian tumor incidence, compared with their control diet fed littermates (P=0.001). The mechanisms mediating the protective effect of prepubertal genistein intake on ovarian cancer risk are being investigated.
Citation Format: E Carney, L. Hilakivi-Clarke, A. Warri, S. de Assis. Prepubertal dietary genistein intake reduces ovarian cancer risk in BRCA+/- mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3700. doi:10.1158/1538-7445.AM2013-3700
Abstract 3736: IL6 feedback loop regulates breast cancer stem cells which mediate trastuzumab resistance.
Authors: Davis April L. , Korkaya Hasan , Ouzounova Maria , Malik Fayaz , Kim Gwangil , Quraishi Ahmed A. , Liu Suling , Clouthier Shawn G. , Wicha Max S. 
Published: August 2014

Abstract
The development of HER2 targeting agents such as trastuzumab and lapatinib represents one of the greatest achievements in clinical oncology demonstrating the effectiveness of molecularly targeted therapeutics (2). Despite the clinical benefits of trastuzumab in improving progression free and overall survival, majority of patients demonstrate “intrinsic” resistance or develop “acquired” resistance within one-to-two years.
Although inactivation of the PTEN gene has been implicated in the development of resistance to the HER2 targeting antibody trastuzumab, the mechanisms mediating this resistance remain to be investigated. We generated trastuzumab resistant cells by knocking down PTEN expression in HER2 overexpressing breast cancer cell lines and demonstrated that development of trastuzumab resistance in these cells is mediated by activation of an IL6 inflammatory feedback loop leading to expansion of breast cancer stem cell (CSC) population. We and others previously demonstrated that cytokines including IL6 and IL8 regulates breast cancer stem cell self-renewal. Furthermore, elevated serum levels of these cytokines in breast cancer patients strongly correlated with metastatic disease and therapeutic resistance. We therefore hypothesized that activation of IL6 feedback loop may mediate trastuzumab resistance. Utilizing these models, we demonstrated that long term trastuzumab treatment generates highly enriched CSCs which display an EMT phenotype secreting over 100-fold more IL6 than parental cells. Recombinant IL6 or conditioned medium from high-IL6 secreting cells resulted in trastuzumab resistance in parental PTEN wild type cells expanding CSCs with EMT phenotype characterized by the CD44+/CD24- expression and EMT gene signature.
An IL6 receptor antibody interrupted this inflammatory feedback loop reducing the cancer stem cell population resulting in decreased tumor growth and metastasis in mouse xenographs. These studies have important clinical implications demonstrating that trastuzumab resistance may be mediated by an IL-6 inflammatory loop and suggest that blocking this loop represents a novel strategy to overcome trastuzumab resistance.
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Citation Format: April L. Davis, Hasan Korkaya, Maria Ouzounova, Fayaz Malik, Gwangil Kim, Ahmed A. Quraishi, Suling Liu, Shawn G. Clouthier, Max S. Wicha. IL6 feedback loop regulates breast cancer stem cells which mediate trastuzumab resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3736. doi:10.1158/1538-7445.AM2013-3736