bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4864: Aroma terpenes prevent UVB-induced sunburn in Skh1 mouse skin.
Authors: Uddin Ahmed N. , Labuda Ivica , Wu Feng , Tchou-Wong KamMeng , Burns Fredric J. 
Published: August 2014

Abstract
Understanding how aroma terpenes prevent sunburn and/or skin cancer in mice could lead to more effective and safer ways of blocking sun damage to human skin. In our previous study, β-damascenone, an aroma terpene, protected against sunburn by activating both keratinocyte and sebaceous gland pathways that fortified and thickened the cornified envelope and sebum layers of mouse epidermis. In the current study, the sunburn preventive activity of d-limonene was examined to confirm that these related compounds work similarly. In addition to sunburn, immunohistochemical analyses of proliferation (PCNA) and a damage-response gene N-Myc Down Regulated Gene 1 (NDRG1) were investigated in control versus d-limonene-treated Skh-1 mice. The mice were treated either topically on the dorsum or orally with different concentrations of d-limonene in liponate (100%, 10%, 1% and 0%) followed by exposure of the dorsum to solar simulation ultraviolet radiation (UVR) of 1.5 kJ/m2 from fluorescent ‘sunlamps’. Either 4 topical 5 μL doses or a single dose of 20 μL (0.95 μg/g body weight) of 100% d-limonene provided complete protection from UVR-induced sunburn. The protection was less but still significant at 10% d-limonene but was absent at 1% d-limonene in comparison to UVR alone. PCNA-labeling showed a marked proliferation increase of epidermal basal cells, outer root sheath cells of hair follicles and sebaceous gland cells by separate exposures to d-limonene and UVR relative to controls. The combined treatment of d-limonene followed by UVR produced fewer PCNA-positive cells in epithelial tissue relative to UVR-only mice. The NDRG1 protein (an indirect measure of DNA damage) was overwhelmingly (∼85% of keratinocytes) induced by UVR indicating heavy DNA damage. The UVR-induced NDRG1 index remained at ∼85% at 1% d -limonene, but was significantly reduced at 10% d-limonene to ∼24% and to less than 1% at 100% d -limonene indicating nearly complete elimination of cellular damage as a pure compound; a finding that is consistent with complete sunburn prevention. The thickness of the cornified envelope plus sebum layers nearly doubled within 5 days after administration of the d-limonene corresponding to the time of UVR application. Overall the results indicate that d-limonene protected against sunburn by activating keratinocyte/sebaceous gland-based pathways that fortified and thickened the cornified envelope plus sebum layers on the skin surface by releasing elevated levels of UVR-absorbing proteins that decreased UVR dose to underlying cutaneous tissues.
Citation Format: Ahmed N. Uddin, Ivica Labuda, Feng Wu, KamMeng Tchou-Wong, Fredric J. Burns. Aroma terpenes prevent UVB-induced sunburn in Skh1 mouse skin. [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 4864. doi:10.1158/1538-7445.AM2013-4864
Abstract 4867: The metabolomic signature of Rhodiola rosea L. extracts- (SHR-5) treated mouse bladder cancer in the UPII-mutant Ha-ras transgenic model.
Authors: Liu Zhongbo , Blair Christopher A. , Zi Xiaolin 
Published: August 2014

Abstract
Rhodiola rosea has been used for centuries in the traditional medicine for reducing depression, enhancing work performance, and preventing high altitude sickness. We have recently shown that Rhodiola rosea L. extract, SHR-5, markedly inhibited the growth of bladder cancer and the survival of mice in the UP-II-mutant Ha-ras transgenic model via inhibition of the mTOR pathway. The purpose of this study was to further investigate the effects of SHR-5 on bladder tumor metabolism. The global metabolic profiles were compared for bladder tumors from mice that were fed with normal drinking water (n=7), 1.25 (n=7) or 6.25 (n=7) mg/ml SHR-5 in water for about five months. The analysis was conducted at Metabolon Inc. with a combination of high-throughput LC- and GC-based MS method. From a metabolomics library consisting of more than 2,000 standards, a total of 341 named metabolites were detected. Phenolic metabolites, such as phenylpropionylglycine, hydroxycinnamate and catechol sulfate, were increased, while prostaglandin metabolites, such as prostaglandins A2, D2 and E2, were decreased in tumors treated with SHR-5. This observation suggested the potential anti-inflammation effect of SHR-5 in bladder tumors. Neurotransmitters GABA, taurine, NAA and 2-oxoindole-3-acetate was more abundant; whereas kynurenine, histamine and aminoadipate were less abundant with SHR-5 treatment. This result is consistent with mood-improving effects of SHR-5. In addition, SHR-5 treatment resulted in increased levels of glucose and glycogen metabolites (e.g. maltotriose, maltose), as well as two glycolysis intermediates (3-phosphoglycerate and 2-phosphoglycerate) and the citric acid cycle (TCA) intermediates (fumarate and malate) compared to control treatment. These patterns suggest that SHR-5 may increase mobilization of glycogen for energy production in glycolysis and TCA cycle. These effects of SHR-5 may be mediated by differential effects on the mTOR pathway. Taken together, we show that global metabolomic profiling provides a unique and efficient tool for studying mechanisms of complex herb extracts’ action.
Citation Format: Zhongbo Liu, Christopher A. Blair, Xiaolin Zi. The metabolomic signature of Rhodiola rosea L. extracts- (SHR-5) treated mouse bladder cancer in the UPII-mutant Ha-ras transgenic model. [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 4867. doi:10.1158/1538-7445.AM2013-4867
Abstract 4873: Genistein and soy isoflavone isolate decreased tumor incidence and multiplicity in a Sprague-Dawley ER-positive breast cancer model.
Authors: Nicastro Holly L. , Lubet Ronald A. , Dunn Barbara K. , Grubbs Clinton J. 
Published: August 2014

Abstract
This study evaluated the chemopreventive efficacy of the pure soy isoflavone genistein and of a soy isoflavone mixture (PTI G-4660) containing roughly 90% genistein in an ER-positive breast cancer model in rats. Female Sprague Dawley rats were injected i.v. with N-nitroso-N -methylurea (MNU) at 50 days of age. In a model examining the effects on cancer initiation, promotion, and progression, rats were fed either a standard Teklad diet or a diet supplemented with genistein (200 or 2000 mg/kg diet) beginning at 43 d of age. Supplemented or standard diets were administered continuously thereafter until the end of the study. In a separate study testing the effects on progression, rats were administered standard Teklad diet or diet supplemented with PTI G-4660 (2000 mg/kg diet) beginning at 55 d of age. All rats were weighed weekly, palpated for mammary tumors twice per week, and checked daily for signs of toxicity. The studies were terminated 126 d after MNU treatment and tumors were weighed. After 126 days, genistein at 200 and 2000 mg/kg diet decreased tumor incidence in a dose-dependent fashion by 15 and 20% (p&lt;0.05), respectively, and significantly decreased tumor multiplicity by 49.6 and 60.3% (p&lt;0.05), respectively. PTI non-significantly decreased tumor incidence by 14% and tumor multiplicity by 24%. In addition, gene expression profiling of livers from rats treated with standard Teklad diet or genistein revealed pathways modified by genistein which may be useful as biomarkers.
Citation Format: Holly L. Nicastro, Ronald A. Lubet, Barbara K. Dunn, Clinton J. Grubbs. Genistein and soy isoflavone isolate decreased tumor incidence and multiplicity in a Sprague-Dawley ER-positive breast cancer model. [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 4873. doi:10.1158/1538-7445.AM2013-4873
Abstract 4874: Bisphenol A exposure negates tamoxifen-mediated chemoprevention in MMTV-erbB2 transgenic mice.
Authors: Yang XiaoHe , Ma Zhikun , Jiang Yunbo 
Published: August 2014

Abstract
Bisphenol A (BPA), the building block of polycarbonate plastics with estrogenic activity, is one of the most common chemicals people are exposed to in daily life. Increasing reports suggest a link between BPA exposure and increased breast cancer risk. Although the effect of early BPA exposure and breast cancer risk later in life has been extensively studied, whether this xenoestrogen interferes with hormonal therapeutic agents, such as tamoxifen, has hardly been documented. In this study, we tested the effect of BPA exposure on mammary tumor development and tamoxifen-mediated chemoprevention in MMTV-erbB2 transgenic mice. BPA (500 ng/kg in sesame oil) was administered daily by subcutaneous injection for 8 weeks, starting from 8 weeks of age. Citrate tamoxifen at a dose of 1 mg/kg/day was administered by oral gavage alone or in combination with BPA. Based on tumor latency, we found that BPA alone accelerated mammary tumor development whereas tamoxifen treatment profoundly delayed the tumorigenesis. A combination of tamoxifen-treatment and BPA exposure, however, significantly (p&lt;0.01) interfered with tamoxifen-mediated prevention as indicated by a shortened tumor latency compared to the tamoxifen group. BrdU incorporation and whole mount analysis of mammary glands at 16 weeks showed that BPA or tamoxifen alone induced distinctive proliferative and inhibitory ductal growth respectively. A combination of tamoxifen and BPA exposure abrogated tamoxifen-mediated growth inhibition. Importantly, altered tumor development and morphogenesis in each group were accompanied by modified signaling in estrogen receptor (ER) and EGFR/erbB2 pathways in mammary tissues. BPA alone induced enhanced phosphorylation/activation of ERα, the receptor tyrosine kinases (erbB2, EGFR and erbB3) and downstream targets (AKT1, and ERK½). Protein and mRNA levels of ERα, cyclin D1, EGFR, erbB3, and c-myc were also increased. In contrast, tamoxifen inhibited the activation of both pathways, as indicated by decreased phosphorylation and expression of those markers. In the combination group BPA exposure blocked tamoxifen-mediated inhibition of ER and erbB2 signaling. Our results demonstrated that BPA exposure promotes erbB2-associated carcinogenesis and negates tamoxifen-mediated chemoprevention. The underlying mechanisms involve BPA-induced activation and crosstalk of ER and erbB2 pathways. Taken together, our data suggests that BPA exposure is a risk factor that may interfere with hormonal therapy, which is of great translational value.
Citation Format: XiaoHe Yang, Zhikun Ma, Yunbo Jiang. Bisphenol A exposure negates tamoxifen-mediated chemoprevention in MMTV-erbB2 transgenic 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 4874. doi:10.1158/1538-7445.AM2013-4874
Abstract 4881: Influence of polyphenols on selenoprotein expression in human colon cancer cells.
Authors: Galinn Sarah E. , Rosenthal Lindsay C. , Barsotti Steven M. , Tsuji Petra A. 
Published: August 2014

Abstract
Selenium, an essential micronutrient, is recognized as a cancer protective agent that functions through low-molecular weight selenocompounds, and, importantly, through selenoproteins. Previous studies suggest that the 15 kDa selenoprotein (Sep15), a gene polymorphic in humans, has an important role in colon cancer in vivo, and that reduction of Sep15 in human HCT116 colon cancer cells reverses their cancer phenotype. Our diet contains a wide array of nutrients, and it is conceivable that these share molecular targets with selenium and regulate selenoprotein expression. The selenoproteins Thioredoxin Reductase 1 (TR1) and Glutathione Peroxidase (GPx) 2 are regulated by the transcription factor Nrf2, whereas GPx1 is not. Some dietary compounds, e.g., Sulforaphane, are known Nrf2-inducers, impacting expression of TR1 and GPx2. However, the effect of Sulforaphane and many polyphenols on other selenoproteins, or, how other polyphenols influence TR1 and GPx2 remains to be elucidated. Using HCT116 cells, we are investigating the effects of polyphenols and Sulforaphane on selenoprotein expression. Cells with wild type or down-regulated expression of Sep15 were exposed to 5 μM Sulforaphane or 20 μM 5,7-Dimethoxyflavone (5,7-DMF) for 48 hours. Subsequently, mRNA was isolated and examined with real-time RT-PCR. Our preliminary results suggest that, Sulforaphane exposure resulted in a slight increase of TR1 mRNA in both control and shSep15 cells, but not GPx2. Interestingly, 5,7-DMF exposure resulted in increased GPx1 (P&lt;0.01) and GPx2 (P&gt;0.05) mRNA in control cells. Surprisingly, GPx2 mRNA appeared significantly down-regulated (P&lt;0.01) in shSep15 cells compared to DMSO treated cells, whereas GPx1 mRNA appeared unaffected. Western blotting and activity measurements are currently underway to support these results.
Citation Format: Sarah E. Galinn, Lindsay C. Rosenthal, Steven M. Barsotti, Petra A. Tsuji. Influence of polyphenols on selenoprotein expression in human colon cancer cells. [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 4881. doi:10.1158/1538-7445.AM2013-4881
Abstract 4884: Involvement of autophagy in penta-1,2,3,4,6-O-galloyl-beta-D-glucose-induced senescence-like growth arrest in human cancer cells.
Authors: Dong Yinhui , Lü Junxuan , Hu Hongbo 
Published: August 2014

Abstract
Autophagy and senescence are two important cellular processes that have been shown to play critical roles in the regulation of carcinogenesis. Our previous studies have demonstrated that cellular features of both autophagy and senescence were induced in response to penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG), a polyphenolic anti-cancer compound, in multiple types of cancer cells. In this follow-up study, we further investigated the cross-talk among these PGG-induced phenotypes and signal transduction mechanisms. In cell culture models, we show that inhibition of autophagy by either chemical inhibitors or genetic approaches (RNA interference) led to a near abolishment of PGG-induced senescence, followed by induction of apoptosis, indicating autophagy is required for the senescent phenotype induced by PGG and antagonistic of apoptosis execution. In addition, we identify unfolded protein responses (UPR) in the endoplasmic reticulum (ER) to play a pivotal role in autophagy-mediated senescence phenotype. Furthermore, our data show that c-Jun NH(2)-terminal kinase (JNK) could be a critical mediator for PGG-induced autophagy. In a subcutaneous xenograft mouse model of human HepG2 liver cancer, we detected biochemical markers of modulations of autophagy, ER stress and senescence induced by PGG intra-peritoneal administration for 16 days. Our findings provided novel insights into cellular processes and signaling mechanisms involved in PGG-induced senescence-like growth arrest in human cancer cells.
Citation Format: Yinhui Dong, Junxuan Lü, Hongbo Hu. Involvement of autophagy in penta-1,2,3,4,6-O-galloyl-beta-D-glucose-induced senescence-like growth arrest in human cancer cells. [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 4884. doi:10.1158/1538-7445.AM2013-4884
Abstract 4887: FTY720 prevent tumorigenesis and suppress the progression of colitis-associated cancer.
Authors: Yamada Akimitsu , Liang Jie , Nagahashi Masayuki , Kim Eugene Y. , Harikumar Kuzhuvelil B. , Huang Wei-Ching , Hait Nitai C. , Allegood Jeremy C. , Price Megan M. , Avni Dorit , Kordula Tomasz , Sheldon Milstien , Takabe Kazuaki , Spiegel Sarah 
Published: August 2014

Abstract
Inflammatory bowel disease is an important risk factor for colorectal cancer. Sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite formed by two sphingosine kinases, SphK1 and SphK2, is involved in inflammation and cancer. Enhanced tumor number and size, with a concomitant increase in tumor load was observed in mice overexpressing SphK1 treated with the colonotropic mutagen azoxymethane (AOM) followed by three rounds of oral administration of the luminal toxin dextran sodium sulfate (DSS) to induce colitis-associated cancer (CAC). There was also a large increase in adenomas with a high grade of dysplasia associated with increased SphK1 expression and formation of S1P. We demonstrated that the SphK1/S1P axis is important for production of IL-6 and is involved in persistent activation of STAT3 and consequent upregulation of one of its target genes, the S1P receptor S1PR1. Because the pro-drug FTY720 modulates the immune system by acting as a functional antagonist of S1PR1, inducing its internalization and degradation, we examined its effect on CAC progression. FTY720 drastically reduced colitis-associated tumorigenesis, when it was administered during CAC induction. Remarkably, FTY720 blocked CAC progression even when it was administered later after the last DSS treatment when tumors were already established. Moreover, it reduced SphK1 expression, production of IL-6, and persistent activation of STAT3. These findings suggest that FTY720 may be beneficial for preventing tumor formation in individuals with inflammatory bowel disease.
This work was supported by grants from the National Institute of Health (R37GM043880, R01CA61774, U19AI077435 to S.S. and R01CA160688 to K.T.). M.N. is a Japan Society for the Promotion of Science Postdoctoral Fellow.
Citation Format: Akimitsu Yamada, Jie Liang, Masayuki Nagahashi, Eugene Y. Kim, Kuzhuvelil B. Harikumar, Wei-Ching Huang, Nitai C. Hait, Jeremy C. Allegood, Megan M. Price, Dorit Avni, Tomasz Kordula, Milstien Sheldon, Kazuaki Takabe, Sarah Spiegel. FTY720 prevent tumorigenesis and suppress the progression of colitis-associated cancer. [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 4887. doi:10.1158/1538-7445.AM2013-4887
Abstract 4888: Axl receptor signaling in required for stem cell traits and metastasis in breast cancer.
Authors: Tiron Crina , Pelissier Fanny , Wnuk-Lipinska Katarzyna , Stefansson Ingunn , Virtakoivu Reeta , Miyano Masaru , Sandal Tone , Micklem David , Garbe James , Stampfer Martha , Ivaska Johanna , Akslen Lars , LaBarge Mark , Lorens James 
Published: August 2014

Abstract
Epithelial-to-mesenchymal transition (EMT) endows carcinoma cells with migratory, survival and stem cell-like attributes that facilitate therapeutic resistance and metastasis. Expression of the Axl receptor tyrosine kinase in aggressive breast cancer correlates with EMT, poor survival and is prevalent in patient metastases. Induction of EMT in immortalized mammary epithelial cells by EMT-transcription factors, TGFbeta or hypoxia upregulates Axl and establishes an autocrine-signaling loop with its ligand, Gas6. Axl receptor signaling is required to maintain EMT-related invasive, drug resistance and cancer stem cell (CSC) traits of malignant breast cancer cells. Targeting Axl signaling with RNAi or pharmacological agents blocks the EMT/CSC gene program and inhibits malignant functions including invasiveness, drug resistance, mammosphere formation, in vivo tumor initiation, and spontaneous metastasis in orthotopic breast cancer models. These results suggest that Axl expression is requisite for the maintenance of EMT and stem cell-like traits during malignant progression. The EMT program is characteristic of normal adult mammary epithelial stem/progenitor cells. Congruently, we show that the Axl receptor expressed on mammary epithelial stem/progenitor cells, and Axl signaling is necessary for mammary epithelial multipotent progenitor activity. Thus Axl receptor signaling represents a novel regulatory pathway linking normal mammary stem/progenitor cells and breast cancer stem cells. Hence, clinical Axl inhibitors represent a novel therapeutic avenue to target EMT/CSC traits of aggressive breast cancer.
Citation Format: Crina Tiron, Fanny Pelissier, Katarzyna Wnuk-Lipinska, Ingunn Stefansson, Reeta Virtakoivu, Masaru Miyano, Tone Sandal, David Micklem, James Garbe, Martha Stampfer, Johanna Ivaska, Lars Akslen, Mark LaBarge, James Lorens. Axl receptor signaling in required for stem cell traits and metastasis in breast cancer. [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 4888. doi:10.1158/1538-7445.AM2013-4888
Abstract 4890: Periostin signaling regulates breast cancer stem cells.
Authors: Lambert Arthur W. , Ozturk Sait , Papageorgis Panos , Abdolmaleky Hamid , Thiagalingam Sam 
Published: August 2014

Abstract
Recent evidence suggests that the molecular heterogeneity inherent to breast cancer, which underlies metastasis, resistance to treatment and disease recurrence, can be driven by a distinct subpopulation of tumor cells referred to as cancer stem cells (CSCs). However, the extracellular cues and intracellular pathways that CSCs rely on remain unclear. Working with a breast cancer progression model system we found the invasive breast cancer cell line to exhibit numerous stem-like characteristics. Gene expression profiling, along with a careful review of the literature, identified a secreted extracellular matrix molecule, periostin (POSTN), which we hypothesized to be required for the maintenance of a cancer stem cell state. POSTN expression was increased in numerous basal-like breast cancer cell lines that contain an expanded CSC population, as well as in cells grown as mammospheres and in the CD44+/CD24- fraction of tumor cells. Furthermore, CSC-like lines displayed increased surface levels of the alpha-v beta-3 integrin heterodimer, a known receptor for POSTN, suggesting that hyperactivation of a POSTN signaling axis could potentially regulate the CSC state. Using stable cell lines expressing an shRNA directed at POSTN we have found that POSTN is required for efficient mammosphere formation and for the maintenance of an ALDH-positive CSC population. In line with this, we found these cells had impaired Erk and Wnt signaling and expressed less IL-6 and IL-8, known regulators of CSCs. Furthermore, high POSTN expression correlates with a worse clinical prognosis in basal-like breast cancer patients. Therefore, we suggest that POSTN signaling through integrin receptors may enrich for highly tumorigenic breast CSCs in a subset of basal-like tumors, leading to aggressive and recurrent malignancies. More broadly, our results imply that a supportive tumor niche can be established and maintained by cancer cells, and raises the possibility of targeting components of this extracellular environment to eradicate breast CSCs.
Citation Format: Arthur W. Lambert, Sait Ozturk, Panos Papageorgis, Hamid Abdolmaleky, Sam Thiagalingam. Periostin signaling regulates breast cancer stem cells. [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 4890. doi:10.1158/1538-7445.AM2013-4890