bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5656: Role for Sphingosine kinase 1 in head & neck cancer
Authors: Shirai Keisuke , Furuya Hideki , Wada Masayuki , Bielawski Jacek , Ogretmen Besim , Hannun Yusuf A. , Obeid Lina M. , Kawamori Toshihiko 
Published: February 2011

Abstract
Novel and effective targets for cancer therapy and prevention are increasingly important in cancer research, especially for head and neck squamous cell carcinoma (HNSCC), which is one of the most lethal cancers. A potential target for this type of cancer might be sphingosine kinase 1 (SphK1) which phosphorylates sphingosine to form sphingosine-1-phosphate (S1P) because it is a critical regulator of sphingolipid-mediated functions and the SphK1/S1P pathway has been implicated in several important biological functions including inflammation and carcinogenesis. To investigate the potential of SphK1 as a target in head and neck cancer development, we used a 4-nitroquinoline-1-oxide (4-NQO)-induced carcinogenesis tongue model in SphK1 knockout mice. All mice were treated with 4-NQO at 40 μg/ml in drinking water for 14 weeks (untreated water was available thereafter, until the end of the experiment). All animals were sacrificed at 20 weeks and animal tongues were examined. We found that SphK1 positively stained in tongue cancer induced by 4-NQO in wild type mice, and 72% SphK1 KO mice developed tongue cancer, whereas 96% of the wild type mice did (P&lt;0.05). Furthermore, tongue cancer volume was significantly decreased in SphK1 KO mice (P&lt;0.05). To understand how SphK1 is responsible for decreasing tongue cancer, we used a BrdU incorporation assay to evaluate cell proliferation and used a cleaved caspase-3 immunohistochemistry assay to indicate apoptosis in tongue cancer tissues. We found that tongue cancers in SphK1 KO mice had significantly less cell proliferation and increased apoptosis compared to in wild type mice (P&lt;0.01 and P&lt;0.001, respectively). Assaying for sphingolipid profiles in mouse blood, we found that S1P was significantly reduced in SphK1 KO mice (P&lt;0.001), and that C16-ceramide was also significantly reduced in SphK1 KO mice compared to wild type mice (P&lt;0.05). These data are consistent with our previous results (Cancer Lett., 256: 101-111, 2007). We also found that 4-NQO-activated phospho-Akt was reduced in tongue cancers in SphK1 KO mice, suggesting that the SphK1/S1P pathway may be involved in PI3K-Akt-mTOR pathway in HNSCC development. Our data suggest that the SphK1/S1P pathway may mediate HNSCC development and that inhibition of this pathway may be an effective and novel target for chemoprevention against HNSCC.
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 5656.
Abstract 5666: Nrf2-mediated induction of phase 2 detoxifying enzymes by an active compound isolated from Chrysanthemum zawadskii
Authors: Seo Jiyeon , Lim Ji Sun , Park Jia , Nam Dae Hwan , Garcia Annalene , Kim Hyo Jung , Lim Soon Sung , Lee Choong Hwan , Park Jung Han Yoon , Kim Jong-Sang 
Published: February 2011

Abstract
Previous study demonstrated that methanolic extract of Chrysanthemum has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR). In this study we further fractionated methanolic extract of Chrysanthemum and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction shown the highest NQO1-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro[4,5]decane (CZ-5) which increased NQO1 enzyme activity in a dose-dependent manner. And the compound (CZ-5), like most phase 2 enzyme inducers, caused a increasing expression pattern of phase 2 detoxifying enzymes in a dose-dependent manner in mouse hepatoma Hepa1c1c7 and BPRc1 cells. Moreover, CZ-5 caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induce antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. CZ-5 also stimulated nuclear accumulation of Nrf2 as evaluated by western blot analysis. In conclusion, our data showed that CZ-5 acted as a potent phase 2 detoxifying enzyme inducer by stimulating the nuclear accumulation of Nrf2 and had potential as chemopreventive agent
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5666.
Abstract 5676: Farnesoid X receptor-mediated carcinogenic effects of bile acid in esophageal cancer: A potential chemoprevention target
Authors: Guan Baoxiang , Xu Xiaochun 
Published: February 2011

Abstract
OBJECTIVES: The incidence of esophageal adenocarcinoma is increasing in the United States. Frequent gastroesophageal reflux or gastroesophageal reflux disease, resulting in Barrett esophagus, may be responsible for the increase. In the present study, we determined the carcinogenic effects of bile acid in esophageal cancer and then explored the use of the farnesoid X receptor (FXR) inhibitor guggulsterone to control tumor cell viability and gene expression. METHODS: Cell culture, Western blot, RT-PCR, gene transfection, and immunohistochemistry assays were used. RESULTS: We found that bile acid inhibited RAR-β2 and RRIG1 but induced COX-2 expression in a dose- and time-dependent manner and that FXR, the bile acid receptor, was responsible. Furthermore, bile acid also induced FXR expression in esophageal cancer cell lines. Knockdown of FXR expression using FXR shRNA antagonized the effects of bile acid in gene expression. We then demonstrated that guggulsterone treatment was able to reduce the viability of esophageal cancer cells and induce RAR-β2 and RRIG1 expression but suppress COX-2 and MMP-9 expression. In addition, ex vivo data demonstrated that FXR was highly expressed in both esophageal squamous cell carcinoma (71%) and adenocarcinoma (81%) tissues and was associated with reduced RAR-β2 and RRIG1 expression. CONCLUSIONS: Suppression of FXR activity using FXR shRNA or its inhibitor guggulsterone was able to antagonize bile acid in regulating gene expression and cancer viability.
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 5676.
Abstract 5678: Kavalactone yangonin induces autophagy, inhibits TSC-mediated translation initiation and acts synergistically with a kava chalcone flavokawain A on growth inhibition in bladder cancer UMUC-3 cells
Authors: Liu Zhongbo , Li Xuesen , Simoneau Anna , Zi Xiaolin 
Published: February 2011

Abstract
Autophagy is a tightly regulated lysosomal self-digestion process that has been shown to suppress primary tumor formation. However, the mechanisms and potential usefulness of autophagy induction in cancer prevention remain controversial and largely unknown. To facilitate the study of the potential of autophagy induction as a mechanism for bladder cancer prevention, we have established a bladder cancer cell line with a stably over-expressed EGFP-LC3 gene (a hallmark gene for autophagy). Using this cell line, we screened out kavalactones yangonin and dehydrokawain as strong autophagy inducers in bladder cancer cells, but not the previously defined apoptosis inducers flavokawains also found in kava root extracts. Yangonin treatment at concentrations of 1.25 to 50 μg/ml for eight hours significantly increases the percentage of EGFP-LC3 cells with punctuate EGFP-LC3 fluorescence up to 80%. The induction of autophagy by yangonin treatment was further confirmed by electron microscopy observation of increased autolysosome formation and by western blotting analysis of LC3-II cleavage. The effect of yangonin on autophagy induction corresponds to its anchorage-dependent and independent growth inhibitory effect in a dose and time dependent manner in UM-UC-3 cells. Similarly, yangonin also induces autophagy and inhibits cell growth in another bladder cancer cell line T24. Further study demonstrated that yangonin is less effective in reducing the cell viability of the primary mouse embryo fibroblasts tuberous sclerosis-1 knockout (MEF TSC1−/−) than that of wild-type cells (MEF TSC1+/+) cells. This result suggested that TSC1 may be, at least in part, required for the growth inhibitory effect of yangonin. Immunoprecipitation experiments showed an increased formation of the TSC1/TSC2 immunocomplex after yangonin treatment in UMUC-3 cells. In addition, yangonin treatment of UMUC-3 cells resulted in a decrease in phosphorylation of mTOR and 4E-BP1 with subsequent increased binding of 4E-BP1 to m7GTP, which is responsible for stoppage of translational initiation. Interestingly, yangonin in combination with flavokawain A, an apoptosis inducer, synergistically inhibits the growth of UMUC-3 cells. Taken together, our results may suggest a novel strategy for bladder cancer chemoprevention through combination of autophagy and apoptosis inducers, yangonin and flavokawain A.
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 5678.
Abstract 5682: Tanshinones in Salvia miltiorrhiza as potential chemopreventive agents against lung cancer
Authors: Li Yanli , Gong Yi , Li Linglin , Zhou Jin-Rong 
Published: February 2011

Abstract
The search for effective regimens with minimal adverse effects for the prevention and treatment of lung cancer remains the top priority research to eradicate this devastating disease. Several essential components determine the opportunity of success in identifying the candidate compounds, which include enhanced tissue levels, preferably in lungs after administration, safety use profiles, and more importantly preclinical evidence that is derived from clinically relevant in vivo systems. A Chinese herb medicine Salvia miltiorrhiza (Danshen) has been widely used for centuries for treatment of cardiovascular diseases without reported side effects to healthy humans. After oral administration, tanshinones are preferably accumulated at the highest levels in lungs. Several Danshen compounds, such as tanshinone IIA (T2A), tanshinone I (T1) and cryptotanshinone (CT), have also been reported to have potent activities in vitro against several cancer types including lung cancer. These promising findings strongly support that tanshinones may have potent anti-cancer, especially anti-lung cancer activities. The long-term goal of this research is to develop tanshinones as effective and safe agents for the prevention and treatment of lung cancer. We first evaluated the effects of tanshinones on the growth inhibition of lung cancer cell lines in vitro. All three tanshinones showed dose-dependent inhibition to the growth of human (H1299, H23, and A549) and murine (LLC) lung cancer cell lines at low μM ranges with T1 the most potent. Interestingly, LLC, which is usually resistant to drug treatment, was the most sensitive cell line to T1 treatment (IC50 at 3μM), but it was insensitive to T2A treatment. Cell cycle analysis showed that CT and T1 arrested cells (H1299) at S phase, whereas T2A arrested cells at G2/M phase. The growth inhibition and cell cycle arrest activities of tanshinones were associated with downregulation of cdc2 and Aurora A expression. Because T1 showed the most potent activity, we are evaluating its effect on the growth inhibition of lung tumors in mice and on the modulation of cellular and molecular markers. It is expected that the studies will provide experimental evidence to support the chemopreventive and/or therapeutic activities of tanshinones against lung cancer.
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 5682.
Abstract 5683: The dietary anti-estrogenic agent 3,3′-diindolylmethane inhibits metastatic propensity in thyroid cancer cells
Authors: Rajoria Shilpi , George Andrea , Shanmugam Arulkumaran , Megwalu Uchechukwu , Schantz Stimson P. , Geliebter Jan , Tiwari Raj K. , Suriano Robert 
Published: February 2011

Abstract
The incidences of thyroid proliferative diseases (TPD) including thyroid cancer and goiter are ever increasing with thyroid cancer being the most common among endocrine cancers. Recent statistics reveal 37,000 new cases diagnosed in US alone in 2008 and worldwide almost 27 million patients are affected. Diet has always been of prime importance in its association with cancer development and prevention. Several studies have found inverse association of cancer risk with consumption of dietary products, such as tomatoes, soy and cruciferous vegetables. We have been studying the effect of DIM (3,3′-diindolylmethane), a chemopreventive agent against hormone responsive cancers. In this study we show that thyroid cells express functional estrogen receptor (ER) -α and ER-β and DIM has anti-cancer effects on estrogen responsive thyroid cancer cells. Interestingly, we found that DIM does not affect the levels of ER but it does target metastatic phenotype of thyroid cells as evidenced by decreased adhesion, invasion and migration in vitro. In an attempt to define the cellular target of this inhibition, we observed that DIM mediates down-regulation of matrix metalloproteinases (MMPs) and cell adhesion proteins, integrins. This correlates with decreased thyroid cell proliferation and inhibition of metastatic propensity by DIM in thyroid cancer cells. These preclinical studies are being extended to the clinic where the anti-estrogenic property of DIM is being examined in goiter 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 5683.
Abstract 5684: B-catenin-dependent and independent changes in gene expression induced by sphingolipids
Authors: Zhou Hui , Schmelz Eva M. 
Published: February 2011

Abstract
Dietary supplementation with sphingolipids inhibits colon tumorigenesis in carcinogen-treated CF1 mice and in multiple intestinal neoplasia (Min) mice that produce intestinal tumors spontaneously. In both cancer models the regulation of β-catenin by sphingolipid metabolites is an important early event. Stabilization and nuclear translocation of β-catenin and its interaction with T-cell factor (TCF)/lymphoid enhancer factor (LEF) play important roles to activate the transcription of genes associated with cancer development and progression. Sphingosine and ceramides, major digestion products of complex sphingolipids in the diet, down-regulate β-catenin transcriptional activity in a dose- and time-dependent manner. Our data indicate that sphingosine and ceramides suppress SW480 human colon cancer cell growth in a concentration-dependent manner. In the present study, we investigated the dependency of sphingosine- and ceramide-induced changes in gene expression on β-catenin transcriptional activity by comparing control and β-catenin siRNA treated cells. We observed changes in the expression of genes involved in signal transduction, transcription factors, cell cycle control and DNA damage repair, cell adhesion, cell invasion and metastasis, angiogenesis, and apoptosis and cell senescence. Most genes were regulated by all metabolites; however, some genes were only targeted by specific metabolites. Furthermore, only a small number of genes regulated by the sphingolipid metabolites relied completely on the activation of the β-catenin transcriptional activity. Further experiments are currently being performed to confirm the function of β-catenin on the regulation of these genes.
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 5684.
Abstract 5685: The effects of spinach and two of its components, spinacetin and patuletin, on the treatment of prostate cancer
Authors: Jackson Glenn A. , Slusarz Anna , Drenkhahn Sara K. , Starkey Nicholas J. , Morelock Teddy E. , Rottinghaus George E. , Pompeu Daniel , Fritsche Kevin L. , Bogener Jennifer L. , Besch-Williford Cynthia L. , Lubahn Dennis B. 
Published: February 2011

Abstract
Prostate cancer possesses long latency periods and is responsive to dietary mediators, making it a target for phytochemoprevention. It has been reported that spinach consumption can reduce the incidence of prostate cancer leading our lab to look at structures of compounds present in spinach. We chose to study spinacetin and patuletin, two novel isoflavones found in spinach. We hypothesized that these spinach compounds would inhibit prostate cancer in vitro in the mouse prostate cancer cell line, TRAMP-C2, and that a spinach-containing diet would reduce cancer incidence in our TRAMP mouse model.
Methods: We first isolated a crude spinacetin-containing fraction and patuletin-containing fraction from whole spinach leaves using HPLC column purification. A further purified extract was also isolated for each compound. Using these extracts we determined the effect of the spinach compounds on growth of TRAMP-C2 cells, and the effect that they have on the concentration of Gli1, an indicator of hedgehog signaling, as measured by RT-PCR and a Gli1-luciferase reporter assay. We also tested ground dried spinach at 0.2% and 2% incorporated into a casein-based diet fed to B6/FVB TRAMP mice, and then evaluated the development of prostate cancer histologically.
Results: The extracts, each containing 0.1% spinacetin or patuletin, both inhibit prostate cancer cell growth in vitro, with the patuletin extract inhibiting approximately 30% and the spinacetin extract inhibiting nearly 50%. In addition, the purified compounds each inhibited Gli1 expression in both TRAMP-C2 (as measured by RTPCR) and Shh Light II cells (as measured by luciferase assay), with patuletin having an effect at 300nM and spinacetin at 1μM. The 2% spinach diet led to a 50% decrease in the incidence of well-differentiated carcinoma, but had no apparent effect on the more aggressive poorly-differentiated carcinoma. In conclusion, spinach and its compounds are capable of inhibiting prostate cancer growth and incidence in in vitro and in vivo mouse models.
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 5685.
Abstract 5694: Zapotin mediates its action by inducing p53 in wild-type p53 positive human lung cancer cells
Authors: Kanade Geetanjali G. , Nathani Rajesh , Huma Loredana , Mehta Rajendra G. , Murillo Genoveva 
Published: February 2011

Abstract
Lung cancer is the most common cancer worldwide, accounting for 1.2 million new cases annually. Despite the availability of several novel medications, very few have been found to be widely applicable or effective. Hence, the aim of present study was to assess the efficacy of Zapotin, a phytochemical present in the Mexican fruit Sapote blanco (Casimiroa edulis), in lung epithelial cells. Zapotin was chemically synthesized and the effects were evaluated on several human non-small cell lung cancer cell lines (A549 (p53 wild type), Calu-1(p53 null), H1993 (p53 mutated)) and the Normal Human Bronchial epithelial cell line (BEAS-2b) using cell proliferation assay (MTT Assay & Cell count method), apoptosis assay (TUNEL Assay), western blot analysis and RT-PCR. Significant growth inhibition of 66.91% and apoptosis was found to be induced in the A549 cells when treated with 1 μM zapotin for 72 hrs. On the other hand, no significant growth inhibition was noted for Beas-2b under the same conditions. Furthermore, the western blot analyses indicated that zapotin increased p53 and p21 protein expression in A549 cells but not in Beas-2b cells. Studies for p53 mRNA expression were completed on A549 and Beas-2b subsequent to treatment with zapotin and it showed to have no significant changes. This suggested that the activation of p53 is at protein level instead of transcriptional level. This is the first report to indicate that zapotin acts through p53 mediated pathway in wild-type p53 positive A549 cells.
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 5694.
Abstract 5697: Cellular iron depletion weakens isothiocyanate-induced HO-1 upregulation
Authors: Loo George 
Published: February 2011

Abstract
Heme oxygenase-1 (HO-1) is an important cytoprotective gene, whose expression is known to be elevated in various carcinomas. Also, overexpression of HO-1 is known to inhibit apoptosis particularly in cancer cells. Interestingly, exposing cancer cells to certain chemopreventive agents such as isothiocyanates causes induction of HO-1, perhaps as an attempt by the cells to help them survive the stressful situation. However, it is not completely known what nutritive factors or related components in cancer cells influence HO-1 induction as caused by isothiocyanates. Thus, the aim was to test the hypothesis that adequate iron is needed to enable cancer cells to optimally express HO-1 when induced by isothiocyanates. In HCT-116 human colon adenocarcinoma cells, phenethylisothiocyanate and sulforaphane increased expression of HO-1 and also heme oxygenase activity. However, cells made iron-deficient with the iron chelator, desferrioxamine (DFO), and then exposed to isothiocyanates had much lower heme oxygenase activity. This suppressive effect of DFO on isothiocyanate-mediated induction of heme oxygenase activity was in association with repression of HO-1 protein and mRNA expression. The suppression by DFO of isothiocyanate-induced HO-1 upregulation was reversed upon replenishing the iron-deficient cells with the missing iron. Additionally, it was found that thiol antioxidants (glutathione and N-acetylcysteine) inhibited isothiocyanate-induced HO-1 upregulation, implying that the HO-1 upregulation involved an oxidant signaling pathway. Indeed, NADPH oxidase (NOX) inhibitors, namely, diphenyleneiodonium (DPI) and apocynin, and a superoxide scavenger (Tiron) inhibited isothiocyanate-induced upregulation of HO-1 as well. DPI was the most potent and also inhibited nuclear translocation of redox-sensitive Nrf-2, which is known to activate the HO-1 gene. These findings suggest the possibility that adequate amounts of iron, which at the atomic level can serve as the pivotal element of heme in NOX, must be present in the cells to permit what appears to be NOX-dependent upregulation of HO-1 by isothiocyanates. It is concluded that iron-deficient HCT-116 cells are less able to increase expression of cytoprotective HO-1 when exposed to isothiocyanates, which may make the cancer cells more susceptible to killing.
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 5697.