bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5691: Significance of combination treatment of antiprogestin and aromatase inhibitors in aromatase overexpressing T47D breast cancer cells
Authors: Gupta Akash , Peng Xinjian , Murillo Genoveva , Mehta Rajeshwari R. , Wiehle Ronald , Mehta Rajendra G. 
Published: February 2011

Abstract
Treatment with aromatase inhibitors (AI) is considered as the first line of treatment for ER+PR+ cancers. However, many patients acquire resistance to aromatase inhibitors. Therefore, there is a need for new approaches to overcome resistance to AI in these patients. In the present study we determined the effects of third generation AI in genetically engineered high aromatase overexpressing T47Darom cells. Treatment of T47Darom cells with Leterozole (L), Anastrazole(A) and Exemestane(E) at 5μM concentration exhibited inhibition of 32% 19% and 18% respectively, however, in combination with proellex overall inhibition increased to 50% suggesting additive effect of proellex along with aromatase inhibitor. Interestingly, Proellex showed dose-dependent inhibition of T47Darom cells incubated with testosterone (1nM and 10nM) suggesting that Proellex also has aromatase inhibitory property. Furthermore, Proellex inhibited cell proliferation of both ER/PR positive (T47D and T47Darom) and ER/PR negative (MDA-MB231cells). These results suggested that the mechanism of action may not be entirely dependent to PR status. Since both T47Darom and MDA-MB231 cells exhibit increased COX2 expression and increased COX2 expression has been associated with enhanced cell proliferation and malignancy in breast cancer, we determined the effects of Proellex on COX2 expression. Results showed that in both these cell lines COX2 expression was decreased as determined by real-time PCR when the cells were treated with Proellex at 10−6M. These studies suggest that Proellex either alone or in combination with aromatase inhibitors may provide a new treatment strategy for breast cancer patients.(This work is supported by Repros Therapeutics)
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 5691.
Abstract 5693: Changes in antioxidant capacities of isolated radish components during growth
Authors: Whitaker Jonathan , Giraldez Evita , Loong Jason , Wagstaff Joel , Robinson Richard , O'Neill Kim L. 
Published: February 2011

Abstract
Radishes have been cultivated and used in the diet since the Hellenistic age and have become a common vegetable in grocery stores in North America. Radishes belong to the genus Brassica and recent research has indicated the consumption of this plant has protective properties against colorectal cancer.
This project examines the antioxidant (AO) properties of the leaves, stems, body, and the roots of cherry belle radishes at different stages of growth from germination to maturity. For this experiment, AO capacity was measured using the oxygen radical absorbance capacity (ORAC) assay. The ORAC assay involves mixing samples from the radish components with fluorescein, a fluorescence agent, and measuring the degradation of fluorescein after AAPH ((2,2′)-azobis-(2-amidinopropane) dihydrochloride), an oxidizer, is added. Using a trolox (6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) standard, the results from the ORAC assay were converted to trolox equivalents per liter (TE/L). Results indicate that shortly after germination, about 14 days after planting, the body of the radish plants have the highest mean AO capacity with a TE/L reading of 32, compared to the leaves’ initial reading at 26 TE/L. As the plant nears maturity, 23 days after planting, the leaves become the best source of AO at 78 TE/L, and the body's mean AO capacity reaches 73 TE/L. The stems begin as a relatively weak source of AO at 22 TE/L, but mature to 71 TE/L. The roots of the radish plant were consistently the lowest source of AO at 16 TE/L at day 14, and 61 TE/L at day 23.
In addition, a cellular model was used to determine how well the AO are taken into cells that have been distressed. This assay measures the uptake of AO in cells over 10, 20, 45, and 60 minutes after the cells have been exposed to a known oxidant, AAPH. Raji cells, a Burkitt's lymphoma cell line, were treated with samples derived from the same parts of the radish plant after they were pretreated with AAPH. Preliminary data indicate cells continually uptake AO derived from the radish leaves up to and possibly beyond 60 minutes. Pre-stressed cells exposed to AO from stems lose AO capacity over the 60 minutes. In the cells exposed to root samples AO uptake does not change significantly over time. In summary, radish leaves at maturity are the best source of antioxidants.
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 5693.
Abstract 5695: Nitric oxide-donating naproxen inhibits β-catenin-mediated TCF signaling in colorectal cancer cells more effectively than naproxen
Authors: Suh EunRan , Ferrara Christina , Kaunga Esther , Cooper Harry S. , Lubet Ronald A. , Chang Wen-Chi L. , Clapper Margie L. 
Published: February 2011

Abstract
Results from recent clinical and epidemiological studies continue to suggest that non-steroidal anti-inflammatory drugs (NSAIDs) are promising chemopreventive agents with activity against colorectal cancer. Nitric oxide (NO)-donating NSAIDs represent a novel class of agents that have been reported to have greater safety and higher efficacy in inhibiting the growth of cancer cells than the parent compounds. However, the mechanism of chemopreventive action of NO-NSAIDs is not well elucidated. Dysregulation of the WNT/ β-catenin pathway is one of the earliest events during tumorigenesis in the colon and thus an attractive molecular target for chemopreventive intervention. The major goal of the current study was to compare the effect of naproxen, an NSAID commonly used to reduce pain, fever and inflammation, and NO-naproxen on β-catenin-mediated TCF4 signaling in colon cancer cells. Human SW480 colon carcinoma cells that express mutant APC were transfected with either pGL3 basic plasmid or a luciferase reporter construct under the control of 3 copies of either wild-type (pGL3-OT) or mutated (pGL3-OF) TCF4 regulatory element using LipofectAmine 2000. Cells were treated with 0.01 - 0.4 mM naproxen or NO-naproxen or vehicle (water or DMSO, respectively) and harvested 48 hrs later. Cell lysates were prepared and luciferase activity was measured using the Promega Luciferase Assay kit. The results demonstrate that NO-naproxen reduces β-catenin-mediated TCF4 transcriptional activity in SW480 cells in a dose dependent manner. At a given dose, the luciferase activity of cells exposed to NO-naproxen was approximately 50% of that of cells treated with the parent compound. In conclusion, these data suggest that the chemopreventive activity of NO-naproxen is attributed in part to its ability to inhibit the transcriptional activation of TCF4; a response that is greater than that of the conventional drug naproxen. The availability of a multiple intestinal neoplasia mouse model that, unlike the conventional strain, develops multiple colorectal adenomas provides a unique opportunity to compare the efficacy of these agents against colorectal tumor growth in vivo. Supported by NIH N01 CN43309.
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 5695.
Abstract 57: Inhibition of human melanoma proliferation by combination treatment with ODC inhibitor and mTOR inhibitor
Authors: Hsueh Eddy C. , Zhang Yanping , Peng Guangyong 
Published: February 2011

Abstract
Recent reports have demonstrated that polyamine synthesis is critical for tumor cell growth. Furthermore, mTOR was also shown to be critical for tumor cell growth. We hypothesized that inhibition of key polyamine synthesis enzyme, ornithine decarboxylase (ODC), and mTOR would have growth inhibitory effect on human melanoma cells.
ODC expression was evaluated in human melanoma and human melanoma cell lines by Western blot using polyclonal goat anti-ODC and quantitative real-time PCR using TaqMan Gene Expression Assay Applied Biosystems). The siRNA duplexes targeting ODC and a scrambled control siRNA were designed and synthesized (Santa Cruz, CA) and transient transfections were performed. Cell proliferation assay was performed using Cell Titer Blue cell proliferation assay according to the manufacturer's protocol. The cells were treated with or without various concentrations of DFMO or rapamycin or combination then incubated up to 96 hours. For comparison between groups, the Student's t test were used and p&lt;0.05 was considered to be statistically significant.
Over-expression of ODC was observed in human melanoma cells compared with tumor asssociated fibroblasts as well as human melanoma cells. Over-expression of ODC was observed in six of the ten human melanoma cell lines on Western blot analysis and RT-PCR analysis. Dose-dependent growth inhibition of human melanoma cells were observed following DFMO treatment (p&lt;0.05) in melanoma cell lines with over expression of ODC and correlated with suppression of ODC expression levels. Grow inhibition was also observed folllowing Rapamycin treatment in the melanoma cell lines. Treatment with ODC-siRNA also resulted in significant growth inhibition of melanoma cell lines. Effects of DFMO induced growth inhibition of melanoma cells were further enhanced with combined treatment with rapamycin.
Overexpression of ODC was observed in human melanoma cells. Inhibition of polyamine synthesis and mTOR can have significant growth inhibitory effects on human melanoma.
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 57.
Abstract 570: Role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the cytotoxicity of the Hsp90 inhibitor 17AAG in human pancreatic cancer cells
Authors: Shieh Biehuoy , Siegel David , Yan Chao , Kepa Jadwiga K. , Ross David 
Published: February 2011

Abstract
Previous work has demonstrated that NQO1 can reduce the benzoquinone ansamycin Hsp90 inhibitor 17-allyamino-demethoxy geldanamycin (17AAG) to the corresponding hydroquinone (17AAGH2). The formation of 17AAGH2 by NQO1 results in a more water soluble molecule and that binds with greater affinity to Hsp90 when compared to the parent quinone 17AAG. Experiments were conducted with the human pancreatic cancer cell line Panc1 which is homozygous for the NQO1*2 polymorphism and contains only trace levels of NQO1 protein and no NQO1 catalytic activity. An isogenic cell line expressing high levels of NQO1 (Panc1-C5) was generated by stable transfection of wild type NQO1 in Panc1 cells. 17AAG was more cytotoxic to Panc1-C5 cells with high levels of NQO1 when compared to NQO1-null parental Panc1 cells. Pretreatment of Panc1-C5 cells with the NQO1 mechanism-based inhibitor ES936 reduced the cytotoxicity of 17AAG to the level observed in Panc1 cells. No difference in the cytotoxicity of the non-quinone Hsp90 inhibitor radicicol was observed between the two cell lines Biomarkers of Hsp90 inhibition were measured in both Panc1 and Panc1-C5 cells following treatment with 17AAG. Higher protein levels of Hsp70 and lower amounts of cRaf, phosphorylated ERK1/2 and phosphylated MEK were observed in Panc1-C5 cells compared to Panc1 cells. In addition, cell cycle analysis revealed a greater number of Panc1-C5 cells arrested in G2M following 17AAG treatment compared to Panc1 cells. Cytotoxicity studies were also performed in additional human pancreatic cancer cell lines (BxPC3 and MiaPaCa2) that contain high levels of catalytically active NQO1*1 protein and in agreement with the studies described above the cytotoxicity of 17AAG could be reduced significantly following pretreatment with the NQO1 inhibitor ES936. The intracellular concentrations of 17AAG and 17AAH2 were measured in human pancreatic cancer cell lines and it was observed that greater amounts of both 17AAG and 17AAGH2 could be detected in cell lines with catalytically active NQO1 when compared to cells lacking NQO1 activity or cells pretreated with ES936. These data demonstrate that in addition to generating a more potent Hsp90 inhibitor (17AAGH2) the reduction of 17AAG to 17AAGH2 by NQO1 leads to significantly greater intracellular concentrations of 17AAG and 17AAGH2. These data confirm the role of NQO1 in sensitivity to 17AAG and suggest that genotyping for the NQO1*2 polymorphism should be considered in patients undergoing 17AAG treatment for pancreatic cancer or other solid tumors that are known to contain high levels of NQO1 activity (Supported by CA51210).
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 570.
Abstract 5705: Inhibition of hedgehog-signaling by extracts of the Sutherlandia and elderberry
Authors: Lu Yuan , Lin Hui , Drenkhahn Sara K. , Starkey Nicholas J.E , Jackson Glenn A. , Thomas Andrew L. , Folk William , Fritsche Kevin L. , Lubahn Dennis B. 
Published: February 2011

Abstract
Many botanical compounds, which have been proposed to prevent cancer, may potentially work via inhibition of the hedgehog-signaling pathway. Here we investigated the potential of Sutherlandia and elderberry to prevent and/or treat prostate cancer by inhibition of the hedgehog-signaling pathway. To determine hedgehog pathway inhibitory activity, we treated Shh light II cells with multiple doses of Sutherlandia extract or elderberry extract, in a Gli1 reporter assay to determine the extracts'effects on Gli1 concentration. The Sutherlandia extract was prepared by methanol extraction of Sutherlandia frutescens, while the elderberry extract was prepared by ethanol extraction of Sambucus nigra berries. We hypothesized that the compounds canavanine, from Sutherlandia, and cyanidin-3-glucoside, from elderberry, were the active compounds able to inhibit hedgehog signaling.
Results: We found that a 1:2000 dilution of Sutherlandia extract and a 1:100 dilution of elderberry extract are able to inhibit hedgehog pathway activity by 99% and 94%, respectively, as monitored by Gli reporter assay. Moreover, cyanidin-3- glucoside (5uM, 10uM and 50uM) can inhibit hedgehog activity by 44%,62% and 81% respectively, and canavanine (1uM and 10uM) can inhibit hedgehog activity by 5% and 15% respectively. These data indicate that, while these two compounds are weak hedgehog inhibitor compounds, they are unlikely to be the major active hedgehog inhibitory compounds in Sutherlandia and elderberry.
Conclusion: Our results suggest that these two plants offer a potentially cheap and effective alternative to cyclopamine for cancer therapies. Additionally, these plants may yield novel targets that potentially could lead to a second generation hedgehog inhibitor, if resistance is found to the first generation drugs currently in clinical trials.
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 5705.
Abstract 5706: High-throughout library screening identifies phytochemical inducers of phase II metabolism enzymes GSTP1 and NQO1 in human lung cells
Authors: Tan Xiang-Lin , Shi Miao , Massimi Aldo , Han Weiguo , Spivack Simon 
Published: February 2011

Abstract
Many phytochemicals possess anti-oxidant and cancer-preventive properties, some putatively through phase II metabolism-mediated mutagen/oxidant quenching. However, in studies to date, most candidate agents are not active in human lung cells. In vitro and in vivo screening studies for discovery are clearly needed for new, more potent chemopreventive agents for lung cancer. Here we applied an mRNA-specific gene expression-based high-throughout screening approach to identify phytochemical inducers of phase II metabolism enzymes GSTP1 and NQO1 in primary normal human bronchial epithelial (NHBE) cells and immortalized human bronchial epithelial cells (HBEC). We have screened 800 compounds in the MicroSource Natural Products Library for inducers of GSTP1 and NQO1 expression, and identified 2, 3-dihydroxy-4-methoxy-4′-ethoxybenzophenone, triacetylresveratrol, ivermectin, sanguinarine sulfate, and daunorubicin as new inducers for GSTP1 and NQO1 mRNA expression. Consistent with this effect, the induction of NQO1 protein expression by immunoblot was found for all these agents in both HBEC and NHBE cells at the same concentration that induced NQO1 mRNA expression. However, GSTP1 protein expression did not significantly change with any selected agents. Proliferation/viability assays showed that HBEC and NHBE were significantly inhibited by ivermectin, sanguinarine sulfate, and daunorubicin. These data demonstrate the feasibility of high-throughput screening for inducers of NQO1. Moreover, the data identify 2, 3-dihydroxy-4-methoxy-4′-ethoxybenzophenone and triacetylresveratrol as the most potent and low toxicity inducers [≥3-6-fold, at the protein level], implying they are potential new agents for further in vitro and preclinical in vivo testing for prevention of oxidant-related disease.
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 5706.
Abstract 571: PK and antitumor activity of DEBIO 0507, a new platinum derivative, in preclinical tumor models
Authors: Mignard Caroline , Bari Virginie , Bichat Francis , Cicurel Lucienne , Vuagniaux Grégoire , Barbier Maryse 
Published: February 2011

Abstract
Background:
Since the introduction of cisplatin, carboplatin and oxaliplatin, several new generations of platinum analogues have been developed as candidates for chemotherapy. DEBIO 0507/NC-4016 is a DACH-Platin Polymeric Micelle. The main objectives of this project were to assess pharmacokinetic (PK) profile of DEBIO 0507 and evaluate its efficacy in preclinical studies against a broad spectrum of experimental tumors including syngenic, xenogenic tumor models and a cisplatin-resistant cell line.
Methods:
PK and biodistribution studies were conducted in multiple matrices (blood, tumor, liver, spleen, kidneys and pancreas) collected in mice bearing C38 mouse colon carcinoma and treated with a single IV injection of DEBIO 0507 at 2 mg Pt/kg.
Antitumor activity of DEBIO 0507 intravenously injected every 4, 7 or 14 days at different doses was investigated in C38 mouse colon carcinoma bearing C57BL/6 mice. Antitumor effect of DEBIO 0507 was also assessed in a panel of human tumor xenografted in nude mice, Calu-6 and A-549 human lung carcinoma, HT-29 human colon carcinoma, PC-3 human prostatic tumor, FaDu human pharynx carcinoma, NIH:OVCAR3 human ovarian tumor, BxPC-3 human pancreas tumor and HepG2 human hepatocarcinoma.
Results:
A concentration of 61 µg Pt/ml was detected in plasma from 5 minutes after injection and persisted during two hours. Platinum was very slowly cleared from plasma as it was still detected 14 days after injection (t1/2α : 40h). An accumulation was observed in tumor from 5 minutes to 8 days after injection and terminal elimination phase was very long since platinum was also detected 14 days after injection. The same PK and BD profiles were observed for other tissues.
DEBIO 0507 was not active in the models of NIH: OVCAR3 human ovarian tumor, BxPC-3 human pancreas tumor and HepG2 human hepatocarcinoma. DEBIO 0507 exhibited a significant and dose-dependent antitumor activity against C38 mouse colon carcinoma when administered every 4, 7 or 14 days (optimal T/C of 0, 0 and 5%, respectively). We also demonstrated growth inhibitory effects of DEBIO 0507 in human PC-3 prostate, Calu-6 lung, FaDu head and neck and A-549 lung tumors xenografted in nude mice when injected with similar doses and schedules (optimal T/C of : 26, 29, 39 and 40%, for each model respectively).
Conclusion:
DEBIO 0507 displayed a marked antitumor activity against a large spectrum of tumor models associated with a long exposure of tumor to Pt. These preclinical results provide useful data to support the design of clinical trials for DEBIO 0507.
DEBIO 0507/NC-4016 was produced by Nanocarrier Co.,Ltd.
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 571.