bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1444: Benzyl isothiocyanate inhibits tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in a BALB/c mouse xenograft model
Authors: Kim Eun Ji , Hong Ji Eun , Eom Soon Ju , Kim Min Hee , Park Jung Han Yoon 
Published: February 2011

Abstract
Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin found in cruciferous vegetables, and has been reported to have anti-tumor properties. In our previous study, we observed that BITC inhibited growth and metastatic capacity of breast cancer cells in vitro cell culture models. The present study examined the in vivo effects of BITC administration on tumor growth and metastasis of breast cancer cells. To establish the in vivo breast cancer model, 4T1 mammary carcinoma cells (5 × 104 cells) were injected into the inguinal mammary fat pad of syngeneic female BALB/c mice. One day later, the mice were divided into 3 groups and subjected to gavage with BITC (0, 5 or 10 mg/kg body weight/day) for 4 weeks. Oral administration of BITC significantly reduced the volume and weight of solid 4T1 cell tumors in BALB/c mice. BITC administration decreased the expression of proliferating cell nuclear antigen, Bcl-2, CD31 and VEGF, but increased the levels of Bax, cleaved caspase-3, −7, −9 and cleaved PARP in the tumors. In addition, Oral administration of BITC resulted in a significant reduction in the numbers of pulmonary tumor nodules and total pulmonary metastatic volume. To understand the mechanisms by which BITC exerts antimetastatic effects, metastasis-related proteins in the sera and lungs were measured by utilizing the relevant ELISA kits and Western blot analysis, respectively. BITC treatment significantly decreased the concentrations of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and urokinase-type plasminogen activator (uPA) in the sera of mice injected with 4T1 cells. However, the concentrations of TIMP-2 and plasminogen activator inhibitor (PAI)-1 were increased in the sera of mice treated with BITC. Additionally, the administration of BITC reduced the levels of MMP-2, MMP-9, TIMP-1, and uPA and increased TIMP-2 and PAI-1 in the lungs of these animals. In this study, we have demonstrated that BITC profoundly suppresses the tumor growth and lung metastasis in mice bearing orthotopic xenografts of 4T1 breast cancer cells. The present results indicate that BITC has potential as an anti-cancer agent for the treatment of breast cancer.
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 1444.
Abstract 1445: Growth inhibitory and anti-metastatic effects of the hexane/ethanol extract of Glycyrrhiza uralensis in a mouse breast cancer xenograft model
Authors: Park So Young , Kwon Sujin , Park Heesook , Lim Soon Sung , Kim Jin Kyu , Kim Jong-Sang , Lee Choonghwan , Park Jung Han Yoon 
Published: February 2011

Abstract
Glycyrrhiza uralensis (licorice) is one of the most frequently prescribed ingredients in Oriental medicine and licorice root extracts have previously been shown to exhibit anti-carcinogenic activities. However, these extracts harbor considerable quantities of glycyrrhizin, which is known to exert anticarcinogenic activities and to induce severe hypokalemia and hypertension. In this study, we evaluated the effects of the hexane/ethanol extract of Glycyrrhiza uralensis (HEGU), which lacks glycyrrhizin, on the metastatic characteristics of 4T1 murine mammary carcinoma cells. When 4T1 cells were cultured on a transwell-filter in an in vitro cell culture model, HEGU inhibited cell migration and adhesion in a dose-dependent manner. Gelatin zymography and Western blot analysis showed that HEGU significantly suppressed the secretion and activation of the matrix metalloproteinase (MMP)-2 and MMP-9. The secretion of tissue inhibitor of metalloproteinase (TIMP)-1 was reduced in HEGU-treated cells. HEGU reduced the protein levels of intercellular adhesion molecule and vascular cell adhesion molecule. To assess the effects of HEGU on lung metastasis in vivo, we injected 4T1 cells (5×104 cells) into the inguinal mammary fat pads of syngeneic, immunocompetent BALB/c mice. One week after 4T1 cell injection, the mice were given HEGU (5 mg/kg body weight/day) in the drinking water for 25 days. HEGU treatment inhibited the solid tumor growth and the number of pulmonary tumor nodules. Immunohistochemistry results revealed that HEGU treatment reduced the expression of CD31, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen and cyclin-dependent kinase 4 in the tumor tissues. In addition, the serum concentrations of MMP-9 and VEGF were decreased in the sera of mice treated with HEGU. In the present study, we have demonstrated in both in vivo and in vitro systems that HEGU greatly inhibits the growth and lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMPs, adhesion molecules and VEGF. These data suggest that HEGU possesses chemotherapeutic efficacy against breast cancer including the growth of tumor and inhibition of metastasis.
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 1445.
Abstract 145: Interactions among DNA methyltransferase isoforms and their effects on DNA methylation
Authors: Van Emburgh Beth O. , Robertson Keith D. 
Published: February 2011

Abstract
Alterations in DNA methylation patterns are a hallmark of cancer development demonstrated as both global hypomethylation and gene specific hypermethylation. This results in genomic instability as well as tumor suppressor gene silencing. Methylation is catalyzed by the DNA methyltransferases (DNMTs) DNMT1, DNMT3A, and DNMT3B and is assisted by DNMT3L. In order to understand the role of the DNMTs in aberrant methylation and cancer, a better understanding of how they function and interact with one another is essential. All of the DNMTs, but especially DNMT3B, are alternatively spliced generating many isoforms of unknown function. Immunodeficiency, centromere instability, and facial anomalies syndrome (ICF), which is caused by mutations in the de novo methyltransferase DNMT3B and results in altered DNA methylation patterns, is a model disease that can be studied to better understand the function of DNMT3B. We have successfully expressed each of the DNMTs using baculovirus and E. coli expression systems along with several of their common splice variants, mutations associated with ICF syndrome, and deletion constructs of Dnmt3b. A novel system was developed for these recombinant enzymes using a plasmid containing a satellite 2 sequence as a template in order to analyze both the amount of methylation and site specific methylation with bisulfite genomic sequencing and pyrosequencing. The effects of common splice variants and mutations/deletions on protein-protein interactions are being ascertained using GST pull downs and effects on their interaction with DNA examined using electrophoretic mobility shift assays. Preliminary analyses suggest that the splice variants and mutations/deletions significantly affect DNA methylation and also alter their interaction with DNMT3L and DNA. For example, Dnmt3b2 demonstrates less DNA methylation activity than Dnmt3b1, but both are enhanced by the addition of DNMT3L. Both Dnmt3b1 and Dnmt3b2 bind DNMT3L in pull down assays, but unlike Dnmt3b1 the interaction between Dnmt3b2 and DNMT3L is lost at higher salt concentrations suggesting a weaker association. Ongoing studies will provide additional insights into how interaction between Dnmt3a and Dnmt3b splice variants influences methylation and what impact mutations or deletions can have on this. We anticipate that our results will allow for an improved understanding of the functional interactions of DNMTs which will, in turn, enhance our understanding of how and why methylation patterns go awry in cancer. (Supported by NCI grants F32CA132327 and R01CA114229)
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 145.
Abstract 1451: Lipid-based Akt inhibitors preferentially kill lung cancer cells with mesenchymal features
Authors: Zhang Chunyu , Messan Koffi S. , Hobbs Evthokia , Chiang Chun-Te , Saber Barbara , Gills Joell J. , Dennis Phillip A. 
Published: February 2011

Abstract
Most solid tumors are epithelial in origin. A loss of epithelial-cell markers and gain of mesenchymal-cell markers (epithelial mesenchymal transition, EMT) has been observed in patient tumor samples, particularly at the leading edge or invasive front of solid tumors such as non-small cell lung cancer (NSCLC). Pathological EMT is often associated with tumor metastasis and can confer a poor prognosis. EMT is promoted by Akt activation, which contributes to the formation, maintenance, and therapeutic resistance of cancer. In this study, we found that lipid-based Akt inhibitors (LBAI) such as phosphatidylinositol ether lipid analogues (PIAs) and alkylphospholipids (perifosine and miltefosine) preferentially kill tumor cells with mesenchymal features. NSCLC cell lines that exhibited epithelial, intermediate and mesenchymal phenotypes (H322, A549 and H157, respectively) were increasingly sensitive to the cytotoxic effects of LBAI. Prolonged treatment of A549 cells with TGFbeta induced a mesenchymal phenotype and increased sensitivity to LBAI. Because EMT can be controlled by the tumor suppressor RhoB, which we previously showed was transcriptionally activated by LBAI, we investigated the role of RhoB in these cell lines. An inverse relationship between Akt activation and RhoB expression was observed in the parental cell lines as well as A549 cells treated with TGFbeta, which correlated with LBAI cytotoxicity. Stable knockdown of RhoB in A549 cells induced features of EMT including loss of E-cadherin expression, induction of vimentin expression and Akt activation, and increased cellular migration. Stable knockdown of RhoB also increased sensitivity to LBAI. These studies show that lung cancer cells with a mesenchymal phenotype are preferentially sensitivity to LBAI, and that RhoB is a critical mediator of EMT.
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 1451.
Abstract 1455: A model to predict possible parameters to assess tumor progression with Optoacoustic Imaging
Authors: Gertsch Andreas G. , Bush Nigel L. , Birtill David CCJ , Bamber Jeff C. 
Published: February 2011

Abstract
Optoacoustic (OA) imaging is a novel technique which allows optical absorption contrast to be visualized noninvasive using laser induced thermoelastically generated ultrasound. In tumors the highest optical absorption contrast is due to the blood/vascularization. Using optoacoustic biomarkers (such as gold nanoparticle-antibody conjugates) the signal of the vascularization could be enhanced or also other specific regions could be targeted. To assess tumor progression the size of the microvessels and the distance between them can be useful information. We found two different methods to quantify these two parameters using OA imaging. OA texture analysis and the analysis of the contrast-to-noise ratio in the reconstructed OA image and the acoustic frequency spectrum analysis in the raw signal. We present a model to predict the potential of using OA texture analysis combined with acoustic frequency spectrum analysis of the OA signal to assess the progression of tumors. The model is based on the simulation of OA signals using a time domain acoustic propagation method and a Fourier reconstruction algorithm, which has been tested with basic phantom studies. The properties of the receive part, the ultrasound (US) probe, such as the element size, center frequency or bandwidth can freely be adapted. This makes it possible to use this model with any OA system using an US system as the receiver. We show that it is possible to assess the size of optoacoustic absobers, such as the size of the microvasculature in tumors, and partly the distance between them using OA imaging. We also show the influence of a limited bandwidth of the US transducer on the outcome and therefore which transducers should be used for which application. The model has also been tested on different tumors in mice.
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 1455.
Abstract 1460: Piceatannol suppresses the migration and invasion of DU145 human prostate cancer cells
Authors: Kwon Gyoo Taik , Kim Jin-Kyung , Park Jung Han Yoon 
Published: February 2011

Abstract
Piceatannol (trans-3,4,3′,5′-tetrahydroxystilbene) is a polyphenol found in grapes, red wine, Rheum undulatum and seeds of Euphorbia lagascae. The purpose of the present study was to investigate the effects of piceatannol on the migration and invasion characteristics of DU145 prostate cancer cells. DU145 cells were cultured in the presence of 0 − 10 μmol/L piceatannol with or without 10 μg/L epidermal growth factor (EGF). Piceatannol inhibited the basal and EGF-induced cell migration and invasion of DU145 cells. Gelatin zymography and Western blot analysis, Fibrin zymography and real time RT-PCR analysis were conducted using conditioned media and cell extracts. Piceatannol reduced the secretion and mRNA levels of matrix metalloproteinase (MMP)-9, urokinase-type plasminogen activator (uPA), and vascular endothelial growth factor (VEGF). Piceatannol decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels in a concentration-dependent manner. Additionally, piceatannol inhibited the phosphorylation of signal transducer and activator of transcription (STAT)3. Furthermore, piceatannol decreased both basal and EGF-induced secretion of IL-6. IL-6 treatment increased the secretion of uPA and VEGF, the phosphorylation of STAT3, and migration of DU145 cells and these increase were suppressed by piceatannol. An IL-6 nutralizing antibody inhibited the EGF-induced phosphorylation of STAT3 and increase in cell migration and invasion of DU145 cells, which may be mediated via the inhibition of MMP-9 and uPA activities and secretion of VEGF. The inhibition of IL-6/STAT3 activation may be one of the mechanisms by which piceatannol regulates the expression of proteins involved in the rehulation of DU145 cell migration and invasion.
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 1460.
Abstract 1461: Zoledronate inhibits proliferation and invasion of inflammatory breast cancer cells
Authors: Hall Carolyn S. , Singh Balraj , Tai Karen , Irving LaTashia R. , Lucci Anthony 
Published: February 2011

Abstract
Introduction: Inflammatory breast cancer (IBC) is aggressive, as approximately one third of patients present with distant metastases. Bisphosphonates are often administered to breast cancer patients for cancer-induced osteolysis. Recent evidence suggests bisphophanates may also have anti-tumor properties. This study examined the effects of the bisphosphonate, zoledronate (ZA), on the proliferation and invasive capabilities of highly aggressive IBC cell lines.
Methods: The IBC cell line SUM149 was cultured utilizing both adherent and serum-free, non-adherent cancer stem cell enriching conditions. An MTT assay was used to quantify proliferation and mammosphere formation of cells. Adherent cell growth was measured at days 1-4 following 0, 0.1, 1, 5, 10, 50 and 100uM zelodronate treatment. Mammosphere formation was measured at 10 days following 0, 0.01, 0.1, 1, 10, and 100uM ZA treatment. Modified Boyden chambers were employed to assess the ability of both adherent and non-adherent cells to invade to SDF-1 (100ng/mL) following 24 hour 1uM ZA treatment. Protein expression was assessed using immunofluorescent staining, protein arrays and Western blotting.
Results: ZA treatment with &lt;5uM did not inhibit SUM149 adherent cell growth at any of the measured time points. ZA concentrations ≥10uM significantly inhibited SUM149 adherent cell growth at day 4 (p≤0.05). SUM 149 mammosphere formation was significantly inhibited following 10uM ZA treatment (p≤0.001). However, significantly more SUM149 non-adherent cells invaded to SDF-1 compared to adherent cells (p≤0.001). SUM 149 non-adherent cell invasion was inhibited by 24 hour 1uM ZA treatment (p≤0.001). SUM 149 non-adherent cells expressed significantly increased levels of the epithelial-mesenchymal transition (EMT) associated proteins smooth muscle actin (SMA), fibronectin, and N-Cadherin. The increased expression of SMA, fibronectin, and N-Cadherin observed in non-adherent cells returned to levels comparable to adherent cells following 24 hour 1uM ZA treatment.
Conclusions: ZA inhibited the growth of IBC cells grown under adherent and non-adherent conditions. SUM 149 non-adherent cells had much greater invasive potential than adherent cells did, and their invasive capability was inhibited following low dose ZA treatment. Interestingly, ZA inhibited up-regulation of EMT associated proteins SMA, fibronectin, and N-Cadherin in SUM 149 non-adherent cells. These results indicate that some IBC cells grown under cancer stem cell enriching conditions have the potential to undergo EMT and invade. ZA may also inhibit metastases through novel mechanisms.
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 1461.
Abstract 1463: Pharmacological impact of epithelial-mesenchymal plasticity in the H358 lung tumor model
Authors: Argast Gretchen M. , Mercado Peter , O'Connor Matthew , Mulford Iain J. , Pachter Jonathan A. , Epstein David M. , Thomson Stuart , Kan Julie L.C. 
Published: February 2011

Abstract
The phenotypic changes associated with epithelial to mesenchymal transition (EMT) give tumor cells at least two attributes that increase metastatic efficiency. First, mesenchymal cells have lost cell-cell contacts and are more invasive and can therefore escape the primary tumor, whereas epithelial cells remain anchored by cell-cell contacts in the primary tumor. Second, mesenchymal cells in vitro are less sensitive than epithelial cells to agents that inhibit the EGFR pathway. This appears to translate into the clinic, since patients with tumors that express mesenchymal markers do not respond to EGFR targeting therapeutics as well as patients with more epithelial tumors. To determine whether we can control sensitivity to EGFR inhibitors by manipulating a cell's epithelial/mesenchymal status, we examined the role of EMT and its reversibility in tumor cell sensitivity to the EGFR inhibitor erlotinib. We studied in vitro models of EMT driven by Transforming Growth Factor β (TGFβ), Hepatocyte Growth Factor + Oncostatin M (HGF+OSM), Snail or Zeb1 in the H358 non-small cell lung carcinoma model. EMT driven by TGFβ or HGF+OSM caused a significant decrease in sensitivity to erlotinib, while EMT driven by induced expression of Snail or Zeb1 was much less effective, suggesting a change in drug sensitivity requires more input than these canonical EMT transcription factors. Once mesenchymal tumor cells have localized to a metastatic site, it is thought the tumor cells must undergo a mesenchymal to epithelial transition (MET) in order to form a cohesive tumor. We examined the reversibility of EMT in our models and the corresponding erlotinib sensitivity, both by withdrawal of ligand and by pharmacological inhibition of the signaling pathways downstream of the drivers. Using these approaches, we found EMT driven by HGF+OSM was reversible as evidenced by morphology and marker changes, and this reversion correlated with an increase in erlotinib sensitivity, comparable to the parental H358 cells. EMT driven by TGFβ was partially reversed by both ligand withdrawal and pharmacological inhibition of the receptor, and the extent of reversion in erlotinib sensitivity correlated with the extent of marker reversion. These results demonstrate that the extent of reversibility of EMT is dependent on the driver. Furthermore, it may be possible to drive some erlotinib-insensitive tumors back to a more erlotinib-sensitive state with pharmacological agents, thus improving patient response.
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 1463.
Abstract 1469: Cyclin D1 plays a critical role in the response of mammary gland to estrogen and progesterone by regulating progesterone receptor expression
Authors: Yang Chuanwei , Chen Li , Li Cuiqi , Lynch Mary C. , Schmidt Emmett V. 
Published: February 2011

Abstract
Estrogen and progesterone are important hormones in normal female development, yet both have critical roles in breast carcinogenesis. Cyclin D1 is a breast cancer oncogene whose amplification is linked to poor prognosis in estrogen and progesterone receptor positive breast cancers. Here we show that cyclin D1 regulates progesterone receptor expression, consequently enhancing responses to estrogen and progesterone in breast development and carcinogenesis. Estrogen treatment of cyclin D1 transgenic mice caused mammary hyperplasias expressing increased progesterone receptors, which were stimulated by progesterone and blocked by a progesterone antagonist. Cyclin D1 regulated progesterone receptor expresion through a novel estrogen- and cyclin D1-responsive enhancer in DNA encoding part of the 3’ untranslated region of the progesterone receptor gene. Small inhibitory RNAs for cyclin D1 decreased progesterone receptor expression in human breast cancer cells, which sensitized them to progesterone-antagonists. Since estrogen and progesterone regulate cyclin D1, our results suggest that cyclin D1's participation in a feed-forward loop could contribute to increased breast cancer risks associated with estrogen and progesterone combinations. Additionally, its regulation of the progesterone receptor identifies a novel role for cyclin D1 in ovarian hormone control of breast development and breast carcinogenesis.
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 1469.