bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A16: External Qi of Yan Xin Qigong induces apoptosis in estrogen-independent breast cancer cells through inhibition of the Akt/NF-κB pathway
Authors: Yan Xin , Shen Hua , Jiang Hongjian , Hu Dan , Zhang Chengsheng , Wang Jun , Wu Xinqi 
Published: May 2012

Abstract
A16
The concept External Qi of Qigong refers to the technology and ability of the “Qi deployment” therapy and health preservation in traditional Chinese medicine (TCM). External Qi therapy of TCM has long been one of the medical practices and under the management of the health authorities in China. Studies have shown substantial beneficial effects of Yan Xin Qigong (YXQ) that originated from TCM on disease management, weight control, and optimizing caloric intake and diet habit. The external Qi of Yan Xin Qigong (YXQ-EQ) has previously been shown to have potent antioxidative properties. In the present study we have investigated the effect of YXQ-EQ on the Akt/NF-κB signaling pathway that is crucial for tumor growth and progression in estrogen-independent breast cancer MDA-MB-231 cells. YXQ-EQ significantly inhibited constitutive and EGF-stimulated Akt phosphorylation. Furthermore, YXQ-EQ substantially inhibited constitutive NF-κB activity and downregulated the expression of NF-κB target genes Bcl-2, Bcl-xL, XIAP and survivin. YXQ-EQ treatment caused a dramatic reduction in the viability of MDA-MB-231 cells, accompanied by DNA fragmentation, cleavage of PARP, and activation of caspase-3 and caspase-9. These findings suggest that YXQ-EQ might induce apoptosis in MDA-MB-231 cells through inactivation of Akt/NF-κB signaling. YXQ-EQ could potentially be a novel approach for breast cancer prevention and therapy.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A16.
Abstract A2: Dauricine inhibits IGF-I-induced HIF-1α protein accumulation and VEGF expression
Authors: Tang Xudong , Li Gang , Zhou Keyuan 
Published: May 2012

Abstract
A2
Dauricine (Dau), a bisbenzylisoquinoline alkaloid derivative isolated from the rhizome of Menispermum dauricum DC, has been found to have anticancer activities. However, the effect of Dau on tumor angiogenesis is still unclear. A growing body of evidence has demonstrated that hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) play an important role in tumor angiogenesis. In this study, we investigated the effect of Dau on HIF-1α and VEGF expression induced by insulin-like growth factor-I (IGF-I) in human breast cancer cells (MCF-7). Our results showed that Dau significantly inhibited IGF-I-induced HIF-1α protein accumulation, but had no effect on HIF-1α mRNA expression. Meanwhile, Dau also remarkably suppressed VEGF expression at both protein and mRNA levels in response to IGF-I. Mechanistically, we found that Dau suppressed IGF-I-induced HIF-1α and VEGF protein expression mainly via blocking the activation of PI-3K/AKT/mTOR signaling pathway. Functionally, we found that Dau dramatically abrogated IGF-I-stimulated formation of capillary tube-like structures in vitro. Taken together, our results suggested that Dau may be a promising antiangiogenic agent for human breast cancer. Supported by National Natural Science Foundation of China (No. 30872944) and Guangdong Administration of Traditional Chinese Medicine (No.2008166).
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A2.
Abstract A20: Deacetylation of histone H3 at lysine 9 with ethanol in human colonic epithelial cells
Authors: Jang Hyeran , Moyer Mary , Choi Sang-Woon 
Published: May 2012

Abstract
A20
Epidemiologic observations have implicated chronic excess ethanol consumption as a risk factor for various cancers including colon cancer. Recent epigenetic studies demonstrated that ethanol causes selective acetylation of histone H3 at lysine 9 (H3K9) in the liver, lung, spleen and testes, indicating that ethanol may inhibit histone deacetylase activity, or enhance histone acetyltransferase activity in those tissues. We therefore investigated the effect of ethanol on histone H3 modifications in colonic epithelial cells. NCM460, human colonic epithelial cells were incubated with 100mM of ethanol for 24, 48, or 72 hr and then the acetylation and methylation states of histone H3K9 were measured by immunoblot analysis using site-specific antibodies. We found that ethanol decreased acetylation of histone H3K9 in a time-dependent manner (71, 21, 17%, respectively, P&lt;0.0001), while the histone deacetylase inhibitor, trichostatin A, which was used as a positive control, increased H3K9 acetylation. However, both ethanol and trichostatin A had little effect on histone H3K9 methylation. This is the first report of the colon-specific post-translational deacetylation of histone H3 with ethanol.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A20.
Abstract A24: Endothelial cell aging and possible role in angioprevention: increased expression of TGFβ and other antiangiogenic factors
Authors: Albini Adriana , Generoso Luca , Mirisola Valentina , Romeo Francesco , Pfeffer Ulrich 
Published: May 2012

Abstract
A24
Alterations of endothelium are associated with increased risk in cardiovascular diseases; they are also involved in tumor angiogenesis, one of the main “rate limiting step” in tumor progression and spreading. For this reason in the last years several agents have been patented for the cancer therapy thanks to their ability to inhibit tumor angiogenesis and now angiogenesis is considered also a target prevention.
Since senescence is considered an “anti-cancer” phenomenon we are evaluating the molecular changes that occur during aging in endothelial cells. We conducted this study on endothelial cells derived from Human Umbilical Vein (HUVECs) of ealry and late passages, fromboth masculin and feminin origin and we have analyzed the expression profile at different stages of in culture aging.
Several genes are regulated during this process; among these there is a significant reduction of the expression of genes such as E-selectin and CCL2 from cells of both male or female origin. This reduction could correlate with a decrease of the ability of endothelial cells to recruit inflammatory cells, and may have implications for metastatic spread of cancer. Angiopoietin 2 (ANG2) also seem to decrease during the endothelial cell senescence; this could be related to a potential impairment of the capacity to undergo remodeling in “aged” vessels. Interestingly, all three genes show a 2-fold higher expression in females as compared to males and the rate of decrease is different although the trend is the same. These data could suggest that there may be important gender-specific differences in gene expression of endothelial cells, and that these may have an effect on the senescence process.
Finally we have evidence that TGFβI, a molecule related to TGFβinduction, is increased with passages in culture and is very high in aged endothelial cells. Probably it could clarify the pro-apoptotic and antiangiogenic activity of TGFβ.
Taken together, these data confirm that physiological endothelial cell senescence could be associated with a reduction in anti-angiogenic potential; this property suggests that some tumors could be less angiogenic in the elderly.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A24.
Abstract A26: IL-1β dependent epithelial-mesenchymal transition in non-small cell lung cancer
Authors: Heinrich Eileen , Charuworn Burt , Dohadwala Miriam , Dubinett Steven 
Published: May 2012

Abstract
A26
Pulmonary diseases associated with a heightened risk of lung cancer, such as emphysema and pulmonary fibrosis, show both increased and deregulated inflammation. Tobacco smoke exposure is associated with chronic airway inflammation and is a strong risk factor for the development of lung cancer. Inflammatory mediators and inflammatory cells are over expressed in the pulmonary microenvironment of both smokers and patients with non-small cell lung cancer (NSCLC). Expression of interleukin 1β (IL-1β) is increased in a number of cancers, including lung cancer and is associated with tumor aggressiveness and poor patient outcomes. A chronic increase in inflammatory mediators in the lung tumor microenvironment can lead to increased tumor promotion, invasion, angiogenesis and metastasis; however the mechanism by which this occurs has yet to be elucidated.
We have found that IL-1β exposure leads to the down regulation of E-cadherin in NSCLC cell lines. Loss of E-cadherin is a hallmark of epithelial-mesenchymal transition (EMT) in which epithelial cells lose cell-cell junctions, undergo cytoskeletal reorganization and basement membrane degradation and switch from cadherin to integrin mediated adhesion. This transformation results in cells with a mesenchymal phenotype. An important feature of mesenchymal cells is their ability to migrate independently and invade locally - prerequisites for metastasis. Following IL-1β exposure we see, along with the loss of E-cadherin, changes in cellular morphology, down regulation of cytokeratin 18 and an up regulation of mesenchymal markers, particularly N-cadherin, vimentin and SNAI2 (Slug) - a transcriptional repressor of E-cadherin. Slug expression is increased at both the mRNA and protein levels and is found via chromatin immunoprecipitation to be bound to the E-cadherin promoter following IL-1β exposure. Further, in NSCLC cell lines which do not express E-cadherin, Slug expression is elevated. Blocking Slug expression using siRNA inhibits IL-1β mediated down regulation of E-cadherin
IL-1β has many well-characterized effects on signaling pathways and protein expression, including the up regulation of COX-2 which has been shown previously to decrease E-cadherin expression. However, the IL-1β mediated effects on E-cadherin expression are COX-2 independent. Blocking COX-2 activity with celecoxib does not abrogate the E-cadherin down regulation seen here. Additionally, others have found that loss of E-cadherin is associated with resistance to epidermal growth factor receptor tyrosine kinase inhibitors which are currently in use as treatment and have been suggested as prevention agents for NSCLC. Thus, the presence of inflammatory mediators in the pulmonary microenvironment may play a specific role in promoting resistance to targeted prevention and therapy.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A26.
Abstract A32: Proteomic signatures of deoxycholic acid and ursodeoxycholic acid treated human colon cancer cells
Authors: Nakanishi Masako , Menoret Antoine , Vella Anthony , Rosenberg Daniel 
Published: May 2012

Abstract
A32
Dietary factors play an important role in the pathogenesis of colorectal cancer (CRC), due in part to the influence of the bile acids. While the secondary bile acid, deoxycholic acid (DCA), has been associated with tumor promotion, one tertiary bile acid in particular, ursodeoxycholic acid (UDCA), has been demonstrated to exert chemopreventive properties in the colon. Although its efficacy against high-grade adenomas has already been demonstrated in phase III clinical trials, mechanisms by which UDCA suppresses colon tumorigenesis remain unclear. In order to gain further insight into the tumor modifying properties of the bile acids, we compared the effects of DCA and UDCA on human colon tumor cells (CaCo-2) using proteomic analyses. In the following study, CaCo-2 cells grown at 70% confluence were treated with either 10 µM deoxycholic acid (DCA) or 1 mM ursodeoxycholic acid (UDCA) for 72 hours. For the proteomic analysis, protein was first fractionated by PF2D isochromatofocusing on a Beckman Coulter ProteomeLab PF2D platform. Fractions corresponding to a linear gradient between pH 8.0 and 4.0 were collected and processed through an automated autoloader for further separation by HPRP-PF2D reverse phase chromatography. Two dimensional protein expression maps displaying isoelectric point (pI) versus hydrophobicity were generated by the ProteoView/DeltaVue software package. Pairwise analysis of these complex protein chromatograms demonstrated common peak profiles (signatures) as well as unique peaks (fingerprints) characteristic of UDCA or DCA treatment. One of these protein peaks that exhibited a differential expression pattern between the two drug treatments was identified by MALDI and tandem mass spectrometry sequencing as heat-shock protein 60 (Hsp60). Furthermore, this protein was found to be less oxidized upon treatment with UDCA, suggesting the attenuation of oxidative stress present in cancer cells. Further analyses on the role of Hsp60 as well as resultant diminished oxidative stress will enable the discovery of potential mechanisms by which DCA and UDCA control cellular pathways.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A32.
Abstract A36: Combinatorial attack on radiation-induced neoplastic transformation by phenylbutyrate: Involvement of Hsp90 molecular chaperone and histone deacetylase
Authors: Miller Alexandra 
Published: May 2012

Abstract
A36
Phenyl fatty acids like phenylacetate (PA) and phenylbutyrate (PB) have shown anti-cancer efficacy in clinical trials and in both in vitro and in vivo models. The mechanism of action of these agents is not fully understood however. In vitro studies have demonstrated that PB treatment induces apoptosis and growth rate effects in a time- and dose- dependent manner in the p21ras-expressing hematopoietic cells, Ras-DC and the human chronic myeloid leukemia blast crisis cells, (CML-BC) K562 cells. Both leukemia cell types are characterized by deregulated activity of the oncoprotein tyrosine kinase known as Bcr-Abl frequently observed in radiation-associated leukemias. Molecular studies are underway to characterize the effect of PB on Bcr-Abl expression in these leukemia cells since Bcr-Abl is a well known client protein for Hsp90. Furthermore, gene expression profile analysis of PB treatment of leukemia cells and human osteoblast cells (HOS) demonstrated that PB down-regulated Hsp90 suggesting that PB may affect molecular chaperoning. The anti-leukemic activity of PB was investigated using the cobalt radiation-induced neoplastic transformation model, HOS cells. HOS cells were exposed to a total of 2 Gy (60Co, 50 cGy/exposure) and transformed foci were formed within 35 days. Cellular incubation with PB either pre- or post-radiation significantly suppressed the radiation-induced transformation. Molecular studies also showed that PB induced acetylation of histones H3 and H4 and apoptosis in this cell model. A radiation leukemia rodent model is currently being employed to evaluate PB’s anti-leukemia efficacy. Although preliminary, these data suggest that PB involvement in both Hsp90 molecular chaperoning and inhibition of histone deacetylase is mechanistically related to its anti-leukemia efficacy.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A36.
Abstract A43: Hops (humulus lupulus) induce detoxification enzymes in vivo
Authors: Dietz Birgit , Hagos Ghenet , Guo Jian , Main Matthew , Lantvit Daniel , Farnsworth Norman , Pauli Guido , van Breemen Richard , Bolton Judy 
Published: May 2012

Abstract
A43
Extracts of hop strobiles, the female parts of Humulus lupulus L., are popular botanical dietary supplements as alternative treatment for menopausal symptoms (1). Cancer preventive properties of hops, which are in part mediated through the induction of detoxification enzymes, have frequently been reported (2). This effect has been mainly attributed to one of its major constituents, xanthohumol (XN) (3). However, the chemopreventive effects have so far only been demonstrated in vitro and have not been confirmed in vivo. Therefore, we conducted an in vivo study in adult female rats and analyzed the effect of oral administration of a standardized hop extract (7.5 g extract/kg BW per day, containing 2% XN) or s.c. injection of XN (20 mg/day) on detoxification enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase (GST). Analysis of various tissues revealed that while pure XN and oral hops significantly induced NQO1 activity in liver and colon tissue, only oral hops and not pure xanthohumol induced NQO1 activity in the uterus. Interestingly, hops but not xanthohumol significantly induced GST activity in the liver and mammary gland suggesting that other hop constituents and/or an additional mechanism might be responsible for these effects. Transcription of many detoxification enzymes is regulated through the antioxidant response element (ARE) and its transcription factor Nrf2, which is repressed under basal conditions by Keap1 (4). It has been shown that XN alkylates Keap1 and therefore enhances the concentration of free Nrf2 in the nucleus which results in ARE activation (5). Another pathway leading to ARE activation is mediated by protein kinase C (PKC) that phosphorylates Nrf2 leading to accumulation of Nrf2 in the nucleus (6). To investigate whether this pathway is involved in the observations described above, additional experiments with HepG2-ARE-luciferase C8 cells were performed. The cells were treated with hop extract or XN with or without the selective PKC inhbitor, Ro-32-0432, and the ARE-luciferase induction was determined. The results revealed that hops- but not XN-regulated ARE induction is in part mediated by PKC. Possible active compounds are under investigation. These results suggest that hop dietary supplements have the potential as preventive agents against cancer through induction of detoxifying enzymes.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A43.
Abstract A47: Drinking water with red beetroot food dye antagonizes esophageal carcinogenesis in NMBA-treated rats
Authors: Lechner John , Wang Li-Shu , Schwartz Steven , Stoner Gary 
Published: May 2012

Abstract
A47
This study was undertaken to determine if the oral consumption of red beetroot dye would result in an inhibition of N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus. Rats were treated with NMBA and given either regular water ad libitum or water containing 78 µg/ml of commercial red beetroot dye, E162. The number of NMBA-induced esophageal papillomas was reduced by 45% (p&lt;0.001) in animals that received the dye when compared to controls. Dye treatment also resulted in reduced rates of cell proliferation in both precancerous esophageal lesions and in papillomas of NMBA-treated rats, as measured by immunohistochemical staining of Ki-67 in esophageal tissue specimens. The effects of beetroot dye on angiogenesis (microvessel density by CD34 immunostaining), inflammation (by CD45 immunostaining), and apoptosis (by TUNEL staining) in esophageal tissue specimens were also determined. When compared to rats treated with NMBA only, the levels of angiogenesis and inflammation in the beetroot dye-consuming animals was reduced and the apoptotic rate was increased. Thus, the mechanism(s) of chemoprevention by the active constituents of red beetroot dye include reducing cell proliferation, angiogenesis and inflammation, and stimulating apoptosis. Importantly, consumption of the dye in the drinking water for a period of 35 weeks did not appear to induce any overt toxicity. Based on the fact that red beetroot dye contains betacyanins, which have strong anti-oxidant activity, it is postulated that these effects are mediated through inhibition of oxygen radical-induced signal transduction.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A47.
Abstract A58: Breast cancer risk estimates from the CARE and GAIL models among black women: Howard University Cancer Center experience
Authors: Adams-Campbell Lucile , Makambi Kepher , Frederick Wayne , McCaskill -Stevens Worta 
Published: May 2012

Abstract
A58
The Gail model has been used to predict invasive breast cancer risk in women using the following risk factors: age, age at menarche, age at first live birth, number of first degree relatives with breast cancer, and number of previous benign breast biopsy examinations. However, this model underestimates breast cancer risk in black women. The Contraceptive and Reproductive Experience (CARE) model has been developed to replace the Gail model in predicting breast cancer risk in black women. Using a sample of 883 black women who were screened for the STAR chemoprevention trial, we compared breast cancer risk estimates from the Gail and CARE models. The mean 5- year breast cancer risk was 0.88% for the Gail model and 1.29% for the CARE model. Using the usual cut-point of 1.67% or above for elevated risk, there is significant difference in the proportion of women with elevated breast cancer risk between the Gail and the CARE models (McNemar’s test, p &lt; 0.0001). Among those with a family history of breast cancer, the mean risk was 1.57% for the Gail model and 1.88% for the CARE model. For both models, there was a significant mean risk difference between those with and without a family history of breast cancer (Wilcoxon rank-sum test, p&lt;0.0001).

Conclusion
The CARE model is an improvement of the Gail model for estimating the risk of invasive breast cancer among black women and will improve counseling, risk assessment, prescribing of chemoprevention agents and eligibility for chemoprevention trials
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A58.
Abstract A61: Pilot study of difluoromethylornithine (DFMO) in patients with Barrett's esophagus and dysplasia
Authors: Sinicrope Frank , Broaddus Russell , Joshi Nina , Morlan Bruce , Kirsch Ilan , Gerner Eugene , Hong Waun 
Published: May 2012

Abstract
A61

Background
Patients with Barrett's esophagus (BE) and dysplasia are ideal candidates for chemopreventive strategies to reduce cancer risk. Difluoromethylornithine (DMFO) is a promising chemopreventive agent that inhibits polyamine synthesis involved in the regulation of cell growth and differentiation. We conducted a pilot study to examine the effects of DFMO on esophageal histopathology, mucosal polyamine content, and gene expression.

Materials and Methods
Patients (n=10) with histologically confirmed BE and low grade dysplasia were enrolled in a single-arm study of DFMO (0.5 g/m2/d) given continuously for 6 months. Esophagoscopy with biopsies (4 quadrants every 1 cm) was performed at baseline, 3 and 6 months, and at 12 months (where available). Grading of dysplasia was performed by a GI pathologist blinded to clinical/biomarker data. Audiology was also performed. Mucosal polyamine content was measured by high-performance liquid chromatography, and analyzed using paired t-tests. Gene expression profiling was performed using a cDNA two-color chip, and was compared between baseline and 6 months. Expression data was normalized using the two-channel fastlo routine and differential expression was computed using a Wilcoxon signed-rank test.

Results
After 6 months of DFMO treatment, histopathological response data demonstrate regression of dysplasia (n= 1), stable disease (n= 8), and progression of dysplasia (n= 1). Within the stable category, 2 patients with extensive low grade dysplasia showed only focal dysplasia based upon 4 or more biopsies at 6 months. Histolopathological improvements seen at 6 months were maintained at 12 months. Overall, DFMO was well tolerated. One patient had subclinical, unilateral ototoxicity. Modulation of polyamines (spermine, spermidine, putrescine, histamine) was shown only for putrescine which decreased with treatment (6 mo., p=0.07) and showed recovery to baseline at 12 months (p= 0.01). Gene expression profiling revealed modulated genes of potential biological importance (KLF5, KAL1, RFC5, TIMM8a, TC10) and of these, Krüppel-like factor 5 (KLF5) was downregulated whereas the others were upregulated.

Conclusion
&gt;Further study of the chemopreventive effect of DFMO upon BE with dysplasia is suggested. DFMO treatment suppressed mucosal putrescine levels and downregulated KLF5, an important mediator of cell proliferation.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A61.