bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2884: Standardized mangosteen fruit extract promotes cell cycle arrest and apoptosis of PC3 cells and inhibits tumor formation in athymic nude mice
Authors: Johnson Jeremy J. , Syed Deeba N. , Adhami Vaqar , Rasmussen John T. , Siddiqui Imtiaz A. , Mukhtar Hasan 
Published: February 2011

Abstract
The purple mangosteen fruit (Garcinia mangostana) is native to southeast Asia and has been reported to contain a variety of health promoting properties that include antioxidant, anti-inflammatory, anit-microbial and anti-diabetic properties. The principle constituents isolated from the mangosteen fruit are the xanthones with well over 50 unique entities isolated to date. Here we report on the properties of a mangosteen fruit extract for cancer chemoprevention and/or chemotherapy using prostate cancer (PCa) as a model disease. Using a mangosteen fruit extract (MFE) a significant decrease in cell viability was observed against four different prostate cancer cell lines (LNCaP, CWR22, PC3, DU145). Several analytical standards were used to identify dietary xanthones by HPLC with alpha-mangostin found to be the most abundant xanthone of MFE representing approximately 59% of the extract. Next, we investigated the ability of MFE to promote cell cycle arrest by flow cytometry and observed a significant increase in cells in G1 phase when treated with 7.5 μg/mL of MFE after 24 hours. Further confirmatory studies were performed by western blot analysis of PC3 cells treated with MFE. To understand the possible interaction between xanthones and cyclins/cdks in a cell free system a biochemical based assay was performed and found to inhibit cyclinD1/CDK4 as well as other kinases. To determine the potential of MFE in an in vivo model we investigated the ability of MFE to inhibit colony formation of CWR22 and PC3 cells. MFE was found to completely inhibit colony formation of CWR22 cells at a concentration of 5 µg/mL. Next, using an athymic nude mouse model implanted with CWR22 cells mice were randomized to receive intraperitoneally the standardized mangosteen fruit extract (MFE) or placebo two times weekly with tumors measured twice weekly until tumors reached a volume of 1200 mm3. At the conclusion of the study the treatment group had a significantly smaller tumor with an average tumor volume of (143 mm3) compared to the placebo group (1135 mm3) representing an 87.5% smaller tumor in the treatment group. Based on these promising results we have evidence suggesting that MFE may be a promising agent for the prevention and/or treatment of prostate cancer. Further studies are needed to determine the potential of purified dietary xanthones from the mangosteen fruit for cancer chemoprevention and chemotherapy.
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 2884.
Abstract 2885: Retinoic acid suppressed HEY cell-induced xenograft tumor possibly through reduction of CD133+ cancer stem cells
Authors: Li Zhong 
Published: February 2011

Abstract
Ovarian cancer is the most lethal gynecologic cancer with the higher recurrence. Increasing evidence indicates that cancer stem cells plays pivotal role in tumorigenesis and chemoresistance. Retinoic acid (RA), a synthetic derivative of vitamin A, has been used for treatment and chemoprevention of ovarian cancer. But it is not clear if RA affects ovarian cancer stem cells. In this paper, we found that all-trans retinoic acid (RA) treated ovarian cancer cell HEY resulted in the significant smaller xenograft tumor in SCID/NOD mice than untreated HEY cells. To understand if RA inhibition of tumor is involved in dysfunction of cancer stem cells, we detected cancer stem cells in HEY-induced tumors. CD133 positive cells in ovarian cancer were reported to have stem-like features. We found that RA-pretreated HEY cell-induced tumors had less of CD133 positive cells (3.0%) than RA-untreated ones (5.5%). To determine if RA affects status of CD133+ cells, we first cultured HEY cells in spheroid condition. HEY cells formed spheroid in suspend culture in which the percentage of CD133+ cells was increased in analyses by flow cytometry and histochemical staining. A single spheroid of Hey cells was peritoneally injected into mice and induced ovarian tumors. Consequently, treatment of RA in initiating spheroid culture attenuated HEY spheroid formation. In analyzing the molecular mechanism of RA in tumor suppression, we found that RA-treated HEY cells increased phosphorylated PTEN and level of p53 and CRABP II, and reduced expression of CD133 in Hey cells in early period (24-48h). PTEN, a tumor suppressor gene and a PI3K functional antagonist, is widely involved in normal and cancer cell proliferation, migration, drug resistance and stem cell maintenance. We further overexpressed PTEN in HEY cells that dramatically suppressed spheroid formation, suggesting that RA-induced early PTEN activation, increases of p53 and CRABP II may be involved in change of malignancy of HEY cells. These results demonstrate that RA treatment of ovarian cancer cells would alternate the cell features that compromise the change of Cd133+ positive stem-like cells which are important in tumorigenesis.
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 2885.
Abstract 290: PDZ protein PDZK1 associates with PTEN and inhibits PTEN phosphorylation
Authors: Zheng Junfang , Yang Longyan , Xiong Ying , Wang Ying , Hu Jia , Zhou Yunying , Zhang Hong , He Junqi 
Published: February 2011

Abstract
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumour suppressor is a lipid and protein phosphatase that inhibits phosphoinositide 3-kinase (PI3K)-dependent signaling by dephosphorylating phosphatidylinositol 3,4,5-trisphosphate (PtdInsP(3)). The carboxyl terminus (CT) of PTEN and PTEN post-translational modification by phosphorylation were reported to regulate PTEN signaling. However, the modes of regulation of PTEN signaling are not completely understood. The CT of PTEN has a typical PDZ domain-binding motif that interacts with several PDZ domain-containing proteins, which regulates PTEN signaling and function. To screen novel PTEN binding proteins, the PTEN CT was used to overlay against the lysates of rabbit tissue, including kidney, heart and brain. The molecular weight of positive band was similar with that of PDZ-domain containing 1 (PDZK1), a scaffolding protein. We further investigated this PTEN-associated protein by using GST pull-down in combination with mass spectrometry-based proteomics assays. PDZK1 was identified as one of the binding partners of PTEN. PTEN associated with PDZK1 via its PDZ domain 2 and 3, with binding affinity of 20 nM and 25 nM respectively, and the last four amino acids of the CT of PTEN were the key determinants of this interaction. Mutation of any one of the four amino acids to alanine abolished the association of PTEN with PDZK1-PDZ2, PDZK1-PDZ3 or PDZK1 full length, indicating that the PDZK1-PTEN association is stringent. Moreover, full-length PTEN was robustly associated with PDZK1, as determined by co-immunoprecipitation experiments in transiently transfected COS-7 cells, and mutation of the last amino acid valine to alanine also led to the abolishment of the interaction between PTEN full length and PDZK1. Immunofluorescence results showed that PTEN full length and PDZK1 can colocalize at cytoplasm of BHK cells. By interacting with PTEN, PDZK1 could inhibit the phosphorylation of PTEN and Akt activation induced by the stimulation of insulin in a dose-dependent manner, indicating PDZK1 can enhance the PTEN protein activity via their interaction. Taken together, these are the first results that present a interaction between PDZK1 and PTEN. PDZK1 interacts with PTEN to inhibit PTEN phosphorylation, leading to an increase in PTEN activity at inhibiting Akt activation. Our results suggest a regulatory role of PDZ domain binding on PTEN function by controlling its phosphorylation status.
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 290.
Abstract 2903: High grade dysplastic polyps: Does size matter
Authors: Tobi Martin , Easler Jeffrey , Antaki Fadi , Levi Edi , Rambus Mary Ann , Lawson Michael 
Published: February 2011

Abstract
Adenomas with high-grade dysplasia (HGD) are recognized to be harbingers of future neoplastic lesions and colonoscopy is repeated in a year. There is little data regarding the neoplastic potential of the colon bearing such lesions. We postulated that lesions &gt;1cm, in contrast to their smaller counterparts, would progress through an adenoma-carcinoma sequence. Conversely, smaller sized lesions might have a greater propensity for recurrence since there may be a priori more biological aggressiveness. Methods: We used the Adnab-9 monoclonal anti-adenoma risk marker to investigate high risk patients with HGD adenomas. Immunohistochemistry on normal-appearing colonic mucosa, ELISA of effluent acquired during colonoscopy and fecal Western blotting and ELISA, the stool collected prospectively was performed. Results: 23 patients with HGD adenomas, the majority found on the index colonoscopy were evaluated (table). A trend existed for increased NSAID intake in the large HGD group 5/7 (71%) compared to 2/7 (29%) in the small (p=0.28) and for increased numbers of metachronous adenomas in the small HGD group. More had symptoms in the large HGD group (67%) compared to 40% in small (NSS). No small HGD lesion was associated with a field effect (FE) in contrast to 100% in those patients with large lesion HGD (p&lt;0.01). Concurrence with location of FE with synchronous adenomas was 5/6 (83%) and 2/5 (40%) with metachronous polyps in those with large HGD (p=0.24).
Conclusions: Small HGD lesions appear to progress by pathways beyond the purview of the adenoma carcinoma sequence characterized by the significant lack of a field effect. They arise in a colon that may be destined for greater than usual risk for CRN even than that seen with larger HGD lesions. Larger prospective studies should be undertaken to confirm these preliminary findings and determine the tumorigenic pathway but in the interim surveillance for smaller lesions should not be limited to a single 1 year of follow-up.ParameterLarge HGDSmall HGDAll HGDN131023Age x±sd (years)65.5±10.064.7±8.765.2±9.3%Race AA53.93043.5BMI30.3±7.127.9±6.229.3±6.6%Left-sided76.97073.9%TA/TVA/VA69.2/23.1/7.760/40/063/32.7/4.3Size x±sd (mm)21.5±13.76.7±3.115.1±12.8Follow-up yrs3.6±2.15.3±2.7(p=0.15)4.2±2.4Synchronous adenomas1.8±3.3 6/14 46.2%1.4±1.5 5/10 50%1.5±2.7 11/24 45.8%Metachronous adenomas1.3±1; 7/10 70%2.1±2.34* 4/7 57% (p=0.6)1.3±1.7 11/17 64.7%%Ad-9 WB+12.528.620FecalAdnab-92/8 (25%)2/7(28.6%)4/15(26.7%)Effluent Elisa+4/9(44.4%)2/7(28.6%)p=.66/16(38%)%Field Effect6/6 (100)**0/5 (0%)6/11(55.5%)**OR 0.007:CI 0.0001-.415;p=0.0022; *p=0.3 Note: F/U time NSS
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 2903.
Abstract 2904: Lyophilized black raspberry extract modulates interleukin 8 expression in human cervical cancer: An insight into phytochemical-based chemoprevention?
Authors: Backes Floor J. , Zhang Zhaoxia , Seamon Leigh G. , Nagel Christa I. , Cohn David E. , Knobloch Thomas J. , Weghorst Christopher M. 
Published: February 2011

Abstract
Introduction
Cervical cancer is the 3rd most common cancer globally. The long latency from dysplasia to invasive cancer makes it amenable to prevention strategies. Phytochemicals, including those in lyophilized black raspberries (LBRs), are of great interest due to their growth inhibitory and anti-tumorigenic effects in preclinical models. Previously we showed that LBR extracts inhibited the proliferation of human cervical cancer cells in vitro in a dose- and time-dependent manner. Angiogenesis is an important part of carcinogenesis. We hypothesized that LBRs modulate the expression of an angiogenesis associated signaling cascade.
Methods
Human cervical cancer cells (SiHa) were treated with vehicle control (.02% DMSO) or LBR extract (200 µg/mL) for 1 or 3 days (d). Cells were harvested at 1d or 3d and RNA was extracted. Gene expression profiling was performed using a TaqMan Gene Signature Angiogenesis Array, which simultaneously screens 94 genes involved in angiogenesis. Genes demonstrating ≥2-fold change in expression following geNorm transformation were used for Ingenuity Pathway Analysis (IPA) network modeling. Biomarkers modulated in a manner favorable for cancer prevention were validated by real time RT-PCR.
Results
Short-term LBR exposure of SiHa cells in vitro resulted in inhibition of cell proliferation, and reduced expression of IL8 and MMP2 genes detected using the Angiogenesis Array. IPA network modeling predicted that MMP2 and NFkB would be part of the IL8 signaling cascade and this is supported in the literature. Validation with real time RT-PCR showed a 24-fold (1d) and 28-fold (3d) reduction in IL8 expression following LBR exposure. However, MMP2 and NFkB did not demonstrate a significant differential expression at either time point.
Conclusion
Short-term exposure of cervical cancer cells to LBR results in a striking reduction of IL8 gene expression. Although MMP2 and NFkB are associated with known IL8 signaling mechanisms, they are not modulated by LBR extract in this in vitro model. Therefore, the growth inhibitory activity and transcriptional repression of IL8 following LBR extract exposure proceed via an MMP2-NFkB-independent cascade. Other signaling mechanisms within the IL8 signaling cascade (HIF, AP1, STAT3) may be involved and will be further explored. Since IL8 plays an important role in tumor growth, metastasis, and angiogenesis, it supports the potential for phytonutrient-based chemoprevention of cervical 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 2904.
Abstract 2906: Curcumin reduces aberrant crypt foci (ACF) number but does not alter prostaglandin E2 (PGE2) or 5-hydroxyeicosanopentaneic acid (5-HETE) concentration in ACF or in normal human colorectal mucosa
Authors: Carroll Robert E. , Turgeon D K. , Vareed Shaiju , Kakarala Madhuri , Tuck Melissa , McLarin Chrisitne , Benya Richard V. , Meyskens Frank , Brenner Dean E. 
Published: February 2011

Abstract
Curcumin, a dietary polyphenol derivative of turmeric, has potent cancer preventive activity in in vivo colon carcinogenesis models. To determine whether curcumin has pharmacodynamic effects on the human colon, we administered curcumin at doses of 2 g or 4 g to separate groups of 20 healthy human smokers who had 8 or more aberrant crypt foci on screening colonoscopy. We removed 3 aberrant crypt foci and 4 flat mucosal biopsies under magnifying endoscopy prior to and after 28 days of daily curcumin dosing. We enrolled 41 subjects (66% African Americans, 27% Caucasian, mean age 55+/−6.5 years). PGE2 and 5-HETE concentrations on tissue biopsies (assayed with liquid chromatography tandem mass spectroscopy) are shown in the Table.
Curcumin concentrations assayed by HPLC in the colonic mucosa were undetectable (&lt;10μg/gm tissue weight) while curcumin conjugate conjuges were detected in the majority of post treatment tissue samples. Curcumin does not reduce PGE2 or 5-HETE in colorectal mucosa after 28 days of administration. A daily dose of 4 g reduces ACF in colorectal mucosa. These data suggest that curcumin may reduce carcinogenesis in human colorectal mucosa but not via inhibition of arachidonic acid metabolism.‡pg/μg protein mean±SD ‡ mean±SEM p&lt;0.05 PGE-2 ACFPGE-2Nl5-HETE ACF5-HETE NlACFPre-Treatment-2g1.2±1.8‡2.1±3.21.4±0.92.3±1.315.7±1.3Post-Treatment-2g1.6±1.82.8±3.71.4±1.02.4±1.215.0±1.5Pre-Treatment-4g3.4±4.82.7±1.92.3±1.32.4±1.517.8±2.0Post-Treatment-4g3.7±3.22.6±2.92.4±1.22.2±1.611.1±2.8†
(Support: NCI N01-35610, F. Meyskens PI Univ California Irvine)
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 2906.
Abstract 2912: F-box protein 10: A novel NF-κB–dependent antiapoptotic protein regulates TRAIL-induced apoptosis
Authors: Ge Rongbin , Wang Zongwei , Zeng Qing , Xu Xiaoyin , Olumi Aria F. 
Published: February 2011

Abstract
Introduction and Objective
Tumor necrosis factor-related apoptosis—inducing ligand (TRAIL) induces selective apoptotic death of human cancer cells while sparing normal human cells. Although TRAIL holds great promise as a potential anti—cancer agent, some tumors develop resistance to TRAIL. Previously, we have shown that the AP—1 family member, c—Fos, is an important modulator of apoptosis. Although FBXL10 has been implicated to regulate an AP—1 family protein, c—Jun, its role in mediating apoptotic pathways has not been previously investigated. Here, we report that FBXL10 is a novel NF—kB dependent anti—apoptotic molecule, which directly binds and represses c—Fos, another AP—1 family member, rather than c—Jun. Repression of c—Fos leads to resistance of cancer cells to TRAIL—induced apoptosis.
Methods
RT—PCR, Western blot and immunofluorescence assays were applied to evaluate protein expression level. RNAi, Chromatin immunoprecipitation (ChIP), EMSA, hydrodynamic—based transfection, oligonucleotide decoy technologies, plasmid reconstruction and site—directed mutation were performed to analyze the interaction between FBXL10, c—Fos and NF—kB. Orthotopic prostate xenografts were carried out for in—vivo analyses.
Results
FBXL10 was suppressed and c—Fos was upregulated in TRAIL sensitive cancer cells and xenografts after treatment with TRAIL. However, in TRAIL resistant cancer cells and xenografts, FBXL10 and c—Fos were not affected. Expression of FBXL11, a FBXL10 homologous protein and c—Jun, was not affected by TRAIL. Silencing of FBXL10 sensitized resistant cells to TRAIL. Conversely, over—expression of FBXL10 repressed TRAIL—induced apoptosis. To behave as an anti—apoptotic molecule, we found that FBXL10 directly binds and represses c—Fos promoter in vitro and in vivo. In addition, FBXL10 regulates c—FLIP, another anti—apoptotic molecule, by a c—Fos dependent pathway. We also found that expression of FBXL10 is NF—kB—dependent, and TRAIL or proteasome inhibitors down—regulate FBXL10 via inhibiting NF—kB signaling. Using ChIP and EMSA assays, we found that NF—kB—p65 directly binds the FBXL10 promoter in vivo and in vitro, and promotes expression of FBXL10.
Conclusions
Differentiating molecular mechanisms between TRAIL sensitive and TRAIL resistant cancer cells will improve the efficacy of apoptotic therapies for cancer patients. In this study, we demonstrates for the first time, that FBXL10 plays an anti—apoptotic role and indicates a novel NF—kB/FBXL10/c—Fos/c—FLIP signaling pathway in TRAIL—mediated apoptosis.
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 2912.
Abstract 2921: Antitumorigenic effects by ERβ in three different human colorectal cancer cell lines
Authors: Edvardsson Karin , Strom Anders , Gustafsson Jan-Ake , Williams Cecilia 
Published: February 2011

Abstract
The estrogen receptor beta (ERβ) is the predominant ER in the human colonic epithelium. Levels of ERβ are reduced in colorectal cancer compared to normal colon tissue. In a previous study, we generated ERβ-expressing colon cancer cells and showed that ERβ inhibits proliferation as well as colon cancer xenograft growth, as a consequence of ERβ mediated inhibition of cell-cycle pathways.
The present study was conducted to investigate genome wide changes by ERβ in three human colon cancer cell lines (SW480, HT29 and HCT116). They have very low or no levels of ERβ expression and were transduced with lentivirus containing an ERβ expression cassette. Microarray studies showed that ERβ regulated 623, 643 and 124 genes for SW480, HT29 and HCT116, respectively.
Comparisons showed few genes in common for the three cell lines. However, over representation analysis showed that several themes, such as cell proliferation, cell communication and apoptosis were regulated in all of the cell lines.
By comparing our results with those from a ChIP-on-Chip assay in breast cancer cells, we found that a considerable proportion of regulated genes had an ERβ binding site nearby or within the gene.
Our preliminary conclusion is that ERβ appears to, at the gene expression level, have related anti-tumorigenic effects in different colon tumor cells, but different genes may be regulated in different cells types. Furthermore, the fact that several of the regulated genes possessed an ERβ DNA binding region nearby or within the gene indicates a direct regulation for many 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 2921.