bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B71: Phellodendron bioactive molecule (PBM): A potential natural agent for prevention of colon cancer
Authors: Chidambara Murthy Kotamballi N. , Kumar Addanki Pratap , Jayaprakasha G. K. , Patil Bhimanagouda S. 
Published: May 2012

Abstract
PBM is a yellow colored compound isolated from extracts of Phellodendron species. In the current study, PBM was subjected to understand the effect on colon cancer using human cancer cell lines. The activity was studied using three cancer cells having different degree if malignancy induction namely, SW-480, HT-29 and Caco-2 cells. The colon fibroblast (112CoN) cells, which are non cancerous were used to understand the toxicity of compound. The cell viability assay of PBM demonstrated both dose and time dependent activity in all the cells. This naturally occurring compound was found be effective after 24 h of treatment (IC50 value at 12 h was more than 75 µM) showing minimum IC50 against SW-480, which was 24, 16 and 5 µM at 24, 48 and 72 h, respectively. The IC50 was in the range of 42–50 µM for HT-29 cells and 18–53 µM for Caco-2 cells. Furthermore, the toxicity to normal cell was not significant indicating the non-toxicity compound at 100 µM in the model. Treatment at 10 µM has shown induction of aneuploidy (35±2% of cells) in SW-480 cells and treatment at 25 and 10 µM has increased accumulation of cells in G0/G1 phase. Protein expression results suggest that, PBM is capable of inhibiting cancer through inducing caspases dependant apoptosis in case of SW-480 cells. The inhibition was also found to be through inhibiting inflammatory proteins. Both the apoptosis and anti-inflammatory activity were higher at 48 and 72 h of treatment. Result of the current study provides an evidence for inhibition of colon cancer by PBM through multiple targets such as cell cycle arrest, apoptosis and inhibition of inflammation. In summary, PBM may be an ideal compound to be considered for in vivo studies to explore its application in colon cancer prevention. This project is based upon work supported by the USDA-CSREES # 2009-34402-19831 “Designing Foods for Health” through the Vegetable and Fruit Improvement Center.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B71.
Abstract B74: Phenethyl isothiocyanate and 4-phenylbutyl isothiocyanate inhibit the proliferation and viability of human renal carcinoma cells in vitro
Authors: Khan Maruf , Ciolino Henry 
Published: May 2012

Abstract
Epidemiological studies have demonstrated a protective association between dietary intake of cruciferous vegetables and the incidence of renal cell carcinoma. Isothiocyanates (ITCs) are a class of sulfur-containing phytochemicals found uniquely and abundantly in cruciferous vegetables (broccoli, cauliflower, brussel sprouts, etc). We hypothesize that the inhibition of renal carcinoma cell growth and viability by ITCs underlies the protective effect of cruciferous vegetables on renal cell carcinoma. To test this hypothesis, we examined the effects of two ITCs: the naturally-occurring phenethyl ITC (PEITC) and the synthetic 4-phenylbutyl ITC (PBITC) on the Caki-1 human renal carcinoma cell line. Both PEITC and PBITC inhibited the proliferation of Caki-1 cells in a concentration-dependent manner. Cell cycle analysis revealed that PEITC and PBITC caused an arrest in the G2/M phase. Additionally, higher concentrations of PEITC and PBITC were cytotoxic to Caki-1 cells (IC50 of 7.0 and 4.8 µM, respectively). PEITC and PBITC induced caspase-3/7 activity in a concentration- and time-dependent manner, indicating that the ITCs induce apoptosis in the cells. These results indicate that PEITC and PBITC may be efficacious against renal cell carcinoma and suggest that the preventive effect of diets rich in cruciferous vegetables is due to their ITC content.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B74.
Abstract B77: Pomegranate extract inhibits MMTV-Wnt-1 mammary tumor cell growth and induces apoptosis in vitro
Authors: Dai Zhaoli , Nair Vidhya , Khan Maruf , Ciolino Henry P. 
Published: May 2012

Abstract
In this study we report the effects of a standardized pomegranate extract (PE), as well as individual phytochemicals derived from pomegranate, on the growth of an aggressive, fast-growing mammary tumor cell line derived from the MMTV-Wnt-1 mouse (designated A4). PE caused a concentration- and time-ependent decrease in A4 cell proliferation (IC50 of approximately 25 microg/ml culture medium). PE also caused a concentration-dependent increase in cell death, with an IC50 of 50 microg/ml culture medium. PE caused an increase in caspase-3 activity in a concentration- and time-dependent manner. We also examined the effect of individual phytochemicals present in PE. Ellagic acid, luteolin, and ursolic acid inhibited the proliferation of A4 cells and induced cell death, but caffeic acid had no effect. These results indicate that PE and pomegranate phytochemicals inhibit the growth and are cytotoxic to MMTV-Wnt-1 mammary tumor cells. PE may therefore be natural and safe chemopreventive agent against breast cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B77.
Abstract B78: In vitro cytotoxic and antiproliferative activitiess of marine macroalgae from Yucatan, Mexico
Authors: Moo-Puc Rosa E. , Robledo Daniel , Freile-Pelegrin Yolanda 
Published: May 2012

Abstract
Extracts from 27 marine algal species (14 Rhodophyta, 5 Phaeophyta and 8 Chlorophyta) from the Yucatan peninsula (Mexico) were evaluated for cytotoxic and anti-roliferative activity by 3[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays, respectively. In order to determine the specificity of the cytotoxic activity on tumor cells selective index (SI) was also calculated. The following cancer cell lines were employed: normal canine kidney cells (MDCK), human laryngeal carcinoma (Hep-2), human cervix adenocarcinoma (HeLa) and human nasopharynx carcinoma (KB). The results indicated that 44 and 51% of algal species tested showed cytotoxic and anti-roliferative activity, respectively. Most of the cytotoxic extracts were species belong to Chlorophyta, Udotea flabellum and Udotea conglutinate showed the highest cytotoxic activity on all cancer cell lines. For Rhodophyta, the extract of Bryothamnion triquetrum showed an outstanding selective cytotoxicity against Hep-2 cells (CC50 8.29 µg mL−1 with SI=12.04). Two out of five species of Phaeophyta tested (Lobophora variegata and Dictyota caribaea) showed high cytotoxicity activity on KB cell line. The data show that these extracts are potential source of compounds for prevention of certain cancer diseases.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B78.
Abstract B79: Xanthohumol from hops (Humulus lupulus L.) is a novel antiandrogen
Authors: Strathmann Julia , Diel Patrick , Laudenbacher-Leschowsky Ute , Zierau Oliver , Mikros Emmanuel , Lamprinidis Giorgos , Gerhauser Clarissa 
Published: May 2012

Abstract
Xanthohumol (XN), a prenylated chalcone from hops, possesses a broad spectrum of chemopreventive actions, including anti-inflammatory, antioxidant, and anti-estrogenic mechanisms, and inhibits tumor growth in vitro and in vivo.
This study aimed to investigate the anti-androgenic potential of XN with regard to prostate carcinogenesis. In hormone-depleted, androgen-sensitive LNCaP human prostate cancer cells, XN at a concentration of 10 µM inhibited prostate specific antigen (PSA) secretion induced by 25 nM dihydrotestosterone (DHT) by more than 90% (p&lt;0.001) after 24, 48 and 72 h of incubation. In a concentration range of 0.4 to 50 µM, XN dose-dependently inhibited PSA secretion (p&lt;0.001) with a halfmaximal inhibitory concentration of 3.1 ± 0.32 µM after 48 h of incubation. Also, DHT-PSA-and insulin like growth factor (IGF-1) mRNA expression was dose-dependently inhibited by increasing XN concentrations (p&lt;0.05), measured by quantitative RT-PCR. Western Blot analyses of cytosolic and nuclear protein lysates revealed that XN inhibited DHT-induced nuclear translocation of the androgen receptor (AR). Furthermore, in a yeast AR assay, XN inhibited AR-transcription at concentrations of 10 to 100 µM. Docking calculations of XN to the AR indicate steric interactions between the prenyl moiety of XN and Trp741, which could destabilize the AR C-terminal helix 12 and thus further explain the antagonist activity of XN.
To investigate anti-androgenic action of XN in vivo, a Hershberger assay with male orchiectomizedWistar rats was performed. Prostate and seminal vesicle weight gain was stimulated by subcutaneous application of 0.2 mg/kg body weight (bw) testosterone propionate (TP). After 12 days, no significant inhibitory effects of oral XN (10 and 30 mg/kg bw) on prostate weights was observed, whereas the anti-androgen flutamide used as a positive control inhibited the 1.2-fold induction of prostate weights by 78% (p&lt;0.001). However, seminal vesicle weight gain induced by TP was significantly reduced by 56 and 29% by XN treatment (10 and 30 mg/kg bw), respectively, and by 92% by flutamide application. Quantitative RT-PCR analyses of prostate RNA confirmed the anti-androgenic effects of XN in vivo. XN and flutamide significantly reduced the expression of androgen-dependent target genes PSA, AR, IGF-1, prostate binding protein C3, myostatin and tyrosine aminotransferase (p&lt;0.05).
Taken together, in the present study XN was identified as a potent novel anti-androgen, which might be of use for future prostate cancer prevention trials.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B79.
Abstract B80: Role for sphingosine kinase 1 in colon carcinogenesis
Authors: Kawamori Toshihiko , Furuya Hideki , Wada Masayuki , Bielawski Jacek , Hannun Yusuf A. , Obeid Lina M. 
Published: May 2012

Abstract
Colorectal cancer remains the 2nd leading cause of cancer-related deaths in the US despite recent advances in screening and therapeutic technology. Recent studies suggest that bioactive sphingolipids are key in regulating the arachidonic acid cascade of inflammation, which is significant in colon cancer pathogenesis. Sphingolipid metabolites such as ceramide, sphingosine, and sphingosine-1-phosphate (S1P) are a new class of lipid messengers that regulate cell functions. Sphingosine kinase 1 (SphK1), phosphorylates sphingosine to form S1P, is a critical regulator of sphingolipid-mediated functions, as it not only produces the pro-growth, anti-apoptotic messenger S1P, but also decreases pro-apoptotic ceramide and sphingosine. Our previous studies implicated the SphK1/S1P pathway in induction of the arachidonic acid cascade, a major inflammatory pathway involved in colon carcinogenesis (FASEB J., 20: 386–388, 2006). Then, we investigated whether the SphK1/S1P pathway is necessary for mediating carcinogenesis in vivo. We report that 89% (n=47) of human colon cancer samples stained positively for SphK1 whereas normal colon mucosa had negative or weak staining. Adenomas had higher SphK1 expression versus normal mucosa, and metastatic colon cancers had higher SphK1 expression than those without metastases. In an azoxymethane (AOM) murine model of colon cancer, SphK1 and S1P were significantly elevated in colon cancer tissues compared to normal mucosa. Moreover, blood levels of S1P were higher in mice with colon cancers than in those without cancers. Importantly, SphK1−/− mice subjected to AOM had significantly less aberrant crypt foci (ACF) formation and significantly reduced colon cancer development. These results suggest that the SphK1/S1P pathway contributes to colon carcinogenesis and that inhibition of this pathway is a potential target for chemoprevention. In this paper, we discuss more details of the role of the SphK1/S1P pathway in colon carcinogenesis and the effects of SphK1 inhibition in cardiovascular risk.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B80.
Abstract B82: The TASK2 potassium ion channel is differentially expressed in ER-negative breast cancer
Authors: Shen Qiang , Brown Powel 
Published: May 2012

Abstract
Current use of selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene, and aromatase inhibitors has reduced breast cancer incidence in high-risk women to develop ER-positive breast cancer. However, a significant portion of ER-positive and all ER-negative breast cancers (both count for ∼60% of all breast cancer) are not prevented with these preventive drugs. Thus, new targets and more effective agents for the prevention of ER-positive and especially ER-negative breast cancer are urgently needed. Ion channels are specific cellular membrane proteins that transport inorganic ions in and out of cells to maintain membrane integrity, cell polarity and cellular homeostasis and may therefore play critical role in transforming normal epithelial cells into malignant cells. The ion channels for transporting Na+, Ca2+, and K+ ions are deregulated in many cancer types including breast cancer. Potassium ion channels are essential in non-excitable cells for regulation of cell volume, secretion of ions and hormones, and are required for maintaining cellular homeostasis. A number of potassium channels such as TASKs, GIRK1, Kca1.1, Kv1.1 and Kv1.3 are differentially expressed in normal breast tissue and breast cancer tissues. We hypothesized that TASKs may be involved in the development of ER-negative breast cancer. We first examined the public microarray databases which contain the mRNA expression profiles from multiple series of human breast cancer samples (http://www.oncomine.org). Transcription of the majority of ion channels for sodium, potassium and calcium were compared in intra-database and inter-database manners. Most of the ion channels show insignificant variations comparing ER-positive versus ER-negative breast cancers. However, TASK2 of the TASKs potassium ion channel family is overexpressed in human breast carcinomas but not in normal mammary gland tissue in three studies. Furthermore, TASK2 is significantly up-regulated in ER-negative vs ER-positive breast cancers in two studies. We then examined expression of TASK2 protein among breast cancer cell lines. TASK2 protein level was undetectable in four ER-positive breast cancer cell lines, while medium/high expression in majority of ER-negative breast cancer cells (all Basal A and Basal B subtypes). We are now investigating the phenotypic alterations in normal and malignant breast cells after overexpressing or knocking down TASK2 gene. Current results suggest that TASK2 may play a role in malignant transformation of breast cells into ER-negative breast cancer cells and maintenance of an ER-negative phenotype. Thus, TASK2 is a potential novel target for future preventive intervention of breast cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B82.
Abstract B86: JS-K, a nitric oxide-donating prodrug, modulates β-catenin/TCF signaling in leukemic Jurkat cells through S-nitrosylation
Authors: Chattopadhyay Mitali , Goswami Satindra , Nath Niharika , Rodes Deborah B. , Saavedra Joseph E. , Keefer Larry K. , Kashfi Khosrow 
Published: May 2012

Abstract
Introduction: Leukemia is the most common form of cancer in children and acute lymphoblastic leukemia (ALL) is the primary cause of cancer-related mortality. The deregulation of theWnt signaling cascade and its components has been implicated in T-cell ALL as well as in B-cell chronic lymphocytic leukemia (CLL). The protein β-catenin has a central role in Wnt signaling pathway and may promote leukemia cell proliferation and differentiation. β-catenin is expressed in T- ALL cells, tumor lines of hematopoietic origin and primary leukemia cells but is undetectable in normal peripheral blood T cells. Among the leukemic cell lines, β-catenin is expressed in high levels in Jurkat T-cells. JS-K [O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1yl]diazen-1-ium-1,2-diolate] is a prodrug of the diazeniumdiolate class that releases NO through a reaction catalyzed by GST utilizing glutathione. This agent has been shown to inhibit the growth of various cancer cell lines. This report highlights the effects of JSK on the growth properties of human Jurkat T-acute lymphoblastic leukemia cells, the β-catenin signaling pathway, and protein S-nitrosylation.
Methods: JS-K: synthesized by us. Cell growth: MTT; cell cycle phase distribution: flow cytometry; apoptosis: subdiploid (sub-G0/G1) peak in DNA content histograms. Transient transfection: luciferase reporter constructs TOPflash or FOPflash. Luciferase activity: kit per manufacturer's instructions. Protein S-nitrosylation: Biotin switch assay (Jaffrey et al, Nature Cell Biology, 2001, 3, 193–197); β-catenin and biotinylated protein levels: immunoblotting.
Results: JS-K inhibited the growth of Jurkat cells, IC50s of 12 ± 3 µM and 7 ± 1 µM at 24 h and 48 hr, respectively. This effect was due, in part, to a dose-dependent induction of apoptosis and alterations in the distribution of the cells in the cell cycle, arrest was in G0/G1. JS-K dose-dependently inhibited β-catenin/TCF-4 signaling by reporter assays, and reduced β-catenin levels in the nucleus and cytoplasm. JS-K treatment for 24 hr at 0.5 × IC50, 1 × IC50 and 2 × IC50 caused an increase in total S-nitrosylated proteins and also caused a reduction in S-nitrosylated β-catenin expression. These effects were reversed by carboxy-PTIO (an NO scavenger).
Conclusions: These findings establish a strong inhibitory effect of JS-K in human Jurkat T-acute lymphoblastic leukemia cells, an effect that is through inhibition of Wnt/β-catenin/TCF-4 signaling and through induction of apoptosis modulated by protein S-nitrosylation.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B86.
Abstract B88: Local delivery of breast cancer chemopreventives using mesenchymal stem cells
Authors: Greene Amy , Parke Donna , Gingery Anne , Zhdankin Olga , Skildum Andrew , Holy Jon , Perkins Edward , Rose-Hellekant Teresa A. 
Published: May 2012

Abstract
The overall goal of this study is to evaluate the ability of bone marrow mesenchymal stem cells (MSCs) to act as vehicles for local delivery of chemopreventives in mice that develop mammary cancer. Recently, efforts to use adult-derived stem cells to deliver therapeutic agents to tumor sites have shown great promise and we currently are extending this concept to include the delivery of gene therapy in the form of chemopreventives. Our goals in this initial project were to (1) isolate and study the behavior of transplanted MSCs in mammary glands of mice and (2) develop a gene expression system which robustly produces gene therapeutics. For gene therapy we aimed to target epidermal growth factor (EGFR/ErbB1/HER1) because activation of this growth factor pathway is a frequent component driving breast cancer proliferation and survival and recent evidence demonstrated that the EGFR pathway is more active in hyperplastic enlarged lobules compared with normal terminal ductal lobular units (AJP 2007 171, 253–262), indicating that EGFR activation is a very early event that precedes cancer development and therefore inhibiting EGFR may abrogate cancer development. To carry out this goal we developed an expression system that produces the natural inhibitory ligand of EGFR, decorin. Decorin is a small leucine rich proteoglycan with known effects in extracellular matrix assembly as well as growth inhibition via reduction in levels and activity of EGFR along with other signaling molecules. Thus far we have demonstrated the ability to isolate, culture and maintain murine MSCs from the FVB/N strain in an undifferentiated state. In addition, these MSCS do not form tumors upon transplantation into mammary glands of syngeneic mice. Furthermore, we have produced secreted decorin in Chinese hamster ovarian cells and MSCs. Finally, we demonstrate the ability of conditioned media containing decorin to inhibit mammary tumor cell proliferation in vitro. Our long-term goal is to test the efficacy of decorin-engineered MSCs as a breast cancer prevention modality in mouse models.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B88.
Abstract B9: Geographic disparity in HPV vaccination among girls in six U.S. states
Authors: Pruitt Sandi L. , Schootman Mario 
Published: May 2012

Abstract
Introduction: The human papillomavirus (HPV) vaccine was approved by the Food and Drug Administration in 2006. Since that time, limited research has examined HPV vaccine uptake among adolescent females and no studies have examined the role of disparities in HPV vaccination. The purpose of this study is to examine geographic disparity in the prevalence of HPV vaccination and to examine individual-, county-, and state-level correlates of vaccination.
Methods: Three-level random intercept logistic regression models were fitted to data from 1,709 girls aged 13–17 living in 6 U.S. states using 2008 Behavioral Risk Factor Surveillance System and 2000 U.S. Census data.
Results: Overall, 34.4% of girls were vaccinated. Significant geographical disparity across states (Var: 0.134 SE: 0.065) and counties (Var: 0.146 SE: 0.063) was present, which was partially explained by state- and county-level poverty rates. Independent of individual-level factors, poverty had differing effects at the state- and county-level: girls in higher poverty states were less likely while girls in higher poverty counties were more likely to be vaccinated. Household income demonstrated a similar pattern to that of county-level poverty: compared to girls in the highest income families, girls in the lowest income families were more likely to be vaccinated.
Conclusions: The results of this study suggest geographic disparity in HPV vaccination and area-level effects of poverty that have not previously been studied. The higher odds of vaccination among girls living in higher poverty counties and low income families may indicate the success of publicly-funded vaccination efforts targeting the underserved or a bias against vaccination among higher income groups. Overall vaccination rates continue to be sub-optimal however, and future research is needed to examine the impact of state- and local-area policies and to increase vaccination among eligible girls.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B9.