bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2869: Chemopreventive efficacy and mechanism of licofelone in mouse lung tumor model
Authors: Lee Jin 
Published: February 2011

Abstract
Our previous study comparing inhalation and aspiration methods of administration of an agent to lung airway epithelia indicated that aspiration can be an equally effective route of exposure while reducing the need for inhalation equipment and amount of chemopreventive agent required. The current study evaluated the chemopreventive efficacy and mechanism of Licofelone, a dual inhibitor of cyclooxygenase-2 (Cox-2) and 5-lipoxygenase (5-Lox), against the strain A/J mouse lung adenoma induced by benzo[a]pyrene (B[a]P). The Licofelone was administered to the lung via oropharyngeal aspiration. Lung adenomas were induced in 8-wk old female strain A/J mice by three oral gavages of B[a]P (2 mg /0.2 ml cotton seed oil). The mice were left for 4 weeks to develop dysplasia, then given one of three doses of Licofelone (0.03, 0.1 and 0.3 mg/kg) for 16 weeks. At different time points, the expression of a series of biomarkers (e.g., Cox-2 and 5-Lox at 2 weeks, survivin, PCNA and apoptosis at 16 weeks) in lung was evaluated by Western Blot and immunohistochemistry. Tumor incidence and multiplicity in the lung were measured following 16-week aspiration of Licofelone and compared with B[a] P only group. The data showed that Licofelone inhibited Cox-2 (26-42%) and 5-Lox (43-61%) in a dose-dependent manner at 2 weeks. Both survivin (16-25%) and PCNA (41-61%) were also inhibited in a dose-dependent manner. There was a 2.4 fold induction of apoptosis at 0.3 mg/kg when compared to the B[a] P only group. Licofelone showed significant dose-related inhibition of B[a]P-induced tumor incidence (p = &lt;0.05) and multiplicity at 0.03 and 0.1 mg/kg following 16-week treatment. In conclusion, this study demonstrated that Licofelone administered by aspiration showed chemopreventive efficacy against mouse lung adenoma with good correlation to early and late biomarkers of lung cancer progression. Also, it showed that the aspiration route can be an excellent alternative to inhalation for direct delivery of drugs to the rodent lung. (Supported by NCI #N01-CN-53301).
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 2869.
Abstract 2871: Pharmacokinetics studies of anticancer gallotannin penta-O-galloyl-beta-D-glucose (PGG) in mice
Authors: Li Li , Zhang Jinhui , Shaik Ahamd , Nhkata Katai , Xing Chengguo , Lü Junxuan 
Published: February 2011

Abstract
Studies by our group and others have shown that 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose (PGG) exhibits in vivo anti-cancer effects against prostate and breast cancer xenograft or lung cancer allograft when administrated by i.p injection or oral gavage. PGG has also been shown in several studies to exhibit anti-diabetic activities both in vitro and in vivo. However, no data have been published on the absorption, distribution, metabolism and elimination (ADME) to provide mechanistic correlates to account for the biological activities. In this study, we developed a method for the analysis of PGG in mouse plasma, using tea polyphenol epigallocatechin gallate (EGCG) as an internal standard (IS). A liquid-liquid extraction (LLE) protocol originally developed for tea polyphenol analyses was optimized for the extraction of PGG from mouse plasma. In brief, plasma (0.2 ml) was acidified with an equal volume of 2% acetic acid, and ethyl acetate was then applied to extract PGG and EGCG (IS). After LLE, PGG was quantitated by HPLC with a UV detection at 280 nm. The method was validated according to FDA guidelines. The extraction efficiency for spiked PGG was ∼70 % in mouse plasma. The limit of detection (LOD) for PGG was approximately 100 ng/ml and the limit of quantitation (LOQ) around 200 ng/ml when using 200 µl mouse plasma. The linear range of the method was 0.2 −25 µg/ml in mouse plasma.
Pharmacokinetics of PGG following a single i.p. injection in mice was studied. The peak plasma PGG concentrations (Cmax) were found to be approximately 4 and 11 µM at administered dose of 20 and 80 mg/kg of PGG, respectively. The apparent half life of the elimination phase for PGG is 3 h. Addition of glucuronidase and sulfatase to plasma did not change extractable PGG. These data suggest that PGG exists in plasma mostly as free extractable form after a single i.p. injection and that the plasma resident time for PGG is several hours.
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 2871.
Abstract 2875: Regulation of gene expression by sphingosine in a mouse cell model of ovarian cancer progression
Authors: Creekmore Amy L. , Schmelz Eva M. , Roberts P. C. 
Published: February 2011

Abstract
Approximately 90% of ovarian cancers are derived from the surface epithelium of the ovary. To study and further understand the early events that lead to epithelial ovarian cancer, we previously developed the syngeneic mouse ovarian surface epithelial (MOSE) model; MOSE cells have undergone spontaneous transformation in cell culture and were categorized into distinct stages by their phenotype, with early passages (MOSE-E) representing a pre-neoplastic, non-tumorigenic phenotype to late passages (MOSE-L) that demonstrate a highly aggressive malignant phenotype both in vitro and in vivo. Sphingosine, a bioactive metabolite of complex sphingolipids, has been shown to have chemopreventive properties in cancer, including colon and ovarian. In these studies we have investigated the hypothesis that sphingosine can prevent or reverse the aberrant gene expression in MOSE-L cells. Using a complete mouse genome microarray, we have identified 1412 genes that were significantly changed in the late malignant MOSE-L versus non-tumorigenic MOSE-E cells. Upon treatment of MOSE-L cells with non-toxic concentrations of sphingosine, microarray analysis revealed the down-regulation of 172 of 701 upregulated genes and up-regulation of 176 of 711 down-regulated genes in MOSE-L cells. Gene ontology analyses showed that these genes were overrepresented in specific categories with up-regulated genes involved in lipid and steroid metabolism, ER, and innate immune response while down regulated genes are involved in cell cycle, cytoskeleton and its regulation, and chromosome stability. A comparison of upregulated genes in MOSE-L cells treated with 5’-azaDC and sphingosine identified genes that are potentially epigenetically silenced by promoter methylation as cells transition from pre-neoplastic to malignant. Also, in addition to changes in gene expression, sphingosine reversed aberrant cytoskeleton organization. Taken together, this indicates that sphingosine acts as a chemopreventive agent by regulating multiple pathways including gene expression.
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 2875.
Abstract 2876: 3,3’-Diindolylmethane inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model
Authors: Cho Han Jin , Park So Young , Kim Eun Ji , Park Jung Han Yoon 
Published: February 2011

Abstract
3,3’-Diindolymethane (DIM) is a major in vivo derivative of indole-3-carbinol, which is present in cruciferous vegetables and has been reported to evidence anti-carcinogenic properties. In the present study, we attempted to determine whether DIM inhibits the development of prostate cancer using the transgenic adenocarcinoma mouse prostate (TRAMP) model. DIM feeding inhibited prostate carcinogenesis in TRAMP mice, reduced the number of cells expressing the SV40 large tumor antigen and proliferating cell nuclear antigen, and increased the number of terminal dUTP nick-end labeling (TUNEL)-positive cells in the dorsolateral lobes of the prostate. Additionally, DIM feeding reduced the expression of cyclin A, cyclin-dependent kinase (CDK)2, and CDK4, and increased Bax expression. To assess the mechanisms by which DIM induces apoptosis, LNCaP and DU145 human prostate cancer cells were cultured with various concentrations (0 – 30 μmol/L) of DIM. DIM induced a substantial reduction in the numbers of viable cells and induced apoptosis in LNCaP and DU145 cells. DIM increased the cleavage of caspase-9, −7, −3, and poly (ADP-ribose) polymerase (PARP). DIM increased mitochondrial membrane permeability and the translocation of cytochrome c and Smac/Diablo from the mitochondria. Additionally, DIM induced increases in the levels of cleaved caspase-8, truncated Bid, Fas, and Fas ligand, and the caspase-8 inhibitor z-IETD-FMK was shown to mitigate DIM-induced apoptosis and the cleavage of caspase-3, PARP, and Bid. These results indicate that DIM inhibits prostate carcinogenesis via induction of apoptosis and inhibition of cell cycle progression. DIM induces apoptosis in prostate cancer cells via the mitochondria- and death receptor-mediated pathways.
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 2876.
Abstract 2881: Benzyl isothiocyanate-mediated growth inhibition of MDA-MB-231 human breast cancer xenograft is associated with reduced cell proliferation, inhibition of angiogenesis, and induction of autophagy
Authors: Bommareddy Ajay , Warin Renaud , Xiao Dong , Arlotti Julie A. , Singh Shivendra V. 
Published: February 2011

Abstract
Benzyl isothiocyanate (BITC), a constituent of many edible cruciferous vegetables, inhibits growth of cultured human breast cancer cells by causing apoptosis. The present study was undertaken to determine in vivo efficacy of BITC using triple negative MDA-MB-231 human breast cancer xenograft as a model. BITC administration retarded growth of MDA-MB-231 cells subcutaneously as well as orthotopically implanted in female nude mice without causing weight loss or any other side effects. BITC-mediated suppression of MDA-MB-231 xenograft growth correlated with reduced cell proliferation as revealed by immunohistochemical analyses of Ki-67 and proliferating cell nuclear antigen expression. Analysis of vasculature in tumors from the BITC-treated mice revealed smaller vessel area compared with control tumors based on immunohistochemistry for angiogenesis marker CD31. BITC-mediated inhibition of angiogenesis in vivo correlated with down-regulation of VEGF-receptor 2 protein level in the tumor. Consistent with these results, BITC treatment suppressed VEGF secretion and VEGF-receptor 2 protein level in cultured MDA-MB-231 cells. Moreover, the BITC-treated MDA-MB-231 cells exhibited reduced capacity for migration compared with vehicle-treated control cells. In contrast to cellular data, BITC administration failed to elicit apoptotic response as judged by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Instead, the tumors from BITC-treated mice exhibited increased cleavage of microtubule-associated protein 1 light chain 3 (LC3), which is a marker of autophagic cell death. In agreement with these results, BITC treatment resulted in several features characteristic of autophagy in cultured MDA-MB-231 cells including formation of membrane vacuoles and acidic vesicular organelles (judged by microscopy after staining with lysosomotropic agent acridine orange), and cleavage of LC3. In conclusion, the present study indicates that BITC administration inhibits growth of MDA-MB-231 xenografts in association with reduced cell proliferation, inhibition of angiogenesis, and induction of autophagy. These preclinical observations underscore in vitro and in vivo differences in mechanisms for anticancer effect of BITC. This investigation was supported by the National Cancer Institute grant 1 RO1 CA129347-03.
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 2881.
Abstract 2887: From fruit extract to structure activity relationship studies: Alpha-mangostin promotes G1 cell cycle arrest in 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. , Handa Harleen , Mukhtar Hasan 
Published: February 2011

Abstract
The angosteen fruit (Garcinia mangostana) is native to southeast Asia and has been receiving increased attention for its 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 alpha-mangostin being the most abundant. Here we report on the properties of dietary xanthones for cancer chemoprevention using prostate cancer (PCa) as a model disease. In a separate abstract we provide promising results suggesting that a standardized mangosteen fruit extract promotes cell cycle arrest and decreases tumor formation in an athymic nude mouse model. To gain an understanding of the pharmacology of xanthones in cancer inhibition we selected alpha-mangostin as the lead compound and evaluated it against fifty different protein kinases deregulated in cancer in a cell free kinase assay. A kinase that is often deregulated in a variety of cancers including prostate is cyclinD1/CDK4 where alpha-mangostin was found to significantly inhibit the activity. Using two different cells lines (PC3 and CWR22) we have evidence suggesting alpha-mangostin promoted G1 cell cycle arrest by flow cytometry and western blot analysis of cyclins and CDKs with observed effects in the range of 5-10 μM. Further confirmatory studies were performed by western blot analysis. A preliminary pharmacokinetic analysis of mice administered 1 mg of alpha-mangostin intraperitoneally resulted in a plasma concentration of 7.3 μM - within the concentration of in vitro mechanistic studies. Next, using an athymic nude mouse model implanted with CWR22Rv1 cells we randomized mice to receive intraperitoneally the alpha-mangostin (&gt;95%) or placebo two times weekly with tumors measured twice weekly. At the conclusion of the study the treatment group had a significantly smaller tumor with an average tumor volume of (400 mm3) compared to the placebo group (1225 mm3) representing a 69% smaller tumor in the treatment group. Based on these promising results we used purified xanthones from the mangosteen fruit and selected 9 xanthones for structure activity relationship studies against cyclinD1/CDK4 using cell free biochemical assays and molecular modeling. Collectively these data indicate that the purified xanthone alpha-mangostin could be a promising agent for PCa prevention.
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 2887.
Abstract 2890: Effects of calcium and vitamin D on markers of vitamin D metabolism in normal colon mucosa: A randomized clinical trial
Authors: Ahearn Thomas , McCullough Marjorie L. , Flanders W. Dana , Long Qi , Fung Jessica , Ofori-Addo Anita , Dawadi Shuva , Bostick Roberd M. 
Published: February 2011

Abstract
Background: In colon cancer cell lines and rodent models calcium and vitamin D favorably modulate cell proliferation, differentiation, and apoptosis and affect and are affected by local expression of the vitamin D receptor (VDR), CYP27B1, and CYP24A1; however, the latter has not been investigated in humans. To evaluate the effects of supplemental calcium and vitamin D3 on VDR, CYP27B1, and CYP24A1 expression in the normal colorectal epithelium, we conducted a randomized, double-blinded, placebo-controlled 2×2 factorial clinical trial.
Methods: Ninety-two men and women with at least one pathology-confirmed sporadic colorectal adenoma were treated with calcium 2 g/day or vitamin D3 800 IU/day, alone or in combination vs. placebo over six months. VDR, CYP27B1, and CYP24A1 were detected in biopsies of normal-appearing colorectal mucosa using standardized automated immunohistochemistry, and their overall expression and distributions within the colon crypts were quantified by novel image analysis methods. The relative treatment effects were calculated and assessed using a MIXED effects model as implemented by SAS v9.2.
Results: Relative to the placebo group, in the calcium + vitamin D3 group VDR expression increased 19% (p=0.13) along the full length of crypts, 19% (p=0.09) in the upper 40% (differentiation zone) of crypts, and 31 % (p=0.13) in the lower 60% (proliferation zone) of crypts. In the vitamin D3 only group CYP27B1 expression increased 259% (p=0.04) along the full length of crypts, 211% (p=0.04) in the upper 40% of crypts, and 210% (p=0.04) in the lower 60% of crypts. CYP24A1 expression along the full length of crypts decreased 21% (p=0.51) in the calcium group, and increased 65% (p=0.22) and 51% (p=0.37) in the vitamin D3 and calcium + vitamin D3 groups, respectively.
Discussion: These preliminary results 1) suggest that, as hypothesized, calcium and vitamin D3, individually or in combination may modulate VDR, CYP27B1, and CYP24A1 expression in the normal-appearing human colorectal epithelium, which may promote normal patterns of cell proliferation, differentiation, and apoptosis; 2) provide further evidence to the potential importance of vitamin D metabolism and its autocrine/paracrine function in colorectal mucosa; 3) provide support for the efficacy of calcium and vitamin D3 in reducing risk for colorectal neoplasms; and 4) present the potential of the VDR and CYP27B1 and CYP24A1 as potential modifiable biomarkers of risk for colorectal neoplasms.
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 2890.
Abstract 2891: Control of nasopharyngeal carcinoma through serologic screening and clinical examination of at-risk subjects
Authors: Ji Mingfang , Shen Yahua , Cheng Weiming , Yu Yuanlong , Su Nianhua , Ng Sp , Ng Mh 
Published: February 2011

Abstract
Background. Nasopharyngeal Carcinoma (NPC) could be successfully treated by radiotherapy when the tumor is localized to the nasopharynx, while further progression to the adjacent tissues is attended by poor treatment outcome. However, 93% of the patients presented to outpatients department are diagnosed with the advanced cancer, while 86% of the localized tumors are asymptomatic, detected by clinical examination of apparently healthy subjects (Ji et al., submitted). Epstein Barr Virus (EBV) antibody levels of NPC patients are raised and maintained at high levels for up to 10 years before clinical onset (Ji et al., 2007). This suggests that repeated serologic screening could serve to monitor the tumor as it enters and transits such preclinical window and clinical examination of that risk subjects could detect the tumor as it is clinically manifested.
Objective: An early NPC detection program was instituted in Zhongshan City in Southern China since December 2007. The objective is to detect NPC while the tumor is confined to the nasopharynx.
Method. Subjects enrolled in this program are screened annually for levels of 3 EBV antibodies, namely IgA EBNA1, IgG EBNA1 and IgG zta, simultaneously. Clinical examination and endoscopy are performed for at-risk subjects who had elevated levels of 3 antibodies or IgA EBNA1 rod≥ 3.
Results: As of July 2009, 1373 adults were enrolled, 11 were assessed as high risk for NPC and 31 with elevated levels of one of 3 antibody. Five NPC cases were detected during clinical examination and all were from among those who had high levels of all the 3 EBV antibodies. Three of these cases showed no or a minimum of symptoms and were diagnosed with localized NPC (T1N0M0). The other 2 were overt cases and diagnosed with advanced loco-regional diseases (T2N1M0 and T3N1M0)
Conclusions: It is possible to control NPC by serologic screening and clinical follow-up of the at-risk subjects.
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 2891.
Abstract 2895: Effects of supplemental calcium and vitamin D3 on serum growth factors in sporadic colorectal adenoma patients in a randomized clinical trial
Authors: Owen Joy R. , Ahearn Thomas , Liang Bill , Fedriko Veronika , Woodard Jill , Bostick Roberd M. 
Published: February 2011

Abstract
Fluctuations in energy homeostasis via perturbation of the intricate balance between nutritional intake, physical/energy expenditure, and genetics are thought to play a role in risk for colorectal neoplasms. Nutritional supplementation with calcium and vitamin D3 may ameliorate risk for colorectal neoplasms and help lead to the development of treatable, non-invasive biomarkers of risk for the disease. Basic science findings indicate that calcium and vitamin D affect the expression of growth factors, such as Insulin-like Growth Factor (IGF-1), but there have been no reports of investigations on the effects of calcium and vitamin D3 on growth factors in humans. We investigated the effects of calcium 2.0 g and/or vitamin D3 800 I.U. daily over six months on serum levels of IGF-1 and Insulin-like Growth Factor Binding Protein (IGFBP-3) in a pilot, randomized, double-blind, placebo-controlled, 2×2 factorial chemoprevention trial (n = 88) in sporadic colorectal adenoma patients. In the calcium relative to the placebo group, both IGF-1 (p = 0.08) and IGFBP-3 levels (p = 0.03) increased by 10%, whereas there was no evidence for treatment effects in the vitamin D3 group. In the calcium plus vitamin D3 relative to the placebo group, IGF-1 increased by 9% (p = 0.12) but there was no evidence for a change in IGFBP-3. These findings tentatively suggest that dietary supplementation with calcium and/or vitamin D3 may affect signal transduction pathways mediating the release of growth factors into the systemic circulation in humans and provide support for developing treatable, non-invasive biomarkers of risk for colorectal neoplasms.
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 2895.