bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4609: Prevention of pancreatic cancer using novel crocetin compound
Authors: Aurora Chetna , Gutheil William G. , Reed Gregory , Anant Shrikant , Dhar Animesh 
Published: June 2012

Abstract
Pancreatic cancer is one of the most lethal malignancies in humans and there is no effective conventional treatment available for the cure of patients with pancreatic cancer. Great demand of new effective drugs and alternative approaches has led to studies evaluating possible anti-cancer agents in fruits, vegetables, herbs and spices. Crocetin, a carotenoid molecule isolated from saffron, has been demonstrated recently by our laboratory that crocetin treatment has potent antimitotic effects on both in vitro and in vivo pancreatic cancer models. Commercial crocetin is a mixture of crocetin esters and recently, novel crocetin compound and its esters are also fractionated from commercial crocetin by us using prepartory HPLC and LC/MS.The aim of this work is to identify most potent fractions separted from crude or commecial crocetin following the signaling mechanisms, responsible for inducing cellular proliferation and tumorigenesis of pancreatic adenocarcinoma. One of the fractions separated from crude crocetin by preparative HPLC, and identified using LC/MS and NMR as crocetinic acid, markedly regressed the proliferation and increased apoptosis in pancreatic cancer cells. Growth related signaling pathways such as epidermal growth factor receptor (EGFR) and its down-stream signaling molecule, Akt phosphorylation were significantly altered by novel crocetin compound derived from crude crocetin. It has also been demonstrated that novel crocetin compound altered histone deacetylase (HDAC) and its substrate acetyl histone H3 Lysine14 that indicates histone modifications by inhibition of deacetylation. Apoptosis was significantly stimulated as indicated by Bax/Bcl-2 ratio by treatment with purified crocetin. Purified crocetin compound showed significant anti-tumorigenic effect at lower doses than commercial or crude crocetin using proliferation and apoptosis as markers. Crocetin can be used as chemopreventive agent for pancreatic cancer in future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4609. doi:10.1158/1538-7445.AM2011-4609
Abstract 4612: Cell-type dependent responses to selenium and knockdown of SBP2
Authors: Li Jin , Suraokar Milind B. , Tsavachidou Dimitra , Menter David G. , Kim Jeri 
Published: June 2012

Abstract
Selenium is a trace element essential for human health. Evidence from previous epidemiologic studies and clinical trials suggested that selenium is associated with prostate cancer prevention, but its failure in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to reduce prostate cancer incidence diminished its promise. The question of whether some patients could benefit from selenium supplementation while others might not demands a clearer understanding of selenium's mechanisms of action. One of the ways in which selenium acts as a chemopreventive agent is through incorporation into selenoproteins, which are antioxidant enzymes required to maintain redox homeostasis; however, selenoproteins’ large number and redundant functions make analyzing their effects on cellular functions difficult. Therefore, we recently targeted selenocysteine insertion sequence-binding protein 2 (SBP2), required for selenoprotein synthesis; knocked down SBP2 expression in different cell lines; and examined the effect on cell survival, cell cycle, and cell survival pathways. We found that knocking down SBP2 resulted in apoptosis in NIH/3T3 and HEK-293 cells, especially in the presence of H2O2. Interestingly abrogation of SBP2 function affected the level of p21 protein in a cell type-specific manner. Additionally, sodium selenite or seleno-methionine treatment led to distinct changes in p21 and p53 protein status in HEK-293, LNCaP, and DU145 cells. Molecular effects induced by knocking down SBP2 were cell-type dependent. Further studies involving a combinational approach are expected to contribute to understanding how selenium and selenoproteins mediate chemopreventive effects in prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4612. doi:10.1158/1538-7445.AM2011-4612
Abstract 4616: A hexane extract of American ginseng suppresses mouse colitis
Authors: Poudyal Deepak , Windust Anthony , Davis Tia , Chumanevich Alexander A. , Chumanevich Alena , Nagarkatti Mitzi , Nagarkatti Prakash S. , Wargovich Michael J. , Hofseth Lorne J. 
Published: June 2012

Abstract
Ulcerative colitis (UC) is a dynamic, idiopathic, chronic inflammatory condition associated with a high colon cancer risk. We have previously shown that American Ginseng (AG) extract prevents and treats colitis. The aim of this study was to better understand the components of American ginseng that suppress colitis. In this study we show that among five different fractions of AG (Butanol, Hexane, Ethylacetate, Dicholoromethane and Water), the Hexane fraction of American ginseng (HAG) has the most effective anti-oxidation and pro-apoptotic effect. This effect of HAG was shown in a mouse macrophage cell line (ANA-1 cells) and in an ex-vivo model (activated primary effector T cells, CD4+/CD25- T cells). Importantly, compared with the entire AG extract, the HAG was more potent in treating colitis in a dextran sulfate sodium (DSS) mouse model. Results from this study move us closer to understanding the molecular components of AG that suppress colitis, and perhaps prevent colon cancer associated with colitis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4616. doi:10.1158/1538-7445.AM2011-4616
Abstract 4624: Cleavage of HER2 by phenethyl isothiocyanate mediates apoptosis in breast cancer cells
Authors: Gupta Parul , Srivastava Sanjay K. 
Published: June 2012

Abstract
Her2 is a well established marker of breast cancer and found to be overexpressed in around 20-30% of cases. It plays role in cell proliferation, angiogenesis, metastasis and drug resistance leading to poor prognosis and survival. Therefore development of novel agents targeting Her2 is highly imminent. Based on several epidemiological and experimental evidences, isothiocyanates have been shown to have anticancer effects. We evaluated the effect of phenethyl isothiocyanate (PEITC) in breast cancer cells. Treatment with PEITC for 24h significantly suppressed the survival of both MCF-7 (estrogen dependent) and MDA-MB-231 (estrogen independent) cells in a concentration dependent manner with an IC50 of about 12µM and 8µM respectively. Substantial apoptosis by PEITC treatment was observed in both the cell lines. Interestingly, PEITC treatment after 24h drastically reduced Her2 expression. The decrease in Her2 expression by PEITC treatment correlated with the cleavage of Her2. The low molecular weight fragments of Her2 increased with increasing PEITC concentration. Caspase-3 specific inhibitor blocked PEITC-mediated cleavage of Her2 and apoptosis indicating the involvement of caspase-3 in the cleavage of Her2. Her2 fragments have been shown to induce mitochondria-mediated apoptosis. In agreement, our results show the cleavage of Bid and increase in Bax level, whereas the expression of Bcl-XL was down regulated. Further, PEITC treatment resulted in the release of cytochrome c from the mitochondria into the cytosol, activating caspase 9/3 and PARP cleavage. Taken togther, our results suggests that cleavage of Her2 by PEITC activates mitochondrial death pathway in breast cancer cells. Further mechanistic studies are in progress. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute].
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4624. doi:10.1158/1538-7445.AM2011-4624
Abstract 4646: Occupational exposure to trichloroethylene and plasma concentrations of IL6, IL10, and TNF alpha
Authors: Bassig Bryan A. , Zhang Luoping , Tang Xiaojiang , Vermeulen Roel , Shen Min , Smith Martyn T. , Qiu Chuangyi , Ge Yichen , Ji Zhiying , Reiss Boris , Liu Songwang , Guo Weihong , Purdue Mark , Hu Wei , Li Laiyu , Rothman Nathaniel , Huang Hanlin , Lan Qing 
Published: June 2012

Abstract
Trichloroethylene (TCE) is a chlorinated solvent primarily used as a vapor degreaser in many industries. TCE is currently classified by IARC as probably carcinogenic to humans (Group 2A), and has been associated with non-Hodgkin lymphoma (NHL) in some epidemiological studies, although the findings have been inconsistent. To explore the biologic plausibility that TCE may be a lymphomagen, we conducted a cross-sectional study of workers exposed to TCE in Guangzhou, China and tested if plasma levels of the cytokines IL6, IL10, and TNF-alpha, which play a critical role in regulating various components of the immune system, were altered in exposed workers. We enrolled 80 workers from factories where TCE was used as well as 96 unexposed controls matched by sex and age from food and clothes manufacturing factories. Personal exposure measurements were taken over a three-week period, two to three per subject, in the exposed subjects for a full work shift using a 3M badge, as well as for a subgroup of the control workers. Blood samples were collected from each subject, and plasma concentrations of IL6, IL10, and TNF-alpha were measured by ELISA. Linear regression using the natural logarithm of each endpoint and adjusting for potential confounders was used to test for differences in marker concentrations between controls and exposed workers. The mean TCE exposure level in exposed subjects was 23.9 ppm (95% C.I. 14.2-33.6 ppm). Compared to unexposed workers, the plasma concentration of IL10 in workers exposed to TCE was decreased by more than 50% compared to controls (p=0.003), while there was no difference in levels of IL6 or TNF-alpha in TCE exposed workers and controls. IL10 plays a critical role in mediating the Th1/Th2 balance, apoptosis, and regulation of inflammation. Genotypes associated with altered IL10 expression have also been associated with the development and progression of NHL. Given that immunologic alterations are suspected to play a role in lymphomagenesis, and IL10 plays an important role in immunologic processes, our findings provide some support for the biologic plausibility that TCE is associated with lymphoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4646. doi:10.1158/1538-7445.AM2011-4646
Abstract 4668: Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer
Authors: Zeng Hongmei , Yu Herbert , Lu Lingeng , Jain Dhanpat , Kidd Mark S. , Saif M Wasif , Chanock Stephen J. , Hartge Patricia , Risch Harvey A. 
Published: June 2012

Abstract
Purpose: Germline genetic variation may affect clinical outcomes of cancer patients. Using an existing genome-wide association study (GWAS) data set, we applied a candidate-gene approach to evaluate the effect of putative markers on survival of patients with pancreatic cancer. We also examined gene-radiotherapy and gene-chemotherapy interactions, aiming to explain inter-individual differences in treatment outcomes.
Patients, Materials and Methods: In total, 211 patients with pancreatic cancer were identified and recruited between February 2005 and June 2008 in a population-based study and followed through June 2010, an average follow-up of 3.4 years. Sixty-four candidate genes associated with cancer survival or treatment response were selected from existing publications. Genotype information was obtained from a previous GWAS analysis of the study subjects. The main effect of genetic variation and gene-specific treatment interactions on overall survival were examined by proportional hazards regression models.
Results: Fourteen genes showed evidence of association with pancreatic cancer survival. Among these, rs1760217, located at the DPYD gene, rs17091162 at SERPINA3 and rs2231164 at ABCG2 had the lowest P-values of 10−4.60, 0.0013 and 0.0023, respectively. We also observed that two genes, RRM1 and IQGAP2, had significant interactions with radiotherapy in association with survival, and two others, TYMS and MET, showed evidence of interaction with the chemotherapeutic agents 5-FU and erlotinib, respectively.
Conclusions: Our study revealed significant associations between germline genetic polymorphisms and overall survival in pancreatic cancer, as well as survival interactions between various genes and radiotherapy and chemotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4668. doi:10.1158/1538-7445.AM2011-4668
Abstract 4683: Inducible knockdown of DNA topoisomerase IIα affects drug sensitivity and cell growth
Authors: Chen Cheng-Fen , He Xiaolong , Beck William T. 
Published: June 2012

Abstract
DNA topoisomerase IIα (Top2α) is an essential nuclear enzyme and target for important anti-cancer drugs, such as etoposide and doxorubicin (Dox). Our teniposide-resistant human leukemic lymphoblastic cells (CEM/VM-1-5) (Danks MK et al., Biochemistry 27(24):8861-8869, 1998) express reduced Top2α protein. To determine the role of Top2α in drug resistance, we knocked down Top2α in parental CEM cells by RNAi. Compared to control cells, CEMshTop2α cells were more resistant to the Top2 inhibitors, etoposide and Dox. The mechanism by which knockdown of Top2α caused resistance to Top2 inhibitors is probably caused by a reduction in Top2-DNA complexes leading to fewer broken DNA strands (Wang JC, Nat Rev Mol Cell Biol 3(6):430-440, 2002). The level of reduced Top2α expression in Top2α knockdown CEM cells was confirmed by Western blot. Importantly, we found no compensatory regulation by Top1 or Top2α overexpression under these conditions. It has been reported that knocking-out of Top2α will cause early embryonic death (Jenkins JR et al. Nucleic acids research 20(21):5587-5592, 1992), but in our cultured CEM cells, knocking Top2α down to 40% of control level had little or no impact on cell growth rate. We subsequently generated and characterized stable CEM-tTR-shTop2α cells where Top2α can be conditionally knocked down to 5% of control levels, as determined by Western blot, through a tetracycline-induced expression of short hairpin RNAs. CEM-tTR-shTop2α cells grow significantly more slowly than the control cells, which indicates that while cells can proliferate with ∼40% of Top2α expression, when Top2α is reduced by 95%, cells can apparently remain viable, but are severely impaired in their ability to grow. Present studies are focused on identifying genes that are targets of Top2α knockdown to provide insights into those genes involved in drug resistance. (Supported in part by CA40570 from NCI and in part by UIC)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4683. doi:10.1158/1538-7445.AM2011-4683
Abstract 4711: Silencing of miR-221 with anti-microRNA oligonucleotides is an effective therapeutic for hepatocellular carcinoma
Authors: Park Jong Kook , Kogure Takayuki , Nuovo Gerard J. , He Lei , Kim Ji Hye , Phelps Mitch A. , Croce Carlo M. , Patel Tushar , Schmittgen Thomas D. 
Published: June 2012

Abstract
Patients with advanced hepatocellular carcinoma (HCC) face a dismal prognosis as there are no standardized therapies to treat this stage of the disease. Inhibition of microRNAs that are overexpressed in the tumor with antisense oligonucleotides represents a novel option to treat HCC. For antisense oligonucleotides to be effective, they must reach the target tumor tissue, inhibit the miRNA, modulate the miRNAs target protein levels and prolong survival. We evaluated anti-miR-221 in normal and tumor bearing mice. Of eight different chemistries evaluated, the cholesterol labeled, 2’ O methyl, phosphorothioate modified anti-miR-221 (chol-anti-miR-221) was the most effective at reducing proliferation in vitro. In the absence of transfection reagents, the in vitro proliferation was reduced by the chol-anti-miR-221 but not the scrambled control. Non specific toxicity was observed in vitro for each of the chemically modified scrambled control oligos when transfected with lipid reagent. Chol-anti-miR-221 had improved pharmacokinetics and liver tissue distribution compared to the non cholesterol labeled oligonucleotide in C57Bl/6 mice. Endogenous miR-221 levels in the liver were reduced by chol-anti-miR-221 in C57Bl/6 mice by 90%, 7 days following the start of the dosing schedule. In situ hybridization demonstrated that chol-anti-miR-221 accumulated in the tumor cells of orthotopic mice. Chol-anti-miR-221 reduced endogenous miR-221 levels in the tumors of orthotopic xenograft mice by &gt; 95% and increased p27Kip1 target protein by 3-fold, 7 days after dosing. Chol-anti-miR-221 produced a survival advantage in orthotopic mice compared to those mice treated with a scrambled control oligo (P &lt; 0.05). Our data demonstrate that chol-anti-miR-221 is efficacious in an orthotopic mouse model of HCC and suggests that such a therapy may be beneficial in patients with advanced HCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4711. doi:10.1158/1538-7445.AM2011-4711
Abstract 4726: Genetic determinants of serum retinol: A genome-wide association study
Authors: Mondul Alison M. , Yu Kai , Weinstein Stephanie J. , Virtamo Jarmo , Jacobs Kevin B. , Kraft Peter , Chanock Stephen J. , Albanes Demetrius 
Published: June 2012

Abstract
Background: Retinol, the most biologically active form of vitamin A, is hypothesized to influence a wide range of diseases. We recently reported results from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study suggesting that higher serum retinol is related to increased prostate cancer risk. Circulating retinol concentrations are influenced by many factors in addition to dietary and supplemental intake, including those related to intestinal absorption, transport, and cleavage of pro-vitamin A compounds to form retinol. Thus, genetic factors that influence retinol concentrations may also impact human disease risk.
Methods: We conducted a genome-wide association study (GWAS) of 4,041 Caucasian individuals drawn from two cohorts: the ATBC Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Our findings were replicated in an independent sample of 2,056 individuals from the Nurses’ Health Study.
Results: We identified two independent SNPs near the genes encoding key retinol carrier proteins, transthyretin (TTR) and retinol binding protein 4 (RBP4), that were associated at the level of genome-wide significance with retinol concentrations: rs1667255 (in 18q12.1) and rs10882272 (in 10q23.33). After meta-analysis with the replication sample, these SNPs remained highly significant (rs1667255: p = 2.33 × 10-14; rs10882272: p = 1.08 × 10-13). In the two GWAS studies, mean serum retinol concentrations increased with number of risk alleles (0,1,2) for TTR from 556-578-602 μg/L in ATBC and 654-688-711 μg/L in PLCO, and decreased for 0,1,2 risk alleles in RBP4 (580-567-541 μg/L in ATBC and 697-668-653 μg/L in PLCO).
Conclusions: This is the first GWAS of circulating retinol levels to reveal novel, genome-wide significant loci, one near TTR and one near RBP4, genes that encode the two major retinol carrier proteins. Understanding the genetic and other determinants of retinol status may help shed light on the etiology of cancer and other diseases associated with vitamin A.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4726. doi:10.1158/1538-7445.AM2011-4726
Abstract 4738: Cellular resistance screening with a novel selective c-Met inhibitor reveals a spectrum of missense mutations that partially overlap with activating mutations found in cancer patients
Authors: Tiedt Ralph , Degenkolbe Elisa , Furet Pascal , Appleton Brent A. , Schoepfer Joseph , Ruddy David , Monahan John , Jones Michael D. , Blank Jutta , Haasen Dorothea , Drueckes Peter , Wartmann Markus , McCarthy Clive , Hofmann Francesco 
Published: June 2012

Abstract
Emergence of resistance is a major concern when treating cancer patients with targeted kinase inhibitors, as exemplified by the appearance of point mutations in Bcr-Abl in CML patients treated with imatinib or a secondary EGFR-T790M mutation in lung cancer patients treated with gefitinib or erlotinib. In vitro approaches to identify resistance mutations in Bcr-Abl have yielded mutation spectra that faithfully recapitulated clinical observations.
In order to predict resistance mutations in the receptor tyrosine kinase c-Met that could emerge during inhibitor treatment in patients, we performed a resistance screen in BaF3 cells transformed with Tpr-Met using the novel selective c-Met inhibitor NVP-BVU972. The observed spectrum of mutations in resistant cells was dominated by substitutions of the residue Y1230 in the activation loop of the c-Met kinase domain, but also included other missense mutations. Intriguingly, some of the c-Met resistance mutations observed in this cellular screen were identical with previously described activating mutations in cancer patients that interfere with inhibitory interactions in the inactive conformation. Co-crystallization of the c-Met kinase domain in complex with NVP-BVU972 revealed a key role for Y1230 in binding of NVP-BVU972. This binding mode has also been reported for multiple other selective c-Met inhibitors, some of which have entered clinical trials, suggesting a broader relevance of the resistance profile obtained with NVP-BVU972.
A second resistance screen in the same format with the c-Met inhibitor AMG 458 yielded a distinct spectrum of mutations that was rich in F1200 alterations. This is consistent with a different predicted binding mode. Again, the mutation profile observed with AMG 458 could be predictive for several other inhibitors that bind c-Met in a similar way.
Collectively, our findings suggest that amino acid substitutions in the c-Met kinase domain of cancer patients need to be carefully monitored prior to and during treatment with c-Met inhibitors, as resistance may pre-exist or emerge. Compounds binding in the same manner as NVP-BVU972 might be particularly susceptible to the development of resistance through mutations in Y1230, a complication that could potentially be overcome by c-Met inhibitors with alternative binding modes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4738. doi:10.1158/1538-7445.AM2011-4738