bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5730: Dosimetric properties of a new thermobrachytherapy seed with ferromagnetic core for treatment of solid tumors
Authors: Subramanian R , Parsai Ishmael E. , Bhoj Gautam R. , Shvydka Diana , John Feldmeier J. 
Published: August 2012

Abstract
Studies of the curative effects of hyperthermia and radiation therapy on treatment of cancer show a strong evidence of a synergistic enhancement when both radiation and hyperthermia modalities are applied simultaneously. Varieties of tissue heating approaches developed up to date still fail to overcome such essential limitations as an inadequate temperature control, temperature non-uniformity, and prolonged time delay between hyperthermia and radiation treatments. We propose a new self-regulating Thermobrachytherapy seed, which serves as a source of both radiation and heat for concurrent administration of brachytherapy and hyperthermia. The proposed seed is based on the BEST Seed Model 2301-I125, where tungsten marker core and the air gap are replaced with a ferromagnetic material. The ferromagnetic core produces heat when subjected to alternating electro-magnetic (EM) field and effectively shuts off after reaching the Curie temperature (TC) of the ferromagnetic material thus realizing the temperature self-regulation. We present the Monte Carlo study of dose rate constant and the other TG-43 radiation characteristic factors for the proposed seed. For the thermal characteristics, we studied a model consisting of 16 seeds placed in the central region of a cylindrical water phantom using a finite-element partial differential equation solver package “COMSOL Multiphysics”. The modeling result shows that temperature of the thermoseed surface rises rapidly and stays constant around TC of the ferromagnetic material. The amount of heat produced by the ferromagnetic core is sufficient to raise the temperature of the surrounding volume to the therapeutic range. The volume of the therapeutic temperature range increases with increase of frequency or magnetic field strength. These studies demonstrate that an optimal isothermal distribution can be achieved on a target volume to match with the radiation isodose distribution for the seed configuration by tuning frequency and intensity of the alternating magnetic field. The proposed combination seed model has a high potential for implementation of concurrent brachytherapy and hyperthermia.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5730. doi:1538-7445.AM2012-5730
Abstract 5732: Mercapturic acid excretion and N7-GA-Gua DNA adduct formation after low dose oral application of acrylamide to rats
Authors: Watzek Nico , Böhm Nadine , Feld Julia , Scherbl Denise , Berger Franz , Merz Karl-Heinz , Lampen Alfonso , Reemtsma Thorsten , Tannenbaum Steven R. , Skipper Paul L. , Baum Matthias , Richling Elke , Eisenbrand Gerhard 
Published: August 2012

Abstract
Acrylamide (AA), a genotoxic carcinogen (IARC class 2A), is a food contaminant formed by thermal treatment of food. The margin of exposure (MOE) of AA, representing the distance between the bench mark dose associated with 10% tumor incidence in rats and the estimated average human exposure, is considered to be low and of human health concern. After uptake, AA is partly converted by CYP450 2E1 into the genotoxic epoxide glycidamide (GA). GA forms DNA adducts, primarily at N7 of guanine (N7-GA-Gua). AA and its genotoxic metabolite GA are conjugated to glutathione and excreted via urine as mercapturic acids (MA), namely N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), and N-acetyl-S-(2-hydroxy-2-carbamoylethyl)-cysteine (GAMA) which are used as biomarkers for exposure. Female Sprague Dawley (SD) rats were kept on an AA free diet. AA was given by gavage in a broad dosage range, covering single doses of 0.1-10,000 µg/kg bw. Formation of urinary MAs and of N7-GA-Gua DNA adducts in liver, kidney and lung was measured 16 h after application. The lowest dosage of 0.1 µg AA/kg bw did not result in significantly enhanced MA excretion, as compared to untreated controls, found to excrete about 0.8 nmol MA. Since the animals may have ingested at best 0.4 nmol AA/d with the diet, this findings suggests a background level of endogenously formed AA. At the lowest dosage (0.1 µg AA/kg bw), N7-GA-Gua adducts above the limit of detection (LOD, 0.2 adducts/10exp8 nucleotides) were not detected in any organ tested. At 1 µg/kg bw, enhanced adduct levels were found in kidney (around 1 adduct/10exp8 nucleotides) and lung (&lt; 1 adduct/10exp8 nucleotides), but not in liver. At 10 and 100 µg/kg bw, adducts were found in all three organs, at levels not significantly different to those found at 1 µg AA/kg bw (about 1-2 adducts/10exp8 nucleotides). Taken together, the results of this in vivo study allow to conclude that exposure to single doses of AA in the range of human dietary exposure leads to N7-GA-Gua adduct levels in tissues of SD rats at the low end of steady state background DNA lesions of various origin in human and rat tissues. This study was supported by ISIC, the Institute for Scientific Information on Coffee.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5732. doi:1538-7445.AM2012-5732
Abstract 5738: Expression profiling of microRNA and mRNA on hepatic inflammation in high-fat induced murine model
Authors: Hur Won Hee , Choi Jung Eun , Kim Sung Woo , Hong Sung Woo , Lee Young Ki , Lyoo KwangSoo , Yoon Seung Kew 
Published: August 2012

Abstract
The inflammation has been identified as a risk factor for cancer and even as a means to prognose/diagnoses cancer at the inception of the inflammatory process. Therefore, it is necessary to discover novel molecules that might play a critical role in the regulation of inflammation, which can be the target of anti-inflammation. Recent reports indicate that microRNAs (miRNAs) have a significant role in the mechanism of inflammation in chronic inflammatory diseases. The goal of this study was to identify and characterize of miRNA in the regulation of inflammatory responses of high-fat induced inflammation mouse model. In this study, we established a mouse model of high-fat-diet-induced inflammation to gain understanding on the biological functions deregulated by aberrant gene expression based on miRNA and mRNA expression profiling analysis. And then we looked for direct miRNA targets by performing pair-wise correlation coefficient analysis on expression levels of mRNAs and by comparing these results with predicted miRNA targets from TargetScan5.1. We used quantitative PCR technology to evaluate the expression of miRNAs and mRNA on liver tissue. Inflammatory foci were observed over 6 months after high-fat induced inflammation mouse. In cDNA microarray analysis, total 2287 genes were differentially expressed between high-fat induced inflammatory group and normal group. Among those genes, the genes related-metabolic pathway were up-regulated at 3 months while those related inflammatory response were up-regulated at late stage of over 6 months in high-fat induced inflammation mouse model. Furthermore, we identified 15 new miRNAs in high-fat induced inflammation model by bioinformatics analysis and further confirmed their expression by stem-loop RT-PCR. GO analysis indicated that many of the identified miRNA targets may function in high-fat induced inflammation model. For three miRNAs (miR-34a, miR-21 and miR-1224), correlated genes were concordant with predicted targets. A gene set enrichment analysis on these genes demonstrated significant enrichment in biological processes related to lipid and glucose metabolism and inflammation. This study represents, to the best of our knowledge, the first integrated analysis of miRNA and mRNA expression in high-fat induced inflammation model. We identified a distinct profile of miRNAs of which expression differed between inflammation and normal, making these miRNAs candidate markers. Supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0014620).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5738. doi:1538-7445.AM2012-5738
Abstract 5739: Characterization of the metabolism and DNA adduct formation of 2-amino-9H-pyrido[2,3-b]indole in human hepatocytes
Authors: Nauwelaërs Gwendoline C. , Tang Yijin , Gu Dan , Fessard Valérie , Turesky Robert J. , Langouët Sophie A. 
Published: August 2012

Abstract
2-Amino-9H-pyrido[2-3-b]indole (AαC) is a heterocyclic aromatic amine (HAA) and considered to be a possible human carcinogen by the International Agency for Research on Cancer (IARC). Like other HAAs, AαC is metabolized in the liver and can undergo bioactivation to produce highly electrophilic derivatives that can form DNA adducts by covalent binding to DNA. Among the HAAs, AαC is of particular interest because it is present at high levels in tobacco smoke and ubiquitous in the environment. AαC was shown to form high levels of DNA adducts in primary cultured human hepatocytes. The adduct levels were higher than those formed by other HAAs such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and comparable to those derived from 4-aminobiphenyl (4-ABP), a known human carcinogen. An understanding of the metabolism of AαC and its potential to form DNA adducts would provide a better assessment of the human health risk posed by AαC. Indeed, the metabolism pathways of MeIQx, PhIP and AαC are different. These differences in metabolic processing of HAAs can lead to variable levels of DNA adducts formed in humans and impact the interindividual susceptibility towards these procarcinogens. Knowledge about the metabolism of AαC in humans is unknown. We have analyzed the role of human cytochromes P450, especially CYP1A2, in the metabolism of AαC and DNA adduct formation. The ring-oxidized 3-HO-AαC and 6-HO-AαC sulfate and glucuronide conjugates, AαC-N2-Gl, N2-acetyl-AαC and the glucuronide conjugates of 2-hydroxyamino-9H-pyrido[2,-3-b]indole (HONH-AαC) and the deoxyguanosine DNA adduct, dG-C8-AαC, were identified and quantified by liquid chromatography coupled with multistage mass spectrometry in human hepatocytes in primary culture. The levels of DNA adducts formed after a 24hr-treatment with AαC were (2 folds) lower when cells were pre-treated with furafylline, a specific CYP1A2 inhibitor; however, the levels of most of the metabolites formed were not significanly affected by furafylline. Our data suggests that CYPs other than CYP1A2 may be involved in AαC metabolism, while CYP1A2 is the main enzyme involved in the production of reactive metabolites leading to the formation of DNA adducts. The identification of CYPs and Phase II enzymes involved in AαC metabolism in human hepatocytes are under study to fully understand the health risk of AαC to humans.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5739. doi:1538-7445.AM2012-5739
Abstract 579: 3, 3′-diindolylmethane enhances the effectiveness of Herceptin by upregulation of miR-200 through down-regulation of FoxM1 in breast cancer cells
Authors: Ahmad Aamir , Ali Shadan , Sakr Wael , Rahman KM 
Published: August 2012

Abstract
Many patients with high levels of HER2/neu experience disease progression even when treated with Herceptin as a single agent. Current Herceptin-based combination therapies involving conventional chemotherapeutic drugs have been shown to increase survival rate in only a portion of patients with high levels of HER2/neu. Furthermore, these treatments are associated with several toxicities. Thus, there is a strong need for developing new tumor selective agents that can be co-administered with Herceptin successfully, and with minimal toxicity, to treat breast cancer patients whose tumors express high levels of HER2/neu. 3,3′-diindolylmethane (DIM), a cruciferous plant-derived and non-toxic chemopreventive agent, has been reported to selectively kill breast cancer cells without affecting normal cells and sensitizes breast cancer cells to chemotherapeutic agents. In this study, we evaluated the effects of Herceptin alone and in combination with DIM on cell viability, apoptosis and clonogenic assays in SKBR3 (HER2/neu overexpressing) and MDA-MB-468 (HER2/neu-negative) breast cancer cell lines. We found that DIM could sensitize breast cancer cells to Herceptin by significantly reducing cell viability, which was associated with the induction of apoptosis and significant inhibition of colony formation when compared with single agent treatment. These results were also consistent with the down-regulation of Akt and NF-κB. Mechanistic investigations revealed a significant upregulation of miR-200, which resulted in the reduction of FoxM1 expression in DIM plus Herceptin-treated breast cancer cells. These results provide experimental evidence, for the first time, that DIM plus Herceptin therapy could be translated to the clinic as a therapeutic modality to improve treatment outcome of patients whose tumors express high levels of HER2/neu.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 579. doi:1538-7445.AM2012-579
Abstract 59: Effects of Cdc42 overexpression on the developing mammary gland
Authors: Bray Kristi M. , Hwang Melissa , Brakebusch Cord , Vargo-Gogola Tracy Vargo-Gogola 
Published: August 2012

Abstract
The Rho GTPase Cdc42 is overexpressed and hyperactivated in human breast cancer; however, its precise role during normal mammary gland (MG) development and the stochastic process of mammary tumor formation in vivo remains unknown. We, therefore, investigated the effects of Cdc42 knockout and overexpression during mammary morphogenesis using conditional mouse models. Previously, we demonstrated that loss of Cdc42 prevents primary mammary acinus formation in a three-dimensional (3D) in vitro culture system. Defects in proliferation, survival, and polarity contributed to the aberrant phenotype. Furthermore, preliminary studies using MMTV-cre mice to conditionally delete Cdc42 in ∼30% of mammary epithelial cells (MECs) in the developing MG suggest that Cdc42 knockout MECs are outcompeted by wildtype MECs in vivo. To investigate the effects of Cdc42 overexpression on MG development, and ultimately tumorigenesis, we generated tetracycline-regulatable Cdc42 overexpressing mice. Interestingly, Cdc42 overexpression results in aberrant terminal end bud (TEB) morphogenesis, increased ductal branching, and ductal dilation, suggesting that Cdc42 overexpression increases MEC proliferation and invasion and may cause defects in cell adhesion and tight junctions. Consistent with these data, Cdc42 overexpressing MECs give rise to dysmorphic, invasive acini in 3D culture assays. Taken together, these data demonstrate that Cdc42 is a key regulator of proliferation and tissue architecture in the developing MG and suggest that Cdc42 overexpression may contribute to tumor formation by disrupting these processes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 59. doi:1538-7445.AM2012-59
Abstract 596: Combination of SAHA with dietary energy restriction for breast cancer prevention
Authors: Zhu Zongjian , Jiang Weiqin , McGinely John N. , Neil Angie , Steiner Danna , Thompson Henry J. 
Published: August 2012

Abstract
Studies of human populations and experimental models indicate that dietary energy restriction (DER) inhibits the development of breast cancer. Of the several candidate mechanisms that DER is known to affect, one that is the widely observed is the induction of class III histone deacetylase sirtuin 1 (SIRT1). Evidence is controversial as to whether induction of SIRT1 is essential for DER's cancer preventive activity or if it limits DER's effectiveness. Therefore an experiment was designed to determine if suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, would diminish or enhance the cancer preventive activity of DER. Female Sprague Dawley rats (n=30/group) were injected with 1-methyl-1-nitrosourea (50 mg/kg) at 21 days of age and 7 days thereafter were randomized to groups and fed either control diet (AIN-93G) or that diet formulation supplemented with 0.1% SAHA (w/w). Other treatment groups were 40% DER, or 0.1% SAHA+40% DER; diets were a modification of AIN93-G that assured that the only variables among groups were DER and/or SAHA. Rats were fed respective diets for 8 weeks. An additional group, 0.1% SAHA+40%DER-release, was fed 0.1% SAHA+40%DER diet for 5 weeks and released to control diet for the final 3 weeks of the experiment. Both 40%DER or 0.1%SAHA+40%DER significantly reduced mammary cancer incidence, the number of mammary adenocarcinomas per rat, and cancer burden, as well as prolonging cancer latency (p&lt;0.01). After releasing rats from SAHA+DER, the number of mammary adenocarcinomas per rat was significantly lower and the cancer latency was still significantly longer than the control gp (p&lt;0.05). The mechanisms of the cancer inhibition include effects on circulating factors, IGF1/IGFBP3, insulin, adiponectin, leptin, and C-reactive protein. Thus it does not appear that SIRT1 induction is not requisite for the cancer preventive activity of DER. Rather inhibition of cancer was associated with cellular AMPK activation and Akt-mTOR down regulation by SAHA+DER with additional effects being mediated via FOXO3a. Supported by PHS grant CA52626 from the National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 596. doi:1538-7445.AM2012-596
Abstract 653: Passive smoking facilitate the risk of CIN1 in high risk HPV-positive women: Korean HPV Cohort Study
Authors: Kim Mi Kyung , Lee Binna , Mishra Siddhartha Kumar , Lee Jae Kwan 
Published: August 2012

Abstract
Cervical cancer is the second most common malignancy and the second most common cause of cancer-related death worldwide. Recently, the International Agency for Research on Cancer (IARC) of the World Health Organization in France completed reviewing all published studies related to cigarette smoke and cancer. Among several risk factors, tobacco smoking has been less explored despite it being a well-established risk factor for cervical precancer and cancer. The epidemiologic and biological studies suggest the association of passive smoking on the risk of cervical cancer; however, the evidence has been suggestive rather than sufficient to implicate the role of passive smoking in the etiology of cervical cancer among lifetime nonsmoking women. We investigated the associations between passive smoking and risk of cervical intraepithelial neoplasia (CIN), and cervical cancer in high risk HPV-positive women in the Korean HPV cohort study (KHPV). The KHPV recruited 1,306 women, aged 18-65, including HPV-positive women with normal cytology (n=577), CIN1 (n=419), CIN2/3 (n=165), and cervical cancer (n=145) from March 2006 to December 2009. Detailed information on passive smoking and other lifestyle factors were collected by questionnaires. Multinomial logistic analysis was performed to estimate multivariate-adjusted odds ratios. Ex- and current smoker had an increased risk of CIN1 (OR = 1.81; 95% CI: 1.26 ∼ 2.60) as compared to nonsmokers. The risk of CIN1 increased with increasing exposure time of passive smoking regardless of smoking after adjusting for potential confounder (OR = 2.09; 95% CI: 1.33 ∼ 3.28, p for trend = 0.0023). In non-smoker, the subject with passive smoking had an increased of CIN1 (OR = 1.48; 94% CI: 1.04-2.10, p for trend = 0.0276) after adjusting for potential confounder. In smoker, the effects of passive smoking were not statistically significant. Both of exposure time separated by two hours per day (p for trend = 0.0003), and 1 hour and 2 hours per day (p for trend = 0.0006) of passive smoking demonstrated significant associations with development of CIN1. This is the first study to demonstrate that passive smoking is an independent and combined risk factor of CIN1. HPV viral load and alcohol synergize to increase the risk of CIN1 among high-risk HPV-positive women.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 653. doi:1538-7445.AM2012-653
Abstract 672: Diabetes mellitus as a risk factor for prostate cancer progression after radical prostatectomy in an Hispanic population
Authors: Guerrios Lourdes , Perez Cynthia , Irizarry-Ramirez Margarita , Freedland Stephen 
Published: August 2012

Abstract
Abstract: Introduction and Objective: Prostate Cancer (PC) mortality is higher in Puerto Rico (PR) versus either US Hispanics or Caucasians, despite lower incidence. Also, PR has the highest self- reported prevalence of diabetes mellitus type 2 (DM) among all states and territories. Data on the association between DM and PC is mixed, but a prior study by our group suggested it may affect PC differentially by White vs. Black race. This has not been studied in Hispanic men. Methods: We conducted a retrospective analysis of men treated with RP between 2000-2010 at the San Juan, PR VA Hospital. Data collection is ongoing with 99 men identified to date treated between 2000 and 2003. The association between DM and PSA recurrence was tested using a Cox proportional hazards model. Results: Of the 99 abstracted to date, 21 had DM (21%). There were no differences in pre-operative features between men with and without DM (all p&gt;0.14). Similarly, pathological features were similar between men with and without DM at surgery (all p&gt;0.13). On unadjusted analyses, DM was significantly associated with increased risk of PSA recurrence (HR 2.81, 95% CI 1.31-6.07, p=0.008). These results did not vary significantly after adjusting for age, BMI, Gleason score, and PSA (HR 2.61, 95% CI 1.16-5.89, p=0.021). Updated data will be presented. Conclusion: In a radical prostatectomy cohort of Hispanic men from PR, our preliminary data showed that men with DM at the time of surgery had significantly higher rates of PSA recurrence. As this is the first study of DM and RP outcomes in Hispanic men, these results require validation both in our full cohort and in other datasets. If confirmed, further research is needed to better understand why DM is linked with aggressive PC in Hispanics and whether this information can be used to identify better prevention and treatment strategies for PC, especially for Hispanic men.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 672. doi:1538-7445.AM2012-672