bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A59: Combination of quercetin and tannic acid as a potential proteasome inhibitor for cancer chemoprevention
Authors: Chang Tsui-Ling , Wang Chi-Hsien 
Published: January 2014

Abstract
To look for oral proteasome inhibitors, the daily food is best source for cancer chemoprevention. A combination of active components from vegetables, coffee, tea, and fruit could be more efficient to inhibit 26S proteasome activities for preventing cancer diseases. Tannic acid and quercetin have been shown to strongly inhibit 26S proteasome activity, but the molecular target involved remains unknown. Overlay assay, peptide assay, western blot, and 2-D gels were used to assess the combination of quercetin and tannic acid as a potential inhibitor. Here, we demonstrated that the combination of quercetin and tannic acid synergistically suppresses chymotrypsin-like, caspase-like, and trypsin-like proteolytic activities and are tightly binding substrates. Quercetin plus tannic acid do not perturb the proteasome structure, inhibit the 26S proteasome affected by ubiquitin, ATP, or β-casein, and inhibit β-casein degradation by the 26S proteasome in vitro. Finally, inhibition of the proteasome by a combination of quercetin and tannic acid in Hep-2 cells resulted in induction of S5a at low dose, accumulation of ubiquitin, and the cleavage of pro-caspase-3, followed by induction of apoptotic cell death. Evaluating the combination of quercetin and tannic acid as an oral drug to prevent cancer may provide a pharmacological rationale to pursue preclinical trials of this combination.
Citation Format: Tsui-Ling Chang, Chi-Hsien Wang. Combination of quercetin and tannic acid as a potential proteasome inhibitor for cancer chemoprevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A59.
Abstract B14: Predicting prostate cancer: a novel, non-invasive approach
Authors: Roberts Matthew J. , Schirra Horst J. , Lavin Martin F. , Gardiner Robert A. 
Published: January 2014

Abstract
Introduction: Current approaches to the detection of prostate cancer require improvement. PSA and other methods fall short in discriminating between benign and malignant prostates, as well as defining the nature of disease.
We hypothesize that multiple markers, in non-invasive samples, can better detect prostate cancer and improve patient outcomes.
Methods: Discriminating mRNA markers in prostatic tissues were identified, and quantified using standard assays, to complement the non-coding gene PCA3. Complementary metabolomic analysis of ejaculate was performed using 500 MHz 1H-NMR spectroscopy.
Results: In 100 patients, RT-PCR for PCA3 and Hepsin from ejaculate in combination with serum PSA provided improved prediction compared with PSA alone. Further mRNA markers marginally improved these results.
Metabolomic analysis of ejaculate was initially confounded by contributions from buffer solution. Appropriate exclusion of confounders provided improved insight into sample and disease pathophysiology, and was combined with the molecular analysis.
Preliminary results have indicated that combining molecular and metabolomic data promise to improve detection rates. Results from this combined data analysis will be presented.
Furthermore, patients with initially negative prostate biopsies have been monitored for disease progression, with a number changing status over time. These findings have been analyzed and will also be presented.
Conclusion: Our results suggest that there is potential for non-invasive detection of prostate cancer. Current methods of detection are improved by combining clinical, genetic and metabolic markers from excreted biofluids. Further insight is provided into the pathophysiology of prostate cancer, which will further advance integration with imaging, as well as advancing the development of an accurate, non-invasive screening test for prostate cancer.
Citation Format: Matthew J. Roberts, Horst J. Schirra, Martin F. Lavin, Robert A. Gardiner. Predicting prostate cancer: A novel, noninvasive approach. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B14.
Abstract B29: Characterizing candidate breast cancer tumor suppressors: MTUS2 and LHX8
Authors: Fru Diane , Ruhl Victoria , Green Michael R. 
Published: January 2014

Abstract
Breast cancer is the most commonly occurring cancer among women in the United States. As with all other cancer types, breast cancer formation is the result of alterations in tumor suppressor genes, which regulate diverse cellular activities to prevent tumor development, and oncogenes, which promote tumor formation. In this study, we further characterized two candidate breast cancer tumor suppressor genes, MTUS2 and LHX8, and their role in breast cancer development. Soft agar assays showed that the knockdown of MTUS2 and LHX8 in MCF10AT cells led to increased colony formation compared to non-silencing control. Furthermore, through q-RT-PCR analysis, we found that the relative mRNA expression of MTUS2 and LHX8 is down-regulated in a panel of breast cancer cell lines compared to the pre-malignant breast epithelial cell line MCF10AT. Finally, when we ectopically expressed MTUS2 or LHX8 in MCF7 cells it resulted in slower proliferation of the cells compared to an empty vector control. Taken together, these results provide further information concerning the roles MTUS2 and LHX8 play in breast tumorigenesis. This study implicates two breast cancer tumor suppressor genes, which can provide a unique tool for identifying novel pathways involved in the formation of breast cancer.
Citation Format: Diane Fru, Victoria Ruhl, Michael R. Green. Characterizing candidate breast cancer tumor suppressors: MTUS2 and LHX8. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B29.
Note: This abstract was withdrawn after the Proceedings was printed and was not presented at the conference.
Abstract B56: Activation of Chk1 by Piperine causes cell cycle arrest and apoptosis in melanoma cells
Authors: Fofaria Neel , Srivastava Sanjay K. 
Published: January 2014

Abstract
The National Cancer Institute estimates that about 76,250 new cases of melanomas will be diagnosed in 2012 in the United States leading to at least 9810 related deaths. Therefore, novel strategies to control and treat melanoma are of prime importance. In this study, we determined the cytotoxic effects of piperine, a major constituent of black (Piper nigrum Linn) and long pepper (Piper longum Linn), in melanoma cell lines. Piperine treatment inhibited the growth of SKMEL-28 and B16-F0 cells in a dose and time-dependent manner. The growth inhibitory effects of piperine were mediated by cell cycle arrest of both the cell lines in G1 phase. The G1 arrest by piperine correlated with the down-regulation of cyclin D1 and induction of p21. Furthermore, this growth arrest was associated with DNA damage caused by piperine treatment as indicated by phosphorylation of H2A.X at Ser139, activation of ataxia telangiectasia and Rad3-related protein (ATR) and checkpoint kinase 1 (Chk1). Pretreatment with AZD 7762, a Chk1 inhibitor not only abrogated the activation of Chk1 but also piperine mediated G1 arrest. Furthermore, transfection of cells with Chk1 siRNA completely protected the cells from G1 arrest induced by piperine treatment. The G1 arrest by piperine was also confirmed with the down-regulation of E2F1 and decreased phosphorylation of retinoblastoma protein (Rb), indicating the inhibition of the dynamic transcription complex. In addition, apoptosis induced by piperine was associated with down-regulation of XIAP and Bid (uncleaved) and cleavage of Caspase-3 and PARP. In addition, our results showed that piperine treatment generated ROS in melanoma cells. Blocking ROS generation by Tiron prevented the cells from piperine mediated cell cycle arrest. Taken together, our results demonstrate that activation of Chk1 is required for piperine induced G1 phase cell cycle arrest. [Supported in part by R01 grants CA 106953 and CA 129038 awarded to S.K.S by National Cancer Institute, NIH]
Citation Format: Neel Fofaria, Sanjay K. Srivastava. Activation of Chk1 by Piperine causes cell cycle arrest and apoptosis in melanoma cells. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B56.
Abstract B98: Parity, breastfeeding and oral contraceptive use and risk of estrogen- and progesterone-negative breast cancer in the Breast Cancer Family Registry
Authors: Work Meghan E. , John Esther M. , Hopper John L. , Andrulis Irene L. , Terry Mary Beth 
Published: January 2014

Abstract
Introduction: Estrogen receptor (ER) and Progesterone receptor (PR) negative breast cancer (ER-PR-) is associated with poor prognosis. Little is known about modifiable risk factors, such as oral contraceptive use or breastfeeding, that can reduce risk of this cancer type; however, emerging evidence suggests that increased parity without breastfeeding may increase the risk of ER-PR- breast cancer, and that breastfeeding specifically will reduce this increased risk. Using population-based ascertained breast cancer cases from the Breast Cancer Family Registry (BCFR), we examined reproductive risk factors in relation to ER-PR- breast cancer.
Methods: Using data from 4,011 incident invasive breast cancer cases and 2,997 population-based controls from the BCFR, we evaluated the association between reproductive and hormonal risk factors with ER and PR status using unordered polytomous logistic regression, comparing two case groups, hormone receptor positive (HR+) breast cancers and ER-PR- breast cancer, to the control group.
Results: High parity without breastfeeding was positively associated only with ER-PR- tumors (odds ratio [OR] =1.57, 95% confidence interval [CI], 1.10-2.24, for ≥3 live births vs. nulliparity). High parity, when coupled with breastfeeding, was no longer associated with ER-PR- breast cancer (OR=0.93, 95%CI 0.71-1.22), and was inversely associated with all other HR+ cancers (OR=0.82, 95%CI 0.68-0.98). Parity (≥1 live birth vs. nulliparity), regardless of breastfeeding history, was protective against HR+ cancers only among postmenopausal women (OR=0.69, 95%CI 0.50-0.94). Oral contraceptive (OC) use was inversely associated with HR+ cancer (OR=0.82, 95%CI 0.69-0.96), but not associated with ER-PR- cancer. However, we found that OC use that commenced prior to 1975 was associated with an increased risk of ER-PR- cancer (OR=1.32, 95%CI 1.04-1.67), whereas OC use remained inversely associated with HR+ cancer only among women who began use in 1975 or later (OR=0.59, 95% CI 0.48-0.72).
Conclusion: As there are few modifiable factors for ER-PR- breast cancers, our findings lend further support to the potential that may be gained through greater promotion of breastfeeding to women at risk of ER-PR- breast cancers, and indicate that OC use is not a source of increased risk for these women.
Citation Format: Meghan E. Work, Esther M. John, John L. Hopper, Irene L. Andrulis, Mary Beth Terry. Parity, breastfeeding, and oral contraceptive use and risk of estrogen- and progesterone-negative breast cancer in the Breast Cancer Family Registry. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B98.
Abstract CN01-01: Inflammation links COPD/emphysema and lung cancer.
Authors: Houghton A. McGarry 
Published: January 2014

Abstract
Numerous epidemiological studies have consistently linked the presence of chronic obstructive pulmonary disease (COPD) to the development of lung cancer, independent of cigarette smoking dosage. The mechanistic explanation for this remains poorly understood. Progress toward uncovering this link has been hampered by the heterogeneous nature of the two disorders, with each being characterized by multiple sub-phenotypes of disease.
COPD can be broadly split into two disease processes, disease of the breathing tubes (airways disease) or destruction of the tiny air-sacks in the peripheral regions of the lung (airspace disease, or emphysema). A few insightful clinical studies have more clearly illustrated the nature of the link between COPD/emphysema and lung cancer by demonstrating that lung cancer risk is conferred by the emphysema component, and not by the airway component.
The current onus on the field is to identify mechanisms of disease common to both emphysema and lung cancer. There are several possibilities, including common genetic susceptibilities, competing forces with respect to apoptotic signaling, and shared inflammatory cell infiltrates.
The characteristic inflammatory cell infiltrate that is operative in emphysema pathogenesis and present within the tumor microenvironment, would appear to be the “low hanging fruit.” As such, this possible mechanistic link has received the most attention in this burgeoning field. Cigarette smoking produces a well-described infiltrate of macrophages, neutrophils, and T lymphocytes. Many of the products released by these cells'proteinases, reactive oxygen species, growth factors'are well known to fuel lung tumor growth, and in some cases, invasiveness as well. This microenvironment is not at all straightforward, however, as CD8+ T cells, present in emphysema, typically function in an antitumor fashion.
Going forward, the advancement of this field will require an improvement in disease models that allow for the simultaneous study of lung carcinogenesis within an emphysematous microenvironment. However, the potential to identify a common chemo-preventive target exists, and would be a welcome addition to clinicians, who have precious few options for patients afflicted with one or both of these diseases.
Citation Format: A. McGarry Houghton. Inflammation links COPD/emphysema and lung cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN01-01.
Abstract CN01-02: Epidemiology and pathogenesis of cancer in the setting of HIV infection
Authors: Casper Corey 
Published: January 2014

Abstract
Cancer has emerged as a leading cause of morbidity and mortality among HIV-infected persons worldwide. The incidence of cancer is increased exponentially in HIV-positive individuals, and in the United States it is estimated that nearly 10% of persons living with HIV will develop cancer in their lifetime. In this presentation, the epidemiology of HIV-associated malignancies in resource-rich and resource-limited settings will be reviewed, and the factors that predispose persons living with HIV to the development of cancer will be explored. The translatability of cancer screening and prevention practices from HIV-negative to HIV-positive patient populations remains unproven, but strategies for cancer prevention in HIV-positive individuals will be reviewed.
Citation Format: Corey Casper. Epidemiology and pathogenesis of cancer in the setting of HIV infection. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN01-02.
Abstract CN04-01: Aspirin for cancer prevention: Are we there yet?
Authors: Chan Andrew T. 
Published: January 2014

Abstract
Remarkably consistent experimental and epidemiologic evidence demonstrates that aspirin is associated with a lower risk of colorectal cancer. Four placebo-controlled randomized controlled trials (RCTs) among individuals with a history of colorectal neoplasia showed that aspirin reduced the risk of recurrent adenomas, the precursors of the vast majority of cancers. Nonetheless, in 2007 the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin to prevent colorectal cancer in individuals at average risk. However, since the USPSTF statement, new information has emerged, persuasively making the case for a broader role for aspirin in cancer prevention. These data include long-term follow-up of a RCT of aspirin among individuals with Lynch syndrome, a hereditary colorectal cancer syndrome and secondary analyses of RCTs of aspirin for cardiovascular prevention. The latter collection of studies also showed a lower risk of all cancer and cancer-related deaths among individuals randomized to aspirin, a finding which could substantially alter the risk-benefit calculus for regular aspirin use in the general population. In addition, there are mounting data supporting an association between aspirin use and improved outcomes among colorectal cancer survivors. In this presentation, we will review the evidence supporting a role for aspirin in the prevention and treatment of cancer, with a focus on novel strategies for risk stratification.
Citation Format: Andrew T. Chan. Aspirin for cancer prevention: Are we there yet? [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN04-01.
Abstract ED01-03: Planning, design, and execution of cancer screening and early detection trials: Application to the National Lung Screening Trial (NLST)
Authors: Hu Ping , Prorok Philip 
Published: January 2014

Abstract
Consider a randomized clinical trial to evaluate the benefit of screening an asymptomatic population. Suppose that subjects are randomized into a usual care and a study group. The study group receives one or more periodic early detection examinations aimed at diagnosing disease early, when there are no signs or symptoms. Early detection clinical trials differ from therapeutic trials in that power is affected by: (i) the number of exams, (ii) the time between exams and (iii) the optimal time of analysis and length of follow-up. These design options do not exist in therapeutic trials. Furthermore long-term follow-up may result in a reduction of power. In general power increases with number of examinations, and the optimal follow-up time is dependent on the spacing between examinations. Clinical trials in which the usual care group receives benefit are also briefly discussed. Two designs are presented, i.e. The “Up-front Design” in which all subjects receive an initial exam and then are randomized to the usual care and study groups and the “Close-out Design” in which the usual care group receives an exam which is timed to be given at the same time as the last exam in the study group. Both families of designs significantly reduce the power. The optimization criterion is to maximize the power of the statistical test for comparing mortalities. Application is made to National Lung Screening Trials (NLST).
Citation Format: Ping Hu, Philip Prorok. Planning, design, and execution of cancer screening and early detection trials: Application to the National Lung Screening Trial (NLST). [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED01-03.
Abstract ED02-02: Notch defines the tumor initiating cell in non-small cell lung cancer
Authors: Zheng Yanyan , Cruz Cecile de la , Sayles Leanne C. , Alleyn-Chin Chris , Knaak Tim D. , Bigos Marty , Xu Yue , Hoang Chuong D , Shrager Joseph , Sweet-Cordero E. Alejandro , Jackson Erica L. 
Published: January 2014

Abstract
We investigated heterogeneity of tumorigenic capacity in KrasG12D and KrasG12D; Trp53 fl/fl mouse models of non-small cell lung cancer. Loss of Trp53 greatly enhances self-renewal in vitro and tumor propagating capacity in vivo. A conserved set of markers including CD24, ITGB4 and Notch enriches for a rare population of tumor initiating cells (TICs) in tumors driven by oncogenic Kras regardless of disease stage, or the presence or absence of Trp53. Notch marks TICs and Notch signaling is also required for their self-renewal and tumor propagating capacity. Using primary human NSCLC ex vivo cultures, we demonstrate a role for Notch signaling in the self-renewal of human tumor cells. Using multiple methods of Notch3 specific inhibition we demonstrate a Trp53-independent role for Notch3 in the maintenance of TICs in mouse lung tumor models.
Citation Format: Yanyan Zheng, Cecile de la Cruz, Leanne C. Sayles, Chris Alleyn-Chin, Tim D. Knaak, Marty Bigos, Yue Xu, Chuong D Hoang, Joseph Shrager, E. Alejandro Sweet-Cordero, Erica L. Jackson,. Notch defines the tumor initiating cell in non-small cell lung cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED02-02.
Abstract ED04-03: Genomic profiles of infection-related cancers in Asia
Authors: Tan Patrick B. 
Published: January 2014

Abstract
Malignancies caused by infectious pathogens represent a unique opportunity for cancer prevention research. In Asia, several highly lethal cancers are known to be caused by pathogens, such as stomach cancers (H. pylori), bile duct cancers (liver flukes), and certain lymphoma subtypes (Epstein-Barr Virus). For many of these conditions, treatment options are still highly limited. In this Educational Session, I will describe how genomic analysis of infection-related Asian cancers can provide insights into cellular processes disrupted by these pathogens, and how such data can be used to identify new therapeutic targets.
Citation Format: Patrick B. Tan. Genomic profiles of infection-related cancers in Asia. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED04-03.