bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4626: Chamomile confers protection against hydrogen peroxide-induced toxicity through activation of Nrf2-mediated defense response
Authors: Bhaskaran Natarajan , Shukla Sanjeev , Gupta Sanjay 
Published: June 2012

Abstract
Cellular damage by reactive oxygen species (ROS) causes aging and remains major factor in the development of various human diseases including diabetes, liver diseases, neurodegenerative and cardiovascular diseases, including cancer. Dietary antioxidants have been considered as an attractive strategy to prevent or attenuate the progression of diseases caused by oxidative stress. Induction of phase 2 detoxifying enzymes in response to naturally occurring agents provides an effective means of protection against oxidative stress. Aqueous extract of chamomile (Matricaria chamomilla) in the form of tea has been used for centuries to treat various inflammatory conditions supporting its traditional use for treating various human ailments. We used aqueous chamomile extract obtained from dried flowers to investigate its effect on Nrf2 activation and induction of phase 2 enzymes in RAW 264.7 murine macrophages and H2O2 as an agent for oxidative stress. Treatment with 50 µM H2O2 for 6 h caused significant increase in cellular stress accompanied by cell death in RAW 264.7 murine macrophages as evident from light microscopy and annexin-V FITC assay. Pre-treatment with chamomile at 10, 20 and 40 µg for 16 h followed by H2O2 treatment protected cell death caused by excessive ROS generation and prevented H2O2-mediated inhibition of cell growth. Chamomile exposure significantly increased the expression of antioxidant enzymes viz. peroxiredoxin (Prx), thioredoxin (Trx) and heme oxygenase (HO-1) in a dose-dependent manner, compared with their respective controls. Furthermore, chamomile exposure to RAW 264.7 murine macrophages increased the nuclear translocation of Nrf2 with increased phosphorylated Nrf2 levels, and it's binding to the antioxidant response element (ARE) in the nucleus. These data provide evidence that chamomile induces the expression of cytoprotective antioxidant enzyme (HO-1) and other redox regulatory enzymes (Prx and Trx) in response to the nuclear translocation of a key redox sensitive transcription factor Nrf2 from the cytoplasm and provide protection from cytotoxicity caused by inflammatory oxidants. Understanding chamomile-mediated molecular events could play a potentially important role in setting up strategies for prevention and treatment of various human diseases including 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 4626. doi:10.1158/1538-7445.AM2011-4626
Abstract 4627: Potent chemotherapeutic activity of green tea polyphenols, blueberry anthocyanidin mixture and cisplatin: Synergistic effects
Authors: Cao Pengxiao , Kausar Hina , Gupta Ramesh 
Published: June 2012

Abstract
A significant progress has been made in the prognosis of several cancers (e.g., breast and prostate cancers). However, the prognosis of lung cancer remains grim. Furthermore, up to 50% of stage I/II non-small-cell lung cancer (NSCLC) patients develop recurrence/metastasis within five years of their treatments. It is eminent that natural compounds or food-based bioactives with minimal toxicity be identified for their use in neo-adjuvant chemotherapy and/or after the primary cancer treatment for enhanced efficacy. Green tea and berries are drawing increased attention due to their potential anti-cancer effects. The active compounds in green tea and berries are polyphenols, e.g., epigallocatechin gallate (EGCG) and anthocyanidins (e.g. delphinidin, cyanidin, peonidin, petunidin, malvidin in blueberry), respectively. We previously demonstrated synergistic antiproliferative activity from these Anths against H1299 lung cancer cells both in vitro and in vivo (Kausar et al. AACR 51: 1884, 2010). In this study we investigated the combined effect of EGCG and the blueberry anthocyanidins (EGCG-Anths) alone and in combination with a common chemotherapeutic drug, cisplatin on lung cancer H1299 cell using MTT assay. The antiproliferative activity of EGCG-Anths (6 μM), measured as IC50, was found to be 2- and 4-fold lower compared with Anths (12 μM) and EGCG (21 μM) alone, respectively. The IC50 of cisplatin was found to be ≈50 μM. However, when combined with the EGCG-Anths (10 μM each), the IC50 of cisplatin was significantly reduced (&lt;3 μM). Flow cytometric analysis for cell cycle distribution and apoptosis revealed cell cycle arrest and enhanced apotosis induced by the combination mixture. Western blot analysis for the involved molecular targets showed that selected proteins (cyclin D1, B1, Cdc2, p21, PCNA, Bax, Bcl-2, PARP, etc.) associated with cell cycle and apoptosis were more significantly modulated by the combination, EGCG-Anths-cisplatin than with the individual entities. Together, our data suggest that combination of EGCG-Anths alone or in combination with suboptimal doses of cisplatin may be effective in neo-adjuvant chemotherapy or can be used as maintenance drug for the prevention of lung cancer recurrence/metastasis and minimize toxicity issues associated with high dose cisplatin (Supported from KLCRP, T32-ES011564 and Agnes Brown Duggan Endowment).
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 4627. doi:10.1158/1538-7445.AM2011-4627
Abstract 4630: Cruciferous vegetable glucosinolate hydrolysis products protect against Benzo[a]pyrene-induced genotoxicity
Authors: David Rhiannon M. , Patel Saroor , Abd Kadir Nurul H. , Rossiter John , Gooderham Nigel 
Published: June 2012

Abstract
Recent epidemiology studies have indicated that cruciferous vegetable intake is inversely correlated with lung cancer risk among smokers (Tang et al., BMC Cancer 2010, 10, 162). Benzo[a]pyrene (BaP) is a prominent contaminant of cigarette smoke, a model genotoxic carcinogen and powerful mutagen. Glucosinolates found in cruciferous vegetables are known to be hydrolysed to compounds that have been shown to be chemopreventive in both animal and cell-based systems, while, paradoxically, evidence is gathering that high concentrations of some of these hydrolysis products are genotoxic.
The aim of the current study was to investigate whether pre-treatment of MCL-5 cells (a metabolically competent human lymphoblastoid cell line) with glucosinolate hydrolysis products conferred protection against the cytotoxicity and genotoxicity induced by a subsequent exposure to BaP. In the case of AITC (allyl isothiocyanate), a model glucosinolate hydrolysis product, toxicity and mutagenicity to MCL-5 cells was established for a range of concentrations. Mutagenicity was assessed through resistance to trifluorothymidine at the thymidine kinase (TK) locus and 6-thioguanine at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus. The chemical treatments revealed a consistent trend for reduced cytotoxicity in cells pre-treated with AITC prior to BaP compared to those treated with BaP alone. Mutation frequency at the TK locus was consistently lower in the cells pre-treated with AITC compared to those treated with BaP alone. High concentrations of AITC induced a prolonged, dose-dependent cytotoxicity with cells only returning to normal growth rate after 7 days.
These data suggest that pre-treatment of MCL-5 cells with glucosinolate hydrolysis products such as AITC affords protection against the genotoxic insult induced by mutagens such as BaP.
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 4630. doi:10.1158/1538-7445.AM2011-4630
Abstract 4637: Intra-individual changes in circulating IGF-1 and IGF-1/IGFBP-3 molar ratio are associated with colorectal adenomatous polyps presence
Authors: Soubry Adelheid , Sedjo Rebecca , Wang Frances , Byers Tim , Rosen Clifford , Yashin Anatoli , Ukraintseva Svetlana , Haffner Steve , D'Agostino Ralph , Il'yasova Dora 
Published: June 2012

Abstract
Background: High levels of circulating insulin-like growth factor-1 (IGF-1) have been associated with increased risks of several cancers, including colorectal cancer.
Methods: In a sub-cohort of the Insulin Resistance and Atherosclerosis Study (IRAS), we examined the associations between circulating IGF-1 and IGF-1/IGFBP-3 molar ratios, as well as their change patterns during 10-year follow-up, with the presence of colorectal adenomatous polyps at the end of the follow-up.
Results: The general trend was decrease of both variables with age. Based on this trend, two patterns were considered: “no increase” (variation within 15% of baseline and/or decrease) and “ever increase” (at least one increase of &gt; 15%). In the subgroup of participants with normal glucose tolerance, “ever increase” was positively associated with colorectal adenoma: ORs were 3.65 (1.30-10.8) and 2.83 (1.00-8.22) for IGF-1 and IGF-1/IGFBP-3, respectively. No association was found between actual levels of IGF-1 or IGF-1/IGFBP-3 at any time point and the presence of colorectal adenoma.
Conclusion: Our data suggest that increase in circulating IGF-1 and IGF-1/IGFBP-3 may represent an unnatural trend of a disturbed signaling pathway, which could favor the development of precancerous lesions, such as colorectal adenoma.
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 4637. doi:10.1158/1538-7445.AM2011-4637
Abstract 4642: Biomarkers for assessment of tissue quality in cancer research
Authors: Li Jie , Eason Arianne , Vortmeyer Alexander 
Published: June 2012

Abstract
Objectives: Much of the progress in molecular cancer research would not have been achieved without access to clinical tissue specimens. However, lack of quality control on these specimens frequently leads to the generation of irreproducible research data, especially when archived samples of uncertain quality are utilized. We hypothesized that biomolecules have different susceptibility to decomposition and that susceptible molecules may serve as indicators to reveal the molecular quality of tissue. We seek to use a proteomic approach to evaluate protein decomposition over time at room temperature (RT) and to mathematically coordinate the extent of decomposition with the RT-exposure time length. This decomposition curve will serve for tissue-quality assessment.
Materials and methods: Cultured cells were used for primary biomarker-screening. Cell origins included kidney (293T), prostate (LNCaP), breast (MDA-MB-231), blood (Jurkat), and lymphoma (Namalwa). Aliquots of cells were randomly assigned to immediate flash-freezing or exposure to RT for 0.5, 4, 8, 24, 48 hours. Lysates were applied in duplicate to Two-Dimensional Fluorescence Difference Gel Electrophoresis (2D DIGE) with pH 3-10 IPG strips and large format PAGE. Proteomic comparison was performed using Decyder software with embedded paired t-/ANOVA-analysis. Spots, consistent in repeats with statistical significance between groups, were sequenced with both LC/MS/MS and MALDI-TOF. Clinical specimens (n=3 for each corresponding organs), procured as above, were used for biomarker validation via regular Western blot and 2-D/IPG-strip Western blot.
Results: 2D-DIGE revealed ∼3000 spots per gel. During the course of exposure to RT, proteomic patterns exhibited dynamic and time-dependent changes in specific subsets of proteins, starting from 0.5 hour. The alterations revealed on 2D-DIGE were changes in molecular weight and/or isoelectric point; the results were validated via Western blot and 2-D/IPG-strip Western blot, respectively. Protein candidates that decomposed in a time-dependent manner allowed for the generation of regression curves using the protein quantity against corresponding time points. Several of above proteins, mostly housekeeping proteins, behaved consistently across all types of observed cell/specimen. Therefore, they could serve as widely applicable biomarkers for indication of exposure time (to RT) and further for assessment of the molecular quality of research specimens.
Conclusions: The study will draw peers’ attention on the molecular quality of their research tissue and offer biomarkers for the quality assessment. Based on the assessment result, the meaning of tissue-research data should be reinterpreted accordingly.
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 4642. doi:10.1158/1538-7445.AM2011-4642
Abstract 4652: Urinary levels of the tobacco-specific carcinogen N′-nitrosonornicotine and its glucuronide are strongly associated with esophageal cancer risk in smokers in the Shanghai Cohort Study
Authors: Yuan Jian-Min , Knezevich Aleksandar D. , Wang Renwei , Gao Yu-Tang , Hecht Stephen S. , Stepanov Irina 
Published: June 2012

Abstract
Background: Experimental studies have shown that the tobacco-specific nitrosamine N′-nitrosonornicotine (NNN) can induce esophageal cancer in rats. However, epidemiological data that directly link NNN to esophageal cancer in humans have been lacking. Methods: A nested case-control study of esophageal cancer including 77 cases and 223 individually matched control subjects within the Shanghai Cohort Study was conducted to examine the association between urinary NNN and risk of developing esophageal cancer among male current smokers. Besides urinary creatinine (Cr) and total cotinine, urinary free NNN and its pyridine-N-glucuronide (NNN-N-Gluc) were quantified separately for each study sample by liquid chromatography- tandem mass spectrometry. A conditional logistic regression method was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for esophageal cancer associated with elevated urinary NNN. All P values reported were two-sided. Results: Esophageal cancer patients had significantly higher urinary levels of free NNN (geometric mean 58.2 fmol/mg Cr), NNN-N-Gluc (49.8 fmol/mg Cr) and the sum of the two, referred to as total NNN (117.9 fmol/mg Cr), than control subjects (geometric means 18.2, 24.4, and 45.1 fmol/mg Cr, respectively) whereas the ratio of NNN-N-Gluc to total NNN was significantly lower in cancer patients (46.7%) than controls (56.4%) (all P's &lt; 0.0001). Compared with the lowest quartile, ORs (95% CIs) for esophageal cancer for the 2nd, 3rd, and 4th quartiles of free NNN were 2.61 (0.80-8.55), 5.74 (1.67-19.75), and 30.64 (7.70-121.93), respectively, after adjustment for smoking intensity and duration (Ptrend &lt; 0.0001). Additional adjustment for urinary cotinine strengthened the association, and ORs (95% CIs) became 4.46 (1.14-17.41), 13.83 (3.21-59.53) and 128.22 (19.9-826.7) (Ptrend &lt; 0.0001). In contrast, the ratio of NNN-N-Gluc to total NNN was inversely associated with esophageal cancer risk. The smoking-adjusted ORs (95% CIs) for the 2nd, 3rd, and 4th quartiles were 0.43 (0.20-0.96), 0.23 (0.09-0.56) and 0.20 (0.08-0.50), respectively, compared with the lowest quartile (Ptrend =0.0002). Additional adjustment for urinary total cotinine did not materially alter the observed ORs. Conclusion: The findings of the present study indicate that the tobacco-specific nitrosamine NNN plays a significant role as a cause of esophageal cancer in smokers. In contrast, the glucuronidation of NNN may protect against the development of tobacco-related esophageal 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 4652. doi:10.1158/1538-7445.AM2011-4652
Abstract 4662: Genetic predictors of clinical outcomes for patients with non-small cell lung cancer
Authors: Pu Xia , Spitz Margaret R. , Amos Chris , Ye Yuanqing , Hildebrandt Michelle A. , Chang David , Lu Charles , Stewart David , Roth Jack A. , Lippman Scott M. , Christiani David , Wu Xifeng 
Published: June 2012

Abstract
Background: Emerging evidence has shown that genetic factors can interact with host factors to influence patient's clinical outcomes. Inflammatory biomarkers have been identified as prognostic factors independent of tumor stage. To test the hypothesis that genetic variants in inflammation-related genes may modulate clinical outcome in non-small cell lung cancer (NSCLC) patients, we conducted a three-stage study, including an initial discovery phase and two validation phases. Methods: In the discovery phase, we analyzed the association between 19,458 SNPs in inflammation-related genes and SNPs from GWAS risk analysis, and clinical outcomes in 1,408 NSCLC patients. In the validation phases, the significant SNPs (p&lt;0.05) were first validated in an additional 1,104 NSCLC patients from MD Anderson and then validated in 978 NSCLC patients from Harvard University. Meta-analysis was used to summarize the combined effect of each SNP in all three stages. Results: A total of 16 SNPs were identified as top candidate predictors of respective outcomes after showing consistent associations in all three stages. Among them, 5 SNPs were associated with overall survival in the entire populations. The most significant SNP is located on chromosome 6 (discovery: HR=1.49, 95%CI=1.10-2.01, P=0.010; combined validation: HR=1.45, 95%CI=1.17-1.78, P=0.001; all combined: HR=1.46, 95% CI=1.23-1.73, P=1.59×10-5). Five SNPs were associated with overall survival in late stage unresectable patients receiving chemotherapy. The most significant SNP, located on chromosome 13, consistently showed increased risk of death in all three phases (discovery: HR=1.40, 95%CI=1.09-1.81, P=0.010; combined validation: HR=1.36, 95%CI=1.14-1.63, P=0.001; all combined: HR=1.37, 95% CI=1.19-1.59, P=2.26×10-5). Six SNPs were consistently associated with progression in early stage patient receiving surgery only. The top SNP was on chromosome 1 with protective effect against developing progression in all three phases (discovery: HR=0.52, 95%CI=0.32-0.86, P=0.033; combined validation: HR=0.63, 95%CI=0.49-0.82, P=0.001; all combined: HR=0.62, 95% CI=0.5-0.79, P=5.47×10-5). To our knowledge, this is the first study to systematically evaluate the association of genetic variations in major inflammation genes and NSCLC patients’ clinical outcomes with a multi-stage design using two of the largest lung studies in the US. Our study provides evidence that genetic variations in inflammation genes may affect clinical outcomes in NSCLC patients.
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 4662. doi:10.1158/1538-7445.AM2011-4662
Abstract 4663: Genetic variation in the p38 signaling pathway as markers for postoperative pulmonary complications in lung cancer patients
Authors: Hildebrandt Michelle A. , Roth Jack A. , Vaporciyan Ara A. , Pu Xia , Ye Yuanqing , Correa Arlene M. , Kim Jae Y. , Swisher Stephen G. , Wu Xifeng 
Published: June 2012

Abstract
Surgical resection is the primary treatment for patients with localized non-small cell lung cancer (NSCLC). Although often a successful treatment option, a portion of these individuals will experience postoperative pulmonary complications, such as pneumonia, acute respiratory distress syndrome, and atelectasis. These complications are difficult to predict and often characterized by a hyper-inflammatory response. The p38 signaling pathway is activated following stress stimuli and in response to inflammatory signals. Because of this important role, we hypothesized that genetic polymorphisms within the core components of this pathway may result in dysregulated response to inflammation following surgery causing unforeseen complications. Therefore, in this study we genotyped 242 common, germline genetic variants from 19 p38 pathway genes in 275 Caucasian NSCLC patients who underwent a lobectomy at MD Anderson. After controlling for clinical risk factors, twenty-three significant associations with any pulmonary complication were observed (P&lt;0.05). Patients carrying at least one variant allele of IRAK2:rs778044 had a complication rate of 49.7% compared to 28.6% for patients with the common genotype for a highly significant 3.10-fold increase in risk (95% Confidence Interval [CI]: 1.76-5.47, P=9.6×10-5). A dose-response effect was evident between number of risk genotypes and risk of complication (P=2.08×10-7). Patients with the highest number of risk genotypes were nearly 14 times more likely to develop a pulmonary complication (95% CI: 5.30-36.87, P=9.73×10-8) compared to those with the fewest risk genotypes. Potential gene-gene interactions were also observed between IRAK2, MYD88, and IL1R1 that identified distinct risk groupings. Patients carrying both the variant genotypes for IRAK2:rs778044 and MYD88:rs11783456 were at highest risk, while those with the common genotype for IRAK2:rs778044 and the protective variant genotype for IL1R1:rs2287047 had the lowest risk. The increase in risk was 23.57-fold for high risk individuals compared to those with the low risk genetic profile (95% CI: 2.75-201.96, P=0.0039). These results strongly implicate the p38 pathway in modulating risk of pulmonary complications following lobectomy for NSCLC. Together with clinical and epidemiological variables, these variants may be useful biomarkers to better identify patients at high risk prior to surgery.
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 4663. doi:10.1158/1538-7445.AM2011-4663