bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 614: Biological clues to potent DNA-damaging activities in food and flavoring.
Authors: Hossain Mohammad Zulfiquer , Gilbert Samuel F. , Patel Kalpesh , Ghosh Soma , Bhunia Anil K. , Kern Scott E. 
Published: August 2014

Abstract
Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.
Citation Format: Mohammad Zulfiquer Hossain, Samuel F. Gilbert, Kalpesh Patel, Soma Ghosh, Anil K. Bhunia, Scott E. Kern. Biological clues to potent DNA-damaging activities in food and flavoring. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 614. doi:10.1158/1538-7445.AM2013-614
Abstract 616: Insulin-like growth factor binding protein-3 (IGFBP-3) facilitates the response to DNA-damaging chemotherapy in triple-negative breast cancer cells.
Authors: Lin Mike Zhen , de Silva Hasanthi C. , Martin Janet Lee , Baxter Robert Charles 
Published: August 2014

Abstract
Introduction. Breast cancer cells frequently develop resistance to DNA-damaging therapy, and epidermal growth factor receptor (EGFR) may play an important role in this process. EGFR can modulate the repair of DNA double strand breaks (DSB) by non-homologous end-joining (NHEJ), by forming protein complexes that include the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). However many ER-negative breast tumors still respond poorly to DNA-damaging drugs even when combined with an EGFR inhibitor. IGFBP-3, an intracellular and secreted protein, is highly expressed in these tumors. Since we previously showed that IGFBP-3 can transactivate EGFR and translocate to the nucleus, the aim of this study was to determine whether IGFBP-3 forms part of the EGFR-DNA-PK complex that regulates the DNA damage response to DSB-inducing chemotherapeutic agents.
Results. In the triple-negative breast cancer cell lines MDA-MB-468 and Hs578T, which express IGFBP-3 highly, protein complex formation and nuclear localization of EGFR, DNA-PKcs and IGFBP-3 were enhanced by exposure to cytotoxic drugs etoposide or doxorubicin and reduced by IGFBP-3 knockdown or the EGFR kinase inhibitor gefitinib. Concomitantly, the co-location of EGFR-IGFBP-3 complexes with lipid rafts, visualized by proximity ligation assay (PLA) and confocal microscopy, decreased in response to drug treatment, consistent with the loss of this complex from the plasma membrane. Furthermore, the phosphorylation of DNA-PKcs at Ser2056 and its substrate Artemis nuclease at S516, and DNA repair capacity as measured by a non-homologous end-joining assay, were all decreased by IGFBP-3 silencing, while H2AX phosphorylation was increased, suggesting that IGFBP-3 has an obligatory role in the DNA repair response to DNA-damaging therapy.
Conclusion. The increased intranuclear interaction between EGFR and DNA-PKcs in response to DNA damage, and the subsequent stimulation of NHEJ activity, require the presence of IGFBP-3, which also forms part of the nuclear complex. This demonstrates a previously unrecognized “caretaker” role for IGFBP-3 in regulating DNA DSB repair by NHEJ. These novel findings suggests the possibility of a therapeutic approach for sensitizing ER-negative breast cancers to chemo- or radiotherapy by targeting the DNA repair function of IGFBP-3. (Supported by Australian Research Council grant DP0984232 to RCB).
Citation Format: Mike Zhen Lin, Hasanthi C. de Silva, Janet Lee Martin, Robert Charles Baxter. Insulin-like growth factor binding protein-3 (IGFBP-3) facilitates the response to DNA-damaging chemotherapy in triple-negative breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 616. doi:10.1158/1538-7445.AM2013-616
Abstract 618: Identification and quantification of human DNA repair protein NEIL1 by liquid chromatography/isotope-dilution tandem mass spectrometry as a potential cancer biomarker.
Authors: Dizdaroglu Miral 
Published: August 2014

Abstract
Accumulated evidence points to DNA repair capacity as an important therapeutic factor in cancer in predicting patient response to DNA-damaging agents such as chemotherapeutic drugs and ionizing radiation. Recent findings suggest that some types of malignant tumors possess increased DNA repair capacity that may affect the therapy and outcome of cancer. Thus, the knowledge of the over-expression or under-expression levels of DNA repair proteins in tumors and disease-free tissues will help develop and guide treatment strategies that will likely lead to the best treatment results for patients. In this context, DNA repair proteins are becoming predictive, prognostic and therapeutic factors in cancer, and also promising drug targets for cancer treatment as DNA repair inhibitors are being developed to increase the efficacy of cancer therapy. We developed assays for the mass spectrometric measurement in tissues of the human DNA repair protein NEIL1 (hNEIL1), which is involved in base excision and nucleotide excision repair pathways of oxidatively induced DNA damage. There is strong evidence for a critical role of NEIL1 in maintaining the genetic stability and in prevention of diseases such as cancer and metabolic syndrome. We applied liquid chromatography/isotope-dilution tandem mass spectrometry (LC-MS/MS), using the fully 15N-labeled analogue of hNEIL1 (15N-hNEIL1) as an internal standard, which we produced, purified and characterized. Both hNEIL1 and 15N-hNEIL1 were hydrolyzed with trypsin. Eighteen tryptic peptides of each protein were identified by LC-MS/MS on the basis of their full-scan mass spectra. These peptides matched the theoretical peptides expected from trypsin hydrolysis of hNEIL1, and provided a statistically significant protein score that would unequivocally identify hNEIL1. The product ion spectra of the tryptic peptides of both proteins were recorded and the characteristic product ions were defined. Selected-reaction monitoring was used to analyze mixtures of hNEIL1 and 15N-hNEIL1 on the basis of product ions. We also showed the detection of these proteins following their separation by gel electrophoresis and in-gel trypsin digestion. Our results suggest that the assays developed would be highly suitable for the positive identification and accurate quantification of hNEIL1 in tissues in vivo as a potential cancer biomarker.
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Citation Format: Miral Dizdaroglu. Identification and quantification of human DNA repair protein NEIL1 by liquid chromatography/isotope-dilution tandem mass spectrometry as a potential cancer biomarker. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 618. doi:10.1158/1538-7445.AM2013-618
Abstract 62: Detection and comparison of EGFR mutations in matched tumor tissue, cell block, pleural effusion and serum with PNA clamping and direct sequencing in NSCLC with malignant pleural effusion.
Authors: Park Chan Kwon , Dong Chang , Jin Woo Jin Woo , Kim Kwan Hyoung , Ha Jick Hwan , Rhee Chin Kook , Kim Young Kyoon , Lee Sang Haak , Park Mi Sun , Yim Hyeon Woo , Kim Seung Joon 
Published: August 2014

Abstract
Background: Peptide nucleic acid (PNA)-mediated real-time PCR clamping was recently used to detect mutations because it has higher sensitivity than conventional direct sequencing. Pleural effusion and serum samples could be good sources of detecting the epidermal growth factor receptor (EGFR) mutational status of non-small cell lung cancer (NSCLC) patients. Methods: We studied 37 NSCLC patients with malignant pleural effusion. In each patient, EGFR mutational status was measured from the samples of tumor tissue, cell block, pleural effusion and serum using both PNA clamping and direct sequencing. The concordance between PNA clamping and direct sequencing, and the diagnostic performance of pleural effusion was investigated. Results: The detection rate of EGFR mutation in the pleural effusion and the serum was 27% and 2.8%, respectively by both PNA clamping and direct sequencing. The κ coefficient between the two methods were 0.68 (p-value = 0.0007), 0.91 (p-value &lt; 0.0001), 0.75 (p-value &lt; 0.0001) and -0.01 (p-value = 0.8639) in tissue, cell block, pleural effusion and serum, respectively. The diagnostic performance of pleural effusion compared with combined tumor tissue plus cell block showed sensitivity 89%, specificity 100%, positive predictive value 100% and negative predictive value 95% with PNA clamping, and sensitivity 67%, specificity 90%, positive predictive value 75% and negative predictive value 86% with directing sequencing. Interestingly, a patient who was confirmed EGFR mutation only with the PNA clamping showed significant response to EGFR TKI (tyrosine kinase inhibitor). Conclusion: Despite the limited role of serum samples, pleural effusion had a diagnostic performance comparable with tumor tissue and cell block to detect EGFR mutational status in NSCLC. Although the diagnostic performance of PNA clamping was similar to that of direct sequencing, additional benefit is expected considering the response to the EGFR TKI.
Citation Format: Chan Kwon Park, Chang Dong, Jin Woo Jin Woo, Kwan Hyoung Kim, Jick Hwan Ha, Chin Kook Rhee, Young Kyoon Kim, Sang Haak Lee, Mi Sun Park, Hyeon Woo Yim, Seung Joon Kim. Detection and comparison of EGFR mutations in matched tumor tissue, cell block, pleural effusion and serum with PNA clamping and direct sequencing in NSCLC with malignant pleural effusion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 62. doi:10.1158/1538-7445.AM2013-62
Abstract 623: The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair.
Authors: Koch Christine A. , Fenton Amanda L. , Shirodkar Purnata , Meng Li 
Published: August 2014

Abstract
APLF is a forkhead associated (FHA)-containing protein with poly(ADP-ribose)-binding zinc finger (PBZ) domains, which undergoes ionizing radiaiton (IR)-induced and ATM-dependent phosphorylation at serine-116 (Ser116). Here we demonstrate that the phosphorylation of APLF at Ser116 in human U2OS cells by ATM is dependent on PARP3 levels and the APLF PBZ domains. The interaction of APLF at sites of DNA damage was diminished by the single substitution of APLF Ser116 to alanine, and the cellular depletion or chemical inhibition of ATM or PARP3 also altered the retention of APLF at sites of laser-induced DNA damage, and impaired the accumulation of Ser116-phosphorylated APLF at IR-induced γH2AX foci in human cells. The data further suggest that ATM and PARP3 participate in a common signaling pathway to facilitate APLF-Ser116 phosphorylation, which, in turn, appears to be required for efficient DNA double-strand break (DSB) repair kinetics and cell survival following IR. Collectively, these findings provide a more detailed understanding of the molecular pathway that leads to the phosphorylation of APLF following DNA damage, and suggest that Ser116-APLF phosphorylation facilitates APLF-dependent DSB repair.
Citation Format: Christine A. Koch, Amanda L. Fenton, Purnata Shirodkar, Li Meng. The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 623. doi:10.1158/1538-7445.AM2013-623
Abstract 635: PARP inhibition in HPV positive head and neck cancers.
Authors: Cooper Tiffiny , Rodriguez Marcela , Trummell Hoa Q. , Weaver Alice , Bonner James A. , Yang Eddy S. 
Published: August 2014

Abstract
Purpose: The human papilloma virus (HPV) has recently become a prevalent cause of human head and neck cancer (HNC), which often exhibits dysregulated epidermal growth factor receptor (EGFR) signaling. We previously reported that in non-HPV-associated HNC, inhibition of EGFR (EGFRi) attenuates DNA double stranded break (DSB) repair and subsequently sensitizes tumors to inhibitors of poly (ADP-ribose) polymerase (PARP), which target DNA repair deficient tumors. Because patients with HPV-associated HNC have been shown to exhibit increased sensitivity to DNA damage, we evaluated the response of HPV (+) HNC cells to combination EGFRi and PARPi compared to HPV (-) HNC cells.
Methods: HPV (-) UM-SCC1 and UM-SCC6, as well as HPV (+) SCC-47 and SCC-90 were utilized for in vitro studies. Cell growth and survival fraction were evaluated via cell proliferation and colony formation assays, respectively. DNA damage studies were performed using standard γ-H2AX and Rad51 foci. Lastly, in vivo studies were conducted in mice bearing HNC tumor xenografts as well as a human tumor explant from a lymph node metastasis of a HPV(+) HNC patient.
Results: Interestingly, HPV (+) HNCs exhibited the greatest sensitivity both in vitro and in vivo to PARP inhibition alone. This correlated with a blunted DNA damage response. In contrast, HPV (-) HNCs were most sensitive to combination EGFRi/PARPi, which correlated with persistent DNA damage.
Conclusions: HPV(+) head and neck cancers may be sensitive to PARP inhibition alone. Our in vitro and in vivo results warrant further testing of PARP inhibitors as part of therapy for HNCs.
Citation Format: Tiffiny Cooper, Marcela Rodriguez, Hoa Q. Trummell, Alice Weaver, James A. Bonner, Eddy S. Yang. PARP inhibition in HPV positive head and neck cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 635. doi:10.1158/1538-7445.AM2013-635
Abstract 641: Correlation of methylation status of deep surgical margins with the local reccurence of head and neck squamous cell carcinoma.
Authors: Hayashi Masamichi , Wu Gaosong , Chang Xiaofei , Li Xiufeng , Ahn Julie , Khan Zubair , Akpeng Belinda , Roh Jong–Lyel , Koch Wayne 
Published: August 2014

Abstract
Background: Locoregional recurrence occurs in as many as 40% of patients undergoing surgery for head and neck squamous cell carcinoma (HNSCC). We have been focused some molecular alterations exsiting even in histologically negative surgical margins. However, in head and neck cancer resection, surgical margins are hard to evaluate because the most of them usually consists of complicated muscular margins. In order to evaluate these deep surgical margins, before collecting some margin tissues, we often conduct tissue imprinting by using one layer nitrocellulose sheet which can collect proteins without hurting surgical samples.
Method: Both 161 deep margin tissues and 166 deep margin imprints were collected from 74 histologically margin negative resections of primary HNSCC from May, 2009 to September, 2012. Bisulfited DNA from samples were amplified using quantitive methylation-specific polymerase chain reaction (QMSP) for 6 genes (DCC, EDNRB, HOXA9, KIF1A, NID2 and NR2B). The cut off value was calculated using QMSP data of tumors and normal muscles, and was applied to deep margin samples. The correlation between the QMSP status of deep margin samples and clinical outcome was evaluated.
Results: The average QMSP of tumor tissues, that of normal muscles and the cut off value are 21.0, 0.6, 2.1 in DCC, 23.3, 0.6, 2.2 in EDNRB, 32.0, 0.7, 2.3 in HOXA9, 20.3, 0.4, 1.3 in KIF1A, 36.0, 3.0, 9.4 in NID2 and 10.7, 0.1, 0.4 in NR2B. Those who has the higher QMSP values of deep margin tissues than the cut off value tends to have a poor recurrence free survival (P=0.073 in DCC, P=0.018 in HOXA9, P=0.005 in KIF1A, P=0.011 in NID2) and a poor overall survival (P=0.076 in HOXA9, P=0.059 in NID2). Also, those who has the higher QMSP values of deep margin imprints than the cut off value tends to have a poor recurrence free survival (P=0.051 in HOXA9) and a poor overall survival (P=0.075 in HOXA9).
Conclusion: The methylation status of HNSCC deep surgical margin samples is correlated with the local recurrence. Especially, hyper-methylated HOXA9 gene of both deep margin tissues and imprints is a significant biomarker of poor recurrence free survival and overall survival.
Citation Format: Masamichi Hayashi, Gaosong Wu, Xiaofei Chang, Xiufeng Li, Julie Ahn, Zubair Khan, Belinda Akpeng, Jong–Lyel Roh, Wayne Koch. Correlation of methylation status of deep surgical margins with the local reccurence of head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 641. doi:10.1158/1538-7445.AM2013-641
Abstract 647: Novel promoter hypermethylation marker for prognostic in cervicouterine cancinogenesis.
Authors: Brebi Priscilla , Andana Alejandra , Hoffstetter Rene , Ili Carmen , Viscarra Tamara , Silva Ramon , Garcia Patricia , Leal Pamela , Weber Helga , Roa Juan C. 
Published: August 2014

Abstract
New biomarkers are needed to improve cervical cancer screening technologies, which are mostly based on cytological examination and HPV detection. However, PAP-smear has a low-sensitivity to detect low grade squamous intraepithelial lesions and not all HPV infected women will develop preneoplastic or neoplastic lesions. Previous results of our group showed that genes Gen Z (patent pending), CDH1 and MEGF9 could be hypermethylated in cervical cancer and not in normal epithelia. The aim of this study was to determinate if promoter methylation status of genes (Gen Z, CDH1 and MEGF9) are related with progression or diagnosis of cervical carcinogenesis.
For this study, 107 citobrush, urine and blood samples were collected from women who attended to gynecological care in a public health center in Temuco, Chile. Citobrush DNA from 50 normal, 40 low grade squamous intraepithelial lesion (LSIL), 40 high grade squamous intraepithelial lesion (HSIL) and 17 squamous cervical cancer were bisulfite converted for methylation specific PCR (MSP). Bisulfite conversion was confirmed by amplification of a 133-bp fragment of the β-actin. MSP primers were specifically design for CpG island of promotor region of each gene.
Gen Z was found 100% methylated in SCC samples, 65% in HSIL, 43% in LSIL and in normal samples only a 26%. MEGF9 and CDH1 genes were found methylated in 36% and 48% of normal samples, 45% and 55% of LSIL, 70% and 77% of HSIL and 47% and 71% of SCC, respectively.
All promoter regions studied showed a higher methylation frequency in LSIL, HSIL and SCC than normal samples. Significant statistical differences in Gen Z and CDH1 Methylation frequencies between normal and SCC samples were found (P&lt;0.05). Methylation of Gen Z increased in a sequential and cumulative way as the lesion progress.
Our results suggest that the Gen Z could be useful tool for identifying women with a higher risk of progression to cervical cancer. Examination of these biomarkers in a larger, independent cohort is warranted. Grant Support: This investigation was financed by Proyect CORFO-INNOVA N°07CN13PBT-222 and Proyect CORFO N° 09CN14-5960 (CEGIN). CI is recipient of grants from FONDECYT Postdoctoral Proyect N° 3130630. PB is recipient of grants from FONDECYT Postdoctoral Proyect N° 3120141
Citation Format: Priscilla Brebi, Alejandra Andana, Rene Hoffstetter, Carmen Ili, Tamara Viscarra, Ramon Silva, Patricia Garcia, Pamela Leal, Helga Weber, Juan C. Roa. Novel promoter hypermethylation marker for prognostic in cervicouterine cancinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 647. doi:10.1158/1538-7445.AM2013-647
Abstract 650: IGSF4 methylation is an independent marker of HPV positive OPSCC.
Authors: Chen Kang Mei , Stephen Josena K. , Mahan Meredith , Havard Shaleta , Divine George , Gardner Glendon , Schweitzer Vanessa P. , Worsham Maria J. 
Published: August 2014

Abstract
Human papilloma virus (HPV) is a known causative agent for oropharyngeal squamous cell cancer (OPSCC). The goal of our study was to determine the relationship of HPV type 16 (HPV16) infection and methylation status in an OPSCC cohort. HPV16 was detected using real-time quantitative PCR (qPCR) in a retrospective cohort of 111 primary OPSCC. A 24 tumor suppressor gene candidate panel was assessed for methylation using the methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) assay. Univariate associations with HPV and gene methylation, age, gender, race and smoking were analyzed using Fisher's exact tests and logistic regression. A final multiple logistic regression model, to include patient characteristics and genes significant on univariate analysis, was built using backwards selection of genes. Statistical significance was set at p&lt;0.05 and all analyses were done using SAS 9.2. In univariate analyses, Caucasian American (CA) OPSCC were more likely to be HPV positive as compared to African American (AA) OPSCC (OR=3.01, 95% CI 1.28, 7.07, p=0.011). Also, smoking (never vs current) [OR=3.60 (1.06, 12.24), p=0.04], and TIMP3, DAPK1, ESR1, and IGSF4 were associated with HPV positive status (OR=5.03, p=0.021; OR=3.71, p=0.04; OR=5.03, p=0.021; OR=7.68, p=0.012, respectively). The final model, after controlling for patient characteristics and after backward elimination of genes, indicated IGSF4 methylation is an independent predictor of HPV positive status [OR=7.07 (1.22, 40.79), p=0.029]. HPV infection status is independently associated with methylation of IGSF4, indicating interplay of DNA methylation and HPV in OPSCC pathogenesis.
Citation Format: Kang Mei Chen, Josena K. Stephen, Meredith Mahan, Shaleta Havard, George Divine, Glendon Gardner, Vanessa P. Schweitzer, Maria J. Worsham. IGSF4 methylation is an independent marker of HPV positive OPSCC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 650. doi:10.1158/1538-7445.AM2013-650