bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4105: Prevalence of breast stem cells in high-risk benign breast lesions and association with breastfeeding
Authors: Atkinson Rachel L. , Symmans Fraser , Bevers Therese B. , Woodward Wendy A. , Brewster Abenaa M. 
Published: May 2015

Abstract
Background: Invasive breast cancers contain a subpopulation of cancer stem cells that are thought to maintain the heterogeneity and self-renewing potential of the tumor. In our previously published data, we demonstrated that stem cells in normal adjacent tissues were associated with triple negative breast cancer. The objective of this study is to determine the presence of stem cells in high risk breast lesions. We hypothesized that stem cells in high-risk lesions and normal adjacent breast tissue may represent a biomarker for increased breast cancer risk. Methods: We identified biopsies from 42 high-risk women seen in the Cancer Prevention Center at The University of Texas MD Anderson Cancer Center between 1988-2011. We collected information on breast cancer risk factors. The biopsies contained high-risk lesions including ductal carcinoma in situ (DCIS) n=21, lobular carcinoma in situ (LCIS) n=5, atypical ductal hyperplasia (ADH) n=7 and atypical lobular hyperplasia (ALH) n=6. The tissues were fluorescently labeled for stem cell markers CD44/CD49f/CD133, and were scored positive if more then 1% cells were positive for all markers using an automated fluorescent microscopy software. The presence of stem cell markers was compared in the normal adjacent tissues and high-risk lesions from a subset of 25 patients. Results: We identified stem cells in 46% of samples containing DCIS, 67% of LCIS, 63% of ALH, and 70% of ADH. There was a 79% concordance in stem cell positive status between the high-risk lesion and adjacent normal tissue. Women with positive stem cell high-risk lesions had no significant difference in age at first birth (24.4 years vs 26.6 years p=0.3), parity (1.7 vs 1.9, p=0.5), or body mass index (27.8 vs 31.8, p=0.07) compared to women without positive stem cell high-risk lesions. Women with positive stem cell high-risk lesions had shorter breastfeeding duration than women without (2.4 months vs 9.0 months p= 0.05). Conclusion: This is the first report, to our knowledge, that stem cells are present in some high-risk lesions and their associated normal breast tissue. Correlation with future development of invasive breast cancer could lay the foundation for future targeted breast cancer prevention strategies.
Citation Format: Rachel L. Atkinson, Fraser Symmans, Therese B. Bevers, Wendy A. Woodward, Abenaa M. Brewster. Prevalence of breast stem cells in high-risk benign breast lesions and association with breastfeeding. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4105. doi:10.1158/1538-7445.AM2014-4105
Abstract 4117: Utilizing RNA aptamers for biomarker discovery in a novel cell culture system for hepatocellular carcinoma
Authors: Naqvi Ibtehaj A. , White Rebekah R. , Moylan Cynthia A. , Diehl Anna Mae , Choi Steve S. 
Published: May 2015

Abstract
Introduction: Current serum biomarkers for hepatocellular carcinoma (HCC) lack the sensitivity and specificity to be effective screening tools. Aptamers are single-stranded RNA oligonucleotides that specifically bind to target proteins with high affinity and are generated by repeatedly screening complex RNA libraries for binding to protein targets. We have utilized this selection process to identify biomarkers from complex targets, such as secreted proteomes (secretomes). Our hypothesis is that aptamers that specifically bind the HCC secretome will identify serum protein biomarkers for HCC.
Methods: We mirrored the microenvironments of HCC and normal liver tissue utilizing two co-culture systems: 1) human HCC cells (Huh-7) with normal hepatic stellate cells (HSCs) to model HCC livers and 2) normal human hepatocyte cells (THLE-2) with HSCs to model normal livers. Co-cultures were grown to confluence then switched to serum free media for collection of secreted cancer proteins (HCC secretome, HS) and normal secretome (NS). A nuclease-resistant RNA pool was then alternately incubated with NS (discarded for negative selection) and HS (recovered and amplified for positive selection).
Results: Binding affinity for HS increased over 7 successive rounds, while binding affinity for NS decreased. The final RNA pool was cloned and sequenced yielding 3 candidate aptamers that were tested for binding to the secretomes and to human serum from patients with HCC and normal controls. In the samples tested we found that one candidate aptamer sequence (G-20) demonstrated increased binding to the sera of HCC pts (N=5) relative to normal sera (N=2) and to a non-binding control aptamer. The maximal percent fraction bound of the G-20 aptamer to cancer serum was 15% compared to only 7% in control. The maximal percent fraction bound of G-20 in normal serum was 8% compared to 6% in control.
Conclusions: This co-culture system may better recapitulate the in vivo environment. Aptamers that specifically bind our cancer secretome over the normal secretome may bind to proteins that are specifically secreted by HCC tumors in vivo. The G-20 aptamer selectively binds to HCC patient sera. Future goals of this work are to utilize affinity purification techniques to identify the target of our G-20 aptamer and to continue testing our G-20 aptamer in patient sera to further validate its ability to differentiate between cancer and normal disease states.
Citation Format: Ibtehaj A. Naqvi, Rebekah R. White, Cynthia A. Moylan, Anna Mae Diehl, Steve S. Choi. Utilizing RNA aptamers for biomarker discovery in a novel cell culture system for hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4117. doi:10.1158/1538-7445.AM2014-4117
Abstract 4122: Anti-cancer activity of rosemary extract in colon cancer cells: Involvement of Nrf2 and ERK pathways
Authors: Yan Miao , Li Gongbo , Patiwala Sakina M. , Householter Emily , Johnson Jeremy J. 
Published: May 2015

Abstract
Background: The Mediterranean herb rosemary has been used for culinary purposes and for their medicinal properties for millennia. Rosemary and its polyphenolic diterpenes (carnosol and carnosic acid) are known to possess anti-oxidant activity that may be beneficial for cancer control. Colorectal cancer is the second leading cause of death from cancer in the United States. Nutrition, particularly intake of vegetables and certain plant components, has been reported to have a major role in colon cancer risk reduction. In our current study, we investigated the anticancer effects of rosemary extract and its two main active ingredients carnosol and carnosic acid on colon cancer cell lines to understand the mechanism. Next, we evaluated the anti-cancer activity of rosemary extract in a nude mice model.
Methods: Two human colon cancer cell lines, HCT116 and SW480, were treated with rosemary extract, carnosol or carnosic acid. MTT, TUNEL and ELISA were used to evaluate cell viability and apoptosis. Western blot and immunofluorescence were used to detect proteins involved in apoptosis. We also evaluated the anti-cancer activity of rosemary extract in nude mouse inoculated with HCT116 cells.
Results: Rosemary extract, carnosol and carnosic acid, increased apoptosis, decreased viability in colon cancer cell lines. Rosemary extract, carnosol and carnosic acid significantly upregulated the expression of Nrf2 and ERK. Rosemary extract also effectively suppressed tumor growth in a xenograft tumor model without affecting body weight.
Conclusions: Rosemary extract inhibits colon cancer cell growth in a xenograft mouse model without observable toxicity. Furthermore, rosemary extract, carnosol and carnosic acid induce the expression of Nrf2 and ERK pathways in colon cancer cells, suggesting further research is needed to evaluate its potential as an anti-cancer and/or chemoprevention agent.
Citation Format: Miao Yan, Gongbo Li, Sakina M. Patiwala, Emily Householter, Jeremy J. Johnson. Anti-cancer activity of rosemary extract in colon cancer cells: Involvement of Nrf2 and ERK pathways. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4122. doi:10.1158/1538-7445.AM2014-4122
Abstract 413: Validation of methylation biomarkers that distinguish normal colon mucosa from cancer patients from normal colon mucosa of patients without cancer
Authors: Cesaroni Matteo 
Published: May 2015

Abstract
We have attempted to validate differences in DNA methylation levels of 30 candidate genes reported to discriminate between normal colon mucosa of colon cancer patients and normal colon mucosa of individuals without cancer. We found that CpG sites in 16 of the 30 candidate genes show significant differences in mean methylation level in normal colon mucosa in an independent cohort of 24 cancer patients and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs set yielded an 18-gene signature, composed of 10 of the validated candidate genes plus 8 additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r=0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These 7 CpGs, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy.
Citation Format: Matteo Cesaroni. Validation of methylation biomarkers that distinguish normal colon mucosa from cancer patients from normal colon mucosa of patients without cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 413. doi:10.1158/1538-7445.AM2014-413
Abstract 4137: Latent class model characterization of neighborhood SES
Authors: Palumbo Aimee , Michael Yvonne , Hyslop Terry 
Published: May 2015

Abstract
Background: Breast cancer is the most common cancer in women and a significant source of mortality. Neighborhood-level socioeconomic status (NSES) has been shown to play a key role in health; poorer health outcomes are observed in deprived neighborhoods even after controlling for individual level SES. Commonly used NSES indexes are difficult to interpret. The relative impact of different factors within the index cannot be evaluated. Latent class models, which use latent variables to create distinct classes, allow for characterization of NSES and estimation of the effects of specific neighborhood characteristics on cancer outcomes.
Methods: We used data from women diagnosed with breast cancer from a teaching hospital in Philadelphia, PA. Census information at the Zip Code Tabulation Area (ZCTA) level was used to obtain NSES variables. Latent class analysis and comparisons of model fit statistics were used to determine the optimal number of classes.
Results: Complete ZCTA-level data was available for 1,664 breast cancer patients. In this population, NSES was best represented by two separate latent variables, each with 2-classes (LC2). When the class variables were compared to a continuous NSES index (NSI), the correlation was 0.85. However, LC2 demonstrated stronger association with race, stage, disease subtype, tumor size, and histologic grade.
Conclusions: We classified neighborhoods based on correlated socioeconomic census-level variables. Latent variables identify specific characteristics associated with living in a neighborhood with low versus high advantage and disadvantage and thus may improve our understanding of critical breast cancer prognostic factors and the targeting of cancer control efforts. Further research will provide overall structural latent models that incorporate information on tumor biology, prognostic variables and survival outcomes to aid in the identification of vulnerable populations.
Table 1. Neighborhood latent class model (LC2) and SES Index (NSI)
Table 1.Neighborhood latent class model (LC2) and SES Index (NSI)LC2 *ModelNSI Model *Prognostic Factor Stage24.5511.61 Race366.44331.01 Subtype18.4315.48 Size22.532.91* Chi-square statistic for association of Prognostic Factor with LC2 class or with NSI quartile. Higher number indicates higher strength of association.
Citation Format: Aimee Palumbo, Yvonne Michael, Terry Hyslop. Latent class model characterization of neighborhood SES. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4137. doi:10.1158/1538-7445.AM2014-4137
Abstract 414: Aberrant DNA methylation and expression of mRNA in EGFR-mutant lung cancer cell line with long-term exposure to gefitinib
Authors: Terai Hideki , Soejima Kenzo , Naoki Katsuhiko , Yasuda Hiroyuki , Sato Takashi , Arai Daisuke , Ohgino Keiko , Ishioka Kota , Kuroda Aoi , Tani Tetsuo , Ohashi Ayano , Nishino Makoto , Miyawaki Masayoshi , Hamamoto Junko , Betsuyaku Tomoko 
Published: May 2015

Abstract
Many of the patients with non-small cell lung cancer (NSCLC) who initially responded well to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) will eventually relapse. The mechanisms of resistance to EGFR-TKIs is not yet fully clarified. The suppression of genes by DNA methylation is reported to be involved in the mechanism of tolerance to cytotoxic drugs. The purpose of this study is to identify epigenetically regulated genes and to clarify the contribution of epigenetic alteration to the acquired resistance to EGFR-TKI. We established gefitinib-resistant PC-9, which was originally gefitinib-sensitive lung cancer cell line, by serial long term exposure to gefitinib. We collected RNA and DNA from both gefitinib-sensitive and -resistant PC-9 cells and performed comprehensive analysis for DNA methylation and mRNA expression using infinium array and cDNA microarray, respectively. We identified 640 genes those DNA methylations were increased in gefitinib-resistant cell line compared to parental cell line. Then, we selected 29 candidate genes those mRNA expression were decreased in resistant PC-9. We are currently underway to elucidate the specific function of each gene and updated data will be presented at the meeting.
Citation Format: Hideki Terai, Kenzo Soejima, Katsuhiko Naoki, Hiroyuki Yasuda, Takashi Sato, Daisuke Arai, Keiko Ohgino, Kota Ishioka, Aoi Kuroda, Tetsuo Tani, Ayano Ohashi, Makoto Nishino, Masayoshi Miyawaki, Junko Hamamoto, Tomoko Betsuyaku. Aberrant DNA methylation and expression of mRNA in EGFR-mutant lung cancer cell line with long-term exposure to gefitinib. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 414. doi:10.1158/1538-7445.AM2014-414
Abstract 4142: Capacity building in cancer management in Africa: Envisioning a future from past challenges
Authors: Williams Christopher K. O. 
Published: May 2015

Abstract
Sub-Saharan African institutions, especially the Uganda Cancer Institute in Kampala, Uganda, led in the development of chemotherapy (CMT) for lymphoma subtypes between 1950 and 1980. Recent WHO emphasis on global non-communicable diseases indicates a need for regional HC paradigm shift in a region long inundated with communicable diseases. Expected barriers in capacity building in medical oncology there are illustrated with challenges of experimental management of Burkitt's lymphoma (BL) at the University College Hospital, Ibadan, Nigeria (UCHIN), where from 1/1984 to 12/1985, a study of tolerability and practicability of high dose cytosine arabinoside (HDAC) CMT was initiated. Included were children (chd) with a diagnosis of BL Ziegler's Stage C or D with or without CNS involvement (CNS±), and life expectancy of at least one month, whose parents/guardians were willing to give oral consent. 60 chd were to be assigned randomly to either the standard treatment (RII) or the investigational (RI) protocol. RI was: Cyclophosphamide (CTX) 1000mg/m2 IV day 1, Vincristine (VCR) 2.0mg/m2 IV day 1, cytosine arabinoside (AC) 50mg/m2 q12hr x 6 doses in cycles 1 and 4, and 1000mg/m2 q12hr x 4 doses and 50mg/m2 q12hr x 2 doses for cycles 2 and 3 cycles q14days x 4cycles. R II was: CTX 1000mg/m2 IV day 1, VCR 2.0mg/m2 IV day 1, AC 50mg/m2 q12hr x 6 doses q14days x 4 cycles. AC 50mg/m2 was given intrathecally days 1 and 5 of each cycle. See Table for results. *MDI: Mean dose intensity. HDAC based CMT was well tolerated with more effective control of systemic and CNS disease compared to conventional CMT. Challenges encountered included ethical issues of medical research in the midst of socio-economic deprivation, technical and manpower inadequacies, unreliable drug supply leading to CMT modifications, communication, lack of compliance and unreliable accessibility to follow-up. Persistence of these problems after &gt;2 decades signals a need for cultural change at all community levels: government, HC administration and among categories of providers.
Table of resultsR-IR-IIp-VALUEDEMOGRAPHY#RANDOMIZED14 (30)16 (30)M/F10/410/6AGE9.5±3.58.5±2.5&gt;0.5STAGEC56D-CNS+46D-CNS-43MDI OF AGENTSVCR0.350.520.09CTX382.6466.40.16IV-AC936.0139.50.001IT-AC33.942.00.034OUTCOMES#EVALUATED1012CR9/95/12PR0/95/12NR0/92/12OS (%)59200.21
Citation Format: Christopher K. O. Williams. Capacity building in cancer management in Africa: Envisioning a future from past challenges. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4142. doi:10.1158/1538-7445.AM2014-4142
Abstract 4144: Genetic and epidemiology characterization of head and neck cancers by targeted sequencing
Authors: Perdomo Sandra , Reis Luciana , Anantharaman Devasena , Mckay James , Brennan Paul 
Published: May 2015

Abstract
Oral and pharyngeal cancer, grouped together, is the sixth most common cancer in the world. The annual estimated incidence is around 275,000 for oral and 130,300 for pharyngeal cancers excluding nasopharynx, two-thirds of these cases occurring in developing countries.
The principal objective of this work was to investigate the somatic genetic changes that influence the risk of head and neck cancer occurrence and outcome, and how they interact with environmental and host factors: HPV infection, alcohol and Smoking.
We selected 205 paired samples diagnosed as head and neck SCC included in two multicenter studies in Europe and Brazil: ARCAGE, a multi center case- control study, conducted between 2002-2005 involving 10 countries across Europe and the Gencapo case- control study in the state of Sao Paulo from 2001 to 2010.
Targeted sequencing was performed independently on both germline DNA and the tumor material using the PGM™ System at an average depth of 250X.Sequencing included the entire coding region of 5 of the most frequently mutated genes in Head and Neck cancer: TP53, NOTCH1, CDKN2A, CASP8, and PTEN. HPV status was achieved by capsid protein serology and DNA genotyping. Statistical tests were carried out in the R statistical programming environment or using STATA statistic software. Kaplan-Meier analysis was used to determine overall survival.
Statistically significant differences in exposure status were found between both series of patients with more prevalent cases of former and current both smokers and alcohol drinkers in Brazil(p=0.001). 76% and 63% of the patients in each series had at least 1 mutation and there were no significant differences in the percentage of mutations found. Most of the mutations were found in TP53 (60%) and NOTCH1 (18%). Smoking status was significantly associated to TP53 mutations (p=0.015). Positive serology for HPV16 E6 oncoprotein was associated to Oropharyngeal tumors all of which lack TP53 mutations.
When comparing the survival of patients according to the mutational profile we found a reduction in overall survival for those patients carrying mutations in TP53 (p=0.002) and CDKN2A (p=0.001).
Combined molecular profiling and exposure data can be a resource to assess the role of lifestyle habits on prognosis, and will help to identify early markers of survival for head and neck cancer patients.
Citation Format: Sandra Perdomo, Luciana Reis, Devasena Anantharaman, James Mckay, Paul Brennan. Genetic and epidemiology characterization of head and neck cancers by targeted sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4144. doi:10.1158/1538-7445.AM2014-4144