bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5580: Characterization of HPV integration sites in the human genome
Authors: Bodelon Clara , Untereiner Micahel , Vinokurova Svetlana , Machiela Mitchell J. , Wentzensen Nicolas 
Published: August 2015

Abstract
Background. Persistent infection with carcinogenic human papillomaviruses (HPV) is known to be cause of the majority of anogenital cancers as well as some head and neck cancers. With the progression of the disease, the HPV genome is commonly integrated within the host DNA, although the mechanism by which integration may promote the progression of the disease is not well-understood. We performed a systematic review of integration events in HPV-related cancers and analyzed the genomic regions where these events occur.
Methods. A PubMed search was performed to collect all published data on integration loci. A total of 29 articles were eligible for the analysis. Determination of genomic integration sites for papers that provided exact nucleotide sequences of integration sites or viral fusion regions was done by using the Basic Local Alignment Search Tool (BLAST, http://blast.ncbi.nlm.nih.gov/Blast.cgi) for the GRCh37/hg19 build. We used the Encyclopedia of DNA Elements (ENCODE) data to investigate if certain genetic features clustered with integrations sites. The Wilcoxon rank sum test was computed to compare the observed and expected distributions of minimal distances from the integration sites with known nucleotide positions to the different genetic features.
Results. As of November 2014, approximately 1,200 integration events were reported in the literature from both tumors and cell lines. The majority of integrations sites (53%) were reported in cervical tumors, 9% in head and neck tumors, 4% of oropharyngeal tumors and 23% in cell lines,. Six percent and 2% of the integration sites were found in high-grade and low-grade cervical lesions, respectively. The majority of reported integration events (77%) were related to HPV16. We found that integration sites from tumors were closer to known genes (p &lt;10−14) and CpG islands (p &lt;10−9) than expected by chance. Among repetitive elements, long terminal repeats (LTR) were enriched in integration sites (P = 0.001). Open chromatin based on the FAIRE-seq peaks showed significant enrichment in integration sites (p &lt;10−11).
Conclusions. In summary, integration sites occur in genomic regions with enrichment for genetic elements, such as gene-rich regions, CpG sites, repetitive elements and open chromatin regions. This corroborates that accessible regions of the genome are preferentially targeted by integration and suggests that host genes may be functionally altered in development of HPV-related cancers.
Citation Format: Clara Bodelon, Micahel Untereiner, Svetlana Vinokurova, Mitchell J. Machiela, Nicolas Wentzensen. Characterization of HPV integration sites in the human genome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5580. doi:10.1158/1538-7445.AM2015-5580
Abstract 5584: Exhaled breath as diagnostic tool for malignant pleural mesothelioma
Authors: Lamote Kevin , Lardon Filip , Van Cleemput Joris , Nackaerts Kristiaan , Thas Olivier , van Meerbeeck Jan P. 
Published: August 2015

Abstract
Background: Malignant Pleural Mesothelioma (MPM) is an asbestos-related disease with a dismal prognosis due to its late detection at an advanced stage. Hence, a diagnostic test is requisite that allows to screen asbestos-exposed persons for earlier MPM detection. As blood biomarkers have not shown to be clinically useful biomarkers for early non-invasive diagnosis, breath is currently explored. Breath is easy to retrieve by physicians in a clinical environment and contains volatile organic compounds (VOCs) that arise from (patho)physiological processes. Since asbestos causes oxidative stress and cancers are known to up regulate their metabolism, we hypothesize that VOCs and, hence, the exhaled breath of MPM patients will differ from healthy controls.
Methods: We compared the breath of 23 MPM patients, 10 asbestos-exposed and 12 non-exposed healthy individuals using a multicapillary column/ion mobility spectrometer (MCC/IMS, B&S Analytik, Dortmund, Germany). After subjects refrained from eating, drinking and smoking for at least 2 hours, 10 ml alveolar air was sampled via a CO2-controlled ultrasonic sensor and subsequently analyzed. Per subject a background sample was taken. Eighty-nine VOC peaks were visually selected via on-board VisualNow 3.7 software. Their intensity was compared between background and breath samples. After calculating the VOCs’ alveolar gradient, we performed a logistic LASSO regression in R (R-Foundation for Statistical Computing, Vienna, Austria). We selected the optimal MPM diagnostic logistic LASSO model by 10-fold cross-validation using age, gender and the alveolar gradient of the peaks and estimated this models’ sensitivity, specificity, AUCROC and positive (PPV) and negative predictive value (NPV).
Results: We were able to discriminate MPM patients from the asbestos-exposed and non-exposed controls with 96% sensitivity and 91% specificity. The AUCROC was 0,94 and the PPV and NPV were resp. 92% and 95%. The VOCs P5, P3, and P1 were the significant discriminators.
Conclusions: Breath analysis in a clinical setting by MCC/IMS allows to discriminate MPM patients from asbestos-exposed and non-exposed healthy controls. It can help to screen asbestos-exposed persons at risk, switching diagnosis to an early phase and hence, better patient survival. Identification of the underlying VOCs and a further validation in different patient cohorts is being undertaken.
Citation Format: Kevin Lamote, Filip Lardon, Joris Van Cleemput, Kristiaan Nackaerts, Olivier Thas, Jan P. van Meerbeeck. Exhaled breath as diagnostic tool for malignant pleural mesothelioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5584. doi:10.1158/1538-7445.AM2015-5584
Abstract 5586: Breast cancer risk prediction: An update to the Rosner-Colditz breast cancer incidence model
Authors: Rice Megan , Tworoger Shelley , Hankinson Susan , Tamimi Rulla , Eliassen A Heather , Colditz Graham , Rosner Bernard 
Published: August 2015

Abstract
Purpose: To update and build on the Rosner-Colditz breast cancer incidence model by evaluating the contributions to breast cancer risk of childhood and adolescent somatotype, fruit and vegetable intake, breastfeeding, and physical activity. Secondarily, we evaluated the contributions of these variables to breast cancer incidence models defined by ER and PR status of the tumor.
Methods: Using data from the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII), we added childhood somatotype (average of somatotype at ages 5 and 10; 9 unit scale), adolescent somatotype (average of somatotype at ages 10 and 20; 9 unit scale), fruit and vegetable intake (servings/day), breastfeeding (months), and physical activity (METs/week) to the Rosner-Colditz breast cancer incidence model to determine whether these variables improved the discriminatory power of the model. We evaluated the contribution of these variables to a model for all invasive breast cancer as well as to models for ER+/PR+, ER+/PR-, and ER-/PR- breast cancer.
Results: In the NHS/NHSII, we accrued over 3000 cases of invasive breast cancer with complete data on the selected breast cancer risk factors. Compared to the original Rosner-Colditz model, the models that included childhood or adolescent somatotype were significantly improved (p&lt;0.001). The relative risk (RR) of invasive breast cancer for a 4 unit change in somatotype was 0.69 for childhood somatotype and 0.59 for adolescent somatotype. Including childhood somatotype increased the age-adjusted concordance statistic from 0.613 to 0.616 whereas including adolescent somatotype increased the age-adjusted concordance statistic from 0.613 to 0.618. Childhood and adolescent somatotypes also significantly improved ER+/PR+ and ER-/PR- breast cancer incidence models (p&lt;0.02). Breastfeeding and vegetable intake suggestively improved the ER-/PR- model. The RR for five servings of vegetables per day was 0.82, while the RR for 12 months of breastfeeding was 0.87. While these variables were significantly associated with ER-/PR- breast cancer risk in the updated models, the differences in concordance statistics comparing models with to models without these variables were not statistically significant.
Conclusion: Childhood and adolescent somatotype significantly improved breast cancer risk classification in the NHS/NHSII.
Citation Format: Megan Rice, Shelley Tworoger, Susan Hankinson, Rulla Tamimi, A Heather Eliassen, Graham Colditz, Bernard Rosner. Breast cancer risk prediction: An update to the Rosner-Colditz breast cancer incidence model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5586. doi:10.1158/1538-7445.AM2015-5586
Abstract 5588: Nevus count and dermoscopic pattern associated with MC1R RHC-variant alleles in a case-control study of melanoma
Authors: McClenahan Phil , Jagirdar Kasturee , Lee Katie , McEniery Elizabeth , Beh Sam , Burke Brian , Duffy David L. , Soyer H. Peter , Sturm Richard A. 
Published: August 2015

Abstract
The total number of acquired melanocytic nevi (TNC) is the strongest known risk factor for cutaneous malignant melanoma (CMM). An increased risk of CMM is also seen with individuals with red hair, fair skin and poor tanning ability (RHC phenotype); and who carry variant alleles of the MC1R gene designated as R. High freckling scores but reduced nevus counts have been reported in individuals with the RHC phenotype. The relationship between these reciprocal phenotypes of lower vs higher nevus counts, both with increased risk of CMM, is complex and supports hypotheses of different pathways to melanoma formation. We have reported on a case-control study of nevi in volunteers from the South-east Queensland area combining an assessment of pigmentation characteristics, nevus phenotype including dermoscopic nevus subtypes with genotypic comparisons and melanoma risk for 573 individuals. This sample set has been further examined to delineate the nevus characteristics of 46 individuals who are homozygous MC1R RHC allele carriers R/R. We wished to determine if there is any commonality in the pigmentation or melanocytic nevus phenotype including number, size, distribution, profile and colour that may distinguish these patients. Body mass index (BMI), body surface area (BSA), TNC and MC1R genotype were analysed and found that participants with personal melanoma history had higher TNC (P&lt;0.005). We found no association between MC1R genotype and BMI but there exists a weak association between BSA and higher TNC. Within the MC1R R/R cohort, melanoma patients are more likely to have high TNC than controls (P&lt;0.01). The signature dermoscopic pattern for the individuals in the MC1R R/R group is at increased odds of being a non-specific pattern (P&lt;0.01). A significant difference in MC1R R/R TNC dependent on melanoma history exists and there is a predisposition towards a non-specific signature nevus pattern.
Citation Format: Phil McClenahan, Kasturee Jagirdar, Katie Lee, Elizabeth McEniery, Sam Beh, Brian Burke, David L. Duffy, H. Peter Soyer, Richard A. Sturm. Nevus count and dermoscopic pattern associated with MC1R RHC-variant alleles in a case-control study of melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5588. doi:10.1158/1538-7445.AM2015-5588
Abstract 5589: Age-stratified risk of unexpected uterine sarcoma following surgery for presumed benign leiomyoma
Authors: Brohl Andrew S. , Li Li , Andikyan Vaagn , Cioffi Angela , Dudley Joel T. , Kasarskis Andrew , Maki Robert G. 
Published: August 2015

Abstract
Background: Estimates of unexpected uterine sarcoma following surgery for presumed benign leiomyoma that utilize age-stratification are lacking.
Patients and Methods: A retrospective cohort of 2075 patients that had undergone myomectomy was evaluated to determine the case incidence of unexpected uterine sarcoma. An aggregate risk estimate was generated using a meta-analysis of similar studies plus our cohort. Database-derived age distributions of the incidence rates of uterine sarcoma and uterine leiomyoma surgery were used to stratify risk by age.
Results: Of 2075 patients in our cohort, six were diagnosed with uterine sarcoma. Our meta-analysis revealed 8 studies from 1980-2014. Combined with our cohort, there are 18 cases of leiomyosarcoma reported in 10120 patients, for an aggregate risk of 1.78 per 1000 [95% CI: 1.1-2.8], or 1 in 562. There are 8 cases of other uterine sarcomas reported in 6889 patients, for an aggregate risk of 1.16 per 1000 [95% CI: 0.5-4.9], or 1 in 861. The summation of these risks gives an overall risk of uterine sarcoma of 2.94 per 1000 [95% CI: 1.8-4.1], or 1 in 340. After stratification by age, we predict the risk of uterine sarcoma to range from a peak of 10.1 cases per 1000, or 1 in 98, for age 75-79 to less than 1 case per 500 for age &lt;30.
Conclusion: The risk of unexpected uterine sarcoma varies significantly across age groups. Our age-stratified predictive model should be incorporated to more accurately counsel patients and to assist in providing guidelines for surgical technique for leiomyoma.
Age-stratified risk of unexpected uterine sarcoma at the time of surgery for presumed leiomyomaAgeEstimated(years)Risk of Uterine Sarcoma (per 1000 procedures)25-291.74(1 in 574)30-342.01(1 in 496)35-392.65(1 in 377)40-442.46(1 in 405)45-493.28(1 in 304)50-544.62(1 in 216)55-596.35(1 in 158)60-646.36(1 in 157)65-697.53(1 in 133)70-748.55(1 in 117)75-7910.1(1 in 98)80-845.57(1 in 179)
Citation Format: Andrew S. Brohl, Li Li, Vaagn Andikyan, Angela Cioffi, Joel T. Dudley, Andrew Kasarskis, Robert G. Maki. Age-stratified risk of unexpected uterine sarcoma following surgery for presumed benign leiomyoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5589. doi:10.1158/1538-7445.AM2015-5589
Abstract 5590: Reliability of medical records in diagnosing inflammatory breast cancer in Egypt
Authors: Le Lynne , Schairer Catherine , Hablas Ahmed , Ramadan Mohamed , Merajver Sofia , Seifeldein Ibrahim , Soliman Amr 
Published: August 2015

Abstract
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by diffuse erythema and edema (peau d’orange) of the skin of the breast. It does not include neglected locally advanced cancer of the breast presenting late in the course of the disease. IBC is primarily a clinical diagnosis, but also requires pathologic confirmation of breast cancer. The purpose of this study was to examine the reliability of medical records for diagnosing IBC in patients at two centers in Tanta, Egypt (Gharbiah Cancer Society and Tanta Cancer Center) which participated in an epidemiologic case-case study of IBC and non-IBC in 2009-2010. IBC patients were recruited to the case-case study at diagnosis based on clinical examination; detailed information on the extent and duration of signs used for the diagnosis of IBC was recorded. Information on signs of IBC similar to those collected in the case-case study was abstracted from the medical records of the hospitals where case-case study patients were recruited during the same time period, then linked and compared to the signs observed from clinical examination for the case-case study.
A total of 40 IBC cases were recruited into the case-case study during 2009-2010. Medical record information was available for 31 of these cases. Twenty-eight of these 31 cases were reported to have erythema and 28 edema/peau d’orange based on the clinical examination for the case-case study. Of those with erythema, 16 (57.1%) also had erythema/inflammation listed in the medical record; of those with edema/peau d’orange, 23 (82.1%) had this mentioned in the medical record. Erythema was noted on the medical record but not recorded in the case-case study for 2 cases; there were no cases in which edema/peau d’orange was present in the medical record and not in the case-case study. Our analysis indicates that medical records at these cancer centers often have missing information regarding the presence of signs that are necessary to the diagnosis of IBC. Overall, this study suggests that medical record review is not sufficient to identify IBC cases for an epidemiologic study.
Citation Format: Lynne Le, Catherine Schairer, Ahmed Hablas, Mohamed Ramadan, Sofia Merajver, Ibrahim Seifeldein, Amr Soliman. Reliability of medical records in diagnosing inflammatory breast cancer in Egypt. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5590. doi:10.1158/1538-7445.AM2015-5590
Abstract 56: Receptor-Interacting protein kinase 1 functions as an oncogenic regulator in human melanoma
Authors: Jin Lei , Liu Xiao Ying , Lai Fritz , Yan Xu Guang , Jiang Chen Chen , Guo Su Tang , Wang Chun Yan , Croft Amanda , Tseng Hsin-Yi , Wilmott James S. , Scolyer Richard A. , Zhang Xu Dong 
Published: August 2015

Abstract
Although many studies in recent years have uncovered an important role of receptor-interacting protein kinase 1 (RIP1) in mediating cell survival and death signaling, its potential part in the pathogenesis of cancer remains less understood. Here we report that RIP1 functions as an oncogenic regulator in human melanoma. While the expression of RIP1 was commonly upregulated in melanoma, knockdown of RIP1 inhibited melanoma cell proliferation in vitro, and retarded melanoma growth in a xenograft model. Conversely, despite induction of apoptosis in a small proportion of melanoma cells, overexpression of RIP1 enhanced proliferation in the remaining cells. The promoting effect of RIP1 on melanoma cell proliferation was mediated by activation of NF-κB, as blockade of NF-κB activation eliminated RIP1 overexpression-triggered increase in cell proliferation, whereas hyperactivation of NF-κB abolished inhibition of cell proliferation caused by RIP1 knockdown. In support, RIP1 knockdown led to reduction, whereas its overexpression caused an increase, in NF-κB activation. Strikingly, ectopic expression of RIP1 enhanced melanocyte proliferation and triggered anchorage-independent growth of the cells similarly in a NF-κB-dependent manner. While upregulation of RIP1 was associated with DNA copy number gain in a subset of melanomas, constitutive ubiquitination and subsequent stabilization of the RIP1 protein driven by TNFα autocrine appeared to be another mechanism commonly responsible for upregulation of RIP1 in melanoma cells. Collectively, these results identify RIP1 as an oncogenic regulator in melanoma, and points to the possibility of targeting the NF-κB activating mechanism of RIP1 as a novel approach in the treatment of the disease.
Citation Format: Lei Jin, Xiao Ying Liu, Fritz Lai, Xu Guang Yan, Chen Chen Jiang, Su Tang Guo, Chun Yan Wang, Amanda Croft, Hsin-Yi Tseng, James S. Wilmott, Richard A. Scolyer, Xu Dong Zhang. Receptor-Interacting protein kinase 1 functions as an oncogenic regulator in human melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 56. doi:10.1158/1538-7445.AM2015-56
Abstract 560: Retrospective evaluation, of the randomized Phase 3 MARQUEE trial of tivantinib (T) + erlotinib (E) versus placebo (P) + erlotinib (E) using VeriStrat in patients with previously treated nonsquamous NSCLC
Authors: Scagliotti Giorgio , Akerley Wallace , von Pawel Joachim , Roder Joanna , Shuster Dale , Schwartz Brian , Spinella Dominic 
Published: August 2015

Abstract
Background: MET, the high-affinity receptor for hepatocyte growth factor, is frequently deregulated in human cancer and is thought to be involved in resistance to EGFR TKIs. Tivantinib is an orally administered MET inhibitor currently under development as a cancer therapy. The Phase 3 MARQUEE trial enrolled 1048 subjects with locally-advanced or metastatic non-squamous NSCLC who had received one or two lines of prior systemic therapy. Patients were randomized 1:1 to T+E (N = 526) or P+E (N = 522) until disease progression. In the ITT population, addition of tivantinib to erlotinib significantly improved PFS and ORR but did not improve OS, the primary endpoint. VeriStrat® (VS) is a multivariate serum protein test that utilizes MALDI-TOF mass spectrometry to assign a “GOOD” (VS-G) or “POOR” (VS-P) classification and has demonstrated broad prognostic and predictive utility for EGFR TKI treatment regimens.
Methods: Pre-treatment serum samples from the MARQUEE study were blinded to clinical outcome and analyzed by VeriStrat. Clinical benefit of T+E vs. P+E was analyzed as a function of VS status, in the ITT population as well as in pre-defined subgroups.
Results: A total of 996 subjects were classified: 718 as VS-G and 278 as VS-P. Subjects testing VS-G had superior outcomes to those testing VS-P in both the T+E arm (OS HR = 0.32, CI: 0.26-0.41, p&lt;0.0001; PFS HR = 0.55, CI: 0.44-0.69, p&lt;0.0001) and P+E arm (OS HR = 0.43, CI: 0.34-0.55, p&lt;0.0001; PFS HR = 0.70, CI: 0.55-0.88, p&lt;0.028). VeriStrat status was a significant, independent predictor of OS, in these erlotinib treated patients, after adjustment for EGFR mutation, KRAS mutation, or MET IHC status. However, VeriStrat did not predict OS or PFS benefit for T+E vs. P+E (treatment * VS interaction p-value for OS of p = 0.09 and PFS of p = 0.19). VS was neither predictive nor prognostic for tivantinib effect in any molecular subgroup.
Conclusion: These data support the previously demonstrated ability of VS to be both prognostic and predictive for survival in erlotinib treated patients, but not for tivantinib treated patients.
Citation Format: Giorgio Scagliotti, Wallace Akerley, Joachim von Pawel, Joanna Roder, Dale Shuster, Brian Schwartz, Dominic Spinella. Retrospective evaluation, of the randomized Phase 3 MARQUEE trial of tivantinib (T) + erlotinib (E) versus placebo (P) + erlotinib (E) using VeriStrat in patients with previously treated nonsquamous NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 560. doi:10.1158/1538-7445.AM2015-560