bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2286: Atopic allergic conditions and risk of pancreatic cancer: the Multiethnic Cohort
Authors: Huang Brian Z. , Marchand Loic Le , Haiman Christopher A. , Monroe Kristine , Wilkens Lynne , Zhang Zuo-Feng , Setiawan Veronica Wendy 
Published: July 2017

Abstract
Background: Previous studies, mostly case-control studies, have suggested that atopic allergic conditions (AACs) are associated with a decreased risk of pancreatic cancer. Scarce data, however, are available from prospective, US multiethnic populations. In this largest prospective study to date, we investigated the association between AACs (asthma, hay fever, or allergy) and risk of developing pancreatic cancer in the US Multiethnic Cohort Study (MEC).
Methods: AACs were assessed via a baseline questionnaire when participants joined the MEC in 1993-1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) for pancreatic cancer incidence by AACs status were calculated using Cox regression, adjusting for age, sex, race/ethnicity, education, smoking status, family history of pancreatic cancer, body mass index, diabetes, and alcohol intake.
Results: During an average of 16.2-year follow-up, 1,455 incident cases of pancreatic cancer were identified among 187,226 white, African-American, Native Hawaiian, Japanese-American, and Latino men and women. AACs were not associated with pancreatic cancer incidence (HR=1.00; 95% CI: 0.88, 1.12). The null association was observed in men and women and across racial/ethnic groups, smoking status, BMI groups, diabetes status, and family history of pancreatic cancer.
Conclusions: Based on these results, AACs is unlikely to be associated with risk of pancreatic cancer.
Citation Format: Brian Z. Huang, Loic Le Marchand, Christopher A. Haiman, Kristine Monroe, Lynne Wilkens, Zuo-Feng Zhang, Veronica Wendy Setiawan. Atopic allergic conditions and risk of pancreatic cancer: the Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2286. doi:10.1158/1538-7445.AM2017-2286
Abstract 229: Establishing reference intervals of human urine proteome for monitoring physiological and pathological changes
Authors: Leng Wenchuan , Ni Xiaotian , Sun Changqing , Malovannaya Anna , Wang Yi , Qin Jun 
Published: July 2017

Abstract
Urine as a true non-invasive sampling source holds great potential for biomarker discovery. But the lack of method for profiling urine proteome in high throughput and systematic evaluation of variations in urine proteomes based on large number of population have been being the major obstacles for successfully finding new biomarkers from urine. Due to low throughput, only limited number of urine samples can be measured in discovery phase of biomarker studies, which make it hard to determine whether proteins differentially expressed between groups represent actual differences between control and disease states or just physiological variations among individuals. So, candidate biomarkers often fail in validation phase. Here, we report a streamlined workflow with capacity of measuring 8 urine proteomes per day per MS at the coverage of more than 1500 proteins. With this workflow, we systematically evaluated variations in 497 human urine proteomes from 167 apparently healthy donors, allowing us to evaluate day to day and inter-personal variation in human urine proteome. Then personal and pan-human reference intervals (RIs) of urine proteome were established based on this large-scale dataset. We demonstrated that RIs can be used to monitor physiological changes by detecting transient outlier proteins, such as trans-continental travel and common flu. And it was also found that if the underlying cause is physiological variation, outlier proteins will fall back to the normal range in the follow up measurement, as exemplified in the intercontinental travel case. Persistent outlier proteins may be indicative of non-physiological conditions. These results indicate that periodical measurements of a person’s urine proteome could establish a personal health archive that would be valuable for detecting future health issues. Furthermore, we proposed a complete novel strategy dependent on RIs-based algorithm for biomarker discovery and validation to screen for diseases, which were exemplified by analyzing 154 urine proteomes from patients with 7 types of cancers. The algorithm can distinguish normal people from cancer patients with specificity of 0.95 and sensitivity of 0.85. This study paves a way to use urine proteome for health monitoring and disease screening.
Citation Format: Wenchuan Leng, Xiaotian Ni, Changqing Sun, Anna Malovannaya, Yi Wang, Jun Qin. Establishing reference intervals of human urine proteome for monitoring physiological and pathological changes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 229. doi:10.1158/1538-7445.AM2017-229
Abstract 2294: Atypical nevi and risk of incident skin cancer in US men: a prospective study
Authors: LI WEN-QING , Cho Eunyoung , Goldstein Alisa , Huang Yen-Tsung , Weinstock Martin , Qureshi Abrar 
Published: July 2017

Abstract
Background and Aims: Atypical nevi (AN) are a strong risk factor as well as a precursor of melanoma. However, most previous studies on the associations between atypical nevi (AN) and the risk of melanoma have been conducted in retrospective case-control settings and the few available prospective studies have been based on small sample sizes. Further, few studies have examined the associations between AN and risk of keratinocyte carcinomas (formerly called non-melanoma skin cancer). We prospectively examined the risk of incident melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) associated with AN.
Methods: In the Health Professionals Follow-up Study, information on AN was collected by self-report. Only those confirmed cases of AN by a supplementary questionnaire, the Atypical Nevus Screening Questionnaire (ANQ), were included in the analyses. Diagnosis of skin cancers was reported biennially and information on melanoma and SCC was pathologically confirmed. A total of 50193 men were included in our study, with 1239 confirmed cases of AN with information on diagnosis year. Cases of AN that were not confirmed or did not respond to the ANQ were excluded from the analyses. Time-dependent Cox-regression analyses were conducted for the associations between AN and risk of incident melanoma, SCC, and BCC respectively.
Results: We identified 545 melanoma cases, 1721 SCC cases, and 13498 BCC cases during the follow-up (1986-2012). A history of AN was significantly associated with increased risk of incident melanoma (hazard ratio [HR]=3.50, 95% confidence interval [CI]: 2.13-5.76) overall and at different body sites (head and neck, trunk, or limbs). The risk of melanoma was particularly augmented with the increasing number of AN that were surgically removed (HR=1.26, 95% CI: 1.16-1.37 per AN) and for cases of AN with tissue re-excision from the nevus removal sites (HR=4.59, 95% CI: 1.70-12.41). A history of AN was also significantly associated with increased risk of BCC (HR=1.84, 95% CI: 1.60-2.10) and was only associated with risk of SCC at the trunk sites (HR=3.09, 95% CI: 1.24-7.72).
Conclusions: A history of AN significantly increased the risk of subsequent melanoma in a prospective study of men. A history of AN may also be associated with increased risk of BCC overall and trunk SCC, which requires further studies to replicate.
Citation Format: WEN-QING LI, Eunyoung Cho, Alisa Goldstein, Yen-Tsung Huang, Martin Weinstock, Abrar Qureshi. Atypical nevi and risk of incident skin cancer in US men: a prospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2294. doi:10.1158/1538-7445.AM2017-2294
Abstract 2301: Genital use of talc and risk of ovarian cancer: A meta-analysis
Authors: Boffetta Paolo , Berge Wera 
Published: July 2017

Abstract
Some epidemiological studies suggest an association between genital use of talc powders and increased risk of ovarian cancer, but the evidence is not consistent. We performed a meta-analysis of epidemiologic studies to formally evaluate this suspected association. A systematic search was conducted in Medline, Embase and Scopus, leading to the identification of 24 case-control studies and 3 cohort studies, including 302,705 women with ovarian cancer. In the meta-analysis, we used a random-effect model to calculate summary estimates of the association between genital use of talc and occurrence of ovarian cancer. We assessed potential sources of between-study heterogeneity and presence of publication bias. The summary relative risk (RR) for ever use of genital talc and ovarian cancer was 1.22 (95% confidence interval [CI] 1.13-1.30). The RR for case-control studies was 1.26 (95% CI 1.17-1.35) and for cohort studies was 1.02 (95% CI 0.85-1.20, p heterogeneity=0.007). Serous carcinoma was the only histologic type for which an association was detected (RR 1.24; 95% CI 1.15-1.34). There was no trend in RR with either duration or frequency of genital talc use. This meta-analysis resulted in a weak but statistically significant association between genital use of talc and ovarian cancer, which appears to be limited to serous carcinoma. The heterogeneity of results by study design and the lack of a trend for duration and frequency of use, however, detract from a causal interpretation of this association.
Note: This abstract was not presented at the meeting.
Citation Format: Paolo Boffetta, Wera Berge. Genital use of talc and risk of ovarian cancer: A meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2301. doi:10.1158/1538-7445.AM2017-2301
Abstract 2302: Differences in risk factor-colorectal adenoma associations according to non-steroidal anti-inflammatory drug use
Authors: Mujtaba Sobia , Bostick Roberd M. 
Published: July 2017

Abstract
Multiple observational studies and large, randomized controlled trials indicate that non-steroidal anti-inflammatory drugs (NSAIDs) strongly reduce risk for colorectal neoplasms. The strengths of these findings suggest that NSAIDs may so mask various risk factor-colorectal neoplasm associations, that they may be undetectable among NSAID users. Temporal changes and between-population differences in regular NSAID use prevalence may account for some of the inconsistencies in reported findings for risk factor-colorectal neoplasm associations. We investigated whether associations of known colorectal cancer risk factors with colorectal adenoma differed by non-aspirin NSAID use using pooled data from 3 colonoscopy-based case-control studies of incident, sporadic colorectal adenoma conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002. Participants (n=789 cases, 2,035 polyp-free controls) provided risk factor data prior to colonoscopy. The multivariable-adjusted odds ratios (OR) (95% confidence intervals [CI]) for those in the highest relative to the lowest quartiles of exposure, by regular non-aspirin NSAID non-use/use, respectively, were 1.57 (CI 0.96, 2.55) vs. 1.22 (CI 0.40, 3.70) for total fat, 1.37 (CI 0.86, 2.18) vs. 0.78 (CI 0.26, 2.35) for saturated fat, 0.92 (CI 0.67, 1.26) vs. 1.31 (CI 0.62, 2.76) for total calcium, 0.88 (CI 0.64, 1.22) vs. 1.38 (CI 0.65, 2.93) for total fruits and vegetables, 1.05 (CI 0.73, 1.50) vs. 0.73 (CI 0.33, 1.62) for red and processed meats, and 0.84 (CI 0.65, 1.10) vs. 0.97 (CI 0.54,1.75) for physical activity. For current smokers relative to never smokers, the ORs (CIs) among regular non-NSAID users/non-users were 2.88 (CI 2.20, 3.77) vs. 1.64 (CI 0.85, 3.17), respectively, and for those who were obese relative to those who were normal weight, they were 1.65 (CI 1.27, 2.16) vs. 1.20 (CI 0.70, 2.04). The associations of age, height, and intakes of alcohol, dietary fiber, and total folate with adenoma did not substantially differ according to NSAID use.
These findings suggest that regular non-aspirin NSAID use may mask, beyond simple confounding, associations of various risk factors with colorectal adenoma, suggesting that differential proportions of regular NSAID users between study populations may explain some inconsistencies in reported risk factor-colorectal neoplasm associations, and support routinely assessing such associations stratified by regular non-aspirin NSAID use.
Citation Format: Sobia Mujtaba, Roberd M. Bostick. Differences in risk factor-colorectal adenoma associations according to non-steroidal anti-inflammatory drug use [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2302. doi:10.1158/1538-7445.AM2017-2302
Abstract 2318: Cyclopamine sensitizes endoplasmic reticulum stress-mediated increase of death receptor 5 and survivin degradation in trail-resistant gastric cancer cells
Authors: Na Yoo Jin , Lee Dae-Hee , Kim Jung Lim , Kim Bo Ram , Park Seong Hye , Jo Min Jee , Jeong Yoon A , Oh Sang Cheul 
Published: July 2017

Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been known as one of the most effective cancer treatment owing to its selective killing effect of cancer but not normal cells. However it has been reported that several gastric cancer cells showed resistance to TRAIL because of scarcity of death receptor 5 (DR5) expressed on the cell surface. In this study, we elucidated cyclopamine sensitizes to TRAIL-induced apoptosis by elevating the expression level of DR5 in gastric cancer cells. Interestingly, survivin hampers existence of DR5 protein under normal condition. Cyclopamine decreases expression level of survivin. It is a reason for cyclopamine to act as a TRAIL sensitizer. Mechanistically, cyclopamine induces endoplasmic reticulum (ER) stress by Reactive Oxygen species (ROS), and CHOP, which as a last protein of ER stress pathway regulates stability of survivin protein by proteasome degradation. Taken together, our results indicate that cyclopamine can be used for the purpose of combination therapy in TRAIL-resistant gastric cancer cells.
Citation Format: Yoo Jin Na, Dae-Hee Lee, Jung Lim Kim, Bo Ram Kim, Seong Hye Park, Min Jee Jo, Yoon A Jeong, Sang Cheul Oh. Cyclopamine sensitizes endoplasmic reticulum stress-mediated increase of death receptor 5 and survivin degradation in trail-resistant gastric cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2318. doi:10.1158/1538-7445.AM2017-2318
Abstract 2319: Deficiency of protease-activated receptor 2 signaling sensitizes EGFR-TKI-induced apoptosis in colorectal cancer
Authors: Li Weiwei , Ma Yiming , He Longmei , Wang Hongying 
Published: July 2017

Abstract
Colorectal carcinoma (CRC) patients show resistance to EGFR-TKI (epidermal growth factor receptor -tyrosine kinase inhibitor) treatment. Protease-activated receptor 2 (PAR2) has been shown to transactivate EGFR. We aim to investigate whether PAR2 sensitizes EGFR-TKI-induced apoptosis in CRC. Firstly, inhibition of PAR2 with shRNA or ENMD-1068 (a selective antagonist of PAR2) significantly sensitized EGFR-TKI (gefitinib or AG1478)-induced apoptosis, which was measured with Annexin V/ PI staining and activation of caspase-3 in different CRC cell lines. In xenograft tumor model, gefitinib treatment dramatically reduced the tumor volume in HT-29-shPAR2 compared with HT-29-vector. Mechanism study showed that PAR2 knockdown significantly reduced bcl-xL expression at both mRNA and protein level. Consistently, activation of PAR2 upregulated bcl-xL. Furthermore, inhibition of protein phosphatase (PP) with okadaic acid significantly downregulated bcl-xL. Moreover, knockdown of PP1 with siRNA blocked PAR2-induced accumulation of bcl-xL. In summary, our findings suggest that inhibition of PAR2 sensitizes EGFR-TKI-induced apoptosis via downregulation of bcl-xL in colorectal cancer. Considering the extensive expression of PAR2 and PAR2-activating proteases in colon, it strongly indicates that inhibition of PAR2 may be a potential avenue to overcome EGFR-TKI resistance in patients with CRC.
Citation Format: Weiwei Li, Yiming Ma, Longmei He, Hongying Wang. Deficiency of protease-activated receptor 2 signaling sensitizes EGFR-TKI-induced apoptosis in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2319. doi:10.1158/1538-7445.AM2017-2319
Abstract 2343: The novel potential of palbociclib (CDK4/6 inhibitor) in the treatment of triple-negative breast cancer
Authors: Kashiwagi Shinichiro , Asano Yuka , Goto Wataru , Takada Koji , Takashima Tsutomu , Morisaki Tamami , Noda Satoru , Onoda Naoyoshi , Hirakawa Kosei , Ohira Masaichi 
Published: July 2017

Abstract
Background: The effectiveness of palbociclib (CDK4/6 inhibitor) for estrogen receptor positive breast cancer has been demonstrated by large-scale clinical studies, with the drug garnering attention as a key drug for breast cancer subtypes with endocrine sensitivity in the future. According to PALOMA-3 trial, palbociclib has been demonstrated to contribute to the extension of progression-free survival in patients with advanced hormone receptor-positive and HER2-negative metastatic breast cancer after endocrine therapy. On the other hand, in the case of triple-negative breast cancer (TNBC), luminal AR (LAR) related to androgen signaling is believed to have endocrine activity. Previous clinical data revealed that palbociclib shows high sensitivity in luminal breast cancer cell lines with endocrine activity, with effectiveness also expected in LAR. In this study, we created TNBC cell lines that forcibly express AR and examined the effectiveness of palbociclib for TNBC.
Materials and Methods: MCF-7 and T-47D were used as luminal breast cancer cell lines, while MDA-MB-231 and BT-549 were used as TNBC cell lines. In addition, we created TNBC cell lines that forcibly express AR, called AR-MDA-MB-231, by the transfection of pEGFP-C1-AR Plasmid Vector using Lipofectamine® 3000 Reagent. We confirmed the expression of AR by qRT-PCR as well as Western blotting and examined the impact of palbociclib on proliferation as well as apoptosis of breast cancer cell lines.
Results: AR was found to have been expressed only in luminal breast cancer cell lines but not TNBC cell lines. It was confirmed that AR was expressed in AR-MDA-MB-231 which are stable cell lines with the properties of LAR. In a CCK assay, palbociclib showed high sensitivity in AR-MDA-MB-231 as in luminal breast cancer cell lines. Furthermore, in an apoptosis assay using FACS and cell cycle assay, apoptosis was induced in AR-MDA-MB-231 and cell cycle arrest at the G1S check point was confirmed.
Conclusion: palbociclib (CDK4/6 inhibitor) showed effectiveness for TNBC cell lines that compulsively express AR, suggesting it may be one treatment option for TNBC in the future.
Citation Format: Shinichiro Kashiwagi, Yuka Asano, Wataru Goto, Koji Takada, Tsutomu Takashima, Tamami Morisaki, Satoru Noda, Naoyoshi Onoda, Kosei Hirakawa, Masaichi Ohira. The novel potential of palbociclib (CDK4/6 inhibitor) in the treatment of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2343. doi:10.1158/1538-7445.AM2017-2343
Abstract 2374: Mixed-Lineage Kinase 3 signals through the FRA1-MMP1 axis to drive triple-negative breast cancer invasion and transendothelial migration
Authors: Rattanasinchai Chotirat , Llewellyn Brandon , Conrad Susan E. , Gallo Kathleen A. 
Published: July 2017

Abstract
Mixed-lineage kinase 3 (MLK3), a mitogen-activated kinase kinase kinase (MAP3K), contributes to metastasis of triple-negative breast cancer (TNBC), in part through its regulation of paxillin phosphorylation and focal adhesion turnover. However the signaling mechanisms through which MLK3 promotes invasion and metastasis are not fully understood. We found that in non-metastatic, estrogen receptor positive (ER+) breast cancer cells, induced MLK3 expression robustly upregulates the oncogenic transcription factor, FOS-related antigen-1 (FRA-1), as well as matrix metalloproteinases (MMPs), MMP-1 and MMP-9. MLK3-induced MMP-1 induction is abrogated by FRA-1 silencing, demonstrating that MLK3 signals through FRA-1 to control MMP-1. In complementary experiments performed in metastatic TNBC models, high levels of FRA-1 are significantly reduced upon gene silencing of MLK3 or by MLK3 disruption using the CRISPR/Cas9n approach. Furthermore, both MMP-1 and MMP-9 are decreased upon ablation of MLK3 or MLK inhibitor treatment. Reduced endothelial permeability and transendothelial migration is observed in experiments with MLK3-depleted TNBC cells compared with parental counterparts. In addition, MLK inhibitor treatment or MLK3 depletion renders TNBC cells defective in Matrigel invasion. Furthermore, circulating tumor cells (CTCs) derived from a TNBC-bearing mouse which show an intermediate epithelial-mesenchymal phenotype display increased levels of MLK3, FRA-1, and MMP-1 compared with parental cells, supporting a role for the MLK3-FRA-1-MMP-1 signaling axis in tumor cell invasion and vascular intravasation. Consistent with the role of MMP-1 in multiple steps of metastasis, high levels of MMP-1 in breast cancer patient tumor samples are associated with increased distant metastases and poorer overall survival, particularly in TNBC. Our results demonstrating the requirement for MLK3 in controlling the FRA-1/MMP-1 axis suggest that MLK3 is a potentially effective therapeutic target for TNBC.
Citation Format: Chotirat Rattanasinchai, Brandon Llewellyn, Susan E. Conrad, Kathleen A. Gallo. Mixed-Lineage Kinase 3 signals through the FRA1-MMP1 axis to drive triple-negative breast cancer invasion and transendothelial migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2374. doi:10.1158/1538-7445.AM2017-2374