bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1134: Developing an early expression-based signature to assess interval colorectal carcinoma risk
Authors: Cheah Peh Yean , Thean Lai Fun , Lam Kuen Kuen , Liew Soo Chin , Wong Michelle , Koh Nicholas , Lo Michelle , Tan Emile , Tang Choong Leong 
Published: September 2020

Abstract
Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer mortality in the developed world including Singapore. Despite an aging populace which is now more compliant to having a baseline colonoscopy at age 50 or earlier, interval cancer (cancer that develops in between colonoscopies) is an unmet critical problem. The identification of early driver genes that can serve as biomarkers for CRC risk will aid in clinical management decision to counter cancer-associated mortality and morbidity. We profiled the genome-wide expression of matched mucosa (M), mucosa next to tumor (MT) and tumor (T) samples of a series of 23 patients using Affymetrix Gene Array. M samples are at least 20 cm away from the tumor and MT samples are adjoining the T samples but maintained the normal colonic crypt architecture of M. We discovered that thirty-nine dysregulated genes in MT samples compared to M samples persists until tumor formation. These early driver genes comprise not only tumor suppressors or oncogenes but included metabolic and transporter genes indicating that transformation towards malignancy requires the disruption of many pathways. Majority of these genes were down-regulated; the top three most drastically down-regulated genes include AQP8 (a water transporter), CA7 (a metabolic gene) and PHLPP2 (a tumor suppressor). Further analysis indicates that the three genes were already down-regulated in the normal appearing mucosa of a ‘healthy' individual compared to age-, gender-, ethnicity-matched (AGE-) controls seven years before recto-sigmoid cancer was diagnosed. This suggests that the dysregulation can occur several years before tumor formation and hence could possibly be used as early or pre-cancer biomarker. We have validated the down-regulation of the 3 genes in an independent series of 135 CRC samples from the same center using real-time RT-PCR assays. Correlation of the expression with clinicopathological features of the patients (gender, tumor site, age-group) and molecular subtypes (CMS 1-4) of the tumors will be ascertained to assess whether the signature is applicable to all CRC subtypes. Furthermore, the expression in matched blood samples will also be determined to explore feasibility of using these samples for assessing interval colorectal carcinoma risk.
Citation Format: Peh Yean Cheah, Lai Fun Thean, Kuen Kuen Lam, Soo Chin Liew, Michelle Wong, Nicholas Koh, Michelle Lo, Emile Tan, Choong Leong Tang. Developing an early expression-based signature to assess interval colorectal carcinoma risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1134.
Abstract 1148: Salivary auto-antibodies as diagnostic markers of oral cavity squamous cell carcinoma
Authors: Hsueh Pei Chun , Wu Chih Ching 
Published: September 2020

Abstract
Oral cavity squamous cell carcinoma (OSCC) is a destructive disease with its increasing new cases annually. OSCC is usually diagnosed at advanced clinical stage which leads to the poor outcomes of patients. Currently, no biomarkers provide capability for sufficient early detection of OSCC. Cancer-associated auto-antibody (auto-Ab) holds potentials as promising biomarkers for cancer detection because auto-Ab is easily detected with well-established secondary reagents. To ameliorate the detection of OSCC, we evaluated the capability of auto-Ab to 9 proteins as the OSCC biomarkers with multiplexed bead-based immunoassay, as the salivary levels of the 9 proteins are elevated in OSCC patients. The multiplexed bead-based assay has been established to simultaneously detect the salivary levels of the 9 auto-Abs and anti-p53, a well-characterized OSCC biomarker. Compared to the healthy individuals, the salivary levels for 8 of 9 auto-Abs as well as anti-p53 were significantly elevated in OSCC patients. The salivary levels of the 7 of 9 auto-Abs were significantly increased in individuals with oral potentially malignant disorder compared to the control group. In addition, the salivary levels of 8 of 9 auto-Abs as well as anti-p53 were statistically significant in early-stage OSCC patients. Moreover, the marker panel of the 9 auto-Abs can improve the detection of OSCC. Collectively, we have established the platform for detection of maker panels and the salivary auto-Abs are potential biomarkers for OSCC screening.
Citation Format: Pei Chun Hsueh, Chih Ching Wu. Salivary auto-antibodies as diagnostic markers of oral cavity squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1148.
Abstract 1175: Race informs survival disparities in head and neck cancer clinical trials
Authors: Liu Jeffrey C. , Egleston Brian , Blackman Elizabeth , Ragin Camille 
Published: September 2020

Abstract
Background: Survival disparities between blacks and whites in head and neck cancer are well documented, with access to care and socioeconomic status (SES) as major contributors. However, the impact of race alone on survival is much less clear. Previous attempts to evaluate the role of race have been limited by access to care/SES as major confounders. We set out to directly assess the role of race in head and neck cancer by evaluating treatment outcomes of subjects enrolled in clinical trials. In this population, access to care and socioeconomic confounders are minimized because all patients receive identical treatments.
Methods: Clinical trial data from the Radiation Therapy Oncology group (now NRG) studies were obtained by request. Seven RTOG Studies (RTOG 0129, 0234, 9003, 9111, 9501, 9512, 9703) were included for study. Studies were included if they were phase II or III trials that employed survival as an endpoint, e.g. progression free survival (PFS), disease free survival (DFS), overall survival (OS). Studies that were small (&lt;200 patients) or did not use survival as an endpoint (e.g. side effect trial) were excluded. For each black patient enrolled in a clinical trial, a white patient matched in the same arm of that trial was used as a control. The study null-hypothesis was that there would be no race derived impact on survival and thus the chance of survival favoring either whites or blacks in each matched pair would be 50%.
Results: Across the seven trials, 468 blacks were identified and matched with 468 white study arm specific controls. Whites had better outcomes than blacks in 60% of matched pairs (p&lt;0.001). Blacks were consistently more likely to have worse outcomes. When outcomes were collapsed by PFS/DFS, the failure rate was significantly higher in blacks (HR=1.46, p&lt;0.001)). Failure was largely due to locoregional failure, and blacks were at higher risk (sHR =1.43, p=0.002). The development of distant metastasis within the paired cohorts was not significantly different (sHR=1.15, p=0.38), suggesting that locoregional failure was the major driver of failure.
Conclusions: In this analysis of head and neck cancer patients in clinical trials, blacks consistently had worse outcomes in comparison to study arm specific white controls. This suggests that race alone confers a worse survival independent of socioeconomic and access to care factors. Further study is needed to confirm these findings, and to explore other causes underlying this disparity.
Citation Format: Jeffrey C. Liu, Brian Egleston, Elizabeth Blackman, Camille Ragin. Race informs survival disparities in head and neck cancer clinical trials [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1175.
Abstract 1190: Comparison of cumulative incidence rates of colorectal cancer among Asians and Pacific Islanders (API) populations in Guam, Hawai'i, and the United States
Authors: Badowski Grazyna 
Published: September 2020

Abstract
Background: Colorectal cancer is one of 4 most common cancers on Guam, Hawai'i (HI) and the US. However, incidence rates vary between ethnic groups and location.
Objective: The objective of the study was to compare cumulative incidence rates (CIRs) among ethnic groups in Guam, HI, and the US; specifically, Chamorros in Guam, Filipinos in Guam, HI and the US, and Native Hawaiians in HI and the US. CIRs are weighted sums of age-specific incidence rates therefore they can be used for comparisons between populations. They are relatively stable and thus provide a good estimate of cumulative risk of cancer.
Methods: This study included all colorectal cancer cases (n=562) reported to the Guam Cancer Registry and all colorectal cancer cases (n=253,782) reported to the Surveillance, Epidemiology, and End Results (SEER) 9-Registry from 2000 to 2014. Cumulative incidence rates were calculated for three time periods: 2000-2004, 2005-2009, and 2010-2014 and compared by age, ethnicity and location.
Results: Differences were seen in CIRs by time-period, age, ethnicity, and location. For all three time periods: 2000-2004, 2005-2009, 2010-2014, the lifetime cumulative incidence rates (age 0-79) were highest for Hawai'i (5.7%, 5.4%, and 5.3% respectively), followed by the US (5.2%, 4.5%, and 3.7%) and Guam (4.3%, 3.3%, and 3.6%). Interestingly, there were large differences in lifetime CIRs between Filipinos in HI, Filipinos in the US and Filipinos on Guam (i.e. 6.5%, 3.7%, and 2.4% respectively in 2005-2009). The Chamorros on Guam had the rate at least 1.5 times higher than Filipinos on Guam (4.3 % vs 3.3%) and close to the rate of Native Hawaiians in HI (4.9%). Overall, there was downward trend for the lifetime CIRs over time. Only for the Filipinos in HI, the rates went up. However, early onset CIRs (age 0-49) went up across all locations and ethnic groups.
Conclusions: Disparities in colorectal cancer incidence were identified. Further study is needed to examine how exposure to risk factors and screening changes with immigration and how this variation contributes to the incidence disparities.
Citation Format: Grazyna Badowski. Comparison of cumulative incidence rates of colorectal cancer among Asians and Pacific Islanders (API) populations in Guam, Hawai'i, and the United States [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1190.
Abstract 1207: Custom next-generation sequencing primer designs for targeted sequencing of multi strain viral targets
Authors: Singh Ratnesh , Li Na , Luo Zunping , McGeachy Anna , Alcantara Antonio F. Martinez , Ewing Aren , Hyland Fiona C. 
Published: September 2020

Abstract
Viruses are infectious agents that can cause many diseases including cancers. A viral species is comprised of many strains each having a unique pathology. For example, over 170 types of HPV have been described, of which only 2 strains, HPV16 and HPV18, are implicated in 70% of cervical cancer cases. Accurate identification of viral strains is often critical and also facilitates research into their association with prognosis or response and personalized therapies. Currently, sequencing virus genes or genome requires complex procedures that involve purifying the virus particle and its genomes from the host genome. Whole genome sequencing is inefficient since viral genomes are orders of magnitude smaller than human genomes, and human DNA is orders of magnitude more abundant than viral DNA. In contrast, targeted next-generation sequencing allows focusing of sequencing and analysis to the region or species of interest using PCR based enrichment.
We developed a viral design pipeline that accepts a multiple sequence alignment of the viral genomes or genomic regions of interest to identify and design primer pairs in conserved regions flanking the variable regions. The presence/absence of a set of 1 or more amplicons is used to precisely differentiate the many strains of a viral species. For whole genome sequencing, the complete viral genomic sequence is used as target to design unique and highly specific amplicons covering the whole genome for enrichment of the entire virus. All primers pass through rigorous quality checks to meet our sensitivity, specificity, and primer quality standards.
We have successfully designed multi-strain Ion Ampliseq custom viral panels for HCV, HIV, CMV, Measles and Pestivirus. Some of these panels were designed with the objective of targeting a specific region on a virus genome; other panels were designed to enrich and sequence the whole virus genome. The panel primers were highly specific to the region of interest in the viral genomes and did not amplify the host genome.
In conclusion, our custom Ion AmpliSeq viral panels enable the enrichment and amplification of the unique regions of interest in the viral genomes or the whole virus genome, avoiding the massive excess of the host genome. These panels allow precise identification of the virus species and strains for many applications including research, phylogenomic classification and comparative genomics.
For Research Use Only. Not for use in diagnostic procedures
Citation Format: Ratnesh Singh, Na Li, Zunping Luo, Anna McGeachy, Antonio F. Martinez Alcantara, Aren Ewing, Fiona C. Hyland. Custom next-generation sequencing primer designs for targeted sequencing of multi strain viral targets [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1207.
Abstract 1209: The association between the cell cycle control pathway and pediatric germ cell tumors
Authors: Hubbard Aubrey K. , Pankratz Nathan , Kelley Spencer T. , Meredith John J. , Poynter Jenny N. 
Published: September 2020

Abstract
Pediatric germ cell tumors (GCTs) account for approximately 6% of childhood cancers. GCTs are heterogeneous but are grouped together due to a common cell of origin, the primordial germ cell. GCTs are predicted to have high heritability, therefore, genetic association studies are paramount in understanding GCT etiology. Genome-wide association (GWA) studies commonly ignore the aggregate effect of SNPs/genes with weaker individual associations. Pathway-based approaches provide the opportunity to interrogate joint SNP effects in pathways of interest. The cell cycle control pathway is a plausible candidate pathway given the knowledge that alterations in the the mitotic-meiotic switch may lead to genetic instability and initiate GCT development. In this analysis we evaluated a set of 94 genes associated with cell cycle control using data from a case-parent triad study of pediatric GCT. Genes involved in cell cycle control were identified using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We also included additional genes based on reports in the literature suggesting a role in cell cycle control in GCTs, including STRA832, 33, CYP26B134, CKS1B35, and E2F636. Variants within 25,000 base pairs upstream or downstream of the gene were selected for inclusion resulting in a total of 2,846 SNPs included in the analysis. Genotyping data were generated using the Illumina HumanCore Exome Array for 867 GCT cases and their unaffected parents. Preliminary results evaluating individual effects of SNPs in the pathway were conducted using the transmission disequilibrium test (TDT). We did not observe any individual SNP associations that reached genome-wide significance; however, suggestive associations were observed for SNPs located in CDKN2C (p=0.000208), MCM7 (p=0.000787), RB1 (p=0.000798), RBL2 (p=0.00250) and TP53 (p=0.00257). Replication of these findings will be conducted using data from a record linkage case-control study from neonatal biobanks in California and Michigan (N=837 cases and 1057 controls). In addition, we will utilize pathway-based approaches to jointly evaluate the effects of genes in this pathway, including Gene Set Enrichment Analysis for Genome wide association study (i-GSEA4GWAS), MetXcan for functional significance, and Family-based rare-variant association analysis (PedGene). In conclusion, our results suggest that genes within the cell-cycle control pathway play a role in the etiology of pediatric GCT.
Citation Format: Aubrey K. Hubbard, Nathan Pankratz, Spencer T. Kelley, John J. Meredith, Jenny N. Poynter. The association between the cell cycle control pathway and pediatric germ cell tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1209.
Abstract 122: Targeting forward and reverse EphB4/EFNB2 signaling by a peptide with dual functions
Authors: Xiong Chiyi , Wen Yunfei , Zhao Jun , Yin Dengke , Xu Lingyun , Chelariu-Raicu Anca , Yao Cody , Leng Xiaohong , Liu Jinsong , Chaudhari Rajan R , Zhang Shuxing , Sood Anil K , Li Chun 
Published: September 2020

Abstract
Introduction: EphB4 is frequently overexpressed in ovarian and other solid tumors and involved in interactions between tumor cells and tumor microenvironment, contributing to metastasis. EphB4 and its membrane-bound ligand ephrin B2 (EFNB2) mediates bi-directional signaling. Currently, no small-molecule-based, peptides with dual functional binding to EphB4 are available. Therefore, we developed an EphB4 agonist that is capable of activating the forward EphB4 signaling and interfering with the reverse EFNB2 signaling.
Methods: A high-affinity bi-directional ephrin agonist peptide (BIDEN-AP) that selectively activated EphB4 was discovered through structural modifications to the known EphB4 antagonist TNYLFSPNGPIARAW (TNYL-RAW) by surface plasma resonance and cell based assays. To improve pharmacokinetics and enhance peptide stability, BINDEN-AP peptide was conjugated to Core-Crosslinked Polymeric Micelles (CCPM). Anti-tumor and anti-angiogenic effects of BINDEN-AP peptide and its conjugate with CCPM were evaluated using orthotopic human A2789cp20-Luc ovarian cancer xenograft model, and PDX model of high grade serous ovarian carcinoma (HGSC).
Results: We found that BIDEN-AP was selectively internalized via receptor-mediated endocytosis, mediated phosphorylation of EphB4 and its downstream adaptor protein Crk1 (MAPK14), and suppressed invasion and epithelial-to-mesenchymal transition in ovarian cancer cells. BIDEN-AP also inhibited endothelial migration and tube formation by 50% (p&lt;0.05). In vivo, BIDEN-AP and CCPM-BIDEN-AP significantly reduced tumor weight (p&lt;0.05) and number of tumor nodules (p&lt;0.01) of intraperitoneally inoculated A2780cp20 ovarian tumors. Moreover, CCPM-BIDEN-AP displayed greater anti-tumor potency than BIDEN-AP with regard to reduction in the number of tumor nodules (p&lt;0.01). Both BIDEN-AP and CCPM-BIDEN-AP compromised angiogenesis as evidenced by significantly reduced microvessel density (p&lt;0.01).
Conclusion: Given the robust anti-tumor effects of BIDEN-AP, these data could have direct relevance for further therapeutic development.
Citation Format: Chiyi Xiong, Yunfei Wen, Jun Zhao, Dengke Yin, Lingyun Xu, Anca Chelariu-Raicu, Cody Yao, Xiaohong Leng, Jinsong Liu, Rajan R Chaudhari, Shuxing Zhang, Anil K Sood, Chun Li. Targeting forward and reverse EphB4/EFNB2 signaling by a peptide with dual functions [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 122.
Abstract 1221: Novel strategies to target autophagy to improve cancer therapy
Authors: Li Yuanpei , Ma Zhao , Zhang Dailn , Ramachandran Mythili , Lin Tzu-yin 
Published: September 2020

Abstract
In cancer research, autophagy is thought to be a double-edged sword because it can either prevent malignant transformation during cancer initiation or sustain tumor metabolism, growth and survival in cancer establishment and progression. For established tumors, especially the advanced or metastatic types, the harsh intercellular conditions activate autophagy so that tumor cells can adapt to the stressful conditions and efficiently recycle their nutrients, while also allowing them to respond to anti-tumor therapeutics. Therefore, interventions that deliberately inhibit autophagy in cancer therapy have been used to reduce cancer cell survival, overcome drug resistance and improve clinical outcomes. The vast majority of autophagy inhibitors used in these therapies are lysosomotopic alkaline agents, such as chloroquine (CQ) and hydroxychloroquine (HCQ). However, their efficacy is considered to be imperfect. New strategy to target autophagy for cancer therapy is needed. Through introducing nanotechnology into initial new drug entity design, we developed a series of new chemical entities, BAQ12-18, and all of them are potential building blocks to self-assemble into the single new-chemical-entity nanomedicines (BAQ SNNs). The selected BAQ12 NP and BAQ13 NP not only improve drug delivery and tumor-targeted biodistribution but also endow unique proton sponge effect to dramatically enhance the existing functions of lysosomal disruption and autophagy blockade, and thus generate significant therapeutic efficacy both in vitro and in vivo. The more striking finding is that BAQ13 NP can potently provide both a uniform drug delivery platform and synergistic effect to the combination drug, indicating a new-generation strategy of combination therapy. Considering their capacity to encapsulate different drugs and broad synergistic effect with various treatments, BAQ SNNs may make a tremendous contribution to the outcome of cancer treatment. To the best of our knowledge, this is the first attempt to extend nanotechnology into the design stage of new small-molecule drug entity. The seamless connection between new drug discovery and nanomedicine-based drug delivery will absolutely inspire researchers to develop increasingly advanced nanomedicines with a wide range of practical values and market for improved the therapy against challenging diseases.
Citation Format: Yuanpei Li, Zhao Ma, Dailn Zhang, Mythili Ramachandran, Tzu-yin Lin. Novel strategies to target autophagy to improve cancer therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1221.