bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4563: Immunoprevention of triple negative breast cancer by a multi-antigen, multi-peptide vaccine
Authors: Wang Yian 
Published: September 2020

Abstract
Triple negative breast cancer (TNBC) is the most aggressive sub-type of breast cancer, comprising approximately 20% of all breast cancers, and has a poor prognosis due to its aggressive behavior and lack of effective targeted therapies. In the present study, we employed transcriptome and protein analyses to select genes that are uniquely overexpressed in human triple-negative breast cancer. Overexpression of selected genes, Cyclin A2, CDK1, Cyclin E2, PRC1, Kif15, TPX2, Ki67, Top2A, were confirmed on human breast cancer tissue microarrays and in TNBC derived cell lines from C3(1)/TAg mice. Antigen-specific MHC class II epitopes with promiscuous high-binding affinity were identified using the “combined scoring system”, based on their potential to elicit a selective Th1 immunity. Furthermore, all peptides were selected to have over 85% amino acid sequence homology between human and mice for potential clinical translation. Strong immunogenic peptides from five antigens were selected by immunogenicity testing in tumor naïve mice based on high IFN-γ and low IL-10 ELISpot response data. The selected peptides, Cyclin A2 (#335), CDK1 (#113), Cyclin E2 (#93, 298, 334), KIF15 (#129), and Top2A (#236, 410, 606), were combined to form a multi-antigen, multi-peptide vaccine (MAMPV). The tumor preventive efficacy of the MAMPV was evaluated in syngraft study using a TNBC model: C3(1)/TAg-REAR mice and a TNBC cell line derived from C3(1)/TAg (M6). MAMPV-vaccinated animals demonstrated a significant reduction in tumor volume, and significantly higher tumor infiltration of CD4+ T cells compared to the control animals. Pathological examination of major organs did not reveal any toxicity associated with the vaccine. Similar tumor preventive efficacy was demonstrated in genetically engineered mouse model (GEMM) using C3(1)/TAg mice. Taken together, our data indicate that formulation of the multi-antigen multi-peptide vaccine is highly immunogenic and has the potential to be safe and efficacious in the immunoprevention of TNBC.
Citation Format: Yian Wang. Immunoprevention of triple negative breast cancer by a multi-antigen, multi-peptide vaccine [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 4563.
Abstract 4571: Development of glycoconjugate based anticancer immunotherapy
Authors: Huang Xuefei 
Published: September 2020

Abstract
Tumor associated carbohydrate antigens (TACAs) are attractive targets for the development of anticancer immunotherapy. Mucin-1 (MUC1) is a representative member of the TACA family. Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen. In order to target these antigens as potential anti-cancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen respectively have been synthesized. Bacteriophage Qβ carrier is a powerful carrier for antigen delivery. The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize the immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units. The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans. Antibodies induced by Qβ-MUC1-Tf showed strongest binding with MUC1 expressing melanoma B16-MUC1 cells and effectively killed these cells in vitro. Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice. This was the first time that MUC1-Tf based vaccine has shown in vivo efficacy in a tumor model. As such, Qβ-MUC1 glycopeptide conjugates have great potentials as anti-cancer vaccines.
Citation Format: Xuefei Huang. Development of glycoconjugate based anticancer immunotherapy [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 4571.
Abstract 4621: Polymorphisms in JAK/STAT signaling pathway genes and risk of breast cancer
Authors: Gago-Dominguez Manuela , Martinez Maria E. , Milne Roger , Matabuena Marcos , Redondo Carmen , Castelao José Esteban , Jamieson Catriona 
Published: September 2020

Abstract
Background. Impaired function of JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway genes leads to immunodeficiency; genetic variation in this pathway could affect breast cancer risk.
Methods. We evaluated associations between genetic polymorphisms (SNPs) in 14 genes in the JAK/STAT pathway (JAK3, STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6, SCOS1, SCOS2, SCOS3, SCOS4, APOBEC and ADAR) and breast cancer risk using data from the OncoArray. As the JAK/STAT pathway interacts with ER and PR, we also examined these associations by breast cancer subtype. We examined a total of 203 genetic variants in 60,106 cases (38,531 ER positive, and 9,363 ER negative) and 46,300 controls.
Results. SNP rs738308 in APOBEC was associated with risk of overall breast cancer (P value &lt;0.001), and ER+ breast cancer (P value &lt; 0.002). SNPs in ADAR1/STAT were associated with risk of ER+ breast cancer (P value &lt; 0.01). The associations were more pronounced for advanced-stage disease. Other SNPs, exhibited potential, weaker associations.
Conclusion. We found increased breast cancer risk associated with rs738308 in APOBEC, and SNPs in ADAR1, both involved in RNA editing processes. APOBEC has been linked with cancer development and cholesterol control. Increased ADAR expression has been found in 50% of triple negative breast cancers (TNBC), which has been associated with increased recurrence and worse survival. RNA seq analysis showed that ADAR1 is among the top 5% of upregulated genes in relapsed lobular breast cancer. Activation of the JAK2/STAT3 pathway has been associated with TNBC poor prognosis. Our next step is to analyze these genetic variants using the iCOGs dataset which includes 116,587 additional patients and controls.
Citation Format: Manuela Gago-Dominguez, Maria E. Martinez, Roger Milne, Marcos Matabuena, Carmen Redondo, José Esteban Castelao, Catriona Jamieson. Polymorphisms in JAK/STAT signaling pathway genes and risk of breast cancer [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 4621.
Abstract 4634: Breastfeeding and prognosis of breast cancer among Chinese women
Authors: Ren Zefang , Wang Xiang , Tang Luying 
Published: September 2020

Abstract
Breastfeeding that linked to breast cancer risk may also influence the prognosis. A few previous studies on this topic have yielded inconsistent results. This study aimed to explore the dose-effect relationship between breastfeeding duration and breast cancer survival among Chinese women. We collected breastfeeding status, first breastfeeding duration (FBD), total breastfeeding duration (TBD) and average breastfeeding duration per child (ABD) from 3110 primary breast cancer patients recruited between October 2008 and June 2016 in Guangzhou, China and followed up until June 30, 2018. Restricted cubic splines and Cox proportional regression models were conducted to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for overall survival (OS) and progression-free survival (PFS) in association with breastfeeding. Long FBD (≥13 months) (HR=1.56 [1.13-2.17]), ABD (≥13 months) (HR=1.43 [1.04-1.96]) and TBD (≥37 months) (HR=1.73 [1.07-2.80]) were found to be associated with an increased risk of progression compared to moderate durations (FBD/ABD of 7-12 months, TBD of 19-36 months). Similar associations were observed for all-cause death. When stratified by ER status, the above effects of long FBD and ABD occurred only among patients with ER-positive tumor and the interactions were significant (FBD: Pinteraction=0.04 and 0.06, ABD: Pinteraction=0.07 and 0.04 for OS and PFS, respectively). Additionally, short FBD (≤6 months) increased the risk of a poor prognosis among young patients (≤45 years) (HR=1.86 [1.04-3.32] and 1.58 [1.06-2.34] for OS and PFS, respectively) but not old women (Pinteraction=0.02 for both OS and PFS). These findings would help clinical counseling and gaining insight into the mechanisms of breast cancer development.
Citation Format: Zefang Ren, Xiang Wang, Luying Tang. Breastfeeding and prognosis of breast cancer among Chinese women [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 4634.
Abstract 4648: Insulinemic and inflammatory dietary patterns and risk of prostate cancer
Authors: Fu Benjamin C. , Tabung Fred K. , Pernar Claire H. , Wang Weike , Gonzalez-Feliciano Amparo G. , Chowdhury-Paulino Ilkania M. , Clinton Steven K. , Folefac Edmund , Song Mingyang , Kibel Adam S. , Giovannucci Edward L. , Mucci Lorelei A. 
Published: September 2020

Abstract
Background: Studies of diet and prostate cancer have primarily focused on individual dietary factors, often with null or mixed findings. Assessment of dietary patterns is an alternative approach and has been increasingly used in nutritional epidemiology, providing the advantage of better accounting for added effects and interactions of dietary components. Hyperinsulinemia and inflammation are interrelated biological pathways that link diet with risk of several cancers, and studies have suggested that these may also increase prostate cancer risk. Whether dietary patterns based on these pathways contribute to the development and progression of prostate cancer is unclear.
Methods: We followed 39,776 men in the Health Professionals Follow-up Study (1986-2014) to examine associations between two empirical hypothesis-oriented dietary patterns with risk of total, local, advanced, and fatal prostate cancer. The two dietary patterns - empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) - were constructed using the weighted sum of food groups that predicted plasma C-peptide (EDIH) and inflammatory biomarkers (EDIP). Dietary scores were calculated from food frequency questionnaires at baseline and updated every 4 years. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression.
Results: We documented 5,682 incident cases of total prostate cancer and 658 cases of fatal prostate cancer over 868,552 person-years of follow-up. In multivariable-adjusted models, men in the highest EDIH quintile had an 18% higher risk of advanced prostate cancer (HR: 1.18, 95% CI: 0.96-1.45; P=0.04 for trend) and a 24% higher risk of fatal prostate cancer (HR: 1.24, 95% CI: 0.96-1.59; P=0.03 for trend) compared to men in the lowest quintile. There were no significant associations for EDIP and prostate cancer risk. BMI did not modify the association for either dietary pattern.
Conclusion: Hyperinsulinemia may be a potential mechanism linking dietary patterns and risk of aggressive prostate cancer. Additional studies to define mechanisms of action and interventions to reduce prostate cancer risk are warranted.
Citation Format: Benjamin C. Fu, Fred K. Tabung, Claire H. Pernar, Weike Wang, Amparo G. Gonzalez-Feliciano, Ilkania M. Chowdhury-Paulino, Steven K. Clinton, Edmund Folefac, Mingyang Song, Adam S. Kibel, Edward L. Giovannucci, Lorelei A. Mucci. Insulinemic and inflammatory dietary patterns and risk of prostate cancer [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 4648.
Abstract 4666: Cigarette smoking and opium use in relation to the oral microbiome in Iran
Authors: Wu Zeni 
Published: September 2020

Abstract
Background: Cigarette smoking and opium use are associated with periodontal disease, which is linked to the changes in oral microbiome. We aimed to study the association between cigarette and/or opium use with the oral microbiome.
Methods: A total of 558 subjects included in the present analysis were from a case-control study of pancreatic cancer in Tehran, Iran conducted from 2011 to 2015. A questionnaire ascertained demographic, cigarette and opium use history, and lifestyle characteristics, and participants provided saliva samples. DNA was extracted using the DSP DNA Virus Pathogen kit and 16S rRNA gene sequencing was performed on the MiSeq. Sequences were clustered into amplicon sequence variants (ASVs) using QIIME2 and taxonomy was assigned against the Human Oral Microbiome Database. Logistic regression, MiRKAT and zero-inflated β regression models were calculated with adjustment for age, sex, body mass index, and case status.
Results: The average number of observed ASVs for users of cigarette only (82.13 ± 38.55), opium only (76.19 ± 40.71), or both cigarette and opium users (77.80 ± 42.83) were significantly lower than never cigarette/opium users (95.10 ± 44.03). Similar trends were observed for the Shannon index. The microbial communities appeared to differ by cigarette and opium use as indicated by the MiRKAT models from the three beta diversity matrices. Four phylum level relative abundances were associated with cigarette and opium use, while the presence/absence of nine genera was associated with users of both cigarette and opium in the zero-inflated β regression models. The phylum Firmicutes and class Bacilla (Firmicutes) were significantly associated with opium only use, which showed marginally significant adjusted P values in users of both cigarettes and opium. No taxa were specifically associated with cigarette use only.
Conclusion: Cigarette and/or opium use were related to overall oral microbiome community composition and the presence/absence as well as relative abundance of multiple taxa. Further studies are needed to investigate the impact of the changes to the oral microbiome through cigarette and/or opium use on human health and disease status.
Citation Format: Zeni Wu. Cigarette smoking and opium use in relation to the oral microbiome in Iran [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 4666.
Abstract 47: Mutation in homologous recombination as a prognostic factor independent of TCGA molecular subtypes in endometrial cancer
Authors: Zhao Luyang , Dai Yibo , Hu Yuanjing , Wang Zhiqi , Li Chengcheng , Wang Guoqiang , Wang Jianliu 
Published: September 2020

Abstract
Background: Endometrial cancers have been categorized into four genomic classes by The Cancer Genome Atlas Research Network (TCGA) with comprehensive genomic analysis. However, TCGA molecular subtypes are hard to utilize in clinic as the expensive cost and a simply version of POLE, TP53 genes cannot fully differentiate the four subtypes. Therefore, more convenient and reliable biomarkers need to be identified for clinical practice.
Methods: Whole-exome sequencing and RNA sequencing data for 529 patients with endometrial carcinomas were downloaded from TCGA. Mutations in 62 genes of homologous recombination repair (HR) signaling were defined as HR mutation. Associations between HR mutation and survival and RNA expression were analyzed.
Results: HR mutation was associated with a prolonged disease specific survival (DSS) (HR, 0.47; 95% CI, 0.28-0.79; P &lt;0.05), progression-free survival (PFS) (HR, 0.50; 95% CI, 0.35-0.72; P &lt;0.05) and overall survival (OS) (HR, 0.48; 95% CI, 0.31-0.73; P &lt;0.05) in endometrial cancers. HR mutation was related with clinical characteristics including FIGO stage (P&lt;0.05), tumor grade (P&lt;0.05) and histological types (P&lt;0.05). HR mutation was enriched in MSI (hypermutated) group (49%) and copy-number low group (19.6%). In the multivariable cox proportional hazards regression model including FIGO 2008, histology types, tumor grade and TCGA subtypes, the association between HR mutation and PFS was still significant (HR, 0.22; 95% CI, 0.05-0.88; P = 0.03), which indicating the HR mutation is an independent prognostic factor for PFS. Gene set enrichment analysis suggested that HR mutation was involved with the increase of genes related to activated T cells, immune cytolytic activity, and IFN-γ release.
Conclusion: HR mutation was related with a favorable prognosis through increasing T cells signature. Identification of HR mutation by genomic profiling provides a potentially novel and convenient approach for endometrial cancer patients to predict the prognosis independent of TCGA four subtype classifications
Citation Format: Luyang Zhao, Yibo Dai, Yuanjing Hu, Zhiqi Wang, Chengcheng Li, Guoqiang Wang, Jianliu Wang. Mutation in homologous recombination as a prognostic factor independent of TCGA molecular subtypes in endometrial cancer [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 47.
Abstract 4708: Comprehensive analysis of 71 VHL germline deletions and rearrangements
Authors: Vocke Cathy D. , Ricketts Christopher J. , Schmidt Laura S. , Ball Mark W. , Peterson James , Middelton Lindsay A. , Linehan W Marston 
Published: September 2020

Abstract
An estimated 35% of von Hippel-Lindau (VHL) disease patients possess a gross germline deletion of one, two, or all three exons of VHL. In this study, 71 germline deletions have been extensively characterized, including 59 partial deletions (PD) and 12 complete VHL deletions (CD). VHL patients possessing germline VHL deletions were enrolled on an IRB-approved protocol. An Agilent custom high-definition comparative genomic hybridization array (aCGH) including 21 probes within the VHL gene at an average probe density of 2 probes per kb was used to map most VHL deletions; 4 patients were evaluated using CLIA-approved VHL deletion/duplication analysis. Primers were designed adjacent to the estimated deletion boundaries, and the breakpoints were mapped by Sanger bidirectional sequencing. Fifty eight deletions (55 PD and 3 CD) have been mapped to the exact breakpoint. Nearly all (55 of 58) deletions involve Alu repeats at both breakpoints. Several novel observations have been made in this cohort, including two cases that have complex rearrangements involving both deletion and inversion, two cases that have inserted extra Alu-like sequences, three cases that involve breakpoints in Alu repeats situated in opposite orientations, and a “hotspot” PD of exon 3 involving the same pair of Alu repeats that is observed in 12 families. In conclusion, this is the largest study to date of germline deletions in VHL patients. Deletions almost always involve Alu repeats, which are enriched in and near the VHL gene. In two cases, both a deletion and an inversion are observed, implying that it may be possible for an inversion to occur in the absence of deletion.
Citation Format: Cathy D. Vocke, Christopher J. Ricketts, Laura S. Schmidt, Mark W. Ball, James Peterson, Lindsay A. Middelton, W Marston Linehan. Comprehensive analysis of 71 VHL germline deletions and rearrangements [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 4708.
Abstract 4759: Nanoscale Huangjing extract from Mount Tai displays enzyme and biofuel enhancing activity: Potential in precision anti-cancer therapy
Authors: Kabulova Aigerim , Razbekova Madina , Xie Yingqiu , Dautov Adilet , Wang Qian , Fan Haiyan 
Published: September 2020

Abstract
Chinese herb Huangjing has been well-known for its anti-cancer characters in xenograft models of cancers and traditional Chinese herbal classical books. However, the mechanisms are largely unknown. The processed Huangjing has the pharmacological function but fresh forms may have toxicity. Mount Tai is famous for its traditional culture and Chinese medicine resources with special environmental and nutritional potential for enrichment of herbal chemical competent. Our study aimed to test phosphatase activity of nanoparticles produced in the process of herb and to identify whether its anti-cancer properties is related to the phosphatase activity. Phosphatase has been known for its function in dephosphorylating of many drug targets therein to inhibit cancer cell growth. We recently reported engineered nanoparticles were proved to exhibit phosphatase activity and here we further demonstrated that nanoscale Huangjing herb from Mount Tai showed positive results on a few phosphatase substrates. The corresponding substrate specificity and kinetics of the reaction including the substrate concentration, pH, and temperature dependence were studied in detail. In addition, using a Biorad Biofeul kit, Huangjing was observed to catalyze p-nitrophenyl glucopyranoside to p-nitrophenol reaction. Our data suggest that Huangjing may cleave the covalent bond between beta glucose and nitrophenol suggesting the biofuel-like activity. We then performed experiments to test the effectiveness of Huangjing at nanoscale for inhibiting growth of cancer cells wherein, the growth of MDA-MB-231 and PC3 cells was greatly inhibited while normal cells are planning for comparison and investigation in mechanisms. The study has a significance in developing potential novel nanoscale drugs with phosphatase-like activity for treatment of certain cancers with combination of targeted kinase inhibitors based therapy or as a drug delivery machinery. Our preliminary results suggest a kinase synergistic based signaling. Thus, our data provided the potential concept of the combination of traditional Chinese medicine with modern chemotherapy.
Citation Format: Aigerim Kabulova, Madina Razbekova, Yingqiu Xie, Adilet Dautov, Qian Wang, Haiyan Fan. Nanoscale Huangjing extract from Mount Tai displays enzyme and biofuel enhancing activity: Potential in precision anti-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 4759.