bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1248: Adult calorie restriction reduces weight gain and mammary tumor incidence in obesity prone MMTV-TFG α mice -
Authors: Grossmann Michael E. , Mizuno Nancy K. , Yang Da-Qing , Liao D. Joshua , Cleary Margot P. 
Published: July 2017

Abstract
Obesity is associated with increased risk of postmenopausal breast cancer resulting in recommendations for weight gain prevention and/or weight loss. However, there is little experimental data indicating if calorie restriction (CR) initiated in adulthood impacts mammary tumorigenesis. We have used female MMTV-TGF-α mice which develop mammary tumors in the 2nd yr of life as a model of postmenopausal breast cancer. From 10-30 weeks of age (woa) mice were fed a diet with 33% fat calories. At 30 woa based on body weight mice were classified as Obesity-Prone (Ob-Pr), Overweight (Ow) or Obesity-Resistant (Ob-R). Half in each weight category were then fed a 25% CR diet with reduced carbohydrate content (43% fat calories). The remaining mice continued on ad libitum (AL) feeding of the 33% fat diet. This resulted in six experimental groups (n = 26-31/group). Food intakes were monitored and body weights and mammary tumor status were determined weekly. Mice were sacrificed either at 90 woa or earlier if tumor size dictated. Mice in the CR-Ob-Pr group lost an average of 1.12 grams while mice in the AL-Ob-Pr group gained 16.03 grams from 30 woa until euthanasia. CR-Ob-Pr mice had a reduced palpable tumor incidence as compared to AL-Ob-Pr mice prior to euthanasia (12.90% versus 61.54% P = 0.0002). Indolent tumors were discovered at euthanasia with the CR-Ob-Pr mice having a larger number than AL-Ob-Pr mice resulting in final tumor positive mice in these groups of 54.84% vs 65.38%, respectively. Interestingly, the Ob-R mice had final tumor incidence of 38.71% and 73.08% for the CR-Ob-R vs the AL-Ob-R (P&lt;0.01). Average tumor weight was highest in the AL-Ob-Pr group with CR resulting in a significantly lower tumor weight (P&lt; 0.01). The AL-Ob-Pr group had the shortest average survival time of 82.96 woa while CR of the Ob-Pr mice resulted in increased survival to 89.77 woa (P &lt; 0.001). A comparison of the survival curves of these two groups showed that CR resulted in significantly increased survival (P &lt; 0.0001). Results of this study indicate that initiation of moderate 25% CR during adulthood reduces weight gain, mammary tumor incidence, and tumor weight as well as increases lifespan even when a moderately high fat diet was consumed. This information supports further efforts to be made to prevent weight gain as women approach menopause to delay or prevent breast cancer development. Support: NIH-CA157012, The Hormel Foundation and Paint the Town Pink.
Citation Format: Michael E. Grossmann, Nancy K. Mizuno, Da-Qing Yang, D. Joshua Liao, Margot P. Cleary. Adult calorie restriction reduces weight gain and mammary tumor incidence in obesity prone MMTV-TFG α mice - [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 1248. doi:10.1158/1538-7445.AM2017-1248
Abstract 1263: Andrographolide inhibits prostate cancer by suppressing cytokine involved in promoting epithelial to mesenchymal transition
Authors: Mir Hina , Kapur Neeraj , Sonpavde Guru , Singh Shailesh 
Published: July 2017

Abstract
Mesenchymal phenotypes are responsible for cancer progression and poor therapeutic response. Hence, approaches targeting mesenchymal phenotype or inhibiting epithelial to mesenchymal transition will significantly prevent cancer progression or improve therapeutic outcome. Using in vitro models and molecular approaches we have shown that Andrographolide (AG), a compound isolated from Andrographis paniculata, shows promising effect on mesenchymal cells. It disposes PCa cells towards epithelial phenotype by modulating E-cadherin, ZEB-1, SNAIL and TWIST. In addition to these, significant inhibition in IL-6, which is known to be a poor prognostic maker, was observed in PCa cells treated with AG compared to untreated cells. This reduction in IL-6 could be due to AG induced suppression of SOCS (Suppressor of cytokine signaling) molecules. Therefore, our data underscores the ability of AG to impede cancer growth by impacting EMT and rationalizes its application as a potent therapeutic agent.
Citation Format: Hina Mir, Neeraj Kapur, Guru Sonpavde, Shailesh Singh. Andrographolide inhibits prostate cancer by suppressing cytokine involved in promoting epithelial to mesenchymal transition [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 1263. doi:10.1158/1538-7445.AM2017-1263
Abstract 1267: Emodin exerts its anticancer effect on colon cancer cells by inhibiting proliferation and inducing apoptosis
Authors: Saunders Ian T. , Mir Hina , Kapur Neeraj , Singh Shailesh 
Published: July 2017

Abstract
Despite state of the art diagnostic and therapeutic options offered in the clinics, colon cancer is still a major health care concern. Therapeutic outcome is often compromised due to late diagnosis and development of resistance against treatment options used to treat advanced disease. Hence, the need to explore new avenue to treat/prevent colon cancer more effectively still exist. In this study we have investigated potential impact of Emodin, an anthraquinone derived from plant (Rheum rhabarbarum) on colon cancer cell proliferation, survival and apoptosis. Our data show that emodin reduces the cell viability and inhibits proliferation of human colon cancer cell (COLO-201 and DLD-1) in a time-dependent manner. Furthermore, FACS analysis show higher percentage of apoptotic cells with Emodin treatment compared to untreated cells. Interestingly, pro-inflammatory and anti-inflammatory cytokines produced by colon cancer cells were modulated with Emodin treatment. Cancer cells often use these cytokines to achieve their goal to progress and escape the treatment. Our data implies Emodin could be a promising agent that could be used for chemoprevention as well as in therapeutic combination to improve efficacy of conventional therapy.
Citation Format: Ian T. Saunders, Hina Mir, Neeraj Kapur, Shailesh Singh. Emodin exerts its anticancer effect on colon cancer cells by inhibiting proliferation and inducing apoptosis [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 1267. doi:10.1158/1538-7445.AM2017-1267
Abstract 1282: Analysis of missense variants in BRCA1 BRCT domains
Authors: Pietro Giuliano Di , Fernandes Vanessa Camara , Amankwah Kwabena , Shields Cara , Golubeva Volha A. , Harro Carly , Carvalho Marcelo Alex , Monteiro Alvaro N. 
Published: July 2017

Abstract
Currently, only ~¼ (133/600) of documented single nucleotide variation leading to missense changes in the BRCA1 gene have been characterized as pathogenic or non-pathogenic (IARC Classes 4 & 5 and 1 & 2, respectively) posing a challenge for carriers of these variants. A detailed understanding of structure-function relationships is critical for the assessment of these variants in the interpretation of data from functional assay and for the development of functional impact predictors. Thus, we have systematically probed the C-terminus of BRCA1 including the N-terminal border of the BRCT domains (M1650, S1651), the BRCT linker region (G1738, D1739, V1740, G1743, H1746, G1748, P1749, R1753, and D1757), and the alpha 1 and alpha’1 helices in BRCT[N] and [C], respectively. We assessed the functional impact of 47 missense variants using a validated transcriptional assay by a protein fusion of the GAL4 DNA-binding domain to BRCA1 C-terminus (aa 1,396-1,863) in HEK 293FT cells. Analysis of functional data redefined the BRCT border (previously thought to be at S1651) at residue M1650. Overall, mutations in the BRCT linker had severe impact on the function. Mutations in the alpha1 and alpha’1 helices also tended to display impaired function despite the lack of functional impact of 16 out of the 17 variants previously analyzed. In summary, our study provides increased granularity in our understanding of BRCA1 regions less tolerant to changes and therefore more likely to contain pathogenic variants. This knowledge will be critical for the assignment of different prior probabilities of pathogenicity given the variant location, improving risk assessment and clinical management of carriers of BRCA1 missense alleles
Note: This abstract was not presented at the meeting.
Citation Format: Giuliano Di Pietro, Vanessa Camara Fernandes, Kwabena Amankwah, Cara Shields, Volha A. Golubeva, Carly Harro, Marcelo Alex Carvalho, Alvaro N. Monteiro. Analysis of missense variants in BRCA1 BRCT domains [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 1282. doi:10.1158/1538-7445.AM2017-1282
Abstract 1283: Mutations in the Duffy Antigen Receptor for Chemokines (DARC/ACKR1) gene result in population-private variants
Authors: Martini Rachel , Jenkins Brittany , Davis Melissa 
Published: July 2017

Abstract
By studying the breast cancer microenvironment, we can specifically address novel aspects of cancer development and progression at the molecular level. Chemokines are small signaling molecules that are an important component of this microenvironment, as they shape cellular composition of this space through recruitment of immune cells, among other functions. DARC, the Duffy Antigen Receptor for Chemokines, is an atypical chemokine receptor (ACKR1) that can bind different classes of chemokines. It is a non-signaling receptor that mainly acts as a regulator of chemokine homeostasis by removing them from circulation to recruit appropriate immune cell types. The purpose of this study is to determine how population-private variants of the DARC/ACKR1 gene across global population render distinct function and define aspects of human diversity in immune responses. A well-studied example of this would be the Duffy-null allele. This allele carries a mutation that is population-specific to recent decedents of Sub-Saharan Africans, and removes expression of DARC on red blood cells. Loss of expression on red blood cells presumably causes these “Duffy-Null” individuals to lose the ability to sequester chemokines, therefore losing homeostatic balance of these molecules in circulation. To identify additional mutations, we completed in silico analysis of minor allele frequencies across the gene in the 1000 Genomes Project data, and identified several other putative functional mutations that likely result in additional gene variants, specific to geographic ancestry groups and likely under similar selection as the Duffy null allele. We have prioritized our initial functional study to include mutations in the regulatory regions of the gene, as these mutations can change how and where the gene is expressed. Future work is focused on investigating these functional variants in situ, using human tissue and human breast cell lines, by isolating and re-engineering ancestry-specific variants in these cell lines. By identifying and determining functional outcomes of these population-specific mutation, we can observe differences in immune responses across these global populations, further defining the role that DARC/ACKR1 plays in the breast tumor microenvironment.
Citation Format: Rachel Martini, Brittany Jenkins, Melissa Davis. Mutations in the Duffy Antigen Receptor for Chemokines (DARC/ACKR1) gene result in population-private variants [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 1283. doi:10.1158/1538-7445.AM2017-1283
Abstract 1285: Analysis of esophageal cancer SNPs and gene expression to predict ESCC risk
Authors: Ding Lilly A. , Ding Molly P. , Song Xin , Wang Lidong , Wang Liang 
Published: July 2017

Abstract
Esophageal cancer is one of most common cancers worldwide and its incidence has increased rapidly over the past decades. The majority of esophageal cancers is the esophageal squamous cell carcinoma (ESCC), which is particularly prevalent in Asian and South African areas. Most cases of ESCC are diagnosed at advanced stages, with an overall 5-year survival rate of 10–20%. Currently, genome-wide association studies (GWAS) are used to identify high risk individuals for the development of ESCC. Many SNPs have been identified to associate with a risk of ESCC. However, the effect size attributable to individual SNPs was typically modest, suggesting that genetic variants may only account for a very small amount of genetic risk and heritability of ESCC. The combined effect of multi genetic variants with altered mRNA expression play critical roles in ESCC. In this study, we used several existing bioinformatics databases (HaploReg, GTEx Portal and cBio Portal). We first selected 450 potential ESCC risk SNPs from HaploReg and then defined which SNPs caused gene expression alterations in the esophagus through expression quantitative trait loci (eQTL). Nine SNPs in eight genes (MUC1, ALS2CR12, ADHB1, TMEM173, XBP1, PLCE1, HEATR3 and SMG6) were identified as having altered mRNA expression. The altered mRNA expression of these seventeen genes are: MUC1, THBS3, GBAP1, EFNA1, SCAMP3, CASP8, CASP10, ALS2CR12, STRADB, ADH4, TMEM173, CYCTM1, DNAJC18, DNAJC20, NOC3L, HEATR3 and SRR. These altered gene expressions in the mucosal layer of the esophagus metabolize enzymes, repair DNA, and prevent cell death and inflammation, all of which may indicate that the existing altered esophageal mRNA levels plus the predisposition of normal esophageal epithelial cells can lead to harmful environmental carcinogens, thus attributing to ESCC development. In order to validate these gene alterations related to ESCC SNPs in screening and early detection of high risk individuals, DNA genotyping of this group of SNPs with a prospective cohort (n=5451) in a high risk area of ESCC will be tested in future studies.
Citation Format: Lilly A. Ding, Molly P. Ding, Xin Song, Lidong Wang, Liang Wang. Analysis of esophageal cancer SNPs and gene expression to predict ESCC risk [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 1285. doi:10.1158/1538-7445.AM2017-1285
Abstract 130: Discovery and characterization of small molecules targeting the DNA-binding ETS domain of ERG in prostate cancer
Authors: Butler Miriam S. , Roshan-Moniri Mani , Hsing Michael , Lau Desmond , Kim Ari , Yen Paul , Mroczek Marta , Nouri Mannan , Lien Scott , Axerio-Cilies Peter , Dalal Kush , Yau Clement , Ghaidi Fariba , Guo Yubin , Yamazaki Takeshi , Lawn Sam , Gleave Martin , Gregory-Evans Cheryl Y. , McIntosh Lawrence P. , Rennie Paul S. , Cherkasov Artem , Cox Michael E. 
Published: July 2017

Abstract
Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half of prostate cancer cases. These alterations result in aberrant, androgen-regulated production of ERG protein variants that directly contribute to disease development and progression. This study describes the discovery and characterization of a new class of small molecule ERG antagonists identified through rational in silico methods. These antagonists are designed to sterically block DNA binding by the ETS domain of ERG and thereby disrupt transcriptional activity. We confirmed the direct binding of a lead compound, VPC-18005, with the ERG-ETS domain using biophysical approaches. We then demonstrated VPC-18005 reduced migration and invasion rates of ERG expressing prostate cancer cells, and reduced metastasis in a zebrafish xenograft model. These results demonstrate proof-of-principal that small molecule targeting of the ERG ETS domain can suppress transcriptional activity and reverse transformed characteristics of prostate cancers aberrantly expressing ERG. Clinical advancement of the developed small molecule inhibitors may provide new therapeutic agents for use as alternatives to, or in combination with, current therapies for men with ERG-expressing metastatic castration-resistant prostate cancer.
Citation Format: Miriam S. Butler, Mani Roshan-Moniri, Michael Hsing, Desmond Lau, Ari Kim, Paul Yen, Marta Mroczek, Mannan Nouri, Scott Lien, Peter Axerio-Cilies, Kush Dalal, Clement Yau, Fariba Ghaidi, Yubin Guo, Takeshi Yamazaki, Sam Lawn, Martin Gleave, Cheryl Y. Gregory-Evans, Lawrence P. McIntosh, Paul S. Rennie, Artem Cherkasov, Michael E. Cox. Discovery and characterization of small molecules targeting the DNA-binding ETS domain of ERG in prostate 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 130. doi:10.1158/1538-7445.AM2017-130
Abstract 1309: Association between insulin resistance and breast cancer risk: A Mendelian randomization analysis of data from 228,000 women of European descent
Authors: Shu Xiang , Wu Lang , Khankari Nikhil K. , Michailidou Kyriaki , Bolla Manjeet K. , Wang Jean , Dennis Joe , Shu Xiao-ou , Simard Jacques , Easton Douglas F. , Zheng Wei 
Published: July 2017

Abstract
Background: Epidemiologic studies suggest that insulin resistance may be associated with breast cancer risk. We conducted Mendelian randomization (MR) analyses to reduce the biases associated with previous studies and provide evidence for causal inference.
Materials and Methods: We used genetic variants identified in genome-wide association studies for circulating fasting insulin (15 variants), early insulin secretion (16 variants), fasting proinsulin (8 variants), fasting glucose (35 variants), and 2-hour glucose (8 variants) as instruments in MR analyses. To reduce possible pleiotropic effects, variants associated with obesity were removed from the instruments. We first evaluated the association of these instruments with type 2 diabetes risk in 110,452 subjects to assess instrument validity. We then investigated the association of these instruments with breast cancer risk using data obtained from 122,977 cases and 105,974 controls of European descent included in the Breast Cancer Association Consortium (BCAC). Odds ratios (OR) were calculated to measure the associations of instrumental variables with risk of overall breast cancer and its subtypes defined by estrogen-receptor [ER] status.
Results: All instrumental variables constructed for this study were strongly associated with type 2 diabetes risk with ORs of 3.01 (p=7.86x10-5), 0.22 (p=3.54x10-14), 1.90 (p=8.28x10-4), 6.11 (p=3.59x10-19), and 1.91 (p=6.8x10-16) for per unit increase of fasting insulin, early insulin secretion, fasting proinsulin, fasting glucose, and 2-hour glucose levels, respectively. Statistically significant associations with overall breast cancer risk were found for fasting insulin (OR=1.36 for per unit increase, 95% CI=1.09-1.70, p=0.011) and fasting proinsulin (OR=1.21, 95% CI=1.06-
1.38, p=0.011). These associations were observed only for ER-positive breast cancer. No statistically significant association at p&lt;0.05 was found for early insulin secretion, fasting glucose, or 2-hour glucose levels.
Conclusions: Our study provides strong support that certain insulin resistance traits may be causally associated with risk of breast cancer, particularly ER-positive breast cancer.
Citation Format: Xiang Shu, Lang Wu, Nikhil K. Khankari, Kyriaki Michailidou, Manjeet K. Bolla, Jean Wang, Joe Dennis, Xiao-ou Shu, Jacques Simard, Douglas F. Easton, Wei Zheng. Association between insulin resistance and breast cancer risk: A Mendelian randomization analysis of data from 228,000 women of European descent [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 1309. doi:10.1158/1538-7445.AM2017-1309
Abstract 1313: Characterization of germline susceptibility to male breast cancer
Authors: Perrakis Eleni , Maguire Sarah , Tomczyk Katarzyna , Swerdlow Anthony , Orr Nick 
Published: July 2017

Abstract
Male breast cancer (MBC) accounts for approximately 1% of all breast cancer cases. Family history is an established risk factor for MBC and 10% of cases have germline BRCA2 mutations. We recently demonstrated that common germline polymorphisms contribute to MBC predisposition and that there is overlap between genetic susceptibility loci for MBC and female breast cancer (FBC).
Here we report a comprehensive evaluation of all 107 known FBC predisposition loci in an association analysis of 1,032 MBC cases and 2,795 population matched controls. A total of 21 FBC predisposition single nucleotide polymorphisms (SNPs) showed evidence of association with risk of MBC. For approximately a third of these SNPs, the risk estimates were significantly larger in MBC than FBC. The magnitude of effects observed suggest that common susceptibility variants may be of value for risk stratification in men who have a high absolute risk of breast cancer such as BRCA2 mutation carriers. Although our data suggests that MBC predisposition shares many features in common with FBC, there are striking differences. Surprisingly, given the predominance of hormone receptor positive tumors in MBC, we observed no evidence of association between SNPs at FGFR2 and MBC risk suggesting that the estrogen receptor status of MBC tumors does not explain the observed SNP associations.
In summary, the data presented in this abstract significantly advance our understanding of genetic factors that contribute to MBC predisposition and further underscore the growing consensus that male breast cancer is not simply analogous to hormone receptor positive female breast cancer.
Citation Format: Eleni Perrakis, Sarah Maguire, Katarzyna Tomczyk, Anthony Swerdlow, Nick Orr. Characterization of germline susceptibility to male 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 1313. doi:10.1158/1538-7445.AM2017-1313