bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 327: Targeting autophagy overcomes enzalutamide resistance in castrate-resistant prostate cancer cells and improves therapeutic response in a xenograft model
Authors: Yang Joy C. , Nguyen Hao G. , Kung Hsing-Jien , Shi Xu-Bao , Tilki Derya , White Ralph W. deVere , Gao Allen C. , Evans Christopher P. 
Published: May 2015

Abstract
Androgen deprivation or treatment with the androgen receptor signaling inhibitor (ARSI), Enzalutamide (MDV-3100, ENZA) or biclutamide induces autophagy in androgen-dependent and castration resistant CaP (CRPC) cell lines. This autophagic process is mediated by AMPK activation and the suppression of mTOR through Raptor phosphorylation (Serine 792). Using autophagy modulators such as clomipramine (CMI) or metformin in combination with ENZA drastically reduces the cell survival in the colony formation assay. Metformin in combination with ENZA causes AR degradation, which is inhibited by proteasome inhibitor MG132. Transcriptome deep sequencing of parental and ENZA resistant C4-2B cells was carried out to examine differential gene expression pattern that may be related to their ability to survive under constant high exposure to ARSI. In-vivo studies with mice orthotopically implanted with ENZA resistant cells demonstrates that the combination of ENZA and autophagy modulators, CMI or metformin significantly reduces tumor growth when compared to control groups (p&lt;0.005). Blocking autophagy pharmacologically or genetically significantly impairs prostate cancer cell survival in- vitro and in-vivo, implying the therapeutics potential of autophagy inhibitors in the antiandrogen resistance setting.This work is supported in part by Stand Up To Cancer - Prostate Cancer Foundation–Prostate Dream Team Translational Cancer Research Grant. This research grant is made possible by the generous support of the Movember Foundation. Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research.
Citation Format: Joy C. Yang, Hao G. Nguyen, Hsing-Jien Kung, Xu-Bao Shi, Derya Tilki, Ralph W. deVere White, Allen C. Gao, Christopher P. Evans. Targeting autophagy overcomes enzalutamide resistance in castrate-resistant prostate cancer cells and improves therapeutic response in a xenograft model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 327. doi:10.1158/1538-7445.AM2014-327
Abstract 3271: The association between germline genetic variants in the PI3K-AKT-mTOR pathway and breast cancer disease free survival
Authors: Pande Mala , Bondy Melissa , Do Kim-Anh , Sahin Aysegul A. , Ying Jun , Mills Gordon B. , Thompson Patricia , Brewster Abenaa 
Published: May 2015

Abstract
Background: PI3K-AKT-mTOR pathway activation in breast tumors is associated with poorer breast cancer disease-free survival and decreased responsiveness to tamoxifen and trastuzumab. However, the role of germline variation in this pathway and breast cancer outcomes has not been previously evaluated. We hypothesized that single nucleotide polymorphisms (SNPs) in candidate genes affecting the PI3K-AKT-mTOR signaling pathway may act as genetic modifiers of breast cancer specific outcomes in patients diagnosed with early stage disease.
Methods: We genotyped 106 SNPs in 13 genes (ADIPOQ, IGF1, INS, IRS1, LEP, LEPR, LEPROT, PIK3CA, PIK3R5, PTEN, TSC1, TSC2, and AKT1) in the P13K-AKT-mTOR pathway in a sample of 1020 women with stages I-II breast cancer treated at the MD Anderson Cancer Center between 1985 and 1999 and for whom long term follow-up on recurrence and death were available. The relationship between SNPs and breast cancer disease free survival (DFS) was assessed using Cox regression analysis. After correcting for false discovery rate (0.10) SNPs significantly associated with DFS in any genetic model (additive, dominant or recessive) were included in multivariable analysis.
Results: After adjusting for race, age at diagnosis, tumor stage and treatment, rs1063539 in ADIPOQ (Hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.19 - 0.86), rs11585329 in LEPROT (HR 0.72, 95% CI 0.53 - 0.98), and rs2519757 in TSC1 (HR 0.29, 95% CI 0.09 - 0.91) were associated with improved DFS and rs1520220 in IGF1 (HR 1.56, 95% CI 1.21 - 2.00) and rs2677760 in PIK3CA (HR 1.43, 95% CI 1.70 - 1.92) were associated with worse DFS. The associations were not modified by type of systemic treatment received. The SNPs were not associated with tumor characteristics such as tumor size, lymph node status, nuclear grade, or hormone receptor status.
Conclusion: In this study, germline allelic variation inthe PI3K-AKT-mTOR pathway appears to modify breast cancer patient outcomes. Future studies are needed to replicate our results and to evaluate the relationship between these polymorphisms and activation of the PI3K-AKT-mTOR pathway in breast tumors.
Citation Format: Mala Pande, Melissa Bondy, Kim-Anh Do, Aysegul A. Sahin, Jun Ying, Gordon B. Mills, Patricia Thompson, Abenaa Brewster. The association between germline genetic variants in the PI3K-AKT-mTOR pathway and breast cancer disease free survival. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3271. doi:10.1158/1538-7445.AM2014-3271
Abstract 3274: SNP-SNP interaction analyses of NQO1 and NF-κB signaling pathway genes on breast cancer survival and treatment outcome
Authors: Jamshidi Maral , Fagerholm Rainer , Khan Sofia , Aittomäki Kristiina , Blomqvist Carl , Schmidt Marjanka K. , Nevanlinna Heli ,   BCAC: Breast Cancer Association Consortium
Published: May 2015

Abstract
To improve individualized therapy, new prognostic and predictive markers are needed to identify patients with expected poor breast cancer outcome and patients who profit most from a given treatment. NF-κB pathway plays a pervasive role in the pathogenesis of cancer through its implication in distinct hallmarks of tumorigenesis. Previous studies have indicated the role of NF-κB transcription factor in promoting cell survival and resistance to chemotherapy in breast carcinoma. We have previously found that NQO1-rs1800566 predicts poor survival among breast cancer patients, particularly after anthracycline-based adjuvant chemotherapy and in patients with p53-aberrant tumors. We have also reported the inverse relationship between NQO1 protein expression and NF-κB activation. We have here analyzed the interaction of SNPs residing within the NF-κB signaling pathway genes, and NQO1-rs6499255 (tagging NQO1-rs1800566 with r2&gt; 0.90) on breast cancer patient survival and treatment outcome. The panel of markers included the NF-κB pathway SNPs available in a custom Illumina iSelect genotyping array designed for Collaborative Oncological Gene-Environment Study (iCOGS) as well as NQO1-rs6499255. For the SNP-SNP interaction analysis on patient survival we conducted a likelihood ratio test that compares Cox's regression model with and without an interaction term to evaluate whether the interaction model is a better fit for the prognostic data. The results obtained from this study will be reported. Identification of interactive SNPs/genes contribute to the elucidation of the mechanisms underlying complex diseases such as breast cancer.
Citation Format: Maral Jamshidi, Rainer Fagerholm, Sofia Khan, Kristiina Aittomäki, Carl Blomqvist, Marjanka K. Schmidt, Heli Nevanlinna, BCAC: Breast Cancer Association Consortium. SNP-SNP interaction analyses of NQO1 and NF-κB signaling pathway genes on breast cancer survival and treatment outcome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3274. doi:10.1158/1538-7445.AM2014-3274
Abstract 3275: Genome-wide association study of childhood body fatness as a risk factor of breast cancer
Authors: Lindstrom Sara , Li Jingmei , Huang Hongyan , Chen Constance , Hunter David J. , Hall Per , Kraft Peter , Tamimi Rulla 
Published: May 2015

Abstract
Girls with large body size have a 15-30% reduced risk of developing breast cancer independent of both birth weight and adult body mass index (BMI). The mechanisms underlying this association are poorly understood, especially since large body size at young age is correlated with earlier pubertal timing, a known risk factor for breast cancer. Self-reported childhood body size, a phenotype which is described in the literature as “childhood body fatness”, has an estimated heritability of 70-80% compared to 40-70% for adult BMI and the correlation between childhood body fatness and adult BMI is only modest (r=0.24-0.30). Still, the literature on genetic associations in pediatric body size-related phenotypes is very sparse.
We conducted a genome-wide association study (GWAS) of childhood body fatness in 10,560 individuals within the Nurses’ Health Study (NHS) and the Health Professional Follow-up Study (HPFS). All subjects were imputed using the 1000 Genomes Phase I v3 reference panel. Analysis was adjusted for top principal components and study/gender. We observed three regions with p&lt;10-7. Two of the regions (TNNI3K and BCDIN3D) have previously been identified as associated with BMI, the former in adolescents. The third region (1p35.2, p=4.8x10-8) constitutes a potential novel locus associated with childhood body fatness. Five additional regions (4 novel) showed suggestive association with childhood body fatness (p&lt;10-6). We are currently replicating these new regions in additional 9,800 subjects from NHS, HPFS and SASBAC, a Swedish breast cancer case-control study. We will also assess the association between identified loci and breast cancer risk. Such analysis will help elucidate the shared genetic component between childhood body fatness and breast cancer and increase our understanding to why early life fatness decreases breast cancer risk.
Citation Format: Sara Lindstrom, Jingmei Li, Hongyan Huang, Constance Chen, David J. Hunter, Per Hall, Peter Kraft, Rulla Tamimi. Genome-wide association study of childhood body fatness as a risk factor of breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3275. doi:10.1158/1538-7445.AM2014-3275
Abstract 3276: Identifying cross-phenotype inflammatory effects in cancer
Authors: Aquino-Michaels Keston , Trubetskoy Vasya , Im Hae Kyung , Cox Nancy 
Published: May 2015

Abstract
Through genome-wide association studies we now better understand many of the genetic factors contributing to cancer. However, the overlap between cancer associated loci and inflammation associated loci remains poorly understood. Inflammation has long been considered the underlying basis to several complex traits and plays well-established roles in elevating risk to various cancer types. In fact, genome-wide association studies have identified loci associated with inflammatory biomarkers and risk of cancer. Therefore we sought to test cross-phenotype genetic effects between cancer and inflammation biomarkers. While genome-wide significant loci on their own typically account for very little of the measured narrow-sense heritability, polygenic approaches show greater promise to account for the missing heritability of complex traits. Therefore we built polygenic signatures from inflammatory biomarker genome-wide association studies. Preliminary analysis of a case control pancreatic cancer dataset (304 cases/1425 controls) where we applied seven inflammatory signatures indicates that polygenic scores built from IL-10 and C-reactive protein (CRP) are significant predictors of case control status. Importantly the directions of effect for IL-10 and CRP are consistent with the canonical roles of these proteins. We extended this approach to a breast cancer dataset (1082 cases/1086 controls) where we found that polygenic scores built from CRP are significant predictors of case control status. In both the pancreatic and breast cancer datasets CRP polygenic scores decrease risk of case status. This approach will not only inform us of the cancers with overlapping inflammatory effects, but also allow us to identify the components of the immune system that mediate cancer risk. Ultimately this understanding may lead to the use of anti-inflammatory medication for individuals at risk for a particular cancer. Therefore this research addresses cancer prevention by studying the inflammatory genetic component to risk.
Citation Format: Keston Aquino-Michaels, Vasya Trubetskoy, Hae Kyung Im, Nancy Cox. Identifying cross-phenotype inflammatory effects in cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3276. doi:10.1158/1538-7445.AM2014-3276
Abstract 328: Novel quantitative autophagy analysis by organelle flow cytometry after cell sonication
Authors: Degtyarev Michael , Reichelt Mike , Lin Kui 
Published: May 2015

Abstract
Autophagy is a dynamic process of bulk degradation of cellular proteins and organelles in lysosomes. Current methods of autophagy measurement include microscopy-based counting of autophagic vacuoles (AVs) in cells. We have developed a novel method to quantitatively analyze individual AVs using flow cytometry. This method, OFACS (organelle flow after cell sonication), takes advantage of efficient cell disruption with a brief sonication, generating cell homogenates with fluorescently labeled AVs that retain their integrity as confirmed with light and electron microscopy analysis. These AVs could be detected directly in the sonicated cell homogenates on a flow cytometer as a distinct population of expected organelle size on a cytometry plot. Treatment of cells with inhibitors of autophagic flux, such as chloroquine or lysosomal protease inhibitors, increased the number of particles in this population under autophagy inducing conditions, while inhibition of autophagy induction with 3-methyladenine or knockdown of ATG proteins prevented this accumulation. This assay can be easily performed in a high-throughput format and opens up previously unexplored avenues for autophagy analysis.
Citation Format: Michael Degtyarev, Mike Reichelt, Kui Lin. Novel quantitative autophagy analysis by organelle flow cytometry after cell sonication. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 328. doi:10.1158/1538-7445.AM2014-328
Abstract 3284: Genome-wide association study identifies new susceptibility loci of epithelial ovarian cancer in Han Chinese
Authors: Li Lian , Chen Kexin , Zang Rongyu , Hao Quen , Hu Zhibin , Lin Dongxin , Ma Ding , Jia Weihua , Shen Hongbing , Wei Qingyi 
Published: May 2015

Abstract
Ovarian cancer is the leading cause of cancer death of gynecological malignancies in the world. To identify risk genetic variants for epithelial ovarian cancer (EOC), we performed a three-stage genome-wide association study (GWAS) in Han Chinese women. We scanned 900,015 single nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls of Chinese women. Forty-one promising SNPs were selected for replication in an independent sample set of 960 EOC cases and 1,799 controls of Chinese women. We further evaluated four significant loci in an additional replication population (492 EOC cases and 1,004 controls of Chinese women) and finally identified two new susceptibility loci at 9q22.33 (rs1413299 in COL15A1, Pmeta = 1.88 × 10-8) and 10p11.21 (rs1192691 near ANKRD30A, Pmeta = 2.62 × 10-8). In addition, two other loci at 12q14.2 (rs11175194 in SRGAP1, Pmeta = 1.14 × 10-7) and 9q34.2 (rs633862 near ABO and SURF6, Pmeta = 8.57 × 10-7) were consistently replicated (P&lt;0.05 in all three stages). These results advance our understanding of the genetic susceptibility to EOC in Han Chinese.
Citation Format: Lian Li, Kexin Chen, Rongyu Zang, Quen Hao, Zhibin Hu, Dongxin Lin, Ding Ma, Weihua Jia, Hongbing Shen, Qingyi Wei. Genome-wide association study identifies new susceptibility loci of epithelial ovarian cancer in Han Chinese. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3284. doi:10.1158/1538-7445.AM2014-3284
Abstract 3287: Mutational analysis of serous ovarian cancer using Ion Torrent sequencing
Authors: Masghati Salome , Dorigo Oliver , Santisvkulvong Chintda 
Published: May 2015

Abstract
Ovarian cancer is a biologically diverse tumor with heterogeneous molecular subtypes. Genetic mutations in various oncogenes have been previously identified in high grade serous ovarian cancer, including RB1, CDK12, BRAF, PI3KCA, and KRAS. To further investigate genetic variants, we screened 104 high grade serous ovarian cancer specimens for 2.855 hotspot regions of 50 oncogenes and tumor suppressor genes using the Ion AmpliSeq™ Cancer Hotspot Panel. The panel contains 207 primer pairs in a single tube, using only 10ng of DNA to allow sequencing. Data analysis was performed via Ion Torrent software version 3.0, Nextgene software version 2.3.2, Excel and Medcalc.
Our analysis resulted in the detection of 240 mutation variants. The most frequent mutation variants detected were in PDGFRA (91.35%), FGFR3 (90.38%), APC (86.54%), RET (82.69%), EGFR (74.04%), and TP53 (52.88%). When only COSMIC hotspot mutations were analyzed, genes with frequent mutations were APC (COSM19349; 91.35%),
KDR (COSM149673; 56.7%), PDGFRA (COSM22413; 36.5%), KIT (COSM28026; 19.23%) and TP53 (COSM10704; 7.69%). The COSM19349 APC hot spot mutation results in a frameshift and has been described in colorectal cancer. The hotspot PDGFRA mutation (COSM22413) is a silent mutation that has been previously reported in gastrointestinal stromal tumors, gliomas and endometrial carcinoma. KDR (COSM149673) is a missense mutation that has been found in stomach cancer. KIT (COSM28026) is a missense mutation that has been confirmed as a somatic mutation in chordomas, hematologic malignancies and Merkel cell carcinoma. The TP53 (COSM10704) hotspot mutation has been found in many different tissues, including serous ovarian cancer, breast cancer and GI tract malignancies.
We used the dbNSFP database (database for nonsynonymous SNPs' functional predictions) via Nextgene for functional prediction analysis using six algorithms (PolyPhen, SIFT, Mutation Taster, LRT and 1000 Genomes). Among the most frequent hotspot mutations, TP53 (COSM10704) was found to be ‘damaging’ via all prediction tools.
KIT (COSM28026) was found to be ‘possibly damaging’ via PolyPhen.
In summary, Ion Torrent sequencing revealed mutation variants in serous ovarian cancer that have not been previously identified. Further studies will be needed to analyze the functional and clinical importance of these variants.
Citation Format: Salome Masghati, Oliver Dorigo, Chintda Santisvkulvong. Mutational analysis of serous ovarian cancer using Ion Torrent sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3287. doi:10.1158/1538-7445.AM2014-3287
Abstract 3290: Glucose-regulated protein 58 modulates β-catenin protein stability in cervical adenocarcinoma
Authors: Liao Chia-Jung , Lin Syuan-ling , Wang Tzu-Hao , Lin Kwang-Huei 
Published: May 2015

Abstract
Cervical cancer is still a serious problem threatening to women health worldwide. The incidence of cervical adenocarcinoma (AD) is rising in more developed countries. Previously we have identified that glucose-regulated protein 58 (Grp58) serves as a poor independent prognostic factor for cervical AD. The molecular mechanism underlying Grp58 involved cervical AD carcinogenesis is unknown. The DNA microarray and enrichment analysis were used to identify pathway maps perturbed by knockdown of Grp58 expression. The WNT singling map is one of the significant enriched pathways. The β-catenin, vital effector of WNT signaling, was stably accumulated in Grp58 knockdown stable cells. A membrane fashion of β-catenin was observed in Grp58 knockdown but not control cells. By using transwell assay, we have demonstrated that accumulation of β-catenin, which was induced by Grp58 knockdown or lithium chloride treatment, inhibited the migration ability of HeLa cell. Furthermore, an exclusive expression pattern of Grp58 and β-catenin was observed in cervix tissues. In sum, we have demonstrated that β-catenin stability is negatively regulated by Grp58. Overpression of Grp58 might result in lost or decreased of membranous β-catenin in cervical cancer to promote cancer progression.
Citation Format: Chia-Jung Liao, Syuan-ling Lin, Tzu-Hao Wang, Kwang-Huei Lin. Glucose-regulated protein 58 modulates β-catenin protein stability in cervical adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3290. doi:10.1158/1538-7445.AM2014-3290
Abstract 3292: Epsin promotes breast cancer progression and metastasis by controlling nf-κb activation
Authors: Cai Xiaofeng , Chen Hong 
Published: May 2015

Abstract
Epsins are a family of endocytic clathrin adaptors. We have previously reported that epsin deficiency inhibits tumor growth by enhancing VEGF signaling in vascular endothelial cells. However, the pattern of tumor-intrinsic expression of epsin and its influence on cancer growth and metastasis is still unclear. Here, we demonstrate that epsin is upregulated in human cancers, including breast cancer, where its high expression correlates with poor relapse-free survival. Epsin promotes cell proliferation and invasion in vitro, and breast tumorigenesis and metastasis in vivo. Mechanistically, epsin interacts with and stabilizes TNFR1 signaling complex in breast cancer cells and enhances NF-κB signaling. Our findings suggest an important role of epsin in contributing to breast cancer progression and metastasis.
Citation Format: Xiaofeng Cai, Hong Chen. Epsin promotes breast cancer progression and metastasis by controlling nf-κb activation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3292. doi:10.1158/1538-7445.AM2014-3292