bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1298: The role of nuclear factor kappa B in survival of human papillomavirus-positive head and neck cancer cell lines.
Authors: Zhang Hongzheng , Hu Zhongliang , Jiang Ning , Marullo Rossella , Doetsch Paul W. , Hunt William D. , Chen Georgia Z. , Shin Dong M. 
Published: August 2014

Abstract
Nuclear factor kappa B (NFκB) has been implicated in the development of head and neck squamous cell carcinoma (HNSCC) from premalignant changes to tumor progression, and in treatment resistance and recurrence. However, the roles of NFκB in the sensitivity to chemoradiation of human papillomavirus (HPV)-associated HNSCC have not been well defined. Previously we reported that high expression of NFκB detected by immunohistochemistry in pretreated HPV+ oropharyngeal cancer patients was significantly associated with poor progression free survival (AACR 2012 Abstract #4489). Therefore, we hypothesized that NFκB could play a role in pro-survival in HPV+ head and neck cancer cells. We first examined the sensitivity of five HPV+ head and neck cancer cell lines (HPV16: UDSCC2, 93-VU-147T, UM-SCC47, UPCI:SCC90, HPV18: SCC1483) to radiation and cisplatin, Consistent with current models, when we knocked down expression of the HPV16E6 oncogene, SCC47 and SCC1483 cells with restored expression of p53 displayed a significant reduction in S phase entry as revealed by cell cycle analysis (SCC47: scrambled control 14.08% ± 0.55% versus siRNA-E6 6.39% ± 2.40, p=0.004; SCC1483: scrambled control 13.39% ± 1.28% versus 7.49% ± 0.83, p=0.002). In addition, all five cell lines displayed reduced sensitivity to cisplatin compared with cells treated with scrambled control siRNA. The basal level of activated NFκB in HPV+ cell lines was correlated with the sensitivity to radiation and cisplatin as assessed by colony formation and cell growth assays. Suppression of NFκBp65 by siRNA resulted in marked increases in apoptosis associated with reduction of Bcl-2 in both SCC47 and SCC1483 cells. This pattern was more pronounced with increasing doses of the proteasome inhibitor bortezomib (32.5 to 130 nM for 48 to 72 hr). Furthermore, SCC47 and SCC1483 cells treated with siRNA NFκBp65 displayed a significantly greater level of apoptosis induced by radiation or cisplatin compared to cells treated with non-targeted control siRNA, indicating a pro-survival effect for NFκB. Further studies are warranted to delineate the effects of HPV oncogene interactions with NFκB signaling pathways on chemoradiation sensitivity. (This study was supported by the V Foundation).
Citation Format: Hongzheng Zhang, Zhongliang Hu, Ning Jiang, Rossella Marullo, Paul W. Doetsch, William D. Hunt, Georgia Z. Chen, Dong M. Shin. The role of nuclear factor kappa B in survival of human papillomavirus-positive head and neck cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1298. doi:10.1158/1538-7445.AM2013-1298
Abstract 1308: ERRβ ligand DY131 regulation of the hedgehog signaling pathway by modulation of Akt phosphorylation.
Authors: Lu Yuan , Merideth Benjamin R. , Lin Hui , Lubahn Dennis B. 
Published: August 2014

Abstract
Nuclear receptor family member, Estrogen Related Receptor β (ERRβ), and hedgehog (Hh)-signaling are reported to be significant for both tumorigenesis and stem cell maintenance. ERRβ itself is a crucial factor in inducing pluripotent stem cells. Here we investigate the hypothesis that ERRβ can interact with Hh signaling pathway, and modulation of ERRβ can influence Hh signaling. NIH3T3 and HEK293 cells, transfected with a Gli response element driven luciferase reporter, were treated with different concentrations of DY131, a synthetic ERRβ ligand, in the presence or absence of exogenous ERRβ. We monitored the Gli reporter activity, as well as Gli1, Akt and phosphorylated Akt via western blot.
Results: We found that DY131 inhibited Hh signaling activity when the pathway was activated by hedgehog peptide-conditioned medium, or the Smoothened Agonist (SAG), with an IC50 of 500nM. We also found that in HEK293 cells, where Gli reporter activity cannot be activated by either conditioned medium or SAG, DY131 dose dependently increased both endogenous and exogenous Gli1-induced reporter activity up to 4 fold. In addition, the transfection of ERRβ potentiated DY131’s effect on Gli reporter activity up to 7 fold. Western blot results, which are consistent with Gli reporter activity in both cell lines, showed that when Hh signaling is activated by Hedgehog peptide-conditioned medium, DY131 decreased Gli1 protein concentration; however when Hh signaling is not activated by conditioned medium, DY131 increases the concentration of Gli1 protein. Phosphorylated Akt, which is a non-canonical activator of Gli1, is up-regulated when Gli1 concentration increases, and down-regulated when the cells are treated with DY131.
Conclusion: Our results suggest a new level of regulation by ERRβ on the Hh-signaling pathway. ERRβ, induced by DY131, can modulate Akt's regulation of Gli1. Additionally, our results indicate that modulation of ERRβ, via ERRβ selective drugs like DY131, may serve as a new target for Hh-driven cancer treatment.
Citation Format: Yuan Lu, Benjamin R. Merideth, Hui Lin, Dennis B. Lubahn. ERRβ ligand DY131 regulation of the hedgehog signaling pathway by modulation of Akt phosphorylation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1308. doi:10.1158/1538-7445.AM2013-1308
Abstract 1321: Castration-resistant prostate cancer: BAY 1024767 blocks function of mutated androgen receptor.
Authors: Haendler Bernard , Sugawara Tatsuo , Lejeune Pascale , Koehr Silke , Faus Hortensia , Busemann Matthias , Cleve Arwed , Luecking Ulrich , von Nussbaum Franz , Brands Michael , Mumberg Dominik 
Published: August 2014

Abstract
Analysis of biopsies from prostate cancer metastases and of circulating tumor cells shows that androgen receptor (AR) mutations are often found in patients developing resistance to antiandrogen therapy, i.e. at the castration-resistant prostate cancer (CRPC) stage. Here we report on preclinical studies with a novel androgen receptor suppressor compound BAY 1024767 that exhibits strong antagonism for wild-type and mutated AR, both in vitro and in vivo.
Mutations located in the AR ligand-binding domain (LBD) and potentially involved in the resistance to the standard of care bicalutamide were generated and tested in cell-based transactivation assays, using 0.1 nM R1881 for stimulation. Bicalutamide showed reduced antagonistic activity for AR E709Y and no antagonism up to 10 μM for AR W741C. In comparison, BAY 1024767 exhibited strong antagonism for these mutants.
Another mechanism leading to CRPC is the elevation of intratumoral androgen levels. To mimick this situation, the transactivation assays were performed at a higher (1 and 10 nM R1881) androgen concentration. Bicalutamide, and also the novel antiandrogen MDV3100, showed much reduced antagonism for wild-type and W741C or E709Y mutant AR. Conversely, antagonism was still observed for BAY 1024767, especially at 1 nM R1881.
The KuCaP-1 model, which is derived from a CRPC patient and harbors the W741C mutation, was obtained from the group of O. Ogawa (Kyoto University). Mice bearing the KuCaP-1 xenograft subcutaneously were treated with bicalutamide (60 mg/kg, PO, qdx20) or BAY 1024767 (50 mg/kg, PO, q2dx10). No effect on tumor growth was observed with bicalutamide (T/C=103%) whereas BAY 1024767 was able to inhibit tumor growth with a T/C of 36% on day 54 post-implantation. In another study we found that MDV 3100 (100 mg/kg, PO) and abiraterone acetate (200 mg/kg, PO) were inactive in the KuCaP-1 model (100% and 73% T/C, respectively).
Citation Format: Bernard Haendler, Tatsuo Sugawara, Pascale Lejeune, Silke Koehr, Hortensia Faus, Matthias Busemann, Arwed Cleve, Ulrich Luecking, Franz von Nussbaum, Michael Brands, Dominik Mumberg. Castration-resistant prostate cancer: BAY 1024767 blocks function of mutated androgen receptor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1321. doi:10.1158/1538-7445.AM2013-1321
Abstract 1325: Chlorinated bisphenol A diglycidyl ether (EPI-001) mediates degradation of the androgen receptor in prostate cancer cells.
Authors: Brand Lucas J. , Dehm Scott M. 
Published: August 2014

Abstract
The androgen receptor is a critical target for the treatment of locally advanced and metastatic prostate cancer (PCa). Blocking AR signaling via castration or antiandrogens such as bicalutamide and enzalutamide results in tumor regression. However, resistance to AR-targeted therapy inevitably develops, marked by the outgrowth of castration-resistant prostate cancer (CRPC) cells. Mechanisms of CRPC include amplification of the AR gene, leading to overexpression of AR mRNA and protein, as well as expression of truncated AR splice variants. AR overexpression can convert bicalutamide to a weak agonist, thereby driving AR reactivation and ongoing cellular proliferation and survival. AR splice variants lack the COOH-terminal AR ligand binding domain (LBD) and function as constitutively-active, ligand-independent transcription factors. Recently, the chlorinated bisphenol A diglycidyl ether, EPI-001, was shown to bind to the AR NH2-terminal domain and inhibit AR signaling by interfering with coactivator recruitment. Here, we show that EPI-001 has a novel activity of mediating degradation of AR protein in various PCa cell lines, including cells driven by AR gene amplification and cells driven by AR splice variants. Cells displaying resistance to the next-generation antiandrogen enzalutamide were growth inhibited at EPI-001 concentrations corresponding to maximal AR degradation. Moreover, using VCaP cells as a model of AR overexpression, we show that EPI-001-mediated AR degradation prevents inappropriate agonist response to bicalutamide. This work provides proof-of-principle that targeting full-length and splice variant forms of the AR for degradation with EPI-001 may enhance the efficacy of conventional and next-generation antiandrogens for treatment of CRPC.
Citation Format: Lucas J. Brand, Scott M. Dehm. Chlorinated bisphenol A diglycidyl ether (EPI-001) mediates degradation of the androgen receptor in prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1325. doi:10.1158/1538-7445.AM2013-1325
Abstract 1331: Ethnic-specific polymorphisms in CHRNA3 and CHRNA9 genes.
Authors: Chikova Anna , Grando Sergei 
Published: August 2014

Abstract
Several recent studies demonstrated significant association of numerous common polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster encoding the α5, α3 and β4 nicotinic acetylcholine receptor (nAChR) subunits with the risk of lung cancer. However, due to high linkage disequilibrium, role of each protein in the tumorigenesis remains unclear. Large number of the single nucleotide polymorphisms (SNPs) including a majority of amino acid substitutions escaped the focus of previous research. Although some ethnic variations in this cluster are known, previous research was focused on the SNPs common for various ethnic groups. Little is currently known about epidemiological role of haplotypes specific for ethnical groups. We have assessed the global frequency distributions of coding and some non-coding nAChR SNPs by direct sequencing of 3 regions of CHRNA3 and 5 regions of CHRNA9 genes in 330 individuals from anthropologically defined human populations. The results revealed statistically significant ethnic-specific differences. In CHRNA3, for 8 SNPs, including one non-synonymous amino acid substitution, and in CHRNA9 for 7, including 2 non-synonymous SNPs. Among these SNPs, some were unique to one or two ethnical groups. For example, Arg110His in CHRNA3 (rs77574318) was seen only in Russians with heterozygosity 0.06. Thus, analysis of any amino acid substitution uniquely present in a particular ethnic group may guide further studies of the role of nAChRs gene polymorphism in various types of cancer
Citation Format: Anna Chikova, Sergei Grando. Ethnic-specific polymorphisms in CHRNA3 and CHRNA9 genes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1331. doi:10.1158/1538-7445.AM2013-1331
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 1332: Functional killer-immunoglobulin-like receptor variation and risk of non-melanoma skin cancer.
Authors: Vineretsky Karin A. , Karagas Margaret R. , Pawlita Michael , Nelson Heather H. 
Published: August 2014

Abstract
Natural killer (NK) cells of the immune system are the first line of defense against transformed and infected cells. NK cell action is determined through binding of killer immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands on target cells. The KIR gene family is diverse and highly polymorphic, is poorly covered on GWAS platforms, and exhibits significant functional copy number variation. The KIR locus has been primarily studied in the context of HCV, HIV, and transplant outcomes. Here, we have tested the hypothesis that KIR genotypes are associated with Non-Melanoma Skin Cancer (NMSC) etiology. These are among the most prevalent malignancies worldwide with rising incidence. In addition, they are highly antigenic tumors, with a possible viral etiology, making NMSC an ideal model to test KIR as a cancer susceptibility trait. A random subset of a population-based case-control study in New Hampshire was selected for the study: 422 basal cell carcinomas (BCC) (1 BCC=243, 2 BCC=131, ≥3 BCC=48), 132 squamous cell carcinomas (SCC), and 222 controls. KIR genotyping was performed with Lifecodes KIR-SSO typing kit on Luminex using buffy coat derived genomic DNA, capturing KIR loci: 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DS1, and 3DL2. Cutaneous HPV status was assessed using serum samples and established Luminex detection assays covering 16 genus beta HPV types.
The KIR2DL2/3 locus was associated with a significantly increased risk of BCC (OR=2.65, 95% CI: 1.08-6.48), which was particularly strong for cases with 3 or more tumors (OR=5.77, 95% CI: 1.30-25.66). For SCC, the KIR3DL1 gene was associated with a significantly increased risk of malignancy (OR=3.73, 95% CI: 1.51-9.22). Next we investigated the association of KIR and SCC within HPV strata. The KIR3DL1-SCC association was strongest among those with no evidence of HPV infection (OR=6.81, 95% CI: 1.78-26.12). In contrast, the non-functional KIR2DS4 variant related to an increased risk and the KIR2DL2 gene related to reduced risk of SCC among those with multiple β-HPV infections. Our results implicate a strong role for KIR in the etiology of NMSC. KIR2DL2/3 may be particularly important in the development of multiple BCC, and KIR3DL1 in the pathogenesis of SCC. Finally, we identified a pattern of KIR-SCC associations that supports a potential etiologic role of cutaneous HPV in SCC occurrence.
Citation Format: Karin A. Vineretsky, Margaret R. Karagas, Michael Pawlita, Heather H. Nelson. Functional killer-immunoglobulin-like receptor variation and risk of non-melanoma skin cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1332. doi:10.1158/1538-7445.AM2013-1332
Abstract 137: Racial differences in physical activity after breast cancer diagnosis.
Authors: Hair Brionna , Hayes Sandi 
Published: August 2014

Abstract
Background: The established benefits of physical activity (PA) after breast cancer diagnosis, including reduced mortality and treatment-related side effects and improved quality of life, suggest that PA should become a component of breast cancer care. Research shows that breast cancer survivors decrease PA post-diagnosis, but these studies have been underpowered to examine racial differences or were not population-based.
Methods: The Carolina Breast Cancer Study, a population-based study of incident breast cancer cases, assesses PA levels pre- and post-diagnosis in a large sample (n=1,735) with a substantial proportion of African-Americans (21%). PA was calculated as the number of minutes spent performing moderate and/or vigorous activity per week.
Results: Women were less likely to meet PA recommendations of &gt;150 minutes of weekly activity after their breast cancer diagnosis (35%) than before diagnosis (61%). African-American, lower income and less educated women were less likely to meet recommendations both pre-diagnosis and post-diagnosis, but the decline in meeting recommendations following diagnosis was consistent across these characteristics. Though the majority of women (63%) decreased activity post-diagnosis, 19% increased and 18% did not change their activity levels. The average decrease in weekly minutes of PA was 230 minutes (95% CI: 190, 270). On average, African-Americans reduced their PA by more minutes than whites (276 versus 218 minutes, respectively; p-value=0.14) as did lower income compared to higher income women (311 versus 199 minutes, respectively; p-value=0.002). Compared to those with decreased post-diagnosis PA, women who were white (OR: 1.3, 95% CI: 1.0, 1.7), higher income (OR: 1.6, 95% CI: 1.2, 2.1), or higher educated (OR: 1.5, 95% CI: 0.9, 2.5) were more likely to increase activity post-diagnosis.
Conclusions: After breast cancer diagnosis, cases who were African-American, had lower income, or were less educated were less likely to meet PA recommendations, less likely to increase activity, and tended to reduce PA by more minutes. Interventions should seek to increase post-diagnosis PA overall, with a focus on these subgroups.
Citation Format: Brionna Hair, Sandi Hayes. Racial differences in physical activity after breast cancer diagnosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 137. doi:10.1158/1538-7445.AM2013-137
Abstract 1377: Guided imagery use in the peri-operative period of gynecologic oncology surgery.
Authors: Dickson Elizabeth L. , Gerber Matt , Jonson Amy L. 
Published: August 2014

Abstract
Objective: To assess the feasibility of using guided imagery therapy in the peri-operative period at the time of Gynecologic Oncology surgery.
Methods: IRB approval was obtained for this randomized control trial. Patients were recruited based on having an exploratory laparotomy surgery with the gynecologic oncology group. Research staff performed a phone interview and obtained written consent. Patients were randomized to standard of care therapy, blank CD which was to simulate noise reduction headphones, or a validated guided imagery CD. The intervention would be used in pre op waiting area, during surgery, and after surgery. VAS scores, amount of narcotics used, amount of anti-emetics used, FACT G and POMS surveys were collected.
Results: 12 patients were attempted to be recruited for the study from April 2012 to the present. Prior to study enrollment, all patients were excited about the study and willing participants. All 12 pre op nurses were a barrier to discuss the study with the patients in the pre op area. 2 patients were unable to be consented due to the pre-operative nursing staff baring the research staff from consenting. 3 of the 10 RNAs stated that the player was dysfunctional, though the players were tested prior to delivery to the pre-operative area. 7 of the 12 patients stated that they ‘forgot’ to listen to the CD prior to surgery, or that the nurses did not let them take the time to listen. Only 2 of the 12 patients actually listened to the CD prior to surgery; only 2 of the 12 had the CD played during surgery. 4 of the 12 never received the CD player and surveys after surgery on the surgical oncology floor. Only 1 of the 12 actually listened to the CD throughout the entire hospital stay. 5 patients were told that it was “too busy” to listen to the CD by the floor nursing staff. 6 CD players were lost or stolen during the course of the study. To date, only 1 patient in the control group completed all surveys. However, 3 patients voiced excitement and satisfaction when using the intervention CD during their immediate peri-operative time, and were documented by external observers to have resolution of their anxiety while using the intervention CD.
Conclusions: While subjectively beneficial for patients to decrease stress responses peri-operatively, integrative medicine techniques such as guided imagery will be difficult to implement until the culture of medicine embraces this novel modality.
Citation Format: Elizabeth L. Dickson, Matt Gerber, Amy L. Jonson. Guided imagery use in the peri-operative period of gynecologic oncology surgery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1377. doi:10.1158/1538-7445.AM2013-1377