bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2536: AP-1/Fra-1 as a target for therapy promotes chemoradiosensitivity of cancer and cancer stem cells
Authors: Das Bhudev C. , Tyagi Abhishek , Roy Bal Gangadhar , Bharti Alok C. 
Published: July 2016

Abstract
Transcription factor activator protein-1 (AP-1) super-family is known to modulate expression of array of genes during development of many cancers. It is also an indispensable factor for efficient expression of high risk HPV oncogenes E6/E7. Recent studies demonstrated the role of AP-1 in promoting stemness/quiescence of cancer stem cells. We have recently reported that HPVE6 oncogene controls stemness and self-renewal of cervical cancer stem cells through Hes1/NOTCH-1expression but little is known about factor(s) responsible for chemo- radioresistance of cancer stem cells. To understand this we have dissected the role of AP-1and its family members by using a herbal compound, curcumin and UV irradiation in cervical cancer. We isolated cervical cancer stem cells and enriched them by sequential gating from HPV+ve and HPV-ve human cervical cancer cell lines (SiHa and C33a) using a set of functional and phenotypic markers (ABCG2, CD49f, CD71, CD133). The isolated cervical cancer stem cells (SP+ve→CD49+veCD71−ve→CD133+ve) designated as CaCxSLCs displayed spheroid forming and self-renewal property with increased expression of HPVE6, AP-1 transcripts and a higher AP-1 DNA-binding activity compared to non-stem cancer cells (NSP−ve→CD49−veCD71+ve→ CD133−ve) or unsorted parental cells. Treatment with UV-radiation alone resulted in clonogenic survival of CaCxSLCs but not non-stem cancer cells with enhanced AP-1 expression and activation. In contrast, CaCxSLCs treated with UV in combination with curcumin, resulted in complete loss of AP-1 DNA-binding activity followed by decrease in sphere formation and percentage of SP cells but an increased expression of the fos-related antigen-1 (Fra-1) which has been earlier shown to us have tumor suppressor activity in cervical cancer.
Our study demonstrates a critical role of AP-1/Fra-1 signaling in imparting radiosensitization of cervical cancer stem cells. Curcumin, which down regulates almost all signalling pathways, including all members of AP-1 except Fra-1 indicating its role in chemo-radiosensitization of cancer stem cells. Thus combining curcumin with conventional cancer drugs may make cancer treatment most effective.
Citation Format: Bhudev C. Das, Abhishek Tyagi, Bal Gangadhar Roy, Alok C. Bharti. AP-1/Fra-1 as a target for therapy promotes chemoradiosensitivity of cancer and cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2536.
Abstract 255: Docetaxel inhibits testosterone mediated activation of the AR pathway by SLCO1B3
Authors: de Morree Ellen S. , Aghai Ashraf , Gibson Alice A. , Mathijssen Ron H.J. , Wiemer Eric A.C. , Sparreboom Alex , van Weerden Wytske M. , de Wit Ronald 
Published: July 2016

Abstract
Background
Docetaxel is the first line of chemotherapy in metastatic castration resistant prostate cancer (mCRPC) patients. More than 50% of prostate cancer tumors express the solute carrier organic anion transporter family member 1B3 (SLCO1B3/OATP1B3), an uptake transporter that actively transports docetaxel into the cell. Interestingly, SLCO1B3 is also a transporter of endogenous substrates, such as testosterone. As the androgen receptor (AR) pathway is still active in mCRPC patients, we hypothesize that docetaxel can interact with the uptake of testosterone through SLCO1B3, which would result in decreased AR-pathway activation and subsequent tumor growth inhibition.
Materials and Methods
SLCO1B3 overexpressing cells (CHO-1B3) were used for uptake experiments with radioactively labeled hormones, such as estradiol-β-glucuronide (E2G). We stably transfected prostate cancers cells (PC346C-DCC and PC346C-DCC-G) with SLCO1B3 or with a green fluorescent protein (GFP) tag only. An androgen responsive element (ARE)-luciferase assay was created as a sensitive measure of AR pathway activation. ARE-activity and prostate specific antigen (PSA) production were analyzed with an ELISA assay after exposure to 1nM testosterone for 30 minutes with or without preincubation with docetaxel 10 μM in SLCO1B3 overexpressing and GFP- tagged control cells.
Results
SLCO1B3 overexpressing cells showed testosterone-mediated activation of the AR pathway: ARE-activity increased 6.4-fold and PSA production 7-fold in SLCO1B3-overexpressing cells as compared to control cells. Pre-incubation of CHO-1B3 cells with docetaxel resulted in reduced uptake of E2G to the level observed in control cells. Similarly, after exposure to testosterone and docetaxel ARE-activity was significantly decreased in SLCO1B3-overexpressing cells compared to that of controls.
Conclusion: Docetaxel inhibits the activation of the AR pathway via SLCO1B3. This is a novel anti-androgenic effect exerted by docetaxel in addition to inhibition of the AR translocation that we demonstrated previously. Experiments are ongoing to investigate if testosterone uptake via SLCO1B3 is inhibited by docetaxel.
Citation Format: Ellen S. de Morree, Ashraf Aghai, Alice A. Gibson, Ron H.J. Mathijssen, Eric A.C. Wiemer, Alex Sparreboom, Wytske M. van Weerden, Ronald de Wit. Docetaxel inhibits testosterone mediated activation of the AR pathway by SLCO1B3. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 255.
Abstract 2550: Identification of novel BRCA founder mutations in middle eastern breast cancer patients using capture and sanger sequencing analysis
Authors: Bu Rong , Siraj Abdul K. , Al-Obaisi Khadija A. S. , Beg Shaham , Al Hazmi Mohsen , Kong Yan , Ajarim Dahish , Al-Dayel Fouad , Al-Kuraya Khawla S. 
Published: July 2016

Abstract
Ethnic differences of breast cancer genomics have prompted us to investigate the spectra of BRCA1 and BRCA2 mutations in different populations. The prevalence and effect of BRCA 1 and BRCA 2 mutations in Saudi population is not fully explored. We conducted this study to characterize the prevalence of BRCA mutations in Middle Eastern breast cancer patients from Saudi Arabia. A total of 486 clinically high risk breast cancer patients were recruited from the King Faisal Specialist Hospital & Research Centre from 1990 and 2011. Comprehensive BRCA1 and BRCA2 mutation screening was performed using capture sequencing and/or Sanger Sequencing of all coding exons of BRCA1 and BRCA2 in 190 cases. Thereafter, the validation was done using a panel of detected mutations in an additional 296 high risk breast cancer cases. Among the total 486 cases analyzed, 9 deleterious BRCA mutations were identified in 28 (5.8%) cases, comprising 25 cases in BRCA 1 and three cases in BRCA 2. The six BRCA 1 recurrent mutations (c. 1140dupG, c.4065_4068delTCAA, c.4136_4137delCT, c.4524G&gt;A, c.5251C&gt;T and c.5530delC) accounted for 96% (24/25) of all BRCA 1 mutant cases in this cohort. The one recurrent BRCA 2
mutation (c.7007G&gt;A) accounted for 66.6% (2/3) of all BRCA2 mutant cases. Haplotype analysis was performed to confirm two BRCA1 recurrent mutations are novel putative founder mutation. In this study our findings suggest that BRCA mutations account for substantial proportion of high risk breast cancer cases in Middle Eastern population. Knowing the spectrum and frequency of founder mutation in this population will help in developing cost-effective rapid screening assay which can facilitate genetic testing and counseling for breast cancer risk assessment.
Citation Format: Rong Bu, Abdul K. Siraj, Khadija A. S. Al-Obaisi, Shaham Beg, Mohsen Al Hazmi, Yan Kong, Dahish Ajarim, Fouad Al-Dayel, Khawla S. Al-Kuraya. Identification of novel BRCA founder mutations in middle eastern breast cancer patients using capture and sanger sequencing analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2550.
Abstract 2555: Promoter DNA methylation patterns in breast tumor and matched adjacent non-tumor tissues in the breast cancer family registry
Authors: Wu Hui-Chen , Hibshoosh Hanina , Santella Regina , Terry Mary Beth 
Published: July 2016

Abstract
Alterations in DNA methylation occur frequently in breast carcinogenesis, but little is known about the DNA methylation changes in familial breast tumors. To examine whether the DNA methylation profiles in breast cancer tissues from high risk women from breast cancer families are similar to breast tumor tissues from The Cancer Genome Atlas project (TCGA), we measured DNA methylation by next generation sequencing in 48 genes identified in TCGA in 40 formalin-fixed, paraffin-embedded tumor tissues, and the corresponding adjacent non-tumor tissues from women with invasive breast cancer at the New York site of the Breast Cancer Family Registry (BCFR). We observed differences in DNA methylation patterns between tumor and normal adjacent tissue for five of the selected genes (RYR2, C1orf14, SLC7A14, SEPW1, and RPTOR). The methylation levels in tumor and adjacent tissues, respectively were 24% and 14% for RYR2, (p = 0.01), 55% and 29% for C1orf14 (p = 0.01), 32% and 21% for SLC7A14 (p = 0.002), 53% and 28% for RPTOR (p = 0.01) and 74% and 38% SEPW1 (p&lt;0.0001). We only confirmed 5 of the 48 loci identified in TCGA in our sample of high risk women, suggesting genes identified from TCGA may be different than those in high-risk women. As tissue-specific methylation may prove to have strong prognostic significance, this suggests a critical need to engage in large-scale studies examining genome-wide DNA methylation profiles in high risk women in order to understand the etiology of familial breast cancer.
Citation Format: Hui-Chen Wu, Hanina Hibshoosh, Regina Santella, Mary Beth Terry. Promoter DNA methylation patterns in breast tumor and matched adjacent non-tumor tissues in the breast cancer family registry. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2555.
Abstract 2557: Germline mutations in renal cancer predisposing genes: Analysis of the Geisinger MyCode population
Authors: Williams Heinric , Metpally Raghu , Mohamed Mahmoud , Krishnamurthy Sarath , Kip Sertac , Carey David J. , Baras Aris , Overton John 
Published: July 2016

Abstract
Renal cell cancer (RCC) is not a single disease but is made up of a number of cancers, each with a unique histology, biology, clinical course and response to therapy. Alterations in at least 16 hereditary genes have been attributed to the risk of developing RCC. In this study, we describe the prevalence and spectrum of germline variants among these genes and highlight correlations between germline genotype with tumor phenotype. Using the Geisinger MyCode cohort, we sequenced the whole exomes of 42,933 subjects. Subjects were divided into those with a renal cancer diagnosis, other cancer diagnosis and no cancer diagnosis. We analyzed the DNA sequences of 16 hereditary renal cancer genes from each of these groups. The damaging mutations was determined by following ACMG guidelines. Among the 42,933 subjects in the Geisinger MyCode cohort, 168 were diagnosed with RCC. None of these subjects had a family history of RCC. Clear cell RCC (ccRCC) was the most predominant histology (77%), followed by Type 1 papillary RCC (7%), chromophobe RCC (6%), and Type 2 papillary RCC (5%). Mutations in all the predisposing genes were identified in all the renal cancer subtypes but only a subset were deemed damaging. The top 2 ccRCC predisposing genes with damaging or likely damaging mutations were TSC2 (8%) and SDHD (4%). While TSC2 damaging variants were also found in the other histologies, novel TSC2 variants were differentially associated with high grade and metastatic disease in ccRCC as compared to those with low grade or non-metastatic disease. The genes harboring damaging or likely damaging variants in Type 1 and Type 2 papillary RCC were MET and FH respectively. Predisposing RCC germline mutations were found in a significant number of subjects with sporadic RCC. Family history was unhelpful in predicting the affected subjects. Knowledge of these mutations would be beneficial in counseling patients and their families as well as improving our understanding of the disease to direct patient care.
Citation Format: Heinric Williams, Raghu Metpally, Mahmoud Mohamed, Sarath Krishnamurthy, Sertac Kip, David J. Carey, Aris Baras, John Overton. Germline mutations in renal cancer predisposing genes: Analysis of the Geisinger MyCode population. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2557.
Abstract 2558: A retrospective analysis of the spectrum of genetic variations associated with hereditary cancers in Indians
Authors: Mahadevan Lakshmi , Nair Aditya , Ramprasad Vedam L. 
Published: July 2016

Abstract
The hereditary cancer burden in India is on the rise due to an increase in awareness of the disease, decrease in the cost of genetic testing and opportunities for genetic counseling. More and more individuals from high risk families are undergoing genetic testing to assess their likelihood of developing the disease. On the other hand, the clinical community is facing a significant challenge on how to interpret and classify a variant as disease-causing or benign. This is because a large fraction of the variants identified in the affected individuals from India have not been reported in hereditary disease databases such as the Breast cancer Information Core (BIC), Clinvar and Swissvar. These variants of unknown significance (VUS) present in individuals from high risk families create a great deal of uncertainty on clinical follow up and disease management. We performed a retrospective analysis on more than 300 affected cases of hereditary ovarian and breast cancer tested at our genomics center in the last three years. We compiled all the known pathogenic variants and compared their distribution in the Indian cohort with what has been reported worldwide. The most prevalent mutation in BRCA1 p.Glu23Valfs*17 (185delAG) was detected at a frequency of 20.34% in line with what has been found worldwide. In addition, frameshift mutations in BRCA1 and BRCA2 were most frequently detected in breast and ovarian cancer in line with previous findings. Additionally, our analysis identified 13 novel previously unreported and potentially pathogenic variants in BRCA1 and BRCA2 genes. Variants were also detected in several moderate penetrance genes such as CHEK2, BARD1 and ATM involved in DNA damage response and in MSH2 and MSH6 genes regulating epigenetic control through chromatin modification. In this study, we report novel pathogenic variants in genes associated with hereditary breast and ovarian cancer in the Indian population.
Citation Format: Lakshmi Mahadevan, Aditya Nair, Vedam L. Ramprasad. A retrospective analysis of the spectrum of genetic variations associated with hereditary cancers in Indians. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2558.
Abstract 2581: Determinants for compliance to colorectal cancer screening in Korea: A multilevel analysis
Authors: Shin Aesun , Woo Hyeongtaek 
Published: July 2016

Abstract
BACKGROUND: This study aimed at investigating the individual and area level factors associated with colorectal cancer screening attendance.
METHODS: Colorectal cancer screening participation as well as other individual level data were gathered from the fifth Korea National Health and Nutrition Examination Survey, 2010-2012. The area level data were extracted from 2009 Health promotion strategies and programs development for health inequalities alleviation (Shin et al.,2009). Multilevel model was used for data analysis.
RESULTS: Information on a total of 8,783 individuals (3,777 men and 5,006 women) aged 50 years and older and deprivation index of each areas were used in the final analysis. Among individual level variables, men were more likely to participated in colorectal cancer screening within 5 years than women (58.0% for men vs 53.9% for women)(Odds Ratio (OR) = 0.85; 95% CI 0.73 to 0.99), and highest among age 60-69 (63.3%). Area level variables's explained class-level variance was 6.4%.
CONCLUSION: In this study, by applying the multilevel analysis we can find that colorectal cancer screening attendance rate is associated with both individual and community factors.
Citation Format: Aesun Shin, Hyeongtaek Woo. Determinants for compliance to colorectal cancer screening in Korea: A multilevel analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2581.
Abstract 2601: Gingerol aspirinate derivatives as novel chemopreventive agents for colon cancer
Authors: Zhu Yingdong , Wang Fang , Zhao Yantao , Wang Pei , Sang Shengmin 
Published: July 2016

Abstract
Regular aspirin use has been convincingly shown to reduce the risk of colorectal cancer. However, long-term use of aspirin leads to gastrotoxicity. Herein, we designed and synthesized a novel class of gingerol- and shogaol-based aspirin prodrugs to simultaneously release aspirin and gingerol or shogaol to attenuate the side effects caused by aspirin. Prodrug GAS exerted enhanced anticancer activities, which are better than a physical mixture of aspirin and 6-gingerol as well as each individual. In addition, GAS eliminated the gastric toxicity induced by aspirin in mice. Metabolism of GAS in mice showed that the majority of GAS is decomposed to release 6-gingerol and aspirin or salicylic acid either in the intestine or after absorption. Mechanistic studies demonstrate GAS could dose-dependently inhibit COX pathway. These findings highlighted the improved anticancer properties of gingerol-based aspirin prodrugs. GAS may represent novel and safe alternatives of aspirin for the purpose of daily use in the future.
Citation Format: Yingdong Zhu, Fang Wang, Yantao Zhao, Pei Wang, Shengmin Sang. Gingerol aspirinate derivatives as novel chemopreventive agents for colon cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2601.
Abstract 2612: Zinc inhibits Orai1-mediated Ca2+ signals and proliferation in esophageal cancer cells
Authors: Choi Sangyong , Cui Chaochu , Luo Yanhong , Ko Jae-Kyun , Ma Jianjie , Fu Liwu , Korichneva Irina , Pan Zui 
Published: July 2016

Abstract
Intracellular Ca2+ signals, including oscillations, regulate proliferation, migration, and other cellular events in cancer cells. Zinc (Zn), an essential micronutrient, has been studied for its chemopreventive effects in several cancers, including esophageal cancer. Although there is a growing research interest in the cross-talk between Ca2+ and Zn signaling, it remains elusive as to how Zn prevents tumor growth and whether Ca2+ signaling is involved. Our previous report demonstrated that Orai1, a store-operated Ca2+ entry (SOCE) channel, is highly expressed in esophageal squamous cell carcinoma (ESCC) compared to normal tissues, and that the elevated expression of Orai1 is strongly associated with poor prognosis in patients. In the current study, we show that physiological levels of Zn can significantly suppress cell proliferation in KYSE-150, a human ESCC cell line. We also show that Zn is able to inhibit Orai1-mediated SOCE and intracellular Ca2+ oscillations, both which are known as proliferation signals. Based on the topology information of Orai1, we hypothesized that the histidine residue in linker region between transmembrane 1 and 2 of Orai1 (H113) as well as three cysteine residues may play a critical role in Zn-inhibitory effects. Using a point mutation approach, we exhibit that the Zn-inhibitory effects on both SOCE and cell proliferation are vanished in KYSE-150 cells containing Orai1 H113A mutant. Furthermore, KYSE-150 cells expressing Orai1 with any mutation in cysteine residues (C126A, C143A and C195A) display significant loss of Zn-inhibitory functions. These results indicate that the four amino acid residues are likely to be involved in Zn-inhibitory effects on SOCE and cell proliferation.
Taken together, our data suggest that dietary Zn may inhibit Orai1-mediated SOCE and intracellular Ca2+ signaling, which in turn suppresses cell proliferation in ESCC. Further studies are required to search for novel and effective prevention strategies as well as therapeutic options targeting on Zn and Ca2+ signaling in ESCC.
Citation Format: Sangyong Choi, Chaochu Cui, Yanhong Luo, Jae-Kyun Ko, Jianjie Ma, Liwu Fu, Irina Korichneva, Zui Pan. Zinc inhibits Orai1-mediated Ca2+ signals and proliferation in esophageal cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2612.