bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4562: Slug knockdown suppresses malignant phenotype of nanomaterial-transformed human lung epithelial cells
Authors: Voronkova Maria , Luanpitpong Sudjit , Wang Liying , Rojanasakul Yon 
Published: August 2015

Abstract
Nanomaterials have increasingly become part of modern everyday life, but their long-term health effects are largely unknown. Previous studies have shown that carbon nanotubes (CNTs), one of the most widely used nanomaterials in industry, can induce or promote tumor formation in animals, but the underlying mechanisms are unclear. We previously found that chronic exposure to CNTs induced malignant transformation of human lung epithelial cells, the primary cellular target of inhaled nanomaterials. The transformed cells exhibited aggressive cancer phenotypes, including increased cell migration, invasion and anchorage-independent cell growth. We hypothesized that such increased aggressiveness may be due to epithelial-mesenchymal transition (EMT). To test this hypothesis, cultured human lung epithelial BEAS-2B cells were continuously exposed to physiologically relevant concentration (0.02 μg/cm2 surface area dose) of single-walled CNT (SWCNT) for a period of 6 months. The cells were then analyzed for EMT markers and aggressive cellular behavior. Western blot analysis of EMT markers indicated an increased expression of mesenchymal markers and decreased epithelial markers, indicating the activation of EMT in the chronic SWCNT-exposed cells. Moreover, the cells exhibited a dramatic increase in one of the EMT master regulators, a transcription factor Slug (Snail2). We hypothesized that Slug upregulation may be responsible for the aggressive phenotype of the cells. We stably downregulated the Slug expression using lentiviral shRNA particles, and examined its effect on cell migration and invasion by Transwell® assays. Our results showed that knockdown of Slug attenuated cell migration and invasion without having any effect on cell proliferation. Together, our results indicated the activation of EMT by SWCNT and demonstrated its role in aggressive cancer phenotype. Slug plays a crucial role in this process and could serve as a potential biomarker for CNT-induced malignancies.
Citation Format: Maria Voronkova, Sudjit Luanpitpong, Liying Wang, Yon Rojanasakul. Slug knockdown suppresses malignant phenotype of nanomaterial-transformed human lung epithelial cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4562. doi:10.1158/1538-7445.AM2015-4562
Abstract 4587: Genome-wide copy number analysis identified a copy number polymorphism at chromosome 8p11 associated with sporadic colorectal cancer risk in Singapore Chinese
Authors: Cheah Peh Yean , Thean Lai Fun , Teo Yik Ying , Koh Woon-Puay , Yuan Jian-Min , Chew Min Hoe , Tang Choong Leong 
Published: August 2015

Abstract
Colorectal cancer (CRC) is one of the most frequent cancers and leading cause of cancer mortality in the developed world. Twin study has attributed about 35% of the etiology of sporadic CRC to genes. Hitherto, more than 20 single nucleotide polymorphism (SNP) loci have been associated with CRC risk. The role of structural variant in CRC, however, remains unclear. We performed genome-wide association study (GWAS) on 2,000 ethnicity-, age-, and gender-matched Singapore Chinese CRC patients (aged 50 or more and with no dominant family history of CRC) and healthy controls. Genome-wide genotyping was performed using Affymetrix SNP 6 platform. Copy number polymorphism (CNP) was interrogated in 1830 samples that passed quality assurance tests using a multivariate segmentation algorithm. A 150 kb region at chromosome 8p11 was identified to be significantly associated (-log10 p-value = 29) with sporadic CRC risk. This CNP was preferentially amplified in the cases compared to the controls. The amplification was not gender-specific suggesting that it is not involved in gender-limiting pathway. It is now being replicated in an independent panel using digital polymerase chain reaction (dPCR) and multiplex endogenous reference technique. In silico analysis of a 1.5 Mb region encompassing the CNP reveals a candidate gene 300kb 5′ of the CNP previously implicated in cancer progression. The expression of this gene in cases with copy number and metastasis status is being interrogated.
Citation Format: Peh Yean Cheah, Lai Fun Thean, Yik Ying Teo, Woon-Puay Koh, Jian-Min Yuan, Min Hoe Chew, Choong Leong Tang. Genome-wide copy number analysis identified a copy number polymorphism at chromosome 8p11 associated with sporadic colorectal cancer risk in Singapore Chinese. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4587. doi:10.1158/1538-7445.AM2015-4587
Abstract 4616: Genome wide association analysis identified 15q24 as a bladder cancer susceptibility locus
Authors: Matsuda Koichi , Takahashi Atsushi , Tanikawa Chizu , Kubo Michiaki , Nakamrua Yusuke 
Published: August 2015

Abstract
Bladder cancer is one of the most frequent cancers, which causes ∼150 000 death per year in the world. Both environmental and genetic factors are involved in the development of bladder cancer, and tobacco smoking is known to be the most important factor to increase the risk of bladder cancer; Recent genome-wide association studies (GWASs) in European populations have identified multiple genetic factors associated with bladder cancer. However, no GWAS has yet been conducted in Asian populations. Through genome wide association analysis and an independent replication study using a total of 1,131 bladder cancer cases and 12,558 non-cancer controls of Japanese populations, here we identified a SNP rs11543198 on chromosome 15q24 as a bladder cancer susceptibility locus. Rs1154319 was associated with bladder cancer risk with odds ratio (OR) of 1.41 and P value of 4.03 × 10-9. Subgroup analysis revealed rs11543198 to have a stronger effect in male smokers with OR of 1.66. Imputational analysis in this region suggested CYP1A2, which metabolizes tobacco-derived carcinogen, as a causative gene. We also confirmed the association of previously-reported loci, SLC14A1, APOBEC3A, PSCA, and MYC, with bladder cancer. Our finding implies the crucial roles of genetic variations on the chemically-associated development of bladder cancer.
Citation Format: Koichi Matsuda, Atsushi Takahashi, Chizu Tanikawa, Michiaki Kubo, Yusuke Nakamrua. Genome wide association analysis identified 15q24 as a bladder cancer susceptibility locus. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4616. doi:10.1158/1538-7445.AM2015-4616
Abstract 4626: Genetic susceptibility to diffuse large B-cell lymphoma in a pooled study of three Eastern Asian populations
Authors: Rothman Nathaniel , Bassig Bryan A. , Cerhan James R. , Au Wing-Yan , Kim Hee Nam , Sangrajrang Suleeporn , Hu Wei , Tse Jovic , Berndt Sonja , Zheng Tongzhang , Zhang Heping , Pornsopone Pattarapong , Lee Je-Jung , Kim Hyeoung-Joon , Skibola Christine F. , Vijai Joseph , Burdette Laurie , Yeager Meredith , Brennan Paul , Shin Min-Ho , Liang Raymond , Chanock Stephen , Lan Qing 
Published: August 2015

Abstract
Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide. Some epidemiologic data have indicated differences in DLBCL incidence rates and subtype distributions between Eastern Asian and Western countries. The first large-scale genome-wide association study (GWAS) of DLBCL with over 4000 cases conducted among individuals of European ancestry recently identified five independent SNPs that achieved genome-wide significance, and two SNPs that showed a suggestive association with DLBCL risk. In order to evaluate whether Eastern Asians and individuals of European ancestry share similar genetic risk factors for this disease, we attempted to replicate these GWAS findings in a pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea, and Thailand. Three of the five genome-wide significant SNPs from the DLBCL GWAS were significantly associated with DLBCL in our study population, including the top finding from the GWAS, EXOC2 rs116446171, which achieved genome-wide significance in our data (per allele OR = 2.04, 95% CI = 1.63-2.56; ptrend = 3.9 × 10-10). Additionally, we observed a significant association with PVT1 rs13255292 (per allele OR = 1.34, 95% CI = 1.19-1.52; ptrend = 2.1 × 10-6), which was the second strongest finding in the GWAS, and with HLA-B rs2523607 (per allele OR = 3.05, 95% CI = 1.32-7.05; ptrend = 0.009). Our study, which provides the first evaluation in Eastern Asians of SNPs definitively associated with DLBCL risk in individuals of European ancestry, indicates that at least some of the genetic factors associated with risk of DLBCL are similar between these populations.
Citation Format: Nathaniel Rothman, Bryan A. Bassig, James R. Cerhan, Wing-Yan Au, Hee Nam Kim, Suleeporn Sangrajrang, Wei Hu, Jovic Tse, Sonja Berndt, Tongzhang Zheng, Heping Zhang, Pattarapong Pornsopone, Je-Jung Lee, Hyeoung-Joon Kim, Christine F. Skibola, Joseph Vijai, Laurie Burdette, Meredith Yeager, Paul Brennan, Min-Ho Shin, Raymond Liang, Stephen Chanock, Qing Lan. Genetic susceptibility to diffuse large B-cell lymphoma in a pooled study of three Eastern Asian populations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4626. doi:10.1158/1538-7445.AM2015-4626
Abstract 4631: AKAP12 is elevated in paclitaxel-resistant ovarian cancer cells and correlates with poor ovarian cancer patient survival
Authors: Bateman Nicholas , Jaworski Elizabeth , Wang Guisong , Dubil Elizabeth , Marcus Charlotte , Conrads Kelly , Teng Pang-ning , Hood Brian , Hamilton Chad , Maxwell Larry , Darcy Kathleen , Conrads Thomas 
Published: August 2015

Abstract
Objective: Although most ovarian cancer patients respond initially to the standard of care involving carboplatinum/paclitaxel-based chemotherapy, the majority will recur with chemotherapeutically resistant disease. Unfortunately, no clinical biomarker(s) for predicting or monitoring chemotherapeutic resistance are available. We sought to identify shed and/or secreted proteins from paclitaxel-resistant human ovarian cancer cells and identify whether any of these correlate with ovarian cancer patient outcome.
Methods: A proteomic analysis of secretomes from high grade serous ovarian cancer (HGSOC) cells (OV90) was compared to that from a syngeneic paclitaxel-resistant variant (OV90-TR) and a cancer cell line developed from a chemorefractory HGSOC patient. Associations between the identified candidates and patient outcome were assessed from publicly available transcript expression data (n = 545 ovarian cancer patients) and validated independently (n = 795 ovarian cancer patients).
Results: Among the 81 differentially abundant proteins identified (q&lt;0.05) from paclitaxel-sensitive vs -resistant HGSOC cell secretomes, AKAP12 was verified to be elevated at the protein and transcript level in all models of paclitaxel-resistant HGSOC. Further, elevated AKAP12 transcript expression was found to significantly correlate with poor progression-free (Hazard Ratio = 1.487 (± 0.148), p = 0.0085 (± 0.002) and overall (Hazard Ratio = 1.22 (± 0.08), p = 0.009 (± 0.013) survival.
Conclusions: These findings suggest that elevation and efflux of AKAP12 is characteristic of paclitaxel-resistant HGSOC cells and that elevated AKAP12 expression correlates with poor ovarian cancer patient survival.
Citation Format: Nicholas Bateman, Elizabeth Jaworski, Guisong Wang, Elizabeth Dubil, Charlotte Marcus, Kelly Conrads, Pang-ning Teng, Brian Hood, Chad Hamilton, Larry Maxwell, Kathleen Darcy, Thomas Conrads. AKAP12 is elevated in paclitaxel-resistant ovarian cancer cells and correlates with poor ovarian cancer patient survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4631. doi:10.1158/1538-7445.AM2015-4631
Abstract 4644: Curcumin C3 ® prevents ultraviolet B radiation-induced acute damage in JB6 keratinocytes and mouse skin via FGF-2/mTOR/NF-KB pathway
Authors: Khandelwal Alok R. , Anandharaj Arun , Oleksandr Ekshyyan , Moore-Medlin Tara , Fleurette Abreo , Nathan Cherie-Ann O. 
Published: August 2015

Abstract
Background and Significance: Aggressive Cutaneous Squamous cell carcinoma (CSCC) of the face has become the second most common type of skin cancer in the USA due to ultraviolet B (UVB) exposure in tanning booths and sun exposure of our military personnel. UVB is a carcinogen and our previous studies established oral administration of Curcumin C3 complex (C3), a standardized preparation of three curcumonoids - Curcumin (76.07%), Demethoxycurcumin (20.28%) and Bisdemethoxycurcumin (3.63%), delayed UVB-induced tumor onset and multiplicity, but not tumor progression. Accordingly, we sort to determine the preventative efficacy of C3® against UVB-induced photodamage in promotion sensitive JB6 skin keratinocytes and SKH-1 hairless mouse epidermis on the early neoplastic events in the development of UVB-induced skin carcinogenesis.
Methods: SKH-1 mice were either administered vehicle or C3 (100mg/kg/b.w) complex orally for 14 days followed by a single exposure to UVB radiation (180mj/cm2). Mice were euthanized 24 hours after UVB exposure and skin tissues and serum were collected. For in vitro studies, promoter-sensitive JB6 mouse epithelial cells were pre-treated with C3® for 2 h and the effects on UVB-induced early molecular signaling events were assessed.
Results: C3® attenuated UVB-induced epidermal hyperplasia and significantly decreased epidermal and plasma levels of fibroblast growth factor-2 (FGF-2); an important mitogen implicated in proliferation and differentiation of skin keratinocytes. In vitro, C3®blocked UVB-dependent FGF-2 induction and proliferation of cultured keratinocytes via down regulation of nuclear factor kappa B (NF-KB) and Mammalian target of rapamycin (mTOR) signaling pathways.
Conclusion: Our findings suggest C3® has the ability to protect mice from UVB-induced acute damage. Further the photo-preventive effects of C3® are mediated, at least in part, via modulation of FGF-2/mTOR/NF-KB signaling.
Citation Format: Alok R. Khandelwal, Arun Anandharaj, Ekshyyan Oleksandr, Tara Moore-Medlin, Abreo Fleurette, Cherie-Ann O. Nathan. Curcumin C3 ® prevents ultraviolet B radiation-induced acute damage in JB6 keratinocytes and mouse skin via FGF-2/mTOR/NF-KB pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4644. doi:10.1158/1538-7445.AM2015-4644
Abstract 4660: Association of longer telomere length with increased risk of chronic hepatitis B and hepatocelluar carcinoma
Authors: Ma Qiang , Cai Jiajing , Cai Yan , Xu Yuan , Chang Fan , Xu Lei , Guo Xiaolan 
Published: August 2015

Abstract
Telomere, which consists of small tandem nucleotide repeats (5′-TTAGGG-3′ in human), plays a critical role in the maintenance of genomic stability in eukaryotic chromosomes. More and more findings have shown that alteration in telomere length was involved in some diseases, however whether the telomere length is associated with the development and/or progression of disease remains poorly understood. Here a case-control study was employed to illustrate the correlation of relative telomere length(RTL) with chronic hepatitis B(CHB) and hepatocellular carcinoma(HCC). In this study, 115 cases of HCC patients, 212 patients with chronic hepatitis B and 184 healthy controls well matched with age and gender were recruited. Genomic DNA was extracted from the peripheral blood leukocytes and fluorescence quantitative polymerase chain reaction(FQ-PCR) was used to detect the telomere repeated numbers. We found that the RTL in HCC group was the longest, followed by CHB patients group and healthy control group was the shortest, showing significant statistical differences. When compared with age, the RTLs of individuals who aged more than 50 years old were obvious shorter than those younger ones in the control group, but not in the HCC and CHB group. Moreover, individuals who had longer RTLs indicated a significant increased risk of chronic hepatitis B (OR: 1.83, 95%CI: 1.22-2.73), and the longest RTLs showed higher incidence of HCC (OR: 3.22, 95%CI: 2.01-5.17) when the healthy control was used as the reference group. Most importantly, when the chronic hepatitis B group was used as the reference group, individuals who had longer RTL also suffered a significant increased risk of HCC(OR: 1.58, 95%CI: 1.03-2.41). Our results suggest that longer RTL is associated with the increased risk of chronic hepatitis B and HCC, which indicates that telomere length might be involved in the development or progression of HCC, also RTL might be used as a potential predicator of HBV relative chronic liver disease and HCC.
Citation Format: Qiang Ma, Jiajing Cai, Yan Cai, Yuan Xu, Fan Chang, Lei Xu, Xiaolan Guo. Association of longer telomere length with increased risk of chronic hepatitis B and hepatocelluar carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4660. doi:10.1158/1538-7445.AM2015-4660
Abstract 4671: Identification of novel drugs for glioblastoma using chemical biology fingerprinting
Authors: Finlay Darren , Dhruv Harshil , Evers Lisa , Peng Sen , Kiefer Jeff , Kim Seungchan , Raizer Jeffrey , Berens Michael , Vuori Kristiina 
Published: August 2015

Abstract
Glioblastoma Multiforme (GBM) is an aggressive brain tumor with very poor prognosis and extremely limited therapeutic options. GBM is the most common malignant brain tumor and the search for novel targets and/ or the repurposing of already extant drugs to treat the disease is therefore of utmost importance. We describe here a comprehensive multidisciplinary approach to identifying said targets and ergo potential therapies. We have applied a novel analytical strategy to The Cancer Genome Atlas (TCGA) GBM expression data to stratify GBM into novel subtypes we call molecular contexts, or mCs. Subsequently, a panel of patient-derived GBM xenografts was ascribed to our novel mCs. Utilizing a technique we term Chemical Biology Fingerprinting, or CBF, short-term cultures derived from these clinically-relevant preclinical models were screened for chemosensitivity with a deeply annotated, yet clinically relevant, chemical library. Agents that were statistically more toxic to one context than another were then re-tested in true drug dose response experiments to confirm sensitivity. Preliminary data demonstrated that mC14, characterized by mutant p53 and transcriptionally similar to the GBM proneural subtype, showed distinct vulnerability to Arsenic Trioxide (ATO) as compared to mC4, enriched for NF1 mutations and with transcriptional patterns similar to the GBM mesenchymal subtype. To validate the ATO vulnerability signature in GBM, we acquired 20 treatment naïve archival patient samples, that were part of a Phase I/II clinical trial to study the efficacy of ATO and Temozolomide in combination with ionizing radiation (NCT00275067). Participants in the trial exhibited varied survival with ATO treatment (91 days to &gt;1000 days) and the clinical samples were subtyped into our molecular contexts using RNAseq data.
In summary, we demonstrate a subclassification of GBM into novel molecular contexts (mCs) and show that these contexts are differentially sensitive to clinically relevant drugs.
Citation Format: Darren Finlay, Harshil Dhruv, Lisa Evers, Sen Peng, Jeff Kiefer, Seungchan Kim, Jeffrey Raizer, Michael Berens, Kristiina Vuori. Identification of novel drugs for glioblastoma using chemical biology fingerprinting. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4671. doi:10.1158/1538-7445.AM2015-4671
Abstract 4692: BGB-283, a novel RAF kinase and EGFR dual inhibitor, displays potent antitumor activity in B-RAF mutated colorectal cancers
Authors: Tang Zhiyu , Yuan Xi , Du Rong , Cheung Shing-Hu , Zhang Guoliang , Wei Jing , Zhao Yuan , Feng Yingcai , Zhang Yi , Du Yunguang , Hu Xiaoxia , Gong Wenfeng , Liu Yong , Gao Yajuan , Hao Rui , Ji Jiafu , Zhang Lianhai , Li Shuangxi , Sutton David , Wei Min , Zhou Changyou , Wang Lai , Luo Lusong 
Published: August 2015

Abstract
Oncogenic B-RAF, which drives cell transformation and proliferation, has been detected in approximately 70% of human malignant melanomas and 5-15% of colorectal cancers (CRC). B-RAFV600E mutation, which gives rise to constitutive MAPK signaling, accounts for at least 90% of oncogenic B-RAF mutations. Despite the remarkable clinical activities achieved by vemurafenib and dabrafenib in treating B-RAFV600E metastatic melanoma, their clinical efficacy in B-RAFV600E CRC is far less impressive. Prior studies suggested that feedback activation of EGFR and MAPK signaling upon B-RAF inhibition contributed to the intrinsic resistance of CRC to the first generation B-RAF inhibitors. This report represents the first characterization of a dual RAF kinase/EGFR inhibitor, BGB-283, which is currently under clinical investigations. BGB-283 is a potent and selective pan-RAF and EGFR inhibitor with IC50 ranging from 5 to 47 nM on RAF and EGFR kinases. In vitro, BGB-283 potently inhibits B-RAFV600E-activated ERK phosphorylation and cell proliferation. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harbouring B-RAFV600E and EGFR mutation/amplification. In B-RAFV600E CRC cell lines, BGB-283 effectively inhibits the reactivation of EGFR and achieved sustained inhibition of MAPK pathway. In vivo, BGB-283 is highly efficacious in inhibiting tumor growth accompanied by partial and complete tumor regressions in both BRAFV600E mutant cell derived CRC xenograft models, including HT29, Colo205, WiDr, as well as two primary human CRC xenograft models. In particular, BGB-283 shows compelling efficacy and potent inhibition of EGFR/MAPK signaling in WiDr xenograft model where EGFR reactivation occurs upon B-RAF inhibition. These findings support BGB-283 as a potent antitumor drug candidate with clinical potential for treating CRC harboring B-RAFV600E mutation.
Citation Format: Zhiyu Tang, Xi Yuan, Rong Du, Shing-Hu Cheung, Guoliang Zhang, Jing Wei, Yuan Zhao, Yingcai Feng, Yi Zhang, Yunguang Du, Xiaoxia Hu, Wenfeng Gong, Yong Liu, Yajuan Gao, Rui Hao, Jiafu Ji, Lianhai Zhang, Shuangxi Li, David Sutton, Min Wei, Changyou Zhou, Lai Wang, Lusong Luo. BGB-283, a novel RAF kinase and EGFR dual inhibitor, displays potent antitumor activity in B-RAF mutated colorectal cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4692. doi:10.1158/1538-7445.AM2015-4692