bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3532A: Development of gene therapy for pancreatic carcinoma: from experimental models to phase I clinical trial.
Authors: Buscail Louis , Bournet Barbara , Vernejoul Fabienne , Lulka Hubert , Cambois Gilles , Hanoun Naima , Gross Fabian , Tiraby Jean , Cordelier Pierre 
Published: August 2014

Abstract
Background: the median survival of patients diagnosed with locally advanced or metastatic pancreatic adenocarcinoma (PDA) is 4 to 6 months. Chemotherapies (gemcitabine, FOLFIRINOX) and molecular targeted therapies only offer a marginal survival benefit. Consequently, we developed new strategies based on therapeutic gene transfer to help alleviate the dismal prognosis of PDA. We demonstrated that transferring SSTR2 gene in PDA experimental models strongly inhibited tumor progression. We generated DCK::UMK fusion gene to chemosensitize tumor cells to gemcitabine to provoke tumor shrinkage in immune competent animals. Based on these promising results, we asked whether combining SSTR2 and DCK::UMK genes delivered by a non-viral vector may impede PDA growth in patients. Methods: in this first-in-man clinical trial, 22 patients (12 first line, 10 second line) were included in the CHU of Toulouse from 12/2010 to 9/2012. Four different doses (125, 250, 500 and 1000μg) of the gene therapy product (GTP) were injected twice using endoscopic ultrasound (EUS) (day 1 and day 28). Patients concomitantly received gemcitabine for 2 months. Results: the feasibility of this approach is excellent, as all the patients were successfully injected despite differences in the site and the size of the primary tumor, and pre-existing treatments (biliary stent, surgical bypass). No serious adverse events related to the GTP were recorded. We found that less than 0.001% of GTP was detected in blood, while urine was negative in all cases. We found that CA 19.19 levels decreased in 68% (15/22) of patients following gene therapy. In first line patients, we demonstrated partial tumor shrinkage in 2 cases (16%), stable disease in 9 cases (75%), and tumor progression in 1 case (8%). In these latter patients, progression-free survival and median survival following gene therapy reached 7 and 11.3 months, respectively. Conclusions: all together, we demonstrated for the first time that delivering antitumoral genes using non-viral vectors by EUS is feasible and safe in patients with advanced PDA. As our preliminary results tend to demonstrate therapeutic efficacy, we are currently designing a phase II trial based on this approach.
Citation Format: Louis Buscail, Barbara Bournet, Fabienne Vernejoul, Hubert Lulka, Gilles Cambois, Naima Hanoun, Fabian Gross, Jean Tiraby, Pierre Cordelier. Development of gene therapy for pancreatic carcinoma: from experimental models to phase I clinical trial. [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 3532A. doi:10.1158/1538-7445.AM2013-3532A
Abstract 3542: Effects of single nucleotide polymorphisms on treatment outcomes and toxicity in patients treated with sunitinib for biliary tract and gastric cancers.
Authors: MAENG Chi Hoon , Lee Jun Ho , Lee Jeeyun , Hong Jung Yong , Choi Moon Ki , Kim Young Saing , Jung Hyun Ae , Park Joon Oh , Park Se Hoon , Park Young Suk , Kang Won Ki , Lim Ho Yeong 
Published: August 2014

Abstract
BACKGROUND: We analyzed the efficacy and toxicity profile of sunitinib according to single nucleotide polymorphisms (SNPs) of VEGFA and KDR among the patients with gastric or biliary tract cancer.
METHODS: We examined 8 known SNPs of VEGFA and 5 SNPs of KDR among patients with gastric or biliary tract cancer who were treated with sunitinib in our two previous phase II studies. We assessed progression free survival (PFS), overall survival (OS), and toxicity and their relationships to these SNPs.
RESULTS: A total of 63 patients were evaluable. Among candidate SNPs, rs2010963, rs833068, and rs1870377 were associated with poor PFS (P = .009, .002, and .029, respectively), while rs1870377 and rs7692791 were associated with poor OS (P = .001 and 0.03, respectively). Multivariate analysis showed that only rs1870377 had significant effects on both PFS and OS. Toxicity evaluation indicated that rs1531289 was associated with grade 3-4 anemia. (P = .03).
CONCLUSIONS: Certain SNPs of KDR may affect treatment outcome and toxicity of patients treated with sunitinib.
Citation Format: Chi Hoon MAENG, Jun Ho Lee, Jeeyun Lee, Jung Yong Hong, Moon Ki Choi, Young Saing Kim, Hyun Ae Jung, Joon Oh Park, Se Hoon Park, Young Suk Park, Won Ki Kang, Ho Yeong Lim. Effects of single nucleotide polymorphisms on treatment outcomes and toxicity in patients treated with sunitinib for biliary tract and gastric cancers. [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 3542. doi:10.1158/1538-7445.AM2013-3542
Abstract 3551: CD44 expression in Ewing sarcoma is associated with reduced chemosensitivity in vitro.
Authors: Dioufa Nikolina , Li Guang , Tsokos Maria 
Published: August 2014

Abstract
CD44 is the primary hyaluronate (HA) receptor in a variety of cell types and has been implicated in several processes, such as cell-to-cell and cell-to-extracellular matrix interactions, cell migration and invasion, as well as metastasis and drug resistance. Even though CD44 expression has been studied in various types of cancer, such as prostate and lung cancer, little is known about its role in Ewing sarcoma, the second most common malignancy of bone and soft tissue in children and adolescents. We assessed the expression of CD44 in 25 cases of Ewing sarcoma by immunohistochemistry and found that CD44 is expressed in 40% of them. Furthermore, we noticed that in 4 out of 10 patients CD44 expression increased in one or more subsequent recurrent or metastatic biopsy samples. Therefore, we hypothesized that CD44+ cells in Ewing sarcoma represent cell clones, which are resistant to treatment and lead to tumor relapses. In order to study the role of CD44 in Ewing sarcoma, we cultured tumor cells for 24 to 72 hours in anchorage-independent sphere forming culture conditions, (low attachment plates), which are known to induce CD44 expression and compared them to adherent cells. CD44 mRNA and protein expression was induced in the anchorage-independent group as early as 24h in all 7 Ewing sarcoma cell lines. We then measured mRNA levels of ABCB5 and ABCC1, members of the superfamily of ATP-binding cassette (ABC) transporters related to drug resistance by real time PCR and found them increased. These data were corroborated by our finding of significantly increased efflux of the fluorescent DNA binding dye, Hoechst 33342, in the anchorage-independent group, indicating that the cells that overexpress CD44 are more effective in effluxing the chemotherapeutic drugs, thus becoming more resistant to chemotherapy. Finally, changes in the expression of efflux proteins were associated with increased resistance to doxorubicin-induced apoptotic cell death documented by increased expression of annexin V. In summary, our data indicate that CD44 is involved in drug resistance in Ewing sarcoma and may be clinically useful in making therapeutic decisions.
Citation Format: Nikolina Dioufa, Guang Li, Maria Tsokos. CD44 expression in Ewing sarcoma is associated with reduced chemosensitivity in vitro. [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 3551. doi:10.1158/1538-7445.AM2013-3551
Abstract 3555: Identification of candidate epigenetic markers for early detection of nasopharyngeal carcinoma.
Authors: Yang Xuesong , Szeto Ying Ying , Cheng Yue , Kwong Dora Lai-wan , Lung Maria Li 
Published: August 2014

Abstract
Nasopharyngeal carcinoma (NPC) is a human malignancy that is particularly prevalent in Southern China and Southeast Asia, and is strongly related to Epstein-Barr virus (EBV) infection. Since early detection of NPC will greatly improve the overall survival, screening becomes important for early NPC diagnosis. In this study, the methylation sensitive-high resolution melting (MS-HRM) method was established for detection of promoter DNA methylation using a panel of five tumor suppressor genes (RASSF1A, WIF1, DAPK1, RARβ2, p16), which were top candidates selected from 13 genes that had been tested in seven NPC cell lines and one immortalized NP cell line and which, showed highly different methylation status between cancer and immortalized cells. Biopsy samples from 52 NPC patients showed methylation for individual genes ranging from 30% to 96%. The combination of WIF1-RASSF1A, WIF1-DAPK1, and WIF1-RARβ2 all reached detection rates of 98% or above in biopsy samples, validating the frequent methylation status of these genes in NPC patients. WIF1, an important secreted Wnt inhibitor, is the most frequently methylated gene in our panel, as reported in many other cancers. In addition, the WIF1-RASSF1A combination showed the highest detection rate, reflecting that both early genetic events in chromosome 3p and the Wnt pathway play important roles in NPC development. To develop non-invasive methods for NPC high-risk screening, early diagnosis and prognosis, more NP brushings and cell-free plasma samples from NPC patients and healthy individuals have been tested for their methylation status of these candidate markers. Preliminary data indicate that the sensitivity and specificity reached more than 90% in certain gene combinations with NP brushings from patients of early NPC stage. The detection rate of methylation in cell-free plasma from NPC patients is even higher than the traditional EBV DNA test, which together show great potential for non-invasive high-risk screening for early NPC and early detection of local recurrence after therapy. In conclusion, a MS-HRM panel of multiple methylation markers is proposed as a complementary test for NPC early detection in combination with more established EBV-based markers.
Citation Format: Xuesong Yang, Ying Ying Szeto, Yue Cheng, Dora Lai-wan Kwong, Maria Li Lung. Identification of candidate epigenetic markers for early detection of nasopharyngeal carcinoma. [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 3555. doi:10.1158/1538-7445.AM2013-3555
Abstract 3560: The chromatin architecture at gucocorticoid receptor binding sites.
Authors: Burd Craig J. , Ward James M. , Burkholder Adam B. , Fargo David C. , Archer Trevor K. 
Published: August 2014

Abstract
Steroid hormone receptors are transcription factors that are implicated in the development and progression of several cancer types. It is clear that receptor activity is deregulated in these disease states. Using the glucocorticoid receptor (GR) as a model factor for transcriptional initiation, we aimed to understand the role chromatin structure plays in defining the specific genetic programs initiated by receptor activation. Using Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE), we examined the chromatin state at GR binding locations. FAIRE-seq data indicated an enrichment of signal, suggesting a more open chromatin state, surrounding the GR binding sites even in the absence of hormone. This enrichment is only seen at binding sites and not at unutilized response elements. This data is in line with recent developments indicating accessibility as a determinant of receptor binding. However, further characterization of binding regions suggests consistent nucleosome occupancy at these binding locations. Taken together, these data suggest that receptor binding may be determined by a very specific chromatin architecture that is defined by a transitional accessibility state.
Citation Format: Craig J. Burd, James M. Ward, Adam B. Burkholder, David C. Fargo, Trevor K. Archer. The chromatin architecture at gucocorticoid receptor binding sites. [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 3560. doi:10.1158/1538-7445.AM2013-3560
Abstract 3573: 17β-estradiol enhances hPygopus2 expression via ERα-SP1 promoter complexes.
Authors: Tzenov Youlian R. , Andrews Phillip G. , Kao Kenneth R. 
Published: August 2014

Abstract
Background: The chromatin remodeling protein Human Pygopus2 (hPYGO2) is widely overexpressed in, and required for the proliferation of several cancer cell lines derived from a variety of tumors. Because of the requirement of hPYGO2 for the G1/S cell cycle transition, its cell cycle dependent expression and its regulation by the Retinoblastoma protein in breast cancer (BC) cells, we hypothesized a fundamental link to the cell cycle. Thus, due to their predominant role in BC, we tested if 17β-estradiol (E2) would cause upregulation of hPYGO2 through Estrogen receptor alpha-SP1 transcription factor (ERα-SP1) promoter complexes.Methods: Eight ERα positive (ER+) and negative (ER-) BC cell lines were grown in low serum conditions and treated with ERα agonists and/or antagonists. mRNA levels were analyzed by Q-PCR and protein by immunoblot. ERα and SP1 promoter binding sites and DNA binding domains were functionally inactivated by site-directed mutagenesis. ERα and SP1 occupancy at the hPYGO2 promoter after treatment with various activators/inhibitors was analyzed by chromatin immunoprecipitation assays. Cell cycle progression was assessed by flow cytometry.Results: hPygopus2 mRNA and protein levels were higher in ER+ BC cells relative to ER- cells. ERα agonists induced, while antagonists inhibited, hPygopus2 mRNA and protein expression. ERα and SP1 occupancy at the hPYGO2 promoter required intact promoter binding sites and functional DNA binding domains. E2 increased, while Fulvestrant decreased, ERα binding to the hPYGO2 promoter while having no effect on SP1 binding. SP1 directed siRNA reduced SP1 occupancy at the hPYGO2 promoter and decreased hPygopus2 mRNA and protein expression in both ER+ and ER- cells. Treatment with betulinic acid, an SP1 inhibitor, resulted in cell cycle arrest in ER- BC cell lines.Conclusion: Our findings indicate that ERα and SP1 regulate hPygopus2 expression via promoter binding and that SP1 continues to play a role in hPYGO2 regulation in ER- cells, thereby revealing the potential efficacy of betulinic acid as a treatment for endocrine-disruptor resistant BC.
Citation Format: Youlian R. Tzenov, Phillip G. Andrews, Kenneth R. Kao. 17β-estradiol enhances hPygopus2 expression via ERα-SP1 promoter complexes. [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 3573. doi:10.1158/1538-7445.AM2013-3573
Abstract 3578: Androgen receptor transcriptionally targets the ErbB3 regulator Nrdp1 in the presence of nuclear Filamin A.
Authors: Savoy Rosalinda M. , Chen Liqun , Siddiqui Salma , Melgoza Frank U. , Durbin-Johnson Blythe , Roy Mohana , Jathal Maitreyee K. , Bose Swagata , Wang Yu , Mooso Benjamin , D'Abronzo Leandro , Fry William H. , Carraway Kermit L. , Ghosh Paramita M. 
Published: August 2014

Abstract
Despite availability of improved androgen receptor (AR) inhibitors for the treatment of castration-resistant prostate cancer (CRPC), resistance to treatment develops, and has been traced to activation of multiple signaling pathways suppressed by the AR. We previously showed that the AR maintained castration sensitivity in prostate cancer (PCa) by transcriptional regulation of the E3 ubiquitin ligase Nrdp1, which degrades the receptor tyrosine kinase (RTK) ErbB3; whereas AR inhibition suppressed Nrdp1 levels, thereby activating ErbB3. This resulted in CRPC growth and AR stimulation, but in CRPC, the AR was unable to regulate Nrdp1 or suppress ErbB3, causing uncontrolled progression. Here, we investigate the mechanism by which the AR regulates Nrdp1 transcription and why this regulation is lost in CRPC. Immunohistochemical studies in human PCa tissue and in PCa mouse models demonstrated Nrdp1 localization in both nucleus and cytoplasm. In vitro studies determined cytoplasmic Nrdp1 as 36kDa while nuclear Nrdp1 is 28kDa, the 36kDa form, but not the 28kDa form, negatively correlated with ErbB3 levels, but both forms positively correlated with AR. We demonstrate that Nrdp1 is a direct transcriptional target of the AR in androgen-dependent cells expressing a truncated form of the structural protein Filamin A (FlnA) in the nucleus, but in CRPC cells which have lost nuclear FlnA expression, the AR is no longer able to bind to the Nrdp1 promoter. Restoration of nuclear FlnA restored the ability of AR to regulate Nrdp1 transcription. Thus dual targeting of ErbB3 and AR will be effective in patients whose tumors express nuclear FlnA.
Citation Format: Rosalinda M. Savoy, Liqun Chen, Salma Siddiqui, Frank U. Melgoza, Blythe Durbin-Johnson, Mohana Roy, Maitreyee K. Jathal, Swagata Bose, Yu Wang, Benjamin Mooso, Leandro D'Abronzo, William H. Fry, Kermit L. Carraway, Paramita M. Ghosh. Androgen receptor transcriptionally targets the ErbB3 regulator Nrdp1 in the presence of nuclear Filamin A. [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 3578. doi:10.1158/1538-7445.AM2013-3578
Abstract 3580: Acetaldehyde and drug hypersensitivities of Fanconi anemia defects: Implications for cancer initiation, prevention, and therapy.
Authors: Ghosh Soma , Sur Surojit , Yerram Sashidhar R. , Rago Carlo , Bhunia Anil K. , Hossain M. Zulfiquer , Paun Bogdan C. , Ren Yunzhao R. , Iacobuzio-Donahue Christine A. , Azad Nilofer A. , Kern Scott E. 
Published: August 2014

Abstract
Studies of cells harboring Fanconi anemia (FA) pathway defects have aided clinical understanding of inherited cancer risks and therapeutic strategies. Here, we observed a novel and large (27X) hypersensitivity of BRCA2- and PALB2-null genotypes to the epidemiologically important ethanol metabolite, acetaldehyde. This prominent acetaldehyde sensitivity may hold evolutionary and clinical significance. Interrogation of a novel panel of cells engineered to be null for various FA genes also revealed two classes of chemical hypersensitivities: the shared and divergent phenotypes. Prominent chemical hypersensitivities to various interstrand crosslinking (ICL) agents in vitro (melphalan, mitomycin C, and cisplatin), to γ-radiation in vitro, and to mitomycin C in vivo were essentially similar among the tested genotypes. A large divergence of responsiveness existed, however, between the cell lines when using the PARP inhibitor KU0058948, the topoisomerase II inhibitor etoposide, and acetaldehyde. These results indicate that, toward some agents, not all FA defects are necessarily equivalent; this divergence among phenotypes may dissect functions differing among FA genes and may presage differing clinical and epidemiological implications. We additionally present the first engineered PALB2-null human cancer cells. The results suggest new applications in cancer epidemiology, prevention, and targeted therapy.
Citation Format: Soma Ghosh, Surojit Sur, Sashidhar R. Yerram, Carlo Rago, Anil K. Bhunia, M. Zulfiquer Hossain, Bogdan C. Paun, Yunzhao R. Ren, Christine A. Iacobuzio-Donahue, Nilofer A. Azad, Scott E. Kern. Acetaldehyde and drug hypersensitivities of Fanconi anemia defects: Implications for cancer initiation, prevention, and therapy. [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 3580. doi:10.1158/1538-7445.AM2013-3580
Abstract 3585: Nicotine contributes to oral cancer by promotion of cell invasion through ASAP1 signaling pathway.
Authors: Chiang Chang Hsu 
Published: August 2014

Abstract
Oral cancer is characterized as prolonged exposure to potential risk factors, including tobacco use or cigarette smoking. However, the underlined mechanism of tobacco leads to cancer is still largely unknown. To shed light on the molecular basis of tobacco induced oral carcinogenesis, we established three sublines of oral cancer cells chronically treated with nicotine (IC30 dose for 3 months). Phenotypic characterization showed that the sublines were tolerant to nicotine, increased cell invasion and migration abilities, along with the altered expressions of epithelial-mesenchymal transition markers. The transcriptomic profiling analysis was performed between parental and the subline cells to global survey and identify nicotine induced genes. Heretical clustering analysis reveals that 1004 genes were differentially expressed, in which 28% of the genes associated with cell mobility. Total of 13 genes were confirmed by RT-PCR assay that over-expressed in the nicotine sublines. ASAP1 was significantly increased in all 3 cell lines, and it was selected for further studied. Knockdown ASAP1 expressions by shRNA reduced nicotine induced cell migration (to 60% ∼ 80%) and invasion (to 55% ∼ 60%) abilities. This ASAP1 silencing further inhibited nicotine- induced MMP2 enzyme activity. Clinical study also supported this finding that ASAP1 was significantly elevated in the oral cancer tissues from patients with smoking habits (P=0.042) but not in the cancer patients without smoking (P=0.714). We therefore concluded that tobacco contributes to oral cancer by the promotion of cell migration and invasion, which was at least in part, through ASAP1 associated signaling pathway.
Citation Format: Chang Hsu Chiang. Nicotine contributes to oral cancer by promotion of cell invasion through ASAP1 signaling pathway. [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 3585. doi:10.1158/1538-7445.AM2013-3585