bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2816: Immune-tolerant elastin-like polypeptide (iTEP) particles promote peptide vaccine presentation by dendritic cells
Authors: Chen Mingnan , Dong Shuyun , Cho Scott 
Published: May 2015

Abstract
T cell epitope-based peptide vaccines are promising experimental therapeutics for cancer and infection due to their unparalleled specificity, yet their presentations by dendritic cells (DCs) are hindered by their intrinsic limitations: short half-lives, non-typical antigen sizes for DCs to take in and process, lack of intrinsic adjuvants, and poor cross-presentation efficiencies. We aimed to boost the presentation by fabricating an immune-tolerant elastin-like polypeptide (iTEP) nanoparticle (NP) to resolve the limitations. The properties of iTEPs that render them as ideal vaccine carriers include their non-immunogenic and non-inflammatory natures, their simple purification method through phase transition, and their ability to fuse the vaccines and peptide adjuvants together.
We first fused a cytotoxic T lymphocyte (CTL) epitope vaccine, SIINFEKL, from ovalbumin to an iTEP amphiphilie and found the fusion is able to self-assemble into NPs. The NP was turned into a size similar to virus-like particles by modulating the iTEP sequences. The NP enhanced the presentation of SIINFEKL with H2b on the surface of DC2.4 cells in comparison with free peptide, ovalbumin, or soluble vaccine-iTEP fusions. Interestingly, another iTEP-vaccine fusion which forms larger, micrometer-sized aggregates led to even stronger vaccine presentation, an observation still under investigation. Moreover, our preliminary data showed that co-delivering the vaccines and an adjuvant peptide from flagellin by iTEPs also augmented the peptide vaccine presentation. Lastly, the iTEP NPs that deliver tumor antigen Kras- and hTERT-derived peptide vaccines were also generated and are currently under study with a hope to improve the efficacy of these vaccines.
In summary, iTEP particles enhanced peptide vaccine presentation. The underlying mechanisms of the enhancing effects of iTEP particles on the vaccine presentation will be studied next.
Supported by the University of Utah Start-up fund and the University of Utah SEED grant
Citation Format: Mingnan Chen, Shuyun Dong, Scott Cho. Immune-tolerant elastin-like polypeptide (iTEP) particles promote peptide vaccine presentation by dendritic cells. [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 2816. doi:10.1158/1538-7445.AM2014-2816
Abstract 2845: Expression of FGFR2b in gastric cancer as measured by immunohistochemistry with a highly specific monoclonal antibody
Authors: Deshpande Amit M. , Palencia Servando , Bellovin David I. , Gemo Abigael T. , Giese Tina , Stohr Bradley , Pierce Kristen L. , Los Gerrit 
Published: May 2015

Abstract
Gastric cancer is the second leading cause of death from cancer worldwide. Amplification of the FGFR2 gene has been reported in ∼ 5 to 7% of gastric cancers, and several studies have also reported overexpression of the FGFR2 protein using immunohistochemistry (IHC). FGFR2 gene amplification and protein overexpression have also been shown to correlate with an aggressive disease phenotype, making FGFR2 an attractive therapeutic target. We have reported elsewhere at this meeting that the b-isoform of FGFR2 is predominantly expressed in these tumors and have developed a therapeutic antibody, FPA144, which specifically targets this isoform. Here we report initial development of a separate monoclonal antibody, FPT mAb, for use as a companion IHC diagnostic (CDx) for selecting patients with high levels of FGFR2b protein.
In specificity studies using cells transfected with various FGFRs we show that FPT mAb specifically detects the b-isoform of FGFR2. In contrast, 7 commercially available anti-FGFR2 antibodies showed cross-reactivity with other FGF receptors. In an assay using cells with inducible FGFR2 gene expression, FPT mAb also was more sensitive for detection of FGFR2b than any of the commercially available antibodies. Furthermore, FPT mAb was able to detect FGFR2b protein expression in gastric cancer cases without FGFR2 gene amplification. We examined FGFR2b protein expression by IHC using the FPT mAb and FGFR2 gene amplification using FISH in 186 gastric cancer samples. 6% of samples showed amplification of the FGFR2 gene as measured by FISH (FGFR2:CEN10 &gt;3), compared to 16.7% of samples positive for FGFR2b expression as measured by IHC (2-3+ staining in &gt;50% of the tumor cells).
In conclusion, we show that the FPT mAb is sensitive and specific for detecting by IHC the b-isoform of FGFR2 expressed in gastric cancers. Further, we demonstrate that more gastric tumors overexpress FGFR2b protein than bear amplifications of the FGFR2 gene. These results suggest that a potentially larger percentage of patients with gastric cancer may be appropriately identified as candidates for FGFR2b-specific therapies.
Citation Format: Amit M. Deshpande, Servando Palencia, David I. Bellovin, Abigael T. Gemo, Tina Giese, Bradley Stohr, Kristen L. Pierce, Gerrit Los. Expression of FGFR2b in gastric cancer as measured by immunohistochemistry with a highly specific monoclonal antibody. [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 2845. doi:10.1158/1538-7445.AM2014-2845
Abstract 2851: Reduced Tip60 expression in human gastric cancer
Authors: Chen Guangdi , Bai Rongpan , Zhao Zhongsheng , Zhou Jianwei , Weng Yu 
Published: May 2015

Abstract
The tumor suppressor Tip60 plays a major role in gene transcription, DNA damage response, apoptosis and cancer development, but its role in gastric cancer is unknown. In this study, we investigated the role of Tip60 in gastric cancer pathogenesis and assessed its prognostic value. Using tissue microarrays consisting of 567 cases of gastric cancers (78 for training set and 489 for validation set), we found that Tip60 expression was significantly reduced in advanced gastric cancer compared to early stages of gastric cancer (P &lt; 0.001). Reduced Tip60 was correlated with gastric cancer lymph node metastasis (P &lt; 0.001) although no significant correlation was found between Tip60 expression and gastric cancer distant metastasis. Kaplan-Meier survival curve analysis showed that reduced Tip60 expression was associated with a poorer five-year overall survival in gastric cancer patients from both training set (P = 0.010) and validation set (P &lt; 0.001). Our data indicate that Tip60 may play an important role in gastric cancer metastasis and serve as a potential biomarker for gastric cancer patient outcome.
Note: This abstract was not presented at the meeting.
Citation Format: Guangdi Chen, Rongpan Bai, Zhongsheng Zhao, Jianwei Zhou, Yu Weng. Reduced Tip60 expression in human gastric 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 2851. doi:10.1158/1538-7445.AM2014-2851
Abstract 2854: Clinical significance of inhibin beta A expression in gastric cancer
Authors: Oshima Takashi , Imada Toshio , Yamamoto Naoto , Sato Tsutomu , Yukawa Norio , Shiozawa Manabu , Yoshikawa Takaki , Rino Yasushi , Kunisaki Chikara , Akaike Makoto , Masuda Munetaka 
Published: May 2015

Abstract
Objective: Inhibin beta A (INHBA), a glycoprotein belonging to the TGF-β superfamily, has recently been reported to participate in cancer-cell proliferation. We comprehensively studied the ratio of INHBA gene expression in gastric cancer tissue to that in adjacent normal mucosa by DNA microarray analysis and found that that INHBA gene expression was 12.8-fold higher in gastric cancer tissue. To extend our previous results, we investigated the clinical significance of INHBA gene expression in gastric cancer.
Methods: We studied 227 patients with gastric cancer followed up for at least 5 years postoperatively. The disease stage was I in 29 patients, II in 59, III in 88, and IV in 51. Of the 147 patients with stage II or III disease, 80 postoperatively received S-1 adjuvant chemotherapy, and 67 received surgery alone. We extracted mRNA from frozen specimens of gastric cancer and adjacent normal mucosa from these patients, calculated relative expression levels of the INHBA gene (quantitative PCR analysis), and studied the relations of INHBA expression to clinicopathological factors and treatment outcomes. We also examined the relation between S-1 adjuvant chemotherapy and INHBA gene expression in patients with Stage II or III gastric cancer, for which adjuvant chemotherapy is standard treatment.
Results: INHBA gene expression was significantly higher in gastric cancer than in adjacent normal mucosa (P&lt;0.0001) and was significantly related to the clinicopathological factors of invasion depth, disease stage, and vascular invasion. High INHBA gene expression was significantly related to poor outcomes (P=0.0320). In stage II and III gastric cancer, survival rates did not differ according to INHBA gene expression in patients who underwent surgery alone. In contrast, survival was significantly poorer in gastric cancer with high INHBA gene expression in patients who received S-1 adjuvant chemotherapy (P=0.003).
Conclusions: INHBA gene expression was suggested to be a useful predictor of poor outcomes in patients with resected gastric cancer. In patients given S-1 adjuvant chemotherapy, INHBA gene expression may be a useful biomarker.
Citation Format: Takashi Oshima, Toshio Imada, Naoto Yamamoto, Tsutomu Sato, Norio Yukawa, Manabu Shiozawa, Takaki Yoshikawa, Yasushi Rino, Chikara Kunisaki, Makoto Akaike, Munetaka Masuda. Clinical significance of inhibin beta A expression in gastric 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 2854. doi:10.1158/1538-7445.AM2014-2854
Abstract 2856: Fibroblast growth factor receptor 1 gene amplification as an independent prognostic factor for recurrence in patients with resected squamous cell esophageal cancer
Authors: Kim Hyo Song , Lee Seung Eun , Bae Yoon Sung , Kim Joo Hang , Kim Hye Ryun , Kim Dae Joon , Kim Hyunki , Choi Yoon-La , Cho Byoung Chul 
Published: May 2015

Abstract
Purpose
To evaluate investigate the prognostic role of fibroblast growth factor receptor 1 (FGFR1) amplification in patients with surgically resected esophageal squamous cell carcinoma (ESCC).
Patients and methods
Gene copy number of FGFR1 was investigated in microarrayed tumors from 549 patients with ESCC who underwent curative esophagectomy. Gene copy number was evaluated by fluorescent in situ hybridization, and an FGFR1 amplified tumor (FGFR1 amp+) was prespecified if one of the following criteria is fulfilled: (I) FGFR1/centromer 8 (CEN8) ration is ≥ 2.0, (II) average gene copy nucleus is ≥ 6.0, and (III) percentage of tumor cells containing ≥ 15 gene copies or large cluster is ≥ 10%.
Results
FGFR1 amplification was detected in 8% (44 of 549) of ESCC. The average copy number per nucleus was 2.7 (range, 0-15.5) and the mean FGFR1/CEN8 ratio was 2.2 (range, 0-6). The 5-year disease free survival of the FGFR1 amp+ group was significantly shorter compared with that of the FGFR1amp- group (38.8% vs 63.7% P=0.012). In Cox proportional hazard model, patients with FGFR1 amp+ had a significantly greater risk of recurrence compare to amp- group after adjusting for sex, smoking status, pathologic stage, histology, and adjuvant chemotherapy (HR 1.74; 95% CI, 1.10-2.76, P=0.018). Of note, there was a trend toward worse overall survival for FGFR1 amp+ group compare to amp- group (5-year OS 32.0% vs 50.8%, P=0.11). FGFR1 amp+ group was significantly more likely to be smokers than FGFR1amp- group (97.7 % vs 2.3%, P=0.001). With increment of total cigarette smoking dosage, the incidence of FGFR1 amp+ significantly increased (P trend=0.005).
Conclusions
FGFR1 amplification is an independent prognostic factor for recurrence in surgically resected ESCC. FGFR1 amplification may have potential clinical application to the development of novel therapeutic strategies for ESCC
Citation Format: Hyo Song Kim, Seung Eun Lee, Yoon Sung Bae, Joo Hang Kim, Hye Ryun Kim, Dae Joon Kim, Hyunki Kim, Yoon-La Choi, Byoung Chul Cho. Fibroblast growth factor receptor 1 gene amplification as an independent prognostic factor for recurrence in patients with resected squamous cell esophageal 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 2856. doi:10.1158/1538-7445.AM2014-2856
Abstract 2864: RPS4X, a new prognostic and predictive biomarker of ovarian and breast cancer
Authors: Tsofack Serges P. , Meunier Liliane , Mes-Masson Anne-Marie , Lebel Michel 
Published: May 2015

Abstract
Epithelial ovarian cancer (EOC) is a disease responsible for more cancer deaths among women in the Western world than all other gynecologic malignancies and breast cancer is leading cause of cancer death among the women worldwide. A major problem with such cancers is chemoresistance; hence the need to identify predictive biomarkers. Interestingly, overexpression of YB-1 in ovarian and breast cancer cells induces cisplatin resistance. Platinum coumpounds like cisplatin is often used in the treatments of these cancers. Y box-binding protein 1 (YB-1) is a multifunctional protein that affects transcription, splicing and translation of mRNA. In this study, we used a tagged YB-1 construct to identify by mass spectrometry the proteins that interacted with YB-1 and required for cisplatin resistance. Using the combination of two bioinformatics databases (Oncomine public microarray and genomic hybridization), we focused on the YB-1 protein partners that are potentially involved in cancer progression. We used the siRNA technique to screen different partners of YB-1 that are directly involve in the cisplatin resistance of MCF7 and MDA-MB-231 cells lines. From this analysis, we found that the RPS4X protein, a new partner of YB-1, would be a good marker of cisplatin resistance in breast cancer patients. Interestingly, the YB-1/RPS4X complex was also found in ovarian cancer cells. Like in the breast cancer cell lines, the depletion of RPS4X protein induced the cisplatin resistance of ovarian cancer cells lines (SKOV3 and OVCAR3). Finally, we used a validate antibodies to assess by immunohistochemistry the protein levels of RPS4X and YB-1 in tumor tissue samples from 192 high-grade serous epithelial ovarian cancer patients. We found that RPS4X correlated significantly with ovarian cancer patient outcome.
Taken together, these results suggest that, the YB-1/RPS4X complex is a significant potential target to counteract cisplatin resistance in breast and ovarian cancers. Also, we have established that RPS4X is a new promising prognostic marker for patients with high-grade ovarian cancer. More importantly, RPS4X is shown to be predictive of cisplatin response. Additional immunohistochemistry studies on low-grade ovarian cancers and breast cancers are required to confirm the predictive value of RPS4X.
Citation Format: Serges P. Tsofack, Liliane Meunier, Anne-Marie Mes-Masson, Michel Lebel. RPS4X, a new prognostic and predictive biomarker of ovarian and 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 2864. doi:10.1158/1538-7445.AM2014-2864
Abstract 287: Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue
Authors: Shi Jianxin , Marconett Crystal , Duan Jubao , Hyland Paula , Li Peng , Wang Zhaoming , Wheeler William , Campan Mihaela , Huang Jing , Zhou Weiyin , Triche Tim , Amundadottir Laufey , Hutchinson Amy , Chen Po-Han , Zhou Beiyun , Chung Brian , Bertazzi Pier Alberto , Bergen Andrew W. , Freedman Mathew , Lee Diane , Siegmund Kim , Warner Andrew Clay , Berman Ben , Pesatori Angela C. , Borok Zea , Consonni Dario , Chatterjee Nilanjan , Tucker Margaret , Caporaso Neil , Chanock Stephen J. , Laird-Offringa Ite A. , Landi Maria Teresa 
Published: May 2015

Abstract
The genetic regulation of the human epigenome is not fully appreciated. Here we describe the effects of genetic variants on the DNA methylome in human lung based on methylation-quantitative trait loci (meQTL) analyses. We report 34,304 cis- and 585 trans-meQTLs, a genetic-epigenetic interaction of surprising magnitude, including a regulatory hotspot. These findings are replicated in both breast and kidney tissues and show distinct patterns: cis-meQTLs mostly localize to CpG sites outside of genes, promoters, and CpG islands (CGIs) while trans-meQTLs are over-represented in promoter CGIs. meQTL SNPs are enriched in CTCF binding sites, DNaseI hypersensitivity regions and histone marks. Importantly, 4 of the 5 established lung cancer risk loci in European ancestry are cis-meQTLs and, in aggregate, cis-meQTLs are enriched for lung cancer risk in a genome-wide analysis of 11,587 subjects. Thus, inherited genetic variation may affect lung carcinogenesis by regulating the human methylome.
Citation Format: Jianxin Shi, Crystal Marconett, Jubao Duan, Paula Hyland, Peng Li, Zhaoming Wang, William Wheeler, Mihaela Campan, Jing Huang, Weiyin Zhou, Tim Triche, Laufey Amundadottir, Amy Hutchinson, Po-Han Chen, Beiyun Zhou, Brian Chung, Pier Alberto Bertazzi, Andrew W. Bergen, Mathew Freedman, Diane Lee, Kim Siegmund, Andrew Clay Warner, Ben Berman, Angela C. Pesatori, Zea Borok, Dario Consonni, Nilanjan Chatterjee, Margaret Tucker, Neil Caporaso, Stephen J. Chanock, Ite A. Laird-Offringa, Maria Teresa Landi. Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue. [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 287. doi:10.1158/1538-7445.AM2014-287
Abstract 2870: ZGPAT gene expression in non-tumor hepatocellular carcinoma tissue is a likely biomarker for survival risk
Authors: Hishida Mitsuhiro , Nomoto Shuji , Inokawa Yoshikuni , Takano Nao , Kanda Mitsuro , Iwata Naoki , Tanaka Chie , Kobayashi Daisuke , Nishikawa Yoko , Yamada Suguru , Nakayama Goro , Fujii Tsutomu , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: May 2015

Abstract
[Background & Aim]
Hepatocellular carcinoma (HCC) often recurs after surgery and multicentric occurrence is more common than intrahepatic metastasis. We therefore examined factors in non-tumor liver tissue in HCC.
[Material & Methods]
Control samples, termed super normal liver tissues (SN), were taken from 11 cases of metastatic liver cancer. One of corresponding samples of normal tissues (CN) was selected for comparison from a typical specimen with chronic hepatitis C and HCC. We performed expression profiling and methylation arrays on these samples, identified genes that differed between SN and CN. We analyzed the identified genes using quantitative real-time reverse-transcriptase polymerase chain reaction on SN from 11 cases of metastatic liver cancer and CN from 109 cases of HCC.
[Results]
We found the zinc finger, CCCH-type with G patch domain (ZGPAT) gene to have expression decreased 4.198-fold in CN, and higher methylation status in CN (0.718), than in SN (0.360). The average expression value of the ZGPAT gene (ZGPAT value ×103 / GAPDH) decreased in CN (9.94 ± 10.68) relative to SN (28.55 ± 22.05). Compared with other patients, those with strongly reduced ZGPAT expression (&lt; 1.5) in their non-tumor liver samples had significantly shorter overall survival (P = 0.024), but not recurrence-free survival (P = 0.515).
[Discussion & Conclusion]
Our results indicate that expression of the ZGPAT gene in non-tumor liver tissue is a good biomarker for the risk of HCC development. ZGPAT gene is reportedly a transcription repressor that negatively regulates expression of epidermal growth factor receptor, which in turn, mediates cell proliferation, survival, migration. In treating HCC, detection of both prognostic factors from non-tumor liver tissue and malignant factors of the primary cancer lesion is important.
Citation Format: Mitsuhiro Hishida, Shuji Nomoto, Yoshikuni Inokawa, Nao Takano, Mitsuro Kanda, Naoki Iwata, Chie Tanaka, Daisuke Kobayashi, Yoko Nishikawa, Suguru Yamada, Goro Nakayama, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera. ZGPAT gene expression in non-tumor hepatocellular carcinoma tissue is a likely biomarker for survival risk. [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 2870. doi:10.1158/1538-7445.AM2014-2870