bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3791: Clinical significance of EpCAM-negative and CEA-positive circulating tumor cells in gastric carcinoma
Authors: Miki Yuichiro , Yashiro Masakazu , Okuno Tomohisa , Kitayama Kishu , Tamura Tatsuro , Toyokawa Takahiro , Tanaka Hiroaki , Muguruma Kazuya , Hirakawa Kosei , Ohira Masaichi 
Published: July 2017

Abstract
&lt;Background&gt;
It has been reported that the examination of circulating tumor cells (CTCs) is beneficial for predicting tumor stage or treatment response. The epitherial cell adhesion molecule (EpCAM) and cytokeratin has been used as epithelial markers for the identification of CTCs. Since the epithelial-mesenchymal transition is one of malignant phenotype of cancer cells, it is necessary to investigate other markers which might detect mesenchymal CTCs.
&lt;Aim&gt;
This study aims to clarify the clinical significance of EpCAM negative and CEA positive CTCs in patients with gastric cancer.
&lt;Methods&gt;
Forty patients who underwent operation for gastric cancer were enrolled in this study. A total of 10ml peripheral blood samples were obtained preoperatively. Informed consent to participate in this study was obtained from all of the patients before their surgery. This study was approved by the Human Ethics Review Committee of our University. After collection of mononuclear cell fraction, these cells were stained by PAPI, anti-CD45, anti-EpCAM, anti-cytokeratin, and anti-CEA (CD66e) antibody. We enumerated the number of cells which showed EpCAM, cytokeratin, and CEA positive expression among CD45 negative cells. ROC analyses were performed for investigating predictive value of these cell counts for distant metastasis. We examined association between these cell counts and clinicopathological features.
&lt;Results&gt;
ROC analyses revealed that the AUC for predicting distant metastasis using EpCAM, Cytokeratin, and CEA positive cell counts were 0.583, 0.638, and 0.769, respectively. The median number of EpCAM negative and CEA positive cells was 231 (range: 0-61897). The cell counts of EpCAM negative and CEA positive cells were significantly associated with Tumor depth (p=0.0084), lymph node metastasis (p=0.0107), and tumor size (p=0.023).
&lt;Conclusions&gt;
CEA might be useful marker for detecting high risk of recurrence in patients with gastric cancer.
Citation Format: Yuichiro Miki, Masakazu Yashiro, Tomohisa Okuno, Kishu Kitayama, Tatsuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. Clinical significance of EpCAM-negative and CEA-positive circulating tumor cells in gastric carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3791. doi:10.1158/1538-7445.AM2017-3791
Abstract 3802: A novel uracil-DNA glycosylase, UdgX, as a new biochemical tool to directly detect uracils in DNA
Authors: Stewart Jessica , Wei Shanqiao , Datta Madhurima , Varshney Umesh , Bhagwat Ashok 
Published: July 2017

Abstract
The enzyme activation-induced deaminase (AID) is essential to the B lymphocyte development and antibody maturation. It converts cytosines in DNA to uracil. The unregulated expression of AID in many B cell cancers is correlated with an increased load of mutations. AID also promotes DNA strand breaks and is required for chromosomal translocations such as IgH/Myc in these tumors. We have previously showed that B cell cancer cell lines and patient tumors which express AID at high levels also have high levels of uracil in their genomic DNA. We accomplished this by excising the uracils using a uracil-DNA glycosylase (Ung) and labeled the resulting in an abasic site with an aldehyde reactive chemical (ARP). ARP contains a biotin tag and it was detected using a fluorescently labeled streptavidin. The results from this assay showed B cell tumors have as much as 100-fold higher levels of genomic uracils. Further development of this assay has allowed the detection of uracils in the blood plasma and buffy coat of B cell cancer patients. This “liquid biopsy” assay technique has the potential to work as a simple surveillance tool for B cell cancer patients who are in remission. In addition, we are exploring the possibility of a direct detection of uracil in DNA, which would provide greater sensitivity to this assay and simplify it. A unique uracil-DNA glycosylase was recently isolated from M. smegmatis, UdgX, that binds covalently to uracils in DNA. We are developing multiple ways to detect uracil-DNA-UdgX complexes and amplifying the resulting signal. We expect that this will allow us to directly visualize uracils in B-NHL tumors and detect uracils in circulating B-NHL tumor DNA from a drop of patient plasma.
Citation Format: Jessica Stewart, Shanqiao Wei, Madhurima Datta, Umesh Varshney, Ashok Bhagwat. A novel uracil-DNA glycosylase, UdgX, as a new biochemical tool to directly detect uracils in DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3802. doi:10.1158/1538-7445.AM2017-3802
Abstract 3808: TM4SF1 regulates cell cycle and ROS status in bladder cancer cells by targeting FOXO3a via PPARγ-SIRT1 negative feedback loop
Authors: Cao Rui , Wang Gang , Qian Kaiyu , Chen Liang , Hu Qingxuan , Xiao Yu , Wang Xinghuan 
Published: July 2017

Abstract
Transmembrane 4 superfamily member 1 (TM4SF1) is a member of tetraspanin family, which locates in the cell membrane, functions as signal transducer to regulate cell development, growth and motility. Currently, TM4SF1 has been reported to be overexpressed in liver cancer, pancreatic cancer and colorectal cancer, but its role in bladder cancer (BCa) has not been illustrated. We have found that TM4SF1 was strongly upregulated in human bladder cancer tissues at both transcription and translation levels, compared with the paracancerous tissues and normal bladder tissues. This result was corroborated with our transcriptome analysis. Moreover, the tissue array data showed that TM4SF1 closely related with survival rate of BCa as the patients with high expression of TM4SF1 have a poorer prognosis. Furthermore, in vitro and in vivo studies suggested that proliferation of BCa cells was significantly suppressed by knockdown of TM4SF1. Moreover, downregulation of TM4SF1 induced G0/G1 phase cell cycle arrest and apoptosis possibly via induced reactive oxygen species (ROS) status in BCa cells. In addition, we observed that phosphorylated/total SIRT1 proteins were considerably reduced in the BCa cells lacking TM4SF1. In contrast, PPARγ as well as its target phosphorylated/total FOXO3a were strongly increased, an important downstream transcriptional factor of PPARγ/SIRT1 negative feedback loop, regulating cell cycle, apoptosis and ROS metabolism. Therefore, we treated the TM4SF1-silencing BCa cells with GW9662 (antagonist of PPARγ) and resveratrol (activator of SIRT1), showing a recovery of the G0/G1 phase cell cycle arrest and scavenge of ROS status. Interestingly, the increase of phosphorylated/total FOXO3a by knockdown of TM4SF1 could also be rescued by using GW9662 and resveratrol. In conclusion, our results suggested that TM4SF1 may regulate cell cycle and ROS status of BCa cells by targeting FOXO3a via the PPARγ-SIRT1 negative feedback loop.
Note: This abstract was not presented at the meeting.
Citation Format: Rui Cao, Gang Wang, Kaiyu Qian, Liang Chen, Qingxuan Hu, Yu Xiao, Xinghuan Wang. TM4SF1 regulates cell cycle and ROS status in bladder cancer cells by targeting FOXO3a via PPARγ-SIRT1 negative feedback loop [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3808. doi:10.1158/1538-7445.AM2017-3808
Abstract 3817: Deciphering the immune system in small intestine: Multiplex strategies for inflammatory bowel disease
Authors: Altree-Tacha David , Yuan Wei Wei , Yang George 
Published: July 2017

Abstract
Introduction
Inflammatory bowel disease (IBD) can affect the lower part of the small intestine (ileum) and the colon. It can, however, occur in any part of the large intestine, small intestine, or stomach. Recent evidence suggests that several factors may tip the balance between homeostasis and intestinal inflammation, presenting future challenges for the development of new therapies for IBD.
In this study, we use normal small intestine as a model to identify multiple immune targets using mouse and rabbit monoclonal antibodies. Peyer Patches are lymphoid tissues in the wall of the small intestine that are involved in the development of immunity to antigens presented in that milieu. Small intestine and cases of IBD were evaluated as a potential model using immunohistochemistry (IHC) to identify categories of immune cells including cytotoxic T-cells, costimulatory cells (agonists), T-regulatory cells (TREGs), T-cell effector cells (regulators) and checkpoint inhibitors. cases of IBD were also examined for the utilization of single and double/triple stains.
Design
Formalin-fixed paraffin-embedded cases of small intestine and IBD were cut to 4 micron thickness and stained with H&E. Mouse and rabbit monoclonal antibodies including CD56 (natural killer cells), CD163 (macrophages), CD8 and CD4 (cytotoxic T-cells and helper T- cells), CD103, OX40 and CD137 (costimulatory), FOXP3 and LAG3 (TREGs), T-bet and RORγT (T-cell effectors), and PD-1 and PD-L1 (immune checkpoints) were tittered for optimization and evaluated for IHC. Several IHC multiplex stains (double and triple stains) were also developed and compared with the relevant single stains.
Results
Single, double and triple stains utilizing CD56, CD163, CD4, CD8, CD103, OX40, CD137, FOXP3, LAG3, T-Bet, RORγT, PD-1 and PD-L1 antibodies were successfully established using small intestine as staining model for IBD cases. All single stains versus double and triple stains gave equivalent results. Double stains and/or co-expression of CD8 + CD103, CD8 + PD-1, and triple stain CD8 + PD-1 + FOXP3 were easily visualized with blue, brown, red or black chromogen staining.
Conclusion
Small intestine is a good model to develop single or multiplex stains for a host of immune cell targets. Enhanced visualization of these targets is possible with the use of double and triple stains; thus, this technique may help facilitate acquisition of important prognostic information and help support new strategies for inflammatory bowel disease in targeted therapeutic treatment.
Note: This abstract was not presented at the meeting.
Citation Format: David Altree-Tacha, Wei Wei Yuan, George Yang. Deciphering the immune system in small intestine: Multiplex strategies for inflammatory bowel disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3817. doi:10.1158/1538-7445.AM2017-3817
Abstract 3818: Identification of a FGFR3-TACC3 fusion in esophageal cancer
Authors: Mizukami Takuro , Sakai Kazuko , Naruki Saeko , Taniyama Tomoko , Horie Yoshiki , Izawa Naoki , Tsuda Takashi , Fujino Takashi , Boku Narikazu , Yasuda Hiroshi , Fukunaga Tetsu , Nakajima Takako Eguchi , Nishio Kazuto 
Published: July 2017

Abstract
Aberrant activation of fibroblast growth factor (FGF) signaling has been found to contribute to carcinogenesis. Recently, activating FGFR fusions are detected in several malignancy. However, limited information is available regarding the existence of FGFR fusions in esophageal squamous cell cancer (ESCC) and gastric cancer (GC). In this report, we explored major FGFR1, FGFR2, and FGFR3 fusion transcripts in ESCC and GC specimens (n = 74 and 114, respectively) using a most comprehensive next-generation sequencing panel. We detected a targetable fusion between exon 18 of FGFR3 and exon 11 of TACC3 at a frequency of 1.4% (1/74) in ESCC, whereas other FGFR fusions were not detected in the ESCC or GC specimens analyzed. Furthermore, split FGFR3 signals were apparent in this specimen by fluorescence in situ hybridization (FISH) with break-apart probes. The patient, a 64-year-old man with unresectable T4bN3M1 poorly differentiated ESCC of stage IV, was treated with palliative chemoradiotherapy followed by taxane chemotherapy. The patient died of cancer progression, with his overall survival time having been 9.5 months.
Our results provide sequence information that should prove useful for development of simple and cost-effective diagnostic assays as an alternative to FISH for patients with ESCC harboring the FGFR3-TACC3 fusion.
Citation Format: Takuro Mizukami, Kazuko Sakai, Saeko Naruki, Tomoko Taniyama, Yoshiki Horie, Naoki Izawa, Takashi Tsuda, Takashi Fujino, Narikazu Boku, Hiroshi Yasuda, Tetsu Fukunaga, Takako Eguchi Nakajima, Kazuto Nishio. Identification of a FGFR3-TACC3 fusion in esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3818. doi:10.1158/1538-7445.AM2017-3818
Abstract 3820: Hepatitis B virus gene pre-S2 mutant as a high risk serum marker for hepatoma recurrence after a hepatic resection
Authors: Huang Wen-Ya 
Published: July 2017

Abstract
Background: Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S2 mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study aimed to evaluate the serum pre-S2 mutant LHBS as a high-risk recurrence marker in HCC patients after a hepatic resection.
Methods: The pre-S gene chip was used to analyze 175 patients with HBV-related HCC who underwent a hepatic resection between 2008 and 2012. Thirty independent pre-S clones in every patient were analyzed for a semi-quantitative detection.
Results: Multivariate regression analysis showed that the serum pre-S2 mutant level (≥ 5%) and the American Joint Committee on Cancer (AJCC) tumor stage were two independent high-risk factors for HCC recurrence. A Cox proportional hazards analysis also showed that the combined evaluations of the AJCC stage and serum pre-S2 mutant level provided a reliable predictive marker for HCC recurrence after primary surgery. We developed a Cox prediction model, which indicated the recurrence-free survival rates along with the time after surgery. This model was validated in an independent HCC cohort. Receiver operating characteristic curve analysis revealed that the model showed close sensitivities in the main and validation cohorts (AUC values: 0.741 and 0.704, respectively).
Conclusions: The relative level of pre-S2 mutant in serum is, independently of tumor stage, an important predictive high-risk marker for HCC recurrence after a primary hepatic resection. The combined evaluations of the AJCC tumor stage and serum pre-S2 mutant level potentially serve as a convenient high-risk predictive marker for HCC prognosis.
Citation Format: Wen-Ya Huang. Hepatitis B virus gene pre-S2 mutant as a high risk serum marker for hepatoma recurrence after a hepatic resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3820. doi:10.1158/1538-7445.AM2017-3820
Abstract 3834: Tracking CAD-ALK gene translocation in urine and plasma of a colorectal cancer patient treated with ALK blockade
Authors: Siravegna Giulia , Sartore-Bianchi Andrea , Mussolin Benedetta , Palmieri Laura , Tosi Federica , Cassingena Andrea , Novara Luca , Buscarino Michela , Corti Giorgio , Crisafulli Giovanni , Bartolini Alice , Erlander Mark , Nicolantonio Federica Di , Siena Salvatore , Bardelli Alberto 
Published: July 2017

Abstract
A metastatic colorectal cancer (mCRC) patient carrying CAD-ALK translocation achieved partial response to an experimental ALK inhibitor and then progressed after 5 months. We studied whether urine cell-free, trans-renal DNA (tr-DNA) could be used to monitor tumor burden and patient’s response. A NGS panel was developed to interrogate 52 common cancer gene rearrangements and 14 frequently mutated genes in cancer patients. A TP53 p.R248W mutation and the CAD-ALK genomic breakpoint (rearrangement) were identified in the tumor tissue and matched plasma circulating tumor DNA (ctDNA) Urine samples were longitudinally obtained from the patient during ALK inhibitor treatment in parallel with blood. To detect the CAD-ALK translocation in urine tr-DNA we designed ultra-short (51 bp amplicon) primer pairs spanning the genomic breakpoint as a unique tumor marker. This approach allowed the non-invasive monitoring of the gene fusion in urine with amounts paralleling tumor burden. Of note, CAD-ALK gene fusion was apparent in urine tr-DNA before radiological confirmation of disease progression. The same strategy was applied to plasma ctDNA and the results were compared. To detect point mutations in urine tr-DNA, we exploited a peptide nucleic acids (PNA)-CLAMP PCR coupled with droplet digital PCR (ddPCR) analysis to specifically suppress amplification of wild-type DNA fragments. Custom PNA probes were designed for TP53 codon 248, and a ddPCR assay was optimized to detect the TP53 p.R248W mutation, which was then identified in all urine tr-DNA samples, with absolute copies correlating with tumor burden throughout ALK inhibitor treatment. In conclusion, we find that urine tr-DNA can be exploited to non-invasively monitor tumor burden by detecting tumor-specific gene fusions as well as point mutations.
Citation Format: Giulia Siravegna, Andrea Sartore-Bianchi, Benedetta Mussolin, Laura Palmieri, Federica Tosi, Andrea Cassingena, Luca Novara, Michela Buscarino, Giorgio Corti, Giovanni Crisafulli, Alice Bartolini, Mark Erlander, Federica Di Nicolantonio, Salvatore Siena, Alberto Bardelli. Tracking CAD-ALK gene translocation in urine and plasma of a colorectal cancer patient treated with ALK blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3834. doi:10.1158/1538-7445.AM2017-3834
Abstract 384: The implications of splicing variant of AIMP2 lacking exon 2 among various cancer types: An analysis of the ICGC/TCGA database and clinical validation
Authors: Kim Dong Chan , Kim Ryul , Kim Daeyoon , Song Hyojin , Shin Dong-Yeop , Kim Inho , Ahn Kwang-Sung , Kwon Nam Hoon , Kim Sunghoon , Yoon Sung-Soo , Koh Youngil 
Published: July 2017

Abstract
Aminoacyl-tRNA synthetase interacting multifunctional proteins (AIMP) is the multiple tRNA synthetase complex protein called the multi-tRNA complex (MRC). In cancer, the splicing variant of AIMP2 derives a several signaling cascades, which are crucial for cancer proliferation. Detecting an exon-2 depleted splicing variant (AIMP2-DX2) is an issue of growing importance in cancer therapy. This study suggests the evidence for interrelation between the AIMP2-DX2 and cancer development. We analyzed AIMP2 and AIMP2-DX2 gene expression and their ratio on 7 commercial cancer cell lines and Multiple myeloma patient derived 536MM cell line by RT-PCR and targeted RNA sequencing. Extended this profile, the distribution of AIMP2-DX2/AIMP2 ratio and AIMP2-related major cancer pathways were analyzed using the samples in the ICGC/TCGA database. Over 23 cancer types, 753 samples were used in WTS analysis. In the DEG set analysis, 10 pre-defined major cancer pathways were analyzed among 16 cancer types. Some cancer types, especially acute myeloid leukemia (AML) showed most significant association with AIMP2-DX2 in terms of cancer signaling pathways. We focused on clinical implications of AIMP2-DX2/AIMP2 ratio in the ICGC/TCGA database. 19 AML samples were used, Overall survival (OS) showed that patients with AIMP2-DX2/AIMP2 ratio higher than Q1 shows poor OS and Most of the genes including MEK1/2, ERK, MNK1/2 in this pathway had positive association with AIMP2-DX2/AIMP2 ratio. In colon carcinoma and hepatocellular carcinoma, OS curves had a tendency in a similar way to AML. For the clinical validation of the prognostic value of AIMP2-DX2, 51 AML patients were included in this analysis. The correlation between AIMP2-DX2 expression and survival outcomes was investigated in clinical validation cohort of AML. The AIMP2-DX2-positive group had significantly inferior OS rate and had worse RFS compare to AIMP2-DX2-negative group. Our sequential data shows that the AIMP2-DX2/AIMP2 expression and their ratio can possibly be an indicator to measure malignancy of various cancer types.
Citation Format: Dong Chan Kim, Ryul Kim, Daeyoon Kim, Hyojin Song, Dong-Yeop Shin, Inho Kim, Kwang-Sung Ahn, Nam Hoon Kwon, Sunghoon Kim, Sung-Soo Yoon, Youngil Koh. The implications of splicing variant of AIMP2 lacking exon 2 among various cancer types: An analysis of the ICGC/TCGA database and clinical validation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 384. doi:10.1158/1538-7445.AM2017-384