bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS02.047: TARGETED SILENCING OF SOX2 BY AN ARTIFICIAL TRANSCRIPTION FACTOR SUPPRESSED THE GROWTH OF ESOPHAGEAL CANCER CELLS
Authors: Yamatsuji Tomoki , Yokota Etsuko , Sera Takashi , Manabe Noriaki , Fukazawa Takuya , Naomoto Yoshio 
Published: September 2018

Abstract

Background
SOX2 is a transcription factor that is fundamental for early development and for the maintenance of stem cells in multiple adult tissues and also plays an important role in squamous cell differentiation. Amplification of chromosome 3q26 is the most common of the genetic alterations found in squamous cell carcinoma (SCC). SOX2 is a candidate oncogene present in this locus and amplification of SOX2 has been reported in lung and esophageal squamous cell SCC. In this study, we have developed a zinc finger-based artificial transcription factor (ATF) to selectively suppress SOX2 expression in cancer cells and termed the system ATF/SOX2.

Methods
We engineered the ATF using six zinc finger arrays designed to target a 19 bp site in the SOX2 distal promoter and a KOX transcriptional repressor domain. A recombinant adenoviral vector Ad-ATF/SOX2 that expresses ATF/SOX2 suppressed SOX2 at the mRNA and protein levels in esophageal SCC cells(TE1 and TE4) expressing SOX2.

Results
Ad-ATF/SOX2 decreased esophageal SCC cells proliferation and colony formation more effectively than the recombinant adenoviral vector Ad-shSOX2, which expresses SOX2 short hairpin RNA (shSOX2). Ad-ATF/SOX2 induced the cell cycle inhibitor CDKN1A more strongly than Ad-shSOX2. Moreover, Ad-ATF/SOX2 effectively inhibited tumor growth in a SCC xenograft mouse model.

Conclusion
In this study, we have shown that the targeted down-regulation of SOX2 using ATF based technologies can be used as an effective tool for the treatment of SCC in esophageal cancers that express SOX2. Our results indicate that ATF/SOX2 would lead to the development of an effective molecular-targeted therapy for esophageal SCC.

Disclosure
All authors have declared no conflicts of interest.
PS02.051: HMGB IS INVOLVED IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PROGRESSION
Authors: Matsubara Daiki , Konishi Hirotaka , Shoda Katsutoshi , Arita Tomohiro , Kosuga Toshiyuki , Shiozaki Atsushi , Kubota Takeshi , Fujiwara Hitoshi , Okamoto Kazuma , Otsuji Eigo 
Published: September 2018

Abstract

Background
High-mobility group box-1 (HMGB1), originally characterized as a non-histone, nuclear DNA-binding protein, acts as a crucial proinflammatory cytokine, mediating a broad range of inflammatory responses as a secretory form. Recently, it has been reported to be involved in the tumorigenesis and progression of various types of malignancies, but it is unclear whether HMGB1 plays an important role in the progression of esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the significance of HMGB1 in ESCC.

Methods
The tissue and plasma samples were obtained from ESCC patients at before or after operative period and healthy volunteers. The ESCC cell lines and normal human cell lines, such as fibroblast (WI-38) or Human umbilical vein endothelial cell (HUVEC), were used in vitro analyses. The expression levels of HMGB1 in tissue samples were measured by quantitative RT-PCR. The protein levels of HMGB1 were measured using the HMGB1 enzyme-linked immunosorbent assay kit in plasma samples, and using immunohistochemical staining or western blotting in tissue samples or cell lines. The functions of HMGB1 on the ESCC cell lines were investigated by proliferation, invasion, or migration assays.

Results
The mRNA and protein expression of HMGB1 in ESCC tissue was significantly higher than that in paired non-cancerous esophageal mucosa tissue. Plasma HMGB1 level was slightly higher, but not significant, in ESCC patients than in healthy volunteers. However, it was significantly higher in ESCC patients with Neoadjuvant chemotherapy (NAC) than in those without NAC. The mRNA and protein expression of HMGB1 were higher in ESCC cell lines than in WI-38 or HUVEC. In ESCC cells with high HMGB1 expression, knockdown of HMGB1 using specific siRNAs inhibited the cell proliferation, migration and invasion.

Conclusion
These findings suggest that HMGB1 plays a crucial role in tumor malignant potential through its overexpression in esophageal squamous cell carcinoma.

Disclosure
All authors have declared no conflicts of interest.
PS02.053: DUAL-STRANDS OF MIR-150-DUPLEX (MIR-150–5P AND MIR-150–3P) ACTED AS ANTI-TUMOR MIRNAS THROUGH TARGETING SPOCK1 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Osako Yusaku , Seki Naohiko , Idichi Tetsuya , Kita Yoshiaki , Omoto Itaru , Sasaki Ken , Uchikado Yasuto , Natsugoe Shoji 
Published: September 2018

Abstract

Background
MicroRNAs (miRNAs) belong to a group of small non-coding RNA molecules that act as pivotal agents responsible for fine-tuning RNA expression in a sequence-dependent manner. A large number of studies showed that dysregulated miRNAs are deeply involved in the development of cancer cells, as well as their metastasis and drug resistance. Based on our original miRNA expression signatures by RNA-sequencing revealed that both strands of miR-150–5p (the guide strand) and miR-150–3p (the passenger strand) was downregulated in several cancers. The general concept of miRNA biogenesis posits that the passenger strand of miRNA (the minor strand or miRNA*) derived from duplex miRNA is degraded and does not regulate gene expression. Here, we aimed that to investigate functional significance of these miRNAs in esophageal squamous cell carcinoma (ESCC).

Methods
Cancer cell proliferation, migration and invasion abilities were performed by using mature miRNAs or siRNAs. Genome-wide gene expression analyses and in silico analyses were applied to identify miRNA target genes in ESCC cells.

Results
Expression levels of miR-150–5p and miR-150–3p were significantly reduced in ESCC clinical specimens and cell lines. Cancer cell aggressiveness was inhibited by ectopic expression of these miRNAs. A total of 12 genes were identified as oncogenic targets by both miR-150–5p and miR-150–3p in ESCC cells. SPOCK1 (SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1) was directly regulated by both miR-150–5p and miR-150–3p by luciferase reporter assay. Overexpression of SPOCK1 was detected in ESCC specimens and knockdown of SPOCK1 by siRNA significantly inhibited cancer cell migration and invasion abilities.

Conclusion
Both strands of miR-150-duplex (miR-150–5p and miR-150–3p) acted as anti-tumor miRNAs in ESCC. Overexpression of SPOCK1 was enhanced cancer cell aggressiveness. Involvement of passenger strand of miRNA in cancer pathogenesis is novel concept in cancer research. We suggest that identification of novel function of passenger strands of miRNAs and the RNA networks they regulate might enhance our understanding of the molecular pathogenesis of ESCC.

Disclosure
All authors have declared no conflicts of interest.
PS02.055: IN ESOPHAGEAL ADENOCARCINOMA (EAC) BARRET LIKE AND CARDIO PYLORIC LIKE SUB TYPES ARE DIFFERENTIATED ACCORDING TO MICRORNA (MIRNA) 221 AND 483–3.P EXPRESSION PROFILES
Authors: Bonora Elena , Isidori Federica , Bozzarelli Isotta , Lugaresi Marialuisa , Malvi Deborah , Räsänen Jari , Kauppi Juha , Sala Claudia , Castellani Gastone , D’Errico Antonietta , Fiocca Roberto , Seri Marco , Krishnadath Kausilia , Mattioli Sandro 
Published: September 2018

Abstract

Background
miRNAs play a key role in cancer development. In esophageal adenocarcinoma (EAC), we analyzed the relationship between miR-221 and 483–3p expression, cancer specific survival, recurrence, their distribution in EAC sub types characterized by the presence/absence of intestinal metaplasia in esophagus (BIM) and stomach (GIM) [BIM + GIM- (Barret's like) and BIM-GIM- (cardio-pyloric like) types].

Methods
RNAs was extracted from 39 formalin-embedded surgical specimens (EAC and normal gastric). miRNA221 and miR-483–3p validation with TaqMan MicroRNA Assay was performed and data were normalized using RNU44. Kruskall-Wallis and Mann-Whitney tests were used to study correlations.

Results
A statistically significant relationship between miRNAs (miR-483–3p P = 0.017; miR-221 P = 0.037) and cancer specific survival and between miR-221 and recurrence (P = 0.043) was detected. miR-221 and miR-483–3p showed a significant decreased expression in the Barret's like group vs Cardio-pyloric-like group (miR-483–3p Kruskall-Wallis test P = 0.009; miR221 Kruskall-Wallis test P = 0.066; miR-483–3p Mann-Whitney test P = 0.002; miR-221 Mann-Whitney test P = 0.047)

Conclusion
In EAC increase of miR-221 and miR-483 is linked with poor survival and recurrence. Their different distribution patterns, support a biological differentiation of Barret's like versus cardio-pyloric like subtypes.

Disclosure
All authors have declared no conflicts of interest.
PS02.057: INDUCTION OF APOPTOSIS IN ESOPHAGEAL ADENOCARCINOMA CELLS BY CURCUMIN
Authors: Thieme René , Michiels Florian , Maurer Luisa , Hoffmeister Albrecht , Eichfeld Uwe , Dietrich Arne , Jansen-Winkeln Boris , Gockel Ines 
Published: September 2018

Abstract

Background
Curcumin naturally occurring in curry powder from Curcuma longa is an anti-inflammatory and anti-proliferative agent. It represses NFκB activation and induces apoptosis in cancer cells. Because, inflammation favours the onset of an intestinal metaplasia in esophageal squamous epithelial cells and esophageal carcinoma cells, a reduction of such processes may contribute to establish a stable disease and/or sensitization for chemotherapeutic approaches.

Methods
Curcumin receptivity was investigated in metaplastic (CP-A), dysplastic (CP-B), adenocarcinoma (OE19, OE33), and esophageal fibroblast (FFE3) cell lines, which were treated with 10 or 25 μM Curcumin for 48h or 72h. Response to Curcumin was measured by proliferation assays as well as by induction of apoptosis and Akt activation by western blot analyses.

Results
The EAC cell lines OE33 and OE19 show a decrease of proliferation with raising curcumin concentration with an IC50 of 9.6 and 14.8 μM, respectively. While the metaplastic and dysplastic cell lines showed a comparable IC50 of 7.7 and 11.6 μM to the EAC cell lines, the FEF3 cell showed a higher IC50 of approx. 20μM. The phosphorylation of Akt was decreased and apoptosis was induced, showing cleaved PARP, when treated with 25μM curcumin after 48h and 72h.

Conclusion
Metaplastic, dysplastic and EAC cells show a higher receptivity to curcumin than esophageal fibroblasts cells. This constrains the NFκB activation and its contribution in the manifestation of the Barrett's esophagus. The usage of curcumin to generate an anti-inflammatory microenvironment will potentially help to develop a stable disease or to reverse the development of the Barrett's esophagus.

Disclosure
All authors have declared no conflicts of interest.
PS02.060: EXPLORATION OF RADIOSENSITIVITY-RELATED LNCRNA IN ESOPHAGEAL CANCER STEM CELL
Authors: Li Jiancheng , Sun Weijie 
Published: September 2018

Abstract

Background
Esophageal cancer stem cells are the most radiation-resistant cells, to study radiosensitivity with esophageal cancer stem cells is a better method, Previously study was only the relevant microRNA research, so we explore radiosensitivity-related LncRNA in esophageal cancer stem cell.

Methods
The Eca109 cells were divided into tumor sphere cells group and adherent cells group by using suspended and adherent culture. Differences in stem cell characteristics of two groups were compared by CD44 positive expression rate, CCK8 cell proliferation and plate cloning formation. Using Arraystar LncRNA microarray analysis the gene expression differences of CD44+ esophageal cancer stem cells and CD44− esophageal cancer cells sorting out by flow separation technology. Bioinformatics analysis and real-time PCR were applied to verified the specific LncRNA related to radiation sensitivity of esophageal cancer stem cells.

Results
1.The result of CCK8 cell proliferation experience showed that the absorbance value of the tumor sphere cells group was significantly higher than and adherent cells group after 24h, 48h and 72h (P < 0.05). The cell clone formation rate of the tumor sphere cells group was higher than adherent cells group (P < 0.05). 2. The plate cloning formation showed that the values of D0, Dq, N and SF2 were significantly higher in the tumor sphere cells group than adherent cells group, and the radiation sensitization ratio was 1.556. 3. Arraystar LncRNA chip analysis showed following the criteria that DEGseq at |log2Ratio| ≥ 1和q < 0.05, 4961 DEGs including 2517 up-regualted genes and 2444 down-regulated genes were identified. 4. We verified the top 10 difference LncRNA genes by realtime PCR. The results showed that MSTRG. 73,085 was down-regulated and its expression level on average was 20.7 times (chip was 49.3 times), CH17–360D5.2, RP11–439E19.10, MSTRG.424, MSTRG.64087, MSTRG.15903 was up-regulated and their expression level on average were 2.7, 8.7, 3.7, 5, 7 (chip were 8.2, 5.2, 78.9, 3, 4.7 times).

Conclusion
We verified the different LncRNA genes by arraystar LncRNA chip and realtime PCR, The results showed that MSTRG. 73,085 was down-regulated and CH17–360D5.2, RP11–439E19.10, MSTRG.424, MSTRG.64087, MSTRG.15903 was up-regulated. These LncRNA genes may be related to the radiosensitivity of esophageal cancer stem cells and could be a potential new target for esophageal squamous carcinoma.

Disclosure
All authors have declared no conflicts of interest.
PS02.068: CORRELATION BETWEEN 18F-FDG PET/CT METABOLIC PARAMETERS AND LYMPH NODE METASTASIS OF ESOPHAGEAL CANCER
Authors: Li Jiancheng , Chen Shaoxing , Wu Haishan , Huan Zhiyu 
Published: September 2018

Abstract

Background
The regional lymph nodes metastasis plays a crucial role in treatment strategies selection. Nowadays, computed tomography (CT) scan and endoscopic ultrasound (EUS) were main examination techniques to assess the regional lymph nodes metastasis. PET/CT metabolic parameters correlated to the lymph node metastasis, but the value of the prediction of lymph node metastasis need to be confirmed in additional studies.

Methods
82 esophageal cancer patients that were pathologically confirmed and received initial treatment in our hospital from October 2011 to September 2016 were retrospectively analyzed. All patients underwent systemic 18F-FDG PET/CT examination within two weeks before operation. The metabolic parameters of primary lesions and postoperative pathological lymph node metastasis of esophageal cancer patients were recorded. The correlation between lymph node metastasis and metabolic parameters of primary lesion of esophageal cancer were analyzed by ROC curve and logistic binary regression.

Results
1. The correlation between metabolic parameters of primary lesion (including SUVmax, SUVmean, MTV, TLG, HF) and lymph node metastasis were analyzed by ROC curve and logistic binary regression. Results showed that the P value obtained from the two methods was less than 0.05, suggesting that there was correlation between metabolic parameters of primary lesion and lymph node metastasis of esophageal cancer. 2. Multivariate analysis showed that only TLG had statistical significance, P = 0.027, suggesting that TLG of primary lesion had a certain diagnostic value for the lymph node metastasis of esophageal cancer. 3. ROC curve analysis showed that, the area under the curve (AUC) was 0.722 when TLG > 24.08, P = 0.001, suggesting that the minimum TLG of lymph node metastasis of esophageal cancer was 24.08. In addition, the thoracic esophageal cancers at the upper and middle segment were statistically significant. When TLG > 23.06, its AUC was 0.755, P = 0.001, suggesting that the minimum TLG was 23.06.

Conclusion
18FDG-PET/CT metabolic parameters (SUVmax, SUVmean, MTV, TLG, HF) is closely related to lymph node metastasis of esophageal cancer. The TLG has a certain diagnostic value for the lymph node metastasis of esophageal cancer.

Disclosure
All authors have declared no conflicts of interest.
PS02.074: ENDOSCOPIC TUMOUR MORPHOLOGY AFFECTS SURVIVAL IN OESOPHAGEAL CANCER
Authors: Habib Wais , Zylstra Janine , Knight William , Bott Rebecca , Mahadeva Ula , Davies Andrew , Gossage James 
Published: September 2018

Abstract

Background
Oesophageal carcinoma can present with a variety of endoscopic morphologies. No previous studies have ascertained whether endoscopic tumour morphology impacts survival. This study describes three distinct endoscopic tumour morphologies; ulcerating, exophytic and stenosing, and analyses their impact on survival.

Methods
This is a retrospective cohort study of 181 patients who underwent diagnostic endoscopy prior to oesophagectomy at St Thomas’ Hospital, London. Univariable and multivariable Cox regression analyses were performed to determine hazard ratios (HR) with 95% confidence intervals for overall survival.

Results
There were 56 ulcerating, 68 exophytic and 57 stenosing lesions. Median survival was 52.7 months for ulcerating lesions, 46.8 months for exophytic lesions and 33.8 months for stenosing lesions (P = 0.01). When compared to stenosing lesions, exophytic and ulcerating lesions demonstrated a significant survival advantage on univariable analysis (exophytic HR 0.53; 95%CI 0.21–0.95, ulcerating HR 0.37; 95%CI 0.19–0.73).

Conclusion
This study demonstrates that endoscopic morphology may be an important prognostic factor in oesophageal cancer. Further studies are needed to confirm whether this is an independent prognostic indicator which may help guide future neoadjuvant and surgical treatment strategies.

Disclosure
All authors have declared no conflicts of interest.
PS02.080: CLINICAL SIGNIFICANCE OF THE NUMBER OF PERITUMORAL LYMPHATIC VESSELS AFTER CHEMOTHERAPY IN ESOPHAGEAL CANCER PATIENTS
Authors: Hara Takeo , Makino Tomoki , Yamasaki Makoto , Tanaka Koji , Miyazaki Yasuyuki , Takahashi Tsuyoshi , Kurokawa Yukinori , Nakajima Kiyokazu , Mori Masaki , Doki Yuichiro 
Published: September 2018

Abstract

Background
Neoadjuvant chemotherapy (NAC), a standard treatment for locally-advanced esophageal cancer, often achieves significant antitumor effect as clinically or microscopically confirmed. However, how chemotherapy histologically impacts upon normal tissues, in particular lymphatic vessels, adjacent to a tumor remains unclear.

Methods
A total of 137 patients who underwent curative esophagectomy with (NAC group n = 62)/without (nonNAC group n = 75) NAC for thoracic esophageal cancer in our department from 2004 to 2012 were analyzed. The number of lymphatic vessels (NLV) adjacent to primary tumor (within 1000μm from the edge of tumor) in lamina propria mucosae layer was assessed by immunostaining of D2–40 and its association with clinico-pathological parameters was analyzed.

Results
The NLV was significantly lower in the NAC group as compared with the nonNAC group (NAC vs nonNAC; 19.1 ± 9.0 vs 22.8 ± 8.6, P = 0.014). In the nonNAC group, when classified into two (high vs low NLV) groups by using the cutoff value of the median NLV in nonNAC group, NLV did not correlated with any clinico-pathological factors including age, gender, tumor location, pT, pN, pM, ly, v, and overall survival. On the other hand, in the NAC group, high NLV (classified by the same cutoff value as noted above) was significantly associated with good histological response (grade1b-2) (high vs low NLV; 52 vs 26%, P = 0.026) and less development of lymph node recurrence (16 vs 40%, P = 0.029) but not with other parameters including age, gender, tumor location, pT, pN, pM, ly, and v. Notably, the high NLV group showed the more favorable 5-year overall survival compared to the low NLV group (61 vs 49%, P = 0.0041). Multivariate analysis of overall survival further identified low NLV (HR = 3.68, 95%CI 1.54–10.83, P = 0.0005) to be one of independent prognostic factors along with pT(HR = 2.87, 95%CI 1.37–6.35, P = 0.0050) and pN(HR = 4.04, 95%CI 1.53–13.89, P = 0.0034) in the NAC group.

Conclusion
NAC might decrease the number of lymphatic vessels adjacent to primary tumor in resected specimen, and this number was associated with tumor response to NAC and long-term outcome in patients who underwent NAC plus surgery.

Disclosure
All authors have declared no conflicts of interest.
PS02.082: OPTIMAL TIMING FOR ASSESSMENT OF TUMOR RESPONSE TO NCRT WITH MRI IN PATIENTS WITH ESOPHAGEAL CANCER
Authors: Borggreve Alicia , Heethuis S , Goense L , Van Rossum P , Van Lier A L H M W , Hillegersberg Richard , Ruurda Jelle , Lagendijk J , Mook Stella , Meijer G J 
Published: September 2018

Abstract

Background
Accurate identification of esophageal cancer patients with a pathologic complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) could enable safe omission of surgery in these patients. Diffusion-weighted (DW-)MRI imaging during the first 2–3 weeks of nCRT has shown promising results in the prediction of pCR to nCRT in esophageal cancer. However, the optimal timing of scanning for pathologic response prediction is unclear. The purpose of this study was to assess the optimal timing of DW-MRI scanning during nCRT to predict pCR.

Methods
Consecutive patients with esophageal cancer undergoing nCRT (carboplatin/paclitaxel combined with 41.4Gy), followed by esophagectomy were eligible for inclusion in this prospective study. Patients underwent 6 sequential MRI scans of which one was performed prior to nCRT, and 5 were performed weekly during nCRT. The relative change in median tumor apparent diffusion coefficient (ADC) of the tumor on DW-MRI was determined at these six time points: ΔADC week(n)(%) = (ADCweek(n)-ADCbaseline)/ADCbaseline*100%. Response to nCRT was determined based on histopathologic evaluation of the resection specimen.

Results
A total of 123 MRI scans of 21 patients with locally advanced esophageal cancer were analyzed. A pCR was found in 23.8% (5/21). Results of the linear mixed model analysis and logistic regression analysis (per week) are depicted in Table 1. The difference in tumor ADC values between pCR and non-pCR patients was most prominent in week 3 of nCRT (after 12–14 fractions, P = 0.04).

Conclusion
The treatment-induced changes on DW-MRI during the first 3 weeks of nCRT appear to be the most promising for prediction of pCR in esophageal cancer patients. This information can be used in future DW-MRI validation studies, and eventually lead to accurate preoperative identification of pCR.

Disclosure
All authors have declared no conflicts of interest.