bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade of TRIM59 to enhance chemosensitivity of esophageal cancer cell to cisplatin by upregulating p53 expression.
Authors: Liu Rong Feng , Shi Jian , Duan Xiaoyang 
Published: May 2020

e16509 Background: TRIM59 is the one of TRIM family characterized by an N-terminal really interesting new gene (RING)-finger domain, followed by two zinc-finger domains named B2 box and a coiled-coil (CC). Ubiquitination plays a vital role in the degradation of many kinds of proteins that function in the intracellular signaling pathway, cell cycle, DNA repair and transcriptional regulation. Because of the RING-finger domain, TRIM59 protein functions as E3 ubiquitin ligase activity and can selectively target ubiquitin-modified proteins for proteasomes or degradation. In additional, accumulating finding results have shown the TRIM proteins promote positively or negatively carcinogenesis. Here we focus on the TRIM59 protein: oncogenic activity in the promoting proliferation and metastasis of esophageal cancer cell. Methods: None. Results: Human esophageal cancer cells’ motility adopts various modes resulting in the HESC progression and poor survival of patients. We proved that TRIM59 is aberrantly up-regulated in metastatic human esophageal cancer (hESC) than adjacent normal esophageal tissue, which is on behalf of poor survival and advanced TNM state among the hESC patients. At the molecular level, we proved TRIM59 as an E3 putative ubiquitin ligase targets the p53 protein leading to the increased degradation of p53 resulting in the less chemotherapy sensitivity to cisplatin. TRIM59 knockdown in hESC cell lines reduced TRIM59 expression and promotes p53 protein level and decreased the proliferation, clone formation, migration. At the same time, hESC cell lines showed more sensitive to the cisplatin in the cell line treated with knockdown of TRIM59. These findings establish the relationship between TRIM59 and p53 and chemotherapy sensitivity of cisplatin and TRIM59 may be a promising prognostic indicator for esophageal squamous cell carcinoma (ESCA) patients. Conclusions: We have confirmed that the up-regulation of TRIM59 in human esophageal cancer tissues closely correlates with poor prognosis of patients and TRIM59 serves as an oncogene promoting the proliferation and metastasis of esophageal cancer. The study demonstrates that knockdown of TRIM59 inhibited the growth and invasion of Eca109 cancer cells and strengthened the chemosensitivity to cisplatin through the mechanism of increasing the p53 expression. These results suggest that combination of TRIM59 knockdown with cisplatin might provide a promising strategy to treat the patients with esophageal cancer.
Initial safety run-in findings with bavituximab plus pembrolizumab in patients with advanced gastric or gastroesophageal cancer.
Authors: Chau Ian , Park Haeseong , Lee Jeeyun , Rege Jessicca Martin , Culm-Merdek Kerry , Bendell Johanna C. 
Published: May 2020

e16537 Background: Bavituximab, an investigational, chimeric monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine (PS), is being evaluated in combination with pembrolizumab in patients with advanced gastric and gastroesophageal junction (GEJ) cancer. Bavituximab binds in a high-affinity complex with β2-glycoprotein and PS to reverse immunological non-responsiveness and activate multiple immune cell receptors. Post-hoc data from the Phase III Sunrise second-line lung cancer study indicated that patients who progressed on study treatment with bavituximab plus docetaxel and continued with a checkpoint inhibitor showed significantly improved overall survival. Cumulative data suggest that bavituximab may potentiate pembrolizumab-mediated checkpoint inhibition, potentially increasing overall clinical benefit. ONCG100 is a phase 2, multicenter, open-label, single-arm global study designed to assess the safety, tolerability and efficacy of bavituximab and pembrolizumab when administered in combination to advanced gastric or GEJ adenocarcinoma patients, regardless of PD-L1 status, who have progressed on or after at least one prior standard therapy (NCT04099641). Methods: The safety run-in phase of the trial evaluated the safety and tolerability of de-escalating doses of bavituximab when administered in combination with the approved dose and schedule of pembrolizumab (200mg, Q3W). Adverse events were evaluated by CTCAE v5.0. Results: Three patients enrolled and completed the safety-run in phase of the study where bavituximab was administered at the starting dose of 3 mg/kg QW in combination with pembrolizumab. There were no dose-limiting toxicities observed during the 21-day monitoring period. A total of 4 treatment emergent adverse events were observed; 2 of which were reported as related to treatment with bavituximab (arthralgia and fatigue, both grade 1). There was one treatment-unrelated SAE reported (chylous ascites, grade 2), which resolved allowing the patient to continue treatment. Conclusions: The 3 mg/kg dose of bavituximab was readily combined during the safety run-in phase of the study with the approved dose of pembrolizumab. The AE profiles for this combination were manageable and expected given the known profiles of each agent. Based upon these findings, the recommended dose for expansion for the combination was declared and the expansion phase of the study opened. Updated safety data from the study will be presented. Clinical trial information: NCT04099641 .
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated to systemic chemotherapy for gastric cancer with diffuse peritoneal metastases in a palliative setting.
Authors: Bonnot Pierre Emmanuel , Rabel Thomas , Lintis Alexandru , Laplace Nathalie , Bakrin Naoual , Kepenekian Vahan , Villeneuve Laurent , Chauvenet Marion , Bouarioua Nadia , Alyami Mohammad , Glehen Olivier 
Published: May 2020

e16538 Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is emerging as a new intraperitoneal laparoscopic delivery of chemotherapy to treat peritoneal metastasis (PM). First results from several malignancies appear promising in small series of patients. Prognosis of PM from gastric cancer (GC) is poor. Median survival is ranging from 3 to 13 months with systemic chemotherapy (SC) alone. Purpose: to evaluate the feasibility and potential benefits of PIPAC associated to SC in GC with PM in a palliative setting Methods: From a prospective database, we identified 91 consecutive patients considered with isolated unresectable PM from GC treated by an alternance of SC and PIPAC with low-dose cisplatin-doxorubicin (ratio 2/1) between January 2016 and January 2019 in our institution. End of follow-up was January 2020. Results: Median age was 56 years, 86% of patients had a signet ring cell adenocarcinoma with 86.7% of synchronous PMs.Median Peritoneal Cancer Index was 16 (3-39). A total of 346 PIPAC were performed with a median of 3 per patient (1-18). Median number of SC lines was 3 (2-3) resulting in a median number of SC cycles of 14 (11-20). After a median follow-up of X months, 21 patients were still alive. In the whole population, median OS from diagnosis was 15.1 months. PIPAC was introduced in association to first-line SC as maintenance or intensification therapy in 75 patients with a median survival from diagnosis of 14.7 months and a median PFS from PIPAC introduction of 6.3 months. For 16 patients, PIPAC was introduced due to progression after a first or second line of SC leading to a median OS of 20 months after diagnosis and 5.9 months after PIPAC introduction. Reasons to stop PIPAC were cancer progression, intraperitoneal access difficulties or PIPAC related morbidity, a cytoreductive surgery attempt in 61.7%, 19.8% and 18.5% respectively. A cytoreduction and HIPEC attempt was performed for 12 patients before 3 PIPAC and 3 after 3 PIPAC or more, leading to a median OS of 19 months for those patients. Twelve (13,2%) patients developed extra-peritoneal metastases during PIPAC. Conclusions: PIPAC appears safe and feasible showing promising results in control of PMs from gastric origin. Further randomized studies are required to document its benefits compared to SC alone.
Outcomes relative to paclitaxel dose-intensity when administered with ramucirumab in gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Allen Michael J , Suzuki Chihiro , Espin-Garcia Osvaldo , Ma Lucy Xiaolu , Honório Marta , Lyra-Gonzalez Ivan , Chen Eric Xueyu , Darling Gail Elizabeth , Yeung Jonathan , Kalimuthu Sangeetha , Wong Rebecca , Veit-Haibach Patrick , Jang Raymond Woo-Jun , Elimova Elena 
Published: May 2020

e16539 Background: Combination paclitaxel (PTX) and ramucirumab (RAM) is standard second-line treatment for gastric and GEJ cancers. Peripheral neuropathy (PN) is considered a potential obstacle to administering a maximal dose of PTX, potentially limiting efficacy. We sought to determine the dose-intensity and outcomes for patients receiving this treatment. Methods: A retrospective analysis of gastric and GEJ cancer patients treated at Princess Margaret Cancer Centre (2012-2017) was performed identifying all patients who received PTX and RAM during their treatment course. The primary objective was to determine the dose-intensity of PTX administration. Secondary objectives included identification of the reason for dose-reduction (DR), and comparing progression-free survival (PFS) and overall survival (OS) in relation to PTX DR. Results: 45 patients were included in the study. Mean age was 57.2y, 34 (76%) were male, 7 (16%) were Asian, 5 (11%) patients were her2 positive. 42 (93%) patients received first-line treatment containing a potential neuro-toxic agent (cisplatin, oxaliplatin, docetaxel or paclitaxel). 22 (49%) subjects required PTX DR. The median number of cycles administered for subjects not requiring a DR and those with dose-reduced PTX was 3 v 6 (p < 0.001) respectively, with the median number of PTX doses administered 8 v 15 (p0.0022). The mean dose-intensity was 100 v 83% (p < 0.001). PN was the reason for DR in 32% (n = 7) of subjects, whilst neutropenia was 41% (n = 9). The reason for treatment cessation was disease progression in 91% of subjects, irrespective of whether they required a DR or not. Median PFS was 2.8m (95% CI 2.1-4.8) (100% dose PTX) and 5.5m (95% CI 4.8-8.6) in those requiring a DR (p0.0006). Median OS, measured from the initial diagnosis of incurable/metastatic disease was 16.4m (95% CI 13.7-22.9) and 18.5m (95% CI 14.9-47.5) respectively (p0.0953). Conclusions: Approximately half of the patients required a PTX DR, of whom a clinically significant 32% were DR due to PN, slightly less than those DR due to neutropenia. PFS was longer in those requiring a DR, which may reflect that those on treatment longer are more likely to experience toxicity and require a subsequent DR. PTX DR did not significantly affect OS, thus whilst PTX toxicity remains a clinical concern we did not identify that a DR resulted in an appreciable difference in treatment efficacy.
Concurrent docetaxel and S-1 compared with oxaliplatin and s-1 as first-line therapy for advanced gastric adenocarcinoma: A retrospective study.
Authors: Tan Siyi , Xie Jiaqi , Wei Jia , Liu Qin , Du Juan , Liu Baorui , Yang Yang 
Published: May 2020

e16540 Background: The aim of this study was to compare the efficacy and safety between docetaxel plus S-1 with oxaliplatin plus S-1 therapy as first-line treatment for advanced gastric adenocarcinoma. Methods: Patients, who had received docetaxel plus S-1 or oxaliplatin plus S-1 as first-line chemotherapy for advanced gastric adenocarcinoma, were retrospectively reviewed. Kaplan–Meier curve and log-rank test were used to analyze the survival. Prognostic factors were estimated by Cox regression. Adverse events (AEs) were evaluated using CTCAE 4.0. Results: One hundred and twenty-nine patients received concurrent docetaxel plus S-1, whereas 130 received oxaliplatin plus S-1. The median progression-free survival (PFS) and overall survival (OS) in docetaxel and oxaliplatin groups were 6.0 and 8.2 months ( P= 0.025), 14.7 and 15.7 months ( P= 0.697), respectively. Multivariate Cox regression suggested that chemotherapy regimen (docetaxel vs oxaliplatin; HR = 1.535, 95% CI:1.092-2.156, P = 0.014), Eastern Cooperative Oncology Group performance status (ECOG PS 3-4 vs 0-2; HR = 4.213, 95% CI: 2.246–7.903, P< 0.001), Lauren type (Intestinal vs Diffuse, HR = 0.471, 95% CI: 0.307–0.725, P= 0.001, Mixed vs Diffuse, HR = 0.649, 95% CI: 0.442–0.953, P= 0.028), and number of metastases (HR = 2.097, 95% CI: 1.421–3.095, P< 0.001) had significant effects on PFS. Multivariate Cox regression suggested that pathologic types (signet-ring cell carcinoma vs adenocarcinoma; HR = 1.688, 95% CI:1.152-2.472, P = 0.007), Lauren type (Intestinal vs Diffuse, HR = 0.637, 95% CI: 0.414–0.982, P= 0.041), number of metastases (HR = 1.7, 95% CI: 1.154–2.504, P= 0.007) had significant effects on OS.The most common grade 3-4 adverse events were leukopenia (3.1% vs 7.8%), neutropenia (7.7 vs 12.3%), anemia (13.2% vs 14.6%), thrombocytopenia (2.3% vs 10.8%), peripheral neuropathy(0.8% vs 7.8%)and Nausea/vomiting/ anorexia (1.6% vs 3.8%). Conclusions: Concurrent oxaliplatin plus S-1 therapy appears to be effective as first-line treatment in advanced gastric and has an acceptable safety profile. For patients in good physical condition, we prefer to recommend oxaliplatin combined with S-1 for treatment.
Preliminary results of a phase II study of neoadjuvant immune checkpoint inhibitor IMC-001 (anti-PD-L1 monoclonal antibody) in patients with resectable gastrointestinal cancers (NeoChance Study).
Authors: Im Hyeon-Su , Song Joon Seon , Jo Woo Ri , Yoo Moon-Won , Kim Yong-Hee , Kim Hyeong Ryul , Song Ho June , Kim Do Hoon , Choi Kee Don , Lee Jeong Hoon , Ahn Ji Yong , Na Hee Kyong , Song Ki-won , Park Sook Ryun 
Published: May 2020

e16542 Background: Immune checkpoint inhibitors have shown survival benefits in unresectable/metastatic gastric cancer (GC), esophageal cancer (EC), and hepatocellular carcinoma (HCC). Based on scientific rationale for neoadjuvant immunotherapy, including enhanced immune recognition, we initiated a phase II study of IMC-001, a novel PD-L1 targeting fully human monoclonal Ab in the neoadjuvant setting for resectable GC, EC, and HCC. Methods: This is a prospective, open-label, phase II study of neoadjuvant IMC-001 (20 mg/kg iv every 2 weeks for 2 cycles) across three cohorts of resectable gastrointestinal cancers (GC, EC, HCC). The primary endpoint is major pathologic response rate ( < 10% of viable tumor cells) and secondary endpoints include safety, feasibility, R0 resection rate, clinical tumor response rate/disease control rate (DCR), progression-free survival, relapse-free survival, and overall survival. Exploratory endpoints include immune monitoring and biomarker analysis in tumor tissues, blood, and stool. Results: From Sep. 2019 to Feb. 2020, 14 eligible patients (pts) (6 HCC; 5 GC; 3 EC) were enrolled; male (79%), median age = 63 yrs (range, 40-72), clinical stage (AJCC 8th) I (57%)/II (21%)/III (21%). 12 pts completed 2 cycles of neoadjuvant IMC-001 and one pt stopped after one cycle due to G3 autoimmune hepatitis, which was only G3 adverse event (AE) and resolved with steroid. Other AE included G2 hyperthyroidism (n = 1), G1 pruritus (n = 2), G1 rash (n = 1), G1 myalgia (n = 1), G1 arthralgia (n = 1), G1 diarrhea (n = 1), G1 cough (n = 1), G1 palate discomfort (n = 1), and G1 chest discomfort (n = 1). So far, 10 clinical response-evaluable pts showed a 100% DCR and underwent surgery, which was all R0 resection. Post-treatment surgery specimens showed various degrees of lymphocyte infiltration in intratumoral or peritumoral areas ranging from 10% to 90%, which was increased compared to pre-treatment biopsies. In HCC pts, adjacent hepatic parenchyma showed mild to moderate, diffuse portal inflammation regardless of Hepatitis B virus status and minimal and moderate fatty change. IHC for PD-L1 using 22C3, SP263 and SP142 clones showed similar results among three Abs with relatively low expression regardless of tumor types (range, 0-20%). Conclusions: Neoadjuvant IMC-001 seems to be well tolerated and have preliminary immune modulating activity in resectable GC, EC, and HCC pts. The study is ongoing and the updated clinical and immunologic results will be presented. Clinical trial information: NCT04196465 .
The microbial characteristics of esophageal squamous cell carcinoma (ESCC) and healthy subjects.
Authors: Lv Wenjing , Zuo Jing , Wang Yudong , Fan Zhisong , Feng Li , Wang Long , Zhang Xue , Zhang Qi , Jiang Da 
Published: May 2020

e16546 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive human malignancies. Investigation of the esophageal microbiome is a relatively new field. Recently, we discovered the microbial characteristics among the healthy subjects and patients with ESCC. Methods: DNA was extracted from blood, oral mucosa, saliva, urine, faeces samples from 28 healthy and 26 ESCC cases. Pfu high fidelity DNA polymerase was used for PCR amplification. The PCR amplification products were quantified. Then the sequencing library was prepared. The V3V4 region of the 16S ribosomal RNA gene was sequenced with Novaseq-PE250. In order to comprehensively evaluate the α diversity of microbial communities, we used Chao1 and Observed Species indices to characterize the richness, Shannon and Simpson indices to characterize the diversity. PCoA, NMDS and Distance Matrix were used to analyze differences in β diversity. Results: At the phylum level, the top 5 microbes in both ESCC and healthy samples are Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria. At the genus level, the microbial composition of patients with ESCC and healthy samples was significantly different. However, the bacteria composition in blood samples was the same as the urine samples not only in patients with ESCC but also in healthy samples. Blood and urine samples of patients with ESCC contained Cupriavidus, Vogesella, Acinetobacter, Sphingomonas, Ochrobactrum, Sediminibacterium and the healthy samples contained Ochrobactrum, Sediminibacterium, Acinetobacter. The same rule occurred in oral mucosa and saliva samples. Faeces samples of esophageal cancer patients included Streptococcus, Lactobacillus, Bifidobacterium, Gemmiger, Blautia, Coprococcus. However, the healthy samples included Gemmiger, Roseburia, Faecalibacterium, Bacteroides, Dialister, Bifidobacterium. A comparison of esophageal cancer patients and healthy samples showed that α diversity was significantly different both in blood samples and urine samples. No statistically significant differences were detected within oral mucosa, saliva, faeces samples of esophageal cancer patients and healthy samples. β diversity was different in urine samples. Conclusions: Further understanding of the changes in the esophageal microbiome may help us understand the pathogenesis and the natural history of disease and present potential therapeutic approaches.
Exploration of the expression and significance of IL-6, STAT3 and PD-L1 in esophageal squamous cell carcinoma.
Authors: Zhou Yicheng , Zhu Honglei , Pang Xuezhou , Shen Yang , He Yu , Ma Daiyuan 
Published: May 2020

e16554 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide and has a very high morbidity and mortality rate. The IL-6/STAT3 axis can simultaneously promote the expansion of immunosuppressive cells.This study detected IL-6, STAT3 and PD-L1 in ESCC and analyzed the potential clinical application value. Methods: Between July 2018 and April 2019, 70 ESCC patients underwent radical thoracic surgery at Affiliated Hospital of North Sichuan Medical College. RT-PCR was used to detect PD-L1, IL-6, and STAT3 mRNA expression in cancer and adjacent normal tissues. Western blot detection of PD-L1, IL-6, and STAT3 was performed in 40 cancer and adjacent normal tissues. The correlation of PD-L1, IL-6 and STAT3 protein expression with tumor invasion depth, tumor size, lymph node metastasis,clinical stage and other clinicopathological characteristics as well as the correlation between the three proteins were analyzed statistically. Results: The mRNA levels of PD-L1, IL-6, and STAT3 in 70 ESCC patients were significantly different between cancerous and adjacent normal tissues (P < 0.001). In 40 ESCC patients, 28 ESCC tissues showed significantly higher PD-L1 expression than adjacent normal tissue (28/12, P < 0.001), 29 ESCC tissues showed significantly higher STAT3 expression (29/11,P = 0.009 ), and 27 ESCC tissues showed significantly higher IL-6 expression (27/13,P = 0.042). There was no correlation between PD-L1 expression and age, sex, tumor site or maximum tumor diameter, but PD-L1 expression showed a positive correlation with T stage (P = 0.009), lymph node metastasis (P = 0.044), and clinical stage (P = 0.033). There was no correlation between STAT3 expression and age, sex, tumor site, maximum tumor diameter, lymph node metastasis or clinical stage, but STAT3 expression showed a positive correlation with T stage (P = 0.025). IL-6 expression was not correlated with age, sex, maximum tumor diameter, lymph node metastasis or clinical stage, but IL-6 expression showed a positive correlation with T stage ( P = 0.003)and tumor site (P = 0.011). In addition, PD-L1 expression showed a positive correlation with STAT3 (P = 0.013) and IL-6 ( P = 0.008), and STAT3 showed a positive correlation with IL-6 ( P = 0.027). Conclusions: PD-L1, IL-6, and STAT3 are highly expressed in ESCC and their protein levels exhibit a positive correlation. The IL-6/STAT3 signaling pathway proteins may be a potential biomarker predicting the efficacy of immunotherapy by affecting the expression of PD-L1.