bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apatinib to enhance chemosensitivity of gastric cancer to paciltaxel and 5-fluorouracil.
Authors: Cheng Xiangdong , Xu Zhiyuan , Chen Jiahui , Zhang Chunli , Yu Jianfa , Teng Fei , Zheng Guowei , Lv Hang 
Published: September 2018

e15545 Background: Patients (pts) with late-stage gastric cancer (GC) have a poor prognosis. Targeted agent combined with chemotherapy is expected to yield clinical benefits. Apatinib, a novel tyrosine kinase inhibitor targeting VEGFR-2, improves outcomes in patients with metastatic GC as a third line of treatment. Hence, we aimed to assess the efficacy and safety of apatinib plus chemotherapy in vivo and in vitro. Methods: The MGC803 cell viability was assessed by CCK-8 assay, and the interactions between apatinib and conventional cytotoxic agents revealed by combined index (CI) values were calculated using Calcusyn 2.0 software. We also used a zebrafish embryo xenograft model to validate the synergistic interactions. Furthermore, 4 pts with late-stage GC were enrolled to receive paclitaxel (PTX)/S1 chemotherapy plus apatinib in conversion surgery. Apatinib was administered 500 mg once a day continuously, PTX 130 mg/m2 was given on day 1, and S-1 was administered at 80 mg/m2for 14 consecutive days, followed by 7 days of rest. Treatment was administered for 3-5 cycles, but the last cycle did not include apatinib. Results: Apatinib showed synergistic interactions with both PTX and 5-Fu in vivo (CIs < 1). The zebrafish embryo xenograft model also demonstrated that addition of 0.25 µg/mL apatinib significantly enhanced the tumor growth inhibition effects of 25 (38.39% vs. 11.77%, P < 0.001) and 50 ng/fish (43.58% vs. 17.88%, P < 0.05) 5-Fu, as well as those of 0.75 ng/fish (53.62% vs. 35.22%, P < 0.001) and 1.5 ng/fish (59.71% vs.46.73%, P < 0.01) PTX. Apatinib plus S1/paclitaxel chemotherapy was well tolerable before surgery. Objective response to preoperative SPA treatment was achieved in all pts. No posteroperative bleeding event or wound-healing complication was observed. No postoperative mortality occurred and morbidity was encountered. Pathological examination showed that all pts had grade Ib pathological response. Conclusions: The experimental data suggested that apatinib improves the efficacy of PTX and 5-Fu both in vitro and in vivo. Clinical evidence showed that combination of PTX/S1 chemotherapy with apatinib has promising efficacy and acceptable safety profile in late-stage GC, especially in the conversion surgery.
Analysis of contrast-enhanced CT textures to predict survival of patients with primary esophageal cancer treated with definitive chemotherapy and radiation therapy.
Authors: Wang Qifeng , Lang Jinyi , Li Tao , Lv Jiahua , Cao Bangrong , Fan Yu , Wang Yi , Xiao Miyong 
Published: September 2018

e15559 Background: To determine the association between tumor heterogeneity, morphologic tumor response, and overall survival in primary esophageal squamous cell cancer (ESCC) treated with chemotherapy and radiation therapy (CRT). Methods: After an institutional review board waiver was obtained, 57 clinical stage III patients with CRT were analysis. All patients underwent contrast-enhanced CT before RT and after RT 40Gy between 2012 and 2015 were analyzed in terms of whole-tumor texture, with quantification of entropy, uniformity, max and mean gray-level intensity, kurtosis, standard deviation of the histogram, mass and skewness for fine to coarse textures (filters 1.0-2.5, respectively). Whole-tumor texture was analyzed using IBEX 1.0β. The association between texture parameters and survival time was assessed by using Kaplan-Meier analysis and a Cox proportional hazards model. Results: The median, 1 and 3 years overall survival (OS)were 20.2 months 75.4% and 32.1% .Only the clinical factor posttreatment volume (median OS, 28.4 vs 14 months; P = 0.016), pretreatment median entropy of 0.069 or greater (median OS, 31.6 vs 17.0 months; P = 0.022), and medium max gray-level intensity of 11 or greater (median OS, 33.2 vs 11.7 months; P = 0.034),Coarse kurtosis of 58.4122 or greater (median OS, 28.4 vs 15.0months; P = 0.036) were associated with improved survival time. Survival models that included a combination of pretreatment entropy and posttreatment volume. We used a 3-point risk classification index with equal weights given to entropy and volume predict OS and progression-free survival (PFS). The median OS for high-, medium-, and low-risk groups were12.2, 19.1, and 31.7 months,respectively (P = 0.013). Validated the risk model in PFS, The median PFS for high-, medium-, and low-risk groups were 8.0, 18.5, and not received months,respectively (P = 0.043). Conclusions: Pretreatment texture parameters are associated with survival time, and the combination of pretreatment texture parameters and post volume performed better in survival models.
Racial differences of iron deficiency anemia in gastric cancer.
Authors: Perimbeti Stuthi , Correa Erika , Degen Kathleen , Hanson Shaun Bryan , Lee William May , Hou Kevin Ye , Jain Maneesh Rajiv , Ward Kristine Marie , Styler Michael , Nandi Neilanjan 
Published: September 2018

e15564 Background: One of the six domains of health care quality identified by the Institute of Medicine in 2001 was equitable care.1 While disparities in cancer are often expressed in terms of mortality, comorbidities such as iron deficiency anemia (IDA) that can be caused by less comprehensive or less timely treatment of gastrointestinal malignancies also impact quality of life and may be considered as a metric of equitable care. Methods: Using data from the Healthcare Cost and Utilization Project (HCUP), total numbers of U.S. admissions with gastric cancer listed as primary diagnosis were recorded for each year between 1999-2014. The subset of these numbers with IDA listed as a secondary diagnosis were recorded to derive a prevalence of IDA within this gastric cancer population. The relative rate of African American and Hispanic IDA prevalence were compared to Caucasians for each year. Within each ethnic subset, cost, length of stay, and inpatient mortality were compared. Results: The relative rate of iron deficiency in gastric cancer for African Americans versus Caucasians was 1.745 and for Hispanics versus Caucasians was 1.665. Hospital cost by ethnic group: Caucasians $55,359, African Americans $62,020, Hispanics $83,914. Length of stay in days by ethnic group: Caucasians 9.13, African Americans 10.12, Hispanics 10.17. Inpatient mortality by ethnic group: Caucasians 4.51%, African Americans 4.02%, Hispanics 2.29%. All values were significant (p < 0.05). Conclusions: African American and Hispanic populations are at increased risk of iron deficiency anemia in the setting of gastric cancer as compared to Caucasians. This was associated with increased cost and length of stay to a lesser degree. Surprisingly, Caucasians still demonstrated the highest mortality rate, followed by African Americans and Hispanics. This suggests that though ethnic disparities are still evident as of 2014 they may not accurately reflect mortality but still continue to impact morbidity. As this comorbidity impacts quality of life, it may be a target for future metrics or interventions.
Regulatory-T cells (Tregs) in tumor infiltrating lymphocytes (TILs) from patients with advanced gastric cancer (AGC) after chemotherapy containing ramucirumab.
Authors: Kotani Daisuke , Togashi Yosuke , Kawazoe Akihito , Doi Toshihiko , Nishikawa Hiroyoshi , Shitara Kohei 
Published: September 2018

e15570 Background: Vascular endothelial growth factor-A (VEGF-A) and VEGF recepter-2 (VEGFR-2) axis is known to induce Tregs in tumor bearing mice. Ramucirumab (RAM), a monoclonal antibody for VEGFR-2, was recently approved for patients with AGC. However, little is known about the influence of RAM on Tregs in TILs from AGC patients. Methods: Patients with AGC who had been planned to receive chemotherapy containing RAM were prospectively enrolled for this study from January 2016 to August 2016. Paired samples were obtained from primary tumor at pre- and post-RAM therapy to analyze immune profiles of TILs using flow cytometry assay. Results: A total of 17 patients were analyzed. Median age was 68 years old (range, 46-79). All patients received one or more previous chemotherapy. RAM containing regimens included RAM+paclitaxel (n = 13), RAM monotherapy (n = 3) and RAM+irinotecan (n = 2). FOXP3highCD45RA-CD4+ T cells (effector Tregs: eTregs) in CD4+ T cells was significantly decreased after RAM therapy compared with that in baseline (mean, 19.5% vs.13.6%, P = 0.036). In contrast, no significant change of CD8+ T cells was observed (mean, 36.7% vs. 36.0%, P = 0.86). Expression of programmed cell death-1 (PD-1) on CD8+ T cells was tended to be decreased after RAM therapy. Conclusions: eTregs in TILs was suggested to be decreased after RAM-containing therapy which warrants further evaluation in a larger cohorts. This observation might be a rationale to use RAM as an immunomodulator in combination of immune checkpoint inhibitors for AGC.
A personalized, web-based prognostic tool for resectable gastric cancer.
Authors: Jabo Brice , Morgan John W. , Aljehani Mayada A. , Selleck Matthew J , Lin Albert Y. 
Published: September 2018

e15575 Background: Gastric cancer (GC) mortality remains high, with a 5-year survival of 30 percent. For patients with resectable GC, mortality varies depending on both patient and tumor characteristics. The current study sought to develop a web-based prognostic model to assist patients and health care providers in decision making regarding either surgery-only or adjuvant chemoradiotherapy (CRT). Methods: California SEER data was used and records, including demographic, pathologic, and treatment information, for 2,583 patients diagnosed with stage IB to III GC and treated with either surgery only or adjuvant CRT from 2006 to 2013 were retrieved. Purposeful selection using Cox regression model was used to identify important mortality predictors. Additionally, with simple random sampling, 70% of the data were assigned to the training set and the remaining 30% were assigned to the test set. Furthermore, generalized boosted classification model was trained using the training set and validated using the test set. Area under the curve (AUC) of the receiver operating characteristic (ROC), sensitivity, specificity and accuracy were determined for 5- and 10-year mortality. Results: The median survival was 33 months for patients in the training set, and 32 for the test set. Predictors included in the model were age, ethnicity (Asian/other, Hispanic, non-Hispanic black and non-Hispanic white), T-stage, histology (intestinal, diffuse and other), presence of signet ring (yes/no), proximal location (yes/no), lymph node ratio, and CRT following surgery (yes/no). Validation of the model on the test set showed as follows: AUC, sensitivity, specificity and accuracy of 0.78(95%CI = 0.75,0.82), 0.75, 0.65 and 0.70 for 5-year survival and 0.77(95%CI = 0.74,0.80), 0.79, 0.55 and 0.70 for 10-year survival. Conclusions: The proposed web-based prognostic tool using readily available patient and tumor characteristic provides validated and personalized prognostic information to aide clinicians and patients in GC adjuvant treatment decision process. [Table: see text]
Survival impact of adjuvant regimens for advanced gastric cancer after radical D2 resection in a Peruvian population.
Authors: Rioja Patricia Elizabeth , Enriquez Daniel , Pacheco Christian , Morante Zaida , Guevara Andres , Castro Victor , Montenegro Paola Catherine , Payet Eduardo 
Published: September 2018

e15576 Background: The benefit of chemoradiotherapy(CRT) or chemotherapy (CT) for gastric cancer with high metastatic lymph node involvement after complete radical D2 resection is still controversial, previous studies had reported better disease free survival (DFS) but no differences in overall survival (OS). Our aim was to compare DFS and OS between CRT and CT. Methods: Retrospectively, 201 medical records were reviewed from patients with advanced gastric cancer (nodes +ve) after complete radical D2 resection between 2008 and 2012 at Instituto Nacional de Enfermedades Neoplasicas (Peru). Patients received CRT (5FU and RT as Macdonald’s protocol) or CT (capecitabine 2g/m2/14days + oxaliplatin 135mg/m2/day1 q21d for 6months). We describe clinical and pathological characteristics, DFS/OS with univariate and multivariate cox analysis were performed. Results: Mean age was 54.4years [19-83] and 17.9% were < 40years. Distal localization (46%), high histological grade (69.7%) and poorly cohesive subtype (38.3%) were most frequent characteristics among patients, 140(69.7%) and 130(64.7%) were T4 and N3, respectively. From 201 patients, 134 underwent to CRT and 67 to CT, with no clinical differences between groups. We observed a significant higher nodal ratio in CT group (0.27 vs 0.35, p = 0.009). 69.5% patients completed treatment with CRT, while only 54.5% in CT (p = 0.04). At 5years median of follow-up, 66 (49.3%) and 26(38.8%) recurrences were documented in CRT and CT groups, respectively. Median DFS were 19 and 23 months in CRT and CT group (HR:1.04, 95%CI:0.7-1.4, p = 0.8), while median OS were 25 and 26 months, respectively (HR:1.07, 95%CI:0.75-1-5, p = 0.6). At multivariate analysis, higher T stage and nodal ratio were associated to worse DFS, and patients who completed treatment were associated to better DFS (HR:0.59, 95%CI:0.4-0.8, p = 0.004). Higher T stage and nodal ratio had significant negative impact on OS. Conclusions: We found a benefit of CT over CRT in gastric cancer with high metastatic lymph nodes, however in our population it was not statistically significant, indeed further larger clinical trials are needed. In this study, higher T stage and nodal ratio were associated to worse prognosis.
Effect of long non-coding RNA EIF3J-AS1 on multi-drug resistance and autophagy in gastric cancer.
Authors: Luo Yuhao , Zhou Rui , Huang Na , Sun Li , Liao Wangjun 
Published: September 2018

e15581 Background: Gastric cancer (GC) is a leading cause of cancer mortality worldwide, oxaliplatin and epirubicin based chemotherapy are one of the most important treatment options for GC patients. However, drug resistance, especially multi-drug resistance remains a major obstacle for successful chemotherapy. Recently, long non-coding RNAs (lncRNAs) have been widely identified to play emerging roles in diverse physiological and pathophysiological processes including drug resistance. Our previous bioinformatics analysis showed long non-coding RNA EIF3J-AS1 was a potential multi-drug resistance gene, but the underlying mechanism is still unknown. Methods: We generated oxaliplatin resistance cells (MGC803/OXA) and epirubicin resistance cells(MGC803/EPI) based on parental gastric cancer cells MGC803. Relative expression levels of EIF3J-AS1 were measured by qRT-PCR. Transmission electron microscopy was used to measure autophagosomes. Rapamycin was applied to inducing autophagy while chloroquine and 3-methyladenine were used to block autophagy. Protein level of autophagy related genes were examined by Western Blot. Coexpression genes of EIF3J-AS1 from TCGA RNA-seq datas were analyzed by cBiportal. RNA immunoprecipitation was used to analyze endogenous microRNAs and mRNAs. Results: EIF3J-AS1 was significantly upregulated in MGC803/OXA and MGC803/EPI cells compared with parental cells MGC803. EIF3J-AS1 inhibition increased chemosensitivity to both oxaliplatin and epirubicin. Moreover, EIF3J-AS1 silence lead to the decrease of autophagy. Autophagy related gene ATG14 was identified as a downstream target gene. EIF3J-AS1 promoted ATG14 expression by directly interacting with and increasing stability of ATG14 mRNA, On the other hand, EIF3J-AS1 competitively sponged miR-188-3p and promoted ATG14 expression in a ceRNA-dependent way. Conclusions: LncRNA EIF3J-AS1 is a crucial regulator of multi-drug resistance by inducing autophagy in gastric cancer. Targeting EIF3J-AS1/ATG14 axis might be a new paradigm for cancer therapeutics.
ERBB pathway alterations in advanced gastric signet-ring cell carcinoma (SRCC) and the implications for targeted therapy.
Authors: Wei Jia , Xu Bo , Jin Shenying , Yu Lixia , Liu Baorui 
Published: September 2018

e15586 Background: Studies have shown that ERBB3 mutations are associated with poor clinical prognosis and ERBB3 targeted therapeutics can be effective against ERBB3 mutant-driven tumors. ERBB signal pathway plays a very important role in the initiation and progression of gastric cancer, however the ERBB2 expression and mutation rate is relative low especially in gastric SRCC. Thus, ERBB3 might be a promising target for the treatment in SRCC patients. The aim of this study is to speculate the prognostic and targeted therapy value in gastric SRCC by evaluating the mutation rate and type of ERBB3. Methods: 92 patients with histological diagnosis of advanced gastric SRCC were retrospectively selected. ERBB3 mutation was evaluated by next generation sequencing from formalin-fixed paraffin-embedded (FFPE) samples. ERBB2 expression was tested by immunohistochemistry. Correlations between ERBB2/3 status and clinical pathologic characteristics and overall survival (OS) were performed. Results: All of the 92 patients were diagnosed as local advanced or metastatic gastric SRCC (92.4% were stage III, 7.6% were stage IV). All the patients received 5-FU-based first-line chemotherapy. 14 out of all 92 patients were ERBB3 mutated SRCC, in which only 2 samples were ERBB2 positive. 12 of all the 14 mutations were in the extracellular domain, 2 were in the transmembrane region. There was no correlation between ERBB3 mutation and serosa invasion (P = 0.389) or lymph node metastasis (P = 1.000). The median OS was 20.5 months (95% CI = 10.05to 30.95 months) for patients with ERBB3 mutation, and 19.0 months (95% CI = 15.54 to 22.46 months) for patients without ERBB3 mutation (P = 0.567). There was no difference in OS according to HER2 positive or negative in ERBB3 mutated patients (14.8 months vs 20.5 month, P = 0.374). Conclusions: Our study demonstrated 15.2% of gastric SRCC patients harboring ERBB3 mutation, providing a potential subgroup of gastric SRCC for targeted treatment on ERBB pathway. No difference of OS was observed, probably due to the relative small sample size and low ERBB2 positive rate in SRCC patients. Further investigation on ERBB3 is warranted to clarify mechanisms of ERBB pathway in gastric SRCC.
Radical esophagectomy for thoracic esophageal squamous cell carcinoma followed by adjuvant radiotherapy with or without chemotherapy: Which is more beneficial?
Authors: Tu Yan , Peng Feng 
Published: September 2018

e15597 Background: The current guidelines of the National Comprehensive Cancer Network for thoracic esophageal squamous cell carcinoma(TESCC) are commended no additional treatments after surgery unless the margins are positive.The optimal therapeutic options in TESCC initially treated after surgery remains controversial .This retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy(RT) and chemoradiotherapy(CRT) in stage II or III TESCC patients who underwent curative esophagectomy. Methods: From January 2006 to December 2013 , 272 cases with pathological confirmed stage II or III TESCC, who had undergone complete esophagectomy, were eligible for analysis.Of these patients, 148 cases received postoperative CRT–at least 2 courses of cisplatin plus fluorouracil or paclitaxel– while the other 124 cases received RT(≥45Gy) alone.The primary end point was overall survival (OS) and the secondary endpoint were disease free survival (DFS) and toxic reactions. Results: In CRT and RTgroups,the OS rates at 1, 3 and 5 years were 91.8% vs 83.8% , 51.3% vs 31.5% and 25% vs 9.68% , respectively(P < 0.01).In CRT and RTgroups, the median OS were 39 months (95% CI, 31.6 to 46.3 months) and 30 months (95% CI, 21.0 to 38.9 months), respectively(P = 0.213), and the median DFS were 23 months (95% CI, 14.7 to 31.3 months) and 16 months (95% CI, 13.3 to 18.6 months),respectively(P = 0.155). Univariate and multivariate analyses showed stage, N stage and the number of lymph nodes removed were independent prognostic factors for OS. There were no statistically differences between the two groups for both recurrence and metastasis rates(P > 0.05). Toxic reactions, including myelosuppression and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P < 0.05). No significant differences in incidence of other toxic reactions were found between the two groups. Conclusions: Our results indicate that, in stage II or III TESCC patients, compared with postoperative RT,CRT has a tendency to improve survival. Toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.
The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.
Authors: Jin Shenying , Xu Bo , Yu Lixia , Fu Yao , Wu Hongyan , Fan Xiangshan , Liu Baorui , Wei Jia 
Published: September 2018

e15609 Background: Recent data supports a potentially significant role for immune checkpoint inhibitors in the treatment of gastric cancer. However, there are few data on the clinical implications of immunotherapy markers in gastric signet-ring cell carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), infiltration by CD3+ T cell, microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the relationship of each factor to survival in SRCC patients. Methods: SRCC samples from 89 patients were stained by immunohistochemistry to evaluate PD-L1, PD-1, CD3+ T cells, and MSI. EBV was detected by DNA in-situ hybridization. Results: All 89 patients had advanced gastric SRCC (89.9% were stage III, 10.1% were stage IV). All patients received 5-FU-based first-line chemotherapy. PD-L1 and PD-1 were expressed in 40.4% and 18.0% of the patients, respectively. There was a significant correlation between PD-L1 and PD-1 expression (r = 0.363, p < 0.001). There was loss of at least 1 of the 4 DNA mismatch repair (DNA-MMR) gene proteins in 32.6% of samples. However, there was no association between the expression of PD-L1, PD-1 or MSI status to overall survival (OS). Only 1 case out of 89 was EBV positive, with concurrent PD-L1 positivity, a high degree of CD3+ T cell infiltration and MSI. Increased CD3+ T cells numbers was associated with increased PD-1 expression (r = 0.256, p = 0.012) and MSI status (r = 0.208, p = 0.05). High CD3+ T cell infiltration was related to better OS (23.7 months, 95% CI: 19.0-38.0 vs 15.8 months, 95% CI: 13.0-22.0, p = 0.033), but was not an independent prognostic factor for survival after multivariate analysis (HR = 0.68, 95% CI: 0.42-1.10, p = 0.116). Conclusions: CD3+ T cell was more infiltrated in PD-1 positive, tumors with MSI and were associated with better OS, indicating an adaptive immune resistance may be occurring. Further research into the cancer characteristics and immunotherapy markers of the gastric SRCC immune microenvironment may highlight targets for immunotherapy.