bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical mucositis and intestinal permeability abnormalities in metastatic colorectal cancer patients treated with irinotecan and 5-fluoruracil.
Authors: Gifoni Markus , Lima Roberto Cesar , Lima Aldo Angelo Moreira , Facanha Adriana , Callado Rodrigo Barbosa , Azevedo Carolina , De Albuquerque Ribeiro Ronaldo 
Published: March 2020

e14183 Background: The comprehension of the mechanisms involved in the adverse events of the cytotoxic drugs available to treat metastatic colorctal cancer (CRC) is necessary to improve their efficacy and safety. The irinotecan, fluoruracil and folinic acid (IFL) bolus regimen have as its major toxicity issue the complex and multi-mediated gastrointestinal mucositis. Nevertheless, it is difficult to obtain a reliable measurement of the intestinal abnormalities and functional consequences caused by intestinal mucositis, as almost all the clinical data available are reported on a patient symptoms-based scale analysis. Methods: With the lactulose/ mannitol permeability test as the experimental platform, we did a prospective case control study with 25 metastatic CRC patients treated with first line IFL. The primary end point was to compare (Wilcoxon test) the lactulose/ mannitol permeability test before the treatment and the same patients tests at the 15th and 29th day of the first IFL cycle. Blood samples of the same individuals were obtained before the treatment and at 15th day of their first IFL cycle to compare the ELISA serum levels of potentially involved cytokines (TNFα, IL-1β, IL-6, IL-18, IL-18bp e IL-33) (paired t-test). Results: In contrast with the pretreatment controls, the lactulose/ mannitol ratio was significantly (p<0,05) increased at the D15 and D29 in patients taking the first IFL cycle. The mannitol excretion rate was also decreased (p<0,05) at the 29th day. This abnormalities also reserve significant (p<0,05 – Spearman coeficient) correlation with the diarrhea and abdominal pain symptoms (NCI-CTC version 4.0) scale reported by the patients. Otherwise, it has not been possible to demonstrate serum levels differences of the addressed cytokines before and after the treatment. Conclusions: The lactulose/ mannitol permeability test is an objective and reliable tool to measure intestinal permeability abnormalities secondary to gastrointestinal mucositis caused by IFL to metastatic CRC patients.This non-invasive test could bring more objetctive measurement of the functional consequences of this limiting toxicity.
Use of plasma level of 5-fluorouracil to predict the efficacy in patients with advanced gastric cancer receiving first-line capecitabine plus cisplatin.
Authors: Song Weifeng , Cai Xun , Li Xiaoyu , Wang Liwei 
Published: March 2020

e14508 Background: Capecitabine is an oral 5-Fluorouracil prodrug that provided prolonged high levels of 5-FU within tumor cells and has improved efficacy and tolerability compared with protracted infusion 5-FU. The aim was to assess the value of plasma level of 5-Fluorouracil predicting the efficacy and safety in patients with advanced gastric cancer receiving first-line capecitabine plus cisplatin. Methods: The clinical data from 113 advanced gastric cancer patients receiving capecitabine plus cisplatin in Shanghai first people hospital from September 2006 to December 2009 were retrospectively collected. Fluorouracil plasma concentrations were examined at each cycle. The relationships between Fluorouracil plasma concentration and overall survival, progress free survival, response rate were determined by statistical analysis. Results: The mean plasma concentration was 24.8ug/L. We divided the patients with high mean 5-FU plasma concentration (> 25ug/L) into group A (n=59) and patients with low mean 5-FU plasma concentration (< 25ug/L) into group B (n=54). Median OS was 14.4 months in the group A and 9.6 months in the group B (HR= 0.36, p=0.000). Median PFS was 8 months in the group A and 4.9 months in the group B (HR= 0.37, p=0.000). The objective response rate was 55.9% for group A and 33.3% for group B (p=0.023). COX multivariate analysis showed that high 5-FU plasma concentration was an independent prognostic factors for improved OS (p=0.000) and PFS (p=0.000). All toxicities occurred more frequently in group A than group B. The grade 3/4 mocositis and hand-foot syndrome were significantly increased in group A compared with group B (19% vs 9%, p=0.08; 22% vs 8%, p=0.036). Conclusions: In advanced gastric cancer, high 5-FU plasma concentration might predict efficacy and toxicities for capecitabine plus cisplatin chemotherapy.
Sensitization of hepatocellular carcinoma (HCC) to tigatuzumab (CS-1008), a humanized anti-DR5 antibody, by sorafenib and its derivative SC-49.
Authors: Chen Kuen-Feng , Chen Hui-Ling , Shiau Chung-Wai , Liu Chun-Yu , Tai Wei-Tien , Ichikawa Kimihisa , Chen Pei-Jer , Cheng Ann-Lii 
Published: March 2020

e14516 Background: Previously, we have shown that sorafenib sensitizes HCC cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Here, we report the effects of sorafenib and SC-49, a sorafenib analog, on sensitizing HCC cells to tigatuzumab, a novel antihuman death receptor 5 (DR5) antibody. SC-49 is a sorafenib derivative that is devoid of kinase inhibition activity. Methods: HCC cell lines (Huh-7, PLC5, and Hep3B) were treated with tigatuzumab and/or sorafenib or SC-49 and analyzed in terms of apoptosis and signal transducers. Effects of tigatuzumab and SC-49 on HCC xenograft tumor growth were also evaluated. Results: Our data indicated that sorafenib, as well as SC-49, down-regulated the phosphorylation of signal transducers and activators of transcription 3 (p-STAT3) at Tyr 705 and subsequently reduced the protein levels of STAT3-regulated proteins, Mcl-1, survivin and cycin D1, in tigatuzumab-treated HCC cells. Knockdown of STAT3 by RNA-interference overcame apoptotic resistance to tigatuzumab in HCC cells, and ectopic expression of STAT3 in HCC cells abolished the sensitizing effect of sorafenib or SC-49 on tigatuzumab-induced apoptosis, indicating that inhibition of STAT3 mediates the effects of the combination. Importantly, inhibition of SHP-1 by adding a specific SHP-1 inhibitor reduced the effects of SC-49 and tigatuzumab on p-STAT3 and apoptosis, whereas co-treatment of tigatuzumab and SC-49 increased the activity of SHP-1, suggesting that SHP-1 mediated the combinational effect of tigatuzumab and SC-49 in HCC. Moreover, the in vivo combination of tigatuzumab and SC-49 inhibited HCC xenograft tumor growth. Conclusions: Sorafenib, SC-49 and tigatuzumab induce apoptosis and inhibit tumor growth in HCC through SHP-1-dependent STAT3 inactivation.
Association of the simultaneous expression of ephrin B3 receptor and E-cadherin in Barrett's adenocarcinoma with favorable clinical staging.
Authors: Schauer Matthias , Stoecklein Nikolas , Baldus Stephan , Feith Marcus , Hoelscher Arnulf , Kroepil Feride , Budach Wilfried , Matuschek Christiane , Boelke Edwin , Knoefel Wolfram Trudo 
Published: March 2020

e14527 Background: In intestinal epithelium tyrosine kinase receptor Ephrin B3 maintains the architecture of the crypt-villus axis by repulsive interaction with its ligand ephrin-B1. While loss of Ephrin B3 is linked to colorectal cancer initiation, overexpression of Ephrin B3 in cancer cell lines inhibits growth and induces functional changes with decreased mesenchymal and increased epithelial markers. In order to study this tumor suppressor activity of Ephrin B3 in esophageal adenocarcinoma we analysed the simultaneous expression of Ephrin B3 and E-cadherin in healthy esophagus and Barrett’s carcinoma. Methods: Simultaneous expression was investigated in samples of 141 patients with Barrett’s carcinoma and of 20 healthy esophagi. For analysis immunhistology and quantitative PCR was used. Results of healthy squamous epithelium, Barrett’s metaplasia and staging specific esophageal adenocarcinoma were correlated. Results: A significantly reduced E-cadherin mRNA activity in adenocarcinoma compared to dysplasia could be detected. Immunhistological activity of E-cadherin and Ephrin B3 was reduced in adenocarcinoma compared to dysplasia or healthy esophageal mucosa. The intracellular E-cadherin distribution changed significantly from the cytoplasm to the membrane, when Ephrin receptor was simultaneously expressed. Simultaneous expression of E-cadherin and Ephrin B3 showed a significant inverse correlation to tumorstage. Conclusions: We present first evidence of the tumor suppressor activity of Ephrin B3 receptor in esophageal adenocarcinoma possibly due to the impact on redistribution of cellular E-cadherin to the membrane. Our results suggest that this effect might play a role in the dysplasia-adenocarcinoma-sequence, the infiltrative growth pattern and the development of lymph node metastases.
RSF-1/HBXAP to predict prognosis in HBV-related hepatocellular carcinoma patients after curative resection.
Authors: Xu Yang , Fan Jia , Anders Robert , Guan Bin , Zhu Qingfeng , Shih Le-Ming 
Published: March 2020

e14538 Background: Remodeling and spacing factor 1(Rsf1, or HBXAP) was demonstrated consistent overexpression in several solid tumors and could be a prognostic marker, while its role in hepatocellular carcinoma (HCC) is still unclear. We try to illustrate the prognostic significance of RSF1 and its mechanism in HBV related HCC patients. Methods: RSF1 expressions were detected in tumor tissue microarrays of 254 HCC patients who underwent curative surgical resection during 2/2004 to 12/2005. Prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. The effects of RSF1 on cell proliferation and migration were tested in RSF1 knockdown and inducible HCC cells. Related genes were screened by cDNA Microarray and then confirmed by qRT-PCR and werstern blot. Results: RSF1 expression in HCC tissues was significantly related to replase of tumor in HCC patients after curative resection, and significantly related to MMP9 and HBV infection. Knockdown (or over-express) of RSF1 in HCC cells significantly inhibited (or enhanced) HCC proliferation and invasion in vitro. RSF1 controlled the expression of MMP9 in HCC cells. Conclusions: RSF1 up-regulates MMP9 and predicts poor prognosis in HBV related HCC patients after curative resection.
Prognosis of adenosquamous carcinoma of the pancreas: A matched case-control study.
Authors: Imaoka Hiroshi , Yamao Kenji , Hijioka Susumu , Hara Kazuo , Mizuno Nobumasa , Tanaka Tsutomu , Kondo Shinya , Tajika Masahiro , Ogura Takeshi , Obayashi Tomohiko , Niwa Yasumasa , Shimizu Yasuhiro 
Published: March 2020

e14540 Background: Adenosquamous carcinoma of the pancreas (ASC), which accounts for only 1-4% of exocrine pancreatic malignancies, is a variant of pancreatic ductal adenocarcinoma (PDAC). However, the prognosis of ASC is still unclear because these reports were based on only case studies and small surgical series with early stage cancers. The purpose of the present study was to clarify the prognosis of ASC using a matched case-control study. Methods: Pathological and clinical records of ASC cases between 2001 and 2011 in our institution were examined. All ASC cases were diagnosed pathologically by a surgical or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimen. First, to examine the efficacy of EUS-FNA for the diagnosis of ASC, the pathological findings of EUS-FNA were compared with the surgical findings in the resected cases of ASC. Next, to clarify the prognosis of ASC, the clinical characteristics of ASC were evaluated. As a control group, PDAC cases matched with ASC cases by sex, age, pretreatment ECOG-PS, location, initial therapy, and the AJCC TNM staging for pancreatic cancer were also included in this study. Results: Of the 914 cases of pancreatic neoplasms, 28 cases of ASC were identified (3.06%), and 56 cases of PDAC were matched as controls. Of 28 cases of ASC, 6 cases underwent curative resection, and 22 cases were unresectable. Of the 6 resected cases of ASC, 5 cases were diagnosed preoperatively by EUS-FNA (κ, 0.83; positive predictive value [PPV], 100%). Overall survival (OS) was significantly worse for ASC than for PDAC, with a hazard ratio (HR) of 1.94 (95% CI, 1.07 to 3.51; p=0.026; median 8.38 months vs. 15.75 months). Of the 22 unresected cases, the OS of ASC was significantly worse than that of PDAC, with an HR of 2.39 (95% CI, 1.27 to 4.51; p=0.007; median 4.67 months vs. 12.36 months). Conclusions: In the present study, EUS-FNA had a high PPV for the diagnosis of ASC, and ASC was found to be more aggressive than PDAC.
Factors associated with octreotide LAR use among elderly patients with carcinoid syndrome: A population-based analysis.
Authors: Shih Ya-Chen T. , Xu Ying , Leary Colleen , Yao James C. 
Published: March 2020

e14549 Background: Octreotide LAR is indicated for the treatment of carcinoid syndrome, diarrhea related to VIPoma, and may delay tumor growth in neuroendocrine tumors (NETs). The pattern of octreotide LAR use in clinical practice has not been well documented. Methods: Using the SEER-Medicare database, we identified patients diagnosed with NETs from July 1999 to Dec 2007. We then excluded those patients with poorly differentiated histology, under age 65 at diagnosis, enrolled in HMOs, and who did not have continuous Part A & B enrollment within 12 months of diagnosis. We further identified patients with potential indication for octreotide LAR use as those having two or more claims indicating carcinoid syndrome, flushing, diarrhea, or malignant islet cell neoplasm within the first year of NETs diagnosis, with the first claim occurring within 6 months of diagnosis. HCPCS codes, J2352 and J2353, were used to identify octreotide LAR use. Multivariate logistic regression analysis was performed to ascertain factors associated with octreotide use; covariates included age, race, region, comorbidity score, urban/rural status, tumor characteristics, neighborhood socioeconomic status and year of diagnosis. Results: Of the 2000 NETs patients with potential indication for octreotide LAR use, 478 (23.9%) were started on octreotide LAR within 6 months of diagnosis. Multivariate analysis showed that older age (≥ 80) (OR=0.61, 95 CI=0.44 – 0.86), southern region (OR =0.67; 95% CI =0.44 – 1.00) and tumor of undetermined grade (OR=0.71, 95% CI=0.52 – 0.98) were associated with lower odds of octreotide use while the odds was positively associated with advanced stage and more recent diagnosis years. By primary site, no clear pattern was identified. Conclusions: Our analyses suggest only a small (< 25%) fraction of patients with eligible diagnoses are receiving indicated therapy with octreotide LAR. Further studies and improved education are needed to improve the management of carcinoid syndrome.
A prospective phase II trial of a S-1/cisplatin-based chemoradiotherapy for locoregionally advanced esophageal cancer.
Authors: Cho Byoung Chul , Chang Hyun , Lee Yong Chan , Kim Dae Joon , Yun Mi Jin , Shin Sung Kwan , Kim Hyun Ki , Kim Han Sang , Lim Sun Min , Kim Joo-Hang 
Published: March 2020

e14559 Background: Concurrent chemoradiation has similar efficacy as surgery for esophageal cancer. Phase II trial was carried out to evaluate the efficacy and safety of chemoradiation with S-1 and cisplatin in locoregionally advanced esophageal cancer. Methods: Eligible patients had stage IIA-IVA esophageal cancer. Patients received two cycles of S-1 (days 1 to 14 and 22 to 35) and cisplatin (day 1 and 22) with concurrent radiotherapy (50.4 Gy total: 1.8 Gy/fraction). Esophagectomy was performed between week 12 and 18 as determined by the specialist multidisciplinary team meeting. Results: Sixty patients were enrolled between March 2008 and August 2011. Of the 60 patients entered, 59 patients were eligible. Clinical stage was ≥T3 in 28 patients (47%) and N1 in 43 patients (73%), with squamous cell carcinoma histology in 57 patients (97%). Fifty-four patients (90%) completed the planned treatment. After the chemoradiation, clinical tumor response rate was 62.7%. The primary grade 3/4 toxicities included neutropenia (24%) and esophagitis (8.5%). All three patients died during chemoradiation (two from pneumonia and one from gastrointestinal origin septic shock). Twenty-five patients (42%) underwent esophagectomy following chemoradiation and 15 (60%) achieved complete pathologic regression. At the median follow-up duration of 34.6 months, the estimated overall survival and progression-free survival rate at 2-year was 56.5% and 45.9%, respectively. Conclusions: Concurrent chemoradiation with S-1 and cisplatin showed an encouraging activity with high complete pathologic regression. Survival data was promising compared with historical data with 5-FU/cisplatin and should be confirmed in a randomized phase III trial. Toxicities were significant but clinically manageable.
A phase II trial of JX-594, a targeted multimechanistic oncolytic vaccinia virus, followed by sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Heo Jeong , Breitbach Caroline , Cho Mong , Hwang Tae-Ho , Kim Chang Won , Jeon Ung Bae , Woo Hyun Young , Yoon Ki Tae , Lee Jun Woo , Burke James , Hickman Theresa , DuBois Kara S , Longpre Lara , Patt Richard H. , Kirn David H. 
Published: March 2020

e14566 Background: JX-594 is a targeted oncolytic vaccinia virus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus GM-CSF expression is accompanied by tumor vascular disruption and anti-tumoral immunity (Reviewed in Nat Rev Cancer 2009). JX-594 was well-tolerated intravenously (IV) (Nature 2011) and intratumorally (IT) (Lancet Oncol 2008). Complementary anti-tumor effects are predicted with JX-594 followed by sorafenib due to acute vascular disruption effects with JX-594 and anti-angiogenic effects with sorafenib. Methods: Treatment-refractory HCC patients received JX-594 for three weeks (Day 1 IV, Day 8 IT and Day 22 IT) followed by sorafenib. An IT boost dose of JX-594 at Week 12 was optional. The primary objective of the study was to determine the safety of JX-594 followed by sorafenib in patients with advanced HCC. Secondary objectives include disease control rate (DCR) based on mRECIST and/or Choi response criteria at Day 6 (optional), Day 25 (after JX-594 only), 6 and 12 weeks. Results: Twenty (20) patients were treated in this study; fifteen (15) were refractory to sorafenib. The sequential treatment regimen was well-tolerated. Transient flu-like symptoms (Grade 1-2) and transient leukopenia (lymphopenia, neutropenia) were the most common adverse events following JX-594 therapy. Sorafenib toxicities were consistent with the expected toxicity profile. At the time of this interim analysis, thirteen patients were evaluable for radiographic response by Choi criteria (mRECIST pending). After JX-594 alone at Day 25, 10 of 13 evaluable patients (77%) had Choi tumor responses (range 19-48% reduced enhancement). Following subsequent sorafenib therapy, 11 of 13 patients (85%) had Choi responses at Week 6-12, including 9 of 10 (90%) sorafenib-failure patients. Conclusions: JX-594 was well-tolerated and associated with Choi tumor responses following IV and IT injections in patients with advanced HCC. Subsequent sorafenib was associated with the expected toxicity profile. Further trials of JX-594 in HCC patients are warranted.
Fluorodeoxyglucose positron emission tomography for evaluating early response during neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.
Authors: Lin Chia-Chi , Hsu Chih-Hung , Tzen Kai-Yuan , Cheng Jason C. , Lee Jang-Ming , Wang Hsiu-Po , Huang Pei-Ming , Hsu Feng-Ming , Chen Wei-Wu , Huang Ta-Chen , Cheng Ann-Lii 
Published: March 2020

e14576 Background: To determine if fluorodeoxyglucose positron emission tomography (FDG-PET) could differentiate between responding and non-responding locally advanced esophageal squamous cell carcinoma (ESCC) early in the course of neoadjuvant chemoradiotherapy (CRT). Methods: Patients (pts) with T3 or N1M0-1a (AJCC, 6th Ed) ESCC first received a 21-D cycle of induction chemo (paclitaxel 70 mg/m2 D 1, 8; cisplatin 30 mg/m2 D 1, 8; fluorouracil 2000 and leucovorin 300 mg/m2 24-hr D 1, 8). This was followed by concurrent CRT (paclitaxel 35 mg/m2 1-hr D 1, 4 /wk, cisplatin 15 mg/m2 1-hr D 2, 5/wk, and radiotherapy 2 Gy D 1-5 /wk) (Lin CC, et al. Ann Oncol 18:93,2007). When the accumulated radiation dose reached 40 Gy, the feasibility of esophagectomy was evaluated. In pts for whom esophagectomy was not feasible, concurrent CRT was continued to a dose of ≥60 Gy. Serial FDG-PETs were performed before and 14 days after start of induction chemo. Pathologic response (PR) was defined as no or microscopic residual disease. PET response was measured using the standardized uptake value (SUV). Receiver operating characteristic (ROC) analysis was used to evaluate the ability of SUV in distinguishing between PR and non-PR. Results: Of 65 pts (M:F = 60:5, median age 55, range 39-71) with locally advanced (M0:M1a = 58:7) ESCC enrolled from March 2008 to December 2011, 40 pts underwent esophagectomy and 26 pts were pathologic responders. The median SUV decrease 14 days after the start of therapy was 75.8% for pathologic responders and 30.1% for non-responders (p <0.05). In ROC analysis, the area under the curve was 0.70 (95% CI = 0.55-0.86). Using a 35% SUV decrease cutoff value, PET correctly identified 24 of 26 responders (sensitivity 92%) and 8 of 14 non-responders (specificity 57%). The corresponding positive and negative predictive values were 80% and 80%, respectively. Conclusions: A 35% SUV decrease 14 days after the start of induction chemo is significantly associated with PR, but its accuracy in detecting non-responders is too low to justify the clinical use of FDG-PET for early discontinuation of neoadjuvant CRT in pts with locally advanced ESCC.