bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid-deprived suppressor cell mediated the prognostic value of platelet-to-lymphocyte ratio for advanced hepatocellular carcinoma patients.
Authors: Li Xing , Wu Xiang-yuan , Jiang Nan , Xing Yan-Fang , Wu Dong-hao , Dong Min 
Published: January 2019

331 Background: Myeloid Deprived Suppressor Cell (MDSC) has been recoganized as a promising target for hepatocellular carcinoma (HCC). However, targeted therapy on MDSC failed to display convincing efficacy. Optimization of patient selection to find the most potential beneficiaries might be a solution to this issue. In the present study, we aimed to identify clinical parameters relevant to MDSC level in HCC patients for future MDSC targeted therapy. Methods: In the present study, a series of 55 HCC patients (prospective group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). Results: As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p< 0.0001). The monocytes (r2= 0.2875, p< 0.0001), neutrophils (r2= 0.3630, p< 0.0001) and platelet counts (r2= 0.0828, p= 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 243 HCC patients (retrospective group). The baseline characteristics of prospective and retrospective group were similar. Platelet-to-lymphocyte ratio (PLR) were confirmed to be an independent predictor for OS ( p= 0.003) with the rest parameters presented negative results. Then, advanced HCC patients were divided into two groups based on PLR value ≤111.23 or > 111.23 according to ROC analysis. Patients with low PLR presented higher 3-month survival rate (57.6% vs 37.6%) compared with patients with high PLR. PLR was associated with aggressive behavior of malignancies, such as distant metastasis and portal vein thrombosis. Conclusions: In summary, the present study firstly indentified blood platelet counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher PLR might be the optimal patient subgroup for MDSC targeted therapy.
MicroRNA-1291 effects on pancreatic cancer (PC) cells sensitivity to arginine deprivation and chemotherapy through modulation of ASS1 and GLUT1.
Authors: Kim Edward Jae-hoon , Tu Mei-Juan , Duan Zhijian , Gonzalez Frank J , Bold Richard J. , Yu Aiming 
Published: January 2019

334 Background: Cancer cells are reprogrammed to become addicted to a continuous supply of nutritional glucose and semi-essential amino acids like arginine, to drive synthesis of critical macromolecules for proliferation, tumorigenesis and metastasis. This dependence on nutritional supply makes cancer cells potentially vulnerable to deprivation by agents like pegylated arginine deiminase (ADI-PEG) which converts arginine back to citrulline. However, this vulnerability depends on limited ability of cancer cells to make arginine. PC cells that express high levels of argininosuccinate synthase 1 (ASS1), the rate limiting enzyme in cellular arginine synthesis, appear to be resistant to ADI-PEG. Our recent study showed that miR-1291 modulates factors in nutrient metabolism including ASS1 and GLUT1. We have developed a novel method to bioengineer miR-1291 agents for treatment. The aim of the current study was to evaluate if miR-1291 could enhance efficacy of metabolism-targeting drugs in PC. Methods: Cell proliferation was measured by CellTiter-Glo assay. Mature miR-1291 levels were determined by stem-loop reverse transcription real-time PCR assay. GLUT1 and ASS1 protein levels in miR-1291-treated pancreatic cancer cell lines were assessed by Western blot. Glucose uptake in AsPC-1 and PANC-1 cell lines was determined with a fluorescent probe, 2-NBDG. Results: A bioengineered pre-miR-1291 was processed to high levels of mature miR-1291 in PC cells. L3.3 and PANC-1 cells endogenously express high levels of ASS-1 and are resistant to arginine deprivation by ADI-PEG. ASS1 protein was downregulated by miR-1291 in L3.3 and PANC-1 cells and sensitized pancreatic cancer cells to ADI-PEG. In addition, miR-1291 significantly downregulated the protein levels of GLUT1 in AsPC-1 cells, leading to a lower glucose uptake capacity and a greater sensitivity to chemotherapy. Conclusions: Our results demonstrate that miR-1291 sensitizes PC cells to arginine deprivation and chemotherapy through downregulation of ASS1 and GLUT1. These results provide new insight into the mechanistic actions of miR-1291 and provide a new strategy for treatment of pancreatic cancer.
Treatment adherence, healthcare resource utilization, and costs in patients with gastrointestinal neuroendocrine tumors (GI NETs).
Authors: Cai Beilei , Broder Michael , Chang Eunice , Yan Jessie Tingjian , Benson Al Bowen 
Published: January 2019

337 Background: This study aimed to assess treatment adherence, healthcare resource utilization and costs in patients with GI NETs who initiated pharmacologic treatments. Methods: In 2 US commercial claims databases, patients ≥18 years with ≥1 inpatient or ≥2 outpatient claims for GI NETs were identified. The first claim for pharmacologic treatments (e.g. somatostatin analogues [SSAs], cytotoxic chemotherapy [CC], targeted therapy) following diagnosis and between 7/1/2009 and 12/31/2013 was defined as the index date. A 6-month clean period before index date and a 6-month pre- and a ≥1-year post-index enrollment were required. Proportion of days covered (PDC) was calculated during the follow up period. Outcomes were reported separately for patients with 1 and 2 years of post-index enrollment. Descriptive statistics including means, standard deviations, and frequencies and percentages for continuous and categorical data, respectively, were reported. Results: Of 1,322 patients with 1-year of follow-up, 847 initiated SSAs, 397 CC, 35 targeted therapies, 2 interferon, and 41 various combinations. Due to sample sizes, remaining results focus only on SSAs and CC. Mean PDC (SD) was 0.669 (0.331) for SSAs and 0.466 (0.236) for CC; SSA users had 20.5 (13.5) office visits and 0.59 (1.03) hospitalizations, CC users had 30.5 (19.8) and 0.89 (1.45) office visits and hospitalizations respectively; total annual cost for SSA-treated patients during the 1st year was $99,691 (82,423) and $134,912 (116,078) for CC. Among 685 patients with 2 years of follow-up, the annual mean costs in the second year were $8,071 and $58,944 lower than the first year for SSAs and CC, respectively. Conclusions: In this descriptive non-comparative study, we reported the resource utilization and costs associated with different treatment therapies. Overall, costs were higher in the first year than in the second year. This 2-database study offers new information on the magnitude and trends in the cost of pharmacologically treated GI NETs. Additional research with a larger sample size would be needed to better understand real-world utilization and costs for GI NET patients treated with different pharmacological therapies.
Liver regeneration after hemihepatectomy in patients with hepatocellular carcinoma.
Authors: Gong Wen-Feng , Zhong Jian-Hong , Ma Liang , Xiang Bang-De , Li Le-Qun 
Published: January 2019

339 Background: We explored clinical factors associated with extent of liver regeneration after hemihepatectomy to treat hepatocellular carcinoma (HCC), as well as how the extent of regeneration influences postoperative recovery of liver function. Methods: In this prospective study of 125 patients who underwent hemihepatectomy, future liver remnant volume (as a percentage of functional liver volume, %FLRV) and remnant liver volume were measured preoperatively and at 1, 5, 9 and 13 weeks postoperatively. Logistic regression was used to identify clinical factors associated with liver regeneration. Influence of liver regeneration on postoperative liver function was evaluated. Results: After hepatectomy, 1 of 125 patients (0.8%) died within 3 months, 13 (10.4%) experienced liver failure and 99 (79.2%) experienced complications. %FLRV was able to predict liver failure with an area under the receiver operating characteristic curve of 0.900, and a cut-off value of 42.7% showed sensitivity of 85.7% and specificity of 88.6%. Postoperative median growth ratio was 21.3% at 1 week, 30.9% at 5 weeks, 34.6% at 9 weeks and 37.1% at 13 weeks. Multivariate analysis identified three predictors associated with liver regeneration: FLRV < 601 cm3 (OR 0.230, 95%CI 0.074-0.717), %FLRV (OR 0.271, 95%CI 0.077-0.960) and liver cirrhosis (OR 7.740, 95%CI 2.748-21.798). At postoperative weeks 1 and 5, liver function indicators were significantly better among patients showing high extent of regeneration than among those showing low extent, but these differences disappeared by postoperative week 9. Conclusions: FLRV, %FLRV and liver cirrhosis strongly influence extent of liver regeneration after hepatectomy. %FLRV values below 42.7% are associated with greater risk of post-hepatectomy liver failure.
STAT3 inhibition for gastroenteropancreatic neuroendocrine tumors: Potential for a new therapeutic target?
Authors: Lopez-Aguiar Alexandra G , Postlewait Lauren McLendon , Zaidi Mohammad , Zhelnin Kristen , Krasinskas Alyssa , Russell Maria C. , Kooby David A. , Cardona Kenneth , El-Rayes Bassel F. , Maithel Shishir 
Published: January 2019

340 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascular tumors with similar treatments applied to all sites. The expression of pro-angiogenic factors (STAT3, VEGF, and HIF-1α) and their association with known adverse pathologic factors and disease recurrence after resection is not known. Methods: All pts with non-metastatic primary GEP-NETs who underwent curative-intent resection at a single institution from 2000-2013 were included. Immunohistochemistry was performed for STAT3, VEGF, HIF-1α, Ki-67 index, and CD31 using tissue microarrays made in triplicate by a pathologist blinded to other clinicopathologic variables. STAT3, VEGF, and HIF-1α were categorized into high vs low expression; CD31 was dichotomized at the median value. Primary outcome was 3-yr recurrence-free survival (3-yr RFS); secondary outcomes were correlation of STAT3, VEGF, and HIF-1α expression with Ki-67 index, adverse pathologic factors, and CD31 expression, a marker of microvascular density. Results: Of 265 GEP-NETs resected, 144 had tissue for analysis. STAT3 expression was high in 12 (8%) and low in 132 (92%). VEGF expression was high in 19 (13%) and low in 125 (87%), and HIF-1α was high in 1 (1%) and low in 143 (99%). High STAT3 expression was associated with worse 3-yr RFS compared to low expression (55% vs 84%; p = 0.003). High VEGF expression had a 3-yr RFS of 76% compared to 82% for low expression (p = 0.098); HIF-1α expression was not associated with RFS. Ki-67 ≥3% was associated with worse 3-yr RFS (≥3%: 51% vs < 3%: 84%; p < 0.001), as was the presence of lymphovascular invasion (LVI: 72% vs 95%; p = 0.001) and increased microvascular density per µm2 (CD31 > median: 75% vs CD31 < median: 86%; p = 0.043). High STAT3 expressing tumors were more likely to have a Ki-67≥3% (42% vs 7%; p < 0.001). LVI was present in 82% of high STAT3 tumors compared to only 50% with low STAT3 (p = 0.058). CD31 overexpression was similar between groups (58% vs 49%; p = 0.5). Conclusions: In resected GEP-NETs, high STAT3 expression is associated with an increased Ki-67 index, presence of lymphovascular invasion, and worse 3-yr RFS. STAT3 inhibition may be a novel therapeutic option for patients undergoing resection of high-risk tumors.
Reduction of T-Box 15 gene expression in tumor tissue as a prognostic biomarker for patients with hepatocellular carcinoma.
Authors: Morine Yuji , Utsunomiya Tohru , Imura Satoru , Ikemoto Tetsuya , Iwahashi Shuichi , Saito Yu , Shimada Mitsuo 
Published: January 2019

341 Background: Genome-wide analysis is widely applied to detect molecular alterations in tumor and non-tumor tissue during oncogenesis and tumor progression. We analyzed DNA methylation profiles of hepatocellular carcinoma (HCC), which was is the third-highest cause of cancer-related deaths worldwide, and investigated the clinical role of most heyper-methylated gene, encodes T-box 15 (TBX15), which was originally involved in mesodermal differentiation. Methods: We used an Illumina Infinium HumanMethylation450 BeadChip Kit to conduct a genome-wide analysis of DNA methylation of tumor and non-tumor tissue of 15 patients with HCC. Methylation scores for CpG sites were assigned a Beta-value. Another validation set, which comprised 58 patients with HCC who underwent radical resection, was analyzed to investigate the relationships between tumor phenotype, prognosis, and TBX15 mRNA expression. Results: TBX15 was the most hyper-methylated gene (Beta-value in tumor tissue = 0.52 compared with non-tumor tissue), and TBX15 mRNA levels in tumor tissues were significantly lower compared with those of non-tumor tissues (p < 0.0001). When we assigned a cutoff value = 0.5-fold to define differential expression of TBX15 mRNA, low TBX15 expression significantly correlated with higher serum DCP levels, and the overall survival 5-year survival rates of the low-expression group (n = 17) were significantly shorter compared with those of the high-expression group (n = 41) (43.3% vs. 86.2%, p = 0.001). Multivariate analysis identified low TBX15 expression as an independent prognostic factor for overall and disease-free survival. Conclusions: Genome-wide DNA methylation profiling indicates that hypermethylation and reduced expression of TBX15 in tumor tissue represents a potential biomarker for predicting tumor progression and poor survival of patients with HCC.
Relationship between tumor-infiltrating lymphocytes (TIL) and absolute lymphocyte count (ALC) or lymphocyte to neutrophil ratio (LTN) in cholangiocarcinoma (CCA).
Authors: Lim Alexander , Coppola Domenico , Chang Young Doo , Anaya Daniel A. , Kim Dae Won , Kim Richard D. 
Published: January 2019

343 Background: Tumor microenvironment is potentially a powerful predictive and prognostic marker of immunotherapy. The presence of CD8 TIL has been suggested as a predictive and prognostic marker of PD-1 inhibitor therapy in several malignancies. However, evaluation of TIL is not always feasible especially during or after immunotherapy. Therefore, easily accessible markers are needed for immune monitoring. In CCA, ALC and LTN in peripheral blood have been reported as prognostic factors. We evaluate the relationship between ALC or LTN and CD8 TILs in CCA. Methods: Formalin-fixed paraffin-embedded tumor samples from 41 patients with resected and histologically verified CCA between 1990 and 2015 were identified and immunohistochemically (IHC) stained with anti-CD8. Absolute lymphocyte and neutrophil count of the patients was obtained within 1 week before surgery. The association between ALC, LTN and CD8+ TIL status was investigated using unpaired Student t test and Spearman rank correlation. Results: The median age was 64 (41-85) with 53% male. 22%, 41% and 37% were stage I, II, and III respectively. In CD8 TIL positive, the average ALC was 1764 and in CD8 TIL negative, the average ALC was 2072. There was no significant difference between the two groups (p = 0.38). No difference of LTN was observed between CD8 TIL positive and negative tumors (0.39 vs 0.38, p = 0.69). The correlation between density of CD8 TILs and ALC or LTN was evaluated. No correlation was observed between CD8 TIL density and ALC (R = 0.02, P = 0.3) or LTN (R = 0.02, P = 0.8). Conclusions: ALC or LTN in peripheral blood may not predict CD8 TIL status in patients with CCA.
Lanreotide for the prolonged control of carcinoid syndrome (CS) in somatostatin analog (SSA)-naïve or experienced patients.
Authors: Wolin Edward M. , Fisher George A. , Liyanage Nilani , Pitman-Lowenthal Susan , Mirakhur Beloo , Pommier Rodney F. , Shaheen Montaser F. , Vinik Aaron 
Published: January 2019

347 Background: In the ELECT study, mean percentage of days with rescue octreotide (OCT) use was significantly lower in lanreotide depot/autogel (LAN) 120 mg vs. placebo (PBO) group during 16-week double blind (DB) phase. We examined prospective data on use of subcutaneous (sc) OCT or other medications as rescue during DB and initial open label (IOL) treatment periods of the ELECT trial to evaluate the direct impact of LAN on patients’ relief of CS symptoms for prolonged periods. Methods: Adults with neuroendocrine tumors (NETs) and CS history, with/without prior SSA use, were randomized to 16 weeks DB LAN 120 mg sc or PBO every 4 weeks, followed by a 32-week IOL LAN phase. Prospectively collected data recorded via Interactive Voice (Web) Response System on the use of sc OCT or other rescue medications during screening, DB and IOL treatment periods was analyzed. Results: During the 16-week DB phase, treatment with LAN was associated with less frequent rescue sc OCT use (least squares mean percentage of usage days (MPUD): 33.7% LAN vs. 48.5% PBO; p = 0.02). Through the 32-week LAN IOL period, rescue sc OCT use in the DB LAN group further decreased to 27.1% MPUD. Following crossover from PBO to active treatment, sc rescue OCT MPUD in the DB PBO group decreased from 48.5% to 20.9% during the IOL period. MPUD of other rescue medications at baseline were: 12.9% LAN; 8.3% PBO and no significant decreases were observed with LAN treatment during the DB phase (8.9% LAN vs. 6.3% PBO). MPUD of the DB LAN group remained relatively unchanged through the IOL phase (8.9% LAN DB; 8.8% LAN IOL). Following crossover from PBO to active treatment, the PBO group exhibited a decrease in MPUD of other rescue medications from 6.3% to 3.1% during the IOL period. Stratified by prior SSA therapy cohorts (naïve vs. prior SSA therapy), no apparent differences were observed in the use of sc OCT or other rescue medications between the two cohorts. Trends in MPUD of rescue medications of the individual cohorts were also similar to the overall group. Conclusions: The results of this study demonstrated that LAN is effective for the prolonged control of CS symptoms in SSA-naïve or experienced patients with NETs. Clinical trial information: NCT00774930.
Secondary resectability in locally advanced pancreatic cancer (LAPC) after nab-paclitaxel/gemcitabine- versus FOLFIRINOX-based induction chemotherapy: Interim results of a randomized phase II AIO trial (NEOLAP).
Authors: Kunzmann Volker , Martens Uwe Marc , Alguel Hana , Siveke Jens T. , Goekkurt Eray , Pelzer Uwe , Siegler Gabriele Margareta , Hennes Elke , Waldschmidt Dirk , Jakobs Ralf , Ferenczy Peter , Keller Ralph , Boeck Stefan Hubert , Kullmann Frank , Kapp Markus , Germer Christoph Thomas 
Published: January 2019

348 Background: Although there is a strong rationale for downstaging non-resectable pancreatic ductal adenocarcinoma (PDAC) for secondary resections by multi-agent chemotherapy, evidence from prospective randomized studies is missing. Methods: This prospective, randomized, open-label, phase II study aims to assess the activity, safety and feasibility of nab-paclitaxel/gemcitabine (nPG)- and FOLFIRINOX-based induction chemotherapy for patients (pts) with non-resectable PDAC. After two cycles of nPG pts are randomly allocated to receive either two additional cycles of nPG (arm A) or four cycles of FOLFIRINOX (arm B). Secondary resectability is assessed by exploratory laparotomy in all pts with at least stable disease (SD) after induction chemotherapy. The primary endpoint is to compare secondary complete macroscopic resection rates (R0/R1) in both arms. Results: We report the results of a planned interim (futility) analysis for efficacy data after at least 50 patients had completed induction chemotherapy and are evaluable for secondary surgical resection. Of pts who underwent randomization 42 pts were allocated to arm A and 44 pts to arm B, respectively. Disease control rate (DCR) after randomization was 93% in arm A and 89% in arm B. Explorative laparotomy was performed in 55% of randomized pts in arm A and 48% in arm B. Complete macroscopic resection (R0/R1) rate of randomized pts was 24% in arm A and 29% in arm B. For pts who received surgical exploration by laparotomy after completion of induction chemotherapy (n = 44) the complete macroscopic resection (R0/R1) rate was 43% in arm A and 62% in arm B. No new safety signals were identified thus far. Conclusions: nPG- and FOLFIRINOX-based induction chemotherapy approach revealed both effective and feasible in pts with LAPC supporting completion of patient recruitment in this trial. Interim results suggest promising secondary resection rates after multi-agent chemotherapy, especially when secondary resectability is assessed by surgical exploration. Clinical trial information: NCT02125136.
Initial dose of apatinib in Chinese patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting: 500 mg or 850 mg?
Authors: Deng Wenying , Qin Shukui , Li Jin , Wen Lu , Wang Junsheng , Zhang Guifang , Zhong Haijun , Yang Jianwei , Ba Yi , Bai Yuxian , Lin Xiaoyan , Wang Mei , Wang Lin , Liu Likun , He Yifu , Tao Min , Xie Congying , Ye Feng , Wu Xiang-yuan , Jia Tongfu 
Published: January 2019

35 Background: A fine balance between maintaining efficacy and reducing toxicity is necessary for drug therapies in many cancers. This study seeks to review the data from phase IV clinical trial of Ahead-G201 to help elucidate the optimal initial dose of apatinib in advanced gastric cancer. Methods: Pts data from the Ahead-G201 study at cut-off date of Jul 10, 2017 were extracted to explore the correlation of apatinib initial dose (500 mg vs 850 mg) with safety and clinical efficacy. Results: 864 of eligible pts received apatinib at an initial dose of 500 mg, and 58 pts received at 850 mg. Dose interruption occurred in 258 pts (33.1%) at 500 mg and in 27 pts (46.5%) at 850 mg. For safety, the most common adverse events (AEs) were proteinuria, hypertension and leukocyte decrease in both groups. Moreover, the incidence of all AEs and grade 3-4 AEs in pts at 500 mg was significantly lower than pts at 850 mg (Table). For efficacy, pts at 500 mg achieved an objective response rate (ORR) of 10.8% and a disease control rate (DCR) of 70.6%, at best response, which were 10.3% and 55.2% in pts at 850 mg. Pts at 500 mg got a significantly longer median progression-free survival (mPFS) and median overall survival (mOS) than pts at 850 mg (PFS, 4.6 mos vs 2.2 mos; OS, 6.8 mos vs 4.0 mos). Multivariate analysis indicated that apatinib treatment at an initial dose of 500 mg was significantly associated with longer mOS in advanced gastric cancer pts (6.8 mos vs 4.0 mos: hazard ratio, 0.5; 95%CI, 0.3 to 0.8), compared to initial dose of 850 mg. Conclusions: Compared to receiving apatinib at initial dose of 850mg, oral administration of apatinib starting from 500 mg seemed to bring more clinical benefit for patients with advanced gastric cancer, whilst with lower toxicities. Clinical trial information: NCT02426034. [Table: see text]