bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between promoter methylation and protein expression of tumor suppressor genes with clinical characteristics in gastric carcinoma and its effect on the biological function of gastric cancer.
Authors: Ying Jieer , Jingjing Li 
Published: September 2018

e15509 Background: Studies showed that the gene promoter methylation may be the third important mechanisms of gene expression regulation. Abnormal methylation of tumor suppressor gene can be detected in the early stage of tumor, by screening the methylation profile of gastric cancer (GC), it can provide theoretical and experimental evidence for early diagnosis, treatment and prognosis. Methods: Detecte p16, hMLH1 and CDH1 promoter methylation, the p16, hMLH1 and E-cadher expression in GC tissues and its correlation with clinicopathological features and prognosis. Detect methylation of hMLH1 promoter and mRNA expression in GC cell line and normal gastric mucosa cell line. Clone formation assay and Transwell test. Results: The methylation of hMLH1 and CDH1 in GC and adjacent tissues were statistically significant . The methylation of hMLH1 was related to alcohol , CA199 level and Borrman. The methylation of CDH1 was related to the CEA level. The methylation of hMLH1 promoter is related to OS in GC patients. The methylation of p16 and CDH1 was not related to the OS ofGC patients. The GC patients with 0 or 1 gene methylation had a better prognosis than those with 3 or 2 gene methylation. The p16, hMLH1 and E-cadherin protein expression in GC and adjacent tissues were statistically significant. The p16 protein expression was related to tumor size. The hMLH1 protein expression was related to the CA199 level and tumor size. The E-cadherin expression in GC patients with drinking history was lower than ones without drinking history. The p16, hMLH1 and E-cadherin protein expression was not related to the OS of GC patients. There was a negative correlation between hMLH1 gene methylation and its protein expression in GC. The number of clones in the control group and the experimental group were 180 ± 3 and 169 ± 6. The number of cells in the control group and the experimental group were 135 ± 4.08 and 125 ± 4.18. Conclusions: The methylation of multiple genes is associated with the prognosis, which can provide theoretical basis for accurate treatment and prognosis for GC patients.
Clinical efficacy and safety of apatinib in treatment of alpha fetoprotein-positive advanced gastric cancer.
Authors: Chen Jia , Chen Lingxiang , Yang Li , Zhu Chunrong , Liu Chaoying 
Published: September 2018

e15513 Background: Alpha fetoprotein (AFP)-producing gastric cancer (APGC) is a minor subtype of gastric cancer (GC) with high malignancy, rapid progress, high metastatic rate and poor prognosis. Treatment of AFP-positive GC is not different from that of AFP-negative GC, but the efficacy can not match for the latter. Apatinib, a novel inhibitor of VEGFR-2, has achieved survival improvement in advanced GC patients. We aimed to evaluate the efficacy and safety of apatinib in AFP-positive advanced gastric cancer patients. Methods: This was a single-arm, open-label, exploratory study design. Eligibility criteria included histologically proven GC; patient age 18-75 years; AFP-positive; clinical stage III or IV; and ECOG performance status of 1 or 2. A history of receiving previous treatment was not required. All the patients were orally given apatinib at an initial dose of 500 mg (qd) until disease progression or death. Dose reduction to 250 mg was allowed. Results: A total of 16 pts including 15 males and 1 female were eligible. The median age was 62.5 years (range 26-74 years). Poorly differentiated adenocarcinoma was the main histological type, and the main metastatic sites were liver (12/16) and abdominal (2/16). Ten pts received gastric surgery and 13 had previous chemotherapy prior to apatinib, and 10 patients received chemotherapy along with apatinib. Among the 16 pts, 14 were available for the efficacy evaluation. Two pts achieved partial response (PR), 10 had stable disease (SD), and 2 had progressive disease (PD). The objective response rate (ORR) and the disease control rate (DCR) were 14.3% (2/14) and 85.7% (12/14), respectively. All pts were included for safety analysis. The incidence of adverse events (AEs) was 87.5%. Main AEs were bone marrow suppression (43.75%), hypertension (50%), and abdominal pain (31.25%). Conclusions: Administration of apatinib make clinical benefit to AFP positive advanced gastric cancer with a comparable disease control and tolerable adverse reactions. Clinical trial information: ChiCTR-OPC-16008295. Clinical trial information: ChiCTR-OPC-16008295.
Evaluation of survival outcome of gastric cancer with pathologic stage III according to the new eighth edition of the AJCC/UICC TNM classification.
Authors: Bando Etsuro , Makuuchi Rie , Kaji Sanae , Hikage Makoto , Irino Tomoyuki , Tokunaga Masanori , Tanizawa Yutaka , Kawamura Taiichi , Kinugasa Yusuke , Sugiura Teiichi , Uesaka Katsuhiko , Terashima Masanori 
Published: September 2018

e15536 Background: Postoperative adjuvant chemotherapy with administration of S-1 for one year is standard treatment in patients with pStageII/III in Japan. However, survival outcome of patients with pStageIII remains unsatisfactory, so several attempt have been made to improve the survival in these patients. However, actual survival according to sub-classification in pStage III has not been elucidated. The eighth edition of the American Joint Committee on Cancer (AJCC) TNM postoperative staging for gastric cancer was published in 2016 and included major revisions of pStageIII. The aim of the current study was to evaluate the validity of the eighth edition TNM classification, especially in pStageIII for gastric cancer based on patients treated in single Japanese high volume cancer center. Methods: A total of 646 gastric cancer patients with pStageIII who underwent R0 resection from 2002 to 2016 were included. Prognostic value was analyzed for validation and compared TNM seventh edition. Results: Some improvement was observed in the separation of pN. Patients with pN3b (5-year survival rates = ysr; 13.4%) had the significant poor survival than those with N3a (5-ysr; 39.1%) (P < 0.001). In pStage III disease, clear survival distribution was observed in eighth edition [IIIA (N = 315); 5-ysr: 67.0%, risk ratio (RR) = 1 (reference), IIIB (N = 230); 5-ysr: 51.1%, RR = 1.694, P < 0.001, IIIC (N = 101); 5-ysr: 30.9%, RR = 2.771, P = 0.002], compared to seventh edition [IIIA (N = 233); 5-ysr: 69.3%, RR = 1;, IIIB (N = 230); 5-ysr: 53.8%, RR = 1.682, P = 0.001, IIIC (N = 183); 5-ysr: 38.7%, RR = 2.571, P = 0.004]. Conclusions: Survival outcome of pStageIIIC (T3-T4bN3b, T4bN3a) in eighth edition is very poor. So, more aggressive regimen should be planned for pStageIIIC gastric cancer in eighth TNM staging.
Combined hepatocellular carcinoma and cholangiocarcinoma: Debate for the ideal surgical option.
Authors: Chhatrala Hardik Satish , Shah Chintan , Kailasam Karthik , Yadav Lokesh , Chandana Sreenivasa Rao 
Published: September 2018

e15644 Background: Current limited evidence from observational studies suggest lack of survival benefit from liver transplantation (LT) for combined hepatocellular carcinoma with cholangiocarcinoma (cHCC-CC) when compared to surgical resection. This is in contrast to hepatocellular carcinoma (HCC) which has clear survival benefit with LT. We hypothesized that cHCC–CC patients have similar overall survival (OS) after LT compared to resection. Methods: Localized HCC and cHCC–CC patients treated with surgical resection versus transplant were identified in SEER Database (1973–2013). Kaplan-Meier method was used to examine survival with LT versus resection. Results: In the total period between 1973-2013, we identified 9,306 (5496 [59.06%] resection, 3810 [40.94%] transplant) patients with HCC, and 175 (107 [61.14%] resection, 68 [38.85%] transplant) patients with cHCC–CC. 3-year OS of patients undergoing LT remains significantly greater for HCC than for cHCC–CC (80.5% vs 59.9%, P < 0.01). Interesting, for period 2008-13, 3-yr OS for cHCC-CC patients undergoing LT was better than resection, although the difference was not statistically significant (66.4% vs 46.27%, p > 0.10). While there has been improved 3-year and 5-year OS from period 2002-07 to 2008-13 after LT for localized HCC patients (83.6% vs 79.4%, p < 0.002 and 76.4% vs 73.6, p < 0.01, respectively), there has been no significant improvement in 3-year or 5-year survival after for HCC-CC (66.4% vs 65.2%, p < 0.4 and 58.3% vs 55.3%, p > 0.4 respectively). Conclusions: Over the past decade, 3-yr OS of cHCC-CC with LT remains dismal and has not improved. However, LT in patients with localized cHCC–CC may have a potential survival benefit over liver resection, although clearly lower than the survival benefit of LT for HCC. Our results argue for a randomized trial for LT versus resection for localized cHCC-CC patients to obtain better understanding of survival benefit from the two surgical options.
Do pancreas cancer stem cells play crucial role in survival outcome?
Authors: Askan Gokce , Sahin Ibrahim Halil , Capanu Marinela , Turkekul Mesruh , Yu Kenneth H. , Lowery Maeve Aine , Basturk Olca , Iacobuzio-Donahue Christine , O'Reilly Eileen Mary 
Published: September 2018

e15721 Background: Recent studies indicate that pancreatic cancer stem cells (CSC) may predict disease behavior and survival outcomes of pancreatic ductal adenocarcinomas (PDACs) patients (pts). Several CSC markers have been reported in PDAC (Fitzgerald, TL, 2014). We herein evaluated the impact of CSC markers including CD44 and Epithelial Specific Antigen (ESA) on survival outcome of PDAC pts who had liver or lung metastasis after initial surgical resection (IR). Methods: Clinicopathologic features and survival of 59 PDACs were analyzed. Pts with IRB approval, and whom had available primary tumor tissue, were included. All neoplasms were immuno labeled with CD44 and ESA. Staining intensity was scored as weak (1), moderate (2), strong (3), while the staining pattern was scored as: few (1), patchy (2), and diffuse (3). The expression for CD44 and ESA was accepted positive if total score ≥4. Time from relapse to death (TRD) was estimated using the Kaplan-Meier method censoring patients that were alive at the last follow up. Survival curves were compared using the log-rank test Results: Of 59 pts, 42 (71 %) had liver, 10 (17%) had lung and 7 (12%) had both liver and lung metastasis. M/F = 34/25; mean age = 64.2 (range, 34-90). Patients were subcategorized as follows; thirteen cases were CD44 (+)/ESA (-) (group1) and 13 were CD44 (-)/ESA (+) (group 2). Eight (61.5%) of group 1 tumors and 2 (15.3%) of group 2 were poorly differentiated. At last follow-up, except one with 63 months survival, all pts died of disease with 23.3 months (range, 3-67) median OS. No significant difference in TRD was observed between group 1 (6.9 months) and 2 (13.8 months) (p = 0.62). However, we observed group 1 tumors had worse OS (12 months) compared to group 2 (36 months). Conclusions:A worse outcome trend was observed for pts with CD44 (+)/ESA (-), albeit not statistically significant and likely limited by small numbers. Further studies are warranted to evaluate the robustness of this observation.
Evolution of pancreatic cancer survival over the past two decades.
Authors: Mariotti Veronica , Parrondo Ricardo Daniel , Gonzalez Velez Miguel , Duma Narjust , Leslie Lori Ann , Gutierrez Martin 
Published: September 2018

e15722 Background: Pancreatic cancer (PaCa) is a highly lethal disease, with a 5-year overall survival (OS) rate of approximately 6%, and a median OS of only 3–6 months (m). Despite recent improvements in surgical techniques and increased use of combination chemotherapy (CT), OS remains poor. This study aims to examine the factors that led to increased OS in PaCa patients (pts) over the past two decades in a single academic institution. Methods: All medical records of pts diagnosed with PaCa at the John Theurer Cancer Center from 1990 to 2012 were reviewed, and 916 PaCa pts were included in this analysis. We compared one group of pts diagnosed from 1990 to 2003 (G1, n = 482), with a group of pts diagnosed from 2004 to 2012 (G2, n = 434) in terms of OS, demographics, tumor features and treatment (tx). Results: Median age at diagnosis was 70.5 years (range 26-96). There was no significant difference between G1 and G2 in terms of age at diagnosis, stage of disease and number of pts who received surgery. A significantly higher percentage of pts received CT in G2 compared to G1 (66.5% vs 51.0%, p = .00). Tumors of the pancreatic head were more common in G1 compared to G2 (51.8% vs 44.4% p = .02). More pts in G2 received two or more CT agents compared to G1 (49.0% vs 34.1%, p = .00). Median OS was significantly longer in G2 compared to G1 (9m vs 5m, p = .00), in pts who received CT compared to pts who did not (3m vs 9m, p = .00) and in pts who received surgery compared to pts who did not (5m vs 19m, p = .00). Pancreatic head location was associated with improved OS compared to other locations (9m vs 5m, p = .00). No OS difference was found between pts who received combination with two or more agents vs single agent CT. Conclusions: In line with multiple studies, analysis of PaCa data from our institution showed an increase OS in pts diagnosed with PaCa in more recent years, and in those who received surgery and CT. CT was administered in a larger number of pts in G2, which might account for the better OS in this group. Pts diagnosed with tumors of the pancreatic head had better survival, which could be explained by earlier presentation leading to earlier diagnosis and tx. Further research in PaCa therapeutics is needed, as long-term OS in PaCa pts remains poor despite recent advances.
Atorvastatin to inhibit pancreatic cancer cells proliferation and invasion via suppression neurotrophin receptor signaling.
Authors: Ji Shengjun 
Published: September 2018

e15725 Background: Pancreatic cancer is an uncommon but fatal malignant tumor, only 20% of which show any significant response to chemo-radiotherapy. Tumor metabolism research revealed that pancreatic cancer cells highly dependent on cholesterol uptake. So, in the present study, we have determined the effectiveness of atorvastatin, one drug originally used to lower cholesterol, against pancreatic carcinogenesis in various pancreatic cancer cell lines. Methods: To investigate atorvastatin effects in pancreatic cancer cells, two cell lines (PANC-1 and SW1990) were treated with different atorvastatin doses. The anti-proliferative, apoptotic and anti-invasive properties of atorvastatin were evaluated using MTS, cytoplasmic histone-DNA fragmentation and matrigel invasive assays, respectively. And western blot was used to evaluate the neurotrophin receptor signaling of NGF/Trk A, BDNF/TrkB and NT3/Trk C. Results: Atorvastatin suppressed pancreatic cancer cells proliferation, clone formation and invasion in a dose-dependent manner. The dose of atorvastatin at 10^-5mmol/L would be able to achieve obvious anti-tumor effect in vitro. Cell-cycle analysis demonstrated that cells were arrested in the S phase. Western blot showed increased protein expression of cleaved caspase-3, caspase-9, p21, p-chk2 and decrease in protein level of NGF/Trk A and NT3/Trk C. Conclusions: The current results demonstrated the anti-tumor effects of atorvastatin on pancreatic cancer cells, providing initial evidence towards its potential therapeutic use. Acknowledgment:This study was supported by Suzhou Cancer Clinical Medical Center Szzx201506.
A systemic review and meta-analysis to evaluate the efficacy and postprogression survival of second-line chemotherapy for gemcitabine-refractory pancreatic cancer.
Authors: Kasuga Akiyoshi , Hamamoto Yasuo , Aoki Yu , Kawasaki Kenta , Suzuki Takeshi , Hirata Kenro , Sukawa Yasutaka , Takaishi Hiromasa , Kanai Takanori 
Published: September 2018

e15768 Background: We previously reported positive relationship between overall survival (OS) and both of postprogression survival (PPS) and post-trial anti-cancer therapies in first-line pancreatic cancer patients. We conducted a meta-analysis to gain a better understanding of the impact of PPS and post-trial anti-cancer therapies on OS and to determine the efficacy of second-line systemic therapy. Methods: We searched randomized trials of second-line systemic therapy for pancreatic cancer patients. We evaluated the relation between OS and either progression-free survival (PFS) or PPS and calculated the pooled effect size by using random effects models. Results: Eleven randomized trials with 23 treatment arms that involved examining 2267 patients were analyzed. Median OS was strongly associated with median PPS and PFS (r = 0.908 and 0.754, respectively), but no correlation between rate of post-trial anti-cancer therapies and OS was detected (r = 0.050). Average OS, PFS and PPS were significantly longer in recent trials than in older trials, (6.08 versus 4.17 months, p < 0.001), (2.65 versus 1.95 months, p < 0.001) and (3.43 versus 2.25 months, p < 0.001), respectively. Overall, experimental therapies compared to control did not significantly improve PFS (HR, 0.83; 95% CI, 0.67-1.03; I2 = 73%) or OS (HR, 0.89; 95% CI, 0.72-1.11; I2 = 69%). When the analysis was restricted to fluoropyrimidine compared to irinotecan or oxaliplatin in combination with fluoropyrimidine, each therapy produced advantage in a term of PFS (HR, 0.65; 95% CI, 0.47-0.88; I2 = 39% for irinotecan, HR, 0.81; 95% CI, 0.67-0.98; I2 = 13% for oxaliplatin) but only irinotecan produced advantage in a term of OS (HR, 0.70; 95% CI, 0.55-0.89; I2 = 0% for irinotecan, HR, 1.04; 95% CI, 0.65-1.65; I2 = 82% for oxaliplatin). Conclusions: Although second-line treatment benefit for OS can be skewed by PPS in patients with gemcitabine-refractory pancreatic cancer, the effects of subsequent therapies are weak in the salvage setting.
Individualized treatment with sunitinib versus standard dosing with sunitinib or pazopanib in patients with metastatic renal cell carcinoma (mRCC): Results from the Canadian Kidney Cancer information system (CKCis).
Authors: Basappa Naveen S. , Lalani Aly-Khan A. , Kalirai Austin , Li Haocheng , Wood Lori , Kollmannsberger Christian K. , Sim Hao-Wen , Kapoor Anil , Hotte Sebastien J. , Czaykowski Piotr , Canil Christina M. , Reaume M. Neil , Bjarnason Georg A. , Vanhuyse Marie , Soulieres Denis , North Scott A. , Heng Daniel Yick Chin 
Published: September 2018

e16078 Background: Recent analysis using CKCis showed that mRCC patients receiving first-line sunitinib (S) had better survival than patients receiving pazopanib (P) and greater than expected survival for a real world sampling. We conducted further analyses to see if an individualized approach (treatment starting at standard dose/schedule with subsequent schedule/dose alterations based on toxicity) using S results in better outcomes in mRCC patients. Methods: Patients within CKCis diagnosed with clear cell mRCC treated with first-line S or P between January 2011 through December 2015 were analyzed by three treatment groups: 1) S as per individualized approach (SI) 2) S as per product monograph (SS) 3) P as per product monograph (PS). Overall survival (OS) and time-to-treatment failure (TTF) were calculated. Cox regression analysis allowed for adjustment of International Metastatic RCC Database Consortium (IMDC) criteria with age as a continuous variable. Results: A total of 598 patients were identified, 351 patients in SI, 151 patients in SS, and 92 patients in PS. Baseline characteristics are noted in Table 1. Median OS was improved in SI vs SS (37.9 vs 22.3 months (m), p<0.001) and SI vs PS (37.9 vs 19.6 m, p<0.001). TTF was better in SI vs SS (12.9 vs 5.6 m, p<0.001) and SI vs PS (12.9 vs 7.0 m, p<0.001). SS vs PS showed no difference in median OS (22.3 vs 19.6 m, p=0.51) or TTF (5.6 vs 7.0 m, p=0.24). Adjusted hazard ratios were: SS vs SI (OS 1.41, p=0.056; TTF 1.77, p<0.001) and PS vs SI (OS 2.18, p<0.001; TTF 1.43, p=0.040). Conclusions: Improvement in OS and TTF is seen using an individualized approach to mRCC patients supporting the growing body of evidence endorsing this practice. Further prospective validation awaits the NCT01499121 study. [Table: see text]
Prognostic score to predict time to castration-resistance in underserved patients with metastatic prostate cancer.
Authors: Mangla Ankit , Mushtaq Muhammad Umair , Yadav Udit , Ahmed Ahmed T , Liu Jiaxiang , Go Muriel Tania , Hassan Ahmed S , Bedrose Sara , Mann Hashim , Mullane Michael Russell 
Published: September 2018

e16518 Background: This study aimed to identify predictors of time to castration-resistance prostate cancer (tCRPC) from initial diagnosis of metastatic prostate cancer (mPC) and develop a prognostic score in the underserved population of an inner-city tertiary care hospital. Methods: We retrospectively reviewed charts of 278 men diagnosed with mPC between 2001 and 2015, of which 155 patients were analyzed. Socio-demographic, clinical and pathologic factors were ascertained at the time of diagnosis. Kaplan-Meier and cox regression analyses were done to explore correlates tCRPC. Crude (HR) and adjusted (aHR) hazard ratios with 95% confidence intervals (CI) were obtained. Results: Over a median follow-up of 46 months (95% CI 23-69), 73.5% of men developed castration-resistance. Median tCRPC was 16 months (95% CI 12.5-19.5). All patients received medical or surgical castration at the time of diagnosis. Significant correlates of short tCRPC included: prostate specific antigen >20 ng/mL (HR 2.56, 95% CI 1.25-5.23, P=0.010), core involvement >50% (HR 2.11, 95% CI 1.43-3.11, P<0.001), bone metastases (HR 2.94, 95% CI 1.36-6.35, P=0.006), visceral metastases (HR 01.65, 95% CI 1.08-2.53, P=0.021), hemoglobin <10 g/dL (HR 2.02, 95% CI 1.26-3.23, P=0.003), alkaline phosphatase (ALP) >240 U/L (HR 2.42, 95% CI 1.62-3.61, P<0.001), lactate dehydrogenase (LDH) >200 U/L (HR 1.68, 95% CI 1.16-2.43, P=0.006) and neutrophil-lymphocyte ratio >2.4 (HR 1.50, 95% CI 1.03-2.20, P=0.035). In multivariate model, core involvement >50% (aHR 2.99, 95% CI 1.79-5.01, P<0.001), ALP >240 U/L (aHR 2.08, 95% CI 1.13-3.84, P=0.019) and LDH >200 U/L (aHR 1.71, 95% CI 1.02-2.86, P=0.043) independently predicted short tCRPC and each factor decreased tCRPC by almost 50%. Mean prognostic score (PS), based on 1 point for each independent predictor (scale 0-3), was 1.23 (SD 0.91) and significantly predicted short tCRPC (P<0.001). [Table] Conclusions: Our PS based on core involvement (>50%), high ALP (>240 U/L) and high LDH (>200 U/L) significantly predicts tCRPC in men with mPC. Prospective studies are warranted to further validate this score. [Table: see text]