tbuckley/cabot-search huggingface dataset:
Risk of unplanned presentations and hospital admission in lung cancer patients: Insights from the experience of a single institution.
Authors: Elisa De Carlo, Vanessa Buoro, Lorenzo Gerratana, Marco Giavarra, Simona Rizzato, Ciro Rossetto, Marianna Macerelli, Monica Cattaneo, Giacomo Pelizzari, Mauro Mansutti, Giuseppe Aprile, Alessandro Follador, Fabio Puglisi, Gianpiero Fasola
Journal: Journal of Clinical Oncology (2016)

e21601 Background: Despite great improvements in lung cancer (LC) treatment over the last years, significant toxicities are still observed that may lead to unscheduled access to the oncology clinic as well as to hospital admission. Furthermore, LC patients (pts) frequently require emergency medical care due to acute unbearable symptoms and life-threatening conditions. Our study aimed to describe the magnitude of this phenomenon in LC pts and to identify risk factors affecting the number and the outcome of unscheduled accesses. Methods: We retrospectively collected a consecutive cohort of 285 LC pts treated at the Department of Oncology of Udine (Italy), from 2012 to 2015. Our analysis focused on the subgroup of pts that experienced an unplanned access to both the Oncology or the Emergency Department (ED). Associations between clinical pathological features and hospitalization were investigated through logistic regression. The impact of patients’ hallmarks at first access on the number of presentations was explored through Mann-Whitney test. Results: Among enrolled pts, 131 experienced an unplanned access to the Oncology or the ED with 1 median access for patient (range 1-10). At first presentation, 74.6% pts had an ECOG PS of 0-1; pain (37.7%), anemia (28.2%), and fever (17.6%) were the main clinical signs recorded during the visit. Neutropenia was observed in 9.2% pts none of whom had febrile neutropenia. Pulmonary embolism (PE) was found in 7.1% pts. Overall 21.5% of pts experienced at least one hospitalization and 5.4% were admitted more than once; 16.1% hospital admission was the result of the first unscheduled access. Direct access to the ED and ECOG PS 2-3 were associated to hospitalization (OR respectively 2.62, 95%CI 1.05-6.52; P = 0.0385 and 6.27 95%CI 2.59-15.31; P < 0.0001). Notably, only a diagnosis of PE significantly increased the number of following accesses (P = 0.0387). Conclusions: The study explored the impact of clinical features on unplanned access pattern and hospitalization in LC pts. Deepening this aspect could be crucial in order to better identify frail patients and minimize quality-of-life impairment and over-hospitalization.
Abstract 19164: Renal Sympathetic Denervation Modulates Natriuretic Peptides by Inhibiting Neprilysin in the Failing Heart
Authors: David J Polhemus, Rishi Trivedi, Juan Gao, Amy Scarborough, John Valentino, Traci Goodchild, Daniel Kapusta, Frank Smart, David J Lefer
Journal: Circulation (2016)

Introduction: Sustained pathological sympathetic activation that accompanies heart failure (HF) contributes to the progression of myocardial injury and left ventricular (LV) dysfunction. Neprilysin (NEP) degrades natriuretic peptides (NP) and attenuates the beneficial effects of natriuretic peptide signaling. We utilized radiofrequency renal nerve denervation (RF-RDN) in a rodent model of hypertension and heart failure to investigate whether renal efferent activity regulates NEP activity and regulates NP levels and signaling. Methods: Spontaneously hypertensive rats (SHR) 20 weeks of age were subjected to 45 min of Left Anterior Descending coronary artery ligation followed by 12 weeks of reperfusion (Rep). 4 weeks following Rep, rats underwent either surgical bilateral radiofrequency RF-RDN (n=9) or sham RF-RDN (n=8) procedure (Biosense Webster Stockert 70 RF generator). Every 2 weeks, transthoracic echocardiograms were performed using Vevo 2100 (Visualsonics) to assess LV function. At 12 weeks plasma bra...
Efficacy analysis of adjuvant therapy with imatinib for gastric intermediate-risk gastrointestinal stromal tumor.
Authors: Peng Zhang, Yuping Yin, Xiangyu Zeng, Weizhen Liu, Ming Cai, Jinbo Gao, Kaixiong Tao
Journal: Journal of Clinical Oncology (2018)

e23510 Background: Accumulating evidence suggests that patients with high-risk gastrointestinal stromal tumor (GIST) can significantly benefit from adjuvant therapy with imatinib. However, the effect of this therapy in intermediate-risk GIST patients, particularly within gastric, has yet to be well demonstrated. Herein, we explored the efficacy of adjuvant imatinib in patients with gastric intermediate-risk GIST (GIGIST). Methods: The clinicopathologic and follow-up data on 93 GIGIST cases diagnosed from January 2005 to December 2016 at Union Hospital, Wuhan China were analyzed retrospectively. Univariate and multivariate analyses were performed to assess the prognostic factors for GIGIST. The patients were divided into three subgroups (Table) according to the multivariate analysis results to evaluate the efficacy of adjuvant imatinib. Results: We examined 43 male and 50 female patients with a median age of 60 years (range, 21-84 years). All patients underwent complete resection, and 42 (45%) patients were prescribed adjuvant imatinib 400 mg/day after surgery. The median adjuvant therapy period was 16 months (range, 12-72 months). The majority of the patients (86% [n = 80]) underwent followed-up for a median period of 46 months (range, 6-120 months). The 1-, 3-, and 5-year recurrence-free survival (RFS) rates in the whole group were 100.0%, 91.5% and 88.5%, respectively. Multivariate analysis revealed that the mitotic count (P = 0.040, relative risk (RR) = 6.078 [95% confidence interval (CI), 0.541-68.274]) and neutrophil-lymphocyte ratio (NLR; P = 0.036, RR = 6.102 [95% CI 0.782-47.632]) were prognostic risk factors for RFS. Adjuvant imatinib markedly increased the RFS rates in patients with a mitotic count greater than 2/50 high-power fields (HPF) and an NLR greater than 2.3 but not in the other two subgroups. Conclusions: GIGIST has a favorable overall prognosis. Patients with a mitotic count greater than 2/50 HPF and an NLR greater than 2.3 were identified as an advantageous group for adjuvant imatinib and targeted therapy longer than 1 year is strongly recommended to increase the RFS rate. Subgroup Mitotic count NLR Number of patients 1 ≤2 HPF Any value 28 2 > 2 to ≤10 HPF ≤2.3 28 3 > 2 to ≤10 HPF > 2.3 24
Methylation of CpG islands in the promoter regions of P16, hMLH1 and CDH1 genes in patients with gastric cancer.
Authors: Jieer Ying
Journal: Journal of Clinical Oncology (2016)

e15531 Background: Aberrant methylation of CpG islands in the promoter regions of tumor suppressor genes has been demonstrated to be one of the mechanisms for tumor development. In this study, we analyzed promoter methylation of the following genes in 120 cases of primary gastric carcinoma: P16, hMLH1, and CDH1, in order to explore their effects in the development of gastric cancer and their relationship to clinical parameters. Methods: We examined the promoter methylation in primary tumor and the matched adjacent tissue from 120 patients with pathologically diagnosed primary gastric cancer by methylation-specific PCR (MSP). All of them did not receive preoperative radiotherapy or chemotherapy Results: Promoter methylation was detected in 36.7% (44/120) cases for P16; 24.2% cases for hMLH1; and 25% cases for CDH1 of samples from primary tumors. In comparison, methylation was also detected in P16 (25.8%), hMLH1 (8.3%), and CDH1 (14.2%) of matched normal mucosa from adjacent tissue. Promoter methylation of hMLH1 and CDH1 was statistically significant (p < 0.05) in primary tumor and adjacent normal tissue. Moreover, methylation of hMLH1 and CDH1 in primary tumor and adjacent normal tissue occurred concordantly. Promoter methylation of P16 and CDH1 did not appear to be statistically correlated with multiple clinical pathological characteristics. Borrmann type (p = 0.030) and alcohol history ( = 0.019) showed statistical significance for promoter methylation of hMLH1 in primary tumor. Methylation of hMLH1 was 66.7% in Bormman type I and II, and 21.9% in type III and IV. Methylation of hMLH1 was 40% (12/30) and 18.9% in patients with or without alcohol history. In addition, there was no statistical significance between promoter methylation of p16 and CDH1 in primary tumor and overall survival. Conclusions: Aberrant methylation of CpG islands in the promoter regions of P16, hMLH1 and CDH1 genes is a frequent event. Promoter methylation of CDH1 and hMLH1 might be an important molecular event in the development of gastric cancer and a molecular marker of early diagnosis. Promoter methylation of hMLH1 might be an independent prognostic factor for gastric cancer.
Adaptive dynamic artificial poly-ligand targeting (ADAPT) of the plasma exosome proteome: A highly multiplexed non-invasive diagnostic discovery platform.
Authors: Valeriy Domenyuk, Zhenyu Zhong, Jie Wang, Adam Stark, Xixi Wei, Patrick Kennedy, Brandon Toussaint, Radhika Santhanam, Symon Levenberg, Nianqing Xiao, Mark Robert Miglarese, David D Halbert, George H. Poste, Michael Famulok, Gunter Mayer, David Spetzler
Journal: Journal of Clinical Oncology (2016)

e23058 Background: Understanding individual biomarkers and multi-molecular complexes in their native states represents a major hurdle in the development of systems biology platforms and requires multiplexing capabilities many orders of magnitude greater than what is currently available. This knowledge is especially important in diseases like cancer, where perturbations in signaling pathways lead to the initiation and propagation of a vast range of molecularly heterogeneous phenotypes. Ideally, this information would be gathered non-invasively from peripheral compartments. We report ADAPT as an unbiased discovery method to identify native proteins and multi-molecular complexes in plasma. Methods: ssDNA libraries of 2x10^11 unique sequences were enriched towards association with exosomes of plasma pools from breast cancer patients (n=60) or from a control cohort of women without breast cancer (n=60). Two thousand ODNs were selected from the enriched library and used to profile 500 plasma samples: 206 breast cancer biopsy positive (BC+), 177 biopsy negative (BC-) and 117 self-declared healthy (H). Results: Random Forest Modeling (RFM) was used to build classifiers for BC+ vs. both BC- and H, BC+ vs. BC- and BC+ vs. H, with AUC values of 0.64, 0.64, and 0.73, respectively. Out-of-bag validation was used for this analysis. Notably, 10-fold cross-validation, repeated 20 times, resulted in ROC AUC values of 0.58 for BC+ vs. both controls, 0.59 for BC+ vs. BC-, 0.62 for BC+ vs. H. This difference between the out-of-bag and cross-validation result suggests that the study is underpowered to define an algorithm capable of handling the heterogeneity found in this set of breast cancer patients. Conclusions: The ADAPT platform uses ultra-high complexity libraries to improve the probability of identifying ODNs which recognize biomolecules in their native state. This unbiased approach quantifies differences between plasma from women with breast cancer and women without breast cancer, likely due to perturbations in molecular pathways. An ADAPT derived breast cancer test may find utility as a diagnostic tool in clinical practice.
TGF-beta/AURKA pharmacologic targeting to halt stemness and TNBC progression.
Authors: Antonino BONAVENTURA D'Assoro
Journal: Journal of Clinical Oncology (2018)

e13127 Background: TGF-b signaling promotes an invasive TNBC phenotype through activation of epithelial to mesenchymal transition (EMT) reprogramming. Breast cancer cells that undergo EMT acquire a CD44high/CD24low/ALDH1high cancer stem-like phenotype characterized by an increased capacity for tumor self-renewal, drug resistance and high metastatic proclivity. We have demonstrated that aberrant activation of Aurora-A kinase (AURKA) also induces EMT and stemness in breast cancer cells. The role of the cross-talk between TGF-b and AURKA oncogenic pathways in tumor progression has never been explored in TNBC. Materials and Methods: 1) TNBC Models: Established MDA-MB 231, SUM149-PT and unique Patient-Derived (PD) TNBC-M14 and –M25 cells. 2) Cell Migration: Real-Time Wound Healing Assay using the IncuCyte ZOOM System. 3) Drug Treatment: TNBC cells were treated in vitro with 500nM Paclitaxel, Galunisertib (TGF-Beta inhibitor) and Alisertib (AURKA inhibitor). 4) Self-Renewal Capacity: TNBC cells were cultured under non-adherent conditions to form secondary mammospheres. 5) Stemness Activity: ALDH1 activity was measured in TNBC cells using the Aldeofluor Kit. 6) Apoptosis: Activation of apoptosis was measured in TNBC cells using an Active Caspase-3 FITC-conjugated antibody. Results: In vitro Real-Time Wound Healing assay showed that combination of alisertib and galunisertib was more effective than single agent treatment to inhibit the migration of MDA-MB 231 TNBC cells. While single-agent treatment had a modest effect in preventing PD TNBC-M25 mammospheres formation, the combination of galunisertib and alisertib resulted in a significant shrinkage of mammospheres area. Combination of galunisertib with alisertib also reduced ALDH1 activity. While paclitaxel alone induced apoptosis in 67% of TNBC-M14 cells, the combination of paclitaxel, alisertib and galunisertib resulted in the strongest effect where 91% of cells were apoptotic. Conclusions: These preliminary studies provide the novel pre-clinical rationale of combining TGF-b and AURKA inhibitors to inhibit stemness, restore chemosensitivity and halt TNBC progression.
TCT-643 Antiplatelet therapy with cangrelor in patients undergoing surgery after coronary stent implantation: a real-world bridging protocol experience
Authors: Roberta Rossini, Giulia Masiero, Fabrizio Rolfo, Federico Pappalardo, Claudia Fruttero, Enrico Passamonti, Elba Calvaruso, Moreno Cecconi, Cesare Carlucci, Elisa Bertone, Nicoletta Barzaghi, Giulio Melloni, Alessia Stanzi, Alessandro Locatelli, Giorgio Baralis, Dominick Angiolillo, Giuseppe Musumeci
Journal: Journal of the American College of Cardiology (2018)
Evaluation of <i>PRUNE2</i> and <i>PCA3</i> expression as metastasis predictors in Gleason 7 prostate cancer.
Authors: Richard C. Lauer, Marc Barry, Jin Wu, Ji-Hyun Lee, Dennis J. McCance, Ruofei Du, Arpit Rao, Andrey S. Dobroff, Emmanuel Dias-Neto, Isan Chen, Renata Pasqualini, Wadih Arap
Journal: Journal of Clinical Oncology (2017)

e16583 Background: There is an urgent need to differentiate from truly localized prostate cancer and micrometastatic disease. PCA3 is an FDA-approved biomarker for prostate cancer; however, it is not a predictor of metastasis behavior. We have recently identified PRUNE2 as an unrecognized tumor suppressor gene. Here we examined if the ratio of PRUNE2 and its corresponding dominant-negative oncogene PCA3 might serve as a better predictor of the metastatic potential of prostate cancer, compared to PCA3alone. Methods: We studied 105 prostate cancer patients who underwent a radical prostatectomy at UNM Hospital from 2001 to 2009. At the time of prostatectomy, these patients had a Gleason score of 7 and organ-confined disease. They had at least 5-year follow-up for disease recurrence, and 19 patients developed recurrent disease. PCA3 and PRUNE2 gene expression was quantified by qRT-PCR and normalized to housekeeping control genes. Each experiment was carried out in triplicates. The Wilcoxon rank sum test was used to evaluate whether or not the difference in gene expression of PRUNE2 or PCA3 or the gene expression ratio ( PRUNE2/ PCA3), between patients with and without recurrence, was significant. The association between the time to recurrence and expression levels of each single gene or ratio were also analyzed by the Kaplan-Meier method along with log-rank test and the COX PH modeling. Results: There was no significant difference in expression levels of PRUNE2, PCA3, or the ratio PRUNE2/ PCA3, between patients who developed recurrent disease relative to those who did not. Conclusions: PRUNE2 and PCA3 expression levels, as well as PRUNE2/ PCA3 ratio, did not predict the metastatic potential of Gleason 7 prostate cancer in our retrospective patient cohort. We postulated that the deregulation of the molecular axis of PRUNE2 and PCA3 might occur early in the development of prostate cancer. We are currently examining this mechanistic hypothesis in other studies. [Table: see text]
Radioiodine I-131 ablation therapy and impaired renal function: Possible impact on guidelines.
Authors: Hossam A El-Zeftawy, Jamal M Zekri, Kamel Farag, Rawan Al-Saadi, Bakr M Bin Sadiq, Salman Miliebari
Journal: Journal of Clinical Oncology (2017)

e17591 Background: Sodium iodide (I-131) is eliminated predominantly through renal clearance. There is no consensus on the ideal dose of I-131 to be administered for patients with impaired kidney function. We aim to compare the rate of I-131 clearance in patients with impaired to those with normal renal functions. Methods: 27 cases (34 treatments) of differentiated thyroid cancer and eGFR 15-59 ml/min/1.73 m2 received I-131 (mean dose of 150 mCi) for remnant ablation between 2010 and 2016. Another 34 patients matched for age, gender, weight and I-131 dose with eGFR ≥ 60 ml/min/1.73 m2 were selected as controls. Endpoints of interest were (a) Length of hospital stay (LOHS) until the patient’s I-131 activity declines to &lt; 30 mCi (b) Exposure rate measured by Geiger counter 0 to 48 hours after treatments (ER 48). Paired t-test was used to compare both groups. Results: Mean LOHS for cases vs. controls was 2.47 vs. 2 days respectively (P = 0.007). Results of ER 48 were available and matched in 18 cases and controls. Mean ER 48 for cases vs. controls was 3.74 vs. 1.8 mR/h respectively (P = 0.002). The mean proportional reduction of exposure rate after 48 hours compared to hour 0 for cases and controls was (-88% vs. -92.6%, P = 0.008), (-93.5% vs. -94.5%, P = 0.5) and (-67.2% vs. 94.3%, P = 0.04) for eGFR 46-59 (n = 13), 30-45 (n = 3) and 15-29 ml/min/1.73m2 (n = 2) respectively. Conclusions: Patients with impaired renal function are subject to longer hospital stay and delayed renal clearance of the tracer with consequent increased radiation exposure. Guidelines should consider adjusting the dose of I-131 in these patients to avoid possible harmful effects of excess I-131 on vital organs.
Abstract 3258: Tissue Engineered Graft Grown in the Mouse Peritoneal Cavity: the role of peritoneal-derived stem/progenitor cells
Authors: Lei Song, Lai Wang, Prediman K Shah, Behrooz G Sharifi
Journal: Circulation (2007)

Backgroud: We have generated bioengineered blood vessels in mouse peritoneal cavity in order to test the hypothesis that the mouse peritoneum contains primitive cells with regenerative potential. M...
Prognostic and diagnostic value of serum hyaluronan in patients with pancreatic carcinoma.
Authors: Inna Chen, Christian Dehlendorff, Astrid Zedlitz Johansen, Benny Vittrup Jensen, Mie Barthold Krüger, Per Pfeiffer, Jon Kroll Bjerregaard, Stig Egil Bojesen, Svend Erik Nielsen, Niels Henrik Hollander, Mette Yilmaz, Louise Skau Rasmussen, Julia S. Johansen
Journal: Journal of Clinical Oncology (2018)

e16249 Background: Hyaluronan (HA) is a major component of the tumor stroma in pancreatic carcinoma (PC). HA accumulation increases tumor interstitial fluid pressure, which in turn compresses blood vessels and compromises blood flow. The aim of this prospective - retrospective biomarker study was to determine the prognostic and diagnostic value of serum HA in patients with PC. Methods: A cohort from the Danish BIOPAC study (ClinicalTrials.gov ID: NCT03311776) including 863 patients with histologically confirmed PC, ampullary carcinoma (n = 42), distal biliary tract cancer (n = 29), chronic pancreatitis (n = 15), intraductal papillary mucinous neoplasm (n = 41), patients subjected to surgery in whom PC was suspected but not histologically confirmed (no tumor) (n = 26), high grade dysplasia (n = 7) and 141 healthy controls were enrolled. Serum HA was determined by ELISA (R&D, catalog DHYALO). The main outcome was overall survival (OS) for patients with PC (male/female: 464/399; age < 50 vs. 50-69 vs. ≥70: 42/480/340; ECOG Performance Status (PS) of 0/1/2+: 285/346/107; stage 1/2/3/4: 15/211/153/484; diabetes yes/no: 208/655; smoking yes/no: 518/345; alcohol yes/no: 184/879; body mass index: low/normal/overweight: 64/436/250). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. Results: Significant risk factors for poor outcome were log2-transformed HA (HR = 1.25, 95% CI 1.16-1.34, P < 0.001) and higher PS and stage in univariate analyses. Multivariable analyses showed that serum HA (HR = 1.21, 1.12-1.31), higher PS and higher stage were independently associated with a short OS. Higher HA was associated with higher stage (P < 0.001). HA was statistically significantly higher in PC patients compared with healthy subjects and benign conditions (P < 0.001, P = 002). No statistically significant difference in HA was observed comparing PC with chronic pancreatitis or other malign diseases. Conclusions: Serum HA was an independent prognostic biomarker in patients with PC. Serum HA may also be useful in differentiation between malignant and benign pancreatic conditions and may distinguish between early and late stage PC.
A genome-wide association study (GWAS) meta-analysis of chemotherapy-associated cognitive impairment (CACI) in Asian early-stage breast cancer patients (ESBC).
Authors: Terence NG, Hui Ling Angie Yeo, Maung Shwe, Yan Xiang Gan, Koon Mian Foo, Wei-Jen Kiley Loh, Si-Lin Koo, Wen Yee Chay, Tira Jing Ying Tan, Sok Yuen Beh, Hsuen Elaine Lim, Guek Eng Lee, Rebecca Alexandra Dent, Yoon Sim Yap, Raymond C.H. Ng, Pak Yan Pat Chu, Chiea Chuen Khor, Han Kiat Ho, Alexandre Chan
Journal: Journal of Clinical Oncology (2017)

10096 Background: Genetic variations among genes regulating neuronal function, neurotransmission and plasticity may contribute to varying risk of CACI. In order to fully elucidate the complex genetic structure underlying CACI, a GWAS meta-analysis was performed to identify genetic variants associated with CACI among ESBC patients. Methods: A GWAS meta-analysis of two independent cohorts totaling 266 chemotherapy-receiving ESBC patients (mean age: 51.0 ± 9.2 years; 80.8% Chinese) was performed. Patients’ self-perceived cognitive function was assessed using the validated FACT-Cog (v.3). Genome-wide genotyping was performed using the Illumina HumanOmniExpress-24 version 1.1 BeadChips kits. Each beadchip contains over 700,000 genetic markers. Covariates included in the meta-analysis were the first two dimensions of the multi-dimensional scaling. Results: After applying stringent quality control measures and removing four population outliers, data from 546,399 SNPs were available for 84 cases and 170 controls. In the meta-analysis, two SNPs (rs6443264 and rs4686371) exceeded the suggestive threshold of P &lt; 1×10 -5 (Table). Following adjustment for the first two MDS dimensions in the meta-analysis, both SNPs remained as top two SNPs with P &lt; 1×10 -4 . Both rs6443264 and rs4686371 are located in chromosome 3p25 and lie in the intronic regions encoding OGG1 and ARPC4 genes, respectively. Alteration of the OGG1 gene could compromise the functions of downstream neuronal genes, and modification of the ARPC4 gene could affect the formation of the actin-related protein 2/3 complex and impair memory formation. Conclusions: To the best of our knowledge, this is the first GWAS meta-analysis to identify two loci, namely rs6443264 and rs4686371 that are suggestive of genome-wide association with CACI among Asian ESBC patients. [Table: see text]