tbuckley/cabot-search huggingface dataset:
Abstract #1217: Interaction of cigarette smoke component NNK and arsenic in enhancement of lung carcinogenic risk
Authors: Louis Chang, Wei Ting Liao, Hsin-Su Yu, Pinpin Lin
Journal: Cancer Research (2009)

Interaction of cigarette smoke component NNK and arsenic in enhancement of lung cancer risk. Louis W. Chang, W.T. Liao, H.S. Yu, and Pinpin Lin. National Health Research Institutes and Kaohsiung Medical University, Taiwan, ROC. Epidemiological evidence indicates that there is a significant enhancement in lung cancer incidence among cigarette smokers in arseniasis areas as compared to that in the general population, suggesting a synergism for lung carcinogenesis between cigarette smoke and arsenic. Reduced p53 status in bronchiolar epithelial cells is found in cigarette smokers. We hypothesize that reduced p53 status (reduced p53 expression, activity, or function) provides the stage for arsenic to promote genomic and chromosomal instability (such as centrosome abnormality) leading to an increase in carcinogenic risk. We treated immortalized human bronchiolar epithelial cells (BEAS-2B) with or without p53 inhibitor (pifithrin) as well as a human lung cancer cell line (H1355), which is known to have p53 mutation, with 1-10 uM of arsenite. We found that arsenic treated cells were more resistant to apoptosis. Furthermore, cells with suppressed p53 status (e.g., pif.-treated BEAS-2B cells) showed a reduced Gadd45a expression and an increased centrosome abnormality (centrosome amplification). An increase in cell colony formation by these cells was also observed. These observations clearly indicate that lowered p53 status provides a stage for arsenic to suppress Gadd45a, which is important for the maintenance of centrosome stability and integrity. With suppression of Gadd45a, arsenic would then promote centrosome abnormality with enhanced cell transformation. We further demonstrated that NNK, a specific component in cigarette smoke, suppressed p53 activity in BEAS-2B cells in a dose depending manner. Co-treatment of NNK (1-5 uM) and arsenite (1-5 uM) also showed dose-corresponded increases in chromosome abnormality (amplification) and cellular anueploidy in BEAS-2B cells. These findings further provide the needed scientific validation, as suggested by epidemiological studies, that there is a synergistic interaction between cigarette smoke (NNK) and arsenic in the enhancement of lung carcinogenic risk.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1217.
Inferior local control for T2bN0 glottic carcinoma with impaired mobility treated with radiation alone: A need for more chemotherapy?
Authors: Priyanka Bhateja, Matthew C Ward, John Greskovich, Chandana A. Reddy, Tobenna Igweonu Nwizu, David J. Adelstein, Shlomo A. Koyfman
Journal: Journal of Clinical Oncology (2014)

6084 Background: Radiation therapy monotherapy (RT) is standard for patients (pts) with T2N0 squamous cell cancer (SCC) of the glottis. The presence of impaired vocal cord mobility (T2b) is known to portend higher failure rates compared to cancers with supra/sub-glottic extension without impaired cord mobility (T2a). This study sought to compare the local control (LC) rates for these pts and also compare them to LC rates in pts with T2b-3N0-2 glottic cancer treated with concurrent chemoradiotherapy (CRT). Methods: In this IRB approved retrospective review, we identified pts with histologically confirmed T2-3N0-2 invasive SCC of the glottis, treated with definitive RT or CRT from 1986 to 2013 at our institution. RT (mean dose 70Gy) was delivered using conventional opposed lateral fields; elective nodal irradiation was used for the majority of pts. Chemotherapy consisted of a 96 hour infusion of cisplatin and 5-fluorouracil on weeks 1 and 5, or single agent cisplatin q3wks. LC, overall survival (OS) and disease free survival (DFS) rates were calculated by the Kaplan-Meier method and compared between the groups using the Log-Rank test. Results: Among the 84 pts identified, RT alone was administered to 27 pts with T2aN0 and 31 pts with T2bN0. CRT was delivered to 26 pts with T2b-3N0-2. With a median follow-up of 34 months, we observed a 3-year LC rate in the T2bN0 pts treated with RT alone of 72.5%, compared to 95% in the T2aN0 pts treated with RT (p=0.01) and 91% in the T2b-3N0-2 pts treated with CRT (p=0.08). There was no difference in OS and DFS rates between the 3 groups. There were 13 local failures, 10 of whom were successfully surgically salvaged. On univariate analysis, lower performance status (p=0.04) and T2b disease treated with RT alone (p=0.02) were the only factors that were significantly associated with inferior LC. Patient age, tumor bulk, anterior commissure involvement, nodal stage and the type of chemotherapy were not associated with LC. The rates of acute and late toxicities were higher in the CRT group. Conclusions: Pts with T2bN0 glottic cancer have a relatively high rate of local failure with RT alone. CRT should be considered to maximize the likelihood of treatment success.
Protocol 15PRT/6090:The Best Services Trial (BeST?): effectiveness and cost-effectiveness of the New Orleans Intervention Model for Infant Mental Health − NCT02653716
Authors: Helen Minnis, Kathleen Boyd, Birdie Fitzpatrick, Matt Forde, Christopher Gillberg, Marion Henderson, Lynn McMahon, Emma McIntosh, Alex McConnachie, Martina Messow, Susanne Millar, Laurence Moore, Dennis Ougrin, Nicholas Watson, Philip Wilson
Journal: The Lancet (2016)
Thrombopoietin (TPO) Receptor Agonist Eltrombopag in Combination with Azacitidine (AZA) for Primary Treatment of Myelodysplastic Syndromes (MDS) Patients with Thrombocytopenia: Outcomes from the Randomized, Placebo-Controlled, Phase III Support Study
Authors: Michael J. Dickinson, Honor Cherif, Pierre Fenaux, Moshe Mittleman, Amit Verma, Maria Socorro O Portella, Paul Burgess, Uwe Platzbecker
Journal: Blood (2016)
Unrelated donor umbilical cord blood transplantation with and without total body irradiation: A single-center experience.
Authors: Jeffrey J. Pu, Elizabeth L Miller, Christopher Davis, Arthur S. Berg, Melanie Comito, Robert Greiner, W. Christopher Ehmann, David Claxton, Witold B. Rybka
Journal: Journal of Clinical Oncology (2015)

e18001 Background: Umbilical cord blood (UCB) is rich in hematopoietic stem cells. Because of its loose HLA-matching requirement and abundant resource available, UCB transplantation (UCBT) is emerging as an effective alternative therapy for HSC transplantations. However, the optimal conditioning regimens for UCBT remain debating. While most published UCBT study using total body irradiation (TBI) as part of conditioning regimens, experience using conditioning regimen without TBI is limited. Methods: This is a retrospective study to analyze the outcomes of 47 patients with various diseases receiving UCBT in last 13 years. Individual patients are characterized by gender, age, weight, disease status, the conditioning regimens, the HLA, ABO and gender compatibilities among UCB units and recipient. The outcomes are analyzed and compared among patients receiving different conditioning regimens, especially between patients using TBI and those didn’t. Results: The age at transplant ranged from 0.5 to 65.4 years old (mean: 14.3). The lengths of follow up ranged from 0.9 to 12.8 years (mean: 6.8). The 5 year overall survival (OS) rate was 55.3%. Twenty-six patients were male (55%) and 21 patients were female (45%). Days to neutrophil engraftment from 10 to 38 days (mean: 21.8). Nine patients (19%) developed severe acute GVHD and 8 patients (8%) had severe chronic GVHD. Twenty eight patients (58%) had systemic infection, 5 of which (11%) were CMV infection. Thirty eight patients received Bu/Cy as the conditioning regimen, 9 patients received Flu/Cy as the conditioning regimen. Thirty four patients didn’t use TBI as part of conditioning regimens and 13 patients used TBI. The outcome comparison between using TBI and not using TBI is listed in the table below. Conclusions: The conditioning regimens not using TBI is comparable to the ones using TBI for unrelated donor UCBT. Use TBI Not use TBI 5 year OS rate 53.8% (7/13) 55.9% (19/34) TRM rate 38.5% (5/13) 32.4% (11/34) Engraftment rate 100% (7/7)* 95.7% (22/23)* Infection rate 53.8% (7/13) 64.7% (22/34) GI complication rate 23.0% (3/13) 14.7% (5/34) GVHD rate 23.0% (3/13) 23.5% (8/34) Growth Impairment Rate 16.7% (1/6) 17.2% (5/29) *: incomplete data
Altered homeostatic regulation of innate and adaptive immunity in lower gastrointestinal tract GVHD pathogenesis
Authors: James L.M. Ferrara, Christopher M. Smith, Julia Sheets, Pavan Reddy, Jonathan S. Serody
Journal: Journal of Clinical Investigation (2017)

Lower gastrointestinal (GI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic stem cell transplantation. Recent data indicate that lower GI tract GVHD is a complicated process mediated by donor/host antigenic disparities. This process is exacerbated by significant changes to the microbiome, and innate and adaptive immune responses that are critical to the induction of disease, persistence of inflammation, and a lack of response to therapy. Here, we discuss new insights into the biology of lower GI tract GVHD and focus on intrinsic pathways and regulatory mechanisms crucial to normal intestinal function. We then describe multiple instances in which these homeostatic mechanisms are altered by donor T cells or conditioning therapy, resulting in exacerbation of GVHD. We also discuss data suggesting that some of these mechanisms produce biomarkers that could be informative as to the severity of GVHD and its response to therapy. Finally, novel therapies that might restore homeostasis in the GI tract during GVHD are highlighted.
Abstract 237: The First Direct Measure of Chylomicron Metabolism in Heart Reveals a Reciprocal Balance Between Mitochondrial Oxidation of Fats From Chylomicron vs Albumin Sources
Authors: J. Michael O’Donnell, E. Douglas Lewandowski, Papasani V Subbaiah
Journal: Circulation Research (2015)

Nearly all studies of fat metabolism in healthy and diseased heart are based on albumin sources of fat, even though lipoproteins (chylomicrons, VLDL) are thought to be a major source of fat. If there are distinct differences in uptake, oxidation, and storage of fatty acids (FA) from lipoproteins compared to albumin sources, then our understanding of disease is far from complete. This study provides the very first investigation of the fate of 13C labeled FA from chylomicrons (CM) in heart, with quantified results of the direct competition between CM-FA vs albumin-FA to support mitochondrial ATP synthesis. Chylomicrons were biosynthetically labeled with 13C-oleate by delivering to the duodenum of rat either (a) emulsified in olive oil, or (b) incorporated into micelles. The labeled chylomicrons were collected as lymph via the thoracic duct for six hours. The olive oil approach, used traditionally to prepare CM to contain radiolabeled fats, resulted in a trace fraction of 13C-labeled FA (&lt;2%). The micelle approach enabled 50% enrichment of CM-FA store. Metabolic studies: Isolated rat hearts were perfused with KH buffer containing 13C-chylomicrons, FA free albumin, and glucose; or 13C-chylomicrons, unlabeled oleate complexed to albumin (equimolar FA from CM and albumin; 0.4 mM), and glucose. Hearts were freeze-clamped, and FA oxidation was assessed via high resolution 13C NMR of heart samples. CM-FA provided 50 ± 5 % of the acetyl CoA to support citric acid cycle synthesis of ATP when FA free albumin was used. In the presence of albumin-FA, only 12 ± 2% of acetyl CoA entering the cycle was from the CM-FA. These direct observations of the competition between CM-FA vs albumin-FA counter prior interpretations based on indirect measures. Those studies suggested no change in CM-FA oxidation when albumin-FA was added. Our novel approach enables direct measurements of CM-FA and albumin-FA oxidation in the mitochondria of intact hearts. The uptake and distribution of fat from either exogenous source were found to contribute to a common intracellular source of activated FA, with mitochondrial oxidation being proportional to the availability of the FA source. Importantly, this new evidence for a common pool significantly simplifies our metabolic paradigm of cardiac disease.
Clinicopathologic features, surgical treatments, and outcomes of small bowel tumors: A retrospective study in China
Authors: Shuisheng Zhang, Cuiling Zheng, Yingtai Chen, Quan Xu, Jie Ma, Wei Yuan, Qinglong Jiang, Yajie Zhao, Jianwei Zhang, Xu Che, Chengfeng Wang, Xiaozhun Huang, Fang Chen, Nianchang Wang, Xiao Ma, Zhongmin Lan
Journal: International Journal of Surgery (2017)
Phase II study of biweekly administration of CPT-11 and gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer in Japan.
Authors: Ryoji Takada, Tatsuya Ioka, Nobuko Ishida, Takuo Yamai, Nobuyasu Fukutake, Reiko Ashida, Hiroyuki Uehara, Kazuhiro Katayama
Journal: Journal of Clinical Oncology (2013)

e15150 Background: The current standard therapies for metastatic pancreatic adenocarcinoma in Japan are the single-agent Gemcitabine (Gem) or S-1 and Gem plus erlotinib. Irinotecan (CPT-11) is one of the promising drugs for Gem-refractory PC pts. Both Irinotecan and Gem have shown activity against these diseases with different mechanisms and are non-cross-resistant with each other. Japanese pts have the different metabolism with Irinotecan rather than pts in western countries. Methods: The aim of this phase II study was to evaluate the efficacy and safety of CPT-11 and Gem in Japanese pancreatic cancer pts. Patients with MPC and PS 0-2 were enrolled in this phase II trial. CPT-11, 100mg/m (2), was administered in 90 min. and Gem, 1000mg/m (2), was administered in 30 min. soon after CPT-11 on day1. Chemotherapy was repeated biweekly. Results: From May 2002 to May 2006 40 pts, with median age of 62 (40-74) years, were enrolled in this study. The overall response rate (RR) was 15% with disease control rate of 50%. The median progression-free survival (PFS) was 4.0 months (range: 1.0-15.0 months), and median overall survival (OS) was 7.5 months (range: 3.0-24.0 months). Grade 3/4 anemia, leucopenia occurred in 26.3, 5.2% of pts. The most common non-hematologic toxities were fatigue, diarrhea, nausea/vomiting and anorexia. Grade 3 diarrhea and nausea occurred in 10.5% of pts. Conclusions: The combination chemotherapy with Gem and CPT-11 showed favorable RR as expected and the treatment was manageable in Japanese pts with MPC. We plan to evaluate this combination chemotherapy for MPC pts after progression of FOLFIRINOX in near the future. Clinical trial information: UMIN000009963.
Trends in Visits to Specialist Physicians Involving Nurse Practitioners and Physician Assistants, 2001 to 2013
Authors: Kristin N. Ray, Grant R. Martsolf, Ateev Mehrotra, Michael L. Barnett
Journal: JAMA Internal Medicine (2017)

notes and could not yet examine section-specific provenance data (eg, physical examination).Future analysis will examine how copied and imported text is used to fulfill the various functions of a note, such as billing or clinical history recall.This finding could spur EHR design that makes copied and imported information readily visible to clinicians as they are writing a note but, ultimately, does not store that information in the note.For example, copied text used as a hospital course record to facilitate the creation of a discharge summary may represent an opportunity for the EHR to provide an alternative space for discharge information.Alternately, copied text that represents a belief that more text leads to higher billing suggests an opportunity for educating clinicians in how notes are coded.As mentioned, this study's limitations included its singlecenter, single-service focus and inability to access sectionspecific provenance data.Clinicians spend time every day writing progress notes.
HPV関連頭頸部扁平上皮癌の免疫耐性におけるPD-1/PD-L1経路の役割に関する証拠
Authors: Lyford-Pike Sofia, Peng Shiwen, D Young Geoffrey, M Taube Janis, H Westra William, Akpeng Belinda, C Bruno Tullia, D Richmon Jeremy, Wang Hao, A Bishop Justin, Chen Lieping, G Drake Charles, L Topalian Suzanne, M Pardoll Drew, I Pai Sara
Journal: Cancer Research (2013)
Evaluation of Genetic Predisposition for MYCN-Amplified Neuroblastoma
Authors: Eric A. Hungate, Mark A. Applebaum, Andrew D. Skol, Zalman Vaksman, Maura Diamond, Lee McDaniel, Samuel L. Volchenboum, Barbara E. Stranger, John M. Maris, Sharon J. Diskin, Kenan Onel, Susan L. Cohn
Journal: JNCI Journal of the National Cancer Institute (2017)

To investigate genetic predispositions for MYCN-amplified neuroblastoma, we performed a meta-analysis of three genome-wide association studies totaling 615 MYCN-amplified high-risk neuroblastoma cases and 1869 MYCN-nonamplified non-high-risk neuroblastoma cases as controls using a fixed-effects model with inverse variance weighting. All statistical tests were two-sided. We identified a novel locus at 3p21.31 indexed by the single nucleotide polymorphism (SNP) rs80059929 (odds ratio [OR] = 2.95, 95% confidence interval [CI] = 2.17 to 4.02, Pmeta = 6.47 × 10-12) associated with MYCN-amplified neuroblastoma, which was replicated in 127 MYCN-amplified cases and 254 non-high-risk controls (OR = 2.30, 95% CI = 1.12 to 4.69, Preplication = .02). To confirm this signal is exclusive to MYCN-amplified tumors, we performed a second meta-analysis comparing 728 MYCN-nonamplified high-risk patients to identical controls. rs80059929 was not statistically significant in MYCN-nonamplified high-risk patients (OR = 1.24, 95% CI = 0.90 to 1.71, Pmeta = .19). SNP rs80059929 is within intron 16 in the KIF15 gene. Additionally, the previously reported LMO1 neuroblastoma risk locus was statistically significant only in patients with MYCN-nonamplified high-risk tumors (OR = 0.63, 95% CI = 0.53 to 0.75, Pmeta = 1.51 × 10-8; Pmeta = .95). Our results indicate that common genetic variation predisposes to different neuroblastoma genotypes, including the likelihood of somatic MYCN-amplification.
CLL: A Prognostic Model Comprising Only Two Biomarkers (IGHV Mutational Status and FISH-Cytogenetics) Separates Patients with Different Prognosis and Simplifies the CLL-IPI.
Authors: Julio Delgado, Michael Doubek, Tycho Baumann, Jana Kotaskova, Pablo Mozas, Alfredo Rivas-Delgado, Sarka Pospisilova, Emili Montserrat
Journal: Blood (2016)
Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages
Authors: Syed F. Hassnain Waqas, Anh Cuong Hoang, Ya-Tin Lin, Grace Ampem, Hind Azegrouz, Lajos Balogh, Julianna Thuróczy, Jin-Chung Chen, Ivan C. Gerling, Sorim Nam, Jong-Seok Lim, Juncal Martinez-Ibañez, José T. Real, Stephan Paschke, Raphaëlle Quillet, Safia Ayachi, Frédéric Simonin, E. Marion Schneider, Jacqueline A. Brinkman, Dudley W. Lamming, Christine M. Seroogy, Tamás Röszer
Journal: Journal of Clinical Investigation (2017)

The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet-fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. Mechanistically, the effects of NPFF involved the suppression of E3 ubiquitin ligase RNF128 expression, resulting in enhanced stability of phosphorylated STAT6 and increased transcription of the M2 macrophage-associated genes IL-4 receptor α (Il4ra), arginase 1 (Arg1), IL-10 (Il10), and alkylglycerol monooxygenase (Agmo). NPFF induced ATM proliferation concomitantly with the increase in N-Myc downstream-regulated gene 2 (Ndrg2) expression and suppressed the transcription of Ifi200 cell-cycle inhibitor family members and MAF bZIP transcription factor B (Mafb), a negative regulator of macrophage proliferation. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs.
Genome editing of factor X in zebrafish reveals unexpected tolerance of severe defects in the common pathway
Authors: Zhilian Hu, Yang Liu, Michael C. Huarng, Marzia Menegatti, Deepak Reyon, Megan S. Rost, Zachary G. Norris, Catherine E. Richter, Alexandra N. Stapleton, Neil C. Chi, Flora Peyvandi, J. Keith Joung, Jordan A. Shavit
Journal: Blood (2017)
HELOISE: Phase IIIb Randomized Multicenter Study Comparing Standard-of-Care and Higher-Dose Trastuzumab Regimens Combined With Chemotherapy as First-Line Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Authors: Manish A. Shah, Rui-hua Xu, Yung-Jue Bang, Paulo M. Hoff, Tianshu Liu, Luis A. Herráez-Baranda, Fan Xia, Amit Garg, Mona Shing, Josep Tabernero
Journal: Journal of Clinical Oncology (2017)

Purpose To compare standard-of-care (SoC) trastuzumab plus chemotherapy with higher-dose (HD) trastuzumab plus chemotherapy to investigate whether HD trastuzumab increases trastuzumab serum trough concentration (Ctrough) levels and increases overall survival (OS) in first-line human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. Patients and Methods Patients with Eastern Cooperative Oncology Group performance status 2, no prior gastrectomy, and ≥ two metastatic sites were randomly assigned at a one-to-one ratio to loading-dose trastuzumab 8 mg/kg followed by SoC trastuzumab maintenance 6 mg/kg every 3 weeks or loading-dose trastuzumab 8 mg/kg followed by HD trastuzumab maintenance 10 mg/kg every 3 weeks until progression; treatment in each arm was combined with cisplatin 80 mg/m2 plus capecitabine 800 mg/m2 twice per day in cycles 1 to 6. The primary objective was HD trastuzumab OS superiority (all randomly assigned patients [full-analysis set]). Final results are from an interim analysis for futility (boundary hazard ratio [HR] ≥ 0.95) at 125 deaths. Results At clinical cutoff, 248 patients had been randomly assigned. A marked increase in mean trastuzumab Ctrough was observed after the first HD trastuzumab cycle versus SoC trastuzumab. In the full-analysis set, median OS was 12.5 months in the SoC trastuzumab arm and 10.6 months in the HD trastuzumab arm (stratified HR, 1.24; 95% CI, 0.86 to 1.78; P = .2401). Results were similar in the per-protocol set (cycle 1 trastuzumab Ctrough < 12 µg/mL). Safety was comparable between arms. Conclusion HD trastuzumab maintenance dosing was associated with higher trastuzumab concentrations, no increased efficacy, and no new safety signals. HELOISE confirms standard-dose trastuzumab (loading dose of 8 mg/kg followed by 6 mg/kg maintenance dose every 3 weeks) with chemotherapy as the SoC for first-line treatment of human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.