tbuckley/cabot-search huggingface dataset:
Nitrogen back-diffusion during multiple-breath washout with 100% oxygen
Authors: Leanna Sullivan, Erick Forno, Knud Pedersen, Jørgen G. Nielsen, Daniel J. Weiner
Journal: European Respiratory Journal (2017)

The lung clearance index (LCI) measured by multiple-breath washout (MBW) is defined as the number of lung volume turnovers needed to reduce the concentration of a blood-insoluble tracer gas by a factor of 40 during tidal breathing [1]. Over the past two decades, the MBW test has proven to be particularly useful in cystic fibrosis, and studies [2, 3] have demonstrated its superior sensitivity to that of forced expiratory volume in 1 s (FEV1). The ideal tracer gas for the LCI test is so insoluble in blood that any gas exchange effects are insignificant, and it can be measured in concentrations low enough that the tracer itself does not affect the physical properties of the respired air or gas mix. Historically, SF6 is the tracer gas that is most often used in the implementation of the MBW test [1]. However, it has been suggested that the LCI can instead be derived from the washout of nitrogen resident in the lungs using 100% oxygen, and this approach is being applied in a number of ongoing clinical trials. Nitrogen diffuses from blood into lung during nitrogen washout which can affect multiple breath washout results <http://ow.ly/9dcy30dOuwZ> Author contributions: J.G. Nielsen and K. Pedersen initiated and designed the study. L. Sullivan, D.J. Weiner and K. Pedersen collected data and performed inert gas rebreathing and lung clearance index measurements. K. Pedersen and E. Forno analysed the data. All authors contributed to (participated in) the writing and reviewing of the manuscript.
Loss of DNA Damage Response in Neuroblastoma and Utility of a PARP Inhibitor
Authors: Masatoshi Takagi, Misa Yoshida, Yoshino Nemoto, Hiroyuki Tamaichi, Rika Tsuchida, Masafumi Seki, Kumiko Uryu, Noriko Hoshino, Rina Nishii, Satoshi Miyamoto, Masahiro Saito, Toshiaki Shimizu, Ryoji Hanada, Hideo Kaneko, Toshiyuki Fukao, Takatoshi Koyama, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Yusuke Sato, Yoichi Fujii, Keisuke Kataoka, Yusuke Okuno, Kenichi Yoshida, Tomohiro Morio, Akira Oka, Miki Ohira, Yasuhide Hayashi, Akira Nakagawara, Seishi Ogawa, Shuki Mizutani, Junko Takita
Journal: JNCI Journal of the National Cancer Institute (2017)

Neuroblastoma (NB) is the most common solid tumor found in children, and deletions within the 11q region are observed in 11% to 48% of these tumors. Notably, such tumors are associated with poor prognosis; however, little is known regarding the molecular targets located in 11q.Genomic alterations of ATM , DNA damage response (DDR)-associated genes located in 11q ( MRE11A, H2AFX , and CHEK1 ), and BRCA1, BARD1, CHEK2, MDM2 , and TP53 were investigated in 45 NB-derived cell lines and 237 fresh tumor samples. PARP (poly [ADP-ribose] polymerase) inhibitor sensitivity of NB was investigated in in vitro and invivo xenograft models. All statistical tests were two-sided.Among 237 fresh tumor samples, ATM, MRE11A, H2AFX , and/or CHEK1 loss or imbalance in 11q was detected in 20.7% of NBs, 89.8% of which were stage III or IV. An additional 7.2% contained ATM rare single nucleotide variants (SNVs). Rare SNVs in DDR-associated genes other than ATM were detected in 26.4% and were mutually exclusive. Overall, samples with SNVs and/or copy number alterations in these genes accounted for 48.4%. ATM-defective cells are known to exhibit dysfunctions in homologous recombination repair, suggesting a potential for synthetic lethality by PARP inhibition. Indeed, 83.3% NB-derived cell lines exhibited sensitivity to PARP inhibition. In addition, NB growth was markedly attenuated in the xenograft group receiving PARP inhibitors (sham-treated vs olaprib-treated group; mean [SD] tumor volume of sham-treated vs olaprib-treated groups = 7377 [1451] m 3 vs 298 [312] m 3 , P = .001, n = 4).Genomic alterations of DDR-associated genes including ATM, which regulates homologous recombination repair, were observed in almost half of NBs, suggesting that synthetic lethality could be induced by treatment with a PARP inhibitor. Indeed, DDR-defective NB cell lines were sensitive to PARP inhibitors. Thus, PARP inhibitors represent candidate NB therapeutics.
PFS to predict long-term OS after first-line treatment for advanced renal cell carcinoma (aRCC): Correlation and power analysis of randomized trials (RCT).
Authors: Michele Milella, Francesco Massari, Francesca La Russa, Francesca Maines, Alessandra Felici, Vanja Vaccaro, Camillo Porta, Sergio Bracarda, Francesco Cognetti, Diana Giannarelli, Giampaolo Tortora, Emilio Bria
Journal: Journal of Clinical Oncology (2012)

4541 Background: Targeted agents (TA) have become standard 1st line aRCC treatment based on evidence of PFS advantage. Retrospective series indicatePFS as a reliable intermediate end-point in this setting; however, correlation, surrogacy testing, and validation are required. Methods: RCT evaluating the efficacy of TA as 1st line treatment for aRCC were eligible. PFS/OS Response/Disease Control rates (ORR, DCR) and HR were extracted from papers/updated presentations. Correlations between 6-, 9-, and 12-mo PFS and OS rates according to parametric (Pearson’s r) and non-parametric (Spearman’s Rho and Kendall’s Tau) coefficients (with 95% CI) were analyzed to avoid lead-time biases. Regression analysis (parametric R2) and a power-analysis-model to determine patients’ sample necessary to detect 3%, 5% and 10% OS gain were developed. Results: Six RCT (4096 pts) were gathered. The best overall correlation between PFS and OS at concurrent timepoints was found at 9 mos. With regard to overall rates, 3- and 6-mo PFS significantly correlated with 9-mo OS, as shown in the table below. Pearson’s coefficients for the correlation between 3-mo PFS and 6- and 12-mo OS were 0.70 (p=0.01) and 0.67 (p=0.01); the correlation between 6-mo PFS and 12-mo OS was also significant (Pearson 0.74, p=0.005; Spearman 0.83, p=0.005; Tau 0.71, p=0.001). The regression equation was: Y=0.391861 + 0.4914X [R2 0.44, p(slope)=0.01]; based on this model, the demonstration of a 3-mo PFS absolute difference of 6%, 10% and 21% (corresponding to a 9-mo OS benefit of 3%, 5% and 10%) would require 2043, 696 and 155 patients, respectively. A significant correlation was also found between DCR and OS. Conclusions: Early PFS is an acceptable intermediate end-point for OS in the context of 1st line TA for aRCC. Individual patient data analysis to verify Prentice criteria would be required for definitive confirmation. [Table: see text]
The Approaches to Cancer Research&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Carl Voegtlin
Journal: JNCI Journal of the National Cancer Institute (1940)

The Approaches to Cancer Research Get access Carl Voegtlin Carl Voegtlin Chief National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 1, 1940-1941, Pages 11–15, https://doi.org/10.1093/jnci/1.1.11 Published: 01 August 1940
Persistent detection of dengue virus RNA in vaginal secretion of a woman returning from Sri Lanka to Italy, April 2017
Authors: Marco Iannetta, Eleonora Lalle, Maria Musso, Fabrizio Carletti, Laura Scorzolini, Alessandra D’Abramo, Pierangelo Chinello, Concetta Castilletti, Giuseppe Ippolito, Maria R Capobianchi, Emanuele Nicastri
Journal: Eurosurveillance (2017)

We describe the dynamics of dengue virus (DENV) infection in a woman in her mid-30s who developed fever after returning from Sri Lanka to Italy in April 2017. Laboratory testing demonstrated detectable DENV-RNA in plasma, urine, saliva, vaginal secretion. Persistent shedding of DENV-RNA was demonstrated in vaginal secretion, and DENV-RNA was detectable in the pelleted fraction up to 18 days from symptom onset. These findings give new insights into DENV vaginal shedding and vertical transmission.
Longitudinal Change in Fasting Blood Glucose and Myocardial Infarction Risk in a Population Without Diabetes
Authors: Cheng Jin, Shuohua Chen, Anand Vaidya, Yuntao Wu, Zhijun Wu, Frank B. Hu, Penny Kris-Etherton, Shouling Wu, Xiang Gao
Journal: Diabetes Care (2017)

OBJECTIVE To examine the change in fasting blood glucose (FBG) during repeated assessments over time and its potential impact on the risk of developing myocardial infarction (MI). RESEARCH DESIGN AND METHODS This prospective cohort study included 68,297 participants without diabetes (mean age 49 years) who were free of MI, stroke, and cancer prior to or in 2010 (baseline of the current analysis). FBG concentrations were measured in 2006, 2008, and 2010. The FBG trajectories during 2006–2010, the primary exposure of the current study, were identified by latent mixture modeling. Incident MI cases were confirmed via review of medical records by cardiologists. RESULTS We identified five discrete FBG trajectories according to FBG range and changing pattern over time: elevated-stable (n = 3,877), elevated-decreasing (n = 7,060), moderate-increasing (n = 10,298), moderate-stable (n = 40,352), and low-stable (n = 6,710). During 4 years of follow-up, we documented 283 incident MI cases. Relative to the moderate-stable pattern (FBG ranged from 4.9 to 5.1 mmol/L), adjusted hazard ratios (HRs) were 1.53 (95% CI 1.04, 2.26) for the elevated-stable pattern (FBG ranged from 6.1 to 6.3 mmol/L) and HR 0.61 (95% CI 0.38, 0.98) for the elevated-decreasing pattern (FBG decreased from 6.0 to 5.4 mmol/L), after adjustment for potential confounders such as age, sex, lifestyle factors, obesity, medical history, blood pressure, blood lipids, and C-reactive protein. Consistently, cumulative average and increasing rate of FBG during 2006–2010, but not a single baseline FBG, predicted future risk of MI. CONCLUSIONS We found that discrete FBG trajectories were significantly associated with subsequent risk of MI in individuals without diabetes. These observations suggest that long-term trajectories of FBG may be important for risk prediction of MI and possibly other macrovascular diseases.
Overall survival (OS) of EGFR mutation-positive non-small cell lung cancer (NSCLC) patients: Real-world treatment patterns of 1,660 Japanese patients (pts).
Authors: Yoshida Kazushi, Akira Inoue, Shunichi Sugawara, Shuji Murakami, Hideo Saka, Satoshi Morita, Young Hak Kim, Fumio Imamura, Koji Takeda, Kazuhiko Nakagawa, Masayuki Takeda, Shinji Atagi, Yoshikazu Hasegawa, Nobuyuki Yamamoto, Nobuyuki Katakami, Hiroshige Yoshioka, Yasuo Iwamoto, Isamu Okamoto, Takashi Seto, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2016)

e20503 Background: Since the 1st epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) was launched in Japan, the survival periods of EGFR mutation positive (EGFR m+) advanced/recurrent NSCLC pts have been getting longer. However, clinical factors contributing to the longer survival remains unclear. We investigated the OS, and potential prognostic factors of EGFRm+ NSCLC pts in the real-world clinical practice. Methods: This is a multi-center, observational, retrospective study. NSCLC pts who started first-line treatment from 1/1/2008 to 31/12/2012 were enrolled. Eligible pts were diagnosed with EGFRm+ advanced/recurrent NSCLC by tissue or cytology samples. The primary objective was OS. The secondary objectives were to determine prognostic factors and treatment patterns. We also conducted “Dynamic Treatment Regimen Analysis (DTRA)” to explore the effects of treatment sequence on OS. Results: One thousand six hundred sixty NSCLCpts were enrolled from 17 hospitals in Japan: 64.8% of female, median age of 67.0 y/o, 95.2% had adenocarcinoma, 50.1% had exon 19 deletions, 66.7% at stage IV, and Performance Status (PS) 0 or 1 were 80.1%. Median OS was 30.8 months (M). Cox regression analysis revealed sex, age, histology, EGFR mutation type, clinical stage and PS were independently associated with OS. Only 3.3% of pts never received EGFR-TKI, whilst 49.8% pts never received platinum (Pt) doublet chemotherapy in his/her whole treatment. The median number of treatment regimens was 2. Most frequently used 1stline treatment category was gefitinib (N = 962, 58.1%), followed by Pt doublet +/- bevacizumab (N = 509, 30.7%). Median OS for each was 29.07 m [ 95% CI, 26.87 to 31.60], and 35.13 m [ 95% CI, 30.70 to 38.30] respectively, although there is no statistical difference by multivariate analysis. For DTRA, survival curves were estimated for treatment sequences by second line and after. Conclusions: Real world treatments of the large data-set in EGFR m+ NSCLC pts were retrospectively investigated. First generation EGFR-TKIs were major components of the treatment regimens for this patient population in Japan either as 1st or 2nd-line therapy. (NCT0247520)
Research Activities of the National Cancer Institute
Authors: Michael B. Shimkin
Journal: JNCI Journal of the National Cancer Institute (1944)

Journal Article Research Activities of the National Cancer Institute Get access Michael B. Shimkin Michael B. Shimkin surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 2, October 1944, Pages 77–88, https://doi.org/10.1093/jnci/5.2.77 Published: 01 October 1944
Residual Blast Cells in Bone Marrow on Day 15 Following Remission Induction Therapy for Acute Myeloid Leukemia Is Associated with Long-Term Prognosis: A Retrospective Analysis of the JALSG AML201 Study
Authors: Maki Hagihara, Shin Fujisawa, Sumihisa Honda, Shigeki Ohtake, Shuichi Miyawaki, Nobuaki Dobashi, Toru Sakura, Yukiyasu Ozawa, Yoshikazu Ito, Katsumichi Fujimaki, Asao Hirose, Hiroyuki Fujita, Kinya Ohata, Tomoya Maeda, Toshi Imai, Hitoshi Kiyoi, Yasushi Miyazaki, Kazunori Ohnishi, Tomoki Naoe, Hideaki Nakajima
Journal: Blood (2016)
アルツハイマー病におけるアポリポ蛋白質E(APOE)ε4とエピソード記憶低下:レビュー【Powered by NICT】
Authors: El Haj Mohamad, Antoine Pascal, Amouyel Philippe, Lambert Jean-Charles, Pasquier Florence, Kapogiannis Dimitrios
Journal: Ageing Research Reviews (2016)
Differences in the transforming capacity and signal transduction properties of Flt3-D835Y versus Flt3-ITD.
Authors: Chunaram Choudhary, Joachim Schwäble, Wolfgang E. Berdel, Carsten Müller-Tidow, Hubert Serve
Journal: Cancer Research (2004)

2419   Activating mutations of the receptor tyrosine kinase Flt3 are found in >30% of patients with acute myeloid leukemia (AML). They represent an attractive drug target. In 25% of the cases, internal tandem duplications (Flt3-ITD) are found that lead to insertion of several amino acids in the juxtamembrane domain of the receptor. The occurrence of these mutations is associated with a bad prognosis. Previously, we have shown that Flt3-ITD induce significant alterations in the signaling properties of Flt3. For example, Flt3-ITD induce a strong activation of STAT proteins. They also inhibit the expression and function of myeloid transcription factors that have found to be interrupted in many cases of AML. The other class of Flt3 mutations occurs with a lower frequency (about 7%) and is less well characterized. It consists of activating point mutations like D835Y, or small insertions in the activation loop of the tyrosine kinase domain. No association of these mutations with a bad prognosis has been shown. Here, we compared the signaling properties of the two classes of Flt3-mutations in 32D cells. We found that Flt3-D835Y induced autonomous growth in suspension cultures similar to ligand-stimulated Flt3-WT. However, in contrast to Flt3-ITD and in accordance to ligand-stimulated Flt3-WT, Flt3-D835Y could not support colony formation in semisolid media. When we compared the signaling properties of ligand-activated Flt3-WT and mutationally activated Flt3-ITD and Flt3-D835Y, we found that Flt3-ITD, but neither Flt3-WT nor Flt3-D835Y induced activation or induction of target genes of STAT5. Also, in contrast to Flt3-ITD, Flt3-D835Y did not lead to the repression of c/EBPalpha or Pu.1 on the mRNA and protein levels. No differences between the receptor isoforms were found when they were analyzed for constitutive receptor autophosphorylation, or the phosphorylation and activation of Erk-1 and –2, Akt, and Shc. In conclusion, we demonstrate profound differences in the signaling properties of Flt3-ITD and Flt3-D835Y that could have important implications for their transforming capacity in AML and for the design of mutation-specific therapeutic approaches.
Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine
Authors: George D. Demetri, Patrick Schöffski, Giovanni Grignani, Jean-Yves Blay, Robert G. Maki, Brian A. Van Tine, Thierry Alcindor, Robin L. Jones, David R. D’Adamo, Matthew Guo, Sant Chawla
Journal: Journal of Clinical Oncology (2017)

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.
Erratum: Sequential measurements of bone lead content by L X-Ray fluorescence in CaNa2EDTA-treated lead-toxic children (Environmental Health Perspectives, 91:57-62 (1990))
Authors: J. F. Rosen, M. E. Markowitz, P. E. Bijur, S. T. Jenks, L. Wielopolski, J. A. Kale-Ezra, D. N. Slatkin
Journal: Environmental Health Perspectives (1991)
エチルセルロースのナノキャリアとナノ結晶は自然な,テープ剥離またはラウリル硫酸ナトリウム曝露のex vivoヒト皮膚へ異なったデキサメタゾン輸送をする ― 皮内ミクロ透析および様々な皮膚層からの抽出による評価
Authors: Doge Nadine, Honzke Stefan, Schumacher Fabian, Balzus Benjamin, Colombo Miriam, Hadam Sabrina, Rancan Fiorenza, Blume-Peytavi Ulrike, Schaefer-Korting Monika, Schindler Anke, Ruehl Eckart, Skov Per Stahl, K Church Martin, Hedtrich Sarah, Kleuser Burkhard, Bodmeier Roland, Vogt Annika
Journal: Journal of Controlled Release (2016)
Methionine PET Might Be Reliable for the Detection of Low M-Protein–Producing Myelomas
Authors: Osamu Imataki, Shumpei Uchida, Shigeyuki Yokokura, Makiko Uemura, Norimitsu Kadowaki
Journal: Clinical Nuclear Medicine (2017)

C-methionine (MET) positron emission tomography (PET) is more sensitive than F-fluorodeoxyglucose (FDG)-PET for detecting myeloma lesion. Many clinical studies support this evidence mainly for multiple myeloma cases of IgG or IgA subtypes. However, this is not confirmed for low monoclonal protein-producing myelomas, such as IgD, IgE, and nonsecretory type. We encountered a 71-year-old man with IgD λ-type myeloma. In this patient, FDG-PET did not reveal any abnormal uptake lesions, whereas MET-PET revealed diffuse bone marrow uptake that relieved after initial chemotherapy. We speculate that the determinants for high serological activity of protein metabolism are transporter system activity or proliferation index.
Feiba Global Outcome Study (FEIBA-GO): Long-Term Real World Data on Apcc (FeibaR) in Patients with Inhibitors. First Demographic Data
Authors: Ana Rosa Cid, Carmen Escuriola, Cedric R. Hermans, Pal André Holme, Claude Negrier, Savita Rangarajan, Angiola Rocino, Jerzy Windyga, Alessandro Gringeri, Roberto Crea
Journal: Blood (2016)
A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study
Authors: Danxia Gu, Ning Dong, Zhiwei Zheng, Di Lin, Man Huang, Lihua Wang, Edward Wai-Chi Chan, Lingbin Shu, Jiang Yu, Rong Zhang, Sheng Chen
Journal: The Lancet Infectious Diseases (2017)
89Zr-Trastuzumab PET/CT for Detection of Human Epidermal Growth Factor Receptor 2–Positive Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Negative Primary Breast Cancer
Authors: Gary A. Ulaner, David M. Hyman, Serge K. Lyashchenko, Jason S. Lewis, Jorge A. Carrasquillo
Journal: Clinical Nuclear Medicine (2017)

The aim of this study was to determine if imaging with Zr-trastuzumab, a human epidermal growth factor receptor 2 (HER2)-targeting PET tracer, can detect HER2-positive metastases in patients with HER2-negative primary breast cancer.As part of an institutional review board-approved, prospective clinical trial of Zr-trastuzumab PET/CT (ClinicalTrials.gov identifier NCT02286843), a second group of 11 patients with HER2-negative primary breast cancer and known metastatic disease were recruited. Patients with confirmed HER2-negative primary breast cancer underwent Zr-trastuzumab PET/CT to screen for Zr-trastuzumab-avid lesions suggestive of unsuspected HER2-positive metastases. Zr-trastuzumab-avid lesions on PET/CT were biopsied and pathologically examined to determine HER2 status.All 11 patients had confirmed HER2-negative primary breast cancer. Four patients demonstrated suspicious foci on Zr-trastuzumab PET/CT. Of these 4 patients, 1 patient had biopsy-proven HER2-positive metastases. The other 3 patients with suspicious Zr-trastuzumab-avid foci had biopsy demonstrating a metastasis that was HER2-negative and were considered false-positive Zr-trastuzumab PET foci. Combined with a published report of the first 9 patients, there have been a total of 20 HER2-negative primary breast cancer patients, with 3 patients (15%) having pathologically confirmed HER2-positive distant metastases and 6 (30%) with suspicious Zr-trastuzumab-avid foci that were HER2-negative on pathology, which were thus considered false-positive Zr-trastuzumab findings.This second group of patients confirms the proof of concept that Zr-trastuzumab PET/CT detects unsuspected HER2-positive metastases in a subset of patients with HER2-negtive primary breast cancer. False-positive Zr-trastuzumab-avid foci present a challenge to using this tracer.