tbuckley/cabot-search huggingface dataset:
Vidéo-gastroscopie électronique par voie nasale à l’endoscope fin avec biopsies à la pince pédiatrique
Authors: M Happi Nono, JC Letard, P Adenis Lamarre, M Lansmann, O Faux, P Rouquier
Journal: Endoscopy (2004)

Introduction: La vidéo gastroscopie électronique à l’endoscope fin a fait l’objet de peu d’études dans la littérature, de plus la qualité des prélèvements obtenus avec des pinces pédiatriques reste à préciser. Nous rapportons notre expérience chez les 146 premiers patients consécutifs explorés par cette technique ainsi qu’une analyse concernant la qualité des prélèvements histologiques obtenus avec des pinces pédiatriques. Patients et Méthodes: De septembre 2002 à août 2003, une nasofibroscopie électronique a été réalisée chez 146 patients âgés de 18 à 95 ans (moyenne d’âge 57,4 ± 16,2). Une anesthésie locale a été effectuée dans tous les cas. La qualité de l’examen était appréciée sur les items suivant: mauvais, moyen, bon, excellent. Pour chaque pince, les prélèvements étaient numérotés puis interprétés en fonction d’une grille histologique spécifiant la visualisation de la muqueuse, musculaire muqueuse, sous muqueuse, musculeuse, séreuse. Résultats: L’examen a été possible par voie nasale dans 116 cas (79,4%) et impossible chez 30-malades du fait des anomalies au niveau de la cloison nasale et des cornets. Les résultats concernant l’examen étaient jugés: excellents (118), bons (21), moyens (7) pour l’ésophage; excellents (120), bons (21), moyens (5) pour la vision fundique directe ; excellents (113), bons (17), moyens (16) pour la rétrovision cardiale; excellents (118), bons (21), moyens (7) pour l’antre et le pylore; excellents (119), bons (21), moyens (6) pour le duodénum. Il a été noté 10 épistaxis modérés tous d’évolution spontanément favorable. Des prélèvements ont été réalisés chez 58/146 patients. Des biopsies antrales ont été effectuées chez 46 patients; la muqueuse était présente dans 46 cas (100%),la musculaire muqueuse dans 29 cas (63%) et la sous muqueuse dans 4 cas (9%). Des biopsies fundiques furent réalisées chez 20 patients; la muqueuse était présente dans 20 cas (100%), la musculaire muqueuse dans 12 cas (60%), la sous muqueuse dans 1 cas(5%). Ces biopsies antrales et fundiques ont permis de poser les diagnostics de gastrite avec ou sans Helicobacter pylori, de cancer, et de polypes glandulo kystiques. Des biopsies ésophagiennes ont été réalisées chez 22 patients la muqueuse était présente dans 22 cas (100%), la musculaire muqueuse dans 12 cas (55%), lasous muqueuse dans 1 cas (4,5%) avec mise en évidence d’endobrachy ésophagen = 7, de cancer n = 4, et d’ésophagite n = 2. Conclusion: La vidéo gastroscopie par voie nasale à l’endoscope fin est réalisable dans 79,4% des cas, la conversion par voie orale étant effectuée avec succès dans tous les cas d’échec. L’examen est jugé excellent dans 77 à 82% des cas, les plus mauvais résultats étant obtenus lors de la rétrovision cardiale. Les pinces à biopsies pédiatriques fonctionnent bien (100% de prélèvements muqueux) mais la musculaire muqueuse n’est présente que dans 50 à 63% des cas et la sous muqueuse dans 3,5 à 9% des cas.
A universal suicide switch for chimeric antigen receptor T cell adoptive therapies.
Authors: Julianne Smith, Julien Valton
Journal: Journal of Clinical Oncology (2016)

7039 Background: Adoptive CAR T cell therapies have been reported to be highly efficient at killing tumor cells and are on the verge of revolutionizing the field of cancer treatment. However, there are safety concerns with CAR T cell treatments which would require intervention, including on-target off-tumor effects, on-tumor toxicities such as cytokine release syndrome and tumor lysis syndrome. Avoiding the aformentionned acute and long term adverse events appears to be mandatory to improve the safety of adoptive cell immunotherapies. To address this issue, different teams developed molecular suicide switch systems to remove the transferred cell population. While these different systems are efficient at promoting eradication of adoptively transferred cells, they are expressed independent of the CAR. This could potentially lead to the generation of a CAR T population devoid of the suicide switch system raising concerns about their utility in the clinic. Methods: To address this issue, we developed a novel CAR architecture containing an integrated suicide switch component. Results: We demonstrated that this CAR architecture was efficiently depleted by an FDA-approved molecule, retained its cytolytic potential and allowed for universal enrichment and detection of CAR T cells. We will present its development and in-depth characterization. Conclusions: We have developed a universal CAR-suicide switch architecture that will improve the safety of T cell adoptive therapies.
Normalization of bone markers and improved survival during zoledronic acid therapy
Authors: A. Lipton, R. Cook, R. E. Coleman, P. Major, E. Terpos, J. Body, M. R. Smith, J. Brown, P. Garnero
Journal: Journal of Clinical Oncology (2007)

9013 Background: In patients (pts) with bone metastases, elevated N-telopeptide of type I collagen (NTX) levels correlate with increased relative risks (RR) of skeletal-related events (SREs), disease progression, and death (Brown et al. J Natl Cancer Inst. 2005;97:59–69; Coleman et al. J Clin Oncol. 2005;23:4925–4935). Therefore, we conducted an exploratory analysis of 3 large, randomized, controlled trials to investigate whether reductions in NTX levels by treatment with zoledronic acid (ZOL) correspond with decreased risks of SREs and death. Methods: Urinary NTX was measured at baseline and at 3 months in pts with bone metastases from breast (BC; n = 379), prostate (PC; n = 314), or lung cancer and other solid tumors (LC/OST; n = 204) who received ZOL for up to 24 months. Pts were stratified by baseline NTX levels (normal, &lt; 64 nmol/mmol creatinine; elevated, = 64 nmol/mmol creatinine). Results: Approximately 50% of pts had elevated baseline NTX, and NTX normalization occurred within 3 months of ZOL treatment in 81% of pts with BC or LC/OST and in 70% of PC pts. For all tumor types, NTX normalization in response to ZOL correlated with reduced risk of first SRE and death compared with pts whose NTX did not normalize ( Table ). Further analyses using NTX level as a continuous variable revealed that, for all tumor types, any reduction in NTX levels correlated with lower risk of first SRE and death regardless of baseline NTX level. Conclusions: Pts whose NTX normalized on ZOL at 3 months had a lower risk of first SRE and death compared with pts whose elevated baseline NTX did not normalize. Regardless of baseline NTX level, a reduction in NTX over 3 months (absolute and % change) provided a continuum of SRE risk reduction and survival benefit. No significant financial relationships to disclose. [Table: see text]
Risk factors for hepatocellular carcinoma
Authors: Antonio Ponzetto, Radhika Sita Srinivasan
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We are writing in response to Ganne‐Carrié et al., who identified variables associated with the risk of developing primary hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)‐positive patients.1 In 2013, HCC was reported as the first cause of cancer mortality in Egypt, Saudi Arabia, Ghana, Nigeria, and Bangladesh and was rated second for cancer mortality in China, India, and the Philippines2; HCC is therefore a serious, globally relevant pathology. In Southern Italy, there is an overwhelming incidence of HCV infection in the 60+ age group; identifying those at risk of developing neoplasia is thus a clinical nightmare. The five risk factors identified in the French cohort1 are highly valuable, but two other potentially curable variables should also be assessed, namely, total body iron and Helicobacter pylori infection. Hemoglobinopathies are highly prevalent among Mediterranean populations; for example, beta thalassemia, which is present (in heterozygosis) in up to 1 in 5 people in some Southern Italian regions, leading to liver iron accumulation in older adults. In addition, 1 in 8 people of European descent carry the hemochromatosis gene; hemochromatosis and siderosis—secondary to thalassemia—lead to a very high risk of developing HCC, but can be easily treated at a relatively low cost. We and others have reported H. pylori infection in the majority of European patients suffering from HCV‐related cirrhosis,3 and HCC has been clearly correlated with the presence of this pathogen in the liver, in both Europe and China.4 Experimental infection of mice with Helicobacter species can cause acute and chronic hepatitis, resulting in HCC within a few months, in susceptible strains. In Turin, we carry out the assessment of total liver iron stores with a superconducting quantum interference device, but routine biochemistry is also sufficient to identify this potential risk factor, and H. pylori infection is easy to identify by the simple urea breath test.
Phase I multicenter trial of perifosine in combination with sorafenib for patients with advanced cancers including renal cell carcinoma
Authors: M. T. Schreeder, R. A. Figlin, J. J. Stephenson, L. Campos, S. P. Chawla, D. R. Spigel, A. Spira, P. Sportelli, L. Gardner, R. Birch, I. C. Henderson
Journal: Journal of Clinical Oncology (2008)

16024 Background: Perifosine (PERI) is an oral alkylphosphocholine with effects on multiple pathways including Akt, MAPK and JNK. Akt is often activated in renal cell carcinoma (RCC) and associated with resistance. To evaluate the single agent activity of PERI, RCC patients (pts) were assessed in a broad phase II trial with 6/9 pts (66%) achieving clinical benefit: 3 PR's, 3 SD ≥ 6 mo's (ASCO 2007 #15622). In vitro PERI is synergistic with MAPK inhibitors. PERI + Sorafenib (SOR) may result in a higher response rate and/or increase in duration of disease control so a phase 1 trial to determine the MTD was initiated. Methods: The trial was designed to accrue 3–6 pts in each of four cohorts. Response by RECIST was a secondary endpoint. PERI was escalated from 50mg qd to 50mg tid and SOR from 400mg qd to 400mg bid. DLT was defined as grade (G) 3 non-hematologic or G4 hematologic toxicity. MTD was the dose below that at which 2/6 pts experienced a DLT. Results: 20 pts were enrolled (12 m/8 f, median age 64 (range 44–87). Median number of prior therapies was 2, (range 1–4). 3 pts were inevaluable due to rapid disease progression. Diagnosis was as follows; RCC (11 pts), sarcoma (5), colorectal (2), hepatocellular (1) and neuroendocrine (1). 17 pts were evaluable for toxicity: No drug related Grade 4 AE's were seen. Suspected DLT of hand-foot syndrome was seen in cohort 4 and additional pts were enrolled. There was no increase in hand-foot syndrome compared to SOR alone. Of interest, 6/9 evaluable RCC pts (67%) had SD >12 wks (median 26 wks, range 12–62+). One hepatocellular pt had SD for 36 wks. After final review, the recommended dose is PERI 50mg bid + SOR 400mg bid. Conclusions: PERI + SOR was well tolerated with no increased hand-foot syndrome compared to SOR alone. 6/9 (67%) RCC pts achieved SD up to 62+ wks. Future studies are currently in development. Cohort 1 N=3 2 N=3 3 N=5 4 N=6 Perifosine Dose (mg) 50 50 100 150 Sorafenib Dose (mg) 400 800 800 800 Adverse Event (AE) Nausea 2 G1 1 G1, 1 G2 3 G1 1 G2 Vomiting 1 G1 2 G1, 1 G2 1 G2 Diarrhea 1 G1, 1 G2 2 G1, 1 G2 2 G1, 2 G2, 1 G3 1 G2 Fatigue 1 G1, 1 G3 1 G1 2 G2 2 G1 Hand-foot Syndrome G2 1 G2 Rash 1 G1 1 G2 1 G1, 1 G2, 1 G3 Hypertension 2 G2 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Keryx Biopharmaceuticals Keryx Biopharmaceuticals Keryx Biopharmaceuticals Keryx Biopharmaceuticals Keryx Biopharmaceuticals
P0654 : Long-term sustained suppression of viral replication is associated with low HBsAg levels in patients with chronic hepatitis B (CHB) treated with nucleos(T)ide analogues (NUCs)
Authors: E. Suárez, M. Prieto, C.A. Navascués, E. Hoyas, V. Hontagas, M.L. González-Gieguez, B. Figueruela, M. García-Eliz, M. Rodríguez
Journal: Journal of Hepatology (2015)
A Randomized Clinical Trial of Lenalidomide and Dexamethasone with and without Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma: Interim Study Results,
Authors: Lijun Dai, Amy O'Sullivan, Ryan Kennedy, Mohammad Abbas, Yongli Shuai, Vida Almario Passero, Carrie Andreas, Diane Gardner, Robert L Redner, G. David Roodman, Stanley M. Marks, Anastasios Raptis, Jing-Zhou Hou, Daniel Petro, Min Sun, Terry Evans, Louis V. Pietragallo, John K. Waas, J. Franklin Viverette, Jennifer Osborn, Vincent Reyes, Richard Pinkerton, Theodore Crandall, Ronald Fierro, Robert Volkin, Daniel Normolle, Markus Y. Mapara, Suzanne Lentzsch
Journal: Blood (2011)
P1-021: Clinical Feature and Effectiveness of Chemotherapy in Elderly Lung Cancer Patients
Authors: Kyoungju Lee, Jinyong Jung, Sungyong Lee, Sangyeub Lee, Jehyeong Kim, Chol Shin, Jaejeong Shim, Kwangho In, Kyungho Kang, Sehwa Yoo
Journal: Journal of Thoracic Oncology (2007)
Topological analysis of metabolic networks integrating co-segregating transcriptomes and metabolomes in type 2 diabetic rat congenic series
Authors: Marc-Emmanuel Dumas, Céline Domange, Sophie Calderari, Andrea Rodríguez Martínez, Rafael Ayala, Steven P. Wilder, Nicolas Suárez-Zamorano, Stephan C. Collins, Robert H. Wallis, Quan Gu, Yulan Wang, Christophe Hue, Georg W. Otto, Karène Argoud, Vincent Navratil, Steve C. Mitchell, John C. Lindon, Elaine Holmes, Jean-Baptiste Cazier, Jeremy K. Nicholson, Dominique Gauguier
Journal: Genome Medicine (2016)

The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus occurs through complex organ-specific cellular mechanisms and networks contributing to impaired insulin secretion and insulin resistance. Genome-wide gene expression profiling systems can dissect the genetic contributions to metabolome and transcriptome regulations. The integrative analysis of multiple gene expression traits and metabolic phenotypes (i.e., metabotypes) together with their underlying genetic regulation remains a challenge. Here, we introduce a systems genetics approach based on the topological analysis of a combined molecular network made of genes and metabolites identified through expression and metabotype quantitative trait locus mapping (i.e., eQTL and mQTL) to prioritise biological characterisation of candidate genes and traits. We used systematic metabotyping by 1H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualize the shortest paths between metabolites and genes significantly associated with each genomic block. Despite strong genomic similarities (95-99 %) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting the metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific mQTLs and genome-wide eQTLs. Variation in key metabolites like glucose, succinate, lactate, or 3-hydroxybutyrate and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing the shortest path length drove prioritization of biological validations by gene silencing. These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulation and to characterize novel functional roles for genes determining tissue-specific metabolism.
Perioperative Efficacy of an Extended Half-Life, Pegylated, Full-Length, Recombinant Factor VIII (BAX 855) in Individual Procedures
Authors: Brigitte Brand, Ralph A. Gruppo, Tung T. Wynn, Laimonas Griskevicius, Maria Fernanda Lopez Fernandez, Thomas Dvorak, Lisa Patrone, Brigitt E. Abbuehl
Journal: Blood (2015)
Longer Duration of Red Blood Cell Storage Induces Progressively Increased Markers of Extravascular Hemolysis and Hepcidin in Autologously Transfused Healthy Volunteers
Authors: Francesca Rapido, Sheila Bandyopadhyay, Richard O. Francis, Mark Soffing, Chaitanya R Divgi, Donald J. McMahon, Gary M. Brittenham, Steven L Spitalnik, Eldad A. Hod
Journal: Blood (2015)
Increased high density lipoprotein cholesterol induced by human apolipoprotein A-1 gene transfer increases adiponectin expression in abdominal adipose tissue
Authors: Sophie Van Linthout, Frank Spillmann, Anna Foryst-Ludwig, Carola Buecker-Gaertner, Marco Meloni, Yingmei Feng, Ulrich Kintscher, Bart De Geest, Heinz-Peter Schultheiss, Carsten Tschoepe
Journal: Circulation (2007)
CD20xCD3 Bispecific Fully Human Antibody Induces Potent Anti-Tumor Activity Against CD20-Expressing Tumors in Immune Competent Mice Humanized for CD20 and CD3
Authors: Bindu Varghese, Jayanthi Menon, Luis Rodriguez, Kara Olson, Pamela Krueger, Tammy Huang, Eric Smith, Gavin Thurston, Jessica R. Kirshner
Journal: Blood (2015)
Comparison of outcome prediction in node-negative breast cancer based on biomarkers uPA/PAI-1 or Adjuvant Online using the 10-year follow-up of the randomized multicenter Chemo N0 trial
Authors: U. Euler, C. Meisner, C. Friedel, M. Schmidt, M. Untch, B. Lisboa, F. Jaenicke, M. Schmitt, C. Thomssen, N. Harbeck
Journal: Journal of Clinical Oncology (2006)

534 Background: Chemo N0 was the first multicenter randomized clinical trial in breast cancer using biomarkers uPA/PAI-1 for risk stratification and chemotherapy selection. Chemo N0 validated uPA/PAI-1 as clinically relevant parameters for risk assessment in N0 breast cancer. About 50% of N0 patients have low uPA/PAI-1 in their primary tumor with excellent 5-year OS (&gt;95%), even without adjuvant therapy. Patients with high uPA/PAI-1 benefit from adjuvant chemotherapy. We evaluated whether biomarkers can predict outcome more accurately than a computer-program. Methods: In Chemo N0, patients (n=689, 1993–98) were stratified according to uPA/PAI-1: High-risk patients were randomized (6x CMF vs. observation), low-risk patients observed. Retrospectively, we divided recruited patients into two groups (chemotherapy vs. no adjuvant therapy) and stratified using uPA/PAI-1 (low vs. high). Individual 10-year OS was calculated by www.adjuvantonline.org (Version 7.0); these estimated values were compared to the observed 10-year OS in Chemo N0. Results: 81/151 patients with already available complete follow-up data 10 years after trial start have 10-year OS results. Median 10-year OS estimated by Adjuvant Online was 77.1% (median 78.6%) taking into account administered adjuvant therapy. 10-year Chemo N0 follow-up revealed an observed 10-year OS of 66.7% (27/81 deceased). 64/81 did not receive chemotherapy: In high-risk untreated patients (n=22), 10-year OS was 54.6% vs. estimated 75.0%. In CMF-treated patients (all high-risk, n=17), observed OS was 58.8% vs. estimated 74.6%. Conclusions: For the first time, risk assessment by novel biomarkers is compared to that by Adjuvant Online in data from a randomized clinical trial. In patients with high uPA/PAI-1, the individual 10-year OS calculated by Adjuvant Online seems to be underestimated compared to observed patient outcome. Further follow-up data will show whether uPA/PAI-1 can predict the individual course of disease more precisely than a computer-program based on large clinical data sets. Final Chemo N0 10-year follow-up is currently being completed. No significant financial relationships to disclose.
Importance of ‘meeting of the minds’: patient-reported outcomes and MRI
Authors: Veena K Ranganath, Vibeke Strand
Journal: Annals of the Rheumatic Diseases (2016)

Patient reported outcomes (PROs) are essential to the judicious care of patients with rheumatoid arthritis (RA).Rheumatologists were pioneers in this field with the first papers using PROs published in the 1940s. 1 Exploring the link between PROs, which are potentially subjective, and the more objective radiographic or MRI measures of structural damage and joint inflammation is important.The former describe the patient experience, which is after all the point of clinical medicine, while the latter provide information about the disease process itself, which can be influenced by clinicians using modern therapeutic approaches.The recent paper published by Baker et al 2 highlights a critical demonstration that inhibition of inflammation and progression of structural damage directly impacts reported pain of patients with RA and physical function, and positively influences their assessment of disease activity.[5][6]
Phase II trial of pemetrexed in children with refractory solid tumors: A Children's Oncology Group study.
Authors: A. B. Warwick, S. Malempati, M. D. Krailo, A. S. Melemed, P. C. Adamson, S. Blaney
Journal: Journal of Clinical Oncology (2010)

9535 Background: Pemetrexed is a multi-targeted antifol that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors to estimate the response rate and further define its toxicity profile. Methods: Pemetrexed, at a dose of 1,910 mg/m2, was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B12 (500–1,000 mcg IM, q 3 courses), daily multivitamin supplementation and dexamethasone (0.1 mg/kg/dose bid × 3 days q course). A two-stage design (10 + 10) was employed for each of the following disease strata: osteosarcoma, Ewing sarcoma/ peripheral PNET, rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/ supratentorial PNET and non-brainstem high-grade glioma. Results: Of 72 eligible subjects (39 males), 68 were evaluable for response. No complete or partial responses were observed. Stable disease, for a median (range) of 5 (4- 8+) cycles, was observed in 5 patients: ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma (n=1 each); one patient with Ewing sarcoma is still on study after 8 cycles. Seventy patients fully evaluable for toxicity received 112 treatment cycles. Rash, a DLT in the phase I study, was generally < grade 2 and occurred in 23% of patients. Other toxicities occurring in >10% of patients overall included: elevated ALT (40%) and AST (36%), fatigue (33%), itching (15%), nausea (24%), vomiting (20%), hypophosphatemia (20%), and hyperglycemia (24%), anemia (40%), and neutropenia (47%), and thrombocytopenia (40%). Neutropenia and elevated ALT were the most commonly recurring toxicities observed in patients receiving multiple cycles. One patient discontinued protocol therapy because of persistently elevated ALT. Two allergic reactions occurred, each with the first dose. Conclusions: Although reasonably well tolerated, pemetrexed as administered in this study has no significant activity in a broad spectrum of refractory pediatric solid tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly Lilly