tbuckley/cabot-search huggingface dataset:
RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: I S Jerchel, A Q Hoogkamer, I M Ariës, E M P Steeghs, J M Boer, N J M Besselink, A Boeree, C van de Ven, H A de Groot-Kruseman, V de Haas, M A Horstmann, G Escherich, C M Zwaan, E Cuppen, M J Koudijs, R Pieters, M L den Boer
Journal: Leukemia (2017)

RAS pathway mutations have been linked to relapse and chemotherapy resistance in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive data on the frequency and prognostic value of subclonal mutations in well-defined subgroups using highly sensitive and quantitative methods are lacking. Targeted deep sequencing of 13 RAS pathway genes was performed in 461 pediatric BCP-ALL cases at initial diagnosis and in 19 diagnosis-relapse pairs. Mutations were present in 44.2% of patients, with 24.1% carrying a clonal mutation. Mutation frequencies were highest in high hyperdiploid, infant t(4;11)-rearranged, BCR-ABL1-like and B-other cases (50–70%), whereas mutations were less frequent in ETV6-RUNX1-rearranged, and rare in TCF3-PBX1- and BCR-ABL1-rearranged cases (27–4%). RAS pathway-mutated cells were more resistant to prednisolone and vincristine ex vivo. Clonal, but not subclonal, mutations were linked to unfavorable outcome in standard- and high-risk-treated patients. At relapse, most RAS pathway mutations were clonal (9 of 10). RAS mutant cells were sensitive to the MEK inhibitor trametinib ex vivo, and trametinib sensitized resistant cells to prednisolone. We conclude that RAS pathway mutations are frequent, and that clonal, but not subclonal, mutations are associated with unfavorable risk parameters in newly diagnosed pediatric BCP-ALL. These mutations may designate patients eligible for MEK inhibitor treatment.
GW28-e1168 Timing of complete revascularization for patients with Acute coronary syndrome complicated with Chronic total occlusion
Authors: Xin Zhao, Chonghuai Gu, Yaling Han, Quanmin Jing, Xiaozeng Wang, Ge Wang, Haiwei LIu, Wang Shuang
Journal: Journal of the American College of Cardiology (2017)
Brote de la enfermedad de los legionarios en dos grupos de turistas hospedados en campings de Francia y España, junio de 1.996
Authors: A Infuso, B Hubert, D Dumas, M Reyrolle, S De Mateo, C Pelaz, C Hemery, I Pérez
Journal: Eurosurveillance (1997)

El 11 de junio de 1.996, el hospital Millau en el suroeste de Francia declaro a las autoridades sanitarias locales tres casos sospechosos de enfermedad de los legionarios registrados en un grupo de 42 turistas holandeses. El grupo (grupo 1) viajaba en caravanas y se habia hospedado en distintos campings de Francia y Espana desde el 15 de mayo. El 15 de junio, dos personas en un segundo grupo de 52 turistas holandeses que seguia el mismo itinerario organizado con un retraso de una semana (grupo 2), fueron ingresadas en el hospital de Millau con neumonia. Este informe ofrece un resumen de las investigaciones epidemiologicas y ambientales que se llevaron a cabo para identificar el foco de infeccion.
Development of the Manchester Cancer Research Centre Molecular Tumour Board for matching patients to clinical trials based on tumour and ctDNA genetic profiling
Authors: A. Gupta, M. Ayub, C. Miller, D. Rothwell, A. Wallace, A. Jordan, N. Cook, F. Thistlethwaite, L. Carter, C. O’Brien, S. Aruketty, E. Dean, A. Hudson, K. Frese, J. Dransfield, A. Hughes, R. Marais, C. Dive, G. Brady, M. Krebs
Journal: Annals of Oncology (2017)
Prognostic Importance of Temporal Changes in Resting Heart Rate in Heart Failure and Preserved Ejection Fraction
Authors: Ali Vazir, Brian Claggett, Bertram Pitt, Inder Anand, Nancy Sweitzer, James Fang, Jerome Fleg, Jean Rouleau, Sanjiv Shah, Marc A. Pfeffer, Scott D. Solomon
Journal: JACC Heart Failure (2017)
Anti-PD-1 therapy in patients with end-stage renal disease on dialysis: A single-center case series.
Authors: Soo Park, Gregory A. Daniels
Journal: Journal of Clinical Oncology (2017)

e14553 Background: Anti-PD-1 monoclonal antibodies (PD1) have clinical activity in several solid tumors. However, experience treating dialysis pts with PD1 is limited. Dosage adjustments are not recommended for renal impairment but PK studies did not include pts with ESRD on dialysis. Two case reports have described objective responses and a tolerable AE profile. We sought to explore the safety and efficacy of PD1 in such pts. Methods: In this single-center case series, we identified 4 pts with ESRD on dialysis who were treated with PD1 between 10/2014 to 11/2016. Data regarding clinical history, PD1 dosing, dialysis regimen, treatment (tx) response, and toxicity were collected. Results: Four pts were evaluable for data collection. Two pts had metastatic renal cell carcinoma (mRCC) and 2 others had unresectable cutaneous squamous cell carcinoma (cuSCC). Age at tx ranged from 66 to 71; all 4 pts were male. Number of doses ranged from 4 to 8. Two pts with mRCC received nivo 3 mg/kg q2wk after dialysis. Two pts with cuSCC received pembro 2 mg/kg q3wk after dialysis; dosing was extended to q4wk for 1 pt due to persistent grade (G) 2 fatigue. Three pts were on hemodialysis 3 times a wk and 1 pt was on peritoneal dialysis. Time to progression was 3 months for 1 mRCC pt and could not be determined for the other mRCC pt who had a PR but died from possible tx-related causes. Two cuSCC pts are still receiving pembro with PR at time of analysis. Immune-related AEs were seen in all 4 pts, including 2 incidences of G2 fatigue and 1 incidence each of G2 rash and G3 pneumonitis.One pt developed acute encephalitis after 4 doses of nivo that improved with steroids but was ultimately fatal. Conclusions: This single-center case series highlights the efficacy and AE profile of PD1 for pts with ESRD on dialysis. While this is a small series, there was significant anti-tumor activity in this group of pts. Despite the reported favorable AE profile of PD1, one pt had a serious and mortal AE that may have been related to tx. This should be considered in future studies. High molecular weight of PD1 suggests these agents are not removed by dialysis but we were limited by lack of PK data. Our experience adds to the 2 cases in the literature. Further studies are warranted in larger cohorts.
Inter-patient and intra-tumoral heterogeneity of oncogenic copy number alterations (CNAs) in gastric and gastroesophageal junction (GEJ) adenocarcinomas
Authors: J. Chao, V. Bedell, M.S. Li, P. Chu, Y-C. Yuan, S.J. Klempner, R-J. Lin
Journal: Annals of Oncology (2017)
Aromatase inhibitor maintenance therapy in high grade advanced ovarian cancer to delay first recurrence.
Authors: Alexandra Maria Knipprath-Mészáros, Marcus Vetter, Celine Montavon, Francesco Vigo, Andreas Schoetzau, Viola A. Heinzelmann-Schwarz
Journal: Journal of Clinical Oncology (2017)

5515 Background: Ovarian cancer (OC) is mostly diagnosed as G3 serous advanced stage disease with survival of only 20% in 5 years. Maintenance therapy after 1st line chemotherapy is increasingly used, particularly with Bevacizumab or PARP inhibitors. However, the effect of antihormonal treatment in breast cancer but also in relapsed gynecological cancers has been shown. Also in low grade OC, data are highly supportive of antihormonal treatment. In a previous study of ours, also high grade serous cancers express high amounts of estrogen receptor (ER). The aim of this study was to analyze whether a maintenance antihormonal therapy in advanced OC adds a benefit in relation to the time of recurrence. Methods: All newly diagnosed G3 FIGO III/IV OC cases at our Hospital were assessed prospectively for ER expression. Patients with positive ER status (&gt; 10%) were treated as maintenance therapy with Letrozol 2.5mg 1x/d or not. Progression free survival was recorded and analyzed according to Kaplan-Meier. Patients with macroscopic residual disease post surgery receiving Bevacizumab maintenance treatment were also included. Results: We identified 51 patients with G3 serous OC FIGO III/IV expressing ER. Hereby, 24 patients received and 27 patients did not receive Letrozol after adjuvant chemotherapy. Time to progression ranged from 4 to 121 months. The use of Letrozol was associated with a significant prolonged progression free interval. After 12 months, only 65% of women in the control group vs 84% in the Letrozol group were progression-free. After 24 months, the effect was even stronger (46% in the control group vs 74% with Letrozol (p= 0.02)). Within the subgroup of patients with residual disease treated with Bevacizumab a similar effect was seen with 41% of patients progression free after 12 months vs 89% when taking Letrozol in addition to Bevacizumab. Conclusions: The use of Letrozol as a maintenance therapy after the 1st line treatment in G3 advanced stage serous OC patients was associated with a longer recurrence free interval in our cohort. These findings warrant a randomized controlled trial comparing all existing maintenance regimen as this might have a major influence on cost development in OC treatment.
Actionable molecular alterations in advanced gynecologic malignancies: First results from the ProfiLER program (NCT01774409) in France
Authors: R. Varnier, I. Ray-Coquard, V. Corset, C. Baudet, D. Pissaloux, V. Attignon, M. Ezzalfani, O. Le Saux, P. Heudel, O. Derbel, B. You, O. Tredan, P. Cassier, N. Bonnin, P. Biron, G. Freyer, V. Trillet-Lenoir, T. Bachelot, D. Perol, J-Y. Blay
Journal: Annals of Oncology (2017)
Government promises “ambitious” science deal with EU
Authors: Anne Gulland
Journal: BMJ (2017)

The UK government has sought to quell fears over Brexit’s effect on the science and research sector, pledging that it was seeking an “ambitious science and innovation agreement with the EU.”

In a written response to Norman Lamb, chair of the House of Commons Science and Technology Committee, Robin Walker, minister at the Department for Exiting the European Union, acknowledged the concern over the impact of Brexit.1

But he added, “This government is committed to ensuring a positive …
Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche
Authors: Vesselin T. Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L. Cosma, Laurence C. Eisenlohr, Timothy J. Nice, Herbert W. Virgin, E. John Wherry
Journal: Immunity (2017)
Abstract 4997: Prospective identification, tracking, and targeting of cancer-initiating cells in breast cancer and glioma via low proteasome activity
Authors: Erina Vlashi, Kwanhgee Kim, Lorenza Della Donna, Tyson McDonald, Chann Lagadec, William H McBride, Pajonk Frank
Journal: Cancer Research (2008)

Abstract Cancer initiating cells (CICs) in breast cancer and glioma are resistant to radiation and chemotherapy. Complete elimination of these cells from the tumor mass determines therapeutic success. Thus, prospective identification of this cell population is key to developing novel targeting strategies for CICs. The current surface marker combinations employed in identifying CICs have several shortcomings. Here we report a novel marker for CICs that allows identification, tracking, and targeting of CICs in-vitro and in-vivo. Proteasome activities of human (U87 and U87viii) and murine (GL261) glioma cells, as well as human (MCF-7 and MDA-MB-231) and murine (67NR) breast cancer cells were analyzed using fluorogenic peptide substrates. Stable cell lines were generated with retroviruses coding for fusion proteins of ZsGreen and the degron of murine ornithine decarboxylase (ODC), or in combimation with thymidine kinase (TK). Accumulation of ZsGreen was monitored by fluorescence microscopy and flow cytometry. Self-renewal capacity was assessed in sphere forming assays, and tumorgenicity was determined by injection of sorted tumor cells into nude mice. Cell populations enriched for CICs demonstrated significantly reduced activities of the 26S proteasome and showed differential expression of proteasome subunits. Accumulation of ZsGreen corresponded with the CD24-/low/CD44+ phenotype in MCF-7 cells, and glioma ZsGreen-positive cells expressed high levels of the stem cell marker, nestin. Cells with low proteasome function exhibited a 5-fold increased sphere forming capacity, and 3-log increased tumorgenicity. Histologically, ZsGreen-positive U87 cells resided in a perivascular niche, and stained negative for Ki67. Optical in-vivo imaging revealed a significant increase in the number of ZsGreen-positive cells after treatment with sublethal doses of radiation. Fractionated sublethal irradiation of these xenografts caused induction of jagged-1 and notch-1 expression, and induced Ki67 expression in the zsGreen-positive population. Treatment of TK-ZsGreenODC-expressing U87 cells with ganciclovir eliminated cells with low proteasome activity, and subsequently prevented sphere formation in-vitro, and caused complete regression of tumors in-vivo. We conclude that low proteasome activity is a unique characteristic of CICs. Cell lines infected with reporter constructs for proteasome activity can be utilized to identify CICs and track their response to cancer treatments. Most importantly, this feature of CICs can be exploited as a specific target for selective elimination of CICs, leading to improved tumor control.
Genomic profiling of 114,200 advanced cancers identifies recurrent kinase domain duplications (KDD) and oncogenic rearrangements (RE) across diverse tumor types
Authors: L.M. Gay, D. Pavlick, J. Chung, S. Ramkissoon, S. Daniel, J.A. Elvin, E. Severson, T. Bivona, K.L. Reckamp, S.J. Klempner, S.-H.I. Ou, A.B. Schrock, V.A. Miller, P.J. Stephens, J.S. Ross, S. Ganesan, C. Lovly, A. Mansfield, S.M. Ali
Journal: Annals of Oncology (2017)
Limited value of currently used germline brca mutations predictive tools in prostate cancer
Authors: L. Oliva Fernández, M.A. Márquez-Aragonés, N. Romero-Laorden, B.I. Pajares Hachero, I. Moreno, M. Ruiz Vico, G. Duran Ogaya, C. Muriel, J. Pascual, C. Fernández de Souza, M.E. Dominguez Recio, G. Grau, M.I. Sáez, A. Montesa, R. Correa, D. Olmos Hidalgo
Journal: Annals of Oncology (2017)
A randomized placebo-controlled phase III study of duloxetine for treatment of aromatase inhibitor (AI)-associated musculoskeletal symptoms in women with early-stage breast cancer: SWOG S1202.
Authors: N. Lynn Henry, Joseph M. Unger, Anne Schott, Lisa Hansen, Danika Lew, James Lloyd Wade, Carol Moinpour, Gabriel N. Hortobagyi, Frank L. Meyskens
Journal: Journal of Clinical Oncology (2014)

TPS9662 Background: Treatment with an aromatase inhibitor (AI) for 5 years improves outcomes for hormone receptor (HR)-positive breast cancer. However, up to 30% of patients discontinue treatment because of AI-associated musculoskeletal symptoms (AIMSS). Preliminary data suggest that treatment with the serotonin norepinephrine reuptake inhibitor duloxetine for 8 weeks decreases AI-associated pain. We are therefore conducting this placebo-controlled, randomized phase III trial of duloxetine for treatment of AIMSS. Specific Aims: To assess if duloxetine as compared to placebo causes a reduction in average pain in women with AIMSS at 12 weeks as measured by the Brief Pain Inventory (BPI). Additional measures include WOMAC, M-SACRAH, FACT-ES, PHQ-9, global rating of change, candidate gene variants, and inflammatory cytokines. Eligibility Criteria: Patients must have stage I-III HR-positive breast cancer and have undergone definitive breast cancer surgery. Patients must be postmenopausal, currently taking an AI (anastrozole, letrozole, or exemestane) for at least 21 days and not more than 36 months prior to registration, and plan to continue for at least 180 days after registration. Patients must have an average joint pain score of at least 4 out of 10 on the BPI, and pain must have started or increased after initiation of AI. Patients must not have a contraindication to duloxetine and must not require antidepressant therapy during study participation. Methods: Patients will be randomized to duloxetine 60 mg daily or matching placebo daily for 12 weeks, including a 7 day run-in period of 30 mg daily. Assessments will be performed at baseline, 2, 6, 12, and 24 weeks. Statistical Methods:We stipulate an alpha=0.05 two-sided test, with an estimated 5% non-adherence, 15% dropout, and 10% contamination rate at 12 weeks after randomization. For a one point difference in average joint pain and a 2.3 point SD at 12 weeks, 270 eligible patients would be required for 80% power under a two-arm normal design. To allow for an ineligibility rate of 8%, 294 total patients will be enrolled. The study was activated in May 2013 and is available on the CTSU. Clinical trial information: NCT01598298.
Action of 5,9, 10-Trimethyl-1,2-Benzanthracene on the Skin of the Mouse
Authors: Jonathan L. Hartwell, Harold L. Stewart
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Action of 5,9, 10-Trimethyl-1,2-Benzanthracene on the Skin of the Mouse Get access Jonathan L. Hartwell, Jonathan L. Hartwell chemist Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold L. Stewart Harold L. Stewart senior pathologist 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 3, Issue 3, December 1942, Pages 277–285, https://doi.org/10.1093/jnci/3.3.277 Published: 01 December 1942
Phase 1 safety and clinical activity of BLU-554 in advanced hepatocellular carcinoma (HCC)
Authors: R. Kim, D. Sarker, T. Macarulla, T. Yau, S.P. Choo, T. Meyer, A. Hollebecque, J. Whisenant, M. Sung, J-H. Yoon, H.Y. Lim, A. Zhu, J-W. Park, S. Faivre, V. Mazzaferro, H. Shi, O. Schmidt-Kittler, C. Clifford, B. Wolf, Y-K. Kang
Journal: Annals of Oncology (2017)
CDK12: New breast and ovarian cancer predisposition gene in Tatar population?
Authors: E. Shagimardanova, O. Brovkina, M. Gordiev, R. Enikeev, L. Shigapova, D. Khodyrev, O. Gusev, A. Kedrova, V. Kosiy, A. Nikitin
Journal: Annals of Oncology (2017)
Adoptive cell therapy with tumor-infiltrating lymphocytes for patients with metastatic ovarian cancer: A pilot study
Authors: M. Pedersen, M. Westergaard, M. Nielsen, T.H. Borch, L.G. Poulsen, H. Hendel, T. Juhler-Nøttrup, Ö. Met, M. Donia, I-M. Svane
Journal: Annals of Oncology (2017)
10 Granulocyte/monocyte apheresis as maintenance therapy in crohn’s disease
Authors: P Rimmer, H Donnelly, H Preedy, R Makins
Journal: Gut (2017)

Background  Granulocyte, monocyte apheresis (GMA), extra-corporeal absorptive circuit used to treat acute ulcerative colitis (UC) and Crohn’s disease. Use in maintenance therapy following remission is uncertain.  Aim  To present the outcomes following treatment of 5 patients with maintenance GMA for Crohn’s disease.  Method  Notes review of patients. Assessed blood results (full blood count, albumin, c-reactive protein) faecal calprotectin (FC), imaging and subjective patient reporting to determine the response  Results  5 patients (P) were included, of whom: 4 were male, mean age 37.4 (24–57) years. All received previous conventional therapies with no or limited effect or had lost response. All had 8 treatments at weekly intervals as acute therapy followed by maintenance at monthly intervals. P1 (30 year old male, small bowel (SB) Crohn’s), 40 columns, consistent normalisation in all markers and FC (from >600 to 248), reversal of temporary colostomy, improvement on MRE, subjective improvement. P 2 (46 year old male, SB Crohn’s) 12 columns, consistent improvement in bloods, subjectively in remission. P3 (24 year old male, Crohn’s colitis) 9 columns, initial subjective improvement, bloods unchanged from baseline but normal, switched to vedolizumab. P4 (30 year old male, SB Crohn’s) 5 columns, no subjective change, stopped. P5 (57 year old female, SB Crohn’s) 4 columns, improvement in C-reactive protein, others consistently normal, no change from baseline, subjective improvement but stopped.  Conclusions  Five patients received maintenance therapy. Consistent biochemical/subjective symptomatic remission was achieved in two (P1 and 2), subjective remission in a third (P5) but no response in P3 and 4. Remission appeared to continue in those with elevated baseline markers of inflammation. SB Crohn’s may respond better than colitis. GMA may have a role as maintenance therapy.
Reuse of single-use sterile medical devices decreased in Danish hospitals after report discouraged it
Authors: M Christensen, M Meyer, O B Jepsen
Journal: Eurosurveillance (1999)

The extent to which sterile medical devices marked for single-use are reused was surveyed recently in 100 hospitals in Denmark, Finland, Norway, and Sweden. The same method was used in a survey of Danish hospitals two years earlier. This has enabled us
Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques
Authors: Diogo M. Magnani, Thomas F. Rogers, Nathan Beutler, Michael J. Ricciardi, Varian K. Bailey, Lucas Gonzalez-Nieto, Bryan Briney, Devin Sok, Khoa Le, Alexander Strubel, Martin J. Gutman, Núria Pedreño-Lopez, Nathan D. Grubaugh, Cassia G. T. Silveira, Helen S. Maxwell, Aline Domingues, Mauricio A. Martins, David E. Lee, Erica E. Okwuazi, Sherrie Jean, Elizabeth A. Strobert, Ann Chahroudi, Guido Silvestri, Thomas H. Vanderford, Esper G. Kallas, Ronald C. Desrosiers, Myrna C. Bonaldo, Stephen S. Whitehead, Dennis R. Burton, David I. Watkins
Journal: Science Translational Medicine (2017)

Neutralizing antibodies prevent Zika infection in nonhuman primates.
Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats
Authors: Chunyan Wu, Su Hyeon Hwang, Yaoyao Jia, Joobong Choi, Yeon-Ji Kim, Dahee Choi, Duleepa Pathiraja, In-Geol Choi, Seung-Hoi Koo, Sung-Joon Lee
Journal: Journal of Clinical Investigation (2017)

Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting the fuel preference to fats. After 6 weeks of administration, mice fed a high-fat diet (HFD) exhibited a marked reduction in adiposity. AzA treatment induced expression of PPAR-α and genes required for FAO in the liver and induced the expression of PPAR-γ coactivator 1-α (Ppargc1a) and uncoupling protein-1 (Ucp1) genes in brown adipose tissue (BAT). Moreover, treatment with AzA increased insulin sensitivity and ketone body levels. This led to a reduction in the respiratory quotient and an increase in the FAO rate, as indicated by indirect calorimetry. AzA treatment had similar antiobesogenic effects in HFD-fed ob/ob mice. Importantly, AzA-associated metabolic changes were completely abrogated in HFD-fed Olfr544-/- mice. To our knowledge, this is the first report to show that Olfr544 orchestrates the metabolic interplay between the liver and adipose tissue, mobilizing stored fats from adipose tissue and shifting the fuel preference to fats in the liver and BAT.
LCZ 696, administered during doxorubicin, trastuzumab or pertuzumab treatment, prevents cardiotoxicity in our in vitro model
Authors: N. Maurea, R. Paciello, G. Piscopo, A. Rienzo, G. Sorrentino, C. Maurea, R. Caputo, M. De Laurentiis, P. Maiolino, C. Coppola, C. De Lorenzo
Journal: Annals of Oncology (2017)