tbuckley/cabot-search huggingface dataset:
PRAME: A target antigen for immunotherapy in Ewing’s sarcoma
Authors: Alfons S. K. De Hooge, Nicola E. Annals, Monique Ten Dam, Jan H. Kessler, R. Maarten Egeler, Cornelis J. M. Melief, Pancras C. W. Hogendoorn, Arjan Lankester
Journal: Cancer Research (2005)

4715  Ewing’s sarcoma is a highly aggressive tumor mainly occurring in children, adolescents and young adults. Despite progress in the conventional treatment of these patients, a large proportion still die of chemotherapy resistant disease progression, thus highlighting the need for an alternative approach. Ewing’s sarcoma is characterized by a specific breakpoint leading to a fusion between the EWS and members of the ETS family. This tumor specific fusion protein could be a potential antigen for immunotherapy. It appeared, however, difficult to develop a general immunotherapy protocol against this fusion protein. The present study investigated the feasibility of T cell mediated immunotherapy in Ewing’s sarcoma focusing on PRAME (PReferentially expressed Antigen of MElanoma), a widely expressed tumor antigen. The expression of PRAME in Ewing’s sarcoma cell lines and primary material was investigated by RT-PCR. PRAME was expressed by 47% (7 out of 15) of the investigated primary tumors and by 70% (7 out of 10) of the investigated Ewing’s sarcoma cell lines. Furthermore, immunohistochemistry performed on Ewing’s sarcoma tissue revealed that there was a homogeneous expression of PRAME protein in PRAME positive tumors. HLA-A2+ and B8+ restricted PRAME-specific CD8+ T cell clones were generated from healthy donors and efficiently recognized and killed PRAME expressing Ewing’s sarcoma cell lines in a standard four hours chromium release assay. Thus, the large proportion of Ewing’s sarcomas that express PRAME as well as their ability to be recognized and lysed by PRAME-specific cytotoxic T cells provides the first evidence that PRAME may be a potential target antigen for T-cell mediated immunotherapy for the treatment of Ewing’s sarcoma. Supported by a grant from the Dutch Cancer Society.
GW28-e1174 Percutaneous coronary intervention to left anterior descending artery guided by intravascular ultrasound
Authors: Bin Wang, Han Yaling, Jing Quanmin, Wang Xiaozeng, Ma Yingyan, Liang Zhenyang, Wang Geng, Xu Kai, Guan Shaoyi, Fang Yi, Wang Shuang
Journal: Journal of the American College of Cardiology (2017)
Development of new transformants of mouse JB6P series cells as tools for understanding redox and transcriptional factor regulation
Authors: Bobbye Misner, Rita Chiu, Frank Meyskens, Sun Yang
Journal: Cancer Research (2007)

4269   The mouse epidermal JB6P cell line consists of tumor promotion sensitive (JB6P+) and tumor promotion resistant cells (JB6P-) that have been widely utilized to study tumor promotion. We transformed the JB6P+ cell line with prolonged low dose, UVBR (10mJ/cm 2 ), H 2 O 2  (10µM), and CdCl 2  (1µg/ml). Cell transformation was confirmed by anchorage-independence. JB6P+ parent cells formed colonies in soft agar culture (13.7±3.5 per 20 high-power fields) which are increased by stimulation with the tumor promotor TPA (44.7±2.9). For the new transformants in the absence of TPA, colonies formed (104.0± 17.3 per 20 high-power fields, JB6P+/UV; 56.7±15.0, JB6P+/H 2 O 2 ; 64.3±22, JB6P+/Cd cells; p 2 O 2  (6.5, 1.3-fold), and JB6P+/Cd cells (3.6,1.4 fold).  Many nuclear transcription factors, for example Activating Protein-1(AP-1), are rapidly activated by elevated ROS stresses. Using Western Blot analysis of nuclear protein extractions, the distinct AP-1 composition patterns are summarized in the table below. We hypothesize that the UVBR, H 2 O 2  and CdCl 2  transformed the JB6P+ cells through different mechanisms.  Relative l densitometric laser measurements of AP-1 subunits  Each band was scanned and the densitometric measurements normalized to the JB6P+ results. ( C-Fos was normalized to JB6P+/UV results). * The zero value represents
Long-Acting β-Agonists (LABA) Combined With Long-Acting Muscarinic Antagonists or LABA Combined With Inhaled Corticosteroids for Patients With Stable COPD
Authors: Nobuyuki Horita, Akimichi Nagashima, Takeshi Kaneko
Journal: JAMA (2017)

<h3>Clinical Question</h3> Are inhaled long-acting muscarinic antagonists (LAMA) combined with long-acting β-agonists (LABA) associated with differences in the incidence of chronic obstructive pulmonary disease (COPD) exacerbation and serious adverse events and with differences in quality of life and forced expiratory volume in the first second of expiration (FEV<sub>1</sub>) vs inhaled LABA plus inhaled corticosteroids therapy for the treatment of stable COPD? <h3>Bottom Line</h3> Compared with inhaled LABA combined with corticosteroids, inhaled LAMA combined with LABA may be associated with a lower risk of COPD exacerbation and with greater improvement in FEV<sub>1</sub>without differences in the incidence of serious severe adverse events or quality of life.
Prognostic associations of prostate-specific antigen (PSA) decline with survival, radiographic response and progression in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide
Authors: A.J. Armstrong, P. Lin, C.S. Higano, P. Iversen, C.N. Sternberg, B. Tombal, D. Phung, T. Parli, A. Krivoshik, T.M. Beer
Journal: Annals of Oncology (2017)
Investigation of biomarkers in patients with adenocarcinoma of the lung receiving nintedanib according to approved label: Non-interventional LUME-BioNIS study
Authors: M. Reck, A.J. Staal-van den Brekel, A. Mellemgaard, N. Morsli, K. Pietzko, T. Kitzing, J. Braunger, K.M. Kerr
Journal: Annals of Oncology (2017)
Enhancing decision-making about adjuvant chemotherapy in ER+, HER2- early breast cancer (EBC) following EndoPredict testing
Authors: L. Fallowfield, S. May, L. Matthews, V. Jenkins, J. Mackay, A. Arbon, B. Hack, J. Hall, C. Harper-Wynne, S. Hinde, A. Moss, E. Thanopoulou, S. Westwell, D. Wlaszly, R. Simcock, G. Patel, D. Bloomfield
Journal: Annals of Oncology (2017)
A phase 1b study of the anti-PD-1 monoclonal antibody BGB-A317 (A317) in combination with the PARP inhibitor BGB-290 (290) in advanced solid tumors.
Authors: Michael Friedlander, Tarek Meniawy, Ben Markman, Linda R. Mileshkin, Paul Harnett, Michael Millward, Joanne Lundy, Alison E. Freimund, Christie Norris, John Wu, Virginia Paton, Lai Wang, Bo Gao
Journal: Journal of Clinical Oncology (2018)

48 Background: The release of tumor-associated antigens may enhance the response to immunotherapy. BGB-A317, a humanized IgG4 variant monoclonal antibody engineered to have no Fc gamma receptor binding, targets the programmed cell death-1 (PD-1) receptor. It is being developed in solid and hematologic malignancies at a dose of 200 mg IV Q3W. BGB-290, a potent inhibitor of PARP 1/2, is hypothesized to promote neoantigen release that may potentially increase the efficacy of BGB-A317. A phase 1 study identified 60 mg BID as the recommended Phase 2 dose (RP2D) for BGB-290. This study consists of initial dose escalation to determine the maximum-tolerated dose (MTD), safety, pharmacokinetic (PK) profile, and preliminary antitumor activity of the combination, followed by expansion into ovarian, breast, prostate, gastric, bladder, pancreatic and small cell lung cancers. Methods: Cohorts of 6–12 patients with advanced solid tumors were treated in each of 5 planned dose levels (DLs). In DLs 1–3, BGB-290 doses ranged between 20–60 mg PO BID with BGB-A317 2 mg/kg IV Q3W. In DLs 4–5, BGB-290 doses were 40 or 60 mg BID; A317 was given at 200 mg IV Q3W based on PK data from a single agent Phase 1 study. Results: As of 31 March 2017, 43 patients [median age 63 years (34–75)] were treated in DLs 1–5. Three patients experienced four dose-limiting toxicities: grade 2 nausea (DL4), grade 2 nausea and grade 2 vomiting (DL5), and grade 4 autoimmune hepatitis (DL5). MTD was identified as BGB-A317 200 mg IV Q3W + BGB-290 40 mg PO BID. The most common adverse event (AE) considered related to both study drugs was fatigue. Immune-related AEs of Grade ≥3 were elevated alanine aminotransferase/aspartate aminotransferase (n = 3), autoimmune hepatitis (n = 3), and hepatitis (n = 1). Complete or partial response was observed in 11 patients, 4 of whom had confirmed PR or CR. Plasma/serum exposure of BGB-290 and BGB-A317 were consistent with those in single-agent trials. Conclusions: The combination of BGB-A317 and BGB-290 was generally well tolerated in patients with advanced solid tumors. These results support the continuation of this trial with enrollment into the disease-specific cohorts. Clinical trial information: NCT02660034.
Cell-free DNA (cfDNA) mutations from clonal hematopoiesis: Implications for interpretation of liquid biopsy tests.
Authors: Pedram Razavi, Bob T. Li, Chenlu Hou, Ronglai Shen, Oliver Venn, Raymond S. Lim, Earl Hubbell, Ino De Bruijn, Qinwen Liu, Ravi Vijaya Satya, Hui Xu, Ling Shen, Amy Sehnert, Tara Maddala, Michael F. Berger, Alex Aravanis, Jorge S. Reis-Filho, Mark Lee, David B. Solit, Jose Baselga
Journal: Journal of Clinical Oncology (2017)

11526 Background: A large fraction of cfDNA fragments are derived from hematopoietic sources. Somatic alterations in cfDNA can be tumor-derived but also could represent somatic changes associated with clonal hematopoiesis. We performed deep sequencing of both plasma cfDNA and matched white blood cell (WBC) genomic DNA (gDNA) to determine the contribution of clonal hematopoiesis to the variants observed in cfDNA. Four cohorts were investigated: metastatic breast (BC), non-small cell lung (NSCLC), castration-resistant prostate cancer (CRPC), and non-cancer participants (pts). Methods: Metastatic cancer pts with de novo or progressive disease were prospectively enrolled. Non-cancer pts were blood bank donors. Plasma cfDNA and matched WBC gDNA were sequenced using a targeted 508-gene panel (2 Mb) to &gt; 60,000X raw depth. Variant calling used a novel pipeline that employed molecular barcoding for error suppression followed by de novo assembly and graph-based variant calling. Results: Of 151 metastatic cancer pts (48 BC, 49 NSCLC, 54 CRPC), median age was 64 (30-87) with 53% female and 33% treatment naive. Of 47 non-cancer pts, median age was 61 (20-78) with 51% female. Analysis of cfDNA identified 1072 variants (AF &gt; 0.1%, &gt; 2 mutant reads, passing bioinformatic quality filters) which were also detected in WBC gDNA as non-germline ( &lt; 35% allele frequency [AF]) non-synonymous variants. For these cfDNA variants, AF ranged from 0.1-14.4% and correlated with AF in WBC gDNA (r 2 = 0.47, p &lt; 0.001). Mutated genes were consistent with clonal hematopoiesis, with the most frequently mutated genes being DNMT3A, TET2, PPM1D, and TP53 (215, 77, 45, and 36 variants, respectively). For both cancer and non-cancer pts (age &gt; 45), median number of overlapping variants was 5 per pt (range 0-22). The number of WBC gDNA and cfDNA variants per individual was positively associated with age (p &lt; 0.001) in both cancer and non-cancer pts (interaction p = 0.08). Conclusions: Somatic cfDNA variants are frequently derived from clonal hematopoiesis and increase with age. Accurate assessment of somatic alterations in cfDNA should account for this phenomenon to distinguish between tumor-derived and WBC-derived variants.
A polymorphism in the promoter of the FRAS1 gene is associated with metastatic prostate cancer
Authors: C.J. Sweeney, M. Geybels, S. Coseo-Markt, V. Wang, K. Penney, T. Gerke, M.M. Pomerantz, G-S.M. Lee, D. Nitsch, C. Huttenhower, L. Mucci
Journal: Annals of Oncology (2017)
Rubella control in France
Authors: D Lévy-Bruhl, C Six, I Parent du Châtelet
Journal: Eurosurveillance (2004)

In the pre-vaccination era, rubella was regarded as only a mild exanthematous acute viral infection of children. The devastating effects of the disease were first identified in the early 1940s by an Australian ophthalmologist, and further confirmed during the 1962-65 rubella pandemic in Europe and the United States. They result from the transmission of the virus by infected pregnant women to their fetus. The resulting congenital rubella syndrome (CRS) comprises a lengthy list of abnormalities. The most common ones are deafness, ocular and cardiac defects and mental retardation. The objective of rubella vaccination, to which France has subscribed, is the elimination of CRS.
Possible importation and subsequent cross-transmission of OXA-48-producing Klebsiella pneumoniae, France, 2010
Authors: D Decre, G Birgand, D Geneste, E Maury, J  C Petit, F Barbut, G Arlet
Journal: Eurosurveillance (2010)

We report the possible first patient-to-patient transmission of Klebsiella pneumoniae with decreased susceptibility to imipenem and producing OXA-48, CTX-M15, TEM-1 and OXA-1 in a French hospital.
Selecting patients with oligo-metastatic breast cancer harboring homologous recombination deficiency (HRD) for intensified chemotherapy: The OLIGO-study
Authors: T.G. Steenbruggen, A.N. Scholten, M-J.T. Vrancken-Peeters, I.A. Mandjes, M. Holtkamp, J. Wesseling, S.C. Linn, G.S. Sonke
Journal: Annals of Oncology (2017)
Brote de infección por Salmonella enteritidis asociado a un pastel glaseado
Authors: P D'Argenio, A Romano, F Autorino
Journal: Eurosurveillance (1999)

Varias personas desarrollaron sintomas graves de gastroenteritis tras un banquete de primera comunion en Benevento, poblacion de 60.000 habitantes al sur de Italia. Al banquete, celebrado el 14 de junio 1998 entre las 14:00 h. y las 18:00 h., asistieron unas 60 personas. Un medico general dio parte del brote a las autoridades sanitarias el 16 de junio e inmediatamente se puso en marcha una investigacion para identificar el agente causante, el alimento contaminado y los posibles errores cometidos durante su elaboracion.
Characteristics and prognostic impact of advanced non-small-cell lung cancer patients who were ineligible for clinical trials
Authors: H. Kawachi, D. Fujimoto, T. Morimoto, M. Ito, S. Teraoka, Y. Sato, K. Nagata, A. Nakagawa, K. Otsuka, Y. Imai, K. Tomii
Journal: Annals of Oncology (2017)
MONARCH 3: Abemaciclib as initial therapy for patients with HR+/HER2- advanced breast cancer
Authors: A. Di Leo, M. Toi, M. Campone, J. Sohn, S. Paluch-Shimon, J. Huober, I.H. Park, O. Tredan, S-C. Chen, L. Manso, O. Freedman, G.G. Jaliffe, T. Forrester, M. Frenzel, S. Barriga, I.C. Smith, N. Bourayou, M.P. Goetz
Journal: Annals of Oncology (2017)
Natural history of alveolar soft part sarcoma (ASPS): Impact of brain metastases and role of anti-angiogenic therapies (AAT)
Authors: G. Malouf, G. Beinse, O. Mir, J. Adam, P. Terrier, J-P. Spano, C. Honore, A. Italiano, J-M. Coindre, J-Y. Blay, A. Lecesne
Journal: Annals of Oncology (2017)
Prime minister promises reviews of organ donation and Mental Health Act
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The prime minister has announced plans to change the law on organ donation in England to presume consent unless people opt out.

The move, aimed at increasing the number of organ donations, was announced by Theresa May in her keynote speech to the Conservative Party conference in Manchester on Wednesday 4 October and will be subject to consultation. The Labour Party made the same commitment at its annual conference in Brighton last week.

The announcement means that England is set to follow Wales in moving to an opt-out system of organ donation. Scotland is also consulting on whether to move to this system.1

May said, “Our ability to help people who need transplants is limited by …
Assessment of abiraterone (ABI) tumor cell activity via in vitro models of androgen (A)-responsive prostate cancer.
Authors: Ian Hickson, Ann Marien, Maarten Derks, Marc Janssen
Journal: Journal of Clinical Oncology (2012)

e15166 Background: Inhibition of CYP17 by abiraterone acetate (AA) blocks A biosynthesis, reduces A levels and results in inhibition of A-dependent tumor growth. AA has been shown to improve survival in patients with metastatic castrate-resistant prostate cancer (HR = 0.74) (Scher, ASCO 2011). AA is converted to ABI in vivo. This study investigates whether direct effects of ABI on tumor cells (ie, blockade of intratumoral A synthesis) may contribute to the clinical efficacy of AA using in vitro models. Methods: LNCaP cells (human prostate cancer cell line [HPCCL]) were grown in 2D and 3D cultures, and ABI activity was assessed by reduction of androgen receptor (AR) output in gene expression profiling (Affymetrix microarray), reporter assay, and by immunoblot for A-responsive signals. Using ABI-sensitive LNCaP cells, responses were further characterized in the presence or absence of ligand (dihydrotestosterone [DHT]) and with A-targeting agents TOK-001 and MDV3100. Results: ABI exposure resulted in dose-dependent modulation of A-dependent gene expression in Affymetrix microarray analysis of 2D and 3D cultures. Similar results were seen in an analysis of AR-dependent protein and in an AR-driven reporter assay in 2D LNCaP or VCaP (another HPCCL) cell culture. In LNCaP, AR output was inhibited by low concentrations of ABI (IC 50 100-300 nM), comparable to TOK-001 (IC 50 30-100 nM) and less potent than MDV3100 (IC 50 10-30 nM). Growth inhibition (MTT assay) occurred at concentrations 10-fold higher for all compounds. For ABI and TOK-001, inhibition of AR output was reduced by DHT (30- to 100-fold increase in IC 50 ); with MDV3100, the shift in IC 50 was less (10-fold) with agonism of AR output at low nM concentrations. Conclusions: ABI has an inhibitory effect on AR output in LNCaP cells. Partially overcoming this inhibition through addition of DHT implies that CYP17 inhibition and the subsequent A reduction play a role in the intratumoral activity of AA. However, persistent inhibition of AR output in the presence of DHT implies additional anti-A effects of AA in prostate tumor cells. This model may provide a useful tool for the study of AR-targeted therapies, combinations of agents, and resistance to agents targeting A.
Long-term survivors with advanced nonsquamous non-small cell lung cancer (nsNSCLC) treated with first-line (1L) chemotherapy (CT) plus bevacizumab (B) and maintenance (mtc) B.
Authors: Javier de Castro, Dolores Isla, Jose Luis Gonzalez Larriba, Sergio Vazquez Estevez, Bartomeu Massuti, Jose Miguel Sanchez Torres, Manuel Domine, Antonio Calles, Jose Vicente Cardona, Pilar Garrido López
Journal: Journal of Clinical Oncology (2012)

e18055 Background: B plus CT followed by mtc B has been shown to improve outcomes in patients (pts) with nsNSCLC. In the clinical setting, some pts are able to receive prolonged mtc treatment (Tx) with B. The aim of our research was to explore their clinical characteristics, in order to assess the behavior of these pts who benefit most from B. Methods: In 30 Spanish institutions we studied retrospectively data from 104 pts with advanced nsNSCLC receiving long-time mtc B defined by a PFS ≥ 9 months (m), which represents an increase in PFS of approximately 50%, as compared with historical data. Clinical and histological characteristics, Tx received, ORR, median PFS and OS, and safety data were recorded. Results: Pts characteristics: median age 57 years (yr); caucasian: 98%; ECOG PS 0/1/2 (%): 61/38/2; male: 61%; current/former/never smokers (%): 36/45/19; baseline hypertension (HTN)/cardiovascular disease (%): 24/9; adenocarcinoma: 82%; stage IV: 84%; 84% of pts presented ≤2 metastatic sites; central tumor location: 30%; tumor cavitation: 4%; among 40 pts tested, 8% presented activating EGFR mutations. 1L CT was: carboplatin/cisplatin doublets (%): 57/43; median no. of cycles for CT/B and mtc B was 6 and 18, respectively. Median B dose was 7.5 mg/kg. ORR: 83%. Of 71% of pts who had evidence of PD to 1L, 90% received second-line (2L) Tx. 77% of pts who progressed to 2L, received a third-line (3L). B was maintained in 26% and 24% of pts receiving 2L and 3L. Median PFS: 15 m (CI 95%:14-16); median OS: 31 m (95% CI: 22-39). 1 and 2 yrs survival rates (%): 97 (95% CI: 93 - 100) and 62 (95% CI: 51 - 73). Most frequent B related toxicities (%): gr 1/2 epistaxis (22/0), gr 1/2 HTN (12/6), grade 1/2/3 asthenia (2/6/4) and gr 1/2/3 proteinuria (3/3/1). Conclusions: To our knowledge, these are the first data reported of long-term survivors with advanced nsNSCLC treated with 1L CT/B plus long-time mtc B. Although prospective evaluation is required, the outstanding median OS (31 m) and 2-yr survival (62%) point out the importance of selecting Tx and the role of mtc B after 1LB. B was very well tolerated, without significant life-threatening toxicities. Subgroup analyses will be presented.
Use and effectiveness of adjuvant ovarian function suppression (OFS) in premenopausal women with early breast cancer
Authors: A.R. Ferreira, J. Ribeiro, A. Mayer, M. Brito, A. Miranda, J.P. Fernandes, J.L. Passos-Coelho, L. Costa, I. Vaz-Luís
Journal: Annals of Oncology (2017)
Two-Step Sequential Approach for Concomitant Skin and Soft Tissue Infection and Osteomyelitis Complicating the Diabetic Foot
Authors: Naïma Berthol, Olivier Robineau, Anne Boucher, Nicolas Blondiaux, Eric Beltrand, Michel Valette, Marie Cazaubiel, Sophie Nguyen, Eric Senneville
Journal: Diabetes Care (2017)

Current guidelines (1,2) do not provide data on the treatment of patients presenting with concomitant soft tissue infection and osteomyelitis of the diabetic foot (DF-STI/DFO). We have developed a two-step sequential approach (TSA) consisting chronologically of 1 ) an empirical antibiotic therapy for diabetic foot soft tissue infection (DF-STI) secondarily adapted to the culture results of a tissue sample taken by curettage from the periphery of the ulcer (step 1), 2 ) an antibiotic-free period of at least 2 weeks, and 3 ) a bone biopsy obtained percutaneously or intraoperatively in case of, respectively, medical or surgical approach of diabetic foot osteomyelitis (DFO) (step 2) chosen according to Lipsky’s recommendations (3). In the present monocentric retrospective 2006–2015 study, 38 adult patients out of a total of 297 patients followed for DFO (12.8%) had concomitant DF-STI and DFO not requiring …
Making Patients and Doctors Happier — The Potential of Patient-Reported Outcomes
Authors: Lisa S. Rotenstein, Robert S. Huckman, Neil W. Wagle
Journal: New England Journal of Medicine (2017)

Interview with Dr. Neil Wagle on how measuring patient-reported outcomes can benefit both patients and doctors. (12:17)Download Interviews with providers suggest that incorporating collection of patient-reported outcomes into routine care can improve physician satisfaction, enhance physician–patient relationships, increase workflow efficiency, and enable crucial conversations.
Population sizes of patients (pts) with node negative (N0), HR+, HER2− primary breast cancer (BC), using standard and TAILORx 21-gene recurrence score (RS) cut-off values (COV)
Authors: J-U. Blohmer, M. Verrill, C. Fortmann, C. Chao, J. Gligorov
Journal: Annals of Oncology (2017)
Insulin pumps are linked to lower risk of complications in young people
Authors: Jacqui Wise
Journal: BMJ (2017)

Insulin pumps are associated with a lower risk of serious complications among young patients with type 1 diabetes than insulin injections, research published in JAMA has found.1

The population based observational study found that pump treatment was associated with lower rates of severe hypoglycaemia and diabetic ketoacidosis and with better glycaemic control than injection treatment.

The National Institute for Health and Care Excellence recommends insulin pumps as a treatment option for adults and children aged over 12 with type 1 diabetes if attempts to reach target glycated haemoglobin (HbA1c) levels with multiple injections have resulted in the patient having “disabling hypoglycaemia” or if HbA1c …