tbuckley/cabot-search huggingface dataset:
Abstract 2268: Detection of T790M mutation in EGFR gene, an EGFR-TKI resistant mutation, in tumor samples unexposed to EGFR TKIs
Authors: Hayato Koba, Hideharu Kimura, Shingo Nishikawa, Taro Yoneda, Takashi Sone, Kazuo Kasahara
Journal: Cancer Research (2016)

Abstract Background: T790M mutation in EGFR gene is the commonest mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR mutation. The third-generation EGFR-TKIs are expected to overcome the resistance caused by T790M existence. On the other hand, several reports using highly sensitive detection assays showed a minute amount of T790M mutation alleles was detected in tumor tissues obtained before EGFR-TKI treatment. Aim: To clear whether T790M dominancy in tumor cells before EGFR-TKI treatment reflects between about the EGFR-mutated lung cancer which was not until exposed EGFR TKI therapy and actual resistance mechanism. Methods: We assessed T790M dominancy in tumor cells from 29 NSCLC patients with EGFR mutations, who had not received EGFR-TKIs. T790M mutation and common mutations, such as deletional mutations in exon 19 and L858R, were detected by droplet digital PCR (ddPCR) separately. T790M dominancy was calculated from each level of mutation-alleles about common mutation and T790M mutation. Results: We can detect the T790M mutation in initial biopsy tissues from 21 cases (72%). The mean value of T790M mutation dominancy ratio before EGFR-TKI treatment was 0.48% (0.00-69.09%) and it is not difference between in patients with T790M-positive at resistance and in that with negative (p = 0.87). Conclusions: T790M mutation was detected in most of the tumor tissues unexposed to EGFR TKIs. T790M mutation dominancy calculated by our assays in tumor tissues before EGFR-TKI treatment may not be related to induce T790M resistance to EGFR-TKIs. Citation Format: Hayato Koba, Hideharu Kimura, Shingo Nishikawa, Taro Yoneda, Takashi Sone, Kazuo Kasahara. Detection of T790M mutation in EGFR gene, an EGFR-TKI resistant mutation, in tumor samples unexposed to EGFR TKIs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2268.
Duration of Antibiotic Treatment in Community-Acquired Pneumonia
Authors: Ane Uranga, Pedro P. España, Amaia Bilbao, Jose María Quintana, Ignacio Arriaga, Maider Intxausti, Jose Luis Lobo, Laura Tomás, Jesus Camino, Juan Nuñez, Alberto Capelastegui
Journal: JAMA Internal Medicine (2016)

The optimal duration of antibiotic treatment for community-acquired pneumonia (CAP) has not been well established.To validate Infectious Diseases Society of America/American Thoracic Society guidelines for duration of antibiotic treatment in hospitalized patients with CAP.This study was a multicenter, noninferiority randomized clinical trial performed at 4 teaching hospitals in Spain from January 1, 2012, through August 31, 2013. A total of 312 hospitalized patients diagnosed as having CAP were studied. Data analysis was performed from January 1, 2014, through February 28, 2015.Patients were randomized at day 5 to an intervention or control group. Those in the intervention group were treated with antibiotics for a minimum of 5 days, and the antibiotic treatment was stopped at this point if their body temperature was 37.8°C or less for 48 hours and they had no more than 1 CAP-associated sign of clinical instability. Duration of antibiotic treatment in the control group was determined by physicians.Clinical success rate at days 10 and 30 since admission and CAP-related symptoms at days 5 and 10 measured with the 18-item CAP symptom questionnaire score range, 0-90; higher scores indicate more severe symptoms.Of the 312 patients included, 150 and 162 were randomized to the control and intervention groups, respectively. The mean (SD) age of the patients was 66.2 (17.9) years and 64.7 (18.7) years in the control and intervention groups, respectively. There were 95 men (63.3%) and 55 women (36.7%) in the control group and 101 men (62.3%) and 61 women (37.7%) in the intervention group. In the intent-to-treat analysis, clinical success was 48.6% (71 of 150) in the control group and 56.3% (90 of 162) in the intervention group at day 10 (P = .18) and 88.6% (132 of 150) in the control group and 91.9% (147 of 162) in the intervention group at day 30 (P = .33). The mean (SD) CAP symptom questionnaire scores were 24.7 (11.4) vs 27.2 (12.5) at day 5 (P = .10) and 18.6 (9.0) vs 17.9 (7.6) at day 10 (P = .69). In the per-protocol analysis, clinical success was 50.4% (67 of 137) in the control group and 59.7% (86 of 146) in the intervention group at day 10 (P = .12) and 92.7% (126 of 137) in the control group and 94.4% (136 of 146) in the intervention group at day 30 (P = .54). The mean (SD) CAP symptom questionnaire scores were 24.3 (11.4) vs 26.6 (12.1) at day 5 (P = .16) and 18.1 (8.5) vs 17.6 (7.4) at day 10 (P = .81).The Infectious Diseases Society of America/American Thoracic Society recommendations for duration of antibiotic treatment based on clinical stability criteria can be safely implemented in hospitalized patients with CAP.clinicaltrialsregister.eu Identifier: 2011-001067-51.
Abstract 4179: Expression profiling of zebrafish rb1- neuroectodermal-like brain tumors: A new model of CNS PNETs
Authors: Maura A. McGrail, Staci L. Solin, Jeffrey A. Haltom, Laura E. Schultz, Jeffrey J. Essner, Heather R. Shive
Journal: Cancer Research (2016)

Abstract We examined the gene expression signature of zebrafish brain tumors induced by somatic inactivation of the retinoblastoma tumor suppressor rb1 to determine the similarity with human CNS primitive neuroectodermal tumors (PNETs). Childhood CNS PNETs are aggressive tumors characterized by undifferentiated cells with features of the embryonic neuroepithelium. Previously our histological analysis showed the majority of zebrafish rb1- lesions were proliferative neuroectodermal-like tumors composed of neoplastic cells with small hyperchromatic nuclei that form rosettes. To obtain the transcription profile of the zebrafish rb1- tumors, RNA-Seq was performed on 10 tumors from fish ranging in age from 3.5 to 10 months of age. Duplicate RNA-Seq libraries were synthesized for each tumor and multiplex sequenced on an Illumina HiSeq NextGen Sequencer at the Genome Sequencing Core, Kansas University. Our initial gene expression profiling of the zebrafish rb1- brain tumors revealed a molecular signature consistent with an undifferentiated tumor phenotype. In each zebrafish tumor sample, standard markers of neuronal differentiation (sypa, sypb, neurod1/2, neurog1/2) and glial differentiation (GFAP, S100β) were not significantly expressed. In contrast, the neural stem/progenitor marker sox2 was highly expressed in all tumors, consistent with the primitive neuroectodermal-like tumor histology. Comparison with human childhood CNS-PNET gene expression analysis revealed a similar profile. Four of the nine genes that define the human oligoneural (group 2) molecular subgroup (olig2, bcan, sox8b, sox10 and ascl1) described by Picard et al, 2012 were highly expressed in the zebrafish tumors. Together, the data indicate the zebrafish brain tumors induced by somatic inactivation of rb1 model human CNS PNETs. Additional gene expression, pathway, and cross-species comparative analyses are in progress. The zebrafish rb1- tumor model will be useful for investigating the molecular pathways driving the aggressive and undifferentiated features of CNS PNETs. Citation Format: Maura A. McGrail, Staci L. Solin, Jeffrey A. Haltom, Laura E. Schultz, Jeffrey J. Essner, Heather R. Shive. Expression profiling of zebrafish rb1- neuroectodermal-like brain tumors: A new model of CNS PNETs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4179.
Indemnisation des accidents du travail et infections professionnelles par le VIH chez les personnels de santé en Allemagne
Authors: J Jarke
Journal: Eurosurveillance (1999)

En 1997, le nombre de cas d‘infections professionnelles par le VIH rapportees dans le monde s’elevait a 286 (1). Un tiers (95 cas), generalement associe a une seroconversion apres une exposition professionnelle specifique, a ete classe en cas certains, et les deux autres tiers (191 cas) en cas possibles d’infections professionnelles par le VIH. Trois des 95 cas certains (2,3) et 22 des 191 cas possibles d’infections professionnelles par le VIH sont survenus chez des personnels de sante allemands (1).
Paroxysmal Nocturnal Hemoglobinuria and Thrombosis Before and After Eculizumab
Authors: Cristina Muñoz-Linares, Miguel Pastrana, Emilio Ojeda, Rafael Fores, Martin Cabero, Daniel Morillo, Guiomar Bautista, Belen Navarro, Isabel Krsnik, Santiago Gil, Carmen Regidor, Almudena de LaIglesia, Jose Luis Bueno, Jose A Garcia-Marco, Jose Rafael Cabrera
Journal: Blood (2013)
PTH-222 Patient-reported gastrointestinal symptom scoring does not identify nutritional risk in systemic sclerosis: Abstract PTH-222 Table 1
Authors: E Harrison, AL Herrick, JT McLaughlin, S Lal
Journal: Gut (2015)

<h3>Introduction</h3> Systemic sclerosis (SSc) is a chronic, multi-organ connective tissue disease. Approximately 90% of patients have gastrointestinal (GI) involvement.<sup>1</sup>In the most severe cases, patients may develop intestinal failure. Malnutrition is common in patients with SSc, with one study finding almost 18% to be at high risk.<sup>2</sup>However, the relationship between GI symptoms and nutritional risk has not been defined. This study aimed to compare malnutrition risk to GI involvement and patient reported GI symptoms. <h3>Method</h3> Unselected outpatients with SSc were recruited over 12 months. Demographics and known GI involvement were recorded. Body mass index (BMI) was determined. Recent unintentional weight loss was assessed and used to calculate the ‘Malnutrition Universal Screening Tool’ (‘MUST’) score.<sup>3</sup>Patients completed the UCLA GI symptom questionnaire 2.0, which has 7 symptom domains assessing symptom frequency over the past 7 days.<sup>4</sup>All domains are scored 0–3, except constipation (0–2.5) and diarrhoea (0–2). The total score (0–2.83) is the mean of all scores except constipation. Statistical analysis sought correlations between ‘MUST’ category and GI involvement and questionnaire scores. This study was granted ethical approval. <h3>Results</h3> 168 patients were recruited (median age 61 (range 25–81)). 31 (19%) were male. 45 (27%) had diffuse cutaneous SSc. Mean BMI was 24.6 kg/m<sup>2</sup>(range 15.6–39.8) and 20 (12%) had an unplanned weight loss of &gt;5% in the past 3–6 months. 12% of patients had a high, 14% a medium and 74% a low ‘MUST’ score. 52% had oesophageal and 18% small intestinal dysmotility. ‘MUST’ scores were associated (linear-by-linear analysis) with small intestinal (p = 0.011) but not oesophageal dysmotility (p = 0.179). The GI symptom score results are shown in the table. There were no associations (Spearman’s) between ‘MUST’ and any of the GI symptom scores. <h3>Conclusion</h3> This study shows an association between malnutrition risk (‘MUST’) and GI involvement but not patient reported GI symptoms. Hence, GI symptoms should not be relied upon to identify patients at risk of malnutrition. <h3>Disclosure of interest</h3> E. Harrison Grant/Research Support from: Raynaud’s and Scleroderma Association, A. Herrick: None Declared, J. McLaughlin: None Declared, S. Lal: None Declared. <h3>References</h3> Thoua NM, <i>et al</i>. Rheumatology (Oxford) 2010;49(9):1770–5 Baron M, <i>et al</i>. J Rheumatol. 2009;36(12):2737–43 Weekes CE, <i>et al</i>. Clin Nutr. 2004;23(5):1104–12 Khanna D, <i>et al</i>. Arthritis Rheum 2009;61(9):1257–63
Antiretroviral Therapy for the Prevention of HIV-1 Transmission
Authors: Myron S. Cohen, Ying Q. Chen, Marybeth McCauley, Theresa Gamble, Mina C. Hosseinipour, Nagalingeswaran Kumarasamy, James G. Hakim, Johnstone Kumwenda, Beatriz Grinsztejn, Jose H.S. Pilotto, Sheela V. Godbole, Suwat Chariyalertsak, Breno R. Santos, Kenneth H. Mayer, Irving F. Hoffman, Susan H. Eshleman, Estelle Piwowar-Manning, Leslie Cottle, Xinyi C. Zhang, Joseph Makhema, Lisa A. Mills, Ravindre Panchia, Sharlaa Faesen, Joseph Eron, Joel Gallant, Diane Havlir, Susan Swindells, Vanessa Elharrar, David Burns, Taha E. Taha, Karin Nielsen-Saines, David D. Celentano, Max Essex, Sarah E. Hudelson, Andrew D. Redd, Thomas R. Fleming
Journal: New England Journal of Medicine (2016)

An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).
Validation of a Spanish language version of the self-administered food allergy quality of life questionnaire for adults (FAQLQ-AF)
Authors: D. Antolin, [No Value] Cerecedo, A. Muriel, A. Cano, M. Dieguez, J. Zamora, B. Flokstra-de Blok, A. Dubois, [No Value] Abraira, B. De la Hoz Caballer
Journal: Allergy (2009)
Abstract 15: Metabolomic profiling of cell death in human lung cancer cells by a novel digitoxin analog
Authors: Yogesh Kulkarni, Neelam Azad, Vivek Kaushik, Juan Sebastian Yakisich, Rajkumar Venkatadri, Clayton Wright, Yon Rojanasakul, George O’Doherty, Anand Krishnan V Iyer
Journal: Cancer Research (2016)

Abstract Background: Digitoxin, a cardiac glycoside had shown considerable promise as an anti-cancer therapeutic. However, doses of digitoxin required to inhibit cancer cell proliferation lead to cardiotoxic side effects. We have previously shown that a novel analog of digitoxin, MonoD, activates apoptosis in human lung cancer cells at much lower concentrations as compared to digitoxin. We postulate that treatment with MonoD leads to distinct metabolic signatures on lung cancer cells as compared to digitoxin, which will help delineate the pathways that dictate MonoD action. Experimental Approach: NCI-H460 cells from identical passages were used for metabolite analysis using an optimized version of the methanol/water (80:20) protocol for metabolite extraction. The supernatant containing metabolites were suspended in 0.1% formic acid spiked with an internal standard for Q-Exactive analysis. The data was analyzed using SIEVETM 2.0 software with the component extraction algorithm that has been specifically designed for optimal data analysis in untargeted metabolomics experiments. Metabolites that were found to be significantly different between treatment groups were detected via Chemspider/HMDB database search. Results: We observed several metabolites along the prostaglandin synthesis pathway which were downregulated in MonoD treated lung cancer cells. Prostaglandins play a key role in the generation of the inflammatory response. Chronic inflammation has been shown to be a causative factor in a variety of cancers. Cyclooxygenase-2 (COX-2) derived prostaglandin has been previously shown to promote tumor growth by binding its receptors and activating signaling pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Using the metabolite profiling data, we posited that COX-2, a key enzyme involved in prostaglandin synthesis, in addition to NFκB, a key transcription factor of proinflammatory signaling pathway are downregulated with MonoD treatment. Immunoblotting confirmed the downregulation of COX-2 and NFκB in MonoD-treated cells. Conclusion: Using metabolite profiling, we have elucidated an important mode of action for MonoD in lung cancer cells, and shown that MonoD exerts its anti-tumorigenic properties by downregulating key factors involved in inflammatory response. Citation Format: Yogesh Kulkarni, Neelam Azad, Vivek Kaushik, Juan Sebastian Yakisich, Rajkumar Venkatadri, Clayton Wright, Yon Rojanasakul, George O’Doherty, Anand Krishnan V Iyer. Metabolomic profiling of cell death in human lung cancer cells by a novel digitoxin analog. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 15.
Pancytopenia or Bicytopenia in a Korean Tertiary Care Center; Etiological Profile Based on Bone Marrow Examination and Suggestion for Diagnostic Approach
Authors: Mi-Hyun Bae, Young-Uk Cho, Bohyun Kim, Seongsoo Jang, Chan-Jeoung Park, Yoon Hwan Chang, In-Suk Kim
Journal: Blood (2015)
Safety, PD-L1 expression, and clinical activity of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with advanced gastric or gastroesophageal junction cancer.
Authors: Hyun Cheol Chung, Hendrik-Tobias Arkenau, Lucjan Wyrwicz, Do-Youn Oh, Keun-Wook Lee, Jeffrey R. Infante, Kevin M. Chin, Anja von Heydebreck, Yoon-Koo Kang, Howard Safran
Journal: Journal of Clinical Oncology (2016)

167 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report safety and clinical activity of avelumab in patients (pts) with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) based on level of PD-L1 expression. This phase Ib JAVELIN study (NCT01772004) enrolled pts who had progressed on prior therapy ( ≥ 2L) and pts who had received 1L chemotherapy but had not yet progressed (switch-maintenance [Mn]) Methods: Pts received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumours were assessed every 6 wks (RECIST 1.1). Best overall response and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry using various cutoff criteria Results: As of Feb 13, 2015, 75 pts with GC/GEJ were treated with avelumab (20 pts, 2L; 55 pts, Mn). Treatment-related treatment-emergent AEs (TR-TEAEs) of any grade occurred in 47 pts (62.7%); the most common ( &gt; 10%) was infusion-related reaction (12 [16.0%], all grade 1/2). Nine pts (12.0%) reported a grade ≥ 3 TR-TEAE, including fatigue (2), thrombocytopenia (2), and anemia (2; each 2.7%). There was 1 treatment-related death (hepatic failure/autoimmune hepatitis). Responses were observed in 7 pts (3/20 2L, all PRs; 4/55 Mn, 1 CR, 3 PRs). PD-L1 expression was evaluable in 55 pts (12/20 2L, 43/55 Mn), including in 3 pts with a response. Median PFS in 2L group was 36.0 wks (95% CI: 6.0, 36.0) for PD-L1+ and 11.6 wks (2.1, 21.9) for PD-L1− ( ≥ 1% cutoff). In Mn group, median PFS for PD-L1+ and PD-L1− status was 17.6 wks (5.9, 18.0) and 11.6 wks (5.7, 17.7), respectively ( ≥ 1% cutoff). Conclusions: Single agent avelumab showed an acceptable safety profile and clinical activity in GC/GEJ pts. Objective responses and disease stabilization were observed in both groups. Median PFS was longer in PD-L1+ pts. Phase III trials in 1L and 3L GC/GEJ are underway.*Proposed INN Clinical trial information: NCT01772004.
Abstract 1585: Molecular subtypes of breast cancers and normal mammary epithelial cells show hierarchical heterogeneity and complexity at single-cell resolution
Authors: Ebrahim Azizi, Justin Colacino, Shamileh Fouladdel, Max S. Wicha
Journal: Cancer Research (2016)

Abstract The analysis of average gene expression in cell populations may obscure the heterogeneity of rare cells such as cancer stem cells (CSCs). The use of CSC markers to enrich for these cell populations has proven valuable in their molecular characterization. However, conventional gene expression analysis of these CSC enriched populations is still not conducive to elucidating their heterogeneity. We exploited single-cell resolution methods using C1 and BioMark HD platform and TaqMan assays in the analysis of CSCs and non-CSCs/differentiated tumor cells. The expression of 96 target genes was studied at single cell level in a multiplex RT-qPCR setting. Breast cancer cell lines including MCF7 (luminal), BT474 (HER2+), SUM149 (Basal), and MDA-MB-231 (Basal-Claudin low) that represent major different subtypes of breast cancers and normal mammary epithelial cells (NM) were studied at single cell resolution. Despite similarities, expression profiles of 96 target genes were distinctly different between subtypes of breast cancers and also with that of NM cells. Interestingly, results of single cell studies revealed significant levels of hierarchical heterogeneities within and between each analyzed population of cells. The observed heterogeneous signatures were due to both different expression levels as well as presence/absence of certain genes. We could identify CSCs with EMT (i.e. CD44+/CD24-/ALDH-/CDH2+/Vimentin+), MET (i.e. ALDH+/CD44-/CD24+/CDH1+/Vimentin-), and dual EMT-MET (CD44+/CD24-/ALDH+/CDH1+ or CDH2+/Vimentin+) characteristics. This methodology enabled us to also identify a range of several different non-CSCs/differentiated single cells with heterogeneous expression patterns for CD44, CD24, ALDH, ESR, PGR, HER2, Vimentin, CDH1, CDH2, EpCAM, and Cytokeratins that were similar to luminal, HER2 overexpressed, basal, and basal-Claudin low breast cancer cells. Additionally, NM single cells also showed significant heterogeneity that was similar to the wide spectrum patterns of some single breast cancer cells described above. This study highlights the use of single cell technologies to redefine tumor cell characterization, revealing heterogeneity of single tumor cells with respect to stem cell properties, metastatic and drug resistance characteristics. This will further improve the identification of new markers/pathways that can be used to develop new target therapies for better therapeutic responses in cancer patients. Citation Format: Ebrahim Azizi, Justin Colacino, Shamileh Fouladdel, Max S. Wicha. Molecular subtypes of breast cancers and normal mammary epithelial cells show hierarchical heterogeneity and complexity at single-cell resolution. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1585.