tbuckley/cabot-search huggingface dataset:
Contribution of Lipocalin-2 from Both Myeloid Cells and Epithelium/Liver Is Required for Optimal Resistance to K. Pneumonia Infection
Authors: Elisabeth Præstekjær Cramer, Sara Louise Dahl, Björn Rozell, Kasper Jermiin Knudsen, Kim Thomsen, Claus Moser, Niels Borregaard, Jack B. Cowland
Journal: Blood (2015)
Preliminary results of phase II trial with combination of gemcitabine and oxaliplatin in elderly patients with advanced NSCLC
Authors: R. Buosi, S. Poletti, V. Cantele, S. Piazza, R. Torazzo, E. Negru, A. Vandone, O. Alabiso
Journal: Journal of Clinical Oncology (2004)

7348 Background: Oxaliplatin (L-OHP) is a novel antineoplastic platinum derivative with a DACH carrier ligand. In preclinical studies it appeared to have clinical activity in many tumor cell lines, including some thatnare resistant to cisplatin and carboplatin. Based upon in vitro studies demostrating synergistic anti-tumor acitvity between L-OHP and new citotoxyc drugs, as Gemcitabine, we have conduced a phase II study to evaluate the toxicity and potential synergistic effect by combining the two drugs in elderly patients with locally advanced or metastatic NSCLC. Methods: 14 chemotherapy naive patients with stage III B and IV NSCLC were enrolled in the study. The patients show these characteristics: 4 females, 10 males, median age 73 years, range 65 - 78, 12 patients with ECOG performance status 0, 2 with ECOG 1. Cancer istotype: 2 adenocarcinoma, 10 squamous cell, 1 large cell, 1 indeterminated carcinoma. 3 patients have bone metastasis, 4 have lung metastasis and 3 with brain lesion. 4,9 cycles for patient are administered. Treatment schedule: L-OHP 65 mg/mq and Gemcitabine 1000 mg/mq, both drugs are administered at days 1–8, to be repeated every 3 weeks Results: 13/14 patient evaluable for response rate: 6 RO (43%) in which 1 RC and 5 RP, 1 PD (7%) and 6 SD (43%). Only 1 patient had a worsenig of PS, 1 patient in RP after 3 cycles is die for unrelated therapy cardiac failure. We observed mild hematological toxicity: 2 pts show grade (Gr) 2 anemia; 3 pts Gr 2 trombocytopenia, and Gr 3 and Gr 4 trombocytopenia we relevate in only 1 pt respectively. Neither Gr 4 neutropenia nor febrile episodes were detected. Also non hematological toxicity is low: nobody experimented Gr >2 nausea and vomiting. Gr. 2 diarrhea and Gr 2 neurotoxicity are manifested in 2 pts and in 4 pts respectively; 1 pt have Gr 2 transaminases increase. The 2 pts with Hb level ≤ 10 g/dl are treated with recombinant human erythropoietin 10.000 UI s.c. 3 times/wk until to normal Hb level Conclusions: these encouraging results indicate that the GEMOX schedule could be used in treatment of advanced NSCLC and so we advise to use this combination in elderly patients. No significant financial relationships to disclose.
Transcription Factor EB Controls Metabolic Flexibility during Exercise
Authors: Gelsomina Mansueto, Andrea Armani, Carlo Viscomi, Luca D’Orsi, Rossella De Cegli, Elena V. Polishchuk, Costanza Lamperti, Ivano Di Meo, Vanina Romanello, Silvia Marchet, Pradip K. Saha, Haihong Zong, Bert Blaauw, Francesca Solagna, Caterina Tezze, Paolo Grumati, Paolo Bonaldo, Jeffrey E. Pessin, Massimo Zeviani, Marco Sandri, Andrea Ballabio
Journal: Cell Metabolism (2016)
MRI characteristics of BRCA-associated breast cancers.
Authors: A. K. Kelekar, S. Mukherjee, C. Mitri, F. Khan, W. Ducaine, L. Dohany, D. Zakalik
Journal: Journal of Clinical Oncology (2011)

1596 Background: Magnetic resonance imaging (MRI) is the preferred imaging modality for screening and diagnosis of breast cancer in BRCA-1and BRCA-2 mutation carriers. However, there is limited data on the radiographic features of BRCA1/2-positive breast cancers on MRI. This study evaluates the MRI characteristics of BRCA1/2 -related breast cancers. Methods: All female BRCA mutation carriers with a biopsy proven breast cancer, imaged with MRI for screening or preoperative evaluation at William Beaumont hospital between April 2002 until January 2011, were included in the study. A total of 47 mutation carriers were identified.All MRI examinations were retrospectively evaluated by an independent radiologist for the following characteristics: shape, margin, enhancement, T2 intratumoral intensity. Results: A majority of BRCA- associated breast tumors were morphologically irregular, hypodense lesions on MRI with heterogeneous enhancement. No statistically significant differences were noted among the BRCA-1 and -2 mutations carriers. Conclusions: Previous studies have reported that BRCA-associated breast cancers demonstrate morphological characteristics that resemble benign tumors i.e.round shape and smooth margins. Our study however, showed features more typical of malignant lesions i.e. irregular shape and margin. Low T2 intratumoral intensity tumors were commonly seen in our cohort, although BRCA1 patients often develop triple negative tumors which typically are high intensity. These differences may be explained by small sample size or population differences. Future reasearch is needed with larger patient cohorts to elucidate the unique MRI characteristics of BRCA- related cancers. MRI Characteristic BRCA1 BRCA2 BRCA1+2 Shape Round 3 4 7 (14.3%) Lobulated 8 3 11 (22.4%) Irregular 19 12 31 (63.3%) Margin Smooth 3 3 6 (12.2%) Irregular 26 17 43 (87.8%) Enhancement Homogenous 5 2 7 (14.3%) Heterogenous 19 13 32 (65.3%) Rim 5 5 10 (20.4%) T2 intratumoral intensity Low 25 21 46 (86.8%) Equal 4 0 4 (7.6%) High 1 2 3 (5.7%)
Additional Chromosomal Abnormalities in Philadelphia Chromosome-Negative Metaphases Appearing during Therapy with Imatinib, Dasatinib, Nilotinib and Ponatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia
Authors: Ghayas C. Issa, Hagop M. Kantarjian, Elias Jabbour, Gautam Borthakur, Srdan Verstovsek, Sherry Pierce, William Wierda, Alessandra Ferrajoli, Guillermo Garcia-Manero, Tapan Kadia, Naval Daver, Naveen Pemmaraju, Farhad Ravandi, Sara Emogene DellaSala, Jorge E. Cortes
Journal: Blood (2015)
104. A Gene Deleted High Capacity Adenoviral Vector for Efficient Delivery of a Multiplex DMD Specific CRISPR/Cas9 Machinery
Authors: Eric Ehrke-Schulz, Rudolf A. Kley, Anja Ehrhardt
Journal: Molecular Therapy (2016)

Recent advances in the field of designer nuclease directed genome editing hold great promise to correct underlying mutations leading to Duchenne muscular dystrophy. Especially the CRISPR/Cas9 system provides an easy way to design and to assemble RNA guided nucleases offering the potential to develop personalized treatments to correct the multiple different mutations leading to this fatal disease. Recent studies showed efficient genome editing in a myoblast cell line derived from DMD patients and mdx mice. Nevertheless viral delivery of all required CRISPR/Cas9 components including Cas9 and one or multiple guide RNA (gRNA) expression units has not been fully exploited. Gene deleted high-capacity adenoviral vectors (HCAdVs) offer the packaging capacity to deliver the complete CRISPR/Cas9 machinery including several gRNA expression units using a single viral vector. By using a new toolbox that facilitates customization, cloning and production of CRISPR-HCAdVs, we assembled a HCAdV genome containing a Streptococcus pyogenes Cas9 (spCas9) gene including two guide RNA (gRNA) expression units specific for DMD that have shown efficiency to delete exon 51 in dystrophic human myoblasts. CRISPR-HCAdV was amplified in medium scale using a shortened protocol yielding high titers. Infection of cultured HEK293 cells and primary human myoblasts with purified DMD specific CRISPR-HCAdV at different MOIs resulted in strong locus specific deletion efficiency for DMD exon 51 as shown with locus specific PCR. As a comparison we also designed and produced DMD-specific TALEN encoding HCAdVs which allow delivery of a complete TALEN pair using a single vector. We found that it was more complicated to produce double TALEN-HCAdVs compared to multiplex CRSIPR/Cas9-HCAdV as they require controlled expression of TALEN genes by inducible promotors. Furthermore the TALEN system is not suitable for multiplexing and showed less efficiency in T7E1 assays. Our platform enables cloning and production of gene deleted adenoviral vectors for the delivery of a DMD specific CRISPR/Cas9 system within a short time providing a valuable tool for viral delivery of customized CRISPR/Cas9 for DMD treatment. Additional gRNAs or gRNAs with other specificities can be easily included in the vector allowing personalized molecular design of the gene transfer vector. We expect that this may pave the way towards broader applications of the CRISPR technology for DMD treatment including preclinical and eventually clinical studies.
Toll-Like-Receptor Expression and Cellular Immune Reconstitution In AML-Patients with Elevated Serum Ferritin Levels After Allogeneic transplant.
Authors: Ahmet Elmaagacli, Nina Steckel, Michael Koldehoff, Sandra Christoph, Hellmut Ottinger, Rudolf Trenschel, Dietrich Beelen
Journal: Blood (2010)
Central nervous system breast cancer metastasis (CNSBC): An outcome research.
Authors: C. Garcia Gerardi, F. Tognelli, E. Gil Deza, D. Niewiadomski, G. Martin Reinas, C. Acuna, N. Gercovich, N. Kohen, B. Rolnik, E. L. Morgenfeld, E. G. J. Rivarola, F. G. Gercovich
Journal: Journal of Clinical Oncology (2011)

e11007 Background: Twenty percent of advanced breast cancer patients develop CNS metastasis. The main objective of the present paper is to evaluate the incidence rate and evolution of this condition in patients treated at the IOHM. Methods: A search of the IOHM breast cancer tumors registry was carried out. In this database all 1,680 tumors were reviewed and classified according to the USA Association of Directors of Anatomic and Surgical Pathology’s recommendations. Only those with breast cancer developing CNS metastases were included in this paper. Results: Between January 2000 and December 2010, 174 patients with advanced breast cancer were identified and 26 (14.9%) of them presented CNS metastasis. Population Characteristics: Median Age 54 years (30-78); Menopause YES/NO 13/13; Histology: IDC= 25,ILC=1; High Tumor Grade=23; Stage (I=1pt. II=13 pts, III=5 pts, IV=7pts); Previous CNS metastases treatment (Adjuvant 18 pts, Advanced 16 pts); CNS metastasis characteristics: Group A) 9 pts (CNS metastasis only) (Solitary metastasis in 2 cases, Multiple metastasis in 7 cases), Group B) (CNS metastasis with other metastatic sites) 17 pts (Solitary CNS metastasis 1 Case, Multiple metastasis 16 cases). CNS Metastasis treatment and follow up: All 26 patients received radiotherapy. In three patients the metastasis was surgically removed prior to radiotherapy and ten patients received chemotherapy after radiotherapy. The median follow up was 60 months (range 1-126); median overall survival 43 months (range 1-126); median post CNS metastasis survival 5 months (range 1-60); after single metastasis surgery (3 cases) the survival was: +15 months, +35 months and +60 months. In patients with multiple metastasis the survival time after radiotherapy was much longer in Group A (7 pts, Median survival: 6 months) than in Group B (16 pts, Median survival: 3.3 months) (Log Rank p=0.05). Conclusions: 1) 15% of this cohort presented with a compromised CNS. 2) The only long survival chance was achieved after the surgical removal of single CNS metastasis (3 pts median survival 35 months). 3) The median survival after developing multiple CNS metastasis was 6 months, it was reduced to 3 months when this affectation followed the compromise of other metastatic locations.
RUNX1 Mutations in Acute Myeloid Leukemia (AML): Correlation with Distinct Cytogenetic Subgroups and Clinical Outcome. Results of the AML Study Group (AMLSG)
Authors: Verena I. Gaidzik, Richard F. Schlenk, Kerstin Wittke, Annegret Becker, Andreas Zimmermann, Brigitte Schlegelberger, Arnold Ganser, Daniela Spaeth, Hartmut Doehner, Konstanze Doehner
Journal: Blood (2008)
Statin therapy now more common than steroids in clinical practice
Authors: Anil Pareek, Nitin Chandurkar
Journal: Annals of the Rheumatic Diseases (2016)

Statin therapy now more common than steroids in clinical practiceDear Editor, In the recent article from Ozen et al 1 , the authors found increased risk of diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) compared with normal US adult population.The authors have also reported increased risk of DM in patients with RA who took glucocorticoids (GCs) and statin therapy.Surprisingly, the HR of diabetes has been found to be higher in the statin group than in the steroid group.It is important to know the duration of exposure to steroids in patients with RA .Not all patients may be exposed to steroids for prolonged period.The authors may comment on the duration of steroids in various patients.While the concomitant use of GC did not alter DM risk reduction with HCQ, the authors have also reported DM risk reduction with concomitant use of HCQ and statin therapy.The authors have mentioned the risk of incident diabetes by steroid dose, HCQ dose, and duration and concomitant GC use in a tabular form (table 4, page no. 5) but similar information is missing for concomitant use of statin and HCQ.We request the authors to throw more light on this.In our study, 'Efficacy and safety of fixed dose combination of atorvastatin and hydroxychloroquine: a randomized, doubleblind comparison with atorvastatin alone among Indian patients with dyslipidemia', we compared the efficacy and safety of atorvastatin (10 mg)+hydroxychloroquine (200 mg) fixed-dose combination tablets in comparison with atorvastatin (10 mg) alone in treatment of dyslipidaemia for 6 months and found in exploratory analysis that 15% patients with prediabetic dyslipidaemia from the monotherapy group and 2% from the combination group developed diabetes. 2ther observational studies have also suggested the potential benefit of hydroxychloroquine in attenuating the risk of diabetes in patients with RA.A population-based cohort study in patients with systemic lupus erythematosus 3 4 demonstrated an increased risk of DM with high dose of GC which was decreased by concomitant use of HCQ in a dose-dependent manner. 5 is important to note that in comparison with GC, which may often be used intermittently for short period, statin therapy is used for long term to reduce cardiovascular risk.Hence, it is important to know the risk of diabetes due to statin exposure in patients with RA and the preventive role of HCQ in the same.
S23 Neural respiratory drive during sleep at high altitude
Authors: J Steier, N Cade, B Walker, J Moxham, CJ Jolley
Journal: Thorax (2016)

<h3>Introduction</h3> Ventilation at altitude changes due to altered levels of pO2, pCO2 and the effect on blood pH. Nocturnal ventilation is particularly exposed to these changes. We hypothesised that increasing neural respiratory drive is associated with the severity of sleep-disordered breathing at altitude. <h3>Subjects and methods</h3> British mountaineers were studied at sea level (London, UK), and at altitude at the Aconcagua (Andes, Argentina). Neural respiratory drive (NRD) was measured as electromyogram of the diaphragm (EMGdi) overnight by a transoesophageal multi-electrode catheter (Yinghui Medical Ltd, Guangzhou, China). Following initial assessment with a polysomnography (London, UK), pulse oximetry measured oxygen concentration and oxygen desaturation indices (4%ODI) at altitude. <h3>Results</h3> Four healthy subjects (3male, age 31 (3) years, body-mass-index 23.6 (0.9) kg/m<sup>2</sup>, neck circumference 37.0 (2.7) cm, FEV<sub>1</sub> 111.8 (5.1)% predicted, FVC 115.5 (6.3)% predicted) were studied. Inspiratory and expiratory muscle strength were normal (PImax 130.7 (29.8) cm H<sub>2</sub>O, PEmax (153.3 (38.4) cm H<sub>2</sub>O). No subject had significant sleep abnormalities at sea level (Total Sleep Time 344.4 (30.5) mins, Sleep Efficiency 86.6 (6.4)%, Respiratory Disturbance Index 0.8 (0.4)/hour, mean SpO<sub>2</sub> 97.5 (1.3%). The oxygen desaturation index increased with the development of periodic breathing at altitude (4% ODI 22.0 (7.2)/hour at 3,380m, 61.4 (26.9)/hour at 4,370m). Average nocturnal SpO2 (84.8 (0.5%)) at 3,380m; 81.0 (4.1%) at 4,370m) and nadir oxygenation (68.1 (8.6%) at 3,380m; 67.4 (7.6%) at 4,370m) dropped with altitude. The average EMGdi was 5.2 (19.1%) max at sea level and increased to 14.1 (3.4%) at altitude when falling asleep at 4,370m, and correlated well with the 4%ODI (r = 0.968, p = 0.032). EMGdi during the last inspiratory effort prior to central apnoea was 5.1 (1.5%) max, while the first inspiratory effort following central apnoea was 10.5 (3.2%) max at 4,370m. <h3>Conclusion</h3> The severity of periodic breathing when asleep deteriorates with an increase in altitude, induced by an elevated neural respiratory drive as a response to hypobaric environmental conditions.
114. Replication-Defective HSV Vector Development for Targeted Gene Delivery
Authors: Bonnie Reinhart, Daniela Leronni, Justus B. Cohen, Joseph C. Glorioso
Journal: Molecular Therapy (2016)

Gene therapy treatment strategies for Huntington's disease (HD) depend on a vector that (i) allows targeted delivery of large therapeutic transgenes to specific cell populations and (ii) is replication-defective and non-cytotoxic. Thus, our goal is to develop a replication-defective HSV-based gene therapy vector to deliver therapeutic transgenes to the cells most affected by expression of the mutant Huntington gene (Htt). Strategies for full retargeting of HSV require virus detargeting from its cognate receptors (HVEM and nectin1), recognized by the virus attachment/entry component glycoprotein D (gD), and introduction of a new ligand into gD that allows entry through recognition of the corresponding cellular receptors. To target an HSV vector for entry exclusively into cells expressing the receptor GFRα1 we employed the ligand GDNF. We replaced the signal peptide and HVEM binding domain of gD with pre-pro-(pp)GDNF to create a GFRα1 targeting protein, gD(Y38)_GDNF, that can still bind nectin1. Virus expressing gD(Y38)_GDNF was propagated on cells expressing nectin1 and purified virus was shown to enter nectin1-deficient J1.1-2 and B78H1 cells in a GFRα1-dependent manner. U2OS cells engineered to express GFRα1 demonstrated the most robust virus entry and spread, allowing us to create and propagate a fully retargeted virus that can no longer bind nectin1, gD(Δ38)_GDNF. Once the functionality of gD(Δ38)_GDNF was confirmed, we transferred this mutation to a replication-defective backbone lacking essential immediate early gene expression. Complementing cells were screened and those cells that best supported growth of the replication-defective backbone were selected. Virus stocks were propagated and tested for receptor specificity in vitro and experiments are currently underway to assess GFRα1-specific entry in vivo. We anticipate that the use of neuronal-specific targeting ligands, such as GFRα1, in replication-defective backbones will promote homing of non-toxic HSV gene therapy vectors to cells affected in HD.
Choosing the right cell line for renal cell cancer research
Authors: Klaudia K. Brodaczewska, Cezary Szczylik, Michal Fiedorowicz, Camillo Porta, Anna M. Czarnecka
Journal: Molecular Cancer (2016)

Cell lines are still a tool of choice for many fields of biomedical research, including oncology. Although cancer is a very complex disease, many discoveries have been made using monocultures of established cell lines. Therefore, the proper use of in vitro models is crucial to enhance our understanding of cancer. Therapeutics against renal cell cancer (RCC) are also screened with the use of cell lines. Multiple RCC in vitro cultures are available, allowing in vivo heterogeneity in the laboratory, but at the same time, these can be a source of errors. In this review, we tried to sum up the data on the RCC cell lines used currently. An increasing amount of data on RCC shed new light on the molecular background of the disease; however, it revealed how much still needs to be done. As new types of RCC are being distinguished, novel cell lines and the re-exploration of old ones seems to be indispensable to create effective in vitro tools for drug screening and more.
PTH-031 <i>Helicobacter pylori</i>resistance: culture as opposed to serology
Authors: A Shenoy, H Sharma, S Fong, M Al-Zaza, B Srivastava
Journal: Gut (2010)

<h3>Introduction</h3> <i>Helicobacter pylori</i> infection is a well recognised in causing a number of gastrointestinal pathologies. At endoscopy, the diagnosis of <i>H pylori</i> is usually done through urease based tests or histopathology on a gastric biopsy. There has been increasing resistance to the first line of antibiotics used1 reported and that failure of first line treatment increases the antibiotic resistance in <i>H pylori</i>.2 The Maastricht III consensus report recommends that culture and sensitivity testing should be routinely performed before clarithromycin-based treatment, if primary resistance to clarithromycin is &gt;15%–20% in the respective area or after two treatment failures with different antibiotics. Our practice is to carry out routine <i>H pylori</i> culture and sensitivity at endoscopy for those with an appropriate indication as a first line test. In this study we aim to look for the pattern of resistance to antibiotics in our cohort of patients. <h3>Methods</h3> We retrospectively identified positive <i>H pylori</i> culture results from Jan 2004 to Dec 2008 from microbiology database and reviewed the endoscopy report of all these patients. <h3>Results</h3> 356 <i>H pylori</i> positive cultures were identified, of these 83 were females and 173 males. The mean age of patients was 67.3 (range 23–97). 169 (47.5%) isolates were resistant to at least one antibiotic of which 141 (39.6%) were resistant to one and 28 (7.8%) were resistant to two or more antibiotics. 137 (38.4%) were resistant to metronidazole, 38 (10.6%) to clarithromycin, 9 (2.5%) to amoxicillin, 4(1%) to tetracycline and 2 (0.5%) to furazolidone. Eradication was confirmed through stool antigen/urea breath test in 38 (10.5%) patients, however 9 (2.5%) of the patients did not eradicate the bacteria despite appropriately selected <i>H pylori</i> eradication therapy. In 309 patients there was no documentation of the eradication, we presume lack of follow-up or patient compliance with the test. <h3>Conclusion</h3> Our study shows a high incidence of resistance to the standard first line antibiotics used in eradication of <i>H pylori</i>. This includes a significant primary resistance. This has implications in clinical and cost effective <i>H pylori</i> eradication. Our study was limited in that we could not ascertain if the patients had previously failed eradication in the community or if they had prior use of these antibiotics for other reasons. We aim to study antibiotic resistance prospectively in our population to elucidate possible causes for the same.