tbuckley/cabot-search huggingface dataset:
Phase I Study of Ruxolitinib for Patients (Pts) with Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) Who Failed at Least One Line of Therapy
Authors: Yasmin Abaza, Elias J. Jabbour, Srdan Verstovsek, Zeev Estrov, Farhad Ravandi, Gautam Borthakur, Tapan M. Kadia, Naval Daver, Courtney D DiNardo, Carlos E. Bueso-Ramos, Juliana E. Hidalgo, Heather Schneider, Guillermo Montalban Bravo, Ana Alfonso, Yue Wei, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2016)
Gemcitabine versus cisplatin concurrent with radiation therapy in locally advanced head and neck squamous cell carcinoma.
Authors: Magda Mostafa, Hesham Atif, Mahmoud Fawzy, Amr Yehia Sakr, Ahmed Alashwah
Journal: Journal of Clinical Oncology (2012)

5557 Background: In locally advanced head and neck squamous cell carcinoma (HNSCC) weekly cisplatin concurrent with radiation therapy is the standared treatment. However some patients cannot tolerate cisplatin. So we conduct a prospective randomized trial comparing cisplatin versus gemcitabine. Methods: This trial was done in Kasr El-Ainy Center of Clinical Oncology and Radiation therapy (NEMROCK), during the period from March 2010 till June 2011. Sixty patients with locally advanced HNSCC were randomized to receive Cisplatin (30 mg/m 2 ) weekly for 6 consecutive weeks (30 patients) or Gemcitabine (50 mg/m 2 ) weekly for 6 consecutive weeks (30 patients) both concomitant with radiation therapy reaching a dose of 70 Gy over 7 weeks. Primary end points include response rate, progression free survival and toxicity. Toxicities were graded according to NCI-CTCAE v3.0. Results: Thewhole study group included 48 (80%) males and 12 (20%) females. Mean age was 47.9 (± 6.5) years (range 26-61). Both arms were comparable regarding their age, gender, performance status and stage. There were 9 (30%) CR, 7 (23.3%) PR, 2 (6.7%) SD and 12 (40%) PD in cisplatin arm versus 12 (40%) CR, 4 (13.3%) PR, 1 (3.3%) SD and 11 (36.7%) PD in gemcitabine arm. Median progression free survival (PFS) in cisplatin arm was 9 months versus 11months in gemcitabine arm with a hazard ratio of 0.08 (95% CI 0.005 – 1.47). We did not reach median overall survival. Radiotherapy induced skin toxicity (slight or patchy atrophy), nausea, vomiting, mucositis, salivary gland affection and weight loss were equally distributed in both arms. Dysphagia and fatigue were markedly higher in gemcitabine arm. While infection and neutropenia were slightly higher in cisplatin arm. Conclusions: Weekly gemcitabine 50mg/m 2 concomitant with radiotherapy was found to be of equal efficacy and toxicity comparable with weekly cisplatin in the treatment of locally advanced HNSCC.
High Prevalence of Ibuprofen Drug-Induced Liver Injury in Spanish and Latin-American Registries
Authors: Miguel E. Zoubek, Andres González-Jimenez, Inmaculada Medina-Cáliz, Mercedes Robles-Díaz, Nelia Hernandez, Manuel Romero-Gómez, Fernando Bessone, Hacibe Hallal, Francisco J. Cubero, M. Isabel Lucena, Camilla Stephens, Raúl J. Andrade
Journal: Clinical Gastroenterology and Hepatology (2017)
GENGHIS KHAN ICE MARATHON: PREPARATION, STRATEGY AND THE EFFECT OF EXERCISE IN AN EXTREME COLD ENVIRONMENT IN A GROUP OF EXPERIENCED ULTRARUNNERS
Authors: Stephen Boyce, Andrew Murray, David Scott
Journal: British Journal of Sports Medicine (2017)

Background The Genghis Khan Ice Marathon took place in January 2016 in the mountains of the Terelj National Park, Mongolia in a temperature of minus 35 0 C. Objective To assess the experience, preparation, race strategy and effect of exercise in a group of ultrarunners undertaking a marathon in extreme cold. Design Prospective observational study. Setting Extreme environment. Participants Multinational group of experienced ultrarunners (n=9, male 5, female 4, age range 25–53 years). Interventions Pre and post race questionnaires. Post-race email surveillance . Main Outcome Measurements Experience, preparation, clothing, equipment, nutritional strategies for race. Adverse effects encountered when competing in the marathon. Perceived effort of race on the Borg Scale. Two weeks post race illness or injury surveillance. Results All nine ultrarunners completed the questionnaires and follow up. Concerns about safety in a remote environment were universal. Consensus was present regarding clothing, equipment, hydration and nutrition. The race was completed in 3:05–5:50. No significant difficulties were encountered. The cold air caused freezing around the nostrils and irritated the airways. No-one experienced cold induced bronchospasm. Clothing froze due to sweat and expired air. There were no cases of hypothermia. There were two cases of frostbite; earlobe (moderate) and nose (mild). Borg scale of perceived exertion values ranged from 13–17 (mean 15). Two week follow up; two cases of viral URTI's reported. No athlete reported DOMS in the post race period. Conclusions All athletes were experienced in ultrarunning. They shared concerns regarding competing in a remote, extreme cold environment. All were adequately prepared pre race in terms of clothing, equipment and race nutrition strategy. This level of experience contributed to the lack of complications during the race and in the post race period. No athletes experienced DOMS presumably related to lack of peripheral muscular perfusion during exercise in extreme cold.
高性能磁気温熱療法による磁鉄鉱銀ハイブリッドナノ粒子の形状制御製造【Powered by NICT】
Authors: Ding Qi, Liu Dongfang, Guo Dawei, Yang Fang, Pang Xingyun, Che Renchao, Zhou Naizhen, Xie Jun, Sun Jianfei, Huang Zhihai, Gu Ning
Journal: Biomaterials (2017)
Secondary malignancies developing during metastatic breast cancer treatment
Authors: N. M. Nikolic, Z. Tomasevic, S. Jelic
Journal: Journal of Clinical Oncology (2009)

e12020 Background: Secondary malignancies (SM) developing during metastatic breast cancer (MBC) are obviously more complicated for diagnosis, potential surgery and for further MBC treatment. However, the frequency of SM during MBC is not well explored, in contrast to SM after nonmetastatic BC. The aim of this paper is to determine frequency of SM in MBC patients and to determine the percentage of surgically treated SM. Methods: Hospital charts of BC patients were retrospectively analyzed at the Institute for Oncology and Radiology of Serbia. Patients who developed SM at any time point after BC were included in this analysis. Patients with contra-lateral BC and acute leukemia were excluded. Patients with SM during MBC were separately analyzed. Results: A cohort of 50 BC patients with SM was identified. Median age was 50 (range 32–78 years) median time to SM was 65.3 months (range 1–276). Forty-six patients had histological confirmation of SM. In 30 patients SM developed during treatment for MBC. Four SM were not confirmed by biopsy due to SM site or high burden of MBC. Median age was 53.4 years (range 34–74), median time to SM development was 78.9 months, and median time to BC metastases was 60.1 months. The most frequent SM in MBC patient were lung (5), endometrial (4, all treated with tamoxifen), ovarian (3), thyroid (3), cervical (3), and colon carcinoma (2). Only 14 patients with SM (14/30: 46%) could be treated with radical surgery and SM did not influenced further MBC treatment. Conclusions: According to our experience, SM develops more frequently in MBC than in non MBC patients, representing 60% (30/50 patients) of all SM in BC patients; 46.6% (14/30) of SM diagnosed during MBC could be surgically resected, and does not influence further MBC treatment. No significant financial relationships to disclose.
AB0626 Epitope profiling of ANTI-RO52 antibodies in patients with systemic sclerosis, systemic sclerosis-associated primary biliary cirrhosis, and primary biliary cirrhosis alone
Authors: C Liaskos, A Gkoutzourelas, T Simopoulou, E Marou, T Scheper, W Meyer, L Sakkas, DP Bogdanos
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Anti-Ro52 antibodies are detected in patients with Sjogren9s syndrome (SjS), systemic sclerosis (SSc) and other autoimmune rheumatic diseases. Epitope mapping studies of anti-Ro52 in autoimmune rheumatic diseases have failed to find any difference on epitope recognition suggesting a common stimulus for the loss of tolerance to Ro52. Such epitope differences, however, were noted between SjS and non-rheumatic diseases and in particular, SjS-associated primary biliary cirrhosis (SjS-PBC) or PBC alone (1). <h3>Objectives</h3> To assess whether or not the Ro52 epitope profile in anti-Ro52+ SSc patients differs from that of SSc-associated PBC (SSc-PBC) or PBC. <h3>Methods</h3> Serum samples were obtained from 63 anti-Ro52-positive (by ELISA) patients (33 SSc, 10 SSc-PBC, 20 PBC alone). Antibody reactivity to full length recombinant Ro52 and 5 baculovirus expressed Ro52 fragments spanning the whole sequence [Ro52–1 (aa 1–129), Ro52–2 (aa 125–268), Ro52–3 (aa 269–475), Ro52–4 (aa 57–180, partly overlapping with Ro52–1 and Ro52–2), and Ro52–5 (aa 181–320, partly overlapping with Ro52–2 and Ro52–3)] were tested by a line immunoassay. <h3>Results</h3> Reactivity was present to: full length Ro52 in all anti-Ro52 positive SSc, PBC-SSc, or PBC patients by line immunoassay; Ro52–1 in 6/33 (18.2%) SSc, 3/10 (30%) SSc-PBC, and 3/20 (15%) PBC; Ro52–2 in 33/33 (100%) SSc, 10/10 (100%) SSc-PBC and 20/20 (100%) PBC; Ro52–3 in 0/33 (0%) SSc, 0/10 (0%) SSc-PBC and 0/20 (0%) PBC; Ro52–4 in 4/33 (12.1%) SSc, 2/10 (20%) SSc-PBC, and 4/20 (20%) PBC and Ro52–5 in 11/33 (33.3%) SSc 4/10 (40%) SSc-PBC, and 9/20 (45%) PBC respectively (p&gt;0.05 for all epitopes amongst the 3 cohorts). No statistically significant correlation was found. <h3>Conclusions</h3> The major epitope of anti-Ro52 does not differ among SSc, PBC-SSc and PBC and is localized on aa125–268, the major epitopic region of anti-Ro52 antibodies in SjS and other rheumatic diseases. Our epitope mapping data suggest that the mechanisms responsible for the loss of tolerance to Ro52 is common amongst diseases. <h3>References</h3> Mytilinaiou, Maria G.; Meyer Wolfgang; Komorowski, Lars; Probst, Christian; Davies, Edward T.; Vergani, Diego; Bogdanos, Dimitrios P. B-cell epitope mapping of anti-Ro52 responses in patients with primary biliary cirrhosis., Hepatology, Vol. 52 (4), 2010, 489. <h3>Disclosure of Interest</h3> C. Liaskos: None declared, A. Gkoutzourelas: None declared, T. Simopoulou: None declared, E. Marou: None declared, T. Scheper Employee of: Euroimmun AG, W. Meyer Employee of: Euroimmun AG, L. Sakkas: None declared, D. Bogdanos: None declared
腫瘍治療と組織再生のためのイガイに触発されたナノ構造を有する生体材料の3D印刷【Powered by NICT】
Authors: Ma Hongshi, Luo Jian, Sun Zhe, Xia Lunguo, Shi Mengchao, Liu Mingyao, Chang Jiang, Wu Chengtie
Journal: Biomaterials (2016)
Enhanced antitumor activity of erlotinib in combination with quinacrine in EGFR WT and L858R/T790M mutant NSCLC.
Authors: Josephine Kam Tai Dermawan, John Pink, Afshin Dowlati, Sarmishtha De, Goutham Narla, George R. Stark, Neelesh Sharma
Journal: Journal of Clinical Oncology (2014)

e22153 Background: Non-small cell lung cancer (NSCLC) cell lines with epidermal growth factor receptor (EGFR) mutations are very sensitive to EGFR inhibitors such as erlotinib (E). However, the efficacy of E is limited in NSCLC cells harboring wild-type (WT) EGFR or second-site mutation EGFR-L858R/T790M. Various mechanisms of resistance have been described including activation of alternate signaling pathways through activation of MET, PI3K and NF-κB. Quinacrine (Q) is member of a group of small molecules called curaxins, which are 9-aminoacridine derivative and known to suppresses NF-κB activity by causing chromatin trapping of the FACT (facilitates chromatin transcription) complex. We evaluated utility of NF-κB inhibition by Q in overcoming the resistance to E in NSCLC cell lines Methods: E resistant NSCLC cell lines, A549 (EGFR WT), H1975 (EGFR-L858R/T790M) and H1993 (Met amplification) were used for drug synergy experiments. MTT assay, flow cytometry, Annexin V/PI staining, western blot and NF-κB luciferase assay were used for analyzing cell proliferation, cell cycle and NF-κB activity. Microarray analysis was performed using the Affymetrix Human Gene 2.0 ST Array. Results: In A549, H1975 and H1993 NSCLC cells, the combination of E and Q is highly synergistic, as quantified by the Chou-Talalay combination indices. Combination treatment significantly inhibited colony formation, induced cell cycle arrest and apoptosis as well as reduced xenograft tumor growth. Upon Q treatment, the FACT subunit SSRP1 disappeared from the soluble protein fraction, and NF-κB dependent luciferase activity was decreased. Knockdown of SSRP1 decreased cell viability and sensitized the cells to E treatment. Whole genome expression analysis of A549 and H1975 cells treated with E only, Q only, or both showed that Q or combination treatment significantly affected genes involved in cell cycle progression or nucleotide metabolism, and many of these genes contain binding sites for transcription factors that regulate SSRP1-enriched genes. Conclusions: We conclude that the combination of Q and E helps overcome E resistance in NSCLC, potentially by targeting FACT and suppressing cell cycle progression.
Epidural Metastases From Follicular Thyroid Cancer Mimicking Meningiomas in 68Ga-DOTATATE PET
Authors: Marcus Unterrainer, Harun Ilhan, Andrei Todica, Peter Bartenstein, Nathalie Lisa Albert
Journal: Clinical Nuclear Medicine (2017)

We report a woman with multifocal lesions suggestive of meningiomas in MRI, which also presented with high Ga-DOTATATE uptake in PET, a finding characteristic for meningioma. A whole-body staging due to a pathological fracture revealed multiple neoplastic lesions throughout the body without detection of a primary site. Subsequent pathological workup of a lung lesion revealed multifocal metastases from follicular thyroid cancer despite thyroidectomy 10 years ago (without pathological finding), and posttreatment scans after radioiodine therapy confirmed the multiple brain lesions to be metastases as well. Our case shows that epidural metastases from endocrine origin might represent a clinical pitfall in Ga-DOTATATE PET.
卵割期:卵割期の遺伝子やMERVL/HERVLレトロトランスポゾンの活性化におけるマウスDUXおよびヒトDUX4の保存された役割
Authors: Hendrickson Peter G, Dorais Jessie A, Grow Edward J, Wike Candice L, Weaver Bradley D, Pflueger Christian, Nix David A, Cairns Bradley R, Emery Benjamin R, Wilcox Aaron L, Peterson C Matthew, Carrell Douglas T, Whiddon Jennifer L, Lim Jong‐Won, Tapscott Stephen J
Journal: Nature Genetics (2017)
Facts Concerning Duexis Prescribing Habits Related to Combination Therapies
Authors: Jeffrey Sherman
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Integrative analysis of gene expression profiling and high-resolution genomic copy number in gastrointestinal stromal tumor (GIST)
Authors: M. Nannini, A. Astolfi, M. A. Pantaleo, M. Di Battista, S. Formica, D. Santini, M. Saponara, A. Maleddu, C. Lolli, G. Martinelli, G. Biasco
Journal: Journal of Clinical Oncology (2009)

10559 Background: Besides mutually exclusive cKIT or PDGFRA mutations, sequential accumulation of other genetic events may be involved in GISTs development and progression, but very few data is still available. Methods: Fresh tissues specimens of GISTs from 10 patients (9 gastric and 1 intestinal) were collected and used for RNA and DNA extraction, labeled and hybridized to HG-U133Plus 2.0 and SNP array 6.0, respectively (Affymetrix). Six patients had exon 9 or exon 11 c-KIT mutation, two PDGFRA mutation, and other two wild-type disease. Gene expression data were quantified by the RMA algorithm, filtered and analysed with supervised techniques (SAM algorithm). Genomic copy number data were analysed with Partek Genomic Suite software against a reference set of 90 Ceu HapMap individuals using a segmentation algorithm with stringent p-value cutoff. Results: Almost all patients exhibited both macroscopic cytogenetic alterations and cryptic microdeletions or amplifications by SNP-array copy number data analysis. The most frequent chromosomal alterations were: 14q complete or partial deletion (7/10), chromosome 19 monosomy (3/10), 22q and 1p deletion (2/10), chromosome 5 trisomy (2/10). The minimal overlapping region ranged from 14q22.3 to 14q32.33, covering a region including 320 genes. The integration of copy number and gene expression data showed that at least 40% of the genes inside the 14q deleted region were significantly downregulated (FDR&lt;10%) in comparison to 14q-diploid patients. In this region several tumor suppressor genes involved in cell cycle checkpoint control (SNW1, CHES1, PPP2R5E), apoptosis induction (PPM1A, MOAP1, PPP1R13B), DNA damage response (MLH3, TDP1), WNT/Notch pathway inhibition (NUMB, DACT1, SEL1L) are located. Conclusions: A wide spectrum of genetic aberrations in GISTs may occur besides c-KIT and PDGFRA mutations. The most frequent is 14q deletion that leads to a significant downregulation of many putative tumor suppressor genes. Combining gene expression and high resolution genomic copy number analysis could identify new haploinsufficient tumor suppressor genes involved in GISTs pathogenesis and tumor progression. No significant financial relationships to disclose.
Abstract 064: The Lipoxigenase Inhibitor Nordihydroguaiaretic Acid Prevents the Development of Hypoxia-Induced Pulmonary Hypertension in Mice
Authors: Andrea Iorga, Gabriel Wong, Denise Mai, Jingyuan Li, Salil Sharma, Mansoureh Eghbali
Journal: Circulation Research (2013)

Pulmonary hypertension (PH) is a chronic lung disease characterized by progressively elevated pulmonary arterial pressures and severe pulmonary vascular remodeling resulting from interactions between oxidized lipoprotein deposition and increased endothelial proliferation. Previously we have shown increased plasma levels of biological oxidation products such as hydroxyoctadecadienoic acids (HODEs) and hydroxyeicosatetraenoic acids (HETEs) in the rat monocrotaline model of PH. Here we investigated the role of HETEs and HODEs in the development of PH and whether their inhibition with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) attenuates the progression of PH. Mice were placed in a hypoxic chamber with O2 concentrations of ≤10% for 21 days and either left untreated to develop PH (n=7) or treated with NDGA daily (10mg/kg/day, i.p., n=4) from day 1. Direct RV catheterization was terminally performed to record RV pressure (RVP). Pulmonary arteriolar thickening and oxidized lipid deposition were assessed by staining lung sections with Masson’s Trichrome or with α-smooth muscle actin and E-06 (marker for oxidized low-density lipoproteins). In vitro, human pulmonary artery smooth muscle cell (hPASMC) proliferation was assessed by MTT assays in the absence or presence of 12-HETE (100ng/ml), 9-HODE (1µg/ml) and 13-HODE (1µg/ml) alone or together with NDGA (10, 25 and 50µM). In-vitro, HETE/HODE treatment increased hPASMC proliferation ~ 2-fold when compared to untreated cells and NDGA significantly inhibited the proliferative effects of all three oxidized lipids. In-vivo, NDGA treatment prevented the development of PH. RVP was lower in the NDGA-treated group vs. the PH group (24.01±1.39mmHg vs. 36.91±5.74mmHg, p&lt;0.05) and was comparable to control normoxic mice (20.93±2.52mmHg). RV hypertrophy index was significantly elevated in the PH mice versus control mice (0.38±0.03 vs. 0.28±0.02 (p&lt;0.001), while NDGA treatment completely prevented the development of RV hypertrophy (0.28±0.04). Lung sections demonstrated arteriolar thickening and E-06 positive deposits in the PH group, which was prevented by NDGA therapy. We conclude that oxidized fatty acid deposition and accumulation might play a role in the development of PH.
交差界:潅流可能組織工学足場としての脱細胞化植物の利用【Powered by NICT】
Authors: R Gershlak Joshua, Hernandez Sarah, Fontana Gianluca, R Perreault Luke, J Hansen Katrina, A Larson Sara, Y K Binder Bernard, M Dolivo David, Yang Tianhong, Dominko Tanja, W Rolle Marsha, J Weathers Pamela, Medina-Bolivar Fabricio, L Cramer Carole, L Murphy William, R Gaudette Glenn
Journal: Biomaterials (2017)
Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension
Authors: Jerome Avouac, Irena Konstantinova, Christophe Guignabert, Sonia Pezet, Jeremy Sadoine, Thomas Guilbert, Anne Cauvet, Ly Tu, Jean-Michel Luccarini, Jean-Louis Junien, Pierre Broqua, Yannick Allanore
Journal: Annals of the Rheumatic Diseases (2017)

Objective To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). Methods IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH. Mice received two doses of IVA337 (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. Results IVA337 demonstrated at a dose of 100 mg/kg a marked protection from the development of lung fibrosis in both mouse models compared with mice receiving 30 mg/kg of IVA337 or vehicle. Histological score was markedly reduced by 61% in the bleomycin model and by 50% in Fra-2 transgenic mice, and total lung hydroxyproline concentrations decreased by 28% and 48%, respectively, as compared with vehicle-treated mice. IVA337 at 100 mg/kg also significantly decreased levels of fibrogenic markers in lesional lungs of both mouse models. In addition, IVA337 substantially alleviated PH in Fra-2 transgenic mice by improving haemodynamic measurements and vascular remodelling. In primary human lung fibroblasts, IVA337 inhibited in a dose-dependent manner fibroblast to myofibroblasts transition induced by TGF-β and fibroblast proliferation mediated by PDGF. Conclusion We demonstrate that treatment with 100 mg/kg IVA337 prevents lung fibrosis in two complementary animal models and substantially attenuates PH in the Fra-2 mouse model. These findings confirm that the pan-PPAR agonist IVA337 is an appealing therapeutic candidate for these cardiopulmonary involvements.