tbuckley/cabot-search huggingface dataset:
Management of rash to erlotinib (E) and cetuximab (C): Results from the SERIES (Skin and Eye Reactions to Inhibitors of EGFR and kinaseS) clinic algorithm
Authors: N. V. Martin, V. Pacifico, S. E. Lai, A. Rademaker, S. Ortiz, M. Aneja, D. P. West, C. Bennett, M. Lacouture
Journal: Journal of Clinical Oncology (2007)

19556 Background: Rash develops in approximately 90% of patients (pts) treated with epidermal growth factor receptor inhibitors (EGFRIs) E and C, leading to significant physical/psychosocial discomfort and inconsistent therapy. This study characterizes outcomes of a rash management algorithm developed in the multidisciplinary dermatology-oncology SERIES clinic. Methods: Retrospective chart analysis was performed of pts with E and C rashes (n=45) who were treated with: oral tetracyclines (doxycycline or minocycline) bid and topical calcineurin inhibitors (pimecrolimus/ tacrolimus) or corticosteroids bid. After a baseline visit, pts were assessed at 2–4 week intervals and CTC graded (G). Management data, skin biopsies and photographs were evaluated. Response was defined as: Complete Response (CR) = severity decrease (decr) by 2G, Partial Response (PR) = 1G decr, Stable Disease (SD) = no G change, and Progressive Disease (PD) = increase by = 1G. Best response (BR) was defined as the patient’s best rash outcome at any point in time. Results: 43 out of 45 pts had evaluable data. Of 27 women and 16 men, mean age = 60 yrs (range 34–88), 60% received E and 40% C. For BR, 51% of patients had a CR, 42% had PR, 7% had SD, and 0% had PD. Age was related to BR (p=0.036), with median ages (in years) of 66, 57.5 and 48 for 22, 18 and 3 pts with CR, PR and SD respectively. BR was related to grade (p=0.045), with CR in 69% of G1 pts, 35% in G2 pts, and 54% in G3 pts. BR was not related to E or C (p=0.40). Dose modification was required in 8% (E) and 22% (C) and dose discontinuation in 0% (E) and 17% (C) pts. Conclusions: SERIES algorithm rash management demonstrates that combined oral tetracyclines, topical calcineurin inhibitors and corticosteroids result in improvement in a majority of subjects. The greater rate of dose modification/discontinuation with C supports the need for proactive/early intervention. Trials are underway to evaluate prophylactic therapies against rash to EGFRIs. No significant financial relationships to disclose.
Association between circulating irisin and insulin resistance in non-diabetic adults: A meta-analysis
Authors: Shanhu Qiu, Xue Cai, Han Yin, Martina Zügel, Zilin Sun, Jürgen Michael Steinacker, Uwe Schumann
Journal: Metabolism (2016)

Exogenous administration of recombinant irisin improves glucose metabolism. However, the association of endogenous circulating (plasma/serum) irisin with insulin resistance remains poorly delineated. This study was aimed to examine this association by meta-analyzing the current evidence without study design restriction in non-diabetic adults.Peer-reviewed studies written in English from 3 databases were searched to December 2015. Studies that reported the association between circulating irisin and insulin resistance (or its reverse, insulin sensitivity) in non-diabetic non-pregnant adults (mean ages ≥18years) were included. The pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity.Of the 195 identified publications, 17 studies from 15 articles enrolling 1912 participants reported the association between circulating irisin and insulin resistance. The pooled effect size was 0.15 (95% CI: 0.07 to 0.22) with a substantial heterogeneity (I(2)=55.5%). This association seemed to be modified by glycemic status (fasting blood glucose ≥6.1mmol/L versus <6.1mmol/L) and racial-ethnic difference (Asians versus Europeans versus Americans), but not by sex difference, sampling time-point, blood sample type, ELISA kits used, baseline age, or body mass index. Circulating irisin was inversely associated with insulin sensitivity (6 studies; r=-0.17, 95% CI: -0.25 to -0.09).Circulating irisin is directly and positively associated with insulin resistance in non-diabetic adults. However, this association is rather small and requires further clarification, in particular by well-designed large epidemiological studies with overall, race-, and sex-specific analyses.
Decline in lung function in patients with alpha-1-antitrypsin deficiency and airflow obstruction
Authors: Robert Stockley, Anilkumar Pillai, Alice Turner
Journal: European Respiratory Journal (2014)

Lung function decline in Alpha-1-antitrypsin Deficiency (AATD) is conventionally assessed as the annual change in FEV1 and in general an accelerated though variable decline is observed. However decline is usually quantified as mls/year and is partly influenced by aging. The purpose of this study was to determine rate of decline in FEV1 in AATD patients (ex and never smokers) with established airflow obstruction accounting for age.  Data was extracted from the UK registry for AATD patients with the ZZ or Znull genotype who had never received augmentation therapy and for whom at least 4 consecutive annual data points were available to determine decline (by linear regression). Data was expressed as decline in % predicted value and patients grouped into no decline ( -0.1and  -0.5 and -1.0%) decline.  Data was available from 406 patients (87 never smokers). 21.2% showed no excessive decline in FEV1 whereas 10.1%; 15.3% and 50.7% showed mild moderate and severe decline respectively. The average decline for these 3 groups was -0.37% predicted (SE 0.16);- 0.87(0.11) and -2.44% (1.04) respectively, equivalent to -19.66 mls/year (1.60); -39.43(8.39) and -84.17(31.15). These data were similar for ex and never smokers and suggest that slow or no excessive decline in spirometry is a feature of half the non smoking patients with AATD.  Many patients with AATD who have never smoked or have ceased smoking have little or no excessive decline in FEV1. Baseline FEV1 alone is not therefore an indication for augmentation therapy and where possible a period of observation should be undertaken to monitor decline before therapy is introduced.
C-met as a therapeutic target for metastatic potential of gastric cancer.
Authors: H. Cho, X. Zhang, M. Jung, W. Kwon, J. Jung, H. Jeung, J. K. Roh, H. C. Chung, S. Y. Rha
Journal: Journal of Clinical Oncology (2010)

e14568 Background: Autophosphorylation of c-met, a transmembrane tyrosine kinase, activates several signaling transduction cascades leading to cancer metastasis-cell proliferation, motility, invasion and angiogenesis. To elucidate the role of c-met activation in gastric cancer invasion and liver metastasis, we analyzed the functional expression and activation of c-met in gastric cancer cell lines and tumor tissues. Methods: Expression of c-met and activated c-met (p-met) was detected in 6 gastric cancer cell lines and 21 gastric cancer patients with liver metastasis. The effects of c-met inhibition were studied on cancer cell proliferation, migration and invasion, using a small molecule tyrosine kinase inhibitor SU-11274. Results: c-met and p-met were detected in 66.7% and 50% of gastric cancer cell lines, respectively. In gastric cancer tissues, c-met was over-expressed both in primary gastric cancer and matched liver metastasis, while activated p-met expression was more prominent in liver metastasis (p < 0.001) by immunohistochemistry. SU-11274 inhibited cell proliferation in p-met positive gastric cancer cell lines with an IC50 between 1 and 2.5 uM. Furthermore, blocking of migration in p-met positive gastric cancer cell line (Hs-746T), but not in p-met negative cell line (AGS) (p < 0.001), was observed with SU-11274 treatment. We also found abrogation of c-met activation with SU-11274 can inhibit cell invasion in Hs-746T, but not in AGS (p < 0.01). Conclusions: c-met activation is strongly associated with gastric cancer invasion and liver metastasis. Targeted therapy against c-met activation might provide a major therapeutic advance in gastric cancer invasion and metastasis. No significant financial relationships to disclose.
Binding of Radioactivity After Transplacental Administration of Tritiated N-Nitrosodiethylamine to Syrian Golden Hamsters2
Authors: Hildegard M. Reznik-Schüller, Joseph E. Tomaszewski
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Binding of Radioactivity After Transplacental Administration of Tritiated N-Nitrosodiethylamine to Syrian Golden Hamsters Get access Hildegard M. Reznik-Schüller, Hildegard M. Reznik-Schüller 3Carcinogenesis Program, NCI Frederick Cancer Research Center, Frederick, Md. 21701. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph E. Tomaszewski Joseph E. Tomaszewski 3Carcinogenesis Program, NCI Frederick Cancer Research Center, Frederick, Md. 21701. 4Present address: Tracor Jitco, Inc., 1776 East Jefferson St., Rockville, Md. 20852. 5We thank Ms. Lee Ann Nutter for excellent technical assistance and Ms. Cheri Rhoderick for typing the manuscript. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 2, February 1980, Pages 373–375, https://doi.org/10.1093/jnci/64.2.373 Published: 01 February 1980 Article history Received: 23 April 1979 Accepted: 30 June 1979 Published: 01 February 1980
Abstract 10706: Directed Differentiation of Patient-specific Induced Pluripotent Stem Cells Identifies The Cardiac Transcriptional Repression During Myocardial Growth and Patterning in Hypoplastic Left Heart Syndrome
Authors: Junko Kobayashi, Masashi Yoshida, Suguru Tarui, Masataka Hirata, Yusuke Nagai, Shingo Kasahara, Keiji Naruse, Hiroshi Ito, Shunji Sano, Hidemasa Oh
Journal: Circulation (2013)

Background: The pathogenesis of hypoplastic left heart syndrome (HLHS) originate as a primary defect in the left ventricular outflow tract (LVOT) mainly at a level of aortic valve, that leads to secondary left ventricle hypoplasia. The genetic basis of patients with HLHS remains unknown and the lack of animal models to reconstitute the cardiac maldevelopment has hampered the study of this disease. The purpose of this study was to investigate the altered control of transcriptional regulatory programs which may affect the development of HLHS by using disease-specific induced pluripotent stem (iPS) cells. Methods and Results: Cardiac tissue specimens were obtained from patients with congenital heart diseases during operation, and cardiac progenitor cells (CPCs) were isolated and infected with retroviruses encoding human transcription factors, Oct4, Sox2, Klf4, and c-myc to generate patient-specific iPS cells. Comparative gene expression of HLHS- and biventricle (BV) heart-derived iPS cells was analyzed to di...
Results of total therapy 2 (TT 2), a phase III randomized trial, to determine the role of thalidomide (THAL) in the upfront management of multiple myeloma (MM)
Authors: B. Barlogie, G. Tricot, J. Shaughnessy, E. Rasmussen, E. Anaissie, M. Zangari, A. Fassas, R. Thertulien, F. van Rhee, J. Crowley
Journal: Journal of Clinical Oncology (2005)

LBA6502 Background: Given the marked activity of THAL in end-stage MM, TT2 was designed (1) to determine THAL’s activity in the context of intensive induction, tandem autotransplants, consolidation and maintenance therapies; and (2) to determine the prognostic implications of serial MRI and gene expression profiling (GEP). Methods: Consenting patients with newly diagnosed active MM, stratified by B2M (<4mg/L, ≥4mg/L) and plasma cell labeling index (PCLI) (<1%, ≥1%), were randomized to receive either THAL or no THAL (applied throughout until relapse). Eligible patients were less than 75yr of age and had SWOG PS <3. The primary endpoint was an increase in 5-yr EFS from 40% to 50% in the THAL arm. Planned sample size of 668 patients gives 80% power, using a 2-sided test with a 0.045 significance level. This study was a prospective, randomized, stratified phase III trial. Survival data comparing THAL vs no THAL will be compared using a stratified log-rank test. Independent DSMB committee has approved release of results in March 2005. Results: Of 668 eligible patients, 345 were randomized to no THAL and 322 to THAL. The current median follow-up is 33 mos (range 9–73). Following 4 cycles of intensive induction chemotherapy, 85% completed 1st and 67% 2nd autotransplant with MEL 200; 64% started consolidation. 602 patients had a baseline MRI exam with a median of 4 follow-up exams. 351 patients, consecutively enrolled since March 2000, also had baseline GEP. Patient characteristics: age ≥60yr, 39%; male, 59%; karyotype abnormalities, 33%; B2M ≥4mg/L, 31%; albumin <3.5gd/L, 15%; LDH ≥190U/L, 30%; IgA isotype, 24%; PCLI ≥1%,14%. Overall 1yr TRM was 1.4%; overall n-CR/CR was 67% with 47% achieving a CR. DVT >3° frequency was significantly higher with THAL vs no THAL (34% vs 16%, p<.0001), but was markedly reduced after introduction of LMWH (24% vs 15%, p=.06). Peripheral neuropathy also was significantly more common with THAL (sensory: 12% vs 4%, p=.001; motor: 21% vs 13%, p=.01). Updated survival by arm will be presented prior to the late breaking abstract deadline. In addition, GEP and MRI data will be presented in the context of survival. Conclusions: To be reached after data become available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Millennium Celgene, Millennium
From the clinician's point of view - What is the status quo of positron emission tomography in patients with brain tumors?
Authors: Norbert Galldiks, Karl-Josef Langen, Whitney B. Pope
Journal: Neuro-Oncology (2015)

The most common type of primary brain tumor is malignant glioma. Despite intensive therapeutic efforts, the majority of these neoplasms remain incurable. Imaging techniques are important for initial tumor detection and comprise indispensable tools for monitoring treatment. Structural imaging using contrast-enhanced MRI is the method of choice for brain tumor surveillance, but its capacity to differentiate tumor from nonspecific tissue changes can be limited, particularly with posttreatment gliomas. Metabolic imaging using positron-emission-tomography (PET) can provide relevant additional information, which may allow for better assessment of tumor burden in ambiguous cases. Specific PET tracers have addressed numerous molecular targets in the last decades, but only a few have achieved relevance in routine clinical practice. At present, PET studies using radiolabeled amino acids appear to improve clinical decision-making as these tracers can offer better delineation of tumor extent as well as improved targeting of biopsies, surgical interventions, and radiation therapy. Amino acid PET imaging also appears useful for distinguishing glioma recurrence or progression from postradiation treatment effects, particularly radiation necrosis and pseudoprogression, and provides information on histological grading and patient prognosis. In the last decade, the tracers O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) and 3,4-dihydroxy-6-[(18)F]-fluoro-L-phenylalanine (FDOPA) have been increasingly used for these indications. This review article focuses on these tracers and summarizes their recent applications for patients with brain tumors. Current uses of tracers other than FET and FDOPA are also discussed, and the most frequent practical questions regarding PET brain tumor imaging are reviewed.
Abstract 18322: A Ligand of Scavenger Receptor Class A Causes Vascular Relaxation Through an Activation of Endothelial Nitric Oxide Synthase in Rat Aorta
Authors: Takafumi Iesaki, Tomoaki Takeuchi, Megumi Okano, Ryota Hashimoto, Ryo Kakigi, Yuko Ishii, Takao Okada
Journal: Circulation (2012)

The class A scavenger receptor (SR-A) are implicated in the development and progression of atherosclerosis. In addition to modified low-density lipoprotein, a diverse group of polyanionic compounds are listed as ligands for SR-A. Fucoidan is a natural sulfated polysaccharide obtained from brown marine algae and is a well-defined nonlipoprotein ligand for SR-A. It is attracting attentions due to its wide variety of biological effects including anticoagulant and antithrombotic activities, however, its effects on vascular tone are not fully elucidated. In the present study, we examined the effects of acute administration of fucoidan (10 μg/ml to 1 mg/ml) to isolated rat thoracic aorta (RA) and explored the mechanism(s) of action. Fucoidan caused RA relaxation in a dose-dependent manner, and this relaxation was significantly attenuated by the removal of endothelium; 88.4±5.8 % (mean±SEM, n=17) in the presence and 24.6±7.5 % (n=10) in the absence of endothelium at 1 mg/ml fucoidan. Fucoidan-induced relaxation was also significantly inhibited by both a nitric oxide (NO) synthase (NOS) inhibitor 300 μM L-NAME (N(G)-nitro-L-arginine methyl ester, 37.8±13.1 %, n=6) and a selective inhibitor of soluble guanylyl cyclase 10 μM ODQ (1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one, 33.0±5.6 %, n=8), but not affected by a cyclooxygenase inhibitor 10 μM indomethacin or various kinds of K + channel blockers including 10 mM tetraethylammonium, 10 μM glibenclamide and a combination of 0.1 μM apamin plus 0.1 μM charybdotoxin which is thought to block endothelium-derived hyperpolarizing factor-mediated reaction. NO production measured by Griess method in cultured human aortic endothelial cells (HAEC) was dose-dependently increased by fucoidan. Western blotting analyses revealed that fucoidan phosphorylated endothelial NOS (eNOS) at Ser-1177 and also phosphorylated protein kinase Akt at Ser-473 in a dose-dependent manner in HAEC, indicating an activation of eNOS. These results indicate that fucoidan, a ligand of SR-A, causes vascular relaxation through an endothelium-dependent and, at least in part, NO/cGMP-mediated mechanism through an activation of eNOS.
Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis
Authors: Dominique Baeten, Joachim Sieper, Jürgen Braun, Xenofon Baraliakos, Maxime Dougados, Paul Emery, Atul Deodhar, Brian Porter, Ruvie Martin, Mats Andersson, Shephard Mpofu, Hanno B. Richards
Journal: New England Journal of Medicine (2015)

Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis.
Concerns about study on maternal H1N1 influenza vaccination and offspring mortality
Authors: Junya Makiyama, Michihiro Kono, Sayaka Shimizu
Journal: BMJ (2016)

We have three concerns about Ludvigsson and colleagues’ article on the association between maternal influenza A(H1N1)pdm09 vaccination during pregnancy and mortality in the offspring.1 

Firstly, the authors defined exposure as vaccination during pregnancy. Accordingly, women who were vaccinated just before pregnancy were …
Maintenance of long term benefits from an outpatient pulmonary rehabilitation programme in COPD
Authors: Francesco Costa, Laura Malagrinò, Sandra Antonelli, Claudia De Simone, Giovanna Decusatis, Dario Nieri, Sabrina Santerini, Barbara Vagaggini, Pierluigi Paggiaro
Journal: European Respiratory Journal (2011)

We evaluated the long term manteinance of benefits of a Pulmonary Rehabilitation Programme (PRP) in COPD patients and to establish which patients require frequent repetitions of PRP.  Fifty-one COPD patients (FEV 1 : 57±17%) underwent 10 weeks outpatient PRP comprehensive of supervised exercise training on cycloergometer and upper limb training. Pre-PRP (T0), post-PRP (T1), 6 months (T2) and 9 months (T3) after the end of PRP we measured: exercise tolerance by 6 minute walking test (6MWT), dyspnoea by MRC, quality of life by St George Respiratory Questionnaire (SGRQ).  All outcomes improved at T1. 6MWT and MRC progressively worsened at T2 and T3 respectively, whereas SGRQ remanained stable up to 9 months from PRP.  The correlation between the baseline indices and the rate of deterioration at T3 demonstrated that a worst MRC at T0 is a good predictor of an early increase of dyspnoea perception after PRP cessation (r=0.30, p=0.03).  When patients were subdivided in responders (N=17) and in non Responders (N=34) to PRP according to an increase in 6MWT of 54 mt, responders showed a greater decline of benefits in exercise tolerance at T3 in comparison with non responders (T1-T3 6MWT: 49.4±66.9 vs 12.3±58.4 mt, p  In conclusion, COPD patients with worst physical performance at baseline have better results from PRP, but they loose benefits more quickly than other ones. As previously reported, benefits in quality of life and dyspnoea persist longer than exercise tolerance.
Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid
Authors: Noortje Ijssennagger, Aafke W.F. Janssen, Alexandra Milona, José M. Ramos Pittol, Danielle A.A. Hollman, Michal Mokry, Bark Betzel, Frits J. Berends, Ignace M. Janssen, Saskia W.C. van Mil, Sander Kersten
Journal: Journal of Hepatology (2016)
Abstract 174: Late I <sub>Na</sub> Inhibition with Ranolazine Blunts Doxorubicin-Induced Cardiac Dysfunction and Remodeling in Mice
Authors: Carlo G Tocchetti, Carmela Coppola, Domenica Rea, Cristina Quintavalle, Antonio Barbieri, Giovanna Piscopo, Giuseppe Palma, Marianna Gala, Antonio Luciano, Aldo Giudice, Rosario V Iaffaioli, Stefania Scala, Gerolama Condorelli, Claudio Arra, Nicola Maurea
Journal: Circulation Research (2012)

Background. Doxorubicin (DOX) produces a well-known cardiomyopathy through multiple mechanisms, which include, among many, Ca2+ overload due to reduced SERCA2a activity and inappropriate opening of the RyR2, and impaired myocardial energetics. DOX generate Reactive Oxygen and Nitrogen Species (ROS and RNS), posing the heart at increased demand for oxygen, setting the stage for metabolic ischemia that also activates late I Na , target of ranolazine (RAN). Here, we aim at assessing whether RAN, diminishing intracellular Ca2+ through inhibition of late I Na , and enhancing myocardial glucose utilization (and/or reverting impairment of glucose utilization caused by chemotherapy) blunts DOX cardiotoxicity. Methods. We measured left ventricular (LV) end-diastolic and end-systolic diameters (LVEDD and LVESD), and evaluated LV function with fractional shortening (FS) by echocardiography in C57BL6 mice, 2-4 mo old, pretreated with RAN (370mg/kg/day, a dose comparable to the one used in humans) per os for 3 days. RAN was then administered for additional 7 days, alone and together with DOX (2.17mg/kg/day ip), according to our well established protocol. Hearts were then excised, mRNA expression was analyzed by RT PCR. Results . After 7 days with DOX, hearts were dilated with depressed function: LVEDD and LVESD increased from 2.8±.03 and 1.1±.03mm to 3.04±.06 and to 1.55±.08mm, respectively (both p&lt;.005 vs sham). FS decreased to 50±2%, p=.002 vs 60±1% (sham). RAN alone did not change LV dimensions nor function. Interestingly, mice treated with RAN and DOX had smaller LVEDD and LVESD (2.85±.05 and 1.22±.03mm, respectively, both p&lt;.05 vs DOX alone), with a better cardiac function: FS was 57±1%, p=.01 vs DOX alone. DOX-cardiotoxicity was accompanied by significant elevation in CTGF and MMP2 genes, showing alterations in extracellular matrix remodeling. Cardiac function improvement with RAN was paralleled by significantly lower levels of these same genes compared to DOX alone. Conclusions . RAN blunts DOX cardiotoxic effects in mice, improving remodeling and function. We plan to test RAN as a cardioprotective agent with other antineoplastic cardiotoxic drugs in mice, and to better characterize the cardioprotective mechanisms of RAN in all these settings.
Radiotherapy is unnecessary in elderly patients with localized agressive non Hodgkin's lymphoma: results of the LNH 93-4 study.
Authors: Christophe Bonnet, Georges Fillet, N. Mounier, C. Thieblemont, C. Fermé, B. Quesnel, C. Martin, M. Blanc, T. Conroy, AM Penny, T. Petrella, F. Reyes
Journal: Annals of Oncology (2002)