tbuckley/cabot-search huggingface dataset:
Comparability of microarray data generated in different laboratories
Authors: L. Reid, W. Jones, S. McPhail
Journal: Journal of Clinical Oncology (2005)

3120 Background: Biomarkers are rapidly entering the field of clinical oncology, as gene expression patterns are used to help classify diseases, predict prognosis and suggest treatment options. Much of the promise of this genomic research relies on the comparison of microarray data generated in multiple facilities. However, the comparability of gene expression results is affected by a variety of technical, biological and data analysis factors. In order to quantify and reduce technical variation, we established a year-long testing program to compare microarray data generated in seventeen different laboratories using the Affymetrix platform and identical RNA samples. Methods: During each round of testing, participating laboratories received six rat 230 2 Affymetrix GeneChips and three replicates of two different RNA sources. The labs prepared targets from the six RNA samples using their own protocols. After hybridization, the image files from each laboratory were collected for data analysis, which included a number of quality, sensitivity, reproducibility and comparability metrics. Results: All of the participating laboratories produced high quality results that repeatedly demonstrated good agreement between the facilities over time. In general, 78% of the differentially-expressed genes identified in one facility were also present on a similar list from another facility. Close examination of the gene lists revealed that most of the “unique” genes showed concordant expression patterns, suggesting that simple gene list comparisons underestimate comparability. Conclusions: Our results demonstrate that similar biological results can be identified using replicate microarray data sets. These results are encouraging as microarrays are incorporated into clinical trials and transition toward clinical use. They also help define the sensitivity, specificity, reproducibility and accuracy of this technology. Such critically important questions must be addressed in preparation for regulatory review. No significant financial relationships to disclose.
New Dietary Guidelines Place Added Sugars in the Crosshairs
Authors: Mike Mitka
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 15120: Chronic Renal Failure Represents an Independent Predictor for Worse Outcome After Transfemoral Aortic Valve Replacement
Authors: Suzanne Fateh-Moghadam, Patrik Htun, Martin Steeg, Karin Mueller, Sebastian Werner, Beqir Sutaj, Rezo Jorbenadze, Iris Mueller, Meinrad Gawaz, wolfgang Bocksch
Journal: Circulation (2013)

Background: Transfemoral Aortic Valve Implantation (TAVI) is an established treatment for high-risk surgical patients with symptomatic aortic valve stenosis (AS). Many of these pts present with chr...
Patients with advanced non-small cell lung cancer (NSCLC): Are research biopsies a barrier to participation in clinical trials?
Authors: Charles Henry Lim, Mike Sung, Nazanin Ziapour Nouriany, Magdalena Sawczak, Tuhina Paul, Nicole Perera-Low, Ronald Feld, Geoffrey Liu, Frances A. Shepherd, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2015)

6534 Background: The evolution of targeted therapy in NSCLC has led to growing complexity of clinical research and a heightened expectation of clinical benefit for participants. Clinical trials in NSCLC increasingly require mandatory tumour samples or research biopsies, both potential barriers for trial participation. We assessed the impact of performing research biopsies in advanced NSCLC on clinical trial enrollment. Methods: We conducted a retrospective chart review of patients with advanced NSCLC evaluated for systemic therapy clinical trials at the Princess Margaret Cancer Center from 2010 to 2014. Results: Of 26 clinical trials reviewed, 21 required tumour samples for enrolment. Eleven required confirmation of a pre-specified biomarker in order to receive investigational treatment. Trial participation was offered to 151 patients at 293 unique study encounters (some enrolled in multiple trials). Forty-three percent proceeded to receive study treatment. Those considering trials without mandatory biopsies or tissue requirement were more likely to proceed to study treatment than those considering trials with these requirements (75% vs. 40%, p = 0.009). For trials requiring mandatory tumour samples, 210 consents for participation were obtained, 170 research biopsies were ordered and 88% were performed. Participants proceeded to study treatment in 57% of encounters; 7% of biopsies yielded insufficient tissue and 34% were “biomarker-negative”. The most common barriers to trial enrollment included lack of the pre-specified biomarker (40%), other study exclusion criteria (17%), patient refusal of biopsy (11%), insufficient biopsy tissue (9%), and deteriorating clinical status/death (10%). Conclusions: With the evolution of personalized medicine, a growing number of NSCLC trials require tumour tissue for treatment eligibility. This has emerged as a significant barrier to clinical trial enrollment. Potential solutions include routine tissue banking at diagnosis, facilitating use of available diagnostic samples (e.g. fine needle aspirates) for trials, development of circulating DNA assays for trials, and more resources for timely tissue acquisition.
Histologic Aspects of Concomitant Resistance Induced by Nonimmunogenic Murine Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R P Meiss, R D Bonfil, R A Ruggiero, C D Pasqualini
Journal: JNCI Journal of the National Cancer Institute (1986)

Concomitant resistance to a second tumor implant was induced in both conventional and nude BALB/c mice by two non immunogenic syngeneic tumors of spontaneous origin, an epidermoid carcinoma and a lymphoid leukemia. In the secondary tumor, which was significantly inhibited by concomitant resistance, histologic examination revealed the presence of well-preserved tumor cells without any sign of necrosis and without any host cell infiltration, contrasting with classical immunologic rejection. Tumor cell proliferation as evaluated by the number of mitoses per high-power field was significantly inhibited in the secondary tumor as compared with the corresponding controls. No effect of concomitant resistance could be detected on primary tumor growth.
Severe Acquired Bleeding Tendency Secondary To An Anti-Thrombin Antibody In a Patient With Monoclonal Gammapathy Of Unknown Significance: Direct In Vivo evidence
Authors: Valerie Proulle, Celine Desconclois, Cecile Lavenu-Bombled, Cecile Goujard, Anish V Sharda, Ali G Turhan
Journal: Blood (2013)
Metabolic control of arthritis: Switch pathways to treat
Authors: George C. Tsokos
Journal: Science Translational Medicine (2016)

A shunting of glucose metabolism to the pentose phosphate pathway in rheumatoid arthritis T cells causes exhaustion of oxidants, enhanced cell proliferation, and differentiation toward the T helper 1 (T H 1) and T H 17 programs (Yang et al ., this issue).
Level of Knowledge, Concerns and Adherence to Asthma Management Guideline Recommendations Among Healthcare Providers in Midwestern USA
Authors: Jonathan M. Rodrigues, Carrie N. Caruthers, Josiah Moulton, Venkatkiran Kanchustambham, Roua Azmeh, Anthony Kruse, Roula Altisheh, Christopher Sutton, Mark S. Dykewicz, Raymond Slavin
Journal: Journal of Allergy and Clinical Immunology (2016)
Prolonged survival with personalized immunotherapy (AGS-003) in combination with sunitinib in unfavorable risk metastatic RCC (mRCC).
Authors: Asim Amin, Arkadiusz Dudek, Theodore Logan, Raymond S. Lance, Jeffrey M. Holzbeierlein, Viraj A. Master, Sumanta Kumar Pal, Jennifer J. Knox, Lawrence Ivan Karsh, Doug Plessinger, Charles A. Nicolette, Robert A. Figlin
Journal: Journal of Clinical Oncology (2013)

357 Background: During the past decade, VEGF targeted therapies have become standard treatment for advanced RCC. While targeted therapies have yielded improved efficacy, durable remissions are rare, particularly in unfavorable risk subjects. In a pivotal trial, treatment with sunitinib yielded a median OS of 5.3 months for poor risk and 20.7 months for intermediate risk subjects. Similarly, the validation dataset for the Heng risk model (ASCO 2011) revealed a median OS of 8 months for poor risk and 21 months for intermediate risk patients treated with VEGF targeted therapies. Durable responses have been elicited by immunotherapy in RCC. We report an update on patients with mRCC treated with combined VEGF TKI (sunitinib) plus autologous immunotherapy (AGS-003). Methods: In this phase II study, subjects with unfavorable prognosis mRCC (poor and intermediate risk) were treated with sunitinib plus autologous dendritic cell immunotherapy (AGS-003). Treatment consisted of standard 6-week cycles of sunitinib plus AGS-003 (once every 3 weeks x5 doses, then every 12 weeks until PD). Tumor response was assessed per RECIST and subjects were followed for PFS and OS. Immune monitoring samples were taken at screening, baseline and after the third and fifth doses of AGS-003 and analyzed by multiparametric flow cytometry. Results: 21 subjects were treated. As previously reported, the median overall PFS was 11.2 months and the final median OS was 30.2 months. When analyzed by baseline Heng risk status, the median PFS was 19.4 months for intermediate (n=11) and 5.8 months for subjects with poor risk features (n=10) at baseline. The median OS is 39.5+ months for intermediate and 9.1 months for subjects with poor risk. Conclusions: The results from this single-arm phase II study represent a near doubling of expected PFS and OS for unfavorable risk subjects treated with AGS-003 plus sunitinib. Updated survival and immunologic findings will be presented, as 8 of 21 subjects are still alive and continue to be followed. These results support the ongoing phase III ADAPT study, which is designed to validate these encouraging clinical and immunologic findings. Clinical trial information: NCT00678119.
Ginkgo Biloba (GB) extract as a neuroprotective agent in oxaliplatin (Ox)-induced neuropathy
Authors: J. Marshall, A. Zakari, J. J. Hwang, V. Papadopoulos, A. Rosenberg, C. Silver
Journal: Journal of Clinical Oncology (2004)

3670 Background:Neurotoxicity is dose-limiting in high proportion of patients (Pts) with metastatic colorectal cancer (CRC) treated with Ox. Two categories of neuropathy (NP) have been described: 1) acute dysesthesia/paresthesia (85–90%) and 2) cumulative sensory NP increasing in intensity with higher cumulative doses. NP has a significant negative impact on patients, limiting duration of Ox treatments. GB is used as neuroprotective agent in neurodegenerative diseases. Potential mechanisms of action include the prevention of uncoupling of oxidative phophorylation and protection of cell membrane through free radical scavenging. Pre-clinical data support anti-cancer benefit of GB through targeted inhibition of peripheral-type benzodiazepine receptors over-expressed on mitochondrial membranes in many tumors including colon cancer. Data suggests that GB synergizes with chemotherapy in addition to potential prevention of neurotoxicity. Methods:We conducted a retrospective analysis of 17 CRC pts treated with either FOLFOX (13) or CAPEOX (4) in either the adjuvant (2) or metastatic (15) setting. GB 120 mg orally bid was added to chemotherapy. No Ca or Mg was given. The Ox-specific neurotoxicity grading scale was used to monitor NP. Results:11/17 pts initiated GB at cycle 1or 2 of treatment, only reporting grade 1 acute NP limited to less than 6 days(d), and 9/11 lasting only 2–3 d. The other 6 pts initiated GB after cycle 2, and 5/6 pts reported decreased intensity and duration in NP from GB. No laryngospasm was observed in any patient. The data on the cumulative sensory NP will be mature and reported at the meeting. No GB related side effects have been observed. Conclusions: GB appears to decrease the intensity and duration of acute dysesthesias caused by Ox and may yield synergistic anti-tumor activity. A phase II trial is underway testing the impact of GB on Ox-induced neurotoxicity and potential additional clinical efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Roche; Sanofi-Synthelabo Institute Henri Beaufour-IPSEN; Sanofi-Synthelabo
PWE-308 Pelvic exenteration for primary advanced and locally recurrent rectal cancer: outcomes and experience at a single institution
Authors: D Patsouras, A Laliotis, E Warner, A Schizas, ML George
Journal: Gut (2015)

<h3>Introduction</h3> Pelvic exenteration is a potential curative treatment for primary advanced rectal cancer (PARC) and locally recurrent rectal cancer (LRRC). The aim of such extensive radical surgery is to achieve clear resection margins. <h3>Method</h3> A retrospective study was performed of pelvic exenteration procedures carried out between 2004 and 2014 in St Thomas’ Hospital for PARC and LRRC. Factors evaluated included age, sex, neo-adjuvant therapy, type of operation, intraoperative blood loss, resection margins, 30day morbidity and mortality and overall survival. <h3>Results</h3> Pelvic exenteration was performed in 71 patients. 51 patients were treated with neoadjuvant chemoradiation. Of the 71 patients, 52 had total, 6 had anterior and 13 had posterior pelvic exenteration; sacrectomy was performed in 4 patients. Thirty nine (39) patients (27males) with median age 61(29–80) years underwent pelvic exenteration for PARC and thirty two (32) patients (10 males) with median age 62(41–80) years had pelvic exenteration for LRRC. The median blood loss was 3700 ml (range 150015000) for PARC and 3750 ml (range 1500–15000) for LRRC. A complete resection (R0) was achieved in 67.6% of all patients; 74.4% for patients with PARC and 59.4% for patients with LRRC. Major complications (Clavien-Dindo, Grade III-IV) were 35.9% and 34.4% respectively. One patient died within 30 days. Overall survival was 32.5 months for PARC and 21.1 months for LRRC. <h3>Conclusion</h3> Pelvic exenteration is associated with considerable morbidity but low mortality and acceptable overall survival, in the absence of other effective treatment modalities. Careful preoperative assessment and a multidisciplinary approach make this extensive surgical technique safe and feasible in an experienced centre. <h3>Disclosure of interest</h3> None Declared.
Abstract 19570: A Multigenic Etiology 0f Hypoplastic Left Heart Syndrome: An Analysis Based on Three Novel Mutant Mouse Models of Hyoplastic Left Heart Syndrome
Authors: Xiaoqin Liu, Shazina Saeed, You Li, Richard Francis, Kimimasa Tobita, Andy J Kim, Wendy Shung, Linda Leatherbury, Cecilia W Lo
Journal: Circulation (2012)

Hypoplastic left heart syndrome (HLHS) is a congenital heart defect characterized by severe hypoplasia of the left ventricle (LV) with aortic and/or mitral valve stenosis. Despite advances in HLHS surgical management, the etiology for HLHS remains unknown. Accumulating evidence supports a genetic etiology for HLHS, but mutant mouse models of HLHS have not been described. We recovered three HLHS mutant mouse models in a large scale recessive mouse mutagenesis screen (Figure). In mutant line 635 named Ohia , 2 mutants with HLHS were recovered (Figure). Exome sequencing analysis identified three mutations in each of three genes: prolidase (Pepd), NAD synthetase (Nadsyn1) and protocadherin b9 (Pcdhb9). All three mutations were homozygous and shared in common in the two HLHS mutants, suggesting a multigenic etiology for HLHS in Ohia . All 3 genes show parallels with defects seen in HLHS patients. Pepd, which regulates proline recycling and collagen metabolism, may have relevance for the marked collagen reduction seen in the LV of HLHS patients. Nadsyn1, which synthesizes NAD, a coenzyme essential for metabolic redox reactions, is of potential importance, given recent study of HLHS patient heart tissue showed many transcript expression changes associated with oxidative phosphorylation. Pcdhb9, which likely mediates cell-cell adhesion, also may have relevance, given the expression of adherens junction related genes is reported to be markedly changed in HLHS heart tissue. Collectively, these findings suggest mutations affecting energy metabolism/oxidative stress, and cell-cell/cell-matrix interactions may play critical roles in HLHS. Consistent with this, preliminary results from the analysis of the other HLHS mutant mouse lines revealed mutations in other genes with overlapping function, including a collagen gene mutation. These observations suggest HLHS has a multigenic etiology, which may account for its apparent complex genetics. Support by U01- HL098180
Extracellular Vesicles from High-Grade Glioma Exchange Diverse Pro-oncogenic Signals That Maintain Intratumoral Heterogeneity
Authors: Franz Ricklefs, Marco Mineo, Arun K. Rooj, Ichiro Nakano, Al Charest, Ralph Weissleder, Xandra O. Breakefield, E. Antonio Chiocca, Jakub Godlewski, Agnieszka Bronisz
Journal: Cancer Research (2016)

Abstract A lack of experimental models of tumor heterogeneity limits our knowledge of the complex subpopulation dynamics within the tumor ecosystem. In high-grade gliomas (HGG), distinct hierarchical cell populations arise from different glioma stem-like cell (GSC) subpopulations. Extracellular vesicles (EV) shed by cells may serve as conduits of genetic and signaling communications; however, little is known about how HGG heterogeneity may impact EV content and activity. In this study, we performed a proteomic analysis of EVs isolated from patient-derived GSC of either proneural or mesenchymal subtypes. EV signatures were heterogeneous, but reflected the molecular make-up of the GSC and consistently clustered into the two subtypes. EV-borne protein cargos transferred between proneural and mesenchymal GSC increased protumorigenic behaviors in vitro and in vivo. Clinically, analyses of HGG patient data from the The Cancer Genome Atlas database revealed that proneural tumors with mesenchymal EV signatures or mesenchymal tumors with proneural EV signatures were both associated with worse outcomes, suggesting influences by the proportion of tumor cells of varying subtypes in tumors. Collectively, our findings illuminate the heterogeneity among tumor EVs and the complexity of HGG heterogeneity, which these EVs help to maintain. Cancer Res; 76(10); 2876–81. ©2016 AACR.
Predictors of smoking abstinence following a single-session restructuring intervention with self-hypnosis
Authors: D Spiegel, E J Frischholz, J L Fleiss, H Spiegel
Journal: American Journal of Psychiatry (1993)

This study examined the relation of smoking and medical history, social support, and hypnotizability to outcome of a smoking cessation program.A consecutive series of 226 smokers referred for the smoking cessation program were treated with a single-session habit restructuring intervention involving self-hypnosis. They were then followed up for 2 years. Total abstinence from smoking after the intervention was the criterion for successful outcome.Fifty-two percent of the study group achieved complete smoking abstinence 1 week after the intervention; 23% maintained their abstinence for 2 years. Hypnotizability and having been previously able to quit smoking for at least a month significantly predicted the initiation of abstinence. Hypnotizability and living with a significant other person predicted 2-year maintenance of treatment response.These results, while modest, are superior to those of spontaneous efforts to stop smoking. Furthermore, they suggest that it is possible to predict which patients are most likely and which are least likely to respond to such brief smoking cessation interventions.
The role of a complement regulatory protein in rat mesangial glomerulonephritis.
Authors: H Nishikage, L Baranyi, H Okada, N Okada, K Isobe, A Nomura, F Yoshida, S Matsuo
Journal: Journal of the American Society of Nephrology (1995)

The host cells are protected from the indiscriminate attack of homologous complement by the membrane-associated complement regulatory proteins. A mouse monoclonal antibody (mAb) 512 (immunoglobulin G1 subclass) has recently been described that recognizes and inhibits the function of a rat complement regulatory protein, a rat homologue of mouse Crry/p65. The aim of this work is to assess the role of a complement regulatory protein (512Ag) recognized by mAb 512 in the complement-dependent glomerular injury induced by mAb OX7 against rat Thy-1.1. For the induction of mesangial injury, the left kidney of a rat was perfused with a combination of OX7 and 512 and the perfusate was discarded from the renal vein (Group I). After the renal artery and vein were restored, the left kidney was connected to the systemic circulation. Rats were euthanized 3 h, 2 days, and 14 days later. Rats perfused either with OX7 (Group II) or with 512 (Group III) or with vehicle only (Group IV) were used as controls. At 3 h, rats of Group I showed more prominent cellular infiltration and mesangial lysis and more C3 deposition in the glomeruli than rats of Group II. Rats of Groups III and IV showed no significant changes. At Day 2, there was still significant mesangial lysis and leukocyte infiltration in Group I rats, whereas rats in other groups showed an almost normal appearance. Glomerular injury in Group I rats returned to normal by Day 14.