tbuckley/cabot-search huggingface dataset:
The 24-Hour Tl-201 Image in Dual Isotope Myocardial Perfusion Scintigraphy: Clinical Utility and Prognostic Significance
Authors: MICHAEL S. KIPPER, JUDITH J. LABARBERA, LINDA D. KROHN
Journal: Clinical Nuclear Medicine (1998)

This study assessed the effect on clinical decision making and the possible prognostic significance of the 24-hour Tl-201 image in patients undergoing Tl-201-MIBI dual-isotope myocardial scintigraphy. The records of all patients who underwent 24-hour Tl-201 imaging as part of their myocardial perfusion study from 1994 to 1996 were reviewed. Follow-up evaluations were obtained from the referring physician or by direct patient contact. Fifty-six patients underwent a total of 57 studies; four patients were lost to follow-up. Of the 53 studies evaluated, 29 showed no change between the standard rest images and the 24-hour images; these patients were reported to have myocardial scar. Of these 29 patients, 25 were treated medically without further evaluation; 24 of these 25 patients remained stable. Four of the 29 patients had further evaluation; 2 patients had coronary artery bypass graft, 1 had a stent placed, and 1 remained stable. Twenty-four patients showed definite improvement or normalization of their study results by 24 hours; they were reported as ischemic. Of these 24 patients, 11 were treated medically without further evaluation; 9 remained stable, whereas 2 had adverse events. The remaining 13 patients required further evaluation; 4 remained stable, whereas 9 had adverse events (4 = increasing angina; 1 = stent; 1 = rotoblator; 2 = percutaneous transluminal coronary angioplasty; 1 = death). Twenty-four-hour imaging contributes to clinical decision making and may identify a subset of patients at risk for subsequent complications.
P47 Continuous Laryngoscopy During Exercise (cle): A Practical And Valuable Test In A Respiratory Service?
Authors: B. Panchasara, G. Haji, S. Ward, A. Menzies-Gow, J. Hull
Journal: Thorax (2014)

<h3>Introduction and rationale</h3> Exertional wheeze and dyspnoea are most frequently attributed to exercise induced bronchoconstriction (EIB), yet may arise secondarily to a temporary closure of the larynx. This condition, termed Exercise induced laryngeal obstruction (EILO), is best characterised by the gold standard technique of direct and continuous laryngoscopy during exercise (CLE). To date most descriptions of the utility of CLE are in young highly athletic populations. <h3>Objectives</h3> Assessment of the safety, utility and application of CLE in subjects with unexplained and/or disproportionate exertional dyspnoea in a general respiratory population (i.e. not confined to athletes). <h3>Methods and measurements</h3> Patients referred for CLE with unexplained breathlessness and other respiratory diagnosis including treatment refractory asthma and COPD were identified. Thereafter clinical and physiological assessments were reviewed. <h3>Results</h3> In total 83 referrals (October 2012–February 2014) for CLE studies were analysed. The overall median (range) age was 43 (17–71) years. The majority of subjects were female (n = 56). Only a total of 4 (5%) subjects were athletes. We made a diagnosis of EILO in 30 (36%) of subjects studied. Prior to CLE 32 (39%) had been given a diagnosis of EIB, and of these we identified 17 (53%) actually had a diagnosis of EILO. Only one minor complication (pre-syncopal episode) was encountered during the procedure. <h3>Conclusion</h3> CLE is a safe effective method for the assessment of disproportionate exercise induced dyspnoea. It is a sensitive diagnostic tool and should not be reserved for use in a highly athletic population. It appears to be particularly useful in patients diagnosed with EIB who are not responding to treatment. Therapeutic intervention in the form of physiotherapy once the diagnosis is made offers the potential for symptomatic improvement and the withdrawal of unneeded pharmacological agents.
Afatinib + Cetuximab First-line in EGFR-Mutant Lung Cancer—Letter
Authors: Alexis B. Cortot, Denis Moro-Sibilot, Jacques Cadranel
Journal: Clinical Cancer Research (2016)

We read with great interest the article by Pirazzoli and colleagues on the ability of afatinib and cetuximab (AC) combination to delay resistance compared with afatinib alone (A) in a mouse model of EGFR-mutant lung adenocarcinoma (1). The main mechanism of resistance to AC in animals was the T790M mutation. It was detected in the same proportion than observed in human tumors that became resistant to first- or second-generation EGFR tyrosine kinase inhibitors (TKI). Assuming that no other new molecular alteration was associated with T790M mutation in the AC-resistant clones, these results suggest that the delayed appearance of resistance is not due to a shift toward other mechanisms of resistance associated with a more indolent disease but rather to the reduced ability of T790M clones to emerge. This may be due to the rapid and deep decrease of proliferated tumor cells that is achieved with AC limiting the emergence of resistance clones. This may also explain why AC is not more effective than A when a high number of resistant cells is already present in the tumor. The importance of rapidly and deeply reducing the pool of resistant clones from which resistance emerges has already been highlighted by the successful use of highly active antiretroviral therapy for HIV patients (2). Together with results from Meador and colleagues showing activity of third-generation TKIs in AC-resistant tumors, these data strongly support the evaluation of AC in TKI-naïve rather than TKI-treated patients (3). Although toxicity of AC is significant, it has been evaluated only in heavily pretreated patients so far, and toxicity of EGFR TKIs is now better managed. Importantly, this approach should not preclude further efficacy of third-generation TKIs. Other perspectives for improvement of first-line treatment of EGFR-mutant adenocarcinoma include combination of bevacizumab to EGFR TKIs, which has shown encouraging results in selected Japanese patients from a phase II trial, and use of third-generation TKIs (4). However, this last approach may delay resistance only in patients who would have developed a T790M mutation, and may favor emergence of heterogeneous mechanisms of resistance which may be more difficult to control (5). For all these reasons, the French Cooperative Thoracic Intergroup IFCT will soon start the IFCT-1503 ACE-Lung study, a randomized phase II study evaluating AC combination as first-line treatment for EGFR-mutant non–small cell lung cancer patients.A.B. Cortot is a consultant/advisory board member for Boehringer Ingelheim. No potential conflicts of interest were disclosed by the other authors.
Abstract 4951: The role of endothelin axis signaling pathway in astrocyte mediated chemoprotection of tumor cells.
Authors: Seung Wook Kim, Sun Jin Kim, Hyun Jin Choi, Ho-Jeong Lee, Junqin He, Qiuyu Wu, Erica J. Lawson, Isaiah J. Fidler
Journal: Cancer Research (2013)

Abstract Purpose: More than 40% of patients with the breast cancer develop brain metastasis that are resistant to conventional chemotherapeutic agents. We have reported that reactive astrocytes establish gap junction communication channels with adjacent tumor cells and protect tumor cells from chemotherapy by up-regulation of survival genes in the tumor cells. We now report on the mechanism by which astrocytes up-regulate expression of the survival genes in tumor cells. Materials and Methods: Human breast cancer cells, MDA-MB-231 cultured with murine astrocytes produce endothelin 1 (ET-1) leading to expression and activation of endothelin receptors (ETRs). Using small interfering RNA (siRNA) of ETAR and ETBR, and ETRs specific antagonists (BQ123, BQ788, and PD145065) demonstrated the correlation between the activation of the endothelin axis in tumor cells and the induction of survival genes (BCL2L1, GSTA5, and TWIST1) leading to chemoresistance. Results: Co-culture of MDA-MB-231 cells and murine astrocytes induced up-regulation of ETRs (ETAR and ETBR) and activation of endothelin receptors axis in tumor cells as well as increased production of ET-1 by murine astrocytes. Activation of the ETRs by exogenous ET-1 up-regulated the expression of survival genes, such as BCL2L1, GSTA5 and TWIST1 via activation of phosphorylated AKT/MAPKinase signal transduction pathways, leading to resistance of tumor cells to several chemotherapeutic agents. Knockdown of both ETAR and ETBR by siRNAs or treatment of tumor cells with dual ETR inhibitor abolished the chemoprotection induced by astrocytes. Conclusion: ET axis signaling pathway plays an essential role in astrocytes-mediated induction of chemoresistance of tumor cells by up-regulation of survival genes in tumor cells. Simultaneous blockade of both ETR can prevent tumor cells from developing resistance to chemotherapeutic agents. Citation Format: Seung Wook Kim, Sun Jin Kim, Hyun Jin Choi, Ho-Jeong Lee, Junqin He, Qiuyu Wu, Erica J. Lawson, Isaiah J. Fidler. The role of endothelin axis signaling pathway in astrocyte mediated chemoprotection of tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4951. doi:10.1158/1538-7445.AM2013-4951
NT-30 * COMPLICATIONS OF LASER INTERSTITIAL THERMAL THERAPY IN PATIENTS WITH BRAIN TUMORS
Authors: M. Schulder, K. Black, A. Mehta, A. Gamble
Journal: Neuro-Oncology (2014)

OBJECTIVE: Laser interstitial thermal therapy (LITT) has been described as a treatment for patients with brain tumors refractory to other treatments, with little emphasis on the risks of the procedure. This report focuses on complications of LITT in patients with tumors of the central nervous system. METHODS: Laser probes were inserted in the operating room using low-field intraoperative MRI (iMRI) guidance (5 patients), frameless stereotaxy (FS) in 2, and frame-based placement in 3. LITT itself was done in a 1.5 Tesla diagnostic MRI. Diagnoses included metastatic tumors in 7 patients, glioma in 2, and pituitary tumor in 1. One patient had a filum terminale ependymoma (with laser placement in the diagnostic MRI). RESULTS: In 1 patient in whom FS was used for image guidance, diagnostic MRI showed the laser fiber to be misplaced. Three complications resulted from the LITT itself. One patient with a glioblastoma of the vermis and fourth ventricle had bilateral palsies of cranial nerves 6 and 7 after treatment. A patient with a recurrent metastatic tumor after stereotactic radiosurgery had worsened left hemiparesis. These two patients were treated with steroids, with partial improvement of their deficits. The patient with the filum terminale ependymoma developed a paraparesis the day after treatment; MRI showed expansion of the intraspinal mass with resolution of enhancement, consistent with tumor ablation. She required a laminectomy and removal of the mass, with a combination of tumor and necrosis on histological examination. CONCLUSIONS: Complications of LITT can result from laser misplacement and from the laser treatment itself. Use of a stereotactic frame can limit the risk of inaccurate placement. Avoiding complications of the LITT itself can be done by undertreating the margin of a target in close proximity to critical structures. Intraspinal LITT should be used with great caution.
A6.01 Unique gene expression profile in osteoarthritis synovium compared with cartilage; analysis of publicly accessible microarray datasets
Authors: JD Ji, R Park
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To identify a gene expression signature in osteoarthritis (OA) synovium and genomic pathways likely to be involved in the pathogenesis of osteoarthritis. <h3>Methods</h3> Four publicly accessible microarray studies from synovium of OA patients were integrated and a transcriptomic and network-based meta-analysis was performed. Based on pathways according to the Kyoto Encyclopaedia of Genes and Genomes (KEGG), functional enrichment analysis was performed. Meta-analysis results of OA synovium were compared to two previously published studies of OA cartilage to determine the relative number of common and specific DEGs of the cartilage and synovium. <h3>Results</h3> According to our meta-analysis, a total of 1,350 genes were found to be differentially expressed in the synovium of OA patients as compared to that of healthy controls. Pathway analysis found 46 significant pathways in the total DEGs, and 23 and 16 pathways in the upregulated and downregulated DEGs respectively. Cell adhesion molecules (CAMs) and cytokine-cytokine receptor interaction were the most significant pathway in the upregulated and downregulated DEGs respectively. Interestingly, IL-1bβ and IL-6 were found to be downregulated in the OA synovium compared to in the healthy synovium. Comparison of meta-analysis results of OA synovium with results of two previous studies of OA cartilage identified 85 common genes and 1632 cartilage specific and 1265 synovium specific DEGs in the first study; and 142 common genes, and 856 cartilage specific and 1208 synovium specific DEGs in the second study. <h3>Conclusion</h3> Our results show a small overlap between the DEGs of the synovium compared to DEGs of the cartilage, suggesting different pathogenic mechanisms that are specific to the synovium.
EARLY DISCHARGE AFTER TRANSFEMORAL TRANSCATHETER AORTIC VALVE IMPLANTATION WITH THE EDWARDS SAPIEN-XT OR SAPIEN-3 PROSTHESIS: A PROSPECTIVE ANALYSIS OF SAFETY AND FEASIBILITY
Authors: Anna Bizios, Guillaume Cellier, Eric Durand, Christophe Tron, Fabrice Bauer, G. Alain Cribier, Bastien Glinel, Helene Eltchaninoff
Journal: Journal of the American College of Cardiology (2016)
Authors' reply to Dunning
Authors: P. Doshi, T. Jefferson
Journal: BMJ (2014)

Dunning questions the relevance of our systematic review, suggesting that any research data—regardless of its quality—that tests the effect of neuraminidase inhibitors on non-pandemic influenza answers the wrong question.1 2 Because all randomised trial evidence is on non-pandemic influenza, he argues that we must look elsewhere and highlights non-randomised observational studies, which conclude that the drugs provide great benefit, contrary to the conclusions that can be drawn from randomised trials.

This line of argument has …
Examination of the Estrogenicity of 2,4,6,2 prime ,6 prime -Pentachlorobiphenyl (PCB 104), Its Hydroxylated Metabolite 2,4,6,2 prime ,6 prime -Pentachloro-4-Biphenylol (HO-PCB 104), and a Further Chlorinated Derivative, 2,4,6,2 prime ,4 prime ,6 prime -Hexachlorobiphenyl (PCB 155)
Authors: Mark R. Fielden, Ih Chen, Brock Chittim, Stephen H. Safe, Timothy R. Zacharewski
Journal: Environmental Health Perspectives (1997)

Several sbtuies hv reported tha rpolklorinated bp l (PCBs) ec at however, it is not dear if thes are associated with the poykinated hydrocar or its hy ted metbolit In order to further test this , a bae of in vtro a in i. assays were used to the eo c and an o c of 2,4,6,2',6-pentachlorobiphenyl (PCB 104), its panhydroxylated dvative 2,4,6,2',6'-pentahoro4-biphenylol (HO-PCB 104), and its pans-chlorinated d tvF 2,4', '-eachlero (CA 155).PCBI 104 ws3 found to 1) with a'd 17fes io r bidin to mouse uterine estrogen receptor (ER; 2) induce e eX MCF bre ccells transientyt e with the Gl4-human ER him (C4HEGO) and the Ga4gul ted ludfe report gene (17m5-GLuc); and 3) incre MCF-7 cel prolifeaion in a dos-dependent manner.HO-PCB 104 ehibited grCater eogeic t than PCB 104 in the ix vin assys examineL Howevwe, gs m phic-ma spectrophotometric analysis of extrap ar from MCF-7 cel incubated with PCI 104 filed t*diec the presence the e major methbolite-PCI 104.The t ofte oraed derivative, PCI 155, was mial p to PCI and HO-PCI 104, but it did t significant antiestrogenic activity following CO-t with 1 M F2 CO- ent of PCI 104 with 1 aM E had no effect on reporter gene epreion compared to E alone, while 10 pM HO-PCB 104 chibited addity with I nM E. At a dose of 202 mg/g PCB 104 in a uterine wet-weight in e omized CD-i mice and induced vaga eCC i at 202, 16, ain 1.7 mg/kg in a (16,18,26-28).
Follow-up Results of Benign-Appearing Submucosal Tumor by EUS
Authors: SJ Lee, YD Cho, JO Kim, SH Eun, YD Kim, IS Jung, JY Cho, JS Lee, SY Jin, CS Shim
Journal: Endoscopy (2006)

Back ground/Aims: EUS has been used for differential diagnosis between benign and malignant submucosal tumor. However, the natural course of benign-appearing submucosal tumor is not clearly elucidated. The aim of this study was to evaluate the natural course of benign-appearing submucosal tumor in EUS in gastrointestinal tract. Methods: We evaluated retrospectively the changes of size, internal echo pattern and marginal regularity in 38 patients who had benign-appearing submucosal tumor more than 1cm and less than 3cm and followed up for more than 1 year. We regarded an increase or a decrease of over 25% in maximal diameter as significant size change. Results: Diagnosis of initial EUS were 19 leiomyoma/GIST, 4 lymphangioma, 6 lipoma, 6 ectopic pancrea, 1 granuloma and 1 hemangioma. Submucosal tumors from the following areas: esophagus 14, stomach 19, duodenum 1 and colon 3. The average size of tumors was 16.9mm. The mean follow-up period was 35.6 months (range 12–94 months). Followed-up revealed no change in echo pattern and size in 69 of 71 patients (94.6%). In one patient, homogenous hypoechoic tumor suggesting gastric leiomyoma increased from 26 to 34mm without the change of internal echo or marginal regularity at surveillance of 24 months, revealing leiomyoma after laparoscopic gastric wedge resection. In the other patients, a 20mm-sized homogenous anechoic lesion with thin septation in initial EUS increased a 30mm-sized anechoic lesion without the change of internal echo or marginal regularity at surveillance of 26 months, revealing cystic lymphangioma by EUS-guided FNA. Conclusion: Most benign-appearing submucosal tumors more than 1cm but less than 3cm by EUS was not changed during a period of 12 months and EUS criteria are effective to conclude to benign submucosal tumors. Benign-appearing submucosal tumors in EUS might be followed at interval of 1 year by EUS.
Abstract 1272: Role of c-Myc, Oct1 and KLF4 in cell metabolism: Involvement of pluripotency factors in metabolic remodeling during tumorigenesis
Authors: Nadege Bellance, Thasni Karedath, Christine Caneba, Lisa Pabst, Syed Asad, Deepak Nagrath
Journal: Cancer Research (2011)

Abstract Embryonic stem cells have the ability to give rise to different cell types and also the self reniewal capacity. Those features are essentially controlled by pluripotency factors which maintain cells into an undifferentiated state. Cancer cells are distinguished from normal cells by a dedifferentiation process in which the expression of pluripotency factors can be increased. c-Myc, Oct4 and KLF4 are pluripotency transcription factors. Oct-1, homologue of Oct-4, have been recently revealed to be pro-tumorigenic and his expression, such as c-Myc, is increased in various cancers. In this study, we investigated the role of this transcription factors into the cell metabolism. The role of the oncogene MYC on tumor cell metabolism has been largely studied. In cancer cells, c-Myc induces the expression of genes involved in glycolysis and glutaminolysis. However, the entire metabolic changes induced by c-Myc have not yet been elucidated. Furthermore, little is known about the role of Oct-1 and KLF4 in cancer metabolism. We have used the metabolic footprinting approach in order to characterize the Oct-1, c-Myc and KLF4 deficient cells and to identify the induced consecutive metabolic remodeling. Because of the variability of mutations observed in cancer cells, we investigated the effects induced by Oct-1, KLF4 and c-Myc deficiencies in mouse and rat embryonic fibroblasts by using UPLC (Ultra performance liquid chromatography). The uptake and release of metabolites was quantified by providing different substrates (glutamine or fatty acid). The glucose consumption and the lactate production which defined as the Warburg effect was measured. The mitochondrial function was investigated by oxygen consumption rate measurement. We found that the metabolites produced by Oct-1, KLF4 and c-Myc deficient cells seems to present a signature which can explain there over-expression in tumors. Our results suggest that embryonic stem cells related pluripotency transcription factors are implicated into the metabolic remodeling of cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1272. doi:10.1158/1538-7445.AM2011-1272
SP0027 High Resolution and Advanced MR Imaging of Cartilage
Authors: S. Trattnig
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Due to the complex, zonally anisotropic internal structure of cartilage resulting in a short T2 relaxation time and because of its thin layer, MRI of articular cartilage is still challenging. Therefore, the highest morphological resolutions at an acceptable signal-to-noise ratio (SNR) are required. Imaging of the articular cartilage is possible at most clinically available MR systems, but it has been shown that a voxel size lower than 300µm is required to reveal fraying of the cartilage. High-field MR scanner, like 3 Tesla and recently ultrahigh field systems operating at 7 Tesla, are able to provide such resolutions in reasonable scan times. Another important part of the hardware is the coil technology with dedicated multi-element coils offering high spatial resolution. These systems provide also the opportunity of 3-D acquisition with high resolution, high SNR and high contrast-to-noise ratio. The use of cartilage-specific sequences combined with a high resolution allows the demonstration of damaged cartilage in a very early stage. The most widespread cartilage-specific MRI techniques are:Intermediate-weighted fast spin-echo (FSE) and 3-D fat-suppressed gradient-echo (GRE) acquisition Each technique has particular properties that complement each other. With sufficient SNR provided by high field MR advanced compositional or biochemical MR imaging of the main components of cartilage such as proteoglycans and collagen fiber network are feasible. <h3>Disclosure of Interest</h3> None Declared