tbuckley/cabot-search huggingface dataset:
Prevention Trial for Prostate Cancer Piques Public Interest
Authors: F. Donodeo
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Prevention Trial for Prostate Cancer Piques Public Interest Get access Fred Donodeo Fred Donodeo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 22, 17 November 1993, Pages 1801–1802, https://doi.org/10.1093/jnci/85.22.1801 Published: 17 November 1993
Abstract 4396: Evaluation of gene expression and transcriptional activation in patients treated with vorinostat
Authors: Jill M. Kolesar, Elim Lau, Songwon Seo, Jens Eickhoff, KyungMan Kim, Anne Traynor, Howard Bailey, George Wilding, William Schelman
Journal: Cancer Research (2011)

Abstract Background: Vorinostat is a histone deacetylase (HDAC) inhibitor that is approved for treatment of cutaneous T-cell lymphoma and is being investigated in a number of solid tumors. Inhibition of HDAC by vorinostat leads to an accumulation of acetylated histones which induces apoptosis though a mechanism that is not completely characterized. This study was performed to assess the potential mechanisms responsible for induction of apoptosis following treatment with vorinostat. Methods: Sixty subjects with advanced malignancies received vorinostat orally days 1-14 combined with bortezomib IV on days 2, 4, 8, and 11 of a 21-day cycle. Peripheral blood mononuclear cells (PBMCs) were collected before and 2hr and 6hr after dosing on Days (D) 1 and 9. Paired tumor biopsies were obtained in ten patients on D0 and D9. Gene expression of downstream targets was evaluated by semi-quantitative RT-PCR in PBMCs, and the interaction between candidates genes and acetylated histone H3 were evaluated in biopsies by the chromatin precipitation assay. A nonparametric Wilcoxon signed rank test was used to examine changes from the pre-treatment value of 1 on D1 based on complete case analysis without multiplicity adjustment. Results: p21, Nur77 and HSP70 gene expression in PBMCs were all significantly induced two hours after vorinostat administration compared to baseline (Table 1). AKT, ERB1 and ERB2 expression were not statistically significantly altered in PBMCs. The expression of all targets increased in tumor biopsies by Day 9, with p21 2.37, Nur77, 1.33 and HSP70 2.35 times baseline expression levels. The chromatin precipitation assay demonstrated that Nur77, HSP70 and p21 interacted with acetylated histone H3, after nine days of treatment with vorinostat, in tissue biopsies. Conclusion: This data suggests that acetylated histones interact transcriptionally with p21, Nur77 and HSP77 to induce gene expression and are a potential mechanism by which vorinostat induces apoptosis. 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 4396. doi:10.1158/1538-7445.AM2011-4396
M271 A Survey Of Trainee Experiences In Interstitial Lung Disease
Authors: C. Sharp, M. Gibbons
Journal: Thorax (2014)

<h3></h3> Interstitial lung disease (ILD) is a major area of respiratory medicine It is important that trainees gain competence and confidence in this area. <h3>Methods</h3> A survey of BTS trainee members was conducted in November 2013 to examine training provision in ILD, including trainee’s opportunities, experience and confidence in aspects of ILD. <h3>Results</h3> There were 104 respondents out of a possible 574. 33% of respondents were not expecting any subspecialty clinics in ILD in the course of their training. 42% of trainees expect to spend 3 months or less attending specialist clinics. Trainee attendance at MDTs is far from guaranteed, with 45% expecting to attend less than half during their period in these hospitals. The majority of trainees are trained in performing BAL for cell differential analysis (73%) and transbronchial biopsies (84%), however only 48% are confident performing transbronchial biopsies. Confidence interpreting investigation results increases with the frequency these are performed. The self rated knowledge in a range of subject areas was also assessed and demonstrated that most areas were moderately well understood, however knowledge of the less frequently encountered IIPs was rated lower. 54% of trainees felt their ILD training was inadequate for SCE preparation. 94% would value a BTS Short Course on ILD to improve their knowledge and confidence. <h3>Discussion</h3> This survey highlights areas where there are clear opportunities to enhance the training of registrars in ILDs. It is worth noting that some of the data is in conflict with previous BTS surveys in this area and there is the possibility of self-selection bias in the response population. Whilst most trainees are trained in performing relevant procedures, their confidence interpreting the results of common investigations in ILD is low. To give evidence of training and competence in this area, deaneries may wish to consider requesting logbook evidence of procedures related to ILD, in addition to evidence of ILD MDT attendance. There is undoubtedly a need for a BTS short course on ILD for trainees.
Pott's Disease with Paraparesis
Authors: B A Shaw
Journal: New England Journal of Medicine (1996)

Figure 1. A 13-year-old boy presented with increasing kyphotic deformity, back pain, and progressive paraparesis seven years after a one-year course of medical therapy for tuberculosis. He reported shock-like sensations in his legs whenever he bent forward and fatigue in his thighs and calves, which limited his activities. Physical findings included a rigid gibbus (Panel A, arrow), inability to tiptoe, hyperreflexia of the ankles with mild clonus, and normal proprioception and sensation to light touch. A magnetic resonance imaging scan (Panel C) showed that the bodies of T9 through L1 had collapsed into one mass, compressing the spinal cord to . . .
Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive Regimen
Authors: A.M. James Shapiro, Jonathan R.T. Lakey, Edmond A. Ryan, Gregory S. Korbutt, Ellen Toth, Garth L. Warnock, Norman M. Kneteman, Ray V. Rajotte
Journal: New England Journal of Medicine (2000)

Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year.
LABELING AND DISTRIBUTION OF CANDIDA ALBICANS IN MICE.
Authors: L. P. Kasi, G. Lopez-Berestein, R. L. Hopfer, K. Mills, M. Jahns, I. Teckemeyer, H. J. Glenn, T. P. Haynie
Journal: Clinical Nuclear Medicine (1983)

Kasi, L. P.; Lopez-Berestein, G.; Hopfer, R. L.; Mills, K.; Jahns, M.; Teckemeyer, I.; Glenn, H. J.; Haynie, T. P. Author Information
Abstract 4762: Effect of the phytochemical crinumaquine on prostate and prostate cancer cell lines
Authors: Run-hui Liu, Huizi Jin, Xi-Song Ke, Yi Qu, Margrete R. Hellem, Kari Rostad, Anne Margrete Oyan, Karl H. Kalland, Wei-Dong Zhang
Journal: Cancer Research (2012)

Abstract We have published a new prostate cell culture model in which benign, immortalized prostate epithelial EP156T cells gave rise to progeny cells with a stepwise accumulation of defined malignant features. In a screen of a panel of phytochemicals using this cell culture model, the small molecular compound crinumaquine exerted differential effects on benign prostate cancer cells compared with progeny cells with accumulated malignant features. The differential effect included proliferation and induction of a striking phenotype of the more malignant cells. The induced phenotype comprised extensive membrane protrusions and cell contacts between neighbouring cells following crinumaquine treatment for 2 - 4 days. Conditioned medium from the changed cultures induced a similar phenotype within hours in non-treated cells. Genome-wide gene expression analysis using the Agilent 44k oligoarray platform revealed that crinumaquine treatment reduced expression of multiple genes involved in cell division and strongly induced several genes involved in apoptosis induction. Furthermore, crinumaquine treatment induced multiple genes of cell adhesion modules such as gap junctions, adherens junctions and desmosomes. These findings have motivated further examinations of the ability of crinumaquine to compromise epithelial to mesenchymal plasticity and its potential in the treatment of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4762. doi:1538-7445.AM2012-4762
Tl-201 Scintigraphy in Multivessel Exercise-Induced Variant Angina
Authors: WAYNE A. KRUITHOFF, FRANK V. SCHRAML, EUGENE D. SILVERMAN
Journal: Clinical Nuclear Medicine (1996)

A 53-year-old man presented for evaluation of nocturnal chest pain, consistent with angina pectoris. An exercise stress test reproduced his symptoms, however, exercise electrocardiograms were nondiagnostic. An exercise-thallium perfusion study confirmed vasospasm as the cause. This knowledge guided subsequent successful medical therapy.
INVESTIGATION OF CLINICAL EFFICACY OF THROMBUS ASPIRATION ON 5-YEAR MORTALITY IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION UNDERGOING PCI
Authors: Hiroki Watanabe, Takeshi Kimura, Takeshi Morimoto, Hiroki Shiomi, Tomohiko Taniguchi, Kenji Nakatsuma, Toshiaki Toyota, Yoshihisa Nakagawa, Yutaka Furukawa, Minoru Horie
Journal: Journal of the American College of Cardiology (2014)
FRI0123 Biologic monotherapy (BMT) as a treatment pattern in ra patients in a developing country.
Authors: E. Mysler, A. Alvarellos, A. Borgia, A. Eimon, R. García Salinas, L. Najún Dubos, L. Re, D. Siri, J. P. Solé, F. Sommerfleck, J. Velasco Zamora, C. Wiederhold
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In RA patients, where biological therapy is needed, combination therapy (CT) with a biological agent plus MTX remains the standard of care. However, in some scenarios (i.e. DMARD intolerance, non-compliance) BMT appears as a therapeutic option. <h3>Objectives</h3> To assess the proportion of RA patients that is currently being treated with BMT in our country and to analyze the reasons behind this treatment pattern. <h3>Methods</h3> This is a cross-sectional analysis of data obtained from medical charts revision of RA patients. Proportion of patients, reasons for BMT utilization, physician's satisfaction with BMT outcomes and main causes of DMARD discontinuation were assessed. <h3>Results</h3> This investigation involved 1148 patients from 32 sites distributed around the country. Main demographic characteristics were: age 54 ± 13 years, 81% female, mean disease duration 12 ± 9 years. Patients receiving BMT represented 21.4% (CI 95%:19-23) of the sample size (246/1148 patients) <h3>Conclusions</h3> A significant proportion of RA patients in our country are treated with BMT. BMT treatment seems to be an accepted therapeutic option in our medical community, both as initial therapy or as part of a sparing strategy. Patterns of BMT for RA patients in a developing country seem to be similar than those observed in developed countries. <h3>References</h3> Soliman MM, et al. Ann Rheum Dis2011; <b>70:</b>583–589. Lee SJ, et al. J Rheumatol2009; 36:1161–7 <h3>Acknowledgements</h3> <h3>Disclosure of Interest</h3> E. Mysler Grant/research support from: Roche Argentina, A. Alvarellos Grant/research support from: Roche Argentina, A. Borgia Grant/research support from: Roche Argentina, A. Eimon Grant/research support from: Roche Argentina, R. García Salinas Grant/research support from: Roche Argentina, L. Najún Dubos Employee of: Roche Argentina, L. Re Employee of: Roche Argentina, D. Siri Grant/research support from: Roche Argentina, J. Solé Employee of: Roche Argentina, F. Sommerfleck Grant/research support from: Roche Argentina, J. Velasco Zamora Grant/research support from: Roche Argentina, C. Wiederhold Grant/research support from: Roche Argentina
P16.23 * A COMPARISON OF 18F-FET AND 18F-FLT MICROPET FOR THE ASSESSMENT OF ANTI-VEGF EFFICACY IN AN ORTHOTOPIC MURINE MODEL OF GLIOBLASTOMA
Authors: M. K. Nedergaard, S. R. Michaelsen, H. S. Poulsen, U. Lassen, M. Stockhausen, A. Kjaer
Journal: Neuro-Oncology (2014)

BACKGROUND: The radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and thymidine analog 3'-deoxy-3'-18F-fluorothimidine (18F-FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, results from comparative studies are scarce. Due to the limited transport of FLT across the intact blood-brain barrier (BBB) we hypothesize that anti-VEGF response assessment with FLT PET primarily reflects changes in the BBB, whereas FET PET is less affected by the tumor vasculature. The aim of this study was therefore to evaluate and compare the value of FLT and FET MicroPET for anti-VEGF response assessment in orthotopic human glioma xenografts. METHODS: Cells of human glioblasoma multiforme (GBM) neurosphere culture (NGBM_CPH048p6_LUC) were injected orthotopically in NMRI nude mice. At confirmed tumor take, mice were treated with anti-VEGF therapy (B20-4.1) or saline as control. Treatment response was followed by weekly bioluminescence, 18F-FLT and 18F-FET MicroPET/CT. The end-point was survival and brains from sacrificed mice were used for immunohistochemistry and subsequent quantification of the Ki67 proliferation index and micro-vessel density (MVD). RESULTS: The relative 18F-FET tumor-to-brain of (T/B) ratio of SUVmax was significantly decreased after one week (99 ± 6%, n = 6 vs. 124 ± 9%, n = 5; p = 0.04) and after two weeks (106 ± 10%, n = 5 vs. 156 ± 17%, n = 4; p = 0.03) in the B20-4.1 group as compared with the control group. However, with 18F-FLT MicroPET there was no significant difference in the T/B ratio of SUVmax neither after one week of treatment (134 ± 12%, n = 6 vs. 144 ± 6%, n = 6; p = 0.49) nor after two weeks of treatment (174 ± 11%, n = 5 vs. 208 ± 30%, n = 5; p = 0.34). We found a significant lower MVD in the B20-4.1 group as compared to the control group (66 ± 8%, n = 8 vs. 100 ± 10%, n = 7; p = 0.02). However, we found no difference in the Ki67 proliferation index in the treatment group as compared to the control group (18.9 ± 1%, n = 7 vs. 19.8 ± 2%; n = 6; p = 0.7). In addition, the median survival was not prolonged in the treatment group as compared to the control group (19 vs. 21 days, p = 0.34). CONCLUSION: In NGBM_CPH048p6_LUC xenografts B20-4.1 anti-VEGF treatment induced changes in the MVD and in 18F-FET uptake without affecting the Ki67 proliferation index. Surprisingly and in contradiction with the hypothesis, the 18F-FLT uptake was not affected by the changes in the MVD.
ENDOGENOUS CONTRAST MRI OF CARDIAC FIBROSIS: BEYOND LATE GADOLINIUM ENHANCEMENT
Authors: Johannes M.I.H. Gho, Joep W.M. van Oorschot, Sanne Jansen of Lorkeers, Martijn Froeling, Peter R. Luijten, Pieter A. Doevendans, Jaco J.M. Zwanenburg, Steven Chamuleau
Journal: Journal of the American College of Cardiology (2014)
Activation of mTORC1 is essential for β-adrenergic stimulation of adipose browning
Authors: Dianxin Liu, Marica Bordicchia, Chaoying Zhang, Huafeng Fang, Wan Wei, Jian-Liang Li, Adilson Guilherme, Kalyani Guntur, Michael P. Czech, Sheila Collins
Journal: Journal of Clinical Investigation (2016)

A classic metabolic concept posits that insulin promotes energy storage and adipose expansion, while catecholamines stimulate release of adipose energy stores by hydrolysis of triglycerides through β-adrenergic receptor (βARs) and protein kinase A (PKA) signaling. Here, we have shown that a key hub in the insulin signaling pathway, activation of p70 ribosomal S6 kinase (S6K1) through mTORC1, is also triggered by PKA activation in both mouse and human adipocytes. Mice with mTORC1 impairment, either through adipocyte-specific deletion of Raptor or pharmacologic rapamycin treatment, were refractory to the well-known βAR-dependent increase of uncoupling protein UCP1 expression and expansion of beige/brite adipocytes (so-called browning) in white adipose tissue (WAT). Mechanistically, PKA directly phosphorylated mTOR and RAPTOR on unique serine residues, an effect that was independent of insulin/AKT signaling. Abrogation of the PKA site within RAPTOR disrupted βAR/mTORC1 activation of S6K1 without affecting mTORC1 activation by insulin. Conversely, a phosphomimetic RAPTOR augmented S6K1 activity. Together, these studies reveal a signaling pathway from βARs and PKA through mTORC1 that is required for adipose browning by catecholamines and provides potential therapeutic strategies to enhance energy expenditure and combat metabolic disease.
“Quality time” for patients with Barrett’s esophagus
Authors: G. Triadafilopoulos
Journal: Endoscopy (2010)

Since the 1970s, the term “quality time” has been increasingly used to refer to time spent with loved ones (family, partners, or friends) that is especially rewarding, productive, or profitable, or to time engaged in some favored activity, such as a hobby [1]. Such quality time is inherently linked to “quality of life”, meaning an individual’s emotional, social, and physical wellbeing, including their ability to function in the ordinary tasks of living. Simply put, quality time (QT) equals quality of life (QoL) times time, or QT = QoL × t. The higher the quality of life and the longer the time the one lives, the better …
Abstract P1-13-13: First planned efficacy analysis of the NNBC 3-Europe trial: Addition of docetaxel to anthracycline containing adjuvant chemotherapy in high risk node-negative breast cancer patients.
Authors: C Thomssen, EJ Kantelhardt, C Meisner, M Vetter, M Schmidt, P-M Martin, C Veyret, D Augustin, V Hanf, D Paepke, W Meinerz, G Hoffmann, W Wiest, FCGJ Sweep, M Schmitt, F Jaenicke, G von Minckwitz, N Harbeck
Journal: Cancer Research (2012)

Abstract Background: Risk assessment in node-negative (N0) breast cancer patients (pts) is routinely performed by established clinico-pathological algorithms (CP) (Schmidt et al. Ann Oncol 2009). ASCO guidelines also recommend invasion markers uPA/PAI-1 (UP; Harris et al. JCO 2007). The prospective randomized multicenter NNBC 3-Europe trial had two questions: 1) Does UP compared to the CP algorithm improve identification of low-risk node-negative breast cancer patients? 2) Does addition of taxanes to adjuvant chemotherapy improve DFS probability in high-risk node-negative breast cancer? Data are mature to report on the second question only. Methods: Between 2002 and 2009, 4,147 node-negative breast cancer pts were recruited. Risk assessment was performed by CP (43 %) or by UP (57 %). High-risk pts were randomized to receive FE100C*3-Doc*3 (FEC-D) versus FE100C*6 (FEC) as adjuvant chemotherapy. Primary endpoint was disease-free survival probability (DFS). It was planned to accrue 2,572 pts allowing detection of 4% reduction in recurrence probability at 5 years with a power of 80 % at a level of α=0.05 (LogRank) after a minimum observation time of 2.5 years for every recruited patient. Results: In the intent-to-treat population (ITT, n=2,541), 1,286 high-risk pts received FEC-D, and 1,255 received FEC. In July 2012, 90.8 % of patients had reached the minimum observation time – median follow-up was 43.8, and 44.4 months. Main patients' characteristics were distributed similarly between the two chemotherapy arms: median age was 53 yrs, 37.4 % of pts were premenopausal, median tumor size was 1.90 cm, grade 3 was seen in 53.8 %, hormone receptor status was negative in 30.1 % and HER2 was overexpressed in 20.0 %. Mastectomy was performed in 11 %. All planned courses of FEC-D were given in 84.4 %, of FEC in 91.4 % (p &amp;lt; 0.0001). DFS after 2.5 yrs was for FEC-D 97.5 % (+/− 0.45 %) and for FEC 97.3 % (+/− 0.47 %). Overall-survival probability (OS) after 2.5 yrs was 99.0 % (+/− 0.29 %) for FEC-D and 99.5 % (+/− 0.20 %) for FEC. The survival differences between the two arms were not statistically significant. Per-protocol analysis did not reveal any additional results. Conclusions: Use of taxanes does not further reduce the rate of early recurrences and led to significantly more treatment discontinuation. Today, with adequate adjuvant chemotherapy even high-risk node-negative breast cancer patients have an excellent prognosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-13.
High sodium chloride consumption enhances the effects of smoking but does not interact with SGK1 polymorphisms in the development of ACPA-positive status in patients with RA
Authors: Xia Jiang, Björn Sundström, Lars Alfredsson, Lars Klareskog, Solbritt Rantapää-Dahlqvist, Camilla Bengtsson
Journal: Annals of the Rheumatic Diseases (2016)

T cell effector function is a central mechanism of adaptive immunity, and accordingly, protection of the host against pathogens. One of the primary effector molecules produced by T cells in response to such pathogens is the cytokine, IFN-γ. Although the signaling pathways associated with the production of IFN-γ are well established, disparate in vivo and in vitro results indicate that distinct pathways may become more prominent dependent upon the nature of the infection, inflammatory milieu and tissue localization. We have examined the roles and requirements of the major IFN-γ-inducing pathways in vivo and in vitro, specifically: strength of TCR signal; paracrine release of IL-12, IL-23, and IL-18; and autocrine production of IFN-γ. Our data show a dynamic interaction between these activation pathways, which allows the host a degree of flexibility and redundancy in the induction of IFN-γ. Upon strong signaling through the TCR, IL-12, IL-18, and IL-23 play negligible roles in the induction of IFN-γ, whereas autocrine IFN-γ is an important component in sustaining its own secretion. However, the absence of any one of these factors during a weaker TCR signal, results in strikingly impaired T cell IFN-γ production. Of note, TLR-activated dendritic cells (DCs) were capable of overcoming the absence of a strong TCR signal, IL-12, IL-23, or IL-18 revealing an important additional mechanism for ensuring a robust IFN-γ response. Our findings clarify the hierarchical requirements of the major IFN-γ inducing pathways and highlight the important role TLR ligand-activated DCs have to preserve them.
INCREMENTAL BENEFIT OF COMPUTED TOMOGRAPHY DERIVED RESTING MYOCARDIAL PERFUSION USING MACHINE LEARNING METHOD AND COMPUTED TOMOGRAPHY DERIVED FRACTIONAL FLOW RESERVE FOR PREDICTING LESION ISCHEMIA
Authors: Ji Hyun Lee, Asim Rizvi, Donghee Han, Briain O. Hartaigh, Heidi Gransar, Fay Lin, James Min, Guanglei Xiong
Journal: Journal of the American College of Cardiology (2016)
Pancreatic metastasis from gastric carcinoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration
Authors: César Lopes, Carlos Oliveira dos Santos, Daniele Malaman, Júlio Pereira-Lima, Antônio Hartmann
Journal: Endoscopy (2014)

Upper digestive endoscopy in a 36-year-old woman complaining of epigastric pain revealed an ulcerative lesion in the gastric body ([Fig. 1 a]). Endoscopic biopsies confirmed a gastric adenocarcinoma ([Fig. 1 b, c]). Endoscopic ultrasonography for cancer staging demonstrated a T2 gastric lesion, and a solid lesion measuring 10.2 mm × 9.6 mm in the pancreatic body ([Fig. 2 a]). Histologic analysis of biopsy samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA; [Fig. 2 b]) showed neoplastic cells with the same histologic findings as those from the primary gastric cancer ([Fig. 2 c]). Chest and abdominal computed tomography detected additional lung and liver metastases, but no pancreatic lesion was found. Palliative chemotherapy was planned for the patient.