tbuckley/cabot-search huggingface dataset:
AB0181 Bone Marrow Derived Dendritic Cells Modified by Lentiviral-Mediated Relb Shrna Possess Tolerogenic Phenotype and Functions on Lupus Splenic Lymphocytes
Authors: H.J. Wu, Y. Lo, A. Chan, M.Y. Mok
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by high morbidity and mortality and remains challenging in treatment. Dendritic cells (DCs) have been shown to participate in the initiation and perpetuation of lupus pathogenesis. DCs that induce tolerogenicity appear as potential cell-based therapy in this condition. <h3>Objectives</h3> In this study, we used lentiviral transduction of RelB-silencing shRNA to modify expression of RelB, a key transcription factor regulating DC maturation, in bone marrow-derived DCs from MRL/MpJ wild type mice and examined their tolerogenic properties using a lupus-prone MRL/lpr model. <h3>Methods</h3> Lentiviral-mediated transduction of RelB-silencing shRNA or scrambled control shRNA were used to treat bone marrow derived DCs from MRL/MpJ mice. LPS-matured DCs, scrambled shRNA-modified DCs and RelB-modiified DCs were compared in terms of their tolerogenic properties. <h3>Results</h3> We found that these MRL/MpJ RelB-modified DCs displayed semi-mature phenotype. These MRL/MpJ RelB-modified DCs were found to be low producer of IL-12p70, can induce hyporesponsiveness of splenic T cells from MRL/MpJ and lupus-prone MRL/lpr mice. Furthermore, they downregulated IFN-γ expression and induced IL-10 producing T cells in MRL/MpJ splenocytes, and attenuated IFN-γ and IL-17 expression in MRL/lpr splenic lymphocytes. Splenocytes primed by RelB-modified DCs demonstrated antigen-specific suppressive effect on allogeneic splenocytes. However, these CD4+ T cells with suppressive function were not found to express Foxp3. In the terms of chemokine receptor expression, there were no differences in the expression of CCR5, CCR7, and CXCR3 bewteen RelB- and scrambled control-modified DCs. <h3>Conclusions</h3> RelB-modified DCs provide a method in the generation of tolerogenic DCs which may have potential therapeutic implications in the treatment of SLE. <h3>Disclosure of Interest</h3> None declared
Re: Jens Sønksen, Neil J. Barber, Mark J. Speakman, et al. Prospective, Randomized, Multinational Study of Prostatic Urethral Lift Versus Transurethral Resection of the Prostate: 12-month Results from the BPH6 Study. Eur Urol 2015;68:643–52
Authors: Matthew Bultitude, Pieter Le Roux
Journal: European Urology (2015)
Associations with Intraocular Pressure in a Large Cohort
Authors: Michelle P.Y. Chan, Carlota M. Grossi, Anthony P. Khawaja, Jennifer L.Y. Yip, Kay-Tee Khaw, Praveen J. Patel, Peng T. Khaw, James E. Morgan, Stephen A. Vernon, Paul J. Foster
Journal: Ophthalmology (2016)

<h3>Purpose</h3> To describe the associations of physical and demographic factors with Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated intraocular pressure (IOPcc) in a British cohort. <h3>Design</h3> Cross-sectional study within the UK Biobank, a large-scale multisite cohort study in the United Kingdom. <h3>Participants</h3> We included 110 573 participants from the UK Biobank with intraocular pressure (IOP) measurements available. Their mean age was 57 years (range, 40–69 years); 54% were women, and 90% were white. <h3>Methods</h3> Participants had 1 IOP measurement made on each eye using the Ocular Response Analyzer noncontact tonometer. Linear regression models were used to assess the associations of IOP with physical and demographic factors. <h3>Main Outcome Measures</h3> The IOPg and IOPcc. <h3>Results</h3> The mean IOPg was 15.72 mmHg (95% confidence interval [CI], 15.70–15.74 mmHg), and the mean IOPcc was 15.95 mmHg (15.92–15.97 mmHg). After adjusting for covariates, IOPg and IOPcc were both significantly associated with older age, male sex, higher systolic blood pressure (SBP), faster heart rate, greater myopia, self-reported glaucoma, and colder season (all <i>P <</i> 0.001). The strongest determinants of both IOPg and IOPcc were SBP (partial <i>R</i><sup>2</sup>: IOPg 2.30%, IOPcc 2.26%), followed by refractive error (IOPg 0.60%, IOPcc 1.04%). The following variables had different directions of association with IOPg and IOPcc: height (−0.77 mmHg/m IOPg; 1.03 mmHg/m IOPcc), smoking (0.19 mmHg IOPg, −0.35 mmHg IOPcc), self-reported diabetes (0.41 mmHg IOPg, −0.05 mmHg IOPcc), and black ethnicity (−0.80 mmHg IOPg, 0.77 mmHg IOPcc). This suggests that height, smoking, diabetes, and ethnicity are related to corneal biomechanical properties. The increase in both IOPg and IOPcc with age was greatest among those of mixed ethnicities, followed by blacks and whites. The same set of covariates explained 7.4% of the variability of IOPcc but only 5.3% of the variability of IOPg. <h3>Conclusions</h3> This analysis of associations with IOP in a large cohort demonstrated that some variables clearly have different associations with IOPg and IOPcc, and that these 2 measurements may reflect different biological characteristics.
Report of solid cancer in patients (pts) with gastrointestinal stromal tumours (GIST)
Authors: M. Chacon, E. Roca, M. Barugel, G. Jankilevich, N. Giacomi, M. Pelati, R. Kowalyszyn, E. Domenechini, M. Galich, E. Huertas
Journal: Journal of Clinical Oncology (2004)

9065
Heterogeneity of Human Natural Killer Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: D Zagury, D A Morgan, M Fouchard, J Bernard, M Feldman, R B Herberman
Journal: JNCI Journal of the National Cancer Institute (1985)

The cell surface antigens and specificity of cultures of human natural killer (NK) cells, propagated in the presence of interleukin 2, were analyzed at the single-cell level. With the use of a micropipette isolation procedure, clones were initiated from cells of defined phenotype. The cell surface markers on the resultant clones were not stable and often diverged from those on the cells selected for initiation. Clones manifesting NK activity had low expression of T4 and T8 and most had some expression of T10, whereas clones without detectable cytotoxic activity had a considerable proportion of cells expressing T4 and/or T8 antigens. Within a cytotoxic clone, single cells shown to have killer activity were shown to express often T10 and infrequently T8; T4 was not detected on any of the reactive cells examined. The NK, reactive cells were found to express also antibody-dependent cell-mediated cytotoxicity and lectin-dependent cell-mediated cytotoxicity (LDCC), and some of the individual NK cells were shown to have the ability to lyse more than one type of target cell. However, there appeared to be considerable heterogeneity among the cells in the clones, with only 50-60% of cells displaying lytic activity against K562 cells at a given time. In addition, one cytotoxic clone appeared to have specific immune alloreactivity as well as NK and LDCC activities. The results of this study indicated that the cell surface phenotype and specificity of cytotoxic reactivity of cultured human NK cells were heterogeneous and suggested that such heterogeneity may be due to variations in the levels of differentiation and/or activation.
275. Pancreatic Transdiffereniation of Human Hepatocytes in the Livers of a Humanized Mouse Model
Authors: Binhai Ren, Bronwyn A. O'Brien, Ian E. Alexander, Najah T. Nassif, Yi Tan, Rosetta Martiniello-Wilks, Ann M. Simpson
Journal: Molecular Therapy (2015)

Type I diabetes (TID) results from the T-cell mediated autoimmune destruction of the insulin producing pancreatic beta (β) cells. Exogenous insulin therapy cannot achieve precise physiologic control of blood glucose concentrations and debilitating complications develop, which greatly increase morbidity and mortality for patients. Gene therapy is one strategy that holds considerable promise to cure TID. In earlier studies using an improved surgical technique that isolates the liver from the circulation, we introduced furin-cleavable human insulin (INS-FUR) to the livers in several animal models of diabetes. Reversal of diabetes with normal glucose tolerance and pancreatic transdifferentiation of the liver tissue was seen in streptozotocin (STZ)-diabetic Wistar rats, non-obese spontaneous diabetic mice and pancreatecomised diabetic pigs using the HMD lentiviral vector to deliver the INS-FUR. The aims of the present study were (1) to determine if STZ-diabetes could be reversed in the FRG mouse model in which chimeric mouse-human livers can be readily established, and (2) to determine if pancreatic transdiffereniation was evident in the engrafted human hepatocytes. Successful engraftment of human hepatocytes was verified by measurement of human albumin levels and diabetes was subsequently induced by STZ. Following delivery of the INS-FUR vector (3.5×108 transduction units) to overtly diabetic FRG mice (blood glucose >13mM), mice were monitored for changes in body weight and blood glucose levels. Reversal of diabetes was seen for a period of 2 months, which was the experimental endpoint. Intraperitoneal glucose tolerance tests (IPGTTs) of the INS-FUR-transduced animals were not significantly different from nondiabetic, control animals. RT-PCR showed expression of human insulin, glucagon and somatostatin and a number of human β-cell transcription factors, including Pdx1, Neurod1 and Neurogenin 3, indicating pancreatic transdifferentiation of hepatocytes in vivo. Double fluorescent staining for human albumin and insulin was seen in transduced liver samples. We have shown, for the first time that using our technology, human hepatocytes can be induced to undergo pancreatic transdiffereniation in vivo. These human hepatocytes have likely contributed to the reversal of diabetes seen in the animals. Our data suggest that this regimen may ultimately be employed clinically to cure TID.
Holding chamber (Spacer) - A potential harbor of pathogenic bacteria
Authors: Aditya Agrawal, Girija Nair, Abhay Uppe, Unni Baby
Journal: European Respiratory Journal (2014)

Introduction: The microbiome of a lung in a patient with obstructive airway is hitherto not defined. Conventional bacterial cultures have always shown that the lower respiratory tract is sterile. Potentially pathogenic bacteria when inhaled in a plume of inhaled medication, could infect the airways and cause an infective exacerbation of airway diseases.  Aim: To identify bacterial species growing on the inside of a holding chamber.  Methods: 52 patients with chronic stable obstructive airway disease using a metered dose inhaler with a spacer, attending our outpatient clinic were recruited. With all aseptic precautions a swab was taken and gram staining, microscopy and plate culture were performed.  RESULTS: The surfaces of 59.61% (31/52) spacers were sterile. 28.84% (15/52) had growth of the environmentally ubiquitous micrococci on the surface. 5.77% (3/52) had growth of Staphylococcus aureus of which 1 was Methicillin Resistant S. aureus (MRSA). Pseudomonas aeroginosa, Escherichia coli and Acinetobater were found on 1.9% (1/52) devices.  Conclusion: Most spacer surface are sterile or have presence of non-pathogenic micrococci. These potentially pathogenic bacteria are not a part of the microbiome in normal healthy individuals less so in those with airway diseases. Inhalation of these bacteria increases risk of infective exacerbation. Each exacerbation permanently reduces lung functions. Prevention of infections will limit loss of airway function and achieve better control of the disease.  Hence, we propose frequent cleansing, minimal handling, use of alcohol wipes to clean the inner surface of a spacer at least once a week and frequent replacement of the device.
The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis
Authors: C.G. Rusthoven, R.A. Rabinovitch, B.L. Jones, M. Koshy, A. Amini, N. Yeh, M.W. Jackson, C.M. Fisher
Journal: Annals of Oncology (2016)
Combined continuous infusion etoposide with high-dose cyclophosphamide for refractory neuroblastoma: a phase II study from the Société Française d'Oncologie Pédiatrique.
Authors: V Méresse, G Vassal, J Michon, C De Cervens, B Courbon, H Rubie, Y Perel, J Landman, P Chastagnier, C De Valck
Journal: Journal of Clinical Oncology (1993)

PURPOSE Patients older than 1 year with stage IV neuroblastoma who fail to achieve complete remission (CRem) have a particularly poor long-term prognosis. In an attempt to improve the outcome of these refractory patients, we tested a new drug combination. PATIENTS AND METHODS Twenty-nine children with advanced neuroblastoma (27 stage IV and two stage III) were entered onto this phase II study. All were refractory to conventional chemotherapy and had measurable disease at the time of the trial. The regimen was a combination of high-dose cyclophosphamide (2 g/m2/d) on days 2, 3, and 4, and etoposide (VP16; 50 mg/m2/d) by continuous intravenous (IV) infusion on days 1 to 5. A pharmacokinetic study of VP16 was conducted in eight patients to determine whether the goal of persistent plasma levels between 1 and 5 micrograms/mL was achieved. RESULTS Patients received a median of two courses, for a total of 58 courses. The median interval between each course was 32 days. In the 28 assessable patients, the overall response rate was 43%, with one CRem and 11 partial remissions (PRems). No life-threatening complication was observed in these heavily pretreated patients. The median duration of neutropenia (&lt; 5 x 10(9)/L) was 14 days, and that of thrombocytopenia (&lt; 50 x 10(9)/L) was 11 days. The overall incidence of sepsis was 27%. Gastrointestinal toxicity was frequent, but mild. Electrolyte disturbance with antidiuretic hormone (ADH)-like syndrome occurred in eight courses, but resolved rapidly. Grade &gt; or = 2 hemorrhagic cystitis was observed in three courses. No cardiac toxicity was observed. There were no treatment-related deaths. Pharmacokinetic analysis showed that mean steady-state plasma levels (Css) of VP16 were greater than 1 microgram/mL during all the courses. CONCLUSION This new drug combination appears to be effective in advanced neuroblastoma. Its toxicity remains manageable, with no life-threatening complications. Further evaluation in patients with less-advanced disease is warranted.
Abstract MP063: The Effects of Lifestyle Interventions on Fruit and Vegetable Intake Assessed by Serum Carotenoids and Self-Report: Results from the PREMIER Trial
Authors: Jessie Parker, Liwei Chen, Diane C Mitchell, Hsin-Chieh Yeh, Cheryl Anderson, Lawrence J Appel
Journal: Circulation (2012)

Background Trials that attempt to increase fruit and vegetable (F/V) intake commonly rely on self-reported dietary intake data that are prone to bias. Our primary objective was to assess the magnitude of the effect of a dietary intervention on F/V consumption, using two different measures: serum carotenoids and 24-hour dietary recall. A secondary goal was to explore the use of serum carotenoid levels as an indicator of F/V consumption. Methods Three intervention groups in the PREMIER trial (n=554) consisted of an Advice Only control group, an Established group that received counseling on weight loss, physical activity and sodium reduction (but no advice on F/V intake), and an Established +DASH group that also received counseling on the DASH diet (with advice to increase F/V intake). Self-reported F/V consumption was measured via two 24-hour dietary recalls administered at baseline, 6- and 18-months. Serum carotenoids were collected via fasting blood samples at each time point. Linear mixed models were used to examine the relationship between intervention assignment and F/V consumption. Pearson correlation and ROC curves informed the secondary objective. Results Compared to the control group, F/V consumption was highest in the Established+DASH group measured by recall (2.95 servings greater, 95% CI 2.43 to 3.47) and serum carotenoids (20.51 ug/dl greater, 95% CI 12.72 to 28.29). However, only 34% (57/167) of the Established+DASH group met the recommended level of 9 servings of F/V per day at 6 months. F/V intake and serum carotenoid levels were similarly and modestly correlated across each time point, ranging from .34 to .42. ROC curves indicated poor or fair performance of carotenoids as indicators of adequate F/V consumption. The area under the curve (AUC) was .692 for 5 servings of F/V, and .697 for 9 servings. Conclusions The PREMIER dietary intervention was successful in increasing F/V consumption as measured by serum carotenoids or self-report, but only a minority of study participants achieved recommended levels. Table 1. Mean fruit and vegetable consumption over study duration, by intervention assignment Intervention Assignment Advice Only (n 1 =186) Established (n=185) Established +DASH (n=183) p-value 2 24-Hour Recall (servings/day: mean, SD) 18 months 4.6 (2.7) 4.8 (2.5) 7.5 (3.5) &lt;.001 Total Carotenoid Levels 3 (ug/dl: mean, SD) 18 months 61.1 (37.0) 63.8 (38.3) 79.8 (49.2) &lt;.001 Total Carotenoid Levels+Lycopene, (ug/dl: mean, SD) 18 months 85.4 (41.3) 85.3 (40.1) 102.3 (51.4) &lt;.001 1 Sample sizes are from baseline visit 2 P-values correspond to difference in mean values across intervention groups 3 Total carotenoids defined as the sum of -carotene, -carotene, -cryptoxanthin and lutein/zeaxanthin
Differing Perspectives on Breast Cancer Chemoprevention—Reply
Authors: Steven A. Narod
Journal: JAMA Oncology (2016)

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Phase III trial of adjuvant capecitabine/cisplatin (XP) versus capecitabine/cisplatin/RT (XPRT) in resected gastric cancer with D2 nodal dissection (ARTIST trial): Safety analysis
Authors: J. Lee, W. Kang, D. Lim, J. Park, Y. Park, H. Lim, T. Sohn, J. Noh, J. Bae, S. Kim
Journal: Journal of Clinical Oncology (2009)

4537 Background: Although the adjuvant chemoradiation therapy has gained popularity and has become the standard of care in patients with resected gastric cancer in U.S., the role of chemoradiation therapy after extended D2 dissection has been questioned. We conducted a phase III trial to compare capecitabine/cisplatin (XP) vs XP + radiotherapy (RT) in curatively D2 resected gastric cancer patients in terms of disease free survival and overall survival. Methods: Eligibility criteria were as follows: stage Ib (T1N1, T2bN0) - IV (M1 excluded), curatively ≥ D2 resected gastric adenocarcinoma. XP only: X 2,000 mg/m 2 /d D1∼14, CDDP 60 mg/m 2 D1 repeated every 3 weeks, 6 cycles; XP + RT: X 2,000 mg/m 2 /d D1∼14, CDDP 60 mg/m 2 D1 x 2 cycles ⋄ RT 45 Gy (25 fractions) + X 1,650 mg/m 2 /d during RT ⋄ X 2,000 mg/m 2 /d D1∼14, CDDP 60 mg/m 2 D1 x 2 cycles. The primary endpoint is 3-year disease-free survival. Results: From October 2004 to April 2008, 458 patients (XP arm: 228 patients; XP/RT arm: 230 patients) were enrolled. In XP arm, 172 (75%) of 228 enrolled patients completed 6 cycles of chemotherapy. In XP + RT arm, 188 (82%) of 230 patients completed the full course of XP 2 cycles - X + RT - XP 2 cycles. Conclusions: Safety and feasibility analysis of the two arms will be reported at the meeting. No significant financial relationships to disclose.
Effects of PKC beta inhibitor enzastaurin on chemoresistant ovarian cancer cell lines
Authors: I. Meinhold-Heerlein, K. Bräutigam, D. Bauerschlag, N. Maass, C. Mundhenke, C. von Kaisenberg, T. Schollmeyer, W. Jonat, N. Arnold, T. Bauknecht
Journal: Journal of Clinical Oncology (2007)

16030 Background: Enzastaurin (LY317615.HCl), a selective inhibitor of protein kinase C beta II (PKCβII), leads to apoptosis and suppression of angiogenesis and represents a promising drug for clinical development. The effects of Enzastaurin were investigated utilizing the ovarian cancer cell line HEY and several chemoresistant subclones. Methods: The cell line HEY was used to develop subclones with selective resistance against cisplatin, etoposide, docetaxel, paclitaxel, gemcitabine, and pemetrexed. PKCβII expression was determined by immunoblotting and RT-PCR analyses. The platin-sensitive ovarian cell line IGROV1 with high expression of PKCβII served as control. All cell lines were exposed to 5 μM Enzastaurin for up to three hours. Immunoblotting analyses determined the expression of Enzastaurin targets PKCβII and glycogen synthase kinase 3β (GSK3β). Proliferation and apoptosis induction after Enzastaurin treatment was evaluated using MTT assay and DAPI staining. Results: All resistant cells showed a significantly higher expression of phosphorylated GSK3β than the parental cells. The highest expression level was detected in cisplatin- and paclitaxel-resistant cells. A decrease of phosphorylation occurred after exposure to Enzastaurin for 30 minutes, most obvious in parental, cisplatin- and gemcitabine-resistant cells. Proliferation and apoptosis assays demonstrated the paclitaxel and docetaxel resistant cells as the most sensitive cells. In contrast, cisplatin-resistant cells exhibited the highest resistance. Enzastaurin resistance also correlated with elevated PKCβII expression. Conclusion: The results indicate that ovarian cell lines with high expression of phosphorylated GSK3β display also a strong dephosphorylation. Though in these cell lines the inhibitory effect of Enzastaurin is most prominent, cell proliferation is hardly affected, nor apoptosis is accelerated. There is cross-resistance between platinum and Enzastaurin in some cell lines; however Enzastaurin demonstrated promising activity against taxane resistant cell lines. [Table: see text]
Minimal Residual Disease by Multiparametric Flow Cytometry Predicts Relapse Free Survival better than Over-Expression of WT1 and BAALC in Acute Myeloid Leukemia
Authors: Syed Khizer Hasan, Nikhil V Patkar, Devanand Vishwakarma, Deepen Rajamanickam, Arvind Sahu, Prashant Tembhare, Sadhna Kannan, Sumeet Gujral, Bhausaheb Bagal, Hari Menon, Manju Sengar, Pratibha Kadam Amare, PG Subramanian, Navin Khattry
Journal: Blood (2014)