tbuckley/cabot-search huggingface dataset:
Abstract 17204: Nucleostemin and Nucleophosmin Express with Up-regulating Telomere Reverse Transcriptase in the Arteriosclerotic Lesions
Authors: Kunimitsu Iwai, Tazuo Okuno, Takurou Morita, Osamu Iritani, Masasi Okuro, Shigeto Morimoto
Journal: Circulation (2014)

Introduction: Nucleostemin (NS) and nucleophosmin (NPM) are the nucleolar proteins which not only regulate the proliferation of stem cells, but also protect myocardial cells from oxidative stress. Hypothesis: We hypothesize that NS and NPM regulate the proliferation of the arterial smooth muscle cell (SMC) and contribute to their survival in the process of arteriosclerosis. This study investigated for the first time the expression pattern of them and consider their roles in arteriosclerosis. Methods and Results: Immunohistochemical examination revealed the expression of NS and NPM in the nuclei of SMCs and endothelial cells (ECs) both in the media and the intima of the human autopsy coronary arteries and the aorta of the apo E-deficient mice. Immunoreactivity was especially strong in the SMCs and ECs constructing the fibrous cap covering the plaques. The immunoreactivity of telomere reverse transcriptase (TERT) was at once observed in these NS- and NPM-positive nuclei, indicating of the strong proliferating activities. In the fibro-muscular proliferating intima after denudation of the endothelium of rat abdominal aorta confirmed the same localization of NS and NPM with TERT. In order to investigate the roles of NS in the SMC, mRNA of NS was knocked down with siRNA in cultured human arterial SMC. The 47S ribosomal RNA reduced to 35%, without reducing 18S ribosomal RNA (real-time PCR), indicating the promoting effect of NS on the pre-ribosomal RNA processing necessary for total protein synthesis. Knocking down of NS mRNA also reduced the expression of TERT to 65% and on the contrary up-regulated p21 mRNA to 150%, indicating anti-senescence activity of NS. Subculture of human SMCs ultimately to the replicative senescence gradually reduced the number of NS positive nucleoli from four to only one per cell, maybe reflecting the reduced activity of NS in the senescence process. Conclusion: These results indicate that NS and NPM promote the proliferation of arterial SMCs and ECs in the arteriosclerotic lesions, collaborating with TERT.
Predictors of outcome in ICU patients with septic shock caused by Klebsiella pneumoniae carbapenemase–producing K. pneumoniae
Authors: M. Falcone, A. Russo, A. Iacovelli, G. Restuccia, G. Ceccarelli, A. Giordano, A. Farcomeni, A. Morelli, M. Venditti
Journal: Clinical Microbiology and Infection (2016)
Osteosarcoma: good news despite crude tools.
Authors: J V Simone, W H Meyer, M P Link
Journal: Journal of Clinical Oncology (1992)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.1.1 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1727911 Osteosarcoma: good news despite crude tools. J V SimonexJ V SimoneSearch for articles by this author , W H MeyerxW H MeyerSearch for articles by this author , M P LinkxM P LinkSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.1.1 PDF "Osteosarcoma: good news despite crude tools.." Journal of Clinical Oncology, 10(1), pp. 1–2© 1992 by American Society of Clinical Oncology
Abstract P223: Larger Effect Sizes of Established BMI Genetic Variants During Adolescence, a Vulnerable Period of Weight Gain
Authors: Mariaelisa Graff, Kari E North, Karen L Mohlke, Leslie A Lange, Ethan M Lange, Caroline S Fox, L. A Cupples, Kathleen M Harris, Penny Gordon-Larsen
Journal: Circulation (2012)

In the past five years genome-wide association studies (GWAS) have identified common genetic loci associated with body mass index (BMI) mainly in European middle-aged adult populations. The influence of these loci in adolescence, a period of risk for weight gain, and whether there are different associations across adolescent groups at highest risk (e.g., ethnic minority populations), remains largely unknown. We examined whether obesity susceptibility loci identified from previous GWAS in adults were associated with BMI in an ethnically diverse adolescent cohort. Using 8918 participants from the National Longitudinal Study of Adolescent Health, or Add Health (aged 12-21 years in 1996, 52.6 % female), we assessed the association of 43 SNPs, selected based on statistical significance in previous GWAS, with BMI across four ethnic US subpopulations (5,296 European Americans, EA, 1,815 African Americans, AfA, 1,356 Hispanic Americans, HA, and 451 Asian Americans, AsA). Buccal cells from participants were extracted and genotyped using TaqMan (sample call rate: 97.5%, SNP call rate: 100%). Inverse normal transformed BMI residuals, adjusted for gender and age, were used in ethnicity-stratified models with SNPs in PLINK, assuming an additive model. An inverse-variance-weighted meta-analysis was used to combine results across the 4 ethnic groups. Average BMI across all ethnic groups was 23.6±5.2 kg/m2, ranging from 22.6±5.2 kg/m2 in AsA to 24.3±5.8 kg/m2 in AfA. The effect estimates for all 43 SNPs were directionally consistent across ethnicity with previously published results. Of the 43 SNPs, 20 were associated with BMI at p&lt;0.05 in the meta-analysis (17 in EA, 7 in AfA, 4 in HA, and 5 in AsA). Based on t-test comparisons, 16 of the 20 SNPs had larger and 2 loci had smaller effect sizes (p&lt;0.05) in the Add Health adolescent sample than published effect sizes for BMI in adults. Only FTO (rs9939609) showed significant heterogeneity across ethnicity (p=0.01 for I2=73.5). TMEM18 (rs6548238, meta-analysis p-value p=1.32E-10), had one of the largest differences in effect size compared to middle-aged European adults (Willer et al 2009) with a per allele increase of 0.70±0.11 kg/m2 in this sample versus 0.26±0.07 kg/m2 in adults (beta[SE] difference = 0.44[0.08]; p=1.4E-08). Variants associated with BMI in adults were also associated with BMI in adolescents, with some comparatively larger effects during this vulnerable period. R01HD057194
Molecular mechanisms of pirfenidone activity in human lung fibroblasts
Authors: Enrico Conte, Mary Fruciano, Elisa Gili, Evelina Fagone, Maria Iemmolo, Carlo Vancheri
Journal: European Respiratory Journal (2014)

Pirfenidone is a broad-spectrum anti-inflammatory and anti-fibrotic molecule that has been shown to inhibit the fibrosis progression in animal models and in patients with idiopathic pulmonary fibrosis. Even though the anti-fibrotic and anti-inflammatory properties of pirfenidone are well established both in vitro and in vivo, its molecular targets and mechanisms of action have not been elucidated.

In this research, we investigated the effects of pirfenidone on proliferation, TGF-β-induced differentiation and fibrogenic activity of primary human lung fibroblasts (HLFs), and related molecular mechanisms.

HLF cultures were established from surgical specimens and used up to passage eight. After 24 h serum starvation, cells were grown for 48h in 2% FCS medium resting or treated with pirfenidone (0.16-1.6 mM) in the absence or presence of TGF-β (5 ng/mL) added at the same time as pirfenidone treatment. Cell proliferation was evaluated by cell count as well as a BrdU incorporation assay. The expression levels of α-smooth muscle actin (SMA) and pro-collagen (Col)-I were evaluated by quantitative RT-PCR and western blot. Phosphorylation status of Smad3, p38, and Akt was assessed by specific immunoblot.

Pirfenidone significantly inhibited fibroblast proliferation and attenuated TGF-β-induced α-SMA and Col-I expression at both mRNA and protein levels. Moreover, pirfenidone reduced TGF-β-induced phosphorylation of Smad3, p38, and Akt, key mediators of the TGF-β pathway.

Considered together, these results demonstrate that pirfenidone regulates HLF proliferation and TGF-β-mediated differentiation into myofibroblasts as well as fibrogenic activity by inhibiting key TGF-β-induced signaling pathways' activation.
Abstract P242: Measuring Frailty in Heart Failure: A Community Perspective
Authors: Sheila M McNallan, Alanna M Chamberlain, Yariv Gerber, Mandeep Singh, Susan A Weston, Ruoxiang Jiang, Veronique L Roger
Journal: Circulation (2012)

Objective: To compare two measures of frailty in a community cohort of heart failure (HF) patients. Background: Frailty is increasingly recognized as an important prognostic indicator in HF. Several methods have been proposed to measure frailty. Some conceptualize frailty as a biological phenotype, while others define it as an accumulation of deficits (impairments, disabilities, comorbid diseases), termed the Cumulative Deficit Index (CDI). Each approach has conceptual strengths and limitations; a distinct feature of the CDI is the ability to extract data from medical records. These two methods have never been compared in a community HF cohort. Methods: Olmsted, Dodge and Fillmore County, MN residents with HF between 10/2007 and 12/2010 were prospectively recruited to assess the frailty phenotype. The biological frailty phenotype was defined as ≥3 of the following: unintentional weight loss &gt;10 lbs. in 1 year, physical exhaustion, weak grip strength, and slowness and low activity measured by the SF-12 physical component score. Intermediate frailty was defined as having 1–2 components. The CDI was based on 33 deficits and defined as the proportion of deficits present for each patient. Results: Among 131 patients (mean age 70.5±14, 62% male), according to the biological frailty phenotype definition 18% were frail, 50% intermediate frail and 31% not frail. The CDI ranged from 0.03–0.70, with a mean (SD) of 0.22 (0.12). The CDI was significantly correlated with the frailty phenotype (r=0.59, p&lt;0.001). The mean (SD) of the CDI was 0.35 (0.14), 0.21 (0.10) and 0.15 (0.07) among the frail, intermediate frail and not frail phenotypes (Figure). Conclusion: The CDI is significantly associated with the biological frailty phenotype and can thus be used as an alternative approach to measure frailty in HF. As the components of the biological frailty phenotype are not routinely assessed clinically, the CDI, which can be ascertained from medical records, is a feasible approach to ascertain frailty in large cohorts.
WITHDRAWN: Amelioration of unesterified cholesterol accumulation by multi-lactose appended β-cyclodextrin in NPC-like HepG2 cells
Authors: Rena Nishiyama, Yumi Hirai, Keiichi Motoyama, Taishi Higashi, Yoichi Ishitsuka, Yuki Kondo, Tetsumi Irie, Takumi Era, Hidetoshi Arima
Journal: Asian Journal of Pharmaceutical Sciences (2015)
Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer
Authors: Sunil R. Hingorani, William P. Harris, J. Thaddeus Beck, Boris A. Berdov, Stephanie A. Wagner, Eduard M. Pshevlotsky, Sergei A. Tjulandin, Oleg A. Gladkov, Randall F. Holcombe, Ronald Korn, Natarajan Raghunand, Samuel Dychter, Ping Jiang, H. Michael Shepard, Craig E. Devoe
Journal: Clinical Cancer Research (2016)

Abstract Purpose: This phase Ib study evaluated the safety and tolerability of PEGylated human recombinant hyaluronidase (PEGPH20) in combination with gemcitabine (Gem), and established a phase II dose for patients with untreated stage IV metastatic pancreatic ductal adenocarcinoma (PDA). Objective response rate and treatment efficacy using biomarker and imaging measurements were also evaluated. Experimental Design: Patients received escalating intravenous doses of PEGPH20 in combination with Gem using a standard 3+3 dose-escalation design. In cycle 1 (8 weeks), PEGPH20 was administrated twice weekly for 4 weeks, then once weekly for 3 weeks; Gem was administrated once weekly for 7 weeks, followed by 1 week off treatment. In each subsequent 4-week cycle, PEGPH20 and Gem were administered once weekly for 3 weeks, followed by 1 week off. Dexamethasone (8 mg) was given pre- and post-PEGPH20 administration. Several safety parameters were evaluated. Results: Twenty-eight patients were enrolled and received PEGPH20 at 1.0 (n = 4), 1.6 (n = 4), or 3.0 μg/kg (n = 20), respectively. The most common PEGPH20-related adverse events were musculoskeletal and extremity pain, peripheral edema, and fatigue. The incidence of thromboembolic events was 29%. Median progression-free survival (PFS) and overall survival (OS) rates were 5.0 and 6.6 months, respectively. In 17 patients evaluated for pretreatment tissue hyaluronan (HA) levels, median PFS and OS rates were 7.2 and 13.0 months for “high”-HA patients (n = 6), and 3.5 and 5.7 months for “low”-HA patients (n = 11), respectively. Conclusions: PEGPH20 in combination with Gem was well tolerated and may have therapeutic benefit in patients with advanced PDA, especially in those with high HA tumors. Clin Cancer Res; 22(12); 2848–54. ©2016 AACR.
Abstract MP42: The Potential Impact of Food Taxation and Subsidies on Cardiometabolic Mortality in The US
Authors: Jose L Penalvo, Ashkan Ashkin, Frederik Cudhea, Colin D Rehm, Gitanjali M Singh, Dariush Mozaffarian
Journal: Circulation (2015)

Penalvo JL, Asfhin A, Rehm CD, Cudhea F, Singh G, Mozaffarian D Tufts Friedman School of Nutrition Science and Policy, Boston MA-02111 Background: Food-specific taxes and subsidies have been proposed as a strategy for the prevention of cardiometabolic diseases (CMD). However, the potential impact of such policies on CMD-mortality in the US, and heterogeneity by age, sex, and race have not been quantified. Aim: To estimate the number of CMD-deaths prevented by the introduction of fiscal interventions on food items related with CMD. Methods: We conducted a Comparative Risk Assessment analysis to estimate the impact of a 10% subsidy for fruits, vegetables, whole grains, and nuts and a 10% tax on processed and unprocessed red meat on deaths due to CMD in the US. Dietary intakes in 2010 by age, sex, and race, were determined from NHANES based on two 24-h recalls. Age-specific, diet-disease relative risks, were derived from meta-analyses (2013 Global Burden of Diseases study). Age, sex, and race-stratified deat...
Evaluation of a temporary vaccination recommendation in response to an outbreak of invasive meningococcal serogroup C disease in men who have sex with men in Berlin, 2013–2014
Authors: Judith Koch, Wiebke Hellenbrand, Susanne Schink, Ole Wichmann, Andreas Carganico, Jochen Drewes, Martin Kruspe, Marlen Suckau, Heike Claus, Ulrich Marcus
Journal: Eurosurveillance (2016)

Meningococcal serogroup C (MenC) vaccination of men who have sex with men (MSM) was temporarily recommended to control an outbreak of invasive MenC disease among MSM in Berlin in 2012-2013. Vaccination was offered to HIV-infected MSM free of charge; others had to request reimbursement or pay out of pocket. We aimed to assess (i) awareness and acceptance of this recommendation through an online survey of MSM, (ii) implementation through a survey of primary care physicians and analysis of vaccine prescriptions, and (iii) impact through analysis of notified cases. Among online survey respondents, 60% were aware of the recommendation. Of these, 39% had obtained vaccination (70% of HIV-infected, 13% of HIV-negative/non-tested MSM). Awareness of recommendation and vaccination were positively associated with HIV infection, primary care physicians' awareness of respondents' sexual orientation, and exposure to multiple information sources. Most (26/30) physicians informed clients about the recommendation. Physicians considered concerns regarding reimbursement, vaccine safety and lack of perceived disease risk as primary barriers. After the recommendation, no further outbreak-related cases occurred. To reach and motivate target groups, communication of a new outbreak-related vaccination recommendation should address potential concerns through as many information channels as possible and direct reimbursement of costs should be enabled.
When Physicians and a Parent Conflict on When to Limit Treatment for a Child With Significant Disabilities
Authors: Teresa A. Savage, Debra M. Michalak
Journal: The American Journal of Bioethics (2016)

My approach as an ethics consultant would be to meet with JR and Marcy and hear why JR opposes further treatment. I would also want to meet with the people who have been treating Marcy and know her...
Final STEPP results of prophylacatic versus reactive skin toxicity (ST) treatment (tx) for panitumumab (pmab)-related ST in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: E. P. Mitchell, M. Lacouture, H. Shearer, N. Iannotti, B. Piperdi, M. Pillai, F. Xu, M. Yassine
Journal: Journal of Clinical Oncology (2009)

CRA4027 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
Evaluation of cost-effectiveness of early KRAS testing in high-risk recurrence colorectal cancer patients in Italy.
Authors: Carmine Pinto, Carlo Barone, Nicola Normanno, Francesco Cognetti, Alfredo Falcone, Lorenzo Capussotti, Lorenzo Mantovani
Journal: Journal of Clinical Oncology (2012)

e14113 Background: KRAS testing is relevant for the choice of the most appropriate first-line therapy for metastatic colorectal cancer (CRC) patients (pts). Early KRAS testing in surgically resected CRC pts at high risk of recurrence might result cost-effective when the results of KRAS test are not available in acceptable time following the diagnosis of metastatic disease. Methods: This study adopted the Delphi technique to reach a consensus to define high risk recurrence CRC and KRAS test optimal timing. We used validated decision analyses models employed by technology assessment agencies (NICE and SMC) for the assessment of KRAS wild-type CRC pts. Alternative therapeutic strategies include FOLFOX4, FOLFIRI, FOLFOX4 + cetuximab, FOLFIRI + cetuximab, FOLFOX4 + bevacizumab. We adapted the models to take into account early KRAS testing in high risk pts for which the test would not be available on time to drive appropriate treatment. The models have been populated with Italian specific cost data incorporating pts’ access schemes. Results: Issues related to KRAS testing were proposed to 108 Italian oncologists and pathologists through two subsequent questionnaires. The following parameters to define CRC pts at high risk of recurrence were identified: pT4, high grading, pN2, intestinal occlusion-perforation, isolated peritoneal carcinomatosis surgically removed and/or positive peritoneal washing and/or removed ovarian metastases. A time interval of more than 10-15 days for KRAS testing was defined as a limit for the therapeutic choices. Early KRAS testing in high risk CRC pts generates incremental cost effectiveness ratios between 6,000 and 13,000 Euro per quality adjusted life year (QALY) gained, depending on alternative treatment of choice. In extensive sensitivity analyses, ICER’s were always below 15,000 Euro per QALY gained, far within the 60,000 Euro/QALY gained threshold currently accepted in Italy. Conclusions: In metastatic CRC a time interval of more than 10-15 days for the response of KRAS testing limits the therapeutic choices. Early KRAS testing in high-risk CRC pts who would not have KRAS test in a reasonable time when they develop metastases is a cost effective strategy.
Epidemiology of triple negative breast cancer in Nigerian women
Authors: C. A. Adebamowo, T. Ogundiran, E. Akang
Journal: Journal of Clinical Oncology (2006)

10504 Background: The epidemiology and immunohistochemistry of breast cancer in indigenous African populations is not well known with many studies relying on small case series. In this communication, we report a preliminary report from our study of the immunohistochemistry of breast tumors in Nigeria, highlighting the epidemiological characteristics of the “triple-negative” breast cancers and comparing these with non-triple negative breast tumors. Methods: 111 consecutive breast cancer patients presenting at the Oncology Clinic of the University College Hospital had tumor biopsied and demographic and epidemiological information collected. Standard histological and immunohistochemical analysis was done for ER, PR and HER2 status. Results: Most tumors were ER+ (65%, 69/106), PR+ (60%, 56/94) and HER2 _ (91%, 82/90). 17% (13/76) of our patients had triple negative tumors. Patients with triple negative tumors were younger than those with triple negative (49.6 vs. 55.3 years p = 0.31), had shorter duration of symptoms (12.2 vs 20.7 months, p-value 0.18), later age at onset of menarche (17.4 vs 15.3, p-value = 0.25), lower BMI (27.2 vs 40.2, p-value = 0.01), greater height (157 vs 148 cm, p-value = 0.03), lower waist-hip ratio (0.84 vs 0.88, p-value = 0.16) and none of them had a positive family history of breast cancer. Conclusions: Contrary to previous reports, tumors in these African patients displayed immunohistochemical characteristics similar to those reported from Caucasian and other populations. Triple negative tumors were more likely to be associated with lower BMI and greater height, but more studies are needed. No significant financial relationships to disclose.
Effects of lanreotide autogel/depot (LAN) in pancreatic neuroendocrine tumors (pNETs): A subgroup analysis from the CLARINET study.
Authors: Alexandria T. Phan, Martyn E. Caplin, Marianne E. Pavel, Jaroslaw B Cwikla, Markus Raderer, Eva Sedláčková, Guillaume Cadiot, Edward M. Wolin, Jaume Capdevila, Lucy Wall, Guido Rindi, Alison Langley, Edda Gomez-Panzani, Philippe B. Ruszniewski
Journal: Journal of Clinical Oncology (2015)

233 Background: The prognosis for patients with metastatic pNETs is generally poor and current treatment options can be complicated by safety considerations. In CLARINET, progression-free survival (PFS) was significantly prolonged with the somatostatin analog LAN 120 mg vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67 &lt;10%) non-functioning enteropancreatic NETs (hazard ratio [HR] for progressive disease [PD]/death: 0.47 [95% CI: 0.30, 0.73]. Here, we more fully characterize treatment effects in the pNET subgroup. Methods: CLARINET was a 96-week randomized double-blind trial. Patients received LAN 120 mg or PBO every 4 weeks, administered by deep s.c. injection (NCT00353496). Subgroup analyses were undertaken to investigate only the consistency of treatment effects as the study was not otherwise designed or powered for such analyses. Results: 91 patients with pNETs received LAN (n=42) or PBO (n=49). At baseline, mean age was 64 years in both groups; overall, 37% had hepatic tumor loads &gt;25%, 95% had stable disease, 77% had received no previous treatment, and 38% had had previous surgery on the tumor. Median PFS in the pNET subgroup was not reached at study end with LAN vs. 12.1 months [95% CI: 9.4, 18.3] with PBO (HR for PD/death: 0.58 [0.32, 1.04]). (Median PFS for LAN at first planned analysis in the open-label extension study was 29.7 months [12.0, 32.4].) The incidence of adverse events (AEs) in the core study was 88% with both LAN and PBO, and the most common AE was diarrhea (LAN, 43%; PBO, 37%). Treatment-related AEs occurred in 55% of the LAN group and 24% of the PBO group. Serious AEs (SAEs) occurred in 29% vs. 43%, respectively; only three of these patients had treatment-related SAEs (two with LAN, one with PBO). Two patients in each group had AEs leading to withdrawal. Conclusions: The evidence in the pNET subgroup suggesting antitumor effects with LAN together with the favorable long-term safety profile support a positive benefit:risk profile for LAN as a first-line treatment for pNETs. Clinical trial information: NCT00353496.