tbuckley/cabot-search huggingface dataset:
Heterogeneity of Epstein-Barr Virus Derived From a Nasopharyngeal Carcinoma That Has Transforming and Lytic Properties&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H Sato, T Takimoto, H Ogura, J Tanaka, M Hatano, R Glaser
Journal: JNCI Journal of the National Cancer Institute (1986)

The biological activities of Epstein-Barr virus (EBV) from a human epithelial hybrid cell line derived from a nasopharyngeal carcinoma (NPC-KT) were studied. low concentrations of virus from the NPC-KT cell line stimulated DNA synthesis of human cord blood lymphocytes (CBL) and induced CBL to form EBV nuclear antigen-positive continuous cell lines. The CBL exposed to higher doses of virus showed stimulated DNA synthesis 2 days after infection, followed by cell lysis. Virus from the NPC-KT cell line induced EBV-specific antigens in non producer Raji cells and reduced the colony-forming ability of the superinfected cells. The ratio of transforming activity to early antigen-inducing ability was not constant during cell passage. The data obtained suggest that NPC-KT clone 1 cells are producing virus with cytotoxic and transforming properties.
Abstract 16607: Pediatric-Onset Disease Does Not Herald Adverse Clinical Course in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Anneline S te Riele, Cynthia A James, Abhishek C Sawant, Brittney Murray, Crystal Tichnell, Ryan Tedford, Jane Crosson, Daniel P Judge, Hugh Calkins, Harikrishna Tandri
Journal: Circulation (2014)

Background: In most genetic cardiomyopathies, early disease onset heralds adverse clinical outcome. However, the clinical attributes and disease course in pediatric cases with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) are largely unknown. Objective: To delineate and compare the clinical characteristics, genetics, and outcome of pediatric-onset ARVD/C. Methods: We obtained detailed phenotypic, genetic, and outcome data of 316 subjects who presented alive and fulfilled diagnostic Task Force Criteria (TFC) for ARVD/C at last follow-up. Patients were grouped into pediatric (diagnosis at <18 years) and adult (diagnosis at ≥ 18 years) ARVD/C. Clinical outcomes regarding sustained ventricular arrhythmia, cardiac transplantation, and death were ascertained. Results: Among 316 definite ARVD/C cases, 43 (14%) were diagnosed prior to the age of 18 years. Pediatric cases were 22 (51%) males, with a mean age of 15.4 ± 1.8 years at time of diagnosis. Compared to adult cases, pediatric cases wer...
The impact of docetaxel (D) in an older population of patients with advanced prostate cancer (PC): A simulation study using TAX327 and SEER Medicare data
Authors: E. Onukwugha, C. D. Mullins, N. Obeidat, B. Seal, A. Hussain
Journal: Journal of Clinical Oncology (2009)

e16074 Background: The survival benefit of D in treatment of hormone refractory PC (HRPC) has been established in the TAX327 trial, but it is unclear how this benefit would translate in a heterogeneous population. This study sought to simulate the survival impact of D in a population of older pts with M1 PC on androgen deprivation therapy (ADT). Methods: A combination of TAX327 trial data and SEER-Medicare (SM) data were used. In pts age 69+ and randomized to D (every 3 weeks, D3P) or mitoxantrone (M), trial data showed a survival benefit for D. Accordingly, SM pts age 69+ diagnosed with M1 PC between 1994 and 2002 and receiving only ADT were selected. Graphical plots and statistical tests were used to find best-fitting parametric survival functions for D3P, M, and SM pts. The survival benefit for D was imposed on unadjusted and covariate-adjusted SM survival curves. The simulated benefit was assessed at 12 mos and 24 mos post-diagnosis of M1 PC in SM pts. Results: There were 326 TAX327 trial pts (D3P = 159, M = 167) used in the analysis. Median survival was 15.7 mos (12.6 - 19) in the M arm and 18.9 mos [17 - 21.8] in the D3P arm (p = 0.03). There were 3,515 SM pts, based on inclusion criteria. Median survival benefit of D was 3.2 mos based on Kaplan-Meier estimates and 2.4 mos using parametric curves in the TAX327 69+ group. Following covariate-adjustment in the SM sample, at 12 mos post-diagnosis, the median survival in mos was 61.7 (CI 36.3 - 87) in the ADT group and 62 (CI 37.6 - 87.1) in the simulated ADT+D group (i.e., 0.3 mos simulated benefit of D). A 0.8 mos simulated benefit was found if D was initiated 24 mos post diagnosis (in pts more likely to have HRPC). Conclusions: The survival benefit of docetaxel from the TAX327 trial is attenuated in a heterogeneous SEER-Medicare sample, and the simulated survival benefit is larger among patients who are more likely to have hormone refractory prostate cancer. [Table: see text]
Aspirations and Strategies for Public Health
Authors: Sandro Galea, George J. Annas
Journal: JAMA (2016)

Public health is responsible for extraordinary achievements over the past century, such as remarkable gains in life expectancy and substantial decreases in infectious disease mortality, and could make similar critical contributions to health in this century.Public health should be ascendant, but ample evidence suggests that it is on the defensive today, underappreciated, and underfunded.Government actions to improve the health of populations are widely suspect, as illustrated by the controversies involving efforts to curb soda container sizes in New York City, state and federal efforts to limit reproductive health rights, and global efforts to address climate change.By contrast, traditional medicine continues to be privileged.The burgeoning precision medicine agenda and the continuing emphasis on the treatment for cancer have captured the imagination of funding agencies and politics at the highest levels.The result is diversion of resources in the direction of individualized efforts at disease prediction through genomic approaches, and away from the structural changes with broader population-based effects that have long characterized public health action.Public health is not alone, sharing funding and infrastructure deficiencies with transportation, education, and even public safety (eFigure in the Supplement).
Successful marrow transplantation for acute myelocytic leukemia following therapy for Hodgkin's disease.
Authors: R B Geller, G B Vogelsang, J R Wingard, A M Yeager, W H Burns, G W Santos, R Saral
Journal: Journal of Clinical Oncology (1988)

Five patients with acute myelocytic leukemia (AML) after combined modality therapy for Hodgkin's disease (HD) were treated with cyclophosphamide and busulfan followed by bone marrow transplantation (BMT). Four patients received allogeneic transplants from histocompatibility locus antigen (HLA)-compatible siblings and the fifth patient received an autologous marrow treated with 4-hydroperoxycyclophosphamide. Two patients died of complications of acute graft-v-host disease (GVHD) despite prophylaxis with either low-dose cyclophosphamide or cyclosporine. The remaining three patients were alive and disease-free 382, 617, and 620 days after transplant. These initial results are encouraging and more patients with treatment-related AML need to be evaluated with both allogeneic and autologous BMT to fully elucidate the potentially curative role of this intensive therapy in an otherwise fatal hematologic malignancy.
CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders
Authors: Xiuying Bai, Dengshun Miao, Sophia Xiao, Dinghong Qiu, René St-Arnaud, Martin Petkovich, Ajay Gupta, David Goltzman, Andrew C. Karaplis
Journal: Journal of Clinical Investigation (2016)

CYP24A1 (hereafter referred to as CYP24) enzymatic activity is pivotal in the inactivation of vitamin D metabolites. Basal renal and extrarenal CYP24 is usually low but is highly induced by its substrate 1,25-dihydroxyvitamin D. Unbalanced high and/or long-lasting CYP24 expression has been proposed to underlie diseases like chronic kidney disease, cancers, and psoriasis that otherwise should favorably respond to supplemental vitamin D. Using genetically modified mice, we have shown that renal phosphate wasting hypophosphatemic states arising from high levels of fibroblast growth factor 23 (FGF23) are also associated with increased renal Cyp24 expression, suggesting that elevated CYP24 activity is pivotal to the pathophysiology of these disorders. We therefore crossed 2 mouse strains, each with distinct etiology for high levels of circulating FGF23, onto a Cyp24-null background. Specifically, we evaluated Cyp24 deficiency in Hyp mice, the murine homolog of X-linked dominant hypophosphatemic rickets, and transgenic mice that overexpress a mutant FGF23 (FGF23R176Q) that is associated with the autosomal dominant form of hypophosphatemic rickets. Loss of Cyp24 in these murine models of human disease resulted in near-complete recovery of rachitic/osteomalacic bony abnormalities in the absence of any improvement in the serum biochemical profile. Moreover, treatment of Hyp and FGF23R1760-transgenic mice with the CYP24 inhibitor CTA102 also ameliorated their rachitic bones. Our results link CYP24 activity to the pathophysiology of FGF23-dependent renal phosphate wasting states and implicate pharmacologic CYP24 inhibition as a therapeutic adjunct for their treatment.
Phenotypic Manifestation of Genetic Risk for Schizophrenia During Adolescence in the General Population
Authors: Hannah J. Jones, Evie Stergiakouli, Katherine E. Tansey, Leon Hubbard, Jon Heron, Mary Cannon, Peter Holmans, Glyn Lewis, David E. J. Linden, Peter B. Jones, George Davey Smith, Michael C. O’Donovan, Michael J. Owen, James T. Walters, Stanley Zammit
Journal: JAMA Psychiatry (2016)

Schizophrenia is a highly heritable, polygenic condition characterized by a relatively diverse phenotype and frequent comorbid conditions, such as anxiety and depression. At present, limited evidence explains how genetic risk for schizophrenia is manifest in the general population.
Incidence of First-Line and Second-Line Myelodysplastic Syndrome in a US Commercial Claims Database
Authors: Christopher R. Cogle, Sandra E. Kurtin, Tanya GK Bentley, Michael S Broder, Eunice Chang, Moira E. Lawrence, Thomas J. McKearn, Scott Megaffin, Rita Percy, Michael E. Petrone, Gordon H Sun
Journal: Blood (2014)
Health-related quality of life (HRQOL) after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC).
Authors: S. Senan, C. Gundy, C. J. Haasbeek, B. J. Slotman, N. K. Aaronson, F. J. Lagerwaard
Journal: Journal of Clinical Oncology (2010)

7079 Background: In patients (pts) with stage I NSCLC who are unfit to undergo surgery, SBRT is a curative treatment which achieves local control rates of >85% in multicenter trials. grade ≥3 toxicity is uncommon after SBRT but HRQOL has not been well studied. However, HRQOL is often compromised in the first 6 months after surgery, and generally fails to return to baseline values, particularly in elderly pts [Schulte 2009]. We analyzed both HRQOL data and clinical outcomes after SBRT. Methods: HRQOL data was prospectively collected from 382 consecutive SBRT pts who were referred from 70 Dutch centers, using the EORTC QLQ-C30 and lung cancer modules. Mean age was 73 years. SBRT was delivered using 3-8 treatment fractions, depending on tumor size and location. HRQOL data were available prior to SBRT (baseline; n=382), at three (n= 282), six (n= 212) and twelve months (n= 144) after SBRT. Completeness of HRQOL data was 76%, 64% and 59% of all pts who were alive and without recurrence at 3, 6 and 12 months, respectively. Thoracic CT scans were performed during each follow-up visit. Results: Mean baseline global QoL and physical functioning scores were 62.9 ± 1.1 (SE of mean) and 61.7 ± 1.1, respectively. Highest baseline symptoms scores were seen for dyspnea (47.1 ± 1.7), fatigue (37.4 ± 1.3) and insomnia (21.1 ± 1.6). Median survival was 39.8 months, and correlated with baseline Charlson comorbidity score (p=0.01), lung function (p=0.03), performance status (p=0.05) and physical functioning (p=0.05). At 2 years after SBRT, local-, regional-, and distant control rates were 94.3%, 87.3% and 78.2%, respectively. Late grade 3 toxicity mainly consisted of chest wall pain (3%) and radiation pneumonitis (2%); rib fractures were observed in 1%. None of the functional or symptom scales showed a significant worsening at any of the follow-up time points. Conclusions: The baseline physical functioning and global QoL of pts referred for SBRT were far poorer than those reported in the surgical literature. However, HRQOL scores did not decline during the first year after SBRT. The observed local control rate of >90% is consistent with literature findings. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Varian Medical Systems Varian Medical Systems
2013 HIPAA Changes Provide Opportunities and Challenges for Researchers: Perspectives from a Cancer Center
Authors: Ralph S. Freedman, Scott B. Cantor, Kelly W. Merriman, Mary E. Edgerton
Journal: Clinical Cancer Research (2016)

Abstract In 2013, the U.S. Department of Health and Human Services modified the Health Insurance Portability and Accountability Act Privacy Rule to “strengthen privacy and security protections” while “improving workability and effectiveness to increase flexibility for and decrease burden on regulated entities.” In this article, we attempt to translate these generalized goals into the real-world implications of these changes. Under the new rules, researchers can obtain participants' permission to use their protected health information for more research activities with a single, upfront authorization (thereby reducing paperwork for participants, researchers, and institutional review boards) while providing potential participants with more information upon which to base their decisions about participation. The combined authorizations can be used in clinical trials and their optional substudies and in stand-alone biospecimen-banking research that includes authorization to permit future research use. We also suggest best practices for taking advantage of the flexibility offered by the new rules while maintaining strong privacy protections for human subjects. Clin Cancer Res; 22(3); 533–9. ©2016 AACR.
Abstract P269: Fasting HDL-C Partially Explains the Association of Postprandial Triglycerides and Coronary Artery Disease Detected by Computed Tomography Angiography
Authors: Henrique L Staniak, Wilson Filho, Marcio Miname, Isabela Benseñor, Paulo Lotufo, Rodolfo Sharovsky, Carlos Eduardo Rochitte, Marcio Bittencourt, Raul Santos
Journal: Circulation (2014)

Background: Postprandial triglycerides (TG) are associated with severe coronary artery disease (CAD), though the underlying mechanisms remain unclear. In this study, we have investigated the effect of clinical and laboratory parameters on the association between postprandial TG and CAD detected by coronary computed tomographic angiography (CTA). Methods: We enrolled 130 patients without previous diagnosis of CAD, (85 with CAD detected by CTA and 45 without); who underwent an oral fat tolerance test. We studied the postprandial lipemia measuring TG from time 0h, 2h, 4h and 6h to analyze the TG change over time. We used a longitudinal multivariable linear mixed effects model with the log of the TG (lnTG) as the primary outcome due to non normal distribution of TG. To evaluate the effect of the other parameters on the longitudinal changes in the TG, each variable has been individually included in the model to evaluate for changes in the lnTG over time. Results: Patients with CAD were older (56.5 ± 6.8 vs 50.4 ± 7.1 years, p&lt;0.001), predominantly male (68.2% vs. 37.8%, p&lt; 0.001) and had lower fasting HDL-C (49 ± 14 vs. 54 ± 12 mg/dL, p=0.015). The majority of individuals with CAD had non-obstructive atherosclerosis (65.6%). The patients with CAD had similar fasting lnTG (2.08 ± 0.20 vs. 2.02 ± 0.18, p=0.069)and increase in lnTG from 0 to 4 hours (p=0.54), but a significantly slower clearance of postprandial lnTG change from 4h to 6h (p=0.040) compared to patients without CAD. Interestingly, although age, gender, fasting glucose, and abdominal circumference did not influence those findings, after the inclusion of fasting HDL-C in the model, the change in the lnTG clearance after 4 hours did not reach statistical significance (Table 1). Conclusion: Patients with CAD had an impaired postprandial metabolism, due to a delayed TG clearance. This association was partially explained by the lower fasting HDL-C. Thus, the contribution of postprandial TG metabolism to the development of CAD, may be partially, related to the low fasting HDL-C concentrations.
SNaPshot genotyping of non-small cell lung cancers (NSCLC) in clinical practice.
Authors: L. V. Sequist, R. S. Heist, A. T. Shaw, P. Fidias, J. S. Temel, I. T. Lennes, E. Bast, B. A. Waltman, M. Lanuti, A. Muzikansky, M. Mino-Kenudson, A. J. Iafrate, D. R. Borger, D. Dias-Santagata, J. A. Engelman
Journal: Journal of Clinical Oncology (2011)

7518 Background: Cancer diagnostic and treatment strategies are shifting from organ-of-origin and histology-based paradigms to genotype-based approaches, especially in NSCLC. Responding to the clinical need for real-time, effective tumor genotyping, we implemented SNaPshot (SS), a clinical genotyping panel that uses formalin-fixed paraffin-embedded tissue. Methods: This was a retrospective chart review of all NSCLC patients (pts) undergoing SS genotyping at Massachusetts General Hospital Cancer Center from March 2009 to May 2010. Tumors were tested for common hot-spot mutations or translocations in 14 cancer-related genes including EGFR, KRAS, ALK, BRAF, PIK3CA, NRAS, TP53, beta-catenin and others. Results: During the study period, 552 of 589 samples (94%) sent for SS were successfully genotyped. Pt median age was 62, with 58% female and 92% white. 81% of cases were adenocarcinoma; smoking status was 24% never, 51% former and 11% current; and 64% had stage III or IV disease. Median turn around time for SS results was 20 days. 48% of samples were positive for a mutation or translocation, including 25% KRAS, 13% EGFR, 5% ALK, 5% TP53, 4% PIK3CA, 2% beta-catenin, 1% BRAF, 1% NRAS, and 1 pt each with HER2 and IDH1. Beta-catenin tended to co-exist with other mutations, including EGFR and PIK3CA. EGFR, ALK and BRAF mutations were associated with low smoking; KRAS and NRAS with heavy smoking. EGFR and KRAS were more common in adenocarcinoma; PIK3CA was associated with squamous cell histology. ALK was associated with younger age and KRAS with earlier stage. Overall, 15% of pts with advanced or recurrent NSCLC during the trial period enrolled on a clinical study of a targeted agent as a result of their genotype and an additional 4% went on an EGFR TKI off-protocol due to SS results. Tumor staging dilemmas were clarified via SS analysis of multiple biopsies in 6 cases. Conclusions: Broad cancer genotyping is increasingly important in NSCLC. In our cohort, about half of pts had an identifiable mutation or translocation. We demonstrated that SS testing is feasible in a clinical setting, and can influence treatment options.
Effects of pulmonary rehabilitation in patients with severe COPD in comparison to patients with severe interstitial lung disease
Authors: Rainer Gloeckl, Inga Heinzelmann, Bernd Sczepanski, Sandra Winterkamp, Jürgen Behr, Klaus Kenn
Journal: European Respiratory Journal (2013)

Background 

There is some evidence that patients with COPD or interstitial lung disease (ILD) may benefit differently from pulmonary rehabilitation (PR).

Objective 

Aim of this retrospective analysis was to compare the effects of a comprehensive 4 week inpatient PR in patients with COPD vs ILD with regards to exercise capacity and quality of life (QoL).

Methods 

314 COPD-patients (62±9 ys, FEV1: 28±8% pred., PaO2: 57±8mmHg) and 96 patients with ILD (63±10 ys, IVC: 53±20%, PaO2: 55±11mmHg) underwent the same multidisciplinary PR consisting of endurance/strength training, breathing retraining, education and psychological support. Patients performed a 6-MWT and completed the SF-36 questionnaire to determine general QoL on admission and discharge.

Results 

Prior to PR patients with COPD and ILD showed a comparable limited exercise capacity (6MWD in COPD: 249±27m vs ILD: 247±30). After PR 6MWD improved significantly in patients with COPD (+64.4m, p<0.001) as well as in ILD-patients (+50.5m, p<0.001). Between-group difference was also significant (13.8m, p<0.05).

Improvement in QoL was comparable in both groups regarding SF-36 mental health score (MHS) (COPD: from 36.7±16.0 to 45.8±14.7, p<0.001 and ILD: from 35.8±15.2 to 43.9±15.5, p<0.001) but showed no significant change in physical health score (PHS) (COPD: from 31.1± 9.7 to 31.2±9.7, n.s. and ILD: from 32.7±10.4 to 32.7±10.7, n.s.).

Conclusion 

It seems that patients with COPD as well as ILD even in advanced stages may improve their 6MWD and their MHS during PR significantly. The benefit in exercise capacity seems to be higher in COPD. PHS remained unchanged in both groups without any significant difference in QoL.
Results from phase Ib studies of PX-12, a thioredoxin inhibitor in patients with advanced solid malignancies
Authors: R. K. Ramanathan, T. Dragovich, D. Richards, J. Stephenson, L. Pestano, A. Hiscox, R. Leos, S. Chow, J. Millard, L. Kirkpatrick
Journal: Journal of Clinical Oncology (2009)

2571 Background: PX-12, a small-molecule inhibitor of Thioredoxin-1 (Trx-1) stimulates apoptosis, down-regulates HIF- 1α, VEGF in animal models. High levels of Trx-1 have been linked to chemoresistance in lung cancers. The phase 2 dose of PX-12 was 226 mg/m 2 given by 3-h infusion IV x 5 days, q 21d (Ramanathan RK et al. CCR 13; 2109; 2007). Two Phase 1b trials of PX-12 in patients with advanced solid tumors have been completed to determine the safety, tolerability and optimal biologic dose when delivered by prolonged infusion. Methods: PX-12 was administered as a 24-h infusion every q7- 14d starting at 150 mg/m 2 /day (n=18); or a 72-h infusion q 21d, starting at 300 mg/m 2 /day (n=14) using a portable delivery pump. Results: Both the 24- or 72-h infusion of PX-12 were well tolerated in patients at doses up to 400 mg/m 2 /day. Common grade 1/2 AE's included fatigue, taste alteration, and odor caused by expired drug metabolite. In the 24 h study the maximal dose evaluated was 450 mg/m 2 . No DLTs were observed in this study. Since no MTD was reached on 24-h infusion up to 450 mg/m 2 dose level, additional higher doses were explored utilizing 72-h infusion. DLT in the 72-h study at the highest dose administered (500 mg/m 2 /day) included reversible hypoxia with or without pneumonitis. Best response was stable disease in 3 pts (SD): liver cancer and colon cancer (24-h infusion) and rectal cancer (72-h infusion). Pharmacodynamics (PD): PX- 12 lowered circulating Trx-1 levels in patients who had starting Trx-1 levels 3-fold greater than that of the normal population (5.4 ng/mL) including all three SD. Circulating VEGF and FGF-2 levels were also lowered over multiple courses of treatment in these patients. The pharmacokinetics of PX-12 showed a dose dependent increase of C max and no accumulation over multiple cycles following a 24 h infusion. Conclusions: Dosing at 400 mg/m 2 /day appears safe and tolerable as a 24–72-h infusion. Extending the infusion time to 72h appears to decrease the intensity of cough and odor compared to bolus 1–3 h infusion. The PD effect produced by PX-12 was apparent only in those patients with elevated plasma Trx-1 levels. Patients with elevated TRX-1 levels appear to have the best probability of having SD. Supported by ProlX Pharmaceuticals/Oncothyreon through an award from the NCI. [Table: see text]