tbuckley/cabot-search huggingface dataset:
The Change From Brand-Name to Generic Aromatase Inhibitors and Hormone Therapy Adherence for Early-Stage Breast Cancer
Authors: Dawn L. Hershman, Jennifer Tsui, Jay Meyer, Sherry Glied, Grace Clarke Hillyer, Jason D. Wright, Alfred I. Neugut
Journal: JNCI Journal of the National Cancer Institute (2014)

Nonadherence to hormonal therapy is common and is associated with increased copayment amount. We investigated the change in adherence after the introduction of generic aromatase inhibitors (AIs) in 2010. Using deidentified pharmacy and claims data from OptumInsight, we identified women older than 50 years on brand-name AIs (BAIs) and/or generic AIs (GAIs) for early breast cancer between January 1, 2007 and December 31, 2012. Clinical, demographic, and financial variables were evaluated. Adherence was defined as a medication possession ratio (MPR) 80% or greater. We identified 5511 women, 2815 (51.1%) on BAI, 1411 (25.6%) on GAI, and 1285 (23.3%) who switched from BAI to GAI. The median 30-day copayment was higher for BAI ($33.3) than for GAI ($9.04). In a multivariable Cox-proportional hazard analysis, women who took GAI were less likely to discontinue therapy (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.57 to 0.84) compared with BAI. Discontinuation was positively associated with a higher monthly copayment of $15 to $30 (HR = 1.21, 95% CI = 1.01 to 1.44) and more than $30 (HR = 1.49, 95% CI = 1.23 to 1.80) compared with less than $15. In a multivariable logistic regression analysis, adherence (medication possession ratio ≥ 80%) was positively associated with GAI use (odds ratio = 1.53, 95% CI = 1.22 to 1.91) compared with BAI and inversely associated with increased monthly copayment. In addition, adherence was associated with a high annual income of more than $100k/year (odds ratio = 1.58, 95% CI = 1.17 to 2.11). Higher prescription copayment amount was associated with nonadherence and discontinuation of AIs. After controlling for copayment, discontinuation was higher and adherence was lower with Brand AIs. Because nonadherence is associated with worse survival, efforts should be directed towards reducing out-of-pocket costs for these life-saving medications.
Changes in Cell-to-Cell Electrical Coupling Associated With Left Ventricular Hypertrophy
Authors: M. Cooklin, W. R. J. Wallis, D. J. Sheridan, C. H. Fry
Journal: Circulation Research (1997)

Abstract The impedance to current flow in the intracellular compartment of guinea pig left ventricular myocardium was measured at 20°C and 37°C using tissue from hypertrophied hearts subjected to aortic constriction. Alternating current of varying frequency was passed longitudinally along myocardial preparations, which revealed two time constants: one attributed to the surface membrane at the ends of the preparation and a second lying in the intracellular pathway. The longitudinal impedance was quantitatively analyzed in terms of a parallel intracellular and extracellular pathway; the former had two series components, one attributable to the sarcoplasm and the other to the low-resistance junctions between adjacent cells. This interpretation was consistent (1) with control experiments using n -heptanol, which increased the component attributed to intercellular junctions but not sarcoplasmic resistivity, and (2) with suspensions of isolated myocytes, which yielded a similar value for the sarcoplasmic resistivity. Aortic constriction increased the heart weight–to–body weight ratio of experimental animals from a mean value of 3.10±0.28 to 5.05±0.83 g/kg after 50 days of constriction and 5.60±0.95 g/kg after 150 days of constriction. An increase of heart weight–to–body weight ratio at 150 days of constriction was associated with an increased intracellular resistivity, which could be attributed solely to an increase of the junctional resistance between adjacent cells by ≈44% at 20°C and 140% at 37°C; the sarcoplasmic resistivity was unchanged. The results are discussed in terms of altered conduction in hypertrophied myocardium as a possible basis for arrhythmias in this tissue.
Maternal exposure to polycyclic aromatic hydrocarbons diminishes murine ovarian reserve via induction of Harakiri
Authors: Andrea Jurisicova, Asako Taniuchi, Han Li, Yuan Shang, Monica Antenos, Jacqui Detmar, Jing Xu, Tiina Matikainen, Adalberto Benito Hernández, Gabriel Nunez, Robert F. Casper
Journal: Journal of Clinical Investigation (2007)

Maternal smoking during pregnancy is associated with a variety of adverse neonatal outcomes including altered reproductive performance. Herein we provide molecular evidence for a pathway involved in the elimination of the female germline due to prepregnancy and/or lactational exposure to polycyclic aromatic hydrocarbons (PAHs), environmental toxicants found in cigarette smoke. We show that ovaries of offspring born to mice exposed to PAHs contained only a third of the ovarian follicle pool compared with offspring of unexposed female mice. Activation of the cell death pathway in immature follicles of exposed females was mediated by the aryl hydrocarbon receptor (Ahr), as ovarian reserve was fully rescued by maternal cotreatment with the Ahr antagonist, resveratrol, or by inactivation of the Ahr gene. Furthermore, in response to PAHs, Ahr-mediated activation of the harakiri, BCL2 interacting protein (contains only BH3 domain), was necessary for execution of cell death. This pathway appeared to be conserved between mouse and human, as xenotransplanted human ovarian cortex exposed to PAHs responded by activation of the identical cell death cascade. Our data indicate that maternal exposure to PAHs prior to pregnancy and/or during lactation compromises ovarian reserve of female offspring, raising the concern about the transgenerational impact of maternal smoking on ovarian function in the human.
T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse
Authors: Amy E. Moran, Keli L. Holzapfel, Yan Xing, Nicole R. Cunningham, Jonathan S. Maltzman, Jennifer Punt, Kristin A. Hogquist
Journal: The Journal of Experimental Medicine (2011)

The ability of antigen receptors to engage self-ligands with varying affinity is crucial for lymphocyte development. To further explore this concept, we generated transgenic mice expressing GFP from the immediate early gene Nr4a1 (Nur77) locus. GFP was up-regulated in lymphocytes by antigen receptor stimulation but not by inflammatory stimuli. In T cells, GFP was induced during positive selection, required major histocompatibility complex for maintenance, and directly correlated with the strength of T cell receptor (TCR) stimulus. Thus, our results define a novel tool for studying antigen receptor activation in vivo. Using this model, we show that regulatory T cells (T(reg) cells) and invariant NKT cells (iNKT cells) perceived stronger TCR signals than conventional T cells during development. However, although T(reg) cells continued to perceive strong TCR signals in the periphery, iNKT cells did not. Finally, we show that T(reg) cell progenitors compete for recognition of rare stimulatory TCR self-ligands.
Improved Survival of Patients With Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma in a Prospective Clinical Trial
Authors: C. Fakhry, W. H. Westra, S. Li, A. Cmelak, J. A. Ridge, H. Pinto, A. Forastiere, M. L. Gillison
Journal: JNCI Journal of the National Cancer Institute (2008)

The improved prognosis for patients with human papillomavirus (HPV)–positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan–Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P = .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [95% CI = 87% to 100%] vs 62% [95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P = .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors. For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival.
Long-term outcome following Helicobacter pylori eradication in a retrospective study of 105 patients with localized gastric marginal zone B-cell lymphoma of MALT type
Authors: A. Stathis, C. Chini, F. Bertoni, I. Proserpio, C. Capella, L. Mazzucchelli, E. Pedrinis, F. Cavalli, G. Pinotti, E. Zucca
Journal: Annals of Oncology (2009)
Trends in mortality from ulcerative colitis in England and Wales
Authors: J. G. Evans
Journal: Gut (1971)

Mortality rates for ulcerative colitis in England and Wales over the years 1946 to 1967 showed trends which varied with age. Between the ages of 15 and 34 rates fell with only minor irregularities. At ages 35 to 64, rates were constant from 1946 to 1957 and then began to decline. At ages 65 and above, rates rose during most of the period but with a recent tendency to stabilize. These trends are discussed in relation to possible effects of the introduction of steroids and other therapies.
Difference in B cell activation between dermatomyositis and polymyositis: analysis of the expression of RP105 on peripheral blood B cells
Authors: Y Kikuchi, S Koarada, Y Tada, O Ushiyama, F Morito, N Suzuki, A Ohta, T Horiuchi, K Miyake, K Nagasawa
Journal: Annals of the Rheumatic Diseases (2001)

<h3>BACKGROUND</h3> It has previously been shown that RP105, a new B cell surface protein, is lost in activated human B cells. <h3>OBJECTIVE</h3> To investigate whether there is a difference in B cell activation between patients with dermatomyositis (DM) and those with polymyositis (PM) using RP105 as a marker. <h3>METHODS</h3> The population of RP105 negative B cells (activated B cells) in the peripheral blood mononuclear cells of seven patients with dermatomyositis (DM) and 11 with polymyositis (PM) was analysed by flow cytometry. <h3>RESULTS</h3> The percentage of RP105 negative B cells in the peripheral blood of patients with PM was low (5.8 (SD 2.4)%), similar to that of normal subjects. In contrast, all patients with DM showed increased RP105 negative B cell populations (33.0 (6.9)%). Bronchoalveolar lavage fluid from a patient with DM and active interstitial pneumonitis contained a large number of RP105 negative B cells. <h3>CONCLUSION</h3> These findings suggest that the expansion of RP105 negative B cells is a hallmark of DM, and that B cell activation in DM may be pathogenetically different from that in PM.
Are Personality Traits Familial Risk Factors for Substance Use Disorders? Results of a Controlled Family Study
Authors: Joel D. Swendsen, Kevin P. Conway, Bruce J. Rounsaville, Kathleen R. Merikangas
Journal: American Journal of Psychiatry (2002)

The well-documented association between maladaptive personality traits and substance use disorders has given rise to diverse explanatory models. In this investigation the authors examined one such explanation, that certain personality traits are familial risk factors for the development of substance abuse or dependence.Data were collected from a controlled family study using direct diagnostic interviews. The Multidimensional Personality Questionnaire was used to assess the personality traits of 325 probands, 205 of whom had diagnoses of substance abuse or dependence, and 262 of their first-degree relatives.Probands with substance use disorders scored higher on alienation and negative emotionality than did probands without substance use disorders, and they scored lower on control, harm avoidance, and constraint. Relatives with substance use disorders also differed from relatives without these conditions on several of these same dimensions. To examine whether such personality traits could be conceptualized as familial risk factors for substance use disorders, a second set of analyses were limited to relatives without substance use disorders themselves but varying in terms of family history for these conditions. These groups of relatives did not differ significantly from each other on any of the identified personality traits.These findings argue for caution in characterizing the personality correlates of substance use disorders as representing familial or heritable risk factors.
A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX30 and chronomodulated XELOX30 as first-line therapy in patients with advanced colorectal cancer
Authors: C. Qvortrup, B.V. Jensen, T. Fokstuen, S.E. Nielsen, N. Keldsen, B. Glimelius, B. Bjerregaard, J. Mejer, F.O. Larsen, P. Pfeiffer
Journal: Annals of Oncology (2009)
Labial salivary gland biopsy assessment in rheumatoid vasculitis.
Authors: R M Flipo, A Janin, E Hachulla, E Houvenagel, A Foulet, T Cardon, A Desbonnet, B Grardel, B Duquesnoy, B Delcambre
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To assess the vascular involvement in labial salivary gland (LSG) from patients with rheumatoid vasculitis (RV). METHODS--Forty seven patients with rheumatoid arthritis (RA) took part in a prospective study. Among them, 12 had proven RV. LSG biopsy was performed after local anaesthesia. RESULTS--Histological appearance of inflammatory vascular damage was observed in all but one patient with proven RV (92%). Inflammatory vascular involvement was also identified in LSG biopsy of seven patients with RA (20%) and only one patient in the control group (8%). A second specimen of LSG was studied after a mean treatment period of six months and failed to show any feature of inflammatory vascular involvement in three of the five cases that were analysed. CONCLUSIONS--The study emphasises the high incidence of immunopathological features of microvascular damage in patients with RV. LSG biopsy is minimally invasive and may be a potential useful tool for the diagnosis of RV especially when skin lesions are absent or impossible to biopsy. The assessment of the predictive value of positive LSG biopsy in RA requires a long term prospective study.
Aripiprazole in the Treatment of Patients With Borderline Personality Disorder: A Double-Blind, Placebo-Controlled Study
Authors: Marius K. Nickel, Moritz Muehlbacher, Cerstin Nickel, Christian Kettler, Francisco Pedrosa Gil, Egon Bachler, Wiebke Buschmann, Nadine Rother, Reinhold Fartacek, Christoph Egger, Javaid Anvar, Wolfhardt K. Rother, Thomas H. Loew, Patrick Kaplan
Journal: American Journal of Psychiatry (2006)

Objective: Aripiprazole is a relatively new atypical antipsychotic agent that has been successfully employed in therapy for schizophrenia and schizoaffective disorders. A few neuroleptics have been used in therapy for patients with borderline personality disorder, which is associated with severe psychopathological symptoms. Aripiprazole, however, has not yet been tested for this disorder, and the goal of this study was to determine whether aripiprazole is effective in the treatment of several domains of symptoms of borderline personality disorder. Method: Subjects meeting criteria for the Structured Clinical Interview for DSM-III-R Personality Disorders for borderline personality disorder (43 women and 9 men) were randomly assigned in a 1:1 ratio to 15 mg/day of aripiprazole (N=26) or placebo (N=26) for 8 weeks. Primary outcome measures were changes in scores on the symptom checklist (SCL-90-R), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), and the State-Trait Anger Expression Inventory and were assessed weekly. Side effects and self-injury were assessed with a nonvalidated questionnaire. Results: According to the intent-to-treat principle, significant changes in scores on most scales of the SCL-90-R, the HAM-D, the HAM-A, and all scales of the State-Trait Anger Expression Inventory were observed in the subjects treated with aripiprazole after 8 weeks. Self-injury occurred in the groups. The reported side effects were headache, insomnia, nausea, numbness, constipation, and anxiety. Conclusions: Aripiprazole appears to be a safe and effective agent in the treatment of patients with borderline personality disorder.
Cytomegalovirus retinitis and low-grade non-Hodgkin's lymphoma: Case report and review of the literature
Authors: L.A. Derzko-Dzulynsky, A.R. Berger, N.L. Berinstein
Journal: American Journal of Hematology (1998)

Patients with non-Hodgkin's lymphoma may develop retinal or choroidal lesions during the course of their disease. New immunosuppressive therapies currently used in reticuloendothelial malignancies have increased the incidence of opportunistic infections in this patient population. The differentiation of lymphomatous infiltration from opportunistic infection as a cause of chorioretinal infiltrates is critical, as the treatments are fundamentally different. We report a case of a patient with non-Hodgkin's lymphoma who developed a chorioretinal infiltrate that was initially thought to represent progressive disease. The patient received radiation treatment appropriate for intraocular lymphoma. The lesion progressed further and after reevaluation a diagnosis of cytomegalovirus retinitis was made and therapy initiated. Review of the literature for intraocular lymphoma and cytomegalovirus retinitis is provided and diagnostic strategies are described. We recommend analysis of intraocular fluid when there is difficulty in clinically differentiating intraocular lymphoma from opportunistic infection. Am. J. Hematol. 57:228–232, 1998. © 1998 Wiley-Liss, Inc.
Prostaglandin E2 Enhances Pancreatic Cancer Invasiveness through an Ets-1-Dependent Induction of Matrix Metalloproteinase-2
Authors: Hiromichi Ito, Mark Duxbury, Eric Benoit, Thomas E. Clancy, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang
Journal: Cancer Research (2004)

Abstract Accumulating evidence suggests an important role for cyclooxygenase-2 (COX-2) in the pathogenesis of a wide range of malignancies. Here we tested the hypothesis that the COX-2 product prostaglandin E2 (PGE2) increases cellular invasive potential by inducing matrix metalloproteinase-2 (MMP-2) expression and activity through an extracellular signal-regulated kinase (ERK)/Ets-1-dependent mechanism in pancreatic cancer. PANC-1 and MIAPaCa-2 pancreatic cancer cells were treated with PGE2 or rofecoxib, a selective COX-2 inhibitor. MMP-2 expression and activity were assayed using Western blot analysis and zymography, respectively. MMP-2 promoter activity was analyzed with a luciferase-based assay. Ets-1 activity was analyzed using gel shift assay. Ets-1 expression was specifically silenced using RNA interference. Cellular invasive and migratory potentials were determined using a Boyden chamber assay with or without Matrigel, respectively. Exogenous PGE2 induced MMP-2 expression and activity and increased ERK1/2 phosphorylation, Ets-1 binding activity, and MMP-2 promoter activity. PGE2 also increased cellular migratory and invasive potentials. The mitogen-activated protein kinase kinase inhibitor PD98059 and Ets-1 silencing each abolished PGE2-induced increases in MMP-2 expression. PD98059 and Ets-1 silencing each abrogated the effect of PGE2 on cellular invasive potential but not on cellular migratory potential. Rofecoxib suppressed MMP-2 expression and activity, Ets-1 binding activity, MMP-2 promoter activity, and cellular migratory and invasive potentials. These results suggest that PGE2 mediates pancreatic cancer cellular invasiveness through an ERK/Ets-1-dependent induction of MMP-2 expression and activity. They also suggest that COX-2 inhibition may represent a strategy to inhibit invasive potential in pancreatic cancer.
Phase I Study of Folate Conjugate EC145 (Vintafolide) in Patients With Refractory Solid Tumors
Authors: Patricia M. LoRusso, Martin J. Edelman, Susan L. Bever, Karen M. Forman, MaryJo Pilat, Mary F. Quinn, Jing Li, Elisabeth I. Heath, Lisa M. Malburg, Patrick J. Klein, Christopher P. Leamon, Richard A. Messmann, Edward A. Sausville
Journal: Journal of Clinical Oncology (2012)

EC145 (vintafolide), a conjugate of folic acid and the vinca alkaloid desacetylvinblastine hydrazide (DAVLBH), is a ligand for the folate receptor (FR), with activity against FR-positive tumor xenografts in vivo. This phase I study determined the maximum-tolerated dose (MTD) of EC145 administered as a bolus intravenous injection or 1-hour infusion in patients with refractory solid tumors.EC145 was administered as a bolus injection or 1-hour infusion on days 1, 3, and 5 and days 15, 17, and 19 of each 28-day cycle with dose escalation in cohorts of three to six patients until the MTD was identified. Plasma pharmacokinetics were determined on days 1 and 3 of the first cycle.The MTD of EC145 was 2.5 mg when administered as either a bolus injection or 1-hour infusion. Constipation was the dose-limiting toxicity with both routes. Constipation, nausea, fatigue, and vomiting were the most commonly reported adverse events. One partial response to therapy was observed in a patient with metastatic ovarian cancer.EC145 administered by bolus injection or as a 1-hour infusion at a dose of 2.5 mg on days 1, 3, and 5 and days 15, 17, and 19 of a 28-day cycle has an acceptable safety profile in patients with advanced cancer. On the basis of these findings, phase II studies of EC145 have been initiated in patients with advanced epithelial ovarian cancer and non-small-cell lung cancer.