tbuckley/cabot-search huggingface dataset:
Genetic Variations in Multiple Drug Action Pathways and Survival in Advanced Stage Non–Small Cell Lung Cancer Treated with Chemotherapy
Authors: Yafei Li, Zhifu Sun, Julie M. Cunningham, Marie C. Aubry, Jason A. Wampfler, Gary A. Croghan, Cassandra Johnson, Danli Wu, Jeremiah A. Aakre, Julian Molina, Liewei Wang, V. Shane Pankratz, Ping Yang
Journal: Clinical Cancer Research (2011)

Variations in genes related to biological activity of anticancer drugs could influence treatment responses and lung cancer prognosis. Genetic variants in four biological pathways, that is, glutathione metabolism, DNA repair, cell cycle, and epidermal growth factor receptor (EGFR), were systematically investigated to examine their association with survival in advanced stage non-small cell lung cancer (NSCLC) treated with chemotherapy.A total of 894 tagging single-nucleotide polymorphisms (SNP) in 70 genes from the four pathways were genotyped and analyzed in a 1,076-patient cohort. Association with overall survival was analyzed at SNP and whole-gene levels within all patients and major chemotherapy agent combination groups.A poorer overall survival was observed in patients with genetic variations in GSS (glutathione pathway) and MAP3K1 (EGFR pathway; HR = 1.45; 95% CI = 1.20-1.77 and HR = 1.25; 95% CI = 1.05-1.50, respectively). In the stratified analysis on patients receiving platinum plus taxane treatment, we observed a hazardous effect on overall survival by the MAP3K1 variant (HR = 1.38; 95% CI = 1.11-1.72) and a protective effect by RAF1 (HR = 0.64; 95% CI = 0.50-0.82) in the EGFR pathway. In patients receiving platinum plus gemcitabine treatment, RAF1 and GPX5 (glutathione pathway) genetic variations showed protective effects on survival (HR = 0.54; 95% CI = 0.38-0.77; HR = 0.67; 95% CI = 0.52-0.85, respectively); in contrast, NRAS (EGFR pathway) and GPX7 (glutathione pathway) variations showed hazardous effects on overall survival (HR = 1.91; 95% CI = 1.30-2.80; HR = 1.83; 95% CI = 1.27-2.63, respectively). All genes that harbored these significant SNPs remained significant by whole-gene analysis.Common genetic variations in genes of EGFR and glutathione pathways may be associated with overall survival among patients with advanced stage NSCLC treated with platinum, taxane, and/or gemicitabine combinations.
The Effectiveness of State-Level Tobacco Control Interventions: A Review of Program Implementation and Behavioral Outcomes
Authors: Michael Siegel
Journal: Annual Review of Public Health (2002)

▪ Abstract In 2001, nearly one billion dollars will be spent on statewide tobacco control programs, including those in California, Massachusetts, Arizona, and Oregon, funded by cigarette tax revenues, and the program in Florida, funded by the state's settlement with the tobacco industry. With such large expenditures, it is imperative to find out whether these programs are working. This paper reviews the effectiveness of the statewide tobacco control programs in California, Massachusetts, Arizona, Oregon, and Florida. It focuses on two aspects of process evaluation—the funding and implementation of the programs and the tobacco industry's response, and four elements of outcome evaluation—the programs' effects on cigarette consumption, adult and youth smoking prevalence, and protection of the public from secondhand smoke. The paper formulates general lessons learned from these existing programs and generates recommendations to improve and inform the development and implementation of these and future programs.
Expression of Frzb/Secreted Frizzled-Related Protein 3, a Secreted Wnt Antagonist, in Human Androgen-Independent Prostate Cancer PC-3 Cells Suppresses Tumor Growth and Cellular Invasiveness
Authors: Xiaolin Zi, Yi Guo, Anne R. Simoneau, Christopher Hope, Jun Xie, Randall F. Holcombe, Bang H. Hoang
Journal: Cancer Research (2005)

Abstract The ability of Frzb/secreted Frizzled-related protein 3 (sFRP3) to inhibit Wnt signaling and the localization of Frzb/sFRP3 on chromosome 2q to a region frequently deleted in cancers have led some investigators to hypothesize that Frzb/sFRP3 is a tumor suppressor gene. Here, we examined the biological effects of Frzb/sFRP3 on an androgen-independent prostate cancer cell model. We showed that expression of Frzb/sFRP3 in PC-3 cells resulted in decreased colony formation in soft agar and a dramatic inhibition of tumor growth in a xenograft mouse model. When cellular morphology was examined, PC-3 cells expressing Frzb/sFRP3 exhibited an increase in cell-cell contact formation accompanied by a pronounced induction of epithelial markers E-cadherin and keratin-8 and down-regulation of mesenchymal markers N-cadherin, fibronectin, and vimentin. This phenomenon suggested a reversal of epithelial-to-mesenchymal transition and a less invasive phenotype. Indeed, further in vitro studies with a Matrigel assay showed that Frzb/sFRP3 decreased the invasive capacity of PC-3 cells. These changes in the biology of PC-3 cells are associated with a decrease in the expression and activities of both matrix metalloproteinase (MMP)-2 and MMP-9 as well as decreases in AKT activation, cytosolic β-catenin levels, T-cell factor transcription activity, and expression of Slug and Twist. In addition, transfection of PC-3 with a dominant-negative low-density lipoprotein receptor–related protein 5 (DN-LRP5) coreceptor showed similar biological effects as Frzb/sFRP3 transfection. Together, these data suggest that Frzb/sFRP3 and DN-LRP5 exhibit antitumor activity through the reversal of epithelial-to-mesenchymal transition and inhibition of MMP activities in a subset of prostate cancer.
Glucocorticosteroid dependent decrease in the activity of calcineurin in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus
Authors: S Sipka
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To compare the activity of calcineurin in the peripheral blood mononuclear cells (PBMC) of 32 patients with systemic lupus erythematosus (SLE) and 35 healthy controls. <h3>METHODS</h3> The activity of calcineurin was assayed in the supernatants of sonicated mononuclear cells. <h3>RESULTS</h3> There was no significant difference in the calcineurin activity of patients with SLE not taking glucocorticosteroids (GCS) compared with the healthy controls. On the other hand, the activity of calcineurin was reduced in patients with SLE taking GCS, correlating negatively with the dose of GCS. The stimulation of PBMC by phorbol ester and calcium ionophore decreased the calcineurin activity both in patients with SLE and in healthy controls. GCS could also reduce calcineurin activity in the mononuclear cells of healthy subjects in vitro. <h3>CONCLUSIONS</h3> In patients with SLE the decrease in the calcineurin activity of PBMC depended on the dose of GCS used for treatment, and it was not a disease specific alteration. The higher the dose of GCS, the greater the inhibition of calcineurin activity. The reduction of calcineurin activity is a new element in the immunosuppressive effects of GCS during the treatment of patients with SLE.
Determinants of airway responsiveness to histamine in children
Authors: S. W. Turner, L. J. Palmer, P. J. Rye, N. A. Gibson, S. Young, J. Goldblatt, L. I. Landau, P. N. Le Souëf
Journal: European Respiratory Journal (2005)

Increased airway responsiveness (AR) is associated with asthma, but not all individuals with increased AR have asthma. The aim of this study was to identify factors, other than physician-diagnosed asthma (PDA), which are associated with increased AR. In a longitudinal study, data were collected on atopy and lower respiratory tract illness (LRTI) in infancy, and AR (expressed as dose–response slope (DRS)), atopy, tobacco-smoke exposure and PDA in childhood. At age 6 yrs, DRS was assessed in 102 children, of whom 22 (22%) had PDA; the corresponding figures at 11 yrs of age were 176 and 29 (15%). At age 6 yrs, DRS was significantly associated with PDA, current atopy and parental smoking (n = 83). At age 11 yrs, DRS was significantly associated with PDA, current atopy and LRTI in the first six months (n = 75). There was a significant positive interaction between atopy at age 12 months and PDA age 11 yrs. In conclusion, these data suggest that factors other than asthma or atopy may determine the level of airway responsiveness in children. In children with asthma, airway responsiveness may be influenced by the early onset of atopy. The current findings may explain the inconsistent relationship between airway responsiveness and asthma.
Pregnancy Out of Wedlock
Authors: E. J. Liberman
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The editorial statement "Illegitimacy—A Professional Concern" (237:574, 1977) overstates some aspects of the problem and may detract from preventive approaches. Recent reports on out-of-wedlock births as a proportion of all births, exceeding 50% in some urban areas, must be viewed in perspective: plummeting fertility among married women, the rise in average age at marriage during the past few years, the large number of adolescents in the population, and the dearth of adequate contraceptive education and services for young people. Rather than attribute the alarming proportion of out-of-wedlock pregnancies to "new life-styles," it is important to recognize that the birth rate among teenagers has been declining, as it has in older women, but in the former it has occurred at a slower rate. Thus, we face a situation in which the contraceptive revolution has reached well into all areas of our population except the unwed, adolescent sector. Providing
The Role of Phosphoinositide 3-Kinase Pathway Inhibitors in the Treatment of Lung Cancer
Authors: Jeffrey A. Engelman
Journal: Clinical Cancer Research (2007)

Abstract The phosphoinositide 3-kinase signaling network is widely implicated in the pathogenesis of human cancer. This pathway is commandeered by cancer cells to promote unrestrained cellular growth and survival. In this brief review, we speculate about the uses of inhibitors of phosphoinositide 3-kinase signaling as treatments for human cancers, with an emphasis on non–small cell lung cancer.
Myeloablation and autologous peripheral blood stem cell rescue results in hematologic and clinical responses in patients with myeloid metaplasia with myelofibrosis
Authors: Jeanne E. Anderson, Ayalew Tefferi, Fiona Craig, Leona Holmberg, Thomas Chauncey, Frederick R. Appelbaum, Philippe Guardiola, Natalie Callander, Cesar Freytes, Yair Gazitt, Betty Razvillas, H. Joachim Deeg
Journal: Blood (2001)
A retrospective analysis of the relationship between changes in serum PSA, palliative response and survival following systemic treatment in a Canadian randomized trial for symptomatic hormone-refractory prostate cancer
Authors: A.J. Dowling, T. Panzarella, D.S. Ernst, A.J. Neville, M.J. Moore, I.F. Tannock
Journal: Annals of Oncology (2001)
Effect of Yoga on Arrhythmia Burden, Anxiety, Depression, and Quality of Life in Paroxysmal Atrial Fibrillation
Authors: Dhanunjaya Lakkireddy, Donita Atkins, Jayasree Pillarisetti, Kay Ryschon, Sudharani Bommana, Jeanne Drisko, Subbareddy Vanga, Buddhadeb Dawn
Journal: Journal of the American College of Cardiology (2013)
Detection of interferon gamma mRNA in the mucosa of patients with coeliac disease by in situ hybridisation.
Authors: M Kontakou, R P Sturgess, R T Przemioslo, G A Limb, J M Nelufer, P J Ciclitira
Journal: Gut (1994)

In situ hybridisation has been used to study interferon gamma (IFN gamma) mRNA expression in the small intestine of patients with coeliac disease. Sections of jejunal biopsies were obtained from five patients with treated and five with untreated coeliac disease and five disease controls. These sections were hybridised with radiolabelled specific DNA oligonucleotide probes. The lamina propria of untreated coeliac disease patients contained a significantly increased number of IFN gamma producing cells compared with controls but there was no significant difference between the coeliac patients treated with a gluten free diet and controls. The results suggest that IFN gamma may play a part in the immunopathogenesis of coeliac disease.
Developmental changes of connexin40 and connexin43 mRNA distribution patterns in the rat heart
Authors: M Van Kempen
Journal: Cardiovascular Research (1996)

Gap junctions have been demonstrated ultrastructurally in cardiac regions where connexin40 (Cx40) and connexin43 (Cx43) protein could not be detected immunohistochemically. We investigated therefore the distribution of their mRNAs with more sensitive techniques.In situ hybridizations with Cx40 and Cx43 cRNA probes were performed on sections of rat hearts from 9 embryonic days (ED 9) to adults.From ED 13, Cx40 and Cx43 mRNA are detectable in atria and ventricles, but not in their flanking myocardium (inflow tract, atrioventricular canal and outflow tract). Even though Cx40 and Cx43 mRNA eventually become expressed in the inflow tract, they remain undetectable in the sinoatrial node, the atrioventricular canal (including atrioventricular node) and outflow tract. Expression of Cx40 is maximal in the fetal period and declines towards birth. Cx40 expression in the left and right ventricles evolves independently, its mRNA disappearing 4 days earlier from the right than from the left ventricle, and earlier from the free wall than from the trabeculations. Expression of Cx43 mRNA increases during development and changes postnatally from uniform to punctate. Prenatally, Cx43 mRNA was strongest in the subepicardial layer of the ventricular free wall. Nevertheless, we did not detect protein in this layer.Cardiac regions without detectable Cx40 or Cx43 mRNA either have extremely low levels of expression or express a different connexin. The temporally separate disappearance of Cx40 mRNA from the fetal ventricles implies that left and right ventricles mature independently with respect to gap-junctional communication. The division of the developing heart in compartments where Cx40 and Cx43 mRNA can and cannot be detected, implies pretranslationally regulated gene expression. The postnatally observed subcellular redistribution of Cx43 mRNA coincides with a reported increase in protein expression.
Impact of Sunscreens on Preventing UVR-Induced Effects in Nevi
Authors: Cristina Carrera, Joan A. Puig-Butillè, Paula Aguilera, Zighereda Ogbah, Josep Palou, Mario Lecha, Josep Malvehy, Susana Puig
Journal: JAMA Dermatology (2013)

Sun damage is the most important environmental factor associated with malignant melanoma. To address the health threat, as well as the economic burden, primary prevention and early detection are crucial.To test the efficacy of a topical sunscreen in the prevention of UV-induced effects in nevi.Prospective study of nevi protected by sunscreen vs a physical barrier.Twenty-three nevi from 20 patients attending a referral hospital.Half of each nevus was protected by either a physical barrier or a sunscreen. Lesions were completely irradiated by a single dose of UV-B.In vivo examination before and 7 days after irradiation and histopathologic-immunopathologic evaluation after excision on the seventh day.The most frequent clinical changes after UV radiation were pigmentation, scaling, and erythema; the most frequent dermoscopic changes were increased globules/dots, blurred network, regression, and dotted vessels. Both physical barrier- and sunscreen-protected areas showed some degree of these changes. More than 30% (7) of nevi did not show any change on clinical examination, and 18% (4) had no dermoscopic change. Immunohistopathologic differences between the halves of each nevus were demonstrable even when in vivo examination detected nothing. Parakeratotic scale, increased number and activation of superficial melanocytes, and keratinocyte proliferation were the most remarkable features. The only difference between both barriers was more enhanced melanocytic activation and regression features in the sunscreen group. No phenotypic features were found to predict a specific UV-B response.Both physical barriers and sunscreens can partially prevent UV-B effects on nevi. Subclinical UV radiation effects, not always associated with visible changes, can develop even after protection. Sunscreens are not quite as effective as physical barriers in the prevention of inflammatory UV-B-induced effects.
Cancer in Twins: Genetic and Nongenetic Familial Risk Factors
Authors: A. Ahlbom, P. Lichtenstein, H. Malmstrom, M. Feychting, N. L. Pedersen, K. Hemminki
Journal: JNCI Journal of the National Cancer Institute (1997)

Familial clustering has been observed for cancers that occur at specific sites. Most findings, which leave little doubt about the involvement of a heritable (i.e., genetic) component in the development of some cancers, are based on data from "cancer-prone" families or interviews with subjects who have cancer. The study of twins should be of value in cancer epidemiology because twins either are genetically identical or share half of their segregating genes.We linked the Swedish Twin Registry to the Swedish Cancer Registry, thereby identifying cases of cancer diagnosed from 1959 through 1992 in twins born in the period from 1886 through 1958, to assess the importance of both genetic and nongenetic (i.e., environmental) familial factors in determining cancer risk.Same-sex twin pairs with both individuals alive and living in Sweden in 1959-1961 or 1970-1972 were identified in the old cohort (born from 1886 through 1925) or the young cohort (born from 1926 through 1958), respectively, of the Swedish Twin Registry; pairs for whom zygosity (i.e., the number of eggs that gave rise to the twins) could be determined were considered further. The association of cancer with combined genetic and nongenetic familial factors was tested by comparing all twin pairs (regardless of zygosity) in which at least one member of the pair had been diagnosed with cancer at one of several specific sites with pairs in which neither twin had that cancer. Heritable effects alone were tested by comparing monozygotic (one egg) and dizygotic (two eggs) twin pairs. Statistical methods used in quantitative genetics and standard methods for epidemiologic research were used in parallel to analyze the data.In the 10503 twin pairs from the old cohort, 361.7 cases of malignant cancer were identified; 918 malignant cancers were identified in the 12883 twin pairs from the young cohort. When cancer sites with a total number of at least 200 cases and at least one twin pair concordant (i.e., both twins affected) for the site were evaluated, namely, cancers of the stomach, colon and rectum, lung, female breast, and prostate, as well as total cancer, profound genetic and/or nongenetic familial effects were identified in twins from the old cohort. Similar findings were obtained for twins in the young cohort for cancers of the prostate and female breast, as well as for total cancer. Genetic and nongenetic familial effects were also identified in twins from both cohorts for in situ cancer of the cervix. The increase in risk of colon and rectum, breast, cervical, and especially prostate cancer, but not stomach or lung cancer, tended to be greater if a monozygotic rather than a dizygotic twin were affected.The identification of familial effects for total cancer in this study is consistent with the idea that individuals may possess a genetic susceptibility to cancer in general.
ISOLATION AND IMMUNOCHEMICAL CHARACTERIZATION OF RABBIT 7S ANTI-I<scp>G</scp>G WITH RESTRICTED HETEROGENEITY
Authors: Viktor A. Bokisch, Jen Wei Chiao, David Bernstein
Journal: The Journal of Experimental Medicine (1973)

7S anti-IgGs were isolated from four rabbit antistreptococcal antisera by the use of immunoabsorbent columns. The isolated proteins were of restricted molecular heterogeneity; they formed a monodisperse band on microzone electrophoresis and had a limited number of light chain bands when analyzed on urea polyacrylamide gel. The binding site of the 7S anti-IgGs was detected in the F(ab')2 portion of the molecule. The binding site has antibody specificity for the Fc portion of IgG. For one 7S anti-IgG the combining site on the Fc portion could further be defined. A pepsin fragment of Fc, described as Pep-III', was a potent inhibitor of the coprecipitation of 7S anti-IgG with antigen-antibody complexes. An idiotypic cross-reaction was detected between the 7S and 19S anti-IgGs isolated from the same rabbit with anti-idiotype sera prepared in guinea pigs. This idiotypic specificity was not detected in the 7S anti-IgGs of 20 other rabbits.
Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in ΔKPQ SCN5A (long QT3) mice
Authors: L Fabritz
Journal: Cardiovascular Research (2003)

Objective: It has been suggested that both pacing and treatment with mexiletine may reduce torsade de pointes (TdP) arrhythmias in patients with long QT syndrome 3 (LQT3), but it is not fully understood how these interventions could prevent TdP. We therefore studied the effects of pacing and mexiletine in mice with a heterozygous knock-in ΔKPQ SCN5AΔ/+ deletion (SCN5A-Tg), a murine LQT3 model. Methods: Three right and left ventricular monophasic action potentials (MAPs) were simultaneously recorded in Langendorff-perfused hearts of SCN5A-Tg and wild type (WT) littermates. AV block was induced, and pacing was performed at baseline and during mexiletine infusion (4 μg/ml). MAP recordings were analysed for action potential duration (APD), APD dispersion, and early afterdepolarisations (EADs) and related to spontaneous arrhythmias. Results: After inducing AV block, SCN5A-Tg hearts were bradycardic [SCN5A-Tg 532±60 vs. WT 284±48 ms cycle length (CL, mean±S.E.M., P<0.05(*))]. EADs occurred in 16/18, and polymorphic ventricular tachycardia (pVT) in 11/18 SCN5A-Tg but not in 19 WT. SCN5A-Tg had longer APD than WT hearts*. At CL of 200 ms and longer, APD dispersion was higher in SCN5A-Tg [dispersion (APD70): 12±3 ms vs. 5±2 ms at CL=200 ms*], and increased to 35±4 ms* directly prior to pVT episodes. Sudden rate accelerations initially increased APD dispersion due to EADs and APD alternans in SCN5A-Tg, but pacing then reduced APD dispersion. Pacing suppressed (n=9/9) and prevented (n=49/50) pVT. Mexiletine shortened APD at long CL*, and suppressed pVT (n=4/5*), but did not prevent pVT during normal rhythm. Conclusions: Bradycardia, increased dispersion of APD and EADs provoke ventricular ectopy and pVT in SCN5A-Tg hearts. Ventricular pacing reduces APD dispersion, suppresses EADs and prevents pVT in SCN5A-Tg hearts. These effects provide a pathophysiological rationale for pacing in LQT3.
Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate
Authors: Nina Westerlund, Justyna Zdrojewska, Artur Padzik, Emilia Komulainen, Benny Björkblom, Emmy Rannikko, Tanya Tararuk, Cristina Garcia-Frigola, Jouko Sandholm, Laurent Nguyen, Tuula Kallunki, Michael J Courtney, Eleanor T Coffey
Journal: Nature Neuroscience (2011)