tbuckley/cabot-search huggingface dataset:
Urine PGE-M as a marker of intratumoral cyclooxygenase-2 activity in non-small cell lung cancer (NSCLC)
Authors: I. Csiki, M. K. Williams, Y. Shyr, A. Sandler, D. P. Carbone, N. Campbell, J. Morrow, D. H. Johnson
Journal: Journal of Clinical Oncology (2004)

9527 Background: Prostaglandin E2 (PGE2) is implicated in the pathogenesis of NSCLC. PGE2 levels are elevated in NSCLC often in association with overexpression of cyclooxygenase-2 (COX2). The most accurate method to assess PG production in vivo in humans is via quantification of urinary metabolites. We hypothesized that urine levels of 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), the major metabolite of PGE2, could be a useful marker of tumor COX2 activity & PGE2 production. Methods: PGE-M levels were determined in urine specimens derived from a previously reported phase II trial employing celecoxib & docetaxel in recurrent NSCLC (Proc. ASCO 22:640, 2003). We employed liquid chromatography electrospray ionization MS using selected reaction monitoring. PGE-M was chemically synthesized & converted to a [2H6] methyloxime isomer for use as an internal standard. After purification, endogenous PGE-M was analyzed as a methyloxime derivative. Assay precision is ± 5%; accuracy is 92%. Results: Pts=57; RR=10.5%; MST=228 days. Urinary PGE-M levels = 11.3 ± 5.7 (mean±2 SD, n=10) & 6.4 ± 3.8 ng/mg creatinine (mean±2 SD, n=10) in normal men & women. In men & women with recurrent NSCLC, PGE-M levels were elevated 2-fold (p<0.01) & 3.1-fold above normal mean (p<0.005). PGE-M levels fell by a mean of 51% (p<0.001) & 43% (P<0.001) respectively in men & women following 5–7 days of celecoxib (400 mg p.o. bid). These data suggest that a large proportion of the PGE2 overproduction is COX2 derived. In a multivariate model accounting for sex, race, smoking history & histology we correlated PGE-M changes with clinical parameters & found a strong association with survival. Pts experiencing a reduction in urine PGE-M levels after celecoxib administration were much less likely to die than those who did not (P<0.005). Conclusion: Changes in urinary PGE-M levels following short course celecoxib may be a useful predictor of intratumoral COX2 inhibition. (Grant support: CA68485; P5090949). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
S119 MicroRNA-200b represses TGF- β1 induced EMT in BEAS-2B and primary bronchial epithelial cells
Authors: S Ladak, C Ward, S Ali
Journal: Thorax (2015)

<h3>Introduction</h3> MicroRNAs (miRNAs) are small non-coding RNAs that function as endogenous gene regulators. They may initiate a process called epithelial-mesenchymal transition (EMT) that leads to aberrant extracellular matrix remodelling and is implicated in a number of airway diseases. Dysregulation of miRNAs has been indicated in chronic lung disorders, the third most common cause of mortality in adults. <h3>Materials and methods</h3> NanoString was used to assay the differential expression of miRNAs at 1, 4 and 24 hrs following TGF-β1 treatment of BEAS-2B cells (immortalised primary bronchial epithelial cells) and control. QRT-PCR validated the expression profile of miR-200b. BEAS-2B and PBECs (primary bronchial epithelial cells) were transfected with miR-200b mimics to study expression of EMT markers at mRNA and protein level. MiRNA targets were identified and validated using multiple computational tools and qRT-PCR respectively. <h3>Results</h3> nCounter assay allowed identification of novel miRNAs including miR-200 family. MiR-200b mimic transfection (24 hrs) followed by TGF-β1 treatment (48 hrs) demonstrated a significant increase in E-Cadherin (p ≤ 0.05, p ≤ 0.001) and a significant decrease in Fibronectin (p ≤ 0.001, p ≤ 0.01) in BEAS-2B cells and PBECs. Protein studies suggested a similar trend in both the cells. The most prominent targets of miR-200b identified were RHOA, SMURF2, ZNF532 and ZEB2. A significant decrease was observed in ZNF532 (p ≤ 0.01) and ZEB2 (p ≤ 0.001) in miR-200b transfected and TGF-β1 treated BEAS-2B cells (n = 3). Differential expression of mRNA targets was observed in two sets of patient derived PBECs. <h3>Conclusion</h3> miR-200b suppressed TGF-β1 induced EMT by maintaining the epithelial framework of BEAS-2B cells and PBECs. Results provide new insights into miR-200b regulation in fibrosis and basis for therapeutic application in lung injury.
Resistance to TRAIL induced apoptosis based on methylation of TRAIL receptor 1 (DR4) and its relevance for a potential treatment option for ovarian cancer
Authors: P. Horak, D. Pils, R. Horvath, S. Tomek, K. Elandt, C. Zielinski, M. Krainer
Journal: Journal of Clinical Oncology (2005)

9691 Background: TRAIL is a type II transmembrane protein, which binds the apoptosis activating receptors DR4 and DR5. TRAIL can efficiently induce apoptosis in transformed tissue, while sparing normal cells. In ovarian cancer, elevated TRAIL expression is associated with favorable overall survival. As we could show earlier, TRAIL also displays a synergistic apoptotic effect on ovarian cancer cells in vitro when combined with cytotoxic agents. Methods: We used a tissue microarray to immunohistochemically assess the expression of TRAIL and its receptors. Additionally, expression of DR4 was measured by qRT-PCR. DR4 promoter hypermethylation was determined using MSP. To evaluate the functional relevance of DR4 expression, we performed demethylation, DR4 overexpression and DR4 siRNA experiments. Results: Analysis of the tissue microarray revealed a correlation of elevated DR4 expression with grading (r= 0.501, p<0.001). High grade tumors also show a trend towards elevated TRAIL levels (r=0.363, p=0.097). DR4 expression was significantly lower in patients of less than 50 years of age (p=0.048) independently from grading. We examined 13 ovarian cancer cell lines and determined cells with low or missing DR4 mRNA expression. Hypermethylation of the DR4 promoter correlated with lower DR4 mRNA levels. Forty primary cancer samples showed 9 cases (22.5%) of DR4 promoter hypermethylation. Finally, we transfected DR4 siRNA transiently into the ES-2 (ATCC) cell line (DR4 +) and overexpressed DR4 in the TRAIL resistant A2780 cell line (DR4-). TRAIL sensitivity was assessed using Annexin V/FITC staining. Conclusions: TRAIL may play an important role in ovarian cancer as a tumor surveillance factor. Unimpaired activity of TRAIL receptors may be crucial to inhibit tumor development and/or growth. Diminished receptor expression may lead to an accelerated tumorigenesis and on the other hand cancer cells may evolve immune escape strategies protecting them from apoptosis. We could show that DR4 methylation is an event occuring frequently in primary ovarian cancer. We would like to stress the determination of TRAIL sensitivity before initiating any TRAIL based therapy in future. No significant financial relationships to disclose.
Lung Cancer and Use of Cigarettes: A French Case-Control Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Benhamou, E Benhamou, M Tirmarche, R Flamant
Journal: JNCI Journal of the National Cancer Institute (1985)

A case-control study of 1,625 cases and 3,091 controls was conducted in France from 1976 to 1980 to compare the effects of different smoking habits, especially the use of filter cigarettes, tobacco types (light or dark), and the use of hand-rolled or manufactured cigarettes on the occurrence of lung cancer. All cases had histologically confirmed lung cancer; the controls were matched by sex, age, hospital of admission, and interviewer. The reported results concern only male nonsmokers and males who smoked (or had smoked) cigarettes exclusively, i.e., a total of 1,217 Kreyberg I and Kreyberg II cancer cases and 1,915 controls. Cigarette smoking was associated with both Kreyberg I and Kreyberg II cell categories although with different relative risks (RR) (17.2 and 3.6, resp.). Within the Kreyberg I category, RR were significantly increased (P<.0001) with certain indices of duration and intensity of cigarette exposure, such as early age at first cigarette smoked, daily consumption, depth of inhalation, and duration of smoking. A significant difference in risk was found within the Kreyberg I category for nonfilter versus filter cigarette smokers (RR = 18.1 and 10.9, resp.) and dark versus light tobacco smokers (RR = 18.1 and 4.9, resp.) but not for hand-rolled versus manufactured cigarette smokers (RR=19.8 and 16.0, resp.). When all the covariates were taken into account in a matched logistic regression, lung cancer risks for nonfilter versus filter cigarette smokers was RR=1.23, for hand-rolled versus manufactured cigarette users RR=1.22, and for dark versus light tobacco users RR=1.94.
Preventing Postpartum Smoking Relapse
Authors: Michele D. Levine, Yu Cheng, Marsha D. Marcus, Melissa A. Kalarchian, Rebecca L. Emery
Journal: JAMA Internal Medicine (2016)

Most women who quit smoking during pregnancy will relapse postpartum. Previous efforts to prevent postpartum relapse have been unsuccessful at increasing rates of sustained abstinence.To evaluate the relative efficacy of 2 different approaches to prevent postpartum smoking relapse.Pregnant women who recently had quit smoking were recruited before the end of pregnancy. Intervention sessions were conducted through a combination of telephone calls and in-person visits beginning at delivery and continuing through 24 weeks postpartum. Participants completed assessments at the prenatal baseline and at 12, 24, and 52 weeks postpartum. Participants were recruited between March 2008 and December 2012. The dates of the analysis were April 2014 to February 2015.Women received postpartum-adapted, behavioral smoking relapse prevention intervention and were randomly assigned to an enhanced cognitive behavioral intervention that included additional specialized strategies and content focused on women's postpartum concerns about mood, stress, and weight (Strategies to Avoid Returning to Smoking [STARTS]) or a supportive, time and attention-controlled comparison (SUPPORT). Intervention began before delivery and continued through 24 weeks postpartum.The primary outcome was biochemically confirmed sustained tobacco abstinence at 52 weeks postpartum. Secondary outcomes were self-reported mood, levels of perceived stress, and degree of concern about smoking-related weight gain.The study cohort comprised 300 participants (150 randomly assigned to each group). Their mean (SD) age was 24.99 (5.65) years. Overall, 38.0% (114 of 300), 33.7% (101 of 300), and 24.0% (72 of 300) of the sample maintained abstinence at 12, 24, and 52 weeks' postpartum, respectively. There were no differences between the intervention groups in abstinence or time to relapse. Self-reported depressive symptoms and perceived stress significantly improved over time, and improvements were similar for both intervention groups. Women with more depressive symptoms and higher levels of perceived stress were more likely to relapse (hazard ratio, 1.02; 95% CI, 1.00-1.04; P = .04 for depressive symptoms and hazard ratio, 1.04; 95% CI, 1.01-1.07; P = .003 for stress).An intervention designed to address women's concerns about mood, stress, and weight did not differentially improve rates of sustained tobacco abstinence postpartum compared with a time and attention-controlled comparison. Women in STARTS and SUPPORT reported postpartum improvements in mood and stress, and the experience of fewer depressive symptoms and less perceived stress was related to sustained abstinence. Given that most pregnant quitters will relapse within 1 year postpartum and that postpartum smoking has negative health consequences for women and children, effective interventions that target postpartum mood and stress are needed.clinicaltrials.gov Identifier: NCT00757068.
A cry from the fringe.
Authors: D E Weissman, J O'Donnell, A Brady
Journal: Journal of Clinical Oncology (1993)

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.1993.11.5.1006 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8487043 A cry from the fringe. D E WeissmanxD E WeissmanSearch for articles by this author , J O'DonnellxJ O'DonnellSearch for articles by this author , A BradyxA BradySearch for articles by this author https://doi.org/10.1200/JCO.1993.11.5.1006 PDF "A cry from the fringe.." Journal of Clinical Oncology, 11(5), p. 1006© 1993 by American Society of Clinical Oncology
Abstract 18196: Excellent Incorporation of Endovascular Aneurysm Repair After Telementoring Program in a Secondary Care Center
Authors: Alessandra Pia Porretta, Mario Alerci, Marcello Di Valentino, Rolf Wyttenbach, Marcel Bogen, Adriano Guerra, Luigi Inglese, Ludwig K. Von Segesser, Augusto Gallino
Journal: Circulation (2012)

BACKGROUND Telemedicine is a developing application which enhances mentoring and technical support for medical operators. Endovascular aneurysm repair (EVAR) represents a minimally invasive approac...
The Challenges of Mobile Health Regulation
Authors: Adam J. Schoenfeld, Neil Jay Sehgal, Andrew Auerbach
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Effects on growth suppression of prostate cancer cell lines by rubber attachment with honeycomb structure: A proposal of an wearable anti-cancer device
Authors: H. Shima, K. Nakae, T. Tamaoki-Hashimoto
Journal: Journal of Clinical Oncology (2005)

4779 Background: An increased incidence of prostate cancer prompted us to find a possible new therapeutic modality without chemotherapy, irradiation, nor surgical intervention. We examined the effect of the rubber with honeycomb structure (Bio Rubber™: Yamamoto Co., Osaka, Japan) on human prostate cancer cells. Bio Rubber, containing highly purified lime stone and titanium powder, radiates infrared wave. Methods: Three prostate cancer cell lines, Du145, LNCap, and PC3, grown in culture dishes, were sandwiched by a set of Bio Rubber, and mRNA expression was analyzed by a human 1.2k cDNA microarray (Clontech). The results were analyzed by using GeneSpring program (Silicon Genetics, Redwood, CA, U.S.A). Morphological changes were also observed, and cells cultured without Bio Rubber attachment were served as controls. For the observation of growth suppression with Bio Rubber, cells were treated with sodium butyrate (SB), an histone deacetylase inhibitor that induces cell differentiation, with or without Bio Rubber attachment in another set of experiment. Results: mRNAs up-regulation higher than 1.4-fold in Du145 cells after 21-day-attachment of Bio Rubber were Fas (1.4 X), FasL(2.3 X), CASP1 and 10 (both 1.7 X), TRADD (1.4 X), and DFF40 (1.7 X); in LNCap, Fas (1.6 X), and CASP8 (1.6 X); in PC3, CD40 (1.4 X), and TNF (1.4 X), indicating that apoptotic pathways were stimulated in a various degree. Several apoptotic features such as mitochondrial condensation and cytoplasmic vacuolization were also observed. Growth suppression rate of Du145 on day 8 was 56 % with Bio Rubber, 78% with 2 mM SB, and 91% in combination; of LNCap, 52%, 35%, and 73%; of PC3, 59%, 0%, and 88%, showing that growth suppression effect of Bio Rubber was enhanced by SB. Conclusions: Bio Rubber attachment suppressed prostate cancer cell growth probably through stimulation of apoptotic pathways, and additive effects were observed in combination with SB. No significant financial relationships to disclose.
Abstract 180: Synergistic Salutary Effects of HMG-CoA Reductase Inhibitor and Angiotensin II Receptor Blocker on Load-induced Heart Failure
Authors: Yasuhiro Maejima, Mitsuaki Isobe
Journal: Circulation Research (2014)

We have shown previously that combined HMG-CoA reductase inhibitor (statin) and angiotensin II receptor blocker (ARB) therapy significantly improves both symptoms and left ventricular (LV) function over time in patients with heart failure (HF) by a clinical study [ HF-COSTAR Trial]. We elucidated the mechanisms of combination therapy with the ARB (losartan, LOS) and long-acting and statin (simvastatin, SIM) for the treatment of load-induced heart failure. Salt-loaded Dahl salt-sensitive (DS) rats were treated with vehicle, LOS (5mg/kg/day), SIM (2mg/kg/day) and LOS + SIM for 16 weeks. LOS and SIM in combination improved LV dysfunction (ΔLV fractional shortening; LOS = 60%, SIM = 42%, LOS + SIM = 24%, p &lt;0.05), limited LV hypertrophy (ΔLV septal thickness; LOS = −21%, SIM = −18%, LOS + SIM = −13%, p &lt;0.05) and reduced cardiac fibrosis (ΔLV collagen density; LOS = −26%, SIM = −16%, LOS + SIM = −28%, p &lt;0.05) more than LOS or SIM alone. Both Rho and matrix metalloprotease-9 (MMP-9) activity in LV tissue were increased in untreated DS rats, and LOS and SIM in combination decreased these changes more than did LOS and SIM monotherapies. We confirmed that the plasma level of Exp-3174 (E3174), a LOS metabolite and a potent inverse agonist of angiotensin II receptor type 1, was higher in rats treated with LOS and SIM in combination than in those treated with LOS alone (E3174/LOS ratio; LOS = 2.6 ± 0.3 vs. LOS + SIM = 3.2 ± 0.2, p &lt;0.05). Next, to mimic the response of volume-overload heart failure in vitro , cultured neonatal rat cardiomyocytes (CMs) were cyclically stretched. Stretch-induced increased CM hypertrophy was suppressed by pretreatment with both SIM and E3174 more than by pretreatment with LOS, E3174, SIM, or LOS and SIM in combination. Mechanical stretch also induced activation of extracellular signal regulated kinase (ERK) and the stretch-induced ERK activation of CMs was also significantly suppressed by SIM + E3174. In conclusion, LOS and SIM had beneficial myocardial effects in rats with salt-sensitive hypertension, partly through promoting the accumulation of plasma E3174. SIM enhanced the myocardial protective effects of LOS through suppression of Rho and MMP-9 activity. Thus, a combination of ARB with statin has a promising potential as a therapeutic strategy for HF.
Comparison Of Two Dosing Schedules For Subcutaneous Injections Of Low-Dose Anti-CD20 Veltuzumab In Relapsed Immune Thrombocytopenia: Final Results Of a Phase I Study
Authors: Howard Liebman, James B Bussel, Mansoor N Saleh, Heather Horne, William A Wegener, David M Goldenberg
Journal: Blood (2013)
Long‐Term Outcomes Among Participants in the WEGENT Trial of Remission‐Maintenance Therapy for Granulomatosis With Polyangiitis (Wegener's) or Microscopic Polyangiitis
Authors: Xavier Puéchal, Christian Pagnoux, Élodie Perrodeau, Mohamed Hamidou, Jean‐Jacques Boffa, Xavier Kyndt, François Lifermann, Thomas Papo, Dominique Merrien, Amar Smail, Philippe Delaval, Catherine Hanrotel‐Saliou, Bernard Imbert, Chahéra Khouatra, Marc Lambert, Charles Leské, Kim H. Ly, Edouard Pertuiset, Pascal Roblot, Marc Ruivard, Jean‐François Subra, Jean‐François Viallard, Benjamin Terrier, Pascal Cohen, Luc Mouthon, Claire Le Jeunne, Philippe Ravaud, Loïc Guillevin
Journal: Arthritis & Rheumatology (2015)

Objective Findings from the WEGENT trial and other short‐term studies have suggested that azathioprine (AZA) or methotrexate (MTX) could effectively maintain remission of granulomatosis with polyangiitis (Wegener's) (GPA) or microscopic polyangiitis (MPA). This study was undertaken to examine whether differences in rates of relapse or adverse events would appear after discontinuation of these 2 maintenance regimens, when assessed over a longer followup period. Methods Long‐term outcomes in patients enrolled in the WEGENT trial were analyzed according to their randomized treatment group (AZA or MTX). Parameters at trial entry were evaluated as potential prognostic factors for death, relapse, or damage in multivariate models. Results Data from 10 years of followup were available for 112 (88.8%) of the 126 original trial participants. The median followup time was 11.9 years (95% confidence interval [95% CI] 11.3–12.5 years). In patients receiving AZA and those receiving MTX, the 10‐year overall survival rates were 75.1% (95% CI 64.8–86.9%) and 79.9% (95% CI 70.3–90.8%) ( P = 0.56), respectively, and relapse‐free survival rates were 26.3% (95% CI 17.3–40.1%) and 33.5% (95% CI 23.5–47.7%) ( P = 0.29), respectively. No between‐treatment differences were observed with regard to rates of relapse, adverse events, damage, survival without severe side effects, and survival without relapse and severe side effects. In analyses limited to the 97 patients with GPA, no between‐treatment differences in survival rates were observed. The 10‐year relapse‐free survival rate was lower in patients with GPA than in patients with MPA. However, in the multivariate analysis, anti–proteinase 3 antineutrophil cytoplasmic antibody (ANCA) positivity, and not GPA, was retained as being independently associated with the relapse rate. Conclusion The results of this long‐term analysis confirm that AZA and MTX are comparable treatment options for maintaining remission of GPA or MPA. Despite achieving good overall survival with these treatments, relapse rates, adverse events, and damage remain matters of concern and further studies are needed to reduce their frequency in these ANCA‐associated vasculitides.