tbuckley/cabot-search huggingface dataset:
Abstract 2879: Anti-cancer effects of REIC/Dkk-3-encoding adenoviral vector for the treatment of non-small cell lung cancer
Authors: Ken Suzawa, Shinichi Toyooka, Kazuhiko Shien, Norimitsu Tanaka, Masami Watanabe, Junichi Soh, Masakiyo Sakaguchi, Keitaro Matsuo, Hiromasa Yamamoto, Masashi Furukawa, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Nam-Ho Huh, Shinichiro Miyoshi, Hiromi Kumon
Journal: Cancer Research (2014)

Abstract Objectives: REIC/Dkk-3 is down-regulated in a broad range of human cancer cells and is considered to function as a tumor suppressor. We previously reported that REIC/Dkk-3-expressing adenovirus vector (Ad-REIC) induced endoplasmic reticulum (ER) stress and cancer-specific apoptosis in human prostate cancer. In this study, we examined the therapeutic impact of Ad-REIC on non-small cell lung cancer (NSCLC). Materials and Methods: We examined the anti-tumor effect of Ad-REIC on 25 NSCLC cell lines in vitro and A549 cells in vivo. Two of these cell lines were artificially established as EGFR-tyrosine kinase inhibitor (TKI) resistant sublines. Results: Ad-REIC-treatment inhibited the cell viability by 40% or more in 13 (52%) of the 25 cell lines at multiplicity of infection (MOI) of 20 (20 MOI). These cell lines were regarded as being highly sensitive cells. The cell viability of a non-malignant immortalized cell line, OUMS-24, was not inhibited at 200 MOI of Ad-REIC. The effects of Ad-REIC on EGFR-TKI resistant sublines were equivalent to those in the parental cell lines. Here, we demonstrated that Ad-REIC treatment activated c-Jun N-terminal kinase (JNK) in NSCLC cell lines, indicating the induction of ER stress with GRP78/BiP (GRP78) up-regulation and resulting in apoptosis. A single intratumoral injection of Ad-REIC significantly inhibited the tumorigenic growth of A549 cells in vivo. As predictive factors of sensitivity for Ad-REIC treatment in NSCLC, we examined the expression status of GRP78 and coxsackievirus and adenovirus receptor (CAR). We found that the combination of the GRP78 and CAR expressional statuses may be used as a predictive factor for Ad-REIC sensitivity in NSCLC cells. Conclusion: Ad-REIC induced JNK activation and subsequent apoptosis in NSCLC cells. Our study indicated that Ad-REIC has therapeutic potential against NSCLC and that the expression statuses of GRP78 and CAR may predict a potential therapeutic benefit of Ad-REIC. Citation Format: Ken Suzawa, Shinichi Toyooka, Kazuhiko Shien, Norimitsu Tanaka, Masami Watanabe, Junichi Soh, Masakiyo Sakaguchi, Keitaro Matsuo, Hiromasa Yamamoto, Masashi Furukawa, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Nam-Ho Huh, Shinichiro Miyoshi, Hiromi Kumon. Anti-cancer effects of REIC/Dkk-3-encoding adenoviral vector for the treatment of non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2879. doi:10.1158/1538-7445.AM2014-2879
26 Piazza di Spagna
Authors: Janice Townley Moore
Journal: JAMA (2002)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Regulation of stearoyl-coenzyme A desaturase and fatty acid delta-6 desaturase-2 expression by linoleic acid and arachidonic acid in human sebocytes leads to enhancement of proinflammatory activity but does not affect lipogenesis
Authors: C.C. Zouboulis, S. Angres, H. Seltmann
Journal: British Journal of Dermatology (2011)

Treatment of SZ95 sebocytes with the essential fatty acid linoleic acid (LA) and the polyunsaturated fatty acid arachidonic acid (AA) leads to sebaceous lipogenesis. Animal data indicate that stearoyl-coenzyme A desaturase (SCD), a key enzyme in fatty acid biosynthesis, is involved in sebaceous lipogenesis and proinflammatory signalling in the sebaceous gland. On the other hand, fatty acid delta-6 desaturase-2 (FADS2) catalyses the conversion of LA to AA.To identify the effects of LA and AA on the expression of SCD and FADS2 and to detect its biological relevance.SZ95 sebocytes were treated with LA (10(-5) and 10(-4) mol L(-1) ), AA (10(-6) and 10(-5) mol L(-1) ) and the combination of LA (10(-4) mol L(-1) ) and testosterone (2 × 10(-8) mol L(-1) ), with or without addition of the SCD inhibitor FPCA (10(-8) and 10(-6) mol L(-1) ). Cytotoxicity was determined by the lactate dehydrogenase assay. SCD and FACS2 mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction and protein expression by Western blot analysis. SZ95 sebocyte lipid content and cell number were measured by the Nile red and the fluorescein diacetate microassays, respectively. Determination of interleukin (IL)-6 and IL-8 release was evaluated by enzyme-linked immunosorbent assay.LA treatment induced an increase of SCD and FADS2 at mRNA and protein levels in SZ95 sebocytes after 1·5 h. Treatment with AA led to an increase of SCD but to a decrease of FADS2 mRNA levels. LA/testosterone cotreatment stimulated lipogenesis in SZ95 sebocytes. A distinct proinflammatory pattern was registered: whereas LA strongly upregulated IL-6 secretion only, AA induced a mild level of IL-6 and IL-8 release from SZ95 sebocytes. Treatment with the SCD inhibitor FPCA reduced the LA/testosterone-upregulated SCD and FADS2 mRNA levels and resulted in an anti-inflammatory effect, but did not affect sebaceous lipogenesis.LA-induced sebaceous lipogenesis is likely to be an SCD-independent effect. Regulation of SCD and FADS2 expression by LA and AA leads to enhancement of proinflammatory activity but does not affect lipogenesis in human sebocytes.
A memorable mistake: Please come back---the patient won't take her cotton wool
Authors: A. Bacon
Journal: BMJ (1998)

Back in 1967, hospital cardiopulmonary resuscitation teams were new, almost as new as my medical degree. My preregistration houseman duties included coronary care, directed by a highly regarded general physician of legendary wisdom and humanity. It was accepted by all that it was inappropriate to admit patients over the age of 70 to coronary care or to resuscitate them on the ward. After all, the bible indicated that a life span of three score years and ten was normal. No ethics committees in those days.

This particular cardiac …
Abstract 15889: C-Terminal Modifications of Akt Kinase Boost Cellular Responses to Insulin by Inhibiting Activation Loop Dephosphorylation
Authors: Tung Chan, Jin Zhang, Brian Tiegs, Linda Yan, Brian Blumhof, Nikhil Keny, Morgan Penny, Xue Li, Roger Armen, John Pascal, Ulrich Rodeck, Raymond Penn
Journal: Circulation (2014)

Introduction: The Akt kinase isoforms (Akt1, Akt2 and Akt3) are activated downstream of the insulin receptor, and exert unique effects on cell growth, survival and metabolism. We recently described a novel ATP-dependent "dephosphorylation-resistance cage" in Akt kinases that controls access of cellular phosphatases to dephosphorylate the Akt activation loop (T308 in Akt1). Hypothesis: Here, we describe that, when Akt is localized at the cell membrane, intramolecular interactions of Akt C-terminal sequences with the hydrophobic groove of the kinase domain protect the phosphorylated activation loop (pT308 in Akt1) from cellular phosphatases. Methods and Results: Charged amino acid replacements of Akt C-terminal phosphorylation sites regulated by MTORC2 (Ser473) and by cyclin-dependent kinase 2 (Ser477) increased phospho-T308 protection from cellular phosphatases regardless of subcellular location. Functionally, these phosphatase-resistant Akt variants were refractory to ceramide-dependent dephosphorylation and amplified insulin-dependent T308 phosphorylation in a regulated fashion (Figure 1). Conclusions: Collectively, these results suggest that modulating phosphatase sensitivity of Akt activation loops via C-terminal hydrophobic groove may provide a platform to develop novel Akt agonists.
Canada's government tries to save healthcare system
Authors: David Spurgeon
Journal: BMJ (2000)

The proposal by Canada's federal health minister, Allan Rock, to save the country's healthcare system by paying half the cost of a national home care programme has been greeted contemptuously by provincial premiers. They say that he should restore billions of dollars of funding he has cut in past years before introducing such “boutique” programmes.

In a letter to the prime minister, Jean Chretien, Ontario's premier, Mike Harris, said that Mr Rock's attempt to position himself as the saviour of Medicare (Canada's health insurance system) was “blatant hypocrisy.” “After all, the federal government is responsible for the largest funding cut in Canadian history,” …
Abstract 12227: Human C-reactive Protein Enhances Thrombus Formation In Transgenic Rabbits
Authors: Shuntaro Matsuda, Atsushi Yamashita, Shuji Kitajima, Jianglin Fan, Yujiro Asada
Journal: Circulation (2010)

Objective: High plasma levels of C-reactive protein (CRP) are a powerful predictive marker of cardiovascular events. Several lines of evidence suggest that CRP may have prothombogenic effects. Howe...
Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del<i>CFTR</i>
Authors: Claire E. Wainwright, J. Stuart Elborn, Bonnie W. Ramsey, Gautham Marigowda, Xiaohong Huang, Marco Cipolli, Carla Colombo, Jane C. Davies, Kris De Boeck, Patrick A. Flume, Michael W. Konstan, Susanna A. McColley, Karen McCoy, Edward F. McKone, Anne Munck, Felix Ratjen, Steven M. Rowe, David Waltz, Michael P. Boyle
Journal: New England Journal of Medicine (2015)

Cystic fibrosis is a life-limiting disease that is caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Phe508del is the most common CFTR mutation.We conducted two phase 3, randomized, double-blind, placebo-controlled studies that were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who had cystic fibrosis and were homozygous for the Phe508del CFTR mutation. In both studies, patients were randomly assigned to receive either lumacaftor (600 mg once daily or 400 mg every 12 hours) in combination with ivacaftor (250 mg every 12 hours) or matched placebo for 24 weeks. The primary end point was the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1) at week 24.A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV1 was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor-ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV1 ranged from 2.6 to 4.0 percentage points (P<0.001), which corresponded to a mean relative treatment difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of pulmonary exacerbations was 30 to 39% lower in the lumacaftor-ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor-ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor-ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor-ivacaftor versus 1.6% among those who received placebo.These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.).
Next‐generation sequencing sheds light on the natural history of hepatitis C infection in patients who fail treatment
Authors: Tamer Abdelrahman, Joseph Hughes, Janice Main, John McLauchlan, Mark Thursz, Emma Thomson
Journal: Hepatology (2014)

High rates of sexually transmitted infection and reinfection with hepatitis C virus (HCV) have recently been reported in human immunodeficiency virus (HIV)-infected men who have sex with men and reinfection has also been described in monoinfected injecting drug users. The diagnosis of reinfection has traditionally been based on direct Sanger sequencing of samples pre- and posttreatment, but not on more sensitive deep sequencing techniques. We studied viral quasispecies dynamics in patients who failed standard of care therapy in a high-risk HIV-infected cohort of patients with early HCV infection to determine whether treatment failure was associated with reinfection or recrudescence of preexisting infection. Paired sequences (pre- and posttreatment) were analyzed. The HCV E2 hypervariable region-1 was amplified using nested reverse-transcription polymerase chain reaction (RT-PCR) with indexed genotype-specific primers and the same products were sequenced using both Sanger and 454 pyrosequencing approaches. Of 99 HIV-infected patients with acute HCV treated with 24-48 weeks of pegylated interferon alpha and ribavirin, 15 failed to achieve a sustained virological response (six relapsed, six had a null response, and three had a partial response). Using direct sequencing, 10/15 patients (66%) had evidence of a previously undetected strain posttreatment; in many studies, this is interpreted as reinfection. However, pyrosequencing revealed that 15/15 (100%) of patients had evidence of persisting infection; 6/15 (40%) patients had evidence of a previously undetected variant present in the posttreatment sample in addition to a variant that was detected at baseline. This could represent superinfection or a limitation of the sensitivity of pyrosequencing.In this high-risk group, the emergence of new viral strains following treatment failure is most commonly associated with emerging dominance of preexisting minority variants rather than reinfection. Superinfection may occur in this cohort but reinfection is overestimated by Sanger sequencing.
Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger
Authors: Patrick J. Schultheis, Lane L. Clarke, Pierre Meneton, Marian L. Miller, Manoocher Soleimani, Lara R. Gawenis, Tara M. Riddle, John J. Duffy, Thomas Doetschman, Tong Wang, Gerhard Giebisch, Peter S. Aronson, John N. Lorenz, Gary E. Shull
Journal: Nature Genetics (1998)
Abstract 15275: The New Cardiac Bedside Assessment: Integrating Hand-Held Cardiac Ultrasound into the Evaluation of Cardiac Patients
Authors: William McIntyre, Julie A Gilmour, Adrian Baranchuk, Paul Ewart, Anthony J Sanfilippo, Wilma M Hopman, James W Tam, Amer M Johri
Journal: Circulation (2014)

Background: As hand held cardiac ultrasound (HHCU) gains widespread use, so grows interest in evaluation of performance and training requirements for non-cardiologists. Our objective was to characterize the experience of senior medicine residents (SIMRs) trained to conduct focused HHCU examinations integrated into the bedside assessment of undifferentiated patients. Methods: Eight SIMRs completed an HHCU training program consisting of 4 hours of online modules, 4 hours of scanning, and 2 hours of cases. Training focused on the evaluation of aortic stenosis, mitral regurgitation, left ventricular (LV) systolic dysfunction, LV hypertrophy and pericardial effusions. Following training, SIMRs assessed undifferentiated patients with a routine history and physical examination and then conducted the HHCU protocol. The sensitivity and specificity of the routine bedside assessment (without HHCU) and the integrated bedside assessment with HHCU was determined for each lesion type, compared to formal transthoracic ec...
Abstract 18097: Diagnostic and Prognostic Value of Serum Concentration of High-Sensitivity Cardiac Troponin T Relative to Heart-Type Fatty Acid-Binding Protein in the Early Hours of Suspected Acute Coronary Syndrome
Authors: Shigeru Matsui, Junnichi Ishii, Tomoko Kawai, Tousei Hattori, Kousuke Hattori, Masanori Okumura, Hiroyuki Naruse, Sadako Motoyama, Hideo Izawa, Masanori Nomura, Yukio Ozaki
Journal: Circulation (2011)

Background: Heart-type fatty acid-binding protein (H-FABP), a low-molecular-mass cytoplasmic protein, has been proposed as an early biomarker for acute myocardial infarction (AMI). Thus, we prospectively investigated the diagnostic and prognostic value of serum level of high-sensitivity troponin T (hsTnT) relative to H-FABP in the early hours of acute coronary syndrome (ACS). Methods: Serum samples for measurements of hsTnT and H-FABP were drawn on admission in 460 consecutive patients (median age, 67.5 yrs) hospitalized to the cardiac emergency department for suspected ACS within 6 hrs (3.5 hrs) after the onset of chest symptom. Cardiac events, which were defined as cardiac death or rehospitalization for ACS or heart failure, were monitored for 12 months after admission. The final diagnosis was adjudicated by two independent cardiologists. Results: 224 (48.7%) patients were diagnosed as AMI [ST-segment elevation myocardial infarction in 154 (33.4%) patients; and emergent coronary angiography within 24 hrs after admission in 195 (42.4%) patients]. The area under the ROC curve was higher for hsTnT than for H-FABP (Table). The sensitivity and predictive accuracy of increased hsTnT (&gt; 0.014 ng/ml of 99th percentile) were higher than those of increased H-FABP (≥ 6.2 ng/ml of upper reference limit). Also, there was no significant difference in specificity between hsTnT and H-FABP. During 12-month follow-up period, there were 38 (8.3%) cardiac events including 11 cardiac deaths. In a stepwise Cox regression analysis, increased hsTnT (relative risk 14.5, P = 0.009), but not H-FABP, was independently associated with cardiac events. Patients with increased hsTnT had a higher risk of cardiac events within 12 months compared with those without (14.1% vs. 0.5%, P &lt; 0.0001). Conclusion: An hsTnT assay may provide diagnostic and prognostic information superior to H-FABP assay in the early hours of suspected ACS.
Caesarean section rate in England and Wales
Authors: W. Caan
Journal: BMJ (2002)

Editor—Dobson reports that deliveries by caesarean section in England rose from 4% in 1970 to 19% in 1999.1 Potentially, this created substantially increased demand on postnatal care within maternity services, at just the time when many hospitals, especially in Greater London, found difficulties even in maintaining numbers of midwives at their former levels.

For 477 women in two former London health trusts, 86 aspects of maternity care were surveyed in 1999.2 In general, the survey showed problems with postnatal hospital care. We re-examined the data to contrast the postnatal experiences of women after a caesarean (88, 18.4%) with those who had a “normal” vaginal delivery (340, 71.3%). We focused on 69 caesarean deliveries without any general anaesthetic (in case anaesthesia affected mothers' recall), 34 in the first trust and 35 in the second trust. We used non-parametric statistics (χ2, Spearman's rank correlation, Mann-Whitney U test), and our threshold for significance was P<0.05.

Caesarean deliveries were associated with some unsurprising differences (such as greater length of stay or more problems with infant feeding) compared with a normal delivery. One key question about postnatal care in both trusts was, “Did you ever feel the midwives were too busy to spend enough time with you?” Patients' answers to this question were highly correlated with overall ratings of their postnatal care while in hospital. Our concerns about the rising rates of caesareans were borne out in the first trust. The 34 women were significantly more likely to feel that the midwives were often too busy and less likely to report that they had known any of these midwives before, compared with the normal group. But this was not the picture in the second trust. Those 35 women were no more likely to report their midwives did not have enough time for them than the normal group, and the service actually arranged that they were more likely to know one or more of these midwives well.

Only a few miles apart, both trusts had a similar range of clients. Organisational responses to more caesarean sections differed. For example, an independent consultancy reported that the first trust exemplified the special difficulties in recruiting and retaining staff in London. The maternity and neonatal workforce group is investigating the organisation of gold standard care.3 A forthcoming national service framework for children's and maternity services offers midwives a fresh chance to develop their work in responsive and far sighted ways.
YC-1 induced DNA damage and Chk2-mediated E2F1 activation leading to breast cancer cell apoptosis
Authors: Cho-Hwa Liao, Shiow-Lin Pan, Jih-Hwa Guh, Chieh-Yu Peng, Tsai-Kun Lee, Ya-Ling Chang, Sheng-Chu Kuo, Fang-Yu Lee, Che-Ming Teng
Journal: Clinical Cancer Research (2007)

B37   In the present study, the anticancer effects of YC-1 were investigated in human breast cancer MCF-7 cells and NCI/ADR-RES cells. YC-1 inhibited MCF-7 cell proliferation in a concentration-dependent manner with a GI 50  of 0.7±0.07 μM. After 1 h treatment, YC-1 caused DNA double-strand breaks as detected by Comet assay, and subsequently, led to ATM-independent Chk2 activation, E2F1 protein induction and p53 protein phosphorylation. Both p53 and p73 proteins, transcribed by E2F1, were markedly increased. The activity of NF-κB, which controlled the survival signals, was decreased and the anti-apoptotic proteins, Mcl-1 and Bcl-2, were diminished. Meanwhile, YC-1 induced massive cell apoptosis along with PARP degradation, caspases-7 activation, and increased oligonucleosomal DNA fragmentation. According to these studies, YC-1-induced apoptotic signaling is probably mediated by Chk2-activated E2F1 accumulation, resulting in induction of p53 and p73 proteins and inhibition on Mcl-1 and NF-κB activity. Similar regulation of E2F1 and Mcl-1 was observed in NCI/ADR-RES cells. Furthermore, the antitumor activity of YC-1 against the human multiple-drug resistant tumor xenograft was found to be superior to that of paclitaxel. Taken together, YC-1 may have therapeutic efficacy in human breast cancer cells.