tbuckley/cabot-search huggingface dataset:
Abstract 1455: Therapeutic synergy between novel tumor suppressor miR-520d-3p and EphA2-targeting siRNA in ovarian cancer
Authors: Maitri Shah, Gabriel Berestein Lopez, Anil Sood, George Calin
Journal: Cancer Research (2014)

Abstract EphA2 has emerged as an important target for ovarian cancer therapy in recent years. In the present study, we identified miR-520d-3p as an independent favorable prognostic marker for epithelial ovarian cancer patients. We demonstrate that dual targeting of EphA2 in vitro using EphA2-siRNA and miR-520d-3p exhibits synergistic downregulation of EphA2 and inhibits cell proliferation, migration and invasion. In vivo treatment using DOPC (1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) nano-liposomes conjugated with miR-520d-3p and EphA2-siRNA showed synergistic therapeutic efficacy and superior inhibition of tumor proliferation and angiogenesis than either monotherapy alone. We also identified that EphA2(low)/EphB2(low)/miR-520d-3p(high) gene signature predicts favorable clinical prognosis for ovarian cancer patients. This study addresses a new concept of RNA inhibition therapy by combining miRNA and siRNA to target oncogenic pathways altered in ovarian cancer. Citation Format: Maitri Shah, Gabriel Berestein Lopez, Anil Sood, George Calin. Therapeutic synergy between novel tumor suppressor miR-520d-3p and EphA2-targeting siRNA in ovarian 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 1455. doi:10.1158/1538-7445.AM2014-1455
The site of visceral metastases (mets) to predict overall survival (OS) in castration-resistant prostate cancer (CRPC) patients (pts): A meta-analysis of five phase III trials.
Authors: Susan Halabi, William Kevin Kelly, Haojin Zhou, Andrew J. Armstrong, David Quinn, Karim Fizazi, Nicole C Solomon, Ian Tannock, Daniel Peter Petrylak, Michael J. Morris, Eric Jay Small
Journal: Journal of Clinical Oncology (2014)

5002 Background: Recent studies have shown that metastatic site is an important predictor of overall survival, but the reports were based on small sample sizes and as such the estimates were unstable. We sought to test two hypotheses: 1) CRPC pts with lung mets have worse survival than pts with non-visceral mets; and 2) pts with liver mets have worse survival than pts with lung mets. Methods: We combined individual patient data from 3,993 chemotherapy-naive mets CRPC pts randomized to receive docetaxel (D) based therapy on 5 phase III trials: CALGB 90401 (D +/- Bevacizumab): SWOG 0421(D +/-atrasentan),ENTHUSE 33 (D +/- zibotentan), TAX327 (D 3 wks, D weekly) and SWOG 9916 (D + estramustine). Site of mets at baseline was categorized as: lymph node (LN) only, bone +/- LN with no visceral mets, any lung mets (but no liver), any liver mets, and other visceral. We used fixed-effects meta-analysis to estimate the pooled hazard ratios (pHR) and 95% confidence intervals (CI) for comparing pts with lung mets vs. non-visceral mets and liver mets vs. lung mets. Results: The pHR for death for pts with lung mets compared to pts with non-visceral mets was 1.3 (95% CI= 1.1-1.5, p<0.001) and the pHR for pts with any liver mets compared with pts with lung mets was 1.4 (1.2-1.7, p<0.001). The median overall survival by site of mets is presented in table below. f mets at baseline was categorized as: lymph node (LN) only, bone +/- LN with no visceral mets, any lung mets (but no liver), any liver mets, and other visceral. Conclusions: As anticipated, CRPC patients with liver mets had the worst OS (12.1 m). While pts with lung mets had better OS (16.5 months) compared to liver mets pts, they had significantly worse survival than pts with non-visceral bone mets (20 months). These data may help in treatment decisions and in the design of future clinical trials in mCRPC pts. Clinical trial information: NCT00110214. Metastatic Site N (%) Median OS in months (95% CI) LN only 187 (5) 27.0 (24.7-32.4) Bone/Bone with LN 3334 (83) 20.3 (19.7-21.0) Lung (+/- bone), no liver 300 (7) 16.5 (14.8-18.4) Liver (LM) (+/- bone) 280 (7) 12.1 (10.1-13.5) Other Visceral (adrenal, brain) 55 (1) 14.4 (12.6-19.1)
Psychiatric disorders among elderly patients admitted to hospital medical wards
Authors: Brian Cooper
Journal: Journal of the Royal Society of Medicine (1987)

A psychiatric investigation was carried out on patients aged 65–80 years who were admitted to the medical wards of six general hospitals in an industrial urban area of West Germany. In all, 626 patients were screened for cognitive and affective disorder using a short standardized interview, and at the second stage all those with abnormal responses, as well as a subsample of the apparently normal patients, were examined in greater detail. After correction for inaccuracies of screening, the frequency of psychiatric illness in this patient population was estimated as 30.2%, made up of 9.1% with organic brain syndromes and 21.1% with functional mental disorders. Comparison with field-study data for the same background population showed that the hospital patients were at increased risk for mental disturbance. At follow up after one year, outcome in terms of mortality, admission to long-term care and dependency on others was worst for patients with organic mental disorder, even after matching for age and initial severity of physical impairment. Functional mental illness was also associated with a relatively poor outcome in terms of dependency. The mental status of elderly medical patients appears to be important for the prognosis.
Preservation of the bladder in patients with rhabdomyosarcoma.
Authors: R Heyn, W A Newton, R B Raney, A Hamoudi, C Bagwell, T Vietti, M Wharam, E Gehan, H M Maurer
Journal: Journal of Clinical Oncology (1997)

PURPOSE To review the pathologic findings from children with gross residual rhabdomyosarcoma (RMS) of the bladder and compare the treatment outcome of those who underwent cystectomy with those who did not. PATIENTS AND METHODS Primary and follow-up records and pathology specimens for 28 patients with gross residual disease entered onto the intergroup Rhabdomyosarcoma Study (IRS) III were reviewed. These patients were assigned to receive 20 weeks of multiagent induction chemotherapy and 4 weeks of radiotherapy. Future therapy decisions were based on clinical and histologic evaluation at 20 weeks. RESULTS All patients had a clinical and histologic response. Thirteen patients underwent cystectomy at intervals that ranged from 1.5 to 38 months after the start of therapy. All but one patient are alive and well without recurrence. Reasons for cystectomy included presumed evidence of tumor growth from imaging studies, findings at cystoscopy, or histologic interpretation of biopsies. In 12 of 14 specimens from 15 patients who retained their bladder, no tumor cells were seen at first or second evaluation. In cystectomy specimens, tumor cellularity was markedly reduced and all tumor cells were in varying degrees of cellular maturation. Review of primary tumor specimens showed a greater degree of cellular maturation in patients with retained bladders than in those who underwent cystectomy. CONCLUSION Bladder RMS is responsive to chemotherapy and radiotherapy. Twelve of 26 patients showed complete loss of tumor cells after induction therapy. Cystectomy specimens showed diminished tumor cells with varying degrees of cellular maturation. It is hypothesized that these tumors may have shown further maturation and ultimate loss of matured cells with continuing therapy.
Predisposing factors for recurrent wheezing in toddlers
Authors: Ioana Ciuca, Liviu Pop, Zagorca Popa, Monica Marc, Voicu Tudorache, Ioan Popa
Journal: European Respiratory Journal (2012)

Background: Recurrent wheezing is frequently found among toddlers and obesity seems to be associated with asthma. In our country early introduction of wheat products in infant9s alimentation is a habit, associating obesity/paratrophy and vitamin D deficiency. The aim of the study is to evaluate the relationship of mentioned factors with recurrent wheezing in a pediatric group without positive familial history of asthma. Methods: Seventy four preschool children (2-5 years), with median age 2.8 years, monitored for recurrent wheeze (more than 4 episodes per year) were included in the study. Retrospective analysis about feeding period, vitamin D supplementation and history of rickets was done. Specific diet anamnesis regarding early introduction of wheat products (before 8 months) was obtained by individual questionnaire. During two summer months, we assessed nutritional status, vitamin D levels and calcium metabolism; investigating also the association of cow9s milk allergy. Results: A considerable percent of 70.27% of wheezing children had a strong association with early introduction of wheat products in diet, 65.38% of them associating obesity. Paratrophic children with wheezing were also deficient in vitamin D(64.7%). In seventeen children (16.36%) we found rickets sequelaes, despite vitamin D supplementation, according our national recommendations. Cow9s milk allergy was found in 32.43% children. Conclusion: Early introduction of wheat products in children alimentation predisposes to obesity associating vitamin D deficiency. Exchange of alimentary tradition and vitamin D supplementation might have a positive role in preventing the recurrent wheezing.
Acceptance of Lesbian, Gay, Bisexual, and Transgender People—Reply
Authors: Nicole Rosendale, S. Andrew Josephson
Journal: JAMA Neurology (2015)

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 Neurology 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 Neurology journal
Abstract 9896: Reduction of Endoplasmic Reticulum Stress Prevent Neointima Formation After Vascular Injury
Authors: Shutaro Ishimura, Masato Furuhashi, Hideki Ota, Tomohisa Yamashita, Masayuki Koyama, Yusuke Okazaki, Marenao Tanaka, Tomohiro Mita, Takahiro Fuseya, Hideaki Yoshida, Tetsuji Miura
Journal: Circulation (2011)

[Background] Restenosis after percutaneous coronary intervention is still a major obstacle in treatment of coronary artery disease. The endoplasmic reticulum (ER) stress and inappropriate adaptation through the unfolded protein response (UPR) is a predominant feature in pathological processes in several types of tissues. However, little is known about the link between ER stress and vascular diseases. In this study, we investigated involvement of ER stress in neointima hyperplasia after vascular injury. [Methods &amp; Results] The femoral artery of 7-8-week male mice was subjected to wire-induced vascular injury. After 4 weeks, immunohistological analysis showed that ER stress markers, including phosphorylation of eukaryotic initiation factor 2α (eIF2α) and inositol-requiring enzyme-1 (IRE1), protein disulfide isomerase (PDI), glucose-regulated protein 94 (GRP94), and C/EBP homologous protein (CHOP) were up-regulated in hyperplastic neointima in injured regions. Treatment with 4-phenylbutyrate (PBA) and tauroursodeoxycholic acid (TUDCA), chemical chaperones, significantly reduced intima/media ratio by 46.6% and 70.9%, respectively, compared with the control. In the second series of experiments, the involvement of ER stress in cell proliferation was examined in human coronary artery smooth muscle cell (CASMC). Stimulation of CASMCs with platelet-derived growth factor (PDGF) led to activation of the UPR, which was indicated by a phosphorylation of IRE1 and eIF2α and an induction of GRP78 and PDI proteins, and the UPR was accompanied by phosphorylation of extracellular signal-regulated kinase (ERK). Elevation of mRNA levels of GRP94, GRP78, PDI, and spliced form of X-box binding protein 1 after PDGF treatment was confirmed by quantitative RT-PCR. PBA significantly suppressed PDGF-induced elevation of protein and mRNA levels of the ER stress markers and inhibited proliferation of CASMC by 62.9%. [Conclusions] Our findings suggest that ER stress plays a significant role of neointima hyperplasia after vascular injury and that reduction of ER stress might be a novel strategy against post-angioplasty restenosis.
Glycoprotein biosynthesis in small intestine
Authors: Young S. Kim, Jose Perdomo
Journal: Journal of Clinical Investigation (1972)

Rat small intestinal mucosa was examined for ability to produce mucins with human blood group A, B, and H activity. Blood group activity of the mucins was compared to antigenic activity of red blood cells in individual rats and the enzymatic basis for differences was investigated. Red cells in all the rats examined contained human blood group A and B antigens. All rats synthesized intestinal mucins having B and H antigenic activity but 57% failed to produce mucins with blood group A activity (A(-)); the remaining 43% (A(+)) produced A substance. The activities of five glycosyltransferases including alpha(1-->2) fucosyltransferase, the determinant of human secretor status, were measured in the intestine of A(+) and A(-) rats. Four enzymes were the same in both groups, while the fifth, N-acetylgalactosaminyltransferase, was present only in A(+) rats. The specificity of this latter enzyme, as found in the rat, appeared similar to that in humans, since it catalyzed addition of N-acetyl-D-galactosamine only to acceptors which had the H determinant structure. In the presence of the enzyme, A(-) mucin could be converted to A(+) mucin; this was shown both by hemagglutination inhibition and immunoprecipitin studies of the products of incubation of A(-) mucin with UDP-N-acetyl-D-galactosamine and the enzyme. These studies indicate that the difference between A(+) and A(-) rats is due to the apparent absence of N-acetylgalactosaminyltransferase in the intestinal mucosa of A(-) rats. These rats may provide experimental models for studies on the effect of ABO and secretor status on susceptibility to ulceration and carcinogenesis.
Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense
Authors: Joni M. Prasad, Oleg V. Gorkun, Harini Raghu, Sherry Thornton, Eric S. Mullins, Joseph S. Palumbo, Ya-Ping Ko, Magnus Höök, Tovo David, Shaun R. Coughlin, Jay L. Degen, Matthew J. Flick
Journal: Blood (2015)
Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)
Authors: Silvia Stacchiotti, Maria A. Pantaleo, Tiziana Negri, Annalisa Astolfi, Marcella Tazzari, Gian Paolo Dagrada, Milena Urbini, Valentina Indio, Roberta Maestro, Alessandro Gronchi, Marco Fiore, Angelo P. Dei Tos, Elena Conca, Elena Palassini, Bruno Vincenzi, Federica Grosso, Silvana Pilotti, Chiara Castelli, Paolo G. Casali
Journal: Clinical Cancer Research (2015)

To report on imatinib mesylate (IM) in patients with metastatic dermatofibrosarcoma protuberans (DFSP)/fibrosarcomatous (FS)-DFSP and on the impact of the treatment on tumor biology.Ten consecutive patients treated with IM from 2007 to 2015 for a metastatic relapse from DFSP/FS-DFSP were identified. FISH analysis for COL1A1-PDGFB was performed. Two IM-treated and 4 naïve FS-DFSP were transcriptionally profiled by RNAseq on HiScanSQ platform. Differential gene expression was analyzed with edgeR (Bioconductor), followed by hierarchical clustering and Principal Component Analysis.All cases featured fibrosarcomatous in the metastasis and retained the COL1A1-PDGFB. Best RECIST response was: 8 partial response, 1 stable disease, and 1 progressive disease. Median progression-free survival was 11 months. Five patients received surgery after IM and all relapsed. IM was restored in 4 patients with a new response. After IM, the most upregulated genes included those encoding for immunoglobulins and those affecting functions and differentiation of endothelial cells. Pathway enrichment analysis revealed upregulation in genes involved in antigen processing and presentation, natural killer-mediated cytotoxicity, and drug and xenobiotics metabolism. Conversely, a significant down-regulation of kinase signaling pathways was detected.All metastatic cases were fibrosarcomatous. Most patients responded to IM, but PFS was shorter than reported in published series which included both DFSP and FS-DFSP. All patients operated after IM had a relapse, suggesting that IM cannot eradicate metastatic cases and that the role of surgery is limited. Transcriptional profile of naïve and posttreatment samples pointed the contribution of immune infiltrates in sustaining the response to IM.
Pancreatic stellate cells stimulate pancreatic cancer growth and metastasis: findings of a novel orthotopic model of pancreatic cancer
Authors: Alain Vonlaufen, Swapna Joshi, Changfa Qu, Phoebe Phillips, Zhihong Xu, Nicole Parker, Cheryl Toi, Ron Pirola, Jeremy Wilson, David Goldstein, Minoti Apte
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

B78 

Pancreatic stellate cells (PSCs) produce the stromal reaction in pancreatic cancer (PC), but their role in cancer progression has not been fully elucidated. Aims: To assess the influence of PSCs on PC growth using i) an orthotopic model of pancreatic cancer and ii) in vitro studies with cultured human PSCs and MiaPaCa2 (a human PC cell line). Methods: I) In vivo model: Athymic mice received an intrapancreatic injection of one of the following - saline (S), human PSCs (P), MiaPaCa2 cells (M), or human PSCs + MiaPaCa2 (1:1; P+M). After 7 weeks, mice were killed and tumour size and metastasis assessed. Tumour histology was assessed with HE (b) MiaPaCa2 apoptosis - TUNEL staining to assess basal and H2O2-stimulated MiaPaCa2 cell apoptosis, in the presence and absence of PSC secretions. Results: I) Orthotopic model: Compared to mice injected with M alone, mice injected with P+M exhibited i) a significant increase in tumour size (20-fold larger tumour); ii) more frequent liver metastasis (50% P+M vs 10% M; p < 0.02); iii) significantly higher epithelial cell numbers; and iv) significantly increased numbers of activated PSCs in fibrotic bands. No tumours were found in mice injected with PSCs alone. II) In vitro studies: (a) MiaPaCa2 proliferation was increased upon exposure to PSC secretions [24h - 217.4±29.5*, 48h - 195.5±15.8*, 72h - 245.6±44.5* % of control; *p<0.005]. (b) MiaPaCa2 apoptosis - Both basal and H2O2 stimulated apoptosis was significantly inhibited by PSC secretions. [Data as fold change : basal apoptosis 1; PSC secretions 0.45±0.05*, H2O2 16.39±2.34**; H2O2+PSC secretions 3.59±0.81*; *p<0.01]. Conclusions: i) Pancreatic tumour growth and metastasis are significantly increased in mice receiving PSCs+MiaPaCa2 compared to those receiving MiaPaCa2 alone. The increase in tumour size is due to increased tumor cell number and not merely to fibrosis. ii) PSC secretions induce proliferation and inhibit apoptosis of PC cells. Implications: PSCs establish an environment that promotes tumour progression by stimulating proliferation and reducing apoptosis of pancreatic cancer cells.
Diagnosis of Pulmonary Embolism in Patients with Proximal Deep Vein Thrombosis
Authors: PHILIPPE GIRARD, MARIELLE DECOUSUS, SILVY LAPORTE, ANDREA BUCHMULLER, PHILIPPE HERVÉ, CHRISTIAN LAMER, FLORENCE PARENT, BERNARD TARDY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To determine the specificity of pulmonary embolism (PE) symptoms and lung scan perfusion defects in patients with deep vein thrombosis (DVT), we analyzed data on 400 patients with phlebography-proven proximal DVT included in a prospective trial. As the incidence of PE during anticoagulant therapy was the main outcome measure of the trial, all patients underwent lung scanning and/or pulmonary angiography within 48 h of inclusion, and then whenever PE was suspected. Angiography was recommended in patients with nondiagnostic lung scan. At baseline, the presence or absence of PE could be ascertained in 350 patients (87.5%), and 197 (56%) had PE. Sensitivity and specificity of symptoms for PE were 74 and 67%, respectively. Among 37 patients with symptoms and nondiagnostic lung scan, only 8 (22%) had PE at angiography. During anticoagulant therapy (3 mo), there were 29 events suspicious for PE, mostly (53%) within 2 wk of inclusion. Repeated perfusion studies with comparison to baseline tests excluded PE in 21 cases. Cumulated 3-mo risks of suspected and confirmed on-treatment PE were 6.8% (95% CI, 5.4- 8.2%) and 2.0% (95% CI, 0.6-3.4%) respectively. Even in patients with known proximal DVT, PE symptoms are unspecific and careful imaging studies are needed for diagnosis, both at baseline and during anticoagulant therapy.
The Epidemiology of Rheumatoid Arthritis in Ontario, Canada
Authors: Jessica Widdifield, J. Michael Paterson, Sasha Bernatsky, Karen Tu, George Tomlinson, Bindee Kuriya, J. Carter Thorne, Claire Bombardier
Journal: Arthritis & Rheumatology (2013)

Epidemiologic assessments of sufficiently large populations are required in order to obtain robust estimates of disease prevalence and incidence, particularly when exploring the influence of various factors (age, sex, calendar time). We undertook this study to describe the epidemiology of rheumatoid arthritis (RA) over the past 15 years.We used the Ontario Rheumatoid Arthritis administrative Database (ORAD), a validated population-based research database of all Ontarians with RA. The ORAD records were linked with census data to calculate crude and age and sex-standardized prevalence and incidence rates from 1996 to 2010. Vital statistics were used to estimate annual all-cause mortality during the study period.As of 2010, there were 97,499 Ontarians with RA, corresponding to a cumulative prevalence of 0.9%. Age and sex-standardized RA prevalence increased steadily over time from 473 (95% confidence interval [95% CI] 469-478) per 100,000 population (0.49%) in 1996 to 784 (95% CI 779-789) per 100,000 population (0.9%) in 2010. Age and sex-standardized incidence per 100,000 population ranged from 62 (95% CI 60-63) in 1996 to 54 (95% CI 52-55) in 2010. All-cause mortality decreased by a relative 21.4% since 1996.Over a 15-year period, we observed an increase in RA prevalence over time. This rise may be attributed to the increasing time to ascertain cases (which may have been latent in the population during earlier years of the study), increasing survival, and/or an increase in the aging background population. Incidence appears to be stable.
Lipoprotein (a) and Genetic Polymorphisms of Clotting Factor V, Prothrombin, and Methylenetetrahydrofolate Reductase Are Risk Factors of Spontaneous Ischemic Stroke in Childhood
Authors: Ulrike Nowak-Göttl, Ronald Sträter, Achim Heinecke, Ralf Junker, Hans-Georg Koch, Gerhard Schuierer, Arnold von Eckardstein
Journal: Blood (1999)