tbuckley/cabot-search huggingface dataset:
SMYD3 as an Oncogenic Driver in Prostate Cancer by Stimulation of Androgen Receptor Transcription
Authors: Cheng Liu, Chang Wang, Kun Wang, Li Liu, Qi Shen, Keqiang Yan, Xiaoqing Sun, Jie Chen, Jikai Liu, Hongbo Ren, Hainan Liu, Zhonghua Xu, Sanyuan Hu, Dawei Xu, Yidong Fan
Journal: JNCI Journal of the National Cancer Institute (2013)

Androgen receptor (AR) is critical for prostate tumorigenesis and is frequently overexpressed during prostate cancer (PC) progression. However, few studies have addressed the epigenetic regulation of AR expression. We analyzed SMYD3 expression in human PC with Western blot and immunohistochemistry. SMYD3 expression was knocked down using short hairpin RNA (shRNA) or small interfering RNA (siRNA). Cell proliferation, colony formation, and apoptosis analyses and xenograft transplantation were performed to evaluate the impact of SMYD3 depletion on PC cells. AR expression and promoter activity were determined using real-time quantitative polymerase chain reaction, western blot, and luciferase reporter assay. AR promoter association with Sp1, SMYD3, and histone modifications was assessed by chromatin immunoprecipitation. Differences in AR mRNA abundance and promoter activity were analyzed using Wilcoxon signed-rank tests, SMYD3 expression was analyzed using with Mann–Whitney U tests for unpaired samples, and tumor weight was analyzed with Student t test. All statistical tests were two-sided. The upregulation of SMYD3 protein expression was observed in seven of eight prostate tumor specimens, compared with matched normal tissues. Immunohistochemical analysis showed a strong SMYD3 staining in the nuclei of PC tissues in eight of 25 (32%) cases and in the cytoplasm in 23 out of 25 (92%) cases, whereas benign prostate tissue exhibited weak immunostaining. Depletion of SMYD3 by siRNA or shRNA inhibited PC cell proliferation (72 hours relative to 24 hours: control shRNA vs SMYD3 shRNA 1: mean fold change = 2.76 vs 1.68; difference = 1.08; 95% confidence interval = 0.78 to 1.38, P < .001), colony formation, cell migration, invasion, and xenograft tumor formation. Two functional SMYD3-binding motifs were identified in the AR promoter region. SMYD3 promotes prostate tumorigenesis and mediates epigenetic upregulation of AR expression.
Vaccination with dendritic cells transfected with mRNA-encoded folate-receptor-α for relapsed metastatic ovarian cancer
Authors: Juan José Hernando, Tjoung-Won Park, Hans-Peter Fischer, Oliver Zivanovic, Michael Braun, Martin Pölcher, Ursula Grünn, Claudia Leutner, Bernd Pötzsch, Walther Kuhn
Journal: The Lancet Oncology (2007)
Crohn's disease of the duodenum.
Authors: F W Nugent, M Richmond, S K Park
Journal: Gut (1977)

Crohn9s disease of the duodenum is uncommon, occurring in approximately 2% of patients with Crohn9s disease. Approximately 165 cases have been reported in small series in the literature. Our report includes 36 patients, most of whom had symptoms of duodenal disease coincident with or after obvious disease elsewhere in the gastrointestinal tract, although occasionally duodenal disease developed first and rarely disease was confined to the duodenum. Upper abdominal pain and symptoms of gastroduodenal obstruction are the commonest patterns of presentation. Significant weight loss is common, and occasionally major upper gastrointestinal bleeding occurs. The commonest pattern of involvement was contiguous disease of the proximal duodenum and distal stomach. Endoscopically, diffuse granularity, nodularity, and ulceration are seen accompanied by lack of distensibility of the involved area. Granulomas are rarely found in endoscopic biopsies. A bypass procedure was carried out on 18 patients, 15 of whom continue to be free of symptoms with an average follow-up of 6-6 years. When symptoms of obstruction dictate, operative bypass is accompanied by favourable long-term results in the large majority of patients.
β2-Adrenoceptor Agonists Enhance Cytokine-Induced Release of Thymic Stromal Lymphopoietin by Lung Tissue Cells
Authors: K. Orihara, K. Futamura, H. Morita, N. Hashimoto, S. Fukuda, R. Moqbel, K. Matsumoto, H. Saito, A. Matsuda
Journal: Journal of Allergy and Clinical Immunology (2010)
Role of Neuropathy and High Foot Pressures in Diabetic Foot Ulceration
Authors: Robert G Frykberg, Lawrence A Lavery, Hau Pham, Carolyn Harvey, Lawrence Harkless, Aristidis Veves
Journal: Diabetes Care (1998)

High plantar foot pressures in association with peripheral neuropathy have been ascertained to be important risk factors for ulceration in the diabetic foot. Most studies investigating these parameters have been limited by their size and the homogeneity of study subjects. The objective of this study was therefore to ascertain the risk of ulceration associated with high foot pressures and peripheral neuropathy in a large and diverse diabetic population.We studied a cross-sectional group of 251 diabetic patients of Caucasian (group C) (n=121), black (group B) (n=36), and Hispanic (group H) (n=94) racial origins with an overall age of 58.5+/-12.5 years (range 20-83). There was an equal distribution of men and women across the entire study population. All patients underwent a complete medical history and lower extremity evaluation for neuropathy and foot pressures. Neuropathic parameters were dichotomized (0/1) into two high-risk variables: patients with a vibration perception threshold (VPT) > or =25 V were categorized as HiVPT (n=132) and those with Semmes-Weinstein monofilament tests > or =5.07 were classified as HiSWF (n=190). The mean dynamic foot pressures of three footsteps were measured using the F-scan mat system with patients walking without shoes. Maximum plantar pressures were dichotomized into a high-pressure variable (Pmax6) indicating those subjects with pressures > or =6 kg/cm2 (n=96). A total of 99 patients had a current or prior history of ulceration at baseline.Joint mobility was significantly greater in the Hispanic cohort compared with the other groups at the first metatarsal-phalangeal joint (C 67+/-23 degrees, B 69+/-23 degrees, H 82+/-23 degrees, P=0.000), while the subtalar joint mobility was reduced in the Caucasian group (C 21+/-8 degrees, B 26+/-7 degrees, H 27+/-11 degrees, P=0.000). Maximum plantar foot pressures were significantly higher in the Caucasian group (C 6.7+/-2.9 kg/cm2, B 5.7+/-2.8 kg/cm2, H 4.4+/-1.9 kg/cm2, P=0.000). Univariate logistic regression for Pmax6 on the history of ulceration yielded an odds ratio (OR) of 3.9 (P=0.000). For HiVPT, the OR was 11.7 (P=0.000), and for HiSWF the OR was 9.6 (P=0.000). Controlling for age, diabetes duration, sex, and race (all P < 0.05), multivariate logistic regression yielded the following significant associations with ulceration: Pmax6 (OR=2.1, P=0.002), HiVPT (OR=4.4, P=0.000), and HiSWF (OR=4.1, P=0.000).We conclude that both high foot pressures (> or =6 kg/cm2) and neuropathy are independently associated with ulceration in a diverse diabetic population, with the latter having the greater magnitude of effect. In black and Hispanic diabetic patients especially, joint mobility and plantar pressures are less predictive of ulceration than in Caucasians.
Expression of muscle-type phosphorylase in innervated and aneural cultured muscle of patients with myophosphorylase deficiency.
Authors: A Martinuzzi, L Vergani, R Carrozzo, M Fanin, L Bartoloni, C Angelini, V Askanas, W K Engel
Journal: Journal of Clinical Investigation (1993)

Patients with McArdle's myopathy lack muscle glycogen phosphorylase (M-GP) activity. Regenerating and cultured muscle of patients with McArdle's myopathy presents a glycogen phosphorylase (GP) activity, but it is not firmly established whether M-GP or non-M-GP isoforms are expressed. We have cultured myoblasts from biopsy specimen of five patients with McArdle's myopathy. Skeletal muscle was cultured aneurally or was innervated by coculture with fetal rat spinal cord explants. In the patients' muscle biopsies and in their cultured innervated and aneural muscle we studied total GP activity, isoenzymatic pattern, reactivity with anti-M-GP antiserum, and presence of M-GP mRNA. There was no detectable enzymatic activity, no immunoreactivity with anti-M-GP antiserum, and no M-GP mRNA in the muscle biopsy of all patients. GP activity, M-GP isozyme, and anti-M-GP antiserum reactivity were present in patients' aneural cultures, increased after innervation, and were undistinguishable from control. M-GP mRNA was demonstrated in both aneural and innervated cultures of patients and control by primer extension and PCR amplification of total RNA. Our studies indicate that the M-GP gene is normally transcribed and translated in cultured muscle of patients with myophosphorylase deficiency.
Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models
Authors: Zobeida Cruz-Monserrate, Wael R Abd-Elgaliel, Tobias Grote, Defeng Deng, Baoan Ji, Thiruvengadam Arumugam, Huamin Wang, Ching-Hsuan Tung, Craig D Logsdon
Journal: Gut (2011)

<h3>Background and Aims</h3> Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. Surgical resection is the only effective treatment; however, only 20% of patients are candidates for surgery. The ability to detect early PDAC would increase the availability of surgery and improve patient survival. This study assessed the feasibility of using the enzymatic activity of cathepsin E (Cath E), a protease highly and specifically expressed in PDAC, as a novel biomarker for the detection of pancreas-bearing pancreatic intraepithelial neoplasia (PanIN) lesions and PDAC. <h3>Methods</h3> Pancreas from normal, chronic pancreatitis and PDAC patients was assessed for Cath E expression by quantitative real-time PCR and immunohistochemistry. Human PDAC xenografts and genetically engineered mouse models (GEMM) of PDAC were injected with a Cath E activity selective fluorescent probe and imaged using an optical imaging system. <h3>Results</h3> The specificity of Cath E expression in PDAC patients and GEMM of pancreatic cancer was confirmed by quantitative real-time PCR and immunohistochemistry. The novel probe for Cath E activity specifically detected PDAC in both human xenografts and GEMM in vivo. The Cath E sensitive probe was also able to detect pancreas with PanIN lesions in GEMM before tumour formation. <h3>Conclusions</h3> The elevated Cath E expression in PanIN and pancreatic tumours allowed in-vivo detection of human PDAC xenografts and imaging of pancreas with PanIN and PDAC tumours in GEMM. Our results support the usefulness of Cath E activity as a potential molecular target for PDAC and early detection imaging.
A trial of inhaled budesonide on airway responsiveness in smokers with chronic bronchitis
Authors: T Engel, JH Heinig, O Madsen, M Hansen, ER Weeke
Journal: European Respiratory Journal (1989)

The aim of the present randomized, double-blind study was to evaluate the effect of inhaled budesonide on daily symptoms, ventilatory capacity, and airway responsiveness in smokers with chronic bronchitis. Twenty-five subjects with a provocative concentration producing a 20% fall in forced expiratory volume in one second PC20(FEV1) less than 2.0 mg.ml-1, by bronchial histamine challenge, were included. Eighteen subjects accomplished the entire 12 week study, eight receiving inhaled budesonide 400 micrograms b.i.d. and ten receiving placebo. Cough decreased significantly in the actively treated group during the treatment period, but no change could be demonstrated in expectoration, dyspnoea, or sleep disturbances. No changes in any of these symptoms were found in the placebo group, and no differences in symptoms scores were found between the groups. No significant differences in ventilatory capacity or bronchial responsiveness could be demonstrated. In conclusion, a moderately high dose of inhaled steroid in eight subjects with chronic bronchitis did not improve the symptom scores, ventilatory capacity, or airway responsiveness to any clinically relevant degree.
Congenital oesophageal respiratory tract fistula presenting in adult life
Authors: MH Danton, J McMahon, J McGuigan, None Gibbons
Journal: European Respiratory Journal (1993)

Congenital oesophageal respiratory tract fistula presenting in adult life is rare. A tracheo-oesophageal and a broncho-oesophageal fistula presenting in a 22 year old female and 68 year male, respectively, are described. In both, symptoms of chronic recurrent pulmonary suppuration were initially attributed to alternative aetiologies, resulting in diagnostic delay and inappropriate management. Correct diagnosis was established by flexible bronchoscopy and oesophageal contrast studies. Surgical division of fistulae resulted in complete symptom resolution.
Randomized, Phase III Trial of Sequential Epirubicin and Docetaxel Versus Epirubicin Alone in Postmenopausal Patients With Node-Positive Breast Cancer
Authors: R. Charles Coombes, Judith M. Bliss, Marc Espie, Frans Erdkamp, Jacob Wals, Alejandro Tres, Michel Marty, Robert E. Coleman, Nicole Tubiana-Mathieu, Marinus O. den Boer, Andrew Wardley, Lucy S. Kilburn, Derek Cooper, Marina W.K. Thomas, Justine A. Reise, Katie Wilkinson, Pierre Hupperets
Journal: Journal of Clinical Oncology (2011)

The Docetaxel Epirubicin Adjuvant (DEVA) trial evaluated the efficacy and toxicity of incorporating docetaxel after epirubicin to create a sequential anthracycline-taxane regimen in early breast cancer.After complete tumor excision, postmenopausal women with node-positive early breast cancer were randomly assigned to either epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks for six cycles (EPI × 6) or three cycles of epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks followed by three cycles of docetaxel 100 mg/m(2) on day 1 every 3 weeks (EPI-DOC). A subset of patients also participated in a quality of life (QOL) study. The primary end point was disease-free survival (DFS).From 1997 to 2005, 803 patients entered DEVA (EPI × 6, n = 397; EPI-DOC, n = 406). At a median follow-up of 64.7 months (interquartile range, 45.2 to 84.4 months), 198 DFS events had been reported (EPI × 6, n = 114; EPI-DOC, n = 84). The 5-year DFS rates were 72.7% (95% CI, 68.0% to 77.3%) for epirubicin alone and 79.5% (95% CI, 75.2% to 83.8%) for epirubicin followed by docetaxel; evidence of improvement in DFS was observed with EPI-DOC (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.91; P = .008). One hundred twenty-seven patients have died (EPI × 6, n = 75; EPI-DOC, n = 52); a reduction in deaths was observed with EPI-DOC (HR, 0.66; 95% CI, 0.46 to 0.94; P = .02). The 5-year overall survival rates were 81.8% (95% CI, 77.7% to 85.9%) for epirubicin and 88.9% (95% CI, 85.5% to 92.2%) for epirubicin followed by docetaxel. Assessment of toxicity and QOL showed that EPI-DOC was associated with greater toxicity but with no difference in QOL between arms during follow-up.These results suggest, within a relatively small trial, that substitution of docetaxel for epirubicin for the last three cycles of chemotherapy results in improved outcome in postmenopausal women with node-positive, early breast cancer compared with six cycles of epirubicin monotherapy.
Abnormal cardiovascular reflexes in patients with gastro-oesophageal reflux.
Authors: T K Chakraborty, A L Ogilvie, R C Heading, D J Ewing
Journal: Gut (1989)

Using five non-invasive tests, abnormalities of cardiovascular reflex function were found in 20 of 50 patients with gastro-oesophageal reflux. Abnormalities of pupil cycle time, an index of non-vagal parasympathetic function, were found in only a few patients, implying that the cardiovascular abnormalities observed were not part of a generalised parasympathetic defect. The findings are consistent with the hypothesis that an abnormality of vagal function may contribute to the pathogenesis of gastro-oesophageal reflux.
Nonspecific resistance to bacterial infections. Enhancement by ubiquinone-8.
Authors: L H Block, A Georgopoulos, P Mayer, J Drews
Journal: The Journal of Experimental Medicine (1978)

A lipid fraction from Escherichia coli was extracted with apolar solvents and was found to protect mice from a number of experimental bacterial infections. The benzoquinone, ubiquinone-8, was isolated from this extract by high pressure liquid chromatography and identified as such by nuclear magnetic resonance and mass spectrometry. At a dose of 25 mg/kg this substance was found to provide complete protection against otherwise lethal infections with gram-negative and gram-positive bacteria in mice. Treatment was most effective when given intravenously 24 h before infection. In comparative studies, ubiquinone-8 had a clearly higher activity than ubiquinones-4, Q6, and Q10. A highly significant increase in the clearance rate of bacteria from the blood by the spleen and the liver of treated animals, correlated well with the protective effect of ubiquinone-8. The compound stimulated the ability of mouse macrophages to incorporate sheep erythrocytes and significantly increased the number of antibody-producing cells in spleens of mice.
Splanchnic sympathectomy prevents translocation and spreading of E coli but not S aureus in liver cirrhosis
Authors: M. Worlicek, K. Knebel, H. J. Linde, L. Moleda, J. Scholmerich, R. H. Straub, R. Wiest
Journal: Gut (2010)

<h3>Introduction</h3> Spontaneous bacterial peritonitis (SBP) is mainly caused by bacterial translocation of enteric Gram-negative bacteria, predominantly <i>Escherichia coli</i>. The sympathetic nervous system (SNS) is activated in advanced cirrhosis, particularly in the splanchic circulation, and exerts potent immunosuppressive actions. However, the role of splanchnic SNS activity in bacterial translocation and bacterial spreading in cirrhosis remains unclear. <h3>Methods</h3> <i>E coli</i> or <i>Stapylococcus aureus</i> (10<sup>6</sup> CFU) were given intraperitoneally. After 6 h, mesenteric lymph nodes (MLN), liver, spleen, lung and peripheral blood were harvested from ascitic cirrhotic rats (LC) and healthy controls with and without splanchnic sympathectomy (SE). The bacterial tissue burden was determined by standard microbiological culture techniques. In vitro phagocytic activity of peritoneal polymorphonuclear leucocytes was assessed by FACS analysis. <h3>Results</h3> Under basal conditions SE reduced bacterial translocation to MLN in LC rats from 45% to 17%. LC rats had a marked increase in bacteraemia after <i>E coli</i> and <i>S aureus</i> challenge and an increased incidence and degree of <i>E coli</i> translocation to MLN, liver, spleen and lung compared with control rats. SE prevented bacteraemia in LC rats after <i>E coli</i> but not after <i>S aureus</i> challenge. Prior SE abolished the difference in incidence as well as the bacterial tissue burden in each organ after <i>E coli</i> application in LC rats, being no longer significantly different from control rats with or without SE. The protective effects of SE against <i>E coli</i> were associated with a greater influx of mononuclear cells into the peritoneal cavity and increased phagocytic activity of peritoneal polymorphonuclear leucocytes. <h3>Conclusions</h3> In cirrhosis with bacterial peritonitis, hyperactivity of the splanchnic sympathetic nervous system contributes to the translocation of <i>E coli</i> but not <i>S aureus</i> to MLN and extraintestinal sites. This indicates a key role for sympathetic drive in the impairment in host defence against Gram-negative bacteria in cirrhosis.
Cyclin D1 Integrates Estrogen-Mediated DNA Damage Repair Signaling
Authors: Zhiping Li, Ke Chen, Xuanmao Jiao, Chenguang Wang, Nicole E. Willmarth, Mathew C. Casimiro, Weihua Li, Xiaoming Ju, Sung Hoon Kim, Michael P. Lisanti, John A. Katzenellenbogen, Richard G. Pestell
Journal: Cancer Research (2014)

The cyclin D1 gene encodes the regulatory subunit of a holoenyzme that phosphorylates the retinoblastoma protein (pRb) and nuclear respiratory factor (NRF1) proteins. The abundance of cyclin D1 determines estrogen-dependent gene expression in the mammary gland of mice. Using estradiol (E2) and an E2-dendrimer conjugate that is excluded from the nucleus, we demonstrate that E2 delays the DNA damage response (DDR) via an extranuclear mechanism. The E2-induced DDR required extranuclear cyclin D1, which bound ERα at the cytoplasmic membrane and augmented AKT phosphorylation (Ser473) and γH2AX foci formation. In the nucleus, E2 inhibited, whereas cyclin D1 enhanced homology-directed DNA repair. Cyclin D1 was recruited to γH2AX foci by E2 and induced Rad51 expression. Cyclin D1 governs an essential role in the E2-dependent DNA damage response via a novel extranuclear function. The dissociable cytoplasmic function to delay the E2-mediated DDR together with the nuclear enhancement of DNA repair uncovers a novel extranuclear function of cyclin D1 that may contribute to the role of E2 in breast tumorigenesis.
Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens.
Authors: A C Braverman, J H Antin, M T Plappert, E F Cook, R T Lee
Journal: Journal of Clinical Oncology (1991)

Cyclophosphamide (CY) cardiotoxicity may be a lethal complication of bone marrow transplantation. Previous echocardiographic studies have reported that left ventricular dysfunction due to CY occurs in over 50% of patients undergoing transplantation. To evaluate the cardiotoxicity of new dosing protocols that included twice-daily rather than once-daily CY, 44 bone marrow transplantation patients were prospectively evaluated with serial ECGs and echocardiograms. Twenty-six patients received a once-daily lower-dose protocol (mean total 87 +/- 11 mg/kg), and 18 patients received a twice-daily higher-dose (mean total 174 +/- 34 mg/kg) CY regimen. In the higher-dose CY group, significant reductions in summed ECG voltage (-20%) (P less than .01) and increases in left ventricular mass index (LVMI) (+10%) (P less than .05) were detected in the first week following therapy. These changes resolved by the third week following CY and were significantly greater than the changes noted in the lower-dose group. However, left ventricular ejection fraction (EF) did not change significantly in either group. Five patients developed clinical cardiotoxicity (four, pericarditis; one, congestive heart failure); four of the five patients were in the higher-dose group (P = .14). Only a prior history of congestive heart failure or a baseline EF less than 50% was an independent correlate of clinical cardiotoxicity (P less than .05). Thus, dose-dependent cardiotoxicity following the use of CY for bone marrow transplantation is evident as reversible decreases in ECG voltage and increases in left ventricular mass, possibly reflecting myocardial edema or hemorrhage. However, systolic dysfunction is much less common with these new twice-daily dosing regimens when compared with earlier studies of high-dose once-daily CY.