tbuckley/cabot-search huggingface dataset:
Gain of Oncogenic Function of p53 Mutants Induces Invasive Phenotypes in Human Breast Cancer Cells by Silencing <i>CCN5/WISP-2</i>
Authors: Gopal Dhar, Snigdha Banerjee, Kakali Dhar, Ossama Tawfik, Matthew S. Mayo, Peter J. VanVeldhuizen, Sushanta K. Banerjee
Journal: Cancer Research (2008)

Abstract CCN5/WISP-2 is overexpressed in noninvasive breast cancer cells and tissue samples, whereas its expression is minimal or undetected in invasive conditions. CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. However, the mechanism of silencing of CCN5 during the progression of the disease has been elusive. Because p53 mutations are associated with breast cancer progression and have been shown to correlate inversely with CCN5/WISP-2 expression in other cancer cell types, the objective of this study was to explore whether p53 mutants suppress CCN5 expression in breast tumor cells resulting in the progression of this disease. We found CCN5 expression is inversely correlated with the mutational activation of p53 in human breast tumor cells. The ectopic expression of p53 mutants in ER-positive noninvasive breast tumor cells silenced the CCN5/WISP-2 expression and enhanced invasive phenotypes, including the induction of morphologic changes from the epithelial-to-mesenchymal type along with the alterations of hallmark proteins of these cell types and an augmentation of the migration of these cells. The suppression of CCN5 by the p53 mutants can be nullified by estrogen signaling in these cells through the transcriptional activation of the CCN5 gene. Moreover, the invasive changes can be imitated by blocking the CCN5/WISP-2 expression through RNA interference or can be reversed by the addition of CCN5/WISP-2 recombinant protein in the culture. Thus, these studies suggest that CCN5 inactivation could be an essential molecular event for p53 mutant–induced invasive phenotypes. [Cancer Res 2008;68(12):4580–7]
Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study
Authors: David Olmos, Daniel Brewer, Jeremy Clark, Daniel C Danila, Chris Parker, Gerhardt Attard, Martin Fleisher, Alison HM Reid, Elena Castro, Shahneen K Sandhu, Lorraine Barwell, Nikhil Babu Oommen, Suzanne Carreira, Charles G Drake, Robert Jones, Colin S Cooper, Howard I Scher, Johann S de Bono
Journal: The Lancet Oncology (2012)
Restoration of p53 Pathway by Nutlin-3 Induces Cell Cycle Arrest and Apoptosis in Human Rhabdomyosarcoma Cells
Authors: Mitsuru Miyachi, Naoki Kakazu, Shigeki Yagyu, Yoshiki Katsumi, Satoko Tsubai-Shimizu, Ken Kikuchi, Kunihiko Tsuchiya, Tomoko Iehara, Hajime Hosoi
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Seventy to eighty percent of rhabdomyosarcoma (RMS) tumors retain wild-type p53. The tumor suppressor p53 plays a central role in inducing cell cycle arrest or apoptosis in response to various stresses. p53 protein levels are regulated by MDM2 through ubiquitin-dependent degradation. In this study, we evaluated whether nutlin-3, a recently developed small-molecule antagonist of MDM2, has an effect on p53-dependent cell cycle arrest and apoptosis in cultured human RMS cell lines. Experimental Design: Five RMS cell lines with different p53 statuses and MDM2 expression levels were treated with nutlin-3. Gene expression patterns, cell viability, cell cycle, and apoptosis after nutlin-3 treatment, and antitumor activity of combination treatment with vincristine or actinomycin D were assessed. Results: Significant p53 activation was observed in wild-type p53 cell lines after nutlin-3 treatment. p53 activation led to cell cycle arrest in parallel with increased p21 expression. Furthermore, these cell lines underwent p53-dependent apoptosis, concomitant with elevation of proapoptotic genes and activation of caspase-3. The effect of nutlin-3 was almost the same in terms of half maximal inhibitory concentration and apoptosis whether or not MDM2 was overexpressed. Nutlin-3 did not induce either cell cycle arrest or apoptosis in p53 mutant cell lines. A combination of vincristine or actinomycin D with nutlin-3 enhanced the antitumor activity in RMS cell lines with wild-type p53. Conclusions: Nutlin-3 effectively restored p53 function in both normal MDM2 expression and MDM2 overexpression RMS cell lines with wild-type p53. p53 restoration therapy is a potential therapeutic strategy for refractory RMS with wild-type p53.
High frequency of K-ras mutations in human colorectal hyperplastic polyps.
Authors: K Otori, Y Oda, K Sugiyama, T Hasebe, K Mukai, T Fujii, H Tajiri, S Yoshida, S Fukushima, H Esumi
Journal: Gut (1997)

BACKGROUND: Hyperplastic polyps are common benign colorectal polyps, and are thought to have little association with malignant tumours in the colorectum. However, several reports suggest that some hyperplastic polyps may develop into colorectal neoplasms. AIM: To clarify genetic alterations in colorectal hyperplastic polyps. METHODS: Twenty eight colorectal polyps having serrated components were resected from patients endoscopically. The K-ras gene mutations in codons 12 and 13 were analysed by PCR-RFLP. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps. CONCLUSION: Some hyperplastic polyps may be true neoplastic lesions, and could be precursors of malignant neoplasia.
A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma
Authors: A. Schmittel, M. Schmidt-Hieber, P. Martus, N.E. Bechrakis, R. Schuster, J.M. Siehl, M.H. Foerster, E. Thiel, U. Keilholz
Journal: Annals of Oncology (2006)
Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor- 1 in airway fibroblasts in asthma
Authors: Rafael Firszt, Dave Francisco, Tony D. Church, Joseph M. Thomas, Jennifer L. Ingram, Monica Kraft
Journal: European Respiratory Journal (2013)

Airway remodelling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodelling is subepithelial fibrosis. Interleukin (IL)-13 is a key T-helper 2 cytokine and is believed to be the central mediator of allergic asthma including remodelling, but the mechanism driving the latter has not been elucidated in human asthma. We hypothesised that IL-13 stimulates collagen type-1 production by the airway fibroblast in a matrix metalloproteinase (MMP)- and transforming growth factor (TGF)-β1-dependent manner in human asthma as compared to healthy controls. Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors. IL-13 significantly stimulated collagen type-1 production in asthma compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-β1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls. In an ex vivo model, IL-13 potentiates airway remodelling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodelling in asthma.
The Pharmacology of the Ductus Arteriosus
Authors: G C Smith
Journal: Pharmacological Reviews (1998)

The ductus arteriosus is a shunt blood vessel of fetal life; it extends between the pulmonary artery and the aorta. It shunts deoxygenated blood from the main pulmonary artery to the descending aorta. Over half of the blood flow in the descending aorta is diverted to the umbilico-placental
Tobacco control: from concern for the lung to global political action
Authors: D YACH
Journal: Thorax (2001)

Three cases of pyogenic vertebral osteomyelitis occurred in which unusual, fastidious, Gram negative coccobacilli belonging to the "HB" group were isolated. The organisms were Haemophilus aphrophilus in case 1, intermediate between H aphrophilus and Actinobacillus actinomycetemcomitans in case 2, and Eikenella corrodens in case 3. All HB bacteria are sensitive to a wide range of antibiotics.
Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites
Authors: Mevlut Kurt
Journal: Hepatology (2010)

I read with great interest the article by Sersté et al.,1 who suggested that the use of beta-blockers was associated with poor survival in patients with refractory ascites. In this study, hepatocellular carcinoma, Child-Pugh class C, underlying etiologies of refractory ascites, and beta-blocker therapy were found to be independent factors predicting death. However, I think that the dose effect of propranolol also should have been included in the statistical analysis because 68 patients (88.3%) in the beta-blocker group were given more than 40 mg of propranolol per day. High doses of the drug may cause poor survival. Mevlut Kurt M.D.*, * Department of Gastroenterology, Turkiye Yuksek Ihtisas Teaching and Research Hospital, Ankara, Turkey.
Statin Attenuates Increase in C-Reactive Protein During Estrogen Replacement Therapy in Postmenopausal Women
Authors: Kwang Kon Koh, William H. Schenke, Myron A. Waclawiw, Gyorgy Csako, Richard O. Cannon
Journal: Circulation (2002)

Background — HMG-CoA reductase inhibitor (statin) therapy reduces cardiovascular risk, mechanisms of which may include diminished arterial inflammation, as suggested by reduction in levels of C-reactive protein (CRP). Because oral estrogens increase CRP in postmenopausal women, with potential inflammatory and thrombotic consequences that could compromise any benefit to cardiovascular risk, we determined whether the coadministration of a statin might modify the estrogenic effect on CRP. Methods and Results — In a double-blind, 3-period crossover study, 28 postmenopausal women (average LDL cholesterol 163±36 mg/dL) were randomly assigned to daily conjugated equine estrogens (CEEs) 0.625 mg, simvastatin 10 mg, or their combination for 6 weeks, with each treatment period separated by 6 weeks. CEEs increased median CRP levels from 0.27 to 0.46 mg/dL, simvastatin decreased CRP from 0.29 to 0.28 mg/dL, and the therapies combined increased CRP from 0.28 to 0.36 mg/dL (all P ≤0.02 versus respective baseline values). Post hoc testing showed that the 29% increase in CRP on the combination of CEEs with simvastatin was significantly less than the 70% increase in CRP on CEEs alone ( P &lt;0.05). The effect of combination therapy on CRP levels did not correlate with baseline CRP or with baseline or treatment-induced changes in levels of interleukin-6, lipoproteins, or flow-mediated dilation of the brachial artery as a measure of nitric oxide bioactivity. Conclusions — The combination of statin with estrogen may attenuate the potential harmful effects of estrogen therapy in postmenopausal women and maximize any benefit to cardiovascular risk.
Comparative Study of Prognostic Value for Coronary Disease Risk Between the U.K. Prospective Diabetes Study and Framingham Models
Authors: Richard J. Stevens, Rury Holman
Journal: Diabetes Care (2004)

The comparison by Protopsaltis et al. (1) of the Framingham risk equations and the U.K. Prospective Diabetes Study (UKPDS) risk engine as predictors of coronary risk in diabetes is of interest, as previous analyses have shown that the Framingham equations can underestimate absolute coronary heart disease (CHD) risk in diabetic subjects by a factor of 2 or more (2,3). The sensitivity and specificity analyses presented by the authors, however, are …
THE JOURNAL's Policy Regarding Release of Information to the Public
Authors: Phil B. Fontanarosa
Journal: JAMA (2000)

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
Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial
Authors: Sung Won Choi, Thomas Braun, Lawrence Chang, James L M Ferrara, Attaphol Pawarode, John M Magenau, Guoqing Hou, Jan H Beumer, John E Levine, Steve Goldstein, Daniel R Couriel, Keith Stockerl-Goldstein, Oleg I Krijanovski, Carrie Kitko, Gregory A Yanik, Michael H Lehmann, Isao Tawara, Yaping Sun, Sophie Paczesny, Markus Y Mapara, Charles A Dinarello, John F DiPersio, Pavan Reddy
Journal: The Lancet Oncology (2013)
Oral insulin administration and residual (β-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial
Authors: Lucy Chaillous, Hervé Lefèvre, Charles Thivolet, Christian Boitard, Najiba Lahlou, Catherine Atlan-Gepner, Béatrice Bouhanick, Agnès Mogenet, Marc Nicolino, Jean-Claude Carel, Pierre Lecomte, Richard Maréchaud, Pierre Bougnères, Bernard Charbonnel, Pierre Saï
Journal: The Lancet (2000)
Role of the Carboxyl Terminal of Connexin43 in Transjunctional Fast Voltage Gating
Authors: Alonso P. Moreno, Marc Chanson, Justus Anumonwo, Isabelle Scerri, Hong Gu, Steven M. Taffet, Mario Delmar
Journal: Circulation Research (2002)

Previous studies show that chemical regulation of connexin43 (Cx43) gap junction channels depends on the integrity of the carboxyl terminal (CT) domain. Experiments using Xenopus oocytes show that truncation of the CT domain alters the time course for current inactivation; however, correlation with the behavior of single Cx43 channels has been lacking. Furthermore, whereas chemical gating is associated with a "ball-and-chain" mechanism, there is no evidence whether transjunctional voltage regulation for Cx43 follows a similar model. We provide data on the properties of transjunctional currents from voltage-clamped pairs of mammalian tumor cells expressing either wild-type Cx43 or a mutant of Cx43 lacking the carboxyl terminal domain (Cx43M257). Cx43 transjunctional currents showed bi-exponential decay and a residual steady-state conductance of approximately 35% maximum. Transjunctional currents recorded from Cx43M257 channels displayed a single, slower exponential decay. Long transjunctional voltage pulses caused virtual disappearance of the residual current at steady state. Single channel data revealed disappearance of the residual state, increase in the mean open time, and slowing of the transition times between open and closed states. Coexpression of CxM257 with Cx43CT in a separate fragment restored the lower conductance state. We propose that Cx43CT is an effector of fast voltage gating. Truncation of Cx43CT limits channel transitions to those occurring across the higher energy barrier that separates open and closed states. We further propose that a ball-and-chain interaction provides the fast component of voltage-dependent gating between CT domain and a receptor affiliated with the pore.
A conductive catheter to improve patient safety during cardiac catheterization.
Authors: M J Lipton, A K Ream, B H Hyndman
Journal: Circulation (1978)

A 60 Hz current, as small as 20 microamperemeter (rms) is capable of causing ventricular fibrillation when directly applied to the heart. Significant cost and engineering effort has been spent to construct monitoring equipment which satisfies the safety regulations requiring maximum leakage currents below this value. Patients undergoing cardiac catheterization are particularly at risk from electrical hazards, primarily because catheters are made from nonconductive materials. A conductive catheter should allow externally applied currents to leak through its walls before reaching the catheter tip. A new electrically conductive catheter was compared with a standard nonconductive catheter. Five dogs were studied, with 81 attempts to cause fibrillation. Sixty-hertz voltage between the catheter and an external electrode was increased until fibrillation occurred or 130 V was reached. Eight states were studied in randomized sequence: conductive or nonconductive catheter, guidewire or saline-filled and tip touching wall, or free in left ventricle (verified by fluoroscopy and cineangiography). The saline-filled and conductive catheter was safer in that fibrillation never occurred, while fibrillation nearly always occurred with the nonconductive catheter. A conductive guidewire negates the protection of the conductive catheter. The application of conductive catheters could reduce instrumentation costs in laboratories and intensive care units and improve patient safety.
Evolutionary conservation of otd/Otx2 transcription factor action: a genome-wide microarray analysis in Drosophila
Authors: Haiqiong Montalta-He, Ronny Leemans, Thomas Loop, Martin Strahm, Ulrich Certa, Michael Primig, Dario Acampora, Antonio Simeone, Heinrich Reichert
Journal: Genome biology (2002)

Homeobox genes of the orthodenticle (otd)/Otx family have conserved roles in the embryogenesis of head and brain. Gene replacement experiments show that the Drosophila otd gene and orthologous mammalian Otx genes are functionally equivalent, in that overexpression of either gene in null mutants of Drosophila or mouse can restore defects in cephalic and brain development. This suggests that otd and Otx genes control a comparable subset of downstream target genes in either organism. Here we use quantitative transcript imaging to analyze this equivalence of otd and Otx gene action at a genomic level. Oligonucleotide arrays representing 13,400 annotated Drosophila genes were used to study differential gene expression in flies in which either the Drosophila otd gene or the human Otx2 gene was overexpressed. Two hundred and eighty-seven identified transcripts showed highly significant changes in expression levels in response to otd overexpression, and 682 identified transcripts showed highly significant changes in expression levels in response to Otx2 overexpression. Among these, 93 showed differential expression changes following overexpression of either otd or Otx2, and for 90 of these, comparable changes were observed under both experimental conditions. We postulate that these transcripts are common downstream targets of the fly otd gene and the human Otx2 gene in Drosophila. Our experiments indicate that approximately one third of the otd-regulated transcripts also respond to overexpression of the human Otx2 gene in Drosophila. These common otd/Otx2 downstream genes are likely to represent the molecular basis of the functional equivalence of otd and Otx2 gene action in Drosophila.
BMP4 Inhibits Breast Cancer Metastasis by Blocking Myeloid-Derived Suppressor Cell Activity
Authors: Yuan Cao, Clare Y. Slaney, Bradley N. Bidwell, Belinda S. Parker, Cameron N. Johnstone, Jai Rautela, Bedrich L. Eckhardt, Robin L. Anderson
Journal: Cancer Research (2014)

Abstract The TGFβ growth factor family member BMP4 is a potent suppressor of breast cancer metastasis. In the mouse, the development of highly metastatic mammary tumors is associated with an accumulation of myeloid-derived suppressor cells (MDSC), the numbers of which are reduced by exogenous BMP4 expression. MDSCs are undetectable in naïve mice but can be induced by treatment with granulocyte colony-stimulating factor (G-CSF/Csf3) or by secretion of G-CSF from the tumor. Both tumor-induced and G-CSF–induced MDSCs effectively suppress T-cell activation and proliferation, leading to metastatic enhancement. BMP4 reduces the expression and secretion of G-CSF by inhibiting NF-κB (Nfkb1) activity in human and mouse tumor lines. Because MDSCs correlate with poor prognosis in patients with breast cancer, therapies based on activation of BMP4 signaling may offer a novel treatment strategy for breast cancer. Cancer Res; 74(18); 5091–102. ©2014 AACR.
Mitochondrial Coupling Factor 6 Is Present on the Surface of Human Vascular Endothelial Cells and Is Released by Shear Stress
Authors: Tomohiro Osanai, Satoko Okada, Kenichi Sirato, Takao Nakano, Masayuki Saitoh, Koji Magota, Ken Okumura
Journal: Circulation (2001)

Background — We showed that mitochondrial coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis, is present in the systemic circulation as a pressor substance in rats. We investigated the possibility of vascular endothelial cells as a source of circulating CF6. Methods and Results — We used 2 cultured endothelial cell lines, human umbilical vein endothelial cells (HUVECs) and ECV 304 cells (transformed HUVECs), for this study. Immunofluorescence microscopy of both ECV 304 and HUVECs confirmed the surface-associated immunoreactivity of anti-CF6 antibody on the plasma membrane. The concentration of CF6 in the medium increased gradually with time in both ECV 304 and HUVECs in static conditions. Exposure of ECV 304 and HUVECs to a fluid shear stress enhanced the release of CF6: In ECV 304, the concentration of CF6 in the medium (ng · well −1 · 6 hours −1 ) was 2.1±0.8 at baseline, 4.3±0.8 after shear at 15 dynes/cm 2 , and 57.7±8.4 after shear at 25 dynes/cm 2 . CF6 contents in the cell homogenate and mitochondria were both significantly increased after exposure of ECV 304 to 6-hour shear at 15 dynes/cm 2 , whereas they were unchanged after shear stress at 25 dynes/cm 2 . The ratio of CF6 to GAPDH mRNA was enhanced significantly, by 1.8±0.2-fold, after 6-hour shear stress at 25 dynes/cm 2 . Flow cytometry analysis revealed that the surface-associated CF6 was significantly increased in a 3-hour static condition after the previous exposure of the cells to shear stress for 3 hours. Conclusions — Vascular endothelial cells are a source of CF6, and shear stress regulates the release of the surface-associated CF6.
Unusual Combination of Tc-99m MDP and In-111 WBC Scans in Gangrene of the Foot
Authors: P. TODD MAKLER
Journal: Clinical Nuclear Medicine (1998)

Two diabetic patients with cellulitis and surgically proven gangrene of the toes were evaluated with combined Tc-99m MDP bone scans and In-111 WBC scans. The bone scans showed unusual "cold" areas in the area of the gangrene. The WBC scans were positive in both cases. In each case, the imaging technique was to label the patients WBCs with 500 µCi of In-111. The next day, a three-phase bone scan was performed using a medium-energy collimator and dual-isotope imaging. This procedure allows precise overlapping of the Tc-99m MDP bone and In-111 WBC images. In each of these cases, the bone tracer was unable to localize in the gangrenous area because of the impairment to blood flow. The WBCs, which had the advantages of a) 24 hours to localize, and b) the fact that WBCs can move outside of vascular channels, were able to identify the infection.