tbuckley/cabot-search huggingface dataset:
Regulatory crosstalk between lineage-survival oncogenes<i>KLF5, GATA4</i>and<i>GATA6</i>cooperatively promotes gastric cancer development
Authors: Na-Yu Chia, Niantao Deng, Kakoli Das, Dachuan Huang, Longyu Hu, Yansong Zhu, Kiat Hon Lim, Ming-Hui Lee, Jeanie Wu, Xin Xiu Sam, Gek San Tan, Wei Keat Wan, Willie Yu, Anna Gan, Angie Lay Keng Tan, Su-Ting Tay, Khee Chee Soo, Wai Keong Wong, Lourdes Trinidad M Dominguez, Huck-Hui Ng, Steve Rozen, Liang-Kee Goh, Bin-Tean Teh, Patrick Tan
Journal: Gut (2014)

<h3>Objective</h3> Gastric cancer (GC) is a deadly malignancy for which new therapeutic strategies are needed. Three transcription factors, KLF5, GATA4 and GATA6, have been previously reported to exhibit genomic amplification in GC. We sought to validate these findings, investigate how these factors function to promote GC, and identify potential treatment strategies for GCs harbouring these amplifications. <h3>Design</h3> <i>KLF5</i>, <i>GATA4</i> and <i>GATA6</i> copy number and gene expression was examined in multiple GC cohorts. Chromatin immunoprecipitation with DNA sequencing was used to identify KLF5/GATA4/GATA6 genomic binding sites in GC cell lines, and integrated with transcriptomics to highlight direct target genes. Phenotypical assays were conducted to assess the function of these factors in GC cell lines and xenografts in nude mice. <h3>Results</h3> <i>KLF5</i>, <i>GATA4</i> and <i>GATA6</i> amplifications were confirmed in independent GC cohorts. Although factor amplifications occurred in distinct sets of GCs, they exhibited significant mRNA coexpression in primary GCs, consistent with KLF5/GATA4/GATA6 cross-regulation. Chromatin immunoprecipitation with DNA sequencing revealed a large number of genomic sites co-occupied by KLF5 and GATA4/GATA6, primarily located at gene promoters and exhibiting higher binding strengths. KLF5 physically interacted with GATA factors, supporting KLF5/GATA4/GATA6 cooperative regulation on co-occupied genes. Depletion and overexpression of these factors, singly or in combination, reduced and promoted cancer proliferation, respectively, in vitro and in vivo. Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, <i>HNF4α</i>, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs. <h3>Conclusions</h3> KLF5/GATA4/GATA6 may promote GC development by engaging in mutual crosstalk, collaborating to maintain a pro-oncogenic transcriptional regulatory network in GC cells.
Hazard rates for recurrent and secondary cutaneous melanoma: An analysis of 33,384 patients in the German Central Malignant Melanoma Registry
Authors: Ulrike Leiter, Petra G. Buettner, Thomas K. Eigentler, Eva B. Bröcker, Christiane Voit, Harald Gollnick, Wolfgang Marsch, Uwe Wollina, Friedegund Meier, Claus Garbe
Journal: Journal of the American Academy of Dermatology (2011)
Symptom-related telephone monitoring and cardiopulmonary exercise testing in the pulmonary embolism follow-up for early detection of chronic thromboembolic pulmonary hypertension (CTEPH)
Authors: Matthias Held, Alexander Hesse, Regina Holl, Tobias Romen, Franziska Walter, Gudrun Huebner, Berthold Jany
Journal: European Respiratory Journal (2013)

The incidence of CTEPH as a serious complication of pulmonary embolism (PE) varies between 0.5 -8%. There are currently no established structured follow-up programs for early detection of CTEPH.  We prospectively studied the follow-up of patients with newly diagnosed PE to evaluate a symptom-related approach which is based on a telephone monitoring program. Patients were contacted after three, six, 12, 24 and 36 months. Patients were further studied if one item of a five item-questionnaire was positive. further imaging studies and right heart catheterization were performed in case that echocardiography or/and cardiopulmonary exercise testing (CPET) revealed abnormalities suggestive of pulmonary hypertension.  We report the results from our 3 months- follow-up and 18- months interim analysis.  3-months follow-up: n=104. Telephone interview suggesting abnormalities: n=32 (29,8 %). Pathological echocardiography: n=7, normal n= 25: CPET n=20: pathological CPET n =7, normal n =13. Further diagnostic work-up: n=15. Diagnosis CTEPH: n=7.  Interim analysis after18 months: n =123:Diagnosis CTEPH: n=10 .3 out of 10 patients had shown a pathological CPET despite normal echocardiographic findings.  The symptom-related follow-up program which is based on a telephone-monitoring and a 5 item-questionnaire detects patients with chronic-thromboembolic pulmonary hypertension. Cardiopulmonary exercise testing may serve as a complementary diagnostic tool. Telephone monitoring and cardiopulmonary exercise testing should be included in a pulmonary embolism follow-up program for early detection of CTEPH.
What Is the Core of Schizophrenia?
Authors: Stephan Heckers
Journal: JAMA Psychiatry (2013)

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 Psychiatry 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 Psychiatry journal
Chemoprevention of Human Prostate Cancer by Oral Administration of Green Tea Catechins in Volunteers with High-Grade Prostate Intraepithelial Neoplasia: A Preliminary Report from a One-Year Proof-of-Principle Study
Authors: Saverio Bettuzzi, Maurizio Brausi, Federica Rizzi, Giovanni Castagnetti, Giancarlo Peracchia, Arnaldo Corti
Journal: Cancer Research (2006)

Abstract Green tea catechins (GTCs) proved to be effective in inhibiting cancer growth in several experimental models. Recent studies showed that 30% of men with high-grade prostate intraepithelial neoplasia (HG-PIN) would develop prostate cancer (CaP) within 1 year after repeated biopsy. This prompted us to do a proof-of-principle clinical trial to assess the safety and efficacy of GTCs for the chemoprevention of CaP in HG-PIN volunteers. The purity and content of GTCs preparations were assessed by high-performance liquid chromatography [(−)-epigallocathechin, 5.5%; (−)-epicatechin, 12.24%; (−)-epigallocatechin-3-gallate, 51.88%; (−)-epicatechin-3-gallate, 6.12%; total GTCs, 75.7%; caffeine, &amp;lt;1%]. Sixty volunteers with HG-PIN, who were made aware of the study details, agreed to sign an informed consent form and were enrolled in this double-blind, placebo-controlled study. Daily treatment consisted of three GTCs capsules, 200 mg each (total 600 mg/d). After 1 year, only one tumor was diagnosed among the 30 GTCs-treated men (incidence, ∼3%), whereas nine cancers were found among the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did not change significantly between the two arms, but GTCs-treated men showed values constantly lower with respect to placebo-treated ones. International Prostate Symptom Score and quality of life scores of GTCs-treated men with coexistent benign prostate hyperplasia improved, reaching statistical significance in the case of International Prostate Symptom Scores. No significant side effects or adverse effects were documented. To our knowledge, this is the first study showing that GTCs are safe and very effective for treating premalignant lesions before CaP develops. As a secondary observation, administration of GTCs also reduced lower urinary tract symptoms, suggesting that these compounds might also be of help for treating the symptoms of benign prostate hyperplasia. (Cancer Res 2006; 66(2): 1234-40)
Experimental Rhinovirus Infection as a Human Model of Chronic Obstructive Pulmonary Disease Exacerbation
Authors: Patrick Mallia, Simon D. Message, Vera Gielen, Marco Contoli, Katrina Gray, Tatiana Kebadze, Julia Aniscenko, Vasile Laza-Stanca, Michael R. Edwards, Louise Slater, Alberto Papi, Luminita A. Stanciu, Onn M. Kon, Malcolm Johnson, Sebastian L. Johnston
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Respiratory virus infections are associated with chronic obstructive pulmonary disease (COPD) exacerbations, but a causative relationship has not been proven. Studies of naturally occurring exacerbations are difficult and the mechanisms linking virus infection to exacerbations are poorly understood. We hypothesized that experimental rhinovirus infection in subjects with COPD would reproduce the features of naturally occurring COPD exacerbations and is a valid model of COPD exacerbations.To evaluate experimental rhinovirus infection as a model of COPD exacerbation and to investigate the mechanisms of virus-induced exacerbations.We used experimental rhinovirus infection in 13 subjects with COPD and 13 nonobstructed control subjects to investigate clinical, physiologic, pathologic, and antiviral responses and relationships between virus load and these outcomes.Clinical data; inflammatory mediators in blood, sputum, and bronchoalveolar lavage; and viral load in nasal lavage, sputum, and bronchoalveolar lavage were measured at baseline and after infection with rhinovirus 16. After rhinovirus infection subjects with COPD developed lower respiratory symptoms, airflow obstruction, and systemic and airway inflammation that were greater and more prolonged compared with the control group. Neutrophil markers in sputum related to clinical outcomes and virus load correlated with inflammatory markers. Virus load was higher and IFN production by bronchoalveolar lavage cells was impaired in the subjects with COPD.We have developed a new model of COPD exacerbation that strongly supports a causal relationship between rhinovirus infection and COPD exacerbations. Impaired IFN production and neutrophilic inflammation may be important mechanisms in virus-induced COPD exacerbations.
Habenula “Cholinergic” Neurons Corelease Glutamate and Acetylcholine and Activate Postsynaptic Neurons via Distinct Transmission Modes
Authors: Jing Ren, Chang Qin, Fei Hu, Jie Tan, Li Qiu, Shengli Zhao, Guoping Feng, Minmin Luo
Journal: Neuron (2011)
Effect of Smad7 Expression on Metastasis of Mouse Mammary Carcinoma JygMC(A) Cells
Authors: Haruhito Azuma, Shogo Ehata, Hideyo Miyazaki, Tetsuro Watabe, Osamu Maruyama, Takeshi Imamura, Takeshi Sakamoto, Satoshi Kiyama, Yuko Kiyama, Takanobu Ubai, Teruo Inamoto, Shiro Takahara, Yuko Itoh, Yoshinori Otsuki, Yoji Katsuoka, Kohei Miyazono, Shigeo Horie
Journal: JNCI Journal of the National Cancer Institute (2005)

Transforming growth factor beta (TGF-beta) facilitates metastasis during the advanced stages of cancer. Smad6, Smad7, and c-Ski block signaling by the TGF-beta superfamily proteins through different modes of action. We used adenovirus-mediated gene transfer of these natural inhibitors in a mouse model of breast cancer to examine the roles of TGF-beta superfamily signaling in tumor growth and metastasis.We systemically administered, by intravenous injection, adenoviruses (AdCMV) containing the mouse cDNAs for Smad7, Smad6, c-Ski, the c-Ski mutant c-Ski (ARPG), or LacZ (control) to nude mice (>19 mice/group) bearing tumors derived from mouse mammary carcinoma JygMC(A) cells, which spontaneously metastasize to lung and liver, and examined their effects on survival and metastasis. High-throughput western blotting analysis was used to examine the expression levels for 47 signal transduction proteins in JygMC(A) cells and primary tumors. We also investigated the proliferation, migration, and invasion of JygMC(A) cells that stably overexpressed Smad6 or Smad7. Nonparametric comparisons were done by Kruskal-Wallis H statistic and Wilcoxon's rank sum tests. Parametric comparisons were done by one-way analysis of variance or two-sided unpaired Student's t tests. All statistical tests were two-sided.Control mice bearing tumors derived from JygMC(A) cells showed many metastases to the lung and liver; all animals died by 50 days after cell inoculation. By contrast, mice treated with AdCMV-Smad7 or AdCMV-c-Ski demonstrated a dramatic decrease in metastasis and statistically significantly longer survival than control mice (Smad7 versus LacZ: medium survival = 55 days versus 41 days, difference = 14 days [95% confidence interval {CI} = 6 days to 22 days], P < .001), whereas mice treated with AdCMV-Smad6 or AdCMV-c-Ski (ARPG) did not. Expression of Smad7 in JygMC(A) cells was associated with increased expression of major components of adherens and tight junctions, including E-cadherin, decreased expression of N-cadherin, and decreases in the migratory and invasive abilities of the JygMC(A) cells.Smad7 inhibits metastasis, possibly by regulating cell-cell adhesion. Systemic expression of Smad7 may be a novel strategy for the prevention of metastasis of advanced cancers.
A Review of Locomotion Systems for Capsule Endoscopy
Authors: Lejie Liu, Shahrzad Towfighian, Amine Hila
Journal: IEEE Reviews in Biomedical Engineering (2015)

Wireless capsule endoscopy for gastrointestinal (GI) tract is a modern technology that has the potential to replace conventional endoscopy techniques. Capsule endoscopy is a pill-shaped device embedded with a camera, a coin battery, and a data transfer. Without a locomotion system, this capsule endoscopy can only passively travel inside the GI tract via natural peristalsis, thus causing several disadvantages such as inability to control and stop, and risk of capsule retention. Therefore, a locomotion system needs to be added to optimize the current capsule endoscopy. This review summarizes the state-of-the-art locomotion methods along with the desired locomotion features such as size, speed, power, and temperature and compares the properties of different methods. In addition, properties and motility mechanisms of the GI tract are described. The main purpose of this review is to understand the features of GI tract and diverse locomotion methods in order to create a future capsule endoscopy compatible with GI tract properties.
Gemcitabine and capecitabine in previously anthracycline-treated metastatic breast cancer: a multicenter phase II study (SOLTI 0301 trial)
Authors: E.M. Ciruelos, J. Cortés, H. Cortés-Funes, J.I. Mayordomo, B. Bermejo, B. Ojeda, E. García, C.A. Rodríguez, M. Muñoz, P. Gómez, L. Manso, R. Andrés, A. Lluch, C. Saura, C. Mendiola, J. Baselga
Journal: Annals of Oncology (2009)
Adenosine Activates Aromatic L-Amino Acid Decarboxylase Activity in the Kidney and Increases Dopamine
Authors: TAKANOBU TAKEZAKO, KEITA NODA, EMIKO TSUJI, MANABU KOGA, MANABU SASAGURI, KIKUO ARAKAWA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Renal sodium handling is important for regulating BP, and renal dopamine and adenosine play an important role in renal sodium handling, however the interaction of these hormones in the kidney was not clarified. In in vivo experiments, adenosine significantly increased water and sodium excretion by 50% compared with vehicle when infused into the left renal artery, accompanied by an increase in urinary dopamine excretion in the left kidney. Neither water-sodium excretion nor dopamine excretion changed in the vehicle-infused kidney. Aromatic L-amino acid decarboxylase activity in the left kidney was significantly higher than that in the noninfused right kidney. The increase in water-sodium excretion induced by adenosine was significantly inhibited by SCH23390, a selective D1 receptor antagonist. In in vitro experiments, porcine renal proximal tubular cells were incubated with 250 μM L-dopa and N 6 -cyclohexyladenosine, an adenosine type 1 receptor agonist, after treatment with adenosine deaminase. N 6 -cyclohexyladenosine significantly increased dopamine formation at a concentration of 10 -9 to 10 -7 M, and this was completely inhibited by 1,3-dipropyl-8-cyclopentylxanthin, an adenosine A1 antagonist. These results show that renal dopamine synthesis is stimulated by adenosine through the activation of aromatic L-amino acid decarboxylase and suggest that adenosine leads to an increase in renal dopamine and natriuresis.
Metastatic Colorectal Cancer: Current State and Future Directions
Authors: Marwan G. Fakih
Journal: Journal of Clinical Oncology (2015)

Substantial improvements have been made in the management of metastatic colorectal cancer over the last two decades. The overall survival of patients diagnosed with unresectable metastatic colorectal cancer has increased from approximately 1 year during the era of fluoropyrimidine monotherapy to more than 30 months with the integration of multiple cytotoxic agents and targeted therapies. More effective therapeutic combinations have increased the rate of curative-intent surgical resections, resulting in median survival in this subgroup that exceed 5 years. Here we review the landscape of systemic therapies for unresectable metastatic colorectal cancer during the current era of targeted therapies, review the effects of RAS and BRAF mutations on clinical decision making, and reflect on future directions for the treatment of metastatic colorectal cancer.
Making a mark during training
Authors: E. Davies
Journal: BMJ (2010)

The junior doctor category of the BMJ Group Awards makes its debut in 2010, with the aim of “rewarding the doctor in training who has done most to improve the world we live in.” We received over 100 nominations from doctors working as far afield as Brazil, Iraq, Australia, and Sudan. Given the size, strength, and diversity of the field, we finally decided on a shortlist of nine doctors, rather than the four in most of the other awards.

Yannick Bejot is a research fellow in neurology at the University of Burgundy, Dijon. He has made a significant contribution to stroke research at an unusually early age. His research is principally on the epidemiology of stroke, and in less than five years since he started his training in neurology he has been the first author of 27 papers on the subject, a large number of which have been published in high impact journals. He has managed to gather …
Sequential high dose chemotherapy as initial treatment for aggressive sub-types of Non-Hodgkin Lymphoma: results of the international randomized phase III trial (MISTRAL)
Authors: D.C. Betticher, G. Martinelli, J.A. Radford, M. Kaufmann, M.J.S. Dyer, U. Kaiser, W.E. Aulitzky, J. Beck, A. von Rohr, T. Kovascovics, S.B. Cogliatti, S. Cina, R. Maibach, T. Cerny, D.C. Linch
Journal: Annals of Oncology (2006)
Reactive Hyperemia in the Dog Heart
Authors: Eduards Eikens, David E. L.Wilcken
Journal: Circulation Research (1974)

With electromagnetic flow transducers and pneumatic cuff occluders on the circumflex branch of the left coronary artery in conscious and in anesthetized dogs, we examined the effects of both a temporary reduction in postocclusion hyperemia and one- and two-cardiac cycle occlusions of the artery on the size and the duration of the hyperemic response. After release of 8-second occlusions, flow was prevented from rising to more than 10-20% above the preocclusion value for the expected duration of the hyperemia. Peripheral coronary arterial pressure measurements established that this maneuver produced a pressure gradient. Temporary restriction of arterial inflow markedly reduced the percent repayment of the flow deficit from 618 ± 34± to 213 ± 17% (mean ± SE) and moderately prolonged the duration of the response from 95 ± 4 seconds to 129 ± 5 seconds ( P &lt; 0.0005 for both). In conscious dogs, the mean percent repayment after a one-cycle (0.7-second) occlusion was 227%. Much larger and longer-lasting responses were obtained with one-cycle (0.4-second) occlusions in anesthetized dogs in which heart rate and blood pressure were considerably higher. Since restricting arterial inflow resulted in a large reduction in reactive hyperemia with only a small increase in its duration, local mechanisms acting in the interstitial space and possibly in the vascular smooth muscle may be relatively more important for the hyperemia that occurs after short occlusions than is the myocardial release of freely diffusible metabolites that are removed by the blood stream. The results with one- and two-cycle occlusions suggest that myogenic responses contribute to the hyperemia, since it is unlikely that such brief occlusions produce myocardial hypoxia under resting conditions.
Modulation of the voltage-dependent K current by intracellular Mg in rat aortic smooth muscle cells
Authors: P TAMMARO, A SMITH, B CROWLEY, S SMIRNOV
Journal: Cardiovascular Research (2004)

Intracellular magnesium ions (Mg2+i) are important in the regulation of a wide range of cellular metabolic processes and modulation of a variety of ion channels. Mg2+ deficiency has been implicated in the aetiology of various cardiovascular diseases. However, potential targets and mechanisms of action of Mg2+i in the cardiovascular system remain poorly understood. We therefore investigated the effect of Mg2+i on the voltage-gated K+ (KV) channels in rat aortic myocytes (RAMs).KV currents (IKv) were investigated in single RAMs isolated from adult Wistar rat thoracic aorta using the whole-cell patch clamp technique. Changes in the vascular reactivity were also assessed in endothelium-denuded rat aortic rings loaded with Mg2+.An increase in Mg2+i caused several significant effects on IKv: (1) slowed down kinetics of activation at high (10 mM) Mg2+; (2) caused inward rectification at positive membrane potentials; (3) shifted the voltage-dependent inactivation, but not steady-state IKv activation; (4) the effect of Mg2+i on IKv inactivation was enhanced in the presence of intracellular ATP. Selective changes in the voltage-dependent characteristics predict a significant inhibition of the whole-cell steady-state IKv ("window current"), resulting in membrane depolarisation and enhanced tissue excitability. An increased sensitivity to KCl and the inhibitors of the IKv, tetraethylammonium and 4-aminopyridine (4-AP), was observed in Mg2+-loaded aortas, confirming this hypothesis.Our results demonstrate that intracellular magnesium can act as a potent modulator of the KV channel function in vascular smooth muscle cells in the physiological range of membrane potentials, representing a novel mechanism for the regulation of KV channel activity in the vasculature.
CASE OF PULMONARY DISEASE: EXUDATION DEPOSIT BETWEEN THE LUNG AND PLEURA
Authors: P. M. Duncan
Journal: BMJ (1853)

After sch concurrence of judgment among the sedical professon in this country, it is unnecessay to llude to that of our brethren abroad.It is all but unanimous; except, perhaps, in Spain and the Italian States, where other motives, besides those of truth and conviction, are well