tbuckley/cabot-search huggingface dataset:
Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas
Authors: Koji Shindo, Shinichi Aishima, Kenoki Ohuchida, Kenji Fujiwara, Minoru Fujino, Yusuke Mizuuchi, Masami Hattori, Kazuhiro Mizumoto, Masao Tanaka, Yoshinao Oda
Journal: Molecular Cancer (2013)

Abstract Background Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer. Methods Expression of PDPN in pancreatic IDCs was assessed by immunohistochemical examination in 105 patients who underwent pancreatic resection. Primary CAFs were established from pancreatic cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis were performed to investigate PDPN expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the functional differences between PDPN+ CAFs and PDPN– CAFs using indirect co-culture with pancreatic cancer cell lines. We also investigated the culture conditions to regulate PDPN expression in CAFs. Results PDPN expression in stromal fibroblasts was associated with lymphatic vessel invasion ( P = 0.0461), vascular invasion ( P = 0.0101), tumor size ≥3 cm ( P = 0.0038), histological grade ( P = 0.0344), Union for International Cancer Control classification T stage ( P = 0.029), and shorter survival time ( P &lt; 0.0001). Primary CAFs showed heterogeneous PDPN expression in vitro . Moreover, migration and invasion of pancreatic cancer cell lines (PANC-1 and SUIT-2) were associated with PDPN expression in CAFs ( P &lt; 0.01) and expression of CD10, matrix metalloproteinase (MMP) 2, and MMP3. In cultured CAFs, PDPN positivity changed over time under several conditions including co-culture with cancer cells, different culture media, and addition of growth factor. Conclusions PDPN-expressing CAFs enhance the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an independent predictor of poor outcome. Understanding the regulation of the tumor microenvironment is an important step towards developing new therapeutic strategies.
Curing “Incurable” Cancer
Authors: James D. Watson
Journal: Cancer Discovery (2011)

Cancer cells are preferentially killed by anticancer agents because key signals for growth and cell division are "always on" as opposed to the alternative "on" and "off" signaling of normal cells. Too much of today's anticancer drug discovery effort may go toward reversing genetically promoted "always on" signals. More effective anticancer drug targets may be found through use of RNAi technologies that pinpoint the key gene regulatory and metabolic weakness of the "always on" cancer cells.
Nonalcoholic Fatty Liver Disease and Insulin Resistance in Youth
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2007)

Perspectives on the News commentaries are now part of a new, free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, is designating this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Effects of Acute Myocardial Ischemia on Intramyocardial Contraction Heterogeneity
Authors: Paolo Colonna, Roberta Montisci, Leonarda Galiuto, Luigi Meloni, Sabino Iliceto
Journal: Circulation (1999)

Background —Subendocardial thickening is greater than subepicardial thickening and acute myocardial ischemia mainly impairs the former. Integrated backscatter cyclic variations (IBScv) reflect regional myocardial contractility and are blunted during myocardial ischemia. We hypothesized that stress-induced myocardial ischemia mainly affects subendocardial IBScv. Methods and Results —Multiplane transesophageal echocardiography and simultaneous atrial pacing were performed in 12 patients without coronary artery disease (CAD) and in 25 with significant CAD. In a transgastric 2-chamber view, we calculated IBScv in subendocardium and subepicardium and a heterogeneity index, both at rest and at peak-pacing. In 27 myocardial segments of patients with normal coronary arteries, and in 16 myocardial segments supplied by coronary artery without significant stenosis in patients with CAD, there was a transmural gradient of IBScv at rest and the heterogeneity index did not change during all the protocol steps. In the 53 myocardial segments related to a significantly narrowed coronary artery, the transmural gradient of IBScv, present at rest, significantly decreased at peak-pacing because of subendocardial blunting, but promptly recovered 5 seconds after pacing interruption. Moreover, the myocardial thickening at rest and peak pacing correlated with the subendocardial IBScv behavior and not with the subepicardial one. Conclusions —IBScv are greater in the subendocardium than in the subepicardium. Atrial pacing stress test does not affect IBScv in segments supplied by nonstenotic coronary arteries, whereas it affects segments supplied by diseased coronary arteries, blunting exclusively subendocardial IBScv. Heterogeneity of IBScv intramyocardial changes caused by stress-induced ischemia must be taken into account when using IBScv for investigating myocardial ischemia.
Effect of Body Size, Ponderosity, and Blood Pressure on Left Ventricular Growth in Children and Young Adults in the Bogalusa Heart Study
Authors: Elaine M. Urbina, Samuel S. Gidding, Weihang Bao, Arthur S. Pickoff, Kaliope Berdusis, Gerald S. Berenson
Journal: Circulation (1995)

Background The measurement of left ventricular mass (LVM) is important because individuals with increased LVM are at increased risk for cardiovascular diseases, including myocardial infarction and congestive heart failure. There are limited longitudinal data on the acquisition of LVM in children and young adults and the relative importance of sex, growth, excess body weight, and blood pressure (BP) on change in LVM. Methods and Results The study cohort consisted of a cross section of 160 healthy children and young adults 9 to 22 years of age at first exam in the biracial community of Bogalusa, La. All had stable BP levels recorded over a 2- to 3-year period. Repeated examinations were performed 4 to 5 years apart. At each exam, 6 BPs were obtained with a mercury sphygmomanometer by trained examiners. The mean of the observations was used, with the fourth Korotkoff phase serving as the measure of diastolic BP. Anthropometric data, including height (HT), weight (WT), and triceps skin fold thickness (TSF), were also obtained, and M-mode echocardiograms were performed. Ponderal index (PI=WT/HT 3 ) was used as a measure of weight-for-height. Tracking of HT ( r =.68 to .76), WT ( r =.73 to .82), PI ( r =.77 to .89), TSF ( r =.70 to .80), BP ( r =.47 to .60), and LVM ( r =.40 to .70) was strong in both sexes ( P &lt;.0001). LVM indexed for linear growth (LVM/HT 2.7 ) tracked in females ( r =.56, P &lt;.0001) but not in males. In univariate cross-sectional analyses, LVM/HT 2.7 correlated with WT, PI, and TSF in both sexes ( r =.21 to .60, P &lt;.05) and with systolic BP (SBP) in females ( r =.23, P &lt;.05). WT was the only independent correlate of LVM/HT 2.7 in both sexes in multivariate cross-sectional analysis in a model containing age, SBP, WT, and TSF as independent variables ( r 2 =.08 to .28, P &lt;.02). In longitudinal univariate analyses, initial measurements of WT, PI, and TSF predicted final LVM/HT 2.7 in both sexes ( r =.28 to .56, P &lt;.01), and SBP was significant for females ( r =.27, P &lt;.05). In multivariate analyses, initial WT was associated with final LVM and LVM/HT 2.7 in both sexes ( r 2 =.27 to .54, P &lt;.01). Finally, baseline LVM correlated with final SBP in both sexes ( r =.21 to .27, P &lt;.05), and initial LVM/HT 2.7 correlated with final SBP in females ( r =.26, P &lt;.05) with a trend for males ( r =.17). Conclusions These data indicate that linear growth is the major determinant of cardiac growth in children and that excess weight may lead to the acquisition of LVM beyond that expected from normal growth. Increased mass may also precede the development of increased BP. The development of obesity may therefore be a significant, and possibly modifiable, risk factor for developing left ventricular hypertrophy and hypertension, risk factors for cardiovascular morbidity and mortality.
Arthritis and Allied Conditions. A Textbook of Rheumatology
Authors: O. Savage
Journal: Annals of the Rheumatic Diseases (1961)

The sixth edition of this well-established textbook, originally based on Comroe's "Arthritis", has been largely re-written and nineteen new chapters have been added.The contributors include many of the leading authorities in the sphere of rheumatic diseases in North America and the volume is packed with up-to-date expert views in this field.Dr. John Lansbury has a new chapter on methods of evaluating rheumatoid arthritis.This is a most impor- tant subject in view of the many clinical trials of anti- rheumatic drugs which are now being carried out.The author has given a clear summary of the present position, pointing out many inadequacies in the methods in use at the present time.He gives stimulating ideas for improvement in techniques though the reviewer doubts whether morning stiffness can yet be measured.Dr. E. P. Engleman has an excellent chapter on the basic treatment of rheumatoid arthritis, pointing out the necessity for systemic, emotional, and articular rest with good advice on analgesics and diet.Dr. J. J. Bunim has contributed a first-class review of the chemistry, physiology, and metabolic effects of corticosteroids, and has included the new work on the cortisol-binding protein transcortin as well as the latest views on absorption and distribution of steroids and of the metabolic fate and excretion of these substances.This is one of the outstanding chapters in the book.He also has an excellent chapter on the use of synthetic corticosteroids in rheumatoid arthritis, including the clinical considerations, limitations, and adverse effects with most helpful advice on individual steroid prepara- tions.Dr. Hollander himself, from his large experience, has written most wisely on the value of intra-articular steroid therapy with helpful diagrams and photographs showing methods of injection for various joints.He deals sensibly with the recent reports that "Charcot's arthropathy" may occur after this treatment, pointing out that it is a possibility and that careful radiological supervision is necessary.In his very large series the incidence of this complication is a fraction of 1 per cent.
Treatment for poikilodermatous erythema of dermatomyositis with the pulsed dye laser
Authors: T. Yanagi, D. Sawamura, A. Shibaki, H. Shimizu
Journal: British Journal of Dermatology (2005)

Journal Article Treatment for poikilodermatous erythema of dermatomyositis with the pulsed dye laser Get access T. Yanagi, T. Yanagi Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7, Kita‐ku, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar D. Sawamura, D. Sawamura Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7, Kita‐ku, Sapporo 060‐8638, Japan Daisuke Sawamura. E‐mail: smartdai@med.hokudai.ac.jp Search for other works by this author on: Oxford Academic Google Scholar A. Shibaki, A. Shibaki Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7, Kita‐ku, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar H. Shimizu H. Shimizu Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7, Kita‐ku, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 4, 1 October 2005, Pages 862–864, https://doi.org/10.1111/j.1365-2133.2005.06855.x Published: 01 October 2005
Statement of the Science Concerning Locoregional Treatments After Preoperative Chemotherapy for Breast Cancer: A National Cancer Institute Conference
Authors: Thomas A. Buchholz, Constance D. Lehman, Jay R. Harris, Barbara A. Pockaj, Nagi Khouri, Nola F. Hylton, Michael J. Miller, Timothy Whelan, Lori J. Pierce, Laura J. Esserman, Lisa A. Newman, Barbara L. Smith, Harry D. Bear, Eleftherios P. Mamounas
Journal: Journal of Clinical Oncology (2008)

Purpose To review the state of the science with respect to diagnostic imaging and locoregional therapy for patients with breast cancer receiving preoperative chemotherapy. Methods Published data relevant to clinical staging, monitoring of tumor response, and locoregional therapy for patients with breast cancer treated with preoperative chemotherapy were reviewed. Results High-quality data from prospective randomized trials are limited. Available data suggest that locoregional therapy decisions should be based on both the pretreatment clinical extent of disease and the pathologic extent of the disease after chemotherapy. Accordingly, physical examination and imaging studies that accurately define the initial extent of disease are required before treatment. Sentinel lymph node biopsy can be performed either before or after preoperative chemotherapy for patients with clinical N0 disease. The success of breast conservation after preoperative chemotherapy depends on careful patient selection and achieving negative surgical margins. Adjuvant breast radiation is indicated for all patients treated with breast conservation. For patients treated with mastectomy, chest-wall and regional nodal radiation should be considered for those who present with clinical stage III disease or have histologically positive lymph nodes after preoperative chemotherapy. Additional prospective studies are needed to determine the value of postmastectomy radiation for patients with stage II breast cancer who have negative lymph nodes after chemotherapy. Conclusion The increased use of preoperative chemotherapy has raised new questions concerning the optimal methods to stage and monitor disease response to treatment and how to optimize locoregional treatment. The available evidence suggests that a multidisciplinary approach improves outcomes.
Evidence of association of the<i>NLRP1</i>gene with giant cell arteritis
Authors: Aurora Serrano, F David Carmona, Santos Castañeda, Roser Solans, José Hernández-Rodríguez, María C Cid, Sergio Prieto-González, José A Miranda-Filloy, Luis Rodríguez-Rodríguez, Inmaculada C Morado, Carmen Gomez-Vaquero, Ricardo Blanco, Bernardo Sopeña, Norberto Ortego-Centeno, Ainhoa Unzurrunzaga, Begoña Marí-Alfonso, Julio Sánchez-Martín, María Jesús García-Villanueva, Ana Hidalgo-Conde, Giulia Pazzola, Luigi Boiardi, Carlo Salvarani, Miguel A González-Gay, Javier Martín
Journal: Annals of the Rheumatic Diseases (2012)

Recent studies have focused attention on the involvement of NLRP1 to confer susceptibility for extended autoimmune/inflammatory disorders, being considered a common risk factor in autoimmunity.1–3 NLRP1 provides a scaffold for the assembly of the inflammasome that activates caspases 1 and 5, required for processing and activation of the proinflammatory cytokines interleukin 1β (IL-1β), IL-18 and IL-33 and promoting inflammation.4 In this study, we examined for the first time whether NLRP1 is associated with giant cell arteritis (GCA), a chronic systemic vasculitis affecting large and medium-sized arteries derived from the aorta, in particular the cranial branches of the carotid artery. GCA is the most common vasculitis in the elderly in Western countries with a female predominance.5 To investigate the possible genetic association of NLRP1 with this disease, we genotyped a single-nucleotide polymorphism (rs8182352), which has been reported to confer risk to the development of autoimmune processes in previous studies,1 ,2 in a total of 3583 individuals, comprising a discovery set from Spain (574 patients diagnosed with biopsy-proven GCA and 2366 healthy controls) and a replication set of subjects from Italy (111 biopsy-proven GCA patients and 532 controls) using a predesigned TaqMan allele discrimination assay. All individuals were of …
Pulmonary Vein Stenosis After Radiofrequency Ablation of Atrial Fibrillation
Authors: Eduardo B. Saad, Antonio Rossillo, Cynthia P. Saad, David O. Martin, Mandeep Bhargava, Demet Erciyes, Dianna Bash, Michelle Williams-Andrews, Salwa Beheiry, Nassir F. Marrouche, James Adams, Ennio Pisanò, Raffaele Fanelli, Domenico Potenza, Antonio Raviele, Aldo Bonso, Sakis Themistoclakis, Joannes Brachmann, Walid I. Saliba, Robert A. Schweikert, Andrea Natale
Journal: Circulation (2003)

Pulmonary vein (PV) stenosis is a complication of ablation for atrial fibrillation. The impact of different ablation strategies on the incidence of PV stenosis and its functional characterization has not been described.PV isolation was performed in 608 patients. An electroanatomic approach was used in 71 and circular mapping in 537 (distal isolation, 25; ostial isolation based on PV angiography, 102; guided by intracardiac echocardiography, 140; with energy delivery based on visualization of microbubbles, 270). Severe (> or =70%) narrowing was detected in 21 patients (3.4%), and moderate (50% to 69%) and mild (<50%) narrowing occurred in 27 (4.4%) and 47 (7.7%), respectively. Severe stenosis occurred in 15.5%, 20%, 2.9%, 1.4%, and 0%, respectively. Development of symptoms was correlated with involvement of >1 PV with severe narrowing (P=0.01), whereas all patients with mild and moderate narrowing were asymptomatic. In the latter group, lung perfusion (V/Q) scans were normal in all but 4 patients. All patients with severe stenosis had abnormal perfusion scans.V/Q scans are useful to assess the functional significance of PV stenosis. Mild and moderate degrees of PV narrowing are not associated with development of symptoms and seem to have no or minimal detrimental effect on pulmonary flow. The incidence of severe PV stenosis seems to be declining with better imaging techniques to ensure ostial isolation and to guide power titration. Mild narrowing 3 months after ablation does not preclude future development of severe stenosis and should be assessed with repeat imaging studies.
Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding.
Authors: A M Feldman, E O Weinberg, P E Ray, B H Lorell
Journal: Circulation Research (1993)

Left ventricular hypertrophy (LVH) is associated with reinduction of the fetal program of gene expression. It is unclear whether this pattern of cardiac gene expression changes with the development of left ventricular decompensation and failure. To answer these questions, we quantified steady-state levels of mRNA by the polymerase chain reaction in the left ventricular myocardium of rats 8 and 20 weeks after ascending aortic banding. Clinical and hemodynamic assessment identified two distinct groups of animals 20 weeks after aortic banding. The first group (20-week nonfailed LVH) demonstrated substantial LVH but no depression in systolic developed pressure per gram left ventricular weight compared with the age-matched control group. In contrast, a second group of rats exhibited clinical signs of congestive failure as well as a marked diminution in left ventricular developed pressure per gram. Assessment of the levels of mRNA encoding a panel of cardiac proteins demonstrated a greater than twofold increase in beta-myosin heavy chain mRNA and an approximately sixfold increase in atrial natriuretic factor mRNA in left ventricular myocardium of all three groups (8-week LVH, 20-week nonfailed LVH, 20-week failed LVH) when compared with appropriate age-matched control groups. In contrast, Ca(2+)-ATPase mRNA levels were decreased by 50% only in the left ventricular myocardium of animals with both clinical signs and hemodynamic indexes consistent with cardiac decompensation (20-week failed LVH). These results suggest that in rats with ascending aortic banding the hypertrophic phenotype is associated with a selective reinduction of the fetal gene program, which persists even after the development of left ventricular failure.(ABSTRACT TRUNCATED AT 250 WORDS)
NKG2D function protects the host from tumor initiation
Authors: Mark J. Smyth, Jeremy Swann, Erika Cretney, Nadeen Zerafa, Wayne M. Yokoyama, Yoshihiro Hayakawa
Journal: The Journal of Experimental Medicine (2005)

The activation NKG2D receptor has been shown to play an important role in the control of experimental tumor growth and metastases expressing ligands for NKG2D; however, a function for this recognition pathway in host protection from de novo tumorigenesis has never been demonstrated. We show that neutralization of NKG2D enhances the sensitivity of wild-type (WT) C57BL/6 and BALB/c mice to methylcholanthrene (MCA)-induced fibrosarcoma. The importance of the NKG2D pathway was additionally illustrated in mice deficient for either IFN-γ or tumor necrosis factor–related apoptosis-inducing ligand, whereas mice depleted of natural killer cells, T cells, or deficient for perforin did not display any detectable NKG2D phenotype. Furthermore, IL-12 therapy preventing MCA-induced sarcoma formation was also largely dependent on the NKG2D pathway. Although NKG2D ligand expression was variable or absent on sarcomas emerging in WT mice, sarcomas derived from perforin-deficient mice were Rae-1+ and immunogenic when transferred into WT syngeneic mice. These findings suggest an important early role for the NKG2D in controlling and shaping tumor formation.
Incidence, Causes, and Outcomes of Out-of-Hospital Cardiac Arrest in Children
Authors: Abdennasser Bardai, Jocelyn Berdowski, Christian van der Werf, Marieke T. Blom, Manon Ceelen, Irene M. van Langen, Jan G.P. Tijssen, Arthur A.M. Wilde, Rudolph W. Koster, Hanno L. Tan
Journal: Journal of the American College of Cardiology (2011)
The effect of right ventricular filling on the pressure-volume relationship of ejecting canine left ventricle.
Authors: W L Maughan, C H Kallman, A Shoukas
Journal: Circulation Research (1981)

Acute shifts in the pressure-volume relationship of the left ventricle occur under several conditions. One potential mechanism for this phenomenon is ventricular interdependence, that is, the influence of right ventricular filling on the left ventricle. This mechanism was studied in an isolated cross-circulated ejecting canine heart preparation with balloons sewn into both right and left ventricles and connected to volumetric chambers allowing continuous and accurate simultaneous measurement of right and left ventricular pressures and volume. Sets of left ventricular pressure-volume loops were obtained under a variety of right ventricular volumes. Experiments were repeated with and without the pericardium. Both diastole and systole were studied. We show that in the pericardium-free heart working over a normal range of volumes, the right ventricle exerts little influence on left ventricular pressure. With the pericardium present, there is a small but significant effect of right ventricular volume on left ventricular pressure during systole and diastole. Over a wider range of volumes imposed in the arrested heart, the right ventricle does influence left ventricular pressure even without the pericardium. Thus we have demonstrated that ventricular interdependence is not likely to lead to large acute pressure-volume shifts, either during diastole or systole, except in the presence of considerably above normal right ventricular volumes.