tbuckley/cabot-search huggingface dataset:
Chromosomal Translocation (14;16)-Positive Multiple Myeloma Shows Negativity for CD56 Expression and Unfavorable Outcome Even in the Era of Novel Drugs
Authors: Tomoko Narita, Atsushi Inagaki, Tsutomu Kobayashi, Yoshiaki Kuroda, Toshihiro Fukushima, Masahiko Nezu, Shin-ichi Fuchida, Hirotaka Sakai, Naohiro Sekiguchi, Isamu Sugiura, Yoshinobu Maeda, Hiroyuki Takamatsu, Norifumi Tsukamoto, Dai Maruyama, Yasushi Kubota, Minoru Kojima, Kazutaka Sunami, Takaaki Ono, Masaki Ri, Kensei Tobinai, Shinsuke Iida
Journal: Blood (2014)
Renal cyclophilin-like protein gene expression parallels changes in sodium excretion in experimental nephrosis and is positively modulated by atrial natriuretic peptide.
Authors: S Orisio, N Perico, L Benatti, L Longaretti, S Amuchastegui, G Remuzzi
Journal: Journal of the American Society of Nephrology (1993)

Experimental evidence is available to indicate that intrarenal mechanisms play a role in the impaired salt excretion of nephrotic syndrome by multiple and still incompletely defined mediators. It is documented herein that the gene encoding for cyclophilin-like protein (Cy-LP) is up-regulated in renal medulla from adriamycin (ADR)-treated rats as compared with control animals. In the cortex of rats with ADR nephrosis, no change in Cy-LP as compared with that in controls was found for the entire observation period. By contrast, in the medulla of nephrotic rats, Cy-LP gene expression was significantly higher than in controls. Values of urinary Na excretion were inversely correlated to Cy-LP mRNA expression levels. Because in ADR nephrosis a blunted natriuretic response to ANP has been previously reported, it was investigated whether ANP infusion modulated Cy-LP mRNA in the renal medulla. ADR-treated rats, but not control rats, infused for 1 h with ANP (1 microgram/kg.min) had a significant (P < 0.05) increase in medullary Cy-LP mRNA as compared with nephrotic animals receiving the vehicle alone. These findings might be taken to suggest that renal Cy-LP gene expression is positively modulated in nephrotic syndrome and parallels changes in sodium excretion.
Effects of Extracorporeal CO<sub>2</sub> Removal on Inspiratory Effort and Respiratory Pattern in Patients Who Fail Weaning from Mechanical Ventilation
Authors: Lara Pisani, Luca Fasano, Nadia Corcione, Vittoria Comellini, Aldo Guerrieri, Marco V. Ranieri, Stefano Nava
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Global Hypomethylation (LINE-1) and Gene-Specific Hypermethylation (GSTP1) on Initial Negative Prostate Biopsy as Markers of Prostate Cancer on a Rebiopsy
Authors: Renata Zelic, Valentina Fiano, Daniela Zugna, Chiara Grasso, Luisa Delsedime, Lorenzo Daniele, Diego Galliano, Andreas Pettersson, Anna Gillio-Tos, Franco Merletti, Lorenzo Richiardi
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Men at risk of missed prostate cancer on a negative biopsy often undergo a rebiopsy. We evaluated whether global hypomethylation, measured through LINE-1 methylation, and GSTP1 hypermethylation on a negative biopsy are associated with subsequent prostate cancer diagnosis. Experimental Design: We performed a case–control study nested in an unselected series of 737 men who received at least two prostate biopsies at least three months apart at the Molinette Hospital (Turin, Italy). Two pathology wards were included for replication purposes. The study included 67 cases and 62 controls in Ward 1 and 62 cases and 66 controls in Ward 2. We used pyrosequencing to analyze LINE-1 and GSTP1 methylation in the negative biopsies. Odds ratios (OR) of prostate cancer diagnosis were estimated using conditional logistic regression. Results: After mutual adjustment, GSTP1 hypermethylation was associated with an OR of prostate cancer diagnosis of 5.1 (95% confidence interval: 1.7–14.9) in Ward 1 and 2.0 (0.8–5.3) in Ward 2, whereas an association was suggested only for low LINE-1 methylation levels (&amp;lt;70% vs. 70%–74%) with an OR of 2.1 (0.5–9.1) in Ward 1 and 1.6 (0.4–6.1) in Ward 2. When the two wards were combined the association was stronger for tumors with Gleason score ≥4+3 [GSTP1 hypermethylation: 9.2 (2.0–43.1); LINE-1 (&amp;lt;70% vs. 70%–74%): 9.2 (1.4–59.3)]. GSTP-1 alone improved the predictive capability of the model (P = 0.007). Conclusions: GSTP1 hypermethylation on a negative biopsy is associated with the risk of prostate cancer on a rebiopsy, especially of high-grade prostate cancer. Consistent results were found only for extremely low LINE-1 methylation levels. Clin Cancer Res; 22(4); 984–92. ©2015 AACR.
Unraveling predicted immunomodulatory effects of novel cancer-associated non-coding RNAs
Authors: Antoine J Tanne, Luciana R Muniz, David T Ting, Alexander V Solovyov, Arnold Levine, Benjamin Greenbaum, Nina Bhardwaj
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Cellular non-coding RNA (ncRNA) transcription and regulation has only recently been systematically investigated. Studies have demonstrated abundant transcription of a set of ncRNAs preferentially within tumors as opposed to normal tissue. In some cases these tumor-associated
Rupture of a pseudoaneurysm caused by endoscopic papillary large-balloon dilation
Authors: Akira Kurita, Takashi Ito, Yasushi Kudo, Shujiro Yazumi
Journal: Endoscopy (2015)

Endoscopic papillary large-balloon dilation (EPLBD) is a relatively new technology for removing large bile duct stones [1]. The efficacy and safety of EPLBD have been reported; however, severe complications occur in approximately 10 % of patients [2]. Hemorrhage is one of the most common complications, and endoscopic hemostasis is effective [3]. Herein, we present a case of rupture of a pseudoaneurysm following EPLBD.
T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment
Authors: Lei Dong, Johannes Nordlohne, Shuwang Ge, Barbara Hertel, Anette Melk, Song Rong, Hermann Haller, Sibylle von Vietinghoff
Journal: Journal of the American Society of Nephrology (2015)

Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient ( LDLr−/− ) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b + CD11c + myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro , fewer T H17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGF β . Polarization of T H17 or T REG cells, or stimulation of splenocytes with TGF β alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGF β induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b + CD11c + myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGF β and is instrumental in enhanced atherosclerosis in renal impairment.
Impaired Lysosomal Function Underlies Monoclonal Light Chain–Associated Renal Fanconi Syndrome
Authors: Alessandro Luciani, Christophe Sirac, Sara Terryn, Vincent Javaugue, Jenny Ann Prange, Sébastien Bender, Amélie Bonaud, Michel Cogné, Pierre Aucouturier, Pierre Ronco, Frank Bridoux, Olivier Devuyst
Journal: Journal of the American Society of Nephrology (2015)

Monoclonal gammopathies are frequently complicated by kidney lesions that increase the disease morbidity and mortality. In particular, abnormal Ig free light chains (LCs) may accumulate within epithelial cells, causing proximal tubule (PT) dysfunction and renal Fanconi syndrome (RFS). To investigate the mechanisms linking LC accumulation and PT dysfunction, we used transgenic mice overexpressing human control or RFS-associated κ LCs (RFS- κ LCs) and primary cultures of mouse PT cells exposed to low doses of corresponding human κ LCs (25 μ g/ml). Before the onset of renal failure, mice overexpressing RFS- κ LCs showed PT dysfunction related to loss of apical transporters and receptors and increased PT cell proliferation rates associated with lysosomal accumulation of κ LCs. Exposure of PT cells to RFS- κ LCs resulted in κ LC accumulation within enlarged and dysfunctional lysosomes, alteration of cellular dynamics, defective proteolysis and hydrolase maturation, and impaired lysosomal acidification. These changes were specific to the RFS- κ LC variable (V) sequence, because they did not occur with control LCs or the same RFS- κ LC carrying a single substitution (Ala30→Ser) in the V domain. The lysosomal alterations induced by RFS- κ LCs were reflected in increased cell proliferation, decreased apical expression of endocytic receptors, and defective endocytosis. These results reveal that specific κ LCs accumulate within lysosomes, altering lysosome dynamics and proteolytic function through defective acidification, thereby causing dedifferentiation and loss of reabsorptive capacity of PT cells. The characterization of these early events, which are similar to those encountered in congenital lysosomal disorders, provides a basis for the reported differential LC toxicity and new perspectives on LC-induced RFS.
Randomized phase II study of neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed primary glioblastoma multiforme.
Authors: K. F. Hofland, S. Hansen, M. Sorensen, H. P. Schultz, A. Muhic, S. Engelholm, A. Ask, C. Kristiansen, C. Thomsen, H. Skovgaard Poulsen, U. N. Lassen
Journal: Journal of Clinical Oncology (2011)

2052 Background: Concomitant temozolomide (T) and radiotherapy (RT) is standard care in patients (pts) with newly diagnosed glioblastoma (GBM). Bevacizumab (B) and irinotecan (I) produces impressive responses as second-line therapy. However, it is unclear how efficacy from BI compares to BT. This study explored if BI should be further investigated in first-line in phase III setting. Methods: Pts with previously untreated GBM after primary surgery/biopsy were randomized to neoadjuvant (neo) chemotherapy (chemo) with either BI or BT for 8 wks. This was followed by concomitant chemoradiotherapy (chemoRT) (RT was 60 Gy in 30 fractions). After completed chemoRT adjuvant BI or BT was administered for another 8 wks. The BI-regimen consisted of B and I q2wks, including during the RT. The BT-regimen consisted of B q2wks with T on a 5/28 days cycle both before and after RT. During chemoRT, T was given daily ad modum Stupp together with B q2wks. Primary endpoint was response at 8 wks. Secondary endpoints were best overall response, PFS-6, PFS-12, survival, and toxicity (tox). Response and tox were assessed every 2 wks according to McDonald criteria using MRI and CTCAE 3.0, respectively. 63 pts were included in the analysis. Results: See table. Hematologic (hem) tox was more frequent with BT than BI. There was one death from febrile neutropenia (BT) and 11 grade 3/4 non-hem tox on both BI and BT. Conclusions: Response at 8 wks seemed to favor BT over BI and to support investigations of adding B to Stupp’s regimen in first-line therapy. Updated secondary endpoints are available May 2011. Characteristics BI (n=31) BT (n=32) Median age (range) 59 (36 – 77) 62 (30 – 73) PS: 0 / 1 / 2 20 / 10 / 1 13 / 17 / 2 M/F 18 / 13 21 / 11 Response after 8 wks of neo chemo (best overall response)* CR 0 (1) 0 (0) PR 6 (11) 10 (14) Minor response** 7 (5) 11 (9) SD 7 (5) 6 (4) PD 6 (6) 4 (4) Not evaluable 5*** 1**** * At time of submission, all MRI were reviewed by an expert neuroradiologist (C.T.), blinded to treatment. ** 50-75% of baseline. *** 3 had nonenhancing tumors at baseline, 2 had poor quality MR at 8 wks. All were clinical non-PD and received planned chemoRT. **** Nonenhancing tumor at baseline.
Human tumor clonogenic assay in patients with unknown primary carcinomas.
Authors: B R Greenberg, S E Salmon
Journal: Journal of Clinical Oncology (1984)

The Human Tumor Clonogenic Assay (HTCA) was used in patients with unknown primary carcinomas (UPC) to evaluate chemosensitivity in vitro for this patient group and to possibly aid in the selection of chemotherapy for clinical trial. A total of 178 drug assays including 15 standard and 13 experimental anti-cancer drugs were performed on tumor cells from 19 patients. A median of six drugs were studied in vitro per patient. Sensitivity was noted in only 3.4% of the studies (six drug assays). The marked in vitro pattern of resistance observed with UPC correlates well with the known clinical experience with this entity. Ten patients were evaluable for clinical correlation of response between in vitro and in vivo sensitivity; however, many received drug combinations and not all the drugs had been tested in vitro. One of six evaluable patients exhibiting in vitro sensitivity and one of four with in vitro resistance achieved remission. Additional single-agent in vitro/in vivo correlations will be needed to establish whether HTCA will have any future impact in the treatment of patients with UPC. A more promising application of HTCA for UPC would appear to be as an aid in screening and discovery of new drugs of potentially greater efficacy for this resistant tumor category.
American Diabetes Association 60th Scientific Sessions,2000
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2001)

This is the fourth of seven reports on the American Diabetes Association (ADA) 60th Scientific Sessions held in San Antonio, TX, in June 2000. It covers topics related to cardiovascular disease (CVD) in diabetes.

At a symposium held in conjunction with the meeting, Richard Nesto, Boston, MA, discussed screening for coronary heart disease (CHD) in diabetes. He stressed the importance of early treatment of acute myocardial infarction (MI), noting the increased mortality in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial with delay in diagnosis (1) and the high prehospitalization mortality in the Finnish Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (FINMONICA) study (2), which suggest the need for screening. This is particularly suggested by recent evidence that intensive risk factor modification improves the prognosis of patients with diabetes and CVD. The patient with diabetes may have either typical or atypical cardiac symptoms. Other patients requiring screening are those with abnormal resting electrocardiogram and those with other evidence of atherosclerosis; peripheral arterial disease, for example, is associated with a fourfold increase in CHD risk. Patients with macroalbuminuria have markedly increased CHD risk as well.

Nesto pointed out that autonomic neuropathy is associated with decreased survival and a high CHD incidence and that this group may respond to treatment with β-blockers in view of their increased sympathetic tone. Cardiac autonomic neuropathy may also result in increased variability in sympathetic activity within the heart, as seen after MI, a potential cause of arrhythmia. Additional indications for CHD screening are the presence of two or more risk factors (dyslipidemia, hypertension, cigarette smoking, or positive family history) and the sedentary patient beginning a vigorous exercise program. The yield of noninvasive testing of patients identified in this fashion is between 10 and 20%.

Nesto described a …
Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides
Authors: A M Zeidan, M A Sekeres, G Garcia-Manero, D P Steensma, K Zell, J Barnard, N A Ali, C Zimmerman, G Roboz, A DeZern, A Nazha, E Jabbour, H Kantarjian, S D Gore, J P Maciejewski, A List, R Komrokji
Journal: Leukemia (2015)
Reactive Oxygen Species Alter Gene Expression in Podocytes
Authors: Stefan Greiber, Barbara Mu[Combining Diaeresis]ller, Petra Daemisch, Hermann Pavensta[Combining Diaeresis]dt
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. It has been suggested that reactive oxygen radicals (ROS) play a crucial role in the pathogenesis of proteinuria and podocyte injury. It was investigated whether changes in gene expression might account for ROS-induced podocyte dysfunction. Differentiated podocytes were incubated with control media or with exogenous ROS from the xanthine/xanthine-oxidase reaction for 4 h. A PCR-based suppressive subtractive hybridization assay was applied to isolate and clone mRNAs that were differentially expressed by exogenous ROS. One differentially expressed clone was identified as the proinflammatory cytokine granulocyte macrophage-colony-stimulating factor (GM-CSF). Regulation of GM-CSF in podocytes was further studied by Northern analysis and enzyme-linked immunosorbent assay. Exogenous ROS caused a concentration-dependent, >10-fold induction of GM-CSF mRNA after 4 h. A >50-fold increase in GM-CSF protein release in podocytes that had been stimulated with ROS could be detected. Induction of GM-CSF protein was inhibited by actinomycin D, which indicated that increased mRNA transcription was involved. The ROS scavengers dimethyl-thio-urea and pyrrolidone-dithio-carbamate strongly inhibited increased GM-CSF production induced by ROS. GM-CSF release was also induced when internal ROS production was triggered with NADH, whereas H2O2 had only a small effect. GM-CSF release by podocytes was also stimulated by lipopolysaccharide (LPS), interleukin-1 (IL-1), and phorbolester (PMA). Dimethyl-thio-urea significantly inhibited the LPS-, IL-1-, and PMA-induced GM-CSF production. Activation of the transcription factor nuclear factor-κB (NF-κB) but not activator protein-1 was involved in the upregulation of ROS-induced GM-CSF production. The data indicate that GM-CSF is differentially expressed by ROS in podocytes. ROS also partially mediate the effects of PMA and IL-1 on podocyte GM-CSF production. Because GM-CSF can enhance glomerular inflammation and induces mesangial proliferation, these data might provide further insight into the mechanisms of ROS-induced glomerular injury.
Revisiting Cardiac Cellular Composition
Authors: Alexander R. Pinto, Alexei Ilinykh, Malina J. Ivey, Jill T. Kuwabara, Michelle L. D’Antoni, Ryan Debuque, Anjana Chandran, Lina Wang, Komal Arora, Nadia A. Rosenthal, Michelle D. Tallquist
Journal: Circulation Research (2016)

Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration.To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart.Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute >60%, hematopoietic-derived cells 5% to 10%, and fibroblasts <20% of the nonmyocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of nonmyocytes. High-dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and 2 commonly assigned fibroblast markers, Sca-1 and CD90, under-represent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population.This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of noncardiomyocytes and are likely to play a greater role in physiological function and response to injury than previously appreciated.
Efficacy and Tolerability of Taxane-Based Chemotherapy in Senior Adults with Metastatic Castration-Resistant Prostate Cancer (MCRPC): A Prospective International Registry
Authors: J. Droz, E. Efstathiou, A. Heidenreich, A. Yildirim, P. Cabrera, C. Kim, A. Horchani, H. Ozen, J.A. Rinck
Journal: Annals of Oncology (2012)
PES in CAP: An acronym to identify "problematic pathogens" in community-acquired pneumonia
Authors: Elena Prina, Miquel Ferrer, Eva Polverino, Catia Cilloniz, Josep Mensa, EncarnaciÃ³n Moreno, Erika Cuenca, Roberto Cosentini, Antoni Torres
Journal: European Respiratory Journal (2012)

Background: Nosocomial and Multidrug-resistant pathogens have been emerging as a cause of community-acquired infections. Recently, Rice has introduced the acronym ESKAPE for the identification of the principle pathogens responsible for nosocomial infection that frequently can “escape” the effect of antibiotic treatment. In order to translate this idea to community-acquired pneumonia (CAP), we purpose the adapted acronym PES: Pseudomonas aeruginosa, Enterobacteriaceae and Staphylococcus aureus.  The aim of our study is to compare clinical characteristics and outcomes of patients with CAP/HCAP due to PES pathogens respect patients with pneumonia due to other pathogens.  Methods: Among 4549 patients evaluated for CAP/HCAP, we analyzed 1470 patients which presented an etiologic diagnosis. We excluded patients with immunosuppression, neoplasm and active tuberculosis.  Results: Pneumonia due to PES was identified in 136 (9%) patients (n=64 P. aeruginosa n=44 Enterobacteriaceae n=35 S. aureus). These patients were older, had more frequently received previous antibiotics and presented a reduced autonomy with higher rate of aspiration episodes (p  Conclusions: PES pathogens are responsible for CAP with high mortality. The attendant physician should be worried to empirically cover PES pathogens in patients with lower autonomy, many comorbidities and previous antibiotic treatment.
A Phase IV Multicenter Study of the Efficacy and Safety of Sunitinib as First-Line Therapy in Chinese Patients with Metastatic Renal Cell Carcinoma (MRCC)
Authors: S. Qin, J. Jin, J. Guo, J. Wang, F. Zhou, Y. Huang, X. Ren, D. Ye, Q. Wang, S. Pan
Journal: Annals of Oncology (2012)
Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer
Authors: O Pagani, C Sessa, G Martinelli, D Crivellari, A Buonadonna, B Thürlimann, D Hess, M Borner, J Bauer, G Zampino, M Zimatore, R Graffeo, A Riva, A Goldhirsch
Journal: Annals of Oncology (1999)