tbuckley/cabot-search huggingface dataset:
CD44 up-regulates the expression of matrix metalloproteinases (MMPs) in ovarian and breast carcinoma cells
Authors: Karl E. Miletti, Giuseppa N. Saglimbeni, Shiling Chen, Lorna Rodriguez-Rodriguez
Journal: Cancer Research (2004)

1823   CD44 comprise a group of cell transmembrane receptors that bind hyaluronan (HA). They exist in a variety of isoforms due to alternative splicing and post-translational modifications. The most common isoform, CD44 standard (CD44s) has been shown to be involved in tumor invasion and metastasis. Matrix metalloproteinases (MMPs) are a group of endopeptidases that degrade most of the ECM. MMPs play an important role in invasion and metastasis of tumors, in which they are frequently overexpressed. Because some MMPs are known to bind CD44 (e.g., MT1-MMP, MMP-9) or are regulated by the CD44s-HA interaction (e.g., MMP-2, MMP-9), we investigated the effect of CD44s expression on MMPs expression and activity in CD44s-negative ovarian (OVCAR-3) and breast (MCF-7) cancer cell lines. We generated CD44s-stable transfectants (i.e., MCF-7/CD44s and OVCAR-3/CD44s). CD44s expression levels were confirmed by RT-PCR and immunoblotting. The in vitro migration and invasion of the clones was determined. The activity of MMPs was assayed by gelatin (MMP-9 and –2) and fibrinogen (MT1-MMP) zymography. OVCAR-3/CD44s clones that expressed CD44s mRNA and protein migrated and invaded more compared to OVCAR-3 cells. The two clones that invaded and migrated the most, showed the expected CD44s band and also a slightly higher molecular weight CD44s band, presumably a posttranslational modified CD44s. These two clones also had an up-regulation of MMP-9 activity and a 50 kDa MMP activity yet to be identified. proMMP-2 processing and MMP-2 activity showed a modest increase in these clones. proMT1-MMP activity was observed in parental as well as in each CD44s clones, but only the most invasive clone showed a band corresponding to active MT1-MMP. MCF-7/CD44s showed a significant up-regulation of MMP-9 compared to MCF-7. No MMP-2 activity was detected for either MCF-7 or MCF-7/CD44s clone. MT1-MMP expression was also up-regulated as shown by RT-PCR. MCF-7/CD44s also showed an increase in migration and invasion compared to MCF-7 cells. In both cell lines, the increase in migration and invasion correlated with an increase in CD44s-mediated MMPs activity. The predominant MMP activity in ovarian and breast cancer cells was MMP-2 and MMP-9, respectively. Experiments are in progress to identify the 50 kDa gelatinolytic activity and the putative modification of CD44s. These findings suggest that CD44s is involved in the regulated expression of MMPs. The ability of CD44 to up-regulate MMPs contributes to a higher metastatic potential and aggressive phenotype.
Prostatic acid phosphatase (PAP) is PI(3)P-phosphatase and its inactivation leads to change of cell polarity and invasive prostate cancer
Authors: Pirkko T. Vihko, Ileana Quintero, Anna E. Rönkä, Annakaisa Herrala, Piritta Jäntti, Katja Porvari, Ylva Lindqvist, Helena Kaija, Anitta Pulkka, Jussi Vuoristo, Raija Sormunen, Ylermi Soini, Maria Halmekytö, Juhani Jänne, Toni Luokkala, Riitta Kurkela
Journal: Cancer Research (2005)

5239  Prostatic acid phosphatase (PAP) was the first tumor marker of prostate cancer, used for detection of cancer and follow-up of therapy. At tissue level the expression of PAP is decreased with increasing prostate malignancy. The biological function of PAP is nevertheless unknown. To study the physiological function of PAP, mice lacking exon 3 of prostatic acid phosphatase gene (PAP, Acpp) were generated. PAPΔ3/Δ3 mice are fertile. The removal of PAP activity inflicts changes in the prostate in every male mouse in the anterior (AP) and dorsolateral (DLP) lobes. The mice develop prostate hyperplasia followed by initiation of prostate cancer with prostate intraepithelial neoplasia (PIN) and invasive adenocarcinoma. We show that PAP, which is a tyrosine phosphatase, is also a lipid phosphatase and effectively dephosphorylates phosphatidylinositol 3-phosphate (PI(3)P). In DLP PAP co-localizes with PI(3)P subcellularly on the endocytic pathway and intercellularly. Knockout of PAP activity changes the traffic of PAP and increasingly of PI(3)P to the basal domain and the nucleus of cells. We detected increased proliferation and decreased apoptosis in PAP-/- prostates. Changes at subcellular level took place early after sexual maturation in PAP-/- prostates. Also gene expressions were remarkably changed. Gene expression analyses were made from total prostates of one and six-month-old mice and from DLP at the age of two months. Main gene expressions changes were in categories: transcription factors, kinase activity, hydrolase activity, receptor activity and ion channel/transport. PI3K/Akt-signaling was also changed in PAP-/- epithelium. Our results show that PAP is not only an important regulator of PI(3)P transport, but also a novel tumor suppressor of prostate epithelial cells.
Abstract 15476: Reduction of Medical Ultrasound Reverberation Artifacts in Cardiac Imaging Using a Data-Adaptive Signal Separation Scheme
Authors: F W Mauldin, Brent A French, John A Hossack
Journal: Circulation (2011)

Introduction: The prevalence of artifacts in ultrasound cardiac imaging is a major limitation in clinical practice that motivates the use of alternative imaging modalities, such as computed tomogra...
Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia
Authors: Steven G. Smith, Ruchong Chen, Melanie Kjarsgaard, Chynna Huang, John-Paul Oliveria, Paul M. O'Byrne, Gail M. Gauvreau, Louis-Philippe Boulet, Catherine Lemiere, James Martin, Parameswaran Nair, Roma Sehmi
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 2044: Selective Head Cooling Initiated during Cpr Induces Post-Resuscitation Carotid Artery Dilation and Increases in Carotid Artery Flow and Cerebral Cortical Microcirculation
Authors: Giuseppe Ristagno, Jun H Cho, Tao Yu, Shijie Sun, Max H Weil, Wanchun Tang
Journal: Circulation (2008)

Introduction. We have previously reported that selective head cooling initiated during CPR prevented increases in brain temperature and improved neurological outcome. In the present study, we explored the relationship between head cooling during CPR and cerebral blood flows. We hypothesized that head cooling during CPR would yield carotid artery dilation with consequent increases in carotid flows and cerebral cortical microcirculation. Methods. Eight pigs weighing 37 ± 1 kg were intubated and mechanically ventilated. The common carotid artery was isolated and a parietal craniotomy was created. Ventricular fibrillation was electrically induced and untreated for 4 min. Animals were then randomized to head cooling or control. Head cooling was initiated with the aid of the RinoChill device (BeneChill Inc) at the beginning of CPR. CPR was performed for 4 min prior to defibrillation. Common carotid artery diameter and flow were assessed with a Doppler transducer. Cerebral cortical capillary density, representing the number of perfused capillaries, was assessed with Sidestream Dark Field imaging (MicroVisionMedical Inc). Brain temperature was measured with a needle sensor inserted in the cerebral cortex. Results. All the animals were resuscitated. After resuscitation, the brain temperature was significantly decreased in animals subjected to head cooling. Significantly greater carotid artery diameters and flows were observed in animals subjected to selective head cooling compared to the control animals. These increases in carotid blood flows were accompanied by significantly greater numbers of perfused capillaries in the cerebral cortices. No differences in cardiac output were observed between the two groups (Table ). Conclusion. Early selective head cooling induces carotid artery dilation and increases in carotid flows and cerebral cortical microcirculation after resuscitation.
A randomised phase III trial by the ELCWP comparing sequential administration of cisplatin-based chemotherapy followed by a taxan and a cisplatin-based chemotherapy with the use of taxan as salvage treatment
Authors: Anne-Pascale Meert, Jean-Jacques Lafitte, Jean-Paul Lecomte, Constantinos Alexopoulos, O Van Cutsem, Vicente Giner, Anna Efremidis, M.C. Berchier, Arnaud Scherpereel, Vincent Ninane, Marianne Paesmans, Thierry Berghmans, Jean-Paul Sculier
Journal: European Respiratory Journal (2006)
Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing
Authors: Patrizia Leone, Simona Berardi, Maria Antonia Frassanito, Roberto Ria, Valli De Re, Sebastiano Cicco, Stefano Battaglia, Paolo Ditonno, Franco Dammacco, Angelo Vacca, Vito Racanelli
Journal: Blood (2015)
Analysis of CD8+ Treg cells in patients with ovarian cancer: a possible mechanism for immune impairment
Authors: Shuping Zhang, Xing Ke, Suyun Zeng, Meng Wu, Jianfang Lou, Lei Wu, Peijun Huang, Lei Huang, Fang Wang, Shiyang Pan
Journal: Cellular and Molecular Immunology (2015)

Regulatory T (Treg) cells may participate in mediating a suppressive microenvironment that blunts successful anti-tumor immunotherapy. Recent studies show that CD8+ Treg cells might impede effective immune responses to established tumors. However, there is limited research regarding CD8+ Treg cells in ovarian cancer (OC) patients. Here, we investigated CD8+ Treg cells in OC patients and their in vitro induction. The immunohistochemistry of tumor-infiltrating lymphocytes revealed a significant correlation between the intratumoral CD8+ T cells and the forkhead box p3 (Foxp3)+ cells in the intraepithelial and stromal areas of advanced OC tissues. We examined the expression of Treg markers in CD8+ T cells from the peripheral blood and fresh tumor tissues of OC patients using flow cytometry. Our results indicated an increase in the CD8+ Treg cell subsets of OC patients compared with those in patients with benign ovarian tumors and healthy controls, including an increased expression of CD25, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and Foxp3 and decreased CD28 expression. To demonstrate whether the tumor microenvironment could convert CD8+ effector T cells into suppressor cells, we used an in vitro transwell culturing system. Compared with the CD8+ T cells cultured alone, the CD8+ Treg cells induced in vitro by coculture with SK-OV-3/A2780 showed increased CTLA-4 and Foxp3 expression and decreased CD28 expression. In addition, the in vitro-induced CD8+ Treg cells inhibited naı¨ve CD4+ T-cell proliferation, which was partially mediated through TGF-β1 and IFN-γ. Our study suggests that CD8+ Treg cells were increased in OC patients and could be induced in vitro, which may be the way that tumors limit antitumor immunity and evade immune surveillance.
Abstract 3052: Initial Human Experiences with a Non-Stented Coronary Sinus Device for the Treatment of Functional Mitral Regurgitation in Heart Failure Patients
Authors: Stefan Sack, Philipp Kahlert, Luc Bilodeau, Luc Pierard, Patrizio Lancellotti, Victor Legrand, Jozef Bartunek, Marc Vanderheyden, Rainer Hoffmann, Patrick Schauerte, Takahiro Shiota, David Marks, Stephen Ellis, Raimund Erbel
Journal: Circulation (2008)

Recently, several approaches have been developed for percutaneous mitral valve repair. The percutaneous transvenous mitral annuloplasty system (PTMA TM , Viacor Inc., Wilmington, USA) is an indirect annuloplasty device deployed within the coronary sinus (CS). Its mechanism is based on reduction of the anterior-posterior diameter of the mitral annulus to decrease mitral regurgitation (MR) by reestablishing leaflet coaptation in functional MR. We report the ongoing first-in-human experience with this non-stented device. 27 heart failure patients (NYHA II–IV) with functional MR II–III were enrolled at 5 centers. Via subclavian access, a multi-lumen diagnostic catheter was positioned within the anterior interventricular vein of the CS. Nitinol rods of various length and stiffness patterns were subsequently introduced into the lumina in order to exert pressure to the posterior mitral leaflet and to reduce AP diameter. Under fluoroscopic and echo guidance, different rod combinations were evaluated for maximal effectiveness before exchanging the diagnostic system to the permanent device. After assuring significant MR reduction by the permanent implant, the whole device was implanted in a subcutaneous pocket. 8 patients were excluded prior procedure due to unfavorable CS anatomy. The remaining 19 patients proceeded through a complete diagnostic exam. While the device was ineffective in 6 cases, echocardiography revealed a significant reduction of MR in 13 patients. 9 of these patients underwent successful implantation of the permanent device. 4 devices were subsequently removed, one at 7 days due to device fracture and the other 3 when the patients were referred for annuloplasty surgery due to device migration or diminished efficacy. Sustained reduction in MR and AP dimensions was noted in the remaining 4 long-term implants. No procedure related adverse events with permanent sequelae were observed in all patients. Initial human experiences with the PTMA TM device demonstrate safety and feasibility of this method as well as sustained favorable geometric modifications of the mitral annulus with reduction of MR in responding patients.
Abstract 12081: Glycemic Variability as Determined by a Continuous Glucose Monitoring System Predicts Left Ventricular Dysfunction in Patients With a First ST-Segment Elevation Myocardial Infarction
Authors: Masaomi Gohbara, Noriaki Iwahashi, Shunsuke Kataoka, Eiichi Akiyama, Nobuhiko Maejima, Kengo Tsukahara, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2014)

Background: Glycemic Variability (GV) may play an important role in development of cardiovascular disease however the clinical significance of GV is not fully understood in patients with ST-segment elevation myocardial infarction (STEMI). We explored the clinical utility of GV using continuous glucose monitoring system (CGMS; iPro2, Medtronic, USA). Methods: Seventy-four patients (66 males, 63±12 years) with a first STEMI were enrolled. STEMI was de[[Unable to Display Character: &amp;#64257;]]ned as chest pain lasting for at least 30 minutes accompanied by ST-segment elevation and an increase in the serum peak-creatine phosphokinase (CPK) level to more than twice the upper limit of normal. All patients were equipped with a CGMS 1 week after admission and GV was assessed by measuring the Mean Amplitude of Glycemic Excursion (MAGE) during 24 hours with 3 regular meals. At 7 month, all patients underwent conventional 2D echocardiography and blood sampling (BNP; brain natriuretic peptide) to explore the effect of GV to their cardiac function. Results: On univariate analysis male, culprit left anterior descending artery (LAD), peak CK-MB and MAGE were predictors of decreased left ventricular ejection fraction (LVEF). On multivariate analysis higher MAGE level was an independent predictor of decreased LVEF. Higher MAGE level was also an independent predictor of higher BNP level at 7 month. Conclusions: GV was an independent predictor of left ventricular dysfunction in patients with a first STEMI.
Abstract 3622: Oxidized LDL-derived Reactive Aldehydes Induce ER Stress and Trigger the Unfolded Protein Response: Implications for Atherosclerotic Lesion Formation
Authors: Elena N Vladykovskaya, Petra Haberzettl, Oleg A Barski, Srinivas D Sithu, Stanley E D’Souza, Aruni Bhatnagar, Sanjay Srivastava
Journal: Circulation (2008)

All stages of atherosclerotic lesion formation are associated with the accumulation of proteins modified by aldehydes that are generated from the oxidation of membrane phospholipids and lipoproteins. Although aldehyde-adducted proteins elicit strong immunogenic responses, the role of lipid peroxidation products in promoting and sustaining atherogenesis remains unclear. To examine aldehyde-induced protein modification and to assess its contribution to vascular stress, vascular smooth muscle and endothelial cells (EC) were exposed to 4-hydroxy-trans-2-nonenal (HNE), one of the most abundant and reactive oxidized lipid-derived aldehyde (LDA). Exposure to HNE (25 μM, 2h) resulted in extensive modification of cellular proteins in both cell types. Majority of these proteins, identified by MALDI/MS analysis, were ER-resident protein chaperones that assist in protein folding. Confocal imaging of HNE treated EC showed that the modified proteins were associated with the ER. Exposure to HNE led to the splicing of the bZIP transcription factor, XBP-1, a characteristic feature of the alarm phase of ER stress, and an increase in the phosphorylation of eIF2α, which regulates the expression of multiple ER-stress dependent transcription factors. These transcription factors, ATF3, ATF4, and CHOP were also strongly (2–5-fold) induced by HNE. Treatment with HNE was associated with a 2–5 fold increase in the expression of ER chaperones, GRP78 and HERP, indicating that HNE triggers the adaptive phase of the response, which increases the protein folding capacity of the ER. Pretreatment with the chemical chaperone, phenylbutyric acid (PBA), to facilitate protein folding, completely abolished HNE-induced increase in the expression of ATF3. EC treated with HNE enhanced monocyte adhesion, which was attenuated by PBA, indicating that early stages of lesion formation may be ER-stress dependent. In intermediate arterial lesion of 20 week old apoE-null mice, HNE-adducted proteins were localized to areas immunopositive for ATF3, ATF4, and phospho-PERK. These results suggest that protein modifications by LDA induce ER stress and the alarm and adaptive responses to this stress may be significant determinants of lesion progression and stability.
Photodynamic gene therapy for lung cancers: Intracellular chemiluminescence using Renilla luciferase and coelenterazine induces apoptosis.
Authors: Jitsuo Usuda, Takeshi Hirata, Keishi Ohtani, Mitsuhiro Kubota, Tatsuo Ohira, Masahiro Tsuboi, Takashi Hirano, Kinya Furukawa, Tetsuya Okunaka, Harubumi Kato
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5189 

Photodynamic therapy (PDT), a treatment for cancer, utilizes a photosnesitizer and laser irradiation to produce reactive oxygen in cells. In Japan, the United States and other many countires, PDT is a standard treatment option for stage 0 (TisN0M0) and stage I (T1N0M0) centrally located early stage lung cancer. PDT can preserve lung function, can be repeated and be used by combined with chemotherapy. Recently, mono-L-aspartyl chlorine e6 (NPe6, Laserphyrin), which was a second generation photosensitize and low photosensitivity, was approved by the Japanese government and the phase II clinical study using the photosensitizer and a new diode laser demonstrated excellent anti-tumor effect and low skin photosensitivity. NPe6 has an absorption profile that closely matches the emission profile of chemiluminescence using Renilla luciferase/coelenterazine. In this study, we proposed that coelenterazine and NPe6 when taken up by Renilla luciferase-transfected cells, as a consequence of their intracellular proximity, produce sufficient light to release singlet oxygen by photoactivation and to trigger individual cell death. We examined the chemiluminescence could kill cancer cell. We transfected Renilla luciferase gene into A549, lung cancer cells. Eight h after the transfection, the cells were treated with NPe6 and coelenterazine. Twenty four h after the transfections, we observed typical morphologicaly apoptosis in A549 cells using fluorescent microscope. These results indicate that the intrafluorescence can produce a high quantum yield of singlet oxygen and kill cancer cells, and this new cancer treatment, photodynamic gene therapy, using trasfection of Renilla lucuferase and photosensitizer, can induce apoptosis. In the future, photodynamic gene therapy without laser irradiation can treat solid tumors through the production of intracellular light.
Abstract 17632: Bivalirudin versus Heparin in Patients with Acute Myocardial Infarction: A Meta-analysis of Randomized Trials
Authors: Giuseppe Ferrante, Paolo Pagnotta, Elena Corrada, Patrizia Presbitero
Journal: Circulation (2014)

Introduction:  There is uncertainty about the impact of bivalirudin, as compared to unfractionated heparin, on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI)   Hypothesis:  We aimed to assess whether bivalirudin is superior to heparin in patients with STEMI.   Methods:  A meta-analysis of randomized trials comparing bivalirudin versus heparin in patients with STEMI undergoing primary percutaneous coronary intervention was performed. Summary odds ratios (OR) with 95% confidence intervals (CI) were calculated using random effects model.   Results:  Three randomized trials enrolling 7612 patients were included. At 30 days, bivalirudin, as compared to heparin, was associated with a similar risk of all-cause mortality (3.03% vs. 3.38%, OR 0.90, 95% CI [0.63 to 1.29], p=0.57). Bivalirudin significantly increased the risk of definite (1.98% vs. 0.86%, OR 2.53, 95% CI [1.31 to 4.87], p=0.006); definite or probable (2.11% vs. 1.10%, OR 2.30, 95% CI [1.08 to 4.90], p=0.03); and acute stent thrombosis (1.39% vs. 0.31%, OR 4.41, 95% CI [2.34 to 8.29], p   Conclusions:  In patients with STEMI, bivalirudin use, as compared to heparin, is associated with similar all-cause mortality at 30 days. However bivalirudin increases the risk of stent thrombosis and ischemia driven revascularization, while no strong evidence that it significantly reduces major bleeding at 30 days is present.
Treatment plans for mental health care
Authors: Knesper Dj, Miller D
Journal: American Journal of Psychiatry (1976)

The authors present a method for the development of standard process criteria for the care of defined subpopulations of psychiatric patients using a two-dimensional problem category system to describe patients. Patient subpopulations, described by both a traditional psychopathological problem cluster and a less traditional psychosocial problem cluster, are matched to a list of problem-solving services to develop a model treatment plan. The authors present this method for developing standard treatment plans as an alternative to APA's Model Criteria Sets.