tbuckley/cabot-search huggingface dataset:
Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation
Authors: Ronald B. Smeltz, June Chen, Jane Hu-Li, Ethan M. Shevach
Journal: The Journal of Experimental Medicine (2001)

Interleukin (IL)-18 has been well characterized as a costimulatory factor for the induction of IL-12-mediated interferon (IFN)-gamma production by T helper (Th)1 cells, but also can induce IL-4 production and thus facilitate the differentiation of Th2 cells. To determine the mechanisms by which IL-18 might regulate these diametrically distinct immune responses, we have analyzed the role of cytokines in the regulation of IL-18 receptor alpha chain (IL-18Ralpha) expression. The majority of peripheral CD4(+) T cells constitutively expressed the IL-18Ralpha. Upon antigen stimulation in the presence of IL-12, marked enhancement of IL-18Ralpha expression was observed. IL-12-mediated upregulation of IL-18Ralpha required IFN-gamma. Activated CD4(+) T cells that expressed low levels of IL-18Ralpha could produce IFN-gamma when stimulated with the combination of IL-12 and IL-18, while CD4(+) cells which expressed high levels of IL-18Ralpha could respond to IL-18 alone. In contrast, T cell stimulation in the presence of IL-4 resulted in a downregulation of IL-18Ralpha expression. Both IL-4(-/)- and signal transducer and activator of transcription (Stat)6(-/)- T cells expressed higher levels of IL-18Ralpha after TCR stimulation. Furthermore, activated T cells from Stat6(-/)- mice produced more IFN-gamma in response to IL-18 than wild-type controls. Thus, positive/negative regulation of the IL-18Ralpha by the major inductive cytokines (IL-12 and IL-4) determines the capacity of IL-18 to polarize an immune response.
Fcγ Receptor–mediated Induction of Dendritic Cell Maturation and Major Histocompatibility Complex Class I–restricted Antigen Presentation after Immune Complex Internalization
Authors: Armelle Regnault, Danielle Lankar, Valérie Lacabanne, Ana Rodriguez, Clotilde Théry, Maria Rescigno, Takashi Saito, Sjef Verbeek, Christian Bonnerot, Paola Ricciardi-Castagnoli, Sebastian Amigorena
Journal: The Journal of Experimental Medicine (1999)

Dendritic cells (DCs) express several receptors for the Fc portion of immunoglobulin (Ig)G (FcγR), which mediate internalization of antigen–IgG complexes (immune complexes, ICs) and promote efficient major histocompatibility complex (MHC) class II–restricted antigen presentation. We now show that FcγRs have two additional specific attributes in murine DCs: the induction of DC maturation and the promotion of efficient MHC class I–restricted presentation of peptides from exogenous, IgG-complexed antigens. Both FcγR functions require the FcγR-associated γ chain. FcγR-mediated MHC class I–restricted antigen presentation is extremely sensitive and specific to immature DCs. It requires proteasomal degradation and is dependent on functional peptide transporter associated with antigen processing, TAP1-TAP2. By promoting DC maturation and presentation on both MHC class I and II molecules, ICs should efficiently sensitize DCs for priming of both CD4+ helper and CD8+ cytotoxic T lymphocytes in vivo.
Human CD59 Inhibitor Sensitizes Rituximab-Resistant Lymphoma Cells to Complement-Mediated Cytolysis
Authors: Weiguo Hu, Xiaowen Ge, Tao You, Ting Xu, Jinyan Zhang, Gongxiong Wu, Zhihai Peng, Michael Chorev, Bertal H. Aktas, Jose A. Halperin, Jennifer R. Brown, Xuebin Qin
Journal: Cancer Research (2011)

Abstract Rituximab efficacy in cancer therapy depends in part on induction of complement-dependent cytotoxicity (CDC). Human CD59 (hCD59) is a key complement regulatory protein that restricts the formation of the membrane attack complex, thereby inhibiting induction of CDC. hCD59 is highly expressed in B-cell non–Hodgkin's lymphoma (NHL), and upregulation of hCD59 is an important determinant of the sensitivity of NHL cells to rituximab treatment. Here, we report that the potent hCD59 inhibitor rILYd4 enhances CDC in vitro and in vivo, thereby sensitizing rituximab-resistant lymphoma cells and primary chronic lymphocytic leukemia cells (CLL) to rituximab treatment. By defining pharmcokinetic/pharmacodynamic profiles of rILYd4 in mice, we showed that by itself rILYd4 does not adversely mediate in vivo hemolysis of hCD59-expressing erythrocytes. Increasing expression levels of the complement regulators CD59 and CD55 in rituximab-resistant cells occur due to selection of preexisting clones rather than de novo induction of these proteins. Moreover, lymphoma cells overexpressing CD59 were directly responsible for the resistance to rituximab-mediated CDC therapy. Our results rationalize the use of rILYd4 as a therapeutic adjuvant for rituximab treatment of rituximab-resistant lymphoma and CLL. Furthermore, they suggest that preemptive elimination of CD59-overexpressing subpopulations along with rituximab treatment may be a useful approach to ablate or conquer rituximab resistance. Cancer Res; 71(6); 2298–307. ©2011 AACR.
Breast Cancer Incidence in the Randomized PEARL Trial of Lasofoxifene in Postmenopausal Osteoporotic Women
Authors: A. Z. LaCroix, T. Powles, C. K. Osborne, K. Wolter, J. R. Thompson, D. D. Thompson, D. C. Allred, R. Armstrong, S. R. Cummings, R. Eastell, K. E. Ensrud, P. Goss, A. Lee, P. Neven, D. M. Reid, M. Curto, S. Vukicevic
Journal: JNCI Journal of the National Cancer Institute (2010)

Currently available selective estrogen receptor modulators reduce the risk of breast cancer, but they are not widely used. In the Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene (PEARL) trial, lasofoxifene was shown to reduce the risk of estrogen receptor–positive (ER+) breast cancer, nonvertebral and vertebral fractures, coronary artery disease, and stroke, but the effects on total breast cancer (invasive and ductal carcinoma in situ, ER+ and estrogen receptor–negative [ER−]) and ER+ invasive breast cancer are unknown. Postmenopausal women (n = 8556) aged 59–80 years with low bone density and normal mammograms were randomly assigned to two doses of lasofoxifene (0.25 and 0.5 mg) or placebo. The primary endpoints of the PEARL trial were incidence of ER+ breast cancer and nonvertebral fractures at 5 years. A nested case–control study of 49 incident breast cancer case patients and 156 unaffected control subjects from the PEARL trial was performed to evaluate treatment effects on risk of total and ER+ invasive breast cancer by baseline serum estradiol and sex hormone–binding globulin levels using logistic regression models. Cox proportional hazards models were used to evaluate risk of total breast cancer and ER+ invasive breast cancer using intention-to-treat analysis. All statistical tests were two-sided. Breast cancer was confirmed in 49 women. Compared with placebo, 0.5 mg of lasofoxifene statistically significantly reduced the risk of total breast cancer by 79% (hazard ratio = 0.21; 95% confidence interval [CI] = 0.08 to 0.55) and ER+ invasive breast cancer by 83% (hazard ratio = 0.17; 95% CI = 0.05 to 0.57). The effects of 0.5 mg of lasofoxifene on total breast cancer were similar regardless of Gail score, whereas the effects were markedly stronger for women with baseline estradiol levels greater than the median (odds ratio = 0.11; 95% CI = 0.02 to 0.51) vs those with levels less than the median (odds ratio = 0.78; 95% CI = 0.16 to 3.79; Pinteraction = .04). A 0.5-mg dose of lasofoxifene appears to reduce the risks of both total and ER+ invasive breast cancer in postmenopausal women with osteoporosis.
Collection devices influence the constituents of exhaled breath condensate: Fig. 1—
Authors: J. Liu, D. H. Conrad, S. Chow, V. H. Tran, D. H. Yates, P. S. Thomas
Journal: European Respiratory Journal (2007)

Collection devices influence the constituents of exhaled breath condensateTo the Editors:The recent paper by ROSIAS et al. [1] reported that silicone and glass inner coatings were superior to the EcoScreen1 system (Erich Jaeger GmbH, Hochberg, Germany), aluminium, polypropylene and Teflon when measuring 8-isoprostane and albumin levels in exhaled breath condensate (EBC) [1][2][3].This raises important issues in the ongoing debate about the optimal collection method for sampling airway biomarkers.We have complemented these important data by comparing the efficiency and reproducibility of EBC biomarkers collected by different devices in six healthy subjects.Four collection systems were compared in a randomised order: glass, siliconised glass, EcoScreen1 and RTube1 (Respiratory Research Inc., Charlottesville, VA, USA).Oxides of nitrogen (NO x ), total protein, mucin and pH were measured and assessed for reproducibility over 3 days [4,5].
Therapeutic Antibody Targeting of CD47 Eliminates Human Acute Lymphoblastic Leukemia
Authors: Mark P. Chao, Ash A. Alizadeh, Chad Tang, Max Jan, Rachel Weissman-Tsukamoto, Feifei Zhao, Christopher Y. Park, Irving L. Weissman, Ravindra Majeti
Journal: Cancer Research (2010)

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and constitutes 15% of adult leukemias. Although overall prognosis for pediatric ALL is favorable, high-risk pediatric patients and most adult patients have significantly worse outcomes. Multiagent chemotherapy is standard of care for both pediatric and adult ALL, but is associated with systemic toxicity and long-term side effects and is relatively ineffective against certain ALL subtypes. Recent efforts have focused on the development of targeted therapies for ALL including monoclonal antibodies. Here, we report the identification of CD47, a protein that inhibits phagocytosis, as an antibody target in standard and high-risk ALL. CD47 was found to be more highly expressed on a subset of human ALL patient samples compared with normal cell counterparts and to be an independent predictor of survival and disease refractoriness in several ALL patient cohorts. In addition, a blocking monoclonal antibody against CD47 enabled phagocytosis of ALL cells by macrophages in vitro and inhibited tumor engraftment in vivo. Significantly, anti-CD47 antibody eliminated ALL in the peripheral blood, bone marrow, spleen, and liver of mice engrafted with primary human ALL. These data provide preclinical support for the development of an anti-CD47 antibody therapy for treatment of human ALL.
Glucokinase and cytosolic phosphoenolpyruvate carboxykinase (GTP) in the human liver. Regulation of gene expression in cultured hepatocytes.
Authors: P B Iynedjian, S Marie, A Gjinovci, B Genin, S P Deng, L Buhler, P Morel, G Mentha
Journal: Journal of Clinical Investigation (1995)

Glucokinase and phosphoenolpyruvate carboxykinase are key enzymes of glucose metabolism in the rat liver. The former is considered to be instrumental in regulating glucose hepatic release/uptake according to the glycaemia level, and cytosolic phosphoenolpyruvate carboxykinase is a major flux-generating enzyme for gluconeogenesis. The level of expression of both enzymes and the regulation of their mRNAs in the human liver cell were investigated. Surgical biopsies of liver from patients undergoing partial hepatectomies and parenchymal hepatocytes derived from the biopsies were used to assay glucokinase, hexokinase and phosphoenolpyruvate carboxykinase activities. Hepatocytes were placed in culture and the actions of insulin, glucagon and cAMP on glucokinase and phosphoenolpyruvate carboxykinase mRNAs were studied. The main results are: (a) glucokinase accounts for 95% of the glucose phosphorylation activity of human hepatocytes, although this fact is masked in assays of total liver tissue; (b) glucokinase activity is set at a lower level in human hepatocytes than in rat hepatocytes, and vice-versa for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase; and (c) as previously shown in rat liver, glucokinase and phosphoenolpyruvate carboxykinase mRNAs are regulated in a reciprocal fashion in human hepatocytes, insulin inducing the first enzyme and repressing the latter, whereas glucagon has opposite effects. These data have interesting implications with respect to metabolic regulation and intracellular hormone signaling in the human liver.
Adaptive Evolution of Foundation Kinetochore Proteins in Primates
Authors: Mary G. Schueler, Willie Swanson, Pamela J. Thomas, Eric D. Green
Journal: Molecular Biology and Evolution (2010)

Rapid evolution is a hallmark of centromeric DNA in eukaryotic genomes. Yet, the centromere itself has a conserved functional role that is mediated by the kinetochore protein complex. To broaden our understanding about both the DNA and proteins that interact at the functional centromere, we sought to gain a detailed view of the evolutionary events that have shaped the primate kinetochore. Specifically, we performed comparative mapping and sequencing of the genomic regions encompassing the genes encoding three foundation kinetochore proteins: Centromere Proteins A, B, and C (CENP-A, CENP-B, and CENP-C). A histone H3 variant, CENP-A provides the foundation of the centromere-specific nucleosome. Comparative sequence analyses of the CENP-A gene in 14 primate species revealed encoded amino-acid residues within both the histone-fold domain and the N-terminal tail that are under strong positive selection. Similar comparative analyses of CENP-C, another foundation protein essential for centromere function, identified amino-acid residues throughout the protein under positive selection in the primate lineage, including several in the centromere localization and DNA-binding regions. Perhaps surprisingly, the gene encoding CENP-B, a kinetochore protein that binds specifically to alpha-satellite DNA, was not found to be associated with signatures of positive selection. These findings point to important and distinct evolutionary forces operating on the DNA and proteins of the primate centromere.
Oncogenic and Angiogenic Growth Factors Accumulate during Routine Storage of Apheresis Platelet Concentrates
Authors: Julie Kanter, Samina Y. Khan, Marguerite Kelher, Lia Gore, Christopher C. Silliman
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Platelet concentrates are important for support of patients with malignancies requiring myelotoxic chemotherapy. During storage, 10% to 15% of platelets may become activated resulting in the release of α-granules, which contain growth factors. We hypothesize that, during storage, growth factors accumulate in the plasma, specifically platelet-derived growth factor, vascular endothelial growth factor (VEGF), transforming growth factor-β, and fibroblast growth factor-2, which may adversely affect cancer patients. Experimental Design: The concentrations of growth factors were measured by ELISA from the plasma of apheresis platelets serially throughout storage (days 1, 3, 5, and 7) and compared with concentrations in fresh plasma from healthy blood donors. Washing was evaluated as a method of growth factor removal, and an in vitro model of platelet transfusion in a patient receiving Bevacizumab (Avastin) using immunoprecipitation was employed to determine if Bevacizumab would be bound by the VEGF in apheresis platelets. Results: VEGF, platelet-derived growth factor, and transforming growth factor-β were increased on day 1 versus fresh plasma and throughout storage reaching a relative maximum at outdate (P &amp;lt; 0.01, day 5 or 7). Fibroblast growth factor-2 concentrations were significantly increased on day 7 alone versus day 1 or to fresh plasma (P &amp;lt; 0.01). Washing removed 41 ± 11% to 56 ± 2% of the growth factors. Bevacizumab effectively bound the VEGF from apheresis platelets, with significant amounts of VEGF remaining in the supernatant. Conclusions: Significant amounts of growth factors are present in apheresis platelets due to the isolation procedures, and these concentrations increase over storage, which may be partially removed by washing. In addition, apheresis platelet transfusion could affect cancer treatment by binding monoclonal antibodies directed against growth factors of tumor origin.
Abrogation of TGFβ Signaling in Mammary Carcinomas Recruits Gr-1+CD11b+ Myeloid Cells that Promote Metastasis
Authors: Li Yang, Jianhua Huang, Xiubao Ren, Agnieszka E. Gorska, Anna Chytil, Mary Aakre, David P. Carbone, Lynn M. Matrisian, Ann Richmond, P. Charles Lin, Harold L. Moses
Journal: Cancer Cell (2008)
Effects of Early Surfactant Treatment Persisting for One Week after Lung Transplantation in Rats
Authors: MICHIEL E. ERASMUS, GERT J. H. HOFSTEDE, ARJEN H. PETERSEN, HENK P. HAAGSMAN, SIDARTO BAMBANG OETOMO, JOCHUM PROP
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We investigated whether pulmonary surfactant in rat lung transplants recovered during the first week post-transplantation, along with symptoms of the reimplantation response, and whether this recovery was affected by early surfactant treatment. The severity of pulmonary injury was varied by transplanting left lungs with 6-h and 20-h ischemia (n = 12 and 19, respectively). Half of the transplants were treated by instillation of surfactant before reperfusion. Lungs from sham operated, and normal rats (n = 4 and 5, respectively) served as controls. The pulmonary injury severely impaired lung transplant function; 10 of the worst affected animals died. After 1 wk, symptoms of reimplantation response and properties of pulmonary surfactant were assessed. If untreated, the reimplantation response had almost resolved in the 6-h but not in the 20-h ischemia group; pulmonary surfactant, however, continued to be deficient in both ischemia groups (low amounts of surfactant phospholipids and surfactant protein A [SP-A]). Surfactant treatment improved the recovery from injury in the 20-h ischemia group resulting in normal lung function and amounts of surfactant phospholipids. Amounts of SP-A were not improved by surfactant treatment. In conclusion, early surfactant treatment enhances recovery from transplantation injury and is persistently beneficial for pulmonary surfactant in lung transplants.
Tumor-Promoting and -Suppressive Roles of Autophagy in the Same Mouse Model of <i>Braf</i>V600E-Driven Lung Cancer
Authors: Song Chen, Jun-Lin Guan
Journal: Cancer Discovery (2013)

Abstract Summary: Although a role of autophagy in cancer development and progression has received increasing appreciation in recent years, there are still significantly uncertain and conflicting results about its tumor-suppressive and -promoting functions, and, more importantly, a lack of understanding of mechanisms underlying these opposing activities. The work presented by Strohecker and colleagues uses an innovative approach to address these challenges by examining the effects of inactivating the key autophagy gene Atg7 at different stages of oncogenic development in a BrafV600E-driven mouse lung cancer model. The authors show that autophagy blockage initially accelerated tumor development, but suppressed tumor progression in later stages, converting adenomas to oncocytomas and increasing mouse survival. Importantly, they identify a critical role of glutamine dependency in the suppression of BrafV600E-induced cancer, thus revealing an important mechanism by which autophagy may promote tumor progression in different cellular contexts. Cancer Discov; 3(11); 1225–7. ©2013 AACR. See related article by Strohecker et al., p. 1272
MULTIPLE ULCERS OF HANDS DUE TO OCCUPATION
Authors: ARTHUR HALL
Journal: British Journal of Dermatology (1901)

OASE OF IDIOPATHIC MULTIPLE PIGMENT SARCOMA (3). 209the characteristics of true sarcomata.In view of these facts, the writer is led to the conclusion that the 8ame name has been applied to two different classes of case, one malignant and the other benign.This appears to be more probable than the assumption that the disease may have an ( ( innocent " period which may or may not be followed by wide dissemination and the other characteristics of ( ( malignancy."There is no evidence that the condition is a chronic infectious process, and though Semenow* and others have found changes in the nervous system, chiefly in the spinal ganglia, the suggestion that the lesions are due to paralytic angioneurosis is purely problematical.
Adjuvant Gemcitabine Alone Versus Gemcitabine-Based Chemoradiotherapy After Curative Resection for Pancreatic Cancer: A Randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase II Study
Authors: Jean-Luc Van Laethem, Pascal Hammel, Françoise Mornex, David Azria, Geertjan Van Tienhoven, Philippe Vergauwe, Marc Peeters, Marc Polus, Michel Praet, Murielle Mauer, Laurence Collette, Volker Budach, Manfred Lutz, Eric Van Cutsem, Karin Haustermans
Journal: Journal of Clinical Oncology (2010)

The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer.Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS).Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3-related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%).Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.
Chemically Reactive Intermediates and Pulmonary Xenobiotic Toxicity
Authors: Theodore E. Gram
Journal: Pharmacological Reviews (1997)

After reading this lengthy review, the reader may consider it foolhardy to attempt to summarize the data contained herein. If so, the author and the reader are in complete accord. I set out to integrate, wherever possible, pathological changes in tissues and cells as determined by light, scanning, and TEM with chemical, biochemical, molecular, biological, and genetic techniques. I am not so naive as to equate correlation with causation, but in experimental biology, one is often compelled to rely on a number correlations to suggest causation. These data may also act as a stepping-off point helping the investigator design experiments to support/confirm or refute/disprove the hypothesis under investigation. Science is rarely black and white but rather gray, and the young investigator must be wary of scientists who argue their points too vociferously, too loudly, or too selectively. The truth in science is often a Gordian knot.
Ticlopidine-aspirin as antithrombotic regimen for intracoronary stenting for unstable angina: is there a need for further antiplatelet therapy?
Authors: M. Angloï, N. Danchin, C. Gangloff, A. Grantzinger, L. Jacquemin, V. Berder, P. Houplon, Y. Julilière, F. Cherrier
Journal: Journal of the American College of Cardiology (1998)
Potential clinical value of circulating chromogranin A in patients with prostate carcinoma
Authors: A. Berruti, L. Dogliotti, A. Mosca, G. Gorzegno, E. Bollito, M. Mari, R. Tarabuzzi, M. Poggio, M. Torta, D. Fontana, A. Angeli
Journal: Annals of Oncology (2001)