tbuckley/cabot-search huggingface dataset:
CD38 expression does not change in B-cell chronic lymphocytic leukemia
Authors: Giovanni D'Arena, Giuseppe Nunziata, Giuseppe Coppola, Maria Luigia Vigliotti, Alfredo Tartarone, Nicola Carpinelli, Rosella Matera, Rosario Colella Bisogno, Giuseppe Pistolese, Nicola Di Renzo
Journal: Blood (2002)
Induction of Metastasis by S100P in a Rat Mammary Model and Its Association with Poor Survival of Breast Cancer Patients
Authors: Guozheng Wang, Angela Platt-Higgins, Joe Carroll, Suzete de Silva Rudland, John Winstanley, Roger Barraclough, Philip S. Rudland
Journal: Cancer Research (2006)

Abstract S100P, an EF-hand calcium-binding protein, has been reported to be associated with the progression of many types of cancers. Transfection of an expression vector for S100P into a benign, nonmetastatic rat mammary cell line causes a 4- to 6-fold increase in its level in all four transformant cell clones. When the resultant transformant cell lines are introduced in turn into the mammary fat pads of syngeneic Furth-Wistar rats, there is a significant 3-fold increase in local muscle invasion and a significant induction of metastasis in 64% to 75% of tumor-bearing animals. In a group of 303 breast cancer patients followed for up to 20 years, antibodies to S100P immunocytochemically stain 161 primary tumors. Survival of patients with S100P-positive carcinomas is significantly worse by about 7-fold than for those with negatively stained carcinomas. There is also a significant association between the class level of immunocytochemical staining of the carcinoma cells and decreased patient survival. Positive staining for S100P is significantly associated with that for two other metastasis-inducing proteins, S100A4 and osteopontin. Patients with tumors that stained positively for both S100P and S100A4 have a significantly reduced survival of 1.1% over patients with either S100 protein alone. Multivariate regression analysis identifies S100P, S100A4, and osteopontin as the most significant independent indicators of death in this group of patients. These results suggest that stratification of patients into groups according to expression of multiple metastasis-inducing proteins may lead to a more accurate prediction of patient survival. (Cancer Res 2006; 66(2): 1199-207)
Decision Making in Medicine and Health Care
Authors: Robert M. Kaplan, Dominick L. Frosch
Journal: Annual Review of Clinical Psychology (2004)

Decision making is central to health policy and medical practice. Because health outcomes are probabilistic, most decisions are made under conditions of uncertainty. This review considers two classes of decisions in health care: decisions made by providers on behalf of patients, and shared decisions between patients and providers. Considerable evidence suggests wide regional variation exists in services received by patients. Evidence-based guidelines that incorporate quality of life and patient preferences may help address this problem. Systematic cost-effectiveness analysis can be used to improve resource allocation decisions. Shared medical decision making seeks to engage patients and providers in a collaborative process to choose clinical options that reflect patient preferences. Although some evidence indicates patients want an active role in making decisions, other evidence suggests that some patients prefer a passive role. Decision aids hold promise for improving individual decisions, but there are still few systematic evaluations of these aids. Several directions for future research are offered.
Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter
Authors: A. Maestro, M. Terdoslavich, A. Vanzo, A. Kuku, F. Tramer, V. Nicolin, F. Micali, G. Decorti, S. Passamonti
Journal: Cardiovascular Research (2009)

AimsIngestion of flavonoid-rich beverages acutely affects endothelial function, causing vasodilation. This effect might be dependent on flavonoid transport into the endothelium. We investigated flavonoid uptake into vascular endothelial cells and whether this was mediated by bilitranslocase (TC 2.A.65.1.1), a bilirubin-specific membrane carrier that also transports various dietary flavonoids.
Greater late lumen loss after successful coronary balloon angioplasty in the proximal left anterior descending coronary artery is not explained by extent of vessel wall damage or plaque burden
Authors: Wouter E.M Kok, Ron J.G Peters, Gerard Pasterkamp, Carlo Di Mario, Patrick W Serruys, Martin Prins, Cees A Visser
Journal: Journal of the American College of Cardiology (2000)
p16Ink4a in Melanocyte Senescence and Differentiation
Authors: E. V. Sviderskaya
Journal: JNCI Journal of the National Cancer Institute (2002)

The Ink4a-Arf tumor suppressor locus encodes two growth inhibitors, p16 and Arf, both of which are also implicated as effectors in cellular senescence. Because human germline defects in the INK4A-ARF locus are associated with familial melanoma, melanocytes may have unusual INK4A-ARF functions or controls of cell senescence. Because senescence is believed to be an anticancer mechanism, we investigated the role of Ink4a-Arf and its individual components in melanocyte senescence.Melanocytes were cultured from littermate mice with zero, one, or two functional copies of the Ink4a-Arf locus. Senescence was evaluated by cumulative population doubling curves and by the assessment of acidic beta-galactosidase (an indicator of senescence) expression. Pigmentation and cell size were evaluated by spectrophotometry and microscopy. p16 and Arf expression in primary and spontaneously immortalized melanocyte or melanocyte precursor cell lines were evaluated by immunoblotting. Retroviral vectors containing normal p16 and Arf complementary DNAs were used to restore expression of these genes in Ink4a-Arf(-/-) melanocytes.Wild-type melanocytes (i.e., Ink4a-Arf(+/+)) senesced within 4-5 weeks of culture. Ink4a-Arf(-/-) melanocytes did not senesce and readily became immortal. Ink4a-Arf(+/-) melanocytes showed defective senescence. Senescent Ink4a-Arf(+/+) melanocytes were heavily pigmented, but Ink4a-Arf(+/-) and Ink4a-Arf(-/-) melanocytes were less pigmented. All of six spontaneously immortalized melanocyte or melanocyte precursor lines from Ink4a-Arf(+/+) mice lacked p16 protein expression, although most retained Arf protein expression. After restoration of p16 but not Arf expression, Ink4a-Arf(-/-) melanocytes stopped growing, became highly melanized, and expressed acidic beta-galactosidase. By contrast, restoration of Arf but not p16 expression led to cell death without evidence of senescence.Normal mouse melanocyte senescence and associated pigmentation require both copies of Ink4a-Arf and appear to depend more on p16 than on Arf function. Mutations of the INK4A-ARF locus may favor tumorigenesis from melanocytes by impairing senescence, cell differentiation, and (where ARF is disrupted) cell death.
Blockade of Paracrine Supply of Insulin-Like Growth Factors Using Neutralizing Antibodies Suppresses the Liver Metastasis of Human Colorectal Cancers
Authors: Shin'ichi Miyamoto, Michio Nakamura, Kenya Shitara, Kazuyasu Nakamura, Yuji Ohki, Genichiro Ishii, Masato Goya, Keiji Kodama, Takafumi Sangai, Hiroyuki Maeda, Zhang Shi-chuang, Tsutomu Chiba, Atsushi Ochiai
Journal: Clinical Cancer Research (2005)

Abstract Environmental stimuli, such as organ-specific growth factors, can influence the metastatic potential of a tumor. The liver is the main source of insulin-like growth factors (IGFs). The importance of IGF signal in hepatic metastasis has been clarified mainly by IGF-I receptor targeting strategies. This study aims to confirm these precedent reports by novel tool, neutralizing antibodies against IGFs and to show that IGFs are promising therapeutic targets for hepatic metastasis in vivo. Hepatic metastasis was induced by intrasplenic injection of human colorectal cancer cell line, HT29. The antimetastatic effects of three antibodies (anti-mouse IGF-I, anti-mouse IGF-II, and anti-human/mouse IGF-II designated KM1468) were tested singly or in combination in the early phase of metastasis. The dose escalation effect of KM1468 and its survival benefit were examined in the early and late phases of metastasis. The mechanism of IGF neutralization was investigated with immunohistochemistry. Dual neutralization of paracrine IGF-I and IGF-II showed modest additive antimetastatic effects than single neutralization of IGF-I or IGF-II. In any phase of metastasis, neutralization led to significant tumor growth inhibition and longer survival. Dose escalation of KM1468 influenced survival only in the late phase of metastasis. Apoptosis increased significantly in the antibody-treated group compared with the control group (P = 0.0025) In conclusion, IGFs are promising therapeutic targets for hepatic metastases of colorectal cancers. However, the IGF dependency is probably variable in the metastatic process.
Natural Killer Cell Consolidation for Acute Myelogenous Leukemia: A Cell Therapy Ready for Prime Time?
Authors: Michael R. Verneris, Stephan A. Grupp
Journal: Journal of Clinical Oncology (2010)

body radiation therapy of non-small cell lung cancer. J Thorac Oncol 2:S115-S117, 2007 10. Timmerman R, Galvin J, Pass H, et al: RTOG 0618: A Phase II Trial of Stereotactic Body Radiation Therapy in the Treatment of Patients With Operable Stage I/II Non-Small Cell Lung Cancer. Philadelphia, PA, Radiation Therapy Oncology Group, 2007, p 67 11. Hurkmans CW, Cuijpers JP, Lagerwaard FJ, et al: Recommendations for implementing stereotactic radiotherapy in peripheral stage IA non-small cell lung cancer: Report from the Quality Assurance Working Party of the randomised phase III ROSEL study. Radiat Oncol 4:1, 2009 12. Dawood O: M. D. Anderson Cancer Center to Lead Study of Surgery vs. CyberKnife Radiosurgery for Operable Lung Cancer Patients. http://www.accuray. com/PressReleases.aspx?release 676 13. Grills IS, Mangona VS, Welsh R, et al: Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non–small-cell lung cancer. J Clin Oncol 28:928-935, 2010 14. Ginsberg RJ, Rubinstein LV: Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 60:615-622, 1995; discussion 622-623 15. Reed CE, Harpole DH, Posther KE, et al: Results of the American College of Surgeons Oncology Group Z0050 trial: The utility of positron emission tomography in staging potentially operable non-small cell lung cancer. J Thorac Cardiovasc Surg 126:1943-1951, 2003 16. Cerfolio RJ, Bryant AS: Survival of patients with true pathologic stage I non-small cell lung cancer. Ann Thorac Surg 88:917-922, 2009; discussion 922-923 17. Lee Y, Auh SL, Wang Y, et al: Therapeutic effects of ablative radiation on local tumor require CD8 T cells: Changing strategies for cancer treatment. Blood 114:589-595, 2009
A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease
Authors: Ted Wun, Denis Soulieres, Andrew Lawrence Frelinger, Lakshmanan Krishnamurti, Enrico M Novelli, Abdullah Kutlar, Kenneth I Ataga, Charles L Knupp, Lillian E McMahon, John J Strouse, Chunmei Zhou, Lori E Heath, Chuke E Nwachuku, Joseph A Jakubowski, Jeffrey S Riesmeyer, Kenneth J Winters
Journal: Journal of Hematology & Oncology (2013)

Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41) or placebo (n = 21) for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain) and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.
Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial
Authors: Janet Lo, Michael T Lu, Ezinne J Ihenachor, Jeffrey Wei, Sara E Looby, Kathleen V Fitch, Jinhee Oh, Chloe O Zimmerman, Janice Hwang, Suhny Abbara, Jorge Plutzky, Gregory Robbins, Ahmed Tawakol, Udo Hoffmann, Steven K Grinspoon
Journal: The Lancet HIV (2015)
Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling.
Authors: M Le Hir, H Bluethmann, M H Kosco-Vilbois, M Müller, F di Padova, M Moore, B Ryffel, H P Eugster
Journal: The Journal of Experimental Medicine (1996)

Using mice double deficient for tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha), we demonstrated that TNF and/or LT alpha are necessary for development of a normal splenic microarchitecture and for isotype switch after immunization with sheep red blood cells (SRBC). In the present study, we extended these observations by determining which TNF receptor (TNFR) is involved in morphological and functional differentiation of the spleen. Spleen morphology and antibody response were investigated in wild-type, TNFR1-/-, TNFR2-/- and TNF/LT alpha-/- mice immunized with SRBC. TNF/LT alpha-/- mice, which have a complete disruption of the TNF/LT alpha signaling system including the LT beta-receptor pathway, displayed an abnormal microarchitecture, and isotype switch did not take place. TNFR1-/- and TNFR2-/- mice displayed a normal spleen microarchitecture and mounted an IgM and IgG antibody response to SRBC. However, the IgG production in TNFR1-/- mice was minimal, with citers leveling off 6 d after immunization. In this strain, immunofluorescence revealed a lack of follicular dendritic cells (FDC) network, detected with FDC-M1 as well as anti-CR1, and a lack of germinal centers, detected with peanut agglutinin. In conclusion, whereas normal splenic microarchitecture and isotype switch might require the LT beta receptor, differentiation of FDC network, development of germinal centers, and full IgG response depend on signaling via TNFR1.
Growth and Chemotherapeutic Response of Cells in a Hollow-Fiber In Vitro Solid Tumor Model
Authors: J. J. Casciari, M. G. Hollingshead, M. C. Alley, J. G. Mayo, L. Malspeis, S. Miyauchi, M. R. Grever, J. N. Weinstein
Journal: JNCI Journal of the National Cancer Institute (1994)

Cancer treatments that appear promising in tissue culture are often less effective in solid tumors, in part because of the proliferative and microenvironmental heterogeneity that develops in these tumors as they grow. Heterogeneous tumor models are thus needed for drug screening.Our goal was to develop and test for drug evaluation a solid tumor model based on cell growth inside biocompatible hollow fibers.Building on the experience of Hollingshead and co-workers with a sparse-cell, hollow-fiber tumor model, we tested six human tumor cell lines for in vitro growth inside 450-microns internal-diameter polyvinylidine fluoride fibers and examined them histologically. Human SW620 colon carcinoma cells grown in hollow fibers were also examined using electron microscopy, and their doxorubicin sensitivity was assessed. A colorimetric assay based on sulforhodamine B was adopted to replace the more cumbersome clonogenic cell survival assay.Five of the human tumor cell lines tested grew to confluence, forming heterogeneous in vitro tumors with subpopulations of viable and necrotic cells. For SW620 hollow-fiber tumors, maximum viable cell populations in excess of 10(8) cells/mL were obtained after 8 days of growth. This viable cell density remained roughly constant for 3-4 days, permitting dose-response experiments over this time interval. Tumor cells in hollow fibers were much more resistant to a 4-hour doxorubicin exposure than were tumor cells in monolayers: LC50 values (i.e., the drug concentrations at which the plating efficiency equals one-half the plating efficiency of untreated cells) of 3.5 microM and 0.16 microM were obtained for hollow-fiber tumors and monolayers, respectively. LC50 values decreased when drug exposure time was increased. Results from the colorimetric assay were in agreement with those from the clonogenic assay.The successful growth of tumor cells to confluence in hollow fibers and the feasibility of performing in vitro drug dose-response experiments with a relatively easy colorimetric assay demonstrate the potential of the hollow-fiber solid tumor model as a tool for experimental therapeutic research.Hollow-fiber solid tumors may prove useful for experimental drug evaluation.
A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If)
Authors: Christian Kranz, Jonas Denecke, Mark A. Lehrman, Sutapa Ray, Petra Kienz, Gunilla Kreissel, Dijana Sagi, Jasna Peter-Katalinic, Hudson H. Freeze, Thomas Schmid, Sabine Jackowski-Dohrmann, Erik Harms, Thorsten Marquardt
Journal: Journal of Clinical Investigation (2001)

We describe a new congenital disorder of glycosylation, CDG-If. The patient has severe psychomotor retardation, seizures, failure to thrive, dry skin and scaling with erythroderma, and impaired vision. CDG-If is caused by a defect in the gene MPDU1, the human homologue of hamster Lec35, and is the first disorder to affect the use, rather than the biosynthesis, of donor substrates for lipid-linked oligosaccharides. This leads to the synthesis of incomplete and poorly transferred precursor oligosaccharides lacking both mannose and glucose residues. The patient has a homozygous point mutation (221T→C, L74S) in a semiconserved amino acid of MPDU1. Chinese hamster ovary Lec35 cells lack a functional Lec35 gene and synthesize truncated lipid-linked oligosaccharides similar to the patient's. They lack glucose and mannose residues donated by Glc-P-Dol and Man-P-Dol. Transfection with the normal human MPDU1 allele nearly completely restores normal glycosylation, whereas transfection with the patient's MPDU1 allele only weakly restores normal glycosylation. This work provides a new clinical picture for another CDG that may involve synthesis of multiple types of glycoconjugates.
The Hematopoietic System–specific Minor Histocompatibility Antigen HA-1 Shows Aberrant Expression in Epithelial Cancer Cells
Authors: Christoph A. Klein, Martina Wilke, Jos Pool, Corine Vermeulen, Els Blokland, Elke Burghart, Sabine Krostina, Nicole Wendler, Bernward Passlick, Gert Riethmüeller, Els Goulmy
Journal: The Journal of Experimental Medicine (2002)

Allogeneic stem cell transplantation (SCT) can induce curative graft-versus-tumor reactions in patients with hematological malignancies and solid tumors. The graft-versus-tumor reaction after human histocompatibility leukocyte antigen (HLA)-identical SCT is mediated by alloimmune donor T cells specific for polymorphic minor histocompatibility antigens (mHags). Among these, the mHag HA-1 was found to be restricted to the hematopoietic system. Here, we report on the HA-1 ribonucleic acid expression by microdissected carcinoma tissues and by single disseminated tumor cells isolated from patients with various epithelial tumors. The HA-1 peptide is molecularly defined, as it forms an immunogenic peptide ligand with HLA-A2 on the cell membrane of carcinoma cell lines. HA-1–specific cytotoxic T cells lyse epithelial tumor cell lines in vitro, whereas normal epithelial cells are not recognized. Thus, HA-1–specific immunotherapy combined with HLA-identical allogeneic SCT may now be feasible for patients with HA-1+ carcinomas.
Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis
Authors: H. J. Schouten, G. J. Geersing, H. L. Koek, N. P. A. Zuithoff, K. J. M. Janssen, R. A. Douma, J. J. M. van Delden, K. G. M. Moons, J. B. Reitsma
Journal: BMJ (2013)

Objective To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values. Design Systematic review and bivariate random effects meta-analysis. Data sources We searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies. Study selection Primary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age×10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2×2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level. Results 13 cohorts including 12 497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories. Conclusions The application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.
Omalizumab Reduced Need for Steroid Bursts and Improved Treatment Effectiveness in Asthmatics on Inhaled Salmeterol and Fluticasone Combination Therapy
Authors: M. Massanari, F. Kianifard, R. Maykut, R. Zeldin, S. Hedgecock, C. Reisner, G. Geba
Journal: Journal of Allergy and Clinical Immunology (2006)