tbuckley/cabot-search huggingface dataset:
Excision Repair Cross Complementation Group 1 Immunohistochemical Expression Predicts Objective Response and Cancer-Specific Survival in Patients Treated by Cisplatin-Based Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma
Authors: Adriana Handra-Luca, Juana Hernandez, Giannis Mountzios, Estelle Taranchon, Jean Lacau-St-Guily, Jean-Charles Soria, Pierre Fouret
Journal: Clinical Cancer Research (2007)

To assess the correlation of excision repair cross complementation group 1 (ERCC1) immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous cell carcinoma treated with cisplatin-based induction chemotherapy.The initial cohort was composed of 107 patients who were treated from 1992 to 1996 by an induction chemotherapy regimen for locally advanced head and neck squamous cell carcinoma. p53 mutations had previously been studied. Pretherapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1 immunohistochemical expression.Of 96 patients, 68 (71%; 95% confidence interval, 61-79%) had tumors that expressed ERCC1 intensively and diffusely. Using the logistic regression method, the 28 (29%) patients with tumors expressing ERCC1 at lower levels had a 4-fold greater odds of benefiting from an objective response to chemotherapy (odds ratio, 4.3; 95% confidence interval, 1.4-13.4; P = 0.01) compared with the group of 68 patients with high ERCC1 expression. ERCC1 and p53 status, but not their interaction, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on age, TNM stage, tumor differentiation, and tumor localization, ERCC1 low expression was associated with a lower risk of cancer death (risk ratio, 0.42; 95% confidence interval, 0.20-0.90; P = 0.04) whereas p53 status had no prognostic value.Our results suggest that those patients characterized by low ERCC1 expression are more likely to benefit from cisplatin induction chemotherapy compared with patients with high ERCC1 expression.
Protease-mediated ectodomain shedding
Authors: Peter Clark
Journal: Thorax (2013)

Ectodomain shedding is the proteolytic cleavage of cell surface proteins resulting in the loss of the extracellular domains. This mechanism is important in a variety of normal and pathological processes, including growth factor signalling, cell adhesion, inflammation and cell survival. Elevated protease activity in the lungs is a key pathological mechanism in emphysema which could enhance ectodomain shedding in lung cells. Here, the major steps and consequences of ectodomain shedding are reviewed.
Frame-mounted tissue heart valves: technique of construction
Authors: I. T. Bartek, M. P. Holden, M. I. Ionescu
Journal: Thorax (1974)

<b>Bartek, I. T., Holden, M. P., and Ionescu, M. I. (1974)</b>. <i>Thorax</i>, <b>29</b>, 51-55. <b>Frame-mounted tissue heart valves: technique of construction</b>. The technical details for the construction and preservation of frame-mounted tissue heart valves are described. The results of clinical and experimental work which have prompted changes and improvements in valve construction are briefly discussed.
In vitro mutagenesis at a single residue introduces B and T cell epitopes into a class I HLA molecule.
Authors: R D Salter, C Clayberger, C E Lomen, A M Krensky, P Parham
Journal: The Journal of Experimental Medicine (1987)

We have studied the interaction of HLA class I antigens with alloreactive cytotoxic T lymphocytes and monoclonal antibodies using site-directed mutagenesis and expression of an HLA-Aw68.1 gene. Two mutants containing distinct substitutions at polymorphic residues near the NH2-terminal end of the alpha 2 domain were made. One mutant with substitutions at positions 95 and 97 corresponding to residues found in HLA-A2.1 showed no alterations in binding of HLA-Aw68- or HLA-A2-specific monoclonal antibodies, but was reactive with some HLA-A2-specific CTL clones. A second mutant, in which glycine at position 107 was replaced with tryptophan found at that position in HLA-A2.1, was recognized by HLA-A2-specific CTL clones and HLA-A2, Aw69-specific monoclonal antibodies. Thus, substitution of a single amino acid residue at position 107 of the HLA-Aw68.1 molecule generates an allospecific determinant shared with HLA-A2.1 and recognized by both B and T lymphocytes.
Adhesion Molecules, Altered Vasoreactivity, and Brain Atrophy in Type 2 Diabetes
Authors: Vera Novak, Peng Zhao, Brad Manor, Ervin Sejdić, David Alsop, Amir Abduljalil, Paula K. Roberson, Medha Munshi, Peter Novak
Journal: Diabetes Care (2011)

To investigate the effects of inflammation on perfusion regulation and brain volumes in type 2 diabetes.A total of 147 subjects (71 diabetic and 76 nondiabetic, aged 65.2 ± 8 years) were studied using 3T anatomical and continuous arterial spin labeling magnetic resonance imaging. Analysis focused on the relationship between serum soluble vascular and intercellular adhesion molecules (sVCAM and sICAM, respectively, both markers of endothelial integrity), regional vasoreactivity, and tissue volumes.Diabetic subjects had greater vasoconstriction reactivity, more atrophy, depression, and slower walking. Adhesion molecules were specifically related to gray matter atrophy (P = 0.04) and altered vasoreactivity (P = 0.03) in the diabetic and control groups. Regionally, sVCAM and sICAM were linked to exaggerated vasoconstriction, blunted vasodilatation, and increased cortical atrophy in the frontal, temporal, and parietal lobes (P = 0.04-0.003). sICAM correlated with worse functionality.Diabetes is associated with cortical atrophy, vasoconstriction, and worse performance. Adhesion molecules, as markers of vascular health, have been indicated to contribute to altered vasoregulation and atrophy.
Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer
Authors: Feng Qian, Jeannine Villella, Paul K. Wallace, Paulette Mhawech-Fauceglia, Joseph D. Tario, Christopher Andrews, Junko Matsuzaki, Danila Valmori, Maha Ayyoub, Peter J. Frederick, Amy Beck, Jianqun Liao, Richard Cheney, Kirsten Moysich, Shashikant Lele, Protul Shrikant, Lloyd J. Old, Kunle Odunsi
Journal: Cancer Research (2009)

Abstract It has been reported that levo-1-methyl tryptophan (L-1MT) can block indoleamine-2,3-dioxygenase (IDO) expressed by human dendritic cells (DC), whereas dextro-1-methyl tryptophan (D-1MT) is inefficient. However, whether L-1MT or D-1MT can efficiently reverse IDO-induced arrest of human T-cell proliferation has not been clarified. Here, we show a marked immunosuppressive effect of IDO derived from INDO-transfected 293 cell, IDO+ ovarian cancer cells, and monocyte-derived DCs on CD4+ Th1 cells, CD8+ T cells, and natural killer cells derived from peripheral blood, ascites, and tumors of ovarian cancer patients. We found that, whereas L-1MT and D/L-1MT can restore proliferation of tumor-derived and peripheral blood T-cell subsets, D-1MT does not effectively restore IDO-induced arrest of T-cell proliferation. Although D-1MT inhibited kynurenine production at high concentrations, L-1MT was more effective in abrogating kynurenine generation and tryptophan depletion, whereas tryptophan was completely depleted by IDO even in the presence of high amounts of D-1MT. Together, the results indicate that, whereas the generation of tryptophan metabolites (kynurenines) by IDO is important in mediating suppression of T-cell proliferation, the degree to which tryptophan depletion is restored by 1MT is also critical in overcoming IDO-induced arrest of T-cell proliferation. [Cancer Res 2009;69(13):5498–504]
Altered TAB1:IκB Kinase Interaction Promotes Transforming Growth Factor β–Mediated Nuclear Factor-κB Activation during Breast Cancer Progression
Authors: Jason R. Neil, William P. Schiemann
Journal: Cancer Research (2008)

Abstract The conversion of transforming growth factor β (TGF-β) from a tumor suppressor to a tumor promoter occurs frequently during mammary tumorigenesis, yet the molecular mechanisms underlying this phenomenon remain undefined. We show herein that TGF-β repressed nuclear factor-κB (NF-κB) activity in normal NMuMG cells, but activated this transcription factor in their malignant counterparts, 4T1 cells, by inducing assembly of TGF-β–activated kinase 1 (TAK1)–binding protein 1 (TAB1):IκB kinase β (IKKβ) complexes, which led to the stimulation of a TAK1:IKKβ:p65 pathway. TAB1:IKKβ complexes could only be detected in NMuMG cells following their induction of epithelial-mesenchymal transition (EMT), which, on TGF-β treatment, activated NF-κB. Expression of a truncated TAB1 mutant [i.e., TAB1(411)] reduced basal and TGF-β–mediated NF-κB activation in NMuMG cells driven to undergo EMT by TGF-β and in 4T1 cells stimulated by TGF-β. TAB1(411) expression also inhibited TGF-β–stimulated tumor necrosis factor-α and cyclooxygenase-2 expression in 4T1 cells. Additionally, the ability of human MCF10A-CA1a breast cancer cells to undergo invasion in response to TGF-β absolutely required the activities of TAK1 and NF-κB. Moreover, small interfering RNA–mediated TAK1 deficiency restored the cytostatic activity of TGF-β in MCF10A-CA1a cells. Finally, expression of truncated TAB1(411) dramatically reduced the growth of 4T1 breast cancers in syngeneic BALB/c, as well as in nude mice, suggesting a potentially important role of NF-κB in regulating innate immunity by TGF-β. Collectively, our findings have defined a novel TAB1:TAK1:IKKβ:NF-κB signaling axis that forms aberrantly in breast cancer cells and, consequently, enables oncogenic signaling by TGF-β. [Cancer Res 2008;68(5):1462–70]
Impairment of myocardial blood flow reserve, in patients with coronary artery disease and heart failure, depents on severity of left ventricular dysfunction and not severity of coronary stenosis
Authors: A.F.M. van den Houvel, D.J. van Veldhuisen, P.K. Blanksma, W. Vaalberg, H.J.G.M. Crijns
Journal: Journal of the American College of Cardiology (1998)
Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model
Authors: J HINAGATA, M KAKUTANI, T FUJII, T NARUKO, N INOUE, Y FUJITA, J MEHTA, M UEDA, T SAWAMURA
Journal: Cardiovascular Research (2005)

LOX-1 is a multi-ligand receptor originally identified as the endothelial oxidized LDL receptor. LOX-1 expression is also induced in smooth muscle cells in response to proinflammatory and oxidative stimuli. Here, we report on the role of LOX-1 in intimal hyperplasia, in which proinflammatory and oxidative stimuli are increased.Left common carotid artery of rat was injured by a balloon catheter. The expression of LOX-1 was significantly increased within 24 h after the balloon injury and peaked at day 7. LOX-1 expression was observed predominantly in medial smooth muscle cells until day 3, and then shifted to predominantly intimal smooth muscle cells. At day 14, the expression was concentrated in the regenerated endothelial cells. To examine the contributory role of LOX-1 in the growth of intimal smooth muscle cells, rats were administered anti-LOX1 antibody intravenously every 3 days after balloon injury. Anti-LOX-1 antibody administration effectively suppressed intimal hyperplasia, oxidative stress, and leukocyte infiltration compared with control IgG. These findings suggest the importance of LOX-1 expression in the pathogenesis of neointimal formation in conjunction with oxidative stress and leukocyte infiltration.The LOX-1 expressed in smooth muscle cells is involved in intimal hyperplasia in a rat model of balloon injury. Manipulation of LOX-1 activity is a novel potential therapeutic target to prevent restenosis after angioplasty.
Exploiting the Head and Neck Cancer Oncogenome: Widespread PI3K-mTOR Pathway Alterations and Novel Molecular Targets
Authors: Ramiro Iglesias-Bartolome, Daniel Martin, J. Silvio Gutkind
Journal: Cancer Discovery (2013)

Abstract Summary: Two studies published in this issue of Cancer Discovery describe the emerging mutational landscape of head and neck squamous cell carcinomas (HNSCC) and their genomic and epigenetic alterations, thus identifying novel actionable cancer drivers and predictive biomarkers for targeted therapies. Most genomic alterations in HNSCC converge in a handful of molecular pathways, resulting in cell-cycle deregulation, genomic instability, cell differentiation defects, and persistent mitogenic signaling, the latter involving aberrant phosphoinositide 3-kinase (PI3K)/mTOR pathway activation, thereby rendering HNSCC responsive to PI3K/mTOR inhibitors. Cancer Discov; 3(7); 722–5. ©2013 AACR. See related article by Lui et al., p. 761 See related article by Pickering et al., p. 770
The Efficient Synthesis and Biological Evaluation of Novel Bi-Functionalized Sarcophagine for <sup>64</sup>Cu Radiopharmaceuticals
Authors: Shuanglong Liu, Dan Li, Chiun-Wei Huang, Li-Peng Yap, Ryan Park, Hong Shan, Zibo Li, Peter S. Conti
Journal: Theranostics (2012)

Purpose We and others have reported that Sarcophagine-based bifunctional chelators could be effectively used in the syntheses of (64)Cu radiopharmaceuticals. The resulted (64)Cu-Sarcophagine complexes demonstrated great in vivo stability. The goal of this study was to further derivatize Sarcophagine cage with amino and maleimide functional groups for conjugation with bioligands.Methods Starting from DiAmSar, three novel chelators (AnAnSar, BaMalSar, and Mal(2)Sar) with two functional groups have been synthesized. Among those, BaMalSar and Mal(2)Sar have been conjugated with cyclic peptide c(RGDyC) (denoted as RGD) and the resulted conjugates, BaMalSar-RGD and Mal(2)Sar-RGD(2) have been labeled with (64)Cu. The tumor targeting efficacy of (64)Cu-labeled RGD peptides were evaluated in a subcutaneous U87MG glioblastoma xenograft model.Results The conjugates, BaMalSar-RGD and Mal(2)Sar-RGD(2) could be labeled with (64)CuCl(2) in 10 min with high purity (>98%) and high radiochemical yield (>90%). Both (64)Cu-BaMalSar-RGD and (64)Cu-Mal(2)Sar-RGD(2) exhibited high tumor uptake and tumor-to-normal tissue ratios.Conclusion Three novel chelators with two functional groups have been developed based on Sarcophagine cage. The platform developed in this study could have broad applications in the design and synthesis of( 64)Cu-radiopharmaceuticals.
The Effects of Fenofibric Acid Alone and With Statins on the Prevalence of Metabolic Syndrome and Its Diagnostic Components in Patients With Mixed Dyslipidemia
Authors: Harold E. Bays, Eli M. Roth, James M. McKenney, Maureen T. Kelly, Kamlesh M. Thakker, Carolyn M. Setze, Katie Obermeyer, Darryl J. Sleep
Journal: Diabetes Care (2010)

To compare fenofibric acid (FA) + statin to respective monotherapies on the prevalence of metabolic syndrome and its diagnostic components in patients with mixed dyslipidemia.Post hoc analysis of over 2,000 metabolic syndrome patients administered either FA + low- or moderate-dose statin; FA alone; or low-, moderate-, or high-dose statin alone.FA + low- or moderate-dose statin combination therapy reduced the presence of metabolic syndrome (35.7 or 35.9%, respectively) more than low-, moderate-, or high-dose statin monotherapy (15.5, 16.6, or 13.8%, respectively), mostly due to improvements in triglycerides and HDL cholesterol levels. Mean glucose levels slightly decreased with FA monotherapy, slightly increased with statin monotherapy, and were essentially unchanged with FA + statin. FA with or without statin also reduced non-HDL cholesterol, apolipoprotein B, total cholesterol, VLDL cholesterol, and high-sensitivity C-reactive protein.FA + statin in patients with mixed dyslipidemia reduces the prevalence of metabolic syndrome.
Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4
Authors: Daniel Scott-Algara, Karl Balabanian, Lisa A. Chakrabarti, Luc Mouthon, Françoise Dromer, Céline Didier, Fernando Arenzana-Seisdedos, Olivier Lortholary
Journal: Blood (2009)
Prodrugs incorporated into nanotechnology-based drug delivery systems for possible improvement in bioavailability of ocular drugs delivery
Authors: Tiantian Ye, Kun Yuan, Wenji Zhang, Shuangshuang Song, Fen Chen, Xinggang Yang, Shujun Wang, Jianwei Bi, Weisan Pan
Journal: Asian Journal of Pharmaceutical Sciences (2013)

Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery, including: ocular prodrugs and nanotechnology-based drug delivery system. The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs, prolonging their duration of action and/or reducing the systemic side-effects, unfortunately, some characteristics of the prodrugs, such as poorly aqueous stability, poorly aqueous solubility and severe eye irritation probably, limit their clinical practice and cannot be ignored. As we all know, nanotechnology for ocular drug delivery can carry poorly soluble drugs, protect the encapsulated molecules from hydrolysis, control the rate of drug delivery and prolong the precorneal retention of drugs. All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery. By reviewing recent advances of prodrugs and nanostructures in ocular drug delivery, this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.
Suppression associated lymphocyte markers in lesions of sarcoidosis.
Authors: C S Munro, D A Campbell, R M Du Bois, D N Mitchell, P J Cole, L W Poulter
Journal: Thorax (1988)

The presence within the epithelioid granulomas of sarcoidosis of lymphocytes of the "helper" (T4 positive) phenotype suggests that, as in granulomatous diseases of known aetiology, active cell mediated immunity plays a part in the disease. It has, however, been noted that T8 positive lymphocytes are also found on occasion in the granulomas. The presence of cells bearing markers associated with suppressor activity in various lesions of sarcoidosis has been investigated with a range of monoclonal antibodies. T4 positive cells were present in all granulomas; T8 positive lymphocytes were present within the epithelioid cell areas in proportions that varied from 5 to 55/100 of T4 cells. Other lymphocyte markers associated with suppression (Leu8 and SN130) were very rare on lymphocytes within granulomas but common on both T4 positive and T8 positive lymphocytes in the perigranulomatous mantle, which suggests that expression of these markers was down regulated in the granuloma or that cells bearing them are unable to migrate into the granuloma. Nevertheless, suppressor cell mechanisms could mediate the spontaneous resolution of most cases of sarcoidosis, and the presence or absence of cells bearing suppression associated phenotypes in the granuloma or its mantle may have prognostic importance.
Waist Circumference and Waist-to-Hip Ratio Are Related to Gestational Glucose Tolerance
Authors: Leandro Branchtein, Maria Inês Schmidt, Sotero S Mengue, Ângela J Reichelt, Maria Cristina G Matos, Bruce B Duncan
Journal: Diabetes Care (1997)

To evaluate the relationship of central fat distribution with gestational glucose tolerance during the usual time for screening gestational diabetes.This cross-sectional study investigated 1,113 consecutive women, > or = 20 years old, pregnant for approximately 21 to 28 weeks, without history of previous diabetes outside pregnancy, who attended two general prenatal care units in Porto Alegre, Brazil, from 1991 to 1993. Weight, height, waist and hip circumferences, and skinfolds were measured, and a 2-h, 75-g glucose tolerance test was performed. Data were analyzed using multiple linear regression models.Waist-to-hip ratio (WHR) and waist circumference were independently associated with higher 2-h glycemia. Glycemic level was 0.11 and 0.13 mmol/l greater for each standard deviation increase in WHR (0.06) and waist circumference (8.0 cm), respectively (P < 0.02). Restricting analyses to the subset of women with uterine height < or = 26 cm improved the association (0.13 and 0.19 mmol/l, respectively, P < 0.02); differences of 0.22 and 0.19 mmol/l were observed for 1 SD changes in the sum of skinfold thicknesses (24.7 mm) and in age (5.5 years), respectively.Central fat distribution measured in pregnancy is an independent predictor of gestational glucose intolerance. This finding supports the concept that NIDDM and gestational diabetes are parts of the same disease, differing basically in their moment of detection. The usefulness of these anthropometric measurements in identifying pregnant women at high risk of having gestational glucose intolerance merits further investigation.
Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.
Authors: M Sobel, P M McNeill, P L Carlson, J C Kermode, B Adelman, R Conroy, D Marques
Journal: Journal of Clinical Investigation (1991)

The intravenous administration of heparin to patients before open heart surgery reduced ristocetin cofactor activity by 58% (P less than 0.01, t test), and this impairment of von Willebrand factor-dependent platelet function was closely related to plasma heparin levels (r2 = 0.9), but not to plasma von Willebrand factor (vWF) levels. We hypothesized that heparin may inhibit vWF-dependent platelet hemostatic functions by directly binding vWF in solution and interfering with vWF-GpIb binding. Using the in vitro techniques of ristocetin-induced platelet agglutination, fluorescent flow cytometric measurement of vWF-platelet binding, and conventional radioligand binding assays we observed that heparin inhibited both vWF-dependent platelet function and vWF-platelet binding in a parallel and dose-dependent manner. Heparin also inhibited platelet agglutination induced by bovine vWF and inhibited the binding of human asialo-vWF to platelets in ristocetin-free systems. The inhibitory potency of heparin was not dependent upon its affinity for antithrombin III, but was molecular weight dependent: homogeneous preparations of lower molecular weight were less inhibitory. Heparin impairment of vWF function may explain why some hemorrhagic complications of heparin therapy are not predictable based on techniques for monitoring the conventional anticoagulant effects of heparin.
Taking folate in pregnancy and risk of maternal breast cancer
Authors: J Martin Bland
Journal: BMJ (2005)

a banner headline on the front page of a popular tabloid newspaper read: "Cancer danger of folic acid" on the basis of a paper by Charles et al on taking folate in pregnancy and risk of maternal breast cancer. 1 2 Although coverage in the broadsheets was more balanced, the overall message would inevitably cause concern to women taking folate to reduce the risk of fetal neural tube defect in a desired pregnancy.Despite the likelihood that the most likely explanation for the reported association is chance, as reported in the commentary to the paper, 2 numerous susceptible women will probably not take folate, and some of these may conceive fetuses with neural tube defects.In addition, what company or government will take responsibility for fortification of wheat and corn flour with folate, now that this question has been raised?The authors themselves point out that the numbers are small and the confidence intervals large.The risk was also associated with a much larger dose of folate than is routinely used to reduce the risk of neural tube defects.Those who write such papers and those who publish them cannot disclaim ethical responsibility for how the data are interpreted and must consider more carefully their ethical responsibilities in such situations.