tbuckley/cabot-search huggingface dataset:
Extracellular Heat Shock Protein 60, Cardiac Myocytes, and Apoptosis
Authors: Se-Chan Kim, James P. Stice, Le Chen, James S. Jung, Sanjiv Gupta, Yin Wang, Georg Baumgarten, Joann Trial, Anne A. Knowlton
Journal: Circulation Research (2009)

Previously, we have found that changes in the location of intracellular heat shock protein (HSP)60 are associated with apoptosis. HSP60 has been reported to be a ligand of toll-like receptor (TLR)-4.We hypothesized that extracellular HSP60 (exHSP60) would mediate apoptosis via TLR4.Adult rat cardiac myocytes were treated with HSP60, either recombinant human or with HSP60 purified from the media of injured rat cardiac myocytes. ExHSP60 induced apoptosis in cardiac myocytes, as detected by increased caspase 3 activity and increased DNA fragmentation. Apoptosis could be reduced by blocking antibodies to TLR4 and by nuclear factor kappaB binding decoys, but not completely inhibited, even though similar treatment blocked lipopolysaccharide-induced apoptosis. Three distinct controls showed no evidence for involvement of a ligand other than exHSP60 in the mediation of apoptosis.This is the first report of HSP60-induced apoptosis via the TLRs. HSP60-mediated activation of TLR4 may be a mechanism of myocyte loss in heart failure, where HSP60 has been detected in the plasma.
Antiviral activity of narlaprevir combined with ritonavir and pegylated interferon in chronic hepatitis C patients
Authors: Joep de Bruijne, Jilling F. Bergmann, Henk W. Reesink, Christine J. Weegink, Richard Molenkamp, Janke Schinkel, Xiao Tong, Jing Li, Michelle A. Treitel, Eric A. Hughes, Jan Jaap van Lier, Andre A. van Vliet, Harry L. A. Janssen, Robert J. de Knegt
Journal: Hepatology (2010)

Narlaprevir (SCH 900518) is a potent inhibitor of the hepatitis C virus (HCV) nonstructural protein 3 serine protease that is primarily metabolized by the cytochrome P450-3A4 system. In order to explore the use of ritonavir-based pharmacokinetic enhancement of an HCV protease inhibitor, this study investigated the safety, tolerability, pharmacokinetics, and antiviral activity of narlaprevir (with or without ritonavir) administered as monotherapy and as combination therapy with pegylated interferon-α-2b (PEG-IFN-α-2b) to HCV genotype 1–infected patients. This was a randomized, placebo-controlled, two-period, blinded study in 40 HCV genotype 1–infected patients (naïve and treatment-experienced). In period 1, narlaprevir was administered for 7 days as 800 mg three times daily without ritonavir or 400 mg twice daily with 200 mg ritonavir twice daily. In period 2, after a 4-week washout, the same dose and regimen of narlaprevir was administered in combination with PEG-IFN-α-2b for 14 days. Upon completion of period 2, all patients initiated PEG-IFN-α-2b and ribavirin treatment. A rapid and persistent decline in plasma HCV-RNA was observed in both treatment-experienced and treatment-naïve patients during period 1, with a mean viral load decline of at least 4 log10 in all treatment groups. A high percentage of both treatment-experienced (50%) and treatment-naïve (≥60%) patients had undetectable HCV-RNA (&lt;25 IU/mL) after period 2. Standard of care resulted in sustained virological response (SVR) rates of 38% and 81% in treatment-experienced and treatment-naïve patients, respectively. Narlaprevir (with or without ritonavir) alone or in combination with PEG-IFN-α-2b was safe and well tolerated. Conclusion: Narlaprevir administration resulted in a robust HCV-RNA decline and high SVR rates when followed by standard of care in both treatment-experienced and treatment-naïve HCV genotype 1–infected patients. (Hepatology 2010
Plakophilin 3 Oncogene as Prognostic Marker and Therapeutic Target for Lung Cancer
Authors: Chiyuki Furukawa, Yataro Daigo, Nobuhisa Ishikawa, Tatsuya Kato, Tomoo Ito, Eiju Tsuchiya, Saburo Sone, Yusuke Nakamura
Journal: Cancer Research (2005)

Abstract We investigated gene expression profiles of non–small cell lung carcinomas (NSCLC) to screen candidate molecules that might be useful as diagnostic markers or for development of novel molecular-targeting therapies. Here we report evidence that a member of the armadillo protein family, plakophilin 3 (PKP3), is a potential molecular target for treatment of lung cancers and might also serve as a prognostic indicator. We documented elevated expression of PKP3 in the great majority of NSCLC samples examined. Treatment of NSCLC cells with small interfering RNAs of PKP3 suppressed growth of the cancer cells; on the other hand, induction of exogenous expression of PKP3 conferred growth-promoting activity on COS-7 cells and enhanced their mobility in vitro. To investigate its function, we searched for PKP3-interacting proteins and identified dynamin 1-like, which was also activated in NSCLC. In addition, a high level of PKP3 expression was associated with poor survival as well as disease stage and node status for patients with lung adenocarcinoma, suggesting an important role of the protein in development and progression of this disease. As our data imply that up-regulation of PKP3 is a frequent and important feature of lung carcinogenesis, we suggest that targeting the PKP3 molecule might hold promise for development of a new therapeutic and diagnostic strategy for clinical management of lung cancers.
Approaching Cardiac Development in Three Dimensions by Magnetic Resonance Microscopy
Authors: T. Mesud Yelbuz, Xiaowei Zhang, Michael A. Choma, Harriett A. Stadt, Marzena Zdanowicz, G. Allan Johnson, Margaret L. Kirby
Journal: Circulation (2003)

C ardiac neural crest (CNC) ablation in embryonic chicks leads to conotruncal anomalies of the heart as a result of altered cardiac looping.Altered looping results from failure of the myocardium from the secondary heart field to be added to the outflow tract.Various imaging techniques have been applied to visualize embryonic heart development.However, morphological abnormalities frequently cannot clearly be identified or appreciated in 2 dimensions, particularly those involving misorientation of cardiovascular structures and changes of myocardial volume.We present here 3-dimensional (3D) reconstructions of the embryonic chick heart at looping stages in sham-operated and CNC-ablated embryos acquired by magnetic resonance microscopy (MRM) using a new dual-contrast method for specimen preparation that combines perfusion fixation and immersion in fixative with a macro-molecular gadolinium-based contrast agent.In contrast to previous techniques, this method provides imaging not only of the cardiac chambers and vessel lumens but also of internal and external cardiac structures, such as the ventricular wall, myocardial trabeculations, cardiac jelly, and endocardial cushions.Furthermore, it allows morphovolumetric analysis of hearts at different stages.There is an excellent correlation between images obtained from MRM and those obtained by routine histology (Figure 1).3D MRM can represent anatomic information ranging from sectional images along arbitrary anatomic planes to volumetric reconstructions of the heart (Figure 2 and Movies I through IV).A great advantage of 3D reconstructions is that rotation of the image around any axis is possible without the limitations associated with interpretation based on a single plane, as shown in Figure 3 and in Movies V and VI.MRM was performed on a 9.4-T magnet using custom-designed radiofrequency coils (Helmholz pair and solenoid coils), resulting in image resolutions of 25-and 31-m 3 isotropic voxels for 2 stages of chick embryos (stage 22 [day 4] and stage 28 [day 5.5 to 6]).The 3D imaging data were postprocessed with ImageJ (NIH).The movies were created in VoxelView (Vital Images) and Matlab (The MathWorks), and the 3D images and slices in Slicer Dicer (PIXOTEC, LLC).
TCT-329 Cardiovascular Imaging Radiation in Coronary Artery Disease: Is It a Real Concern?
Authors: Ana M. Krepsky, Andrea R. Trasel, Guilherme Zwetsch, Mariana Furtado, Rochelle Lykawka, Gabriela Porto, Carisi Polanczyk
Journal: Journal of the American College of Cardiology (2013)
Nephrotoxicity and Renal Cell Carcinoma After Use of Iron- and Aluminum-Nitrilotriacetate Complexes in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Y Ebina, S Okada, S Hamazaki, F Ogino, J L Li, O Midorikawa
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Nephrotoxicity and Renal Cell Carcinoma After Use of Iron- and Aluminum-Nitrilotriacetate Complexes in Rats Get access Yoshihito Ebina, Yoshihito Ebina Search for other works by this author on: Oxford Academic PubMed Google Scholar Shigeru Okada, Shigeru Okada Search for other works by this author on: Oxford Academic PubMed Google Scholar Shuji Hamazaki, Shuji Hamazaki Search for other works by this author on: Oxford Academic PubMed Google Scholar Fumio Ogino, Fumio Ogino Search for other works by this author on: Oxford Academic PubMed Google Scholar Jia-li Li, Jia-li Li Search for other works by this author on: Oxford Academic PubMed Google Scholar Osamu Midorikawa Osamu Midorikawa Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 1, January 1986, Pages 107–113, https://doi.org/10.1093/jnci/76.1.107 Published: 01 January 1986 Article history Received: 28 March 1985 Accepted: 23 September 1985 Published: 01 January 1986
Mutational hot spots in Ig V region genes of human follicular lymphomas.
Authors: S Levy, E Mendel, S Kon, Z Avnur, R Levy
Journal: The Journal of Experimental Medicine (1988)

The genes coding for the Ig light chains expressed in two cases of human follicular lymphoma were cloned and sequenced. In each case, multiple independent isolates of the tumor population were compared. Although each tumor represented a single clone of B cells with a unique V/J joint, different cells within each tumor had accumulated multiple point mutations in the V gene during clonal expansion. Most of the mutations observed were silent, but some resulted in amino acid replacements. Identical silent mutations were often observed in independent isolates of each tumor. By combining the current data with VH sequences obtained previously from the same cells, it was apparent that the repetitive silent mutations could not be explained solely by a genealogic tree. Such mutations could represent hot spots whose tendency to mutate may be influenced by neighboring DNA sequences or by the methylation of specific cytosine residues.
Stem and progenitor cells for liver repopulation: can we standardise the process from bench to bedside?
Authors: P Sancho-Bru, M Najimi, M Caruso, K Pauwelyn, T Cantz, S Forbes, T Roskams, M Ott, U Gehling, E Sokal, C M Verfaillie, M Muraca
Journal: Gut (2008)

In-vitro experiments using 203Pb were performed to identify the lead binding components in human peripheral blood. The distribution of lead in plasma, in the red cell membrane, and within the red cell was also investigated. Studies of the distribution of 203Pb in whole blood showed that at a lead concentration of 2.45 mumol/l (50 micrograms/100 ml) about 94% of lead had been incorporated by the erythrocytes and 6% remained in the plasma. After extraction of lipid by a methanol/chloroform mixture, about 75% of the lead was found to be associated with the protein fraction. The lipid contained about 21% of the 203Pb, the remainder being in the aqueous plasma. SDS polyacrylamide gel electrophoresis of blood plasma showed that almost 90% of the 203Pb was present in the albumin fraction; the remainder was likely to be associated with high molecular weight globulins. Several binding sites were identified on the erythrocyte membrane. The high molecular weight component, about 130 000-230 000, was the most important 203Pb binding site. Chemical modification of membrane proteins suggested that the carboxyl groups are the major ligand responsible for most of the lead binding. SH groups of the membrane may have a minor role, but amino groups did not appear to affect the lead binding. The binding of lead to erythrocytes was not confined to membranes, over 80% of lead in blood penetrates into erythrocytes and binds to intracellular components. Gel chromatography of the haemolysate showed that over 90% of the 203Pb was attached to the haemoglobin molecule.
Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer
Authors: J.Y. Douillard, S. Siena, J. Cassidy, J. Tabernero, R. Burkes, M. Barugel, Y. Humblet, G. Bodoky, D. Cunningham, J. Jassem, F. Rivera, I. Kocákova, P. Ruff, M. Błasińska-Morawiec, M. Šmakal, J.L. Canon, M. Rother, K.S. Oliner, Y. Tian, F. Xu, R. Sidhu
Journal: Annals of Oncology (2014)

BackgroundThe Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab–FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study.Patients and methodsPatients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled.ResultsA total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3–11.4 months] for arm 1 and 8.6 months (95% CI 7.5–9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67–0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3–27.7 months) for arm 1 and 19.7 months (95% CI 17.6–22.7 months) for arm 2; HR = 0.88; 95% CI 0.73–1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70–0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis.ConclusionsIn WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab–FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab–FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.
Effects of Epitope Modification on T Cell Receptor–Ligand Binding and Antigen Recognition by Seven H-2Kd–restricted Cytotoxic T Lymphocyte Clones Specific for a Photoreactive Peptide Derivative
Authors: Benedikt M. Kessler, Paolo Bassanini, Jean-Charles Cerottini, Immanuel F. Luescher
Journal: The Journal of Experimental Medicine (1997)

We tested for antigen recognition and T cell receptor (TCR)-ligand binding 12 peptide derivative variants on seven H-2Kd-restricted cytotoxic T lymphocytes (CTL) clones specific for a bifunctional photoreactive derivative of the Plasmodium berghei circumsporozoite peptide 252-260 (SYIPSAEKI). The derivative contained iodo-4-azidosalicylic acid in place of PbCS S-252 and 4-azidobenzoic acid on PbCS K-259. Selective photoactivation of the N-terminal photoreactive group allowed crosslinking to Kd molecules and photoactivation of the orthogonal group to TCR. TCR photoaffinity labeling with covalent Kd-peptide derivative complexes allowed direct assessment of TCR-ligand binding on living CTL. In most cases (over 80%) cytotoxicity (chromium release) and TCR-ligand binding differed by less than fivefold. The exceptions included (a) partial TCR agonists (8 cases), for which antigen recognition was five-tenfold less efficient than TCR-ligand binding, (b) TCR antagonists (2 cases), which were not recognized and capable of inhibiting recognition of the wild-type conjugate, (c) heteroclitic agonists (2 cases), for which antigen recognition was more efficient than TCR-ligand binding, and (d) one partial TCR agonist, which activated only Fas (C1)95), but not perforin/granzyme-mediated cytotoxicity. There was no correlation between these divergences and the avidity of TCR-ligand binding, indicating that other factors than binding avidity determine the nature of the CTL response. An unexpected and novel finding was that CD8-dependent clones clearly incline more to TCR antagonism than CD8-independent ones. As there was no correlation between CD8 dependence and the avidity of TCR-ligand binding, the possibility is suggested that CD8 plays a critical role in aberrant CTL function.
Massive hepatic resection for the carcinoid syndrome
Authors: R. Zeegen, R. Rothwell-Jackson, M. Sandler
Journal: Gut (1969)

Removal of the right lobe of the liver which was occupied largely by metastases, together with resection of ileal primary tumours, brought about complete remission of symptoms and signs in a 43-year-old man with a six-year history of the carcinoid syndrome. Investigations should be orientated toward surgery. When practicable, radical surgery of the type described here appears to offer the best hope of alleviating the distressing clinical features of the condition.
Long-Term Outcome of Open or Endovascular Repair of Abdominal Aortic Aneurysm
Authors: Jorg L. De Bruin, Annette F. Baas, Jaap Buth, Monique Prinssen, Eric L.G. Verhoeven, Philippe W.M. Cuypers, Marc R.H.M. van Sambeek, Ron Balm, Diederick E. Grobbee, Jan D. Blankensteijn
Journal: New England Journal of Medicine (2010)

For patients with large abdominal aortic aneurysms, randomized trials have shown an initial overall survival benefit for elective endovascular repair over conventional open repair. This survival difference, however, was no longer significant in the second year after the procedure. Information regarding the comparative outcome more than 2 years after surgery is important for clinical decision making.We conducted a long-term, multicenter, randomized, controlled trial comparing open repair with endovascular repair in 351 patients with an abdominal aortic aneurysm of at least 5 cm in diameter who were considered suitable candidates for both techniques. The primary outcomes were rates of death from any cause and reintervention. Survival was calculated with the use of Kaplan-Meier methods on an intention-to-treat basis.We randomly assigned 178 patients to undergo open repair and 173 to undergo endovascular repair. Six years after randomization, the cumulative survival rates were 69.9% for open repair and 68.9% for endovascular repair (difference, 1.0 percentage point; 95% confidence interval [CI], -8.8 to 10.8; P=0.97). The cumulative rates of freedom from secondary interventions were 81.9% for open repair and 70.4% for endovascular repair (difference, 11.5 percentage points; 95% CI, 2.0 to 21.0; P=0.03).Six years after randomization, endovascular and open repair of abdominal aortic aneurysm resulted in similar rates of survival. The rate of secondary interventions was significantly higher for endovascular repair. (ClinicalTrials.gov number, NCT00421330.)
LFA-1-deficient mice show normal CTL responses to virus but fail to reject immunogenic tumor.
Authors: R Schmits, T M Kündig, D M Baker, G Shumaker, J J Simard, G Duncan, A Wakeham, A Shahinian, A van der Heiden, M F Bachmann, P S Ohashi, T W Mak, D D Hickstein
Journal: The Journal of Experimental Medicine (1996)

The leukocyte integrin LFA-1 (CD11a/CD18) plays an important role in lymphocyte recirculation and homotypic interactions. Leukocytes from mice lacking CD11a displayed defects in in vitro homotypic aggregation, in proliferation in mixed lymphocyte reactions, and in response to mitogen. Mutant mice mounted normal cytotoxic T cell (CTL) responses against systemic LCMV and VSV infections and showed normal ex vivo CTL function. However, LFA-1-deficient mice did not reject immunogenic tumors grafted into footpads and did not demonstrate priming response against tumor-specific antigen. Thus CD11a deficiency causes a selective defect in induction of peripheral immune responses whereas responses to systemic infection are normal.
Bisphosphonate Use After Estrogen Receptor-Positive Breast Cancer and Risk of Contralateral Breast Cancer
Authors: G. M. Monsees, K. E. Malone, M.-T. C. Tang, P. A. Newcomb, C. I. Li
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundA growing body of evidence suggests that nitrogenous bisphosphonates may reduce the risk of developing a first breast cancer and may prevent metastases among breast cancer survivors. However, their impact on risk of second primary contralateral breast cancer is uncertain.
Constitutive NF-κB Activation in Colorectal Carcinoma Plays a Key Role in Angiogenesis, Promoting Tumor Growth
Authors: Kei Sakamoto, Shin Maeda, Yohko Hikiba, Hayato Nakagawa, Yoku Hayakawa, Wataru Shibata, Ayako Yanai, Keiji Ogura, Masao Omata
Journal: Clinical Cancer Research (2009)

Nuclear factor kappaB (NF-kappaB) is an important transcription factor in various biological processes. Constitutive NF-kappaB activation has been noted in many tumors, including colorectal cancers. However, the precise role of this activation in colorectal cancer is unclear.Constitutive NF-kappaB activation was evaluated in colorectal cancer tissues and cell lines. To inhibit NF-kappaB activation, we established cancer cells with stable knockdown of IkappaB kinase gamma (NF-kappaB essential modulator), which is the regulatory subunit of the IkappaB kinase complex, by RNA interference. Cell growth and apoptosis were evaluated in wild-type cells (WT) and knocked-down cells (KD). Microarray and protein array analysis were also done. To determine involvement of angiogenesis, human umbilical vein endothelial cells were used. By s.c. transplantation of the cells into nude mice, tumor sizes, vascularity, and chemodrug sensitivity were analyzed.Constitutive NF-kappaB activation was observed in 40% of colorectal cancer tissues and 67% of cell lines. Cell proliferation was not different between WT and KD in vitro, whereas apoptosis mediated by tumor necrosis factor-alpha and 5-fluorouracil were increased in KD. Several angiogenic chemokines were decreased in KD. Human umbilical vein endothelial cells incubated in WT supernatant showed more branch points than in KD, suggesting that constitutive NF-kappaB activation was involved in angiogenesis. Subcutaneous tumor expansion was suppressed to 23% in KD, and vessels were also decreased. By 5-fluoruracil treatment, tumor expansion was suppressed to a greater extent in KD (to 6%) than in WT (to 50%).NF-kappaB inhibition may represent a potent treatment modality in colorectal cancer, especially in cases with constitutive NF-kappaB activation.
RAG2:GFP Knockin Mice Reveal Novel Aspects of RAG2 Expression in Primary and Peripheral Lymphoid Tissues
Authors: Robert J Monroe, Katherine J Seidl, Frank Gaertner, Shuhua Han, Feng Chen, JoAnn Sekiguchi, Jiyang Wang, Roger Ferrini, Laurie Davidson, Garnett Kelsoe, Frederick W Alt
Journal: Immunity (1999)