tbuckley/cabot-search huggingface dataset:
Abstract 1995: Huachansu inhibits proliferation of non-hodgkin lymphoma cells by induction of apoptosis
Authors: Ekem T. Efuet, Lorenzo Cohen, Peiying Yang
Journal: Cancer Research (2012)

Abstract Huachansu, a hot water extract of venom or the skin glands of Bufo gargarizans or B. melanostictus, has been used in the treatment of various cancers in Asia and in China. Despite extensive use in the treatment of various solid tumors such as pancreatic, hepatocellular, non-small-cell lung carcinomas, its effect on the growth of malignancies of hematopoietic and non-hematopoietic origin, particularly lymphomas, is limited. Here we investigated the anti-proliferative effect and molecular mechanisms of Huachansu in non-Hodgkin lymphoma Raji, Ramos, BJAB and Namalwa cells. These cells were treated with Huachansu (0 to 50 αl/ml) for 72 hrs and cell proliferation was assessed by WST-1 assay. The molecular mechanism associated with Huachansu's anti-proliferative effect was examined by western blotting, cell cycle and apoptosis as determined by PI and Annexin V staining. Huachansu inhibited proliferation of all four lymphoma cell lines tested with IC50 ranging from 6.7 αl/ml to 17.1 αl/ml. At a low concentration of 25 αl/ml, Huachansu triggered a sub G1 arrest in both Raji and Ramos cells, indicative of cell death while also causing a marked increase of early to late apoptotic cell death in both cell lines. Intriguingly, the expression of MCL-1 proteins was markedly reduced by Huachansu at 12.5 αl/ml in Raji cells, while completely blocked at 25 αl/ml in Ramos cells. At 50 αl/ml, Huachansu decreased total Akt more robustly in Ramos compared to Rajis cells, with no significant reduction in the levels of survivin. Huachansu (25 αl/ml) inhibited the expression of pRB proteins in Raji cells and substantially increased the levels of caspase-3 in Ramos (12.5 αl/ml) in a concentration dependent manner, indicative of apoptosis. Given that bufalin is one of the major bioactive components of Huachansu, we tested its effect on the proliferation of Ramos cells. Bufalin (125 ng/ml) indeed suppressed the proliferation of Ramos cells. The effect of both Huachansu and bufalin on transcriptome of Ramos cells is currently being investigated and will be reported. Collectively, our data suggest that Huachansu is effective in inducing cell death and apoptosis, in part, by upregulatiing caspase-3 activity and inhibiting the phosphorylation of RB protein in lymphomas. Considering that the concentration of Huachansu needed to inhibit cell proliferation by 50% was similar to the dose of Huachansu routinely used in the clinics in China, our preliminary data suggests that Huachansu has a great potential to be developed as an anticancer agent for non-Hodgkin lymphoma and warrant further investigation. This study is supported in part by Gabrielle's Angel Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1995. doi:1538-7445.AM2012-1995
AB0148 T-cell phenotype and intracellular cytokine-production in t-cells in patients with systemic sclerosis
Authors: M. Klein, G. Almanzar, K. Höfner, M. Schmalzing, S. Kleinert, H.-P. Tony, S. Benoit, H. Hamm, M. Goebeler, M. Prelog
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic Sclerosis (SSc) is a disease with mostly unknown etiology. Until now, various cytokines have been identified that may play a role in the pathogenesis of the disease. <h3>Objectives</h3> Our aim was to investigate the peripheral T-cell phenotype and intracellular cytokines in 27 SSc patients compared to 30 age-matched healthy donors (HD). <h3>Methods</h3> Peripheral blood mononuclear cells (PBMCs) were isolated and characterized into naive (CD45RA+CD28+), central-memory (CD45RA-CD28+), memory/effector (CD45RA-CD28-) and terminally-differentiated T-cells (TEMRA) (CD45RA+CD28-) and by their intracellular cytokines (IL-17, TNFalpha, IFNgamma) using flowcytometry. <h3>Results</h3> In 21 SSc patients with the diffuse form lower proportions of naive T-cells were found (SSc: 57.8%, HD: 64.2%). Significantly higher proportions of CCR7+ cells in CD4+ TEMRA were found in SSc patients (66.5%) compared to HD (50.4%). Patients with diffuse SSc had higher proportions of CD4+CCR6+RORgt+ T-cells (SSc: 4.8%, HD: 3.2%) with higher IL-17 production (5.6%) compared to HD (4.7%). SSc patients showed a higher production of TNFalpha (64.4%) compared to HD (54.6%), concomitantly expressing CCR7 (SSc: 46.1%, HD: 37.1%). There are nearly equal proportions of IFNgamma producing CD4 T-cells in SSc patients (10.3%) and HD (11.0%). <h3>Conclusions</h3> Our preliminary results showed that SSc patients had a different cytokine profile in T-cells that includes abundance of CCR6+ and CCR7+ memory T-cells and more TNFalpha and IL-17 production. These findings may account for the chronic T-cell stimulation and inflammation in the pathogenesis in SSc. <h3>Disclosure of Interest</h3> None Declared
PMO-131 FGF inducible protein 14 is upregulated in neovessels during chronic inflammatory liver disease and promotes intrahepatic endothelial cell angiogenesis in vitro following stimulation via tweak
Authors: M Munir, E Humphreys, A Wilhelm, B Stephenson, J Caamano, L Burkly, D Adams, S Afford
Journal: Gut (2012)

<h3>Introduction</h3> TWEAK and Fn14 members of the TNF superfamily of ligands and receptors collectively regulate a diverse range of immune, inflammatory and regenerative responses. Recent studies indicate a potential role of TWEAK and Fn14 in tissue repair following liver injury where they may promote angiogenesis and neovessel growth. TWEAK/Fn14 could therefore facilitate inflammatory cell recruitment and promote portal associated lymphoid tissue development during inflammation. <h3>Aims</h3> (1). To investigate TWEAK/Fn14 expression in human liver tissue during chronic liver disease. (2) To study Fn14 expression in isolated intra-hepatic endothelial cells (IHEC). (3) To determine angiogenic responses of IHEC to TWEAK. <h3>Methods</h3> Tissue sections from explanted human livers at the time of hepatobiliary surgery, including normal donor; normal tissue adjacent to malignant lesions; HCV; ALD; NASH; Chronic Allograft Rejection; PSC and PBC, were subjected to immunohistochemistry or dual immunofluorescence using antibodies to TWEAK, Fn14 and phenotypic markers CD31 and CD68. Isolated IHEC were cultured with combinations of TNFα, IFNg, FGF, and assessed for TWEAK/Fn14 expression using flow cytometry. In addition IHEC were incubated with recombinant TWEAK in presence ± TNFα and assessed using a matrigel angiogenesis assay for vessel formation and branching. <h3>Results</h3> Fn14 expression was low in normal tissue in portal vessels and sinusoids, whereas in disease portal neovessels (CD31 +ve) were highly positive for Fn14. TWEAK expression was low in normal tissue but highly expressed in CD68+ve monocytic cells surrounding areas of neovascularisation and inflammatory cell aggregation. Fn14 expression significantly up-regulated on isolated IHEC when stimulated with the TNFα. Confocal imaging showed that the expression of Fn14 was predominantly cytoplasmic unless stimulated with TNF which enhanced cell surface expression. IHEC were consistently negative for TWEAK and TWEAK stimulation increased IHEC angiogenesis, where a change in cell morphology and enhanced branching of capillary like structures was observed. Pre-incubation with Fn14 antagonistic mAb completely abrogated vessel formation and branching. <h3>Conclusion</h3> These new data show that Fn14 activation stimulates neovessel branching in IHEC and that TNF-α promotes mobilisation of cytoplasmic Fn14 to the cell surface suggesting an important regulatory role for TWEAK/Fn14 in neovascularisation and portal lymphoid aggregation during hepatic inflammation. <h3>Competing interests</h3> None declared.
Eventration of the Diaphragm Repaired with Tantalum Mesh
Authors: David T. Monahan
Journal: New England Journal of Medicine (1951)

IT HAS long been considered that eventration of the diaphragm is a condition not amenable to surgical therapy. Furthermore, the opinion has been held that while distressful symptoms may be associated with eventration, serious complications do not occur. Graham1 quotes Clopton to the effect that "the prognosis in the cases of eventration is good and death has never been observed as a direct consequence of the condition." He notes that complications, "other than those which arise from the involvement of the organs that enter into the abnormal displacement, are rarely more serious than are seen with normally placed viscera."Recently, . . .
Abstract 3564: ARID1A promotes endocrine resistance in ER+ breast cancer cells.
Authors: Catherine Chabot, Mark Basik
Journal: Cancer Research (2013)

Abstract We recently identified the ARID1A gene as a new candidate tumor suppressor gene (TSG), mutated in the T47D cells, an ER+ breast cancer cell line. We have shown previously that re-expression of ARID1A in T47D cells inhibits both proliferation and anchorage-independent growth and also that nuclear expression of ARID1A is progressively decreased during the later stages of breast tumor progression. ARID1A encodes a member of the SWI/SNF family of proteins, which function to ‘remodel’ chromatin and thereby regulate gene expression programs. Most breast cancers express the estrogen receptor (ER), and are thus responsive to the mitogenic effects of the estrogen hormone as well as to the anti-proliferative effects of anti-estrogen therapies. To uncover the potential role of ARID1A in the regulation of estrogen signaling in ER+ breast cancer cells, we tested if re-expression of ARID1A may also affect estrogen-dependent growth. Surprisingly, we found that re-expression of ARID1A in T47D cells results in a decrease in the proliferative response of these cells to estrogen but also to a decrease in the viability of the cells in hormone-depleted conditions. Then, to further investigate if the loss of ARID1A may promote estrogen-independent growth, we silenced ARID1A expression by shRNA in MCF-7 cells that express moderate levels of ARID1A protein. We found that ARID1A-silencing increases the survival of MCF-7 cells in the absence of hormones. In addition, we also observed that phosphorylation of FAK and Src, whose activities have been suggested to be important in endocrine resistance, is highly increased in the absence of ARID1A. All together, these results suggest that loss of ARID1A can promote endocrine-resistance in ER-positive breast cancer cells. Citation Format: Catherine Chabot, Mark Basik. ARID1A promotes endocrine resistance in ER+ breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3564. doi:10.1158/1538-7445.AM2013-3564
THIRD TIME’S A CHARM: TREATMENT OF TRANSCATHETER AORTIC VALVE REPLACEMENT PARAVALVULAR LEAK WITH A “VALVE-IN-VALVE-IN-VALVE” PROCEDURE WITH INTRAVASCULAR ULTRASOUND GUIDANCE
Authors: Allan Chen, Aarti Patel, Gregory Hartlage, Fadi Matar, Arthur Labovitz
Journal: Journal of the American College of Cardiology (2016)
Detection of Malignant Tumors Using Tc-99m Labeled Fab' Fragments From a Monoclonal Antibody With Specificity for D-Dimer of Cross-Linked Fibrin
Authors: SOCRATES ANGELIDES, FOOK T. LEE, ANTHONY BASTEN, RICHARD M. LAMBRECHT, KAREN Z. WALKER, PETER G. BUNDESEN, GEORGE J. BAUTOVICH
Journal: Clinical Nuclear Medicine (1996)

The authors present the case studies of two patients whose malignant tumors were detected with a Tc-99m labeled antifibrin monoclonal antibody (DD-3B6/22), which is specific for cross-linked fibrin. The first case was a malignant fibrous histiocytoma involving the proximal aspect of the left thigh, whereas in the second case, the patient was receiving treatment for a squamous cell carcinoma of the right mainstem bronchus. The results highlight the potential of this anti-D-dimer radiopharmaceutical for noninvasive detection of malignant tumors.
SAT0361 Hyperuricemia: Cause or Consequence of Increased Cardiovascular Risk
Authors: I. Meek, H. E. Vonkeman, M. A. van de Laar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Reports on cardiovascular (CV) disease in hyperuricemia and gout show conflicting results. Some studies show hyperuricemia to be an independent risk factor for CV events and death, others find no such associations or only with gouty arthritis. Gout and hyperuricemia have also been associated with individual CV risk factors such as increasing age, male sex, overweight, hypertension, dyslipidemia, diabetes and inflammation. Studies evaluating the complex associations between serum uric acid, inflammation, gouty arthritis and CV risk are lacking. <h3>Objectives</h3> to investigate the associations between serum uric acid and cardiometabolic risk factors and estimated CV risk in patients with gouty arthritis, non-gouty arthritis, and degenerative joint disease. To explore the effect of uric acid lowering therapy (ULT) on CV risk. <h3>Methods</h3> Analysis of the relation between serum uric acid and estimated 10-year risk of CV death (SCORE risk calculation, low risk version corrected for diabetes by increasing age with 15 years) and individual CV risk factors, i.e. systolic blood pressure (SBP), TC/HDL ratio (TC/HDL), diabetes and smoking in patients with osteoarthritis (OA, n=197), rheumatoid arthritis (RA, n=675) and gouty arthritis (GA, n=201) in a cohort of consecutive patients attending the Arthritis Center Twente in 2009. Subanalysis of the effect of uric acid lowering therapy (ULT; allopurinol or benzbromarone, target serum uric acid 0.36 mmol/L) on estimated 10-year CV risk in GA patients. Differences between groups and associations between CV risk variables and tertiles of serum uric acid were tested with ANOVA (for continuous cardiovascular risk factors) or Chi squared statistics (for nominal cardiovascular risk factors), adjusted for differences by age and sex. <h3>Results</h3> mean estimated 10-year CV risk was significantly higher in GA (GA 9.5% vs 5.7% in OA and RA, p&lt;0.05). In RA and OA mean estimated 10-year cardiovascular risk as well as individual cardiometabolic parameters (OA: mean SBP, mean TC/HDL; RA: mean SBP, mean TC/HDL, prevalence diabetes. p&lt;0.05) correlated with serum uric acid values. None of these correlations were present in GA. In GA plasma uric acid was lower in patients on ULT (0.32 mmol/l ULT vs 0.47 mmol/l non-ULT, p&lt;0.05), age and frequency of CV events did not differ from non-ULT users. ULT did not affect mean estimated 10-year CV risk (9.7% ULT vs 8.9% non-ULT, p&lt;0.05). <h3>Conclusions</h3> Gouty arthritis is a red flag for increased CV risk, as shown by higher prevalence of previous CV events and increased metabolic parameters of CV risk. Serum uric acid is associated with metabolic parameters of CV risk and 10-year risk of CV death. Effective ULT does not affect 10-year CV risk. Increased serum uric acid is therefore probably secondary to a high cardiometabolic risk profile. <h3>Disclosure of Interest</h3> None Declared
Abstract 2156: Preclinical combinations of vemurafenib, a selective BRAF inhibitor, with other targeted therapies in BRAFV600E colorectal cancer models
Authors: Hong Yang, Brian Higgins, Kenneth Kolinsky, Jiakui Li, Richard Margolis, Zenaida Go, Aruna Railkar, Kathryn Packman, Gideon Bollag, Fei Su
Journal: Cancer Research (2012)

Abstract Mutations in BRAF at codon 600 promote catalytic activity and are associated with 8% of all human (solid) tumors, including about 10% of colorectal cancers (CRCs). Vemurafenib (RG7204, PLX4032) is a first-in-class, BRAF-specific small molecule inhibitor that dose-dependently inhibits tumor growth in BRAFV600E CRC xenografts. Despite these encouraging preclinical findings, unlike the remarkable responses observed in melanoma, single agent vemurafenib in a Phase I extension trial of 21 patients with previously treated metastatic CRC resulted in a modest 5% response rate. We therefore explored a range of combinations of vemurafenib with different novel targeted therapies including a MEK inhibitor, an AKT inhibitor, a PI3K inhibitor, an mTOR/PI3K dual inhibitor and an EGFR inhibitor in BRAFV600E CRC cell lines. The consequences of these combinations on proliferation were analyzed by MTT assay and the combined effect was determined by combination index (CI) calculated using CalcuSyn software. Western analysis and Annexin V staining were utilized to evaluate combination effects on downstream signaling events and apoptosis induction. Optimized doses of both vemurafenib and a MEK inhibitor were tested as single agents and in combination in CRC xenograft models in nude mice. Synergistic anti-proliferative effects were observed with combinations of vemurafenib and other targeted therapies in the BRAFV600E positive CRC cell lines tested. More effective signaling inhibition and apoptosis induction were observed with the combinations than either agent alone. Combining vemurafenib with a MEKi delivered greater anti-tumor activity and increased life span of animals in the LS411N CRC xenograft model. In a BRAF-mutant CRC xenograft model with inherent resistance to vemurafenib (RKO), tumor growth inhibition by vemurafenib was enhanced by combining with an AKT inhibitor. These in vitro and in vivo data suggest that the administration of vemurafenib in combination with novel targeted therapies may be effective in delivering enhanced and sustained clinical antitumor efficacy in colorectal cancers harboring the BRAFV600E mutation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2156. doi:1538-7445.AM2012-2156
Improvements in US healthcare could save 75 000 lives a year, report says
Authors: K. Epstein
Journal: BMJ (2012)

Pseudomonas cepacia infection has become increasingly common among patients with cystic fibrosis in North America. In a large cystic fibrosis centre in the United Kingdom 11 cases have been identified during the last six years, with a maximum prevalence of 7% in 1988. Three patients have died, two of whom deteriorated rapidly shortly after acquisition of the organism despite intensive treatment with appropriate antibiotics. Analysis of possible causes of the increase in P cepacia infection suggested that neither patient to patient transmission nor the use of nebulised antibiotics was associated with an increased risk of infection.
AB0063 Gammadelta t cells and their intracellular cytokine profile in peripheral blood of patients with systemic lupus erythematosus
Authors: Z. Lu, X. Li, L. Sun
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Gammadelta T cells represent a minor population of human peripheral blood T lymphocytes. As very rapid cytokine-producing cells, gammadelta T cells can regulate other lymphocytes activation and assist their local inflammatory function, thus are involved in some autoimmune diseases. Systemic lupus erythematosus (SLE) is a multi-organ damage autoimmune disease characterized by lymphocytes dysfunction and aberrant cytokines production. <h3>Objectives</h3> The aim of this study was to detect gammadelta T cells numbers in the peripheral blood mononuclear cells (PBMCs) and analyze their intracellular cytokines profile (IFN-γ, IL-4, IL-10, IL-17, TGF-β). <h3>Methods</h3> Gammadelta T cells were detected in peripheral blood from 42 SLE patients and 20 normal controls by flow cytometry (FACS). Lupus disease activity was evaluated with a SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score. Active SLE was defined as SLEDAI≥8. Anniex-V/PI double-staining FACS analysis was employed to observe the proportion of the apoptotic gammadelta T cellsin 6 active SLE patients and 6 normal controls, respectively. The percentages of cytoplasmic cytokines including IFN-γ, IL-4, IL-10, IL-17 and TGF-β were examined in20 SLE patients and 10 normal controls by using FACS anlysis. <h3>Results</h3> The percentages of gammadelta T cells were remarkably down-regulated in active SLE patients (2.96±1.84%, n=30) compared with that of inactive (5.31±3.05%, n=12) and normal controls (6.83±2.85%, n=20, both p&lt;0.01). The absolute number of gammadelta T cells decreased significantly in active SLE patients (1.72±1.58×10<sup>7</sup>/L, n=30) than that in inactive SLE (5.27±3.60×10<sup>7</sup>/L, n=12, p&lt;0.01), both lower than in normal controls (10.07±4.99 ×10<sup>7</sup>/L, n=20, both p&lt;0.01). There was increased gammadelta T cells apoptosis (17.03±8.71%, n=6) in SLE patients than in normal controls (6.67±1.18%, n=6, p&lt;0.05). The positive rate of gammadelta T intracellular IFN-γ, IL-4, IL-10 and TGF-β production in 20 SLE patients were 33.19±20.20%, 1.04±0.93%, 1.91±0.98% and 2.20±1.97%, significantly higher than that of 10 normal controls (IFN-γ: 5.87±4.63%, IL-4:0.30±0.34%, IL-10:0.18±0.31%, TGF-β: 0.21±0.22%, all p&lt;0.01). While there were no differences in the percentages of IL-17-positive gammadelta T cells between SLE patients (0.14±0.24%, n=20) and normal controls (0.18±0.31%, n=10). <h3>Conclusions</h3> Gammadelta T cells are down-regulated in SLE partly due to excessive apoptosis. GammadeltaT cells secret both pro- and anti-inflammatory cytokinesin SLE microenvironment, suggesting these cells participate in both the regulation and the propagation of lupus. <h3>Disclosure of Interest</h3> None Declared
Clinical Production of Pharmaceutical Grade Tc-99m Dextran 70 for Lymphoscintigraphy
Authors: RAYMOND N. DANSEREAU, BRUCE R. LINE
Journal: Clinical Nuclear Medicine (2000)

Lymphoscintigraphy is an established means to determine the lymphatic drainage patterns from malignant tissues and edematous extremities. Unfortunately, there are no commercially available dedicated radiopharmaceuticals labeled for use in lymphoscintigraphy studies. The authors report a simple way to extemporaneously compound pharmaceutical-grade Tc-99m dextran 70 to meet this need. Pharmaceutical-quality Tc-99m dextran 70 injection is prepared by a simple rapid method from drug intermediates that are marketed as parenteral drug products. The radiolabeling process yields a product of high radiochemical purity, with good in vitro and in vivo stability. The authors illustrate the use of this product in a patient with melanoma to show the lymphatic drainage pattern before surgery. The method described permits rapid compounding of Tc-99m dextran 70 injection from drug components that are intended for parenteral administration. Tc-99m dextran 70 provides the option of performing lymphoscintigraphy in any clinical nuclear medicine setting.
Assisted Suicide and Euthanasia in Michigan
Authors: Jerald G. Bachman, David J. Doukas, Richard L. Lichtenstein, Kirsten H. Alcser
Journal: New England Journal of Medicine (1994)

To the Editor: Physician-assisted suicide and active euthanasia are topics of contentious debate in Michigan. After Dr. Jack Kevorkian assisted in a number of highly publicized suicides, the state ...
Hyperprolactinemia-related 131I Uptake in Nonlactating Breasts
Authors: Lien-Hsin Hu, Shih-Jhen Wang, Ren-Shyan Liu
Journal: Clinical Nuclear Medicine (2012)

Concentration of radioiodine is well known in breast milk and lactating breast, but is rare in nonlactating breast. We reported a menopausal female with proved papillary thyroid carcinoma, of which total thyroidectomy and radioiodine ablative treatment were carried out. Postablative whole-body scan showed remarkable concentration of radioiodine in bilateral breasts. Hyperprolactinemia caused by microadenoma of the pituitary gland was found to correlate with 131I accumulation in the nonlactating breasts of this particular case.