tbuckley/cabot-search huggingface dataset:
Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Authors: Hiroaki Wakimoto, Santosh Kesari, Christopher J. Farrell, William T. Curry, Cecile Zaupa, Manish Aghi, Toshihiko Kuroda, Anat Stemmer-Rachamimov, Khalid Shah, Ta-Chiang Liu, Deva S. Jeyaretna, Jason Debasitis, Jan Pruszak, Robert L. Martuza, Samuel D. Rabkin
Journal: Cancer Research (2009)

Abstract Glioblastoma, the most malignant type of primary brain tumor, is one of the solid cancers where cancer stem cells have been isolated, and studies have suggested resistance of those cells to chemotherapy and radiotherapy. Here, we report the establishment of CSC-enriched cultures derived from human glioblastoma specimens. They grew as neurospheres in serum-free medium with epidermal growth factor and fibroblast growth factor 2, varied in the level of CD133 expression and very efficiently formed highly invasive and/or vascular tumors upon intracerebral implantation into immunodeficient mice. As a novel therapeutic strategy for glioblastoma-derived cancer stem–like cells (GBM-SC), we have tested oncolytic herpes simplex virus (oHSV) vectors. We show that although ICP6 (UL39)–deleted mutants kill GBM-SCs as efficiently as wild-type HSV, the deletion of γ34.5 significantly attenuated the vectors due to poor replication. However, this was significantly reversed by the additional deletion of α47. Infection with oHSV G47Δ (ICP6−, γ34.5−, α47−) not only killed GBM-SCs but also inhibited their self-renewal as evidenced by the inability of viable cells to form secondary tumor spheres. Importantly, despite the highly invasive nature of the intracerebral tumors generated by GBM-SCs, intratumoral injection of G47Δ significantly prolonged survival. These results for the first time show the efficacy of oHSV against human GBM-SCs, and correlate this cytotoxic property with specific oHSV mutations. This is important for designing new oHSV vectors and clinical trials. Moreover, the new glioma models described in this study provide powerful tools for testing experimental therapeutics and studying invasion and angiogenesis. [Cancer Res 2009;69(8):3472–81]
Trace-Metal Analysis of Cancerous and Non-cancerous Human Tissues&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Indumati L. Mulay, Rustum Roy, B. E. Knox, N. H. Suhr, William E. Delaney
Journal: JNCI Journal of the National Cancer Institute (1971)

To ascertain whether any significant differences in the concentration of trace metals exist between cancerous and noncancerous human tissues, 22 trace metals and 2 bulk metals were examined by means of emission spectrography. Both cancerous and corresponding noncancerous tissue samples were taken from the same individual, and the clinical and histopathologic information was obtained. The following types of cancers were studied: ductal and scirrhous carcinoma of the breast, bronchogenic carcinoma of the lung, and adenocarcinoma of the colon. The results showed that the copper, magnesium, manganese, and zinc content of cancerous breast tissue was significantly higher than that of the noncancerous tissue. In bronchogenic carcinoma of the lung, the iron content of the cancerous tissue was significantly lower and the zinc content significantly higher than contents in the noncancerous bronchial tissue. In adenocarcinoma of the colon, the concentration of tin was considerably lower in cancerous than in noncancerous tissue. Significant differences in the concentration of selective metals were noticeable between cancerous tissues. It was also apparent that these differences pertain to a specific type of cancer. This specificity indicates that all types of cancers cannot be grouped under one category; for interpretation, each type should be regarded as a separate entity.
Human eosinophils express, relative to other circulating leukocytes, large amounts of secretory 14-kD phospholipase A2
Authors: M Blom, A T Tool, P C Wever, G J Wolbink, M C Brouwer, J Calafat, Arne Egesten, E F Knol, C E Hack, D Roos, A J Verhoeven
Journal: Blood (1998)
Comparison of Controlled-Release Ketoprofen and Diclofenac in the Control of Post-Surgical Dental Pain
Authors: Y M A Tai, R Baker
Journal: Journal of the Royal Society of Medicine (1992)

Preoperative treatment with controlled-release ketoprofen or diclofenac was compared in 56 outpatients, for control of postoperative dental pain, following unilateral or bilateral surgical removal of lower third molars. Six patients were excluded due to non-compliance, leaving 50 evaluable patients. Patients were assessed by the dental surgeon, on the day of the operation and one week later, prior to removal of sutures. Additionally, patients completed a daily diary during the postoperative week. Following surgery, scores for graded dental pain, consumption of paracetamol, incidence of dental bleeding, dysphagia, sleep disturbance and trismus were similar for the two treatment groups. However, median pain scores were consistently elevated in the diclofenac group over those seen with the ketoprofen group. The four adverse events reported were all minor and posed no problem to patient management.
A review of the carotid and femoral intima-media thickness as an indicator of the presence of peripheral vascular disease and cardiovascular risk factors
Authors: Koon Sung Cheng, Dimitri P Mikhailidis, George Hamilton, Alexander M Seifalian
Journal: Cardiovascular Research (2002)

Peripheral vascular disease (PVD) is a common condition often associated with cardiovascular risk factors and events. With the aid of B-mode ultrasound scanning, evidence is emerging that these risk factors and events are significantly related to an increased carotid and femoral intima-media thickness (IMT). More importantly, treatment of these risk factors is associated with a decrease or a diminished progression of the IMT, paralleled by a reduction in cardiovascular events and an improvement in the symptoms associated with PVD. This evidence is particularly strong for lipid lowering therapy. Additional predictors of cardiovascular risk like the IMT, could now influence the decision to intervene with medication.
Achaete-Scute Complex Homologue 1 Regulates Tumor-Initiating Capacity in Human Small Cell Lung Cancer
Authors: Tianyun Jiang, Brendan J. Collins, Ning Jin, David N. Watkins, Malcolm V. Brock, William Matsui, Barry D. Nelkin, Douglas W. Ball
Journal: Cancer Research (2009)

The basic helix-loop-helix transcription factor achaete-scute complex homologue 1 (ASCL1) is essential for the development of normal lung neuroendocrine cells as well as other endocrine and neural tissues. Small cell lung cancer (SCLC) and non-SCLC with neuroendocrine features express ASCL1, where the factor may play a role in the virulence and primitive neuroendocrine phenotype of these tumors. In this study, RNA interference knockdown of ASCL1 in cultured SCLC resulted in inhibition of soft agar clonogenic capacity and induction of apoptosis. cDNA microarray analyses bolstered by expression studies, flow cytometry, and chromatin immunoprecipitation identified two candidate stem cell marker genes, CD133 and aldehyde dehydrogenase 1A1 (ALDH1A1), to be directly regulated by ASCL1 in SCLC. In SCLC direct xenograft tumors, we detected a relatively abundant CD133(high)-ASCL1(high)-ALDH1(high) subpopulation with markedly enhanced tumorigenicity compared with cells with weak CD133 expression. Tumorigenicity in the CD133(high) subpopulation depended on continued ASCL1 expression. Whereas CD133(high) cells readily reconstituted the range of CD133 expression seen in the original xenograft tumor, CD133(low) cells could not. Our findings suggest that a broad range of SCLC cells has tumorigenic capacity rather than a small discrete population. Intrinsic tumor cell heterogeneity, including variation in key regulatory factors such as ASCL1, can modulate tumorigenicity in SCLC.
BCL9 Promotes Tumor Progression by Conferring Enhanced Proliferative, Metastatic, and Angiogenic Properties to Cancer Cells
Authors: Mala Mani, Daniel E. Carrasco, Yunyu Zhang, Kohichi Takada, Moshe E. Gatt, Jui Dutta-Simmons, Hiroshi Ikeda, Felipe Diaz-Griffero, Victor Pena-Cruz, Monica Bertagnolli, Lois L. Myeroff, Sanford D. Markowitz, Kenneth C. Anderson, Daniel R. Carrasco
Journal: Cancer Research (2009)

Abstract Several components of the Wnt signaling cascade have been shown to function either as tumor suppressor proteins or as oncogenes in multiple human cancers, underscoring the relevance of this pathway in oncogenesis and the need for further investigation of Wnt signaling components as potential targets for cancer therapy. Here, using expression profiling analysis as well as in vitro and in vivo functional studies, we show that the Wnt pathway component BCL9 is a novel oncogene that is aberrantly expressed in human multiple myeloma as well as colon carcinoma. We show that BCL9 enhances β-catenin–mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases cell proliferation, migration, invasion, and the metastatic potential of tumor cells by promoting loss of epithelial and gain of mesenchymal-like phenotype. Most importantly, BCL9 knockdown significantly increased the survival of xenograft mouse models of cancer by reducing tumor load, metastasis, and host angiogenesis through down-regulation of c-Myc, cyclin D1, CD44, and vascular endothelial growth factor expression by tumor cells. Together, these findings suggest that deregulation of BCL9 is an important contributing factor to tumor progression. The pleiotropic roles of BCL9 reported in this study underscore its value as a drug target for therapeutic intervention in several malignancies associated with aberrant Wnt signaling. [Cancer Res 2009;69(19):7577–86]
Metabolic Studies in an Unusual Case of Asymptomatic Familial Hypobetalipoproteinemia with Hypoalphalipoproteinemia and Fasting Chylomicronemia
Authors: Daniel Steinberg, Scott M. Grundy, Henry Y. I. Mok, John D. Turner, David B. Weinstein, W. Virgil Brown, John J. Albers
Journal: Journal of Clinical Investigation (1979)

A new kindred with asymptomatic hypobetalipoproteinemia is reported. The proband, age 67, differs from previously described cases in several respects: (a) unusually low levels of low density lipoprotein (LDL) cholesterol (4-8 mg/dl); (b) normal triglyceride levels; (c) low levels of high density lipoprotein; (d) mild fat malabsorption; and (e) a defect in chylomicron clearance. On a high-carbohydrate diet his plasma triglyceride levels, instead of rising, actually fell. Turnover of triglycerides in very low density lipoproteins (VLDL) was low (2.8 mg/kg per h). Fractional catabolic rate of LDL protein was just above the normal range (0.655/d) but net turnover was <10% of normal (0.65 mg/kg per d). The half-life of his chylomicrons was 29 min, five times the normal value. Postheparin lipoprotein lipase activity was normal and apolipoprotein C-II, the activator protein for lipoprotein lipase, was present and functional. Apolipoprotein C-III1, however, was not detected in the VLDL fraction, a finding previously reported in patients with abetalipoproteinemia. Fecal excretion of cholesterol was almost twice normal; total sterol balance was increased by ≅40%. The unusual features in the proband that distinguish him from previously described cases and from his affected first-degree relatives suggested that, in addition to the basic gene defect affecting LDL metabolism, he might have a second abnormality affecting clearance of chylomicrons and VLDL. The ratio of apolipoprotein E3 to E2 in his VLDL fraction was 0.93, just below the lower limit of normal, suggesting heterozygosity for E3 deficiency. Whether or not this contributes to his hypertriglyceridemia remains to be established.
Comparison of DNA Damage by Methylmelamines and Formaldehyde&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W E Ross, D R McMillan, C F Ross
Journal: JNCI Journal of the National Cancer Institute (1981)

The cytoxicity and DNA damaging activity of S9-activated hexamethylmelamine (HMM) and pentamethylmelamine (PMM) were compared with suspected active metabolites in mouse leukemia L1210 cells. The presence of semicarbazide hydrochloride did not alter the cytotoxicity of S9-activated HMM and PMM or that of their hydroxylated analogs monomethylolpentamethylmelamine (MPM) and trimethyloltrimethylmelamine (TTM), which have been suggested as active metabolites. Following treatment of L1210 cells with high concentrations of activated HMM and PMM, there were no DNA single-strand breaks or interstrand cross-links observed by DNA alkaline elution and only a low frequency of DNA-protein cross-links. Formaldehyde (FA) at nonlethal concentrations caused far greater DNA-protein cross-linking. In contrast, the polyfunctional TTM produced both DNA-protein cross-linking and DNA interstrand cross-linking. The cytotoxicities of HMM and PMM were found unlikely to be related to extracellular or intracellular release of FA.
Effect of positive end-expiratory pressure on intrapulmonary shunt at different levels of fractional inspired oxygen.
Authors: A Oliven, U Taitelman, F Zveibil, S Bursztein
Journal: Thorax (1980)

In 10 patients undergoing ventilation, venous admixture was measured at different values of positive end-expiratory pressure (PEEP). The measurements were performed at the level of fractional inspired oxygen (FIO2) at which each patient was ventilated, and at FIO2=1. In patients ventilated at FIO2 between 0.21 and 0.3 venous admixture was not modified by PEEP, while in patients ventilated with FIO2 between 0.4 and 0.6, venous admixture decreased significantly (p less than 0.01). With FIO2=1, increased PEEP produced a reduction in venous admixture in all cases (p less than 0.05). These observations suggest that in patients similar to ours, PEEP does not reduce venous admixture at low levels of FIO2 (0.21--0.3), and the observed reduction with PEEP at FIO2=1 may be misinterpreted.
Affinity purification and characterisation of human ACPAs
Authors: Elena Ossipova, Cátia Cerqueira, Evan Reed, Nastya Kharlamova, Ailbhe Comyn, Lena Israelsson, Anca I Catrina, Lars Klareskog, Per-Johan Jakobsson, Karin Lundberg
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Autoimmunity in rheumatoid arthritis (RA) is characterised by autoantibodies to citrullinated proteins/peptides (ACPA). These antibodies, present in 60–70% of patients, antedate clinical onset and associate with an erosive disease course, suggesting a direct pathogenic involvement in disease initiation and progression. With this study, the authors aimed to develop an efficient method for the purification of human ACPA, and to characterise their frequency and fine-specificity pattern in synovial fluid (SF) and plasma of RA patients. <h3>Materials and methods</h3> SF and plasma samples were collected with informed consent and ethical approval from patients (fulfilling the American college of rheumatology criteria for RA) with high anti-CCP antibody levels. SF samples (n=36) were first treated with hyaluronidase to decrease viscosity, then proteins were precipitated with ammonium sulphate, dissolved and further dialysed against PBS, before the IgG fractions were purified on Protein G columns (GE Healthcare, Uppsala, Sweden).Plasma samples (n=10) were diluted in PBS before applied to the Protein G column. ACPAs were further purified using CCP2 affinity columns, kindly provided by Euro-Diagnostica. Recovery and purity of total IgG and anti-CCP immunoglobulin G (IgG) were analysed using SDS-PAGE, Nanodrop (Thermo Scientific, Wilmington, DE, USA) and the CCP2-ELISA kit. Fine-specificity of the purified ACPAs were investigated using inhouse ELISAs, with peptides from citrullinated α-enolase (CEP-1), -vimentin (Cit-vim), -fibrinogen (Cit-fib) and -collagen type II (Cit-C1). <h3>Results</h3> Anti-CCP IgG could efficiently be purified from SF and plasma, using ProteinG-, followed by CCP2-, columns. No CCP IgG response could be detected in the flow-through fractions. Higher concentrations of total IgG were found in plasma (13.6 mg/ml) compared to SF (4.2 mg/ml), while a higher percentage of CCP-specific IgG was detected in SF (3%), compared to plasma (2%). The purified anti-CCP IgG fractions cross-reacted with CEP-1, Cit-vim, Cit-fib and Cit-C1, while no reactivity to these citrullinated antigens were detected in the IgG flow-through fractions. Anti-CCP IgG dilution curves (starting at 10 µg/ml of purified antibodies), demonstrated differences in affinity between patients, which may correspond to the different ACPA-fine specificity patterns seen in patients. <h3>Conclusions</h3> The described methodology efficiently purifies ACPAs with multiple specificities, which will allow for their use in in vivo and in vitro studies, to further elucidate their arthritogenic and pathogenic capacity. In addition, the ACPAs will be tools for future immunoprecipitation-, immunoblotting- and immunohistochemistry experiments.
Transformation of Late Passage Insulin-Like Growth Factor-I Receptor Null Mouse Embryo Fibroblasts by SV40 T Antigen
Authors: Susan L. Spence, Arthur L. Shaffer, Louis M. Staudt, Sewit Amde, Sutana Manney, Cheryl Terry, Keith Weisz, Peter Nissley
Journal: Cancer Research (2006)

There is evidence that the insulin-like growth factor-I (IGF-I) receptor is required for transformation by a variety of viral and cellular oncogenes in a mouse embryo fibroblast model. To further investigate the IGF-I receptor signaling pathways that are required for the permissive effect of the receptor on transformation by SV40 T antigen, we established three independent fibroblast cell lines each from wild-type and IGF-I receptor null embryos (R-). We transfected the wild-type and R- cell lines with an SV40 T antigen plasmid and selected three clones from each cell line that expressed T antigen. As in previous reports, none of the cloned R- cell lines expressing T antigen were transformed as measured by the ability to form large colonies in soft agar. However, with further passage, all three T antigen-expressing clones from one of the R- cell lines (R(-)3) formed large colonies in soft agar and the transformation of these T antigen-expressing clones was confirmed by tumorigenesis experiments in immunodeficient mice. DNA microarray analysis comparing gene expression between early passage and late passage R(-)3/T antigen clones showed, among other changes, an increase in the expression of ErbB-3 mRNA in the late passage clones. Also, the expression of ErbB-3 protein was dramatically increased in the late passage R(-)3/T antigen clones. We conclude that late passage IGF-I receptor null mouse embryo fibroblasts can be transformed by SV40 T antigen, and that ErbB-3 may play a role in permitting transformation by T antigen.
Intra-abdominal adhesions: Cellular mechanisms and strategies for prevention
Authors: Allison H. Maciver, Michael McCall, A.M. James Shapiro
Journal: International Journal of Surgery (2011)

Postoperative intra-abdominal adhesions represent a serious clinical problem. In this review, we have focused on recent progress in the cellular and humoral mechanisms underpinning adhesion formation, and have reviewed strategies that interfere with these pathways as a means to prevent their occurrence. Current and previous English-language literature on the pathogenesis of adhesion formation was identified. As the burden of surgical disease in the world population increases, and the frequency of reoperation increases, prevention of adhesion formation has become a pressing goal in surgical research.
Decreased release of lipoprotein lipase is associated with vascular endothelial damage in NIDDM patients with microalbuminuria.
Authors: K Kashiwazaki, T Hirano, G Yoshino, M Kurokawa, H Tajima, M Adachi
Journal: Diabetes Care (1998)

OBJECTIVE: To explore mechanisms for hypertriglyceridemia in diabetic patients with microalbuminuria, we examined an association between heparin-releasable lipoprotein lipase (LPL) and the von Willebrand factor (vWF), based on the hypothesis that LPL bound to endothelium is decreased by generalized endothelial damage. RESEARCH DESIGN AND METHODS: A total of 37 NIDDM patients with microalbuminuria and 69 patients with normoalbuminuria were studied. Plasma LPL mass in post-heparin plasma and plasma vWF antigen were quantified by sandwich-enzyme immunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS: The NIDDM patients with microalbuminuria had higher plasma triglyceride (TG) and lower HDL cholesterol concentrations compared with the patients with normoalbuminuria. Heparin-releasable LPL mass was significantly lower in the microalbuminuric than in the normoalbuminuric subjects. Plasma level of vWF, a marker for endothelial damage, was significantly increased in microalbuminuric subjects compared with their normoalbuminuric counterparts. The LPL mass was inversely correlated with plasma vWF level at a high correlation coefficient value. The LPL mass was inversely related to TG and positively to HDL cholesterol concentrations. CONCLUSIONS: These results suggest that widespread endothelial damage occurred in NIDDM patients with microalbuminuria, thereby LPL moiety bound to the endothelium is decreased, which results in an impaired catabolism of TG-rich lipoproteins.
Modified release prednisone in patients with rheumatoid arthritis
Authors: J. W. G. Jacobs, J. W. J. Bijlsma
Journal: Annals of the Rheumatic Diseases (2010)

The current issue of the Journal contains three articles related to sex offenders. The first, by Scott and Holmberg, discusses legislation that mandates either "chemical or surgical castration." The second, by Saleh and Guidry, reviews diagnostic and treatment considerations. The third, by Scott and Gerbasi, discusses sex offender registration and community notification. Much of the relevant sex offender legislation, including that pertaining to testosterone-lowering treatments, has been enacted in response to intense public passion. When it comes to the issue of sex offenders, there is a pressing need to develop a coherent body of evidence-based forensic concepts and knowledge that can rationally inform both clinical practice and future public policy. That may require a closer collaboration between both the criminal justice and legislative sectors, and the scientific-medical communities. The three papers published in this issue provide useful information that may assist toward such a goal.
Probiotics in functional intestinal disorders and IBS: proof of action and dissecting the multiple mechanisms
Authors: P. Marteau
Journal: Gut (2010)

Probiotics are widely consumed and the widespread advertising is often not really justified by the evidence. Many products were never studied as such and some companies use studies performed with other (and different) products for advertising even during medical conventions. Evidence of benefit is still patchy and the clinician has to take into account the variability of the strains, the doses, the quality of the trials and clinical relevance of end points.

In this issue of Gut , Mohayyedi and colleagues (see page 325) have made an interesting systematic analysis on the randomised controlled trials testing various probiotics in patients with irritable bowel syndrome (IBS).1 They show that many trials are of good quality, that positive results were obtained with some strains, or products combining several strains, but also that studies are heterogeneous and that funnel plot asymmetry suggests biases in the publications (ie, there are more reports on the positive studies than of the negative ones). I agree with the authors that meta-analysis is not wise as the active ingredients and mechanisms of action of various probiotics are very likely to …