tbuckley/cabot-search huggingface dataset:
CD44 Potentiates the Adherence of Metastatic Prostate and Breast Cancer Cells to Bone Marrow Endothelial Cells
Authors: Jayne E. Draffin, Suzanne McFarlane, Ashleigh Hill, Patrick G. Johnston, David J. J. Waugh
Journal: Cancer Research (2004)

Abstract The aim of this current study was to examine the significance of CD44 expression in mediating cancer cell adhesion to human bone marrow endothelial cell(s) (hBMEC). Differential CD44 expression on two metastatic prostate cancer cell lines, PC3 (CD44 +ve) and DU145 (CD44 −ve) and four breast cancer cell lines was confirmed by immunoblotting and immunocytochemistry. In cell adhesion assays, PC3 but not DU145 cells demonstrated a rapid adhesion to hBMECs. Treatment of PC3 cells with a neutralizing antibody against CD44 standard (CD44s) and CD44 splice variants decreased PC3 cell adhesion to hBMECs. Similarly, depletion of CD44 expression using RNA interference decreased the ability of PC3 cells and two CD44 +ve breast cancer cell lines (MDA-MB-231 and MDA-MB-157) to bind FITC-conjugated hyaluronan (FITC-HA) and to adhere to hBMECs. In contrast, transfection of DU145 cells or the T47D and MCF-7 breast cancer cell lines to express CD44s increased cell surface binding of FITC-HA and cell adherence to hBMECs. Treatment of PC3 and MDA-MD-231 cells but not hBMECs with hyaluronidase attenuated cell adhesion, suggesting that cell surface expression of CD44 on prostate and breast cancer cells may promote the retention of a HA coat that facilitates their initial arrest on bone marrow endothelium.
In vitro analysis of allogeneic lymphocyte interaction. VII. I-A-restricted self-reactive and alloreactive helper components of allogeneic effect factor are distinct donor T cell-derived Ia-molecules that recognize Ia determinants on antigen-presenting cells.
Authors: T L Delovitch, K Kaufman, R M Gorczynski
Journal: The Journal of Experimental Medicine (1983)

An allogeneic effect factor (AEF) derived from mixed lymphocyte reaction (MLR) cultures of alloactivated A.SW (H-2s) responder T cells and irradiated T cell-depleted A/WySn (H-2a) stimulator spleen cells was fractionated on the basis of molecular size and charge into two I-A-restricted helper components. The cellular origin of these components is believed to be an Lyt-1+2- -activated responder T helper (TH) cell. One alloreactive component, TIAH-1, recognizes allo-I-A determinants on an A/WySn antigen-presenting cell (APC). The other self-reactive component, TIAH-2, recognizes self-I-A determinants on an A.SW APC. The interaction of each of these components with the appropriate APC subsequently activates an in vitro primary anti-SRBC PFC response of either stimulator haplotype- or responder haplotype-derived B cells. These data demonstrate that the activity of TIAH-1 and TIAH-2 is dependent on the genotype of the APC and not the B cell, and that the target cell of action of these AEF TH components is an APC. TIAH-1 and TIAH-2 are 68,000 mol wt single polypeptide chains that have an isoelectric point (pI) of 5.8 and 5.5, respectively. Their charge difference is not attributable to altered amounts of sialylation or phosphorylation, but probably is due to other forms of altered glycosylation and/or to changes in their amino acid sequence. They share approximately 80% of their tryptic peptides and likely constitute homologous but nonidentical molecules. Papain cleaves TIAH-1 and TIAH-2 into a 40,000 mol wt fragment. TIAH-1 and TIAH-2 may represent structurally very related but nonidentical secreted forms of activated responder TH cell-derived receptors for allo-I-A and self-I-A determinants, respectively.
414 IMPACT OF SHEAR-WAVES CHARACTERISTICS ON THE MEDIAN LIVER STIFFNESS MEASURE (LSM) ASSESSED BY FIBROSCAN: EVALUATION WITH LIVER BIOPSY (LB) OF RISK OF FALSE NEGATIVE RESULTS
Authors: M. Munteanu, Y. Ngo, A. Varaud, P. Ingiliz, P. Lebray, F. Charlotte, V. Ratziu, T. Poynard
Journal: Journal of Hepatology (2010)
Prevalence of basidiomycete allergy in the USA and Europe and its relationship to allergic respiratory symptoms
Authors: S.B. Lehrer, J. M. Hughes, L. C. Altman, J. Bousquet, R. J. Davies, L. Gell, J. Li, M. Lopez, H. J. Malling, D. A. Mathison, J. Sastre, G. Schultze‐Werninghaus, H. J. Schwartz
Journal: Allergy (1994)

A total of 701 adults living in the USA or Western Europe who had symptoms of allergic respiratory disease were skin prick tested with extracts prepared from eight basidiomycetes species and four Fungi Imperfecti species. In these subjects, the presence of asthma, rhinitis, or both was determined by questionnaire. Overall, 178/701 (25.4%) of the participants reacted to at least one basidiomycete extract. There was no difference in the prevalence of reactivity detected in the USA and Europe ( P &lt; 0.005); however, the prevalence of reactors in individual centers from both areas varied significantly. Psilocybe cuhensis was the most potent allergen source in both the USA (12.3% reacted) and Europe (16.0%). Pleurotus ostreatus was second overall (10.6%) and in the USA (10.7%), and third in Europe (10.3%). Pisolithus tinctorius and Coprinus quadrifidus produced the least potent allergens, with only 5.4% of the population reacting. There was a significant relationship ( P &lt; 0.005) between basidiospore reactivity and the presence of atopy, asthma, and asthma and rhinitis. Basidiospore reactivity was not associated with the presence of rhinitis alone ( P = 0.312). These results suggest that basidiomycetes are important sources of aeroallergens in geographically disparate regions and may be particularly important in patients with asthma. Lehrer SB, Hughes JM, Altman LC, Bousquet J, Davies RJ, Gell L, Li J, Lopez M, Mailing HJ, Mathison DA, Sastre J, Schultze‐Werninghaus G, Schwartz HJ. Prevalence of basidiomycete allergy in the USA and Europe and its relationship to allergic respiratory symptoms.
The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Its Associated Research Resource
Authors: C. S. Zhu, P. F. Pinsky, B. S. Kramer, P. C. Prorok, M. P. Purdue, C. D. Berg, J. K. Gohagan
Journal: JNCI Journal of the National Cancer Institute (2013)

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses' Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues.
Stereotactic Body Radiation Therapy in Multiple Organ Sites
Authors: Robert D. Timmerman, Brian D. Kavanagh, L. Chinsoo Cho, Lech Papiez, Lei Xing
Journal: Journal of Clinical Oncology (2007)

Stereotactic body radiation therapy (SBRT) uses advanced technology to deliver a potent ablative dose to deep-seated tumors in the lung, liver, spine, pancreas, kidney, and prostate.SBRT involves constructing very compact high-dose volumes in and about the tumor. Tumor position must be accurately assessed throughout treatment, especially for tumors that move with respiration. Sophisticated image guidance and related treatment delivery technologies have developed to account for such motion and efficiently deliver high daily dose. All this serves to allow the delivery of ablative dose fractionation to the target capable of both disrupting tumor mitosis and cellular function.Prospective phase I dose-escalation trials have been carried out to reach potent tumoricidal dose levels capable of eradicating tumors with high likelihood. These studies indicate a clear dose-response relationship for tumor control with escalating dose of SBRT. Prospective phase II studies have been reported from several continents consistently showing very high levels of local tumor control. Although late toxicity requires further careful assessment, acute and subacute toxicities are generally acceptable. Patterns of toxicity, both clinical and radiographic, are distinct from those observed with conventionally fractionated radiotherapy as a result of the unique biologic response to ablative fractionation.Prospective trials using SBRT have confirmed the efficacy of treatment in a variety of patient populations. Although mechanisms of ablative-dose injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in the treatment arsenal.
Epirubicin and cytosine arabinoside for the induction therapy of childhood acute nonlymphocytic leukemia
Authors: Der‐Cherng Liang, Chang‐Jen Jiang
Journal: American Journal of Hematology (1991)

Epirubicin, a new anthracycline, was used in combination with cytosine arabinoside for the induction therapy of de novo acute nonlymphocytic leukemia in childhood. The treatment consisted of epirubicin 20 mg/m2/day for 3 days and cytosine arabinoside 100 mg/m2/day for 7 days. The treatment could be repeated every 3 weeks. Remission induction rate was 80% (20/25). Moreover, in 13 patients, the remissions were obtained after a single course. In general, the side effects of epirubicin and cytosine arabinoside were tolerable. However, the main causes of all the three deaths were infections. Our study suggests that epirubicin is acceptable and effective for the induction therapy for de novo acute nonlymphocytic leukemia in childhood.
SMAD proteins are involved in apoptosis induction in ventricular cardiomyocytes
Authors: D SCHNEIDERS, J HEGER, P BEST, H MICHAELPIPER, G TAIMOR
Journal: Cardiovascular Research (2005)

The transcription factor AP-1 is a mediator of hypertrophic growth and apoptosis in cardiomyocytes. This puts AP-1 in the center of two important processes found in the failing heart and implies that variations (i) in the AP-1 composition itself or (ii) in additional, interacting transcription factors are responsible for the diverse actions of AP-1. To test this hypothesis, we performed studies on isolated ventricular cardiomyocytes of rat under hypertrophy- or apoptosis-inducing conditions.The NO donor SNAP (100 microM), which is a pro-apoptotic stimulus in cardiomyocytes, activated AP-1 within 2 h. c-Jun, JunB and FosB are identified as the main components of this AP-1 complex. This complex formation is identical to the composition of AP-1 found under hypertrophic growth stimulation by phenylephrine (PE, 10 muM). Analysis of other transcription factors able to interact with AP-1 revealed activation of SMAD activity only during stimulation with SNAP to 131+/-9.6% (p < 0.05 vs. control, n = 9). The SMAD complex is formed from SMAD4 and 3. Intracellular scavenging of SMAD proteins by transformation of cardiomyocytes with SMAD decoy oligonucleotides or inhibition of SMAD4 synthesis using SMAD4 antisense oligonucleotides reduced the number of apoptotic cells under stimulation with SNAP from 13.3 +/- 1.2% to control levels (8 +/- 1%, p < 0.05, n = 6). TGFbeta, which is a known stimulator of SMAD proteins, is also shown to stimulate apoptosis in cardiomyocytes. Again, simultaneous activation of AP-1 and SMAD is needed for this apoptosis induction.In conclusion, AP-1/SMAD signaling has been identified as a common pathway in cardiomyocyte apoptosis. In contrast, SMAD proteins are dispensable for AP-1-mediated hypertrophic growth. This finding characterizes SMAD proteins as potential candidates for proteins that shift AP-1 signaling from hypertrophy to apoptosis.
The Effectiveness of Psychodynamic Therapy and Cognitive Behavior Therapy in the Treatment of Personality Disorders: A Meta-Analysis
Authors: Falk Leichsenring, Eric Leibing
Journal: American Journal of Psychiatry (2003)

The authors conducted a meta-analysis to address the effectiveness of psychodynamic therapy and cognitive behavior therapy in the treatment of personality disorders.Studies of psychodynamic therapy and cognitive behavior therapy that were published between 1974 and 2001 were collected. Only studies that 1) used standardized methods to diagnose personality disorders, 2) applied reliable and valid instruments for the assessment of outcome, and 3) reported data that allowed calculation of within-group effect sizes or assessment of personality disorder recovery rates were included. Fourteen studies of psychodynamic therapy and 11 studies of cognitive behavior therapy were included.Psychodynamic therapy yielded a large overall effect size (1.46), with effect sizes of 1.08 found for self-report measures and 1.79 for observer-rated measures. For cognitive behavior therapy, the corresponding values were 1.00, 1.20, and 0.87. For more specific measures of personality disorder pathology, a large overall effect size (1.56) was seen for psychodynamic therapy. Two cognitive behavior therapy studies reported significant effects for more specific measures of personality disorder pathology. For psychodynamic therapy, the effect sizes indicate long-term rather than short-term change in personality disorders.There is evidence that both psychodynamic therapy and cognitive behavior therapy are effective treatments of personality disorders. Since the number of studies that could be included in this meta-analysis was limited, the conclusions that can be drawn are only preliminary. Further studies are necessary that examine specific forms of psychotherapy for specific types of personality disorders and that use measures of core psychopathology. Both longer treatments and follow-up studies should be included.
Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain
Authors: D. E. Stange, F. Engel, T. Longerich, B. K. Koo, M. Koch, N. Delhomme, M. Aigner, G. Toedt, P. Schirmacher, P. Lichter, J. Weitz, B. Radlwimmer
Journal: Gut (2010)

<h3>Background and aims</h3> Liver metastases are the leading cause of death in colorectal cancer. To gain better insight into the biology of metastasis and possibly identify new therapeutic targets we systematically investigated liver-metastasis-specific molecular aberrations. <h3>Methods</h3> Primary colorectal cancer (pCRC) and matched liver metastases (LMs) from the same patients were analysed by microarray-based comparative genomic hybridisation in 21 pairs and gene expression profiling in 18 pairs. Publicly available databases were used to confirm findings in independent datasets. <h3>Results</h3> Chromosome aberration patterns and expression profiles of pCRC and matched LMs were strikingly similar. Unsupervised cluster analysis of genomic data showed that 20/21 pairs were more similar to each other than to any other analysed tumour. A median of only 11 aberrations per patient was found to be different between pCRC and LM, and expression of only 16 genes was overall changed upon metastasis. One region on chromosome band 11p15.5 showed a characteristic gain in LMs in 6/21 patients. This gain could be confirmed in an independent dataset of LMs (n=50). Localised within this region, the growth factor <i>IGF2</i> (p=0.003) and the intestinal stem cell specific transcription factor <i>ASCL2</i> (p=0.029) were found to be over-expressed in affected LM. Several <i>ASCL2</i> target genes were upregulated in this subgroup of LM, including the intestinal stem cell marker <i>OLFM4</i> (p=0.013). The correlation between <i>ASCL2</i> expression and four known direct transcriptional targets (<i>LGR5</i>, <i>EPHB3</i>, <i>ETS2</i> and <i>SOX9</i>) could be confirmed in an independent expression dataset (n=50). <h3>Conclusions</h3> With unprecedented resolution a striking conservation of genomic alterations was demonstrated in liver metastases, suggesting that metastasis typically occurs after the pCRC has fully matured. In addition, we characterised a subset of liver metastases with an <i>ASCL2</i>-related stem-cell signature likely to affect metastatic behaviour of tumour cells.
High-Normal HbA1c Is a Strong Predictor of Type 2 Diabetes in the General Population
Authors: Enzo Bonora, Stefan Kiechl, Agnes Mayr, Giacomo Zoppini, Giovanni Targher, Riccardo C. Bonadonna, Johann Willeit
Journal: Diabetes Care (2011)

OBJECTIVE Glycosylated hemoglobin (HbA1c) recently has been recommended for the diagnosis of diabetes by the American Diabetes Association, but its value in the prediction of type 2 diabetes is poorly understood. In this study we evaluated how high-normal HbA1c levels predict type 2 diabetes. RESEARCH DESIGN AND METHODS We measured HbA1c in 919 Caucasian subjects, aged 40–79 years, and recorded new cases of type 2 diabetes in the following 15 years. Diabetes was diagnosed with HbA1c. RESULTS Subjects were stratified according to baseline HbA1c (&amp;lt;5.0, 5.00–5.49 [reference], 5.50–5.99, and 6.00–6.49%). Sex- and age-adjusted hazard ratios (95% CI) for type 2 diabetes were 1.11 (0.30–4.41), 1.00, 3.79 (1.79–8.06), and 12.50 (5.51–28.34), respectively. Results did not change after adjusting for several putative confounding factors and were confirmed when models with updated variables were used. CONCLUSIONS HbA1c is an independent risk factor for type 2 diabetes. Subjects with high-normal levels of HbA1c deserve particular attention because they have a strong risk of developing diabetes.
Prevention of Coagulase-Negative Staphylococcal Central Venous Catheter–Related Infection Using Urokinase Rinses: A Randomized Double-Blind Controlled Trial in Patients With Hematologic Malignancies
Authors: Cornelis J. van Rooden, Emile F. Schippers, Henri F.L. Guiot, Renée M. Barge, Marcel M.C. Hovens, Felix J.M. van der Meer, Frits R. Rosendaal, Menno V. Huisman
Journal: Journal of Clinical Oncology (2008)

Fibrin deposition at the intraluminal surface of the indwelling part of the central venous catheter (CVC) surface increases the risk of CVC-related coagulase-negative staphylococci (CoNS) infection. Therefore, repetitive enzymatic dissolution of fibrin by urokinase might reduce the risk of CVC-related infection. We undertook this study to investigate whether three times weekly urokinase rinsing of CVC reduces the incidence or severity of CVC-related infections by CoNS in patients undergoing intensive cytotoxic treatment for hematologic malignancies.In a double-blind setting, all consecutive patients with a CVC were randomly allocated to receive either urokinase rinses (5 mL of 5,000 U/mL) or placebo (saline), both three times weekly.The percentage of patients with at least one positive culture with CoNS was lower in patients receiving urokinase compared with patients receiving placebo (26% v 42%, respectively; relative risk [RR] = 0.61; 95% CI, 0.39 to 0.94). Major CVC-related CoNS infection occurred less frequently in patients receiving urokinase versus placebo (1.2% v 14.1%, respectively; RR = 0.09; 95% CI, 0.01 to 0.50). Secondary complications, including CVC-related thrombosis, were observed less frequently in the urokinase group compared with the placebo group (1.3% v 9.0%, respectively; RR = 0.14; 95% CI, 0.02 to 0.82). No severe bleeding complications attributable to urokinase were observed.Three times weekly urokinase rinsing reduces the incidence of CVC-related CoNS infection in patients treated with intensive cytotoxic therapy for hematologic malignancies, with acceptable safety.
Implementation of device therapy (cardiac resynchronization therapy and implantable cardioverter defibrillator) for patients with heart failure in Europe: changes from 2004 to 2008
Authors: Dirk J. van Veldhuisen, Alexander H. Maass, Silvia G. Priori, Pelle Stolt, Isabelle C. van Gelder, Kenneth Dickstein, Karl Swedberg
Journal: European Journal of Heart Failure (2009)
Thinking In and Out of the Box When It Comes to Gastric Cancer and Cyclooxygenase-2
Authors: Julie G. Izzo, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2007)

Prostaglandin G/H synthetase or cyclooxygenase (COX) was discovered in the 1970s, when it was noted that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) inhibited its proinflammatory activity. Subsequent studies in humans revealed that COX-2, one of the two COX isoforms, participated in colon cancer progression (familial adenomatous polyposis [FAP], Gardner’s syndrome, and sporadic colon cancer) and that its inhibition by the NSAIDs could have a preventive effect. These studies generated a great deal of scientific and commercial enthusiasm culminating in the approval of celecoxib in 1999 by the US Food and Drug Administration for the prevention of colorectal polyps in patients with FAP. COX-2 is the key in the metabolism of arachidonic acid and it catabolizes the biosynthesis of five function-specific prostaglandins (PG) including PGE2, PGD2, PGF2a, PGI2, and thromboxane. 9 As opposed to COX-1, which is physiologically constitutively expressed in a variety of tissues, COX-2 expression is absent under normal conditions but its expression is rapid in response to proinflammatory cytokines and certain hormones. COX-2 expression is aberrantly upregulated in a wide variety of human preneoplastic and neoplastic (breast, gastrointestinal, bladder, lung, and prostate) conditions. COX-2 overexpression can lead to the production of PGE2 and to a lesser extent thromboxane, both implicated in angiogenesis, cell proliferation, cell survival, migration, invasion, and modulation of host immune cells. Importantly, COX-2–derived PGE2 can cross-talk with other molecular pathways important for cancer progression (Fig 1). An example would be the activation of the epidermal growth factor receptor pathway responsible for increased cell motility, invasion, and metastases (Fig 1). Since 1992, there have been approximately 10,962 COX-2– related publications and many studies of human cancer have associated its overexpression with poor patient outcome as well as with large tumor size and lymph node and distant metastases. In this issue of the Journal, de Maat et al report on COX-2 in gastric cancer by adopting a novel approach to judge the impact of “underexpression or lack of expression” on patient outcome. To our