bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitumor activities and on‐target toxicities mediated by a TRAIL receptor agonist following cotreatment with panobinostat
Authors: Martin Ben P. , Frew Ailsa J. , Bots Michael , Fox Stephen , Long Fenella , Takeda Kazuyoshi , Yagita Hideo , Atadja Peter , Smyth Mark J. , Johnstone Ricky W. 
Published: August 2010

AbstractThe recent development of novel targeted anticancer therapeutics such as histone deacetylase inhibitors (HDACi) and activators of the TRAIL pathway provide opportunities for the introduction of new treatment regimens in oncology. HDACi and recombinant TRAIL or agonistic anti‐TRAIL receptor antibodies have been shown to induce synergistic tumor cell apoptosis and some therapeutic activity in vivo. Herein, we have used syngeneic preclinical models of human solid cancers to demonstrate that the HDACi panobinostat can sensitize tumor cells to apoptosis mediated by the anti‐mouse TRAIL receptor antibody MD5‐1. We demonstrate that the combination of panobinostat and MD5‐1 can eradicate tumors grown subcutaneously and orthotopically in immunocompetent mice, while single agent treatment has minimal effect. However, escalation of the dose of panobinostat to enhance antitumor activity resulted in on‐target MD5‐1‐mediated gastrointestinal toxicities that were fatal to the treated mice. Studies performed in mice with knockout of the TRAIL receptor showed that these mice could tolerate doses of the panobinostat/MD5‐1 combination that were lethal in wild type mice resulting in superior tumor clearance. Given that clinical studies using HDACi and activators of the TRAIL pathway have been initiated, our preclinical data highlight the potential toxicities that could limit the use of such a treatment regimen. Our studies also demonstrate the power of using syngeneic in vivo tumor models as physiologically relevant preclinical systems to test the antitumor effects and identify potential side effects of novel anticancer regimens.
Analysis of tumor antigen‐specific T cells and antibodies in cancer patients treated with radiofrequency ablation
Authors: Widenmeyer Melanie , Shebzukhov Yuriy , Haen Sebastian P. , Schmidt Diethard , Clasen Stephan , Boss Andreas , Kuprash Dmitri V. , Nedospasov Sergei A. , Stenzl Arnulf , Aebert Hermann , Wernet Dorothee , Stevanović Stefan , Pereira Philippe L. , Rammensee Hans‐Georg , Gouttefangeas Cécile 
Published: August 2010

AbstractRadiofrequency (RF) ablation is a minimally invasive technique routinely applied for the treatment of primary and secondary liver tumors. It induces cell death by thermal coagulative necrosis of tumor tissues, whereas cellular metabolism can still take place in a transition zone surrounding the necrotic area. An increase in heat shock protein expression occurs shortly after treatment, suggesting that the induction of activating signals may stimulate the host immune system. In addition, various effects on immune effectors have also been observed, including stimulation of tumor‐directed T lymphocytes. Here, we prospectively assessed the activation of tumor antigen‐specific antibodies, as well as antigen‐specific CD4+ and CD8+ T cells in patients suffering from primary or secondary malignancies and treated by RF ablation with or without concomitant chemotherapy. An increase of antibodies (in 4 patients of 49), CD4+ T cells or CD8+ T cells (in 2 patients of 49) could be detected several weeks to months following intervention. These findings suggest that in addition to the local control of tumor growth, RF ablation can provide the appropriate conditions for activating tumor‐antigen specific immune responses.
Transcriptional characteristics of familial non‐BRCA1/BRCA2 breast tumors
Authors: Fernández‐Ramires Ricardo , Gómez Gonzalo , Muñoz‐Repeto Iván , de Cecco Loris , Llort Gemma , Cazorla Alicia , Blanco Ignacio , Gariboldi Manuela , Pierotti Marco Alessandro , Benítez Javier , Osorio Ana 
Published: August 2010

AbstractTo better understand the alterations present in the group of the so‐called BRCAX tumors, we have used a cDNA microarray containing genes related to tumorigenesis and analyzed a series of 49 tumors consisting of 13 BRCA1, 14 BRCAX and 22 sporadic. We have confirmed that the BRCAX tumors are heterogeneous and can be divided in at least two main subgroups, so‐called A and B, transcriptionally distinguishable and with different altered pathways within each of the groups. We have found that BRCAX‐A and B subgroups, can be classified as Luminal A and Luminal B, respectively, taking into account the intrinsic phenotypes defined for the sporadic breast tumors. We have found that, at the somatic level, the BRCAX‐B tumors are identical to their sporadic Luminal B counterparts, whereas BRCAX‐A, despite having a Luminal A phenotype, shows additional genomic alterations. We have found 21 deregulated genes in the BRCAX‐A group that we have called “the BRCAX susceptibility pathway” and suggested it as a candidate to search for new genes involved in the inherited susceptibility underlying the disease in this group.
The B cell antigen receptor in atypical chronic lymphocytic leukemia with t(14;19)(q32;q13) demonstrates remarkable stereotypy
Authors: Schweighofer Carmen D. , Huh Yang O. , Luthra Rajyalakshmi , Sargent Rachel L. , Ketterling Rhett P. , Knudson Ryan A. , Barron Lynn L. , Medeiros L. Jeffrey , Keating Michael J. , Abruzzo Lynne V. 
Published: August 2010

AbstractThe t(14;19)(q32;q13) is a recurrent chromosomal translocation reported in a variety of B‐cell leukemias and lymphomas, including chronic lymphocytic leukemia (CLL). CLL cases associated with t(14;19) often have atypical morphologic and immunophenotypic features and unmutated immunoglobulin heavy chain (IGH) variable region (V) genes, associated with an aggressive clinical course. We analyzed IGHV somatic mutation status and gene use in 11 patients with t(14;19)‐positive CLL. All cases were unmutated, and the IGHV genes in 10 cases showed minimal deviation from germline sequences. In 7 of 11 patients, we found homologous heavy chain rearrangements using IGHV4‐39; light chain analysis revealed identical IGKV1‐39 use. Corresponding V‐(D)‐J sequences demonstrated remarkable stereotypy of the immunoglobulin heavy and kappa light chain complementarity determining region 3 (H/K CDR3) genes. These findings raise the possibility that specific antigen drive is involved in the clonal development and/or selection of t(14;19)(q32;q13)‐positive CLL cells. Our findings support the hypothesis that stimulatory signals through specific antigen receptors may promote the expansion of either CLL precursor cells or CLL clones that harbor distinct chromosomal abnormalities.
The role of hepatocyte growth factor activator inhibitor (HAI)‐1 and HAI‐2 in endometrial cancer
Authors: Nakamura Keiichiro , Hongo Atsushi , Kodama Junichi , Hiramatsu Yuji 
Published: August 2010

AbstractHepatocyte growth factor activator inhibitors (HAI‐1 and HAI‐2) are Kunitz‐type serine protease inhibitors that have a broad inhibitory spectrum against serine proteases. This is the first study to investigate the role of HAI‐1 and HAI‐2 in endometrial cancer. We investigated the biological functions of HAI‐1 and HAI‐2 using KLE and HEC‐251 endometrial cancer cell lines, thus HAI‐1 and HAI‐2 were examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. HAI‐1 and HAI‐2 showed potential inhibitory effects on cell proliferation, migration and cellular invasion by reduction of matriptase and hepsin expression. This in turn led to an increase in the levels of E‐cadherin and Slug, and a reduction in the levels of Vimentin, SIP1, Snail and Twist, and hence ER and PR signal transduction in endometrial cancer cells. The levels of HAI‐1 and HAI‐2 expression were significantly decreased in endometrial cancer specimens relative to the corresponding normal endometrium specimens. Low HAI‐1 and HAI‐2 expression was a significant predictor for a poor prognosis compared with high HAI‐1 and HAI‐2 expression. These findings indicate that HAI‐1 and HAI‐2 could be considered as therapeutic targets and used as favorable prognosis markers for endometrial cancer.
Pattern and clinical significance of cancer‐testis gene expression in head and neck squamous cell carcinoma
Authors: Cuffel Cyril , Rivals Jean‐Paul , Zaugg Yannick , Salvi Suzanne , Seelentag Walter , Speiser Daniel E. , Liénard Danielle , Monnier Philippe , Romero Pedro , Bron Luc , Rimoldi Donata 
Published: August 2010

AbstractCancer‐testis (CT) antigens comprise families of tumor‐associated antigens that are immunogenic in patients with various cancers. Their restricted expression makes them attractive targets for immunotherapy. The aim of this study was to determine the expression of several CT genes and evaluate their prognostic value in head and neck squamous cell carcinoma (HNSCC). The pattern and level of expression of 12 CT genes (MAGE‐A1, MAGE‐A3, MAGE‐A4, MAGE‐A10, MAGE‐C2, NY‐ESO‐1, LAGE‐1, SSX‐2, SSX‐4, BAGE, GAGE‐1/2, GAGE‐3/4) and the tumor‐associated antigen encoding genes PRAME, HERV‐K‐MEL, and NA‐17A were evaluated by RT‐PCR in a panel of 57 primary HNSCC. Over 80% of the tumors expressed at least 1 CT gene. Coexpression of three or more genes was detected in 59% of the patients. MAGE‐A4 (60%), MAGE‐A3 (51%), PRAME (49%) and HERV‐K‐MEL (42%) were the most frequently expressed genes. Overall, the pattern of expression of CT genes indicated a coordinate regulation; however there was no correlation between expression of MAGE‐A3/A4 and BORIS, a gene whose product has been implicated in CT gene activation. The presence of MAGE‐A and NY‐ESO‐1 proteins was verified by immunohistochemistry. Analysis of the correlation between mRNA expression of CT genes with clinico‐pathological characteristics and clinical outcome revealed that patients with tumors positive for MAGE‐A4 or multiple CT gene expression had a poorer overall survival. Furthermore, MAGE‐A4 mRNA positivity was prognostic of poor outcome independent of clinical parameters. These findings indicate that expression of CT genes is associated with a more malignant phenotype and suggest their usefulness as prognostic markers in HNSCC.
Tumor infiltration by FcγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma
Authors: Sconocchia Giuseppe , Zlobec Inti , Lugli Alessandro , Calabrese Diego , Iezzi Giandomenica , Karamitopoulou Eva , Patsouris Efstratios S. , Peros George , Horcic Milo , Tornillo Luigi , Zuber Markus , Droeser Raoul , Muraro Manuele G. , Mengus Chantal , Oertli Daniel , Ferrone Soldano , Terracciano Luigi , Spagnoli Giulio C. 
Published: August 2010

AbstractThe prognostic significance of macrophage and natural killer (NK) cell infiltration in colorectal carcinoma (CRC) microenvironment is unclear. We investigated the CRC innate inflammatory infiltrate in over 1,600 CRC using two independent tissue microarrays and immunohistochemistry. Survival time was assessed using the Kaplan–Meier method and Cox proportional hazards regression analysis in a multivariable setting. Spearman's rank correlation tested the association between macrophage and lymphocyte infiltration. The Basel study included over 1,400 CRCs. The level of CD16+ cell infiltration correlated with that of CD3+ and CD8+ lymphocytes but not with NK cell infiltration. Patients with high CD16+ cell infiltration (score 2) survived longer than patients with low (score 1) infiltration (p = 0.008), while no survival difference between patients with score 1 or 2 for CD56+ (p = 0.264) or CD57+ cell (p = 0.583) infiltration was detected. CD16+ infiltrate was associated with improved survival even after adjusting for known prognostic factors including pT, pN, grade, vascular invasion, tumor growth and age [(p = 0.001: HR (95% CI) = 0.71 (0.6–0.9)]. These effects were independent from CD8+ lymphocyte infiltration [(p = 0.036: HR (95% CI) = 0.81 (0.7–0.9)] and presence of metastases [(p = 0.002: HR (95% CI) = 0.43 (0.3–0.7)]. Phenotypic studies identified CD16+ as CD45+CD33+CD11b+CD11c+ but CD64− HLA‐DR‐myeloid cells. Beneficial effects of CD16+ cell infiltration were independently validated by a study carried out at the University of Athens confirming that patients with CD16 score 2 survived longer than patients with score 1 CRCs (p = 0.011). Thus, CD16+ cell infiltration represents a novel favorable prognostic factor in CRC.
Thermal processes in red blood cells exposed to infrared laser tweezers (λ = 1064 nm)
Authors: Krasnikov Ilya , Seteikin Alexey , Bernhardt Ingolf 
Published: August 2010

AbstractContinuous‐wave laser micro‐beams are generally used as diagnostic tools in laser scanning microscopes or in the case of near‐infrared (NIR) micro‐beams, as optical traps for cell manipulation and force characterization. Because single beam traps are created with objectives of high numerical aperture, typical trapping intensities and photon flux densities are in the order of 106 W/cm2 and 103 cm–2 s–1, respectively. The main idea of our theoretical study was to investigate the thermal reaction of RBCs irradiated by laser micro‐beam. The study is supported by the fact that many experiments have been carried out with RBCs in laser NIR tweezers. In the present work it has been identified that the laser affects a RBC with a density of absorbed energy at approximately 107 J/cm3, which causes a temperature rise in the cell of about 7–12 °C. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of vertical trabeculae on the compressive strength of the human vertebra
Authors: Fields Aaron J , Lee Gideon L , Liu X Sherry , Jekir Michael G , Guo X Edward , Keaveny Tony M 
Published: August 2010

Abstract
Vertebral strength, a key etiologic factor of osteoporotic fracture, may be affected by the relative amount of vertically oriented trabeculae. To better understand this issue, we performed experimental compression testing, high-resolution micro–computed tomography (µCT), and micro–finite-element analysis on 16 elderly human thoracic ninth (T9) whole vertebral bodies (ages 77.5 ± 10.1 years). Individual trabeculae segmentation of the µCT images was used to classify the trabeculae by their orientation. We found that the bone volume fraction (BV/TV) of just the vertical trabeculae accounted for substantially more of the observed variation in measured vertebral strength than did the bone volume fraction of all trabeculae (r2 = 0.83 versus 0.59, p &lt; .005). The bone volume fraction of the oblique or horizontal trabeculae was not associated with vertebral strength. Finite-element analysis indicated that removal of the cortical shell did not appreciably alter these trends; it also revealed that the major load paths occur through parallel columns of vertically oriented bone. Taken together, these findings suggest that variation in vertebral strength across individuals is due primarily to variations in the bone volume fraction of vertical trabeculae. The vertical tissue fraction, a new bone quality parameter that we introduced to reflect these findings, was both a significant predictor of vertebral strength alone (r2 = 0.81) and after accounting for variations in total bone volume fraction in multiple regression (total R2 = 0.93). We conclude that the vertical tissue fraction is a potentially powerful microarchitectural determinant of vertebral strength. © 2011 American Society for Bone and Mineral Research.
Elevated cytokine production restores bone resorption by human Btk-deficient osteoclasts
Authors: Danks Lynett , Workman Sarita , Webster David , Horwood Nicole J 
Published: August 2010

Abstract
Mutations in Bruton's tyrosine kinase (Btk) cause the B-cell disorder X-linked agammaglobulinaemia (XLA) in humans, but the effect of Btk deficiency in human bone health has not been investigated previously. In this study, we show that human Btk-deficient osteoclasts are defective at resorption activity in vitro owing to a dysregulation of the actin cytoskeletal function. Contrary to expectation, XLA patients did not exhibit increased bone density or alterations in serum markers of bone turnover, indicating that a potential compensation mechanism normalizes bone homeostasis. In contrast to the bone turnover markers, the levels of inflammatory cytokines interleukin 6 (IL-6), IL-1β, and tumor necrosis factor α (TNF-α) were significantly elevated in XLA patients' serum compared with control individuals. Supplementation of osteoclast cultures from normal and XLA subjects with serum from XLA patients or recombinant inflammatory cytokines IL-6, IL-1β, and TNF-α resulted in a stimulation of osteoclast activity in vitro, whereas the addition of cytokine-neutralizing antibodies inhibited this stimulatory effect, confirming that elevated inflammatory cytokines in XLA serum heightened osteoclast activity in vitro. This study provides novel evidence that Btk signaling is crucial for optimal actin cytoskeletal organization and lacunar resorption in isolated osteoclasts. In XLA patients, however, these inherent osteoclast defects are corrected by increased inflammatory cytokine levels, restoring osteoclast activity and leading to the normalization of bone density. © 2011 American Society for Bone and Mineral Research.
Isolated sleep paralysis and fearful isolated sleep paralysis in outpatients with panic attacksb
Authors: Sharpless Brian A. , McCarthy Kevin S. , Chambless Dianne L. , Milrod Barbara L. , Khalsa Shabad‐Ratan , Barber Jacques P. 
Published: August 2010

AbstractIsolated sleep paralysis (ISP) has received scant attention in clinical populations, and there has been little empirical consideration of the role of fear in ISP episodes. To facilitate research and clinical work in this area, the authors developed a reliable semistructured interview (the Fearful Isolated Sleep Paralysis Interview) to assess ISP and their proposed fearful ISP (FISP) episode criteria in 133 patients presenting for panic disorder treatment. Of these, 29.3% met lifetime ISP episode criteria, 20.3% met the authors' lifetime FISP episode criteria, and 12.8% met their recurrent FISP criteria. Both ISP and FISP were associated with minority status and comorbidity. However, only FISP was significantly associated with posttraumatic stress disorder, body mass, anxiety sensitivity, and mood and anxiety disorder symptomatology. © 2010 Wiley Periodicals, Inc. J Clin Psychol 66:1–15, 2010.
A comparison of the millon behavioral medical diagnostic and millon behavioral health inventory with medical populations
Authors: Wise Edward A. , Streiner David L. 
Published: August 2010

AbstractThere is a lack of normative data on broadband omnibus types of personality tests with medical populations. In fact, the only two tests normed on medical populations are the Millon Behavioral Medicine Diagnostic (MBMD) and the Millon Behavioral Health Inventory (MBHI). The internal consistency, test‐retest reliabilities, and validity studies of these instruments are reviewed and compared in an effort to aid clinicians in discerning their relative psychometric strengths and weaknesses. Due to the lack of validity studies with the MBMD and the fact that reliability limits the ceiling of validity coefficients, the MBMD has yet to meet the challenges it was designed to meet. Implications for practice are addressed. © 2010 Wiley Periodicals, Inc. J Clin Psychol 66:1–11, 2010.
Kinetics and modeling of fructo‐oligosaccharide synthesis by immobilized fructosyltransferase from Rhodotorula sp.
Authors: Alvarado‐Huallanco Mónica B. , Maugeri‐Filho Francisco 
Published: August 2010

AbstractBACKGROUND: Fructosyltransferase synthesizes fructo‐oligosaccharides from sucrose. Data used in this work were obtained by an enzyme produced by Rhodotorula sp., a microorganism isolated from fruit samples from the Brazilian Atlantic Forest, which was immobilized in an inorganic support, consisting of a niobium and graphite alloy.RESULT: All essays were conducted using enzymes at two purification grades, highly and partially purified enzymes, as comparison. The results were not significantly different between the two enzyme grades, mainly concerning the final fructo‐oligossacharides yield, which were around 46%. Concerning the kinetics, the enzyme follows the Michaelis–Menten equation with inhibition by sucrose (above 60%). Also, a competitive inhibition by glucose was observed on sucrose, kestose and nystose uptakes. The immobilization of the enzyme was by ion exchange on the surface of the particles, since the support is a charged and compact solid, with negligible porosity. The mathematic model includes mass balances, considering the resistance to external mass transfer. A parameter sensitivity analysis and parameter fitting were performed by simulations and the model was validated by comparison with experimental data.CONCLUSION: The model fitted experimental data well, with deviations lower than 5% concerning FOS concentrations, indicating that it can be used in the design and control of bioreactors, either using purified or partially purified enzyme. Copyright © 2010 Society of Chemical Industry
Use of a low profile ultrasound transducer for coronary sinus cannulation: A pilot study
Authors: Chandraratna Premindra A. , Kosar Erol , Gajanayaka Ranil , Makkena Surendra M. , Gupta Anjlie , Ranasinghe Sachini 
Published: August 2010

AbstractBackground.Cardiac resynchronization therapy with biventricular pacing has been shown to be beneficial in improving heart failure in patients with prolonged QRS duration (≥120 ms) and low ejection fraction (≤35%). Unsuccessful cannulation of the coronary sinus (CS) has been reported in up to 10% of cases. The feasibility of the transthoracic continuous cardiac imaging for coronary sinus cannulation has not been previously demonstrated.Methods and Results.We developed a 2.5‐MHz hemi‐spherical continuous cardiac imaging transducer (CONTISON), mounted in an external housing, to permit steering in 360°. The transducer was attached to the chest wall using an adhesive ring. The CS was easily imaged by echocardiography by placing the transducer just medial to the apex and tilting it dorsally. The feasibility study was done in 11 patients. CS ostium and body were imaged in all patients. Cannulation was successfully achieved in nine patients with a mean cannulation time of 1 minute 16 seconds. In two patients, poor image quality precluded adequate visualization of CS. Fluoroscopy was not used for cannulation.Conclusion.We demonstrated the feasibility of using the CONTISON echography transducer for the guidance CS cannulation. This technique could expedite CS cannulation and reduce radiation exposure. Further studies comparing ultrasound versus fluoroscopy for CS cannulation appear warranted. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:426–429, 2010