bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined GM-CSF and IL-12 gene therapy synergistically suppresses the growth of orthotopic liver tumors
Authors: Chang Chun-Jung , Chen Yi-Hsiang , Huang Kai-Wen , Cheng Hao-Wei , Chan Suit-Fong , Tai Kuo-Feng , Hwang Lih-Hwa 
Published: February 2007

Abstract

Immunotherapy is often effective only for small tumor burdens and, in many cases, is restricted to subcutaneous tumors. Here, we investigated the antitumor effects of combination therapy with GM-CSF and IL-12 on orthotopic liver tumors with intermediate or large tumor volumes, or on chemically-induced multifocal liver tumors in animals. Adenoviruses encoding GM-CSF or IL-12 were injected intratumorally to animals bearing transplanted tumors, or injected via intrahepatic artery in animals with primary multifocal liver tumors induced by diethylnitrosamine. Our results demonstrated that IL-12, but not GM-CSF, monotherapy displayed significant therapeutic effects, whereas combination therapy with both cytokines displayed synergistic antitumor effects not only on transplanted tumor models with intermediate or large tumor loads, but also on carcinogen-induced multifocal liver tumors. Effector cell analyses, revealed by

in vivo

cell subset depletion, flow cytometry analysis, and immunohistochemical staining of tumor infiltrates, indicated that NK cells were the prominent antitumor effectors for the IL-12–mediated antitumor activity, whereas CD8+ T cells, NKT cells, and macrophages were more important than NK cells in the combination therapy–mediated antitumor effects. Both IL-12 monotherapy and combination therapy could induce various types of effectors and high levels of IFN-γ; however, the latter induced much higher levels than the former, which may explain why combination therapy is superior to IL-12 monotherapy.

Conclusion:

Combination therapy with GM-CSF and IL-12 represents a promising immunotherapy strategy for treating orthotopic, widespread liver tumors. (Hepatology 2007;45:746–754.)
Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis
Authors: Pockros Paul J. , Jeffers Lennox , Afdhal Nezam , Goodman Zachary D. , Nelson David , Gish Robert G. , Reddy Rajender K. , Reindollar Robert , Rodriguez-Torres Maribel , Sullivan Sarah , Blatt Lawrence M. , Faris-Young Sima 
Published: February 2007

Abstract

Interferon-γ1b (IFN-γ1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-γ1b 100 μg (group 1, n = 169), IFN-γ1b 200 μg (group 2, n = 157), or placebo (group 3, n = 162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score = 5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively;

P

> 0.05). Analysis of IFN-γ–inducible biomarkers revealed that interferon-inducible T cell–alpha chemoattractant (ITAC), an IFN-γ–inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-γ1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis.

Conclusion:

IFN-γ1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-γ1b. (Hepatology 2007;45:569–578.)
The model for end-stage liver disease (MELD)
Authors: Kamath Patrick S. , Kim Ray W. 
Published: February 2007

Abstract

The Model for End-stage Liver Disease (MELD) was initially created to predict survival in patients with complications of portal hypertension undergoing elective placement of transjugular intrahepatic portosystemic shunts. The MELD which uses only objective variables was validated subsequently as an accurate predictor of survival among different populations of patients with advanced liver disease. The major use of the MELD score has been in allocation of organs for liver transplantation. However, the MELD score has also been shown to predict survival in patients with cirrhosis who have infections, variceal bleeding, as well as in patients with fulminant hepatic failure and alcoholic hepatitis. MELD may be used in selection of patients for surgery other than liver transplantation and in determining optimal treatment for patients with hepatocellular carcinoma who are not candidates for liver transplantation. Despite the many advantages of the MELD score, there are approximately 15%-20% of patients whose survival cannot be accurately predicted by the MELD score. It is possible that the addition of variables that are better determinants of liver and renal function may improve the predictive accuracy of the model. Efforts at further refinement and validation of the MELD score will continue. (Hepatology 2007;45:797–805.)
The effects of HCV infection and management on health-related quality of life
Authors: Younossi Zobair , Kallman Jillian , Kincaid John 
Published: February 2007

Abstract

Infection with HCV leads to an array of symptoms that compromise health-related quality of life (HRQL). Chronic hepatitis C is treated primarily with pegylated interferon (peg-IFN) and an inosine 5′ monophosphate dehydrogenase inhibitor, ribavirin (RBV), with the goal of achieving a sustained virologic response (SVR). SVR reduces the rate of hepatic fibrosis and other disease-related complications and, in turn, increases HRQL. Although combination therapy with peg-IFN and RBV produces SVRs in more than 50% of treated patients, it is associated with side effects that can reduce short-term HRQL, can lead to dose reductions and discontinuations, and may impair treatment response. Fatigue and depression are common symptoms of chronic HCV infection that may also be caused by IFN-based therapy. Hemolytic anemia and IFN-mediated bone marrow suppression are well-known consequences of IFN/RBV therapy, often resulting in dose reductions or discontinuations, and have the potential to affect SVR rates. Management of these symptoms is vital to successful outcomes and generally relies on therapy that is adjunctive to the primary treatment of the viral infection itself. Several new drugs with the potential to increase SVR rates without compromising HRQL are in development.

Conclusion:

The relationship of chronic HCV infection, treatment, and HRQL is complex. Successful treatment of chronic hepatitis C requires an understanding of the intricacies of this relationship and appropriate management of treatment-related symptoms. (Hepatology 2007;45:806–816.)
Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity
Authors: Rollier Christine S. , Paranhos-Baccala Glaucia , Verschoor Ernst J. , Verstrepen Babs E. , Drexhage Joost A. R. , Fagrouch Zahra , Berland Jean-Luc , Komurian-Pradel Florence , Duverger Blandine , Himoudi Nourredine , Staib Caroline , Meyr Marcus , Whelan Mike , Whelan Joseph A. , Adams Victoria A. , Larrea Esther , Riezu José I. , Lasarte Juan José , Bartosch Birke , Cosset Francois L. , Spaan Willy J. M. , Diepolder Helmut M. , Pape Gerd R. , Sutter Gerd , Inchauspe Genevieve , Heeney Jonathan L. 
Published: February 2007

Abstract

Broad T cell and B cell responses to multiple HCV antigens are observed early in individuals who control or clear HCV infection. The prevailing hypothesis has been that similar immune responses induced by prophylactic immunization would reduce acute virus replication and protect exposed individuals from chronic infection. Here, we demonstrate that immunization of naïve chimpanzees with a multicomponent HCV vaccine induced robust HCV-specific immune responses, and that all vaccinees exposed to heterologous chimpanzee-adapted HCV 1b J4 significantly reduced viral RNA in serum by 84%, and in liver by 99% as compared to controls (

P

= 0.024 and 0.028, respectively). However, despite control of HCV in plasma and liver in the acute period, in the chronic phase, 3 of 4 vaccinated animals developed persistent infection. Analysis of expression levels of proinflammatory cytokines in serial hepatic biopsies failed to reveal an association with vaccine outcome. However, expression of IDO, CTLA-4 (1) and PD-1 levels in liver correlated with clearance or chronicity.

Conclusion:

Despite early control of virus load, a virus-associated tolerogenic-like state can develop in certain individuals independent of vaccination history. (Hepatology 2007;45:602–613.)
A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis
Authors: Oertelt Sabine , Rieger Roman , Selmi Carlo , Invernizzi Pietro , Ansari Aftab A. , Coppel Ross L. , Podda Mauro , Leung Patrick S.C. , Gershwin Eric M. 
Published: February 2007

Abstract

The antimitochondrial response in primary biliary cirrhosis (PBC) is the most highly directed and specific self-reacting antibody in human immunopathology. Originally, antimitochondrial antibodies (AMAs) were detected by indirect immunofluorescence (IIF) and found in approximately 90% of well-documented patients with PBC. The introduction of recombinant autoantigens and the use of immunoblotting have increased the sensitivity and specificity of AMAs, and they are now considered positive in approximately 95% of patients with PBC. Clearly, accurate autoantibody detection represents one of the fundamental requirements for reliable diagnostics in autoimmunity. To address the 5% of AMA-negative patients with PBC, we have generated and validated a bead assay for the detection of AMA. We enrolled 120 patients with PBC, including a non-random group of 30 rigorously proven AMA-negative patients, 50 healthy subjects, and 74 controls with autoimmune diseases (18 with primary sclerosing cholangitis, 16 with autoimmune hepatitis, and 40 with systemic lupus erythematosus). Individual bead assays were done with the three mitochondrial autoantigens, PDC-E2, BCOADC-E2, and OGDC-E2. As expected, 90 of 90 previously known AMA-positive patients remained positive with this assay but, interestingly, 20% of the rigorously defined AMA-negative patient group had antibodies to one or more of the mitochondrial autoantigens. Furthermore, 100% of these newly detected AMA-positive patients were anti-nuclear antibody (ANA) positive.

Conclusion:

The development of this assay reflects the potential for automated detection with rapid and reliable assaying and further highlights the diminished number of truly AMA-negative PBC patients. (Hepatology 2007;45:659–665.)
Bone regeneration of porous β‐tricalcium phosphate (Conduit™ TCP) and of biphasic calcium phosphate ceramic (Biosel®) in trabecular defects in sheep
Authors: Bodde Esther W.H. , Wolke Joop G.C. , Kowalski Rick S.Z. , Jansen John A. 
Published: February 2007

AbstractIn this study bone regeneration between porous β‐tricalcium phosphate (Conduit™ TCP) and biphasic calcium phosphate ceramic (Biosel®), with a hydroxyapatite/β‐TCP ratio of 75/25, was compared. The ceramic particles were implanted in sheep trabecular bone for 3, 12, and 26 weeks. Histomorphometrical analysis revealed that Conduit™ degraded significantly during time and only 36% of the material was left at 26 weeks implantation time. Biosel®, in contrast, remained nearly intact. The degradation of Conduit™ was due to dissolution as well as cell‐mediated. Biosel® showed a high cellular intervention, although this material did not degrade. Both materials were osteoconductive. The amount of newly formed bone appeared greater in the Conduit™ group after 26 weeks (46% ± 8% as compared to 37% ± 8% for Biosel®), but this difference was not significant. Bone distribution over the defect was homogeneous in Conduit™, whereas Biosel® showed significantly more bone in the periphery of the defect after 26 weeks in comparison to the center. In conclusion, both ceramics are biocompatible and osteoconductive. Degradation showed a difference in amount and in cellular events, with more degraded Conduit™ TCP with less cellular intervention as compared to Biosel®. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
The release of nickel from orthodontic NiTi wires is increased by dynamic mechanical loading but not constrained by surface nitridation
Authors: Peitsch T. , Klocke A. , Kahl‐Nieke B. , Prymak O. , Epple M. 
Published: February 2007

AbstractThe influence of dynamic mechanical loading and of surface nitridation on the nickel release from superelastic nickel–titanium orthodontic wires was investigated under ultrapure conditions. Commercially available superelastic NiTi arch wires (size 0.018 × 0.025″) without surface modification (Neo Sentalloy) and with nitrogen ion implantation surface treatment (Neo Sentalloy Ionguard) were analyzed. Mechanical loading of wire segments with a force similar to the physiological situation was performed with a frequency of 5 Hz in ultrapure water and saline solution, respectively. The release of nickel was monitored by atomic absorption spectroscopy for up to 36 days. The mechanically loaded wires released significantly more nickel (∼45 ng cm−2 d−1) than did nonloaded wires (<1 ng cm−2 d−1). There was no statistically significant effect of the testing solution (water or NaCl) or of the surface nitridation. The total amount of released nickel was small in all cases, but may nevertheless account for the occasional clinical observations of adverse reactions during application of NiTi‐based orthodontic appliances. The surface nitridation did not constrain the release of nickel from NiTi under continuous mechanical stress. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
In vitro studies of platelet adhesion, activation, and protein adsorption on curcumin‐eluting biodegradable stent materials
Authors: Pan C.J. , Shao Z.Y. , Tang J.J. , Wang J. , Huang N. 
Published: February 2007

AbstractA major complication of coronary stenting is in‐stent restenosis (ISR) due to thrombus formation. We hypothesized that locally released curcumin from coronary stent surface would inhibit ISR due to thrombus formation because of antithrombosis of curcumin. In the present work, curcumin‐eluting polylactic acid‐co‐glycolic acid (PLGA) films were fabricated and their properties in vitro were investigated. The in vitro platelet adhesion and activation, as well as protein adsorption on curcumin‐loading PLGA films were investigated to evaluate the blood compatibility of curcumin‐eluting films. The structure of curcumin‐eluting PLGA film and control was examined by Fourier transform infrared spectroscopy and X‐ray photoelectron spectroscopy indicating that the peaks of curcumin did not shift in curcumin‐eluting films. The results of contact angle and surface free energy indicated that loading curcumin in PLGA would make PLGA become more hydrophilic, which contributed to the increase of polar fraction of surface free energy. With the increase of curcumin in films, platelets adhering to the curcumin‐eluting films decreased significantly. The number of activation platelets decreased after incorporating curcumin in PLGA films. Loading curcumin in PLGA film can markedly reduce the fibrinogen adsorption. All results indicated that incorporating curcumin in PLGA film can improve the blood compatibility of PLGA films. It can be used to fabricate drug‐eluting stent to prevent thrombosis formation. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Surface modified poly(L‐lactide‐co‐ε‐caprolactone) microspheres as scaffold for tissue engineering
Authors: Garkhal Kalpna , Verma Shalini , Tikoo K. , Kumar Neeraj 
Published: February 2007

AbstractP‐15 modified poly(L‐lactide‐co‐ε‐caprolactone) (PLCL) microspheres were investigated as scaffolds for tissue engineering applications. PLCL copolymer was synthesized by ring opening polymerization and was composed of a soft matrix of mainly ε‐caprolactone moieties and hard domains containing more of L‐lactide units thus exhibiting a rubber like elasticity responsible for providing mechanical strength to scaffolds. Microspheres were fabricated by solvent evaporation method and surface modified with P‐15, a synthetic analogue of collagen. These were then evaluated for cell adhesion, ECM formation and cell proliferation. Anchorage dependent cell lines LLCPK‐1 and L6 were seeded on PLCL microspheres (unmodified surface activated microspheres) and P‐15‐PLCL microspheres (P‐15 modified microspheres). P‐15 modified microspheres showed significantly higher cell adhesion and viability than unmodified microspheres. Scanning electron microscopy also revealed copious amount of extra‐cellular matrix production by P‐15. Initial results of cell culture experiment on two different cell lines suggested that the growth of LLCPK‐1 in a 3D environment with P‐15 modified microspheres is via spreading and flattening on the surface of scaffold followed by formation of a sheet‐like structure while L6 grew in the form of multilayered structures with formation of interparticulate cellular bridges. The 3D moldable nature, combined with modification of surface chemistry with cell adhesion molecules such as P‐15 to enhance proliferation of epithelial cells and myoblasts, recommends further investigation of P‐15‐PLCL microspheres for production of an ideal scaffold for soft tissue engineering. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Biocompatilibity‐related surface characteristics of oxidized NiTi
Authors: Danilov Anatoli , Tuukkanen Tuomas , Tuukkanen Juha , Jämsä Timo 
Published: February 2007

AbstractIn the present study, we examined the effect of NiTi oxidation on material surface characteristics related to biocompatibility. Correspondence between electron work function (EWF) and adhesive force predicted by electron theory of adsorption as well as the effect of surface mechanical stress on the adhesive force were studied on the nonoxidized and oxidized at 350, 450, and 600°C NiTi alloy for medical application. The adhesive force generated by the material surface towards the drops of α‐minimal essential medium (α‐MEM) was used as a characteristic of NiTi adsorption properties. The study showed that variations in EWF and mechanical stress caused by surface treatment were accompanied by variations in adhesive force. NiTi oxidation at all temperatures used gave rise to decrease in adhesive force and surface stress values in comparison to the nonoxidized state. In contrary, the EWF value revealed increase under the same condition. Variations in surface oxide layer thickness and its phase composition were also followed. The important role of oxide crystallite size in EWF values within the range of crystallite dimensions typical for NiTi surface oxide as an instrument for the fine regulation of NiTi adsorption properties was demonstrated. The comparative oxidation of pure titanium and NiTi showed that the effect of Ni on the EWF value of NiTi surface oxide is negligible. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Comparative in vitro study of the proliferation and growth of human osteoblast‐like cells on various biomaterials
Authors: Itthichaisri C. , Wiedmann‐Al‐Ahmad M. , Huebner U. , Al‐Ahmad A. , Schoen R. , Schmelzeisen R. , Gellrich N.‐C. 
Published: February 2007

AbstractIn vitro studies about the growth behavior of osteoblasts onto biomaterials is a basic knowledge and a screening method for the development and application of scaffolds in vivo. In this in vitro study human osteoblast‐like (HOB) cells were cultured on seven different biomaterials used in dental and craniomaxillofacial surgery, respectively. The tested biomaterials were synthetic biodegradable (MacroPore®, Ethisorb®, PDS®, Beriplast® P) and nonbiodegradable polymers (Palacos®) as well as calcium phosphate cement (BoneSource®) and titanium. The cell proliferation and cell colonization were analyzed by scanning electron microscopy and EZ4U‐test. Statistical analysis were performed. HOB‐like cells cultivated on Ethisorb showed the highest proliferation rate. The proliferation rate was statistically significant compared with Palacos, MacroPore, and BoneSource. Whereas, Beriplast, PDS, and titanium yielded lower proliferation rates. However, there was no statistically significant difference compared with Palacos, MacroPore, and BoneSource. SEM analysis showed no significant difference in individual cell features and cell colonization. But an infiltration and a growth of HOB‐like cells throughout the porous structure of Ethisorb, which is formed by crossing fibers, is a striking different feature (macrotopography). This feature can explain the highest proliferation rate of Ethisorb. The results showed that HOB‐like cells appear to be sensitive to substrate composition and topography. Moreover, the basis for further studies with such biomaterial/osteoblast constructs in vivo are provided. Further focusing points are developing techniques to fabricate three‐dimensional porous biomaterial/cell constructs, studying the tissue reaction and the bone regeneration of such constructs compared with the use of autologous bone. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Surface characterization and platelet adhesion studies for the mixed self‐assembled monolayers with amine and carboxylic acid terminated functionalities
Authors: Chuang Wen‐Hsi , Lin Jui‐Che 
Published: February 2007

AbstractThe mixed self‐assembled monolayers (SAM) prepared from long chain alkanethiols, HS(CH2)11NH2 and HS(CH2)10COOH, on gold are employed as the model surface for investigating the interactions between the biological environment and synthetic surface. A distinctive SAM preparation scheme was utilized in this investigation. The triethylamine was added to the alkanethiol solution during SAM formation and then followed by additional rinsing of SAM with 10% CH3COOH or 1% HCl ethanolic solution. The contact angle values of NH2 + COOH mixed SAMs were between those of the pure SAMs, except that it was prepared with solution mole fraction of amine‐terminated alkanethiol at 0.2. X‐ray photoelectron spectroscopy (XPS) analysis has indicated that these two distinctive SAM preparation procedures had both resulted in a reduction in oxidized sulfur species on pure NH2 terminated SAM. However, the procedure utilizing 1% HCl ethanolic washing solution was more effective in reducing the unbound thiol fraction and to form a pure NH2 SAM with better quality. XPS analysis has also revealed that the surface of NH2 + COOH mixed SAMs was “amine‐rich”. In vitro platelet adhesion assay has shown that the amount of adherent platelets on pure positive charged NH2 terminated SAM is less than that on anionic COOH terminated counterpart in both acidic ethanolic washing schemes. Moreover, the lowest platelet adhesion density was noted on the mixed SAM surfaces with surface amine mole fraction at 0.51 and 0.57. This finding suggests that the surface charge with near neutrality might be of importance in reducing platelet adhesion and activation on artificial biomaterial. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007