bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients
Authors: Ellebaek Eva , Iversen Trine Zeeberg , Junker Niels , Donia Marco , Engell-Noerregaard Lotte , Met Özcan , Hölmich Lisbet Rosenkrantz , Andersen Rikke Sick , Hadrup Sine Reker , Andersen Mads Hald , thor Straten Per , Svane Inge Marie 
Published: August 2012

Abstract

Background
Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections.

Methods
This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day.

Results
Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission.

Conclusion
Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.
Induction of interleukin-10 is dependent on p38 mitogen-activated protein kinase pathway in macrophages infected with porcine reproductive and respiratory syndrome virus
Authors: Hou Jun , Wang Lianghai , Quan Rong , Fu Yi , Zhang Hexiao , Feng Wen-hai 
Published: August 2012

AbstractBackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure and respiratory illness in pigs and usually establishes a persistent infection. Previous studies suggested that interleukin-10 (IL-10) could play a critical role in PRRSV-induced immunosuppression. However, the ability of PRRSV to induce IL-10 in infected cells is controversial. In this study, we further investigated this issue using PRRSV strain CH-1a, which is the first North American genotype strain isolated in China.ResultsPRRSV strain CH-1a could significantly up-regulate IL-10 production both at mRNA and protein levels in porcine alveolar macrophages (PAMs), bone marrow-derived macrophages (BMDMs), and monocyte-derived macrophages (MDMs). However, up-regulation of IL-10 by PRRSV was retarded by specific inhibitors of p38 mitogen-activated protein kinase (MAPK) (SB203580) and NF-κB (BAY11-7082). Additionally, p38 MAPK and NF-κB pathways but not ERK1/2 MAPK were actually activated in PRRSV-infected BMDMs as demonstrated by western blot analysis, suggesting that p38 MAPK and NF-κB pathways are involved in the induction of IL-10 by PRRSV infection. Transfection of PAMs and PAM cell line 3D4/21 (CRL-2843) with viral structural genes showed that glycoprotein5 (GP5) could significantly up-regulate IL-10 production, which was dependent on p38 MAPK and signal transducer and activator of transcription-3 (STAT3) activation. We also demonstrated that a full-length glycoprotein was essential for GP5 to induce IL-10 production.ConclusionsPRRSV strain CH-1a could significantly up-regulate IL-10 production through p38 MAPK activation.
The continual presence of C3d but not IgG glomerular capillary deposition in stage I idiopathic membranous nephropathy in patients receiving corticosteroid treatment
Authors: Zhang Rui , Zheng Zhi-yong , Lin Jian-song , Qu Li-juan , Zheng Feng 
Published: August 2012

Abstract

Background
Pathologic diagnosis of stage I idiopathic membranous nephropathy (MN-I) requires electron microscopy or immunohistochemistry that shows a glomerular capillary staining pattern of IgG and C3. However, it is not uncommon that renal biopsy did not obtain sufficient material for electron microscopy and that IgG and C3 staining in glomeruli largely lost at biopsy due to corticosteroid treatment. Since C3d is one of the final degradation products of C3 that is more stable in vivo, we determine if C3d staining could be used as a novel immunohistochemical marker for MN-I.

Methods and results
74 MN-I patients with electron microscopy proven MN-I were examined by immunoperoxidase staining of C3d. Intensive C3d staining was present in glomerular capillary like the staining pattern of IgG and C3 in MN-I. Importantly, in 40 MN-I patients who underwent corticosteroid treatment at biopsy the intensity and glomerular capillary pattern of C3d staining remained largely intact while the staining for IgG had substantially reduced and the pattern of glomerular capillary staining became unrecognizable.

Conclusions
C3d glomerular capillary staining may be a novel marker for pathologic diagnosis of MN-I that is continuously present at biopsy in patient who has received corticosteroid treatment.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2120780075734479
Primary central nervous system angiosarcoma: two case reports
Authors: Hackney James R , Palmer Cheryl Ann , Riley Kristen O , Cure Joel K , Fathallah-Shaykh Hassan M , Nabors Louis B 
Published: August 2012

Abstract

Introduction
Primary angiosarcoma of the brain is extremely rare; only 15 cases have been reported in adults over the last 25 years.

Case presentations
We describe two cases of primary angiosarcoma of the brain that are well characterized by imaging, histopathology, and immunohistochemistry. Case 1: our first patient was a 35-year-old woman who developed exophthalmos. Subtotal resection of a left extra-axial retro-orbital mass was performed. Case 2: our second patient was a 47-year-old man who presented to our facility with acute visual loss, word-finding difficulty and subtle memory loss. A heterogeneously-enhancing left sphenoid wing mass was removed. We also review the literature aiming at developing a rational approach to diagnosis and treatment, given the rarity of this entity.

Conclusions
Gross total resection is the standard of care for primary angiosarcoma of the brain. Adjuvant radiation and chemotherapy are playing increasingly recognized roles in the therapy of these rare tumors.
Non-Hodgkin’s Lymphoma of the synovium discovered in total knee arthroplasty: a case report
Authors: Visser Jetze , Busch Vincent JJF , de Kievit-van der Heijden Ineke M , ten Ham Arno M 
Published: August 2012

Abstract

Background
Musculoskeletal involvement occurs in 25% of patients with non-Hodgkin’s lymphoma (NHL). Primary lymphoma in the joint is rare. It can present as a bone lesion or as atypical soft tissue proliferation. NHL has an increased incidence in patients with autoimmune rheumatic diseases.

Case presentation
We present a case in which non-Hodgkin’s lymphoma was found coincidentally in the synovium during knee joint replacement surgery in a 69-year old woman with rheumatoid arthritis. Pigmented, vitreous tissue was resected, which turned out to be a diffuse large B-cell lymphoma after histological examination. The coincidental intraoperative finding of intra-articular non-Hodgkin’s lymphoma was reported twice before, presenting as synovial proliferation in elbow and shoulder surgery. In a few other cases non-Hodgkin’s lymphoma presented most often in the knee, as a bone lesion or, when soft tissue was involved, as arthritis.

Conclusion
Non-Hodgkin’s lymphoma should be considered in patients with autoimmune rheumatic diseases. In case of persistent arthritis, non-respondent to anti-inflammatory drugs, a biopsy might be warranted. Moreover, when arthroscopy or arthrotomy is planned, any atypical tissue should be sent for histological analysis. Early diagnosis of NHL can contribute to improved outcome of its rapidly developing treatment options.
Decreased expression of LATS1 is correlated with the progression and prognosis of glioma
Authors: Ji Tianhai , Liu Dan , Shao Wei , Yang Wensheng , Wu Haiqiao , Bian Xiuwu 
Published: August 2012

Abstract

Background
LATS1 is a tumor suppressor genes implicated in the pathogenesis of certain types of tumors, but its role is not known in human glioma.

Methods
Using real-time PCR and immunohistochemistry, we detected the mRNA and protein expression of LATS1 in glioma. The effect of LATS1 on cell growth and invasion were investigated.

Results
We found that mRNA and protein of LATS1 expression is significantly downregulated in glioma compared with normal control brain tissues. Furthermore, reduced LATS1 expression was markedly negatively correlated with WHO grade and KPS (p<0.001 and p<0.001) in glioma patients. Patients with lower LATS1 expression had a significantly shorter overall survival time than did patients with higher LATS1 expression. Multivariate analysis suggested that the level of LATS1 expression was an independent prognostic indicator (p<0.001) for the survival of patients with glioma. Forced expression of LATS1 in glioma U251 cells not only significantly suppressed cell growth, migration and invasion, but retarded cell cycle progression from G2/M to G1 in vitro. Finally, we found that overexpressed LATS1 markedly inhibited the expression level of cell cycle factor CCNA1.

Conclusion
These results indicate that LATS1 is an important candidate tumor suppressor and its downregulated expression may contribute to glioma progression.
High preoperative blood levels of HE4 predicts poor prognosis in patients with ovarian cancer
Authors: Kalapotharakos Grigorios , Asciutto Christine , Henic Emir , Casslén Bertil , Borgfeldt Christer 
Published: August 2012

Abstract

Abstract
The aim of this study was to assess the clinical value of preoperative blood levels of HE4 as a predictor of overall survival in patients with ovarian cancer and to validate previous data of HE4 and the ROMA algorithm including HE4 and CA125 in discriminating benign and malignant ovarian tumors.

Experimental design
The preoperative plasma levels of HE4 and CA125 were analyzed with ELISA in 312 patients with adnexal lesions. Tumors were classified as benign (n= 206), borderline (i.e. low malignant potential tumors) (n= 25), and well (n= 14), moderately (n= 15), and poorly (n= 51) differentiated malignant.

Results
In univariate Cox regression analyses high levels (dichotomized at the median) of HE4, CA125, increased age (continuous variable), advanced-stage of disease 2–4, histological grade 3 and non-optimal tumor debulking at primary surgery were all significantly associated with shorter overall survival. A multivariate Cox regression model including pre-operative available covariates HE4 and CA125 both dichotomized at median in addition to age as continuous variable showed that high levels of HE4 was an independent prognostic marker for worse prognosis HR 2.02 (95% CI 1.1-3.8). In postmenopausal women the ROMA algorithm gave the highest AUC of 0.94 (95% CI, 0.90-0.97) which was higher than the separate markers HE4 AUC 0.91 (95% CI 0.86-0.95) and CA125 AUC 0.91(95% CI 0.87-0.96).

Conclusions
High concentration of plasma HE4 is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The algorithm ROMA discriminates in postmenopausal women between malignant and benign tumors with an AUC of 0.94.
Rhinovirus‐induced basic fibroblast growth factor release mediates airway remodeling features
Authors: Skevaki Chrysanthi L , Psarras Stelios , Volonaki Eleni , Pratsinis Harris , Spyridaki Irini S , Gaga Mina , Georgiou Vassiliki , Vittorakis Stylianos , Telcian Aurica G , Maggina Paraskevi , Kletsas Dimitris , Gourgiotis Dimitrios , Johnston Sebastian L , Papadopoulos Nikolaos G 
Published: August 2012

AbstractBackgroundHuman rhinoviruses, major precipitants of asthma exacerbations, induce lower airway inflammation and mediate angiogenesis. The purpose of this study was to assess the possibility that rhinoviruses may also contribute to the fibrotic component of airway remodeling.MethodsLevels of basic fibroblast growth factor (bFGF) mRNA and protein were measured following rhinovirus infection of bronchial epithelial cells. The profibrotic effect of epithelial products was assessed by DNA synthesis and matrix metalloproteinase activity assays. Moreover, epithelial cells were exposed to supernatants from cultured peripheral blood mononuclear cells, obtained from healthy donors or atopic asthmatic subjects and subsequently infected by rhinovirus and bFGF release was estimated. bFGF was also measured in respiratory secretions from atopic asthmatic patients before and during rhinovirus‐induced asthma exacerbations.ResultsRhinovirus epithelial infection stimulated mRNA expression and release of bFGF, the latter being positively correlated with cell death under conditions promoting rhinovirus‐induced cytotoxicity. Supernatants from infected cultures induced lung fibroblast proliferation, which was inhibited by anti‐bFGF antibody, and demonstrated increased matrix metalloproteinase activity. Rhinovirus‐mediated bFGF release was significantly higher in an in vitro simulation of atopic asthmatic environment and, importantly, during rhinovirus‐associated asthma exacerbations.ConclusionsRhinovirus infection induces bFGF release by airway epithelium, and stimulates stroma cell proliferation contributing to airway remodeling in asthma. Repeated rhinovirus infections may promote asthma persistence, particularly in the context of atopy; prevention of such infections may influence the natural history of asthma.
Effectiveness of First-Line Management Strategies for Stage I Follicular Lymphoma: Analysis of the National LymphoCare Study
Authors: Friedberg Jonathan W. , Byrtek Michelle , Link Brian K. , Flowers Christopher , Taylor Michael , Hainsworth John , Cerhan James R. , Zelenetz Andrew D. , Hirata Jamie , Miller Thomas P. 
Published: August 2012

PurposeThe optimal management of stage I follicular lymphoma, according to consensus guidelines, is based on uncontrolled experiences of select institutions. Diverse treatment approaches are used despite guidelines that recommend radiation therapy (XRT).Patients and MethodsWe analyzed outcomes of patients with stage I follicular lymphoma enrolled onto the National LymphoCare database.ResultsOf 471 patients with stage I follicular lymphoma, 206 patients underwent rigorous staging as defined by both a bone marrow aspirate and biopsy and an imaging study (a computed tomography [CT] scan of the whole body, a positron emission tomography [PET]/CT scan, or both). Rigorously staged patients had superior progression-free survival (PFS) compared with nonrigorously staged patients (hazard ratio [HR], 0.63). Treatments given to rigorously staged patients were rituximab/chemotherapy (R-chemo; 28%), XRT (27%), observation (17%), systemic therapy + XRT (13%), rituximab monotherapy (12%), and other (3%). With a median follow-up of 57 months for PFS, there were 44 progression events (in 21% of patients) for rigorously staged patients. For these patients, PFS was significantly improved with either R-chemo or systemic therapy + XRT compared with patients receiving XRT alone after adjustment for histology, LDH, and the presence of B symptoms. There were no differences in overall survival.ConclusionIn this largest, prospectively enrolled group of patients with stage I follicular lymphoma, variable treatment approaches resulted in similar excellent outcomes, which challenges the paradigm that XRT should be standard for this presentation.
The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-κB signalling
Authors: McKelvey Laura , Gutierrez Humberto , Nocentini Giuseppe , Crampton Sean J. , Davies Alun M. , Riccardi Carlo R. , O’keeffe Gerard W. 
Published: August 2012

Summary
NF-κB transcription factors play a key role in regulating the growth of neural processes in the developing PNS. Although several secreted proteins have been shown to activate NF-κB to inhibit the growth of developing sympathetic neurons, it is unknown how the endogenous level of NF-κB activity present in these neurons is restricted to allow neurite growth to occur during their normal development. Here we show that activation of the glucocorticoid-induced tumour necrosis factor receptor (GITR) inhibits NF-κB activation while promoting the activation of Erk in developing sympathetic neurons. Conversely, inhibition of GITR results in an increase in NF-κB dependent gene transcription and a decrease in Erk activation leading to a reduction in neurite growth. These findings show that GITR signalling can regulate the extent of sympathetic neurite growth through an inverse modulation of Erk and NF-κB signalling, which provides an optimal environment for NGF-promoted growth.
Drosophilasosiefunctions with βH-Spectrin and actin organizers in cell migration, epithelial morphogenesis and cortical stability
Authors: Urwyler Olivier , Cortinas-Elizondo Fabiola , Suter Beat 
Published: August 2012

SummaryMorphogenesis in multicellular organisms requires the careful coordination of cytoskeletal elements, dynamic regulation of cell adhesion and extensive cell migration. sosie (sie) is a novel gene required in various morphogenesis processes in Drosophila oogenesis. Lack of sie interferes with normal egg chamber packaging, maintenance of epithelial integrity and control of follicle cell migration, indicating that sie is involved in controlling epithelial integrity and cell migration. For these functions sie is required both in the germ line and in the soma. Consistent with this, Sosie localizes to plasma membranes in the germ line and in the somatic follicle cells and is predicted to present an EGF-like domain on the extracellular side. Two positively charged residues, C-terminal to the predicted transmembrane domain (on the cytoplasmic side), are required for normal plasma membrane localization of Sosie. Because sie also contributes to normal cortical localization of βH-Spectrin, it appears that cortical βH-Spectrin mediates some of the functions of sosie. sie also interacts with the genes coding for the actin organizers Filamin and Profilin and, in the absence of sie function, F-actin is less well organized and nurse cells frequently fuse.
Reaction Kinetics and Product Distribution of Slow Pyrolysis of Indian Textile Wastes
Authors: Chowdhury Ranjana , Sarkar Aparna 
Published: August 2012

Abstract
In this present investigation, textiles samples of non-polymeric nature, e.g, cotton, silk etc. of Indian origin were pyrolysed in a 50 mm diameter and 640 mm long packed bed pyrolyser placed in a tubular furnace from 573K to 1173K in a nitrogen atmosphere. Experiments were designed to investigate the effects of temperature of pyrolysis on yields of char, pyro-oil and gas and their characteristics. A kinetic scheme has been proposed where two parallel reactions occur simultaneously to produce volatiles and char. The kinetic rate constants of both the reactions have been determined in the temperature range under study. The activation energies and pre-exponential factors of all products (solid reactant, volatile and char) have been determined. A mathematical model for the pyrolysis of textile waste has been developed using the kinetic parameters determined under the present study. Calorific values of pyro-oil and char obtained at different temperature have been determined. The structural characteristics of char at different temperatures of 573, 873 and 1173K has also been analysed using SEM.
WHO's Got Yellow Rain: An Analysis of the Yellow Rain Incident and the Possible Involvement of the World Health Organization
Authors: Allen Zack 
Published: August 2012

Abstract
This article seeks to answer the question: What would have changed, had the World Health Organization spearheaded the investigation of the Yellow Rain Incident instead of the U.S. State Department? This article will begin with a brief discussion of the Yellow Rain Incident. It will then describe the role and function of the World Health Organization. Next, it will begin analyzing ways in which the World Health Organization could have participated in the investigation of the Yellow Rain Incident. This discussion will also analyze the level at which the World Health Organization could participate in an investigation had the Yellow Rain Incident happened today. Finally, the discussion will return to the original question and attempt to offer an answer after having considered all of the facts and data.
Epigenetic control of cell invasion – the trophoblast model
Authors: Serman Alan , Simon Filip , Fabijanovic Dora , Serman Ljiljana 
Published: August 2012

AbstractTrophoblast implantation and placentation allow the survival of the young embryo and its normal development inside the uterus. In order for these processes to function properly, the trophoblast has to undergo a series of characteristic changes that lead to its adhesion and invasion of the uterus. This is achieved, among other mechanisms, by inactivation of specific tumor suppressor genes, commonly by methylation of their promoters. Cell adhesion and tissue invasion are also characteristics of malignant tumors and patterns of methylation similar to that seen in trophoblast are found in various tumor types. Another important mechanism that aids trophoblast cells invasion is their transition from epithelial to mesenchymal phenotype. Such a transition is also a common characteristic of invading malignant cells. Thus, studying tissue invasion and its control mechanisms can benefit the understanding of both the trophoblast and malignant cells behavior.
Minor improvement of venous blood specimen collection practices in primary health care after a large-scale educational intervention
Authors: Bölenius Karin , Söderberg Johan , Hultdin Johan , Lindkvist Marie , Brulin Christine , Grankvist Kjell 
Published: August 2012

AbstractBackground:Venous blood specimen collection is a common health care practice that has to follow strict guidelines, non-compliance among sampling staff may compromise patient safety. We evaluated a large-scale 2 h educational intervention that emphasised guideline adherence to assess possible improvements of venous blood specimen collection practices.Methods:Blood specimen haemolysis is usually caused by inadequate venous blood specimen collection and handling, reflecting overall pre-analytical handling. We monitored haemolysis of serum samples with haemolysis index corresponding to ≥150 mg/L of free haemoglobin for specimens sent from 11 primary health care centres and analysed on a Vitros 5,1 clinical chemistry analyser before (2008, n=6652 samples) and after (2010, n=6121 samples) the intervention.Results:The total percentage of haemolysed specimens was 11.8% compared to 10.5% (p=0.022) before the intervention. As groups, rural primary health care centres demonstrated a significant reduction [Odds ratios (OR)=0.744] of haemolysed specimens after intervention, whereas urban primary health care centres demonstrated a significant increase (OR=1.451) of haemolysis.Conclusions:A large-scale 2 h educational intervention to make venous blood specimen collection staff comply with guideline practices had minor effects on collection practices. Educational interventions may be effective in wards/care centres demonstrating venous blood specimen collection practices with larger deviations from guidelines.