bluuebunny/crossref_metadata_2025_split huggingface dataset:
WT1 Expression Distinguishes Astrocytic Tumor Cells from Normal and Reactive Astrocytes
Authors: Schittenhelm Jens , Mittelbronn Michel , Nguyen Thai‐Dung , Meyermann Richard , Beschorner Rudi 
Published: March 2008

AbstractParticularly in small brain biopsies, it might be difficult to distinguish reactive astrogliosis from low‐grade or infiltration zones of high‐grade astrocytomas. So far no immunohistochemical marker allows a reliable distinction. Recently, the over‐expression of Wilms' tumor gene product WT1 was reported in astrocytic tumor cells. However, no sufficient data on WT1 expression in normal or reactive astrocytes are available. Therefore, we investigated WT1 expression in paraffin‐embedded brain sections from 28 controls, 48 cases with astrogliosis of various etiology and 219 astrocytomas [World Health Organization (WHO) grades I–IV] by immunohistochemistry. In normal brains and in astrogliosis, expression of WT1 was restricted to endothelial cells. In astrocytomas, WT1‐positive tumor cells were found in pilocytic astrocytomas (66.7% of cases), diffuse astrocytomas (52.7%) WHO grade II (52.7%), anaplastic astrocytomas (83.4%) and glioblastomas (98.1%). Overall, the majority of all astrocytic neoplasms (84.5%) expressed WT1. Establishing a cut‐off value of 0% immunoreactive tumor cells served to recognize neoplastic astrocytes with 100% specificity and 68% sensitivity and was associated with positive and negative predictive values of 1 and 0.68, respectively. Therefore, WT1 expression in astrocytes indicates a neoplastic origin and might represent an important diagnostic tool to differentiate reactive from neoplastic astrocytes by immunohistochemistry.
Pineocytoma and Pineal Parenchymal Tumors of Intermediate Differentiation Presenting Cytologic Pleomorphism: A Multicenter Study
Authors: Fèvre‐Montange Michelle , Szathmari Alexandru , Champier Jacques , Mokhtari Karima , Chrétien Fabrice , Coulon Alix , Figarella‐Branger Dominique , Polivka Marc , Varlet Pascale , Uro‐Coste Emmanuelle , Fauchon François , Jouvet Anne 
Published: March 2008

AbstractCytologic pleomorphism has been described in a limited number of benign pineal tumors, namely pineocytoma (PC) and pineal parenchymal tumors (PPTs) of intermediate differentiation (PPTID). We examined the clinicopathologic features in a retrospective series of 14 cases (seven females and seven males aged from 10 to 65 years) of pleomorphic PPT. Seven cases were PC, with no mitoses and with areas of tumoral cells forming large pineocytomatous rosettes and other areas with giant cells containing hyperchromatic nuclei. The other seven were PPTID, presenting few mitoses (≤2), a Ki67 proliferation index between 3% and 7%, and predominantly composed of small neoplastic cells and scattered giant cells, sometimes multinucleated. In the 14 tumors, the proportion of pleomorphic areas was variable. Most tumoral cells showed extensive neuronal differentiation with strong expression of neuron‐specific enolase, synaptophysin and neurofilaments. Some of the neoplastic cells expressed S100 protein. The follow‐up period ranged from 1.2 to 13 years and only one PC and one PPTID progressed after stereotactic biopsy or incomplete resection. The lack of invasiveness and the low proliferation index of these tumors suggest a benign clinical course despite the marked pleomorphism, the latter of which can lead to upgrading.
Anaplastic Oligodendroglial Tumors: Refining the Correlation among Histopathology, 1p 19q Deletion and Clinical Outcome in Intergroup Radiation Therapy Oncology Group Trial 9402
Authors: Giannini Caterina , Burger Peter C. , Berkey Brian A. , Cairncross J. Gregory , Jenkins Robert B. , Mehta Minesh , Curran Walter J. , Aldape Ken 
Published: March 2008

AbstractIntergroup Radiation Therapy Oncology Group Trial 9402 study, a phase III trial of chemotherapy plus radiotherapy (PCV‐plus‐RT) vs. radiotherapy alone for pure and mixed anaplastic oligodendroglioma confirmed the prognostic significance of 1p 19q deletion and showed that only progression‐free survival (PFS) was prolonged in PCV‐plus‐RT‐treated patients and only in association with 1p 19q deletion. We reviewed tumor histopathology, separating 115 tumors deemed to be classic for oligodendroglioma (CFO) from 132 lacking classic features of oligodendroglioma (NCFO) and evaluated the relationship of histopathology and 1p 19q status to treatment and outcome. The study disclosed: (i) overall survival (OS) of patients with CFO was significantly longer than for patients with NCFO (P < 0.0001) and was not affected by necrosis. Median OS for CFO patients with and without necrosis was 6.6 and 6.3 years (OS log‐rank P = not significant), respectively, in contrast to NCFO showing 1.9 and 3.3 years respectively (OS log‐rank P = 0.014). (ii) Classic oligodendroglial morphology was highly associated with 1p 19q deletion, present in 80% of CFO and only in 13% of NCFO. (iii) On multivariate analysis, both classic oligodendroglial morphology and 1p 19q deletion remained significantly associated with PFS and OS. (iv) Patients with CFO treated with PCV‐plus‐RT showed a trend toward increased survival compared with CFO treated with RT (P = 0.08). Median OS was not reached in the PCV‐plus‐RT group and was 6.3 years in RT group. These findings suggest that classic oligodendroglial morphology combined with 1p 19q deletion may in the future be predictive of chemotherapeutic response and survival.
CD133 Expression and Cancer Stem Cells Predict Prognosis in High‐grade Oligodendroglial Tumors
Authors: Beier Dagmar , Wischhusen Jörg , Dietmaier Wolfgang , Hau Peter , Proescholdt Martin , Brawanski Alexander , Bogdahn Ulrich , Beier Christoph P. 
Published: March 2008

AbstractHigh‐grade oligodendroglial tumors, that is, anaplastic oligodendroglial tumors and glioblastomas with oligodendroglial component, differ significantly in terms of prognosis and response to chemotherapy. Differentiation might be difficult because the histological differences are vague and reliable markers are not established. We correlated the presence of putative cancer stem cells (CSC) in high‐grade oligodendroglial tumors (WHO grades III and IV) with clinical outcome. Tumors with favorable prognosis neither contained CSC nor did they show CD133 expression. Tumor cells resembled lineage‐restricted progenitor cells with limited proliferative capacity and differentiation profile. In contrast, CD133 expression and stem cell‐like tumor cells characterized tumors with poor prognosis. They showed neurosphere‐like growth, differentiated into cells of all neural lineages, and were tumorigenic in nude mice. In our series, CSC and expression of CD133 predicted the clinical course of disease better than the histological grading. To confirm these results, we retrospectively analyzed 36 high‐grade oligodendroglial tumors. Again, CD133 expression indicated shorter survival and predicted clinical outcome more reliable than the histological assessment.Our data show that detection of CSC and expression of CD133 is predictive of prognosis in high‐grade oligodendroglial tumors. The presence or absence of CD133+ CSC might explain the crucial biological difference between WHO grade III and IV oligodendroglial tumors.
The Evolution of Our Understanding on Glioma
Authors: Martin‐Villalba Ana , Okuducu Ali Fuat , Von Deimling Andreas 
Published: March 2008

AbstractThe description of neuroglia by Virchow in 1848 may be considered the starting point of our understanding of primary brain tumors. At the beginning of the 20th century, surgical removal of primary brain tumors became possible, and therefore, tissue for microscopic analysis and clinical data on survival became available. During this time, research on gliomas beyond improving surgical procedures focused on their classification. The classification schemes developed emphasized parameters for sorting tumors with regard to (i) cytological aspects; (ii) presumed tumor cell origin; (iii) histological appearance of the tissue; or (iv) clinical outcome. Over the years, experimental studies have greatly improved our knowledge on gliomas. Gliomas induced by viruses, chemicals, radiation, transgenes and knock‐out technology contributed to the understanding of their pathogenesis and still serve as preclinical models for the testing of novel therapies. Recent advances in developmental neurobiology and the identification of stem cells provided new insights into the origin of brain tumors and the molecular mechanisms of tumor formation. This review briefly compiles the evolution of our concepts on gliomas, focusing on the latest developments.
Amoeboid Microglia in the Periventricular White Matter Induce Oligodendrocyte Damage through Expression of Proinflammatory Cytokines via MAP Kinase Signaling Pathway in Hypoxic Neonatal Rats
Authors: Deng YiYu , Lu Jia , Sivakumar Viswanathan , Ling Eng Ang , Kaur Charanjit 
Published: March 2008

AbstractHypoxic injury in the perinatal period results in periventricular white matter (PWM) lesions with axonal damage and oligodendroglial loss. It also alters macrophage function by perpetuating expression of inflammatory mediators. Relevant to this is the preponderance of amoeboid microglial cells (AMC) characterized as active macrophages in the developing PWM. This study aimed to determine if AMC produce proinflammatory cytokines that may be linked to the oligodendroglial loss observed in hypoxic PWM damage (PWMD). Wistar rats (1 day old) were subjected to hypoxia, following which upregulated expression of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), TNF receptor 1 (TNF‐R1) and IL‐1 receptor 1 (IL‐1R1) was observed. This was coupled with apoptosis and expression of TNF‐R1 and IL‐1R1 in oligodendrocytes. Primary cultured microglial cells subjected to hypoxia (3% oxygen, 5% CO2 and 92% nitrogen) showed enhanced expression of TNF‐α and IL‐1β. Furthermore, mitogen‐activated protein (MAP) kinase signaling pathway was involved in the expression of TNF‐α and IL‐1β in microglia subjected to hypoxia. Our results suggest that following a hypoxic insult, microglial cells in the neonatal rats produce inflammatory cytokines such as TNF‐α and IL‐1β via MAP kinase signaling pathway. These cytokines are detrimental to oligodendrocytes resulting in PWM lesion.
Reduced Glioma Growth Following Dexamethasone or Anti‐Angiopoietin 2 Treatment
Authors: Villeneuve Jérôme , Galarneau Hugo , Beaudet Marie‐Josée , Tremblay Pierrot , Chernomoretz Ariel , Vallières Luc 
Published: March 2008

AbstractAll patients with glioblastoma, the most aggressive and common form of brain cancer, develop cerebral edema. This complication is routinely treated with dexamethasone, a steroidal anti‐inflammatory drug whose effects on brain tumors are not fully understood. Here we show that dexamethasone can reduce glioma growth in mice, even though it depletes infiltrating T cells with potential antitumor activity. More precisely, T cells with helper or cytotoxic function were sensitive to dexamethasone, but not those that were negative for the CD4 and CD8 molecules, including gammadelta and natural killer (NK) T cells. The antineoplastic effect of dexamethasone was indirect, as it did not meaningfully affect the growth and gene expression profile of glioma cells in vitro. In contrast, hundreds of dexamethasone‐modulated genes, notably angiopoietin 2 (Angpt2), were identified in cultured cerebral endothelial cells by microarray analysis. The ability of dexamethasone to attenuate Angpt2 expression was confirmed in vitro and in vivo. Selective neutralization of Angpt2 using a peptide‐Fc fusion protein reduced glioma growth and vascular enlargement to a greater extent than dexamethasone, without affecting T cell infiltration. In conclusion, this study suggests a mechanism by which dexamethasone can slow glioma growth, providing a new therapeutic target for malignant brain tumors.
Phenotypic and Genotypic Characterization of Orthotopic Human Glioma Models and Its Relevance for the Study of Anti‐glioma Therapy
Authors: Claes An , Schuuring Janneke , Boots‐Sprenger Sandra , Hendriks‐Cornelissen Sandra , Dekkers Marieke , Van Der Kogel Albert J. , Leenders William P. , Wesseling Pieter , Jeuken Judith W. 
Published: March 2008

AbstractMost human gliomas are characterized by diffuse infiltrative growth in the brain parenchyma. Partly because of this characteristic growth pattern, gliomas are notorious for their poor response to current therapies. Many animal models for human gliomas, however, do not display this diffuse infiltrative growth pattern. Furthermore, there is a need for glioma models that represent adequate genocopies of different subsets of human gliomas (e.g., oligodendrogliomas). Here, we assessed the intracerebral growth patterns and copy number changes [using multiplex ligation‐dependent probe amplification (MLPA)/comparative genomic hybridization (CGH)] of 15 human glioma lines in nude mice. Most xenografts present with compact growing lesions intracerebrally. Only the E98 and, to a lesser degree, E106 xenograft lines (propagated through subcutaneous growth) consistently produced intracerebral tumors, displaying diffuse infiltrative growth in the brain parenchyma. In contrast, four xenograft lines (E434, E468, E473 and E478), established by direct intracerebral inoculation of human glioma cells and serially propagated intracerebrally, consistently showed extensive diffuse infiltration throughout the brain. After several passages, the neoplastic cells still carry typical chromosomal aberrations [(−1p/−19q in oligodendroglioma, +7/−10 in glioblastoma multiforme (GBM)]. Especially these latter four models and the E98 line thus represent adequate geno‐ and phenocopies of human gliomas and form an attractive platform to investigate different therapeutic approaches in a preclinical setting.
Adrenomedullin Expression is Up‐regulated by Acute Hypobaric Hypoxia in the Cerebral Cortex of the Adult Rat
Authors: Serrano Julia , Fernández Ana Patricia , Sánchez Jaime , Rodrigo José , Martínez Alfredo 
Published: March 2008

AbstractHypobaric hypoxia can produce neuropsychological disorders such as insomnia, dizziness, memory deficiencies, headache and nausea. Here we report the changes in adrenomedullin (AM) expression observed in rats exposed to hypobaric hypoxia and different times of reoxygenation. AM immunoreactivity was transiently elevated in the cerebral cortex after 7 h of exposure to a simulated altitude of 8325 m (27 000 ft). This higher expression was seen in all pyramidal cells and in a subset of small interneurons. AM‐positive nonpyramidal neurons contained also calbindin and calretinin, but no parvalbumin immunoreactivity, thus identifying them as bipolar and double bouquet cells. Small blood vessels and related astroglia also became immunoreactive following the hypobaric insult. AM up‐regulation decreased progressively with the time of reoxygenation, reaching almost control levels after 5 days. Real‐time PCR quantification of AM mRNA and Western blotting confirmed the up‐regulation of AM expression following hypobaria. In addition, hypobaria modulates alternative splicing of the AM gene resulting in a higher production of AM. Our data show that AM expression regulation constitutes a cortical response to hypobaria, suggesting that AM modulation may provide new therapeutic avenues to prevent and/or treat the symptoms produced by hypobaria.
On the ecology of Thelypteris limbosperma — a synecological investigation of T. limbosperma‐dominated stands in W Norway
Authors: Odland Arvid 
Published: March 2008

The investigation is based on phytosociological and ecological analyses of T. limbosperma‐dominated stands from different parts of W Norway. The distribution and floristical composition of the stands are related to different environmental parameters, such as climate, soil and topography. The data are analysed by numerical methods, of which two‐way indicator species analysis (TWINSPAN), canonical correspondence analysis (CCA), and simple discriminant functions (DISCRIM) are the most useful. The broad‐scale distribution of T. limbosperma stands is determined by climatic factors. Within its distribution area soil factors and human influence govern the floristic composition and development of different types of such stands. Based on the TWINSPAN classification 9 different stand types are distinguished.The first major division of the TWINSPAN classification is mainly correlated with soil factors. Most of the stands growing on the richest soils are interpreted as representing regeneration stages after intensive human influence. Divisions at lower levels are well correlated with altitude and temperature conditions.The stands are all characterized by low pH and base saturation. Some types are concentrated to certain geographical regions, indicating that both altitudinal and west‐east‐gradients are important in influencing the floristic composition of the different types. The investigations indicate that T. limbosperma has a rather narrow realised phytosociological niche. It is mainly concentrated to stands that are floristically most related to the poorest part of Vaccinio‐Piceion communities. Occasionally it is also dominant in Alno‐Padion and Lactucion alpinae communities.
Escherichia coli Nissle 1917 Facilitates Tumor Detection by Positron Emission Tomography and Optical Imaging
Authors: Brader Peter , Stritzker Jochen , Riedl Christopher C. , Zanzonico Pat , Cai Shangde , Burnazi Eva M. , Ghani E.Rashid , Hricak Hedvig , Szalay Aladar A. , Fong Yuman , Blasberg Ronald 
Published: March 2008

Abstract
Purpose: Bacteria-based tumor-targeted therapy is a modality of growing interest in anticancer strategies. Imaging bacteria specifically targeting and replicating within tumors using radiotracer techniques and optical imaging can provide confirmation of successful colonization of malignant tissue.
Experimental Design: The uptake of radiolabeled pyrimidine nucleoside analogues and [18F]FDG by Escherichia coli Nissle 1917 (EcN) was assessed both in vitro and in vivo. The targeting of EcN to 4T1 breast tumors was monitored by positron emission tomography (PET) and optical imaging. The accumulation of radiotracer in the tumors was correlated with the number of bacteria. Optical imaging based on bioluminescence was done using EcN bacteria that encode luciferase genes under the control of an l-arabinose–inducible PBAD promoter system.
Results: We showed that EcN can be detected using radiolabeled pyrimidine nucleoside analogues, [18F]FDG and PET. Importantly, this imaging paradigm does not require transformation of the bacterium with a reporter gene. Imaging with [18F]FDG provided lower contrast than [18F]FEAU due to high FDG accumulation in control (nontreated) tumors and surrounding tissues. A linear correlation was shown between the number of viable bacteria in tumors and the accumulation of [18F]FEAU, but not [18F]FDG. The presence of EcN was also confirmed by bioluminescence imaging.
Conclusion: EcN can be imaged by PET, based on the expression of endogenous E. coli thymidine kinase, and this imaging paradigm could be translated to patient studies for the detection of solid tumors. Bioluminescence imaging provides a low-cost alternative to PET imaging in small animals.
Endometrial Glandular Dysplasia with Frequent p53 Gene Mutation: A Genetic Evidence Supporting Its Precancer Nature for Endometrial Serous Carcinoma
Authors: Jia Lin , Liu Yongjuan , Yi Xiaofang , Miron Alexander , Crum Christopher P. , Kong Beihua , Zheng Wenxin 
Published: March 2008

Abstract
Purpose: Endometrial glandular dysplasia (EmGD) has been recently proposed to be a putative precursor to endometrial serous carcinoma (ESC). The purpose of this study is to determine if EmGD is genetically linked to ESC and if it can be used for early detection.
Experimental Design: The tumor suppressor p53 gene was sequenced from serial samples of benign and neoplastic endometria with serous differentiation. The study group contained 15 neoplastic uteri and the control group had 12 age-matched benign uteri. A total of 139 informative samples were obtained, including 55 resting endometrium, 37 EmGD, 25 serous endometrial intraepithelial carcinoma (EIC), and 22 ESC. At least one representative section from each uterus was used for p53 immunohistochemical staining to correlate p53 overexpression with gene mutation status.
Results: The mutations of p53 were detected in 0%, 43%, 72%, and 96% in resting endometrium, EmGD, serous EIC, and ESC, respectively. More than 50% of the neoplastic uteri showed at least one identical p53 gene mutant among lesions of EmGD, serous EIC, and/or ESC. The majority of lesions showed overexpression of p53 protein, which was significantly correlated with p53 gene mutation (P &lt; 0.01).
Conclusions: This genetic evidence strongly supports that EmGD represents the precancer of ESC or serous EIC. Mutation of p53 gene is probably one of the most important factors to initiate the endometrial serous carcinogenesis. Correct identification of EmGD will provide us an opportunity of early diagnosis and a potentially effective therapeutic modality to control ESC.
Urbanization Effects on Observed Surface Air Temperature Trends in North China
Authors: Ren Guoyu , Zhou Yaqing , Chu Ziying , Zhou Jiangxing , Zhang Aiying , Guo Jun , Liu Xuefeng 
Published: March 2008

Abstract
A dataset of 282 meteorological stations including all of the ordinary and national basic/reference surface stations of north China is used to analyze the urbanization effect on surface air temperature trends. These stations are classified into rural, small city, medium city, large city, and metropolis based on the updated information of total population and specific station locations. The significance of urban warming effects on regional average temperature trends is estimated using monthly mean temperature series of the station group datasets, which undergo inhomogeneity adjustment. The authors found that the largest effect of urbanization on annual mean surface air temperature trends occurs for the large-city station group, with the urban warming being 0.16°C (10 yr)−1, and the effect is the smallest for the small-city station group with urban warming being only 0.07°C (10 yr)−1. A similar assessment is made for the dataset of national basic/reference stations, which has been widely used in regional climate change analyses in China. The results indicate that the regional average annual mean temperature series, as calculated using the data from the national basic/reference stations, is significantly impacted by urban warming, and the trend of urban warming is estimated to be 0.11°C (10 yr)−1. The contribution of urban warming to total annual mean surface air temperature change as estimated with the national basic/reference station dataset reaches 37.9%. It is therefore obvious that, in the current regional average surface air temperature series in north China, or probably in the country as a whole, there still remain large effects from urban warming. The urban warming bias for the regional average temperature anomaly series is corrected. After that, the increasing rate of the regional annual mean temperature is brought down from 0.29°C (10 yr)−1 to 0.18°C (10 yr)−1, and the total change in temperature approaches 0.72°C for the period analyzed.