bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged survival of mice with established intracerebral glioma receiving combined treatment with peroxisome proliferator-activated receptor–γ thiazolidinedione agonists and interleukin-2–secreting syngeneic/allogeneic fibroblasts
Authors: Spagnolo Alessandra , Glick Roberta P. , Lin Henry , Cohen Edward P. , Feinstein Douglas L. , Lichtor Terry 
Published: January 2008

Object
In this study the authors explored the benefits of treating C57Bl/6 mice with an established intracerebral glioma by combining immunotherapy with interleukin (IL)-2–secreting syngeneic/allogeneic fibroblasts administered into the tumor bed along with the chemotherapeutic agent pioglitazone, a thiazolidinedione (TZD). The TZDs are agonists of the peroxisome proliferator-activated receptor–γ. They have been found to exert antiproliferative effects on several transformed cell lines. Data from prior studies by these authors have revealed the immunotherapeutic properties of the IL-2–secreting fibroblasts in treating intracerebral gliomas in mice.

Methods
The sensitivity of GL261 glioma cells and primary astrocytes to pioglitazone was determined in vitro by incubating the cells with increasing amounts of the drug. Viability was assessed by measuring lactate dehydrogenase release, and effects on metabolism were determined by measuring superoxide production and levels of superoxide dismutase. The GL261 cells were injected intracerebrally into C57Bl/6 mice, followed by treatment with pioglitazone either orally or intracerebrally into the tumor bed. The effect of the combined therapy was determined by injecting C57Bl/6 mice with an established intracerebral GL261 glioma with IL-2–secreting allogeneic fibroblasts and pioglitazone directly into the tumor bed through a unique cannula system.
Pioglitazone was found to induce cell death in GL261 glioma cells grown in vitro while causing only modest damage to astrocytes. The application of pioglitazone also resulted in a significantly greater induction of cellular superoxide in glioma cells than in astrocytes, which can activate apoptotic pathways. Pioglitazone administered intracerebrally (p < 0.05) but not orally was found to prolong survival in mice harboring an intracerebral glioma. Synergistic effects of combination therapy on prolonging survival were found in mice receiving both pioglitazone and IL-2–secreting fibroblasts (p < 0.005, compared with untreated animals). Pioglitazone induces metabolic and oxidative stresses that are tolerated by astrocytes but not glioma cells, which could account for selective vulnerability and increased sensitivity to IL-2, suggesting potential for the use of this Food and Drug Administration–approved drug in the treatment of brain tumors.

Conclusions
The data indicate the beneficial effects of combination therapy using pioglitazone and immunotherapy in mice harboring intracerebral glioma.
Magnetic resonance imaging of in vitro glioma cell invasion
Authors: Bernas Lisa M. , Foster Paula J. , Rutt Brian K. 
Published: January 2008

Object
An understanding of single glioma cell invasion has been limited by the static picture provided by histological studies. The ability to nondestructively assess cell invasion dynamically in a full 3D volume would improve the quality and quantity of information available from both in vivo and in vitro experiments. The purpose of this study was to observe glioma cell invasion in a 3D in vitro model using a microimaging protocol at 1.5 tesla and to assess the uptake of micron-sized particles of iron oxide (MPIO) and the consequent effects on cell function.

Methods
Rat C6 glioma cells were labeled with MPIO to a sufficient extent to allow single cell detection in vitro without significant effects on cell proliferation or plating efficiency. When placed on agar-coated plates, the cells formed stable multicellular tumor spheroids (MCTSs), which were embedded in collagen type I gel and serially visualized using magnetic resonance (MR) imaging and phase-contrast microscopy over 8 days. The MCTSs initially appeared as large susceptibility artifacts on MR images, but within 2 days, as cells moved away from the main MCTS, small discrete areas of signal loss, possibly due to single cells, could be observed and tracked.

Conclusions
Glioma cell invasion can be nondestructively observed using MR imaging. The sensitivity of MR imaging, along with its ability to represent full 3D volumes noninvasively over time, makes it ideal for longitudinal in vivo cell tracking studies.
Synergistic cytotoxicity through the activation of multiple apoptosis pathways in human glioma cells induced by combined treatment with ionizing radiation and tumor necrosis factor–related apoptosis-inducing ligand
Authors: Nagane Motoo , Cavenee Webster K. , Shiokawa Yoshiaki 
Published: January 2008

Object
Malignant gliomas remain incurable despite modern multimodality treatments. Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL), also known as Apo2L, a member of the TNF family, preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, suggesting that it may serve as a potential therapeutic agent for intractable malignant gliomas. Here, the authors show that genotoxic ionizing radiation synergistically enhances TRAIL-induced cell death in human glioma cells expressing DR5.

Methods
Combination treatment with soluble human TRAIL plus radiation induced robust cell death, while each of them singly led to only limited cytotoxicity. The combination resulted in cleavage and activation of the apoptotic initiator caspase-8 and the effector caspase-3 as well as cleavage of Bid and another initiator caspase-9, a downstream component of the apoptosome. Accordingly, it augmented the release of cytochrome c from the mitochondria into the cytosol, as well as apoptosis-inducing factor. Synergistic cell death was suppressed by TRAIL-neutralizing DR5-Fc, caspase inhibitors, expression of dominant-negative Fasassociated protein with death domain and CrmA, which selectively blocks caspase-8, and overexpression of Bcl-XL. Finally, combination treatment had no influence on the viability of normal human astrocytes.

Conclusions
These results suggest that combination treatment with TRAIL and ionizing radiation kills human glioma cells through the activation of DR5-mediated death receptor pathways. This therapy involves direct activation of effector caspases as well as mitochondria-mediated pathways and provides a novel strategy in which TRAIL could be synergistically combined with DNA-damaging radiation.
Irinotecan: a potential new chemotherapeutic agent for atypical or malignant meningiomas
Authors: Gupta Vinay , Su Yuzhuang S. , Samuelson Christian G. , Liebes Leonard F. , Chamberlain Marc C. , Hofman Florence M. , Schönthal Axel H. , Chen Thomas C. 
Published: January 2008

Object
There is currently no effective chemotherapy for meningiomas. Although most meningiomas are treated surgically, atypical or malignant meningiomas and surgically inaccessible meningiomas may not be removed completely. The authors have investigated the effects of the topoisomerase I inhibitor irinotecan (CPT-11) on primary meningioma cultures and a malignant meningioma cell line in vitro and in vivo.

Methods
The effects of irinotecan on cellular proliferation in primary meningioma cultures and the IOMM-Lee malignant meningioma cell line were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. Apoptosis following drug treatment was evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and the DNA laddering assays. The effects of irinotecan in vivo on a meningioma model were determined with a subcutaneous murine tumor model using the IOMM-Lee cell line.
Irinotecan induced a dose-dependent antiproliferative effect with subsequent apoptosis in the primary meningioma cultures (at doses up to 100 μM) as well as in the IOMM-Lee human malignant meningioma cell line (at doses up to 20 μM) irinotecan. In the animal model, irinotecan treatment led to a statistically significant decrease in tumor growth that was accompanied by a decrease in Bcl-2 and survivin levels and an increase in apoptotic cell death.

Conclusions
Irinotecan demonstrated growth-inhibitory effects in meningiomas both in vitro and in vivo. Irinotecan was much more effective against the malignant meningioma cell line than against primary meningioma cultures. Therefore, this drug may have an important therapeutic role in the treatment of atypical or malignant meningiomas and should be evaluated further for this purpose.
Endoscopic identification and biopsy sampling of an intraventricular malignant glioma using a 5–aminolevulinic acid–induced protoporphyrin IX fluorescence imaging system
Authors: Tamura Yoji , Kuroiwa Toshihiko , Kajimoto Yoshinaga , Miki Yoshihito , Miyatake Shin-Ichi , Tsuji Masao 
Published: January 2008

✓Several neurosurgical studies have provided descriptions of the utility of fluorescence-guided tumor resection using a microscope. However, fluorescence-guided endoscopic detection of a deep-seated brain tumor has not yet been reported. The authors report their experience with an endoscopic biopsy procedure for a malignant glioma within the third ventricle using a 5–aminolevulinic acid (5-ALA)–induced protoporphyrin IX fluorescence imaging system. A 5-ALA–induced fluorescence image of an intraventricular tumor is barely visible with the typical fluorescence endoscopic system used in other clinical fields because the intensity of excitation light at wavelengths of 390 to 405 nm through a cutoff filter is too weak to delineate a brain tumor.
The technique described in this study made use of a laser illumination system with a high-powered output that delivered a violet-blue light at wavelengths of 405 nm. In addition, a common ultraviolet cutoff filter was fitted between the endoscope and the high-sensitivity camera to block the backscattered excitation light. A 5-ALA–induced fluorescence endoscopy performed using this system allowed the intraventricular tumor to be clearly visualized as a red fluorescent lesion. Several biopsy specimens obtained from the fluorescent lesion provided a definitive histological diagnosis. The results indicate that this endoscopic system is useful in detecting an intraventricular fluorescent tumor.
Sex and genetic associations with cerebrospinal fluid dopamine and metabolite production after severe traumatic brain injury
Authors: Wagner Amy K. , Ren Dianxu , Conley Yvette P. , Ma Xiecheng , Kerr Mary E. , Zafonte Ross D. , Puccio Ava M. , Marion Donald W. , Dixon C. Edward 
Published: January 2008

Object
Dopamine (DA) pathways have been implicated in cognitive deficits after traumatic brain injury (TBI). Both sex and the dopamine transporter (DAT) 3′ variable number of tandem repeat polymorphism have been associated with differences in DAT protein density, and DAT protein affects both presynaptic DA release, through reverse transport, and DA reuptake. Catecholamines and associated metabolites are subject to autooxidation, resulting in the formation of reactive oxygen species that may contribute to subsequent oxidative injury. The purpose of this study was to determine associations between factors that affect DAT expression and cerebrospinal fluid (CSF) DA and metabolite levels after severe TBI.

Methods
Sixty-three patients with severe TBI (Glasgow Coma Scale score ≤ 8) were evaluated. The patients' genotypes were obtained using previously banked samples of CSF, and serial CSF samples (416 samples) were used to evaluate DA and metabolite levels. High-performance liquid chromatography was used to determine CSF levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) during the first 5 days after injury.
Mixed-effects multivariate regression modeling revealed that patients with the DAT 10/10 genotype had higher CSF DA levels than patients with either the DAT 9/9 or DAT 9/10 genotypes (p = 0.009). Females with the DAT 10/10 genotype had higher CSF DA levels than females with the DAT 9/9 or DAT 9/10 genotypes, and sex was associated with higher DOPAC levels (p = 0.004). Inotrope administration also contributed to higher DA levels (p = 0.002).

Conclusions
In addition to systemic administration of DA, inherent factors such as sex and DAT genotype affect post-TBI CSF DA and DA metabolite levels, a phenomenon that may modulate susceptibility to DA-mediated oxidative injury.
Motor tract monitoring during insular glioma surgery
Authors: Neuloh Georg , Pechstein Ulrich , Schramm Johannes 
Published: January 2008

Object
Surgery for insular gliomas incurs a considerable risk of motor morbidity. In this study the authors explore the validity and utility of continuous motor tract monitoring to detect and reverse impending motor impairment during insular glioma resection.

Methods
Motor evoked potentials (MEPs) were successfully monitored during 73 operations to remove insular gliomas. Seventy-two cases were assessable, and one patient died during the early postoperative course. In this prospective observational approach, MEP monitoring results were correlated with intraoperative events and perioperative clinical data.
Intraoperative recordings of MEPs remained stable in 40 cases (56%), indicating unimpaired motor outcome and allowing safe completion of the hazardous steps of the procedure. Deterioration of MEPs occurred in 32 cases (44%). This deterioration was reversible after intervention in 21 cases (29%), and there was no new motor deficit except for transient paresis in nine of these cases (13%). Surgical measures could not prevent irreversible MEP deterioration in 11 cases (15%). Transient mild or moderate paresis occurred if complete MEP loss was avoided. Irreversible MEP loss in seven cases (10%) occurred after completion of resection in four of these seven cases, and was consistently an indicator of both a stroke within the deep motor pathways and permanent paresis, which remained severely disabling in three patients (4%). In contrast, permanently severe paresis occurred in two (18%) of 11 cases without useful MEP monitoring.

Conclusions
Continuous MEP monitoring is a valid indicator of motor pathway function during insular glioma surgery. This method indicates that remote ischemia, in this study the leading cause of impending motor deterioration, helps to avert definitive stroke of the motor pathways and permanent new paresis in the majority of cases. The rate of permanently severe new deficit appears to be greater in unmonitored cases.
Association between fluorine-18–labeled fluorodeoxyglucose uptake and 1p and 19q loss of heterozygosity in World Health Organization Grade II gliomas
Authors: Stockhammer Florian , Thomale Ulrich-Wilhelm , Plotkin Michail , Hartmann Christian , von Deimling Andreas 
Published: January 2008

Object
Oligodendroglial tumors harboring combined 1p and 19q loss (1p/19q LOH) are characterized by a favorable prognosis and response to chemotherapy and radiotherapy, but detection of 1p/19q LOH relies on postoperative procedures. The authors investigated the potential of fluorine-18–labeled fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) to predict 1p/19q LOH preoperatively in tumors whose appearance on initial magnetic resonance images was consistent with that of low-grade glioma.

Methods
The study population comprised 25 patients who had undergone preoperative FDG-PET followed by tumor resection. Neuronavigation ensured a precise match of FDG uptake wi th the site of biopsy. All tumor specimens were graded according to the World Health Organization (WHO) classification system. Microsatellite analysis was used to identify 1p/19q LOH.
In this series, 16 of 25 gliomas corresponded to WHO Grade II. In eight of these 16, 1p/19q LOH was detected. Raised glucose utilization within the tumor was seen in the six of eight WHO Grade II gliomas with 1p/19q LOH and in none of the WHO Grade II gliomas without this genetic alteration (p = 0.003).

Conclusions
These findings demonstrate the potential of FDG-PET to predict 1p/19q LOH in WHO Grade II gliomas.
Protection of mitochondrial function and improvement in cognitive recovery in rats treated with hyperbaric oxygen following lateral fluid-percussion injury
Authors: Zhou Zhengwen , Daugherty Wilson P. , Sun Dong , Levasseur Joseph E. , Altememi Nabil , Hamm Robert J. , Rockswold Gaylan L. , Bullock M. Ross 
Published: January 2008

Object
Hyperbaric oxygen (HBO2) has been shown to improve outcome after severe traumatic brain injury, but its underlying mechanisms are unknown. Following lateral fluid-percussion injury (FPI), the authors tested the effects of HBO2 treatment as well as enhanced normobaric oxygenation on mitochondrial function, as measured by both cognitive recovery and cellular adenosine triphosphate (ATP) levels.

Methods
Adult male Sprague–Dawley rats were subjected to moderate lateral FPI or sham injury and were allocated to one of four treatment groups: 1) FPI treated with 4 hours of normobaric 30% O2; 2) FPI treated with 4 hours of normobaric 100% O2; 3) FPI treated with 1 hour of HBO2 plus 3 hours of normobaric 100% O2; and 4) sham-injured treated with normobaric 30% O2. Cognitive outcome was assessed using the Morris water maze (MWM) on Days 11 to 15 after injury. Animals were then killed 21 days postinjury to assess hippocampal neuronal loss. Adenosine triphosphate was extracted from the neocortex and measured using high-performance liquid chromatography. The results showed that injured animals treated with HBO2 or normobaric 100% O2 alone had significantly higher levels of cerebral ATP as compared with animals treated using normobaric 30% O2 (p ≤ 0.05). The injured animals treated with HBO2 had significant improvements in cognitive recovery, as characterized by a shorter latency in MWM performance (p ≤ 0.05), and decreased neuronal loss in the CA2/3 and hilar regions as compared with those treated with 30% or 100% O2 (p ≤ 0.05).

Conclusions
Both hyperbaric and normobaric hyperoxia increased cerebral ATP levels after lateral FPI. In addition, HBO2 treatment improved cognitive recovery and reduced hippocampal neuronal cell loss after brain injury in the rat.
Historical evolution of stereotactic amygdalotomy for the management of severe aggression
Authors: Fountas Kostas N. , Smith Joseph R. 
Published: January 2008

✓Friedrich Goltz first reported in the 1890s that temporal lobe removal had a taming effect in animals. The results of studies by Klüver and Bucy, and later Terzian and Ore, demonstrated that an amygdalectomy combined with a temporal lobectomy had a significant taming effect in both animals and humans. Based on these observations, Narabayashi and colleagues reported the first clinical series of patients with temporal lobe epilepsy and/or severe behavioral disturbances in which stereotactic amygdalotomy was performed to address aggressive disorders, using a frame-based stereo-tactic device designed by Narabayashi. Use of pneumoencephalography, combined with physiological localization by means of olfactory stimulation and field potential recordings, enabled these investigators to define the lateral part of the amygdala, while simultaneously using wax injections to create lesions. Chitanondh used a similar localization technique to produce medial amygdala lesions by injecting a mixture of olive oil, wax, and iodized oil.
In 1966, Heimburger and coworkers reported results from a series of 25 patients with epilepsy and aggressive behavior who underwent stereotactic amygdalotomy. Their technique was slightly different and their target localization was solely anatomical, based on pneumoencephalography or contrast ventriculography, and they utilized a cryoprobe to make lesions. In 1970, Balasubramaniam and Ramamurthi reported the largest clinical series to date on this technique; pneumoencephalography or contrast ventriculography was used for anatomical localization, and depth electrode recordings were used to obtain physiological confirmation of their targets, whereas either diathermy or a Bertrand loop was used for making lesions. The development of magnetic resonance imaging technology in late 1980 allowed for a more accurate anatomical localization of the amygdala, and the improvement of radiofrequency generators also made lesioning more precise. Despite these and subsequent technological advances, the number of amygdalotomies performed has geometrically decreased during the last 20 years.
Language Representation
Authors: Rutten Geert-Jan , Ramsey Nick 
Published: January 2008

Dissociated language functions are largely invalidated by standard techniques such as the amobarbital test and cortical stimulation. Language studies in which magnetoencephalography (MEG) and functional magnetic resonance (fMR) imaging are used to record data while the patient performs lexicosemantic tasks have enabled researchers to perform independent brain mapping for temporal and frontal language functions (MEG is used for temporal and fMR imaging for frontal functions). In this case report, the authors describe a right-handed patient in whom a right-sided insular glioma was diagnosed. The patient had a right-lateralized receptive language area, but expressive language function was identified in the left hemisphere on fMR imaging– and MEG-based mapping. Examinations were performed in 20 right-handed patients with low-grade gliomas (control group) for careful comparison with and interpretation of this patient's results. In these tests, all patients were asked to generate verbs related to acoustically presented nouns (verb generation) for fMR imaging, and to categorize as abstract or concrete a set of visually presented words consisting of three Japanese letters for fMR imaging and MEG.
The most prominent display of fMR imaging activation by the verb-generation task was observed in the left inferior and middle frontal gyri in all participants, including the patient presented here. Estimated dipoles identified with the abstract/concrete categorization task were concentrated in the superior temporal and supra-marginal gyri in the left hemisphere in all control patients. In this patient, however, the right superior temporal region demonstrated significantly stronger activations on MEG and fMR imaging with the abstract/concrete categorization task. Suspected dissociation of the language functions was successfully mapped with these two imaging modalities and was validated by the modified amobarbital test and the postoperative neurological status. The authors describe detailed functional profiles obtained in this patient and review the cases of four previously described patients in whom dissociated language functions were found.