Influence of interleukin-6 on the development of peritumoral brain edema in meningiomas

2010 ◽  
Vol 112 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Kyung-Jae Park ◽  
Shin-Hyuk Kang ◽  
Yang-Seok Chae ◽  
Mi-Ok Yu ◽  
Tai-Hyoung Cho ◽  
...  

Object Peritumoral brain edema (PTBE) is associated with perioperative neurological deficits in patients with meningiomas. However, the pathogenesis of meningioma-associated edema remains unclear. In the present study, the authors investigated the expression of interleukin-6 (IL-6) and its relationship with PTBE in resected meningiomas. Methods Thirty-six benign meningiomas obtained in 36 patients were studied retrospectively. Edema volume was assessed on MR images, and an edema index (EI) was calculated. Interleukin-6 mRNA and protein expression were examined by real-time reverse transcriptase polymerase chain reaction and immunohistochemical staining. Results Peritumoral brain edema was found in 16 patients (44%). Neither age, sex, histological subtype, nor tumor location were related to PTBE. The level of IL-6 mRNA was 7.72 times greater in the edema group (EI > 0.2) than in the nonedema group (EI < 0.2; p = 0.011). On immunohistochemical analysis, IL-6 protein was found localized in the cytoplasm of the tumor cells, and was detected in 12 (75%) of 16 cases of edematous meningiomas, but in only 6 (30%) of 20 nonedematous cases. There was a significant correlation between the severity of PTBE and IL-6 expression (p = 0.004). Conclusions The authors' results in this study indicate that IL-6 expression may contribute to the development of brain edema associated with meningiomas.

2001 ◽  
Vol 94 (1) ◽  
pp. 97-101 ◽  
Author(s):  
Christine Rolhion ◽  
Frédérique Penault-Llorca ◽  
Jean-Louis Kémény ◽  
Jean-Jacques Lemaire ◽  
Christiane Jullien ◽  
...  

Object. Glioblastomas multiforme (GBMs) grow rapidly and are highly resistant to treatment compared with other glioma types and grades. Consequently, it is of major interest to identify markers of aggressiveness in these tumors that could represent new therapeutic targets. Interleukin (IL)—6 is frequently produced in gliomas and, given its manifold properties, could be considered as a candidate marker. Expression of IL-6 may be involved in cell growth, resistance to chemotherapy and radiotherapy (via an antiapoptotic pathway), and angiogenesis. This study was conducted to test this hypotheses and to evaluate the suitability of IL-6 as a target in the treatment of GBMs. Methods. The authors studied the relationship between the level of IL-6 gene expression as assessed using semiquantitative reverse transcription—polymerase chain reaction and by determining various histological types and grades in a series of 59 gliomas. It was found that GBMs displayed a significantly higher level of IL-6 expression than other types of glioma (p < 0.001). Immunohistochemical analysis revealed that IL-6 was produced mainly by malignant cells and a few vascular endothelial cells. Conclusions. It can be inferred from these findings that IL-6 gene expression is related to glioma aggressiveness and that IL-6 may play a central role in GBM behavior. Interleukin-6, therefore, could be considered as a new potential target in the treatment of GBMs.


2017 ◽  
Vol 12 (1) ◽  
pp. S935
Author(s):  
Katalin Fabian ◽  
Márton Gyulai ◽  
József Furák ◽  
Péter Várallyay ◽  
Márta Jäckel ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Cheng Hong Toh ◽  
Tiing Yee Siow

ObjectivesRodent experiments have provided some insights into the changes of glymphatic function associated with glioma growth. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with glioma. We aimed to investigate the factors associated with glymphatic function changes in patients with glioma.Materials and MethodsA total of 201 glioma patients (mean age = 47.4 years, 116 men; 86 grade II, 52 grade III, and 63 grade IV) who had preoperative diffusion tensor imaging for calculation of the ALPS index were retrospectively included. Information collected from each patient included sex, age, tumor grade, isocitrate dehydrogenase 1 (IDH1) mutation status, peritumoral brain edema volume, tumor volume, and ALPS index. Group differences in the ALPS index according to sex, tumor grade, and IDH1 mutation status were assessed using analysis of covariance with age adjustment. Linear regression analyses were performed to identify the factors associated with the ALPS index.ResultsGroup comparisons revealed that the ALPS index of grade II/III gliomas was significantly higher than that of grade IV gliomas (p &lt; 0.001). The ALPS index of IDH1 mutant gliomas was significantly higher than that of IDH1 wild-type gliomas (p &lt; 0.001). On multivariable linear regression analysis, IDH1 mutation (β = 0.308, p &lt; 0.001) and peritumoral brain edema volume (β = −0.353, p &lt; 0.001) were the two independent factors associated with the ALPS index.ConclusionIDH1 wild-type gliomas and gliomas with larger peritumoral brain edema volumes were associated with a lower ALPS index, which may reflect impaired glymphatic function.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Dong Xiang ◽  
Tao Wu ◽  
Cheng-Yang Feng ◽  
Xi-Ping Li ◽  
Yan-Jiao Xu ◽  
...  

Intrahepatic cholestasis is a main cause of hepatic accumulation of bile acids leading to liver injury, fibrosis, and liver failure. Our previous studies proved that Calculus Bovis Sativus (CBS) can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) in 17α-ethynylestradiol- (EE-) induced intrahepatic cholestasis rats. The regulation mechanism of CBS on these transporters, however, remains unclear. This study was designed to evaluate the possible relationship between the effect of CBS on transport activities and the regulation of CBS on the expression of PDZK1, a mainly scaffold protein which can regulate MRP2 and BCRP. Intrahepatic cholestasis model was induced in rats with injection of EE for five consecutive days and then the biliary excretion rates and cumulative biliary excretions were measured. The mRNA and protein expression levels of PDZK1 were detected by reverse transcription-quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analysis. When treated with CBS, cumulative biliary excretions and mRNA and protein expressions of PDZK1 were significantly increased in intrahepatic cholestasis rats. This study demonstrated that CBS exerted a beneficial effect on EE-induced intrahepatic cholestasis rats by restoring biliary transport function, which may result from the upregulation of PDZK1 expression.


1999 ◽  
Vol 7 (1) ◽  
pp. E2 ◽  
Author(s):  
Ross E. Mantle ◽  
Boleslaw Lach ◽  
Mauricio R. Delgado ◽  
Salleh Baeesa ◽  
Gerard Bélanger

Object The goal of this study was to determine whether the quantity of peritumoral brain edema displayed on computerized tomography (CT) scanning could be correlated with brain invasion and subsequent recurrence of meningiomas. Methods One hundred thirty-five patients who underwent resection of intracranial meningiomas at the Ottawa Civic Hospital were followed during the period 1980 to 1998. A complete resection was defined as one in which tumor, invaded bone, and involved dura were removed. Tumors were examined microscopically for evidence of brain invasion. The mean follow-up period was 9 years (± 4 years, standard deviation [SD]) and the mean time to recurrence was 5 years (± 4 years, SD). The authors used a simple grading system based on the average thickness (in centimeters) of edema seen on an axial CT slice showing the most tumor. Edema grade was linearly related to edema volume determined by digitizing the scans (r = 0.96; 29 cases). The chance of brain invasion increased by 20% for each centimeter of edema (rs = 1, p < 0.0001; 124 cases). The presence of brain invasion was predictive of recurrence after complete resection with an accuracy of 83%, a sensitivity of 89%, and a specificity of 82%. The chance of recurrence within 10 years after complete resection was given by the equation: percentage chance of recurrence = (centimeter of edema)3 X 0.7, which can be used to predict the chance of recurrence based on findings on CT scans (rs = 1.00, p < 0.0001; 86 patients). Statistical significance was confirmed using Kaplan-Meier and univariate and multivariate analyses. Completeness of resection was the most powerful predictor of recurrence (p < 0.00001, r = 0.6), followed by edema grade and brain invasion (both p = 0.02, r = 0.1). Patient age and gender and tumor location, size, and histological subtype were nonsignificant factors. Conclusions Brain invasion causes peritumoral edema. Invaded brain tissue is also the source of residual cells in cases of tumor recurrence after gross-total resection.


Oncology ◽  
2016 ◽  
Vol 91 (5) ◽  
pp. 237-242 ◽  
Author(s):  
Katalin Fábián ◽  
Márton Gyulai ◽  
József Furák ◽  
Péter Várallyay ◽  
Márta Jäckel ◽  
...  

2017 ◽  
Vol 127 (4) ◽  
pp. 905-916 ◽  
Author(s):  
Martin Piazza ◽  
Jeeva Munasinghe ◽  
Roger Murayi ◽  
Nancy Edwards ◽  
Blake Montgomery ◽  
...  

OBJECTIVETo study peritumoral brain edema (PTBE), it is necessary to create a model that accurately simulates vasogenic brain edema (VBE) without introducing a complicated tumor environment. PTBE associated with brain tumors is predominantly a result of vascular endothelial growth factor (VEGF) secreted by brain tumors, and VEGF infusion alone can lead to histological blood-brain barrier (BBB) breakdown in the absence of tumor. VBE is intimately linked to BBB breakdown. The authors sought to establish a model for VBE with chronic infusion of VEGF that can be validated by serial in-vivo MRI and histological findings.METHODSMale Fischer rats (n = 182) underwent stereotactic striatal implantation of MRI-safe brain cannulas for chronic infusion of VEGF (2–20 µg/ml). Following a preinfusion phase (4–6 days), the rats were exposed to VEGF or control rat serum albumin (1.5 µl/hr) for as long as 144 hours. Serial MRI was performed during infusion on a high-field (9.4-T) machine at 12–24, 24–36, 48–72, and 120–144 hours. Rat brains were then collected and histological analysis was performed.RESULTSControl animals and animals infused with 2 µg/ml of VEGF experienced no neurological deficits, seizure activity, or abnormal behavior. Animals treated with VEGF demonstrated a significantly larger volume (42.90 ± 3.842 mm3) of T2 hyper-attenuation at 144 hours when compared with the volume (8.585 ± 1.664 mm3) in control animals (mean difference 34.31 ± 4.187 mm3, p < 0.0001, 95% CI 25.74–42.89 mm3). Postcontrast T1 enhancement in the juxtacanalicular region indicating BBB breakdown was observed in rats undergoing infusion with VEGF. At the later time periods (120–144 hrs) the volume of T1 enhancement (34.97 ± 8.99 mm3) was significantly less compared with the region of edema (p < 0.0001). Histologically, no evidence of necrosis or inflammation was observed with VEGF or control infusion. Immunohistochemical analysis demonstrated astrocyte activation, vascular remodeling, and increased claudin-5 expression in juxtacanalicular regions. Aquaporin-4 expression was increased in both control and VEGF animals in the juxtacanalicular regions.CONCLUSIONSThe results of this study show that chronic brain infusion of VEGF creates a reliable model of VBE. This model lacks necrosis and inflammation that are characteristic of previous models of VBE. The model allows for a precise investigation into the mechanism of VBE formation. The authors also anticipate that this model will allow for investigation into the mechanism of glucocorticoid action in abrogating VBE, and to test novel therapeutic strategies targeting PTBE.


1994 ◽  
Vol 72 (05) ◽  
pp. 762-769 ◽  
Author(s):  
Toshiro Takafuta ◽  
Kingo Fujirmura ◽  
Hironori Kawano ◽  
Masaaki Noda ◽  
Tetsuro Fujimoto ◽  
...  

SummaryGlycoprotein V (GPV) is a platelet membrane protein with a molecular weight of 82 kD, and one of the leucine rich glycoproteins (LRG). By reverse transcription-polymerase chain reaction (RT-PCR), GPV cDNA was amplified from mRNA of platelets and megakaryocytic cell lines. However, since there are few reports indicating whether GPV protein is expressed in megakaryocytes as a lineage and maturation specific protein, we studied the GPV expression at the protein level by using a novel monoclonal antibody (1D9) recognizing GPV. Flow cytometric and immunohistochemical analysis indicated that GPV was detected on the surface and in the cytoplasm of only the megakaryocytes in bone marrow aspirates. In a megakaryocytic cell line UT-7, GPV antigen increased after treatment with phorbol-12-myri-state-13-acetate (PMA). These data indicate that only megakaryocytes specifically express the GPV protein among hematopoietic cells and that the expression of GPV increases with differentiation of the megakaryocyte as GPIb-IX complex.


2014 ◽  
Vol 68 (2) ◽  
pp. 85-88
Author(s):  
Natalija Dolnenec-Baneva ◽  
Dijana Nikodijevic ◽  
Gordana Kiteva-Trenchevska ◽  
Igor Petrov ◽  
Dragana Petrovska-Cvetkovska ◽  
...  

AbstractIntroduction.Several mechanisms in formation of perihemorrhagic edema are activated after contact of brain tissue-extravasated blood in intracerebral hemorrhage. Cysteinyl leukotrienes (cysLT) (C4, D4, E4) are included in this process as significant edema factors and they determine the neurological deficit and outcome. The study aim was a 5-day follow-up (admission/3 day/5 day) of urinary cysLT, hematoma volume, edema volume values and their correlation in patients after spontaneous, primary supratentorial intracerebral hemorrhage.Methods.An enzyme immunoassay was used for urinary cysLT measured in 62 patients and 80 healthy controls. Hematoma and edema volumes were visualized and measured by computed tomography and mathematically calculated with a special spheroid shape formula (V=AxBxC/2).Results.CysLT of hemorrhagic patients (1842.20±1413.2, 1181.54±906.2, 982.30±774.2pg/ml/mg creatinine) were significantly excreted (p<0.01). Brain edema (12.86±13.5, 22.38±21.1, 28.45±29.4cm3) was significantly increased (p<0.01). Hematoma volume values (13.05±14.5, 13.13±14.7, 12.99±14.7cm3) were not significant (p>0.05). A high correlation (multiple regression) between cysLT, hematoma and edema was found on the 3rdday (R=0.6) and a moderate correlation at admission (R=0.3) and on the 5thday (R=0.3).Conclusion.In our 5-day follow-up study a significant cysLT brain synthesis and significant brain edema progression versus constant hematoma volume values in hemorrhagic patients was found. A high correlation between cysLT, hematoma and edema volume was found on the 3rdday, a moderate correlation on admission and on the 5thday, which means that high cysLT and hematoma values were associated with high/moderate edema values.


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