Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme.

Background: Glioblastoma multiforme (GBM) is the vicious malignant brain tumor in adults. Despite advances multi-disciplinary treatment, GBM constinues to have a poor overall survival. CDDO-trifluoroethyl-amide (CDDO-TEFA), a trifluoroethylamidederivative of CDDO, is an Nrf2/ARE pathway activator. CDDO-TEFEA is used to inhibit proliferation and induce apoptosis in glioma cells. However, it not clear what effect it may have on tumorigenesis in GBM. Methods: This in vitro study evaluated the effects of CDDO-TFEA on GBM cells. To do this, we treated GBM8401 cell lines with CDDO-TFEA and assessed apoptosis, cell cycle. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis. Results: CDDO-TFEA significantly inhibited the cell viability and induced cell apoptosis on GBM 8401 cell line. The annexin-FITC/PI assay revealed significant changes in the percentage of apoptotic cells. Treatment with CDDO-TFEA led to a significant reduction in the GBM8401 cells' mitochondrial membrane potential. A significant rise in the percentage of caspase-3 activity was detected in the treated cells. In addition, treatment with CDDO-TFEA led to an accumulation of G2/M-phase cells. In addition, these results suggest that regarding increased protein synthesis during mitosis in the MPM-2 staining, indicative of a delay in the G2 checkpoint. An analysis of Cyclin B1, CDK1, Cyclin B1/CDK1 complex and CHK1 and CHK2 expression suggested that cell cycle progression seems also to be regulated by CDDO-TFEA. Therefore, CDDO-TFEA may not only induce cell cycle G2/M arrest, it may also exert apoptosis in established GBM cells. Conclusion: CDDO-TFEA can inhibit proliferation, cell cycle progression and induce apoptosis in GBM cells in vitro, possibly though its inhibition of Cyclin B1, CDK1 expression, and Cyclin B1/CDK1 association and the promotion of CHK1 and CHK2 expression.

RTA404, an Activator of Nrf2, Activates the Checkpoint Kinases and Induces Apoptosis through Intrinsic Apoptotic Pathway in Malignant Glioma.

Background: Malignant glioma (MG) is an aggressive malignant brain tumor. Despite advances in multidisciplinary treatment, overall survival rates remain low. A trifluoroethyl amide derivative of 2-cyano-3-,12-dioxoolean-1,9-dien-28-oic acid (CDDO), CDDO-trifluoroethyl amide (CDDO-TFEA) is a nuclear erythroid 2-related factor 2/antioxidant response element pathway activator. RTA404 is used to inhibit proliferation and induce apoptosis in cancer cells. However, its effect on tumorigenesis in glioma is unclear. Methods: This in vitro study evaluated the effects of RTA404 on MG cells. We treated U87MG cell lines with RTA404 and performed assessments of apoptosis and cell cycle distributions. DNA content and apoptosis induction were subjected to flow cytometry analysis. The mitotic index was assessed based on MPM-2 expression. Protein expression was analyzed through Western blotting. Results: RTA404 significantly inhibited the cell viability and induced cell apoptosis on the U87MG cell line. The Annexin-FITC/PI assay revealed significant changes in the percentage of apoptotic cells. Treatment with RTA404 led to a significant reduction in the U87MG cells' mitochondrial membrane potential. A significant rise in the percentage of caspase-3 activity was detected in the treated cells. In addition, these results suggest that cells pass the G2 checkpoint without cell cycle arrest by RTA404 treatment in the MPM-2 staining. An analysis of CHK1, CHK2, and p-CHK2 expression suggested that the DNA damage checkpoint system seems also to be activated by RTA404 treatment in established U87MG cells. Therefore, RTA404 may not only activate the DNA damage checkpoint system, it may also exert apoptosis in established U87MG cells. Conclusions: RTA404 inhibits the cell viability of gliomas and induces cancer cell apoptosis through intrinsic apoptotic pathway in Malignant glioma. In addition, the DNA damage checkpoint system seems also to be activated by RTA404. Taken together, RTA404 activated the DNA damage checkpoint system and induced apoptosis through intrinsic apoptotic pathways in established U87MG cells.

In-hospital mortality prediction in patients receiving mechanical ventilation in Taiwan.

BACKGROUND: Few studies have used pooled data for more than 2 years and few have analyzed data for patients receiving mechanical ventilation in Taiwan. Objective To validate the use of an artificial neural network model for predicting in-hospital mortality in patients receiving mechanical ventilation in Taiwan and to compare the predictive accuracy of the artificial neural network model with that of a logistic regression model. METHODS: Retrospective comparison of 1000 pairs of data sets processed by logistic regression and artificial neural network models based on initial clinical data for 213 945 patients receiving mechanical ventilation. For each pair of artificial neural network and logistic regression models, the area under the receiver operating characteristic curves, Hosmer-Lemeshow statistics, and accuracy rate were calculated and compared by using t tests. Global sensitivity analysis and sensitivity score approach were also used to assess the relative significance of input parameters in the system model and the relative importance of variables. RESULTS: Compared with the logistic regression model, the artificial neural network model had a better accuracy rate in 96.3% of cases, better Hosmer-Lemeshow statistics in 41.2% of cases, and a better area under the curve in 97.6% of cases. Hospital volume was the most influential (sensitive) variable affecting in-hospital mortality, followed by Charlson comorbidity index, length of stay, and hospital type. CONCLUSIONS: Compared with the conventional logistic regression model, the artificial neural network model was more accurate in predicting in-hospital mortality and had higher overall performance indices.

Intraoperative intracranial pressure and cerebral perfusion pressure for predicting surgical outcome in severe traumatic brain injury.

Intraoperative intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were evaluated for use as prognostic indicators after surgery for severe traumatic brain injury (TBI), and threshold ICP and CPP values were determined to provide guidelines for patient management. This retrospective study reviewed data for 66 patients (20 females and 46 males) aged 13-83 years (average age, 48 years) who had received decompressive craniectomy and hematoma evacuation for severe TBI. The analysis of clinical characteristics included Glascow Coma Scale score, trauma mechanism, trauma severity, cerebral hemorrhage type, hematoma thickness observed on computed tomography scan, Glasgow Outcome Scale score, and mortality. Patients whose treatment included ICP monitoring had significantly better prognosis (p < 0.001) and significantly lower mortality (p = 0.016) compared to those who did not receive ICP monitoring. At all three major steps of the procedure, i.e., creation of the burr hole, evacuation of the hematoma, and closing of the wound, intraoperative ICP and CPP values significantly differed. The ICP and CPP values were also significantly associated with surgical outcome in the severe TBI patients. Between hematoma evacuation and wound closure, ICP and CPP values differed by 6.8 ± 4.5 and 6.5 ± 4.6 mmHg, respectively (mean difference, 6 mmHg). Intraoperative thresholds were 14 mmHg for ICP and 56mmH for CPP. Monitoring ICP and CPP during surgery improves management of severe TBI patients and provides an early prognostic indicator. During surgery for severe TBI, early detection of increased ICP is also crucial for enabling sufficiently early treatment to improve surgical outcome. However, further study is needed to determine the optimal intraoperative ICP and CPP thresholds before their use as subjective guidelines for managing severe TBI patients.

Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC).

Lung cancer is the most common cause of cancer-related death. Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents. In recent studies, Simvastatin (SIM) has demonstrated anti-tumor activity, as well as potent chemopreventive action. As an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), SIM has been shown to stimulate apoptotic cell death. In this study, an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer (Non-small cell lung cancer; NSCLC) cells (NCI-H460); however, induced apoptosis was not observed in NCI-H460 cells. Protein expression levels of cell cycle regulating proteins Cdk4, Cyclin D1, p16 and p27 were markedly altered by SIM. Collectively, our results indicate that SIM inhibits cell proliferation and arrests NCI-H460 cell cycle progression via inhibition of cyclin-dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27. Our findings suggest that, in addition to the known effects on hypercholesterolemia therapy, SIM may also provide antitumor activity in established NSCLC.

Dengue virus enhances thrombomodulin and ICAM-1 expression through the macrophage migration inhibitory factor induction of the MAPK and PI3K signaling pathways.

Dengue virus (DV) infections cause mild dengue fever (DF) or severe life-threatening dengue hemorrhagic fever (DHF). The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM) is a glycoprotein expressed on the surface of vascular endothelial cells that plays an important role in the thrombin-mediated activation of protein C. Prior studies have shown that the serum levels of soluble TM (sTM) and macrophage migration inhibitory factor (MIF) are significantly increased in DHF patients compared to levels in DF patients or normal controls. In this study, we investigated how MIF and sTM concentrations are enhanced in the plasma of DHF patients and the potential effect of MIF on coagulation through its influence on two factors: thrombomodulin (TM) and intercellular adhesion molecule-1 (ICAM-1) in endothelial cells and monocytes. Recombinant human macrophage migration inhibitory factor (rMIF) was used to treat monocytic THP-1 cells and endothelial HMEC-1 cells or primary HUVEC cells. The subsequent expression of TM and ICAM-1 was assessed by immunofluorescent staining and flow cytometry analysis. Additionally, the co-incubation of THP-1 cells with various cell signaling pathway inhibitors was used to determine the pathways through which MIF mediated its effect. The data provided evidence that severe DV infections induce MIF expression, which in turn stimulates monocytes or endothelial cells to express TM and ICAM-1 via the Erk, JNK MAPK and the PI3K signaling pathways, supporting the idea that MIF may play an important role as a regulator of coagulation.

Growth inhibition and apoptosis of neuroblastoma cells through ROS-independent MEK/ERK activation by sulforaphane.

Deregulation of apoptosis alters the balance of cell proliferation and cell death, resulting in a variety of diseases, including cancer. In recent studies, sulforaphane (SFN) has demonstrated potent anti-tumor and chemopreventive activities. A possible signal transduction pathway has also been elucidated for SFN-induced apoptosis in human neuroblastoma SH-SY5Y cells. The present study further investigates the anti-proliferation activities of SFN through induced apoptosis in SH-SY5Y cells. We found that treating SH-SY5Y cells with SFN resulted in the depletion of mitochondrial membrane potential (Δψ), which in turn increased caspase 9, caspase 3, and the up-regulation of phosphorylated MEK/ERK without generating reactive oxygen species. Results were confirmed by MTT assay, which demonstrated the cytotoxic activity of SFN against SH-SY5Y cells (IC50 values of 20 µM).

Effect of sulforaphane on growth inhibition in human brain malignant glioma GBM 8401 cells by means of mitochondrial- and MEK/ERK-mediated apoptosis pathway.

In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant and anti-tumor activities as well as potent chemopreventive action against cancer. The present study investigates the anti-proliferation (using MTT assay, SFN demonstrated cytotoxic activity against GBM 8401 cell with IC(50) values at 35.52 µM) and induced apoptosis of SFN 24-h treatment in the cells of human brain malignant glioma GBM 8401 cells. We studied the MMP, caspase, MEK/ERK activation, and NF-κB transcription factor activity. Our results indicate that SFN inhibits cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects increased in proportion to the dosage of SFN, and apoptosis was induced via mitochondria- and caspase-dependent pathways. Daily s.c. injections of SFN for 3 weeks in severe combined immunodeficient mice (SCID) with GBM8401 s.c. tumors resulted in a decrease in mean tumor weight of 69-75 % compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, SFN may provide antitumor activity in established malignant glioma.

Demethoxycurcumin Retards Cell Growth and Induces Apoptosis in Human Brain Malignant Glioma GBM 8401 Cells.

Demethoxycurcumin (DMC; a curcumin-related demethoxy compound) has been recently shown to display antioxidant and antitumor activities. It has also produced a potent chemopreventive action against cancer. In the present study, the antiproliferation (using the MTT assay, DMC was found to have cytotoxic activities against GBM 8401 cell with IC(50) values at 22.71 µM) and induced apoptosis effects of DMC have been investigated in human brain malignant glioma GBM 8401 cells. We have studied the mitochondrial membrane potential (MMP), DNA fragmentation, caspase activation, and NF-κB transcriptional factor activity. By these approaches, our results indicated that DMC has produced an inhibition of cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dosage of DMC treatment, and the apoptosis was induced by DMC in human brain malignant glioma GBM 8401 cells via mitochondria- and caspase-dependent pathways.

Anterior discectomies and interbody cage fusion without plate fixation for 5-level cervical degenerative disc disease: a 5-year follow-up.

Anterior discectomy and interbody fusion have been proven to be a safe and effective procedure for the treatment of cervical degenerative disc disease. Clinical results for 1- to 4-level interbody cage fusion without plate fixation are encouraging. Five-level cervical interbody cage fusion without plate fixation has not yet been previously reported. We report a 63-year-old female patient suffering from severe pain of the bilateral shoulders and left upper extremity with numbness and weakness of legs. Magnetic resonance imaging showed cervical degenerative disc herniation with cord compression between the levels of C2 and C7. Anterior cervical discectomy and interbody cage fusion without plate fixation were performed. Pain and neurological function improved dramatically after surgery. Asymptomatic subsidence of the cage occurred at the level of C6-7 two months postoperatively with no further progression of subsidence 5 years postoperatively. Good stability of the cages was seen on flexion and extension radiographs 5 years postoperatively. We report the first case with good long-term results of 5-level interbody cage fusion without plate fixation for anterior cervical degenerative disc surgery.

Posterior epidural migration of sequestrated lumbar disc fragments into the bilateral facet joints: case report.

BACKGROUND AND IMPORTANCE: Symptomatic lumbar disc herniation is common. Migration of a free disc fragment is usually found in rostral, caudal, or lateral directions. Posterior epidural migration is very rare. We report the first case with posterior epidural migration and sequestration into bilateral facet joints of a free disc fragment. CLINICAL PRESENTATION: A 78-year-old female presented with low back pain and right leg pain. Plain radiographs showed lumbar spondylolisthesis. Magnetic resonance imaging revealed a posterior epidural mass and intrafacet mass, which was hypointense on T1-weighted images and hyperintense on T2-weighted images. The lesion in the left L3-4 facet joint had rim enhancement, whereas the right one was not contrasted after gadolinium injection. Preoperative differential diagnosis included abscess, tumor, hematoma, or synovial cyst. An interbody cage fusion at L3-4 and L4-5 for spondylolisthesis was performed, and a hybrid technique was applied with the Dynesys flexible rod system at L3-S1 for multisegment degenerative disc disease. The lesion proved to be an epidural disc fragment with sequestration into bilateral facet joints. CONCLUSION: A free disc fragment should be considered in the differential diagnosis of posterior epidural lesions, and even in the facet joint.

Functional outcome analysis: instrumented posterior lumbar interbody fusion for degenerative lumbar scoliosis.

PURPOSE: Although instrumented posterior lumbar interbody fusion (PLIF) has been becoming a popular and effective method for treating degenerative lumbar scoliosis, the clinical outcome is rarely reported. We retrospectively evaluated the clinical and radiographic outcomes in patients with degenerative lumbar scoliosis after instrumented PLIF. MATERIALS AND METHODS: A total of 58 patient's clinical characteristics had been reviewed retrospectively including clinical presentations, preoperative medical comorbidities, intraoperative status, and postoperative status. Oswestry disability index (ODI), visual analog scale (VAS), and patient satisfaction were evaluated before surgery and last follow-up period. The relationship between the difference of radiographic parameter and functional outcome was evaluated. RESULTS: Functional outcomes including ODI scores and VAS were significantly improved at the last visit. The ODI was 28.1 ± 8.0 before surgery and 12.2 ± 8.8 at the last visit. VAS was 7.4 ± 2.0 before surgery and 2.4 ± 2.0 at the last visit. Patient satisfaction was 72% at the last visit. ODI was significantly related to postoperative radiographic parameters including Cobb's angle (p < 0.001), L4 inclination (p = 0.011), coronal balance (p = 0.007), lateral vertebral translation (p < 0.001), Nash-Moe grade (p = 0.033), Nash-Moe degree (p = 0.025), and sagittal balance (p = 0.041) Using multiple regression analysis, ODI was significantly related to female gender, number of levels fixed, coronal balance, lateral vertebral translation, and Nash-Moe degree. The was no significant correlation between postoperative radiographic parameters and pain (VAS). Only lateral vertebral translation demonstrated a significant correlation in multiple regression analysis. CONCLUSIONS: Based on the VAS and ODI instrument, our studies demonstrated that instrumented PLIF for adult degenerative lumbar scoliosis can achieve a high rate of patient satisfaction and improvement in radiographic and clinical outcomes at a minimum of 2 years of follow-up.

Curcuminoids suppress the growth and induce apoptosis through caspase-3-dependent pathways in glioblastoma multiforme (GBM) 8401 cells.

Curcuminoids, natural plant components, have been recently shown to display antioxidant and anti-inflammatory activities. They also produce potent chemo-preventive action against several types of cancer. In the present study, the anti-proliferative and induced apoptosis effects of curcuminoids have been investigated in human brain glioblastoma multiforme (GBM) 8401 cells. Results indicated that curcuminoids have produced an inhibition of cell proliferation in a dose-dependent manner as dosage increased from 12.5 to 100 µM (n = 6) via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dose of curcuminoids. We have studied the mitochondrial membrane potential (ΔΨm), DNA fragmentation, caspase-3, caspase-8, and caspase-9 activation, and nuclear factor κB (NF-κB) transcriptional factor activity to analyze apoptosis in GBM 8401 cells. From these approaches, apoptosis was induced by curcuminoids in human brain GBM 8401 cells via mitochondria and a caspase-dependent pathway. The results observed with proliferation inhibition (y = 94.694e(-0.025x), R(2) = 0.9901, and n = 6) and apoptosis (y = 0.9789e(-0.0102x), R(2) = 0.99854, and n = 3) depend upon the amount of curcuminoid treatment in the cancer cells.

A comparative study of the patients with bilateral or unilateral chronic subdural hematoma: precipitating factors and postoperative outcomes.

BACKGROUND: : Chronic subdural hematoma (CSDH) is a relatively frequent problem in neurologic or neurosurgical practice. Although CSDH is a well-known disease, data on bilateral CSDH are scarce compared with data on unilateral CSDH. The purpose of this study was to compare the clinical presentations, precipitating factors, computed tomography (CT) scan findings, postoperative complications, and outcomes between patients with bilateral and unilateral CSDH. METHODS: : A retrospective study was performed on 129 surgical patients with CSDH from January 2002 to January 2005. These patients were divided into two groups: bilateral CSDH (45 cases) and unilateral CSDH (84 cases). Clinical presentations, precipitating factors, CT scan findings, postoperative complications, and outcomes of patients were analyzed. RESULTS: : The mean age was 75 years for patients with bilateral CSDH and was 68 years for patients with unilateral CSDH (p = 0.696). Males predominated in each group (p = 0.696). The frequency of presenting symptoms of nausea and vomiting, headache, or unsteady gait was significantly greater in bilateral CSDH than in unilateral CSDH (p < 0.05). The incidence of usage of anticoagulant and antiplatelet therapy was significantly higher in bilateral CSDH group than in unilateral CSDH group (p < 0.05). The frequency of marked midline shift on CT scans was significantly greater in unilateral CSDH than in bilateral CSDH (p < 0.05). Coexisting systemic diseases, postoperative complications, and outcomes had no significant differences between both groups. CONCLUSIONS: : Bilateral CSDH tended to occur more in patients with anticoagulant or antiplatelet therapy. Compared with patients with unilateral CSDH, patients with bilateral CSDH had more symptoms of increased intracranial pressure and lower incidences of midline shift on CT scans. Most patients with either bilateral or unilateral CSDH had a good postoperative outcome.

Low-grade astrocytoma associated with abscess formation: case report and literature review.

A rare case of low-grade astrocytoma associated with abscess formation occurred in a 52-year-old man presenting with Broca's aphasia. He underwent craniotomy and tumor removal under the impression of brain tumor with necrotic cystic change. Abscess accumulation within the intra-axial tumor was found intraoperatively. Literature related to brain abscess with brain tumor is reviewed, with an emphasis on abscesses with astrocytoma. We discuss the common brain tumors that are associated with abscess, pathogens that coexist with brain tumor, and the pathogeneses of coexisting brain abscess and tumor. It is very important to know how to differentiate between and diagnose a brain abscess and tumor, or brain abscess with tumor, preoperatively from clinical presentation and through the use of computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging or magnetic resonance spectroscopy.

Analysis of surgically treated intraspinal tumors in southern Taiwan.

The medical records of 117 patients with spinal tumors who underwent surgery with pathologic confirmation from January 1999 to April 2004 at Kaohsiung Medical University Hospital were reviewed. Data from this review were compared with those obtained from the same institution 10 years earlier (covering the period 1988-1995) and from other reported series. There were 69 male and 48 female patients aged from 13 to 87 years old (mean age, 51.9). The most common pathologic findings were metastasis in 45.3% (53/117), nerve sheath tumors in 28.2% (33/117), meningiomas in 12% (14/117) and neuroepithelial tumors in 6% (7/117). The peak ages at diagnosis were 41-50 years and 61-70 years. A slight male predominance was noted for all tumors, except meningiomas. Motor weakness, even paralysis, was the major clinical presentation (64-86%), followed by sensory deficits (50%) and pain (42%). The location of tumors was most often in the thoracic (50.4%; 59/117), lumbosacral (27.4%; 32/117) and cervical spine (22.2%; 26/117) segments. Among the metastatic tumors, the lung (22.6%) and breast (15.1%) were the most common primary sites of origin, followed by unknown origin, the liver (hepatocellular carcinoma), the gastrointestinal tract and the nasopharynx (nasopharyngeal cancer).

Differentiation among metastatic brain tumors, radiation necroses, and brain abscesses using proton magnetic resonance spectroscopy.

Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) were evaluated for differentiating metastatic brain tumors, radiation necroses, and brain abscesses. Twelve histologically verified lesions in 12 patients were studied using preoperative MRI and proton MRS. The signal intensities of four major metabolites, N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and lactate (Lac), were observed over the region of interest. Metastatic brain tumors showed a decrease in NAA/Cr and an increase in Cho/Cr ratios. Radiation necroses showed a decrease in NAA/Cr and no change in Cho/Cr ratios. Brain abscesses showed an increase in Lac/Cr ratio. Correlation with histopathologic findings showed that a high Cho signal was suggestive of a metastatic brain tumor. Lac signals were observed in brain abscesses, presumably reflecting the anerobic glycolysis of living cells. Although more cases and studies are necessary, metabolic information provided by proton MRS combined with MRI is useful for differentiating among metastatic brain tumors, radiation necroses, and brain abscesses.

The alteration of prostaglandin E2 levels in patients with brain tumors before and after tumor removal.

BACKGROUND: Both experimental and human tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). This compound may play an important role in tumor growth and immunosuppression. Little is known of the production of PGE2 by brain tumors. The present study was designed to investigate the levels of PGE2 in the plasma of human brain tumors before and after tumor removal. METHODS: The plasma PGE2 levels of brain tumors before and after tumor removal were measured by high-performance liquid chromatography (HPLC). RESULTS: There is a significantly high concentration of PGE2 in malignant brain tumor before tumor removal. Significantly decrease of PGE2 concentration after total removal of the tumor was found both in the malignant and benign brain tumor groups (P = 0.0001 and P = 0.0039 respectively). However, compared to the control group, only malignant brain tumor showed a significant decrease of PGE2 concentration after tumor removal (P = 0.0009). CONCLUSION: Our study demonstrates the malignant brain tumor synthesized higher relative proportions of PGE2 and surgical removal of the brain tumor can reduce the production of PGE2.