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This study aimed to investigate the regulatory role of Aldo-keto reductase family 1 member B1 (AKR1B1) in glioma cell proliferation through p38 MAPK activation to control Bcl-2/BAX/caspase-3 apoptosis signaling. AKR1B1 expression was quantified in normal human astrocytes, glioblastoma multiforme (GBM) cell lines, and normal tissues by using quantitative real-time polymerase chain reaction. The effects of AKR1B1 overexpression or knockdown and those of AKR1B1-induced p38 MAPK phosphorylation and a p38 MAPK inhibitor (SB203580) on glioma cell proliferation were determined using an MTT assay and Western blot, respectively. Furthermore, the AKR1B1 effect on BAX and Bcl-2 expression was examined in real-time by Western blot. A luminescence detection reagent was also utilized to identify the effect of AKR1B1 on caspase-3/7 activity. The early and late stages of AKR1B1-induced apoptosis were assessed by performing Annexin V-FITC/PI double-staining assays. AKR1B1 expression was significantly downregulated in glioma tissues and GBM cell lines (T98G and 8401). Glioma cell proliferation was inhibited by AKR1B1 overexpression but was slightly increased by AKR1B1 knockdown. Additionally, AKR1B1-induced p38 MAPK phosphorylation and SB203580 reversed AKR1B1′s inhibitory effect on glioma cell proliferation. AKR1B1 overexpression also inhibited Bcl-2 expression but increased BAX expression, whereas treatment with SB203580 reversed this phenomenon. Furthermore, AKR1B1 induced caspase-3/7 activity. The induction of early and late apoptosis by AKR1B1 was confirmed using an Annexin V-FITC/PI double-staining assay. In conclusion, AKR1B1 regulated glioma cell proliferation through the involvement of p38 MAPK-induced BAX/Bcl-2/caspase-3 apoptosis signaling. Therefore, AKR1B1 may serve as a new therapeutic target for glioma therapy development.

Intracranial gliomas are the most common primary central nervous system tumors in humans, and glioblastoma multiforme is the most malignant intracranial glioma. The nucleotide-binding domain leucine-rich repeat (NLR)-containing family are crucial regulators of inflammatory and innate immune responses. NLRP12 codes for the monarch-1 protein, which regulates immune responses in humans. Data from a next-generation sequencing database indicated that NLRP12 expression is increased in glioma cells. However, the relationship between NLRP12 levels and gliomas is unclear.To explore the role of NLRP12-related translation factors and proteins in glioma, we evaluated the clinical data and paraffin sections from glioma patients. The expression of NLRP12 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests.The degree of malignancy and prognosis highly correlated with NLRP12 levels. In addition, the siRNA-mediated downregulation of NLRP12 in glioma cell lines decreased proliferation, invasion, and migration. The levels of VEGF, N-cadherin, and cyclin D1 were downregulated after knockdown of NRLP12 in glioma cell lines, as observed using western blotting in vitro. Knockdown of NLRP12 attenuated the tumor progression in vivo.The expression of NLRP12 may be an independent prognostic factor and a potential target for the treatment of intracranial glioma.

Background. Glioblastoma multiforme (GBM) is one of the most deadly and recalcitrant illnesses of the neurocentral nervous system in humans. MicroRNAs (miRNAs) are a class of noncoding RNAs that play important roles in the regulation of gene expression and biological processes, including radiosensitivity. In this study, we demonstrated the relationship between miR-3059-3p and radiation in GBM. Materials and Methods. Radioresistant (RR) cells were obtained by exposing GBM8401 cells to 80 Gy radiation in 20 weekly 4 Gy fractions. miR-3059-3p mRNA and DNA replication helicase/nuclease 2 (DNA2) protein expressions were detected using real-time polymerase chain reaction and immunoblotting. Using flow cytometry, colony formation and apoptosis were identified using miR-3059-3p mimic, miR-3059-3p inhibitor, DNA2 siRNA, and DNA2 plasmid. Immunoblotting was used to detect DNA repair proteins. Results. Low levels of miR-3059-3p and high levels of DNA2 were observed in RR cells. Colony formation and apoptosis assays revealed that miR-3059-3p targeted DNA2 to regulate radioresistance. Immunoblotting revealed that miR-3059-3p regulated the homologous recombination (HR) pathway (Rad51 and Rad52) but not the nonhomologous end joining pathway (ku70 and ku80). Conclusion. Downregulation of DNA2 via miR-3059-3p enhanced the radiosensitivity of GBM cells through the inhibition of the HR pathway.

Although the expression of p53 and epidermal growth factor receptor (EGFR) is associated with therapeutic resistance and patient outcomes in many malignancies, the relationship in astrocytomas is unclear. This study aims to correlate p53 and EGFR expression in brain astrocytomas with overall patient survival. Eighty-two patients with astrocytomas were enrolled in the study. Semi-quantitative p53 and EGFR immunohistochemical staining was measured in tumor specimens. The mean follow-up after astrocytoma surgery was 18.46 months. The overall survival rate was 83%. Survival was reduced in EGFR-positive patients compared with survival in EGFR-negative patients (p < 0.05). However, no significant differences in survival were detected between patients with high and low p53 expression. In patients with low p53 expression, positive EGFR staining was associated with significantly worse survival compared with patients with negative EGFR staining (log-rank test: p < 0.001). Survival rates in positive and negative EGFR groups with high p53 protein expression were similar (log-rank test: p = 0.919). The IC50 of an EGFR inhibitor was higher in GBM cells with high p53 protein expression compared with the IC50 in cells with low p53 expression. Combined EGFR and p53 expression may have prognostic significance in astrocytomas.

Yu-Feng Su,1– 3 Tai-Hsin Tsai,2– 4 Keng-Liang Kuo,2,4 Chieh-Hsin Wu,2,4 Cheng-Yu Tsai,1,2 Yen-Mou Lu,5 Shiuh-Lin Hwang,6 Pei-Chen Lin,7 Ann-Shung Lieu,2 Chih-Lung Lin,1,2,4 Chih-Hui Chang1,2,4 1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3Division of Neurosurgery, Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 4Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6Department of Spinal Surgery, Chi-Hsien Spine Hospital, Kaohsiung, Taiwan; 7Department of Oral Hygiene, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Chih-Hui Chang, Email chchang20@gmail.comBackground: The aim of this study was to investigate the learning curve of robotic spine surgery quantitatively with the well-described power law of practice.Methods: Kaohsiung Medical University Hospital set up a robotic spine surgery team by the neurosurgery department in 2013 and the orthopedic department joined the well-established team in 2014. A total of consecutive 150 cases received robotic assisted spinal surgery. The 150 cases, with 841 transpedicular screws were enrolled into 3 groups: the first 50 cases performed by neurosurgeons, the first 50 cases by orthopedic surgeons, and 50 cases by neurosurgeons after the orthopedic surgeons joined the team. The time per screw and accuracy by each group and individual surgeon were analyzed.Results: The time per screw for each group was 9.56 ± 4.19, 7.29 ± 3.64, and 8.74 ± 5.77 minutes, respectively, with p-value 0.0017. The accuracy was 99.6% (253/254), 99.5% (361/363), and 99.1% (222/224), respectively, with p-value 0.77. Though the first group took time significantly more on per screw placement but without significance on the nonlinear parallelism F-test. Analysis of 5 surgeons and their first 10 cases of short segment surgery showed the time per screw by each surgeon was 12.28 ± 5.21, 6.38 ± 1.54, 8.68 ± 3.10, 6.33 ± 1.90, and 6.73 ± 1.81 minutes. The first surgeon who initiated the robotic spine surgery took significantly more time per screw, and the nonlinear parallelism test also revealed only the first surgeon had a steeper learning curve.Conclusion: This is the first study to demonstrate that differences of learning curves between individual surgeons and teams. The roles of teamwork and the unmet needs due to lack of active perception are discussed.Keywords: human computer communication, human–robot collaboration, learning curve, robotic spine surgery, teamwork

Numerous studies have considered galectin-3 or Glycogen synthase kinase 3 beta (GSK3B) as a potential prognosis marker for various cancers. However, the correlation between the protein expression of galectin-3/GSK3B and the clinical parameters of astrocytoma has not been reported. This study aims to validate the correlation between the clinical outcomes and protein expression of galectin-3/GSK3B in astrocytoma. Immunohistochemistry staining was performed to detect galectin-3/GSK3B protein expression in patients with astrocytoma. The Chi-square test, Kaplan−Meier evaluation, and Cox regression analysis were used to determine the correlation between clinical parameters and galectin-3/GSK3B expression. Cell proliferation, invasion, and migration were compared between a non-siRNA group and a galectin-3/GSK3B siRNA group. Protein expression in galectin-3 or GSK3B siRNA-treated cells was evaluated using western blotting. Galectin-3 and GSK3B protein expression were significantly positively correlated with the World Health Organization (WHO) astrocytoma grade and overall survival time. Multivariate analysis revealed that WHO grade, galectin-3 expression, and GSK3B expression were independent prognostic factors for astrocytoma. Galectin-3 or GSK3B downregulation induced apoptosis and decreased cell numbers, migration, and invasion. siRNA-mediated gene silencing of galectin-3 resulted in the downregulation of Ki-67, cyclin D1, VEGF, GSK3B, p-GSK3B Ser9 (p-GSK3B S9), and β-catenin. In contrast, GSK3B knockdown only decreased Ki-67, VEGF, p-GSK3B S9, and β-catenin protein expression but did not affect cyclin D1 and galectin-3 protein expression. The siRNA results indicated that GSK3B is downstream of the galectin-3 gene. These data support that galectin-3 mediated tumor progression by upregulating GSK3B and β-catenin protein expression in glioblastoma. Therefore, galectin-3 and GSK3B are potential prognostic markers, and their genes may be considered to be anticancer targets for astrocytoma therapy.

Introduction: Toona sinensis is a traditional Chinese medicine commonly used in South-East Asia. The aqueous extracts of T. sinensis leaves (TSL) exhibit anticancer effects in various types of cancer. In this study, we assessed the effectiveness of TSL treatment for glioblastoma multiforme (GBM). Methods After treating A172 and U251 GBM with TSL, cell cycle and apoptotic cells were evaluated by flow cytometry, as well as anti-proliferative efficacy by MTT assay. Reactive oxygen species (ROS) and ATP production were quantified by CellROX, Dihydroethidium (DHE) and Tetramethylrhodamine methyl ester (TMRM). Apoptosis and MEK/ERK pathway related protein levels were detected by western blot. Results TSL treatment induced cell cycle arrest at G2/M and apoptosis. It also caused excessive ROS and decreased ATP production via blockage of electron transport chain (ETC) complexes, leading to ROS regulated mitochondrial dysfunction. Under TSL treatment in two GBM cells, the Bax and Puma protein level were elevated whereas Bcl-2 was descended. The mitochondria-mediated apoptosis and caspase-dependent pathway related proteins including cleaved caspase-3, cleaved caspase-9, and cleaved PARP were induced. Finally, U0126 as an inhibitor of MEK/ERK kinase was applied to demonstrate that the MEK/ERK pathway was responsible for the inhibition of ROS-regulated mitochondrial dysfunction and promoted apoptosis. Conclusion TSL treatment suppressed MEK/ERK activation to induce apoptosis through ROS-regulated mitochondrial dysfunction in GBM cells and provide a therapeutic potential in GBM therapy.

Meningioma has the second highest incidence among primary intracranial tumors. There is no effective treatment or targeted therapy for meningioma except excision and radiotherapy. Sp1 (specificity protein 1) is a transcription factor that regulates tumor growth, but the literature describing the relationship between Sp1 and meningioma is scarce. The purpose of this study was to investigate the relationship between Sp1 expression and the clinicopathological parameters in meningioma by immunohistochemical staining.We collected samples from 74 patients from 2008-2012 in Kaohsiung Medical University Hospital, with staging and prognosis of the pathological section of the meningioma.Our results show that Sp1 expression was significantly associated with World Health Organization grade, malignancy, and recurrence in patients with meningioma.High expression of Sp1 in patients with meningioma was linked to poor prognosis of recurrence-free time. Therefore Sp1 may be a candidate biomarker of prognosis and therapy target in meningioma.

Yu-Feng Su,1,2 Tai-Hsin Tsai,1,3 Ann-Shung Lieu,1,3,4 Chih-Lung Lin,1– 3 Chih-Hui Chang,1,2 Cheng-Yu Tsai,4– 6 Hui-Yuan Su1,3 1Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung, Taiwan; 6Post Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Cheng-Yu Tsai; Hui-Yuan Su, Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung, 80708, Taiwan, Tel +886-7-3215049, Fax +886-7-3215039, Email moutzyy691010@yahoo.com.tw; latimeria8@hotmail.comPurpose: Severe complications, including screw loosening events and low fusion rates, in spinal fusion surgery using the traditional open method are problematic. This retrospective study aimed to evaluate the rate of screw loosening and the clinical outcomes of bone-mounted miniature robot-assisted pedicle screw placement in patients treated for degenerative spinal disease.Patients and Methods: Data were collected from the medical records of 118 patients (mean age, 69 years). Differences in clinical outcomes, including the Oswestry disability index, visual analog scale score, screw loosening rate, cage fusion rate, and complications, were evaluated among different bone mineral densities.Results: The screw loosening and cage fusion rates for all patients, normal bone mineral density, osteopenia, and osteoporosis groups were 12%, 8.6%, 13.1%, and 14%, respectively, and 85.3%, 93%, 82.5%, and 81.4%, respectively. There was a higher screw loosening rate and a lower cage fusion rate in the osteopenia and osteoporosis groups than in the normal bone density group. The accuracy of the screw placement was 97.3%. There were no statistically significant differences in the Oswestry disability index and visual analog scale scores, and no major complications for dural tear or vascular or visceral injury.Conclusion: Our study demonstrated an acceptable screw loosening rate in patients with osteoporosis compared to that in patients with normal bone mineral density. The robotic system resulted in accurate screw placement in patients with osteoporosis.Keywords: robotic surgery, screw loosening rate, spinal fixation, spinal fusion, spinal fusion rate

Background. Glioblastoma multiforme (GBM) is the most common malignant brain tumor in the world. Despite advances in surgical resection, radiotherapy, and chemotherapy, GBM continues to have a poor overall survival. CDDO (2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid), a synthetic triterpenoid, is an Nrf2 activator used to inhibit proliferation and induce differentiation and apoptosis in various cancer cells. One new trifluoroethylamide derivative of CDDO, RTA 404, has been found to have increased ability to cross the blood-brain barrier. However, it is not clear what effect it may have on tumorigenesis in GBM. Methods. This in vitro study evaluated the effects of RTA 404 on GBM cells. To do this, we treated GBM840 and U87 MG cell lines with RTA 404 and assessed apoptosis, cell cycle, cell locomotion, and senescence. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis. Results. RTA 404 significantly inhibited the proliferation of tumor cells at concentrations higher than 100 nM ( p < 0.05 ) and reduced their locomotion ability. In addition, treatment with RTA 404 led to an accumulation of RTA 404-treated G 2 / M phase cells and apoptosis. An analysis of the p21/AKT expression suggested that RTA 404 may not only help prevent brain cancer but it may also exert antitumor activities in established GBM cells. Conclusion. RTA404 can inhibit proliferation, cell locomotion, cell cycle progression, and induce apoptosis in GBM cells in vitro, possibly through its inhibition of N-cadherin and E-cadherin expression via its inhibition of the AKT pathway.

Pineal apoplexy is a rare clinical condition. Its common symptoms include headaches, nausea, vomiting, ataxia, and gaze paralysis. These symptoms are mainly caused by obstructive hydrocephalus or direct compression of the cerebellum or midbrain. There have been no previous reports on the development of a recurrent pineal parenchymal tumor of intermediate differentiation (PPTID) with intratumoral hemorrhage. We report a case of PPTID with intratumoral hemorrhage. A 44-year-old woman developed recurrent PPTID following tumor removal and ventriculoperitoneal shunting in 2010. She visited the emergency department in April 2021 for sudden-onset dizziness and generalized weakness. Blurring of vision occurred and progressed over the previous month. Neurological examination revealed upward conjugate gaze paralysis. Brain computed tomography revealed a hyperdense lesion in the pineal region, and a recurrent tumor with hemorrhage was suspected. Magnetic resonance imaging of the brain confirmed a pineal tumor with intratumoral hemorrhage. The pineal tumor and hematoma were surgically removed via the suboccipital transtentorial approach. The patient was discharged from the hospital 2 weeks after the surgery. The pathological findings were consistent with the diagnosis of recurrent PPTID. PPTID is a rare tumor, accounting for less than 0.1% of primary central nervous system tumors. Pineal apoplexy is rare, and its incidence and clinical significance remain unclear. There have only been nine reported cases of pineal apoplexy, associated with pineal parenchymal tumors. The recurrence of PPTID with apoplectic hemorrhage after 10 years has not been reported. Despite its rarity, PPTID with apoplexy should be considered in patients with PPTID who develop sudden-onset neurological symptoms.

Background and objectives: Managing people with trigeminal neuralgia (TN) and osteoporosis is challenging due to their debilitating conditions. Currently, the exact association between TN and osteoporosis in patients remains unknown, although there is potential overlapping of pathophysiological mechanisms. In response, we calculated TN risk in patients who have osteoporosis. Materials and Methods: 45,393 patients aged over 50 years diagnosed with osteoporosis were matched with 45,393 non-osteoporosis patients aged over 50 years (1:1 ratio) who were used as the control group, using data from 1996 to 2010 from Taiwan’s National Health Insurance Research Database. The cumulative incidences of subsequent TN and the hazard ratio were estimated using Cox proportional hazards modeling and the Kaplan–Meier method, respectively. Results: Among the total sample, 333 patients were diagnosed with TN during the follow-up period: 205 in the osteoporosis cohort and 128 in the control cohort. Through covariate adjustment, the overall TN incidence showed a 1.80-fold increase in the osteoporosis cohort in comparison with the control cohort (0.60 vs. 0.18 per 1000 person-years, respectively). The High Charlson Comorbidity Index, hypertension, and migraines were risk factors of TN. Conclusions: Osteoporosis patients had a higher TN risk than that of the control cohort. Therefore, early recognition of pain and symptoms in osteoporotic people may help to identify possible TN patients who need prompt therapy.

Background: The aim of this study was to investigate the learning curve of robotic spine surgery quantitatively with the well-described power law of practice.Methods: Kaohsiung Medical University Hospital set up a robotic spine surgery team by the neurosurgery department in 2013 and the orthopedic department joined the well-established team in 2014. A total of 150 cases and 841 transpedicular screws were enrolled into 3 groups: the first 50 cases performed by neurosurgeons, the first 50 cases by orthopedic surgeons, and 50 cases by neurosurgeons after the orthopedic surgeons joined the team. The time per screw and accuracy by each group and individual surgeon were analyzed.Results: The time per screw for each group was 9.56±4.19, 7.29±3.64, and 8.74±5.77 minutes respectively. The accuracy was 99.6% (253/254), 99.5% (361/363), and 99.1% (222/224), respectively. The first group took significantly more time per screw, but without significance on the nonlinear parallelism test. Analysis of 5 surgeons and their first 10 cases of short segment surgery showed the time per screw by each surgeon was 12.28±5.21, 6.38±1.54, 8.68±3.10, 6.33±1.90, and 6.73±1.81 minutes. The first surgeon who initiated the robotic spine surgery took significantly more time per screw and the nonlinear parallelism test also revealed only the first surgeon had a steeper learning curve. Conclusions: This is the first study to demonstrate that differences of learning curves between individual surgeons and teams. The roles of teamwork and the unmet needs due to lack of active perception are discussed.

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.

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.

Meningiomas are the most common extra-axial primary central nervous system tumors. There is no effective treatment or targeted therapy for meningioma except excision and radiotherapy. glycogen synthesis kinase 3β interaction protein (GSKIP) is an A-kinase anchor protein that has cytosolic scaffolding function and binds to a protein kinase A and glycogen synthesis kinase 3β to modulate different biological processes and malignant tumorigenesis through the Wnt pathway. The purpose of this study was to investigate the relationship between GSKIP expression and the clinico-pathological parameters in meningioma using immunohistochemical staining. We collected samples from 74 patients, from 2008 to 2012, in the Kaohsiung Medical University Hospital that had data on the staging and prognosis of the meningioma pathological section. Chi-square, Kaplan-Meier method, and cox regression were used to analyze the correlation between clinical parameters and immunohistochemistry staining for GSKIP. Following our immunohistochemical score, we found that higher expression of GSKIP was associated with high World Health Organization grading, recurrence, malignant transformation, and reduced overall survival time and recurrence-free survival time in meningioma. GSKIP may be a biomarker of poor prognosis and a target protein for therapy in meningioma.

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, a trifluoroethylamidederivative of CDDO, is an Nrf2/ARE pathway activator. RTA 404 is used to inhibit proliferation and induce differentiation and apoptosis in glioma cells. However, it not clear what effect it may have on tumorigenesis in GBM.MethodsThis in vitro study evaluated the effects of RTA 404 on GBM cells. To do this, we treated GBM8401 cell lines with RTA 404 and assessed apoptosis, cell cycle. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis.ResultsRTA 404 significantly inhibited the proliferation induced cell apoptosis on GBM 8401 cell line. Typical plasma membrane undergoes structural changes that cause translocation of phosphatidylserine from the inside to outside. Due to cell external pressure cause mitochondrial membrane potential change lead to cell apoptosis. Caspase-3 active respond to apoptosis phenomenon, continuous progression of apoptosis.In addition, treatment with RTA 404 led to an accumulation of G2/M-phase cells. An analysis of Cyclin B1, CDK1 and Cyclin B1/CDK1 complex association suggested that cell cycle progression seems also to be regulated by RTA 404. Therefore, RTA 404 may not only induced cell cycle G2/M arrest, it may also exert apoptosis in established GBM cells. ConclusionRTA 404 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.

Intracranial germinomas mostly occur in teenagers and young adults. The common sites are pineal and suprasellar regions. Males with Klinefelter syndrome, compared with males without chromosomal abnormalities, are known to have a higher incidence of developing pineal or suprasellar germinomas. As for germinoma in the medulla oblongata, this is rare, with only 21 previous cases reported. Due to the rarities, any relationship between people with Klinefelter syndrome and medulla oblongata germinomas remains undetermined. We present a rare case of medulla oblongata germinoma in a 25-year-old man. It is the second case of medulla oblongata germinoma in association with Klinefelter syndrome. We emphasize the importance of karyotyping in every case of germinoma, especially those with intracranial germinomas at atypical locations.

Therapeutic resistance in recurrent glioblastoma multiforme (GBM) after concurrent chemoradiotherapy (CCRT) is a challenging issue. Although standard fractionated radiation is essential to treat GBM, it has led to local recurrence along with therapy-resistant cells in the ionizing radiation (IR) field. Lines of evidence showed cancer stem cells (CSCs) play a vital role in therapy resistance in many cancer types, including GBM. However, the molecular mechanism is poorly understood. Here, we proposed that autophagy could be involved in GSC induction for radioresistance. In a clinical setting, patients who received radiation/chemotherapy had higher LC3II expression and showed poor overall survival compared with those with low LC3 II. In a cell model, U87MG and GBM8401 expressed high level of stemness markers CD133, CD44, Nestin, and autophagy marker P62/LC3II after receiving standard fractionated IR. Furthermore, Wnt/β-catenin proved to be a potential pathway and related to P62 by using proteasome inhibitor (MG132). Moreover, pharmacological inhibition of autophagy with BAF and CQ inhibit GSC cell growth by impairing autophagy flux as demonstrated by decrease Nestin, CD133, and SOX-2 levels. In conclusion, we demonstrated that fractionated IR could induce GSCs with the stemness phenotype by P62-mediated autophagy through the Wnt/β-catenin for radioresistance. This study offers a new therapeutic strategy for targeting GBM in the future.

Background and Objectives: Minimally invasive spine surgery reduces destruction of the paraspinal musculature and improves spinal stability. Nevertheless, screw loosening remains a challenging issue in osteoporosis patients receiving spinal fixation and fusion surgery. Moreover, adjacent vertebral compression fracture is a major complication, particularly in patients with osteoporosis. We assessed long-term imaging results to investigate the outcomes of osteoporosis patients with two-level degenerative spine disease receiving minimally invasive surgery with the assistance of a robotic system. Materials and Methods: We retrospectively analyzed consecutive osteoporosis patients who underwent minimally invasive surgery with the assistance of a robotic system at our institution during 2013–2016. All patients were diagnosed with osteoporosis according to the World Health Organization criteria. All patients were diagnosed with two levels of spinal degenerative disease, including L34, L45, or L5S1. The study endpoints included screw-loosening condition, cage fusion, and vertebral body heights of the adjacent, first fixation segment, and second fixation segments before and after surgery, including the anterior, middle, and posterior third parts of the vertebral body. Differences in vertebral body heights before and after surgery were evaluated using the F-test. Results: Nineteen consecutive osteoporosis patients were analyzed. A lower rate of screw loosening was observed in osteoporosis patients in our study. There were no significant differences between the preoperative and postoperative vertebral body heights, including adjacent and fixation segments. Conclusions: According to our retrospective study, we report that minimally invasive surgery with the assistance of a robotic system provided better screw fixation, a lower rate of screw loosening, and a lesser extent of vertebral compression fracture after spinal fixation and fusion surgery in osteoporosis patients.

We previously reported that Aurora-A and the hNinein binding protein AIBp facilitate centrosomal structure maintenance and contribute to spindle formation. Here, we report that AIBp also interacts with Plk1, raising the possibility of functional similarity to Bora, which subsequently promotes Aurora-A–mediated Plk1 activation at Thr210 as well as Aurora-A activation at Thr288. In kinase assays, AIBp acts not only as a substrate but also as a positive regulator of both Aurora-A and Plk1. However, AIBp functions as a negative regulator to block phosphorylation of hNinein mediated by Aurora-A and Plk1. These findings suggest a novel AIBp-dependent regulatory machinery that controls mitotic entry. Additionally, knockdown of hNinein caused failure of AIBp to target the centrosome, whereas depletion of AIBp did not affect the localization of hNinein and microtubule nucleation. Notably, knockdown of AIBp in HeLa cells impaired both Aurora-A and Plk1 kinase, resulting in phenotypes with multiple spindle pole formation and chromosome misalignment. Our data show that depletion of AIBp results in the mis-localization of TACC3 and ch-TOG, but not CEP192 and CEP215, suggesting that loss of AIBp dominantly affects the Aurora-A substrate to cause mitotic aberrations. Collectively, our data demonstrate that AIBp contributes to mitotic entry and bipolar spindle assembly and may partially control localization, phosphorylation, and activation of both Aurora-A and Plk1 via hNinein during mitotic progression.

Based on the protein kinase A (PKA)/GSK3&beta, interaction protein (GSKIP)/glycogen synthase kinase 3&beta, (GSK3&beta, ) axis, we hypothesized that these might play a role in Tau phosphorylation. Here, we report that the phosphorylation of Tau Ser409 in SHSY5Y cells was increased by overexpression of GSKIP WT more than by PKA- and GSK3&beta, binding defective mutants (V41/L45 and L130, respectively). We conducted in vitro assays of various kinase combinations to show that a combination of GSK3&beta, with PKA but not Ca2+/calmodulin-dependent protein kinase II (CaMK II) might provide a conformational shelter to harbor Tau Ser409. Cerebrospinal fluid (CSF) was evaluated to extend the clinical significance of Tau phosphorylation status in Alzheimer&rsquo, s disease (AD), neurological disorders (NAD), and mild cognitive impairment (MCI). We found higher levels of different PKA&ndash, Tau phosphorylation sites (Ser214, Ser262, and Ser409) in AD than in NAD, MCI, and normal groups. Moreover, we used the CRISPR/Cas9 system to produce amyloid precursor protein (APPWT/D678H) isogenic mutants. These results demonstrated an enhanced level of phosphorylation by PKA but not by the control. This study is the first to demonstrate a transient increase in phosphor-Tau caused by PKA, but not GSK3&beta, in the CSF and induced pluripotent stem cells (iPSCs) of AD, implying that both GSKIP and GSK3&beta, function as anchoring proteins to strengthen the cAMP/PKA/Tau axis signaling during AD pathogenesis.

Cowden syndrome (CS) is a rare genetic disease which puts patients at an increased risk of developing mucocutaneous lesion, multiple hamartomas, breast cancer, thyroid cancer, and Lhermitte–Duclos disease (LDD). This article reviews the role of LDD in the diagnosis of CS. It is important for all clinicians to identify these patients due to the high risk of other associated malignancies.

Spinal dura arteriovenous fistula (SDAVF) is not an uncommon vascular malformation but is rare at craniocervical junction. The initial presentation is usually subarachnoid hemorrhage or cervical myelopathy caused by venous hypertension of the drainage vein. We report a male patient who has sudden onset of paraplegia, anesthesia of bilateral lower limbs, and urine retention. Cervical spinal cord edema and engorgement of posterior and anterior spinal veins were noted on magnetic resonance image study. Angiogram disclosed a SDAVF feeding by meningeal branch of the left vertebral artery and drainage inferiorly through posterior and anterior spinal vein. Complete obliteration of the fistula was achieved by transarterial embolization with n-butyl cyanoacrylate. The muscle power of lower limbs improved after the embolization. In previous studies, functional outcome is most correlated with pretreatment condition. Early diagnosis and treatment of the lesion will prevent permanent neurological deficit.

Background Primary melanocytic neoplasms (PMNs) are rare neoplasms, especially within the central nervous system. Meningeal melanocytomas, a subtype of PMN, are even rarer. Nevus of Ota results from the incomplete migration of melanocytes from the neural crest. Synchronous nevus of Ota and meningeal melanocytoma are infrequently encountered in clinical practice. Objective To evaluate and elucidate 12 cases of synchronous meningeal melanocytoma and nevus of Ota, thereby improving the understanding of the relationship between these 2 diseases. Methods We reviewed cases and searched the English-language literature from the PubMed database and collected clinical parameters of 12 cases of synchronously occurring nevus of Ota and meningeal melanocytoma. Results Among the 12 cases, 90.90% and 91.66% of the lesions were located ipsilaterally and supratentorially, respectively. Conclusions Our findings indicated a trend for both types of lesion to be located ipsilaterally and supratentorially. When a patient with nevus of Ota is found to harbor an intracranial neoplasm, the most likely diagnosis is PMN.

Spinal venous malformations are vascular malformations of the central nervous system. Progressive or sudden neurological deficits can result in the deterioration of the quality of life, owing to the nature of the disease. Surgery is recommended after 2–6 weeks in patients with acute symptoms, to facilitate better surgical planning. Steroids are administered during the preoperative planning and rehabilitation period. However, the patient reported in this study developed a perforated peptic ulcer 1 week after surgery and died due to sepsis. Therefore, we questioned the optimum time for surgery, i.e., we considered whether early or delayed surgery would result in better patient outcomes.

Glioblastoma multiforme is the most common and aggressive primary malignant brain tumor and usually invades the intracranial space. Extracranial invasion is uncommon, and skin invasions are even less common. Here, we present an extremely rare case of aggressive skin invasion by glioblastoma multiforme. Once skin invasion occurs, its spread is too rapid to be resectable in only a few weeks and is often accompanied by deterioration of the primary lesion and short-term survival. Recognizing small cutaneous tumors adjacent to a previous surgical site is vital at the initial stage of skin invasion. Early recognition of cutaneous lesions, resection, and pathological confirmation, followed by chemotherapy and radiotherapy, may be beneficial for these patients.

Treatment options for recurrent glioblastoma are rare, with their response uncertain. This study aimed to determine the response of chemotherapy including bevacizumab in combination with vincristine and carboplatin for glioblastoma at first recurrence in a single-institution cohort. Clinical data of patients who received chemotherapy including bevacizumab, vincristine, and low-dose carboplatin for recurrent glioblastoma between 2008 and 2014 were analyzed. Differences between those who received combination chemotherapy (chemotherapy-positive) and those who did not (chemotherapy-negative) were estimated by Fisher exact test or Wilcoxon rank-sum test, as appropriate. Survival curves were estimated using the Kaplan–Meier method, and differences between survival curves were estimated by the log-rank test. Univariate analysis of treatment response for all recurrent glioblastoma patients and secondary recurrence patients under different conditions were evaluated using Wilcoxon rank-sum test or the Kruskal–Wallis test. Although mortality rates were similar between the chemotherapy-negative and chemotherapy-positive groups (26.7% vs 28.6%), median overall survival was significantly longer in the chemotherapy-positive group than the chemotherapy-negative group (P = .006). There were no chemotherapy-related serious complications such as gastrointestinal perforation, serious bleeding, or new-onset seizure during chemotherapy, whereas others side effects including proteinuria and hypertension were more common albeit well controlled by medication. This study revealed combination regimen of bevacizumab, vincristine, and low-dose carboplatin as a potentially effective therapeutic approach in recurrent glioblastoma. More in-depth understanding of the mechanism underlying this combination treatment and potential contribution of alternative genetic therapeutic in recurrent glioblastoma is necessary.

GSK3β interacting protein (GSKIP) is a naturally occurring negative regulator of GSK3β and retains both the Protein Kinase A Regulatory subunit binding (PKA-RII) domain and GSK3β interacting domain. Of these two domains, we found that PKA-RII is required for forming a working complex comprising PKA/GSKIP/GSK3β/Drp1 to influence phosphorylation of Drp1 Ser637. In this study, bioinformatics and experimental explorations re-analyzing GSKIP's biofunctions suggest that the evolutionarily conserved Domain of Unknown Function (DUF727) is an ancestral prototype of GSKIP in prokaryotes, and acquired the C-terminal GSK3β binding site (tail) in invertebrates except for Saccharomyces spp., after which the N-terminal PKA-RII binding region (head) evolved in vertebrates. These two regions mutually influence each other and modulate GSKIP binding to GSK3β in yeast two-hybrid assays and co-immunoprecipitation. Molecular modeling showed that mammalian GSKIP could form a dimer through the L130 residue (GSK3β binding site) rather than V41/L45 residues. In contrast, V41/L45P mutant facilitated a gain-of-function effect on GSKIP dimerization, further influencing binding behavior to GSK3β compared to GSKIP wild-type (wt). The V41/L45 residues are not only responsible for PKA RII binding that controls GSK3β activity, but also affect dimerization of GSKIP monomer, with net results of gain-of-function in GSKIP-GSK3β interaction. In addition to its reported role in modulating Drp1, Ser637 phosphorylation caused mitochondrial elongation; we postulated that GSKIP might be involved in the Wnt signaling pathway as a scavenger to recruit GSK3β away from the β-catenin destruction complex and as a competitor to compete for GSK3β binding, resulting in accumulation of S675 phosphorylated β-catenin.

Bcl2L12 as a new member of the Bcl2 family, which contains a BH2 domain and shares a lower amino acid similarity with other Bcl2 family proteins. Bcl2L12 is reported to be involved in apoptosis regulation, but this role remains controversial in different cancer type. Temozolomide (TMZ) is currently used to intervene glioma multiforme (GBM), but an acquired chemotherapeutic resistance maybe occurred due to undesired autophagy. Previous studies uncovered that Bcl2L12 may interact with Bcl-xL and may harbor a BH3-like domain. Therefore, we investigated whether this BH3-like domain is responsible for the Bcl2L12 anti-apoptotic property. Moreover, we tested whether ABT-737, a BH3 mimetic agent, can be combined with TMZ to treat GBM. We aligned Bcl2L12 with Bcl2 family members, compared interacting pattern of BH3 domain and their protein 3D structure. We identified that Bcl2L12 interacts with Bcl-xL and Bcl2 in yeast two-hybrid system. Bcl2L12192-220 was a minimal region for Bcl2L12-Bcl-xL interaction. Five-point mutations with respect to hydrophobic and charge residues were generated to test whether they are the key residue of BH3-like domain. Our data showed that both h1 (L213) and h2 residue (L217) are essential for Bcl2L12 interacting with Bcl2 family proteins. Ectopically expressed h1 or h2 mutant in U87MG cell line resulted in reactivation of cleaved-PARP, caspase-3 and cytochrome c releasing compared to Bcl2L12 wt group. Implementing ABT-737 combined with TMZ provided a superior effect on apoptosis induction in Bcl2L12 wt group, which effectively reactivated apoptotic markers. Altogether, our findings indicated that Bcl2L12 retains a BH3-like domain, which is important for the Bcl2L12 anti-apoptotic property and TMZ-induced autophagy. Our results basically support the idea of using ABT-737 to counteract the anti-apoptotic role of Bcl2L12 and sensitize drug response of the GBM cells to TMZ.

We present a patient with systemic lupus erythematous (SLE) and visited emergency department, due to the progressive incoherent speech and disoriented to time in these few days. There were no obvious contact history or symptoms of infection. Due to the focal seizure, the brain magnetic resonance imaging (MRI) with gadolinium enhanced was arranged and revealed multiple ring enhancement picture and the brain abscess were suspected. The initial pathology suspected the lupus cerebritis, due to the vasculitis characteristic. Finally, according to the Immunohistochemistry study, the rare CNS infection of SLE patients– cerebral toxoplasmosis was confirmed the diagnosis.

Cerebellar anaplastic astrocytoma is infrequently encountered even nowadays, and drop metastasis with progression into spinal glioblastoma is not reported in the English literature. We report a case of cerebellar anaplastic astrocytoma receiving operation and subsequent concurrent chemoradiotherapy. One year later, progressive weakness of both lower limbs and unsteady gait occurred. Spine magnetic resonance imaging showed cervical and thoracic spine intramedullary tumor. We then performed laminectomy and tumor biopsy. The histopathological report demonstrated primary spinal cord glioblastoma multiforme with positive glial fibrillary acidic protein, high MIB-1 labeling index and negative staining of isocitrate dehydrogenase-1 mutation. After reviewing the English literature to date, most metastatic spinal glioblastoma resulted from previous intracranial glioblastoma, and there are few studies mentioning spinal glioblastoma originating from intracranial low-grade gliomas. Over time, improvement in local control of the primary tumor has raised patient risk of the possibility of spinal metastasis, and clinical physicians should be aware of this aspect so that quicker diagnosis and management will be accomplished, even in patients with lower grade of intracranial gliomas.

Background: The differences in clinical presentation and surgical outcome between children and adults with craniopharyngioma have not been well-described and there are few data available for Asian population. The aim of this study is to investigate the differences between paediatric and adult patients with craniopharyngioma at a single medical centre in southern Taiwan. Methods: The clinical records of 40 patients with craniopharyngioma who were all surgically treated at Kaohsiung Medical University Hospital from January 1990 to December 2012 were reviewed. The patients were divided into two groups based on age: children (= 20 years) and adults (>20 years). MRI and CT images were obtained pre- and post-operatively. Histopathological examination diagnosed tumors. Statistical analyses were performed to compare the differences in the two groups. Results: Among the patients, 17 were children and 23 were adults. The children group demonstrated more diagnoses of large or giant tumors (p

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

Transforming growth factor-beta 1 (TGF-β1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-β1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-β1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-β1 before tumor removal was ≥ 2.52 ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-β1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p0.05); there was no significant change in TGF-β1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-β1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ=0.597, p=0.002). The findings show that plasma TGF-β1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-β1 might be useful as a tumor marker for astrocytomas.

Dysregulated centrosomal expression has been observed in high grade gliomas. Thus, this study aimed to examine the expression of Aurora family kinase and various centrosomal proteins, including centrin, γ-tubulin, and hNinein isoforms, in human brain tumors, including 29 meningiomas, 34 astrocytomas, 6 pituitary adenomas, and 6 metastatic tumors. mRNA expression was evaluated using reverse transcription polymerase chain reaction. The role of hNinein isoform 6 expression in cell differentiation was assessed in BrdU-treated IMR-32 cells. Differential expression of centrosomal proteins of brain tumors and cell lines was observed. Specifically, centrin 2 and centrin 3 expression levels were classified as moderate or abundant in >97% of samples in the meningioma group, 63% of astrocytomas, >83% of metastatic and pituitary tumors. Alternatively, hNinein isoform 6 expression was only detected in normal brain and astrocytoma tumors (17/34); however, it was not expressed in meningioma (0/29), metastatic tumors (0/6) (P < 0.001). Of the six neuroblastoma cell lines analyzed only IMR-32 cells expressed hNinein isoform 6. Furthermore, downregulated expression of hNinein isoform 6 and upregulation of γ-tubulin was correlated to astrocytoma tumor grade (P < 0.001). Increased hNinein isoform 6 mRNA expression was observed in response to BrdU treatment, and its expression was greater in teratomas as compared to embryonic stem cells. Further studies are necessary to determine if hNinein isoform 6 functions as a tumor-suppressor gene in brain tumors. Differential centrosomal protein expression may result in altered centrosome function that is observed the in progression of various brain tumors. © 2012 International Union of Biochemistry and Molecular Biology, Inc.

The prognosis of patients with brain tumor diagnoses is often uncertain. Therefore, the primary caregivers of these patients must not only adjust their lives to patient care but also often deal with patient anxiety and depression, which may significantly increase patient-care needs.The present study explores the care needs of primary caregivers of patients awaiting brain tumor surgery and the factors that are associated with these needs.A correlational research design was used. Convenience sampling was used to recruit 80 pre-brain-tumor operation patient/caregiver pairs. Data were collected using a questionnaire survey, which included Supportive Care Needs Survey-PartnersCaregivers 45 (SCNS-PC45) and the Hospital Anxiety and Depression Scales (HADS). Descriptive and inferential statistics were used for data analysis.The information-needs and healthcare-service-needs subscales earned the highest subscale scores on the SCNS-PC45. Higher anxiety perception (r = .37, p.01) and higher depression status (r = .27, p.05) were significantly correlated with increased care needs. In addition, decreased patient functional status was significantly associated with increased depression in the primary caregiver. Anxiety perception was the only significant predictor of care needs that was identified (R(2) = 12.8%).Healthcare providers should provide patient education on the disease and disease-related care information soon after a diagnosis of brain tumor in order to decrease the anxiety and depression perceptions of caregivers and to reduce the care needs of caregivers.腦瘤手術前病人的主要照顧者之照護需求及相關因素之探討.腦瘤主要照顧者在面對病人疾病的不確定性與必須調整自己的生活以照顧病人，可能出現焦慮及憂鬱，進而產生更高的照護需求。.探討腦瘤病人在接受手術前之主要照顧者照護需求及其相關因素。.採相關性研究設計，以方便取樣招募80位腦瘤病人及其主要照顧者進行問卷填答，於病人在被診斷為腦瘤並等待手術前，以支持性照護需求量表—照顧者45及醫院焦慮憂鬱量表進行資料收集。以描述性統計及推論性統計法進行資料分析。.本研究發現在主要照顧者照護需求方面，以訊息需求與健康照護服務需求二層面之需求最高。較高的焦慮感受（r = .37, p.01）及憂鬱狀態（r = .27, p.05）與較高的照護需求有關，此外，病人的身體功能狀態愈差時，主要照顧者較容易有憂鬱狀態，而「焦慮感受」為照護需求的最重要之預測因子（R臨床醫護人員於病人被診斷出腦瘤在等待手術前，即應開始進行與疾病及照護有關之衛教，有助於主要照顧者減輕其焦慮及憂鬱，進而降低其照護需求。.

Transforming growth factor (TGF) β1 may be a candidate for a serologic tumor marker. In this study, the plasma levels of TGF-β1 in patients with brain tumors were measured using enzyme-linked immunosorbent assay before and after tumor removal. Patients were divided into four groups, the control group and the benign, malignant, and metastatic brain tumor groups. All brain tumor groups showed significant increases in the levels of TGF-β1 before tumor removal (6.36 ± 3.94, 17.0 ± 9.7, and 12.2 ± 10.3 ng/ml for the benign, malignant, and metastatic groups, respectively). When compared with the results obtained in the control group (1.12 ± 0.74 ng/ml), significant decreases in TGF-β1 concentrations after total tumor removal were found in both the benign and malignant brain tumor groups (2.55 ± 2.00 and 8.93 ± 5.73 ng/ml, respectively; p = 0.0001 and p = 0.003, respectively). On the other hand, plasma TGF-β1 levels in the metastatic brain tumor group showed a slight but significant increase (14.7 ± 9.3 ng/ml, p = 0.035) after tumor removal. In a case of low-grade astrocytoma, plasma levels of TGF-β1 were found to be 3.6 and 1.1 ng/ml before and after tumor removal, respectively. However, recurrent tumor was noted in this patient 7 months later, and the levels of TGF-β1 were 26.2 and 8.4 ng/ml before and after the second operation, respectively. The data show that plasma TGF-β1 was elevated in the circulation of patients with brain tumors and that significant decreases in TGF-β1 levels were observed after the removal of benign and malignant tumors. The results also suggest that TGF-β1 may be a useful serologic marker for brain tumors.

Eosinophilic granuloma (EG) refers to the most common and benign form of the disorder known as Langerhans’ cell histiocytosis. The disease is typically found in children and adolescents and rarely affects adults. We present a case of EG in the occipital bone in a 36-year-old man, who visited our hospital with the chief complaint of left occipital palpable tumor mass with local tenderness and pain for one month. An X-ray of the skull revealed a rounded osteolytic lesion. A computed tomography scan revealed a shadow of soft tissues in the left occipital site involving the entire thickness of the calvaria, which was indicative of marked destruction of the bone. The soft mass was successfully removed. The margins of the skull lesion were excised, and cranioplasty was performed simultaneously with bone cement. A definitive diagnosis of EG was made by histopathology and immunohistochemical detection of S-100 antigen in the tissue samples. With respect to management, we believe surgery is the best option for most accessible cranial lesions of EG. A cranioplasty with bone cement or autologous bone can be performed in the same session to repair the cranial defect.

Rationale Radiotherapy (RT) is widely used for both malignant and benign tumors in order to reduce the risk of recurrence, to promote tumor control, and to improve survival. However, there have been studies reported that RT is also a risk factor of secondary cancer. Very few cases of secondary malignancy after RT to high grade brain cancer have been reported due to short survival of this disease, and most RT-induced malignancies presented with sarcomatous histology. Here we present a patient with basal cell carcinoma (BCC) 14 years after RT to his brain. Patient concerns A 28-year-old man without any underlying disease had suffered from left side weakness and clonic-tonic seizures for 12 days. Diagnoses His brain images showed a tumor in the right frontal lobe. The pathologic report confirmed anaplastic astrocytoma (WHO Grade III). Interventions After craniotomy and tumor biopsy, RT was delivered. Fourteen years later, a gray-colored skin papule was noted in the previously irradiated area. The scalp biopsy revealed BCC. The scalp BCC was adequately resected. He then suffered from brain tumor recurrence and received further craniotomy for three times combined with chemotherapy with temozolomide. Outcomes After treatment, follow-up brain images showed that the disease was under control. There was no neurological sequela. For scalp BCC, no skin tumor recurrence has been noted to date after the resection 14 years after initial RT. He has survived for more than 26 years since his initial diagnosis of anaplastic astrocytoma, and more than 12 years from the diagnosis of scalp BCC. Lessons Notwithstanding the risk of radiation-induced skin cancer, RT contributed to this patient's survival. The possible late adverse events should be informed to the patients.

Rationale: Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and the prognosis in most cases of spinal PNETs appears to be poor, with a median patient survival of 1 to 2 years. We present a case with recurrent spinal PNET with brain and bone metastases that was successfully treated by multimodality treatment. Patient concerns: A 14-year-old teenage girl had suffered from progressive left upper back pain with bilateral lower legs weakness and numbness for 1 year. After treatment, left neck mass was noted 3 years later. Diagnoses: Initially, magnetic resonance imaging (MRI) showed neurogenic tumor involving intradural extramedullary space of T5-T10. Pathology report showed PNET (World Health Organization grade IV) featuring lobules of neoplastic cells with round regular nuclei, high nucleus-to-cytoplasm ratio, and fibrillary cytoplasm. At the time of tumor recurrence, chest MRI then showed recurrent tumor at T2-T3 level of the epidural space with right neural foramina invasion. Brain MRI showed extensive bilateral calvarial metastases and leptomeningeal metastases in the right frontoparietal regions. Bone scan showed multiple bone metastases. Interventions: T-spine tumor removal and adjuvant radiotherapy (RT) to T-spine tumor bed were performed in the initial treatment. After clinical tumor recurrence, tumor removal was done again. She then received chemotherapy followed by whole brain irradiation with hippocampal sparing with 35 gray in 20 fractions. Outcomes: After treatment, follow-up images showed that the disease was under control. There was no neurological sequela. She has survived more than 7 years from diagnosis and more than 4 years from recurrence to date. Lessons: Multimodality treatments including operation, RT, and chemotherapy should be considered in the initial treatment planning, and salvage chemotherapy was useful in this case.

BACKGROUND Brain tumors are uncommon etiologies of parkinsonism. The clinical manifestations of tumoral parkinsonism may sometimes resemble those of idiopathic origin. Increased awareness of this rare entity is important for an earlier prompt diagnosis and treatment. REVIEW SUMMARY A previously healthy, 60-year-old man developed slowly progressive right-sided resting tremor and bradykinesia over 8 months. Although idiopathic Parkinson disease was the initial diagnosis, the parkinsonian symptoms were not responsive to medical treatment with levodopa and a dopamine agonist. Brain computed tomography failed to reveal an intracranial lesion. Brain magnetic resonance imaging demonstrated an infiltrative, slightly enhancing mass in the left mesial temporal lobe extending to the left basal ganglion and insula. Histopathologic findings confirmed the diagnosis of high-grade astrocytoma. The parkinsonian symptoms subsided after tumor removal; however, ipsilateral hemiparesis developed postoperatively. CONCLUSIONS Neuroimaging is recommended for investigation of atypical parkinsonism. We suggest that brain magnetic resonance imaging is preferred for patients with drug-resistant parkinsonism or concurrent signs apart from extrapyramidal symptoms, because some mass lesions are not observed by computed tomography scan.

A 53-year-old man presented with a history of slight weakness in the right lower limb. Giant invasive cauda equina schwannoma was diagnosed according to the criteria of Sridhar et al. Schwannomas are usually benign and common tumors arising from nerve sheath cells, particularly from sensory nerves. Giant invasive schwannomas, however, are rare, and most of patients with them present with severe neurologic deficits independent of daily activity, although in the case presented here, in spite of the large size of the tumor causing pedicle erosion, expansive destruction of the vertebral body and widening of the neural foramina, there were only minimal neurologic deficits. We have therefore decided to report this case, with a review of the relevant English literature emphasizing clinical presentations, plain film images and magnetic resonance image findings of giant invasive cauda equina schwannoma for early diagnosis and differential diagnosis.

Background Coldness, numbness, or causalgia usually affects the lower limbs in patients after back surgeries. The treatment of causalgia is still the source of continuing debate. We treated patients presenting with causalgia secondary to LD with CT-guided CLS and determined the therapeutic outcome at long-term follow-up. Methods From January 2002 to December 2002, a total of 15 patients (16 limbs) with causalgia after LD underwent the percutaneous CT-guided CLS. There were 7 male patients and 8 female patients, with an average age of 49.1 years. A total of 14 patients underwent unilateral procedures, and 1 patient underwent staged bilateral procedures. We followed up our patients for at least 24 months (24-36 months). Results There were 13 patients (14 limbs) diagnosed as Drucker stage I and 2 patients as stage II. There were 88% (14 limbs) that had an early satisfactory outcome after CLS and 75% (12 limbs) that had a late satisfactory outcome (more than 24 months after CLS). Stage I patients had more satisfying early and late outcome than stage II patients ( P = .014 and P = .039, respectively). Female patients were more likely to have satisfactory late outcome than male patients ( P = .034). There was no operative mortality. A patient had a complication of genitofemoral neuralgia, which had recovered in a month. Conclusions We concluded that the percutaneous CT-guided CLS is an easy, safe, and reproducible technique, and it carries long-term benefit to patients with pain after LD presenting with causalgia, especially for patients with Drucker stage I and female patients.

Patients who have liver cirrhosis are at increased risk of bacterial infections, such as bacteremia, meningitis, pneumonia, urinary tract infections, and spontaneous bacterial peritonitis, due to immunodeficiency associated with the severity of the cirrhosis. Although bacterial infections are frequent in cirrhotic patients, only isolated cases of brain abscess have been reported. In these cirrhotic patients, the initial presentation of brain abscess may not be fever or leukocytosis, but focal neurologic deficits. In addition, for consideration of blood-brain barrier penetration, the anti-biotic choice postoperatively is also quite different from other infections outside the central nervous system. We will discuss two cases of brain abscess in cirrhotic patients with special emphasis on the clinical presentation, magnetic resonance spectroscopic findings, organism encountered, therapeutic strategy, and prognosis.