Jin-Cherng Chen

Resveratrol Suppresses the Angiogenesis and Tumor Growth of Gliomas in Rats

Purpose: We wanted to investigate the antitumor effects and effect on angiogenesis of resveratrol in rat RT-2 gliomas. Experimental Design: RT-2 glioma cells were treated with resveratrol, and then cytotoxicity was assayed, apoptosis was measured by flow-activated cell sorter flow cytometry, and expression of vascular endothelial growth factor was measured by reverse transcription-PCR. Tumor size, animal survival time, and survival rate were followed in resveratrol-treated rats with s.c. or intracerebral gliomas. Furthermore, in vitro proliferation was assayed to explore the effect of resveratrol on the proliferation of ECV304 human umbilical vein endothelial cells. Expression of CD31 in resveratrol-treated gliomas was followed immunohistochemically to study the effect of resveratrol on the glioma-induced angiogenesis. Results: Resveratrol was demonstrated to exert cytotoxic effects and induce glioma cell apoptosis in a concentration- and time-dependent manner (P < 0.05). Resveratrol (40 mg/kg/day) exerted significant antitumor effects on s.c. tumors, including slower tumor growth rate, longer animal survival time, and higher animal survival rate (P < 0.05). In contrast, resveratrol affected intracerebral tumors at only an increased dose (100 mg/kg/day), prolonging animal survival (P < 0.05) without affecting survival rate. The expression of vascular endothelial growth factor in the glioma cells and the proliferation of ECV304 cells were inhibited by resveratrol in a concentration-dependent manner. Immunohistochemical analyses showed that the s.c. gliomas from resveratrol-treated rats had fewer microvessel densities than did control rats (P < 0.01). Conclusions: Resveratrol caused significant glioma cell cytotoxicity and apoptosis, exerted antitumor effects on the s.c. and intracerebral gliomas, and inhibited angiogenesis in s.c. gliomas. Thus, resveratrol might be considered a possible treatment strategy for gliomas.

Tetrandrine induces apoptosis and growth suppression of colon cancer cells in mice

Tetrandrine, a bisbenzylisoquinoline alkaloid, exerts antitumor effects against some cancers. We explored tetrandrines effects on colon cancer with cultured mouse CT-26 cells and with subcutaneous tumors. Tetrandrine induced apoptosis in concentration- and time-dependent manner. Tetrandrine increased expression of ERK 1/2 and p38 MAPK; inhibition of p38 MAPK reduced tetrandrine-induced apoptosis; inhibition of ERK1/2 did not. Tetrandrine had significant effects on tumors including slower growth and longer animal survival time and higher survival rate. Higher dose and earlier treatment were more effective than lower dose and delayed treatment. TUNEL staining showed prominent tetrandrine-induced apoptosis of tumors. These data suggest that tetrandrine induced significant apoptosis of cultured and subcutaneous CT-26 cells. Tetrandrine-induced apoptosis might be at least partially related to activation of the p38 MAPK signaling pathway.

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers, but its effects on gliomas are unknown. In this study, we investigated the effects of tetrandrine on the growth and angiogenesis of rat RT‐2 gliomas. We treated RT‐2 glioma cells with tetrandrine and then measured cytotoxicity, apoptosis and expression of vascular endothelial growth factor (VEGF). We also examined the cytotoxic effect of tetrandrine on the ECV304 human umbilical vein endothelial cells and the effects of tetrandrine on the in vivo angiogenesis. Tumor size and animal survival were followed in tetrandrine‐treated rats with subcutaneous or intracerebral gliomas. Expression of CD31 in tetrandrine‐treated gliomas was followed to study its effect on glioma‐induced angiogenesis. Tetrandrine had cytotoxic effects and induced apoptosis of glioma cells in a concentration‐ and time‐dependent manner. Tetrandrine also inhibited the expression of VEGF in glioma cells, induced cytotoxicity effect on the ECV304 cells and suppressed the in vivo angiogenesis. Tetrandrine (150 mg/kg/day) had significant antitumor effects on subcutaneous tumors and led to slower tumor growth rate, longer animal survival time and higher animal survival (p < 0.05). Tetrandrine also affected intracerebral tumors and prolonged animal survival (p < 0.05) without affecting survival rate. Immunohistochemical analyses showed that the subcutaneous gliomas from tetrandrine‐treated rats had fewer microvessel densities than control rats (p = 0.01). The results demonstrate that tetrandrine is cytotoxic to RT‐2 glioma cells, has antitumor effects on subcutaneous and intracerebral gliomas, and inhibits angiogenesis in subcutaneous gliomas. Tetrandrine has potential as a treatment for gliomas.

Radiation-induced temporary alopecia after embolization of cerebral arteriovenous malformations

Alopecia after endovascular embolization of cerebral arteriovenous malformations (AVMs) is uncommon. In this report, we present a 33-year-old man who developed temporary alopecia after staged embolization of a cerebral AVM. Four days after the last procedure, this patient had hair loss over his right temporoparietal and occipial areas. No scalp erythema or other sign of dermatitis was noted. The hair regrew 2 months later. The alopecia was considered to be related to repeated exposure to radiation during embolization. The experience in this case and review of the literature suggest that interventional neuroradiological procedures may cause substantial radiation exposure to the patient. Therefore, radiation use should be limited to the least amount necessary to complete the endovascular procedure to prevent radiation-induced biological changes and morbidity. Patients should be well informed of adverse effects such as alopecia.

Sylvian fissure dermoid cyst with intratumoral hemorrhage: case report

It is rare for a dermoid cyst to develop intratumoral hemorrhage. A 61-year-old woman had a sudden-onset left hemiparesis and slow response to verbal requests for one week when unenhanced computed tomography scanning revealed a mixed iso- and hypo-dense heterogeneous lesion in the right fronto-temporal area. T1-weighted magnetic resonance imaging (MRI) of the brain showed a mixed hyper- and hypo-intense tumor in the right fronto-temporal area. The tumor became hyperintense on T2-weighted MRI and was faintly enhanced at tumor periphery on T1-weighted MRI. The tumor was excised and pathological examination revealed a dermoid cyst with intratumoral hemorrhage. The post-operative course was complicated by hemorrhage in the tumor bed, which was evacuated immediately. The patient improved and could walk without support two weeks after the second operation. After 1 year of follow-up, she was well and without neurological deficits. To the best of our knowledge after a literature review, only two previous cases of dermoid cyst have featured intratumoral hemorrhage.

Tetrandrine Increased the Survival Rate of Mice With Lipopolysaccharide-induced Endotoxemia

BACKGROUND Endotoxemia usually causes significant morbidity and mortality, and treatment of endotoxemia is often ineffective. The effects of tetrandrine (a bisbenzylisoquinoline alkaloid) on lipopolysaccharide (LPS)-induced endotoxemia were investigated in mice. METHODS The peritoneal macrophages were stimulated with LPS and treated with or without tetrandrine. The amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 secreted by peritoneal macrophages were measured by enzyme-linked immunosorbent assay. Mice were intraperitoneally injected with LPS to induce endotoxemia and were treated or not treated with oral gavage with 150 mg/kg tetrandrine 1 hour before or after LPS injection. The survival rate of the mice was determined after they were treated with various regiments. The amounts of TNF-alpha, IL-1beta, IL-6, and IL-10 in the serum of the mice were measured by enzyme-linked immunosorbent assay, and the high mobility group box 1 (HMGB1) concentration was studied by Western blot analysis. RESULTS Tetrandrine suppressed the LPS-induced increase of TNF-alpha, IL-1beta, and HMGB1 secretion by peritoneal macrophages but did not affect the IL-6 and IL-10 concentrations. The animals treated with tetrandrine either 1 hour before or after LPS injection had a 100% survival rate, which was significantly higher than that of the control group (40%) (p = 0.005). The LPS-induced increase in serum TNF-alpha, IL-1beta, and HMGB1 concentrations was reduced by tetrandrine treatment administered either 1 hour before or after LPS injection (p < 0.0001). In contrast, tetrandrine prolonged the LPS-induced elevation in serum IL-10 concentrations only mildly changed the serum IL-6 concentrations. CONCLUSIONS Tetrandrine treatment either 1 hour before or 1 hour after LPS injection reduced the mortality rate of the mice with LPS-induced endotoxemia. The effects of tetrandrine on LPS-induced endotoxemia might be related to the suppression of TNF-alpha, IL-1beta, and HMGB1 concentrations.

Effects of irradiated tumor vaccine and infusion of granulocyte-macrophage colony-stimulating factor and interleukin-12 on established gliomas in rats

Purpose: We investigated granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12) infused into the injection site of irradiated tumor vaccine (TV) as therapy for gliomas. Methods: Rats with subcutaneous RT-2 gliomas were treated with irradiated TV and/or subcutaneous infusion of GM-CSF and/or IL-12 via osmotic minipump 5 days after tumor-cell inoculation. Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activity were analyzed to investigate immune responses. Rats with intracerebral gliomas were treated with irradiated TV and infused GM-CSF/IL-12 3 days after tumor-cell inoculation. Tumor growth rates and animal survival were followed. Survivors were re-challenged with wild-type RT-2 cells subcutaneously or intracerebrally to study long-term anti-tumor immunity. Results: Rats with subcutaneous gliomas treated with GM-CSF and IL-12 or TV plus GM-CSF or IL-12 did not have increased survival rate (P>0.2), but did have prolonged survival time (P<0.05); in contrast, rats treated with TV plus GM-CSF/IL-12 had increased survival rate (P<0.05) and prolonged survival time (P<0.05) compared with controls. These treatment strategies showed enhanced CTL and NK cell activities. Rats with intra-cerebral gliomas treated with TV plus GM-CSF/IL-12 did not have increased survival rate (P=0.11), but did have prolonged survival time (P<0.0001). Survivors in each group were re-challenged with wild-type RT-2 cells, and all had long-term survival. Conclusions: Irradiated TV plus continuous localized infusion of GM-CSF/IL-12 may induce a tumor-specific anti-tumor immune response on established subcutaneous or intra-cerebral gliomas, and such a treatment strategy deserves consideration as adjuvant treatment for glioma.

Cervical dumbbell meningioma and thoracic dumbbell schwannoma in a patient with neurofibromatosis

The occurrence of both dumbbell meningioma and dumbbell schwannoma in one patient has not been reported in the literature. We present a 16-year-old female patient, who had progressive bilateral hearing impairment for 5 years and a progressively enlarged, non-tender neck mass for 1.5 years. Mild motor weakness over her right upper limb was noted 1 week before admission. No café-au-lait spot was noted. Magnetic resonance imaging (MRI) revealed bilateral cerebellopontine angle tumors, a C1-2 dumbbell tumor, and a T5-6 dumbbell tumor. Neurofibromatosis type 2 was diagnosed. The cervical spine and thoracic spine tumors were removed via one-staged combined posterior (laminectomy) and antero-lateral (transforaminal or thoracoscopic) approaches during two operations performed 1 month apart. The pathology revealed meningioma and schwannoma, respectively. The patient had good recovery after these two operations and her motor function improved. Six months after the second surgery, radiosurgery was performed for the bilateral acoustic tumors, because of enlarged tumor size on follow-up MRI. To the best of our knowledge, this is the first case reported in the literature of a patient, having both dumbbell meningioma and dumbbell schwannoma. A literature review of the dumbbell tumors was done, and their treatment strategies were discussed.

Calcified Chronic Subdural Hematoma — Case Report

Calcified or ossified chronic subdural hematoma is a rare entity that usually presents as a space-occupying lesion over the cerebral convexity. We report a case of calcified and ossified chronic subdural hematoma in an unusual location that has not been previously reported. A 24-year-old man with a history of tonic-clonic convulsions since 7 months of age was admitted because of increasing frequency and duration of seizures. Computed tomography and magnetic resonance imaging demonstrated a fusiform extra-axial lesion just above the tentorium and adjacent to the cerebral falx. A calcified and ossified chronic subdural hematoma was noted and was almost completely removed by craniotomy. Better seizure control was achieved by removal of the calcified chronic subdural hematoma. Calcified subdural hematoma, calcified epidural hematoma, calcified empyema, meningioma, calcified arachnoid cyst, and calcified convexity of the dura mater with acute epidural hematoma should be considered for the differential diagnosis of an extra-axial calcified lesion.

Neurohypophyseal Granular Cell Tumor with Intratumoral Bleeding: Report of a Case

Background: Symptomatic neurohypophyseal granular cell tumors (GCTs) are rare, and their main presenting symptoms are usually nonspecific. Rarely, neurohypophyseal GCTs manifest intratumoral bleeding. Case Description: A 77year-old woman presented with a 2-year history of headache and blurred vision, and sudden onset of visual disturbance one week before. Neurologically, she had constricted visual fields and endocrine studies revealed pituitary dysfunction. Brain computed tomography showed a hyperdense pituitary lesion with suprasellar extension, and magnetic resonance imaging demonstrated a pituitary tumor with a mixed isointense and hyperintense center surrounded by a hypointense rim on both T1 and T2 images. The tumor had mild heterogeneous enhancement at the center and linear enhancement at the margin. Subtotal tumor excision via the transsphenoidal approach was performed and nonclotted blood was found in the tumor. The postoperative course was complicated with meningitis and diabetes insipidus. After treatment with antibiotics and pitressin, her condition stabilized and her vision improved. Pathology revealed a granular cell tumor with bleeding. After 18 months of follow up, she was doing well with regular hormone replacement therapy. The patient refused radiotherapy for her residual tumor. Conclusion: Neurohypophyseal granular cell tumor rarely manifested as intratumoral bleeding. We present the clinical features of this patient and review the literature.