Sheng-Hong Tseng

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.

Micro-RNA-21 regulates the sensitivity to cisplatin in human neuroblastoma cells

BACKGROUND/PURPOSE Drug resistance often causes treatment failure in neuroblastomas. Increasing evidence has implicated that the micro-RNAs (miRNAs) are involved in the development of drug resistance. In this report, we aimed to investigate the role of miRNA in cisplatin resistance of neuroblastoma cells. MATERIALS AND METHODS The cell viability of the neuroblastoma cells after cisplatin treatment was analyzed. The expression of the miRNAs and phosphatase and tensin homolog (PTEN) messenger RNA in the neuroblastoma cells was studied by real-time polymerase chain reaction. Overexpression of miRNA or suppression of miRNA expression by antagomir was used to investigate the effects of miRNA on the cisplatin-induced cell death or proliferation. RESULTS The expression of miR-21 was increased in the cisplatin-resistant (CisR) neuroblastoma cells as compared with the parental cells, and the antagomir against miR-21 converted the resistant cells into sensitive ones. Ectopic expression of pre-miR-21 in parental cells resulted in decreased sensitivity to cisplatin treatment. In addition, overexpression of pre-miR-21 markedly increa sed the proliferation rate of neuroblastoma cells. The level of PTEN messenger RNA and protein in the CisR cells was lower than that in the parental cells. Transfection of pre-miR-21 into the parental cells reduced the PTEN expression, and transfection of anti-miR-21 into the CisR cells increased the PTEN expression. CONCLUSION Micro-RNA-21 regulated the drug resistance and proliferation in neuroblastoma cells.

Ruptured cervical disc after spinal manipulation therapy: report of two cases.

Study Design. Case reports of ruptured cervical disc after spinal manipulation therapy. Objectives. To present the rare cases of ruptured cervical disc temporally related to spinal manipulation therapy. Summary of Background Data. The complication of ruptured cervical disc was rare in the literature. Methods. Two patients developed cervical myelopathy or radiculopathy after spinal manipulation therapy, and magnetic resonance imaging showed herniated cervical discs at C4–C5 and C6–C7, respectively. Results. Anterior cervical discectomy was performed, and ruptured disc fragments were removed in these two patients. Both patients had good neurologic recovery after operation, and no neurologic deficits were noted after 15 and 6 months of follow-up, respectively. Conclusions. The experience of these two patients reminds us that cervical disc rupture can occur during a course of cervical spinal manipulation. Full neurologic recovery is achievable if accurate diagnosis and prompt surgical treatment are done.

Valproic acid affected the survival and invasiveness of human glioma cells through diverse mechanisms.

The effects of valproic acid (VPA) on the viability, apoptosis, and invasiveness of two glioma cells (A172 and T98G) and the underlying mechanisms were studied. VPA induced cytotoxicity and apoptosis, and suppressed the invasiveness of both cells. VPA increased the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 in A172 cells, but decreased it in T98G cells. siRNA blockade of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression partially reversed VPA-mediated effects in T98G cells, but had no effect on A172 cells. VPA increased the expression of phospho-JNK1 and phospho-ERK1/2 in A172 cells, but decreased it in T98G cells. Inhibition of JNK1 and/or ERK1/2 partially reversed the VPA effects in A172 cells. In conclusion, the effects of VPA (loss of viability, increased apoptosis, and decreased invasiveness) are, at least partly, mediated through the RECK-MMPs pathway in T98G cells and the mitogen-activated protein kinase pathways in A172 cells. The action of VPA seems to be cell type-specific in glioma cells.

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.

The Potential of Tetrandrine as a Protective Agent for Ischemic Stroke

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.

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.