Hisae Mori

Effects of combination chemotherapy with biscoclaurine-derived alkaloid (Cepharanthine) and nimustine hydrochloride on malignant glioma cell lines.

In the treatment of malignant glioma, chemotherapy plays a critical role as do surgical resection and irradiation. Cepharanthine (CEP), a biscoclaurine-derived alkaloid, reportedly potentiates the effects of antitumor agents and induces apoptosis in some cancer cells. Here, we examined the effects of CEP, alone and in combination with nimustine hydrochloride (ACNU), on the in vitro proliferation of malignant glioma cells. The cell lines used were U87MG, U251MG, and T98G. At concentrations from 1 to 10 μg/ml, CEP-promoted cell proliferation somewhat; growth inhibition was noted at concentrations of 15 μg/ml and higher. Phase-contrast microscopy showed that cells tended to detach from the culture dishes and that cell density became sparse at the higher concentrations. DAPI fluorescence nuclear staining revealed condensation and fragmentation of nuclei, indicating the induction of apoptosis. To examine the cascade of apoptosis, the caspase inhibitors YVAD and DEVD were added. They inhibited CEP-induced apoptosis in U251MG cells (a p53-mutant cell line), but not in U87MG cells (a p53 wild-type cell line), suggesting that in CEP-induced apoptosis two possible cascades are in play. In combination with ACNU, the effects of the higher concentrations of CEP were enhanced.

Adenovirus-mediated gene transfer of basic fibroblast growth factor promotes the survival of primary-cultured rat neuronal cells

We constructed two replication-deficient recombinant adeno-virus vectors coding human basic fibroblast growth factor (bFGF), one with and one without the interleukin-2 (IL-2) secretory signal sequence and examined their neurotrophic effects on primary neuronal cells in vitro. The primary neuronal cells were successfully infected at a high efficiency with the adenovirus vectors. bFGF protein was detected in the culture medium of the neurons infected with both these vectors. The cells infected with the bFGF-expressing adenovirus containing the IL-2 signal sequence showed 2- to 10-fold higher levels of secretion levels than cells infected with the native bFGF-expressing adenovirus alone. Both bFGF-expressing vectors augmented the survival of primary neuronal cells in an in vitro culture, compared with a mock infection or control virus infection. Notably, the cells infected with the bFGF-expressing adenovirus containing the IL-2 signal sequence were markedly enhanced cell survival in the early phase of the culture, compared with the control cells and even those infected with the bFGF-expressing adenovirus without the IL-2 signal sequence. However, in the late phase of neuronal culture, neither viral vector could support the cell survival. In contrast the co-infection of the bFGF-expressing vector with a Bcl-xL-expressing vector was extremely effective on neuronal survival.

Superselective Provocative Test with Propofol Using Motor-Evoked Potential Monitoring for Managing Cerebral Arteriovenous Malformations Fed by the Anterior Choroidal Artery.

When feeder artery obliteration is performed via an endovascular procedure to treat cerebral arteriovenous malformation (AVM), it is important to prevent the ischemic complications that are associated with feeder occlusion. A provocative test may be beneficial in some cases to protect against ischemic complications. We report the case of a 57-year-old man who developed an intracerebral hematoma in the left internal temporal lobe and who had an AVM with a varix in the ambient cistern, which was primarily fed by a branch of the left anterior choroidal artery (AChA) and the posterior lateral choroidal artery, and drained into the basal vein. Therefore, we planned endovascular obliteration of the AChA, followed by gamma knife radiosurgery for the residual posterior component. The patient underwent a superselective provocative test with a 3 mg of propofol under general anesthesia using motor-evoked potential monitoring. The feeder embolization was performed as planned after the provocative test, and the patient exhibited no neurological deficits, such as hemiparesis, during the procedure.

A dyad symmetry element in the fibroblast growth factor-2 gene promoter with different levels of activity in astrocytoma and hepatocelluar carcinoma cell lines

SummaryFibroblast growth factor‐2 (FGF‐2) gene expression is reported to be spatially and temporally regulated in the process of development, normal growth, and wound healing. We postulated that its constitutive expression in human malignant astrocytoma cells is due to loss of function of the regulatory mechanism of FGF‐2 gene expression. Here, we report the characterization of a unique element in the FGF‐2 gene promoter. We investigated the transcriptional regulation of the FGF‐2 gene in a human malignant astrocytoma (U87MG) and a human hepatocellular carcinoma (HepG2) cell line. We found that a dyad symmetry element (DSE) in the FGF‐2 gene promoter exhibited different promoter activities; in HepG2 cells it did, while in U87MG cells it did not, exhibit repressive activity. Examination of the relative promoter activities of the DSE in a thymidine kinase promoter revealed it exerted different activities, just as it did in the 2 cell lines studied.Gel shift assay demonstrated that 2 proteins bound to the DSE in nuclear extracts from HepG2 cells and that one protein was missing in nuclear extracts from U87MG cells. These results suggest that the DSE has a crucial role as a transcriptional regulatory element of FGF‐2 gene expression.

Neurosurgical Management and Outcomes of Cerebrovascular Disease in Pediatric Patients with Heart Disease

Antithrombotic treatment has substantial risks, even in pediatric patients. We retrospectively evaluated the management and outcomes of consecutive pediatric patients who underwent neurosurgical treatment for cerebrovascular disease with cardiovascular disease between 1998 and 2017. Patients were divided into patients with comorbid cardiovascular disease (group I); and patients with cardiovascular disease as a primary disease of intracranial complication, without (group IIa) or with (group IIb) extracorporeal circulations. Postoperative resumption of antithrombotic agents was generally initiated within 48 h. Our study included 26 patients; five were categorized as group I, 15 as group IIa, and six as group IIb. All intracranial diseases in groups IIa and IIb were exclusively hemorrhagic. Preoperative anticoagulation therapy was used in one patient (20%) in group I, 13 patients (86.7%) in group IIa, and six patients (100%) in group IIb. Postoperative intracranial hemorrhagic events were observed in one patient (20%) in group I, three patients (20%) in group IIa, and four patients (66.7%) in group IIb. Re-operations were conducted in two (13.3%) and three patients (50%) in groups IIa and IIb, respectively. Death occurred in five (33.3%) and four patients (66.7%) in groups IIa and IIb, respectively. The remaining two patients in group IIb returned to candidate status for implantation. Emergent surgery for patients with intracranial hemorrhage associated with cardiovascular disease has a high risk of postoperative hemorrhagic events and high rate of re-operations with poor vital outcomes, especially in patients with extracorporeal circulations. We should consider maximum neurosurgical treatment achievable with optimal management of antithrombotic treatment.