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Shin-Ichi Miyatake

Publications and source records attributed to Shin-Ichi Miyatake.

At least 19 recordsLinked to original sources
PubMed2007

Analysis of boron distribution in vivo for boron neutron capture therapy using two different boron compounds by secondary ion mass spectrometry.

The efficiency of boron neutron capture therapy (BNCT) for malignant gliomas depends on the selective and absolute accumulation of (10)B atoms in tumor tissues. Only two boron compounds, BPA and BSH, currently can be used clinically. However, the detailed distributions of these compounds have not been determined. Here we used secondary ion mass spectrometry (SIMS) to determine the histological distribution of (10)B atoms derived from the boron compounds BSH and BPA. C6 tumor-bearing rats were given 500 mg/kg of BPA or 100 mg/kg of BSH intraperitoneally; 2.5 h later, their brains were sectioned and subjected to SIMS. In the main tumor mass, BPA accumulated heterogeneously, while BSH accumulated homogeneously. In the peritumoral area, both BPA and BSH accumulated measurably. Interestingly, in this area, BSH accumulated distinctively in a diffuse manner even 800 microm distant from the interface between the main tumor and normal brain. In the contralateral brain, BPA accumulated measurably, while BSH did not. In conclusion, both BPA and BSH each have advantages and disadvantages. These compounds are considered to be essential as boron delivery agents independently for clinical BNCT. There is some rationale for the simultaneous use of both compounds in clinical BNCT for malignant gliomas.

Animals↗
PubMed2006

Pharmacokinetic study of BSH and BPA in simultaneous use for BNCT.

In order to improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, we examined the optimization of the administration of boron compounds in brain tumor animal model. We analyzed the concentration of boron atoms in intracranial C6 glioma -bearing rats using inductively coupled plasma atomic emission spectrometry. Each tumor-bearing rat received one of two different amounts of sodium borocaptate (BSH) and/or 500 mg/kg of boronophenylalanine (BPA) via intraperitoneal injection. We compared the boron concentrations of the tumor, the contralateral normal brain and the blood in rats of 3 different treatment groups (BSH alone, BPA alone and a combination of both BSH and BPA). Our results show that the tumor boron concentration increased much more than 30 microg/g by the coadministration of both compounds. Additionally, the blood boron concentration remained below 30 microg/g and the boron concentration in the normal brain was low (mean 4.7+/-1.1 microg/g). Even in comparison with the administration of BPA alone, coadministration of BPA and BSH shows an improved tumor/normal brain ratio of boron concentrations.

Animals↗
PubMed2006

Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours.

Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger.

Air↗
PubMed2006

Novel therapeutic strategy for stroke in rats by bone marrow stromal cells and ex vivo HGF gene transfer with HSV-1 vector.

Occlusive cerebrovascular disease leads to brain ischemia that causes neurological deficits. Here we introduce a new strategy combining mesenchymal stromal cells (MSCs) and ex vivo hepatocyte growth factor (HGF) gene transferring with a multimutated herpes simplex virus type-1 vector in a rat transient middle cerebral artery occlusion (MCAO) model. Gene-transferred MSCs were intracerebrally transplanted into the rats' ischemic brains at 2 h (superacute) or 24 h (acute) after MCAO. Behavioral tests showed significant improvement of neurological deficits in the HGF-transferred MSCs (MSC-HGF)-treated group compared with the phosphate-buffered saline (PBS)-treated and MSCs-only-treated group. The significant difference of infarction areas on day 3 was detected only between the MSC-HGF group and the PBS group with the superacute treatment, but was detected among each group on day 14 with both transplantations. After the superacute transplantation, we detected abundant expression of HGF protein in the ischemic brain of the MSC-HGF group compared with others on day 1 after treatment, and it was maintained for at least 2 weeks. Furthermore, we determined that the increased expression of HGF was derived from the transferred HGF gene in gene-modified MSCs. The percentage of apoptosis-positive cells in the ischemic boundary zone (IBZ) was significantly decreased, while that of remaining neurons in the cortex of the IBZ was significantly increased in the MSC-HGF group compared with others. The present study shows that combined therapy is more therapeutically efficient than MSC cell therapy alone, and it may extend the therapeutic time window from superacute to acute phase.

Animals↗
PubMed2006

Preferential recurrence of a sarcomatous component of a gliosarcoma after boron neutron capture therapy: case report.

Gliosarcoma, a rare pathological entity composed of 2-8% malignant gliomas, is characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. Here we report the preferential recurrence of a sarcomatous component in gliosarcoma after boron neutron capture therapy (BNCT), while a gliomatous component disappeared as a result of the treatment. A 56-year-old woman with a left frontal tumor was introduced to our clinic. After stereotactic biopsy, craniotomy was applied and 90% of the mass was resected. The histological diagnosis was glioblastoma with small amounts of sarcomatous component, that is, gliosarcoma. BNCT was applied 30 days after craniotomy. Two weeks after BNCT, almost all of the contrast-enhanced mass had disappeared on magnetic resonance images; however, a half year later, the mass recurred just below the original site and extended posteriorly. Irrespective of repetitive salvage surgeries, the patient died of the recurrent tumor. At autopsy, tumor cells of the frontal lobe were absent. A well-circumscribed mass of the parietal and occipital lobes was composed of sarcomatous material, with very little glial fibrillary acid protein-positive glial material. We found in this patient the preferential recurrence of the sarcomatous component of a gliosarcoma after potent radiotherapeutics in the form of BNCT.

Biopsy↗
PubMed2006

Model analysis of coil embolization of cerebral aneurysms: prediction of thrombus formation in aneurysms based on the coil embolization rate.

OBJECTIVES: Intra-aneurysmal coil embolization has been established as a common method for the intravascular treatment of cerebral aneurysms, but few studies have evaluated its long-term results. Because there is no sufficient objective landmark of complete embolization, determination of its application depends on a surgeon's experience. METHODS: A glass cerebral aneurysm model was produced, and the changes in intra-aneurysmal hemodynamics were examined. Nylon thread with a diameter of 0.33 mm, resembling the coils clinically used for embolization, was used to fill in the model. After perfusion of glycerin solution to represent human blood, the half life of a dye injected into the aneurysm was optically measured, and the relationship between the half life and the volume embolization rate (VER) of nylon thread in the aneurysm was examined. RESULTS: The maximal VER obtained by filling nylon thread in the aneurysm was 41.7+/- 2.9%. The half life of the dye increased with the VER and was significantly increased at VER>30%. DISCUSSION: The half life of the dye in the aneurysm reflected stagnation of intra-aneurysmal hemodynamics, suggesting that the prolongation of the half life enhances thrombus formation. The results of this study suggested that VER>30% is sufficient for effective coil embolization.

Carotid Artery Thrombosis↗
PubMed2006

Oncolytic recombinant herpes simplex virus for treatment of orthotopic liver tumors in nude mice.

Cell-specific, replicating viruses are being developed as a new class of oncolytic agents. A novel approach to viral gene therapy with the use of replication-competent herpes simplex virus has been described; G92A is a replication-competent, multimutant oncolytic herpes simplex virus (HSV) that has been evaluated for anticancer effects and selectivity in the treatment of subcutaneous tumors. G92A replicates efficiently in albumin-producing tumor cell lines but not in non-albumin-producing tumor cell lines, whereas both types are equally susceptible to a non-tissue-specific recombinant HSV, hrR3. In this study, we analyzed the antitumoral efficacy of a single intrasplenic G92A or hrR3 injection in nude mice. In vivo, G92A replicated well in liver xenografts of human albumin-producing hepatoma cells (Hep3B) but not in liver xenografts of a non-albumin-producing malignant colon tumor cell line (HT29), whereas hrR3 replicated well in both tumor types. G92A effectively and selectively replicated throughout liver tumors without apparent hepatotoxicity and inhibited tumor growth, leading to a significantly increased survival time. By monitoring lacZ histochemical staining, we determined the oncolytic potential of recombinant HSV against liver tumors. Our results indicate that G92A warrants further investigation as a clinical therapy against malignant liver tumors.

Animals↗
PubMed2005

Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Fibroblast growth factor-2 (FGF-2) administration and bone marrow stromal cell (MSC) transplantation could improve neurological deficits after occlusive cerebrovascular disease. In the present study, we examined the effects of neurological improvement after transient middle cerebral artery occlusion (MCAO) in rats by a novel therapeutic strategy with FGF-2 gene-transferred MSCs by the herpes simplex virus type 1 (HSV-1) vector. METHODS: Adult Wistar rats were anesthetized. Nonmodified MSCs, FGF-2-modified MSCs with HSV-1 1764/-4/pR19/ssIL2-FGF-2, or PBS was administered intracerebrally 24 hours after transient right MCAO. All animals underwent behavioral tests for 21 days, and the infarction volume with 2-3-5-triphenylterazolium was detected 3 days and 14 days after the MCAO. Three days and 7 days after the MCAO, the FGF-2 production in the ipsilateral hemisphere of the MCAO was measured with ELISA. Seven and 14 days after the MCAO, immunohistochemical staining for FGF-2 was applied. RESULTS: The stroke animals receiving FGF-2-modified MSCs demonstrated significant functional recovery compared with the other groups. Fourteen days after the MCAO, there was a significant reduction in infarction volume only in FGF-2-modified MSC-treated group. FGF-2 production in the FGF-2-modified MSC-treated brain was significantly higher compared with the other groups at 3 and 7 days after MCAO. Administrated FGF-2-modified MSCs strongly expressed the FGF-2 protein, which was proven by ELISA. CONCLUSIONS: Our data suggest that the FGF-2 gene-modified MSCs with the HSV-1 vector can contribute to remarkable functional recovery after stroke compared with MSCs transplantation alone.

Animals↗
PubMed2005

Downregulation of survivin by siRNA diminishes radioresistance of pancreatic cancer cells.

BACKGROUND: Survivin is a member of the inhibitor of apoptosis protein family, which inhibits apoptosis and regulates cell division. Survivin is expressed by the majority of human cancers, including pancreatic adenocarcinoma. We have reported that its expression is correlated with shorter survival of pancreatic cancer patients, so regulation of this molecule could be a new strategy for fighting pancreatic cancer. METHODS: In 3 pancreatic cancer cell lines (AsPC-1, SUIT-2, and Panc-1), survivin promoter activity was determined by the luciferase reporter assay, and survivin messenger RNA (mRNA) expression was examined by quantitative reverse transcriptase-polymerase chain reaction. The dose-dependent cytotoxity of radiation was also assessed, while caspase-3 activity and induction of DNA fragmentation were evaluated. Furthermore, the effect of silencing or nonsilencing short interfering RNA (siRNA) expression plasmids directed against the survivin gene on AsPC-1 cells, the most radioresistant cell line, was evaluated. RESULTS: Pancreatic cancer cell lines expressed varying levels of survivin mRNA in association with transcriptional activity of the survivin promoter. Both survivin promoter activity and mRNA expression were correlated with tumor cell radiosensitivity. Radiation significantly increased survivin promoter activity and survivin mRNA expression in all cell lines. Radiation induced a significant increase in caspase-3 activity and DNA fragmentation in AsPC-1 cells. After silencing siRNA treatment of AsPC-1 cells (AS-S cells), there was a significant decrease in survivin mRNA expression and increase in caspase-3 activity, compared with the effect of nonsilencing scramble siRNA on AsPC-1 cells (AS-NS cells). AS-S cells were more radiosensitive than AS-NS cells. Radiation induced higher caspase-3 activity and more DNA fragmentation in AS-S cells, compared with AS-NS cells. CONCLUSIONS: Survivin may play an important role as 1 of the radioresistance factors. Downregulation of survivin by siRNA can diminish the radioresistance of pancreatic cancer cells, so combined therapy with survivin inhibition and radiation may be useful for the treatment of pancreatic cancer.

Cell Line, Tumor↗
PubMed2005

Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages.

OBJECT: To improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, the authors used epithermal rather than thermal neutrons for deep penetration and two boron compounds-sodium borocaptate (BSH) and boronophenylalanine (BPA)-with different accumulation mechanisms to increase the boron level in tumors while compensating for each other's faults. METHODS: Thirteen patients, 10 of whom harbored a glioblastoma multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one an anaplastic oligoastrocytoma, were treated using this modified BNCT between January 2002 and December 2003. Postoperatively, neuroimaging revealed that only one patient with a GBM had no lesion enhancement postoperatively. The patients underwent 18F-BPA positron emission tomography, if available, to assess the accumulation and distribution of BPA before neutron radiotherapy. The neutron fluence rate was estimated using the Simulation Environments for Radiotherapy Applications dose-planning system before irradiation. The patients' volume assessments were performed using magnetic resonance (MR) imaging or computerized tomography (CT) scanning. Improvements in the disease as seen on neuroimages were assessed between 2 and 7 days after irradiation to determine the initial effects of BNCT; its maximal effects were also analyzed on serial neuroimages. The mean tumor volume before BNCT was 42.3 cm3. Regardless of the pre-BNCT tumor volume, in every patient harboring an assessable lesion, improvements on MR or CT images were recognized both at the initial assessment (range of volume reduction rate 17.4-71%, mean rate 46.4%) and at follow-up assessments (range of volume reduction rates 30.3-87.6%, mean rate 58.5%). More than 50% of the contrast-enhanced lesions disappeared in eight of the 12 patients during the follow-up period. CONCLUSIONS: This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages.

Adult↗
PubMed2005

Correlation between transcriptional expression of survivin isoforms and clinicopathological findings in human colorectal carcinomas.

Survivin, a novel member of the inhibitor of apoptosis protein (IAP) family, has been markedly overexpressed in most types of human carcinoma, and recognized as a potential target in anticancer therapy. In addition, two splice variants of survivin, survivin-2B and survivin-deltaEx3, have recently been identified. However, expression analysis on its splice variants has not been reported in colorectal carcinomas. Therefore, we investigated the transcription levels of survivin and its splice variants in human colorectal carcinomas, and the correlation between transcript expression levels and pathological findings was analyzed. Tumor tissue samples were provided from 52 cases with colorectal adenocarcinoma resected at the Osaka Medical College from 1995 to 1996. Transcription levels were measured by performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) using primer pairs specific for survivin and either of its splice variants, then normalized by the glyceraldehyde 6-phosphate dehydrogenase. The transcription levels of survivin and its splice variants were significantly higher in the tumor tissue samples, and significantly lower in the normal tissue samples. In addition, approximately 40% of the normal tissue samples did not have any survivin expression. The relative expression level of survivin-2B to survivin (survivin-2B/survivin) was significantly higher in the tumor tissue samples than in the normal ones. In contrast, survivin-deltaEx3/survivin revealed no difference between tumor and normal samples. When Comparing the histological disease stages (stage I and II vs. stage III and IV), there were no significant differences in the expression levels of survivin and its splice variants. The expression level of survivin-2B/survivin for stage III and IV was lower than the one for stage I and II. In addition, a higher level of survivin-2B/survivin significantly correlated with a better prognosis in the present series. The present study demonstrates high expression level of survivin and its splice variants, which is relatively specific in tumor tissue and suggests that they have important roles in the progression of human colorectal carcinomas.

Adenocarcinoma↗
PubMed2004

Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels in rabbit model of hind limb ischemia.

PURPOSE: In our previous study, adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promoted significant collateral vessel development in a rabbit model of hind limb ischemia. The present study examined how to control the efficacy and safety of this gene therapy, and also evaluated the feasibility of repeat application of this procedure. METHODS: Modified hFGF gene with the secretory signal sequence was adenovirally transferred to cultured autologous fibroblasts, and various numbers of the cells (2 x 10(5), 1 x 10(6), 5 x 10(6), or 2.5 x 10(7)) or vehicle was injected through the left internal iliac artery in rabbits in whom the left femoral artery had been excised 21 days previously. Twenty-eight days after cell administration, calf blood pressure ratio, angiographic score, blood flow in the internal iliac artery, and capillary density of muscle tissue were measured to analyze collateral vessel development and tissue perfusion in the ischemic limb. To assess delivery efficiency and viral contamination, the distribution of injected cells and the time course of blood anti-adenovirus antibody titer were examined in rabbits treated with various numbers of gene-transduced cells. In addition, animals received two injections, 21 days apart, of fibroblasts infected with adenovirus vector containing the luciferase gene, and luciferase expression was measured to evaluate whether the present therapy is repeatable. RESULTS: At 28 days after cell administration, significant collateral vessel development without detectable side effects was observed in rabbits who received 5 x 10(6) or 2.5 x 10(7) cells, compared with those who received vehicle, and no significant development was detected in animals with fewer than 5 x 10(6) cells (P <.01 for calf blood pressure ratio and capillary density, P <.05 for angiographic score and maximum blood flow). There was no difference in collateral augmentation between rabbits with 5 x 10(6) and 2.5 x 10(7) cells. However, in animals with 2.5 x 10(7) cells a large number of injected cells accumulated in the lungs, anti-adenovirus antibody titer increased significantly, and calf blood pressure in the left hind limb of two rabbits decreased immediately after injection. Luciferase analysis showed very low gene expression after repeated administration. CONCLUSION: These findings suggest that 5 x 10(6) is a suitable number of cells to induce appropriate collateral vessel development and minimize potential side effects of this procedure. Despite use of ex vivo gene transfer, repeat administration of the cells was not feasible. Clinical relevance Since the present study determined the appropriate conditions for effective and safe stimulation of collateral vessels, the clinical relevance of the ex vivo therapy might be carried forward. However, the findings raised another issue that should be resolved before clinical application; that is, the number of gene-transduced cells able to be injected was strictly limited. To estimate the therapeutic range of cell number in humans, additional experiments using large animals are desirable.

Adenoviridae↗
PubMed2004

Survivin expression is a prognostic marker in pancreatic cancer patients.

BACKGROUND: In this study, we assessed survivin expression in pancreatic cancer specimens from patients who underwent either pancreatic resection alone or pancreatic resection plus postoperative radiation therapy (PORT) to evaluate whether survivin expression is predictive of sensitivity to PORT and outcome in pancreatic cancer patients. METHODS: Fifty-two patients who underwent pancreatic resection for ductal adenocarcinomas were included in this study. Forty-seven pancreatic ductal adenocarcinoma and 5 normal pancreatic tissues were evaluated for survivin expression by immunohistochemistry. Then the relationship between survivin expression and clinicopathologic data were analyzed. RESULTS: Sixty-eight percent (32/47) of pancreatic cancer tissues were positive for survivin expression; 32% (15/47) were negative. Normal pancreatic exocrine tissues were negative for survivin expression (0/5). Survival of the patients with positive survivin was significantly shorter than those with negative survivin (P = .02). Survivin was an independent variable that correlated with overall survival (P = .01). There was no difference in survival time between patients with and without PORT. Likely, PORT showed no impact on survival time in survivin-positive patients (P = .12) as well as in survivin-negative patients (P = .95). CONCLUSIONS: The results suggest that survivin expression in pancreatic cancer tissues could be a useful prognostic marker in pancreatic cancer patients.

Aged↗
PubMed2004

Osteoinduction by bone morphogenetic protein 2-expressing adenoviral vector: application of biomaterial to mask the host immune response.

We constructed a human bone morphogenetic protein 2 (BMP-2)-expressing adenoviral vector, AxCABMP-2, which showed osteoinduction in immunosuppressed rats. In immunocompetent rats, new bone was not induced, because of the rapid elimination of transduced cells. Biomaterials such as collagen can be used as carriers for the delivery of DNA vectors, allowing prolonged expression of plasmid DNA in normal animals. We evaluated osteoinduction with AxCABMP-2 and atelopeptide type I collagen in immunocompetent rats. Collagen plus AxCABMP-2 (BMP group), collagen plus AxCALacZ (LacZ group), or collagen alone (CL group) was implanted into calf muscle pouches in immunocompetent rats, or AxCABMP-2 alone (injection group) was injected into the calf muscle. On days 3, 7, 14, and 21 after treatment, osteoinduction was evaluated. In the BMP group, bone formation was not observed on days 3 and 7. On day 14, radiographic formation was seen, but little bone formation was detected histologically. On day 21, new bone formation was observed both radiologically and histologically. In the other groups, osteoinduction was not found at any time. Immunohistochemical analysis on days 3 and 7 revealed decreased immunogenicity in the BMP group compared with the injection group. These findings suggested that collagen was an effective masking material for our vector.

Adenoviridae↗
PubMed2004

Postischemic intraventricular administration of FGF-2 expressing adenoviral vectors improves neurologic outcome and reduces infarct volume after transient focal cerebral ischemia in rats.

Fibroblast growth factor (FGF)-2 is a potent neurotrophic and angiogenic peptide. To examine possible protective effects of FGF-2 gene expression against transient focal cerebral ischemia in rats, a replication defective, recombinant adenovirus vector expressing FGF-2, was injected intraventricularly 2 hours after middle cerebral artery occlusion (MCAO). The treatment group showed significant recovery compared with the vehicle-treated groups in terms of serial neurologic severity scores over the 35 days after MCAO. Further, 2,3,5-triphenyltetrazolium chloride staining showed that FGF-2 gene transfer decreased infarct volume by 44% as compared with that in the vehicle-treated groups at 2 days after MCAO. The same tendency of gene transfer effects on infarct volume was confirmed at 35 days after MCAO with hematoxylin/eosin staining. Enzyme-linked immunosorbent assay revealed that FGF-2 concentration was increased significantly at 2 days after MCAO, not only in cerebrospinal fluid but also in cerebral substance in the lesioned and treated animals. These results suggested that FGF-2 gene transfer using these adenoviral vectors might be a useful modality for the treatment of occlusive cerebrovascular disease even after the onset of stroke.

Adenoviridae↗
PubMed2003

Adenovirus-mediated gene transfer of fibroblast growth factor-2 increases BrdU-positive cells after forebrain ischemia in gerbils.

BACKGROUND AND PURPOSE: Progenitor cells continue to generate neurons in the adult mammalian brain, and cerebral ischemia induces neurogenesis. We examined the efficacy of the intraventricular injection of a recombinant adenovirus-expressing fibroblast growth factor-2 (FGF-2) (AxCAMAssbFGF) on neurogenesis in both normal and ischemic brains. METHODS: We used a gerbil model of transient global ischemia and counted the number of BrdU-positive cells after injection of AxCAMAssbFGF into the brain with or without ischemia. RESULTS: Intraventricular AxCAMAssbFGF produced robust FGF-2 protein increases in diverse regions of the brain and markedly increased FGF-2 concentrations in cerebrospinal fluid 2 days after administration and evoked significant proliferation of BrdU-positive cells not only in the subventricular zone and dentate gyrus of the hippocampus but also in the cerebral cortex, and some BrdU-positive cells differentiated into neurons. Continuous intraventricular infusion of FGF-2 protein increased FGF-2 concentration in cerebrospinal fluid but not in brain tissues and produced BrdU-positive cell proliferation only in the subventricular zone of the lateral ventricle. CONCLUSIONS: Adenovirally mediated transfer of the FGF-2 gene promoted progenitor cell proliferation more efficiently in widespread regions of the brain after transient global ischemia than continuous intraventricular infusion of FGF-2 protein.

Adenoviridae↗