Search

Purpose The Flow Re-direction Endoluminal Device (FRED) has recently become available for flow diversion in Japan. We have encountered cases that failed to deploy the FRED. In this study, we report our initial experience with the FRED for cerebral aneurysms and clarify the causes of failed FRED deployment. Methods A retrospective data analysis was performed to identify patients treated with the FRED between June 2020 and March 2021. Follow-up digital subtraction angiography was performed at 3 and 6 months and assessed using the O’Kelly-Marotta (OKM) grading scale. Results Thirty-nine aneurysms in 36 patients (average age: 54.4 years) were treated with the FRED. The average sizes of the dome and neck were 9.9 mm and 5.2 mm, respectively. In nine patients, additional coiling was performed. In one patient (2.6%), proximal vessel injury caused direct carotid-cavernous fistula during deployment. Ischaemic complications were encountered in one patient (2.6%) with transient symptoms. Angiographic follow-up at 6 months revealed OKM grade C or D in 86.6% of patients. FRED deployment was successful in 35 (92.1%) procedures. In the failure group, the differences between the FRED and the minimum vessel diameter (P = 0.04) and the rate of the parent vessel having an S-shaped curve (P = 0.04) were greater than those in the success group. Conclusions Flow diversion using the FRED is effective and safe for treating cerebral aneurysms. The use of the FRED for patients with an S-shaped curve in the parent vessel and oversizing of more than 2 mm should be considered carefully.

Some aneurysmal subarachnoid hemorrhage (SAH) patients are delayed in their presentation. This can cause a washout of the subarachnoid hematoma and a potential misdiagnosis. As a result, they may suffer re-rupture of the aneurysm and preventable deterioration. We investigated the factors that influence delayed SAH presentation.Aneurysmal SAH patients treated at nine stroke centers from 2002 to 2020 were included. Age, gender, pre-SAH modified Rankin scale (mRS), World Federation of Neurological Surgeons (WFNS) grade, Fisher group, day of presentation, aneurysm treatment method, past history of cerebral stroke, comorbidity of hypertension and/or diabetes mellitus, and mRS at discharge were assessed retrospectively. We formed two groups based on the day of presentation after the onset of SAH: day 0 ∼ 3 (early) and other (delayed). Logistic regression analyses detected the factors that influenced the day of presentation and outcome for SAH. A p-value0.05 was considered significant.Delayed presentation comprised 282 cases (6.3%) of 4,507 included cases. Logistic regression analyses showed that patients in an urban area, of male gender, low WFNS grade, and low Fisher group correlated significantly with a delayed presentation. But delayed presentation did not influence outcome at discharge.Area of residency and gender correlated with delayed presentation after SAH in Japan. Urbanization, male gender and mild SAH lead patients to delay presentation. The factors underlying these tendencies will be analyzed in a future prospective study.

Surgical clipping of anterior communicating artery (ACoA) aneurysms remains challenging due to their complex anatomy. Anatomical risk factors for ACoA aneurysm surgery require further elucidation. The aim of this study is to investigate whether proximity of the midline perforating artery, subcallosal artery (SubCA), and associated anomaly of the ACoA complex affect functional outcomes of ACoA aneurysm surgery. A total of 92 patients with both unruptured and ruptured ACoA aneurysms, who underwent surgical clipping, were retrospectively analyzed from a multicenter, observational cohort database. Association of ACoA anatomy with SubCA origin at the aneurysmal neck under microsurgical observation was analyzed in the interhemispheric approach subgroup (n = 56). Then, we evaluated whether anatomical factors associated with SubCA neck origin affected surgical outcomes in the entire cohort (both interhemispheric and pterional approaches, n = 92). In the interhemispheric approach cohort, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was stratified to have the highest probability of the SubCA neck origin by a decision tree analysis. Then, among the entire cohort using either interhemispheric or pterional approach, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was significantly associated with poor functional outcomes by multivariable logistic regression analysis (OR 6.76; 95% CI 1.19–38.5; p = 0.03) as compared with A1 symmetry group in the acute subarachnoid hemorrhage settings. Combination of A1 asymmetry and larger aneurysmal size was significantly associated with SubCA aneurysmal neck origin and poor functional outcomes in ACoA aneurysm surgery. Interhemispheric approach may be proposed to provide a wider and unobstructed view of SubCA for ACoA aneurysms with this high-risk anatomical variant.

The World Federation of Neurosurgical Societies (WFNS) scale is widely accepted for predicting outcomes for subarachnoid hemorrhage (SAH) patients. However, it is difficult to definitely predict outcomes for the most poor grade, WFNS grade 5. The present study aimed to investigate the prognostic ability of a novel classification using computed tomography perfusion (CTP) findings, called the cortical blood flow insufficiency (CBFI) scores. CTP was performed on admission for aneurysmal SAH followed by radical treatments within 72 hours of onset. Twenty-four cerebral cortex regions of interest (ROIs) were defined. CBFI was defined as Tmax > 4 s in each ROI, and CBFI scores were calculated based on the total number of ROIs with CBFI. Using the optimal cutoff value based on receiver operating characteristics (ROC) analysis to predict patient functional outcomes, CBFI scores were divided into “high” or “low” CBFI scores. Patient functional outcomes at 90 days were categorized based on modified Rankin Scale scores (0–3, favorable group; 4–6 unfavorable group) (0–4, non-catastrophic group; 5–6, catastrophic group). Fifty-seven patients were included in this study, of whom 21 (36.8%) and 13 (22.8%) were in the unfavorable and the catastrophic groups, respectively. A factor predicting unfavorable and catastrophic outcomes was CBFI score cutoff value of 7 points (area under the curve, 0.73 and 0.81, respectively). In multivariable logistic regression analysis for unfavorable outcome, high CBFI scores (odds ratio (OR), 8.6; 95% confidence interval (CI), 1.1–65.4; P = 0.04) and WFNS grade 5 (OR, 30.0; 95% CI, 4.5–201.0; P

The PulseRider (Cerenovus, JohnsonJohnson Medical Devices, New Brunswick, NJ, USA) is a neck reconstruction device that is used for the treatment of unruptured wide-necked bifurcation aneurysms. Herein, we describe the case of a 51-year-old male patient with a basilar apex aneurysm who was treated with PulseRider but had post-procedural brainstem infarctions caused by one of the proximal markers covering the origin of a perforator. In such cases, repositioning of the PulseRider should be performed to avoid infarctions.

The posterior condylar vein is an emissary vein that connects the extracranial and intracranial venous systems through the posterior condylar canal (PCC). Dural arteriovenous fistulas (DAVF) of the PCC are rare, and only seven cases have been reported. Transvenous embolization (TVE) is the first-line treatment for PCC DAVF and is predominantly performed through the internal jugular vein. Herein, we report a case of PCC DAVF treated with TVE through the deep cervical vein. This is the first case report of a PCC DAVF treated with TVE through the deep cervical vein.

This study aimed to determine the impact of the approval of prothrombin complex concentrates on the treatment of vitamin K antagonist-related intracerebral hemorrhage.We retrospectively studied all patients with vitamin K antagonist-related intracerebral hemorrhage treated with prothrombin complex concentrate at our institutes between January 2010 and June 2021. Before approval, prothrombin complex concentrate was administered as either 500 or 1000 IU at the physician's discretion (previous dose group). After approval, we adopted the manufacturer's recommended regimen (recommended dose group). The primary outcome was post-administration international normalized ratio. Secondary outcomes were the amount of prothrombin complex concentrate administered and proportion of post-administration international normalized ratio1.5, hematoma expansion, thrombotic events within 30 days, modified Rankin scale 0-3 at discharge, and in-hospital mortality.Thirty-two and 19 patients in the previous and recommended dose groups, respectively, were included. The post-administration international normalized ratio significantly differed between groups. The prothrombin complex concentrate dose and proportion of patients achieving post-administration international normalized ratio1.5 were significantly higher in the recommended dose group than in the previous dose group (1500 IU vs. 500 IU, p0.001 and 100% vs. 68%, p = 0.008). The proportions of hematoma expansion, thromboembolic events, modified Rankin scale 0-3, and mortality did not differ between groups.After prothrombin complex concentrate approval, prothrombin time-international normalized ratio correction was more effective with a significant increase in the prothrombin complex concentrates dose for vitamin K antagonist-associated intracerebral hemorrhage; however, there was no apparent difference in clinical outcomes.

Purpose Endovascular treatment of posterior communicating artery aneurysms with fetal-type posterior communicating artery originating from the aneurysm dome is often challenging because, with conventional techniques, dense packing of aneurysms for posterior communicating artery preservation is difficult; moreover, flow-diversion devices are reportedly less effective. Herein, we describe a novel method called the λ stenting technique that involves deploying stents into the internal carotid artery and posterior communicating artery. Methods Between January 2018 and September 2020, the λ stenting technique was performed to treat eight consecutive cases of aneurysms. All target aneurysms had a wide neck (dome/neck ratio < 2), a fetal-type posterior communicating artery with hypoplastic P1, and a posterior communicating artery originating from the aneurysm dome. The origin of the posterior communicating artery from the aneurysm, relative to the internal carotid artery, was steep (< 90°: V shape). Results The maximum aneurysm size was 8.0 ± 1.9 mm (6–12 mm). The average packing density (excluding one regrowth case) was 32.7 ± 4.2% (26.8–39.1%). Initial occlusion was complete occlusion in 6 (75.0%) patients and neck remnants in 2 (25.0%) patients. Follow-up angiography was performed at 18.4 ± 11.6 months (3–38 months). There were no perioperative complications or reinterventions required during the study period. Conclusion The λ stenting technique enabled dense coil packing and preservation of the posterior communicating artery. This technique enabled safe and stable coil embolization. Thus, it could become an alternative treatment option for this sub-type of intracranial aneurysms.

Background The anterior inferior cerebellar artery–posterior inferior cerebellar artery (AICA–PICA) common trunk anomaly is reportedly one of the most common vessel variants in the posterior circulation, but reports of hemifacial spasm (HFS) associated with AICA–PICA common trunk are very rare. In the present study, we describe methods of microvascular decompression (MVD) for HFS caused by AICA–PICA common trunk compression. Methods Among 159 patients who underwent MVD for HFS, 16 patients had compression of the root exit zone by the AICA–PICA common trunk anomaly. The types of compression were classified into 2 groups: common trunk artery compression group and branching vessel compression group. Results The common trunk artery compression group consisted of 11 patients (69%), and the branching vessel compression group consisted of 5 patients (31%). The rostral branch (feeding the original AICA territory) coursed between the seventh and eighth cranial nerves in 5 patients, and in 13 patients (81%), the offending vessel harbored perforators around the root exit zone. Among 16 patients, 14 (87.5%) required interposition of the common trunk or the branching vessel, and in 2 patients, decompression was completed by the transposition method. Fifteen patients experienced sufficient results, and 1 had severe residual spasm. Transient facial palsy developed in 2 patients. No patients encountered recurrence. Conclusions Reports concerning decompression methods of AICA–PICA common trunk anomaly are very rare. The tortuosity of the common trunk and perforators from the offending vessel make the usual repositioning of the offending artery much more difficult, and adequate decompression techniques are required for successful MVD.

Background Carotid artery stenting (CAS) with distal filter protection allows continuous cerebral perfusion, although it is associated with a greater risk of cerebral ischemic complications than other protection systems. To reduce cerebral ischemic complications, CAS was performed under combined cerebral protection using both flow reversal (FR) and a distal filter. Methods Fifty-six stenoses of 52 patients were treated with CAS using the combined protection of FR and a distal filter, with intermittent occlusion of both the common carotid artery (CCA) and the external carotid artery. The blood flow was reversed into the guiding catheter to the central venous system via an external filter, which collected the debris. Clinical outcomes, the rates of capturing visible debris, and new ischemic signals on diffusion-weighted magnetic resonance imaging (DWI-MRI) were evaluated. Results The overall technical success rate was 92.9% (52/56). Successful stent deployment was achieved in 100% (56/56) of the cases. No procedural-related emboli causing a neurologic deficit were observed. In 38.5% (20/52) of the cases, visible debris were captured by only the external filter, and in 17.3% (9/52), visible debris were captured by both external and distal filters. In no case was visible debris noted in only the distal filter. New ischemic signals on DWI-MRI were detected in 9.6% (5/52). The 30-day myocardial infarction, stroke, and death rates were 0%. Conclusions The additional use of a distal filter captures emboli in 17.3% of cases, and because the occlusion is only intermittent, the procedure is potentially applicable even in those who cannot tolerate prolonged balloon occlusion of the CCA.

Background and purpose The ED coil-10 Extra Soft (EDC-10 ES) is an extremely soft coil with excellent operability for embolization of cerebral aneurysms and is frequently used as a ‘finishing coil’. The aim of this study was to evaluate the efficacy and safety of this coil. Methods Clinical data were analyzed retrospectively for 92 consecutive aneurysms for which at least one EDC-10 ES was used. Follow-up angiography at 6 months was available for 69 aneurysms. Initial and follow-up outcomes were evaluated using three-category occlusion grading. Factors that affect the packing density were also investigated. Results Of the 92 aneurysms, 63 (68.5%) were classified as complete occlusion, 11 (12.0%) as having a neck remnant and 18 (19.6%) with dome filling immediately after the embolization procedure. The mean±SD packing density was 29.5±10.6%. Periprocedural complications were observed in three cases (3.3%). At 6 months the rate of completely occluded cases increased to 78.3% (54/69) and those for neck remnant and dome filling decreased to 11.8% (8/69) and 10.1% (7/69), respectively. Recanalization occurred in six aneurysms and one aneurysm was retreated during the follow-up period, giving an overall recurrence rate of 10.0% (7/70). Linear regression analysis showed a significant association of packing density with the percentage EDC-10 ES volume (p

症例は41歳，女性．2007年10月の検診マンモグラフィ（MMG）で左乳房の局所的非対称性陰影を指摘されたが，2008年1月の精査では異常を認めず，2008年9月のMMGも異常はなかった．しかし2009年7月右乳房腫瘤を触知し当院を受診した．触診では右乳頭直下に弾性硬腫瘤を認め，MMGでは右M領域に辺縁微細鋸歯状，高濃度腫瘤を認めカテゴリー4であった．超音波検査では辺縁不整，内部不均一な30×23mmの腫瘤を認めカテゴリー4であった．造影CTでは腫瘤辺縁がリング状に造影された．針生検を施行し，基質産生癌と診断した．ER，PgR，HER2は全て陰性であった．胸筋温存乳房切除術，腋窩リンパ節郭清を施行した．病理診断は基質産生癌で，腋窩リンパ節転移（1/19）を認めた．術後補助化学療法を施行し，現在無再発生存中である．基質産生癌は頻度が低く，本邦報告例の検討と文献的考察を加え報告する．

症例は35歳，女性．原因不明の腹痛で当院受診歴があった．2008年7月同様の腹痛と発熱が出現し再診．腹部造影CTでは内部に低吸収域を伴う胃壁の肥厚を認め，胃壁内膿瘍と診断し入院となった．上部消化管内視鏡検査では，胃幽門部大弯側に粘膜下病変を認めた．抗生剤投与により腹痛は消失，退院となった．2009年4月再び腹痛が出現し，再診．CTでは前回入院時と同様の所見を認め，上部消化管内視鏡検査では，同病変頂部に潰瘍と膿の排出を認めた．以上より再燃性の胃壁内膿瘍と診断，手術を施行した．病変は直径3cm大の境界不明瞭な硬結として触知し，胃部分切除術を施行した．病理組織学的検査では病変部に膵腺房細胞と拡張した導管を認め，膿瘍部では高度慢性炎症の像を呈しており，異所性膵に併発した胃壁内膿瘍と診断した．症状を伴う異所性膵は稀であり，文献的考察を加え報告する．

症例は78歳，男性．胆管癌に対し幽門温存膵頭十二指腸切除術術後1年6カ月，下腹部痛を訴え，気尿も認めたために，当科入院した．CT検査で，膀胱内に膵胃吻合部に留置した膵管ロストチューブの迷入，および注腸検査でS状結腸膀胱瘻を認め，経尿道的に膵管ロストチューブを除去した．しかし，その後気尿が再燃したために，開腹S状結腸膀胱瘻閉鎖術を施行した．本症例はS状結腸憩室症を合併しており，憩室を経由してロストチューブが膀胱に穿通したものと推測された．一般にロストチューブは自然脱落したあと経肛門的に排出されるが，本症例のように腸管外に迷入する可能性もあることを念頭に置き，経過観察すべきと思われた．

症例は44歳，女性．2007年6月下血を主訴に当院を紹介受診．大腸内視鏡検査では肛門縁より約10cmの部位に中心部に浅い陥凹を伴う粘膜下腫瘍様の隆起性病変を認めた．生検で，高分化腺癌と診断された．注腸X線検査ではRs～Raにかけて前壁に長さ約5cmの片側性の陰影欠損像を認めた．立ち上がりはなだらかで鋸歯状変化を認めた．腹部造影CT検査では子宮壁および直腸壁は濃染され境界は不明瞭であった．以上より直腸癌，あるいは卵巣癌の直腸浸潤と診断し，2007年8月27日手術を施行した．病理組織学的には子宮内膜間質を伴った腺管の増殖を認め，直腸子宮内膜症と診断した．直腸間膜リンパ節内にも子宮内膜組織を認めた．腸管子宮内膜症で所属リンパ節に病変を伴うものは極めて稀である．実際に悪性腫瘍との鑑別が困難であった症例であり，若干の文献的考察を加えて報告した．

Object The receptor for hyaluronan-mediated motility (RHAMM) is frequently overexpressed in brain tumors and was recently identified as an immunogenic antigen by using serological screening of cDNA expression libraries. In this study, which was conducted using a mouse glioma model, the authors tested the hypothesis that vaccination with dendritic cells transfected with RHAMM mRNA induces strong immunological antitumor effects. Methods The authors constructed a plasmid for transduction of the mRNAs transcribed in vitro into dendritic cells, which were then used to transport the intracellular protein RHAMM efficiently into major histocompatibility complex class II compartments by adding a late endosomal–lysosomal sorting signal to the RHAMM gene. The dendritic cells transfected with this RHAMM mRNA were injected intraperitoneally into the mouse glioma model 3 and 10 days after tumor cell implantation. The antitumor effects of the vaccine were estimated by the survival rate, histological analysis, and immunohistochemical findings for immune cells. Mice in the group treated by vaccination therapy with dendritic cells transfected with RHAMM mRNA survived significantly longer than those in the control groups. Immunohistochemical analysis revealed that greater numbers of T lymphocytes containing T cells activated by CD4+, CD8+, and CD25+ were found in the group vaccinated with dendritic cells transfected with RHAMM mRNA. Conclusions These results demonstrate the therapeutic potential of vaccination with dendritic cells transfected with RHAMM mRNA for the treatment of malignant glioma.

尿膜管遺残症は若年者に発症することが多く, 美容的な面も考慮すると可能であれば腹腔鏡下に切除するのが望ましい. 今回腹腔鏡下に摘出した尿膜管遺残症の3例を経験したので報告する. 症例はいずれも臍炎を主訴として発症した男性で, 平均年齢は25歳であった. 3本の5mmポートを挿入して尿膜管の剥離・切断を行った. 摘出に際しては臍直下に弧状の小切開を置き体外にて臍部の切断を行った. いずれも膀胱側の切断部には最初の1例のみエンドループを用いたが, 残りの2例は3-0吸収糸による体外結紮で行った. 平均手術時間は92分, 術後在院日数は平均2.7日であった. 腹腔鏡手術が普及した現在, 尿膜管切除に対して腹腔鏡手術は十分標準手術になりうると考えた.

BF 2 + implanted strained silicon/SiGe was characterized with the aim of maximizing the performance of strained-silicon pMOSFETs. Recovery of implantation damage in the strained-silicon layer was achieved by annealing at 900 °C or higher, but end-of-range defects remained in the SiGe layer after annealing. Germanium recoil and vacancy-enhanced redistribution of germanium caused by BF 2 + implantation are not negligible issues in strained-silicon MOSFET fabrication. Boron diffusion during annealing was retarded in SiGe compared to that in silicon, and as a result, a higher-concentration and shallower boron-doped region than that in silicon can be formed in strained silicon/SiGe. Hole mobility in boron-doped strained silicon is about 30% higher than in silicon. These results suggest that lower source and drain resistance can be achieved in the strained-silicon pMOSFET than in the silicon pMOSFET.

Background The aim of this study was to compare the efficacy of surgery for spontaneous intracerebral hemorrhage with that of medical treatment, based on data from the Japan Stroke Registry Study. Methods From 1999 to 2001, 1010 patients with spontaneous intracerebral hemorrhage were registered in the Japan Standard Stroke Registry Study from 45 stroke center hospitals in Japan. The National Institutes of Health Stroke Scale (NIHSS), Japan Stroke Scale (JSS), and modified Rankin Scale scores were used to compare severity and improvement in patients given surgical and medical treatment. Conclusions Surgically treated patients, especially those with cerebellar hemorrhage, had significantly greater improvement in NIHSS or JSS score compared with medically treated patients. Our findings indicated that the patients who underwent surgery appeared to have better outcomes. But, because the study was not randomized, this observation cannot be interpreted as indicating that surgery is advantageous.

This retrospective study investigated the functional outcomes of patient with glioblastoma receiving radical surgery before and after the adoption of the navigation-guided fence-post (NGFP) procedure and neurophysiological monitoring. We investigated 42 glioblastoma patients receiving radical surgery in our institute between 1980 and 2005. Of the 42 patients, 18 patients from 1980 to 1996 (1st term) underwent radical surgery without navigation system guidance, NGFP, or neurophysiological monitoring; 11 patients from 1997 to 2002 (2nd term) underwent surgery with simple navigation system guidance but without NGFP procedure or neurophysiological monitoring, and 13 patients from 2003 to 2005 (3rd term) underwent surgery with the NGFP procedure and neurophysiological monitoring as appropriate. There were no significance differences between any of the three term groups in age, gender, preoperative KPS score, or 'surgical staging for glioma' according to the difficulty of surgery. The rates of 95% or greater volume reduction in each term were 38.9%, 54.5% and 76.9%. The rates of morbidity were 38.9%, 18.1% and 0%. The change in KPS scores (delta KPS) before and after the perioperative period in each term were -16.1 +/- 6.6 SEM, -9.0 +/- 5.8 SEM and +8.5 +/- 3.7 SEM, respectively. The delta KPS in the 3rd term was significantly better than those of 1st and 2nd terms (P0.01, Kruskal-Wallis rank test). The rate of patients who were discharged to home and who resumed daily useful life without assistance was 38.9%, 63.6% and 84.6% in each term, respectively. The mean survival times in each term were 9.9, 14.0 and 16.8 months. The introduction of the NGFP procedure and neurophysiological monitoring in glioblastoma radical surgery improved the functional outcome of patients.

We investigated re-crystallization, the redistribution of arsenic and germanium, and the electrical properties of strained-silicon/Si0.7Ge0.3 heterostructures with implanted arsenic ions. Our aim was to acquire basic information regarding the fabrication of strained-silicon MOSFETs with low-resistance source and drain regions. The strained-silicon layers were completely re-crystallized with rapid thermal annealing at 900 °C or higher. Arsenic diffusivity was identical in strained and unstrained silicon but was higher than both of these in SiGe. Germanium recoil produced by implanting arsenic in the SiGe layer was observed. The solubility limit for arsenic was 2×1020 cm−3 in both strained and unstrained silicon but was lower, 1×1020 cm−3, in Si0.7Ge0.3. Electron mobility was greater in strained silicon than in unstrained silicon by about 20–30% and lower in Si0.7Ge0.3 than in silicon by about 20–30%. A thicker layer of strained silicon is thus desirable for reducing parasitic resistance in the source and drain region.

For strained-silicon metal-oxide-semiconductor field-effect-transistors (MOSFETs), the formation of a low-resistance source and drain region is as important in terms of enhanced performance as optimizing the strain-induced increase in inversion-carrier mobility. The crystallographic, compositional, and electrical properties of an arsenic-ion implanted strained silicon/Si0.7Ge0.3 heterostructure were investigated in order to acquire basic information for fabricating low-resistance source and drain region of the n-channel strained-silicon MOSFET. The strained-silicon layer is completely recrystallized by rapid thermal annealing after arsenic implantation, but misfit dislocations were formed by annealing (at 1000 °C) in the case thickness of the strained-silicon layer exceeding the critical thickness. Arsenic diffusivity in strained silicon was identical to that in silicon, whereas that in SiGe was higher than that in silicon. Germanium recoil and enhanced diffusion caused by arsenic implantation to the SiGe...

OBJECTIVE: In a syngeneic mouse brain tumor model, we tested the hypothesis that vaccination with tumor cells genetically modified to express B7.1 molecules induces tumor-specific T cells and immunological antitumor effects. METHODS: Malignant glioma cell (RSV-MG) derived from a C3H/He mouse induced by Schmidt-Ruppin Rous sarcoma virus (RSV) were infected with an adenovirus encoding the 87,1 gene (AdB7). to investigate the effects of B7,1 expression on the tumorigenicity of RSV-MG cells, intected cells were implanted subcutaneously into C3H/He mice. The C3H/He mice were vaccinated with AdB7 transiectants injected subcutaneously and 2 weeks later were challenged intracerebrally with wild-type RSV-MG cells to determine whether or not the expression of B7,1 would enhance the immunogenicity of RSV-MG cells. RESULTS: Immunocytochemistry confirmed the expression of B7,1 and major histocompatibility complex Class I antigen on the intected cells. The growth of subcutaneous tumors was markedly retarded in the AdB7 group, whereas tumors had formed and progressively increased in size in the other control groups, in the vaccine experiments, the mice immunized with AdB7 transfectants survived longer than did themice of the other groups, and a significant difference in survival times was noted. Immunocytochemistry nocytochemistry revealed that brain tumors in mice previously vaccinated with AdB7 infectants had been infiltrated by a larger number of CD3+ lymphocytes and that these CD3+ lymphocytes contained not only CD4+ and CD8+ T cells but also CD25+ activated T cells. In addition, a cytotoxicity assay confirmed that vaccination with the AdB7 transfectants induced tumor-specitic cytotoxicity. CONCLUSION: These results demonstrate the therapeutic potential of vaccination with tumor cells expressing B7,1 for the treatment of malignant glioma.

The purpose of the present study was to determine if adenovirus-mediated transfection of a syngeneic mouse brain tumor with the gene encoding B7.1 enhances immunogenicity against tumor. Malignant astrocytoma cells were transfected with adenoviral vectors carrying the B7.1 gene (AdB7). Immunocytochemical analysis confirmed the expression of B7.1 in vitro and in vivo. To investigate the effects of B7.1 expression on tumorigenicity of the malignant astrocytoma, mice were implanted intracerebrally with B7.1-transfected glioma cells. There was no significant difference in proliferation between B7.1-transfected cells and controls in vitro. Nevertheless, mice implanted with B7.1-transfected cells survived significantly longer than those in the control groups. Immunocytochemical analysis of the tumors showed that there was infiltration of a number of CD8+ T-cells and CD25+ activated T-cells in the brain implanted with B7.1-transfected glioma cells. The results showed the possibility that adenovirus-mediated B7.1 gene transfection to a brain tumor induced activation of CD8+ cytotoxic T-lymphocytes.