Therapeutic implication of genetic variants of IL13 and STAT4 in airway remodelling with bronchial asthma.

BACKGROUND: Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched. OBJECTIVE: We determined the effects of high-dose inhaled corticosteroids (ICSs) on decreased pulmonary function in asthmatic Japanese patients with variants of IL13 and STAT4 during long-term treatments with low to mild doses of ICS. METHODS: In this study, 411 patients with bronchial asthma who were receiving ICSs and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations. The effects of 2 years of high-dose ICSs administered to asthmatic patients who were homozygous for IL13 AA of rs20541 or STAT4 TT of rs925847 and who progressed to airway remodelling were investigated. RESULTS: High-dose ICS treatment increased the pulmonary function of patients homozygous for IL13 AA of rs20541 but not of patients homozygous for STAT4 TT of rs925847. The increased concentrations of the mediators IL23, IL11, GMCSF, hyaluronic acid, IL24, and CCL8 in bronchial lavage fluid (BLF) were diminished after high-dose ICS treatment in patients homozygous for IL13 AA of rs20541. CONCLUSION AND CLINICAL RELEVANCE: IL13 AA of rs20541 and STAT4 TT of rs925847 are potential genomic biomarkers for predicting lower pulmonary function. The administration of high-dose ICSs to asthmatic patients with genetic variants of IL13 AA may inhibit the advancement of airway remodelling. The genetic variants of STAT4 TT did not respond to high-dose ICSs. Therefore, using medications other than ICSs must be considered even during the initial treatment of bronchial asthma. These genetic variants may aid in the realization of personalized and phenotype-specific therapies for bronchial asthma.

Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET.

Ovarian cancer is one of the most aggressive female reproductive tract tumors. Paclitaxel (PTX) is widely used for the treatment of ovarian cancer. However, ovarian cancers often acquire chemotherapeutic resistance to this agent. We investigated the mechanism of chemoresistance by analysis of microRNAs using the ovarian cancer cell line KFr13 and its PTX-resistant derivative (KFr13Tx). We found that miR-31 was downregulated in KFr13Tx cells, and that re-introduction of miR31 re-sensitized them to PTX both in vitro and in vivo. miR-31 was found to bind to the 3'-UTR of mRNA of MET, and the decrease in MET correlated to higher sensitivity to PTX. Furthermore, co-treatment of KFr13Tx cells with MET inhibitors sensitized the tumor cells to PTX both in vitro and in vivo. In addition, lower levels of miR31 and higher expression of MET in human ovarian cancer specimens were significantly correlated with PTX chemoresistance and poor prognosis. This study demonstrated miR31-dependent regulation of MET for chemoresistance of ovarian cancer, raising the possibility that combination therapy with a MET inhibitor and PTX will increase PTX efficacy.

Application of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET imaging to predict highly malignant tumor grades and hypoxia-inducible factor-1α expression in patients with glioma.

BACKGROUND AND PURPOSE: Hypoxic tissue evaluation in glioma is important for predicting treatment response and establishing antihypoxia therapy. In this preliminary study, (62)Cu-ATSM PET was used to determine its validity as a biomarker for distinguishing tumor grade and tissue hypoxia. MATERIALS AND METHODS: (62)Cu-ATSM PET was performed in 22 patients with glioma, and the (62)Cu-ATSM SUV(max) and T/B ratio were semiquantitatively evaluated. (62)Cu-ATSM uptake distribution was qualitatively evaluated and compared with MR imaging findings. HIF-1α expression, a hypoxia marker, was compared with (62)Cu-ATSM uptake values. RESULTS: The (62)Cu-ATSM SUV(max) and T/B ratio were significantly higher in grade IV than in grade III gliomas (P = .014 and .018, respectively), whereas no significant differences were found between grade III and grade II gliomas. At a T/B ratio cutoff threshold of 1.8, (62)Cu-ATSM uptake was predictive of HIF-1α expression, with 92.3% sensitivity and 88.9% specificity. The mean T/B ratio was also significantly higher in HIF-1α-positive glioma tissue than in HIF-1α-negative tissue (P = .001). Using this optimal threshold of T/B ratio, (62)Cu-ATSM PET showed regional uptake in 61.9% (13/21) of tumors within the contrast-enhanced region on MR imaging, which was significantly correlated with presence of a necrotic component (P = .002). CONCLUSIONS: Our results demonstrated that (62)Cu-ATSM uptake is relatively high in grade IV gliomas and correlates with the MR imaging findings of necrosis. Moreover, the (62)Cu-ATSM T/B ratio showed significant correlation with HIF-1α expression. Thus, (62)Cu-ATSM appears to be a suitable biomarker for predicting highly malignant grades and tissue hypoxia in patients with glioma.

Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin 1A receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan.

Yokukansan (YKS), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situation for treating psychiatric disorders such as aggressiveness in patients with dementia. We previously demonstrated that YKS and Uncaria hook (UH), which is a constituent herb of YKS, had a partial agonistic effect to 5-HT(1A) receptors in vitro. However, it has still been unclear whether this in vitro effect is reflected in in vivo, and what the active ingredients are. The purpose of the present study is to find the active ingredient in YKS and to demonstrate the effect in in vivo. In the present study, we first studied the effect of YKS and UH on aggressiveness and sociality in socially isolated mice. YKS and UH ameliorated the isolation-induced increased aggressiveness and decreased sociality, and these ameliorative effects were counteracted by coadministration of 5-HT(1A) receptor antagonist WAY-100635, or disappeared by eliminating UH from YKS. These results suggest that the effect of YKS is mainly attributed to UH, and the active ingredient is contained in UH. To find the candidate ingredients, we examined competitive binding assay and [(35)S] guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding assay of seven major alkaloids in UH using Chinese hamster ovary cells expressing 5-HT(1A) receptors artificially. Only geissoschizine methyl ether (GM) among seven alkaloids potently bound to 5-HT(1A) receptors and acted as a partial agonist. This in vitro result on GM was further demonstrated in the socially isolated mice. As did YKS and UH, GM ameliorated the isolation-induced increased aggressiveness and decreased sociality, and the effect was counteracted by coadministration of WAY-100635. These lines of results suggest that GM in UH is potent 5-HT(1A) receptor agonist and a candidate for pharmacological effect of YKS on aggressiveness and sociality in socially isolated mice.

Efficient growth inhibition of human osteosarcoma cells using a peptide derived from the MDM-2-binding site of p53.

Protein transduction therapy is a promising alternative to gene therapy, but has not previously been investigated for osteosarcoma. We here demonstrate efficient growth inhibition of human osteosarcoma cells using a p53 peptide. Our result suggests that protein transduction therapy has significant potential as a novel therapeutic approach for osteosarcoma.

Neuroprotective effects of yokukansan, a traditional Japanese medicine, on glutamate-mediated excitotoxicity in cultured cells.

To clarify the mechanism of yokukansan (TJ-54), a traditional Japanese medicine, against glutamate-mediated excitotoxicity, the effects of TJ-54 on glutamate uptake function were first examined using cultured rat cortical astrocytes. Under thiamine-deficient conditions, the uptake of glutamate into astrocytes, and the levels of proteins and mRNA expressions of glutamate aspartate transporter of astrocytes significantly decreased. These decreases were ameliorated in a dose-dependent manner by treatment with TJ-54 (100-700 microg/ml). The improvement of glutamate uptake with TJ-54 was completely blocked by the glutamate transporter inhibitor DL-threo-beta-hydroxyaspartic acid. Effects of TJ-54 on glutamate-induced neuronal death were next examined by using cultured PC12 cells as a model for neurons. Addition of 17.5 mM glutamate to the culture medium induced an approximately 50% cell death, as evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TJ-54 (1-1000 microg/ml) inhibited the cell death in a dose-dependent manner. Furthermore, competitive binding assays to glutamate receptors showed that TJ-54 bound potently to N-methyl-D-aspartate receptors, in particular, to its glutamate and glycine recognition sites. These results suggest that TJ-54 may exert a neuroprotective effect against glutamate-induced excitotoxicity not only by amelioration of dysfunction of astrocytes but also by direct protection of neuronal cells.

Spinal cord hemangioblastomas in von Hippel-Lindau disease.

STUDY DESIGN: Retrospective data analysis. OBJECTIVE: To clarify the clinical features and surgical management of spinal cord hemangioblastomas in patients with von Hippel-Lindau disease (VHL). SETTING: Clinical VHL Research Group in Japan, Japan. METHODS: Forty-eight out of 66 patients with associated spinal cord hemangioblastoma among 142 VHL patients were retrospectively examined with respect to clinical features, accompanying lesions and outcome of surgical treatment. RESULTS: Among these 48 patients, 46 of them (95.8%) also had a central nervous system (CNS) hemangioblastoma at another site: 42 (87.5%) with cerebellar hemangioblastoma and 11 (22.9%) with brain stem hemangioblastoma. Twenty-three patients (47.9%) had more than one spinal cord hemangioblastoma. The 48 patients with spinal cord hemangioblastomas collectively had a total of 74 tumors. The tumor was accompanied with a syrinx in 64 and without it in 10 patients. Forty of the 48 patients underwent surgical treatment for their spinal cord hemangioblastomas, and 7 of these 40 underwent surgical treatment twice. When functional changes in the patients after these 47 operations were examined by postoperative evaluation by McCormick's classification, 39 of these operations (83.0%) resulted in improvement/no change and 8 (17.0%) in aggravation of symptoms. CONCLUSION: Von Hippel-Lindau disease patients bearing spinal cord hemangioblastomas mostly had a CNS hemangioblastoma at another site. These tumors can be removed in the majority of VHL patients without aggravation. In these patients, when the timing of treatment for spinal cord hemangioblastoma is determined, the probability of occurrence and treatment of other lesions should be considered.

Adhesion of Epstein-Barr virus-positive natural killer cell lines to cultured endothelial cells stimulated with inflammatory cytokines.

Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is characterized by chronic recurrent infectious mononucleosis-like symptoms. Approximately one-fourth of CAEBV patients develop vascular lesions with infiltration of EBV-positive lymphoid cells. Furthermore, EBV-positive natural killer (NK)/T cell lymphomas often exhibit angiocentric or angiodestructive lesions. These suggest an affinity of EBV-positive NK/T cells to vascular components. In this study, we evaluated the expression of adhesion molecules and cytokines in EBV-positive NK lymphoma cell lines, SNK1 and SNK6, and examined the role of cytokines in the interaction between NK cell lines and endothelial cells. SNKs expressed intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) at much higher levels than those in EBV-negative T cell lines. SNKs produced the larger amount of tumour necrosis factor (TNF)-alpha, which caused increased expression of ICAM-1 and VCAM-1 in cultured human endothelial cells, than that from EBV-negative T cell lines. Furthermore, SNKs exhibited increased adhesion to cultured endothelial cells stimulated with TNF-alpha or interleukin (IL)-1beta, and the pretreatment of cytokine-stimulated endothelial cells with anti-VCAM-1-antibodies reduced cell adhesion. These indicate that the up-regulated expression of VCAM-1 on cytokine-stimulated endothelial cells would be important for the adhesion of EBV-positive NK cells and might initiate the vascular lesions.

Surgical method for catheter placement via the occipital artery by an approach from the posterior of the mastoid process.

Catheter placement for continuous intra-arterial chemotherapy in head and neck cancer is generally performed via the superficial temporal artery. If placement via this artery is impossible, other arteries, such as the occipital artery, are chosen. A surgical method has been developed for catheter placement in the occipital artery by approaching from the posterior of the mastoid process. Catheter placement was performed by this method in 15 patients with oral squamous cell carcinoma. Target arteries were the lingual artery in seven cases, facial artery in three cases, maxillary artery in three cases, superior thyroid artery in one case, and the occipital artery itself in one case. The occipital artery was exposed without fail and catheter placement was completed in all patients. The wound healed without complication after treatment. This approach via the occipital artery is a useful technique to achieve continuous intra-arterial chemotherapy in head and neck cancer, especially for cases in which catheter placement is impossible via the superficial temporal artery.

Adhesion of peripheral blood mononuclear cells and CD4+ T cells from patients with psoriasis to cultured endothelial cells via the interaction between lymphocyte function-associated antigen type 1 and intercellular adhesion molecule 1.

BACKGROUND: The adhesion of CD4+ T cells to endothelial cells and their subsequent migration to skin tissue are essential to develop the psoriatic skin lesion. However, few studies have examined the role of adhesion molecules in the binding of T cells from patients with chronic plaque psoriasis to endothelial cells in vitro; thus, the adhesion molecules responsible for the development of skin lesions are still unclear. OBJECTIVES: To identify the responsible adhesion molecules in the interaction between CD4+ T cells in patients with chronic plaque psoriasis and cytokine-stimulated endothelial cells. METHODS: An in vitro adhesion assay between Calcein-labelled peripheral blood mononuclear cells (PBMC) and cytokine-stimulated human endothelial cultures, which exhibit a higher adhesion capacity to PBMC, was established, and the adhesion-inhibitory effects of a panel of antiadhesion molecule antibodies on the adhesion of PBMC from patients with psoriasis to endothelial cells were examined. Then, the inhibitory effects of selected antibodies acting on the interaction between CD4+ T cells from patients with psoriasis (purified by negative magnetic cell sorting) and cultured endothelial cells were examined. RESULTS: A significant increase (P < 0.01) in the adhesion of psoriatic PBMC to both endothelial cultures, human skin microvascular endothelial cells from adults (HMVEC-Ad) and human coronary arterial endothelial cells (HCAEC), compared with healthy PBMC, was demonstrated in our in vitro cell adhesion assay. Pretreatment of both endothelial cultures with tumour necrosis factor (TNF)-alpha (1000 U mL(-1)) induced the most frequent adhesion of PBMC from patients with psoriasis among the three inflammatory cytokines examined, i.e. TNF-alpha, interleukin-1beta and interferon-gamma [TNF-alpha-treated vs. nontreated: P < 0.001 (in both HMVEC-Ad and HCAEC)]. In both endothelial cultures treated with TNF-alpha, PBMC from patients with psoriasis exhibited significantly more frequent adhesion compared with those from healthy individuals (P < 0.001). The TNF-alpha-stimulated HMVEC-Ad, which exhibited the most frequent adhesion of PBMC, were selected for adhesion-inhibition experiments using monoclonal antibodies (mAbs) to adhesion molecules that are upregulated in psoriatic lesions, and the combination of antilymphocyte function-associated antigen type 1 (LFA-1) and anti-intercellular adhesion molecule 1 (ICAM-1) mAbs gave the greatest reduction of adhesion of PBMC from patients with psoriasis (approximately 69% reduction; P < 0.01). This combination of mAbs significantly reduced also the adhesion of CD4+ T cells from patients with psoriasis to TNF-alpha-stimulated HMVEC-Ad (approximately 62% reduction), compared with pretreatment with isotype control mAbs (P < 0.01). CONCLUSIONS: These findings indicate that the LFA-1/ICAM-1 interaction plays a major role in the adhesion of CD4+ T cells to endothelial cells and that TNF-alpha might play an important role for the induction of adhesion molecules on endothelial cells at psoriatic skin lesions.

Progressive wild-type transthyretin deposition after liver transplantation preferentially occurs onto myocardium in FAP patients.

To elucidate whether progressive wild-type transthyretin (TTR) deposition can actually occur after liver transplantation (LT), amyloid fibrils were investigated in two familial amyloid polyneuropathy patients with TTR Val30Leu variant, who died 1 year after LT. Amyloid fibrils were extracted from cardiac muscles, sciatic nerves and kidney, which were investigated by the immunoprecipitation-mass spectrometry method and liquid chromatography-ion trap mass spectrometry analysis. The ratio of wild-type to variant TTR in cardiac muscle was approximately 5:5 before LT, but greatly increased to about 9:1 after transplantation. The ratios in sciatic nerves and kidney obtained at autopsy were approximately 5:5. Wild-type TTR was undetectable in kidney amyloid obtained before LT. Our results indicate that paradoxical wild-type TTR deposition after LT can preferentially occur in myocardium, leading to fatal cardiac dysfunction, but it is quite likely that this phenomenon can also occur in other visceral organs.

First-trimester prenatal diagnosis of pyruvate kinase deficiency in an Indian family with the pyruvate kinase-Amish mutation

Pyruvate kinase (PK) deficiency is a rare red cell glycolytic enzymopathy. The purpose of the present investigation was to offer prenatal diagnosis for PK deficiency to a couple who had a previous child with severe enzyme deficiency and congenital non-spherocytic hemolytic anemia. PK deficiency was identified in the family by assaying the enzyme activity in red cells. Chorionic villus sampling was performed in an 11-week gestation and the mutation was located in exon 10 of the PKLR gene characterized by polymerase chain reaction and using restriction endonuclease digestion with the MspI enzyme, which was confirmed by DNA sequencing on the ABI 310 DNA sequencer. Both the parents were heterozygous for the 1436G-->A [479 Arg-->His] mutation in exon 10 and the proband was homozygous for this mutation. The fetus was also heterozygous for this mutation and the pregnancy was continued. Prenatal diagnosis allowed the parents with a severely affected child with PK deficiency to have the reproductive choice of having the fetus tested in a subsequent pregnancy.

Downregulation of inhibitor of apoptosis proteins in apoptotic human chondrocytes treated with tumor necrosis factor-alpha and actinomycin D.

OBJECTIVE: Apoptosis of chondrocytes plays a pivotal role in cartilage degeneration. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine and has been assumed to cause the degradation of human cartilage. To investigate the mechanisms of TNF-alpha-mediated apoptosis of human chondrocytes from a point of view of the balance between the caspase-cascade and the expression of inhibitor of apoptosis proteins (IAPs), although both of them are induced with TNF-signals. METHODS: The expression of TNF-receptors (TNF-Rs) in normal human articular chondrocyte (NHAC-kn) was examined with immunocytochemistry. Subconfluent cultures of NHAC-kn were tested with TNF-alpha and/or actinomycin D (actD), and the induction of apoptosis was evaluated by the frequency of apoptotic cells visualized with nuclear staining using Hoechst 33342. The activation of caspases and the expression of IAPs were examined with Western blot analyses. RESULTS: NHAC-kn expressed TNF-R1 and -R2. When NHAC-kn was treated with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml) for 24 h, the frequency of apoptotic cells increased to more than 25%. TNF-alpha alone, however, induced the apoptosis insufficiently (up to 8.3%), even when used at the concentration of 100 ng/ml for 48 h. In apoptotic human chondrocytes induced with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml), the caspase-3, -8, and -9 were activated and the protein expression of XIAP and c-IAP1 decreased. CONCLUSIONS: In apoptotic human chondrocytes induced with TNF-alpha and actD, the balance between caspase activation and IAPs' expression lay with the executioner caspase (caspase-3) and led to decreased expression of XIAP and c-IAP1.

Meningioma showing VHL gene inactivation in a patient with von Hippel-Lindau disease.

The genetic mechanism of the tumorigenesis of meningioma in conjunction with von Hippel-Lindau (VHL) disease is unclear. The authors present a case of VHL disease associated with a posterior fossa meningioma and with multiple cerebellar hemangioblastomas. A germline mutation of the VHL gene and loss of heterozygosity on the VHL gene locus in 3p were detected in the meningioma. Tumorigenesis of a meningioma associated with VHL disease could be caused by inactivation of both alleles of the VHL gene.

A novel autoimmune pancreatitis model in MRL mice treated with polyinosinic:polycytidylic acid.

In this study we established a new animal model for exploring the pathogenesis of autoimmune pancreatitis. We have found previously that MRL/Mp-+/+(MRL/+) mice develop pancreatitis spontaneously by an autoimmune mechanism but only when they are more than 34 weeks old. Because this disease might be a model of multi-factorial diseases controlled by genetic and environmental factors, beginning at 6 weeks old, we injected polyinosinic:polycytidylic acid (poly I:C) into MRL/+ mice and in addition, into MRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr). Poly I:C induced chronic severe pancreatitis in all the MRL/+ mice and to a lesser extent in the MRL/lpr mice by 18 weeks of age. There was no pancreatitis in control mice of both strains at the same age. Other than chronic pancreatitis, no severe autoimmune diseases were observed in MRL/+ mice. Immunohistochemical examinations revealed predominant infiltration of CD4+ T cells and Mac-2+ activated macrophages in the pancreatic lesions. Splenic expression of the mRNAs for TNF-alpha and IL-10, which is known to suppress the development of pancreatitis, were increased in both strains of mice. These findings suggest that an MRL strain of mice treated with poly I:C might be a good model for developing new approaches to the study of the pathogenesis of autoimmune pancreatitis.

Effects of preconditioning on ischemia/reperfusion injury of hepatocytes determined by immediate early gene transcription.

Ischemia reperfusion (I-R) of the liver induces various events leading to cell death (apoptosis) and subsequent cells proliferation. Recent experimental studies have described the protective effect of ischemic preconditioning (IPC) on I-R injury of the liver. However, the mechanisms involved in this protection remain unknown. The protein products of immediate early genes (IEGs) behave as crucial transcriptional regulators not only in apoptosis but also in cell proliferation. Here, we evaluated the effects of IPC on IEG transcription after I-R injury, using a rat liver I-R injury model. Injury to hepatocytes was evaluated by measuring serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) and that to endothelial cells by plasma concentration of hyaluronic acid (HA). The extent of necrosis was evaluated by H&E staining, while cell proliferation and apoptosis were evaluated by proliferating cell nuclear antigen (PCNA) and terminal deoxy(d)-UTP nick end labelling (TUNEL) staining, respectively. Alterations in the transcription of IEGs (c-fos and c-jun) were examined by Northern blotting. Rats subjected to 40-min liver ischemia, preceded by 10-min preconditioning, showed significantly lower AST, ALT, LDH, and HA levels at 6 h after I-R than untreated animals (P < 0.05; n at least 5 rats per group). The percentage of necrotic areas at 24 h after I-R was significantly lower in IPC-treated animals than in the controls. The numbers of apoptotic cells at 24 h after I-R and the numbers of PCNA-positive cells at 24 and 48 h after I-R were significantly lower in IPC-treated rats than in controls. Transcription levels of IEGs were low in IPC-treated rats, particularly c-jun at 1 and 1.5 h after I-R (P < 0.05). Our results indicate that IPC provides a significant protective effect on for liver cells against I-R injury and that its effect is evidenced by a significant decrease in the transcription levels of IEGs following the insult.

[Successful treatment of a patient with low pressure syndrome associated with gait disturbance].

The authors report an unusual case of low intracranial pressure (ICP) syndrome that was successfully treated by the placement of an anti-siphon device (ASD). This 36-year-old male had suffered suprasellar germinoma with hydrocephalus and had had a V-P shunt following radiotherapy. Sixteen years later he developed gait disturbance and somnolence and MRI demonstrated a small lateral ventricle as well as a diffuse dural enhancement. A lumbar tap revealed a low ICP of 12 mmH2O. Because of this, an ASD was placed in the patient. Postoperatively, his symptoms of gait and consciousness disturbance improved. Typical clinical findings of low ICP syndrome such as headache were not observed in this case. To our knowledge, no symptom of gait disturbance with low ICP has been reported previously. We present an interesting case of low ICP syndrome with gait disturbance and discuss the mechanism of the symptoms. Symptoms of this patient were due at first to brain ischemia. After convulsion and consciousness disturbance due to low intracranial pressure, the symptoms increased in strength until gait disturbance occurred. The possibility is suggested that gait disturbance in this patient was due both to brain ischemia and low intracranial pressure.

[Surgical reconstruction for radiation-induced extracranial vertebral artery stenosis: a case report].

We report a case of symptomatic extracranial vertebral artery stenosis after radiation therapy. This 49-year-old female received radiation therapy to the neck for nasopharyngeal carcinoma 11 years earlier, was admitted because of continuous dizziness and a floating sensation. Magnetic resonanse imaging showed no abnormalities, but an aortography demonstrated complete occlusion of the right common carotid artery as well as occlusion of the right vertebral artery and severe stenosis of the left vertebral artery at its origin, which was presumed to be the result of previous radiation therapy. Percutaneous transluminal angioplasty (PTA) for the left vertebral artery was performed using conventional balloon treatment, which resulted in wall dissection. Because of this, she underwent end-to-side vertebral artery to subclavian artery transposition, and she has had no further ischemic events science that time. PTA has been successfully performed as the first treatment of choice for vertebral artery stenosis, but surgical reconstruction can be a therapeutic management of choice for cases of failed PTA.