Performance of an ambulatory electroencephalogram sleep monitor in patients with psychiatric disorders.

Key clinical symptoms observed among individuals with psychiatric disorders include difficulty falling asleep or maintaining sleep, poor sleep quality and nightmares. Those suffering from sleep disorders often present with symptoms of discontent with regard to sleep quality, timing and quantity, and these symptoms have an adverse impact on function and quality of life. A minimally invasive technique would be preferable in patients with psychiatric disorders, who tend to be sensitive to environmental change. Accordingly, we evaluated the performance of Zmachine Insight Plus, an ambulatory electroencephalography sleep monitor, in patients with psychiatric disorders. One hundred and three patients undergoing polysomnography were enrolled in this study. Zmachine Insight Plus was performed simultaneously with polysomnography. Total sleep time, sleep efficiency, wake after sleep onset, rapid eye movement (REM) sleep, light sleep (stages N1 and N2) and deep sleep (stage N3) were assessed. Total sleep time, sleep efficiency, wake after sleep onset, REM sleep duration and non-REM sleep duration of Zmachine Insight Plus showed a significant correlation with those of polysomnography. Lower sleep efficiency and increased frequency of waking after sleep onset, the arousal index and the apnea-hypopnea index on polysomnography were significantly associated with the difference in sleep parameters between the two methods. Among patients with psychiatric disorders who are sensitive to environmental change, Zmachine Insight Plus would be a useful technique to objectively evaluate sleep quality.

Candidatus Mycoplasma haemohominis in Human, Japan.

Hemotropic mycoplasmas are common pathogens in animals, but it remains unclear what role these pathogens play in human infections. We report clinical and biologic characterization of Candidatus Mycoplasma haemohominis infection in a 42-year-old man in Japan. The patient had severe hemophagocytic syndrome 1 month after an accidental needlestick injury. Metagenomic deep sequencing identified Candidatus M. haemohominis and determined its draft genome for an isolate from serum of the patient. A high copy number of the Candidatus M. haemohominis genome was detected in serum and bone marrow samples. Electron microscopy examination showed morphologic characteristics of Candidatus M. haemohominis. Levofloxacin monotherapy induced resistance caused by a gyrase A gene mutation in the quinolone resistance-determining region, but a combination treatment with moxifloxacin and minocycline was effective. We identified Candidatus M. haemohominis in a patient who had life-threatening symptoms related to multiple organ infection. Human infection with this mycoplasma might occur more frequently than has been generally recognized.

The Ability for Basic Movement Scale II Can Predict Functional Outcome and Discharge Destination in Stroke Patients.

OBJECTIVES: This study aims to identify whether the Ability for Basic Movement Scale II (ABMS II) at admission would predict the functional status and discharge destination in convalescent stroke patients. METHODS: Ninety-four stroke patients admitted to convalescent rehabilitation ward were investigated. Their functions were evaluated by the ABMS II and Functional Independence Measure (FIM) at admission, FIM and Functional Ambulation Category at discharge. Furthermore, the age, gender, diagnosis, lesion side, onset type, interval between onset and convalescent admission, length of stay (LOS) and discharge destination were recorded. Discharge destination was divided into home and facility. RESULTS: Multiple linear regression identified the ABMS II at admission as a significant predicator of discharge FIM in convalescent stroke patients (ß = .747, P < .05). Binary logistic regression analysis showed the ABMS II significantly predicting basic walk ability (odds ratio 1.29) and home discharge (odds ratio 1.241) of these patients. Receiver operating characteristic analysis indicated that an optimal cutoff of 18 points of ABMS II predicted basic walk ability (area under the curve = .863, P < .05) and home discharge (area under the curve = .827, P < .05). Moreover, a significant negative correlation between the ABSM II at admission and LOS was found (Correlation coefficients -.680, P < .05). CONCLUSIONS: Higher score of the ABMS II at admission predicted better functional recovery, shorter LOS and more possibility to home in convalescent stroke patients. This new, easy scale is expected to be widely used for stroke patients.

Three cases of histologically proven hepatic epithelioid hemangioendothelioma evaluated using a second-generation microbubble contrast medium in ultrasonography: case reports.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is rare; it is reported in < 1 person in 1,000,000 individuals. For accurate diagnosis, information regarding multiple graphic modalities in HEH is required. However, there is very little information concerning Sonazoid® contrast enhanced ultrasonography (CEUS) in HEH. CASE PRESENTATION: The present report describes the histologically proven three HEH cases evaluated using Sonazoid® CEUS. Case 1 was a 33-year-old female patient with no relevant past medical history, who experienced right upper quadrant pain. Conventional abdominal US revealed multiple low echoic liver nodules with vague borderlines. In CEUS, the vascularity of the nodules was similar to that seen in the neighboring normal liver. Later in the portal venous and late phases (PVLP) and post vascular phase, washout of Sonazoid® was detected in the nodules. Case 2 was a 93-year-old female patient with a previous medical history including operations for breast cancer and ovary cancer in her 50's. Conventional abdominal US revealed multiple low echoic nodules, some of which contained cystic lesions. In the early vascular phase of CEUS, nodules excluding the central anechoic regions were enhanced from peripheral sites. Although the enhancement inside the nodules persisted in both the PVLP and post vascular phase, anechoic areas in the center of some nodules were not enhanced at all. Case 3 was a 39-year-old male patient presented with right upper-quadrant pain, without any relevant past medical history. Conventional abdominal US revealed multiple low echoic liver nodules. In the early vascular phase of CEUS, nodules were gradually enhanced from the peripheral sites as ringed enhancement. Sonazoid®was washed out from the nodules in the PVLP and post vascular phase. CONCLUSIONS: The most important feature was peripheral enhancement in the early vascular phase. In case 2, the enhancement of the parenchyma of liver nodules persisted even in the PVLP; indicating the lower degree of malignant potential than others. Actually, the tumors did not extend without any treatment in case 2. Since case 2 is the first case report of HEH with cystic lesions, in patients with liver nodules including cystic lesions, HEH is a potential diagnosis.

Enhanced B-cell differentiation driven by advanced cirrhosis resulting in hyperglobulinemia.

BACKGROUND AND AIM: The mechanism underlying hyperglobulinemia in cirrhosis, a long appreciated phenomenon, has never been clearly understood. The aim of this study is to investigate the basis for changes in humoral immunity observed in cirrhosis. METHODS: We retrospectively reviewed our medical record to analyze serum immunoglobulin (Ig) levels in patients with liver disease. We also prospectively analyzed peripheral blood mononuclear cells and sera from liver disease patients. Peripheral blood mononuclear cell surface marker expressions were measured by flow cytometry and serum B-cell-activating factor was measured by enzyme-linked immunosorbent assay. Expression of specific gene expression in magnetically separated B cells was also analyzed by real-time polymerase chain reaction. RESULTS: In retrospective analysis, we found that advancing cirrhosis, irrespective of underlying etiology or hepatocellular carcinoma, resulted in progressively increasing levels of serum IgG and IgA. In prospective analysis using clinical samples, we demonstrated that advancing cirrhosis stage was associated with increased toll-like-receptor (TLR)9 expression in CD27+ B cell and serum B-cell-activating factor levels but decreased CD27+ memory B-cell frequency. The remaining CD27+ B cells in peripheral blood exhibited increased activation-induced cytidine deaminase mRNA expression. Finally, we also demonstrated isolated B cells from advanced cirrhosis were more reactive to TLR9 stimulation that drove antibody secreting cells differentiation leading to hyperimmunoglobulinemia in vitro. CONCLUSIONS: Enhanced TLR9-induced differentiation into antibody secreting cell may explain peripheral reductions of circulating CD27+ memory B cells as well as increased serum Ig levels in cirrhosis.

Discovery of novel 2-(4-aryl-2-methylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3ß inhibitors.

We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3ß inhibitors from our promising compounds containing a 3-methylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3ß inhibitors. SAR studies focused on the nitrogen atom of the piperazine moiety revealed that a phenyl group afforded potent inhibitory activity toward GSK-3ß. Docking studies indicated that the phenyl group on the piperazine nitrogen atom and the methyl group on the piperazine make cation-π and CH-π interactions with GSK-3ß respectively. 4-Methoxyphenyl analogue 29 showed most potent inhibitory activity toward GSK-3ß with good in vitro and in vivo pharmacokinetic profiles, and 29 demonstrated a significant decrease in tau phosphorylation after oral administration in mice.

Discovery of novel 2-(3-phenylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3ß inhibitors.

We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3ß inhibitors from our promising compounds containing a 2-phenylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3ß inhibitors. SAR studies focused on the phenyl moiety revealed that a 4-fluoro-2-methoxy group afforded potent inhibitory activity toward GSK-3ß. Based on docking studies, new hydrogen bonding between the nitrogen atom of the piperazine moiety and the oxygen atom of the main chain of Gln185 has been indicated, which may contribute to increased activity compared with that of the corresponding phenylmorpholine analogues. Effect of the stereochemistry of the phenylpiperazine moiety is also discussed.

Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3ß inhibitors for Alzheimer's disease.

We herein describe the results of further evolution of GSK-3ß inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3ß inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models.

6-(4-Pyridyl)pyrimidin-4(3H)-ones as CNS penetrant glycogen synthase kinase-3ß inhibitors.

The discovery of a series of 6-(4-pyridyl)pyrimidin-4(3H)-ones derived from a hit compound with low molecular weight and sufficient chemical space is reported. Transformation of substituents led to subnanomolar potent inhibitors with in vivo tau phoshorylation lowering activity.

2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3ß inhibitors.

A series of 2-(2-phenylmorpholin-4-yl)pyrimidin-4(3H)-ones was synthesized and examined for their inhibitory activity against glycogen synthase kinase-3ß (GSK-3ß). We found 21, 29 and 30 to possess potent in vitro GSK-3ß inhibitory activity with good in vitro PK profiles. 21 demonstrated significant decrease of tau phosphorylation after oral administration in mice and excellent PK profiles.

Iliopsoas abscess caused by Aspergillus fumigatus complicated by pulmonary aspergillosis.

We report a case of iliopsoas abscess caused by Aspergillus fumigatus with pulmonary complications. A 60-year-old man was admitted to the Showa University Hospital Department of Gastroenterology with fulminant hepatitis B on April 14, 2010, and treated with steroids. Although fulminant hepatitis B was improved by steroid and symptomatic therapy, he developed a fever on hospital day 39. The chest X-ray film showed a nodular lesion in the right middle-lower lung field, and both the (1 â†’ 3)-ß-D: -glucan and Candida mannan antigen tests were positive. The ß-D: -glucan level increased despite treatment with fluconazole and other drugs, including low-dose micafungin. Abdominal computed tomography showed a low-density area in the right iliopsoas muscle. He was then referred to the Department of Clinical Infectious Diseases. A. fumigatus was isolated from the iliopsoas lesion and the pulmonary lesion after specimens were obtained by aspiration and bronchofiberscopy, respectively, leading to a diagnosis of fungal iliopsoas abscess. Steroid therapy was tapered early, the abscess was drained, and the micafungin dose was increased. This treatment led to improvement of the fever, inflammatory reaction, ß-D: -glucan level, and lesions of the lung and iliopsoas muscle. In preparation for discharge, treatment was changed to voriconazole (parenteral â†’ per oral) followed by itraconazole (per oral). His clinical course was satisfactory, and there was no recurrence after antifungal therapy was stopped. We conclude that after invasive pulmonary aspergillosis developed, A. fumigatus spread hematogenously to create an extremely rare iliopsoas abscess. The ß-D: -glucan level closely reflected the response to treatment and was useful for follow-up.

Immune response of cytotoxic T lymphocytes and possibility of vaccine development for hepatitis C virus infection.

Immune responses of cytotoxic T lymphocytes (CTLs) are implicated in viral eradication and the pathogenesis of hepatitis C. Weak CTL response against hepatitis C virus (HCV) may lead to a persistent infection. HCV infection impairs the function of HCV-specific CTLs; HCV proteins are thought to actively suppress host immune responses, including CTLs. Induction of a strong HCV-specific CTL response in HCV-infected patients can facilitate complete HCV clearance. Thus, the development of a vaccine that can induce potent CTL response against HCV is strongly expected. We investigated HCV-specific CTL responses by enzyme-linked immuno-spot assay and/or synthetic peptides and identified over 40 novel CTL epitopes in the HCV protein. Our findings may contribute to the development of the HCV vaccine. In this paper, we describe the CTL responses in HCV infection and the attempts at vaccine development based on recent scientific articles.

Decreased expression of interferon-stimulated genes in B cells of patients with chronic hepatitis C during interferon-free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study.

AIMS: Hepatitis C virus (HCV) infection is monitored by the host innate immunity that includes the endogenous interferon (IFN), which up-regulates IFN-stimulated genes (ISGs). HCV is both hepatotropic and lymphotropic, but HCV replication in lymphoid cells is a controversial issue. Here, we analyzed the mRNA levels of the ISGs in B cells of HCV-infected patients during antiviral therapy and investigated the effects of viral eradication. METHODS: One hundred and eighty-one patients with chronic hepatitis C and 26 healthy volunteers were enrolled in this study. Levels of HCV RNA and mRNA of ISGs in B cells isolated from the patients were monitored before, during, and after antiviral therapy. RESULTS: HCV RNA was detected in B cells of 133/175 (76.0%) patients who achieved sustained virologic response (SVR) before therapy was started. The positive ratio of HCV RNA in B cells was higher in patients with genotype 1 and the non-major genotype of interleukin 28B. HCV RNA in B cells of most patients disappeared 1 week after antiviral therapy was started. The baseline expression of ISG mRNA was significantly higher in the patients than in the healthy volunteers. Levels of ISG mRNA were increased and remained high throughout the IFN-based therapy. In contrast, levels of ISG mRNA in patients who achieved SVR were significantly decreased 1 week after the IFN-free therapy was started and remained low during the therapy. CONCLUSIONS: These results suggested that IFN-free therapy potentially eradicated HCV in the B cells, leading to the down-regulation of endogenous ISGs. The level of ISG mRNA could be used as a marker for viral eradication in B cells.

Magnitude of CD8 T-cell responses against hepatitis C virus and severity of hepatitis do not necessarily determine outcomes in acute hepatitis C virus infection.

AIM: We investigated the relationship between the magnitude of comprehensive hepatitis C virus (HCV)-specific CD8(+) T-cell responses and the clinical course of acute HCV infection. METHODS: Six consecutive patients with acute HCV infection were studied. Analysis of HCV-specific CD8(+) T-cell responses was performed using an interferon-gamma-based enzyme-linked immunospot assay using peripheral CD8(+) T-cells, monocytes and 297 20-mer synthetic peptides overlapping by 10 residues and spanning the entire HCV sequence of genotype 1b. RESULTS: Five patients presented detectable HCV-specific CD8(+) T-cell responses against a single and different peptide, whereas 1 patient showed responses against three different peptides. Neither the magnitude of HCV-specific CD8(+) T-cell responses nor the severity of hepatitis predicts the outcome of acute hepatitis. The maximum number of HCV-specific CD8(+) T-cells correlated with maximum serum alanine aminotransferase level during the course (r = 0.841, P = 0.036). CONCLUSIONS: HCV-specific CD8(+) T-cell responses were detectable in all 6 patients with acute HCV infection, and 6 novel HCV-specific CTL epitopes were identified. Acute HCV infection can resolve with detectable HCV-specific CD8(+) T-cell responses, but without development of antibody against HCV.

The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer's disease in rodents.

Glycogen synthase kinase 3 (GSK3) has been identified as a promising target for the treatment of Alzheimer's disease (AD), where abnormal activation of this enzyme has been associated with hyperphosphorylation of tau proteins. This study describes the effects of the selective GSK3 inhibitor, SAR502250, in models of neuroprotection and neuropsychiatric symptoms (NPS) associated with AD. In P301L human tau transgenic mice, SAR502250 attenuated tau hyperphosphorylation in the cortex and spinal cord. SAR502250 prevented the increase in neuronal cell death in rat embryonic hippocampal neurons following application of the neurotoxic peptide, Aß25-35. In behavioral studies, SAR502250 improved the cognitive deficit in aged transgenic APP(SW)/Tau(VLW) mice or in adult mice after infusion of Aß25-35. It attenuated aggression in the mouse defense test battery and improved depressive-like state of mice in the chronic mild stress procedure after 4 weeks of treatment. Moreover, SAR502250 decreased hyperactivity produced by psychostimulants. In contrast, the drug failed to modify anxiety-related behaviors or sensorimotor gating deficit. This profile confirms the neuroprotective effects of GSK3 inhibitors and suggests an additional potential in the treatment of some NPS associated with AD.

Dendritic cells stimulated with cytidine-phosphate-guanosine oligodeoxynucleotides and interferon-alpha-expressing tumor cells effectively reduce outgrowth of established tumors in vivo.

Dendritic cells (DC) are potent antigen-presenting cells that elicit immune responses to foreign antigens. We have previously demonstrated the synergistic effects of cytidine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODN) and interferon (IFN)-alpha on DC maturation in vitro. In the present study, the antitumor effects of DC preincubated with IFN-alpha gene-overexpressing murine colorectal cancer MC38 cells (MC38-IFN-alpha) and CpG ODN were evaluated in a poorly immunogenic murine cancer system. When we injected DC preincubated with MC38-IFNalpha and CpG ODN subcutaneously to mice bearing MC38 wild-type tumors, the outgrowth of the established parental tumors was suppressed significantly compared with that following administration of DC with MC38-IFN-alpha (P = 0.008). All mice injected with DC preincubated with MC38-IFN-alpha and CpG ODN rejected a subsequent parental tumor challenge. Immunohistochemical and flow cytometric analyses showed that CD4(+), CD8(+), and NK1.1(+) cells markedly infiltrated the established tumors of mice treated with DC preincubated with MC38-IFN-alpha and CpG ODN. From the results in immune cell-depleted mice, CD4(+) and asialo-GM-1(+) cells seemed to contribute to the antitumor effects induced by the combination DC therapy. Furthermore, non-specific cytolysis was detected when splenocytes of mice inoculated with DC preincubated with MC38-IFNalpha and CpG ODN were used as effector cells. Using an interleukin (IL)-12-neutralizing antibody it was suggested that IL-12 stimulates natural killer cells and contributes in part to the antitumor effects induced by DC incubated with CpG ODN and IFN-alpha. As DC-based immunotherapy with CpG ODN and IFN-alpha-expressing tumor cells induces a potent antitumor immune response, it should be considered for clinical application.

Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics.

PURPOSE: Allogeneic glioma cell lines that are partially matched to the patient at class I human leukocyte antigen (HLA) loci and that display tumor-associated antigens (TAA) or antigenic precursors [tumor antigen precursor proteins (TAPP)] could be used for generating whole tumor cell vaccines or, alternatively, for extraction of TAA peptides to make autologous dendritic cell vaccines. EXPERIMENTAL DESIGN: Twenty human glioma cell lines were characterized by molecular phenotyping and by flow cytometry for HLA class I antigen expression. Twelve of the 20 cell lines, as well as analyses of freshly resected glioma tissues, were further characterized for protein and/or mRNA expression of 16 tumor antigen precursor proteins or TAA. RESULTS: These 20 human glioma cell lines potentially cover 77%, 85%, and 78% of the U.S. Caucasian population at HLA-A, HLA-B, and HLA-C alleles, respectively. All cells exhibited multiple TAA expressions. Most glioma cells expressed antigen isolated from immunoselected melanoma-2 (Aim-2), B-cyclin, EphA2, GP100, beta1,6-N-acetylglucosaminyltransferase V (GnT-V), IL13Ralpha2, Her2/neu, hTert, Mage, Mart-1, Sart-1, and survivin. Real-time PCR technology showed that glioblastoma specimens expressed most of the TAA as well. Tumor-infiltrating lymphocytes and CD8(+) CTL killed T2 cells when loaded with specific HLA-A2(+) restricted TAA, or gliomas that were both HLA-A2(+) and also positive for specific TAA (Mart-1, GP100, Her2/neu, and tyrosinase) but not those cells negative for HLA-A2 and/or lacking the specific epitope. CONCLUSIONS: These data provide proof-in-principle for the use of allogeneic, partially HLA patient-matched glioma cells for vaccine generation or for peptide pulsing with allogeneic glioma cell extracts of autologous patient dendritic cells to induce endogenous CTL in brain tumor patients.

Adoptive transfer of type 1 CTL mediates effective anti-central nervous system tumor response: critical roles of IFN-inducible protein-10.

The development of effective immunotherapeutic strategies for central nervous system (CNS) tumors requires a firm understanding of factors regulating the trafficking of tumor antigen-specific CTLs into CNS tumor lesions. Using C57BL/6 mice bearing intracranial (i.c.) ovalbumin-transfected melanoma (M05), we evaluated the efficacy and tumor homing of i.v. transferred type 1 or 2 CTLs (Tc1 or Tc2, respectively) prepared from ovalbumin-specific T-cell receptor-transgenic OT-1 mice. We also tested our hypothesis that intratumoral (i.t.) delivery of dendritic cells that had been transduced with IFN-alpha cDNA (DC-IFN-alpha) would enhance the tumor-homing and antitumor effectiveness of adoptively transferred Tc1 via induction of an IFN-gamma-inducible protein 10 (IP-10). In vitro, DC-IFN-alpha induced IP-10 production by M05 and enhanced the cytolytic activity of Tc1. In vivo, i.v. transferred Tc1 trafficked efficiently into i.c. M05 and mediated antitumor responses more effectively than Tc2, and their effect was IP-10 dependent. I.t. injections of DC-IFN-alpha remarkably enhanced the tumor homing, therapeutic efficacy, and in situ IFN-gamma production of i.v. delivered Tc1, resulting in the long-term survival and persistence of systemic ovalbumin-specific immunity. These data suggest that Tc1-based adoptive transfer therapy may represent an effective modality for CNS tumors, particularly when combined with strategies that promote a type 1 polarized tumor microenvironment.

Identification of interleukin-13 receptor alpha2 peptide analogues capable of inducing improved antiglioma CTL responses.

Restricted and high-level expression of interleukin-13 receptor alpha2 (IL-13Ralpha2) in a majority of human malignant gliomas makes this protein an attractive vaccine target. We have previously described the identification of the IL-13Ralpha2(345-353) peptide as a human leukocyte antigen-A2 (HLA-A2)-restricted CTL epitope. However, as it remains unclear how efficiently peptide-based vaccines can induce specific CTLs in patients with malignant gliomas, we have examined whether analogue epitopes could elicit heteroclitic antitumor T-cell responses versus wild-type peptides. We have created three IL-13Ralpha2 analogue peptides by substitutions of the COOH-terminal isoleucine (I) for valine (V) and the NH(2)-terminal tryptophan (W) for either alanine (A), glutamic acid (E), or nonsubstituted (W; designated as 1A9V, 1E9V, and 9V, respectively). In comparison with the native IL-13Ralpha2 epitope, the analogue peptides 9V and 1A9V displayed higher levels of binding affinity and stability in HLA-A2 complexes and yielded an improved stimulatory index for patient-derived, specific CTLs against the native epitope expressed by HLA-A2(+) glioma cells. In HLA-A2-transgenic HHD mice, immunization with the peptides 9V and 1A9V induced enhanced levels of CTL reactivity and protective immunity against an intracranial challenge with IL13Ralpha2-expressing syngeneic tumors when compared with vaccines containing the native IL-13Ralpha2 epitope. These findings indicate highly immunogenic IL-13Ralpha2 peptide analogues may be useful for the development of vaccines capable of effectively expanding IL-13Ralpha2-specific, tumor-reactive CTLs in glioma patients.