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Cystic meningiomas are radiologically difficult to differentiate from malignant brain tumors, particularly when the tumors are intraparenchymally located. In such cases, a surgical strategy relies on intraoperative histological diagnosis. A 60-year-old man had a tumor with multiple cysts in the left parietal lobe that was diagnosed radiologically as malignant glioma. In operative findings, there was no dural attachment of the tumor, and the border between the tumor and normal brain tissue was unclear. Intraoperative histological examination supported the diagnosis of malignant glioma based on a high cellularity and an existence of a multinuclear giant cell in the tumor tissue. We finished the surgery with partial tumor resection; however, postoperative histological diagnosis of the tumor was a typical meningothelial meningioma showing characteristic whorl formations, and in conclusion, a definite diagnosis of the tumor was an intraparenchymal cystic meningioma. In further histological investigations, the tumor tissue around cysts exhibited significantly different features from meningothelial meningioma, demonstrating small lymphocytes and histiocytes with a large nucleus, which resembled intraoperative histological findings. We deliberated that the removal of the tumor tissue from the degenerated portion for intraoperative histological examination might lead to the misdiagnosis of malignant glioma. Operative strategy is strongly influenced by intraoperative histological diagnosis. Therefore, surgeons are obliged to facilitate more precise intraoperative histological examinations by obtaining sufficient tissue from different parts of the tumor.

Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for cancer vaccine therapy. CTA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CTA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CTA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CTA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CTA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients., ((c) 2010 Wiley-Liss, Inc.)

The oral apparatus in lancelets undergoes a remarkable modification during larval development, especially during metamorphosis, when the oral innervation is radically altered. The larval mouth opens on the left side at the early larval stage, and a peripheral nerve network, the oral nerve ring (ONR), develops around it. The ONR enlarges as the mouth expands caudally, eventually receiving fibers from nerves as far back as the tenth on the left side. The mouth shrinks during metamorphosis, and with this change the ONR regresses; the posterior sixth to tenth nerves become freed from the connection with the ONR, whereas the fourth and fifth nerves retain their connections. This modification is the basis for the asymmetric innervation to the velum. There is no mesodermal or mesenchymal restriction for guiding nerve patterning as typically found in vertebrate cranial nerves. Rather, it seems to be the ONR, which has no counterpart in vertebrates, that plays pivotal roles for patterning the nervous system in the oral region. The oral innervation pattern in lancelets represents a derived character state that may be related to the asymmetry of the ancestral body and head.

Purpose: Positron emission tomography (PET) is a powerful tool for measuring in vivo functions such as blood flow, metabolism, enzyme activity, receptors, and transporters. However, plural measuring instruments (i.e., the dose-calibrator, the auto well gamma counter, the continuous blood sampling system) are necessary for the quantitative PET measurement as well as the PET scanner. The purpose of this study was to investigate the reliability of plural measuring instruments from the maintenance data for 6 years., Methods: Four kinds of measuring instrument were evaluated: a dose-calibrator (CAPINTEC, CRC-15R), an auto well gamma counter (ALOKA, ARC-400), a continuous blood sampling system (ESPEC Techno, PH type), and a dedicated PET scanner (Siemens, ECAT EXACT HR+). We examined whether the initial performance for system sensitivity is maintained. The reliability of the PET scanner was evaluated from the value of mean time between failures (MTBF) for each part of the system obtained from the maintenance data for 6 years., Results: The sensitivity of a dose-calibrator and an auto well gamma counter were maintained virtually constant during the 6 years, but the sensitivity of a continuous blood sampling system was 0.1+/-3.2%. The sensitivity of a PET scanner was decreased to 92.3% of the initial value. Fifty-one percent of the problems with the PET scanner were for detector block (DB) and analog processor (AP) board. The MTBF of DB and AP board module were 199 and 244 days, respectively. The MTBF of the PET scanner was 56 days., Conclusion: The performance of three measuring instruments, excepting the PET scanner, was relatively stable. The reliability of the PET scanner strongly depends on the MTBF of the DB and AP board. For quantitative PET measurement, it is effective to evaluate the reliability of the system and to make it known to the users.

Purpose: Iterative reconstruction has been successfully used in whole-body PET imaging because of reductions in noise and scanning time. However, there are plural algorithms for image reconstruction such as OSEM, RAMLA and Dynamic RAMLA. Dynamic RAMLA (DRAMA) is an iterative algorithm similar to RAMLA, but the relaxation parameter is controlled in such a way that the propagation of noise from projection data to the reconstructed image. The purpose of this study was to investigate differences in the DRAMA and OSEM algorithms, in terms of real space and frequency space., Method: A whole-body torso phantom (NEMA image-quality phantom) filled with F-18 was scanned with a dedicated PET scanner. The smallest four spheres, with internal diameters of 10, 13, 17, and 22 mm, were filled with F-18 at an 8:1 concentration with respect to the background. The two largest spheres, with diameters of 28 and 37 mm, were not filled with water (empty). The emission scan for a 50 cm axial range varied from 5-20 minutes, to examine the effect of the count statistics on the quality of the reconstructed images. The images were reconstructed with OSEM by changing the number of subsets from 1 to 128 in each study. As to the number of iterations, both iterative reconstruction algorithms were one. As a reference standard, images with maximum counts (60 minutes) were reconstructed with a filtered-back projection method. The quality of the reconstructed images was evaluated in terms of contrast, background variability, and two-dimensional power spectrum analysis., Results: As for the real space results, OSEM with more than 32 subsets decreased contrast because of images with checkerboard noise. The DRAMA algorithm provided stable contrast even when count statistics were poor. A two-dimensional power spectrum analysis also revealed that the OSEM algorithm enhanced noise components in reconstruction with more than 32 subsets., Conclusion: Our preliminary data suggested that the OSEM algorithm requires few iterations with a small number of subsets for whole-body imaging. However, the DRAMA algorithm provides a reasonable signal-to-noise ratio with satisfactory spatial resolution even with one iteration. Especially in clinical whole-body PET, DRAMA was most useful because of its fast convergence and small computer burden.

Primary malignant melanoma of the esophagus (PMME) is a very rare disease with an extremely poor prognosis. Surgery is currently considered its best treatment, while any other measures are ineffective. We studied the effect of active specific immunotherapy using monocyte-derived dendritic cells (DCs) pulsed with the epitope peptides of melanoma-associated antigens (MAGE-1, MAGE-3) in patients with PMME after surgery, for the first time. The patient received passive immunotherapy with lymphokine-activated killer cells concomitantly. Two HLA-A24-positive patients with PMME were treated. Both patients initially received radical esophagectomy with regional lymphadenectomy, followed by adjuvant chemotherapy with dacarbazine, nimustine, vincristine and interferon-alpha. In the case 1 patient, active specific immunotherapy was used to treat a large abdominal lymph node metastasis that became obvious 21 months after surgery. The disease remained stable for 5 months, and the patient survived for 12 months after the initiation of immunotherapy. In the case 2 patient, immunotherapy was tried as post-operative adjuvant treatment after adjuvant chemotherapy. There was no tumor recurrence for 16 months after the immunotherapy. As of 49 months after esophagectomy, the patient is still alive. In both patients, the ability of peripheral lymphocytes to produce IFN-gamma in vitro in response to peptide stimulation was significantly enhanced and delayed-type hypersensitivity skin test response to MAGE-3 peptide was turned positive after immunotherapy. In conclusion, active specific immunotherapy for PMME with the use of DCs and MAGE peptides was safe and capable of inducing peptide-specific immune responses. This case report warrants further clinical evaluation of this immunotherapy for PMME.

The aim of this study was to investigate the correlation between noise equivalent count (NEC) rates and the signal-to-noise ratio (S/N) in reconstructed images. The NEC rates were determined using uniform 20 cm and 70 cm tall, 20 cm diameter cylinders filled with 11C. The phantoms were scanned in both two-dimensional and three-dimensional modes. The reconstructed image noise was evaluated using FBP and OSEM algorithms (4 iterations and 8 subsets). The images were filtered to a final image resolution of 6.5 mm. From the reconstructed image sets, averages and standard deviations of images were generated, from which the average image S/N (=average/standard deviation) was calculated within an 18 cm central ROI. The S/N of a central slice and an end slice was compared with the NEC. The NEC was found to have a linear relationship to the image S/N of all slices, depending on differences in noise properties specific to the reconstruction algorithm. In two-dimensional mode, although the image S/N of the central slice and the edge slice showed a linear relationship with the NEC, in three-dimensional mode, the S/N of the central slice did not show a relationship with the NEC. The linear relationship was also found in both two- and three-dimensional acquisition modes, as well as for the different activity distributions. These results indicate that the NEC is not only a measure for comparing the count rate performance of imaging systems. However, an absolute evaluation is impossible to depend on reconstruction algorithm, slice number, and phantom type.

Unlabelled: Transmission scanning can be successfully performed with a Cs-137 single-photon-emitting point source for three-dimensional PET imaging. This method was effective for postinjection transmission scanning because of differences in physical energy. However, scatter contamination in the transmission data lowers measured attenuation coefficients. The purpose of this study was to investigate the accuracy of the influence of object scattering by measuring the attenuation coefficients on the transmission images. We also compared the results with the conventional germanium line source method., Methods: Two different types of PET scanner, the SET-3000 G/X (Shimadzu Corp.) and ECAT EXACT HR(+) (Siemens/CTI) , were used. For the transmission scanning, the SET-3000 G/X and ECAT HR(+) were the Cs-137 point source and Ge-68/Ga-68 line source, respectively. With the SET-3000 G/X, we performed transmission measurement at two energy gate settings, the standard 600-800 keV as well as 500-800 keV. The energy gate setting of the ECAT HR(+) was 350-650 keV. The effects of scattering in a uniform phantom with different cross-sectional areas ranging from 201 cm(2) to 314 cm(2) to 628 cm(2) (apposition of the two 20 cm diameter phantoms) and 943 cm(2) (stacking of the three 20 cm diameter phantoms) were acquired without emission activity. First, we evaluated the attenuation coefficients of the two different types of transmission scanning using region of interest (ROI) analysis. In addition, we evaluated the attenuation coefficients with and without segmentation for Cs-137 transmission images using the same analysis. The segmentation method was a histogram-based soft-tissue segmentation process that can also be applied to reconstructed transmission images., Results: In the Cs-137 experiment, the maximum underestimation was 3% without segmentation, which was reduced to less than 1% with segmentation at the center of the largest phantom. In the Ge-68/Ga-68 experiment, the difference in mean attenuation coefficients was stable with all phantoms., Conclusion: We evaluated the accuracy of attenuation coefficients of Cs-137 single-transmission scans. The results for Cs-137 suggest that scattered photons depend on object size. Although Cs-137 single-transmission scans contained scattered photons, attenuation coefficient error could be reduced using by the segmentation method.

Unlabelled: The SET-3000 G/X (Shimadzu Corp., Kyoto, Japan) has a large aperture and functions as a three-dimensional (3D) dedicated PET scanner. However, the large number of line of responses in the SET-3000 G/X scanner creates a large volume of sinogram data and prolongs reconstruction time in iterative reconstruction. The purpose of this study was to optimize basic acquisition parameters (maximum ring difference and span) for sensitivity and spatial resolution for 3D whole-body (18)F-FDG PET., Methods: Detector rings and image planes numbered 50 and 99, respectively. In sensitivity measurement, the maximum ring difference (MRD) was changed from 1 to 49. In the measurement of spatial resolution, the span was changed from 3 to 21. For sensitivity and spatial resolution measurements, the standard protocols defined by the Japan Radioisotope Association (JRIA) 1994 and the National Electrical Manufacturers Association (NEMA) NU 2-2001 were used. We also evaluated the corresponding image noise by placing identical ROI on the reconstructed images., Results: The total sensitivity of MRD=49 was 85.7 cps/Bq/ml in a uniform phantom (15 cm diameter, 30 cm tall cylinder) filled with (18)F. This was approximately two times higher than MRD=13. The image noise in the center of the axial FOV decreased with increasing MRD. Spatial resolution was slightly decreased as MRD increased, but axial resolution deteriorated with a span of more than 11., Conclusion: Optimum basic data-acquisition parameters for whole-body (18)F-FDG PET were MRD 49 to obtain maximum sensitivity and span 9 to avoid decreasing spatial resolution. Additionally, it was concluded that the basic data-acquisition parameters should be carefully selected for 3D whole-body (18)F-FDG PET in order to maximize the efficiency of PET measurement.

Nocardial brain abscesses are uncommon and are not preceded by clear infectious symptoms in most cases. Delayed identification of the bacteria is responsible for a high mortality rate. A 58-year-old afebrile woman was admitted to our hospital because of progressive right hemiparesis and aphasia. Magnetic resonance imaging (MRI) showed a single ring-enhanced lesion in the left frontal lobe. It was extremely difficult to establish the diagnosis of brain abscess, because the laboratory data provided little evidence of bacterial infection, (201)TlCl-scintigraphy revealed definite accumulation of thallium in the lesion, and follow-up MRI demonstrated rapid enlargement of the lesion. Total resection was performed because of the possibility of a malignant brain tumor, but brain abscess was finally diagnosed with histological examination. A nocardial species was detected through microscopic examination of the pus obtained at surgery, and this precise diagnosis of nocardial brain abscess in the early stage enabled the administration of appropriate antibiotics and the patient's quick recovery. Nocardial brain abscesses are often misdiagnosed as malignant brain tumors, and a definitive diagnosis may not be possible without detecting bacteria from the lesion. Total excision of the abscess can produce good results when the abscess is large and located superficially, but incomplete aspiration and drainage of a lesion is associated with a high chance of relapse.

Objective: To establish the basis for use of allogeneic dendritic-tumor fusion cells., Study Design: Fusion cells were created by electrofusion. We used 2 allogeneic murine tumor lines (D5 and 4T1) that were virally transduced to express the antigen (beta-galactosidase) as a surrogate tumor marker., Results: Cross-immunization was achieved with irradiated allogenic tumor cells. Successful electrofusion of dendritic cells and tumor cells was confirmed by using fluorescence-activated cell sorting and cytospin. Significant responses were shown in immunized mice against tumor challenge and established 3-day pulmonary metastasis with fusion cells., Conclusions: Allogeneic tumor sharing a common tumor antigen can immunize against syngeneic tumor challenge. Fusion cells showed successful immunization against tumor challenge and showed regression of 3-day established pulmonary metastasis., Significance: These preclinical studies provide evidence that an allogenic tumor-dendritic cell fusion vaccine is a valid approach for head and neck cancer immunotherapy.

Background: Alterations of the p53 tumor suppressor gene are the most commonly observed genetic abnormalities in many different types of human malignancies. The accumulation of mutant p53 often leads to the production of p53 antibody (p53-Ab) in the sera of patients with various cancers. To evaluate the clinical implications of serum p53-Abs in patients with gastric cancer, we compared p53-Abs with conventional tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9., Methods: Serum samples were obtained preoperatively from 40 patients with histologically confirmed gastric adenocarcinoma, including 28 (70%) patients in stage Ia. The serum p53-Abs were assessed by enzyme-linked immunosorbent assay, using a new version of a highly specific, quantitative p53-Abs Kit (MESACUP Kit II)., Results: p53-Abs were detected in 6 (15%) of 40 patients with gastric cancer, including 3 patients with early gastric cancer. Seven (17.5%) of the 40 patients were positive for CEA in serum. However, none of 7 patients with high CEA levels were positive for p53-Abs. No significant correlation of p53-Abs with patient age, sex, pathological parameters, tumor markers such as CEA and CA19-9, or poor survival (P = 0.116) was observed., Conclusion: Although we employed the latest version of the p53-Abs Kit, the sensitivity of serum p53-Ab in gastric cancer patients was relatively low. No correlation was found between the presence of p53-Ab and the staging of cancer or survival. However, serum p53-Ab was detectable in patients with gastric cancer even in the early stages of disease. In addition, it may be independent of CEA and CA19-9.

Hepatic arterial infusion (HAI) with pharmacokinetic modulating chemotherapy (PMC) has been well known to be one of the most effective protocols for unresectable liver metastases from colorectal cancer. PMC is a combination of oral UFT and continuous hepatic arterial 5-FU infusion. We present herein the cases of two patients with multiple liver metastases from colorectal cancer in whom complete regression (CR) was achieved by HAI with PMC in combination with Lentinan (immunostimulator). These patients received HAI via an implantable port system with a 4-24-hour continuous perfusion of 5-FU at 1,000 mg/m2 plus Lentinan at 2 mg/body once a week, and oral administration of UFT at 200-300 mg/m2/day everyday. CR of all metastatic lesions in the liver was achieved 4 months after the initiation of the treatment in both patients. One patient maintained CR for 3 months, but he died due to a recurrence of liver metastases and peritoneal dissemination 19 months after the initiation of the treatment. The other patient has been well without recurrence for 21 months. Because the liver is the largest immunologic organ, Lentinan could have activated lymphocytes and macrophages in the liver. Judging from the clinical experience of these two cases, HAI with PMC in combination with Lentinan could be one of the most promising treatment strategies for unresectable liver metastases from colorectal cancer.

The findings summarized here provide a direct comparison of the immunogenicity of various DC loading strategies included pulsing with protein, peptide, tumor cell lysate, irradiated tumor cells and electrofusion of DCs and tumor cells. For the treatment of 3-day established pulmonary metastases, electrofusion of DCs and tumor cells generated a therapeutic vaccine far superior to other methods of DC loading. Consistent with their therapeutic activity, fusion hybrids stimulated the release of the largest amount of interferon-gamma from immune T cells. However, IL-10 secretion did not correlate with in vivo therapeutic reactivity. In conclusion, DC-tumor fusion hybrids were the most effective vaccine to eradicate existing tumors. These data support the use of DC-tumor electrofusion cells for the treatment of human cancer.

This case report describes an 11-year-old boy with primitive neuroectodermal tumor (PNET), which remains the pediatric brain tumor with the worst prognosis despite combination treatment with surgery, irradiation and anti-cancer drugs. The boy was successfully treated with intratumoral administration of interferon-beta (IFN-beta) following surgical resection and irradiation. Two million units of IFN-beta were locally administered into the post-operative cavity through the Ommaya's reservoir every two weeks after discharge. He was managed as an outpatient without serious side-effects to IFN. The patient has shown no tumor recurrence, mental retardation, or neuroendocrine impairment for over three years and has lived a normal school life with a full Karnofsky Performance Status score. The local administration of IFN-beta may be warranted for maintenance therapy in children with PNET.

Antigen presentation by dendritic cells (DCs) has the potential to elicit therapeutic immune responses against malignant tumors. One strategy utilizing DC-tumor fusion hybrids as cancer vaccine is particularly attractive because of polyclonal presentation of a diverse array of unaltered tumor antigens. We have recently developed a large-scale electrofusion technique for generating DC-tumor heterokaryons and demonstrated their superb immunogenicity. Here, employing the weakly immunogenic MCA205 sarcoma, a single vaccination with electrofusion hybrids eradicated tumors established in the lung, skin, and brain. Immunotherapy required intra-lymphoid vaccine delivery and co-administration of adjuvants such as OX-40R antibody. Tumor eradication was immunologically specific and involved the participation of both CD4 and CD8 T cells. Consistent with DC's functionality of MHC-restriction, the use of syngeneic DCs for fusion was an obligatory requirement. Fusion with allogeneic DCs completely lacked therapeutic effects. These findings provide a strong impetus for treating cancer patients with similarly generated DC-tumor hybrids.

We are under development of a 3D PET scanner with depth of interaction (DOI) capable of high sensitivity and high resolution. In this paper, we estimated the data transfer rate of data acquisition system of this PET scanner by the simulation studies. A maximum data transfer rate of coincidence pair's event information is 10 Mcps and one coincidence event is a 64-bit data format. A data acquisition system, which fulfills the specification of this scanner, is considered for parallel collection with banks including several coincidence units. Simulator of parallel collection system composed of two stand-alone simulators and the server PC. Each stand-alone simulator is composed of data generation PC, data processing circuit, SCSI and data acquisition PC. As the result of simulation studies, the maximum data transfer rate of the stand-alone simulator was 12.0 MB/s, and the maximum data transfer rates at the server PC with one and two nodes were 11.0 and 21.8 MB/s, respectively. Data transfer rate was improved by parameter optimization of a message size and multi-processing of data acquisition software using RAM-DISK.

To elicit a therapeutic antitumor immune response, dendritic cells (DCs) have been employed as a cellular adjuvant. Among various DC-based approaches, fusion of DCs and tumor cells potentially confers not only DC functionality, but also a continuous source of unaltered tumor antigens. We have recently demonstrated successful generation of fusion hybrids by a large-scale electrofusion technique. The immunogenicity and therapeutic potential of fusion hybrids were further analyzed in a model system of a murine melanoma cell line expressing beta-galactosidase (beta-gal) as a surrogate tumor antigen. A single vaccination with fusion hybrids plus IL-12 induced a therapeutic immune response against 3-day established pulmonary metastases. This immunotherapy was beta-gal specific and involved both CD4 and CD8 T cells. In vitro, fusion hybrids stimulated specific IFN-gamma secretion from both CD4 and CD8 immune T cells. They also nonspecifically induced IL-10 secretion from CD4 but not CD8 T cells. Compared to other DC loadings, our results demonstrate the superior immunogenicity of fusion. The current technique of electrofusion is adequately developed for clinical use in cancer immunotherapy.