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In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases.

Background Undifferentiated pleomorphic sarcoma (UPS) is a sarcoma with a poor prognosis. A clinical trial, SARC028, revealed that treatment with anti-PD-1 drugs was effective against UPS. Studies have reported that UPS expresses PD-L1, sometime strongly (≥ 50%). However, the mechanism of PD-L1 expression in UPS has remained still unclear. CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) was identified as a novel regulator of PD-L1 expression. The positive relationship between PD-L1 and CMTM6 has been reported in several studies. The aim of this study was to examine CMTM6 expression in UPS and evaluate the relationship between PD-L1 and CMTM6. Materials and methods Fifty-one primary UPS samples were subjected to CMTM6 and PD-L1 immunostaining. CMTM6 expression was assessed using proportion and intensity scores. CMTM6 gene copy number was also evaluated using a real-time PCR-based copy number assay. We also analyzed the mRNA expression and copy number variation of PD-L1 and CMTM6 in The Cancer Genome Atlas (TCGA) data. Results TCGA data indicated that the mRNAs encoded by genes located around 3p22 were coexpressed with CMTM6 mRNA in UPS. Both proportion and intensity scores of CMTM6 positively correlated with strong PD-L1 expression (≥ 50%) (both p = 0.023). CMTM6 copy number gain increased CMTM6 expression. Patients with UPS with a high CMTM6 intensity score had worse prognosis for overall survival. Conclusions CMTM6 expression was significantly correlated with PD-L1 expression. CMTM6 expression induced strong PD-L1 expression (≥ 50%). CMTM6 copy number gain promoted CMTM6 expression and increased PD-L1 expression in UPS.

Giant cell tumor of bone (GCTB) is an intermediate malignant bone tumor that is locally aggressive and rarely metastasizes. Denosumab, which is a receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, can be used to treat GCTB. We focused on potential immunotherapy for GCTB and investigated the tumor microenvironment of GCTB. Programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression and signal-regulatory protein alpha (SIRPα), forkhead box P3 (FOXP3), and cluster of differentiation 8 (CD8) infiltration were assessed by immunohistochemical studies of 137 tumor tissues from 96 patients. Of the naive primary specimens, 28% exhibited PD-L1 expression and 39% exhibited IDO1 expression. There was significantly more SIRPα+, FOXP3+, and CD8+ cell infiltration in PD-L1- and IDO1-positive tumors than in PD-L1- and IDO1-negative tumors. The frequency of PD-L1 expression and SIRPα+ cell infiltration in recurrent lesions treated with denosumab was significantly higher than in primary lesions and recurrent lesions not treated with denosumab. PD-L1 expression and higher SIRPα+ cell infiltration were significantly correlated with shorter recurrence-free survival. PD-L1 and SIRPα immune checkpoint inhibitors may provide clinical benefit in GCTB patients with recurrent lesions after denosumab therapy.

Malignant rhabdoid tumor (MRT) is a rare, highly aggressive sarcoma with an uncertain cell of origin. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is very poor. Novel antitumor agents are needed for MRT patients. Forkhead box transcription factor 1 (FOXM1) is overexpressed and is correlated with the pathogenesis in several human malignancies. In this study, we identified the clinicopathological and prognostic values of the expression of FOXM1 and its roles in the progression of MRT. We investigated the FOXM1 expression levels and their clinical significance in 23 MRT specimens using immunohistochemistry and performed clinicopathologic and prognostic analyses. We also demonstrated correlations between the downregulation of FOXM1 and oncological characteristics using small interfering RNA (siRNA) and FOXM1 inhibitor in MRT cell lines. Histopathological analyses revealed that primary renal MRTs showed significantly low FOXM1 protein expression levels (p = 0.032); however, there were no significant differences in other clinicopathological characteristics or the survival rate. FOXM1 siRNA and FOXM1 inhibitor (thiostrepton) successfully downregulated the mRNA and protein expression of FOXM1 in vitro and the downregulation of FOXM1 inhibited cell proliferation, drug resistance to chemotherapeutic agents, migration, invasion, and caused the cell cycle arrest and apoptosis of MRT cell lines. A cDNA microarray analysis showed that FOXM1 regulated FANCD2 and NBS1, which are key genes for DNA damage repair. This study demonstrates that FOXM1 may serve as a promising therapeutic target for MRT.

Background/aim Malignant peripheral nerve sheath tumor (MPNST) is a rare soft-tissue tumor, and its diagnosis is usually made histopathologically. The effectiveness of chemotherapy and radiotherapy has not been established. We elucidated prognostic factors, diagnostic markers, and therapeutic targets. Materials and methods Cases of MPNST were studied using next-generation sequencing. A total of 24 tumor samples, 11 from von Recklinghausen's disease-associated MPNST (vRH-MPNST), 11 from sporadic non-vRH MPNST, and two neurofibroma (NF) cases were retrieved, on which next-generation sequencing and survival analysis were performed. Results We identified NF1 gene mutations, including three mutations in two NFs, and 10 mutations in eight MPNSTs (five vRH-MPNSTs and three sporadic MPNSTs). Meningioma 1 (MN1) gene alteration was detected in six cases of vRH-MPNST. It is considered that MN1 gene alteration is related to the tumorigenesis of vRH-MPNST. Conclusion MN1 gene mutation was detected in more than half of our cases, it may have potential for use as a therapeutic target in vRH-MPNST.

The original version of this article unfortunately contained mistakes introduced during the production process. Tables 1 and 2 were presented incorrectly. The original article has been corrected.

We describe a Case of a 74-year-old Japanese man with poorly differentiated carcinoma of the anterior mediastinum. The patient underwent anterior mediastinal tumor resection through median sternotomy. The tumor, 7.0 × 5.0 cm, had invaded surrounding tissues (pericardium, right lung, right and left brachiocephalic veins, and superior vena cava). Complete resection of the tumor was not performed. One month after the operation, the patient developed multiple pulmonary metastases, right pleural dissemination, and carcinomatous pleurisy. He was treated with lenvatinib, a novel multi-kinase inhibitor, to which the metastasis responded favorably. This case reports for the first time the clinical usefulness of lenvatinib for poorly differentiated carcinoma of the anterior mediastinum. Management of side effects by several methods, including suspending use of medication on weekends (called a weekends-off strategy), is another strong argument to continue lenvatinib administration.

The RNA-binding protein HuC/D displays a neuron-specific expression and is involved in neuronal differentiation and the maintenance of the nervous system. Here we investigated the diagnostic value of HuC/D in neuroblastomas. We evaluated 85 neuroblastic tumors: 81 neuroblastomas; 3 ganglioneuroblastomas, intermixed; 1 ganglioneuroma, maturing; and 101 other tumors consisting of 34 Ewing sarcomas, 14 nephroblastomas, 11 rhabdomyosarcomas, 15 pulmonary small cell carcinomas, 18 pancreatic neuroendocrine tumors, and 9 pheochromocytomas. Immunohistochemistry for HuC/D, PHOX2B, and tyrosine hydroxylase was performed. The immunoreactivity for HuC/D was semiquantified using the total score (TS; range, 0-8). HuC/D positivity was defined as a TS ≥6. The TS of the neuroblastic tumors (mean TS, 7.94) was significantly higher than those of the other small round cell tumors and neuroendocrine tumors (P < .001) except for the pheochromocytomas (mean TS, 6.89; P = .074). HuC/D was positive in all 85 neuroblastic tumors, 1 (2.9%) Ewing sarcoma, 1 (6.7%) pulmonary small cell carcinoma, and 8 (89%) pheochromocytomas. PHOX2B was positive in all of the neuroblastic tumors and pheochromocytomas. Tyrosine hydroxylase was positive in 80 (94%) neuroblastic tumors, 1 (9.1%) rhabdomyosarcoma, and all of the pheochromocytomas. Therefore, HuC/D serves as a highly sensitive diagnostic marker to distinguish neuroblastomas from other small round cell tumors. The combination of HuC/D and PHOX2B staining may be valuable for the diagnosis of neuroblastic tumors, especially in the assessment of small sections. HuC/D expression in tumors may be related to catecholamine production or a neural crest-derived cell origin.

The escape behavior of wild and hatchery-reared juvenile Japanese flounder Paralichthys olivaceus from a dummy predator, gray goblinfish Minous monodactylus, was investigated under artificial light in an experimental tank. When the dummy predator approached, both the juveniles quickly emerged from the sand, escaping primarily by swimming close to the bottom (benthic swimming) rather than off the bottom (off-bottom swimming). It is suggested that juvenile flounders might escape in this manner from a diurnal visual feeder in the daytime, owing to the flounder being virtually undetectable visually when close to the bottom. The average escape swimming speed of an individual of 9.3 total length (TL)/s in wild fish and 9.8 TL/s in hatchery-reared fish was similar to the maximum speed of many fish species. Juvenile flounder escaped more quickly and had a higher swimming speed (v cm/s), when their distance (d cm) to the dummy predator decreased (v = −2.7d + 82.1, r = −0.33; anova, P

In order to clarify the mechanisms of neoteny in the ice goby (Leucopsarion petersii), we examined effects of thyroid hormone and thiourea (TU) treatments on their neotenic characteristics and the pituitary-thyroid axis. Adult ice goby were exposed to 3, 5, 3'-triiodothyronine (T3, 0.1 ppm), TU (inhibitor of thyroid hormone synthesis, 30 ppm), or the combination of the two for 2 weeks. Observations of whole body T3 levels, thyroid follicles and TSH immunoreactive cells in the pituitary suggests the presence of a functioning thyroidal system. However, all of the neotenic features did not disappear in T3-treated fish, suggesting the absence of T3 responsiveness in peripheral tissues. These results indicate the similarity between neoteny of the ice goby and obligatory-type neoteny of urodeles.

Larval and juvenile ayu from seven year-groups (1986, 1987, 1992, 1995, 1996, 1999 and 2000) were collected in the Shimanto Estuary and adjacent coastal waters. The present study focuses on the variation among year-groups in the hatching period estimated by age determination using the otolith. The hatching period of the dominant cohorts in the 1986, 1987 and 1992 year-groups occurred from late October to mid-November. A delay of the hatching period of the dominant cohort was observed from the 1995 year-group, which occurred in late November to early December, and the dominant periods in the 1996, 1999 and 2000 year-groups were observed from early to late December. It appears that the delay of the hatching period of dominant cohorts was not due to a delay of spawning, but a high mortality of early hatched larvae. The water temperature in autumn in the coastal waters adjacent to the Shimanto River has tended to rise over the past 20 years and this trend was especially notable in the late 1990s. The delay in the hatching period of the dominant cohort observed from the 1995 year-group was likely to be related to the rise in seawater temperatures in autumn.

To elucidate the recruitment and movement process of larval ayuin the surf zone of a sandy beach facing Tosa Bay, 31 collectionswere made with a small seine net at intervals of approximately 5days from November 1990 to April 1991. On the basis of seasonalvariations in larval abundance, size, age, duration of residence,and the occurrence patterns of ayu in the surf zone, larval ayuwere classified into two groups: short-term resident (

Effects of mitigation and suppression of vapor explosion have been investigated by adding a surfactant, polymer, and neutral salt into the water droplet impinging onto a molten alloy pool surface. This configuration was selected to attain good reproducibility and visibility, because premixing events prior to the triggering restrained. In addition, an adequate amount of a surfactant can be adsorbed at the vapor/liquid interface compared to that in the case of conventional configurations such as a molten alloy droplet injecting into a water pool. Dilute anionic and nonionic surfactant aqueous solutions did not affect the triggering conditions or the pressure pulse generated by vapor explosion, even if the surfactant was added up to a density 25 times higher than the critical micelle concentration. Polymeric additives, which increase the viscosity of a fluid, have little suppression effect on vapor explosion. Spontaneous vapor explosion was, however, suppressed by a 200 wppm polyethylene glycol (molecular weight of 4×10 6 ) solution, since deposition of the solute due to cloudy-point phenomenon may stabilize the vapor film and prevent the solution from mixing finely. In order to exert this effect, molecular weight should be heavier so that a cloudy-point temperature is below the boiling point at the tested system pressure. Additionally, this threshold concentration became denser as the impingement velocity increased. Thus, a denser concentration and heavier molecular weight should be used to suppress vapor explosion when the vapor film may be subjected to large inertia and/or external force. When a neutral salt was added, the initial molten alloy temperature range where vapor explosion occurred shifted to a higher temperature and became wider. Vapor explosion was observed on the molten zinc surface, which does not explode spontaneously for water.

To clarify the habitats of the ayu in the early stages of development in the Shimanto Estuary, the size and hatching date of the larval and juvenile ayu were examined. Sizes of larvae and juveniles were larger in the center of the flow area than in the waters adjacent to the estuary’s banks, which suggests that larvae shift habitat to the center of flow from the waters along the estuary’s banks. This shift began at approximately 20 mm body length. However, the resident term in the waters adjacent to the estuary’s banks changed with the hatching dates; that is, the early and late-hatched larvae became short and long-term residents, respectively. A similar phenomenon was found also in the juveniles collected in the freshwater section that were migrating upstream. The growth rates of larval ayu in the waters adjacent to the banks tended to decrease with hatching dates. The fluctuations in growth rate with hatching date appear to be a factor leading to the variation of resident term.

To clarify the characteristics of the larval and juvenile fish community in a Japanese estuary, monthly collections were conducted in the shallow waters of the Shimanto Estuary, Japan from July 1985 to June 1987. A total of 49 101 fishes of more than 100 species from 44 families were sampled over the 2-year period. Numerically, Gerres equulus was most common, accounting for 20.02% of the total abundance. Rhyncopelates oxyrhynchus was ranked second, followed by Acanthopagrus latus, Acanthogobius flavimanus, Mugil cephalus cephalus, Parioglossus dotui, and Acanthopagrus schlegeli. Thus, fishes observed in the estuary were mostly marine species that spawn in the sea. The majority of these fish first appeared within the estuary at late postlarval and/or early juvenile stages. Based on their utilization of the shallow waters in the estuary, the majority of species could be categorized as residents. In the Shimanto Estuary, shallow waters are studded with shelters, especially eelgrass beds, which serve as important nursery grounds for coastal and euryhaline fishes.

In order to prevent the expansion of tube damage and to maintain structural integrity in the steam generators (SGs) of fast breeder reactors (FBRs), it is necessary to detect precisely and immediately the leakage of water from heat transfer tubes. Therefore, an active acoustic method, which detects the sound attenuation due to bubbles generated in the sodium-water reactions, is being developed.In this study, in order to evaluate the detection sensitivity of the active method, the signal processing methods for emitter and receiver and the detection method for leakage are investigated experimentally. In-water experiments performed by using an SG full-sector model that simulates the actual SGs.As an experimental result, the received sound attenuation for 10s was more than 10dB from air bubble injection when injected bubble of 10l/s (equivalence water leak rate about 10g/s). The attenuation of sound are least affected by bubble injection position of heat transfer tubes bunch department. It is clarified that the background noise hardly influenced water leak detection performance as a result of having examined influence of background noise.

The near-shore migration and settlement phases of Japanese and American flounders of the genus Paralichthys are compared and discussed relative to differences in coastal environments. Field sampling was conducted in Wakasa Bay, Kyoto Prefecture, Japan, where the shelf is narrow, estuarine habitat limited and tidal range slight, and in Onslow Bay, North Carolina, USA, where the shelf is broad, estuarine habitat extensive and tide relatively strong. Distribution of larvae and juveniles suggests Japanese flounder spawn in close proximity to nursery grounds relative to flounder in Onslow Bay. Sampling of planktonic and benthic flounder just seaward of nursery grounds resulted in capture of a wide range of developmental stages in Wakasa Bay (early planktonic to juvenile), but was limited to metamorphosing larvae in Onslow Bay. Vertical distribution of larvae during the night also differed between the Bays. At night most larvae in Wakasa Bay remained near the bottom regardless of tidal stage. In contrast, larvae in Onslow Bay exhibited selective tidal stream transport. Laboratory experiments conducted to examine the behaviour of recently captured wild and laboratory-reared larvae indicated that wild flounder from Onslow Bay had an endogenous rhythm of activity that corresponded to the tide at the time of capture. In contrast, wild flounder from Wakasa Bay and laboratory-reared larvae showed no distinct activity pattern. These results suggest that physical characteristics of the environment influence the early life history patterns of flounders by modifying behaviour of migrating larvae.

Reactor Vessel Auxiliary Cooling System (RVACS) is a simple and passive decay heat removal system for FBRs. However the heat removable capability of this system is small compared to that of immersed type of decay heat exchangers. So, RVACS has limit in applicability up to about 400MWe pool type LMFBR.The objectives of this report are to confirm its heat removal capability, to estimate its applicability limit of this RVACS for FBRs and to evaluate the effects of design parameters. In this report, the plant transient analyses have been performed with thermal-hydraulic code CERES. The main results are as follows:(1) The RVACS with heat collector have large heat removal capability to reduce the peak temperature of primary Coolant by 20°C than that without heat collector.(2) The effects of stack height and level difference of overflow liner on the heat removal capability are not so large.(3) The RVACS with heat collector is applicable up to 500MWe pool type LMFBR.

In the amphidromous form of ayu Plecoglossus altivelis Temminck et Schlegel, generally the prelarvae hatched in rivers in autumn are drifted down into the sea, where they live throughout the larval and early juvenile stages until spring. In the Shimanto estuary, however, an appreciable number of postlarval ayu occurred not only during March to May, but also during October to February. Furthermore, there was little difference in the size and age between the larvae occurring in the estuary and sea. In the estuary, they reside in the bank waters, during 10-75 day ages and 10-30mm SL. Thereafter, they seem to ascend the river without going out to the sea. The growth rate estimated from the otolith daily rings was higher in the estuary than in the sea beach.

The reactor vessel auxiliary cooling system (RVACS) is one of the decay heat removal systems for the fast breeder reactor. This system is so simple that it can attain high reliability and plant cost reduction. However, the heat removal capacity of this system is small compared to that of an immersed type of decay heat exchanger, because the heat transfer coefficient at the outside of the reactor vessel is not large. The object of this study is to propose a new method which is able to use thermal radiation effectively. The tests reveal that the heat transfer coefficient, using high-porosity porous bodies as a heat collector, surpasses that with no collector, especially at the upper end.

In Shijiki Bay of Hirado Island, diel discrete-depth horizontal tows with a larva net in May 1983 resulted in a total of 2, 350 larval and juvenile red sea bream (2.1-10.7mm SL), and 347 larval black sea bream (2.4-6.2mm SL) being collected. During the daytime, black sea bream larvae were concentrated near the surface, but red sea bream larvae near the bottom, with these tendencies becoming more evident with their growth. During the nighttime, the larvae of both species were dispersed throughout the water column. In the surf zone of the sandy-beaches located in the innermost part of the bay, collections with a small seine net in June and July 1983 gave a total of 241 late-larval and early-juvenile black sea bream (6.2-20.1mm SL), but no red sea bream. The separation of juvenile habitats between these related species seemed to be a consequence of the species-specific vertical distribution pattern differentiated during the pelagic larval period. A possible mechanism for inshore migration in the black sea bream was discussed in relation to their surface occurrence.

In order to study the characteristics of neoteny in teleosts, development of the thyroid system and digestive tract of a neotenic goby (ice goby, Leucopsarion petersii) and a non-neotenic goby (ukigori, Gymnogobius urotaenia) were compared. In juvenile ukigori, the intestine was found to be convoluted once in the antero-midpart, and gastric glands were present. In the ice goby, the alimentary canal was straight, and no gastric gland was observed even in adult, suggesting that the ice goby retains larval features, not only in appearance but also in internal organs. A marked difference was also found in the thyroid system. In ukigori, activity of the thyroid gland and thyroid stimulating hormone (TSH) cells increased between flexion and postflexion larval phases. However, in the ice goby, thyroid glands remained inactive, and no TSH cells were observed. A delayed development of the thyroid system was suggested as a major factor contributing to neoteny in the ice goby.

The experiments about the gas lift pump in lead-bismuth eutectic are performed with risers of three kinds of diameters [{phi}69.3 mm (SD case), {phi}106.3 mm (MD case), {phi}155.2 mm (LD case)]. The main results are as follows: (1) The coefficient of the drift flux model was derived from the experimental results. (2) The LBE flow rate obtained from the design method based on water/gas system with the relation of the drift flux model corresponds to the experimental results obtained in the MD and the SD cases. It is considered that the evaluation method can be used for the LBE gas lift pump in a small diameter riser. (3) In the LD, the design method excessively evaluates the lead-bismuth circulating flow rate. It thought that the circulation head will not occur in the experimental loop. The following factors are considered to be the causes of this: the three-dimensional behavior of bubbles becomes significant, and the local descending flow is generated in the riser when the riser diameter increases. (author)

The larval distribution and feeding habits of Cynoglossus abbreviatus and Cynoglossus lighti were investigated around the Rokkaku estuary in Ariake Bay during October 2004 and March and April 2005. Cynoglossus abbreviatus started and completed metamorphosis at larger sizes than C. lighti. Developmental phases consisted primarily of individuals at metamorphosis and postmetamorphosis, which were mainly distributed inside and just outside the Rokkaku River in March–April for C. abbreviatus and October for C. lighti. Tidal changes in vertical distribution just outside the river mouth differed between the closely related species; C. abbreviatus was distributed in the surface and middle layers at flood tide, and aggregated near the bottom (where the current speed was lowest) at ebb tide. Cynoglossus lighti stayed mainly near the bottom during all tidal phases. Larvae of both Cynoglossus species selectively fed on copepods (Pseudobradya sp.), which were scarce in the waters. These facts suggest that the nursery grounds of the two Cynoglossus species were different in terms of their tidal vertical distribution patterns.

The total Nusselt number increases with decreases in: (i) the conduction-radiation ratio contribution and (ii) the number of intermediate plates.

Fish larvae and juveniles were collected in the waters of wading depth along sandy beaches of western Japan with a 0.7-mm-mesh, 1.3- by 5-m seine. Presence of Chanos chanos, Salangichthys microdon, Plecoglossus altivelis, Allanetta bleekeri, Gerres oyena, Sparus sarba, Acanthopagrus schlegeli, A. latus, and Lateolabrax latus and absence of Engraulis japonica, Gonorhynchus abbreviatus, Upeneus bensasi, and Macrorhamphosus scolopax distinguished the larval ichthyofauna of surf zones from those in other known biotopes of fish nursery. The surfichthyofauna was usually more diverse in spring and summer than in autumn and winter. Monthly total catches of individuals fluctuated greatly according to the abundances of a few influential species such as Clupanodon punctatus in spring and Plecoglossus altivelis in autumn to winter. Most larval fishes seemed to inhabit surf zones only during daytime. An influence of tidal phases on occurrence of larval fishes was not apparent. Categories of pelagic and demersal components were suggested for surf zone ichthyofauna., Transactions of the American Fisheries Society: Vol. 114, No. 4 pp. 609?618; 1985