Takenori Kato

Occurrence and field relationships of ultrahigh-pressure metagranitoid and coesite eclogite in the Su-Lu terrane, eastern China

Coesite eclogite is associated with metagranitoid in a 50×100 m2 outcrop within the regionally developed amphibolite-facies Su-Lu orthogneiss. Primary intrusive relationships between the metagranitoid and basic rocks and bulk-chemistry analyses show that together they represent a composite igneous body that has subsequently been strongly deformed and metamorphosed. The presence of rutile, sodie pyroxene, corona garnet, and possible pseudomorphs after coesite all suggest very high pressures of metamorphism in the metagranitoid. This is the first documented occurrence of ultrahigh-pressure (UHP) metagranitoid outside of the European Alps. The existence of UHP metagranitoid shows that low density of rocks does not necessarily prevent subduction to mantle depths. Even at peak metamorphic conditions the UHP composite igneous body reported here would have a bulk density less than the mantle. Buoyancy forces may, therefore, have been important in the early exhumation of this unit. Other outcrops of coesite eclogite in the Su-Lu region may also have been originally metamorphosed along with low-density granitoid rocks.

Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery

Object Little is known about long-term outcomes, including tumor control and adverse radiation effects, in patients harboring vestibular schwannomas (VSs) treated with stereotactic radiosurgery > 10 years previously. The aim of this study was to confirm whether Gamma Knife surgery (GKS) for VSs continues to be safe and effective > 10 years after treatment. Methods A total of 440 patients with VS (including neurofibromatosis Type 2) treated with GKS between May 1991 and December 2000 were evaluable. Of these, 347 patients (79%) underwent GKS as an initial treatment and 93 (21%) had undergone prior resection. Three hundred fifty-eight patients (81%) had a solid tumor and 82 (19%) had a cystic tumor. The median tumor volume was 2.8 cm(3) and the median marginal dose was 12.8 Gy. Results The median follow-up period was 12.5 years. The actuarial 5- and ≥ 10-year progression-free survival was 93% and 92%, respectively. No patient developed treatment failure > 10 years after treatment. According to multivariate analysis, significant factors related to worse progression-free survival included brainstem compression with a deviation of the fourth ventricle (p < 0.0001), marginal dose ≤ 13 Gy (p = 0.01), prior treatment (p = 0.02), and female sex (p = 0.02). Of 287 patients treated at a recent optimum dose of ≤ 13 Gy, 3 (1%) developed facial palsy, including 2 with transient palsy and 1 with persistent palsy after a second GKS, and 3 (1%) developed facial numbness, including 2 with transient and 1 with persistent facial numbness. The actuarial 10-year facial nerve preservation rate was 97% in the high marginal dose group (> 13 Gy) and 100% in the low marginal dose group (≤ 13 Gy). Ten patients (2.3%) developed delayed cyst formation. One patient alone developed malignant transformation, indicating an incidence of 0.3%. Conclusions In this study GKS was a safe and effective treatment for the majority of patients followed > 10 years after treatment. Special attention should be paid to cyst formation and malignant transformation as late adverse radiation effects, although they appeared to be rare. However, it is necessary to collect further long-term follow-up data before making conclusions about the long-term safety and efficacy of GKS, especially for young patients with VSs.

Glioma-initiating cells and molecular pathology: implications for therapy

There is now compelling evidence that gliomas harbor a small population of cells, termed glioma-initiating cells (GICs), characterized by their ability to undergo self-renewal and initiate tumorigenesis. The development of therapeutic strategies targeted toward GIC signaling may improve the treatment of malignant gliomas. The characterization of GICs provides a clue to elucidating histological heterogeneity and treatment failure. The role of the stem cell marker CD133 in the initiation and progression of brain tumors is still uncertain. Here, we review some of the signaling mechanisms involved in GIC biology, such as phosphatase and tensin homolog (PTEN), sonic hedgehog, Notch, and WNT signaling pathways, maternal embryonic leucine-zipper kinase (MELK), BMI1, and Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling. In addition, we discuss the role of microRNAs in GICs by focusing on microRNA-21 regulation by type I interferon.

The Modulation of MicroRNAs by Type I IFN through the Activation of Signal Transducers and Activators of Transcription 3 in Human Glioma

Type I IFNs are involved in double-stranded RNA responses. Here, we investigated the possibility that IFN-β may induce or downregulate cellular microRNAs (miRNA) in human neoplasms and thereby use the RNA interference system to show antitumor effects. Because of its known connection to glioma biology, we focused on miR-21 among seven miRNAs influenced by IFN-β. We analyzed the effect of IFN-β treatment on miR-21 expression in glioma cells and intracranial glioma xenografts. IFN-β treatment reduced miR-21 expression in glioma cells markedly, and IFN-β administration suppressed the growth of glioma-initiating cell–derived intracranial tumors. The levels of primary miR-21 gene transcripts, precursor miR-21, and mature miR-21 decreased 6 hours after the addition of IFN-β, indicating that the reduction in miR-21 levels was due to transcriptional suppression. We did reporter assays to elucidate the IFN-β–mediated suppression of miR-21; the addition of signal transducers and activators of transcription 3 (STAT3)–expressing vectors induced the IFN-β–mediated suppression of miR-21, whereas STAT3-inhibiting agents inhibited the miR-21 suppression. Thus, the results of our study show that the downregulation of miR-21 contributes to the antitumor effects of IFN-β and that miR-21 expression is negatively regulated by STAT3 activation. These results highlight the importance of understanding the transcriptional regulation of the miRNAs involved in oncogenesis. (Mol Cancer Res 2009;7(12):2022–30)

Induction of oligodendrogenesis in glioblastoma-initiating cells by IFN-mediated activation of STAT3 signaling

The response of cancer patients to interferon (IFN) treatment is long-lasting, indicating that IFN may act on small cancer stem cell populations. Glioma-initiating cells (GICs) can self-renew and induce the formation of heterogeneously differentiated tumor cells and are resistant to chemotherapeutic agents like temozolomide. In this study, we showed that via STAT3 signaling, IFN-beta suppressed the proliferation, self-renewal, and tumorigenesis of GICs, induced their terminal differentiation to mature oligodendroglia-like cells, and exhibited synergistic cytotoxicity with temozolomide. Therefore, IFN may be a potential therapeutic agent for inducing the terminal differentiation of GICs.

Stereotactic Radiosurgery as the Initial Treatment for Patients with Nonfunctioning Pituitary Adenomas

OBJECTIVE The aim of this study was to confirm the efficacy and safety of stereotactic radiosurgery as the initial treatment for patients with nonfunctioning pituitary adenomas (NFPAs) and to decide the optimum dose to achieve long-term tumor control as well as preservation of pituitary endocrine function. METHODS The study was a single-center retrospective analysis of 16 patients with primary NFPAs that were treated with gamma knife surgery (GKS). Fifteen of 16 NFPAs were growing to the suprasellar region and slightly compressing or very close to the optic apparatus. Initial GKS was selected to avoid visual disturbance caused by further tumor growth that would require surgical resection under general anesthesia. The median tumor volume was 2.0 cm(3), and the median tumor margin dose was 15 Gy. RESULTS The median clinical follow-up period was 98 months. The last follow-up images demonstrated tumor regression in 15 patients and stable tumor in 1. No patient developed tumor progression. One patient who had pituitary apoplexy before treatment required hormone replacements 2 years after GKS. The other patients did not experience pituitary insufficiency requiring hormone-replacement therapy during the clinical follow-up period. No patient developed cranial nerve injury or radiation-induced neoplasm. CONCLUSIONS GKS is a safe and effective treatment option in patients with primary NFPAs, especially for patients with advanced age or comorbidity. Attention should be paid to late adverse radiation effects such as hypopituitarism, optic neuropathy, and radiation-induced neoplasms. However, stereotactic radiosurgery with a conformal treatment plan sparing the normal pituitary gland will contribute to avoidance of such complications as well as achievement of long-term tumor control.

Long-term results for trigeminal schwannomas treated with gamma knife surgery.

PURPOSE Surgical resection is considered the desirable curative treatment for trigeminal schwannomas. However, complete resection without any complications remains challenging. During the last several decades, stereotactic radiosurgery (SRS) has emerged as a minimally invasive treatment modality. Information regarding long-term outcomes of SRS for patients harboring trigeminal schwannomas is limited because of the rarity of this tumor. The aim of this study was to evaluate long-term tumor control and functional outcomes in patients harboring trigeminal schwannomas treated with SRS, specifically with gamma knife surgery (GKS). METHODS AND MATERIALS Fifty-three patients harboring trigeminal schwannomas treated with GKS were evaluated. Of these, 2 patients (4%) had partial irradiation of the tumor, and 34 patients (64%) underwent GKS as the initial treatment. The median tumor volume was 6.0 cm(3). The median maximum and marginal doses were 28 Gy and 14 Gy, respectively. RESULTS The median follow-up period was 98 months. On the last follow-up image, 7 patients (13%) had tumor enlargement, including the 2 patients who had partial treatment. Excluding the 2 patients who had partial treatment, the actuarial 5- and 10-year progression-free survival (PFS) rates were 90% and 82%, respectively. Patients with tumors compressing the brainstem with deviation of the fourth ventricle had significantly lower PFS rates. If those patients with tumors compressing the brainstem with deviation of the fourth ventricle are excluded, the actuarial 5- and 10-year PFS rates increased to 95% and 90%, respectively. Ten percent of patients had worsened facial numbness or pain in spite of no tumor progression, indicating adverse radiation effect. CONCLUSIONS GKS can be an acceptable alternative to surgical resection in patients with trigeminal schwannomas. However, large tumors that compress the brainstem with deviation of the fourth ventricle should be surgically removed first and then treated with GKS when necessary.

Strontium Isotope Analysis using Resonance Ionization Mass Spectrometry for Determination of Bone Origin

We have considered the applicability of strontium isotope analysis, using Laser Ablation-assisted Resonance Ionization Mass Spectrometry (LA-RIMS), to the determination of bone origin. We separated the uncertainty into two categories: ion counting statistics, and short-term or uncontrollable shifts of experimental conditions; only the former decreases with increasing signal intensity. Additionally, we confirmed that long-term shifts of isotope ratio in LA-RIMS can be cancelled by an internal correction method. We preliminarily estimated the precision of our technique to be 0.7% (1σ) for 105 laser shots; the accuracy is also confirmed within the present uncertainty through the comparison with a reference value.

A mechanism for Nb incorporation in rutile and application of Zr-in-rutile thermometry: A case study from granulite facies paragneisses of the Mogok metamorphic belt, Myanmar

Abstract Rutile grains occur extensively in host phases of biotite and quartz-feldspar aggregate in high-temperature paragneisses of the Mogok metamorphic belt of Myanmar. They occur as an isolated phase and sometimes show intergrowth texture with ilmenite. Most rutile grains contain up to 3.7 wt.% Nb2O5, which shows positive correlations with Fe and trivalent elements. Niobium substitutes for Ti by a coupled substitution with the trivalent cations (M3+) of Nb5+M3+Ti4+-3. Fine-grained rutile grains included in ilmenite are distinctly poor in Nb (<0.1 wt.% as Nb2O5) and contain Fe of 1.7-3.2 wt.% as Fe2O3, suggesting vacancybearing substitution of Fe3+4 Ti4+-3□-1, where □ indicates a vacancy. The rutile grains in the felsic phases contain high Zr contents of up to 4200 ppm, suggesting equilibrium temperatures over 800°C using the Ti-in-rutile geothermometer. These high-temperature conditions are consistent with those estimated by conventional methods reported in the literature and suggest widespread occurrences of the upperamphibolite and granulite facies metamorphic rocks in the middle segment of the Mogok metamorphic belt. In contrast, the Zr contents of rutile grains in biotite are usually <1000 ppm, implying equilibrium temperatures lower than 750°C. Most of the rutile grains poorer in Zr might have been included in biotite and were isolated from the zircon-bearing system during an early stage of prograde metamorphism. Some other rutile grains poorer in Zr might have been an exsolved phase from Ti-rich biotite during retrograde metamorphism, which was furthered by the infiltration of metamorphic fluid under lower-amphibolite facies conditions.

Monazite Behaviour and Time-scale of Metamorphic Processes along a Low-pressure/High-temperature Field Gradient (Ryoke Belt, SW Japan)

Low-pressure/high-temperature metamorphic rocks exposed in the western part of the Ryoke belt (Iwakuni–Yanai area, SW Japan) include a section with increasing temperature conditions from 425 to 880 C. We use this setting to explore the evolution of monazite grain size, texture and composition, and variations in the whole-rock composition of 11 metapelite, metapsammite or metachert samples collected along the metamorphic field gradient. Monazite grain size increases with rising metamorphic grade, regardless of the whole-rock composition. From lowto high-grade conditions we infer: (1) the initial nucleation of monazite aggregates after allanite ( 425 C); (2) monazite coarsening and coalescence driven by incipient monazite recycling; that is, dissolution of small grains to grow larger ones by Ostwald ripening (500–600 C); (3) a first major recycling stage enhanced by fluid liberation owing to muscovite breakdown (600–630 C); (4) a second recycling stage assisted by an increase in the proportion of anatectic melt owing to biotite breakdown (> 850 C). A succession of four compositional domains is recognized in monazite. We emphasize the usefulness of comparing their Ce/ThMnz, Ce/YMnz and Th/UMnz molar ratios with those derived from whole-rock analyses to constrain the origin of each domain. Domain I, with variable ratios, reflects the progressive transfer of Th 6 U from allanite to monazite at low-grade conditions. Domain II, with Ce/ThMnz matching the whole-rock values, indicates growth under rock(decimetre)scale equilibrium conditions. Domains II and III, with Th/UMnz and Ce/YMnz departing from the whole-rock values, record the competition with zircon (for U) and garnet (for Y) during growth at peak P–T conditions. Domain IV points to Y supply by garnet resorption during retrograde chloritization (< 550 C). In the highest-grade sample, zircon grains included in garnet or cordierite show metamorphic rims with sillimanite and Si-rich inclusions. These rims formed at suprasolidus conditions (650–880 C) and yield Pb/U ages of 103–97 Ma (6 5 Ma), which bracket the timing of high-temperature metamorphism. Monazite dating by electron microprobe and laser ablation inductively coupled plasma mass spectrometry reveals two age groups. For domains I–III, some relatively old Pb/U ages (99–95 6 3–5 Ma) represent minimum estimates for the timing of prograde to peak metamorphism, whereas the similar oldest Pb/U age for domain IV VC The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 1109 J O U R N A L O F P E T R O L O G Y Journal of Petrology, 2018, Vol. 59, No. 6, 1109–1144 doi: 10.1093/petrology/egy056 Advance Access Publication Date: 11 June 2018