bluuebunny/crossref_metadata_2025_split huggingface dataset:
10205-TB-8 ABSENCE OF RNF213 IN MEDULLOBLASTOMA INDUCES STARVATION RESISTANCE VIA GAS6 AND RESULTS IN TUMOR PROGRESSION
Authors: Takahiko Kamata , Mineharu Yohei , Matsui Yasuzumi , Tezuka Toru , Oichi Yuki , Morimoto Takaaki , Tanji Masahiro , Sano Noritaka , Terada Yukinori , Kobayashi Hatasu , Okuda Hiroko , Harada Koji , Koizumi Akio , Arakawa Yoshiki 
Published: December 2023

Abstract
RNF213 gene, initially identified as a disease-causing gene for moyamoya disease, has recently been recognized as a tumor regulator. We investigated the functions of RNF213 in tumorigenicity of medulloblastoma. Knockout of Rnf213 in Ptch1+/- spontaneous medulloblastoma mouse model increased the incidence of SHH type medulloblastoma from 19.8% to 76.5% (p&lt;0.001) at 9 months. Subcutaneous implantation of the tumors showed that depletion of Rnf213 increased tumor formation frequency and tumor size. Unexpectedly, knockout of RNF213 in human Daoy cells decreased tumor growth and invasion in vitro. However, they were resistant to serum starvation and showed higher growth rate when implanted subcutaneously in nude mice. Transcriptome analysis of mouseRnf213-/- cells indicated that downregulation of Igf2 decreased tumor growth and upregulation of Gas6 increased resistance to starvation. In fact, GAS6 was upregulated in serum-free conditions and further upregulated in RNF213-/- cells. Survival advantage in serum starved conditions was lost by GAS6 knock-down in RNF213-/- Daoy cells. In conclusion, the effect of RNF213 depletion was context dependent. Resistance to starvation seems to outweigh growth retardation in normal conditions and is important for tumorigenicity and aggressiveness in vivo.
10206-GGE-21 MOLECULAR LANDSCAPE AND TUMOR EVOLUTION IN ASTROBLASTOMA
Authors: Yamamoto Ryo , Nakashima Takuma , Sugihara Yuriko , Funakoshi Yusuke , Goto Hironori , Ushida Eri , Yamasaki Kai , Yamasaki Fumiyuki , Gomi Akira , Arakawa Yoshiki , Washio Kana , Tateishi Kensuke , Suzuki Tomonari , Saito Ryuta , Narita Yoshitaka , Nobusawa Sumihito , Suzuki Hiromichi 
Published: December 2023

Abstract
Astroblastoma is an extremely rare malignant brain tumor characterized by distinctive gene fusions, including MN1-BEND2 and EWSR1-BEND2 fusions. Despite its indolent nature, frequent local recurrence affects the quality of life for patients. However, there remains a lack of investigation into the genome of astroblastoma. To elucidate the molecular landscape and clonal evolution of astroblastoma, we conducted deep whole-genome sequencing, RNA-seq, and DNA methylation array on 11 cases, including multi-time point samples from 3 cases. Additionally, we integrated publicly available RNA-seq and/or DNA methylation array data from 9 cases. The cohort consists of 13 cases with MN1-BEND2 fusion and 7 cases with EWSR1-BEND2 fusion. Astroblastoma exhibits a relatively silent genome, with median mutation rate is 0.60/Mb (0.22 - 1.09), which is associated with patient age. While EWSR1-BEND2 fusions result from simple translocation, MN1-BEND2 fusions predominantly arise from complex chromosomal rearrangements between chromosome X and 22, frequently involving an additional chromosome, leading to massive oscillation of copy number states in the affected chromosome. Breakpoints in BEND2 within EWSR1-BEND2 fused cases are located near the N-terminus while breakpoints in BEND2 within MN1-BEND2 fused cases cluster in the middle of the gene, suggesting that functional region in BEND2 fusion is distinct based on its partner. Based on DNA methylation, astroblastoma can be divided into three subgroups: MN1-child, MN1-adult, and EWSR1-BEND2 fusion. Gene set enrichment analysis reveals the activation of mitochondrial metabolism in EWSR1-BEND2 fused cases. MN1-adult cases exhibit activation of oxidative stress and DNA replication, whereas MN1-child cases show activation of NOTCH signaling. Multi-time point analysis demonstrates the architecture of clonal evolution. Ionizing radiation appears to be associated with an increase in mutations and deletions, with a radiation-related signature. Our comprehensive analysis provides a detailed view of the genome and evolutionary trajectory of astroblastoma.
10213-GMC-16 A DECADE REVIEW: BEVACIZUMAB'S IMPACT ON GLIOBLASTOMA TREATMENT
Authors: Miyake Keisuke , Yamauchi Yutaka , Fuke Tomono , Tatano Masaki , Ishikawa Momo , Kanda Takahiro , Suzuki Kenta , Fujimori Takeshi , Toyota Yasunori , Ogawa Daisuke , Hatakeyama Tetsuhiro , Okauchi Masanobu , Kawanishi Masahiko 
Published: December 2023

Abstract

OBJECTIVE
This study aims to assess the efficacy of Bevacizumab (Bev) therapy, ten years after its initiation in treating glioblastoma patients at our department.

METHODS
Eighty-four patients treated with Bev from July 2013 to December 2022 were classified into three groups: the initial treatment group given the Stupp regimen with Bev (first-dose group), the group given the Stupp regimen plus Bev followed by tumor resection (neoadjuvant group), and those receiving the Stupp regimen post tumor resection (recurrence group). PET scans were conducted pre- and post- Bev therapy, and variations in Tumor-to-Normal ratio (TNR), Tumor-to-Blood ratio (TBR), and Metabolic Tumor Volume (MTV) were investigated.

RESULTS
The median Progression-Free Survival (PFS) and Overall Survival (OS) rates in the first, neoadjuvant, and recurrence groups were respectively (7.86, 14.27, 4.33) and (12.53, 21.57, 13.23) months. Notably, changes in MET and FMISO MTV in the first-treatment group, MET MTV and FMISO TBR changes in the recurrence group, and MET MTV change in the neoadjuvant group significantly influenced prognosis. In the recurrence group, patients who underwent total resection during initial treatment experienced a prolonged period of 25.9 months from initial treatment to the administration of Bev due to recurrence. Furthermore, cases where the FMISO TBR at recurrence was higher than at the initial treatment observed an extended median OS of 18.63 months upon administering Bev treatment at recurrence.

CONCLUSION
Bev neoadjuvant therapy demonstrated a significant correlation with enhanced PFS and OS outcomes, notably in patients subjected to total resection. In the context of recurrent disease, while the initiation of Bev administration was delayed, a distinct elevation in treatment effectiveness was observed in patients exhibiting an augmented FMISO TBR at the point of recurrence. The observed decreases in MET MTV and FMISO TBR emerge as robust predictors of the efficacy of Bev treatment.
10233-GMC-17 CLINICAL SIGNIFICANCE OF GENETIC ANALYSIS FOR GLIOMA CASES IN OUR INSTITUTE
Authors: Yamaguchi Junya , Ohka Fumiharu , Motomura Kazuya , Kibe Yuji , Shimizu Hiroki , Nishikawa Tomohide , Maeda Sachi , Takido Yuhei , Saito Ryuta 
Published: December 2023

Abstract
The WHO Classification the 5th edition describes that identification of alterations in IDH gene, histone H3 gene, CDKN2A gene, and other genes are quite important for the diagnosis and grading of diffuse gliomas. It is important to efficiently analyze important genetic abnormalities and utilize them in actual clinical practice. In our institute, we have recently performed genetic analysis which is important for the diagnosis of glioma in all patients. Here, we report the results of these analyses. From March 2019 to June 2023, we performed Sanger sequencing for analyses of IDH1/2, H3F3A, TERT promoter, BRAF, and FGFR1 mutation in 235 patients with suspected glioma who underwent biopsy or resection at our hospital and affiliated institutions. In 145 cases, we performed MLPA analyses for detection of 1p/19q codeletion, CDKN2A homozygous deletion (HD), EGFR amplification, and Chromosome 7p gain/10q loss. Sanger sequencing identified 81 TERT promoter mutations, 70 IDH mutations (including 3 IDH2 mutations), 8 BRAF V600E mutations, 4 H3 K27M mutations, 3 H3 G34R/V mutations, and 1 FGFR1 mutation The alterations most frequently identified in MLPA were CDKN2A HD in 26 cases and 1p/19q codeletion in 19 cases. Of the 214 cases in which the pathology diagnosis was neoplastic disease, 85 (39.8%) had no abnormalities in the above genetic analysis. In 32 of these cases, the pathological diagnosis was glioblastoma, IDH-wildtype, while in many other cases, the pathological diagnosis was low-grade glioma. Genetic analysis focusing on important genes for diagnosis according to WHO classification the 5th edition was useful for diagnosis in many cases, but careful consideration is needed for diagnosis in cases without these genetic alterations.
10235-TB-9 TRANSLATIONAL RESEARCH OF BORON NEUTRON CAPTURE THERAPY FOR SPINAL CORD AND SPINE TUMOR IN ANIMAL MODELS
Authors: Fujikawa Yoshiki , Kawabata Shinji , Kayama Ryo , Tsujino Kohei , Kashiwagi Hideki , Fukuo Yusuke , Hiramatsu Ryo , Takata Takushi , Tanaka Hiroki , Suzuki Minoru , Hu Naonori , Miyatake Shin-Ichi , Takami Toshihiro , Wanibuchi Masahiko 
Published: December 2023

Abstract

BACKGROUND
Boron Neutron Capture Therapy (BNCT) is a particle beam therapy that can target at the cellular level. This study evaluated the effectiveness of BNCT on spinal cord gliomas using animal models.

METHODS
F98 rat glioma or 9L rat gliosarcoma cell lines were implanted in rats' spinal cords to create a model. BPA, a boron compound, was administered and the biodistribution compared. Neutron irradiation was performed post-BPA injection, and the effectiveness was evaluated by survival period and hindlimb muscle strength using the Basso-Bresnahan-Beattie (BBB) score.

RESULTS
Significant boron accumulation was observed in tumors. In irradiation experiments, the BNCT group showed suppressed BBB score decrease and a significantly extended survival period compared to other groups. No cases of death or lower limb function decline were observed in the sham-BNCT group.

CONCLUSION
BNCT for spinal cord gliomas was shown to be safe and effective. The spinal cord is an organ at risk in irradiation for spinal cord and spine tumors. As it has a history of being a safety evaluation organ when applying BNCT to the central nervous system, BNCT may be applicable to cases such as recurrence after radiation therapy.
10243-IMT-3 LONG-TERM OUTCOME OF A COCKTAIL WILMS' TUMOR 1 (WT1) VACCINATION USING TWO HLA CLASS I PEPTIDES AND ONE CLASS II PEPTIDE AGAINST RECURRENT MALIGNANT GLIOMAS
Authors: Kagawa Naoki , Oji Yusuke , Hirayama Ryuichi , Kijima Noriyuki , Oka Yoshihiro , Sugiyama Haruo , Kishima Haruhiko 
Published: December 2023

Abstract

PURPOSE
Our clinical trials show the safety and clinical efficacy of Wilms' tumor 1 (WT1) human leukocyte antigen (HLA) class I (Izumoto S et al. J Neurosurg. 2008) and class II (Tsuboi A et al. Cancer Immunol Immunother. 2019) peptide vaccination for recurrent malignant gliomas have been established. We have developed a cocktail vaccine (WT1 trio) containing two class I peptides (HLA-A*24:02 and HLA-A*02:01) and one II class peptide to improve more effective immunological response and improve patient's prognosis. Clinical trial of a cocktail vaccination using WT1 HLA class I and II peptides for recurrent malignant gliomas is planned to verify its safety, clinical efficacy and usefulness of surrogate markers. Patients and

METHODS
Twenty-three patients with recurrent malignant gliomas, which showed WT1-positive in tumor samples and HLA-A*24:02 or HLA-A*02:01-positive in blood sample, were enrolled. These patients (age: 26-72 years old, average: 49.4) included 15 cases of glioblastomas and 8 of anaplastic astrocytomas. Patients received a WT1 trio vaccine intradermally, 7 times at 2-week intervals during 3 months.WT1-DTH and WT1-IgG antibody were regularly measured. Vaccine-related adverse events, best clinical response and the transfer rate of long-term administration of WT1 trio vaccination were estimated.

RESULTS
WT1-DTH positive cases were 12, WT1-IgG antibody positive were in 11. In most patients, WT1 -DTH positiveness coincided with that of WT1-IgG antibody. 9 of 11 cases showed stable disease at 3 months and transferred long-term administration of WT1 trio vaccination. Transfer rate in GBM and AA of long-term administration was 33% and 25%, respectively. Grade1 skin eruption was observed at the injection sites in 15 cases, but no significant adverse events related with vaccination were shown. Conclusion: WT1-DTH and WT1-IgG antibody may be useful surrogate markers. Long-term outcome of WT1 trio vaccination was verified for recurrent malignant gliomas.
10247-ET-8 HHYPOXIA-TARGETING RADIOPHARMACEUTICAL 64CU-ATSM FOR PET MONITORING WITH LOCAL THERAPY IN HIGH-GRADE GLIOMA PATIENT-DERIVED XENOGRAFT MODEL
Authors: Tateishi Kensuke , Hihara Fukiko , Oshima Akito , Yamamoto Tetsuya , Yoshii Yukie 
Published: December 2023

Abstract
High-grade gliomas (HGGs) are highly aggressive brain cancers characterized by the presence of hypoxia within a rapidly-growing tumor mass. Due to invasion to the surrounding brain parenchyma, these tumors commonly recur locally,, and novel local approaches are required. Here, we show a positron emission tomography (PET) integrated local therapy (PETx), to target HGGs. This technique consists of a one-step local theranostic application, followed by PET monitoring, with a hypoxia-targeting radiopharmaceutical64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM). We examined the safety and therapeutic potential of 64Cu-ATSM PETx for HGG patient-derived xenograft (PDX) tumors. PDX models were recapitulated the parent tumor phenotype of high expression of HIF-1 alpha and BNIP3, biomarkers of tissue hypoxia. We confirmed that HIF-1 alpha and BNIP3 were highly upregulated under hypoxia and 64Cu-ATSM was retained with potent cytotoxic effect under hypoxic condition in vitro. We determined that determined the maximum tolerated dose (MTD) to be 3.7 MBq in mouse. PETx using the MTD dose of 64Cu-ATSM indicated high tumor penetration, distribution, and retention of 64Cu-ATSM in PDX tumors, as compared to sham-treated mice. The 64Cu-ATSM PETx promoted DNA double-strand breaks, followed by apoptosis in tumors, and extensively prolonged overall survival with tolerable systemic toxicity. These findings indicate the potential of 64Cu-ATSM PETx to induce high uptake in the hypoxic tumor microenvironment, and strong therapeutic effects in PDX models. These findings establish 64Cu-ATSM PETx as a potential novel theranostic approach to facilitate local control of HGGs.
10252-COT-27 TWO CASES OF OVARIAN HYPERSTIMULATION SYNDROME IN A YOUNG FEMALE PATIENTS WITH GLIOMA WHO UNDERWENT OOCYTE CRYOPRESERVATION.
Authors: Nonoguchi Naosuke , Takai Satoshi , Yagi Ryokichi , Kazuki Rina , Ryu Masae , Umegaki Osamu , Fujita Taisuke , Fukuo Yusuke , Hiramatsu Ryo , Kosaka Takuya , Kameda Masahiro , Furuse Motomasa , Kawabata Shinji , Takami Toshihiro , Wanibuchi Masahiko 
Published: December 2023

Abstract
Young women with malignant gliomas may wish to have their oocytes preserved prior to the start of chemotherapy in order to maintain fertility. In such cases, fertility drugs make it possible to mature and retrieve multiple oocytes in the ovaries. However, the ovaries may overreact and mature many oocytes at once, resulting in adverse symptoms such as abnormal swelling of the ovaries, abdominal discomfort and pain, nausea and vomiting, abdominal distention, fluid retention (edema), and difficulty breathing. This is called ovarian hyperstimulation syndrome (OHSS), in which excessive secretion of estradiol associated with multiple follicle development leads to excessive production of VEGF, which rapidly increases the vascular permeability of systemic organs, resulting in a fluid shift into the third space, which is thought to cause ascites and pulmonary edema. In severe cases, intravascular dehydration and decreased circulating plasma volume can cause hypotension and oliguria, and the increased coagulation capacity associated with hemoconcentration can cause serious thrombotic complications. The severity of OHSS is classified into three levels: mild, moderate, and severe, based on four findings: subjective symptoms, the amount of pleural effusion, the degree of ovarian enlargement (ovarian diameter), and blood test findings. Early detection and appropriate management are essential. We have had two cases of OHSS, one of which was moderate and resolved successfully, while the other became severe, and we had to postpone the start of radiotherapy for a week longer than planned. Severe OHSS is a medical complication that neurosurgeons rarely encounter, and we report this case with a literature review.
10268-NI-13 T2-FLAIR MISMATCH SIGN CORRELATES WITH11C-METHIONINE UPTAKE IN LOWER-GRADE DIFFUSE GLIOMAS
Authors: Ebiko Yusuke , Tamura Kaoru , Hara Shoko , Inaji Motoki , Tanaka Yoji , Nariai Tadashi , Ishii Kenji , Maehara Taketoshi 
Published: December 2023

Abstract

PURPOSE
The T2-FLAIR mismatch sign is recognized as an imaging finding highly suggestive of IDH-mutant astrocytomas. This study was designed to determine whether the T2-FLAIR mismatch sign correlates with uptake of 11C-methionine in lower-grade gliomas.

METHODS
We included 78 histopathologically verified lower-grade gliomas (grade 2: 31 cases, grade 3: 47 cases) in this study. 78 patients underwent 11C-methionine positron emission tomography (MET-PET) scans and magnetic resonance (MR) imaging scans prior to histological diagnosis. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. MR imaging scans were evaluated for the presence of the T2-FLAIR mismatch sign by three independent reviewers. We compared molecular status, the T2-FLAIR mismatch sign and 11C-methionine uptake among patients with different lower-grade glioma molecular types.

RESULTS
The 78 lower-grade gliomas were assigned to one of three molecular groups: Group A (IDH-mutant and 1p/19q non-codeleted, n=22), Group O (IDH-mutant and 1p/19q codeleted, n=20), and Group W (IDH wildtype, n=36). T2-FLAIR mismatch was found in 16 cases (20.5%) that were comprised of 8 (36.4%), 0 (0%), 8 (22.2%) cases in the molecular group A, O and W, respectively. The median T/N ratio of MET-PET in tumors with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.83, p&lt;0.001, Mann-Whitney U test). In the Groups A and W (excluding Group O), the median T/N ratio on MET-PET in groups A and W (but not group O) with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.81, p=0.002, Mann-Whitney U test).

CONCLUSION
The T2-FLAIR mismatch sign correlated with lower 11C-methionine uptake in lower grade gliomas.
10269-ET-10 ARRAYS FOR DELIVERING TUMOR TREATING FIELDS (TTFIELDS) TO THE MOUSE HEAD
Authors: Zbidat Sewar , Blatt Roni , Sellevoll Mariell , Gabay Martin , Schlachet Inbar , Cahal Shay , Davidi Shiri , Tzchori Itai , Enjo Kentaro , Haber Adi , Giladi Moshe , Palti Yoram 
Published: December 2023

Abstract

INTRODUCTION
Tumor Treating Fields (TTFields) therapy is an approved treatment for glioblastoma (GBM), the most common malignant brain tumor. TTFields therapy is delivered continuously by two pairs of arrays placed orthogonally on the skin surrounding the tumor region. Investigational in vivo work in the field of GBM currently utilizes mouse models. To expand the possibility for TTFields-GBM in vivo studies, TTFields arrays for the mouse head are needed. The small dimensions and specific geometries of the mouse head make the development of such arrays challenging.

METHODS
We tested a variety of layouts for the arrays to identify one that will be suited to the geometries of the mouse head, and that will minimally restrict head movement. Efficient treatment delivery requires good adherence to the skin; hence, we investigated different skin attachment adhesive tapes. To validate the ability of the selected arrays to deliver therapeutic field intensity to the desired region, we performed direct fields measurements and simulations.

RESULTS
We employed 2 strategies to overcome the small size and confining geometries of the mouse head: (1) only two of the four arrays were situated on the head – opposing arrays were placed on the mouse torso; (2) the arrays on the head were each divided into two small disks instead of just one large disk. We identified an adhesive tape for securing the arrays to the skin that was thin and transparent, facilitating correct positioning of the arrays on the mouse head. The tape also offered good tackiness, and allowed for easy removal without leaving residual adhesive on the skin, facilitating repeated array placement. The arrays met the requirements for efficient treatment: field intensity ≥ 1 V/cm RMS, current ≥ 50 mA, usage ≥ 75%.

CONCLUSIONS
We were able to develop flexible mouse head arrays, that adheres strongly to the skin, enabling efficient electric field delivery with minimal animal discomfort. These arrays provide means to expand TTFields-GBM treatment research, and will contribute to advance this field.
A LINE-1 mediated deletion resulting in germline retinoblastoma predisposition
Authors: Macke Erica L , Miller Anthony R , Stonerock Eileen , Olshefski Randal , Zajo Kristin , Bedrosian Tracy A , Mardis Elaine R , Akkari Yassmine M N , Cottrell Catherine E , Schieffer Kathleen M 
Published: December 2023

Abstract
Retinoblastoma is an ocular cancer associated with genomic variation in the RB1 gene. In individuals with bilateral retinoblastoma, a germline variant in RB1 is identified in virtually all cases. We describe herein an individual with bilateral retinoblastoma for whom multiple clinical lab assays performed by outside commercial laboratories failed to identify a germline RB1 variant. Paired tumor/normal exome sequencing, long-read whole genome sequencing, and long-read isoform sequencing was performed on a translational research basis ultimately identified a germline likely de novo Long Interspersed Nuclear Element (LINE)-1 mediated deletion resulting in a premature stop of translation of RB1 as the underlying genetic cause of retinoblastoma in this individual. Based on these research findings, the LINE-1 mediated deletion was confirmed via Sanger sequencing in our clinical laboratory, and results were reported in the patient's medical record to allow for appropriate genetic counseling.