bluuebunny/crossref_metadata_2025_split huggingface dataset:
“I Go on This Golf Trip Every Year, but It Hurts to Swing a Club.”: Back Pain and Golf
Authors: Bires Seth , Standaert Christopher J. , Jayabalan Prakash 
Published: November 2024

Abstract
Low back pain (LBP) is one the most common injuries seen in professional and recreational golfers, accounting for 25% of all golf injuries. Multiple factors are linked to the increased risk of LBP in golfers, including the repetitive nature of the golf swing, carrying a golf bag, and individual demographics and physical characteristics. The management of LBP in golfers involves integrating an understanding of LBP and spine pathology, in general, with the biomechanics of the golf swing. A golf swing uses a wide range of musculature throughout the body and exposes the lumbar spine to significant compressive and torsional forces. Specific to golfers, history should include previous LBP with golf and the amount of general and golf-specific activity the patient performs on a regular basis. Treatment involves the introduction of exercise and skill training to improve the mechanics and performance of an individual’s swing and to improve overall fitness.
10109- ANGI-4 INTRATUMORAL THROMBOSIS AS A HISTOLOGICAL BIOMARKER FOR PREDICTING EPIDERMAL GROWTH FACTOR RECEPTOR ALTERATION AND POOR PROGNOSIS IN PATIENTS WITH GLIOBLASTOMAS
Authors: Negoto Tetsuya , Furuta Takuya , Yoshitake Hidenobu , Moritsubo Mayuko , Hashimoto Aya , Takeshige Nobuyuki , Sakata Kiyohiko , Nakamura Hideo , Morioka Motohiro 
Published: November 2024

Abstract

PURPOSE
Intratumoral thrombosis is a specific finding in glioblastomas and considered the origin of palisading necrosis. Its distribution and contribution to the glioblastoma pathophysiology and systemic thrombosis are obscure, although deep vein thrombosis is a common complication in glioblastoma cases.

METHODS
Clinicopathological and genetic analyses were performed on 97 glioblastoma tissue specimens to elucidate the role of thrombotic events and associated molecular abnormalities.

RESULTS
Morphologically, intratumoral thrombosis was observed more frequently in vessels composed of single-layered CD34-positive endothelium and/or αSMA-positive pericytes in the tumor periphery, compared to microvascular proliferation with multi-channeled and pericyte-proliferating vessels in the tumor center. Intratumoral thrombosis was significantly correlated with the female sex, high preoperative D-dimer levels, and epidermal growth factor receptor (EGFR) amplification. The presence of one or more thrombi in 20 high-power fields was a predictive marker of EGFR amplification, with a sensitivity of 81.5% and specificity of 52.6%. RNA sequencing demonstrated that the group with many thrombi had higher EGFR gene expression levels than the group with few thrombi. The tumor cells invading along the vessels in the tumor periphery were positive for wild-type EGFR but negative for EGFRvIII, whereas the cells around the microvascular proliferation (MVP) in the tumor center were positive for both wild-type EGFR and EGFRvIII. Intratumoral thrombosis is an independent poor prognostic factor.

CONCLUSIONS
Aberrant but exquisitely regulated EGFR can induce thrombosis in non-MVP vessels in the tumor invasion area and then promote palisading necrosis, followed by hypoxia, abnormal angiogenesis, and further tumor cell invasion.
10180- ANGI-5 COMPREHENSIVE ANALYSIS OF MECHANISM OF INVASION AND DISSEMINATION FOR MALIGNANT BRAIN TUMOR USING XENOGRAFT MODELS
Authors: Kijima Noriyuki , Tachi Tetsuro , Achiha Takamune , Kuroda Hideki , Murakami Koki , Nakagawa Kanji , Wada Yuki , Kishima Haruhiko 
Published: November 2024

Abstract

BACKGROUND
Malignant brain tumors are frequently resistant to current treatments and have a poor prognosis. Many malignant brain tumors invade the surrounding brain tissue and/or show leptomeningeal metastasis when they recur. Thus, elucidating the mechanisms of invasion and leptomeningeal metastasis is important to improve the prognosis of malignant brain tumors. In this study, we comprehensively analyzed the mechanisms of invasion and leptomeningeal metastasis of malignant brain tumors using mouse xenograft models.

METHODS
Patient derived glioblastoma cells (GDC519) and breast cancer cell line, MDA-MB-231, were labeled with GFP and luciferase. GDC519 were transplanted into the right cerebral cortex of immunodeficient mice and when the mice got tumors, the right and left cerebrum were dissected separately. We sorted tumor cells by flow cytometry and extracted RNA from tumor cells in right and left cerebrum, respectively. We performed RNA sequencing and analyzed the transcriptome differences. On the other hand, MDA-MB-231 cells were injected into the right ventricle of immunodeficient mice. Tumor cells from cerebrospinal fluid, and spinal cords were sorted and analyzed the transcriptome differences by RNA sequencing.

RESULTS
In the model in which GDC519 was transplanted, we found significant differences in expressions of extracellular matrix related proteins, cell motility related proteins, and cell adhesion related proteins between tumor cells in right and left cerebrum. In addition, in the model in which MDA-MB-231 was transplanted into the right ventricle, we found significant differences in expressions of extracellular matrix related proteins and PI3K-Akt signaling pathway related proteins between tumor cells from cerebrospinal fluid and spinal cord.

CONCLUSION
These results suggest that it would be possible to identify molecules involved in the invasion and leptomeningeal metastasis of malignant brain tumors using a mouse xenograft model. Further studies are necessary to examine the functional role of these genes in invasion and leptomeningeal metastasis.
10096- CBMS-3 CURCUMIN ANALOGUE A SHOWS ANTI-TUMOR EFFECTS AT LOWER CONCENTRATIONS THAN CURCUMIN IN GLIOBLASTOMA CELLS
Authors: Ito Ryo , Hamabe Toshihide , Ono Masaya , Iwashimizu Sonoka , Inai Kyoko , Nakanishi Shunsuke , Sunagawa Yoichi , Katanasaka Yasufumi , Hawke Phillip , Arakawa Yoshiki , Miura Masatomo , Hasegawa Koji , Morimoto Tatsuya 
Published: November 2024

Abstract

PURPOSE
Curcumin (Cur), a natural compound, possesses antitumor activity against glioblastoma cells (GBM). However, the bioavailability of Cur is too low to exhibit beneficial effects in vivo. We hypothesized that Cur analogues with enhanced anti-tumor activity against GBM could increase bioavailability and effectiveness. This study investigated the anti-tumor activity of a Cur analog, Compound A (ComA), against GBM.

METHODS AND RESULTS
To evaluate the anti-tumor activity of ComA against GBM, an MTT assay was performed. Human GBM cell lines U251 and T98G were pre-treated with Cur or ComA, and then cell viability was examined using a CCK-8 kit. The IC50 values for U251 were 10.9 μM (Cur) and 2.9 μM (ComA), and those for T98G were 16.6 μM (Cur) and 4.7 μM (ComA). To examine the effects of Cur and ComA on non-tumor cells, the same MTT assay was performed on primary cultured astrocytes from neonatal rats. Neither Cur nor ComA resulted in reduced cell viability in astrocytes at concentrations that had had an anti-tumor effect on GBM cells. Next, a cell cycle analysis was performed on U251 and T98G cells using flow cytometry with PI staining. ComA induced G2/M phase arrest at lower concentrations than Cur. Furthermore, the amount of cellular uptake of Cur and ComA in these cells was quantified. Cellular uptake of ComA was 3.8 times higher than Cur in U251 cells and 3.5 times higher in T98G cells. Finally, when mice were orally administrated with Cur or ComA, the maximum plasma concentration of ComA was about 30 times higher than that of Cur.

DISCUSSION
These results suggest that ComA has an anti-tumor effect due to cell cycle arrest against GBM that occurs at lower concentrations than Cur. Further in vivo studies are required to develop ComA-based novel therapeutic agents against GBM.
10292- CBMS-7 HISTOLOGICAL GRADING AND MOLECULAR GENETIC BACKGROUND OF MENINGIOMAS
Authors: Eguchi Seiichiro , Zaitsu Kei , Ohtani Yuto , Iguchi Akira , Kawamata Takakazu 
Published: November 2024

Abstract

OBJECTIVES
In recent years, due to advances in omics analysis, new findings regarding the malignancy, growth potential, and prognosis of meningiomas have been reported. A classification based on molecular biology and genetic findings has a higher correlation with prognosis. Here, we report a comparative study of the histological malignancy and molecular genetic background of meningiomas using multi-omics analysis.

MATERIALS & METHODS
This study focused on 42 meningioma specimens including 17 meningothelial (G1), 18 atypical (G2) and 7 anaplastic (G3) subtypes, that were removed at our hospital. Metabolome and transcriptome analyses were performed on frozen specimens, multivariate analysis including PCA and PLS-DA was performed on the data obtained from the former, and DEG analysis, GO/pathway and hierarchical cluster analysis were performed on the latter data.

RESULTS
As a result of metabolome analysis, four samples were identified in G2 that had significantly different metabolic profiles from the others. These were designated as the G2 subtype (G2m). Transcriptome analysis confirmed the expression of just under 54,000 genes, and DEG analysis of these revealed that G2m had a significantly different gene expression profile from other G2s. Furthermore, pathway analysis revealed that the MAPK signaling pathway was enhanced in G2m, which was similar to that in G3. However, hierarchical cluster analysis showed that G2m was not similar to any of the profiles of G1-3 in the metabolome hierarchy.

DISCUSSIONS / CONCLUSIONS
It has been shown that among atypical meningiomas, there are subtypes that are molecular genetic similar to anaplastic meningiomas. It is thought that some subtypes of atypical meningiomas exhibit behavior similar to G1, while others are closer to G3. Furthermore, the influence of heterogeneity cannot be ignored even within the same tumor. In the future, it will be necessary to proceed with studies using single-cell RNA analysis.
10296- CBMS-8 CURCUMIN, AN INHIBITOR OF P300-HAT ACTIVITY, SUPPRESSED GLIOBLASTOMA CELL PROLIFERATION IN A STRUCTURE-ACTIVITY RELATIONSHIP STUDY
Authors: Inai Kyoko , Hamabe-Horiike Toshihide , Ono Masaya , Iwashimizu Sonoka , Ito Ryo , Nakanishi Syunsuke , Kawase Yuto , Naruta Ryuya , Sunagawa Yoichi , Katanasaka Yasufumi , Hawke Philip , Arakawa Yoshiki , Hasegawa Koji , Morimoto Tatsuya 
Published: November 2024

Abstract

PURPOSE
Glioblastoma (GBM) is the most common malignant brain tumor. In the treatment of GBM, it is difficult to completely remove tumor tissue by surgery alone, and radiotherapy and chemotherapy are typically used to treat the remaining tissue. However, GBM has a very poor prognosis, with a 5-year survival rate of approximately 10%. In recent years, molecular targeted therapies are becoming more common for all types of cancer, and histone acetylase (HAT) activity has attracted attention as a potential therapeutic target. It has been reported that the HAT activity of the transcriptional co-activator p300 plays a key role in the progression of pancreatic cancer. However, it is not clear whether p300-HAT activity is also crucial for the growth of GBM cells.

METHODS AND RESULTS
We previously reported that while the natural compound curcumin (Cur) inhibits p300-HAT activity, the Cur derivative GO-Y041 does not. To assess the role of p300-HAT activity in GBM cell proliferation, we compared the effect of Cur and GO-Y041 on the cells with an MTT assay. The human GBM cell line U87MG was treated with the two compounds, and cell viability was examined using CCK-8 kit. The results showed that the viability of the cells was significantly decreased by 10 μM Cur compared to the untreated group, while no decrease in viability was observed with 10 μM GO-Y041.

DISCUSSION
These results suggest that p300-HAT activity may play an important role in the proliferation of GBM cells. However, as Cur also acts on proteins other than p300, it is still not completely clear whether p300-HAT activity is essential for GBM growth. To provide insights into the role of p300-HAT activity in GBM cell growth, we will generate cells in which p300-HAT activity alone can be abolished using genetic engineering techniques to pursue the development of novel GBM therapies.
10159- SPDR-4 A RUNX1 SWITCH-OFF APPROACH INHIBITS THE PIF1-P21 AXIS, ONE OF THE MECHANISMS OF GLIOBLASTOMA MALIGNANCY MAINTENANCE
Authors: Yamamoto Etsuko , Masuda Tatsuya , Matsui Yasuzumi , Mineharu Youhei , Makino Yasuhide , Takada Shigeki , Sano Noritaka , Tannji Masahiro , Kamikubo Yasuhiko , Sugiyama Hiroshi , Arakawa Yoshiki 
Published: November 2024

Abstract

BACKGROUND
Glioblastoma is a high-grade brain tumor and Long-term survival is difficult even with multidisciplinary treatment, necessitating the development of novel therapeutic approaches. Although the transcription factor RUNX1 has been implicated in the maintenance of glioblastoma malignancy, its role is still unclear. We have previously demonstrated that administration of a new drug that inhibits transcription of the RUNX family, chlorambucil-conjugated PI polyamide (Chb-M’, co-developed by Kamikubo and Sugiyama), or RUNX1 knockdown, results in cell growth inhibition in glioblastoma cell lines and that the RUNX1-BIRC5-p21 axis is implicated.

METHODS AND RESULTS
Since RUNX1 is a transcription factor associated with multiple gene transcription, we performed microarray experiments using Chb-M’. Since PIF1 association was suggested, chromatin immunoprecipitation and reporter assay were performed, and these showed that RUNX1 directly regulates PIF1. The RUNX1-PIF1-p21 pathway was also found to be involved in the mechanism of glioblastoma malignancy maintenance, as RUNX1 knockdown decreased PIF1 and PIF1 knockdown suppressed cell proliferation and increased p21. Chb-M’ administration in mice glioblastoma model clearly reduced tumor size and prolonged survival compared to controls. In addition, FITC-binding Chb-M’ was administered to mice, and FITC selectively accumulated in tumors, indicating that Chb-M’ was shown to have tumor-specific effects.

DISCUSSION AND CONCLUSION
Chb-M’ has been shown to exert its antitumor effect via the PIF1/p21 axis, and Chb-M’ acts in vivo in a tumor-specific manner, making it a potential new therapeutic agent for glioblastoma. Furthermore, Chb-N’, which has higher cellular affinity than Chb-M’, has been developed and is currently under preclinical investigation.
10082- ET-9 ANTITUMOR AROMA THERAPY WITH FRANKINCENSE ESSENTIAL OIL FOR GLIOBLASTOMA
Authors: Saito Norihiko , Hirai Nozomi , Koyahara Yuki , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Ito Keisuke , Iwabuchi Satoshi 
Published: November 2024

Abstract

INTRODUCTION
Aromatic essential oils have antibacterial, antifungal, antiviral, anti-inflammatory, and antitumor effects. We previously investigated the antitumor effects of aromatic essential oils administered by inhalation as a novel treatment for glioblastoma. The aromatic monoterpene α-pinene, a component of many essential oils, is known to inhibit tumor growth. This study analyzed the antitumor effects of frankincense essential oil, mainly composed of α-pinene, and explored its potential for antitumor aroma therapy in glioblastoma.

METHODS AND RESULTS
Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used. Tumor cells cultured in the presence of frankincense essential oil for 72 hours showed growth inhibition, suggesting that the evaporated components acted on nearby tumor cells. α-Pinene and limonene, the main components of frankincense, also showed similar effects alone. Inhalation studies in mice demonstrated that 30 minutes of α-pinene inhalation had the same brain transfer effect as 90 minutes. Intraperitoneal administration of α-pinene showed minimal brain transfer. For limonene, brain transfer increased with 90 minutes of inhalation compared to 30 minutes. Inhalation resulted in higher brain transfer than intraperitoneal administration. Additionally, α-pinene’s antitumor effects suggested induction of apoptosis and cell cycle arrest.

DISCUSSION
α-Pinene, comprising about 40% of frankincense essential oil, was found to inhibit tumor cell growth in malignant gliomas. This study suggests that α-pinene exerts antitumor effects when administered by inhalation.

CONCLUSION
α-Pinene in frankincense essential oil has antitumor effects and may be a novel “aroma” therapy for treating glioblastoma.
10199- ET-16 NEAR-INFRARED PHOTOIMMUNOTHERAPY FOR THE TREATMENT OF MALIGNANT BRAIN TUMORS
Authors: Natsumeda Manabu , On Jotaro , Shibuma Satoshi , Watanabe Jun , Tsukamoto Yoshihiro , Okada Masayasu , Ogura Ryosuke , Oishi Makoto 
Published: November 2024

Abstract

BACKGROUND
Near-infrared photoimmunotherapy (NIR-PIT) is a novel intraoperative local therapy. It involves a photosensitizer a near-infrared dye (IR700) conjugated to monoclonal antibodies targeting surface antigens of cancer cells. After binding the monoclonal antibody-IR700 conjugate, irradiation with near-infrared light causes highly selective and potent cell death.

METHODS AND RESULTS
The antibodies used for NIR-PIT are as follows: podoplanin for malignant gliomas, SSTR2 for malignant meningiomas, and SSTR5 for GHoma. Expression of surface antigens in cell lines was confirmed by western blot and flow cytometry. We developed lasers for in vitro and in vivo assays. Time-lapse video recordings showed cell rupture and cell viability assays showed irradiation dose-dependent cytotoxicity after treatment with antibody-IR700 conjugate and near-infrared irradiation. In vivo and ex vivo studies were also performed, showing cell death. High selectivity and potency of NIR-PIT were observed, but proper penetration of light and kinetics of antibody were issues that remain to be solved. Preliminary studies confirmed that NIR-PIT is an exciting potential treatment for malignant brain tumors.
10176- IM-7 B7-H3-TARGETED CAR-T AND CAR-NK CELLS AGAINST HUMAN GLIOBLASTOMA
Authors: Tachi Tetsuro , Kijima Noriyuki , Kuroda Hideki , Murakami Koki , Hosen Naoki , Kishima Haruhiko 
Published: November 2024

Abstract
Glioblastoma multiforme (GBM) is the most lethal primary brain tumor, necessitating novel therapies. Chimeric antigen receptor (CAR) T-cell therapy has recently shown efficacy against GBM. However, this approach is costly and time-consuming due to its personalized nature. Alternatively, CAR-transduced natural killer (NK) cells offer a potential “off-the-shelf” immunotherapy option, as they do not cause graft-versus-host disease. This study aimed to assess the anti-GBM efficacy of CAR T and NK cells targeting B7-H3, a protein highly expressed in GBM. To achieve this, CAR T cells targeting B7-H3 were developed using known anti-B7-H3 scFv sequences. Additionally, cord blood-derived NK cells were transduced with the B7-H3 CAR. Both types of CAR-modified cells were tested for their anti-GBM activity in vitro. Moreover, their anti-tumor effects were evaluated in an in vivo xenograft model using patient-derived GBM cells. The results demonstrated that both B7-H3 CAR T cells and CAR NK cells exhibited significant cytotoxicity against patient-derived GBM cells in vitro. Furthermore, intracranial injection of these CAR-modified cells into the xenograft model significantly reduced tumor growth. In conclusion, B7-H3 targeted CAR T cells and cord blood-derived CAR NK cells both show potential in eliminating GBM cells, suggesting promising avenues for future GBM treatment strategies.
10185- BOT-2 ANTITUMOR AROMA THERAPY WITH LEMONGRASS ESSENTIAL OIL FOR GLIOBLASTOMA
Authors: Hirai Nozomi , Saito Norihiko , Koyahara Yuki , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Ito Keisuke , Iwabuchi Satoshi 
Published: November 2024

Abstract

BACKGROUND
In glioblastoma, the only chemotherapy with a clear prognostic effect is temozolomide. Research and development of novel therapies to overcome glioblastoma resistance to treatment is ongoing. We have been studying antitumor aromatherapy using aromatic compounds in aromatic essential oils as a new treatment for glioblastoma. In this study, we focus on citral, the main component of lemongrass essential oil, and report that lemongrass essential oil shows anti-tumor effects in glioma cells and mouse brain tumor models.

METHODS
We used human glioma cells (U251, T98G) and mouse brain tumor cells (RSV-M). We examined the proliferation ability of lemongrass in glioma cells by transpiration and direct administration. The antitumor aroma effect of lemongrass essential oil inhalation in a mouse glioma brain tumor model was evaluated by survival time analysis using the Kaplan-Meier method.

RESULTS
After 72 hours of incubation of tumor cells in the presence of lemongrass essential oil, U251, T98G, and RSV-M all showed anti-proliferative effects, suggesting that the transpired lemongrass essential oil components acted on tumor cells in the vicinity. Direct administration of lemongrass essential oil also inhibited cell proliferation in all glioma cells in a dose- and time-dependent manner. Then, we examined the antitumor effect of lemongrass essential oil in a mouse brain tumor model using RSV-M. The results showed that the survival period was significantly prolonged in the lemongrass essential oil-inhaled group (n=6) compared to the control group (n=6) (p=0.0102), and the cumulative survival rate was not less than 50% at the end of the study.

CONCLUSION
Citral is the main component of lemongrass essential oil, containing about 80%. Citral may have an antitumor effect on glioblastoma, as evidenced by its transpiration effect. In addition, its antitumor effect was also observed in animal experiments, suggesting that it could be a new treatment for glioblastoma.
10154- ACT-8 CURRENT STATUS AND PROBLEMS OF GLIOBLASTOMA TREATMENT USING THE NOVOTTF-100A SYSTEM
Authors: Ogawa Takahiro , Takahashi Yoshinobu , Taniyama Ichita , Yamanaka Takumi , Hashimoto Naoya 
Published: November 2024

Abstract

PURPOSE
The AC electric field tumor therapy system (NovoTTF-100A system: NovoTTF) in combination with temozolomide chemotherapy is now covered by insurance as maintenance therapy for glioblastoma. While the system is expected to prolong survival, it is recommended to be used for at least 18 hours per day (75% of the time), making it difficult for some patients to continue using the system. We investigated the effect of NovoTTF usage rate on the efficacy of treatment based on our own experience.

METHOD
Thirteen patients with first-episode glioblastoma treated with NovoTTF between January 1, 2020 and June 30, 2024 were included in this study. 6 patients in the high daily use rate group (&gt;75%) and 7 patients in the low daily use rate group (&lt;75%) were compared.

RESULTS
The median age of patients in the high-use group was 63 (50-78) years, and 74 (50-79) years in the low-use group. 2-year survival rates were 33.3% and 0%, respectively, with some patients in the high-use group surviving longer than 2 years. Skin lesions occurred in 33.3% of the high-use group and 71.4% of the low-use group, with a higher incidence of skin lesions in the low-use group. The mean daily use rate was 86.0% (78.8-97.0) in the high use group and 38.3% (26.0-69.0) in the low use group, and the mean days of use were 342.5 (5-1086) and 88.7 (20-240), respectively. The median KPS was 90 (50-100) in the high use group and 90 (60-100) in the low use group.

CONCLUSION
The high NovoTTF use rate group tended to be younger and had a lower frequency of skin lesions, and there were cases of long-term survival. It is important to increase the use of NovoTTF for elderly patients and skin disorders.