Clinical characteristics and pathological features of undetectable clinically significant prostate cancer on multiparametric magnetic resonance imaging: A single-center and retrospective study.

Objectives: The objectives of this study were to clarify the pathological features of clinically significant prostate cancer (csPC) that is undetectable on multiparametric magnetic resonance imaging (mpMRI). Material and Methods: This single-center and retrospective study enrolled 33 men with prostate cancer (PC), encompassing 109 PC lesions, who underwent mpMRI before radical prostatectomy. Two radiologists independently assessed the mpMR images of all lesions and compared them with the pathological findings of PC. All PC lesions were marked on resected specimens using prostate imaging reporting and data system version 2.1 and classified into magnetic resonance imaging (MRI)-detectable and MRI-undetectable PC lesions. Each lesion was classified into csPC and clinically insignificant PC. Pathological characteristics were compared between MRI-detectable and MRI-undetectable csPC. Statistical analysis was performed to identify factors associated with MRI detectability. A logistic regression model was used to determine the factors associated with MRI-detectable and MRI-undetectable csPC. Results: Among 109 PC lesions, MRI-detectable and MRI-undetectable PCs accounted for 31% (34/109) and 69% (75/109) of lesions, respectively. All MRI-detectable PCs were csPC. MRI-undetectable PCs included 30 cases of csPC (40%). The detectability of csPC on mpMRI was 53% (34/64). The MRI-undetectable csPC group had a shorter major diameter (10.6 ± 6.6 mm vs. 19.0 ± 6.9 mm, P < 0.001), shorter minor diameter (5.7 ± 2.9 mm vs. 10.7 ± 3.4 mm, P < 0.001), and lower percentage of lesions with Gleason pattern 5 (17% vs. 71%, P < 0.001). Shorter minor diameter (odds ratio [OR], 2.62; P = 0.04) and lower percentage of Gleason pattern 5 (OR, 24; P = 0.01) were independent predictors of MRI-undetectable csPC. Conclusion: The pathological features of MRI-undetectable csPC included shorter minor diameter and lower percentage of Gleason pattern 5. csPC with shorter minor diameter may not be detected on mpMRI. Some MRI-undetectable csPC lesions exhibited sufficient size and Gleason pattern 5, emphasizing the need for further understanding of pathological factors contributing to MRI detectability.

Hibernoma in the renal sinus: A case mimicking malignancy.

Introduction: Hibernomas are benign tumors of brown adipose tissue. Hibernoma in the renal sinus is extremely rare. Herein, we present the third known case of renal hibernoma. Case presentation: A 71-year-old man reported to our department with a left kidney tumor with an average growth rate of 5 mm/year and a progressive contrast effect on computed tomography. It was diagnosed as a hibernoma following a laparoscopic radical nephrectomy. Conclusion: We encountered a rare case of a hibernoma in the renal sinus. Development of new and accurate diagnostic methods for hibernoma, without resorting to nephrectomy, is essential.

A case of uterine adenomyoma of endocervical type that was suspected as minimal deviation adenocarcinoma on biopsy, MRI findings, and literature review.

Uterine adenomyomas of endocervical type are rare benign tumors of the uterine cervix commonly presented as cyst-like, dilated glandular structures within polypoid masses. A premenopausal woman in her 50s was referred to our hospital because of an increasing watery vaginal discharge. A multifocal cyst measuring 5 × 4.5 cm in size projecting into the endocervical canal was revealed on a contrast-enhanced MRI. The fluid within the tumor showed a hypointense signal on T1-weighted imaging (T1WI) and a hyperintense signal on T2-weighted imaging (T2WI). On T2WI, most of the septa within the tumor showed a slightly hyperintense to hypointense signal, whereas some areas revealed a strong hypointense signal; the contrast effect on the septum was satisfactory. On the T2WI taken 2 years previously, the tumor was a 4.5 × 3.5 cm polypoid mass protruding from the posterior endocervical wall. Contrastingly, the current T2WI showed that the stem was no longer identifiable because of tumor growth. Because previous imaging showed that the tumor was a stalked tumor protruding from the posterior endocervical wall, the imaging diagnosis was uterine adenomyoma of the endocervical type. A biopsy suggested the possibility of a minimal deviation adenocarcinoma (MDA). Hence, a total hysterectomy was performed. The final diagnosis confirmed the uterine adenomyoma of endocervical type. Uterine adenomyoma of the endocervical type might be difficult to differentiate from MDA in small biopsy specimens; therefore, evaluation of morphology by MRI is considered important in preoperative diagnosis.

Chemical and Chemoenzymatic Synthesis of Peptide and Protein Therapeutics Conjugated with Human N-Glycans.

Glycosylation is one of the most ubiquitous post-translational modifications. It affects the structure and function of peptides/proteins and consequently has a significant impact on various biological events. However, the structural complexity and heterogeneity of glycopeptides/proteins caused by the diversity of glycan structures and glycosylation sites complicates the detailed elucidation of glycan function and hampers their clinical applications. To address these challenges, chemical and/or enzyme-assisted synthesis methods have been developed to realize glycopeptides/proteins with well-defined glycan morphologies. In particular, N-glycans are expected to be useful for improving the solubility, in vivo half-life and aggregation of bioactive peptides/proteins that have had limited clinical applications so far due to their short duration of action in the blood and unsuitable physicochemical properties. Chemical glycosylation performed in a post-synthetic procedure can be used to facilitate the development of glycopeptide/protein analogues or mimetics that are superior to the original molecules in terms of physicochemical and pharmacokinetic properties. N-glycans are used to modify targets because they are highly biodegradable and biocompatible and have structures that already exist in the human body. On the practical side, from a quality control perspective, close attention should be paid to their structural homogeneity when they are to be applied to pharmaceuticals.

Long-term outcomes of multidisciplinary treatment combining surgery and stereotactic radiotherapy with Novalis for craniopharyngioma.

Craniopharyngiomas are difficult to resect completely, recurrence is frequent, and hypothalamic/pituitary function may be affected after surgery. Therefore, the ideal treatment for craniopharyngiomas is local control with preservation of hypothalamic and pituitary functions. The purpose of this study is to retrospectively evaluate the long-term efficacy and adverse events of stereotactic radiotherapy (SRT) with Novalis for craniopharyngioma. This study included 23 patients with craniopharyngiomas who underwent surgery between 2006 and 2021 and underwent SRT as their first irradiation after surgery. The median post-irradiation observation period was 88 months, with the overall survival rates of 100 % at 10 years and 85.7 % at 20 years. One patient died of adrenal insufficiency 12 years after irradiation. The local control rate of the cystic component was 91.3 % at 5 years, 83.0 % at 15 years, with no increase in the solid component. No delayed impairment of visual or pituitary function due to irradiation was observed. No new hypothalamic dysfunction was observed after radiation therapy. No delayed adverse events such as brain necrosis, cerebral artery stenosis, cerebral infarction, or secondary brain tumors were also observed. SRT was safe and effective over the long term in patients irradiated in childhood as well as adults, with no local recurrence or adverse events. We believe that surgical planning for craniopharyngioma with stereotactic radiotherapy in mind is effective in maintaining a good prognosis and quality of life.

Left ventricular remodeling and long-term outcomes of aortic stenosis patients receiving 19 mm Mosaic.

Mosaic valve shows higher pressure gradient after aortic valve replacement compared to other same size labeled prostheses in postoperative echocardiogram. The purpose of this study was to evaluate the mid-term echocardiogram findings and long-term clinical outcomes of patients receiving a 19 mm Mosaic. Forty-six aortic stenosis patients receiving 19 mm Mosaic and 112 patients receiving either 19 mm Magna or Inspiris, who underwent mid-term follow-up echocardiogram were included in the study. Mid-term hemodynamic measurements evaluated by trans-thoracic echocardiogram and long-term outcomes were compared. Patients receiving Mosaic were significantly older (Mosaic: 76 ± 5.1 years vs. Magna/Inspiris: 74 ± 5.5 years, p = 0.046) and had smaller body surface area (Mosaic: 1.40 ± 0.114m2 vs. Magna/Inspiris: 1.48 ± 0.143m2, p < 0.001). There were no significant differences in comorbidities and medications. Post-operative echocardiogram performed at 1 week after the surgery showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 38 ± 13.5 mmHg vs. Magna/Inspiris: 31 ± 10.7 mmHg, p = 0.002). Furthermore, mid-term echocardiogram follow-up performed at median duration of 53 ± 14.9 months after the surgery continuously showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 45 ± 15.6 mmHg vs. Magna/Inspiris: 32 ± 13.0 mmHg, p < 0.001). However, there were no significant difference in changes in left ventricular mass from baseline in both groups. Kaplan-Meyer curve also showed no difference in long-term mortality and major adverse cardiac and cerebrovascular event between the two groups. Although the pressure gradient across the valve evaluated by echocardiogram was higher in 19 mm Mosaic compared to 19 mm Magna/Inspiris, there were no significant differences in left ventricular remodeling and long-term outcomes between the two groups.

Primary renal neuroendocrine tumor: A case report with computed tomography findings.

We report a rare case of a primary renal neuroendocrine tumor. The patient was a 64-year-old woman. The patient's chief complaint was gross hematuria. Dynamic contrast-enhanced computed tomography (CT) revealed a hypovascular mass 13 cm in diameter in the right kidney. The border of the mass was clear. A grossly contrast-impaired area and internal granular calcification were observed. A right radical nephrectomy was performed. Macroscopically, the mass was hemorrhaged and necrotic. It was diagnosed as a neuroendocrine tumor (NET) (Grade 2) histologically. Findings, such as hypovascularity, calcification, and necrosis, in our case were similar to those in previous reports. These findings are considered relatively characteristic of primary renal NETs.

Evaluation of virtual monochromatic imaging with dual-energy computed tomography of small liver metastases from malignant abdominal tumours: Quantitative and qualitative analyses.

Background: The assessment of small metastatic liver tumours using dual-energy computed tomography (DECT) has not been fully established. Purpose: To assess the effect of low-keV virtual monochromatic imaging (VMI) with non-contrast and contrast-enhanced DECT on the qualitative and quantitative image parameters of small liver metastases. Material and methods: Two radiologists retrospectively evaluated 92 metastatic liver tumours (5-20 mm) in 32 patients. Non-contrast and contrast-enhanced VMI were reconstructed at seven energy levels (40-100 keV) with 10-keV intervals. Lesion boundary, lesion delineation, image noise, and overall image quality were evaluated using the visual analogue scale. A high subjective score indicates good overall image quality, clear nodal boundaries and delineation, and less noticeable image noise. Subjective scores were compared using the Kruskal-Wallis test. A quantitative analysis involving the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) was performed. Results: The lesion boundary was highest at 40 keV and significantly improved during the non-contrast portal venous phase compared to that at higher keV (p < .005). The lesion delineation score was significantly higher at 40 keV and tended to decrease at higher keV. Image noise and overall image quality were rated low at low keV; however, those at 80, 90, and 100 keV were rated the highest (p < .005). The CNR and SNR were highest for non-contrast CT at 100 keV. During the portal venous phase, no significant differences were observed in CNR and SNR at each keV. Conclusion: Low-keV imaging using non-contrast and contrast-enhanced DECT is useful for delineating small hepatic metastatic tumours.

[Non-A Non-B Aortic Dissection Complicated with Right Aortic Arch Treated by Extended Thoracic Aortic Repair].

A 44-year old man with a history of Stanford type B acute aortic dissection was admitted for the treatment of acute aortic dissection. Computed tomography( CT) scan showed a descending entry-type non-A non-B aortic dissection with a maximum diameter of 65 mm occurring in a patient with Edwards typeⅢ right aortic arch whose left subclavian artery was obliterated. The patient was initially treated conservatively and underwent one-stage extended aortic repair from the ascending aorta to the descending thoracic aorta via median sternotomy 22 days after the symptom onset. Although the patient suffered from right empyema postoperatively, he was discharged from the hospital on postoperative day 64 after 4 weeks antibiotics therapy. The patient was also complicated by right recurrent nerve palsy, hoarseness improved over the 8 months after surgery.

Cell shape instability during cytokinesis in tetraploid HCT116 cells.

Tetraploidy is a hallmark of broad cancer types, but it remains largely unknown which aspects of cellular processes are influenced by tetraploidization in human cells. Here, we found that tetraploid HCT116 cells manifested severe cell shape instability during cytokinesis, unlike their diploid counterparts. The cell shape instability accompanied the formation of protrusive deformation at the cell poles, indicating ectopic contractile activity of the cell cortex. While cytokinesis regulators such as RhoA and anillin correctly accumulated at the equatorial cortex, myosin II was over-accumulated at the cell poles, specifically in tetraploid cells. Suppression of myosin II activity by Y27632 treatment restored smooth cell shape in tetraploids during cytokinesis, indicating dysregulation of myosin II as a primary cause of the cell shape instability in the tetraploid state. Our results demonstrate a new aspect of the dynamic cellular process profoundly affected by tetraploidization in human cells, which provides a clue to molecular mechanisms of tetraploidy-driven pathogenic processes.

Low-dose nafamostat mesilate ameliorates tissue injury and inhibits 5-hydroxytryptamine synthesis in the rat intestine after methotrexate administration.

We aimed to clarify the effect of nafamostat mesilate (nafamostat) on intestinal mucositis as well as the potentiation of intestinal 5-hydroxytryptamine (5-HT) dynamics induced by methotrexate, an anti-cancer drug, in rats. Rats received intraperitoneal methotrexate at 12.5 mg/kg/day for 4 days. In addition, 1, 3, or 10 mg/kg/day of nafamostat was given subcutaneously for 4 days. Ninety-six hours after the first administration of methotrexate, jejunal tissues were collected for analysis. The results showed that 1 mg/kg, but not 3 or 10 mg/kg, of nafamostat significantly ameliorated the methotrexate-induced body weight loss. Moreover, 1 mg/kg of nafamostat significantly improved methotrexate-induced mucositis, including villus atrophy. Nafamostat (1 mg/kg) significantly inhibited the methotrexate-induced mRNA expression of pro-inflammatory cytokines and cyclooxygenase-2, as well as methotrexate-induced 5-HT content and tryptophan hydroxylase (TPH) activity. In addition, it tended to inhibit the number of anti-TPH antibody-positive cells and significantly inhibited the number of anti-substance P antibody-positive cells. These findings suggest that low-dose nafamostat ameliorates tissue injury and 5-HT and substance P synthesis in methotrexate-induced mucositis. Nafamostat may be a novel therapeutic strategy for the prevention and treatment of mucositis as well as 5-HT- and/or substance P-related adverse effects in cancer chemotherapy.

Lynch syndrome-associated chordoma with high tumor mutational burden and significant response to immune checkpoint inhibitors.

Chordoma is a rare malignant bone tumor arising from notochordal tissue. Conventional treatments, such as radical resection and high-dose irradiation, frequently fail to control the tumor, resulting in recurrence and re-growth. In this study, genetic analysis of the tumor in a 72-year-old male patient with refractory conventional chordoma of the skull base revealed a high tumor mutational burden (TMB) and mutations in the MSH6 and MLH1 genes, which are found in Lynch syndrome. The patient and his family had a dense cancer history, and subsequent germline genetic testing revealed Lynch syndrome. This is the first report of a chordoma that has been genetically proven to be Lynch syndrome. Chordomas usually have low TMB; however, this is an unusual case, because the TMB was high, and immune checkpoint inhibitors effectively controlled the tumor. This case provides a basis for determining the indications for immunotherapy of chordoma based on the genetic analysis. Therefore, further extensive genetic analysis in the future will help to stratify the treatment of chordoma.

CDKAL1 Drives the Maintenance of Cancer Stem-Like Cells by Assembling the eIF4F Translation Initiation Complex.

Cancer stem-like cells (CSCs) have a unique translation mode, but little is understood about the process of elongation, especially the contribution of tRNA modifications to the maintenance of CSCs properties. Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. CDKAL1 expression is upregulated in patients with worse prognoses and is essential for maintaining CSCs in rhabdomyosarcoma (RMS) and common cancers. Translatome analysis reveals that a group of mRNAs whose translation is CDKAL1-dependent contains cytosine-rich sequences in the 5' untranslated region (5'UTR). Mechanistically, CDKAL1 promotes the translation of such mRNAs by organizing the eIF4F translation initiation complex. This complex formation does not require the enzyme activity of CDKAL1 but requires only the NH2 -terminus domain of CDKAL1. Furthermore, sites in CDKAL1 essential for forming the eIF4F complex are identified and discovered candidate inhibitors of CDKAL1-dependent translation.

Granulomatosis with polyangiitis presenting as multiple renal masses: A case report with MRI findings.

It is extremely rare for granulomatosis with polyangiitis to form masses in the kidneys. Magnetic resonance imaging findings of renal masses caused by this disease have been infrequently reported. In this study, we report a case of renal masses caused by granulomatosis with polyangiitis with different findings. While on steroid treatment for a recently diagnosed granulomatosis with polyangiitis, a man in his 60s underwent computed tomography for a hepatic dysfunction. Computed tomography showed incidental findings of a 40 mm × 35 mm mass in the left kidney and two 8 mm × 8 mm masses in the right kidney; all masses were hypovascular. On magnetic resonance imaging, the left renal mass showed a hyperintense signal with slightly hypointense signal rim on T2-weighted imaging. The left renal mass showed a strong hypointense signal where the mass abutted the renal capsule. On diffusion-weighted imaging, the left renal mass showed an isointense signal with a hyperintense signal rim. Both right renal masses showed an isointense signal with slightly hypointense signal rim on T2-weighted imaging and hyperintense signal on diffusion-weighted imaging. Suspecting renal masses caused by the disease, the patient was then treated with steroids and methotrexate. After 6 months of treatment, both right renal masses resolved; however, the left renal mass shrank but abnormal signal remained. Based on the treatment course, it is conceivable that the renal masses were caused by granulomatosis with polyangiitis.

Tetraploidy-linked sensitization to CENP-E inhibition in human cells.

Tetraploidy is a hallmark of cancer cells, and tetraploidy-selective cell growth suppression is a potential strategy for targeted cancer therapy. However, how tetraploid cells differ from normal diploids in their sensitivity to anti-proliferative treatments remains largely unknown. In this study, we found that tetraploid cells are significantly more susceptible to inhibitors of a mitotic kinesin (CENP-E) than are diploids. Treatment with a CENP-E inhibitor preferentially diminished the tetraploid cell population in a diploid-tetraploid co-culture at optimum conditions. Live imaging revealed that a tetraploidy-linked increase in unsolvable chromosome misalignment caused substantially longer mitotic delay in tetraploids than in diploids upon moderate CENP-E inhibition. This time gap of mitotic arrest resulted in cohesion fatigue and subsequent cell death, specifically in tetraploids, leading to tetraploidy-selective cell growth suppression. In contrast, the microtubule-stabilizing compound paclitaxel caused tetraploidy-selective suppression through the aggravation of spindle multipolarization. We also found that treatment with a CENP-E inhibitor had superior generality to paclitaxel in its tetraploidy selectivity across a broader spectrum of cell lines. Our results highlight the unique properties of CENP-E inhibitors in tetraploidy-selective suppression and their potential use in the development of tetraploidy-targeting interventions in cancer.

Therapeutic intervention based on gene sequencing analysis of microbial 16S ribosomal RNA of the intrauterine microbiome improves pregnancy outcomes in IVF patients: a prospective cohort study.

PURPOSE: A Lactobacillus-dominated microbiota in the endometrium was reported to be associated with favorable reproductive outcomes. We investigated in this study whether 16S ribosomal RNA (rRNA) gene sequencing analysis of the uterine microbiome improves pregnancy outcomes. METHODS: This prospective cohort study recruited a total of 195 women with recurrent implantation failure (RIF) between March 2019 and April 2021 in our fertility center. Analysis of the endometrial microbiota by 16S rRNA gene sequencing was suggested for all patients who had three or more failed embryo transfers (ETs). One hundred and thirty-one patients underwent microbial 16S rRNA gene sequencing (study group) before additional transfers, while 64 patients proceeded to ET without that analysis (control group). The primary outcome was to compare the cumulative clinical pregnancy rate of two additional ETs. MAIN RESULTS: An endometrial microbiota considered abnormal was detected in 30 patients (22.9%). All but one of these 30 patients received antibiotics according to the bacterial genus detected in their sample, followed by treatment with probiotics. As a result, the cumulative clinical pregnancy rate (study group: 64.5% vs. control group: 33.3%, p = 0.005) and the ongoing pregnancy rate (study group: 48.9% vs. control group: 32.8%, p = 0.028) were significantly increased in the study group compared to the control group. CONCLUSION: Personalized treatment recommendations based on the microbial 16S rRNA gene sequencing of the uterine microbiota can improve IVF outcomes of patients with RIF. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trial Registry: UMIN000036050 (date of registration: March 1, 2019).

Pure ductal adenocarcinoma of the prostate protruding into the prostatic urethra: A case report of MRI findings and literature review.

Ductal adenocarcinoma of the prostate (DCa) is the histological variant of prostatic carcinoma. The macroscopic finding of DCa arising from primary duct by urethroscopy is papillary excrescences in the prostatic urethra. But the finding of MRI remains poorly understood, since there is no coherent report on the MRI finding of DCa arising from primary duct. We herein report a case of DCa arising from primary duct and forming papillary excrescences in the prostatic urethra. The patient was a male in his 70s and presented with gross hematuria a few days ago. Blood test showed elevated prostate specific antigen (PSA). Prostate MRI was performed. There were two lesions in the prostatic urethra and the right transition zone (TZ). On T 2-weighted image (T2WI), the lesion in the prostatic urethra was identifiable, but the lesion in the right TZ was difficult to identify. On diffusion-weighted image (DWI), both lesions showed hyperintense signal and could be identified, and there was continuity between them. Urethroscopy was performed, there was the lesion with papillary excrescences developing from the right dorsal side of prostatic urethra. Transurethral resection of the prostate was performed. The pathological diagnosis was DCa (pure type). A review of previous literature showed that DCa had a slightly hypointense signal on T2WI. It may be difficult to identify DCa in the TZ because DCa and the TZ show similar signals on T2WI. DWI may be useful to accurately assess DCa arising from primary duct.

Noncontact measurement of puncture needle angle using augmented reality technology in computed tomography-guided biopsy: stereotactic coordinate design and accuracy evaluation.

PURPOSE: This study aims to introduce a new handheld device application for noncontact and real-time measurements of the angle of a biopsy needle using augmented reality (AR) image tracking technology. Furthermore, this study discusses the methods used to optimize the related coordinate design for computed tomography (CT)-guided biopsy procedures. METHODS: An in-house noncontact angle measurement application was developed using AR platform software. This application tracks the position and direction of a printed texture located on the handle of a biopsy needle. The needle direction was factorized into two directions: tilting or rolling. Tilting was defined following the tilting of the CT gantry so that rolling would match the angle measured in CT images. In this study, CT-guided tumor biopsies were performed using a conventional guiding method with a protractor. The true value of needle rolling was measured by CT imaging and was then compared to the rolling measurement provided by the application developed in the current study using a mobile phone. RESULTS: This study enrolled 18 cases of tumor biopsy (five renal tumors, five lung tumors, four retroperitoneal tumors, one soft tissue tumor, one thyroid tumor, one mesentery tumor, and one bone tumor). The measurement accuracy was - 0.2°, which was the average difference between AR and CT, and the measurement precision was 2.0°, which was the standard deviation of the difference between AR and CT measurements. The coefficient of determination (R2) was 0.996. CONCLUSION: The noncontact needle measurement software using AR technology is sufficiently reliable for use in clinical settings. A real-time display of the needle angle that also shows the direction of the CT gantry is expected to enable a simple biopsy needle navigation.

Mice lacking full length Adgrb1 (Bai1) exhibit social deficits, increased seizure susceptibility, and altered brain development.

The adhesion G protein-coupled receptor BAI1/ADGRB1 plays an important role in suppressing angiogenesis, mediating phagocytosis, and acting as a brain tumor suppressor. BAI1 is also a critical regulator of dendritic spine and excitatory synapse development and interacts with several autism-relevant proteins. However, little is known about the relationship between altered BAI1 function and clinically relevant phenotypes. Therefore, we studied the effect of reduced expression of full length Bai1 on behavior, seizure susceptibility, and brain morphology in Adgrb1 mutant mice. We compared homozygous (Adgrb1-/-), heterozygous (Adgrb1+/-), and wild-type (WT) littermates using a battery of tests to assess social behavior, anxiety, repetitive behavior, locomotor function, and seizure susceptibility. We found that Adgrb1-/- mice showed significant social behavior deficits and increased vulnerability to seizures. Adgrb1-/- mice also showed delayed growth and reduced brain weight. Furthermore, reduced neuron density and increased apoptosis during brain development were observed in the hippocampus of Adgrb1-/- mice, while levels of astrogliosis and microgliosis were comparable to WT littermates. These results show that reduced levels of full length Bai1 is associated with a broader range of clinically relevant phenotypes than previously reported.

Macrophage/microglia-derived IL-1ß induces glioblastoma growth via the STAT3/NF-κB pathway.

Glioblastoma is a glioma characterized by highly malignant features. Numerous studies conducted on the relationship between glioblastoma and the microenvironment have indicated the significance of tumor-associated macrophages/microglia (TAMs) in glioblastoma progression. Since interleukin (IL)-1ß secreted by TAMs has been suggested to promote glioblastoma growth, we attempted to elucidate the detailed mechanisms of IL-1ß in glioblastoma growth in this study. A phospho-receptor tyrosine kinase array and RNA-sequencing studies indicated that IL-1ß induced the activation of signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. Glioblastoma cells stimulated by IL-1ß induced the production of IL-6 and CXCL8, which synergistically promoted glioblastoma growth via signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. By immunohistochemistry, IL-1ß expression was seen on TAMs, especially in perinecrotic areas. These results suggest that IL-1ß might be a useful target molecule for anti-glioblastoma therapy.