Antiproliferative effects of D-allose associated with reduced cell division frequency in glioblastoma.

Recent studies have shown that D-allose, a rare sugar, elicits antitumor effects on different types of solid cancers, such as hepatocellular carcinoma, non-small-cell lung cancer, and squamous cell carcinoma of the head and neck. In this study, we examined the effects of D-allose on the proliferation of human glioblastoma (GBM) cell lines (i.e., U251MG and U87MG) in vitro and in vivo and the underlying mechanisms. D-allose treatment inhibited the proliferation of U251MG and U87MG cells in a dose-dependent manner (3-50 mM). However, D-allose treatment did not affect cell cycles or apoptosis in these cells but significantly decreased the cell division frequency in both GBM cell lines. In a subcutaneous U87MG cell xenograft model, intraperitoneal injection of D-allose (100 mg/kg/day) significantly reduced the tumor volume in 28 days. These data indicate that D-allose-induced reduction in cell proliferation is associated with a subsequent decrease in the number of cell divisions, independent of cell-cycle arrest and apoptosis. Thus, D-allose could be an attractive additive to therapeutic strategies for GBM.

Six-month Outcomes after PulseRider- and Conventional Single Stent-assisted Embolization for Bifurcation Aneurysms: A Propensity-adjusted Comparison.

Endovascular treatment of wide-necked bifurcation aneurysms (WNBAs) remains challenging despite using a stent. PulseRider is a novel device specifically designed to treat WNBAs, protecting both daughter branches, but the outcomes have not been compared with conventional single stent-assisted embolization. This study aimed to compare the six-month outcomes of PulseRider and single stent-assisted embolization for intracranial unruptured WNBAs using propensity score adjustment. Between February 2012 and October 2021, 46 unruptured WNBAs (34 basilar and 12 middle cerebral arteries) smaller than 10 mm in diameter were treated with PulseRider-assisted embolization (n = 17) or single stent-assisted embolization (n = 29). The immediate and six-month outcomes were compared using inverse probability of treatment weighting analysis. The immediate adequate occlusion rates for the PulseRider- and single stent-assisted embolization were similar (47.1% vs. 62.1%). At six months, adequate occlusion rates for the two groups were also similar (94.1% vs. 86.2%). However, the complete obliteration rate was significantly high after PulseRider-assisted embolization (88.2% vs. 41.4%, adjusted OR 10.54, 95% CI 1.93-57.63). The angiographical improvement rate was also significantly high after PulseRider-assisted embolization (70.6% vs. 37.9%, adjusted OR 6.06, 95% CI 1.54-23.76). The neurologic thromboembolic complication rate was 0% after PulseRider-assisted embolization and 3.4% after single stent-assisted embolization. PulseRider-assisted embolization of WNBAs smaller than 10 mm in diameter was associated with complete obliteration and angiographical improvement at six months. The unique shape of the PulseRider might contribute to the improved midterm aneurysm occlusion.

Effects of a monoclonal antibody against (pro)renin receptor on gliomagenesis.

Glioblastoma is characterized by a strong self-renewal potential and poor differentiated state. We have reported previously that the (pro)renin receptor [(P)RR] is a potential target for glioma therapy by silencing the (P)RR gene. Here, we have examined the effects of a monoclonal antibody against (P)RR on gliomagenesis. Human glioma cell lines (U251MG and U87MG) and a glioma stem cell line (MGG23) were used for the in vitro study. The expressions of the Wnt/ß-catenin signaling pathway (Wnt signaling pathway) components and stemness markers were measured by Western blotting. The effects of the (P)RR antibody on cell proliferation, sphere formation, apoptosis and migration were also examined. Subcutaneous xenografts were also examined in nude mice. Treatment with the (P)RR antibody reduced expression of Wnt signaling pathway components and stemness markers. Furthermore, the (P)RR antibody reduced cell proliferation and decreased sphere formation significantly. The treatment also suppressed migration and induced apoptosis. In a subcutaneous xenograft model, systemic administration of the (P)RR antibody reduced tumor volume significantly. These data show that treatment with the (P)RR antibody is a potential therapeutic strategy for treating glioblastoma.

Endovascular Treatment for Posterior Communicating Artery Aneurysms with Oculomotor Nerve Palsy.

Objective: Coil embolization for the treatment of internal carotid artery-posterior communicating artery aneurysms (PComAAn) associated with oculomotor nerve palsy (ONP) remains controversial in terms of the therapeutic effect to improve ONP. Patients with PComAAn treated in our hospital were retrospectively analyzed to evaluate the effectiveness of coil embolization on ONP. Methods: Twenty-three patients who had coil embolization for PComAAn with ONP were included in the analysis. In the evaluation of postoperative outcome of ONP, complete resolution of all symptoms was considered as a total recovery. ONP with a few residual symptoms that are stable and not disabling was considered as a subtotal recovery and that with only a slight improvement as a partial recovery. Results: Preoperative ONP was complete palsy in 14 and partial palsy in nine cases. The mean maximum diameter of the aneurysms was 9.1 ± 3.5 mm (3-17 mm), and the mean time from the onset to treatment was 46.3 ± 98.4 days (0-300 days). The embolization state immediately after the procedure was complete occlusion in seven, neck remnant in eight, and body filling (BF) in eight cases. Total recovery was observed in nine, subtotal recovery in 11, and partial recovery in three cases. The mean time to any improvement in ONP was 6.0 ± 6.0 months (0.5-25 months). Comparing 20 cases with total plus subtotal recovery and three cases with partial recovery, five (25.0%) and three (100%) cases showed BF immediately after the procedure, respectively, which was statistically significant (P = 0.015). Conclusion: The analysis indicated that coil embolization for the treatment of PComAAn with ONP resulted in satisfactory recovery of ONP in 87% of the cases and the outcome of aneurysm embolization was related to improvement in ONP.

Case Series of Endovascular Therapy for Blood Blister-Like Aneurysm in Acute Phase.

Objective: Blood blister-like aneurysms (BBAs) of the internal carotid artery are highly challenging to treat due to their variable morphology and tendency for rupture and regrowth. Here, we report a single-institution experience of endovascular therapy (EVT) for BBA treatment. Methods: We retrospectively reviewed patients with ruptured BBA from 2006 to 2019. All patients in whom BBA was treated with EVT were included. Patients' aneurysmal characteristics, progression status, aneurysm occlusion on follow-up angiography, and modified Rankin Scale (mRS) score were recorded. Results: A total of 11 patients (5 women and 6 men) with the mean age of 46 ± 10 years were included in this study. As initial treatment, 9 patients were treated with stent-assisted coiling (SAC). Immediate angiographic results showed that 2 cases were body filling, 4 were neck remnant, and 3 were complete obliteration. Perioperative ischemic complications were not observed. On postoperative day 1, 2 patients suffered from rerupture, and their prognoses were poor. Retreatments were performed in 5 patients. Parent artery occlusion (PAO) was performed in 6 patients including 2 initial treatments and 4 retreatments. Symptomatic infarction developed in 2 patients. In 3 patients, bypass in combination with PAO was performed. Clinical data revealed discharge mRS scores of 0-2 and 3-6 in 4 and 7 patients, respectively. Conclusion: SAC is effective for the management of BBA. Careful follow-up and response are necessary after treatment with SAC.

Clinicopathologic Factors Associated with Tumor Necrosis after Preoperative Embolization of Meningiomas.

Objective: Preoperative embolization of meningiomas induces necrosis prior to surgery and facilitates resection. Lack of contrast enhancement on postembolization MRI correlates with pathological findings of necrosis and can be used to assess embolization efficacy. This study aimed to examine clinicopathologic factors associated with tumor necrosis after embolization. Methods: A total of 119 patients with intracranial meningioma who underwent 145 surgical resections between 2010 and 2019 at our institute were reviewed. Inclusion criteria for the study were preoperative embolization with trisacryl gelatin microspheres (Embosphere) or absorbable gelatine sponge (Gelfoam). Postembolization Gd-enhanced T1-weighted and angiographic imaging, and histopathologic examination results were reviewed to evaluate the effectiveness of embolization. Results: In all, 66 patients satisfied the inclusion criteria. In total, 36 patients were embolized with Embosphere and 30 patients were embolized with Gelfoam. Patients embolized with Embosphere had a significantly higher necrosis rate (NR) than patients with Gelfoam (21% vs. 7.1%, P <0.01). The 36 Embosphere patients were analyzed regarding clinicopathologic factors associated with NR. Tumors in 12 patients were located in the parasagittal/falx region; these patients had a significantly lower NR compared with tumors in other locations (10.6% vs. 26.2%, P = 0.016). In all, 13 patients had feeders arising from only the middle meningeal artery (MMA), which was associated with a significantly higher NR (29.3% vs. 14.4%, P = 0.015). In total, 11 patients had meningeal feeders arising from internal carotid artery (ICA), which was associated with a significantly lower NR (9.0% vs. 26.3%, P <0.01). Conclusion: This study showed embolization agent, tumor location, and blood supply were important factors predicting necrosis after preoperative embolization.

A Rare Case of Postoperative Symptomatic Cyst Formation After Resection of a Large Convexity Meningioma.

BACKGROUND: Symptomatic cyst formation after brain tumor resection is a rare complication of the early postoperative phase. We describe a complicated case of postoperative symptomatic cyst formation after gross total removal of a convexity meningioma. CASE DESCRIPTION: A 59-year-old woman presented with recent onset motor aphasia. Magnetic resonance imaging revealed a left convexity tumor. We performed gross total resection of the tumor, which was pathologically diagnosed as an atypical meningioma. Tumor resection and decompression of the normal cerebral hemisphere improved aphasia. However, 3 days after surgery, her motor aphasia worsened. Computed tomography scan confirmed that the frontal lobe was being compressed by an enlargement of the postoperative tumor cavity. Conservative therapy did not shrink the cavity, and her motor aphasia persisted. Therefore, 21 days after surgery, a drainage tube was inserted into the enlarged cavity using a neuroendoscope, which promoted shrinkage of the cavity and improved her motor aphasia. We suspected that the enlargement of the postoperative cavity was because of the presence of a valve-like structure. CONCLUSIONS: Even though formation of symptomatic cystic lesions after brain tumor resection is rare, neurosurgeons should be aware of such early postoperative complications and their management strategies.

Arachidonate 12-Lipoxygenase Inhibitors Promote S100A3 Citrullination in Cultured SW480 Cells and Isolated Hair Follicles.

The human hair shaft is covered with multiple scale-like cuticular layers. During the terminal differentiation stage of immature cuticular cells within the hair follicle, cysteine-rich calcium binding S100A3 protein is predominantly translated, and its arginine residues are converted to citrullines by peptidylarginine deiminases (PADI). In this study, we found several naturally occurring compounds (e.g., hinokitiol, escletin, and quercetin) elevate S100A3 citrullination in a human colorectal adenocarcinoma cell line (SW480). Selected compounds similarly promoted cuticular differentiation within isolated human hair follicles. Their promotive activities correlated with the previously reported inhibitory activities of arachidonate 12-lipoxygenase (ALOX12) in vitro. Microarray analysis revealed that ALOX12 inhibitor remarkably up-regulated heparin-binding epidermal growth factor-like growth factor (HBEGF). ALOX12 inhibitor and recombinant HBEGF similarly regulated expression of PADI genes in SW480 cells. In isolated hair follicles, arachidonic acid strongly promoted S100A3 citrullination along with elevation of HBEGF. These results suggest that ALOX12 inhibition efficiently triggers hair cuticle maturation by modulating arachidonate metabolism in concert with HBEGF.

The Usefulness of CT-Diffusion Weighted Image Mismatch in Patients with Mild to Moderate Traumatic Brain Injury.

Traumatic brain injury (TBI) has a complex and heterogeneous pathology. It is frequently difficult to predict the neurological deterioration of patients with TBI, and unpredictable change may occur even when TBI is mild to moderate. When computed tomography (CT) findings are considered to be inconsistent with the traumatic origin or with the neurological deterioration of patients observed on admission, magnetic resonance imaging (MRI) is employed based on the standards of our ethical committee. In this retrospective study, we compared CT and diffusion weighted imaging (DWI) of patients with mild to moderate TBI in the very acute phase. When the high-intensity lesions on DWI are larger than the high-density lesions on CT images, we defined the imaging finding as a 'CT-DWI mismatch'. Between January 2010 and December 2013, 92 patients were inspected using both CT and MRI at admission, and we detected a CT-DWI mismatch in 35 patients. CT-DWI mismatch was 92.6% (95% confidence interval 79.8-97.9) sensitive and 84.6% (95% confidence interval 79.3-86.3) specific for the prediction of enlargement of the hemorrhagic lesions on repeat CT. CT-DWI mismatch is considered to be useful as one of the predictors of the enlargement of hemorrhagic lesions in patients with mild to moderate TBI.

[A Case of Transorbital Penetrating Brain Injury Caused by a Steel Wire Entirely Embedded in the Brain Parenchyma].

Penetrating brain injury(PBI)is very rare in Japan. Because there is a very wide variety of pathological condition of PBI, the guideline for the treatment of PBI has not been established yet. We report the unique case of PBI caused by a steel wire piece completely embedded in the brain parenchyma. A 75-year-old man was brought to the emergency department due to ocular injury caused by a steel wire piece. Neurological examination revealed only left visual disturbance. CT scan revealed a steel wire piece located intraparenchymally between the left frontal lobe and the ventricles, but digital subtraction angiography showed no significant vascular injury in the surrounding structures. We performed an open surgery and removed the steel wire piece. Because the steel wire piece was completely embedded in the brain, we used intraoperative X-ray fluoroscopy to choose a less invasive approach for the brain. The patient suffered no additional neurological deficit and no sign of cerebral infection or seizure after surgery. He was discharged after a 4-week administration of antibiotics. In most cases of PBI caused by low velocity injury, foreign bodies are not completely embedded in the brain except for remnants after surgical removal. This is the first report of low velocity PBI caused by a foreign body completely embedded in the brain.

[Intrapituitary adenoma metastasis from lung cancer with progressive cranial nerve palsies: a case report and literature review].

We report a rare case of metastasis to a preexisting pituitary adenoma. An 80-year-old man with a history of pituitary adenoma and lung cancer presented with recent onset of bilateral visual impairment, oculomotor nerve palsies, and severe headache. A CT scan revealed a pituitary tumor expanding into the suprasellar region and infiltrating the bilateral cavernous sinuses. We performed transsphenoidal surgery and diagnosed the tumor as lung cancer metastasis to the pituitary adenoma. After the surgery, visual impairment and severe headache were resolved, and the patient underwent radiation therapy for the residual tumor. To the best of our knowledge, 20 cases of metastases to pituitary adenomas have been reported in the literature. Clinical features of metastasis to a pituitary adenoma are different from those of metastasis to normal pituitary gland. In the case of a pituitary lesion with acute aggravation, one should be aware of the possibility of metastasis to preexisting pituitary adenomas.