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Takahito Miyazawa, Shinji Fukui, Naoki Otani, Nobusuke Tsuzuki, Hiroshi Katoh, Shoichiro Ishihara, Hiroshi Nawashiro, Kojiro Wada and Katsuji Shima

✓ The authors report the case of a 53-year-old woman who experienced visual hallucinations diagnosed as peduncular hallucinosis (PH). The cause of the PH was compression of the quadrigeminal plate and/or the splenium due to a meningioma originating from the falcotentorial junction (pineal meningioma). The nature of the visual hallucinations was depicted in drawings created by the patient herself. This is the first report of PH caused by a tumor located in the pineal region.

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Naoki Fukui, Toshio Yawata, Takahito Nakajo, Yu Kawanishi, Youichirou Higashi, Tatsuyuki Yamashita, Takaaki Aratake, Koichi Honke and Tetsuya Ueba

OBJECTIVE

Glioma stem cells (GSCs) are responsible for tumor initiation, therapeutic resistance, and recurrence. CD146 is mainly expressed in dividing GSCs and regulates cell cycle progression. However, the evaluation of the efficacy of targeted therapy against CD146 in vivo remains to be investigated. In this study, the authors aimed to develop gene therapy targeting GSCs using chitosan oligosaccharide lactate (COL) nanoparticles (NPs) conjugated with folic acid–polyethylene glycol (FA-PEG-COL NPs) for in vitro and in vivo delivery of CD146 small-interfering RNA (siCD146) and to determine the effect of CD146 knockdown on tumor growth.

METHODS

To examine the uptake of NPs by tumor cells, immunofluorescence staining, flow cytometry, and in vivo imaging were performed. The knockdown effect of siCD146 was measured by western blot and water-soluble tetrazolium salt–8 assay in mouse glioma cells. The efficacy of siRNA therapy–targeted GSCs was evaluated by monitoring tumor growth through in vivo imaging and histological analysis.

RESULTS

In vivo accumulation of the FA-PEG-COL NPs in subcutaneous and intracranial gliomas following NP administration via a mouse tail vein was observed. Additionally, in vitro delivery of siCD146 ionically cross-linked NPs, reduced CD146 levels, and suppressed growth in the glioma tumor sphere. Evaluation of the in vivo therapeutic effects of siCD146–cross-linked NPs in a mouse glioma model revealed significant suppression of intracranial tumor growth, with complete removal of the tumor observed in some mice on histological examination. Furthermore, delivery of siCD146 significantly reduced the Ki-67 index in residual tumor tissues relative to that in control mice.

CONCLUSIONS

CD146 is a potential therapeutic target, and folic acid–conjugated NPs delivering siRNA may facilitate gene therapy in malignant gliomas.

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Hitoshi Fukuda, Hitoshi Ninomiya, Yusuke Ueba, Tsuyoshi Ohta, Toshiaki Kaneko, Tomohito Kadota, Fumihiro Hamada, Naoki Fukui, Motonobu Nonaka, Yuya Watari, Shota Nishimoto, Maki Fukuda, Satoru Hayashi, Tomohiko Izumidani, Hiroyuki Nishimura, Akihito Moriki, Benjamin Lo and Tetsuya Ueba

OBJECTIVE

Several environmental factors have been reported to correlate with incidence of spontaneous subarachnoid hemorrhage (SAH). However, because of different patient selection and study designs among these studies, meteorological factors that trigger the incidence of SAH in a short hazard period remain unknown. Among meteorological factors, daily temperature changes may disrupt and violate homeostasis and predispose to cerebrovascular circulatory disturbances and strokes. The authors aimed to investigate whether a decline in the temperature from the highest of the previous day to the lowest of the event day (temperature decline from the previous day [TDP]) triggers SAH in the prefecture-wide stroke database.

METHODS

All 28 participating institutions with primary or comprehensive stroke centers located throughout Kochi Prefecture, Japan, were included in the study. Data collected between January 2012 and December 2016 were analyzed, and 715 consecutive SAH patients with a defined date of onset were enrolled. Meteorological data in this period were obtained from the Kochi Local Meteorological Observatory. A case-crossover study was performed to investigate association of TDP and other environmental factors with onset of SAH.

RESULTS

The increasing TDP in 1°C on the day of the SAH event was associated with an increased incidence of SAH (OR 1.041, 95% CI 1.007–1.077) after adjustment for other environmental factors. According to the stratified analysis, a significant association between TDP and SAH was observed in women, patients < 65 years old, and patients with weekday onset. Among these factors, increasing TDP had a great impact on SAH onset in patients < 65 years old (p = 0.028, Mann-Whitney U-test).

CONCLUSIONS

TDP, temperature decline from the highest of the previous day to the lowest of the day, was correlated with the incidence of spontaneous SAH, particularly in younger patients < 65 years old.