The bulletin of the Yamaguchi Medical School

PISSN : 0513-1812
EISSN : 2436-696X

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Androgen receptor (AR)-signaling plays an important role in promoting tumor cell survival and the development of castration-resistant prostate cancer (CRPC). Androgen deprivation therapy is the basic therapeutic strategy for AR signaling blockade, but that effects wonʼt last long and most of metastatic prostate cancer show castration resistance. Recently, new agents, AR Axis Targeted agents (ARAT), have been developed. We have been developing our bench-to-bedside translational research to elucidate the mechanisms of drug resistance in prostate cancer. This review describes our investigational results and recent advances in CRPC with ARAT treatment strategy.
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The hippocampal dentate gyrus has been identified to play a critical role in maintaining contextual memory in many mammalian species. To evaluate learninginduced synaptic plasticity of granule cells, we subjected male rats to an inhibitory avoidance (IA) task and prepared acute hippocampal slices. In the presence of 0.5 μM tetrodotoxin, we recorded miniature excitatory post synaptic currents (mEPSCs) and inhibitory post synaptic currents (mIPSCs) in male rats experiencing four groups: untrained, IA-trained, unpaired, and walk-through. Compared with the untrained, IA-trained, unpaired, and walk-through groups, the unpaired group significantly enhanced mean mEPSC amplitudes, suggesting the experience-induced plasticity at AMPA receptor-mediated excitatory synapses. For inhibitory synapses, both unpaired and walk-through groups significantly decreased mean mIPSC amplitudes, showing the experience-induced reduction of postsynaptic GABAA receptor-mediated currents. Unlike the plasticity at CA1 synapses, it was difficult to explain the learning- specific plasticity at the synapses. However, overall multivariate analysis using four variables of mE(I)PSC responses revealed experience-specific changes in the diversity, suggesting that the diversity of excitatory/inhibitory synapses onto granule cells differs among the past experience of animals include the learning. In comparison with CA1 pyramidal neurons, granule cells consistently showed greater amplitude and frequency of mE(I)PSCs. Fluctuation analysis further revealed that granule cells provide more postsynaptic AMPA receptor channels and greater single-channel current of GABAA receptors of than CA1 pyramidal neurons. These findings show functional differences between two types of principal cells in the hippocampus.
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Incontinentia pigmenti (IP; OMIM# 308300) is a rare inherited disease caused by a mutation of IKBKG, which is also known as NEMO, located on Xq28. IP patients usually present with abnormalities of skin, eyes, nails and central nervous system. The neurological damege, which occur usually from neonatal through the early infantile period, leads to neulogical complication such as development retardation, motor paralysis and epilepsy. However, there has been little study done concerning the effect of therapy for the neural abnormalities. We have investigated the clinical findings in a female IP case with a novel mutation of IKBKG for six years due to disclosing the neurological prognosis and the immunological features. It is hoped that the present study will contribute to a better management of IP patients.
Sakata Yasufumi Hirano Reiji Yasudo Hiroki Shimomura Yutaka Takada Hidetoshi Suehiro Yutaka Ohga Shouichi Hasegawa Shunji
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