Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability

Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI

若年成人女性における仙腸関節部愁訴の発生要因の検討

研究報告Original Articles［目的］本研究は，若年成人女性を対象に，仙腸関節不安定テストによる仙腸関節部愁訴と身体特性および体幹筋力との関連について調査することを目的とした．［方法］対象者は若年成人女性100名（平均年齢21.1±1.0 歳）とした． 4つの仙腸関節不安定テスト（Patrick test，Newton test変法，Gaenslen test，仙腸関節引き離しテスト）を実施し，1つ以上で仙腸関節部に疼痛や違和感を訴えた者を愁訴あり群と分類した．また，身体特性，等速性体幹筋力の測定を行った．［結果］仙腸関節不安定テストによる愁訴あり群は，対象者100名中23名であった．愁訴あり群の身長は，愁訴なし群に比べ，有意に高い値を示した（160.6±5.7 cm vs 158.1±5.2 cm，p＜0.05）．その他の身体特性，体幹筋力においては，愁訴あり群となし群の間で有意差がなかった．［結論］若年成人女性において，身長が高いという身体特性が，仙腸関節部愁訴の要因の一つである可能性が示唆された．また，仙腸関節の安定性を体幹の動的な粗大筋力のみで把握することは難しい．[Purpose]　The purpose of this study was to investigate the physical characteristics and trunk muscular strength of young adult women with sacroiliac joint discomfort by means of instability tests.[Methods]　One hundred women (mean age, 21.1 ± 1.0 years) participated in the study. After undergoing four instability tests, i.e. Patrick test, modified Newton test, Gaenslen test, and sacroiliac distraction test, the study participants were classified into a sacroiliac joint discomfort group and a non-discomfort group. Physical characteristics (height, weight, body mass index, body fat percentage, and waist circumference) were recorded, and isokinetic trunk muscle strength was assessed.[Results] Twenty-three participants experienced discomfort according to instability tests. Participants’ height in the sacroiliac joint discomfort group was significantly greater than that in the non-discomfort group (160.6 ± 5.7 cm vs 158.1 ± 5.2 cm, p < 0.05). However there were no significant inter-group differences with regard to the other parameters measured.[Conclusion]　In young adult women, a taller stature may contribute to sacroiliac joint discomfort. The stability of the sacroiliac joint should not be assessed on the basis of the dynamic gross trunk muscle strength alone

DNA polymerases ν and θ are required for efficient immunoglobulin V gene diversification in chicken

Polν and Polθ have specialized functions in immunoglobulin gene rearrangements and only contribute to DNA repair when other homologous recombination–related DNA polymerases are absent

A Single Amino Acid Mutation in SNAP-25 Induces Anxiety-Related Behavior in Mouse

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC) phosphorylates Ser187 of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser187 of SNAP-25 with Ala using “knock-in” technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects