Is the Importance of Achieving Stable Disease Different between Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Cytotoxic Agents in the Second-Line Setting for Advanced Non-small Cell Lung Cancer?

BackgroundIt is controversial whether achieving stable disease leads to a survival benefit and whether the importance of achieving stable disease differs between cytotoxic agents and molecular targeted agents. To examine these questions, the authors retrospectively reviewed phase II and III studies in the second-line setting for advanced non-small cell lung cancer using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic agents separately.MethodsThe authors chose 45 trials for the chemotherapy group and nine for the EGFR TKI group by searching the PubMed database. All nine trials in the EGFR TKI group concern gefitinib and erlotinib.ResultsThe median survival time increased 0.0375 month with each 1% increase in stable disease rate (p = 0.039), and each 1% increase in response rate resulted in 0.0744 (p < 0.001) month of median survival time in the analysis combined with both cytotoxic agents and EGFR TKIs. Main and interaction terms for EGFR TKI treatment were not statistically significant. With respect to time to progression, only response rate showed a statistically significant relationship with survival.ConclusionsTo obtain response seems to be more important than to achieve stable disease for both cytotoxic agents and EGFR TKIs, although achieving stable disease is still valuable. The relationship between survival and response or stable disease appears similar for cytotoxic agents and EGFR TKIs

Inhibition of microRNA-33b in humanized mice ameliorates nonalcoholic steatohepatitis

マイクロRNA-33bの阻害は非アルコール性脂肪肝炎を改善する --核酸医薬による治療応用へ--. 京都大学プレスリリース. 2023-06-13.Nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma in their advanced stages; however, there are currently no approved therapies. Here, we show that microRNA (miR)-33b in hepatocytes is critical for the development of NASH. miR-33b is located in the intron of sterol regulatory element–binding transcription factor 1 and is abundantly expressed in humans, but absent in rodents. miR-33b knock-in (KI) mice, which have a miR-33b sequence in the same intron of sterol regulatory element–binding transcription factor 1 as humans and express miR-33b similar to humans, exhibit NASH under high-fat diet feeding. This condition is ameliorated by hepatocyte-specific miR-33b deficiency but unaffected by macrophage-specific miR-33b deficiency. Anti-miR-33b oligonucleotide improves the phenotype of NASH in miR-33b KI mice fed a Gubra Amylin NASH diet, which induces miR-33b and worsens NASH more than a high-fat diet. Anti-miR-33b treatment reduces hepatic free cholesterol and triglyceride accumulation through up-regulation of the lipid metabolism–related target genes. Furthermore, it decreases the expression of fibrosis marker genes in cultured hepatic stellate cells. Thus, inhibition of miR-33b using nucleic acid medicine is a promising treatment for NASH

Review Article : Feudalism or Absolute Monarchism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68809/2/10.1177_009770049001600304.pd

microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity

褐色脂肪細胞の燃焼を促す新たなメカニズムを解明 --体の熱産生にマイクロRNA-33が関与--. 京都大学プレスリリース. 2021-02-17.Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress

Myths of restorative features in the Japanese justice system and society: The role of apology, compensation and confession, and application of reintegrative shaming

Suzuki, M ORCiD: 0000-0002-7925-2141Restorative justice (RJ) has experienced rapid growth. Along with its development, myths about RJ have emerged. Although several scholars have challenged these, two myths about restorative features in the Japanese justice system and society—(1) the role of apology, compensation and confession; and (2) the application of reintegrative shaming—arguably remain pervasive. In this paper, we aim to advance a critical analysis of these two ostensibly restorative features of the Japanese justice system and society. We argue that the reality is more nuanced. We conclude by analysing why these myths have emerged and what functions they have performed

Myths of restorative features in the Japanese justice system and society: The role of apology, compensation and confession, and application of reintegrative shaming

Restorative justice (RJ) has experienced rapid growth. Along with its development, myths about RJ have emerged. Although several scholars have challenged these, two myths about restorative features in the Japanese justice system and society—(1) the role of apology, compensation and confession; and (2) the application of reintegrative shaming—arguably remain pervasive. In this paper, we aim to advance a critical analysis of these two ostensibly restorative features of the Japanese justice system and society. We argue that the reality is more nuanced. We conclude by analysing why these myths have emerged and what functions they have performed