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The sonic hedgehog (Shh) pathway is activated in ∼30% of human medulloblastoma resulting in increased expression of downstream target genes. In about half of these cases, this has been shown to be a consequence of mutations in regulatory genes within the pathway, including Ptc1, Smo, and Sufu. However, for some tumors, no mutations have been detected in known pathway genes. This suggests that either mutations in other genes promote tumorigenesis or that epigenetic alterations increase pathway activity in these tumors. Here, we report that 3% to 4% of mice lacking either one or both functional copies of Cxcr6 develop medulloblastoma. Although CXCR6 is not known to be involved in Shh signaling, tumors derived from Cxcr6 mutant mice expressed Shh pathway target genes including Gli1, Gli2, Ptc2, and Sfrp1, indicating elevated pathway activity. Interestingly, the level of Ptc1 expression was decreased in tumor cells although two normal copies of Ptc1 were retained. This implies that reduced CXCR6 function leads to suppression of Ptc1 thereby increasing Smoothened function and promoting tumorigenesis. We used a direct transplant model to test the sensitivity of medulloblastoma arising in Cxcr6 mutant mice to a small-molecule inhibitor of Smoothened (HhAntag). We found that transplanted tumors were dramatically inhibited in mice treated for only 4 days with HhAntag. These findings suggest that HhAntag may be effective against tumors lacking mutations in known Shh pathway genes. [Cancer Res 2007;67(8):3871–7]

Supplementary Figure 1 and Tables 1-2 from Medulloblastomas Derived from Cxcr6 Mutant Mice Respond to Treatment with a Smoothened Inhibitor

Background: Human resource management may be difficult for community pharmacists because of recent drastic changes in work volume and content. In Japan, few studies have been conducted on job satisfaction, well-being, and quality of work life (QWL) among community pharmacists. Focusing on QWL, a more comprehensive concept than job satisfaction, this study aimed to develop a multi-trait-based QWL scale for Japanese community pharmacists (QWLS for JCP) and test its reliability and validity. Methods:A questionnaire survey was conducted among 2027 pharmacists working in pharmacies, with the cooperation of 20 corporations running pharmacies. The collected data were subjected to principal component factor analysis with Promax rotation using SPSS28. Results: The following five significant components were identified based on factor analysis using data from 1966 pharmacists. These form the basis of the QWLS for JCP: “Influence of work on mind and body,” “Relationships with colleagues,” “Relationship with the boss,” “Meaning of existence in the workplace,” and “Pride in work.” Cronbach’s alpha, which expresses reliability, was between 0.585 and 0.854 for these subscales. Conclusions: The QWLS for JCP significantly explained the concept of QWL, which means that its validity was sufficient.

The establishment and implementation of a healthy lifestyle is fundamental to public health and is an important issue for working-aged people, as it affects not only them but also the future generations. However, due to the COVID-19 pandemic and associated behavioural restrictions, lifestyles have altered, and, in certain environments, significantly worsened. In the present study, we conducted a project to improve the intestinal environment by focussing on the dietary habits of participants, utilising the living laboratory as a social technology to explore how to adapt to this drastic environmental change. We held eight workshops for voluntary participants and implemented a self-monitoring process of recording dietary behaviours (n = 78) and testing the intestinal environment (n = 14). Through this initiative, we developed a personalised wellness enhancement programme based on collaboration with multiple stakeholders and a framework for using personal data for research and practical purposes. These results provide an approach for promoting voluntary participation and behavioural changes among people, especially under the COVID-19 pandemic, as well as a practical basis for the government, academia, and industry to intervene effectively in raising people’s awareness of health and wellness.