[Experience with Nivolumab in the Treatment of Metastatic Gastric Cancer].

Immunological checkpoint inhibitors have effects on various advancedcancers. Nivolumab was approvedfor advanced gastric cancer after third-line treatment in 2017. In our hospital, 10 patients were treatedwith nivolumab from October 2017 to March 2018. Thus, we retrospectively examinedthe clinical background, treatment outcomes, andad verse events of those patients. The median age was 70 years; male-to-female ratio was 6:4; recurrence sites were peritoneal dissemination, liver, lymph nodes, brain, ovaries, and bone(8, 2, 2, 1, 1, and1 , respectively); andtreatment lines were third, fourth, andfifth(in 6, 3, and1 patients, respectively). The minimum number of cycles was 1 course, while the maximum was 11 courses. The best tumor response evaluation was SD, andthe adverse event was an itching sensation in only one patient. It was suggestedthat long-term SD couldbe maintainedwhen the nivolumab treatment was initiatedin a patient with goodPS. In the future, biomarker analysis is expectedto identify effective cases.

Downregulation of ARID1A, a component of the SWI/SNF chromatin remodeling complex, in breast cancer.

Recent studies unraveled that AT-rich interactive domain-containing protein 1A (ARID1A), a subunit of the mammary SWI/SNF chromatin remodeling complex, acts as a tumor suppressor in various cancers. In this study, we first evaluated ARID1A expression by immunohistochemistry in invasive breast cancer tissue specimens and assessed the correlation with the prognosis of patients with breast cancer. Non-tumorous mammary duct epithelial cells exhibited strong nuclear ARID1A staining, whereas different degrees of loss in ARID1A immunoreactivity were observed in many invasive breast cancer cells. We scored ARID1A immunoreactivity based on the sum of the percentage score in invasive cancer cells (on a scale of 0 to 5) and the intensity score (on a scale of 0 to 3), for a possible total score of 0 to 8. Interestingly, partial loss of ARID1A expression, score 2 to 3, was significantly correlated with poor disease free survival of the patients. Subsequently, we performed siRNA-mediated ARID1A knockdown in cultured breast cancer cells followed by comprehensive gene profiling and quantitative RT-PCR. Interestingly, many genes were downregulated by partial loss of ARID1A, whereas RAB11FIP1 gene expression was significantly upregulated by partial loss of ARID1A expression in breast cancer cells. In contrast, a more than 50% reduction in ARID1A mRNA decreased RAB11FIP1gene expression. Immunoblotting also demonstrated that partial downregulation of ARID1A mRNA at approximately 20% reduction significantly increased the expression of RAB11FIP1 protein in MCF-7 cells, whereas, over 50% reduction of ARID1A mRNA resulted in reduction of RAB11FIP1 protein in cultured breast cancer cells. Recent studies reveal that RAB11FIP1 overexpression leads to breast cancer progression. Altogether, the present findings indicated that partial loss of ARID1A expression is linked to unfavorable outcome for patients with breast cancer, possibly due to increased RAB11FIP1 expression.

Six secoiridoid glucosides from Adina racemosa.

Six novel secoiridoid glucosides, adinosides A (1), B (2), C (3), D (4), E (5), and grandifloroside 11-methyl ester (6) were isolated, together with 27 known compounds, from the dried leaves, flowers, and twigs of Adina racemosa. The structures of the new compounds were determined by spectroscopic (NMR, MS) and chemical means.