[A case of pembrolizumab responding to recurrent small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome].

An advanced small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome was resected, and we started capecitabine plus oxaliplatin (CapeOX) as adjuvant therapy. However, local recurrence was noted, and the tumor increased even after CapeOX plus bevacizumab and fluorouracil plus leucovorin plus irinotecan plus panitumumab (FOLFIRI plus panitumumab). Pembrolizumab was administered after confirming high-frequency microsatellite instability, and the tumor shrank markedly and remained shrunk for 20 months.

Multi-center phase II study of FLOX for advanced colorectal cancer patients in Japan: SWIFT 3 study.

AIM: This is a multicenter phase II study to assess the efficacy and toxicity of the 5-FU, leucovorin, and oxaliplatin (FLOX) (SWIFT 3) regimen in Japanese patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS: Fifty-two patients were enrolled and evaluated from 12 institutions. The median age was 66 years, with 40.4% of patients with colon cancer and 59.6% with rectal cancer. RESULTS: Forty-one patients underwent chemotherapy for first-line therapy and 11 patients for second-line. The response rate for first-line was 46.3% and that for second-line was 9.1%. The response rates categorized by metastatic sites were 59.4% for liver, 33.3% for lung, and 22.2% for lymph nodes. Grade 3/4 neutropenia occurred in 21.2% and Grade 3/4 non-hematologic toxicity in 46.1%. There were no deaths within 60 days following the administration. CONCLUSION: Standard FLOX regimen can be administered for Japanese patients. It is suggested that FLOX is an appropriate option for adjuvant therapy in CRC.

Sesamin, a lignan of sesame, down-regulates cyclin D1 protein expression in human tumor cells.

Sesamin is a major lignan constituent of sesame and possesses multiple functions such as antihypertensive, cholesterol-lowering, lipid-lowering and anticancer activities. Several groups have previously reported that sesamin induces growth inhibition in human cancer cells. However, the nature of this growth inhibitory mechanism remains unknown. The authors here report that sesamin induces growth arrest at the G1 phase in cell cycle progression in the human breast cancer cell line MCF-7. Furthermore, sesamin dephosphorylates tumor-suppressor retinoblastoma protein (RB). It is also shown that inhibition of MCF-7 cell proliferation by sesamin is correlated with down-regulated cyclin D1 protein expression, a proto-oncogene that is overexpressed in many human cancer cells. It was found that sesamin-induced down-regulation of cyclin D1 was inhibited by proteasome inhibitors, suggesting that sesamin suppresses cyclin D1 protein expression by promoting proteasome degradation of cyclin D1 protein. Sesamin down-regulates cyclin D1 protein expression in various kinds of human tumor cells, including lung cancer, transformed renal cells, immortalized keratinocyte, melanoma and osteosarcoma. Furthermore, depletion of cyclin D1 protein using small interfering RNA rendered MCF-7 cells insensitive to the growth inhibitory effects of sesamin, implicating that cyclin D1 is at least partially related to the antiproliferative effects of sesamin. Taken together, these results suggest that the ability of sesamin to down-regulate cyclin D1 protein expression through the activation of proteasome degradation could be one of the mechanisms of the antiproliferative activity of this agent.