Cotransplantation of preactivated mesenchymal stem cells improves intraportal engraftment of islets by inhibiting liver natural killer cells in mice.

The activation of natural killer (NK) cells in the liver inhibits engraftment of intraportally transplanted islets. We attempted to modulate the activity of NK cells by cotransplanting mesenchymal stem cells (MSCs) with islets in mice. We first investigated the ability of MSCs to secrete prostaglandin E2 , a predominant inhibitor of NK cell function, in various combinations of inflammatory cytokines. Notably, we found that prostaglandin E2 production was partially delayed in MSCs activated by inflammatory cytokines in vitro, whereas liver NK cells were activated early after islet transplant in vivo. Accordingly, preactivated MSCs, but not naive MSCs, substantially suppressed the expression of activation markers in liver NK cells after cotransplant with islets. Similarly, cotransplant with preactivated MSCs, but not naive MSCs, markedly improved the survival of islet grafts. These results highlight MSC cotransplant as an effective and clinically feasible method for enhancing engraftment efficiency.

[A case of advanced gastric cancer effectively treated with weekly paclitaxel as neoadjuvant chemotherapy].

We report a patient with advanced gastric cancer responding remarkably to neoadjuvant chemotherapy consisting of weekly paclitaxel. The patient was a 50-year-old male who had large advanced gastric cancer, suspected of invasion to the duodenum and pancreas and severe lymph node metastasis [cT4 (pancreas), cN2, cH0, cP0, cM0, cStage IV]. He was treated with weekly paclitaxel as neoadjuvant chemotherapy. According to gastroscope and CT findings, a significant tumor reduction was obtained after 3 courses. Therefore, distal gastrectomy with D2 nodal dissection were performed. The histological diagnosis was pT2, pN2, pStage IIIA, and the histological effect of the main tumor was judged to be Grade 2. The patient has now been in good health without recurrence for 3 years after surgery. This case suggests that neoadjuvant chemotherapy with weekly paclitaxel is a potentially effective regimen for advanced gastric cancer.

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis.

AIM: We investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells. METHODS: We classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences. RESULTS: There were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural-killer group 2, member D (NKG2D)- positive NK cells in PBMC and percentage of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, NKp30-, and signal regulatory protein ß (SIRPß)-positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPß in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)-2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups. CONCLUSION: Colorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.