No abstract

In gastric cancer, primary systemic chemotherapy is the standard approach for the management of patients with initially unresectable metastasis, and it occasionally leads to a reduction in the size of the lesion, which facilitates surgical resection. The aim of this study was to examine the prognosis of patients who were able to undergo complete resection following chemotherapy. A total of 10 patients who underwent radical surgery for stage IV primary gastric cancer after chemotherapy between 2009 and 2015 at the Department of Surgery of Hokkaido Social Work Association Obihiro Hospital (Obihiro, Japan) were retrospectively investigated. Three regimens were used (S-1, n=1; S-1 + cisplatin, n=8; and S-1 + docetaxel, n=1). The mean time from chemotherapy to surgery was 210 days. One total gastrectomy + splenectomy + colectomy, one total gastrectomy + splenectomy, four total gastrectomies and three distal gastrectomies were performed. There were two cases of pancreatic fistula formation postoperatively. All the patients survived for >1 year. Of the 10 patients, 5 survived without recurrence. The median survival time was 871.1 days after diagnosis. Therefore, curative resection after chemotherapy is associated with a better prognosis in stage IV gastric cancer patients.

L-Carnitine (LC) plays an important role in the metabolism of fatty acids, and LC deficiency is associated with a feeling of weakness or general fatigue. Cancer patients receiving chemotherapy often develop LC deficiency, which is considered to be a factor contributing to general fatigue. The aim of the present study was to evaluate the efficacy of LC supplementation as a treatment for general fatigue in cancer patients during chemotherapy. A total of 11 cancer patients who were suffering from general fatigue during chemotherapy in our hospital between September 2014 and December 2015 were examined (6 cases involved adjuvant chemotherapy and 5 cases involved chemotherapy for unresectable or recurrent disease). The patients were administered 1,500 mg/day of levocarnitine per os, and the change in mean daily fatigue from the baseline to 8 weeks was assessed using the Brief Fatigue Inventory. The change in the plasma levels of albumin and the lymphocyte counts from the baseline to 8 weeks were also assessed. LC supplementation reduced general fatigue in all cases. Moreover, LC supplementation maintained the plasma levels of albumin and lymphocyte counts during chemotherapy, and enabled patients to continue chemotherapy sequentially without dose reduction. Therefore, LC supplementation improved general fatigue in all the examined cancer patients during chemotherapy. This treatment may make improve the tolerability of chemotherapy in cancer patients by reducing general fatigue and improving the nutritional status.

Background Arginase-1 (ARG1), a urea cycle-related enzyme, catalyzes the hydrolysis of arginine to urea and ornithine, which regulates the proliferation, differentiation, and function of various cells. However, it is unclear whether ARG1 controls the progression and malignant alterations of colon cancer. Methods We established metastatic colonization mouse model and ARG1 overexpressing murine colon cancer CT26 cells to investigate whether activation of ARG1 was related to malignancy of colon cancer cells in vivo. Living cell numbers and migration ability of CT26 cells were evaluated in the presence of ARG inhibitor in vitro. Results Inhibition of arginase activity significantly suppressed the proliferation and migration ability of CT26 murine colon cancer cells in vitro. Overexpression of ARG1 in CT26 cells reduced intracellular l-arginine levels, enhanced cell migration, and promoted epithelial-mesenchymal transition. Metastatic colonization of CT26 cells in lung and liver tissues was significantly augmented by ARG1 overexpression in vivo. ARG1 gene expression was higher in the tumor tissues of liver metastasis than those of primary tumor, and arginase inhibition suppressed the migration ability of HCT116 human colon cancer cells. Conclusion Activation of ARG1 is related to the migration ability and metastatic colonization of colon cancer cells, and blockade of this process may be a novel strategy for controlling cancer malignancy.

The induction of antitumor effector T cells in the tumor microenvironment is a crucial event for cancer immunotherapy. Neurokinin receptor 2 (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), regulates diverse physiological functions. However, the precise role of NKA–NK2R signaling in antitumor immunity is unclear. Here, we found that an IFN‐γ–STAT1 cascade augmented NK2R expression in CD8 + T cells, and NK2R‐mediated NKA signaling was involved in inducing antitumor effector T cells in vivo. The administration of a synthetic analog of double‐stranded RNA, polyinosinic–polycytidylic acid (poly I:C), into a liver cancer mouse model induced type I and type II IFNs and significantly suppressed the tumorigenesis of Hepa1‐6 liver cancer cells in a STAT1‐dependent manner. The reduction in tumor growth was diminished by the depletion of CD8 + T cells. IFN‐γ stimulation significantly induced NK2R and tachykinin precursor 1 (encodes NKA) gene expression in CD8 + T cells. NKA stimulation combined with anti‐CD3 monoclonal antibody (mAb) treatment significantly augmented IFN‐γ and granzyme B production by CD8 + T cells compared with the anti‐CD3 mAb alone in vitro. ERK1/2 phosphorylation and IκBα degradation in activated CD8 + T cells were suppressed under NK2R deficiency . Finally, we confirmed that tumor growth was significantly increased in NK2R‐deficient mice compared with that in wild‐type mice, and the antitumor effects of poly I:C were abolished by NK2R absence. These findings suggest that IFN‐γ–STAT1‐mediated NK2R expression is involved in the induction of antitumor effector T cells in the tumor microenvironment, which contributes to the suppression of cancer cell tumorigenesis in vivo. In this study, we revealed that IFN‐γ–STAT1‐mediated NK2R expression is involved in the induction of antitumor effector CD8 + T cells in the tumor microenvironment, which contributes to suppressing the tumorigenesis of liver cancer cells in vivo.