Chemoradiotherapy for patients with recurrent lymph-node metastasis or local recurrence of gastric cancer after curative gastrectomy

Objectives

Whether chemoradiotherapy (CRT) is clinically beneficial for the management of postoperative recurrence of advanced gastric cancer remains unclear. We retrospectively studied treatment outcomes in patients who had unresectable localized recurrence after surgery for advanced gastric cancer and evaluated the safety and efficacy of CRT.

Methods

The study group comprised 21 patients who received concurrent CRT for unresectable localized recurrence after undergoing R0 resection for stage II/III advanced gastric cancer. Localized recurrence was defined as a few or limited recurrent lesions.

Results

The recurrence pattern was anastomotic recurrence in 7 patients, abdominal lymph-node recurrence in 12, and anastomotic recurrence plus abdominal lymph-node recurrence in 2. The median total dose of radiotherapy was 48.6 Gy (range 39.6–56.0), and the CRT completion rate was 100 % (21 of 21 patients). CRT-related grade 3 or higher toxicity comprised neutropenia in 33.3 % of patients and anorexia in 9.5 %. The response rate was 61.9 % (complete response 38.1 %, partial response 23.8 %). The median overall survival was 35.0 months.

Conclusions

We conclude that CRT may become one treatment strategy for the management of unresectable localized recurrence after curative resection of advanced gastric cancer.

     

Impact of synthetic ghrelin administration for patients with severe body weight reduction more than 1 year after gastrectomy: a phase II clinical trial

Purpose

Ghrelin is mainly secreted from the stomach and plays a role in appetite, weight gain, and the promotion of a positive energy balance. The levels of ghrelin decrease immediately after gastrectomy. We herein investigated the effect of the administration of synthetic ghrelin to treat postoperative severe weight loss in a prospective, one-arm clinical trial to develop new strategies for weight gain.

Methods

Ten patients (four distal gastrectomy and six total gastrectomy) received ghrelin treatment. Eligibility criteria included patients who underwent gastrectomy more than 1 year previously and 15 % body weight loss from the preoperative weight or a body mass index under 19. Synthetic human ghrelin (3 μg/kg) was administered to the patients twice a day for 1 week. Oral intake of calories, appetite [evaluated using the visual analog scale (VAS)], and body weight before and during administration of ghrelin were compared.

Results

There was a significant difference in the oral food intake before and during treatment (before treatment: 1236 ± 409 kcal vs. during treatment: 1398 ± 365 kcal, p = 0.039), and the VAS for appetite significantly improved with each day of ghrelin administration (p < 0.05). Significant amounts of body weight were gained (39.5 ± 6.8 vs. 40.1 ± 6.9, p = 0.037).

Conclusions

The administration of synthetic ghrelin improved the food intake and was effective for treating appetite loss and body weight loss. Synthetic ghrelin may be a promising new therapy for severe body weight loss following gastrectomy.

     

Strong cytoplasmic expression of NF-κB/p65 correlates with a good prognosis in patients with triple-negative breast cancer

Purpose

Recent studies have indicated that constitutive NF-κB activity could be involved in the proliferation of triple-negative breast cancer.

Methods

The NF-κB/p65 expression and the effects of a NF-κB inhibitor, (?)-DHMEQ, were examined in triple-negative MDA-MB-231 breast cancer cells. Women with triple-negative breast cancer treated with neoadjuvant chemotherapy between 2002 and 2012 were retrospectively analyzed for their expression of NF-κB/p65, Bcl2 and Ki67 by immunohistochemistry in pre- and post-treatment specimens. The factors predicting the response to neoadjuvant chemotherapy and the prognosis were analyzed.

Results

NF-κB/p65 was predominantly expressed in the cytoplasm of MDA-MB-231 cells. Of 34 triple-negative breast cancer patients, positive staining for NF-κB/p65 expression was detected in the nuclei of a few cells in seven tumors before neoadjuvant chemotherapy, while the expression of NF-κB/p65 in the cytoplasm was detected in almost all tumor cells of 33 tumors. The expression levels of NF-κB/p65 were not associated with the response to neoadjuvant chemotherapy, although the cytoplasmic NF-κB/p65 staining intensity was significantly decreased in the post-treatment tumor samples compared with the pretreatment samples. All patients whose tumors showed strong cytoplasmic NF-κB/p65 expression before neoadjuvant chemotherapy are currently disease free.

Conclusion

Our results suggest that strong cytoplasmic NF-κB/p65 expression could be a prognostic marker for patients with triple-negative breast cancer.

     

Analysis of the effect of leptin on immune function in vivo using diet-induced obese mice

Leptin can regulate several immune functions. However, the role of leptin on lymphocyte function has not been recognized in vivo. Accordingly, we have investigated the effect of leptin on starvation-induced immune dysfunction using diet-induced obese mice. To induce obesity, C57BL/6J mice were fed a high-fat diet for 14 weeks and control mice were fed a standard diet for the same period. The obese and control groups of mice were then starved for 48 h, and received intraperitoneal injections of recombinant leptin or phosphate-buffered saline four times during starvation. Other control mice in both diet groups were free fed without being starved. Although starvation of the control mice dramatically reduced the weights of the immune organs, cytokine production and increased proliferation of cultured splenocytes, these levels returned to those of the free-feeding groups with exogenous leptin administration. However, these effects of leptin were not observed in obese mice. These findings provide some evidence that leptin can regulate the immune function in vivo. It is also suggested that the action of leptin might not appear in obesity.     

Oolong tea increases plasma adiponectin levels and low-density lipoprotein particle size in patients with coronary artery disease

BACKGROUND: Oolong tea has been studied for its effect on cardiovascular disease and obesity. Plasma adiponectin levels are reduced in obesity, in patients with type 2 diabetes mellitus and in coronary artery disease (CAD). OBJECTIVE: To investigate prospectively, whether intake of Oolong tea influences plasma adiponectin levels, low-density lipoprotein (LDL) particle size, total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, serum triglyceride and plasma glucose levels in patients with CAD. METHODS: Twenty two patients in our study consumed Oolong tea (1000 ml) or water for 1 month in our randomized cross-over study design. RESULTS: There was a significant difference in plasma adiponectin levels before and after 1 month intake of Oolong tea (6.26 +/- 3.26 microg/ml versus 6.88 +/- 3.28 microg/ml, P < 0.05), and in plasma level LDL particle size (25.02+/-0.67 nm versus 25.31+/-0.60 nm, P < 0.01). The water-consuming control group showed no changes (6.28+/-3.28 microg/ml versus 6.23+/-3.21 microg/ml) in adiponectin levels or LDL particle sizes (25.03+/-0.70 nm versus 25.02+/-0.72 nm). We also observed a significant difference in hemoglobin A1c levels (7.23 +/- 4.45% versus 6.99 +/- 4.30%, P < 0.05) before and after intake of Oolong tea. CONCLUSION: Oolong tea may have beneficial effects on the progression of atherosclerosis in patients with CAD.     

Lactobacillus GG-fermented milk prevents DSS-induced colitis and regulates intestinal epithelial homeostasis through activation of epidermal growth factor receptor

Background

Fermented milk is considered one of the best sources for efficient consumption of probiotic strains by hosts to promote good health. The purpose of this study was to investigate the effects of orally administering LGG-fermented milk (LGG milk) on intestinal inflammation and injury and to study the mechanisms of LGG milk’s action.

Methods

LGG milk and non-LGG-fermented milk (non-LGG milk) were administered through gavage to mice before and during dextran sodium sulfate (DSS)-induced intestinal injury and colitis. Inflammatory/injury score and colon length were assessed. Intestinal epithelial cells were treated with the soluble fraction of LGG milk to detect its effects on the epidermal growth factor receptor (EGFR) and its downstream target, Akt activation, cytokine-induced apoptosis, and hydrogen peroxide (H₂O₂)-induced disruption of tight junctions.

Results

LGG milk treatment significantly reduced DSS-induced colonic inflammation and injury, and colon shortening in mice, compared to that in non-LGG milk-treated and -untreated mice. The soluble fraction of LGG milk, but not non-LGG milk, stimulated the activation of EGFR and Akt in a concentration-dependent manner, suppressed cytokine-induced apoptosis, and attenuated H₂O₂-induced disruption of tight junction complex in the intestinal epithelial cells. These effects of LGG milk were blocked by the EGFR kinase inhibitor. LGG milk, but not non-LGG milk, contained two soluble proteins, p40 and p75, that have been reported to promote survival and growth of intestinal epithelial cells through the activation of EGFR. Depletion of p40 and p75 from LGG milk abolished the effects of LGG milk on prevention of cytokine-induced apoptosis and H₂O₂-induced disruption of tight junctions.

Conclusions

These results suggest that LGG milk may regulate intestinal epithelial homeostasis and potentially prevent intestinal inflammatory diseases through activation of EGFR by LGG-derived proteins.