Effect of type II collagen extract on immunosuppression induced by methotrexate in rats.

This study investigated the effect of type II collagen extract on SD rats with deteriorated immunity caused by methotrexate. The test samples were dosed once a day for 28 days by gastric gavage at dosage 250 mg/kg and 500 mg/kg after methotrexate treatment, and the changes on body weight, total blood leukocyte numbers, the percentages of B-cells, CD4+ T-cells and CD8+ T-cells in the blood and spleen were observed. The changes on body weight, the total blood leukocyte numbers, the total lymphocyte numbers in the spleen, the ratio of CD4+ and CD8+ T-cells in the blood and spleen were increased significantly in type II collagen extract groups as compared with the control group. According to the above results, type II collagen extract has an effect of increasing immune responses on rats with deteriorated immunity caused by methotrexate.

The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

Expression of tumoral FOXP3 in gastric adenocarcinoma is associated with favorable clinicopathological variables and related with Hippo pathway.

FOXP3 is a transcription factor and well-known hallmark of immune suppressive T regulatory cells (Tregs). Recent studies indicate that, in addition to its association with Treg function in the immune system, FOXP3 plays an important role in tumor development. And important tumor suppressor relay between the FOXP3 and Hippo pathways was found in human cancer. Thus, we investigated tumoral FOXP3, infiltrated Tregs count, Lats2, and YAP expression in gastric adenocarcinoma, and the relationships between expression of these three proteins and p53, Ki67, and other clinicopathological variables. We used 118 gastric adenocarcinoma tissues via immunohistochemical analysis, using a tissue microarray, in relation to survival and other clinicopathological factors. We report the several novel observations about the relationship between tumoral FOXP3 and Hippo pathway components in gastric adenocarcinoma. Positive tumoral FOXP3 expression was significantly related with smaller tumor size, tubular tumor type, lower histological grade, lower T stage, lower recurrence rate, less lymphatic invasion, and less neural invasion. Furthermore, patients with positive tumoral FOXP3 experienced significantly better disease-free and overall survival compared to patients with negative tumoral FOXP3. These findings show that tumoral FOXP3 expression is associated with favorable clinicopathological variables in gastric adenocarcinoma. And we report the novel observation of a relationship between tumoral FOXP3 and Hippo pathway components in gastric adenocarcinoma. Tumoral FOXP3 expression, infiltrated Tregs count, and Lats2 expression were all positively correlated with YAP expression. These findings suggest that the Hippo pathway in gastric adenocarcinoma might be influenced by both tumoral FOXP3 and infiltrated Tregs. In conclusion, the loss of FOXP3 expression in cancer cells is thought to contribute to tumorigenesis and progression of gastric adenocarcinoma. The expression of FOXP3 in gastric adenocarcinoma is related with Lats2 and YAP expression of the Hippo pathway.

Tumoral FOXP3 has potential oncogenic function in conjunction with the p53 tumor suppressor protein and infiltrated Tregs in human breast carcinomas.

FOXP3 is a transcription factor and a well-known hallmark of immune suppressive T regulatory cells. Recent studies indicate that in tumor cells, FOXP3 plays an important role in tumor development in addition to its well-established Treg function in the immune system. We investigated tumoral FOXP3 expression in breast carcinoma, and the relationships between tumoral FOXP3 expression and p53, HER-2/ErbB2, Ki67, infiltrated Tregs, and other clinicopathological variables. Tissue samples from 272 cases of breast carcinoma were used. We assessed tumoral FOXP3, p53, HER-2/ErbB2, Ki67, and infiltrated Tregs using immunohistochemical staining. Positive expression of tumoral FOXP3 was observed in 38.6% (105/272) of breast carcinomas. Positive tumoral FOXP3 expression was significantly related with positive p53 and higher Ki67 expression. Higher histological grade was significantly correlated to increased tumoral FOXP3 expression. Tumoral FOXP3 expression was positively correlated with infiltrated FOXP3-expressing Tregs. From these data, we argue that tumoral FOXP3 has a potential oncogenic function in conjunction with the p53 tumor suppressor protein and infiltrated Tregs in human breast carcinomas.

Association of polymorphisms in monocyte chemoattractant protein-1 promoter with diabetic kidney failure in Korean patients with type 2 diabetes mellitus.

Monocyte chemoattractant protein-1 (MCP-1) is suggested to be involved in the progression of diabetic nephropathy. We investigated the association of the -2518 A/G polymorphism in the MCP-1 gene with progressive kidney failure in Korean patients with type 2 diabetes mellitus (DM). We investigated -2518 A/G polymorphism of the MCP-1 gene in type 2 DM patients with progressive kidney failure (n=112) compared with matched type 2 DM patients without nephropathy (diabetic control, n=112) and healthy controls (n=230). The overall genotypic distribution of -2518 A/G in the MCP-1 gene was not different in patients with type 2 DM compared to healthy controls. Although the genotype was not significantly different between the patients with kidney failure and the diabetic control (p=0.07), the A allele was more frequent in patients with kidney failure than in DM controls (42.0 vs. 32.1%, p=0.03). The carriage of A allele was significantly associated with kidney failure (68.8 vs. 54.5%, OR 1.84, 95% CI 1.07-3.18). In logistic regression analysis, carriage of A allele retained a significant association with diabetic kidney failure. Our result shows that the -2518 A allele of the MCP-1 gene is associated with kidney failure in Korean patients with type 2 DM.