Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas.

Mitogen-activated protein kinase phosphatase 5 (MKP-5)/DUSP10 acts as a phosphatase of stress-activated kinases (JNK and p38), but its activity towards ERK has not been demonstrated. In the present study we observed that MKP-5 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription. These data suggested a novel MKP-5 function as a scaffold protein for the ERK pathway.

Infiltration of CD40-positive tumor-associated macrophages indicates a favorable prognosis in colorectal cancer patients.

Background/aims: Recently the role of tumor-associated macrophages (TAMs) on immunity has been variously discussed. We studied a series of cell surface antigens in TAMs in colorectal cancer tissues and their corresponding normal tissues using flow cytometry to find out prognostic indicators of these patients.

Methodology: We assessed the numbers of CD14+ macrophages positive for each of the cell surface antigens (CD80, CD86, HLA-DR, CD1a, CD40 and CD83) in cancer tissues and corresponding normal tissues among 31 patients with colorectal cancer, and performed the univariate and multivariate analysis to find out prognostic indicators for overall survival among the patients.

Infiltration of CD14-positive macrophages at the invasive front indicates a favorable prognosis in colorectal cancer patients with lymph node metastasis.

Background/aims: To clarify the distribution of CD14+ macrophages in colorectal cancer using flow cytometry and immunohistochemistry, and to elucidate the roles of CD14+ macrophages in colorectal cancer.

Methodology: We studied the paired cancerous and corresponding normal tissues from 52 patients with colorectal cancer for the distribution of CD14+, CD1a+, CD83+ and CD68+ cells, and correlated the findings with the clinicopathological characteristics and with the expression of CD86 and CD80 in the CD14+ macrophages, which are co-stimulatory factors for T cell activation.

Results: 1) CD14+ macrophages were distributed predominantly at the invasive front of colorectal cancer tissues, rather than in the normal tissues, 2) a high percentage of the CD14+ macrophages expressed CD86 and CD80, and 3) in the colorectal cancer cases with lymph node metastasis, the 5-year overall survival rate of the high CD14 group, in which the number of CD14+ macrophages was higher than the median, was better than that of the low CD14 group.

DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression.

The dual-specificity phosphatase (DUSP) 13 gene encodes two atypical DUSPs, DUSP13B/TMDP and DUSP13A/MDSP using alternative exons. DUSP13B protein is most highly expressed in testis, particularly in spermatocytes and round spermatids of the seminiferous tubules, while that of DUSP13A is restricted to skeletal muscle. Here, we show that DUSP13B inactivated MAPK activation in the order of selectivity, JNK = p38>ERK in cells, while DUSP13A did not show MAPK phosphatase activity.

Cancer-associated splicing variants of the CDCA1 and MSMB genes expressed in cancer cell lines and surgically resected gastric cancer tissues.

Background: Alternative splicing is a molecular mechanism by which different combinations of exons can be alternatively spliced to produce different mRNA isoforms. Recently, several databases have been published to predict the alternative splicing of mRNA; cancer-specific alternative splicing has also been predicted with these databases. Those variants may be potentially useful targets for cancer therapy, however, the accuracy and veracity of these databases have yet to be confirmed.

Outcomes after pylorus-preserving gastrectomy for early gastric cancer: a prospective multicenter trial.

The aim of the present study was to compare in a prospective, multicenter trial the results early and late after pylorus-preserving gastrectomy (PPG) versus conventional distal gastrectomy (CDG) with Billroth I anastomosis for early gastric cancer. Eighty-one patients with early gastric cancer were randomized and then underwent either PPG or CDG. Duration of operation, intraoperative blood loss, days until removal of the nasogastric tube, days until start of oral intake, and decrease in body weight were studied as parameters for outcomes early after the surgery.

Effect of ileo-jejunal transposition on ileal longitudinal smooth muscle contractility in vitro in rats.

The aim of the present paper was to study the effects of ileo-jejunal transposition (IJT) on ileal contractile activity in vitro in rats. Male Sprague-Dawley rats were divided into three groups: control, IJT, and sham. In rats with IJT, the distal ileum was interposed isoperistaltically into the proximal jejunum.

Evidence for existence of oligoclonal tumor-infiltrating lymphocytes and predominant production of T helper 1/T cytotoxic 1 type cytokines in gastric and colorectal tumors.

Tumor-infiltrating lymphocytes (TIL) play a central role in cellular immunity against tumor. We have revealed the characteristics of TILs in terms of T-cell receptor (TCR) repertoire, T-cell clonality, and cytokine production. TCR repertoire analyses and CDR3 size spectratyping were performed using peripheral blood mononuclear cells (PBMCs) and tissue specimens of gastric or colorectal cancers surgically resected from 11 patients.

[Thymidine phosphorylase expressed in monocyte-macrophages enhanced anticancer effect of 5'-deoxy-5-fluorouridine on colorectal carcinoma cells].

Objective: To detect the thymidine phosphorylase (dThdPase) expression in colorectal carcinoma tissue, and clarify whether dThdPase expressed in macrophage-like cell lines, and monocytes from human peripheral blood can modulate the anticancer effect of 5'-deoxy-5-fluorouridine (5'-DFUR) on colorectal carcinoma cells.

Methods: Forty specimens resected from 40 patients with colorectal carcinoma were immunohistochemically stained by the monoclonal antibodies 654-1 (anti-dThdPase) and PG-M1 (anti-macrophage marker CD68). Then morphometrical analysis and positive cell counting were performed.

New reconstructive procedure after intestinal resection for Crohn's disease: modified side-to-side isoperistaltic anastomosis with double Heineke-Mikulicz procedure.

Although side-to-side isoperistaltic anastomosis is a useful strictureplasty technique when long segments of intestinal stenosis complicate Crohn's disease, concerns have been raised regarding disease recurrence adjacent to the anastomosis. We performed side-to-side isoperistaltic anastomosis without spatulated intestinal ends as a method of reconstruction after intestinal resection for Crohn's disease; both intestinal ends were transversely closed like a Heineke-Mikulicz-type strictureplasty. With this procedure, the luminal diameter proximal and distal to the anastomosis became wider than the original diameter of the intestine.

Expression of thymidine phosphorylase by macrophages in colorectal cancer tissues.

Aim: To detect the thymidine phosphorylase (dThdPase) expression in human colorectal cancer tissues and cells.

Methods: Forty specimens resected from patients with colorectal cancer were immunohistochemically stained by 654-1, anti-dThdPase monoclonal antibody, PG-M1, anti-macrophage marker CD68 monoclonal antibody. Morphometrical analysis and positive cell counting were performed.

Thymidine phosphorylase expressed in macrophages enhances antitumor effect of 5'-deoxy-5-fluorouridine on human colorectal carcinoma cells.

Background: Thymidine phosphorylase (dThdPase) is a key enzyme in the activation of the pro-drugs of 5-fluorouracil (5-FU), 5-deoxy-5-fluorouridine (5'-DFUR) and capecitabine. In colorectal carcinoma (CRC), the major cells expressing dThdPase have been shown to be stromal cells, particularly macrophages.

Materials And Methods: The present study was designed to clarify whether dThdPase expressed in macrophage-like cell lines, THP-1 and U937, and monocyte-rich mono-nuclear cells (MoMNCs) from human peripheral blood can modulate the antitumor effect of 5'-DFUR on CRC cells.

Interleukin-12 administration is more effective for preventing metastasis than for inhibiting primary established tumors in a murine model of spontaneous hepatic metastasis.

Purpose: The effect of interleukin-12 (IL-12) on tumor growth at the primary site and its therapeutic efficacy against metastasis were examined using a model of spontaneous hepatic metastasis.

Methods: IL-12 was peritumorally injected into RL male1 tumor-bearing BALB/c male mice at the different tumor stage.

Results: Striking inhibition of hepatic metastasis in both athymic and euthymic mice was induced by the administration of IL-12 irrespective of the stage of tumor progression.