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A 55-year-old man visited our hospital for a detailed examination of a gastric submucosal tumor that was first detected 10 years prior. The tumor continued to grow and had developed a depressed area in its center. A histopathological examination of biopsy specimens revealed gastric adenocarcinoma of the fundic gland type (GA-FG). It was diagnosed as T2 based on the invasion depth as determined by white-light endoscopy and endoscopic ultrasonography. A total gastrectomy with lymphadenectomy was performed and a GA-FG in the mucosa and submucosa was confirmed histopathologically. However, there was a gradual transition to an infiltrative tubular adenocarcinoma with poorly differentiated components in the muscular and subserosal layers. Metastasis was identified in a dissected lymph node (LN). This is the first report of a GA-FG progressing to an aggressive cancer with LN metastasis. These findings modify our understanding of the pathophysiology of GA-FG. [ABSTRACT FROM AUTHOR]

IDO, an enzyme that degrades the essential amino acid l-tryptophan to N-formylkynurenine, is known to exert immunomodulatory effects in a number of diseases and disorders. IDO expression is increased in tumors, where it is thought to be involved in tumor evasion by suppressing the immune response. A competitive inhibitor of IDO is currently being tested in clinical trials for relapsed or refractory solid tumors; however, there remains a concern that attenuation of the immunosuppressive function of IDO might exacerbate inflammatory responses. In this study, we investigated the role of IDO in 2,4,6-trinitrobenzene sulfate (TNBS)-induced colitis in mice by gene deletion and pharmacological inhibition. TNBS treatment induced significantly more severe colitis in Ido1 gene-deficient (Ido1-/-) mice than in Ido1 wild-type (Ido1+/+) mice, indicating a role for IDO1 in suppression of acute colitis. Consistent with this, the expression of Ido1 was increased in the colonic interstitial tissues of TNBS-treated Ido1+/+ mice. Furthermore, transplantation of Ido1+/+ bone marrow cells into Ido1-/- mice reduced the pathological damage associated with colitis, altered the expression of cytokines, including IFN-γ, TNF-α, and IL-10, and increased the number of CD4+ Foxp3+ regulatory T cells in the colon. Pharmacological inhibition of IDO enzymatic activity by oral administration of 1-methyltryptophan (1-methyl-l-tryptophan or 1-methyl-d-tryptophan) significantly increased the severity of TNBS-induced colitis in mice, demonstrating that both stereoisomers can promote colitis. Collectively, our data indicate that IDO1 plays an important immunoregulatory role in the colon. [ABSTRACT FROM AUTHOR]

Activation of peroxisome proliferator-activated receptor (PPAR) a disrupts growth-related activities in a variety of human cancers. This study was designed to determine whether fenofibrate, a PPARa agonist, can suppress 4-nitroquinoline 1-oxide (4-NQO)-induced proliferative lesions in the lung of obese hyperlipidemic mice. Male Tsumura Suzuki Obese Diabetic mice were subcutaneously injected with 4-NQO to induce lung proliferative lesions, including adenocarcinomas. They were then fed a diet containing 0.01% or 0.05% fenofibrate for 29 weeks, starting 1 week after 4-NQO administration. At week 30, the incidence and multiplicity (number of lesions/mouse) of pulmonary proliferative lesions were lower in mice treated with 4-NQO and both doses of fenofibrate compared with those in mice treated with 4-NQO alone. The incidence and multiplicity of lesions were significantly lower in mice treated with 4-NQO and 0.05% fenofibrate compared with those in mice treated with 4-NQO alone (p < 0.05). Both doses of fenofibrate significantly reduced the proliferative activity of the lesions in 4-NQO-treated mice (p < 0.05). Fenofibrate also significantly reduced the serum insulin and insulin-like growth factor (IGF)-1 levels, and decreased the immunohistochemical expression of IGF-1 receptor (IGF-1R), phosphorylated Akt, and phosphorylated Erk1/2 in lung adenocarcinomas. Our results indicate that fenofibrate can prevent the development of 4-NQO-induced proliferative lesions in the lung by modulating the insulin-IGF axis. [ABSTRACT FROM AUTHOR]

The forced reduction of global DNA methylation suppresses tumor development in several cancer models in vivo. Nevertheless, the mechanisms underlying these suppressive effects remain unclear. In this report, we describe our findings showing that a genome-wide reduction in the DNA methylation levels induces cellular differentiation in association with decreased cell proliferation in ApcMin/+ mouse colon tumor cells in vivo. Colon tumor-specific DNA methylation at Cdx1 is reduced in the DNA-hypomethylated tumors accompanied by Cdx1 derepression and an increased expression of intestinal differentiation-related genes. Furthermore, a histological analysis revealed that Cdx1 derepression in the DNA-hypomethylated tumors is correlated with the differentiation of colon tumor cells. Similarly, the treatment of human colon cancer cell lines with a hypomethylating agent induces differentiation-related genes, including CDX1. We herein propose that DNA demethylation exerts a tumor suppressive effect in the colon by inducing tumor cell differentiation. [ABSTRACT FROM AUTHOR]

A solid pseudopapillary neoplasm (SPN) of the pancreas has distinct histopathological features. A solid pattern of growth with pseudopapillary structures that result from degeneration is observed. On rare occasions, the tumor may vary from being entirely solid to completely cystic. The present study describes two unique cases of SPN. A 25-year-old male presented with a pancreatic tumor showing a predominantly solid pattern with no degenerative change, although the pre-operative cytological specimens that were obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) revealed pseudopapillary structures. The second case was of an 11-year-old female who presented with a pancreatic tumor with prominent degeneration. Nests and cords of the remaining neoplastic cells were located only at the periphery, with perineural invasion. An immunohistochemical analysis revealed that the tumor cells in the two cases were positive for CD10 and β-catenin and negative for trypsin. An awareness of the broad morphological variability of SPN and an immunohistochemical panel that includes CD10, β-catenin and trypsin are useful for establishing an accurate diagnosis. [ABSTRACT FROM AUTHOR]