Overexpressed LPCAT1 protein in gastric mucosa appears to play important roles in the tumorigenic process of gastric cancer by converting LPC to PC.

Tumor angiogenesis plays a critical role in colorectal cancer progression. Recent randomized clinical trials have revealed the additive effect of bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF)‐A, to conventional chemotherapy in the improved survival of patients with metastatic colorectal cancer. However, a number of preclinical reports indicate the development of resistance to anti‐angiogenic therapy. In this study, we addressed the effects of anti‐VEGF antibodies on the growth and malignant behavior of colorectal cancer cells. TK‐4, a solid tumor strain derived from a colon cancer patient, was subcutaneously or orthotopically implanted into nude mice. Short‐term administration of anti‐VEGF antibodies inhibited the growth of cecal tumors at day 14 by suppressing mitosis, but prolonged treatment resulted in the recovery of cellular proliferation and suppression of apoptosis at day 35. Intratumoral hypoxia induced by anti‐VEGF antibody treatment resulted in activation of hypoxia inducible factor‐1α protein and an increased number of aldehyde dehydrogenase 1‐positive tumor cells. In microarray analysis, stanniocalcin 2 (STC2) was the most highly upregulated gene in anti‐VEGF antibody‐treated tumors. In vitro analyses showed that the growth and migration of SW480 colon cancer cells under hypoxic conditions were significantly inhibited by knockdown of STC2. In vivo serial transplantation of TK‐4 revealed that long‐term administration of anti‐VEGF antibodies increased the tumorigenicity of colon cancers and accelerated tumor growth when transplanted into secondary recipient mice. Our data provide a potential molecular explanation for the limited clinical effectiveness of anti‐VEGF antibodies.

Background:Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis.Methods:Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays.Results:Hierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis (P<0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival (P=0.005; n=139) and liver metastasis-free survival (P=0.001; n=128).Conclusions:Alterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.

Control of liver metastasis is an important issue in the treatment of colorectal cancer (CRC). MicroRNAs have been shown to be involved in the development of many cancers, but little is known about their role in the process of colorectal liver metastasis. We compared miRNA expression between primary colorectal tumors and liver metastasis to identify those involved in the process of metastasis. Cancer cells were isolated from formalinfixed paraffin-embedded primary CRC samples and their corresponding metastatic liver tumors in six patients using laser capture microdissection, and miRNA expression was analyzed using TaqMan miRNA arrays. The most abundant miRNA in liver metastasis compared with primary tumors was miR-122. Immunohistochemical analysis revealed that the expression levels of cationic amino acid transporter 1 (CAT1), a negative target gene of miR-122, were lower in liver metastases than primary tumors (P < 0.001). Expression levels of CAT1 in 132 primary tumors were negatively correlated with the existence of synchronous liver metastasis (P = 0.0333) and tumor stage (P < 0.0001). In an analysis of 121 colon cancer patients without synchronous liver metastasis, patients with CAT1-low colon cancer had significantly shorter liver metastasis-free survival (P = 0.0258) but not overall survival or disease-free survival. Overexpression of miR-122 and concomitant suppression of CAT1 in the primary tumor appears to play important roles in the development of colorectal liver metastasis. Expression of CAT1 in the primary CRC has the potential to be a novel biomarker to predict the risk of postoperative liver metastasis of CRC patients. (Cancer Sci 2013; 104: 624-630) C olorectal cancer (CRC) is a major cause of cancer death worldwide. Compared to Western Europe and the USA, CRC is less common in Japan, however, the incidence rate is increasing and over 100 000 new cases arise per year. (1) Liver metastasis, which is the most common site for metastatic spread of CRC, is observed in 20-25% of patients at initial diagnosis, and eventually develops after resection of the primary CRC in a further 40-50% of patients. (2) Although the prognosis of patients with colorectal liver metastasis has been improved by recent advances in multidisciplinary treatments, liver metastasis is still one of the major determinants of survival. (3) To control this metastatic disease, and thereby improve patient survival, the mechanisms of colorectal liver metastasis require elucidation.Recently, it was reported that miRNAs are involved in cancer development. As small non-coding single-stranded lengths of RNA consisting of 21-25 nucleotides, miRNAs can associate with the RNA-induced silencing complex (RISC). (4) The miRNA-RISC complex binds to complementary sequences located mainly in the 3′-UTR of target mRNAs and causes the translational repression or cleavage of these mRNA sequences. (4,5) This post-transcriptional regulation of gene expression has been found in a wide variety of human cancers, and miRNAs are thought to play importa...

We report a rare case of paraganglioma that developed in the mesentery of terminal ileum. A 78-yearold woman complained of right-sided abdominal pain. Abdominal computed tomography revealed a solid heterogeneously enhanced mass in the right lower abdomen. The tumor was laparoscopically excised. The mesenteric tumor was well circumscribed, ovoid, and encapsulated and measured 3 cm × 1.5 cm × 1.5 cm. Histological examination showed a cellular neoplasm comprised of nests and groups of tumor cells separated by fibrovascular connective tissue, giving a characteristic nested Zellballen pattern. Immunohistochemically, the tumor cells were positive for chromogranin, synaptophysin, CD56, and vimentin and negative for cytokeratins, SMA, CD34, CD117/c-kit and S100. On the basis of histologic and immunohistochemical features, a diagnosis of mesenteric paraganglioma was made. The operative and postoperative courses were unremarkable, and the patient was discharged on postoperative day 7. She was doing well 1 year after the surgery with no signs of recurrence. Extra-adrenal paragangliomas most commonly develop adjacent to the aorta, particularly the area corresponding to the organ of Zuckerkandl. Mesenteric paraganglioma, as in our case, is extremely rare; only 11 cases have been reported in the literature. We herein discuss the clinical findings of these cases.