A case of gastric granular cell tumor

We herein describe an extremely rare case of gastric granular cell tumor (GCT). The gastric submucosal tumor showed a central tiny depression on the surface with a molar tooth-like appearance on esophagogastroduodenoscopy. Our case highlights that gastric GCT should be considered as differential diagnosis of gastric submucosal tumors

The role of the SWI/SNF chromatin remodeling complex in pancreatic ductal adenocarcinoma

ATP-dependent chromatin remodeling complexes are a group of epigenetic regulators that can alter the assembly of nucleosomes and regulate the accessibility of transcription factors to DNA in order to modulate gene expression. One of these complexes, the SWI/SNF chromatin remodeling complex is mutated in more than 20% of human cancers. We have investigated the roles of the SWI/SNF complex in pancreatic ductal adenocarcinoma (PDA), which is the most lethal type of cancer. Here, we reviewed the recent literature regarding the role of the SWI/SNF complex in pancreatic tumorigenesis and current knowledge about therapeutic strategies targeting the SWI/SNF complex in PDA. The subunits of the SWI/SNF complex are mutated in 14% of human PDA. Recent studies have shown that they have context-dependent oncogenic or tumor-suppressive roles in pancreatic carcinogenesis. To target its tumor-suppressive properties, synthetic lethal strategies have recently been developed. In addition, their oncogenic properties could be novel therapeutic targets. The SWI/SNF subunits are potential therapeutic targets for PDA, and further understanding of the precise role of the SWI/SNF complex subunits in PDA is required for further development of novel strategies targeting SWI/SNF subunits against PDA

Multimodality imaging to identify lipid-rich coronary plaques and predict periprocedural myocardial injury: Association between near-infrared spectroscopy and coronary computed tomography angiography

BackgroundThis study compares the efficacy of coronary computed tomography angiography (CCTA) and near-infrared spectroscopy intravascular ultrasound (NIRS–IVUS) in patients with significant coronary stenosis for predicting periprocedural myocardial injury during percutaneous coronary intervention (PCI).MethodsWe prospectively enrolled 107 patients who underwent CCTA before PCI and performed NIRS–IVUS during PCI. Based on the maximal lipid core burden index for any 4-mm longitudinal segments (maxLCBI4mm) in the culprit lesion, we divided the patients into two groups: lipid-rich plaque (LRP) group (maxLCBI4mm ≥ 400; n = 48) and no-LRP group (maxLCBI4mm < 400; n = 59). Periprocedural myocardial injury was a postprocedural cardiac troponin T (cTnT) elevation of ≥5 times the upper limit of normal.ResultsThe LRP group had a significantly higher cTnT (p = 0.026), lower CT density (p < 0.001), larger percentage atheroma volume (PAV) by NIRS–IVUS (p = 0.036), and larger remodeling index measured by both CCTA (p = 0.020) and NIRS–IVUS (p < 0.001). A significant negative linear correlation was found between maxLCBI4mm and CT density (rho = −0.552, p < 0.001). Multivariable logistic regression analysis identified maxLCBI4mm [odds ratio (OR): 1.006, p = 0.003] and PAV (OR: 1.125, p = 0.014) as independent predictors of periprocedural myocardial injury, while CT density was not an independent predictor (OR: 0.991, p = 0.22).ConclusionCCTA and NIRS–IVUS correlated well to identify LRP in culprit lesions. However, NIRS–IVUS was more competent in predicting the risk of periprocedural myocardial injury

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

BACKGROUND:Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. METHODS:CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. RESULTS:We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). CONCLUSIONS:We confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD. These results give us supporting evidence that DNA methylation mediates genetic effects on disease susceptibility

Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study

Abstract Background Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. Methods We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. Results Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2–41) and 6 (1–14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p < 0.001). Conclusion The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB

The relation between genotype of rs36221701 and the expression levels of genes around rs36221701.

<p>The relation between genotype of rs36221701 and the expression levels of genes around rs36221701.</p

Allele-specific bisulfite pyrosequencing.

<p>To analyze the allele-specific DNA methylation, we individually measured the DNA methylation of each allele and compared methylation between the two alleles. Thus, the allele-specific polymerase chain reaction (PCR) was performed and the methylation levels of each of the two alleles, given allele-specific amplicons, were measured separately using pyrosequencing. The allele-specific PCR primers were designed such that each primer of 3′ end was a pair of base of heterozygous SNP. (a) The reference sequence of rs36221701 before and after bisulfite conversion. Rs36221701 contained two CpG sites denoted as CpG1 and CpG2 in 5′ to 3′ direction. By bisulfite conversion, unmethylated C is converted to U (U is converted to T by PCR). Rs362210701 (C/T) is converted to (T/T); it was impossible to distinguish the converted T and original T. Thus, we were unable to detect the origin of the allele for this SNP by PCR primers. (b) Allele-specific PCR. We designed PCR primer for rs13239907 (A/G), which is located 297 bp downstream of rs36221701 and was in complete linkage disequilibrium with rs36221701 (A→C, G→T: r² = 1.0) in JPT data from 1,000 genome project. The forward primer was common to both alleles; reverse primers were designed such that each primer of 3′ end was a pair of bases of genotypes (A or G: complementary strand). (c) Allele-specific pyrosequencing. The two given allele-specific amplicons were separately analyzed using pyrosequencing. Sequence primer 1 targeted rs13239907 and was used to check the accuracy of allele-specific PCR, whereas sequence primer 2 targeted CpG1 and CpG2 was used to analyze the ratio of methylation around rs36221701. (d) Primer details. The 3′ end of PCR primer R was a pair of base of heterozygous SNP. 5′ end of PCR primer R was biotinylated.</p