Search

Acquired genetic and epigenetic alterations in normal cells give rise to transformed cells, which lead to tumor development. Elucidation of the precise mechanisms underlying primary and metastatic tumor formation is required. MicroRNAs (miRNAs) are small noncoding RNAs that play a major role in post-transcriptional gene regulation during various biological processes. Accumulating evidence suggests that dysregulation of miRNAs is intimately involved in the carcinogenesis, progression and metastasis of many cancers, including gastric cancers (GCs), while the alteration of certain miRNAs provides biomarkers to detect early GCs. This review summarizes the most recent findings into the mechanisms of miRNA-mediated regulation of GCs, which will support the development of diagnostic biomarkers and novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Jumonji-domain containing 3 (JMJD3) affects transcriptional regulation by demethylating lysine 27 residue of histone 3. We investigated its function and prognostic significance in colorectal cancer (CRC). Methods: The influence of JMJD3 on cell proliferation was assessed using quantitative RT-PCR and western blot on the downstream target gene of JMJD3, in knock-down (KD) experiments and clinical samples from 151 CRC patients. Results: Cells with KD JMJD3 significantly increased proliferation through cell cycle progression and apoptosis suppression. Expression of P15INK4B was remarkably decreased in KD JMJD3 cells; and JMJD3 expression strongly correlated with p15INK4B expression in clinical CRC samples ( P < 0.001, r = 0.566). Low JMJD3 also was an independent predictor of poor prognosis ( P = 0.042) in surgically resected CRC patients. Conclusions: JMJD3 has prognostic significance in CRC and mediates p15INK4B expression. These results imply that elucidation of the JMJD3 role may lead to a new therapeutic approach for CRC patients. [ABSTRACT FROM AUTHOR]

Background: Smoking is one of the risk factors for postoperative morbidity. There were no studies on the correlation between the duration of smoking cessation and the incidence of morbidities after esophagectomy. Methods: A total of 246 patients undergoing elective esophagectomy with 2- or 3-field lymphadenectomy for esophageal cancer between April 2005 and February 2015 were retrospectively analyzed. Patients were divided into five groups according to the duration of smoking cessation [no smoking cessation (including cessation for a few days), cessation for 7-30, 31-90, ≥91 days, never smoker]. Results: Any morbidity of Clavien-Dindo classification (CDc) ≥II, pneumonia, any pulmonary morbidity, surgical site infection, cardiovascular morbidity, and severe morbidities of CDc ≥IIIb frequently occurred in patients with no smoking cessation. The incidence of pneumonia and severe morbidities decreased as the duration of smoking cessation became longer. Logistic regression analysis suggested that no smoking cessation was the independent risk factor for any pulmonary morbidity (HR 3.68, 95 % CI 1.152-11.74; p = 0.028). Smoking cessation ≤30 days was also the independent risk factor for pneumonia (HR 2.89, 95 % CI 1.141-7.301; p = 0.025). Smoking cessation ≤90 days was the independent risk factor for severe morbidities of CDc ≥IIIb (HR 2.82, 95 % CI 1.072-7.427; p = 0.036). Conclusions: Preoperative smoking cessation more than 90 days is ideal to reduce morbidities after esophagectomy. When patients with insufficient smoking cessation undergo esophagectomy, careful perioperative management is required. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of lipid and amino acid metabolism in patients with liver diseases results in obesity-related carcinogenesis and decreased levels of branched-chain amino acids (BCAA), respectively. This study assessed the clinical and prognostic impact of visceral fat amount (VFA) and its association with amino acid metabolism in patients with hepatocellular carcinoma (HCC). Methods: In this study, 215 patients who underwent hepatic resection for HCC were divided into two groups based on VFA criteria for metabolic abnormalities in Japan. Computed tomography was used to measure VFA at the third lumbar vertebra in the inferior direction. Results: Of the 215 patients, 132 had high and 83 had low VFA. High VFA was significantly associated with older age and higher body mass index (BMI), subcutaneous fat amount, and BCAA, but not with liver function, nutrient status, or tumoral factors. VFA was positively correlated with BMI ( P < 0.0001; r = 0.63) and BCAA levels ( P < 0.0001; r = 0.29). Overall survival was significantly greater in the high than in the low VFA group ( P = 0.002). Multivariate analyses showed that high VFA [hazard ratio (HR) 7.06; P = 0.024] and neutrophil/lymphocyte ratio (HR 3.47; P = 0.049) were significantly prognostic of overall survival, whereas subcutaneous fat amount, BMI, BCAA, serum albumin, and prognostic nutritional index were not. Conclusions: High VFA was associated with a high BCAA level, with high VFA prognostic of improved overall survival in Japanese patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Excess visceral adipose tissue may promote cancer development and progression via an obesity-related metabolic derangements, including adipocytokine-related inflammation, insulin resistance, and hypoxia. The relationship between visceral fat content and patient prognosis has been reported in some types of cancers, but not in the upper gastrointestinal cancer. The purpose of this retrospective study was to investigate the relationship between visceral fat status and clinical outcome in patients with upper gastrointestinal cancers (esophageal cancer and gastric cancer) treated by surgical resection. Methods: This retrospective study was conducted in a single, academic hospital in Kumamoto, Japan, and involved 507 patients with upper gastrointestinal cancers between April 2005 and December 2010. Preoperative visceral fat content was quantified by radiologic measures using standard computed tomography scans. Results: Higher visceral fat mount was correlated with male sex, presence of preoperative comorbidity, absence of preoperative therapy, low tumor depth, low tumor stage, and gastric cancer. Compared to high visceral fat cases, low visceral fat cases experienced a higher overall mortality rate [log-rank p = 0.0050; univariate hazard ratio (HR) = 1.73, 95 % confidence interval (CI) 1.16-2.54; p = 0.0075; multivariate HR 1.57; 95 % CI 1.02-2.37; p = 0.031]. Interestingly, the influence of low visceral fat on patient outcome was modified by age at surgery ( p for interaction = 0.036); low visceral fat was associated with a poor prognosis, especially in elderly patients (log-rank p < 0.0001). Conclusion: Visceral fat content in the upper gastrointestinal cancers was associated with a poor prognosis, thus suggesting that it has potential for use as a prognostic biomarker. [ABSTRACT FROM AUTHOR]

Purposes: Primary mucosal malignant melanoma (PMMM) is a rare and highly lethal neoplasm associated with a poor prognosis. CXC chemokine receptor 4 (CXCR4) is expressed on various tumor cells, including malignant melanoma. Recent data indicate that CXCL12 and CXCR4 play a critical role in the behavior of cancer cells and in the survival of cancer patients. However, there has been no study that has addressed the expression and function of CXCR4/CXCL12 signaling in PMMM. Methods: Immunohistochemical staining for CXCL12 and Ki67 in biopsy tissues from 10 cases of PMMM was performed. We analyzed the correlations between the clinicopathological features and expression levels of CXCL12 and Ki67. Results: Six cases showed a high level of CXCL12 expression, while four cases had a low level of expression. High expression of CXCL12 correlated with a poor prognosis, although statistical significance was not reached ( p = 0.054). Ki67 was highly expressed in five cases, while the expression in the other five cases was low. There was no correlation between the Ki67 expression and prognosis. Conclusions: The findings of this study suggest that CXCL12 expression may play an important role in the biological behavior of PMMM and may be associated with a poor prognosis of PMMM patients. [ABSTRACT FROM AUTHOR]

Background: Infection with Helicobacter pylori is the main risk factor for development of gastric cancer. CD44 overexpression, especially that of variant 9 (CD44v9), has also been implicated in the local inflammatory response and metaplasia-carcinoma sequence in human stomach. We recently identified miR-328 as one of the microRNAs targeting CD44 in gastric cancer. The aim of the current study was to determine the relationship between miR-328 and CD44v9 expression in H. pylori-infected gastric mucosa during the development of preneoplastic lesions. Methods: Immunohistochemical staining of myeloperoxidase and CD44v9 was performed using paraffin-embedded tissue sections obtained from 54 patients who underwent gastric resection without preoperative treatment. The levels of miR-328 expression in the gastric mucosa were measured in the same patients using quantitative reverse transcription polymerase chain reaction. Results: Both infiltration of myeloperoxidase-positive inflammatory cells and expression of proinflammatory cytokines closely correlated with H. pylori infection in the cancer-afflicted gastric mucosa. High CD44v9 expression levels, identified in the gastric mucosa in 61 % of samples (33/54), correlated significantly with H. pylori infection in the gastric mucosa. Notably, high CD44v9 expression was significantly associated with low miR-328 expression, whereas low CD44v9 expression was significantly associated with high miR-328 expression. Conclusions: We showed that miR-328 downregulation and de novo expression of CD44v9 occurred in H. pylori-infected gastric mucosa adjacent to gastric cancer compared with gastric mucosa not infected with H. pylori adjacent to gastric cancer. CD44v9-overexpressing cells are known to acquire reactive oxygen species resistance; thus, these cells may avoid cell death caused by various stress inducers, which may be linked to the origin of gastric cancer development. [ABSTRACT FROM AUTHOR]

Lymphangiomas are rare cystic tumors that may be present in the retroperitoneum. Retroperitoneal lymphangiomas account for approximately 1 % of all lymphangiomas. We experienced an adult patient with a retroperitoneal cystic lymphangioma coexisting with an esophageal hiatus hernia. Abdominal ultrasonography showed a cyst in the abdomen of a 76-year-old woman. She was admitted to our clinic because of an enlargement of the cyst and epigastric pain after meals. She had a long history of heartburn after meals and had not undergone any treatment. She had no record of previous illnesses. Computed tomography revealed a single bunch cystic tumor with septations, located from the mediastinum to the retroperitoneal space. The tumor was not enhanced, and there was no solid part. She was diagnosed with a retroperitoneal cyst. Laparoscopic total excision was performed because the cyst was increasing in size and the patient had symptoms. The cyst was successfully removed. Although laparoscopic excision of retroperitoneal cystic lymphangiomas is the treatment of choice, surgical methods should be carefully chosen in selected patients. [ABSTRACT FROM AUTHOR]

Although cancer-associated fibroblasts (CAFs) mainly produce CXCL12 and stimulate CXCL12/CXCR4 signaling in cancer cells, the significance of this interaction in adenocarcinoma of the esophagogastric junction (AEG) was unclear. This study investigated the functional characteristics of CAF-derived CXCL12 in AEG. Immunohistochemical staining for CXCL12 was performed on sections from 123 AEG patients and analyzed against clinicopathological data. Newly isolated CAFs and normal fibroblasts were examined for phenotype. An invasion assay was performed with AEG cells co-cultured with CAFs isolated from AEG. CXCL12 expression was significantly associated with age, depth of invasion, lymphatic invasion, and lymph node metastases. High CXCL12 expression significantly correlated with poor prognosis. Isolated CAFs had abundant α-smooth muscle actin expression and showed various CXCL12 expression patterns. Notably, AEG cells co-cultured with CXCL-expressing CAFs invaded more than when co-cultured with CXCL-expressing CAFs; these invasive properties were impeded by CXCR4 antagonist AMD3100. We demonstrated that AEG cells co-cultured with CXCL12 CAFs were significantly more invasive than those co-cultured with CXCL12 CAFs and that high CXCL12 expression correlates with poor prognosis in AEG patients. CXCL12 derived from CAFs in tumor microenvironment stimulates CXCL12/CXCR4 signaling in AEG cells and promotes their invasive ability, resulting in tumor progression. [ABSTRACT FROM AUTHOR]

The DNA methylation alterations occurring in human cancers have two types: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Recently, to assess global DNA methylation, long interspersed nucleotide element 1 (LINE-1) retrotransposons, constituting a substantial portion of the human genome, attracts much attention. The aim of the current study was to clarify the significance of LINE-1 methylation level for epigenetic field defects and the relationships among LINE-1 methylation level in gastric mucosae, clinical and pathological features, including infection by Helicobacter pylori ( H. pylori), a bacterium implicated in gastric cancer. By bisulfite-PCR pyrosequencing, we quantified the LINE-1 methylation levels in noncancerous gastric mucosae and cancer tissues from 87 gastric cancer patients, in gastric mucosae from 17 autopsied individuals without gastric cancers and in 20 gastric fresh frozen samples from non-gastric cancer patients. LINE-1 methylation in the noncancerous gastric mucosae of gastric cancer patients was significantly higher than in cancer tissues ( P = 0.0006), but significantly lower than in the gastric mucosae of the autopsied individuals ( P = 0.026), suggesting the formation of epigenetic field defect in noncancerous gastric mucosae. Moreover, LINE-1 hypomethylation of noncancerous gastric mucosae in gastric cancer patients significantly correlated with H. pylori infection ( P = 0.037). We prospectively confirmed the similar result in 20 non-gastric cancer patients ( P = 0.010). LINE-1 hypomethylation of gastric mucosae significantly correlated with H. pylori infection, supporting the potential of LINE-1 methylation level as a surrogate marker of epigenetic field defects for gastric cancer cancerization, particularly induced by H. pylori. [ABSTRACT FROM AUTHOR]