• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2003.10a
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• pp.11-11
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• 2003

Peroxisome proliferator-activated receptor (PPAR) is nuclear hormone receptors that can be activated by a variety of compounds. Two PPAR gamma isoforms are expressed at the protein level in mouse, gamma 1 and gamma 2. And PPAR gamma is intimately associated with cell differentiation and proliferation[1]. So aim of this study, investigated where express PPAR gamma in mouse gastric cancer tissues, including human gastric cancer cell lines and expression pattern of PPAR gamma. (omitted)

• Journal of Gastric Cancer
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• v.14 no.1
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• pp.58-62
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• 2014

We report an extremely rare case of primary squamous cell carcinoma of the stomach. A 69-year-old man was admitted to our hospital with a 2-month history of dysphagia and tarry stools. Endoscopic examination revealed a cauliflower-shaped protruding mass along the lesser curvature of the gastric cardia. Biopsy of the lesion revealed squamous cell carcinoma of the stomach. Computed tomography revealed a thickened stomach wall and a mass protruding into the gastric lumen. Total gastrectomy with splenectomy, distal pancreatectomy, and Roux-en-Y reconstruction was performed, together with a lower thoracic esophagectomy via a left thoracotomy. Histopathological examination of the specimen revealed well-differentiated squamous cell carcinoma of the stomach. Postoperative follow-up was uneventful for the first 18 months. However, multiple liver metastases and para-aortic lymph node metastasis developed subsequently. Despite systemic combination chemotherapy, the patient died because of progression of the recurrent tumors. Here, we review the characteristics of 56 cases of gastric squamous cell carcinoma reported in Japan.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2765-2769
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• 2013

Background: A close association between patterns identified by magnifying narrow-band imaging (M-NBI) and histological type has been described. M-NBI patterns were also recently reported to be related to the mucin phenotype; however, detials remain unclear. Materials and Methods: We investigated the cellular differentiation of gastric cancer lesions, along with their mucosal distribution observed by M-NBI. Ninety-seven depressed-type early gastric cancer lesions (74 differentiated and 23 undifferentiated adenocarcinomas) were visualized by M-NBI. Findings were divided into 4 patterns based on abnormal microvascular architecture: a chain loop pattern (CLP), a fine network pattern (FNP), a corkscrew pattern (CSP), and an unclassified pattern. Mucin phenotypes were judged as gastric (G-type), intestinal (I-type), mixed gastric and intestinal (M-type), and null (N-type) based on 4 markers (MAC5AC, MUC6, MUC2, and CD10). The relationship of each pattern of microvascular architecture with organoid differentiation indicated by cancer cell differentiation and its distribution in each histological type of early gastric cancer was investigated. Results: All CLP and FNP lesions were differentiated. The cancer cell distribution showed organoid differentiation in 84.2% (16/19) and 61.1% (22/36) of the two types of lesions, respectively, and there was a significant difference from the unclassified pattern with organoid differentiation (p<0.001). Almost all (94.7%; 18/19) CSP lesions were undifferentiated, and organoid differentiation was observed in 72.2% (13/18). There was a significant difference from the unclassified pattern with organoid differentiation (p<0.05). Conclusions: Cellular differentiation and distribution are associated with microvascular architecture observed by M-NBI.

• Journal of Pharmacopuncture
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• v.15 no.3
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• pp.31-38
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• 2012

Sophorae Radix (SR) plays a role in a number of physiologic and pharmacologic functions in many organs. Objective: The aim of this study was to clarify the potential role for transient receptor potential melastatin 7 (TRPM7) channels in SR-inhibited growth and survival of AGS and MCF-7 cells, the most common human gastric and breast adenocarcinoma cell lines. Methods: The AGS and the MCF-7 cells were treated with varying concentrations of SR. Analyses of the caspase-3 and - 9 activity, the mitochondrial depolarization and the poly (ADPribose) polymerase (PARP) cleavage were conducted to determine if AGS and MCF-7 cell death occured by apoptosis. TRPM7 channel blockers ($Gd^{3+}$ or 2-APB) and small interfering RNA (siRNA) were used in this study to confirm the role of TRPM7 channels. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS and MCF-7 cell growth and survival. Results: The addition of SR to a culture medium inhibited AGS and MCF-7 cell growth and survival. Experimental results showed that the caspase-3 and -9 activity, the mitochondrial depolarization, and the degree of PARP cleavage was increased. TRPM7 channel blockade, either by $Gd^{3+}$ or 2-APB or by suppressing TRPM7 expression with small interfering RNA, blocked the SR-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SR-induced cell death. Conclusions: These findings indicate that SR inhibits the growth and survival of gastric and breast cancer cells due to a blockade of the TRPM7 channel activity. Therefore, TRPM7 channels may play an important role in the survival of patients with gastric and breast cancer.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.326.1-326.1
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• 2002

We applied serological analysis of cDNA expression library technique to identify cancer-associated genes. We screened cDNA expression libraries of human testis and gastric cancer cell lines with sera of patients with gastric cancers. We identified a gene whose expression is testis-specific among normal tissues. We cloned and characterized this novel gene. It contains D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. It showed wide expression in various cancer tissues and cancer cell lines. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4607-4610
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• 2013

The aim of this study was evaluated the prevalence of Treg cells in peripheral blood in patients with gastric cancer, and investigate the effect of gastric cancer cells on their differentiation. ELISA was employed to assess the concentrations of TGF-${\beta}$ and IL-10 in gastric cancer patients' serum. Then, mouse gastric cancer cells were co-cultured with T lymphocytes or T lymphocytes + anti-TGF-${\beta}$. Flow cytometric analysis and RT-PCR were then performed to detect Treg cells and TGF-${\beta}$ and IL-10 expression in gastric cancer cells. Our data showed that the expression of TGF-${\beta}$ and IL-10 in the patients with gastric cancer was increased compared to the case with healthy donors. The population of Treg cells and the expression levels of TGF-${\beta}$ and IL-10 in the co-culture group were much higher than in the control group (18.6% vs 9.5%) (P<0.05). Moreover, the population of Treg cells and the expression levels of TGF-${\beta}$ and IL-10 in the co-culture systerm were clearly decreased after addition of anti-TGF-${\beta}$ (7.7% vs 19.6%) (P<0.01). In conclusion, gastric cancer cells may induce Treg cell differentiation through TGF-${\beta}$, and further promote immunosuppression.

• Journal of Pharmacopuncture
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• v.19 no.2
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• pp.129-136
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• 2016

Objectives: The crude extracts of Scutellaria barbata D. Don (SB) have traditionally demonstrated inhibitory effects on numerous human cancers both in vitro and in vivo. Gastric cancer is one of the most common types of cancer on world. The authors investigated the effects of an ethanol extract of Scutellaria barbata D. Don (ESB) on the growth and survival of MKN-45 cells (a human gastric adenocarcinoma cell line). Methods: The MKN-45 cells were treated with different concentrations of ESB, and cell death was examined using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Analyses of sub-G1 peaks, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to determine the anti-cancer effects of SB on MKN-45 cells. Also, intracellular reactive oxygen species (ROS) generation was investigated. Results: ESB inhibited the growth of MKN-45 cells, caused cell cycle arrest, and increased the sub-G1 population. In addition, ESB markedly increased mitochondrial membrane depolarization and the activities of caspase-3 and -9. ESB exerted anti-proliferative effects on MKN-45 cells by modulating the mitogen-activated protein kinase (MAPK) signaling pathway and by increasing the generation of ROS. Furthermore, combinations of anti-cancer drugs plus ESB suppressed cell growth more than treatments with an agent or ESB, and this was especially true for cisplatin, etoposide, and doxorubicin. Conclusion: ESB has a dose-dependent cytotoxic effect on MKN-45 cells and this is closely associated with the induction of apoptosis. ESB-induced apoptosis is mediated by mitochondria-, caspase- and MAPK dependent pathways. In addition, ESB enhances ROS generation and increases the chemosensitivity of MKN-45 cells. These results suggest that treatment with ESB can inhibit the proliferation and promote the apoptosis of human gastric adenocarcinoma cells by modulating the caspase-, MAPK- and ROS-dependent pathway.

• Journal of Gastric Cancer
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• v.14 no.2
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• pp.117-122
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• 2014

Purpose: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in select patients with gastric cancer and peritoneal metastases. It remains unclear, however, whether this multimodal treatment protocol is also beneficial for signet-ring cell gastric cancer (SRC) patients with peritoneal metastases. Materials and Methods: Clinical data of patients scheduled for upfront systemic chemotherapy consisting of 5-FU (2,600 $mg/m^2$), folinic acid (200 $mg/m^2$), docetaxel (50 $mg/m^2$), and oxaliplatin (85 $mg/m^2$) followed by CRS and HIPEC using cisplatin (50 $mg/m^2$) at the Comprehensive Cancer Center, University Hospital T$\ddot{u}$bingen, Germany were retrospectively analyzed. Results: Eighteen consecutive patients for whom irresectability has been ruled out by a computed tomography scan were enrolled. However, complete cytoreduction could only be achieved in 72% of patients. When categorizing patients with respect to the completeness of cytoreduction, we found no difference between both groups considering tumor- or patient-related factors. The overall complication rate following complete cytoreduction and HIPEC was 46%. Within a median follow-up of 6.6 (0.5~31) months, the median survival for CRS and HIPEC patients was 8.9 months as opposed to 1.1 months for patients where complete cytoreduction could not be achieved. Following complete cytoreduction and HIPEC, progression-free survival was 6.2 months. Conclusions: In SRC with peritoneal metastases, the prognosis appears to remain poor irrespective of complete CRS and HIPEC. Moreover, complete cytoreduction could not be achieved in a considerable percentage of patients. In SRC, CRS and HIPEC should be restricted to highly selective patients in order to avoid exploratory laparotomy.

• Journal of Gastric Cancer
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• v.19 no.4
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• pp.393-407
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• 2019

Purpose: To identify the potential therapeutic role of postoperative radiotherapy (RT) in patients with locally advanced (stage II and stage III) gastric signet ring cell carcinoma (SRC). Materials and methods: Patients with locally advanced gastric SRC from the Surveillance, Epidemiology, and End Results program database between 2004 and 2012 were included in our study. Univariate and multivariate Cox proportional models were performed, and survival curves were generated to evaluate the prognostic effect of postoperative RT and surgery alone on SRC patients. Propensity score matching (PSM) was used to avoid selection bias among the study cohorts. Results: We found that patients with postoperative RT had better probability of survival compared with those who did not receive RT (overall survival [OS], P<0.001; cancer-specific survival [CSS], P<0.001). After PSM, analysis of both overall and CSS showed that patients who underwent postoperative RT had better prognosis than those receiving surgery alone in the matched cohort (OS, P=0.00079; CSS, P=0.0036). Multivariate Cox proportional model indicated that postoperative RT had better effect on prognosis compared with surgery alone with respect to both overall (hazard ratio [HR], 0.716; 95% confidence interval [95% CI], 0.590-0.87; P=0.001) and CSS (HR, 0.713; 95% CI, 0.570-0.890; P=0.003). Conclusions: Postoperative RT had better prognosis compared with surgery alone for both overall and CSS for patients with locally advanced gastric SRC.

• Oncology Letters
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• v.41 no.6
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• pp.3464-3474
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• 2019

The EF-hand calcium binding protein tescalcin (TESC) is highly expressed in various human and mouse cancer tissues and is therefore considered a potential oncogene. However, the underlying mechanism that governs TESC expression remains unclear. Emerging evidence suggests that TESC expression is under epigenetic regulation. In the present study, the relationship between the epigenetic modification and gene expression of TESC in gastric cancer was investigated. To evaluate the relationship between the methylation and expression of TESC in gastric cancer, the methylation status of CpG sites in the TESC promoter was analyzed using microarray with the Illumina Human Methylation27 BeadChip (HumanMethylation27_270596_v.1.2), gene profiles from the NCBI Dataset that revealed demethylated status were acquired, and real-time methylation-specific PCR (MSP) in gastric cancer cells was conducted. In the present study, it was demonstrated that the hypermethylation of TESC led to the downregulation of TESC mRNA/protein expression. In addition, 5-aza-2c-deoxycytidine (5'-aza-dC) restored TESC expression in the tested gastric cancer cells except for SNU-620 cells. ChIP assay further revealed that the methylation of the TESC promoter was associated with methyl-CpG binding domain protein (MBD)1, histone deacetylase (HDAC)2, and Oct-1 and that treatment with 5'-aza-dC facilitated the dissociation of MBD1, HDAC2, and Oct-1 from the promoter of TESC. Moreover, silencing of TESC increased MBD1 expression and decreased the H3K4me2/3 level, thereby causing transcriptional repression and suppression of cell survival in NCI-N87 cells; conversely, overexpression of TESC downregulated MBD1 expression and upregulated the H3K4me2 level associated with active transcription in SNU-638 cells. These results indicated that the differential expression of TESC via the modification status of the promoter and histone methylation controled cell survival in gastric cancer cells. Overall, the present study provided a novel therapeutic strategy for gastric cancer.