• Journal of Gastric Cancer
• /
• v.4 no.3
• /
• pp.180-185
• /
• 2004

Recently, we experienced two advanced gastric cancer (AGC) patients younger than 17 years of age. The first case was a 15-year, 2-month-old male who had suffered from epigastric soreness for 5 weeks. His grandfather died of gastric cancer at 39 years of age. Under the diagnosis of AGC, he underwent a total gastrectomy with D2 lymph node dissection. There was no evidence of distant metastasis. Pathologic examination revealed a 4.5$\times$4 cm, signet ring cell adenocarcinoma with subserosal invasion and with metastasis in 9 of 42 regional lymph nodes (T2bN2M0). The second case was a 17-year, 11-month-old male who had suffered from epigastric pain for 2 years without familial clustering. Under the diagnosis of AGC, he underwent a distal subtotal gastrectomy with D2 lymph node dissection. There was no evidence of distant metastasis. Pathologic examination revealed a 3$\times$2 cm, signet ring cell adenocarcinoma with subserosal invasion and with metastasis in 9 of 45 regional lymph nodes (T2bN2M0). The two patients have been alive without recurrence for 27 months and 4 months, respectively. Even among teenagers, patients with abdominal complaints should be subjected to a thorough examination of the gastrointestinal tract.

• Journal of Gastric Cancer
• /
• v.3 no.4
• /
• pp.201-205
• /
• 2003

Purpose: Telomerase activity is generally absent in primary cell cultures and normal tissues. Telomerase is known to be induced upon immortalization or malignant transformation of human cells. Telomerase activity can be increased in immature lymphocytes and activated lymphocytes, but it is not detected in the peripheral blood of normal persons. The authors analyzed peripheral blood telomerase from patients of gastric cancer to evaluate the possibility of using it for diagnosis and as a prognostic factor. Materials and Methods: We obtained blood samples from 11 inflammatory patients and 64 gastric cancer patients. The telomerase activity was measured using the [PCR-ELISA] method. The results were correlated with the T, N, M stage, cell differentiation, vascular, neural, and lymphatic invasion, tumor size, and tumor location. Results: In the 11 inflammatory patients, telomerase activity was not detected while in the gastric cancer patients, a positive rate of $28.1\%$ was noted. The peripheral telomerase activity was not related with tumor size, tumor site, lymphatic and vascular invasion, stage, or histologic differentiation. Conclusion: The peripheral blood telomerase activity for patients of gastric cancer can be utilized as a marker for the diagnosis of not only advanced gastric cancer, but also relatively early stage gastric cancer, but not as a prognostic factor.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.3
• /
• pp.325-332
• /
• 2020

Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.

• Journal of Life Science
• /
• v.16 no.6
• /
• pp.964-971
• /
• 2006

The cancer cells, characterized by local invasion and distant metastasis, are very dependant on extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Among the human MMPs, matirx metalloproteinase-2 (MMP-2) and matrix metalloproteinse-9 (MMP-9) are key enzymes that degrade type IV collagen of the matrix. Here, we studied the effect of disulfiram, an anti-tumor compound, on the suppression of the tumor invasion and the activity of MMP-2, MMP-9 in human osteosarcoma cells (U2OS). Disulfiram had the type IV collagenase inhibitory activity, the effect of inhibition of gene and protein expression, and these inhibitions were responsible for blocking invasion through cell mediated and non-cell mediated pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9, and regulated the invasion of U2OS, Caki-1 and Caski. These observations raise the possibility of clinical therapeutic applications for disulfiram used as a potential inhibitor of cancer invasion.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.9
• /
• pp.3667-3671
• /
• 2015

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

• BMB Reports
• /
• v.50 no.8
• /
• pp.411-416
• /
• 2017

The endoplasmic reticulum (ER) membrane protein complex subunit 6 (EMC6) is a novel human autophagy-related molecule. Here, using tissue microarray and immunohistochemistry, we report that EMC6 protein is lost or reduced in glandular cells of patients with gastric adenocarcinoma, compared to normal stomach mucosa. Overexpression of EMC6 in gastric cancer cells inhibited cell growth, migration, invasion, and induced apoptosis and cell cycle arrest at S-phase. Further investigation suggested that EMC6 overexpression in BGC823 human adenocarcinoma gastric cancer cells reduced tumorigenicity in a xenograft model, demonstrating that EMC6 has the characteristics of a tumor suppressor. This is the first study to show that EMC6 induces cell death in gastric cancer cells. The molecular mechanism of how EMC6 functions as a tumor suppressor needs to be further explored.

• BMB Reports
• /
• v.57 no.6
• /
• pp.273-280
• /
• 2024

Cancer cells metastasize to distant organs by altering their characteristics within the tumor microenvironment (TME) to effectively overcome challenges during the multistep tumorigenesis. Plasticity endows cancer cell with the capacity to shift between different morphological states to invade, disseminate, and seed metastasis. The epithelial-to-mesenchymal transition (EMT) is a theory derived from tissue biopsy, which explains the acquisition of EMT transcription factors (TFs) that convey mesenchymal features during cancer migration and invasion. On the other hand, adherent-to-suspension transition (AST) is an emerging theory derived from liquid biopsy, which describes the acquisition of hematopoietic features by AST-TFs that reprograms anchorage dependency during the dissemination of circulating tumor cells (CTCs). The induction and plasticity of EMT and AST dynamically reprogram cell-cell interaction and cell-matrix interaction during cancer dissemination and colonization. Here, we review the mechanisms governing cellular plasticity of AST and EMT during the metastatic cascade and discuss therapeutic challenges posed by these two morphological adaptations to provide insights for establishing new therapeutic interventions.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.6
• /
• pp.3831-3836
• /
• 2013

Background: S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigated using MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model. Results: S100A14 was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner grade and vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant and independent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidence interval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro and in vivo. Conclusion: These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.3
• /
• pp.1193-1196
• /
• 2014

Senescence marker protein 30 (SMP30), a hepatocellular carcinoma (HCe) associated antigen had been identified by our research group. To study its mechanisms of regulation and associations with the occurrence and development of HCe, we inhibited expression by RNAi technique, and observed effects on the biological characteristics of Hep G2 cells. In cell viability assays, cell growth in the experimental group (with siRNA transfection) was elevated. In Transwell invasion assays, compared with blank and control groups, numbers of invading cells in the experimental group were significantly increased, whereas in apoptosis assays, the percentage apoptosis demonstrated no differences, but after UV irradiation, that in the experimental group was higher than the other two groups. In a word, SMP30 can inhibit the proliferation and invasion of human hepatoma cells and thus can be regarded as a cancer suppressive factor.

• BMB Reports
• /
• v.48 no.3
• /
• pp.159-165
• /
• 2015

Although the short isoform of ErbB3-binding protein 1 (Ebp1), p42 has been considered to be a potent tumor suppressor in a number of human cancers, whether p42 suppresses tumorigenesis of lung cancer cells has never been clarified. In the current study we investigated the tumor suppressor role of p42 in non-small cell lung cancer cells. Our data suggest that the expression level of p42 is inversely correlated with the cancerous properties of NSCLC cells and that ectopic expression of p42 is sufficient to inhibit cell proliferation, anchorage-independent growth, and invasion as well as tumor growth in vivo. Interestingly, p42 suppresses Akt activation and overexpression of a constitutively active form of Akt restores the tumorigenic activity of A549 cells that is ablated by exogenous p42 expression. Thus, we propose that p42 Ebp1 functions as a potent tumor suppressor of NSCLC through interruption of Akt signaling.