Piezo type mechanosensitive ion channel component 1 facilitates gastric cancer omentum metastasis.

The peritoneum, especially the omentum, is a common site for gastric cancer (GC) metastasis. Our aim was to expound the role and mechanisms of Piezo1 on GC omentum metastasis. A series of functional assays were performed to examine cell proliferation, clone formation, apoptosis, Ca2+ influx, mitochondrial membrane potential (MMP) and migration after overexpression or knockdown of Piezo1. A GC peritoneal implantation and metastasis model was conducted. After infection by si-Piezo1, the number and growth of tumours were observed in abdominal cavity. Fibre and angiogenesis were tested in metastatic tumour tissues. Piezo1 had higher expression in GC tissues with omentum metastasis and metastatic lymph node tissues than in GC tissues among 110 patients. High Piezo1 expression was associated with lymph metastasis, TNM and distant metastasis. Overexpressed Piezo1 facilitated cell proliferation and suppressed cell apoptosis in GC cells. Moreover, Ca2+ influx was elevated after up-regulation of Piezo1. Piezo1 promoted cell migration and Calpain1/2 expression via up-regulation of HIF-1α in GC cells. In vivo, Piezo1 knockdown significantly inhibited peritoneal metastasis of GC cells and blocked EMT process and angiogenesis. Our findings suggested that Piezo1 is a key component during GC omentum metastasis, which could be related to up-regulation of HIF-1α.

MicroRNA-34c-5p exhibits anticancer properties in gastric cancer by targeting MAP2K1 to inhibit cell proliferation, migration, and invasion.

Purpose: Gastric cancer(GC)is one of the deadliest digestive tract tumors worldwide，existing studies suggest that dysregulated expression of microRNAs (miRNAs) plays an important role in the pathogenesis and progression of GC. This study aimed to investigate the expression, biological function, and downstream mechanism of miR-34c-5p in GC, provide new targets for gastric cancer diagnosis and treatment. Methods: The expression of miR-34c-5p in GC tissues and cell lines was examined by RT-qPCR. Cell wound healing, transwell and cell cloning assays were used to detect the effect of miR-34c-5p on the migration and invasion abilities, respectively, of GC cells. Western blot was performed to detect the expression of related proteins. Bioinformatics analysis was used to predict the binding of MAP2K1 to miR-34c-5p and the targeting relationship was confirmed by dual luciferase reporter assay. Results: The expression level of miR-34c-5p was significantly decreased in GC tissues and cell lines. miR-34c-5p overexpression inhibited migration, invasion, and colony formation of gastric cancer cells, the related protein E-cadherin expression was significantly increased and N-cadherin, vimentin, and PCNA expression were significantly decreased, while miR-34c-5p knockdown exerted the opposite effects. In addition, the targeting relationship between miR-34c-5p and MAP2K1 was predicted and confirmed, and further confirmed by rescue experiments that MAP2K1 alleviated the inhibitory effect of miR-34c-5p in GC. Conclusion: MiR-34c-5p is lowly expressed in GC, and it can target MAP2K1 to exert inhibitory effects on GC proliferation, invasion, and migration. These findings provide a promising biomarker and a potential therapeutic target for gastric cancer.

Dextran Sulfate Inhibits Angiogenesis and Invasion of Gastric Cancer by Interfering with M2-type Macrophages Polarization.

PURPOSE: To explore the effect of dextran sulfate (DS) on the angiogenesis, invasion, and migration of gastric cancer cells by interfering with the polarization of M2-type macrophages. METHODS: The infiltration of M2-type macrophages and microvascular density in gastric cancer and paracancerous tissues were analyzed using immunohistochemistry and immunofluorescence. The effects of DS on M2-type macrophages and the angiogenesis in metastatic tumors were investigated in the nude mice intraperitoneal metastasis model using immunohistochemistry and western blot. The differentiation and polarization of macrophages, immunocytochemistry, western blot, ELISA, and transwell migration assay were used to evaluate the effect of DS on the polarization of macrophages, immunocytochemistry, western blot, ELISA, and transwell migration assay were used to evaluate the effect of DS on the polarization and recruitment capacity of macrophages. Immunocytofluorescence, tube formation assay, transwell invasion assay, wound healing assay, and western blot were used to investigate the effect of DS on the angiogenesis, invasion, and migration-promoting phenotype of M2- type macrophage in a co-culture system of macrophages and gastric cancer cells. RESULTS: The infiltration of M2-type macrophages and the microvascular density were highly expressed and positively correlated in the human gastric cancer tissue. DS can significantly inhibit the intraperitoneal metastases of gastric cancer in nude mice, and reduce the infiltration of M2-type macrophages and the angiogenesis in intraperitoneal metastatic tumors. Moreover, DS can prevent the polarization of M0-type macrophages to M2 type, reduce the expression of M2-type macrophage markers (CD206, CD163, IL-10, and Arg-1), down-regulate the IL-6-STAT3 pathway, and inhibit the recruitment capability of M2-type macrophages. Finally, the co-culture experiment showed that DS significantly reduced the enhancing effects of M2-type macrophages on the angiogenesis, invasion, and migration of gastric cancer cells, as well as down-regulated the related expressions of proteins (VEGF, N-cadherin, MMP-2 and Vimentin) in gastric cancer cells. CONCLUSION: DS can reduce the infiltration of M2-type macrophages and the microvascular density in intraperitoneal metastases of gastric cancer in nude mice, and inhibit the angiogenesis, invasion, and migration of gastric cancer cells by interfering with the polarization of M2-type macrophages through repression of the IL-6/STAT3 signaling pathway.

Inhibition of Nrf2/HO-1 signaling pathway by Dextran Sulfate suppresses angiogenesis of Gastric Cancer.

Purpose: To investigate the role of Nrf2/HO-1 signaling pathway in angiogenesis and whether dextran sulfate (DS) could suppress angiogenesis by inhibiting Nrf2/HO-1 signaling pathway in gastric cancer. Methods: In vitro; Western blot analyzed the expression of Nrf2 in gastric cell lines. Tube formation assay observed the effect of gradient concentration DS on the angiogenic potential of HGC-27 cells. Immunofluorescence,western blot and qPCR analyzed the effects of DS on the expression of Nrf2, HO-1 and VEGF under gradient hypoxia time. Immunofluorescence,western blot,qPCR and tube formation assay analyzed the effects of up-regulating or down-regulating Nrf2/HO-1 signaling pathway on VEGF expression and angiogenic potential in HGC-27 cells. In vivo: Construct nude mouse intraperitoneal implantation metastasis model. Immunohistochemistry and western blot analyzed the effects of DS on the expression of Nrf2, HO-1, VEGF and MVD in nude mice. Immunohistochemistry detected the expression of Nrf2, HO-1, VEGF and MVD in human paracancerous tissue and gastric cancer tissues with different degrees of differentiation. Results: The expression of Nrf2 increased most significantly in HGC-27 cell line. DS reduced the angiogenic potential and the expression of Nrf2, HO-1 and VEGF in HGC-27 cells. Down-regulation of Nrf2/HO-1 signaling pathway decreased VEGF expression and angiogenic potential in HGC-27 cells. Up-regulation of Nrf2/HO-1 signaling pathway increased VEGF expression and angiogenic potential in HGC-27 cells. DS reduced the expression of Nrf2, HO-1, VEGF and MVD in nude mice. Nrf2, HO-1, VEGF and MVD showed low expression in paracancerous tissue but high expression in gastric cancer tissues. They were weak, moderate and strong in well, moderately and poorly differentiated gastric cancer tissues, respectively. Conclusion: Nrf2/HO-1 signaling pathway may positively regulate gastric cancer angiogenesis and DS may suppress the angiogenesis by inhibiting Nrf2/HO-1 signaling pathway in gastric cancer.

Dextran Sulfate Inhibits Cell Proliferation and Induces Apoptosis by Regulating EZH2 in Gastric Carcinoma.

BACKGROUND: Gastric cancer (GC) is one of the most common gastrointestinal malignancies. According to reports, the enhancer of zeste homolog 2 (EZH2) exhibits carcinogenic function in a variety of cancers. Therefore, EZH2 may be a potential therapeutic target for the treatment of human cancer. Macromolecular Dextran Sulfate (DS) has been displayed to play a critical role in tumor inhibition. However, the molecular mechanism by which DS mediates this effect is unclear. OBJECTIVES: In this study, we explored the effects of DS on the proliferation and apoptosis of gastric cancer and the related mechanisms. Cell proliferation and counting assays, as well as cell colony formation assays, revealed that DS inhibited the proliferation and tumorigenesis of GC cells. Additionally, flow cytometry analysis displayed that DS blocked the cell cycle of GC cells in the G1/S phase and promoted their apoptosis. METHODS: Bioinformatics analyses, enzyme-linked immunosorbent assays, immunohistochemistry, and other methods were applied to measure the expression of EZH2 in human GC cells and tissues. RESULTS AND DISCUSSION: Further studies have shown that DS treatment can reduce the expression of proliferating cell nuclear antigen (PCNA) and increase the level of the ratio of Bax: Bcl-2 protein in GC cells. In addition, DS reduced EZH2 levels and increased CXXC finger protein 4 levels both in vitro and in vivo. In addition, down-regulation of EZH2 with EZH2 inhibitors reversed the inhibitory effect of DS on gastric cancer cells. CONCLUSION: Collectively, our work demonstrates that DS suppresses proliferation and promotes apoptosis of GC cells by regulating EZH2. Our study suggests that DS is a promising therapeutic compound for the treatment of GC.

Targeting ADAR1 suppresses progression and peritoneal metastasis of gastric cancer through Wnt / ß-catenin pathway.

Objective: Peritoneal metastasis frequently occurs in advanced gastric cancer, which is typically not eligible for radical surgery. Here, this study observed the function and regulatory mechanism of ADAR1 in peritoneal metastasis of gastric cancer. Methods: ADAR1, CALR and ß-catenin proteins were detected in normal mucosa, primary gastric cancer, metastatic lymph node and metastatic omentum tissues by immunohistochemistry, western blot, and immunofluorescence. After silencing ADAR1 by siADAR1, the effect and mechanism of ADAR1 on gastric cancer metastasis were observed in nude mouse models of gastric cancer with peritoneal metastasis as well as HGC-27 and AGS gastric cancer cells. Result: Our results showed that ADAR1 was significantly up-regulated in gastric cancer, metastatic lymph node and metastatic omentum tissues. Its up-regulation was significantly correlated to lymph node metastasis and peritoneal metastasis. Silencing ADAR1 significantly reduced the volume of peritoneal metastatic tumors and weakened oncogene CALR expression, Wnt / ß-catenin pathway and epithelial-mesenchymal transition (EMT) process in vivo. Furthermore, ADAR1 knockdown distinctly suppressed cell viability, colony formation and migration of HGC-27 and AGS cells and ameliorated the effects of Wnt pathway activator on tumor progression. The similar findings were investigated when treated with ADAR1 inhibitor 8-Azaadenosine. Conclusion: Collectively, this study identified a novel oncogenic function of ADAR1 in peritoneal metastasis of gastric cancer via Wnt / ß-catenin pathway. Hence, ADAR1 could be a novel marker and therapeutic target against gastric cancer metastasis.

Nrf2/HO-1 Axis Regulates the Angiogenesis of Gastric Cancer via Targeting VEGF.

PURPOSE: Gastric cancer (GC) is one of the most fatal digestive tumors worldwide. Abnormal activation or accumulation of the nuclear factor-erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) axis is a malignant event in numerous solid tumors. However, its involvement in angiogenesis of GC remains unknown. This study investigated the role of the Nrf2/HO-1 axis in angiogenesis of GC. METHODS: The expression of Nrf2, HO-1, and vascular endothelial growth factor (VEGF) in BGC-823 cells under hypoxia was analyzed using immunocytochemistry, immunofluorescence, Western blotting, and quantitative polymerase chain reaction. The effects of brusatol (Nrf2 inhibitor) and tert-butylhydroquinone (Nrf2 inducer) on these factors and angiogenesis were examined using immunofluorescence, Western blotting, quantitative polymerase chain reaction, and tube formation assay. Moreover, immunohistochemistry and Western blotting were used to determine these factors and microvessel density in tumor and normal tissues of tumor-bearing and tumor-free mice, respectively. Immunohistochemistry and Western blotting were employed to examine these factors and microvessel density in human paracancerous tissues, well-differentiated GC, and poorly differentiated GC. The correlations between Nrf2, HO-1, and VEGF gene expression in 375 patients with GC from The Cancer Genome Atlas cohort were analyzed. RESULTS: The expression of Nrf2, HO-1, and VEGF was increased in hypoxic BGC-823 cells (P<0.05). Although brusatol decreased their expression and angiogenesis (P<0.05), tert-butylhydroquinone had the opposite effect (P<0.05). Moreover, the expression of Nrf2, HO-1, and VEGF, and microvessel density in tumor tissues was higher than that recorded in normal tissues of nude mice (P<0.05). Similarly, these parameters were low in paracancerous tissues, but high in GC tissues (P<0.05). Also, they were weak in well-differentiated GC, but strong in poorly differentiated GC (P<0.05). In addition, there was a significant correlation between Nrf2, HO-1, and VEGF (P<0.05). CONCLUSION: The Nrf2/HO-1 axis may regulate the angiogenesis of GC via targeting VEGF. These findings provide a promising biomarker and potential treatment target for GC.

Dextran Sulfate Effects EMT of Human Gastric Cancer Cells by Reducing HIF-1α/ TGF-ß.

The peritoneal implant metastasis is one of the main pathway and main cause for high mortality for gastric cancer metastasis. Researchs show that epithelial-mesenchymal transition (EMT) playing essential role in modulating gastric cancer metastasis, and the expression of hypoxia inducible factor-1α (HIF-1α) can promote EMT in tumor cells. This research aims to explore the influence and mechanism of Dextran Sulfate (DS) affecting EMT of human gastric cancer. In the present study, we found that DS can enter into the cytoplasm and function in it. Inhibition of HIF-1α or DS significantly inhibit the migration and invasion of human gastric cancer cells, and decrease the mRNA and protein expressions of HIF-1α, matrix metalloproteinase-2 (MMP-2), transforming growth factor-ß (TGF-ß), Twist and N-cadherin (N-cad), rise E-cadherin (E-cad) expression, DS with HIF-1α knockdown has a stronger effect. In vivo studies indicated that compared with using DS or HIF-1α knockdown alone, DS with HIF-1α knockdown can better suppress the volume and number of metastatic tumors, and reduce the mRNA and protein expressions of HIF-1α, MMP-2, TGF-ß, Twist and N-cad in metastatic tumor tissues of nude mice. We further demonstrated that the expression of HIF-1α, MMP-2, TGF-ß , Twist and N-cad were higher in well and poorly differentiated gastric cancer than paracancerous tissue, and poorly differentiated gastric cancer were even higher, while E-cad expression was opposite. Taken together, this study shows that DS can interfere the expression of HIF-1α, thereby inhibiting TGF-ß-mediated EMT of gastric cancer cells, and demonstrated a promising application of DS in gastric cancer therapy.

Effect of preoperative intraperitoneal injection of Sapylin in advanced gastric cancer.

BACKGROUND AND OBJECTIVE: Sapylin is one of the biological response modifiers. It has been used in the comprehensive treatment for advanced cancer, and its clinical efficacy has been proved. This study was to evaluate the effect of preoperative intraperitoneal injection of Sapylin in treatment of advanced gastric cancer. METHODS: Seventy-nine patients eligible for radical gastrectomy were randomly divided into the treatment group (Sapylin + mitomycin C, 40 patients) and the control group (mitomycin C alone, 39 patients). In the treatment group, 5 KE Sapylin was injected intraperitoneally 48 h before operation and 4 mg of mitomycin C was injected into peritoneal cavity before the closure of the peritoneum. In the control group, only 4 mg mitomycin C was injected into peritoneal cavity before the closure of the peritonium. RESULTS: There was no operative mortality or duodenal stump leakage in the two groups. Postoperative complications were anastomotic leakage (2.5%, 1/40) and incision rupture (2.5%, 1/40) in the treatment group, and incision rupture (2.6%, 1/39) in the control group, with no significant difference between the two groups (P > 0.05). The 3-year survival rate was significantly higher in the treatment group than in the control group (76.5% vs. 49.4%, P < 0.05). CONCLUSIONS: Preoperative intraperitoneal injection of Sapylin can raise the 3-year survival rate after radical gastrectomy , without increasing the incidence rate of operative complications. Preoperative intraperitoneal injection of Sapylin is therefore a valuable therapy for advanced gastric cancer in clinic.

The Regulatory Mechanism and Biological Significance of Mitochondrial Calcium Uniporter in the Migration, Invasion, Angiogenesis and Growth of Gastric Cancer.

OBJECTIVE: Increasing evidences suggest that mitochondrial calcium uniporter (MCU), a selective channel responsible for mitochondrial Ca2+ uptake, is involved in the progression of several cancers. In this study, we aimed to observe the clinical implications and biological functions of MCU in gastric cancer. METHODS: The expression of MCU in 90 pairs of gastric cancer tissues and adjacent normal tissues was examined using immunohistochemistry and correlation between MCU expression and clinical features was analyzed. After construction of stable MCU knockdown or overexpression gastric cancer cells, mitochondrial membrane potential (MMP), wound healing and transwell assays were performed to examine MMP levels, migration and invasion. Subcutaneous xenograft tumors induced by gastric cancer cells transfected with MCU siRNAs or controls were constructed. Immunofluorescence was used to detect CD34 expression. Western blot was used to detect the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), epithelial-mesenchymal transition (EMT)-related proteins. RESULTS: MCU had a higher expression in gastric cancer tissues than normal tissues. Compared to gastric cancer tissues, its expression was significantly higher after omental metastasis. MCU expression was significantly correlated with depth of invasion (p=0.048), lymph metastasis (p=0.027), TNM stage (p=0.036) and distant metastasis (p=0.029). Patients with high MCU expression indicated a worse prognosis than those with its low expression (p=0.0098). MCU significantly increased the MMP levels of gastric cancer cells. Wound healing and transwell assay results showed that MCU promoted migration and invasion of gastric cancer cells. In vivo, MCU knockdown significantly inhibited tumor growth and angiogenesis. Both in vitro and in vivo, silencing MCU suppressed the expression of HIF-1α and VEGF as well as activity of EMT processes. CONCLUSION: Our findings suggested that highly expressed MCU could promote migration, invasion, angiogenesis and growth of gastric cancer, which could become a potential therapeutic marker for gastric cancer.

Dextran sulfate inhibition on human gastric cancer cells invasion, migration and epithelial-mesenchymal transformation.

The objective of the present study was to observe the influence of dextran sulfate (DS) on the proliferation, invasion and migration of AGS, BGC-23, GES-1, MGC-803 and SGC-7901 cells. Additionally, the possible inhibition mechanism of DS on BGC-823 cells epithelial-mesenchymal transition (EMT) was explored. The cells in the control and experimental group were treated with PBS and DS respectively. The effect of DS on the invasion and migration of these five types of cells were investigated using Transwell invasion and migration assays. Immunocytochemistry, western blotting and reverse transcription-polymerase chain reaction (RT-PCR) assays were used to measure gene and protein expression of hypoxia-inducible factor 1α (HIF1-a) and EMT associated factors [Twist, E-cadherin, N-cadherin and ß-catenin] of BGC-823 cells. According to the results of CCK-8, DS significantly decreased the proliferation of AGS, SGC-7901 and BGC-823 cells to different extents, but there were no notable differences for MGC-803 cells. Transwell migration and invasion results demonstrated that, compared with the control group, DS reduced the migration and invasion of every types of cells to different extents, and the inhibition to BGC-823 cells invasion is the most notably. Immunofluorescence, RT-PCR and western blot analysis results indicated that HIF-1α, Twist and N-cad expressions levels had different degrees of reduction in the experimental group following DS treatment; however, the expression level of E-cad had increased. In conclusion, DS inhibited the proliferation of AGS, BGC-823, SGC-7901 and GES-1 cells, the inhibition degree may be associated with the differentiation degree of every cancer cell, the higher the differentiation degree, the stronger the inhibition. DS inhibited migration and invasion of the five types of gastric cancer cells in different degree. DS may inhibit EMT of BGC-823 by inhibiting Wnt signaling.

Inhibition of lysyl oxidase expression by dextran sulfate affects invasion and migration of gastric cancer cells.

In the present study, the effect of dextran sulfate (DS) on the metastasis and invasion of human gastric cancer cells and its key underlying mechanism were investigated. The levels of hypoxia­inducible factor 1α (HIF­1α), transforming growth factor ß (TGF­ß) and lysyl oxidase (LOX) expression were evaluated in human gastric cancer and peritumoral tissues by immunohistochemical analysis. Cell proliferation and apoptosis were also examined using the Cell Counting Kit­8 assay and flow cytometry. The effect of DS on the invasion and migration of BGC­823 cells was assessed using a Transwell assay. BGC­823 cells were divided into the control (phosphate­buffered saline­treated) and experimental (DS­treated) groups, and cultured for different times under hypoxic conditions. Subsequently, LOX and TGF­ß expression levels in the cells were measured by immunocytochemistry, immunofluorescence, reverse transcription­quantitative polymerase chain reaction and western blot analysis. HIF­1α, TGF­ß and LOX expression levels were significantly higher in human gastric cancer tissues as compared with that in adjacent tissues. DS influenced cell proliferation and apoptosis in a dose­dependent manner. Furthermore, DS reduced the number of invaded and migrated cells. Under hypoxic conditions, DS reduced HIF­1α, TGF­ß and LOX expression levels in BGC­823 cells. After 12 h, the effect of combination of DS and ß­aminopropionitrile (BAPN) on LOX and TGF­ß protein levels was more significant compared with that of DS or BAPN alone. Therefore, DS may inhibit the invasion and migration of human gastric cancer cells under hypoxic conditions by influencing LOX.

Inhibition of the peritoneal metastasis of human gastric cancer cells by dextran sulphate in vivo and in vitro.

The present study investigated the inhibitory effects of dextran sulphate (DS) on the peritoneal metastasis of gastric cancer by observing the adhesion and implantation of human gastric cancer cells in the omenta of nude mice. DS or PBS was added to the culture medium of gastric cancer MKN1 cells. The adhesion of the cancer cells to the culture dishes, and the morphological changes of fixed and living cancer cells were observed using fluorescence staining and confocal microscopy. In addition, the expression of integrin ß1 was measured using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Gastric cancer BGC-823 cells were peritoneally injected into nude mice to develop an animal model. DS and PBS were peritoneally injected into the experimental and control groups, respectively, concurrently with the tumour cells. Haematoxylin and eosin staining was performed, and the number of carcinoma nodules with celiac implantation was counted. Integrin expression was determined by immunohistochemistry and RT-PCR. The results showed that MKN1 cells strongly expressed integrin ß1 in the cell membrane and clustered in vitro. DS inhibited the expression of integrin ß1 and reduced cluster formation. In addition, the number of pseudopodia formed by the cells decreased, and the cells maintained a rounded shape. The expression of integrin ß1 in the adherent and free cells in the experimental group was reduced to 74 and 38% of the levels in the control group, respectively. In the in vivo study, significantly fewer tumour nodules were observed in the experimental group than in the control group (P<0.01). Integrin ß1 expression in the experimental group was decreased significantly compared with that in the control group (P<0.01). The present study indicates that DS inhibits the adhesion of human gastric cancer cells, accompanied by a decrease in the expression of integrin ß1. DS may inhibit the metastatic celiac implantation of human gastric cancer cells by downregulating integrin ß1.

Inhibition of peritoneal metastasis of human gastric cancer cells by dextran sulphate through the reduction in HIF-1α and ITGß1 expression.

The aim of the present study was to investigate the effects of dextran sulphate (DS) on HIF-1α and integrin ß1 (ITGß1) expression in human gastric cancer cells, the correlation between HIF-1α and ITGß1 expression and the influence of DS on the peritoneal metastasis of human gastric cancer cells. In in vitro experiments, BGC-823 cells in the experimental and control groups were administered DS and PBS, respectively, and exposed to hypoxic conditions for different periods. Immunocytochemistry, western blot and RT-PCR analyses were used to evaluate HIF-1α and ITGß1 expression levels. In in vivo experiments, an animal model was established by injecting BGC-823 cells into nude mice. The experimental and control groups received DS and PBS injections, respectively. The mice were euthanized at different times, and the number of tumor nodules in the celiac implantation was recorded. Immunohistochemistry, RT-PCR and western blot analyses were used to detect HIF-1α and ITGß1 expression in the tumor nodules of the greater omentum. The in vitro and in vivo results revealed that HIF-1α and ITGß1 expression levels in the experimental group were significantly lower than those in the control group (P<0.05), and the expression levels of these factors were positively correlated with each other. The number of tumor nodules in the in vivo experiments was notably less in the experimental group than that noted in the control group (P<0.01). In conclusion, DS may act through inhibition of HIF-1α expression, which decreased ITGß1 expression, consequently reducing tumor metastasis.

Local injection of M-CH combined with i.p. hyperthermic hypo-osmolar infusion is an effective therapy in advanced gastric cancer.

Treatment failure of surgically treated gastric cancer is attributed to the spread of gastric cancer cells into the abdominal cavity and lymphatic or hematogenic canals. In the present study, local injection of mitomycin C bound to activated carbon (M-CH) combined with i.p. hyperthermic hypo-osmolar infusion (IPHHOI) was intraoperatively administered to prevent lymph node recurrence and peritoneal recurrence of gastric cancer. Between April 1998 and August 1999, 79 patients with advanced gastric cancer were allocated randomly to two groups. Forty patients underwent M-CH plus IPHHOI combined with surgery (M-CH1+IPHHOI group) and the remaining 39 underwent surgery alone (control group). Lymph node and peritoneal recurrence were significantly decreased in the M-CH1+IPHHOI group compared to that in the control group (p<0.05). The 1- and 2-year survival rates for the M-CH1+IPHHOI group were 91.2 and 72.1%, and those for the control group were 78.9 and 45.5%. The M-CH1IPHHOI group reaped a significant survival benefit (p=0.0352) compared to the control group. Although this study was conducted randomly for a small number of patients and short time, compared with the control group, the M-CH1+IPHHOI group had a beneficial effect in preventing lymph node recurrence and peritoneal recurrence after curative gastrectomy for advanced gastric cancer.