Abstract Patients with diabetes are prone to concurrent infection. The mechanism of concurrent infection is related to factors such as hyperglycemia and weakened defense function. The infections of patients with diabetes include general and special infections. General infection includes infections in the respiratory system, urinary system, hepatobiliary system, and skin mucosa. Meanwhile, special infection includes invasive otitis externa, nasal mucormycosis, necrotizing fasciitis, and emphysema infection. Patients with special infections also have a higher mortality rate than those with general ones. Complicated infection with diabetes is difficult to treat and has poor prognosis. Therefore, a patient requires active treatment once infected with this infection.

Objective To explore a highly sensitive and highly specific method to detect the serum MG7 antigen（Ag）level for early gastric cancer diagnosis.Methods The serum MG7-Ag level was detected by enzyme-linked immunosorbent assay（ELISA）method in 116 preoperative gastric cancer patients,63 postoperative gastric cancer patients,41 patients with precancerous lesion,37 pa-

Tartrate-resistant acid phosphatase 5 (ACP5), which is essential for bone resorption and osteoclast differentiation, promotes cell motility through the modulation of focal adhesion kinase phosphorylation. However, whether ACP5 contributes to the metastasis and progression of hepatocellular carcinoma (HCC) remains unknown. In this paper, a complementary DNA microarray, serial deletion, site-directed mutagenesis and a chromatin immunoprecipitation assays confirmed that ACP5 is a direct transcriptional target of Forkhead box M1 (FoxM1). ACP5 expression was markedly higher in HCC tissues compared with adjacent noncancerous tissues. ACP5 overexpression was correlated with microvascular invasion, poor differentiation and higher tumor-node-metastasis stage. HCC patients with positive ACP5 expression had poorer prognoses than those with negative ACP5 expression. A multivariate analysis revealed that ACP5 expression was an independent and significant risk factor for disease recurrence and reduced-patient survival following curative resection. Transwell assays and an orthotopic metastatic model showed that the upregulation of ACP5 promoted HCC invasion and lung metastasis, whereas ACP5 knockdown inhibited these processes. The knockdown of ACP5 significantly attenuated FoxM1-enhanced invasion and lung metastasis. Immunohistochemistry revealed that ACP5 expression was positively correlated with FoxM1 expression in human HCC tissues, and their coexpression was associated with poor prognoses. In summary, ACP5 is a direct transcriptional and functional target of FoxM1. This novel FoxM1/ACP5 signaling pathway promotes HCC metastasis and may be a candidate biomarker for prognosis and a target for new therapies.

A growing amount of evidence indicates that miRNAs are important regulators of multiple cellular processes and, when expressed aberrantly in different types of cancer such as hepatocellular carcinoma (HCC), play significant roles in tumorigenesis and progression. Aberrant expression of miR-199a-5p (also called miR-199a) was found to contribute to carcinogenesis in different types of cancer, including HCC. However, the precise molecular mechanism is not yet fully understood. The present study showed that miR-199a is frequently down-regulated in HCC tissues and cells. Importantly, lower expression of miR-199a was significantly correlated with the malignant potential and poor prognosis of HCC, and restoration of miR-199a in HCC cells led to inhibition of the cell proliferation and cell cycle in vitro and in vivo. Furthermore, Frizzled type 7 receptor (FZD7), the most important Wnt receptor involved in cancer development and progression, was identified as a functional target of miR-199a. In addition, these findings were further strengthened by results showing that expression of FZD7 was inversely correlated with miR-199a in both HCC tissues and cells and that over-expression of miR-199a could significantly down-regulate the expression of genes downstream of FZD7, including β-catenin, Jun, Cyclin D1 and Myc. In conclusion, these findings not only help us to better elucidate the molecular mechanisms of hepatocarcinogenesis from a fresh perspective but also provide a new theoretical basis to further investigate miR-199a as a potential biomarker and a promising approach for HCC treatment.

MicroRNAs (miRNAs) can negatively regulate gene expression and also induce or inhibit viral replication. In the present study, we found 10 miRNAs were differentially expressed in a stable HBV-producing cell line (HepG2.2.15) compared with its control cell line (HepG2) by miRNA array analysis. miR-501 was significantly up-regulated in HepG2 cells and tissues with high-HBV replication. miR-501 expression was significantly up-regulated in hepatocellular carcinoma tissues, where HBV replication kept high. Down-regulating miR-501 could significantly inhibit HBV replication, but not influence the growth of HepG2.2.15 cells. Luciferase reporter and western blot assays revealed that HBXIP, an inhibitor of HBV replication, was a potential target of miR-501. Moreover, knockdown of HBXIP rescued the inhibition of HBV that occurred after the loss of miR-501 in HepG2.2.15 cells, suggesting that miR-501 induced HBV replication partially by targeting HBXIP. Thus, knockdown of miR-501 might provide a new mechanism and therapeutic target for inhibiting HBV replication.

<正>转录因子FoxM1(Forkhead box M1)对肿瘤细胞的生长和存活有重要的调节作用,从而在肝细胞癌的发生发展中扮演着重要的角色。然而,上调FoxM1表达的确切分子机制仍然不甚明了。本研究中我们发现,肿瘤坏死因子α(tumor necrosis factorα,TNF-α)可以转录激活FoxM1,上调其表达。我们通过5’端序列截断以及位点突

Gastric cancer is one of the most common cancers and accounts for a large proportion of cancer-related deaths in the world, while the pathogenesis of it is still not clear. Epigenetic changes have been found to participate in the development and progression of gastric cancer. Epigenetic changes involve methylation of cytosines in DNA, modifications of histone, chromatin remodeling, and alterations in the expression of microRNAs. MicroRNAs, a family of small non-coding RNAs, have been demonstrated to participate in many fundamental biological processes including the carcinogenesis of gastric cancer. Previous studies have shown that the downregulation of microRNAs are often caused by the methylation in the CpG islands of microRNA promoters. Here, we have summarized the functions and molecular mechanisms of gastric cancer related methylated microRNAs in gastric carcinogenesis. We further envisage the clinical application of microRNA methylation in the early diagnosis, treatment and prognosis assessment of gastric cancer.

Background The major reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients is lymph node (LN) metastases. Methodology/Principal In the present study, gene expression profiling assay (GEP) was performed to identify the differences in gene expression profiles between primary ESCC tumors that were with LN metastases (N+) and those without LN metastases (N-). Conclusions/Significance A total of 23 genes were identified as being significantly elevated, and 30 genes were sharply decreased in ESCC tumors that were N+ compared with N- tumors. Among these genes, two transcripts of the short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) were observed 7 times more frequently in N+ compared with N- tumors. Immunohistochemical staining showed that SDR9C7 expression closely correlated with metastasis, and would be a prognostic marker for ESCC patients. To investigate the role of SDR9C7 in the ESCC metastasis, repeated transwell assays were adopted to establish highly and non-invasive ESCC sublines, and western blot showed that SDR9C7 expression was markedly higher in highly invasive cells compared with non-invasive ones. Down-regulation of SDR9C7 dramatically inhibited the metastatic abilities in vitro and in vivo, and repressed the expression of MMP11 in highly invasive cells, indicating that SDR9C7 promotes ESCC metastasis partly through regulation of MMP11, and might be a potential prognostic and therapeutic marker for ESCC patients.

Recurrence and metastasis remain the most common causes of lethal outcomes in hepatocellular carcinoma (HCC) after curative resection. Thus, it is critical to discover the mechanisms underlying HCC metastasis. Forkhead box C1 (FoxC1), a member of the Fox family of transcription factors, induces epithelial‐mesenchymal transition (EMT) and promotes epithelial cell migration. However, the role of FoxC1 in the progression of HCC remains unknown. Here, we report that FoxC1 plays a critical role in HCC metastasis. FoxC1 expression was markedly higher in HCC tissues than in adjacent noncancerous tissues. HCC patients with positive FoxC1 expression had shorter overall survival times and higher recurrence rates than those with negative FoxC1 expression. FoxC1 expression was an independent, significant risk factor for recurrence and survival after curative resection. FoxC1 overexpression induced changes characteristic of EMT and an increase in HCC cell invasion and lung metastasis. However, FoxC1 knockdown inhibited these processes. FoxC1 transactivated Snai1 expression by directly binding to the Snai1 promoter, thereby leading to the inhibition of E‐cadherin transcription. Knockdown of Snai1 expression significantly attenuated FoxC1‐enhanced invasion and lung metastasis. FoxC1 expression was positively correlated with Snai1 expression, but inversely correlated with E‐cadherin expression in human HCC tissues. Additionally, a complementary DNA microarray, serial deletion, site‐directed mutagenesis, and a chromatin immunoprecipitation assay confirmed that neural precursor cell expressed, developmentally down‐regulated 9 (NEDD9), which promotes the metastasis of HCC cells, is a direct transcriptional target of FoxC1 and is involved in FoxC1‐mediated HCC invasion and metastasis. Conclusions: FoxC1 may promote HCC metastasis through the induction of EMT and the up‐regulation of NEDD9 expression. Thus, FoxC1 may be a candidate prognostic biomarker and a target for new therapies. (HEPATOLOGY 2013;)

The proliferation-specific transcription factor Forkhead box M1 (FoxM1) acts as a master regulator of cancer cell growth and survival and plays an important role in the development of hepatocellular carcinoma. However, the molecular mechanisms that regulate FoxM1 expression remain largely unknown. In the current study, we demonstrated that tumor necrosis factor (TNF)-αα induced FoxM1 expression and transactivated its promoter activity in hepatoma cells. Serial 5" deletion and site-directed mutagenesis revealed that the induction of FoxM1 expression by TNF-α was dependent upon the hypoxia-inducible factor 1 (HIF1)-1 and HIF1-3/4 binding sites within the FoxM1 promoter. Furthermore, at the transcriptional level, the stabilization of HIF-1α via reactive oxygen species generation led to the binding of HIF-1α to the FoxM1 promoter and resulted in increased FoxM1 expression. The inhibition of both HIF-1α expression and reactive oxygen species generation significantly decreased TNF-α-induced FoxM1 overexpression. Consequently, the upregulation of FoxM1 promoted the proliferation of hepatoma cells and enhanced their resistance to TNF-α-induced apoptosis. Consistently, there was a positive correlation between HIF-1α and FoxM1 expression in 406 human hepatocellular carcinoma tissues, and the combination of these two parameters was a powerful predictor of poor prognosis in hepatocellular carcinoma patients after curative resection. Here, we report a new molecular mechanism by which FoxM1 expression is regulated by the TNF-α/reactive oxygen species/HIF-1 pathway, and this mechanism results in the proliferation of hepatoma cells and their resistance to apoptosis.

Background Studies have been shown that miR-125a plays an important role in carcinogenesis, however, the role of miR-125a in hepatocellular carcinoma (HCC) remains elusive. Methodology/Principal Real time-PCR (qRT-PCR) was performed to test the significance of miR-125a in HCC. Ectopic expression of miR-125a was used to test the influences of miR-125a on proliferation and metastasis of HCC cells in vitro and in vivo. Predicted target genes of miR-125a were determined by dual-luciferase reporting, qRT-PCR, and western blot (WB) analyses. Then immunohistochemical staining (IHC) was used to detect the expression of target genes, and the correlations and prognostic values of miR-125a and its target genes were also investigated. Conclusions/Significance Decreased miR-125a was observed in both HCC tissues and cell lines, and associated with patients’ aggressive pathologic features. Up-regulating miR-125a significantly inhibited the malignant phenotypes by repressing the expression of matrix metalloproteinase 11 (MMP11) and vascular endothelial growth factor A (VEGF-A) both in vitro and in vivo. Furthermore, miR-125a expression was inversely correlated with both MMP11 and VEGF-A expression in HCC tissues. Inhibiting miR-125a could increase both MMP11 and VEGF-A expression, and RNA interference targeting MMP11 or VEGF-A mRNA could rescue the loss of miR-125a functions. MiR-125a inhibits the proliferation and metastasis of HCC by targeting MMP11 and VEGF-A. Up-regulation of miR-125a might be a promising approach and a prognostic marker for HCC.

Objective:To investigate the expression of ATM gene in six human gastric cancer cell lines and cellular responses to DNA damage.Methods:Western-blot analysis was performed on six human gastric cancer cell lines,and the apoptosis kinases and cellular responses were observed after two cell lines MKN28 and MGC803 were treated with the DNA damage reagent CDDP.Results:It was found that ATM was strongly expressed in MGC803,MKN28,MKN45,SGC7901 cell lines,but it weekly expressed in BGC823 and AGS cell lines.The level of ATM protein and apoptosis kinases in BGC823 were increased after treated with CDDP,while the G 2 phase checkpoint of MKN28 cells was deficient because the expressions of ATM,p-chk1 and p-chk2 were weak after treated with CDDP ( P 0.05).Conclusion:ATM deficiency may lead to apoptosis and sensitiveness to DNA damage.ATM may control multiple component elements in cell cycle and monitor cell cycle check point to restoration of cells after DNA damage.

To explore a novel approach for the detection of gastric carcinoma-associated MGAgs by serum quantitative immuno-PCR and to confirm its significance in diagnosis of early gastric cancer,the serum levels of MGAgs were quantifying by real time immuno-PCR in 43 cases of gastric cancer and 37 cases of healthy donor. There was statistical difference (P0.01) in serum MGAgs between gastric cancer and healthy donor by using the real time immuno-PCR. As real time immuno-PCR shown that the cut-off value of MGAgs for gastric cancer was equivalent to 5972 MKN45 cells in 50 μL of serum. The quantitative detection of gastric carcinoma-associated MGAgs in serum from patients with gastric cancer by real time quantitative immuno-PCR is highly sensitive and maybe useful for the diagnosis of gastric cancer.

The invention relates to a detection method of MG7-Ag contained in serum, belonging to the technical field of biology. The detection method comprises the following steps of: accurately quantitating and detecting the content of the trace antigen MG7-Ag contained in the serum by combining a real-time fluorescence quantitative immune PCR detection method on the basis of antigen signal transformation through the identification and the capture of the MG7-Ag by double antibodies; combining a real-time fluorescence quantitative PCR technology with a specific antigen and antibody reaction system to establish a real-time fluorescence quantitative immune PCR technology, wherein the real-time fluorescence quantitative immune PCR technology identifies the MG7-Ag contained in the serum through the specificity of the double antibodies, then respectively combines biotinylated MG7 with biotinylated DNA through streptavidin, converts a content signal of the MG7-Ag contained in the serum into a nucleic acid signal and then enters a real-time fluorescence quantitative PCR expanding way, thereby accurately detecting the trace antigen MG7-Ag contained in the serum.

MG7 is a gastric cancer-specific MAb with high specificity and sensitivity. By using MG7 MAb, we found that MG7Ag was increasingly detected in superficial gastritis, atrophic gastritis, intestinal metaplasia, atypical hyperplasia, and gastric cancer, indicating that MG7Ag could be considered an important early warning molecule of gastric cancer and MG7 MAb could be used as a tool for screening gastric cancer. We have developed a new and sensitive system, immuno-realtime PCR, for detection of MG7Ag in the serum. The use of qIPCR assays enabled the detection of MG7Ag in complex biological samples that were poorly accessible by conventional immunoassays.

Objective:MG7 is a novel tumor-associated antigen in most gastric carcinoma tissues.In this study,we explored MG7 expression in gastric precancerous lesion and its correlation with the expression of COX-2. Methods:The expressions of MG7-Ag and COX-2 were detected in 334 cases of gastric precancerous lesion by immunohistochemical analysis. Results:The positive rates of MG7-Ag and COX-2 expression were 49.1% and 56.6% in gastric precancerous lesion,respectively.From superficial gastritis,atrophic gastritis, intestinal metaplasia,dysplasia to gastric cancer,expressions of MG7-Ag and COX-2 were increased gradually(P0.05).MG7-Ag and COX-2 were expressed coherently in gastric precancerous tissues. Conclusion:The expressions of MG7-Ag and COX-2 had relativity in gastric precancerous tissues.

Acupuncture is an important part of Chinese medicine theory and it has proved to be highly effective in the treatment of more than 300 diseases[[1]]. It is commonly used in China and western countr...

目的:探讨血管特异结合短肽GNSNPKS受体(GNSNPKSR)在胃癌和结肠癌中的表达及与肿瘤分化程度的关系。方法:采用免疫组化SP法检测GNSNPKSR在胃癌和结肠癌中的表达及其分化程度。结果:GNSNPKSR在高、中、低度分化胃癌的血管中表达率依次为12/18(67%)、17/23(74%)、22/24(92%);在高、中、低度分化结肠癌的血管中的表达率依次为3/16(19%)、5/21(24%)和7/23(30%)。GNSNPKSR在胃癌组织中的表达明显高于结肠癌组织(P<0.05),在低分化胃癌组织中的表达明显高于高分化和中分化胃癌组织(P<0.05)。结论:GNSNPKS与胃癌的血管特异结合,可作为肿瘤血管抑制治疗的靶向载体。

Mohammadali M. Shoja Tuberculosis and Lung Disease Research Center, Tabriz Medical University, Postal code: 51738-47661, Amir Kabir Avenue, Kar Pisheh Crossing, Tabriz, Iran Tel.: +98 411 4443502; fax: +98 411 4438523 E-mail address: shoja.m@gmail.com R. Shane Tubbs Department of Cell Biology, Section of Pediatric Neurosurgery, University of Alabama and Children’s Hospital Birmingham, Alabama, USA

The function of cellular prion protein (PrP(C)), the essential protein for the pathogenesis and transmission of prion diseases, is still largely unknown. The putative roles of PrP(C) are thought to be related to cell signaling, survival, and differentiation. In a previous study, we showed that PrP(C) was overexpressed in gastric cancer tissues. In the present report, we show that ectopic expression of PrP(C) could promote tumorigenesis, proliferation, and G1/S transition in gastric cancer cells. Furthermore, CyclinD1, a protein related to cell cycle, was shown to be significantly up-regulated by PrP(C) at both mRNA and protein levels. PI3K/Akt pathway mediated above PrP(C) signal since PrP(C) increased the expression of phosphorylated Akt, and the specific inhibitor of Akt, LY294002, could markedly suppress growth of SGC7901 and transactivation of CyclinD1 induced by PrP(C). Octapeptide repeat region played a vital role in this function, as deletion of this region abolished or reduced these effects. Collectively, this study demonstrates that overexpression of PrP(C) might promote the tumorigenesis and proliferation of gastric cancer cells at least partially through activation of PI3K/Akt pathway and subsequent transcriptional activation of CyclinD1 to regulate the G1/S phase transition, in which octapeptide repeat region might be an indispensable region.