Class incremental learning of remote sensing images based on class similarity distillation.

When a well-trained model learns a new class, the data distribution differences between the new and old classes inevitably cause catastrophic forgetting in order to perform better in the new class. This behavior differs from human learning. In this article, we propose a class incremental object detection method for remote sensing images to address the problem of catastrophic forgetting caused by distribution differences among different classes. First, we introduce a class similarity distillation (CSD) loss based on the similarity between new and old class prototypes, ensuring the model's plasticity to learn new classes and stability to detect old classes. Second, to better extract class similarity features, we propose a global similarity distillation (GSD) loss that maximizes the mutual information between the new class feature and old class features. Additionally, we present a region proposal network (RPN)-based method that assigns positive and negative labels to prevent mislearning issues. Experiments demonstrate that our method is more accurate for class incremental learning on public DOTA and DIOR datasets and significantly improves training efficiency compared to state-of-the-art class incremental object detection methods.

Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis.

Background: Necroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development via the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown. Methods: The data of 11,057 cancer samples were downloaded from the TCGA database, along with clinical information, tumor mutation burden, and microsatellite instability information of the corresponding patients. We used the TCGA data in a pan-cancer analysis to identify differences in mRNA level as well as single nucleotide variants, copy number variants, methylation profiles, and genomic signatures of miRNA-mRNA interactions. Two drug datasets (from GDSC, CTRP) were used to evaluate drug sensitivity and resistance against necroptosis genes. Results: Necroptosis genes were aberrantly expressed in various cancers. The frequency of necroptosis gene mutations was highest in lung squamous cell carcinoma. Furthermore, the correlation between necroptosis gene expression in the tumor microenvironment and immune cell infiltration varied for different cancers. High necroptosis gene expression was found to correlate with NK, Tfh, Th1, CD8_T, and DC cells. These can therefore be used as biomarkers to predict prognosis. By matching gene targets with drugs, we identified potential candidate drugs. Conclusion: Our study showed the genomic alterations and clinical features of necroptosis genes in 33 cancers. This may help clarify the link between necroptosis and tumorigenesis. Our findings may also provide new approaches for the clinical treatment of cancer.

Construction and Validation of a m7G-Related Gene-Based Prognostic Model for Gastric Cancer.

Background: Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. Chinese cases of GC account for about 40% of the global rate, with approximately 1.66 million people succumbing to the disease each year. Despite the progress made in the treatment of GC, most patients are diagnosed at an advanced stage due to the lack of obvious clinical symptoms in the early stages of GC, and their prognosis is still very poor. The m7G modification is one of the most common forms of base modification in post-transcriptional regulation, and it is widely distributed in the 5' cap region of tRNA, rRNA, and eukaryotic mRNA. Methods: RNA sequencing data of GC were downloaded from The Cancer Genome Atlas. The differentially expressed m7G-related genes in normal and tumour tissues were determined, and the expression and prognostic value of m7G-related genes were systematically analysed. We then built models using the selected m7G-related genes with the help of machine learning methods.The model was then validated for prognostic value by combining the receiver operating characteristic curve (ROC) and forest plots. The model was then validated on an external dataset. Finally, quantitative real-time PCR (qPCR) was performed to detect gene expression levels in clinical gastric cancer and paraneoplastic tissue. Results: The model is able to determine the prognosis of GC samples quantitatively and accurately. The ROC analysis of model has an AUC of 0.761 and 0.714 for the 3-year overall survival (OS) in the training and validation sets, respectively. We determined a correlation between risk scores and immune cell infiltration and concluded that immune cell infiltration affects the prognosis of GC patients. NUDT10, METTL1, NUDT4, GEMIN5, EIF4E1B, and DCPS were identified as prognostic hub genes and potential therapeutic agents were identified based on these genes. Conclusion: The m7G-related gene-based prognostic model showed good prognostic discrimination. Understanding how m7G modification affect the infiltration of the tumor microenvironment (TME) cells will enable us to better understand the TME's anti-tumor immune response, and hopefully guide more effective immunotherapy methods.

Efficacy of DC-CIK Immunotherapy Combined with Chemotherapy on Locally Advanced Gastric Cancer.

The aim of the study is to explore the efficacy and safety of dendritic cell-cytokine-induced killer cell (DC-CIK) immunotherapy combined with chemotherapy in the treatment of locally advanced gastric cancer (LAGC). Among 106 patients with LAGC, 53 received the treatment of oxaliplatin-5-fluorouracil chemotherapy (control group), while the remaining 53 received DC-CIK immunotherapy combined with chemotherapy (DC-CIK group). The short-term efficacy and the changes in immune function indexes (cluster of differentiation (CD)3+, CD4+, CD8+, CD4+/CD8+, and natural killer (NK) cells) were analyzed. The overall response rate (ORR) was 47.2% (25/53) and 41.5% (22/53), and the disease control rate (DCR) was 69.8% (37/53) and 50.9% (27/53), respectively, in the DC-CIK group and the control group. It could be seen that the ORR had no statistically significant difference between the two groups, while the DCR in the DC-CIK group was significantly better than that in the control group. After treatment, the proportions of CD3+ T lymphocytes, CD4+ T lymphocytes, CD4+/CD8+ cells, and NK cells obviously rose, while the proportion of CD8+ T lymphocytes obviously declined in the DC-CIK group compared with those in the control group. After treatment, the scores in the function module of the QLQ-C30 scale were greatly higher in the DC-CIK group than those in the control group, while the scores of loss of appetite, constipation, dyspnea, fatigue, pain, and sleep disorders in the symptom module were significantly lower in the DC-CIK group than those in the control group. The median survival time was 23.4 months and 18.6 months, respectively, in the DC-CIK group and the control group. The results of the log-rank test showed that the OS in the DC-CIK group was remarkably superior to that in the control group. DC-CIK immunotherapy combined with chemotherapy can improve the immune cell function, ameliorate the quality of life, and prolong the survival time of LAGC patients, with fewer adverse reactions.

ERCC6L promotes cell growth and metastasis in gastric cancer through activating NF-κB signaling.

ERCC6L has been reported to act as a potential oncogenic protein in various cancers. However, the role of ERCC6L in the progression of gastric cancer (GC) remains to be elucidated. Herein, we aimed to assess the clinical significance, the role, and the underlying mechanism of ERCC6L in GC progression. In this study, the mRNA and protein expression levels of ERCC6L were measured in GC specimens by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry, and its clinical significance was assessed. The effect of ERCC6L overexpression or knockdown on GC cell growth, migration, and invasion was explored by functional experiments. Notably, the possible mechanisms underlying the action of ERCC6L were also investigated. We found that ERCC6L was upregulated in GC tissues, and its expression was associated with tumor size, clinical stage, and poor prognosis in GC patients. Besides, ERCC6L facilitated GC cell proliferation and metastasis in vitro and in vivo. Mechanically, ERCC6L modulated GC cell behavior via activation of NF-κB signaling. Our results indicated that ERCC6L played a critical role in GC progression and metastasis. In addition, ERCC6L promoted GC cell growth and metastasis via activation of NF-κB signaling, thus possibly providing a target for GC.

Galectin-1 promotes vasculogenic mimicry in gastric adenocarcinoma via the Hedgehog/GLI signaling pathway.

BACKGROUND: Galectin-1 (GAL-1), which is encoded by LGALS1, promotes vasculogenic mimicry (VM) in gastric cancer (GC) tissue. However, the underlying mechanism remains unclear. METHODS: Immunohistochemical (IHC) and CD34-periodic acid-Schiff (PAS) double staining were used to investigate Glioma-associated oncogene-1(GLI1) expression and VM in paraffin-embedded sections from 127 patients with GC of all tumor stages. LGALS1 or GLI1 were stably transduced into MGC-803 cells and AGS cells, and western blotting, IHC, CD34-PAS double staining and three-dimensional culture in vitro, and tumorigenicity in vivo were used to explore the mechanisms of GAL-1/ GLI1 promotion of VM formation in GC tissues. RESULTS: A significant association between GAL-1 and GLI1 expression was identified by IHC staining, as well as a significant association between GLI1 expression and VM formation. Furthermore, overexpression of LGALS1 enhanced expression of GLI1 in MGC-803 and AGS cells. GLI1 promoted VM formation both in vitro and in vivo. The effects of GLI1 on VM formation were independent of LGALS1. Importantly, the expression of VM-related molecules, such as MMP2, MMP14 and laminin5γ2, was also affected upon GLI1 overexpression or silencing in GC cell lines. CONCLUSION: GAL-1 promotes VM in GC through the Hh/GLI pathway, which has potential as a novel therapeutic target for treatment of VM in GC.

Evaluating critical barriers and pathways to implementation of e-waste formalization management systems in Ghana: a hybrid BWM and fuzzy TOPSIS approach.

The majority of developing countries are facing enormous challenges in implementing sustainable waste electrical and electronic equipment (e-waste) management systems. Informal e-waste management practices in Ghana have become a critical challenge to the government and the various stakeholders owing to its environmental and health impacts. However, the effort to implement e-waste formalization management practices has been threatened with many barriers. This study aims to identify and evaluate barriers and pathways to the implementation of e-waste formalization management systems in Ghana. A three-phase methodology consisting of the Delphi method, the hybrid best-worst method and the fuzzy TOPSIS technique is employed. The first phase involves extensive literature review and the use of the Delphi method to identify barriers, pathways, and data collection for e-waste formalization. In the second phase, the best-worst method was employed to analyze the relative weight and ranking of the barriers. The third phase involves the application of fuzzy TOPSIS to rank and prioritize pathways to e-waste formalization systems. Fuzzy logic was applied to handle the subjectivity of decision-makers' preferences. A sensitivity analysis was carried out to check the robustness of the framework and address any effect of bias. The outcome of the study indicates that economic and financial limitations are the most significant barriers to e-waste formalization. "Setting up resourced environmental government agencies for effective monitoring and auditing at the regional levels for appropriate e-waste management practices" is the most prominent pathway. The present study can potentially inform policy makers to develop systematic and strategic policies for the implementation of e-waste formalization management systems.

High versus low ligation of inferior mesenteric artery during laparoscopic radical resection of rectal cancer: A retrospective cohort study.

Laparoscopic radical resection is standard treatment for resectable rectal cancer. However, whether high or low inferior mesenteric artery (IMA) ligation should be performed remains controversial. This retrospective cohort study compared the advantages and disadvantages of low vs high IMA ligation in patients undergoing laparoscopic total mesorectal excision for rectal cancer.Rectal cancer patients (n = 322) undergoing total mesorectal excision at our institution in 2010 to 17 were enrolled; 174 underwent high IMA ligation group and 148 low IMA ligation (LIMAL group). Baseline data on patients, operative indices, economic indices, pathology findings, perioperative complications, and survival in the 2 groups were analyzed retrospectively.The low IMA ligation group had significantly higher anus retention ratio (P = .022), shorter hospital stay (P = .025), lower medical expenses (P = .032), fewer cases of anastomotic leakage (P = .023) and anastomotic stricture (P < .001), and lower incidence of postoperative genitourinary dysfunction (P = .003). Cox regression analysis indicated that local recurrence, distant metastasis, tumor differentiation, and tumor-node-metastasis stage were independently associated with survival.Low ligation of the IMA during laparoscopic radical resection of rectal cancer appears to be associated with a lower risks for anastomotic leakage, anastomotic stricture, and genitourinary dysfunction, a shorter hospital stay, and lower costs. In contrast, the rate of lymph node harvest, tumor recurrence rate, metastasis, or mortality was not found to be related with the level of IMA ligation.

TYRO3 facilitates cell growth and metastasis via activation of the Wnt/ß-catenin signaling pathway in human gastric cancer cells.

It has become increasingly important to identify valuable therapeutic targets to improve the prognosis of cancer patients. Although emerging evidence has suggested TYRO3 as a potential therapeutic target in various types of cancers, less is known about its role in gastric cancer (GC) development. Herein, we investigated the functional and molecular mechanisms by which TYRO3 influenced GC. TYRO3 mRNA and protein were evaluated by quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry. Other methods including stable transfection of TYRO3 into GC cells, wound healing, Transwell assays, CCK-8 assays, colony formation assays, immunocytochemistry in vitro, and tumorigenesis in vivo were also conducted. Our results indicated that high levels of TYRO3 significantly correlated with clinical metastasis and poor prognoses in patients with GC. In addition, TYRO3 silencing distinctively suppressed GC cell growth, invasion, and metastasis both in vitro and in vivo. Conversely, TYRO3 overexpression led to the opposite effects. Mechanistic analyses revealed that the Wnt/ß-catenin signaling pathway might be involved in TYRO3-facilitated GC cell behavior. Collectively, we demonstrated that elevated TYRO3 expression contributed to GC cell growth and metastasis via the Wnt/ß-catenin pathway, suggesting a novel therapeutic target for GC.

Galectin-1 Promotes Vasculogenic Mimicry in Gastric Cancer by Upregulating EMT Signaling.

Background: Galectin-1 (Gal-1) expression was positively associated with vasculogenic mimicry (VM) in primary gastric cancer (GC) tissue, and that both Gal-1 expression and VM in GC tissue are indicators of poor prognosis. However, whether Gal-1 promotes VM, and by what mechanismsremains unknown. Methods: To investigate the underlying mechanisms,wound healing assay, proliferation assay, invasion assay, and three-dimensional culture were used to evaluate the invasion, metastasis and promoted VM formation effects of the Gal-1. We monitored the expression level of sociated proteins in GC tissues, cell lines in vitro and nude mice tumorigenicity in vivo by immunohistochemistry and western blot. Results: Gal-1 overexpression significantly promoted the proliferation, invasion, migration, and VM formation of MGC-803 cells. Gal-1 was associated with E-cadherin and vimentin in vitro and in clinical samples. The epithelial-to-mesenchymal transition (EMT) induced in MGC-803 cells by TGF-ß1 was accompanied by Gal-1 activation and promotion of VM formation, while knockdown of Gal-1 reduced the response to TGF-ß1, suggesting that Gal-1 promotes VM formation by activating EMT signaling. Overexpression of Gal-1 accelerated subcutaneous xenograft growth and facilitated pulmonary metastasis in athymic mice, enhanced the expression of EMT markers, and promoted VM formation in vivo. Conclusion: Our results indicated that Gal-1 promotes VM in GC by upregulating EMT signaling; thus, Gal-1 and this pathway are potential novel targets to treat VM in GC.

Single vs. double purse-string anastomosis during laparoscopic low anterior rectal resection (SINGLE-DOUBLE trial): study protocol for a randomized controlled trial.

BACKGROUND: An inappropriate anastomosis method during laparoscopic anterior rectal resection can increase the risk of anastomotic complications and affect surgical, economic, and oncological outcomes. The aim of this study is to compare the incidence of anastomotic complications and the surgical, economic, and oncological outcomes following single versus double purse-string anastomosis during laparoscopic total mesorectal excision (TME) for low rectal cancer. METHODS/DESIGN: This randomized controlled trial (the SINGLE-DOUBLE study) will randomly assign middle and low rectal adenocarcinoma patients to receive either single or double purse-string anastomosis during laparoscopic low anterior rectal resection. Patients will be eligible for inclusion only if they (1) have adenocarcinoma confirmed by preoperative colonoscopy and biopsy, (2) have a tumor situated less than 12 cm from the anal verge, (3) do not have the anal sphincter involved, and (4) do not have distant metastases. The primary endpoint measure will be the incidence of anastomotic complications (leakage, narrowing, and bleeding). The secondary endpoints will be surgical, economic, and oncological outcomes. A total of 500 patients will be enrolled in the study. Sample size calculation was based on previous reports and our retrospective analysis. DISCUSSION: This randomized single-center controlled trial is expected to demonstrate which anastomosis method (single or double purse-string anastomosis) is better for reducing complications and improving prognosis in rectal cancer patients undergoing laparoscopic TME for low or middle rectal cancer. TRIAL REGISTRATION: Registration number: ChiCTR 1800016116 . Protocol Registration Receipt: May 13, 2018.

A-kinase-interacting protein 1 facilitates growth and metastasis of gastric cancer cells via Slug-induced epithelial-mesenchymal transition.

A-kinase-interacting protein 1 (AKIP1) has previously been reported to act as a potential oncogenic protein in various cancers. The clinical significance and biological role of AKIP1 in gastric cancer (GC) is, however, still elusive. Herein, this study aimed to investigate the functional and molecular mechanism by which AKIP1 influences GC. AKIP1 mRNA and protein expressions in GC tissues were examined by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. Other methods including stably transfected against AKIP1 into gastric cancer cells, wound healing, transwell assays, CCK-8, colony formation, qRT-PCR and Western blot in vitro and tumorigenesis in vivo were also performed. The up-regulated expression of AKIP1 in GC specimens significantly correlated with clinical metastasis and poor prognosis in patients with GC. AKIP1 knockdown markedly suppressed GC cells proliferation, invasion and metastasis both in vitro and in vivo. In contrast, AKIP1 overexpression resulted in the opposite effects. Moreover, mechanistic analyses indicated that Slug-induced epithelial-mesenchymal transition (EMT) might be responsible for AKIP1-influenced GC cells behaviour. Our findings demonstrated that high AKIP1 expression significantly correlated with clinical metastasis and unfavourable prognosis in patients with GC. Additionally, AKIP1 promoted GC cells proliferation, migration and invasion by activating Slug-induced EMT.

Aberrant Cytokeratin 20 mRNA Expression in Peripheral Blood and Lymph Nodes Indicates Micrometastasis and Poor Prognosis in Patients With Gastric Carcinoma.

Several studies suggest that peripheral blood and lymph node micrometastases may be a causative factor for gastric cancer recurrence. Cytokeratin 20 shows enriched expression in intestinal epithelial cells. This study aimed to evaluate the clinical utility of monitoring cytokeratin 20 levels in peripheral blood and lymph nodes of patients with gastric cancer for detecting micrometastasis and predicting prognosis. We detected messenger RNA levels of cytokeratin 20 in gastric cancer cell lines and in the peripheral blood of 125 patients (85 patients with gastric cancer and 40 patients with benign neoplasm) by fluorescence quantitative real-time polymerase chain reaction both before and after radical resection. In all, 1586 lymph node samples from 85 patients with gastric cancer were evaluated for cytokeratin 20 expression using real-time polymerase chain reaction, as well as by immunohistochemistry staining with anti-pan-keratin and anti-cytokeratin 20 antibodies. All patients underwent follow-up until cancer-related death or for more than 3 years after tumor resection. We found that elevated cytokeratin 20 expression in peripheral blood as detected by quantitative real-time polymerase chain reaction closely correlates with poor clinicopathological characteristics. Detecting cytokeratin 20 messenger RNA in the lymph nodes by quantitative real-time polymerase chain reaction enabled more accurate determination of the clinicopathological staging of gastric cancer, best treatment approach, and prognosis. Our findings show that patients with increased cytokeratin 20 messenger RNA expression in the peripheral blood or lymph nodes have a shorter time to recurrence and poorer overall survival.

TRIM37 promotes cell invasion and metastasis by regulating SIP1-mediated epithelial-mesenchymal transition in gastric cancer.

BACKGROUND: Tripartite motif containing 37 (TRIM37) has been demonstrated to function importantly during the progression of various cancers. However, the role of TRIM37 in gastric cancer (GC) remains elusive. MATERIALS AND METHODS: TRIM37 mRNA and protein expressions were determined by qRT-PCR, Western blot, and immunohistochemical staining in GC specimens. The effects of TRIM37 on GC cells behavior were evaluated by transwell assays in vitro and metastasis assay in vivo, respectively. Besides, qRT-PCR, Western blot, and immunofluorescence staining were employed to detect the expressions of TRIM37 and epithelial-mesenchymal transition (EMT)-related markers. RESULTS: The present study revealed that TRIM37 mRNA or protein expression was significantly increased in GC tissues compared with that in paracancerous control tissues, and its aberrant overexpression was closely associated with clinical metastasis and poor prognosis in patients with GC. TRIM37 knockdown significantly suppressed GC cells migration and invasion in vitro, as well as metastasis in vivo. Inversely, TRIM37 overexpression exerted the opposite effects. Mechanistic studies suggested that SIP1-mediated EMT might be responsible for TRIM37-facilitated GC cells migration and invasion. CONCLUSION: Our findings revealed that high TRIM37 expression was associated with clinical metastasis and poor survival in patients with GC. TRIM37 promoted GC cells migration and invasion via EMT, mediated by the transcription factor SIP1, thus providing a candidate target for GC treatment.

Galectin-1 Promotes Metastasis in Gastric Cancer Through a Sphingosine-1-Phosphate Receptor 1-Dependent Mechanism.

BACKGROUND/AIMS: Increased expression of galectin-1 (Gal-1) in gastric cancer (GC) promotes metastasis and correlates with poor prognosis. The mechanisms by which Gal-1 promotes GC metastasis remain unknown. METHODS: Gal-1and Sphingosine-1-phosphate receptor 1 (S1PR1) were determined by immunohistochemistry(IHC) and quantitative real time polymerase chain reaction (qRT-PCR) in GC specimens. Stably transfected Gal-1 or S1PR1 into SGC7901 and MGC-803 cells, western blot and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. RESULTS: Overexpression of Gal-1 enhanced expression of S1PR1 in SGC-7901 cells, and increased cell invasion, while knockdown Gal-1 in MGC-803 cells reduced S1PR1 expression and diminished invasion. Simultaneous knockdown of Gal-1 and overexpression of S1PR1 in MGC803 cells rescued invasive ability of MGC803 cells. S1PR1 was associated with expression of epithelial-to-mesenchymal transition (EMT) markers in vitro and in clinical samples. EMT induced in MGC-803 cells by TGF-ß1 was accompanied by S1PR1 activation, while knockdown of S1PR1 reduced response to TGF-ß1, suggest that Gal-1 promotes GC invasion by activating EMT through a S1PR1-dependent mechanism. Overexpression of S1PR1 promoted subcutaneous xenograft growth and pulmonary metastases, and enhanced expression of EMT markers. CONCLUSION: Galectin-1 promotes metastasis in gastric cancer through a S1PR1- dependent mechanism, our results indicate that targeting S1PR1 may be a novel strategy to treat GC metastasis.

CPEB4 promotes growth and metastasis of gastric cancer cells via ZEB1-mediated epithelial- mesenchymal transition.

BACKGROUND: Cytoplasmic polyadenylation element-binding protein 4 (CPEB4) has previously been reported to be associated with biological malignancy in various cancers. However, its function in tumor growth and metastasis in gastric cancer (GC) remains obscure. Here, we explored the functional and molecular mechanisms by which CPEB4 influences GC. MATERIALS AND METHODS: The expression of CPEB4 was assessed using Western blot and immunohistochemistry in GC specimens. The roles of CPEB4 in GC cell proliferation, migration, and invasion were investigated by cell-counting kit-8 (CCK-8), colony formation, and EdU assay; wound-healing assay; and transwell assay, respectively. Quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence staining were performed to detect the expressions of CPEB4 and epithelial-mesenchymal transition (EMT)-related markers. The function of CPEB4 on GC cell growth and metastasis was also determined in vivo through establishing subcutaneous xenograft tumor and lung metastatic mice model. RESULTS: The results revealed that the expression of CPEB4 was increased in GC tissues compared with matched normal tissues. High expression level of CPEB4 was significantly associated with clinical metastasis and unfavorable prognosis in patients with GC. Furthermore, CPEB4 silencing remarkably inhibited GC cells' proliferation, invasion, and metastasis in vitro and in vivo. Conversely, CPEB4 overexpression achieved the opposite effects. Mechanically, we proved that ZEB1-mediated EMT might be involved in CPEB4-facilitated GC cells' proliferation, invasion, and metastasis. CONCLUSION: Our findings implied that CPEB4 expression predicted a worse prognosis in patients with GC. Besides, CPEB4 contributed to GC cells' proliferation, migration, and invasion via ZEB1-mediated EMT.

Prognostic significance of galectin-1 and vasculogenic mimicry in patients with gastric cancer.

INTRODUCTION: We evaluated the expression of galectin-1 (Gal-1) and vasculogenic mimicry (VM) in gastric cancer (GC) and investigated their relationships with the clinicopathological factors and prognostic significance in GC. MATERIALS AND METHODS: Immunohistochemical (IHC) staining and CD34-periodic acid-Schiff double stain were used to investigate Gal-1 expression and VM in paraffin-embedded sections from 127 patients with GC of all tumor stages. The relationships between Gal-1 expression and VM, clinicopathological variables, and survival were analyzed. P < 0.05 was considered statistically significant. RESULTS: Among the 127 cases, 86 (67.7%) were positive for Gal-1; VM was detected in 29 cases (22.8%). There was a significant association between VM and the Gal-1 IHC staining; all cases with VM were positive for Gal-1 staining. Gal-1 expression and VM in primary GC tissue were associated with tumor size, differentiation, depth of tumor invasion, stage, lymph node metastases, and tumor emboli in microvessels (all, P < 0.05). Kaplan-Meier analysis revealed that the overall survival time was 52.56 ± 2.44 months (95% confidence interval [CI]: 47.77-57.35) for patients with Gal-1-negative and VM-negative primary GC tissue, 43.83 ± 2.17 months (95% CI: 39.58-48.08) for patients with Gal-1-positive but VM-negative primary GC tissue, and 23.97 ± 2.44 months (95% CI: 19.18-28.76) for patients with Gal-1-positive and VM-positive primary GC tissue (χ2 = 60.21, P < 0.01). Gal-1 expression was positively associated with VM in primary GC tissue. CONCLUSION: Both Gal-1 expression and VM in primary GC tissue are indicators of poor prognosis for GC after gastrectomy, and Gal-1 may be a novel target for treating VM in GC.

Alpha B-crystallin promotes the invasion and metastasis of gastric cancer via NF-κB-induced epithelial-mesenchymal transition.

Alpha B-crystallin (CRYAB) is overexpressed in a variety of cancers. However, little is known about its specific function and regulatory mechanism in gastric cancer. Here, we first explore the role of CRYAB in gastric cancer progression and metastasis. The expression of CRYAB was determined by western blot and immunohistochemistry in gastric cancer tissues. Besides, methods including stably transfected against CRYAB into gastric cancer cells, western blot, migration and invasion assays in vitro and metastasis assay in vivo were also conducted. The expression of CRYAB is up-regulated in gastric cancer tissues compared with matched normal tissues. High expression level of CRYAB is closely correlated with cancer metastasis and shorter survival time in patients with gastric cancer. Additionally, CRYAB silencing significantly suppresses epithelial-mesenchymal transition (EMT), migration and invasion of gastric cancer cells in vitro and in vivo, whereas CRYAB overexpression dramatically reverses these events. Mechanically, CRYAB facilitates gastric cancer cells invasion and metastasis via nuclear factor-κ-gene binding (NF-κB)-regulated EMT. These findings suggest that CRYAB expression predicts a poor prognosis in patients with gastric cancer. Besides, CRYAB contributes to gastric cancer cells migration and invasion via EMT, mediated by the NF-κB signalling pathway, thus possibly providing a novel therapeutic target for gastric cancer.

SPOCK1 promotes the invasion and metastasis of gastric cancer through Slug-induced epithelial-mesenchymal transition.

Metastasis is a crucial impediment to the successful treatment for gastric cancer. SPOCK1 has been demonstrated to facilitate cancer metastasis in certain types of cancers; however, the role of SPOCK1 in the invasion and metastasis of gastric cancer remains elusive. SPOCK1 and epithelial-mesenchymal transition (EMT)-related biomarkers were detected by immunohistochemistry and Western blot in gastric cancer specimens. Other methods including stably transfected against SPOCK1 into gastric cancer cells, Western blot, migration and invasion assays in vitro and metastasis assay in vivo were also performed. The elevated expression of SPOCK1 correlates with EMT-related markers in human gastric cancer tissue, clinical metastasis and a poor prognosis in patients with gastric cancer. In addition, knockdown of SPOCK1 expression significantly inhibits the invasion and metastasis of gastric cancer cells in vitro and in vivo, inversely, SPOCK1 overexpression results in the opposite effect. Interestingly, SPOCK1 expression has no effect on cell proliferation in vitro and in vivo. Regarding the mechanism(s) of SPOCK1-induced cells invasion and metastasis, we prove that Slug-induced EMT is involved in SPOCK1-facilitating gastric cancer cells invasion and metastasis. The elevated SPOCK1 expression is closely correlated with cancer metastasis and patient survival, and SPOCK1 promotes the invasion and metastasis of gastric cancer through Slug-mediated EMT, thereby possibly providing a novel therapeutic target for gastric cancer.

Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer.

BACKGROUND/AIMS: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. METHODS: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. RESULTS: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. CONCLUSION: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.