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According to our prior findings, ARID1A expression is decreased in colon cancer, which has a poor prognosis. In this study, we investigated the ARID1A-VIM/CDH1 signalling axis's role in colon cancer proliferation and migration. The differentially expressed genes in cells that might be controlled by ARID1A were discovered by a database screening for ARID1A knockout. qPCR was used to analyse ARID1A and EMT markers expression levels in colon cancer. We utilized siRNA RID1A to explore the influence of ARID1A silencing on EMT in CRC cells. The function of ARID1A in the colon was investigated utilizing the wound healing, transwell and CCK-8 WST- assays. The molecular mechanism by which ARID1A regulates VIM and CDH1 was elucidated using chip-qPCR. Numerous genes involved in EMT were dysregulated in the absence of ARID1A. VIM expression increased in cells lacking ARID1A expression and vice versa. Many COAD samples with high ARID1A mRNA expression had low VIM mRNA expression, despite the relevance. CDH1 gene was positively correlated with ARID1A. Moreover, siRNA-ARID1A-transfected cells accelerated cell migration and invasion and increased cell proliferation rate in vitro. Chip-qPCR analysis showed that ARID1A binds to the promoters of both genes and changes their expression in colon cancer. ARID1A inactivation is associated with VIM activation and CDH1 suppression, which might serve as crucial molecules influencing COAD prognosis, accelerate tumour progression, and shorten patients' survival time, and promote metastases of COAD. Thus, depletion of ARID1A can be therapeutically exploited by targeting downstream effects to improve cancer treatment-related outcomes.

DC-SIGN is previously focused on its physiologic and pathophysiologic roles in immune cells. Little is known about whether DC-SIGN is expressed in malignant epithelial cells and how DC-SIGN participates in tumor progression. Here we showed that DC-SIGN expression was increased in metastatic colorectal cancer (CRC) cell lines and patient tissues. The overall survival in CRC patients with positive DC-SIGN was remarkably reduced. Gain of DC-SIGN function facilitated the CRC metastases both in vitro and in vivo, and this effect was reversed by miR-185. DC-SIGN and Lyn interacted physically, and Lyn maintained the stability of DC-SIGN in cells. DC-SIGN activation recruited Lyn and p85 to form the DC-SIGN-Lyn-p85 complex, which promoted CRC metastasis by increasing PI3K/Akt/β-catenin signaling in tyrosine kinase Lyn-dependent manner. Furthermore, activation of DC-SIGN promoted the transcription of MMP-9 and VEGF by increasing PI3K/Akt/β-catenin signaling, and induced TCF1/LEF1-mediated suppression of miR-185. Our findings reveal the presence of the DC-SIGN–TCF1/LEF1–miR-185 loop in cancer cells with metastatic traits, implying that it may represent a new pathogenic mechanism of CRC metastasis. This character of the loop promises to provide new targets for blocking CRC invasive and metastatic activity.

A single molecule with multicolour luminescence, especially white emission, is crucial for developing luminescent materials, but it is arduous to be obtained. Herein, we proposed a facile method to fabricate an intriguing single molecule by uniting aggregation-induced emission (AIE) and stimuli-responsive aggregation-caused quenching (ACQ) fluorophores for continuous adjustment of multicolor luminescence. Such a method overcame the challenge and readily achieved a broad, continuous and distinguishable multicolour fluorescence by dual regulation (pH and water fraction) only. By simply tuning pH and water fraction, AIE, ACQ and FRET (fluorescence resonance energy transfer) effects were synergistically regulated, which enabled us to continuously produce over six luminescent colours including orange-red, orange, white, blue, cyan and green. Significantly, the quantum yield of white-light emission with Commission International de L’Eclairage (CIE) coordinates of (0.31, 0.29) could reach up to 12.2%. Furthermore, this unimolecular entity could be applied for multicolour gels and multichannel cell imaging with preferable stability, flexibility and versatility. Particularly, the innovative design concept of synergistically uniting AIE and a responsive ACQ chromophore paves a new way for multifunctional materials in colour-on-demand fields.

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related protein (DC-SIGNR) is a type II transmembrane protein that has been reported to bind to various pathogens and participate in immunoregulation and tumorigenesis. However, further research is required to investigate whether the level of DC-SIGNR and cervical cancer are associated. The present study aimed to explore the clinical diagnostic significance of DC-SIGNR in cervical cancer. Immunohistochemical staining of DC-SIGNR was performed in samples from 25 patients with early stage cervical cancer, 14 patients with cervical intraepithelial neoplasia (CIN) and cervical polyp samples from 15 individuals. DC-SIGNR expression in cervical cancer tissue was significantly higher compared with that in CIN and cervical polyp tissue (P=0.0184 and P=0.0236, respectively). However, there was no significant difference in DC-SIGNR expression between CIN and cervical polyp tissue (P=0.8103). Additionally, the serum DC-SIGNR levels in 84 cervical cancer patients and 69 healthy female individuals were measured using an ELISA. Serum (s)DC-SIGNR levels were significantly higher in cervical cancer patients compared with healthy female individuals (P

Background The molecular mechanisms of gastric cancer (GC) development are very complicated. Recent studies revealed that DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein (DC-SIGNR) is involved in colon cancer and GC biological processes. However, the exact roles of DC-SIGN in GC remain unrevealed. Methods DC-SIGN overexpression and knockdown experiments were performed by using DC-SIGN shRNA or DC-SIGN plasmid to investigate the biological roles of DC-SIGN in proliferation, cell cycle progression, migration and invasion of GC cells in vitro. Furthermore, the lncRNA profiles of SGC-7901 cells with control shRNA and DC-SIGN shRNA were generated by using microarray analysis. Mechanistically, the relationship between DC-SIGN, RP11-181G12.2 and the JAK2/STAT3 signaling pathway was then investigated using qRT-PCR and western blot assays. Additionally, we analyzed DC-SIGN and RP11-181G12.2 expression levels in GC specimens based on the Cancer Genome Atlas database. Results In this study, the results showed that DC-SIGN was highly expressed in GC cells and significantly correlated with advanced clinical stage and lymphatic metastasis. Downregulation of DC-SIGN significantly inhibited the proliferation, cell cycle progression, migration and invasion of GC cells in vitro. The reverse results could partly be seen with the upregulation of DC-SIGN. Mechanistically, knockdown of DC-SIGN inactivated the JAK2/STAT3 signaling pathway, and overexpression of DC-SIGN activated the JAK2/STAT3 signaling pathway. In addition, through LncPath microarray analysis, we identified a lncRNA, RP11-181G12.2, that was significantly upregulated after knockdown of DC-SIGN; this was also confirmed by qRT-PCR. Furthermore, RP11-181G12.2 knockdown enhanced DC-SIGN expression in GC cells, further activating the JAK2/STAT3 signaling pathway. In contrast, DC-SIGN overexpression suppressed RP11-181G12.2 expression. Conclusions Our study suggests that DC-SIGN might be involved in the progression of GC by regulating the JAK2/STAT3 signaling pathway and affecting lncRNA RP11-181G12.2 expression.

A Correction to this paper has been published: https://doi.org/10.1038/s41418-021-00736-9

Colorectal cancer (CRC) is among the most frequent causes of cancer-related deaths worldwide. Thus, there is a need for the development of new therapeutic approaches for the treatment of CRC. Accumulating evidence has revealed that niclosamide, an anthelminthic drug, exerts antitumor activity in several types of cancer, including colon cancer. However, the underlying molecular mechanisms responsible for the effects of this drug remain elusive. Previous studies have shown that the aberrant Notch signaling pathway contributes to the carcinogenesis of colon cancer. Herein, we examined the effects of niclosamide on the growth, migration and apoptosis of colon cancer cells, and the role of the Notch signaling pathway. By performing MTT, wound-healing and Transwell migration assays, we observed that niclosamide suppressed the growth and migration of colon cancer cells, and flow cytometry demonstrated that cell apoptosis was induced. This was associated with the decreased protein expression of Notch1, Notch2, Notch3 and Hey1, and the increased expression of the tumor suppressor microRNA (miR or miRNA)‑200 family members (miR‑200a, miR-200b, miR-200c, miR-141 and miR-429) that are typically downregulated in colon cancer. Collectively, these findings demonstrate that niclosamide potentially inhibits the progression of colon cancer by downregulating Notch signaling and by upregulating the miR-200 family members.

Background: Previous studies have reported that lncRNAs have acted as new players during tumorigenesis by gene regulation in the transcriptional and posttranscriptional levels. Metallothionein plays an important role in tumorigenesis and progression. It is mainly considered to be involved in the process of cell proliferation, oxidative stress and multidrug resistance. However, the potential involvement of metallothionein-related long noncoding RNAs (lncRNAs) in colon cancer remains poorly understood. Methods: Those MT1M-related lncRNAs were screened out by lncRNA microarray assay. Detection of lncRNA STEAP3-AS1 expression in colon cancer tissue and cell lines was conducted by qRT-PCR and bioinformatic analysis. MTT, transwell migration, wound-healing and cell-cycle assays were investigated for the biological properties of STEAP3-AS1 in vitro. Additionally, a xenograft model of human colon cancer was established for the tumor growth effect of STEAP3-AS1 in vivo. Furthermore, we disclosed its mechanism in colon cancer by qRT-PCR, Western blot, bioinformatics, etc. Findings: We found that MT1M affects the expression of lncRNA STEAP3-AS1. STEAP3-AS1, located in physical contiguity with STEAP3, was notably increased in colon cancer tissues and cells. In vitro assay, knockdown of STEAP3-AS1 could inhibit colon cancer cells proliferation, migration and arrest colon cancer cells at the G0-G1 phase. In tumorigenicity assay, STEAP3-AS1 knockdown could strongly inhibit tumor growth. Mechanistic investigations demonstrated that STEAP3-AS1 downregulation could increase the expression of cyclin dependent kinase inhibitor 1C (CDKN1C) by STEAP3 upregulation. Interpretation: Overall, we identify the underlying role of MT1M-related lncRNA STEAP3-AS1 in colon cancer progression, which provides a novel strategy for colon cancer therapy. Funding: This work was supported by grants from the Chinese National Science Foundation Projects (31470800, 81372669 and 31270867), the Science and Technology Planning Project of Liaoning province, China (2012225020), and the Project of Chinese Ministry of Health (W2012RQ23). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: All animal experimental procedures were conducted by the Institutional Animal Care and Use Committee of Dalian Medical University.

The development of multidrug resistance (MDR) has seriously impeded the efficacy of drug treatment of chronic myeloid leukemia (CML). Recent studies have indicated that S100 calcium-binding protein A8 (S100A8) is associated with the occurrence and development of MDR. Traditional Chinese medicine may provide drugs with the potential to be used as multidrug resistance reversal agents with low toxicity and multi-target characteristics. The present study selected K562/DOX cells, a CML drug-resistant cell line, as a research model, and aimed to examine whether curcumin was able to reverse the resistance to doxorubicin (DOX), and elucidate the underlying molecular mechanisms. An MTT cytotoxicity assay indicated that curcumin at 0.5-2 µM reversed DOX resistance with a reversal index of 1.3-9.3. Western blot analysis revealed that curcumin treatment caused a downregulation of the expression of P-glycoprotein (P-gp) and S100A8 in a dose- and time-dependent manner. To study the internal association between S100A8 and P-gp, and the S100A8 role in drug resistance reversal, an RNA knockdown assay was conducted; however, S100A8 did not regulate the expression of P-gp or vice versa. After inhibiting the expression of S100A8 with specific small interfering RNA (si-S100A8), the sensitivity of K562/DOX cells to DOX was enhanced. In addition, si-S100A8 did not increase the intracellular accumulation of DOX, but increased the intracellular free calcium ion content, and the expression and activity of apoptosis-associated proteins, thereby inducing apoptosis. In conclusion, the present study suggested that inhibition of S100A8 expression increased DOX-induced apoptosis, and curcumin acted independently on S100A8 and P-gp to exert its drug resistance reversal effects.

Here, we report a feasible approach to constructing well-defined POSS dendrimers with unique aggregation-induced emission (AIE) effects and pH-responsive properties, which were employed as sensitive fluorescent probes for trivalent metal cations and acid gases.

P2X7R is an ATP-gated cation channel that participates in cell proliferation and apoptosis. TCP-1 assists with the protein folding. According to our previous research, the P2X7R has a potential role in P388D1 lymphoid neoplasm cells dissemination to peripheral lymph nodes. In order to make a further exploration about the probable mechanism, the lymph nodes which metastasized by P2X7R-silenced P388D1 cells or non-silenced cells were analyzed by 2DE and a MALDI-TOF-based proteomics approach. In the 64 proteins which were differentially expressed between two groups, TCP-1 was found to be significantly decreased in P2X7R shRNA group compared to controls. This correlation was also found in subsequent experiments in vivo and in vitro. The positive correlation between P2X7R and TCP-1 was also proved in both lymphoma and benign lymphadenopathy tissues from patients. It indicates that TCP-1 may be a crucial downstream molecular of P2X7R and plays a novel role in lymphoid neoplasm metastasis.

Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein (DC-SIGNR) is a type II transmembrane protein which has been reported to bind a variety of pathogens as well as participate in immunoregulation. But the association between the level of DC-SIGNR and lung cancer is unknown. To investigate the clinical diagnostic significance of DC-SIGNR in lung cancer, we investigated serum DC-SIGNR levels in 173 lung cancer patients and 134 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Results showed that serum DC-SIGNR levels in lung cancer patients were lower than that in healthy controls (P = 0.0003). A cut-off value of 3.8998 ng/L for DC-SIGNR predicted the presence of lung cancer with 78.03 % sensitivity and 49.25 % specificity (area under the curve = 0.6212, P = 0.0003). Strikingly, serum DC-SIGNR levels were significantly higher in lung cancer patients with brain metastasis compared to those without metastasis (P = 0.0283). Moreover, the serum concentrations of DC-SIGNR in lung cancer patients also correlated significantly with serum natural killer cells percentage (P = 0.0017). In addition, immunohistochemistry assay demonstrated that the expression of DC-SIGNR in lung tissues of 31 lung cancer patients and 13 tuberculosis patients was significantly lower than that in 18 normal lung tissues (P = 0.0418, 0.0289), and there is no significant difference between tuberculosis tissues and lung cancer tissues (P = 0.2696). These results suggest that DC-SIGNR maybe a promising biological molecule that has the potential for clinical research of lung cancer, whereas its underlying roles are needed to be investigated in further studies. Electronic supplementary material The online version of this article (doi:10.1007/s11010-015-2465-4) contains supplementary material, which is available to authorized users.

The aims of the current study were to systematically analyze the regulation of the expression of NALP3 by the P2X7 receptor in P388D1 murine macrophage‑like cells, and to investigate the association between the P2X7 receptor and the NALP3 at the molecular level. Cell culture, RNA transfection, adenosine triphosphate (ATP)‑induced expression of NALP3, reverse transcription polymerase chain reaction and western blotting were used to explore the association between the P2X7 receptor and NALP3‑encoding gene in P388D1 murine macrophage‑like cells at the molecular level. The ATP‑activated P2X7 receptor can induce the upregulation of NALP3 expression at the gene and protein levels in P388D1 cells. These results demonstrated that the activation of P2X7 increases the expression levels of NALP3 in P388D1 murine macrophage‑like cells.

Purpose Compare and analyze the clinicopathological features and prognosis of 1315 patients with colorectal cancer located at different anatomical subsites. Methods A retrospective study was conducted to analyze the clinicopathological features and prognosis from 1315 patients with colorectal cancer who underwent surgery in the department of gastrointestinal surgery at the Second Affiliated Hospital of Dalian Medical University from January 2013 to January 2019. Among them, 287 patients were divided into the right-sided colon cancer (RCC) group; 329 patients were included into the left-sided colon cancer (LCC) group and the remaining 699 patients were assigned to the rectal cancer (RC) group. Clinicopathological features such as gender, age, pathological differentiation, neurovascular invasion, TNM stage, related tumor markers, maximum tumor diameter (MTD), median survival time and overall survival rate were extracted and analyzed. Results Patients in the RCC group had the oldest age of onset, highest positive rate of serum CA199 and greatest number of poorly differentiated adenocarcinomas among the three groups and significant statistical differences were found. The RC group had the highest positive rate of vascular invasion (42.9%) and the greatest number of patients in stage I and IV (19% and 3.9%, respectively). Besides, the number of patients with stage T1-T2 adenocarcinoma in RC group was also the highest among the three groups. There were no significant differences in gender, perineural invasion as well as serum levels of CEA, CA724 and CA242. The median survival time of RCC, LCC and RC were 72, 70 and 73 months, respectively, with significant inter-group differences (P = 0.049). Conclusion The age of onset of right-sided colon cancer is the oldest on average and poorly differentiated tumors accounted for the highest proportion. Besides, average maximum tumor diameter is the largest in right-sided colon cancer. In terms of median survival time, LCC is worse than RCC and RC. Colorectal cancer at different anatomical subsites has different epidemiological, clinicopathological features and prognosis. Fully understanding the clinicopathological features of colorectal cancer at different anatomical subsites is of certain guiding significance for the clinical diagnosis and treatment of colorectal cancer, and is conducive to individualized treatment and accurate treatment.

Aiming at the problem of impact ground pressure caused by the hard roof of goaf in coal mining face, the research on pre-cutting of hard coal seam roof by directional blasting was carried out. According to the principle of energy accumulation in directional blasting, a similar simulated experiment was designed on the basis of theoretical analysis of stress wave propagation law, crack development law and forced roof caving distance. The experimental results show that the roof is pre-cut by directional blasting, the integrity of the roof in front of the working face is reduced, effective pressure relief effect is obtained, the large area of overhanging roof in goaf is prevented, and the impact ground pressure disaster of the working face is relieved.

The present study aimed to compare the clinical outcomes of laparoscopic-assisted surgery versus open surgery for colorectal cancer and investigate the oncological safety and potential advantages and disadvantages of laparoscopic-assisted surgery for colorectal cancer. The medical records from a total of 160 patients who underwent surgery for colorectal cancer between January 2009 and January 2013 at The Second Hospital of Dalian Medical University (Dalian, China) were retrospectively analyzed. The patients who underwent laparoscopic-assisted surgery showed significant advantages due to the minimally invasive nature of the surgery compared with those who underwent open surgery, namely, less blood loss (P=0.002), shorter time to flatus (P

The C-type lectins DC-SIGN, DC-SIGNR and LSECtin are encoded by the lectin gene cluster on chromosome 19p13.3 and perform cell-adhesion and pathogen recognition functions on dendritic cells, liver cells and lymph node sinusoidal endothelial cells. DC-SIGN and DC-SIGNR share similar overall gene and protein molecule structures, and they exhibit high affinity for high-mannose carbohydrates. LSECtin, a Ca2+-dependent C-type lectin, interacts with mannose, NAcGlc and fucose. These lectins allow pathogen recognition (e.g., viruses, bacteria and allergens) and cell adhesion for dendritic and endothelial cells in different tissues, which may enhance the infection and facilitate the spread of those pathogens. A better understanding of these lectins may yield information about how pathogens are captured by particular cells and how they spread in different tissues. These studies would provide more detail about the physiopathological mechanisms of viral and bacterial infections and may also lead to new strategies to treat or prevent infections.

Colorectal cancer is one of the leading causes of cancer-related mortality, being the third most commonly diagnosed cancer among men and the second among women. Accumulating evidence regarding carbohydrate antigen (CA) demonstrated that tumor-associated antigens are clinically useful for the diagnosis, staging and monitoring of human gastrointestinal cancers, particularly colorectal cancer. There has been an extensive investigation for sensitive and specific markers of this disease. Currently, the gastrointestinal cancer-associated carbohydrate antigen 19-9 (CA19-9) is the most widely applied tumor marker in cancer diagnosis. Despite a similar etiology and cancer incidence rates, there are anatomical and clinical differences between colon and rectal cancer, as well as differences regarding tumor progression and adjuvant treatments. To investigate whether CA19-9 is differentially expressed between colon and rectal cancer, we conducted a differential analysis of serum CA19-9 levels among 227 cases of colorectal cancer, analyzing gender, age, Dukes’ stage and distant metastasis for human colon and rectal cancer as a single entity, separately and as matched pairs. We demonstrated that the serum CA19-9 levels in colorectal cancer were upregulated in advanced stages with distant metastasis. By contrast, the serum CA19-9 levels in colon cancer displayed a differential and upregulated behavior in advanced stages with distant metastasis. By analyzing as matched pairs, the upregulated serum CA19-9 levels in rectal cancer during the early stages without distant metastasis further supported our hypothesis that the expression of CA19-9 displays a site-specific differential behavior. The integrative analysis suggested a significant difference between human colon and rectal cancer, justifying individualized therapy for these two types of cancer.

Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein (DC-SIGNR), a type II integral membrane protein and a member of the C-type lectins, has been reported to bind various strains of HIV-1, HIV-2, and simian immunodeficiency virus. Serum DC-SIGNR is not currently available for the detection of non-Hodgkin lymphoma (NHL). Using an enzyme-linked immunosorbent assay (ELISA), we assessed the serum levels of DC-SIGNR in 70 cancer patients and 100 healthy controls. Additionally, using immunohistochemistry, we determined the expression of DC-SIGNR in the lymph nodes. Using the ELISA, low serum levels of DC-SIGNR were detected in the patients (median, 4.513 ng·L−1; range, 1.066–9.232 ng·L−1; p = 0.0003). Serum concentrations of DC-SIGNR correlated significantly with age (p = 0.0077) and lactic acid dehydrogenase (p = 0.0046) and β2-microglobulin (p = 0.0491) levels. However, we found no statistically significant correlation between serum DC-SIGNR levels and clinical data such as sex, Ann Arbor stage, B symptoms, and histologic subtypes. Moreover, NHL patients with a lower level of serum DC-SIGNR expression in lymphatic endothelial cells also showed negative immunostaining levels. These results suggest that DC-SIGNR is a biological molecule that may be potentially useful in NHL clinical settings.

Endostatin is an endogenous angiogenesis inhibitor whose specific functional site has not yet been determined. In the present experiment, 13 amino acids (LCIENSFMTSFSK) were selectively deleted from the C-terminal of endostatin and the resulting mutant endostatin was named EM13. To determine the effect of the C-terminal deletion on the biological activity of endostatin, EM13, wild-type endostatin and empty plasmid were transfected into H22 cells. After 48 h, the three types of transfected cells were harvested and injected into nude mice. The results demonstrated that there was no significant difference in tumor size, as determined by hematoxylin and eosin staining, between the EM13-transfected group and the endostatin and empty plasmid groups, although the nude mice that were injected with EM13-transfected H22 cells exhibited smaller tumors and lower density of blood vessels compared to those injected with endostatin- and empty plasmid-transfected H22 cells. The results suggested that the 13 amino acids of the C-terminal of endostatin do not play an important role in the tumorigenic potential of H22 cells. This experiment was unsuccessful in reproducing the results of several investigators. Therefore, the mechanism underlying the tumorigenesis of H22 cells remains to be elucidated.

Background Tumor metastasis is an essential cause of the poor prognosis of colon cancer. DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DC-SIGNR, has been demonstrated to participate in colon cancer liver metastasis. Due to the similarities in the expression pattern and structure of the two proteins, we speculated that DC-SIGNR could also be involved in this process. Methods Colon cancer cells were treated with the DC-SIGNR protein or control IgG, after which cell migration, invasion, and morphology were assayed. Xenograft mouse models were used to determine the role of DC-SIGNR in colon cancer liver metastasis in vivo. In addition, a human gene expression array was used to detect differential gene expression in colon cancer cells stimulated with the DC-SIGNR protein. The serum level of DC-SIGNR was examined in colon cancer patients by ELISA, and the significance of DC-SIGNR was determined. Results In our research, we investigated whether DC-SIGNR promotes colon cancer cell adhesion, migration, and invasion. Knocking down mouse DC-SIGNR decreased the liver metastatic potency of colon cancer cells and increased survival time. Expressing human DC-SIGNR enhanced colon cancer liver metastasis. Furthermore, DC-SIGNR conferred metastatic capability on cancer cells by upregulating various metallothionein isoforms. To validate the above results, we also found that the serum DC-SIGNR level was statistically higher in colon cancer patients with liver metastasis compared with those without metastasis. Conclusions These results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0383-x) contains supplementary material, which is available to authorized users.

The table shows the clinical data of the colon cancer patients in DC-SIGNR ELISA study. (DOCX 24 kb)

The table exhibits the primer sequences used for quantitative real-time PCR. (DOCX 13 kb)

Table S4. Target sequences for DC-SIGNR knockdown and overexpression, for HNRNPKP2 siRNA, for STAT5A siRNA and overexpression (DOCX 13 kb)

Table S5. List of target genes regulated by DC-SIGNR (DOCX 12 kb)

Table S3. The names of the genes and sequences of primers (DOCX 22 kb)

Table S2. List of lncRNAs regulated by DC-SIGNR (DOC 114 kb)

We demonstrate a facile approach to constructing aggregation induced emission (AIE) fluorescent vesicles assembled using a PEG–POSS–(TPE)7 polymer. The narrow wall thickness provides an ideal confined space for creating fluorescence resonance energy transfer (FRET) systems between TPE donors and encapsulated FITC or DOX acceptors.

Sodium butyrate (NaBu) is a short-chain fatty acid (SCFA), which has been proposed as a potential anticancer agent. Apoptosis-associated speck-like protein (ASC) is a pro-apoptotic signaling factor that is subjected to epigenetic silencing in human cancers. Modulation by the aberrant methylation of CpG islands of ASC is a well-characterized epigenetic mechanism, and the methylation-induced silencing of ASC has been observed in several types of tumors. NaBu induces cell cycle arrest, markers of cell differentiation and apoptosis in colon cancer. NaBu promotes transcriptional activation by relaxing the DNA conformation and displays anti-proliferative and differentiating activity in a wide variety of cancers. Thus, we used NaBu to investigate the relationship between the status of cell proliferation and the re-expression of ASC in colon carcinoma LS174T cells. Our experiments determined ASC re-expression at the protein level using western blotting. In addition, we used reverse transcription-polymerase chain reaction to detect the expression levels of ASC mRNA and an MTT assay to detect the inhibitory rate of cell growth. The apoptosis rate was also detected for further validation of the re-expression of ASC. The results showed that ASC re-expression was significantly increased in the LS174 cells following NaBu treatment in a time- and dose-dependent manner. The expression of ASC also induced the apoptosis of LS174T cells. These results suggest that NaBu plays a role in the reactivation of ASC expression and that the latter promotes the apoptosis of LS174T cells.

Background β-elemene, extracted from ginger plant Rhizoma zeodaria exerts anticancer effect in a variety of tumor diseases including liver cancer by inhibiting tumor cells growth or promoting apoptotic cell death. c-Met is a receptor tyrosine kinase was widely found overexpressed in neoplastic tissues and participates in the cell proliferation, migration, invasion, survival. To explore the primary mechanism of action of β-elemene in cancer, we identified whether there are some relations between the expression level of c-Met and anticancer actions of β-elemene. Methods The presence of c-Met in the H22 cells was confirmed by RT-PCR, Western blot and immunofluorescence analysis. In vitro, H22 cells were treated with β-elemene and the expression of c-Met was measured by RT-PCR, immunofluorescence analysis and Western blot. In vivo, an experimental H22 hepatocellular carcinoma (HCC) xenograft transplantation model, treating with different dose-dependent β-elemene, the expression of c-Met was measured by RT-PCR, Immunohistochemical staining assay. Results c-Met more highly expressed in H22 cells than that in murine liver cells; after treating with β-elemene for 48 h, the expression of c-met decreased markedly in H22 cells; furthermore, we showed that high-dosage groups significantly reduced tumor weights and down regulated the expression of c-Met compared to control groups in H22 transplanted tumor. Conclusions Down-regulation of c-Met expression by β-elemene induces growth inhibition in murine hepatocellular carcinoma.

The P2X7 receptor (P2X7R) is a nucleotide receptor expressed predominantly on hemopoietic, bone, and epithelial cells. The P2X7R can be activated by extracellular ATP and induces the influx of calcium, releases cytokines, and participates in cell proliferation and apoptosis. CD44 is an adhesion molecule. The effects of CD44 include cell–cell and cell–matrix adhesion interactions, lymphocyte activation, and cell migration. Many studies have shown that P2X7R and CD44 play important roles in hematological malignancies, but no study exists regarding the relationship between P2X7R and CD44. In the present study, we characterized P388D1 cells for the surface expression of CD44 and analyzed ATP-induced shedding. The data showed that P388D1 cells express CD44. Incubation of P388D1 cells with ATP induced a rapid loss of CD44 from the P388D1 cell surface. In addition, using a receptor inhibitor and P2X7R short hairpin RNA, we showed that the loss of CD44 is mediated via the P2X7R. Finally, we demonstrated that activation of P2X7R by ATP induces CD44 shedding. Copyright © 2011 John Wiley & Sons, Ltd.

Apoptosis-associated speck-like protein (ASC) is a bipartite adaptor molecule that participates in inflammation and apoptosis. ASC silencing has been observed in a significant proportion of human cancers. Here, we examined the role of ASC overexpression in the metastasis of the P388D1 murine lymphoma cell line to the liver, lung, spleen and kidney. First, we determined that the P388D1 cells express ASC. Then, ASC overexpression in P388D1 was achieved by transfecting pEGFP-ASC-C2 into the P388D1 cells. Furthermore, after the ASC-overexpressing P388D1 cells were injected into DBA/2 mice through the vena caudalis, their metastasis to the lung and the liver was significantly reduced in the pEGFP-ASC-C2-transfected group. These data indicate that ASC overexpression affects the in vivo metastatic properties of P388D1 cells. Copyright © 2011 John Wiley & Sons, Ltd.

The P2X 7 R (P2X 7 receptor) is an ATP-gated cation channel expressed in normal cells that participates in both cell proliferation and apoptosis. Here, we have confirmed P2X 7 R expression on murine P388D1 lymphoid neoplasm cells. In addition, ATP-stimulated P2X 7 R expression was found to trigger increased intracellular calcium flux. Furthermore, silencing with short hairpin RNA and blocking with P2X 7 R antibody significantly reduced the metastasis of P388D1 cells to lymph nodes. These results indicate that inhibition of the expression and function of P2X 7 R attenuates the metastatic ability of murine lymphoid neoplasm cell line P388D1, which represents a new potential target for anti-metastatic therapy.

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147), which is a plasma membrane glycoprotein enriched on the surface of many malignant tumors promotes adhesion, invasion and metastasis of tumor cells. In addition, tumor-associated CD147 also induces vascular endothelial growth factors (VEGFs) expression. To investigate the possible role of CD147 in the mouse hepatocarcinoma cell line Hca-F with highly metastatic potential in the lymph nodes, we used an RNA interference (RNAi) approach to silence CD147 expression. The results showed that CD147 depletion in Hca-F cells resulted in the significantly decreased expression of matrix metalloproteinase-11 (MMP-11), VEGF-A at both mRNA and protein levels. The reduced CD147 expression also attenuated the invasive, adhesive, metastatic ability of Hca-F cells to lymph nodes both in vitro and in vivo. Our current findings reveal that the tumor biological marker CD147 functionally mediates MMP-11, VEGF-A expression and tumor lymphatic metastasis.

Only 3–5% of gastrointestinal stromal tumors (GISTs) are located in the duodenum. They are associated with an increased risk of fatal gastrointestinal bleeding, which is a primary manifestation. A small GIST (less than 2 cm in size) is easily confused with a duodenal papilla. In the 2 cases presented in this study, endoscopic examination alone resulted in a misdiagnoses of hemobilia. To the best of our knowledge, this is the first case report of this type in the literature. Patient 1 is a 66-year-old male who was admitted to The Second Affiliated Hospital of Dalian Medical University with syncope. Emergent upper gastrointestinal endoscopy identified bleeding from what appeared to be a duodenal papilla, and the patient was diagnosed with hemobilia. However, the angiography did not support this result. To save the patient’s life, an exploratory laparotomy was conducted. We identified a small tumor in the descending part of the duodenum and a wedge resection was successfully conducted. The final diagnosis was duodenal GIST with no further risk to the patient. Patient 2 is a 71-year-old female who was admitted to the hospital diagnosed with hemobilia. The patient underwent a barium swallow examination and a contrast-enhanced computed tomography (CT) scan, in which a tumor on the descending part of the duodenum was identified. Patient 2 also underwent a wedge resection. The final diagnosis was duodenal GIST with no further risk to the patient. Gastroscopy may be a useful procedure for duodenal GIST diagnosis; however, the endoscopic findings may be confused with hemobilia when the tumor diameter is less than 2 cm in size and heavily accompanied with blood clots. A barium swallow examination and contrast-enhanced CT may prevent a misdiagnosis of hemobilia.

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), a member of the C-type lectin superfamily, has been reported to bind to various pathogens and several tumor cells and to participate in immunoregulation. It is still unclear whether there is a significant association between the level of DC-SIGN and non-Hodgkin lymphoma (NHL). To investigate the clinical diagnostic significance of DC-SIGN in NHL, we conducted a study with 52 NHL patients and 104 healthy individuals. Enzyme-linked immunosorbent assay and tissue microarray technology were utilized for the analysis. The serum sDC-SIGN levels in the NHL patients were significantly lower than those in the healthy controls (P = 0.0019). A cutoff value of 1.499 µg/ml for sDC-SIGN predicted the presence of NHL with 78.85 % sensitivity and 53.85 % specificity [area under the curve (AUC) = 0.6531, P = 0.0019]. The serum sDC-SIGN levels in NHL patients were also significantly correlated with β2-microglobulin (P = 0.0062). Moreover, tissue microarray analysis demonstrated that the expression of DC-SIGN in the lymph nodes or tissues of 96 NHL patients was significantly lower than that in 18 normal lymph nodes (P

Despite recent progress in the identification of genetic and molecular alternations in colorectal carcinoma, the precise molecular pathogenesis remains unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization domain-like receptor family of proteins that are key organization proteins in the inflammasome. It is reported that NALP1 plays a central role in cell apoptosis, pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2-deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined the expression of NALP1 in human normal and cancerous colon tissues using tissue microarray, western blot and quantitative real-time PCR and we measured the expression of NALP1 in three kinds of colon cancer cell lines and animal models before and after treatment with DAC. Furthermore, we examined the treatment effects of DAC on colon cancer in our animal model. Our data indicate that NALP1 is expressed low in human colorectal tumoral tissues relative to paratumoral tissues and was associated with the survival and tumor metastasis of patients. The expression of NALP1 increased after treatment with DAC both in vitro and in vivo. Furthermore, DAC suppressed the growth of colon cancer and increased lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.

The aim of the present study was to investigate the levels of the serum tumor biomarker carcinoembryonic antigen (CEA) in patients with carcinoma of the colon and rectum in different clinical stages. Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer worldwide and previous studies have reported rapidly updated therapeutic regimes. While the majority of studies focus on CRC as a single entity, certain studies distinguish colon cancer (CC) from rectal cancer (RC), as there is a hypothesis stating that CC and RC are two naturally different entities. CEA is reported to be an important tumor-associated antigen overexpressed in CRC, which is routinely detected as a significant indicator of CRC. Our study aimed to identify potential differences in the expression of CEA between CC and RC, which may, to some degree, reflect the natural differences between the two. We investigated 240 CRC cases between July, 2010 and December, 2012 from The First and Second Affiliated Hospitals of Dalian Medical University, including 117 CC and 123 RC patients with tumors classified by Duke’s staging as A-D. The serum CEA level was measured preoperatively by radioimmunoassays as a routinely used auxiliary indicator. The expression of CEA differed between CC and RC, with the former exhibiting variation among the four stages, whereas no variation was observed in RC. In addition, there were differences between CC and RC regarding the CEA level in stage C and D. Furthermore, the CEA level in stage C of CC was significantly lower compared to that in any other stage. In conclusion, the intrinsic distribution of the CEA level between CC and RC suggests that CC and RC may be two naturally different entities; the significantly low CEA level in stage C of CC indicates that stage C may be crucial in the evolution of CC.