NDRG2 acts as a negative regulator of the progression of small-cell lung cancer through the modulation of the PTEN-AKT-mTOR signalling cascade.

N-myc downstream-regulated gene 2 (NDRG2) has been recognised as a negative regulator of the progression of numerous tumours, yet its specific role in small-cell lung carcinoma (SCLC) is not fully understood. The purpose of the current study was to investigate the biological role and mechanism of NDRG2 in SCLC. Initial investigation using the Gene Expression Omnibus (GEO) dataset revealed marked downregulation of NDRG2 transcripts in SCLC. The decreased abundance of NDRG2 in SCLC was verified by examining clinical specimens. Increasing NDRG2 expression in SCLC cell lines caused significant changes in cell proliferation, cell cycle progression, colony formation, and chemosensitivity. NDRG2 overexpression decreased the levels of phosphorylated PTEN, AKT and mTOR. In PTEN-depleted SCLC cells, the upregulation of NDRG2 did not result in any noticeable impact on AKT or mTOR activation. Additionally, the reactivation of AKT reversed the antitumour effects of NDRG2 in SCLC cells. Notably, increasing NDRG2 expression retarded the growth of SCLC cell-derived xenografts in vivo. In conclusion, NDRG2 serves as an inhibitor of SCLC, and its cancer-inhibiting effects are achieved through the suppression of AKT/mTOR via the activation of PTEN. This work suggests that NDRG2 is a potential druggable target for SCLC treatment.

Zinc finger protein 367 exerts a cancer-promoting role in small cell lung cancer by influencing the CIT/LATS2/YAP signaling cascade.

A remarkable cancer-related role of zinc finger protein 367 (ZNF367) has been demonstrated in multiple malignancies. However, whether ZNF367 has a role in small-cell lung cancer (SCLC) remains unexplored. The purpose of this work was to explore the potential role and mechanism of ZNF367 in SCLC. In silico analysis using the Gene Expression Omnibus (GEO) dataset revealed high levels of the ZNF367 transcript in SCLC. Examination of clinical tissues confirmed the significant abundance of ZNF367 in SCLC tissues compared with adjacent non-malignant tissues. The genetic depletion of ZNF367 in SCLC cells led to remarkable alterations in cell proliferation, the cell cycle, colony formation and chemosensitivity. Mechanistically, ZNF367 was shown to regulate the activation of yes-associated protein (YAP) associated with the up-regulation of phosphorylated large tumour suppressor kinase 2 (LATS2). Further investigation revealed that ZNF367 affected the LATS2-YAP cascade by regulating the expression of citron kinase (CIT). Re-expression of constitutively active YAP diminished the tumour-inhibiting function of ZNF367 depletion. Xenograft experiments confirmed the tumour-inhibiting effect of ZNF367 depletion in vivo. In summary, our results demonstrate that the inhibition of ZNF367 displays anticancer effects in SCLC by inhibiting YAP activation, suggesting it as a potential druggable oncogenic target.

The high-risk features and effect of postoperative radiotherapy on survival for patients with surgically treated stage IIIA-N2 non-small cell lung cancer.

OBJECTIVES: Although postoperative radiotherapy (PORT) could reduce the incidence of local recurrence in patients with IIIA-N2 non-small cell lung cancer (NSCLC), the role of PORT on survival in patients with surgically treated stage IIIA-N2 NSCLC remains controversial. Therefore, this study was designed to evaluate the effect of PORT on survival for patients with surgically treated stage IIIA-N2 NSCLC. MATERIALS AND METHODS: This study population was chosen from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) and cancer special survival (CSS) outcomes. To balance baseline characteristics between the non-PORT group and PORT group, propensity score matching (PSM) with 1:1 propensity nearest-neighbor match by 0.001 matching tolerance was conducted by R software. Furthermore, a Kaplan-Meier curve was used to visualize the OS and CSS between the PORT group and non-PORT group survival probability. RESULTS: Of all evaluated cases, 4511 with IIIA-N2 NSCLC were eligible for inclusion, of which 1920 were enrolled into the PORT group. On univariate analysis and multivariate analysis, sex, age, year of diagnosis, race, histologic type, T stage, PORT, use of chemotherapy, and positive regional nodes were significantly associated with OS and CSS in IIIA-N2 NSCLC (P < 0.05). However, PORT was not significantly associated with OS (univariate HR = 0.92, 95%CI 0.85-0.99, P = 0.02; multivariate HR = 1.01, 95%CI 0.93-1.08, P = 0.91) and CSS (univariate HR = 0.92, 95%CI 0.85-1.01, P = 0.06; multivariate HR = 1.103 95%CI 0.94-1.12, P = 0.56) in IIIA-N2 NSCLC. Meanwhile, after PSM, neither OS nor CSS did differ significantly between the non-PORT group and PORT group (OS HR = 1.08, 95%CI 0.98-1.19, P = 0.12; CSS HR = 1.10, 95%CI 0.99-1.23, P = 0.07). CONCLUSION: PORT did not contribute to a survival benefit in patients with surgically treated stage IIIA-N2 NSCLC.

CDX2 inhibits epithelial-mesenchymal transition in colorectal cancer by modulation of Snail expression and ß-catenin stabilisation via transactivation of PTEN expression.

BACKGROUND: Emerging evidence suggests the involvement of caudal-related homoeobox transcription factor 2 (CDX2) in tumorigenesis of various cancers. Although CDX2 functions in cancer invasion and metastasis, fewer studies focus on the role of CDX2 during the induction of epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC). METHODS: Immunohistochemical analysis of CDX2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of CDX2 in the invasion and metastasis of CRC. RESULTS: CDX2 was downregulated in CRC tissues and reduced CDX2 correlated with poor prognosis. Knockdown of CDX2 promoted colon cancer cell invasion in vitro and facilitated liver metastasis in vivo with inducing EMT phenotypes. Further investigation indicated that CDX2 retarded Akt and GSK-3ß phosphorylation, and thereby diminished Snail expression, ß-catenin stabilisation and nuclear translocation. The depletion of ß-catenin neutralised the regulation of Slug and ZEB1 by CDX2 knockdown. Mechanistically, CDX2 antagonised PI3K/Akt activity in CRC by modulating PTEN expression. CDX2 directly bound to the promoter of PTEN and transactivated its expression. CONCLUSIONS: Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and ß-catenin stabilisation via transactivation of PTEN expression.

GW4064 enhances the chemosensitivity of colorectal cancer to oxaliplatin by inducing pyroptosis.

Repeated and long-term oxaliplatin therapy leads to drug resistance and severe adverse events, which limit its clinical use. These difficulties highlight the importance of identifying potent and specific drug combinations to enhance the antitumor effects of oxaliplatin. The farnesoid X receptor (FXR) deficiency in colorectal cancer (CRC) suggests that restoring FXR function might be a promising strategy for CRC treatment. A drug combination study showed that the GW4064 acted synergistically with oxaliplatin in colon cancer cells. The combination of oxaliplatin plus GW4064 inhibited cell growth and colony formation, induced apoptosis and pyroptosis in vitro, and slowed tumor growth in vivo. Mechanistically, GW4064 enhanced the chemosensitivity of cells to oxaliplatin by inducing BAX/caspase-3/GSDME-mediated pyroptosis. Furthermore, the combination of oxaliplatin and GW4064 synergistically inhibited STAT3 signaling by restoring SHP expression. Our study revealed that GW4064 could enhance the antitumor effects of oxaliplatin against CRC, which provides a novel therapeutic strategy based on a combinational approach for CRC treatment.

Farnesoid X receptor activation induces antitumour activity in colorectal cancer by suppressing JAK2/STAT3 signalling via transactivation of SOCS3 gene.

Farnesoid X receptor (FXR, encoded by NR1H4), a bile acid-activated nuclear receptor, is widely implicated in human tumorigenesis. The FXR agonist obeticholic acid (OCA) has preliminarily displayed tumour suppressor potential. However, the anticancer effects of this agent on colorectal cancer (CRC) remain unclear. In this study, the treatment of colon cancer cells with OCA inhibited cell proliferation and invasion in vitro, retarded tumour growth in vivo and prevented the G0 /G1 to S phase transition. Moreover, the expression of active caspase-3, p21 and E-cadherin was up-regulated and the expression of cyclin D1, c-Myc, vimentin, N-cadherin and MMP9 was down-regulated in OCA-treated colon cancer cells. Mechanistic studies indicated that OCA treatment suppressed the activity of JAK2/STAT3 pathway by up-regulating SOCS3 expression. Colivelin, an agonist of JAK2/STAT3 pathway, antagonized the tumour-suppressive effect of OCA on colon cancer cells. Dual-luciferase reporter and quantitative chromatin immunoprecipitation (qChIP) assays further confirmed that OCA promoted SOCS3 transcription by enhancing the binding of FXR to the FXRE/IR9 of the SOCS3 promoter. In conclusion, our study demonstrates that targeting FXR and improving its function might be a promising strategy for CRC treatment.

The role of surgery in patients aged 85 years or older with resectable gastric cancer: a propensity score matching analysis of the SEER database.

Introduction: An increasing number of newly diagnosed resectable gastric cancer (GC) patients are over 85 years of age. However, studies on surgical treatment in these patients are limited. This study aimed to explore the prognosis of a large sample of the oldest old GC patients receiving surgery.Methods: A total of 2914 oldest old patients with stage I-III GC were included in the linked Surveillance, Epidemiology, and End Results (SEER) database from 2006 to 2015. Based on their treatment, we assigned these patients to the surgery and no surgery groups. We used propensity score matching (1:1) to balance the baseline characteristics. The Kaplan-Meier method was used for the survival analysis. Multivariate Cox regression analysis was used to analyse the independent risk factors.Results: After propensity score matching, the median overall survival (OS) times in the surgery and no surgery groups were 24.0 (95% CI: 20.3-27.7) and 4.0 (95% CI: 3.5-4.5) months, respectively (p < .01). Age, sex, stage, histological type, and treatment with surgery and chemotherapy were independent risk factors for OS in the oldest old patients with GC. In total, 19% of the oldest old patients with GC died from causes unrelated to cancer.Conclusions: The current large-scale study demonstrated that the oldest old patients with stage I-III GC could benefit from elective surgery.

Design, synthesis and antiproliferative evaluation of tetrahydro-ß-carboline histone deacetylase inhibitors bearing an aliphatic chain linker.

The use of histone deacetylase inhibitors (HDACis) is an effective approach for cancer treatment. In this work, a series of hydroxamic acid-based HDACis with a tetrahydro-ß-carboline core and aliphatic linker have been designed and synthesized. The optimal compound 13d potently inhibited HDAC1 and showed good antiproliferative activity against different tumor cell lines in vitro. Molecular docking of 13d was conducted to rationalize the high binding affinity for HDAC1. Therefore, this work provides a new structure design for HDAC inhibitors and also offers a promising treatment for solid tumors.

A novel mitochondrial metabolism-related gene signature for predicting the prognosis of oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide. Due to the important role of mitochondrial metabolism in cancer progression, a clinical prognostic model based on mitochondrial metabolism and clinical features was constructed in this study to predict the prognosis of ESCC. Firstly, the mitochondrial metabolism scores (MMs) were calculated based on 152 mitochondrial metabolism-related genes (MMRGs) by single sample gene set enrichment analysis (ssGSEA). Subsequently, univariate Cox regression and LASSO algorithm were used to identify prognosis-associated MMRG and risk-stratify patients. Functional enrichment, interaction network and immune-related analyses were performed to explore the features differences in patients at different risks. Finally, a prognostic nomogram incorporating clinical factors was constructed to assess the prognosis of ESCC. Our results found there were differences in clinical features between the MMs-high group and the MMs-low group in the TCGA-ESCC dataset (P<0.05). Afterwards, we identified 6 MMRGs (COX10, ACADVL, IDH3B, AKR1A1, LIAS, and NDUFB8) signature that could accurately distinguish high-risk and low-risk ESCC patients. A predictive nomogram that combined the 6 MMRGs with sex and N stage to predict the prognosis of ESCC was constructed, and the areas under the receiver operating characteristic (ROC) curve at 1, 2 and 3 years were 0.948, 0.927 and 0.848, respectively. Finally, we found that COX10, one of 6 MMRGs, could inhibit the malignant progression of ESCC in vitro. In summary, we constructed a clinical prognosis model based on 6 MMRGs and clinical features which can accurately predict the prognosis of ESCC patients.

Nebulized inhalation of LPAE-HDAC10 inhibits acetylation-mediated ROS/NF-κB pathway for silicosis treatment.

Silicosis is a serious silica-induced respiratory disease for which there is currently no effective treatment. Irreversible pulmonary fibrosis caused by persistent inflammation is the main feature of silicosis. As an underlying mechanism, acetylation regulated by histone deacetylases (HDACs) are believed to be closely associated with persistent inflammation and pulmonary fibrosis. However, details of the mechanisms associated with the regulation of acetylated modification in silicosis have yet to be sufficiently established. Furthermore, studies on the efficient delivery of DNA to lung tissues by nebulized inhalation for the treatment of silicosis are limited. In this study, we established a mouse model of silicosis successfully. Differentially expressed genes (DEGs) between the lung tissues of silicosis and control mice were identified based on transcriptomic analysis, and HDAC10 was the only DEG among the HDACs. Acetylomic and combined acetylomic/proteomic analysis were performed and found that the differentially expressed acetylated proteins have diverse biological functions, among which 12 proteins were identified as the main targets of HDAC10. Subsequently, HDAC10 expression levels were confirmed to increase following nebulized inhalation of linear poly(ß-amino ester) (LPAE)-HDAC10 nanocomplexes. The levels of oxidative stress, the phosphorylation of IKKß, IκBα and p65, as well as inflammation were inhibited by HDAC10. Pulmonary fibrosis, and lung function in silicosis showed significant improvements in response to the upregulation of HDAC10. Similar results were obtained for the silica-treated macrophages in vitro. In conclusion, HDAC10 was identified as the main mediator of acetylation in silicosis. Nebulized inhalation of LPAE-HDAC10 nanocomplexes was confirmed to be a promising treatment option for silicosis. The ROS/NF-κB pathway was identified as an essential signaling pathway through which HDAC10 attenuates oxidative stress, inflammation, and pulmonary fibrosis in silicosis. This study provides a new theoretical basis for the treatment of silicosis.

BMP2 inhibits cell proliferation by downregulating EZH2 in gastric cancer.

Gastric cancer is among the most common gastrointestinal malignancies. Recent studies have suggested that bone morphogenetic protein-2 (BMP2) is related to the development and progression of various cancers. Meanwhile, evidence suggests that BMP2 might lead to epigenetic changes in gastric cancer. Thus, we investigated whether BMP2 plays a role in the development of gastric cancer via epigenetic regulation. Cell viability, colony formation, and cell cycle assays were performed to assess the effect of recombinant human BMP2 (rhBMP2) in gastric cancer cells. LDN-193189 and Noggins were used as antagonists of the canonical BMP-SMAD signaling pathway. The protein levels were determined using a western blot analysis. Lentiviral vectors with EZH2 shRNA or EZH2 overexpression were used to mediate the role of EZH2 and the relationship between BMP2 and EZH2 in gastric cancer. We found that rhBMP2 inhibits cell proliferation by arresting the cell cycle in HGC-27 and SNU-216 gastric cancer cells. Neither LDN-193189 nor Noggins, antagonists of the canonical BMP-SMAD signaling pathway, can reverse the effect of rhBMP2 on gastric cancer. Molecularly, rhBMP2 downregulates the expression of EZH2 and H3K27me3, leading to increases in P16 and P21 and decreases in CDK2, CDK4, and CDK6. Altogether, in this study, we demonstrate that BMP2 serves as a tumor suppressor in gastric cancer cells by downregulating EZH2 and H3K27me3 through the non-SMAD BMP pathway, suggesting that BMP2 might be a new therapeutic target for gastric cancer treatment. Abbreviations: BMP: bone morphogenetic protein; TGF-ß: transforming growth factor-beta; EZH2: enhancer of zeste homolog 2; H3K27me3: trimethylation histone H3 lysine 27; HRECs: human retinal endothelial cells; PcG: polycomb group; PRC: polycomb repressive complexes.

A novel chromatin regulator signature predicts the prognosis, clinical features and immunotherapy of colon cancer.

Aim: To elucidate the potential function and prognostic value of chromatin regulators (CRs) in colon cancer. Materials & methods: A comprehensive analysis of CR RNA expression data from public databases was conducted. Results: The authors successfully established and validated a 17 CR-based signature using public databases. Ten CRs of the signature were eventually verified at the protein level using the Human Protein Atlas database. Functional enrichment showed that CRs were significantly enriched in cancer-related pathways. This signature was remarkably relevant to immune cell infiltration, immune checkpoints, tumor immune dysfunction and exclusion (TIDE) score and drug sensitivity. Conclusion: The authors identified a novel, reliable prognostic signature for colon cancer. The study provided new insights into the function of CRs and has important clinical implications for immunotherapy for colon cancer.

DFNA5 inhibits colorectal cancer proliferation by suppressing the mTORC1/2 signaling pathways via upregulation of DEPTOR.

The human deafness, autosomal dominant 5 gene (DFNA5), a newly discovered executor of pyroptosis, has been strongly implicated in the tumorigenesis of several human cancers. However, an understanding of the functional role of DFNA5 in the development and progression of colorectal cancer (CRC) is limited. In this study, we demonstrated that DFNA5 was downregulated in CRC tissues. Ectopic expression of DFNA5 inhibited tumor cell growth in vitro, retarded tumor formation in vivo, and blocked a cell-cycle transition from the G0/G1 to the S phase, whereas a DFNA5 knockdown promoted cell proliferation. Western blotting showed that the levels of cell cycle-related proteins, including cyclin D1, cyclin E, CDK2, and p21, were accordingly altered upon DFNA5 overexpression or DFNA5 knockdown. Mechanistic studies indicated that DFNA5 exerted its tumor suppressor functions by antagonizing mTORC1/2 signaling via upregulation of DEPTOR. In addition, blockage of mTORC1/2 signaling by Torin-1 abolished the accelerative proliferation by DFNA5 knockdown. In conclusion, these results indicated that DFNA5 inhibits the proliferation and tumor formation of colon cancer cells by suppressing mTORC1/2 signaling.

Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role.

The complex interaction between tumor-associated macrophages (TAMs) and tumor cells through several soluble factors and signaling is essential for colorectal cancer (CRC) progression. However, the molecular mechanism involved remains elusive. In this study, we demonstrated that MMP1 derived from TAMs markedly facilitated colon cancer cell proliferation via accelerating cell cycle transition from G0/G1 to S and G2/M phase. Moreover, exogenous MMP1 activated cdc25a/CDK4-cyclin D1 and p21/cdc2-cyclin B1 complexes through altering c-Myc and ETV4. Mechanistic studies indicated that inhibition of PAR1 or blockage of MAPK/Erk signaling eliminated the proliferation induced by exogenous MMP1 in vitro and in vivo. In addition, ETV4 could bind to the promoter of MMP1 and activate MMP1 transcription, which confirmed the MMP1/ETV4/MMP1 positive feedback. Altogether, our study identified a cytokine paracrine manner between colon cancer cells and TAMs. MMP1/PAR1/Erk1/2/ETV4 positive feedback loop may represent to be a therapeutic target and prognostic marker in CRC.

Multilevel regulation of Wnt signaling by Zic2 in colon cancer due to mutation of ß-catenin.

Zinc-finger of the cerebellum 2 (Zic2) is widely implicated in cancers, but the role of Zic2 in tumorigenesis is bilateral. A recent study indicated that Zic2 could render colon cancer cells more resistant to low glucose-induced apoptosis. However, the functional roles of Zic2 in colon cancer and the underlying molecular mechanism remain elusive. Herein, we demonstrated that Zic2 was highly expressed in colon cancer tissues and correlated with poor survival. Knockdown of Zic2 inhibited colon cancer cell growth, arrested the cell cycle transition from G0/G1 to S phase, and suppressed tumor sphere formation in vitro; in addition, silencing Zic2 retarded xenograft tumor formation in vivo. Consistently, ectopic expression of Zic2 had the opposite effects. Mechanistically, Zic2 executed its oncogenic role in colon cancer by enhancing Wnt/ß-catenin signaling. Zic2 directly binds to the promoter of Axin2 and transcriptionally represses Axin2 expression and subsequently promotes the accumulation and nuclear translocation of ß-catenin. Meanwhile, Zic2 could activate Wnt signaling by interacting with ß-catenin. Intriguingly, in HCT116 cells with intrinsic Ser45 mutation of ß-catenin, which blocks the degradation-related phosphorylation of ß-catenin by CK1, modified Zic2 expression did not affect the protein level of ß-catenin. Altogether, our findings uncover a novel multilevel mechanism for the oncogenic activity of Zic2 in colon cancer and suggest Zic2 as a potential therapeutic target for colon cancer patients.

Knockdown of MMP­1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c­myc signaling pathway and EMT.

The present study aimed to investigate the role of matrix metalloproteinase­1 (MMP­1) in the development of colorectal cancer and reveal the mechanism underlying this progression. Bioinformatics methods and a public dataset were first used to analyze MMP­1 gene expression in a public dataset. MMP­1 expression in colorectal cancer patients was assessed by immunohistochemistry; its association with clinicopathological parameters and its significance for prognosis were analyzed. Then proliferation, scratch and Transwell assays and a xenograft model were used to assess the change in malignant behavior in cells transfected with an MMP­1 shRNA. Changes involved in epithelial­mesenchymal transition (EMT) and the Akt signaling pathway were detected by western blotting. According to the results, MMP­1 expression was higher in colorectal cancer tissues than it was in matched adjacent noncancerous tissues, and its high expression was significantly related to lymphatic metastasis as well as TNM stage (P<0.05). Downregulation of MMP­1 expression inhibited the progression of colorectal cancer in vitro and in vivo. Furthermore, after the cells were stably transfected with MMP­1 shRNA, the expression of N­cadherin, vimentin and Twist1 decreased while that of E­cadherin increased. The expression of p­Akt and c­Myc also decreased. In conclusion, MMP­1 may promote malignant behavior in colorectal cancer via EMT and the Akt signaling pathway.

Farnesoid X receptor antagonizes Wnt/ß-catenin signaling in colorectal tumorigenesis.

Farnesoid X receptor (FXR, encoded by NR1H4), a critical regulator of bile acid homeostasis, is widely implicated in human tumorigenesis. However, the functional role of FXR in colorectal cancer (CRC) and the precise molecular mechanism remain unclear. In this study, we demonstrated that FXR expression was downregulated in colon cancer tissues and decreased expression of FXR predicted a poor prognosis. Knockdown of FXR promoted colon cancer cell growth and invasion in vitro, and facilitated xenograft tumor formation and distant metastasis in vivo, whereas ectopic expression of FXR had the reserved change. Mechanistic studies indicated that FXR exerted its tumor suppressor functions by antagonizing Wnt/ß-catenin signaling. Furthermore, we identified an FXR/ß-catenin interaction in colon cancer cells. The FXR/ß-catenin interaction impaired ß-catenin/TCF4 complex formation. In addition, our study suggested a reciprocal relationship between FXR and ß-catenin, since loss of ß-catenin increased the transcriptional activation of SHP by FXR. Altogether, these data indicated that FXR functions a tumor-suppressor role in CRC by antagonizing Wnt/ß-catenin signaling.

Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model.

BACKGROUND: Among all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model. MATERIALS AND METHODS: Forty-eight rats were randomly divided into six groups. Except for the sham-operated group, all rats underwent cecal abrasion to establish an adhesion model. After the operation, the rats in the DHI-treated groups received different doses of DHI via the tail vein daily, while the other group was treated with the same volume of saline solution. Seven days after the operation, all rats were sacrificed, and the degree of adhesion was evaluated by Nair's scoring system. The extent of inflammation in the adhesion tissue was detected by HE staining and the expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß). The collagen deposition was assessed by Sirius red staining and α-SMA, MMP9, t-PA, and PAI-1 levels. Oxidative stress was indicated by the level of reactive oxygen species (ROS) in adhesion tissues and by immunohistochemical labeling of Nrf2. Furthermore, rat primary peritoneal mesothelial cells (RPMCs) were treated with H2O2 and DHI, and NF-κB phosphorylation was detected to illustrate the effect of DHI on oxidative stress. RESULTS: The intra-abdominal adhesion scores were significantly decreased in the groups treated with a high dose of DHI compared with the control groups, and the degree of inflammation, fibrosis, and oxidative stress was also significantly decreased. DHI treatment significantly reduced the levels of TNF-α, TGF-ß1, and PAI and increased the expression levels of MMP9, Nrf2, and t-PA in the adhesion tissues. ROS levels and NF-κB phosphorylation were significantly reduced in DHI-treated RPMCs compared with the control RPMCs. CONCLUSION: DHI alleviates the formation of postoperative intra-abdominal adhesions by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model and may serve as a promising drug to prevent intra-abdominal adhesions.

Poor prognostic role of the pretreatment platelet counts in colorectal cancer: A meta-analysis.

BACKGROUND: Recently, a wide variety of studies have suggested that elevated platelet counts are associated with survival in patients with colorectal cancer. On one hand several studies suggest a negative connection in colorectal cancer patients with pre-operative thrombocytosis, on the other hand other studies contradicts this. However, it remains unknown whether elevated platelet counts are associated with survival in colorectal cancer patients. We therefore conducted this meta-analysis to evaluate the prognostic role of platelet counts in colorectal cancer. METHODS: PubMed, Embase, and the Cochrane Library databases were searched from their inception to October 15, 2016 to identify relevant studies that have explored the prognostic role of platelet counts in colorectal cancer. Studies that examined the association between platelet counts and prognoses in colorectal cancer and that provided a hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) and/or disease-free survival (DFS) were included. RESULTS: This meta-analysis included 9 retrospective cohort studies involving 3413 patients with colorectal cancer. OS was shorter in patients with elevated platelet counts than in patients with normal counts (HR 2.11, 95% CI: 1.68-2.65). For DFS, an elevated platelet count was also a poor predictor (HR 2.51, 95% CI: 1.84-3.43). CONCLUSION: In this meta-analysis, we suggest that an elevated platelet count is a negative predictor of survival in both primary colorectal cancer and resectable colorectal liver metastases.