Upregulation of MED7 was associated with progression in hepatocellular carcinoma.

OBJECTIVE: MED subunits have been reported to be associated with various types of tumors, however, the potential role of MED7 in hepatocellular carcinoma (HCC) was still unclear. The aim of the study was to explore the role of MED7 in HCC. METHODS: In this study, MED7 mRNA expression levels between HCC and adjacent normal tissues were first analyzed by several public datasets. Then we utilized a tissue microarray (TMA) to investigate the clinical role of MED7 in HCC by immunohistochemistry (IHC). Meanwhile, the potential mechanisms of MED7 based on gene-gene correlation analyses were also explored. RESULTS: High mRNA level of MED7 correlated with advanced stage and worse grade of differentiation. IHC results showed that MED7 protein level was upregulated in HCC and associated with Edmondson grade and Microvascular invasion in 330 cases of HCC. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that MED7 co-expressed genes participate primarily in ribonucleoprotein complex biogenesis, protein targeting, mRNA processing and nucleoside triphosphate metabolic process et cetera. Further analysis also revealed that MED7 mRNA level has significant correlation with immune cells infiltration levels. CONCLUSION: MED7 was upregulated in HCC and correlated with progression of HCC. Meanwhile, MED7 may promote HCC through participating in multiple gene networks to influence tumorigenesis as well as immune response in HCC microenvironment.

PHF21A expression as a biomarker of hepatocellular carcinoma progression and prognosis.

Previous studies have shown that PHF21A is associated with the initiation and progression of various tumors. However, its role in hepatocellular carcinoma (HCC) is still unclear. Thus, this study aimed to determine the expression and clinical significance of PHF21A in HCC. PHF21A expression in 201 liver cancer samples and 129 adjacent normal tissues was detected by immunohistochemistry. The correlation between PHF21A expression and the clinicopathological features and prognosis of HCC was verified in 70 other liver tissue microarray samples. The relationship between PHF21A expression and HCC immune cell infiltration was explored via the Tumor Immune Estimation Resource (TIMER). The mechanism underlying the effect of PHF21A on HCC progression was analyzed by gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analysis. Immunohistochemical staining showed that PHF21A expression in HCC tissue was significantly lower than that in adjacent nontumor liver tissue and was associated with patient sex, tumor size, metastasis, and Edmondson grade (p<0.05). Kaplan-Meier analysis demonstrated that low PHF21A expression was associated with a poor prognosis, and Cox regression analysis showed that PHF21A was an independent predictor of prognosis. TIMER analysis showed that PHF21A is positively correlated with tumor immune cell infiltration levels. Functional annotation indicated that PHF21A is involved in important pathways, including transcriptional deregulation pathways in cancer. Finally, in vitro experiments confirmed the low expression of PHF21A in HCC cells. PHF21A affects the progression and prognosis of HCC, suggesting that PHF21A may play an important role in monitoring and preventing the development of HCC.

Nano-Technological Approaches for Targeting Kidney Diseases With Focus on Diabetic Nephropathy: Recent Progress, and Future Perspectives.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. With the rising prevalence of diabetes, the occurrence of DN is likely to hit pandemic proportions. The current treatment strategies employed for DN focus on the management of blood pressure, glycemia, and cholesterol while neglecting DN's molecular progression mechanism. For many theranostic uses, nano-technological techniques have evolved in biomedical studies. Several nanotechnologically based theranostics have been devised that can be tagged with targeting moieties for both drug administration and/or imaging systems and are being studied to identify various clinical conditions. The molecular mechanisms involved in DN are discussed in this review to assist in understanding its onset and progression pattern. We have also discussed emerging strategies for establishing a nanomedicine-based platform for DN-targeted drug delivery to increase drug's efficacy and safety, as well as their reported applications.

High expression of PPM1G is associated with the progression and poor prognosis of hepatocellular carcinoma.

BACKGROUND: PPM1G, a member of the serine/threonine protease family, dephosphorylates various proteins and may be involved in cancer development. The role and mechanism of PPM1G in HCC still needs to be verified. OBJECTIVE: This study aims to explore the role of PPM1G in the occurrence, development and prognosis of HCC. METHODS: Using bioinformatics (UALCAN, cBioPortal, Linkedomics, STRING and GSEA) to analyze the expression of PPM1G mRNA in HCC, its clinical relevance and possible involved signaling pathways. The expression of PPM1G protein was determined by immunohistochemistry in 311 cases of HCC to evaluate the association between PPM1G and clinical features and prognosis. RESULTS: The expression of PPM1G was significantly upregulated in HCC (P< 0.001), correlated with the metastasis (P= 0.020), pathological grade of HCC (P= 0.032), microvascular invasion (P= 0.040), and HBV infection (P= 0.041). Cox multivariate regression showed high expression of PPM1G was an independent prognostic factor for HCC. Its role in HCC may relate to methylation and frequency mutation. Furthermore, the database showed PPM1G is involved in the signal pathway such as cell cycle, WNT pathway, and mTOR pathway in HCC. CONCLUSION: PPM1G showed an essential function involving in tumor-related pathways in HCC, providing a biological basis for targeted treatment of HCC clinically.

High Expression of SLC41A3 Correlates with Poor Prognosis in Hepatocellular Carcinoma.

PURPOSE: SLC41A3 is a member of the solute carrier family 41 (SLC41) and is involved in many cellular processes as a magnesium ion transporter. Although it plays an important role in cancer formation and development, the correlation between the expression of SLC41A3 and the occurrence and prognosis of hepatocellular carcinoma (HCC) remains unclear. Therefore, this study was focused on the evaluation of the relationship between SLC41A3 and the development and prognosis of HCC. PATIENTS AND METHODS: Firstly, we collected the mRNA expression of SLC41A3 in HCC through the platform of Oncomine. Then, the subgroups of HCC were performed by the UALCAN website and the prognosis of HCC was analyzed by Kaplan-Meier Plotter database. Subsequently, immunohistochemistry (IHC) method was used to detect SLC41A3 expression in 323 clinically confirmed HCC samples and 184 non-cancerous liver tissues. Finally, function enrichment analysis was done using the LinkInterpreter module in LinkedOmics, and gene set enrichment analysis (GSEA) was performed using TCGA data set. RESULTS: The Oncomine database and immunohistochemical (IHC) showed higher SLC41A3 expression in HCC tissue compared to normal tissue. The expression of SLC41A3 was significantly correlated with tumor metastasis, Edmondson grade, microvascular invasion, and AFP level. Kaplan-Meier and Cox regression analyses verified that high SLC41A3 expression is a significant prognostic factor for reduced overall survival in HCC patients. CONCLUSION: Our results demonstrated that high expression of SLC41A3 was the predictor of poor prognosis in HCC patients, suggesting that this protein may be a potential target for HCC therapy.

Expression of VAT1 in hepatocellular carcinoma and its clinical significance.

The objective of this study was to investigate the expression of vesicular amine transporter 1 (VAT1) in hepatocellular carcinoma (HCC) and its prognostic value and to analyze the relationship between VAT1 expression and clinicopathological features of HCC. First, several public databases, including Ualcan, GEPIA, and Oncomine, were used to analyze the expression of VAT1 in HCC and normal liver tissue. Next, 330 HCC and 190 normal liver samples were stained by immunohistochemistry and scored. Finally, we evaluated the clinical significance of VAT1 as a prognostic factor according to the clinicopathological characteristics. We observed that the expression level of VAT1 in HCC samples was significantly higher than that in normal liver tissues, and the high expression of VAT1 protein in HCC was significantly correlated with patient age, tumor size, number of tumors, and vascular metastasis (p<0.05). The average survival time of HCC patients with high expression of VAT1 was significantly lower than that of patients with low expression of VAT1. Further analysis demonstrated that VAT1 expression was significantly correlated with the length of overall survival in HCC patients. In conclusion, VAT1 may have an essential function in the progression of HCC, and the level of its expression may effectively predict the invasion and prognosis of HCC. Moreover, the combination of information contained in public databases and the results of the analysis of clinical samples can help us to understand better the mechanism of action of molecular oncogenes in HCC.

Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy.

BACKGROUND: Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis (UC). Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice. Resveratrol exerts anti-inflammatory functions by regulating autophagy. AIM: To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis mice. METHODS: Male C57BL/6 mice were divided into four groups: negative control group, DSS model group, DSS + resveratrol group, and DSS + 5-aminosalicylic acid group. The severity of colitis was assessed by the disease activity index, serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay. Colon tissues were stained with haematoxylin and eosin, and mucosal damage was evaluated by mean histological score. The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis. In addition, the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot, and morphology of autophagy was observed by transmission electron microscopy. RESULTS: The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42, 3.81, and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α, interleukin-6 and interleukin-1ß, respectively, in DSS-induced colitis mice compared with DSS group (P < 0.05). The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased, and were increased in resveratrol-treated colitis group. Resveratrol also increased the levels of LC3B (by 1.39-fold compared with DSS group) and Beclin-1 (by 1.49-fold compared with DSS group) (P < 0.05), as well as the number of autophagosomes, which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy. CONCLUSION: Resveratrol treatment decreased the expression of inflammatory factors, increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction; this effect may be achieved by enhancing autophagy in intestinal epithelial cells.

Role of Treg/Th17 Imbalance, Microbiota and miRNAs in Pancreatic Cancer: Therapeutic Options.

Pancreatic cancer is one of the most lethal kinds of cancer; numerous patients die from it every year all over the word. Fewer than 5% of people with pancreatic cancer survive death and recover. Recent evidence suggests that inflammation parameters, such as Th17 cells and Tregs, affect the progression and even the diagnosis and treatment of pancreatic cancer. In the inflammation process, T lymphocytes play an essential role in inflammation intensity, and related cytokines modulate immune responses in the tumor microenvironment. Their function is to establish a balance between destructive inflammation and defense against tumor cells via immune system, and Treg/Th17 imbalance is a common problem in this cancer. The role of microbiota in the development of some cancers is clear; microbiota may also be involved in the pancreatic cancer development. All risk factors for pancreatic cancer, such as chronic pancreatitis-related to microbiota, influence the acute or chronic immune response. Some evidence has been presented regarding the role of the immune response in carcinogenesis. In addition, miRNAs are very important in suppressing and stimulating the growth of cancer cells, and a variety of them have been identified. Some miRNAs are abnormally expressed in many cancers and have main roles as post-transcriptional regulators. They show oncogenic or tumor-suppressive functions by binding to marked mRNAs. In this review, we highlight recent findings regarding the role of Treg/Th17 imbalance, microbiota functions, and miRNAs performance in pancreatic cancer. We also present the evidence regarding therapeutic options.

Roles of lncRNAs in cancer: Focusing on angiogenesis.

Approximately 98% of the human genome consists of non-coding sequences that are classified into two classes by size: small non-coding RNAs (≤200 nucleotides) and long non-coding RNAs (≥200 nucleotides). Long non-coding RNAs (lncRNAs) are involved in various cellular events and act as guides, signals, decoys, and dynamic scaffolds. Due to their oncogenic and tumor suppressive roles, lncRNAs are important in cancer development and growth. LncRNAs play their roles by modulating cancer hallmarks, including DNA damage, metastasis, immune escape, cell stemness, drug resistance, metabolic reprogramming, and angiogenesis. Angiogenesis is vital for solid tumors which guarantees their growth beyond 2 mm3. Tumor angiogenesis is a complex process and is regulated through interaction between pro-angiogenic and anti-angiogenic factors within the tumor microenvironment. There are accumulating evidence that different lncRNAs regulate tumor angiogenesis. In this paper, we described the functions and mechanisms of lncRNAs in tumor angiogenesis.

Ceramide-Graphene Oxide Nanoparticles Enhance Cytotoxicity and Decrease HCC Xenograft Development: A Novel Approach for Targeted Cancer Therapy.

Despite substantial efforts to develop novel therapeutic strategies for treating hepatocellular carcinoma (HCC), the effectiveness and specificity of available drugs still require further improvement. Previous work has shown that exogenous ceramide can play a key role in inducing the apoptotic death of cancer cells, however, the poor water-solubility of this compound has hampered its use for cancer treatment. In the present study, we used polyethylene glycol (PEG) and polyethylenimine (PEI) co-conjugated ultra-small nano-GO (NGO-PEG-PEI) loaded with C6-ceramide (NGO-PEG-PEI/Cer) as a strategy for HCC treatment. We assessed the biological role of NGO-PEG-PEI/Cer, and we assessed its antitumor efficacy against HCC both in vitro and in vivo in combination with the chemotherapeutic drug sorafenib. We found that NGO-PEG-PEI significantly enhanced the cellular uptake of C6-ceramide. By investigating the mechanism of cellular delivery, we determined that the internalization of NGO-PEG-PEI/Cer progressed primarily via a clathrin-mediated mechanism. The combination of NGO-PEG-PEI/Cer and sorafenib exhibited synergy between these two drugs. Further work revealed that NGO-PEG-PEI/Cer may play a role in subverting multidrug resistance (MDR) in HCC cells by inactivating MDR and Akt signaling. NGO-PEG-PEI/Cer also significantly inhibited tumor growth and improved survival times in vivo, and the synergetic effect of NGO-PEG-PEI/Cer combined with sorafenib was also observed in drug-resistant HCC xenografts. In conclusion, our NGO-PEG-PEI nanocomposite is an effective nano-platform for loading C6-ceramide for therapeutic use in treating HCC, exhibiting high cancer cell killing potency in this tumor model. The NGO-PEG-PEI/Cer/sorafenib combination additionally represents a promising potential therapeutic strategy for the treatment of drug-resistant HCC.

The correlation of NLRC3 expression with the progression and prognosis of hepatocellular carcinoma.

NLRC3 is a member of the nucleotide-binding domain and leucine-rich repeat (NLR) family protein that plays a role in inflammation and immunity. Although chronic inflammation has been identified as a hallmark of cancer, NLRC3 expression correlation with the development and prognosis of hepatocellular carcinoma (HCC) is unclear. In the present study, we first used Oncomine and OncoLnc database to determine the clinical significance of NLRC3 in HCC. Then we performed quantitative real-time polymerase chain reaction, Western blot, and immunohistochemical staining (IHC) and analyzed the correlation between NLRC3 expression and clinicopathological features of HCC in a Chinese population. We found that high levels of NLRC3 messenger RNA (mRNA) correlated with a favorable clinical outcome; furthermore, expression of NLRC3 was significantly reduced in the cancer tissue in patients compared with noncancerous hepatic tissues. NLRC3 reduction was correlated with Edmondson grade and metastasis. Kaplan-Meier survival analysis revealed that HCC patients with high expression of NLRC3 have a more favorable prognosis compared with those with low expression of NLRC3. We then used short hairpin RNA to knock down NLRC3 expression in HCC cell lines and evaluated its effect on cell proliferation and apoptosis. Suppression of NLRC3 expression promoted cell proliferation and inhibited apoptosis in vitro. Genomic analysis of the OncoLnc database also showed that NLRC3 mRNA level was directly correlated with mRNA levels of inflammasome components caspase-1, IL-1ß, and IL-18. Based on our present study, down-regulated expression of NLRC3 may play an important role in cancer progression and prognosis of HCC by acting as a tumor suppressor.

Molecular Imaging of Cancer with Nanoparticle-Based Theranostic Probes.

Although advancements in medical technology supporting cancer diagnosis and treatment have improved survival, these technologies still have limitations. Recently, the application of noninvasive imaging for cancer diagnosis and therapy has become an indispensable component in clinical practice. However, current imaging contrasts and tracers, which are in widespread clinical use, have their intrinsic limitations and disadvantages. Nanotechnologies, which have improved in vivo detection and enhanced targeting efficiency for cancer, may overcome some of the limitations of cancer diagnosis and therapy. Theranostic nanoparticles have great potential as a therapeutic model, which possesses the ability of their nanoplatforms to load targeted molecule for both imaging and therapeutic functions. The resulting nanosystem will likely be critical with the growth of personalized medicine because of their diagnostic potential, effectiveness as a drug delivery vehicle, and ability to oversee patient response to therapy. In this review, we discuss the achievements of modern nanoparticles with the goal of accurate tumor imaging and effective treatment and discuss the future prospects.

High level of homeobox A9 and PBX homeobox 3 expression in gastric cancer correlates with poor prognosis.

The homeobox protein homeobox (HOXA9) is a transcriptional factor that regulates patterning during embryogenesis and controls cell differentiation. HOXA9 dysfunction has been implicated in certain cancers. However, the role of HOXA9 in gastric cancer is poorly understood. The present study investigated HOXA9 and its cofactor PBX homeobox 3 (PBX3) expression in patients with gastric cancer. Paired tissue samples from 24 patients and paraffin embedded tissues of gastric cancer patients (104 males and 24 females) were included. HOXA9 and PBX3 expression levels were determined by reverse transcription quantitative polymerase chain reaction in fresh tissues, and by immunohistochemical staining in paraffin embedded tissues. The association between HOXA9/PBX3 expression and clinicopathological features was established. The results demonstrated that HOXA9 and PBX3 mRNA levels were significantly upregulated (P=0.032 for HOXA9 and P=0.031 for PBX3) in gastric cancer tissue. Immunohistochemical staining revealed that HOXA9 expression was associated with differentiation, lymph node metastasis and tumor-node-metastasis (TNM) stage, and PBX3 expression was associated with lymph node metastasis and TNM stage. Correlation analysis revealed a high coincidental expression of HOXA9 and PBX3 levels in gastric cancer (r=0.391; P<0.001). Survival analysis showed that high expression of HOXA9 or PBX3 was associated with poor survival of gastric cancer, and multivariate analysis using Cox's regression model showed that PBX3 expression was an independent prognostic factor in gastric cancer. There was elevated expression of HOXA9 and PBX3 in gastric cancer patients, and high-level expression of those proteins was associated with poor prognosis of gastric cancer. The present study underlines the significance of HOXA9/PBX3 in the development of gastric cancer.

Decreased expression of Zwint-1 is associated with poor prognosis in hepatocellular carcinoma.

BACKGROUND AND AIM: ZW10 interacting kinetochore protein 1 (Zwint-1), one of the major kinetochore proteins, is essential for kinetochore function, such as spindle assembly checkpoint function and kinetochore-microtubule attachment. Recently, it has been found over-expressed in some human cancers, including ovarian cancer, bladder cancer, and pulmonary adenocarcinoma. However, few studies of the expression of Zwint-1 in hepatocellular carcinoma (HCC) have been reported. This study is aimed to investigate the expression of Zwint-1 and its relationship with clinical pathological characters in HCC. METHODS: The expression of Zwint-1 protein was analyzed by immunohistochemistry staining on tissue microarrays containing 171 HCC tissues and 187 control non-tumorous liver tissues. The relationships between the Zwint-1 expression and the clinicopathological parameters, and survival analysis were investigated using SPSS software 13.0. RESULTS: Zwint-1 was found uniformly expressed in adjacent non-tumorous liver tissues (184/187, 98.40%), while was significantly decreased in HCC tissues, or even absent (150 of 171, 61.82%, P<0.001). The expression of Zwint-1 was negatively associated with age, tumor size, and Edmondson Grade. Besides, HCC patients with low Zwint-1 expression were also correlated with poor overall survival of the patients. CONCLUSIONS: Decreased expression of Zwint-1 was associated with poor prognosis in HCC.

Downregulation of ALDOB is associated with poor prognosis of patients with gastric cancer.

OBJECTIVES: To examine the expression of ALDOB in gastric cancer (GC) tissue and to reveal its potential clinicopathological and prognostic significance. MATERIALS AND METHODS: We screened for genes that were differentially expressed between GC and nontumor tissues using a microarray, specifically the Affymetrix U133 Plus 2.0 Array platform. We then verified the transcriptional and translational levels of ALDOB by performing quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). In addition, a merged data set based on the Gene Expression Omnibus was generated and a survival analysis performed. RESULTS: The microarray analysis revealed that ALDOB was downregulated (more than sevenfold) in GC compared with nontumor tissue. Both qRT-PCR and IHC validated the decrease of ALDOB in GC tissue. Moreover, we found that the expression of ALDOB was significantly related to tumor-invasion depth, lymph-node metastasis, distant metastasis, and TNM stage. The survival analysis, based on the IHC and merged data set, indicated that the overall survival was better in patients with high ALDOB expression. The Cox regression analysis showed that ALDOB expression was an independent prognostic factor for GC. CONCLUSION: The expression of ALDOB in GC tissue was significantly related to the clinicopathological features and prognosis of the disease, thus suggesting that ALDOB could act as a novel molecular marker for GC.

Loss of coxsackie and adenovirus receptor expression in human colorectal cancer: A potential impact on the efficacy of adenovirus-mediated gene therapy in Chinese Han population.

The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and critical factor for the efficacy of therapeutic strategies that employ the adenovirus. However, data on CAR expression levels in colorectal cancer are conflicting and its clinical relevance remains to be elucidated. Immunohistochemistry was performed on tissue microarrays containing 251 pairs of colon cancer and adjacent normal tissue samples from Chinese Han patients to assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR expression (40.6% vs. 95.6%; P<0.001) was observed in colorectal cancer samples. The CAR immunopositivity in tumor tissues was not significantly associated with gender, age, tumor size, differentiation, TNM stage, lymph node metastasis or distant metastasis in patients with colon cancer. However, expression of CAR is present in 83.3% of the tumor tissues from patient with colorectal liver metastasis, which was significantly higher than those without liver metastasis (39.6%; P=0.042). At the plasma membrane, CAR was observed in 29.5% normal mucosa samples, which was significantly higher than in colorectal cancer samples (4.0%; P<0.001). In addition, the survival analysis demonstrated that the expression level of CAR has no association with the prognosis of colorectal cancer. CAR expression was observed to be downregulated in colorectal cancer, and it exerts complex effects during colorectal carcinogenesis, potentially depending on the stage of the cancer development and progression. High CAR expression may promote liver metastasis. With regard to oncolytic therapy, CAR expression analysis should be performed prior to adenoviral oncolytic treatment to stratify Chinese Han patients for treatment.

High expression of substance P and its receptor neurokinin-1 receptor in colorectal cancer is associated with tumor progression and prognosis.

BACKGROUND: Epidemiologic evidence suggests that chronic inflammation and/or chronic infection is associated with cancer development, and the inflammatory process may play a crucial role in the carcinogenesis and prognosis of colorectal cancer (CRC). Substance P (SP) belongs to the family of tachykinins and acts as an immunomodulator, binding to the neurokinin-1 receptor (NK1R) to initiate tumor cell proliferation, angiogenesis, and migration, steps that are critical for tumor cell invasion and metastasis. It is suggested that SP/NK1R signaling may play an important role in cancer progression and metastasis. However, the exact involvement and significance of SP and NK1R in CRC pathologies remain to be adequately deciphered. PATIENTS AND METHODS: We performed immunohistochemistry staining on tissue microarrays containing 267 pairs of CRC and adjacent normal tissues to evaluate the clinical significance of SP or NK1R in the progression and prognosis of CRC. We also explored the potential correlation between SP and NK1R in CRC development. RESULTS: Expression levels of SP and NK1R were upregulated in CRC compared with their expressions in adjacent normal tissues (P<0.001). High expression of SP in CRC was significantly associated with lymph node metastasis (P<0.001). We also found that high expression of NK1R in CRC was significantly related to TNM (tumor node metastasis) stage (P=0.010) and lymph node metastasis (P=0.019). A high correlation between SP and NK1R expression was also observed (r=0.419, P<0.001). Survival analysis showed that CRC patients with high expression of SP or NK1R have a poor prognosis when compared to patients with low SP or NK1R expression (log rank test, P<0.05). Multivariate analysis using Cox regression model showed that survival was independently correlated with lymph node metastasis, distant metastasis, and SP expression (P<0.05). CONCLUSION: Upregulation of SP-NK1R may play a crucial role in CRC progression. Moreover, SP-NK1R expression may also be used as a predictor for CRC prognosis.

The CDH1 -160C/A polymorphism is associated with breast cancer: evidence from a meta-analysis.

BACKGROUND: Numerous epidemiological studies have evaluated the association between the CDH1 -160C/A polymorphism and the risk of breast cancers. However, these studies have yielded conflicting results. To derive a more precise estimation of this association, this meta-analysis was conducted. METHODS: A comprehensive search using the keywords "CDH1," "E-Cadherin," "polymorphism," "SNP," and "variant" combined with "breast," "cancer," "tumor," or "carcinomas" was conducted. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were appropriately calculated using a fixed effect or random effect model. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 checklist was used for this meta-analysis. RESULTS: Four publications including five studies were identified. It was found that the CDH1 -160C/A polymorphism was significantly associated with breast cancer risk in the dominant model (CA + AA vs. CC: OR = 1.207, 95 % CI = 1.031-1.412, P = 0.019). CONCLUSIONS: Our meta-analysis demonstrated that the -160C/A polymorphism in the CDH1 gene might contribute to breast cancer susceptibility. Further investigations using a much larger sample including different ethnicities are still needed to verify this association.

Delivery systems of ceramide in targeted cancer therapy: ceramide alone or in combination with other anti-tumor agents.

INTRODUCTION: Ceramide is a bioactive lipid which functions as a tumor suppressor, regulating processes such as cell proliferation, differentiation, senescence and apoptosis. However, several challenges need to be overcome in order to realize the therapeutic potential of such a bioactive lipid combination regimen, including the hydrophobic and hemolytic nature of the lipids. AREAS COVERED: In this review, we briefly describe the biological function of ceramide, then the delivery systems that have been developed to improve the pharmacology of ceramide have been summarized. In addition, combination therapies based on these delivery systems to reveal the interactions between therapeutic drugs and ceramide were also highlighted. Furthermore, future perspective before the extension of ceramide's applications in cancer treatment will also be discussed. EXPERT OPINION: Although ceramide has attracted tremendous attention in targeted cancer treatment, its levels are usually suppressed by over-expression of ceramide-metabolizing enzymes or down-regulation of ceramide-generating enzymes. Thus, finding ways to increase ceramide by exogenous treatment in cancer cells is desired. Therefore, translating these bioactive lipids into clinical usage requires a variety of methods, and appropriately designed delivery systems may play the direct and important role in this process.