PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway.

Objective: Colorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or the presence of various core driver gene mutations that confer resistance may limit the utility of targeted therapy. Therefore, it is of great significance to further elucidate novel mechanisms of invasion and metastasis of CRC and find potential novel therapeutic targets. Protein Kinase C Delta (PKCδ) plays an important role in various diseases, including tumors. In CRC, the function of PKCδ on proliferation and differentiation is mostly studied but various research results were reported. Therefore, the role of PKCδ in CRC needs to be further studied, especially in tumor invasion and metastasis in CRC which few studies have looked into. Methods: The expression of PRKCD was analyzed by the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases and Immunohistochemical (IHC). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to explore the biological functions and pathways related to PRKCD. Lentivirus transfection was used to construct CRC cell lines with overexpression and knock-down of PKCδ or N-myc Downstream Regulated Gene 1 (NDRG1). Cell invasion and migration assay, wound healing assay were used to detect the function of PKCδ and NDRG1 in the invasion and migration of cells. Flow cytometry analysis was used to detect the influence of PKCδ on the CRC cell cycles .Immunofluorescence histochemistry ,Immunoprecipitation Assay and qPCR were used to detect the relationship of PKCδ and NDRG1. Xenograft model was used to verify the role of PKCδ in vivo. Results: PKCδ is overexpressed in CRC and could promote Epithelial-Mesenchymal Transition (EMT) and the invasion and migration of CRC in vitro. We confirmed that PKCδ and the tumor suppressor factor NDRG1 had a co-localization relationship in CRC. PKCδ inhibited NDRG1 transcription and protein expression. Overexpressing NDRG1 could inhibit the function of PKCδ in promoting tumor invasion and migration. PKCδ could regulate c-Myc, one transcription factor of NDRG1, to down-regulate NDRG1. In vivo, overexpressing PKCδ could promote xenograft growth and volume. Thus, our results showed that PKCδ reduced the expression of NDRG1 through c-Myc, promoting the invasion and migration of CRC through promoting EMT. Conclusion: The increased expression of PKCδ in CRC tumor tissue could promote the invasion and migration of tumor cells, and one of the mechanisms may be regulating c-Myc to inhibit the expression of NDRG1 and promote EMT.

[Control of Cadmium Migration and Transformation in Alkaline Paddy Soil-Rice Using Cotton Stalk Biochar].

We investigated the effects of cotton stalk biochar addition on the soil nutrient characteristics of alkaline paddy soil and the migration and transformation of cadmium in a soil-rice system. An outdoor pot experiment was conducted with Tefengyou 2 rice as the testing material. We added cotton stalk biochar (0%, 1%, 2.5%, and 5%) in the alkaline paddy soil with cadmium content of 0, 1, 4, and 8 mg·kg-1. After rice harvesting, the effects of different concentrations of cotton stalk biochar on alkaline soil physical and chemical properties, cadmium enrichment and transfer in rice, and the occurrence of cadmium in soil were analyzed under different concentrations of cadmium stress. The results showed that ① adding cotton stalk biochar can effectively increase soil nutrient (P<0.05). After the addition of cotton stalk biochar, the organic matter increased by 25.74%-47.53%, and the available potassium content increased by 3.16-4.25 times. ② Cotton stalk carbon can reduce the cadmium content in soil and rice, especially after the application of 5% cotton stalk carbon, The cadmium content of brown rice at Cd4 and Cd8 concentrations decreased from 0.31 mg·kg-1 and 0.43 mg·kg-1 to 0.15 mg·kg-1 and 0.10 mg·kg-1, respectively, reaching the national standard. Cotton stalk biochar can significantly reduce the enrichment and transfer coefficient of cadmium in soil-rice systems and can increase the cadmium content in the residual cadmium but decrease the acid extractable cadmium, reducible cadmium, and oxidizable cadmium content (P<0.05). ③ Soil pH, conductivity, and nutrient indicators were significantly negatively correlated with cadmium content in rice and acid extractable cadmium, reducible cadmium, and oxidizable cadmium content in soil and were positively correlated with cadmium content in residual cadmium. The above results indicate that the application of cotton stalk biochar can significantly improve the soil nutrient of alkaline cadmium-contaminated paddy soil, and the application of cotton stalk biochar has a significant control effect on the migration and transformation of cadmium in alkaline soil and rice.

Overexpression of Glutathione S-transferase P1 Inhibits the Viability and Motility of Prostate Cancer via Targeting MYC and Inactivating the MEK/ERK1/2 Pathways.

Prostate cancer (PC) is one of the most common malignancies of men. Glutathione S-transferase P1 (GSTP1) has been suggested to play a protective role in the prostate. The proto-oncogene MYC has been extensively proved to be a key regulator of tumor transformation from early stage to malignant. Our study aims to investigate the mechanism of GSTP1 in the biological behavior of PC. Compared with normal prostate tissues, the expression of GSTP1 was decreased in PC tissues. Conversely, the level of MYC was increased in PC tissues compared with normal tissues. MYC was convinced a direct target of GSTP1. Besides, the overexpression of GSTP1 or MYC siRNA strongly reduced cell viability via decreasing the volume of cell spheres and cell proliferation rate. GSTP1 overexpression or MYC siRNA also decreased cell motility of PC via reducing the closing rate of scratch wounds and the number of invasive cells. We further explored the underlying mechanism, and found that the level of p-MEK and p-ERK1/2 was strongly decreased in PC3 cells with pcDNA-GSTP1 or MYC siRNA transfection compared with control group. The inhibitory effect on cell viability, p-MEK and p-ERK1/2 was stronger when pcDNA-GSTP1 and MYC siRNA function together. Finally, the in vivo experiment displayed that pcDNA-GSTP1 transfection reduced tumor growth and tumor volume in PC xenografts. The decreased level of metastasis-related proteins VEGF (vascular endothelial growth factor) and MMP (metal matrix proteinase)-9 in GSTP1 overexpression model mice was detected by immunohistochemistry. Besides, the expression of MYC, p-MEK and p-ERK1/2 was strongly inhibited in mice with pcDNA-GSTP1 transfection. Taken together, our research indicates that GSTP1 overexpression inhibits the viability and motility of PC in vitro and in vivo, and may through targeting MYC and inactivating MEK/ERK1/2 pathway.

hsa-mir-3199-2 and hsa-mir-1293 as Novel Prognostic Biomarkers of Papillary Renal Cell Carcinoma by COX Ratio Risk Regression Model Screening.

Papillary renal cell carcinoma(PRCC) is the second most common and aggressive renal cell carcinoma. Identification of novel microRNA biomarkers could be beneficial for the diagnosis and prognosis of PRCC patients. We aimed to screen differentially expressed miRNAs that can act as prognostic factors and to predict the survival of PRCC patients. High-throughput data of miRNAs of 274 PRCC samples were downloaded from TCGA (The Cancer Genome Atlas) dataset and interested miRNAs were identified. Hierarchical clustering and principal component analysis (PCA) were performed on these miRNAs. Critical genes that can act as prognostic factors were screened by LASSO. What's more, Kaplan-Meier survival analysis and ROC (Receiver Operating Characteristic) growth curve were used to testify the accuracy of the model. Biological processes of putative targets of miRNAs were analyzed by bioinformatics methods such as GO (Go Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. A total of 105 differentially expressed miRNAs were screened out in PRCC samples compared with healthy controls. Two critical miRNAs, hsa-mir-3199-2, and hsa-mir-1293, were screened out by LASSO (Least Absolute Shrinkage and Selection Operator), including 197 and 189 target genes, respectively. Furthermore, its' accuracy was testified by ROC analysis with the AUC (Area under the curve) value of 0.7774968 and 0.6743466. These miRNAs were significantly enriched in pathways as platelet activating factor biosynthetic process, epithelial cell maturation, and IkappaB kinase complex. In conclusion, hsa-mir-3199-2 and hsa-mir-1293 that can act as prognostic biomarkers of PRCC were screened out, which can provide new insights for the clinical treatment of the disease. J. Cell. Biochem. 118: 3488-3494, 2017. © 2017 Wiley Periodicals, Inc.

Intermittent tri-weekly docetaxel plus bicalutamide in patients with castration-resistant prostate cancer: a single-arm prospective study using a historical control for comparison.

Whether continuous docetaxel (DTX) chemotherapy offers an advantage over intermittent therapy for castration-resistant prostate cancer (CRPC) is unknown. In this study, we evaluated the efficacy, toxicity and quality of life (QoL) of intermittent tri-weekly DTX with bicalutamide in CRPC. Forty-two patients (group A) with CRPC were enrolled. The patients received intravenous DTX (75 mg m(-2)) once tri-weekly with oral bicalutamide (50 mg) once daily. Patients had a DTX holiday when the prostate-specific antigen (PSA) level declined ≥50%. DTX was restarted in patients with a PSA increase ≥25%. Sixty patients (group B) who had matching characteristics and had continuously received DTX without bicalutamide for 10-12 cycles were also enrolled. There were no statistically significant differences in progression-free survival (8 months vs. 9 months, P=0.866) or overall survival (19 months vs. 21 months, P=0.753) between groups A and B; however, the proportions of patients in group A with all grades of neutropenia (33% vs. 58%, P=0.013) and nausea/vomiting (11% vs. 29%, P=0.024) were significantly less compared to group B. A significant improvement in the global health and fatigue scores was recorded for group A post-chemotherapy compared to pre-chemotherapy (P<0.05). The fatigue, nausea/vomiting and appetite loss scores in group B were increased post-chemotherapy compared to pre-chemotherapy (P<0.05). In conclusion, intermittent tri-weekly DTX plus bicalutamide is well tolerated and has the potential to achieve comparable disease control with an improvement in QoL for patients with CRPC.

[Tolterodine tartrate combined with alpha-receptor blocker for benign prostatic hyperplasia with detrusor overactivity].

OBJECTIVE: To evaluate the efficacy and safety of Tolterodine Tartrate combined with the alpha-receptor blocker in the treatment of benign prostatic hyperplasia with detrusor overactivity (BPH-DO). METHODS: A total of 113 patients with BPH-DO were randomly assigned to receive Tolterodine Tartrate combined with Cardura (Group A) and Cardura alone (Group B), both for 12 weeks. Then we recorded and compared their average 24 h urinary frequency, IPSS and QOL score, maximum urinary flow rate, residual urine volume and urinary retention times before and after the treatment. RESULTS: After the treatment, Group A showed significantly better improvement in the average 24 h urinary frequency and scores on IPSS and QOL than Group B. No significant differences were found between the two groups in the maximum urinary flow rate and residual urine volume. No acute urinary retention occurred in either group. CONCLUSION: The combined use of Tolterodine Tartrate and the alpha-receptor blocker can effectively relieve the symptoms of dysuria, urinary frequency and urinary urgency in patients with BPH-DO, with neither significant adverse effects on the maximum flow rate and residual urine volume nor increase in the incidence of acute urinary retention.