Search

Background: Localized radiation therapy is the first-line option for the treatment of nonmetastatic prostate cancer (PCa). Previous studies revealed that long non-coding RNAs (lncRNAs) had crucial roles in disease progression. However, the mechanisms of lncRNAs underlying prostate cancerrelated fatigue remained largely unclear. Objective: The present study aimed to uncover the key genes related to PCa related fatigue during localized radiation therapy by constructing mRNA and lncRNA regulatory networks. Methods: We analyzed GSE30174, which included 10 control samples and 40 PCa related fatigue samples, to identify differently expressed lncRNAs and mRNAs in PCa related fatigue. A proteinprotein interaction network was constructed to reveal the interactions among mRNAs. Co-expression network analysis was applied to identify the key lncRNAs and reveal the functions of these lncRNAs in PCa related fatigue. Results and Discussion: This research found 1271 dysregulated mRNAs and 205 dysregulated lncRNAs in PCa related fatigue using GSE30174. Bioinformatics analysis showed that PCa related fatigue with mRNAs and lncRNAs were associated with inflammatory response and immune response related biological processes. Furthermore, we constructed a PPI network and lncRNA co-expression network related to fatigue in PCa. Of note, we observed that the dysregulated lncRNAs and mRNAs, such as SEC61A2, ADCY6, LPAR5, COL7A1, ALB, COL1A1, SNHG1, LINC01215, LINC00926, GNG4, LMO7, and COL4A6, in PCa related fatigue could predict the outcome of PCa patients. Conclusions: This research could provide novel mechanisms underlying fatigue and identify new biomarkers for the prognosis of PCa.

BackgroundAndrogen deprivation therapy (ADT) is still the first line treatment of prostate cancer (PCa). However, after a certain period of therapy, primary PCa inevitably progresses into castration-resistant PCa (CRPC). Enzalutamide (MDV3100) is an androgen receptor (AR) signal inhibitor which can delay the progression of CRPC and increase survival of patients with metastatic CRPC. However, the mechanisms involved in enzalutamide-resistant (EnzR) CRPC are still controversial. MethodsWe collected RNA-seq data of the EnzR CRPC cell line LNCaP (EnzR LNCaP) from GSE44905, GSE78201, and GSE150807. We found the hub genes from the three datasets. Then we tested the expression of the hub genes in the Cancer Genome Atlas (TCGA) database and the potential drugs that affect the hub genes. Finally, we verified the hub gene expression and drug function.ResultsFrom GSE44905, GSE78201 and GSE150807, we found 45 differently expressed genes (DEGs) between LNCaP and EnzR LNCaP. Ten hub genes were found in the protein-protein interaction (PPI) network. The hub genes expression and survival analysis were analyzed by GEPIA depend on the TCGA database. We found that cyclin-dependent kinase 6 (CDK6) was highly expressed in both the EnzR LNCaP cell and PCa patients. Ten potential small molecules could suppress CDK6 expression as per CMap findings. Finally, we found the expression of CDK6 increased in both PCa patients’ samples, CRPC cell lines and EnzR PCa cell lines. Three potential CDK6 inhibitors, namely apigenin, chrysin and fisetin, can decrease cell proliferation.ConclusionsThe study proved that CDK6 mutation may be a reason behind EnzR CRPC occurrence and suppression CDK6 expression may help treat EnzR CRPC.

BackgroundAndrogen deprivation therapy (ADT) is still the first line method to treat PCa. However, after a period of therapy, primary PCa will inevitably progress into castration-resistant prostate cancer (CRPC). Enzalutamide (MDV3100) is an androgen receptor (AR) signal inhibitor which can delay the progression of CRPC and increase survival of patients with metastatic CRPC. However, the mechanisms of enzalutamide resistant castration-resistant prostate cancer (EnzR CRPC) are still controversial. MethodsWe collected RNA-seq data of enzalutamide resistant castration-resistant prostate cancer cell line LNCaP (EnzR LNCaP) from GSE44905, GSE78201 and GSE150807. We found hub gene from the three datasets. Then we tested the expression of hub gene in TCGA database and potential drug that has effect on hub gene. Finally, we verified the hub gene expression and drug function.ResultsFrom GSE44905, GSE78201 and GSE150807, we found 45 differently expressed genes (DEGs) between LNCaP and EnzR LNCaP. Ten hub gene were found in protein-protein interaction (PPI) network. The hub gene expression and survival analysis were analyzed by GEPIA depend on TCGA database. We found that CDK6 was highly expressed in both EnzR LNCaP cell and prostate cancer patients. Ten potential small molecules can suppress CDK6 expression from CMap. Finally, we verified the expression of CDK6 in both CRPC patients’ samples and prostate cancer cell lines. The function of three potential CDK6 inhibitors, apigenin, chrysin and fisetin, was tested in prostate cancer cell lines.ConclusionsThe study proved that the mutation of CDK6 maybe a reason to the occurrence of CRPC and suppress CDK6 expression may be a potential way in treating CRPC.

The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for intrahepatic cholangiocarcinoma (ICC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes.A total of 711 consecutive patients who underwent curative liver resection for hepatitis B virus-related ICC were retrospectively analyzed. The different impact of the RM status (narrow,1 cm, or wide, ≥1 cm) and MVI (positive, +, or negative, -) on overall survival (OS) and recurrence-free survival (RFS) were analyzed.The 1-, 3-, and 5-year OS rates were 67.6%, 42.5%, and 33.2% in wide RMMVI (-), 58.0%, 36.1%, and 26.5% in narrow RMMVI (-), 51.0%, 27.0%, and 24.3% in wide RMMVI (+), and 39.0%, 20.4% and 14.3% in narrow RMMVI (+) (Combined analysis of RM and MVI can better stratify the risks of postoperative death and recurrence in patients with HBV-related ICC, which may help subsequent adjuvant therapy and closer follow-up.

// Lei Liang 1, 2, * , Xue Yang 1, * , Yang Yu 1, 3, * , Xiaoyong Li 1, 2 , Yechen Wu 1, 2 , Rongyu Shi 1 , Jinghua Jiang 1 , Lu Gao 1 , Fei Ye 1 , Qiudong Zhao 1 , Rong Li 1 , Lixin Wei 1 , Zhipeng Han 1 1 Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China 2 Medical College of Soochow University, Suzhou, China 3 Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200065, China * These authors contributed equally to this work Correspondence to: Zhipeng Han, email: hanzhipeng0311@126.com Lixin Wei, email: weilixin_smmu@163.com Keywords: hepatic fibrosis, hepatic stellate cells, chinese medicine, Babao Dan, toll-like receptor 4 Received: August 01, 2016 Accepted: October 12, 2016 Published: October 20, 2016 ABSTRACT Babao Dan (BBD), a traditional Chinese medicine, has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the protective effect of BBD on rat hepatic fibrosis induced by diethylnitrosamine (DEN) and explore it possible mechanism. BBD was administrated while DEN was given. After eight weeks, values of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicated that BBD significantly protected liver from damaging by DEN and had no obvious side effect on normal rat livers. Meanwhile, BBD attenuated hepatic inflammation and fibrosis in DEN-induced rat livers through histopathological examination and hepatic hydroxyproline content. Furthermore, we found that BBD inhibited hepatic stellate cells activation and proliferation without altering the concentration of lipopolysaccharide (LPS) in portal vein. In vitro study, serum from BBD treated rats (BBD-serum) could also significantly suppress LPS-induced HSCs activation through TLR4/NF-κB pathway. In addition, BBD-serum also inhibited the proliferation of HSCs by regulating TLR4/ERK pathway. Our study demonstrated that BBD may provide a new therapy strategy of hepatic injury and hepatic fibrosis.

To evaluate the antitumor effect of sinoporphyrin sodium mediated photodynamic therapy (DVDMS-PDT) against human colorectal cancer (CRC) and to investigate the role of autophagy in its effect. Shrunken cells, condensed nuclei and increased levels of cleaved caspase-3 and Bax were observed in DVDMS-PDT treated HCT116 cells, reminiscent of apoptosis. DVDMS-PDT showed better antitumor efficiency in HCT116 cells than Photofrin mediated photodynamic therapy (PF-PDT) both in vitro and in vivo. And DVDMS-PDT caused autophagic characteristics: double membrane autophagosome structures and changes in autophagy-related protein expression (ATG7, P62, Bcl-2 and LC3-Ⅱ). In addition, inhibition of autophagy by chloroquine (CQ) promoted apoptosis, suggesting a possible protective role of autophagy in DVDMS-PDT-treated HCT116 cells, which was proved by flow cytometry and western blotting. The results of xenograft mouse model showed markedly increased apoptosis and significantly reduced tumor size in DVDMS-PDT treated group than Control, and DVDMS-PDT exhibited better antitumor efficiency than PF-PDT. Further, no visible tumor was observed in the CQ+DVDMS-PDT group at the end of the xenograft mouse experiment, which confirmed the hypothesis that autophagy was protective to DVDMS-PDT treated HCT116 cells. Our findings suggest that DVDMS is a promising photosensitizer and the combined use of autophagy inhibitor can remarkably enhance the DVDMS-PDT mediated anti-cancer efficiency in HCT116 cells both in vitro and in vivo.

Through analyzing the statistical properties of measured vibratory data for X-type aircraft, it confirms that non-Gaussian or nonstationary vibration environment exist in transportation and employment of equipments. The deficiencies of the existing vibration test methods and standard are pointed out, and the vibration test methods and flow chart based on measured data are proposed, which can effectively avoid the problem of over-test or under-test.