Aurora-a confers radioresistance in human hepatocellular carcinoma by activating NF-κB signaling pathway.

BACKGROUND: Radiotherapy failure is a significant clinical challenge due to the development of resistance in the course of treatment. Therefore, it is necessary to further study the radiation resistance mechanism of HCC. In our early study, we have showed that the expression of Aurora-A mRNA was upregulated in HCC tissue samples or cells, and Aurora-A promoted the malignant phenotype of HCC cells. However, the effect of Aurora-A on the development of HCC radioresistance is not well known. METHODS: In this study, colony formation assay, MTT assays, flow cytometry assays, RT-PCR assays, Western blot, and tumor xenografts experiments were used to identify Aurora-A promotes the radioresistance of HCC cells by decreasing IR-induced apoptosis in vitro and in vivo. Dual-luciferase reporter assay, MTT assays, flow cytometry assays, and Western blot assay were performed to show the interactions of Aurora-A and NF-κB. RESULTS: We established radioresistance HCC cell lines (HepG2-R) and found that Aurora-A was significantly upregulated in those radioresistant HCC cells in comparison with their parental HCC cells. Knockdown of Aurora-A increased radiosensitivity of radioresistant HCC cells both in vivo and in vitro by enhancing irradiation-induced apoptosis, while upregulation of Aurora-A decreased radiosensitivity by reducing irradiation-induced apoptosis of parental cells. In addition, we have showed that Aurora-A could promote the expression of nuclear IkappaB-alpha (IκBα) protein while enhancing the activity of NF-kappaB (κB), thereby promoted expression of NF-κB pathway downstream effectors, including proteins (Mcl-1, Bcl-2, PARP, and caspase-3), all of which are associated with apoptosis. CONCLUSIONS: Aurora-A reduces radiotherapy-induced apoptosis by activating NF-κB signaling, thereby contributing to HCC radioresistance. Our results provided the first evidence that Aurora-A was essential for radioresistance in HCC and targeting this molecular would be a potential strategy for radiosensitization in HCC.

[Cyberknife stereotactic body radiotherapy for liver metastases from prostate cancer].

OBJECTIVE: To investigate the effectiveness and adverse effects of Cyberknife stereotactic body radiotherapy (SBRT) on liver metastases from PCa. METHODS: From June 2009 to September 2016, we treated 20 cases of PCa liver metastases by Cyberknife SBRT, at a total dose of 36 (30－50) Gy, on 1－3 liver metastatic lesions, for 3－5 times, with a prescription isodose line of 70－92%. We assessed the therapeutic effect according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), calculated the survival and disease-control rates using the Kaplan-Meier method, and analyzed the adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events－Version 4.0 (CTCAE 4.0). RESULTS: Of all the cases treated, complete response (CR) was found in 8 (40.0%), partial response (PR) in 9 (45.0%), stable disease (SD) in 2 (10.0%), and progressive disease (PD) in 1 (5.0%), with a local control rate (CR+PR) of 85.0% and a disease-control rate (CR+PR+SD) of 95.0%. Among the 14 patients with elevated PSA, 10 (71.4%) showed a significant decrease after treatment. The median follow-up time was 17 months, the 1- and 2-year survival rates were 85.0% and 15.0%, respectively, and the median survival time of the 20 patients was 16.5 months (95% CI: 12.12－22.88). Cyberknife SBRT was well tolerated in all the patients, with only a few mild adverse events (mainly grades 1 and 2 but no 4 and 5) during the whole course of treatment. CONCLUSIONS: Cyberknife SBRT is safe and effective in the treatment of PCa liver metastases, with a high local control rate, and capable of reducing the PSA level and raising the long-term survival rate of the patients.

MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2.

BACKGROUND/AIMS: Accumulating evidence revealed that microRNAs (miRNAs) have been demonstrated as critical molecules in tumor development and progression. MiR-26a, located in a fragile chromosomal region associated with various human cancer, has been reported to be involved in regulating various cellular process, such as proliferation, apoptosis and invasion through targeting multiple oncogene. Docetaxel-mediated chemotherapy has been applied in improving the survival and prognosis of patients with advanced lung adenocarcinoma (LAD). However, chemoresistance remains a major impediment to clinical application of this agent. It has been presented that decreased miR-26a expression lead to cisplatin resistance and promoted growth and migration in human lung cancer. Enhancer of zeste homolog 2 (EZH2) is the target of miR-26a. The present study aimed to investigate the function of miR-26a/EZH2 in the acquisition of malignant behaviors of LAD. METHODS: MiR-26a and EZH2 expression levels in the dcetaxel-insensitive groups (n = 19) and the docetaxel-sensitive groups (n = 18) were assessed by qRT-PCR. Colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays and western blotting were performed to assess the effects of miR-26a on proliferation, apoptosis and epithelial-to-mesenchymal (EMT) phenotypes in docetaxel resistant LAD cells in vitro. Xenograft transplantation, immunohistochemistry, tunel assays and western blotting assays were employed to demonstrate the role of miR-26a in docetaxel resistant LAD cells in vivo. The expression level of EZH2 in docetaxel-resistant LAD cells and corresponding parental cells was detected by qRT-PCR and western blotting. The relationship between miR-26a and EZH2 was confirmed by luciferase reporter assay. And rescue assays were performed to further confirm that miRNA-26a contributes to the acquisition of malignant behaviors of docetaxel-resistant LAD cells through targeting EZH2. RESULTS: MiR-26a was significantly down-regulated in the dcetaxel-insensitive groups (n = 19) compared with the docetaxel-sensitive groups (n = 18) assessed by qRT-PCR. MiR-26a decreased the proliferation, increased the apoptosis rate and reversed EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro. EZH2 was confirmed as target of miR-26a. Rescue assays further verified that the function of miR-26a exerts in docetaxel-resistant LAD cells is through targeting EZH2. CONCLUSIONS: Our data revealed that overexpression of miR-26a in docetaxel-resistant LAD cells could decrease the proliferation, increase the apoptosis rate and reverse EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro and such function is partially exerted via downregulating EZH2. MiR-26a/EZH2 signal pathway makes contribute to the malignant phenotype of docetaxel-resistant of LAD cells which indicated that miR-26a exerts pivotal functions in the molecular etiology of chemoresistant lung adenocarcinoma.

Long non-coding RNAs in non-small cell lung cancer as biomarkers and therapeutic targets.

Lung cancer-associated mortality is the most common cause of cancer death worldwide. Non-coding RNAs (ncRNAs), with no protein-coding ability, have multiple biological roles. Long non-coding RNAs (lncRNAs) are a recently characterized class of ncRNAs that are over 200 nucleotides in length. Many lncRNAs have the ability of facilitating or inhibiting the development and progression of tumours, including non-small cell lung cancer (NSCLC). Because of their fundamental roles in regulating gene expression, along with their involvement in the biological mechanisms underlying tumourigenesis, they are a promising class of tissue- and/or blood-based cancer biomarkers. In this review, we highlight the emerging roles of lncRNAs in NSCLC, and discuss their potential clinical applications as diagnostic and prognostic markers and as therapeutic targets.

MicroRNA-145: a potent tumour suppressor that regulates multiple cellular pathways.

MicroRNAs are endogenous, small (18-25 nucleotides) non-coding RNAs, which regulate genes expression by directly binding to the 3'-untranslated regions of the target messenger RNAs. Emerging evidence shows that alteration of microRNAs is involved in cancer development. MicroRNA-145 is commonly down-regulated in many types of cancer, regulating various cellular processes, such as the cell cycle, proliferation, apoptosis and invasion, by targeting multiple oncogenes. This review aims to summarize the recent published literature on the role of microRNA-145 in regulating tumourigenesis and progression, and explore its potential for cancer diagnosis, prognosis and treatment.

MicroRNAs: key players of taxane resistance and their therapeutic potential in human cancers.

The successful long-term use of taxane for cancer therapy is often prevented by the development of drug resistance in clinic. Thus, exploring the mechanisms involved is a first step towards rational strategies to overcome taxane resistance. Taxane resistance-related microRNA (miRNAs) are under investigation and miRNAs could induce the taxane resistance of tumour cells by regulating cell cycle distribution, survival and/or apoptosis pathways, drug transports, epithelial-mesenchymal transition and cancer stem cell. This article summarizes current research involving miRNAs as regulators of key target genes for tanxanxe chemoresistance and discusses the complex regulatory networks of miRNAs. Also, the authors will envisage future developments towards the potential use of targeting miRNAs as a novel strategy for improving response of tumour patients to taxane. miRNAs play critical roles in taxane chemoresistance and the miRNA-based therapies will be helpful for overcoming drug resistance and developing more effective personalized anti-cancer treatment strategies. Further research studies should be performed to promote therapeutic-clinical use of taxane resistance-related miRNAs in cancer patients, especially in those patients with taxane-resistant cancers.

MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung adenocarcinoma cells by targeting E2F3.

BACKGROUND: MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. METHODS: We detected miRNA-200b (miR-200b) expression in different lung adenocarcinoma cell lines and then focused on its roles in regulation of docetaxel chemoresistance. We also identified E2F3 as a novel target of miR-200b. RESULTS: Based on miRNA microarray data, miR-200b was identified as the most down-regulated miRNA in docetaxel-resistant SPC-A1/DTX cells compared with parental SPC-A1 cells. Ectopic miR-200b expression reversed docetaxel chemoresistance of lung adenocarcinoma cells through cell proliferation inhibition, apoptosis enhancement, and G(2) /M cell cycle arrest. In a nude mouse xenograft model, up-regulation of miR-200b significantly enhanced response of SPC-A1/DTX cells to docetaxel. Luciferase reporters containing the 3' untranslated region sequence of E2F3 messenger RNA were used to demonstrate that miR-200b could directly target E2F3. Small interfering RNA-mediated E2F3 knockdown revealed similar effects as that of ectopic miR-200b expression. Decreased miR-200b expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with docetaxel-based chemotherapy and was proved to be correlated with high expression of E2F3, decreased sensitivity to docetaxel, and poor prognosis. CONCLUSIONS: Our results suggest that down-regulation of miR-200b could lead to E2F3 overexpression and in turn contribute to chemoresistance of lung adenocarcinoma cells to docetaxel.

Overexpression of survivin is correlated with increased invasion and metastasis of colorectal cancer.

BACKGROUND: The aim of this study was to investigate the association of survivin expression with metastasis of colorectal cancer (CRC). METHODS: RT-PCR and Western blot assays were performed to detect survivin expression in CRC cells and normal intestinal epithelial cell. The expression of survivin gene was also detected in 15 CRC tissues, surrounding and adjacent colon tissues. Moreover, survivin expression in 48 CRC tissues with or without lymph node metastasis was analyzed. Multivariate analysis for lymph node metastasis was performed using logistic regression model. RNA interference was used to inhibit survivin expression in CRC cells and analyze its effect on invasion and metastasis of CRC cells. RESULTS: The expression levels of survivin mRNA and protein were higher in CRC cells than in normal intestinal epithelial cell line. The average levels of survivin mRNA and protein were higher in CRC tissues than surrounding or adjacent colon tissues (P < 0.05). High survivin expression was an independent factor for predicting lymph node metastasis of CRC (P = 0.043). RNAi-mediated survivin knockdown could significantly inhibit in vitro invasion and in vivo metastasis of CRC cells, which might be inactivation of matrix metalloproteinases. CONCLUSION: Targeting survivin will be a potential strategy to suppress metastasis of CRC.

Nimotuzumab increases chemosensitivity of human lung adenocarcinoma cell lines to docetaxel.

Overexpression of epidermal growth factor receptor (EGFR) is common in non-small-cell lung cancer (NSCLC) and has been recently shown to contribute to cancer chemoresistance. It has been reported that the EGFR antibodies such as cetuximab in combination with chemotherapy could lead to an absolute benefit of overall survival (OS) compared with chemotherapy alone. In this study, we investigated the effects of nimotuzumab (h-R3), a humanized anti-EGFR antibody, in combination with docetaxel (DTX), on DTX-resistant human lung adenocarcinoma cell line SPC-A1 (SPC-A1/DTX) both in vitro and in vivo. Immunohistochemistry and FCM assays demonstrated that SPC-A1/DTX cells had a relatively higher rate of EGFR overexpression than SPC-A1 cells. Accordingly, SPC-A1/DTX cells were approximately 13.7 times resistant to DTX than SPC-A1 cells. The combined therapy of h-R3 and DTX showed strong synergistic suppressive effect on cell proliferation of SPC-A1/DTX cells in vitro. The synergistic antitumor effect was also observed in SPC-A1/DTX xenograft-bearing nude mice. Further study showed that h-R3 could lead to a significant cell arrest at G1 phase of cell cycle in both SPC-A1DTX and SPC-A1 cells. A dramatic increase of apoptosis rate was detected in h-R3-treated SPC-A1/DTX but not SPC-A1 cells. Moreover, when combined with DTX, h-R3 brought higher apoptosis rate in SPC-A1/DTX cells rather than in SPC-A1 cells. In conclusion, our results suggested that h-R3 could significantly enhance chemosensitivity of human lung adenocarcinoma cells to DTX, at least partially by induction of G1 phase arrest and cell apoptosis.

[Targeted therapies for hormone-refractory prostate cancer].

Prostate cancer is one of the most common type of cancer among men after middle age. Androgen withdrawal can delay its progression in the initial stage, but it finally becomes independent of androgens in almost all the cases. The combination of docetaxel with prednisone is currently a standard first-line treatment for patients with hormone-refractory prostate cancer (HRPC), but hitherto there is no established second-line therapy. In view of the molecular pathogenesis of HRPC, this article presents an overview on several promising drugs that target specific pathways, involving angiogenesis, cell signaling, apoptosis and proliferation, and immune modulation, either as single agents or in combination with cytotoxic chemotherapy.

XRCC1 genetic polymorphism Arg399Gln and gastric cancer risk: A meta-analysis.

AIM: To evaluate the association between X-ray cross-complementing gene 1 (XRCC1) genetic polymorphism Arg399Gln and gastric cancer risk by means of meta-analysis. METHODS: We searched PubMed and NCBI up to June 1, 2008. A total of 16 clinical trials and reports were identified, but only 8 trials qualified under our selection criteria. Statistical analysis was performed with the software program Review Manage, version 4.2.8. RESULTS: Of the 8 case-control studies selected for this meta-analysis, a total of 1334 gastric cancer cases and 2194 controls were included. For Arg399Gln, the Gln/Gln genotype carriers did not have a decreased cancer risk compared with those individuals with the Arg/Arg genotype (OR = 0.92, 95% CI, 0.71-1.19; P = 0.51). Similarly, no associations were found in the recessive and dominant modeling (Gln/Gln vs Arg/Gln + Arg/Arg: OR = 0.96; 95% CI, 0.77-1.19; P = 0.70 and Gln/Gln + Arg/Gln vs Arg/Arg: OR = 0.90, 95% CI, 0.77-1.05; P = 0.18). CONCLUSION: No association is found between the XRCC1 polymorphism Arg399Gln and gastric cancer risk.

Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients.

AIM: To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma. METHODS: Methylation-specific polymerase chain reaction (MSPCR) was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease (30 with benign gastric disease and 30 with benign colorectal disease), and 30 healthy donor controls. A paired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postoperative serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy. RESULTS: The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric (34.0%) and colorectal (28.9%) adenocarcinoma patients were significantly higher than those in patients with benign gastric (3.3%) or colorectal (6.7%) disease or in healthy donors (0%) (P < 0.01). The methylation status of RASSF1A promoter in serum samples was consistent with that in paired primary tumors, and the MSPCR results for RASSF1A promoter methylation status in paired preoperative samples were consistent with those in postoperative serum samples. The serum RASSF1A promoter hypermethylation did not correlate with patient sex, age, tumor differentiation grade, surgical therapy, or serum carcinoembryonic antigen level. Although the serum RASSF1A promoter hypermethylation frequency tended to be higher in patients with distant metastases, there was no correlation between methylation status and metastasis. CONCLUSION: Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.

[Analysis of RASSF1A promoter hypermethylation in serum DNA of non-small cell lung cancer].

OBJECTIVE: To detect the hypermethylation status of RASSF1A promoter in serum DNA of non-small cell lung cancer (NSCLC) patient and evaluate its correlation with clinicopathological parameters. METHODS: Serum DNA was extracted from the peripheral blood of 75 NSCLC patients and another 35 patients with benign pulmonary disease and 15 healthy donors. The methylation status of RASSF1A promoter was determined using methylation-specific PCR (MSP), and the correlation of methylation profiles with clinicopathological parameters was statistically analyzed. RESULTS: Aberrant methylation of RASSF1A was detected in 23 of 75 (30.7%) cancer patients, but in none of patients with benign pulmonary disease or in healthy donors (P <0.001). RASSF1A hypermethylation status was found to be correlated with late stage and poor differentiation (P < 0.05), but not with gender, age or histopathology in NSCLC patients. CONCLUSION: Hypermethylated RASSF1A promoter is frequently found in the serum DNA of non-small cell lung cancer patient, and RASSF1A may become a promising novel biomarker for diagnosis and prognosis prediction in lung cancer.

[P27Kip1 expression and its prognostic implication in breast carcinoma: a meta-analysis].

OBJECTIVE: To evaluate the relationship between p27Kip1 low expression in breast cancer and its prognostic implication in breast carcinoma patients. Methods All data that were associated with the study of the relationship between p27Kip1 and the prognosis for breast cancer was pooled from Cochrane library, PubMed, Embase and Medlinebase. The outcome was measured using the risk ratio (RR). Data pooling was performed by RevMan 4. 2. Results 6457 patients from 20 studies were included in this meta-analysis. RR estimate of overall survival (OS) for patients with low level p27Kip1 was 2.07 [1.66,2.60] (P<0.01). For disease free survival (DFS), the pooled RR was 1.27 [1.10,1.47] (P<0.05). The combined RR estimate of relapse free survival (RFS) for patients with low level of p27Kip1 was 1.49 [0.92, 2.42] (P >0.05). In patients with lymph node negative breast carcinoma, the combined RR for OS and RFS were 1.98 [1.34,2.91] (P <0.01) and 1.28 [0.45,3.65] (P > 0.05), respectively. Among the patients with lymph node positive breast carcinoma, the combined RR for OS and RFS was 1.92 [1.31, 2.82] (P=0.0009) and 1.35 [0.96,1.89] (P>0.05) respectively. Conclusions Low level of p27Kip1 appears to be an independent prognostic factor to OS and DFS of breast cancer patients but not to RFS. Additional studies with large patient number and widely accepted practical methods are required to derive the precise prognostic significance of p27Kip1 expression in breast cancer patients.

SNHG16/miR-140-5p axis promotes esophagus cancer cell proliferation, migration and EMT formation through regulating ZEB1.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Long noncoding RNAs (lncRNAs) have been identified to be associated with many diseases including tumors, and involved in the regulation of a wide array of pathophysiological processes. Small nucleolar RNA host gene 16 (SNHG16), also known as noncoding RNA expressed in aggressive neuroblastoma, was newly identified as a potential oncogene in many cancers. However, its role in ESCC has not been investigated. In the current study, the level of SNHG16 in the ESCC tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR). Then loss-of-function assays were performed to explore the biological effects of SNHG16 in ESCC cell. Based on the online database analysis tools, we uncovered that miR-140-5p could interact with SNHG16 and the level of miR-140-5p was inverse correlated with SNHG16 in ESCC specimens. Moreover, RIP, RNA pulldown system and dual luciferase reporter assay further provided evidence that SNHG16 directly targets miR-140-5p by binding with microRNA binding site harboring in the SNHG16 sequence. Furthermore, bioinformatics analysis revealed that ZEB1 is a target of miR-140-5p in ESCC. Collectively, our findings suggested that SNHG16 could act as an oncogenic lncRNA that promotes tumor progression through acting as an endogenous 'sponge' by competing with miR-140-5p, thereby regulating target ZEB1.

HDAC3-mediated silencing of miR-451 decreases chemosensitivity of patients with metastatic castration-resistant prostate cancer by targeting NEDD9.

BACKGROUND: Treatment of metastatic castration-resistant prostate cancer (mCRPC) with docetaxel often fails due to the emergence of chemoresistance. Thus, restoring chemosensitivity to docetaxel-based therapies remains a challenge in mCRPC treatment. METHODS: microRNA (miR)-451 expression was measured in docetaxel-treated prostate cancer cells and tumor tissues by quantitative reverse-transcription polymerase chain reaction . Cell-counting kit 8 assay was performed to determine docetaxel chemoresistance. Neural-precursor-cell-expressed developmentally downregulated protein 9 (NEDD9) was identified as a novel target of miR-451 by dual-luciferase reporter system. Chromatin immunoprecipitation and co-immunoprecipitation assay were performed to confirm that histone deacetylase 3 (HDAC3)/Sp1 (a highly evolutionarily conserved transcription factor) interacted with the Sp1 binding sites in miR-451 promoter. RESULTS: miR-451 was found to be silenced in docetaxel-treated prostate cancer cells and mCRPC tissues. Low miR-451 expression was closely associated with a high Gleason score, high Eastern Cooperative Oncology Group performance status score, visceral metastasis and poor prognosis. Low expression of miR-451 was significantly correlated with short progression-free survival (PFS) and overall survival (OS) according to Kaplan-Meier analysis, and miR-451 was determined to be an independent poor prognostic factor for PFS and OS in mCRPC patients by univariate and multivariate Cox regression analyses. NEDD9 was identified as a new and functional target of miR-451. Restoration of NEDD9 partially reversed the effects of miR-451 on enhancing chemosensitivity of prostate cancer cells. HDAC3 was confirmed to be involved in silencing of miR-451 expression in prostate cancer cells. CONCLUSIONS: The current data revealed a new HDAC3/Sp1/miR-451/NEDD9 signaling axis that regulates the chemosensitivity of prostate cancer cells and represents a novel therapeutic target for chemosensitizing mCRPC.

(18)F-DG PET/CT in detection of recurrence and metastasis of colorectal cancer.

AIM: To evaluate the value of (18)F-DG PET/CT in detecting recurrence and/or metastasis of colorectal cancer (CRC). METHODS: Combined visual analysis with semiquantitative analysis, the (18)F-DG PET/CT whole-body imaging results and the corresponding clinical data of 68 postoperative CRC patients including 48 male and 20 female with average age of 58.1 were analyzed retrospectively. RESULTS: Recurrence and/or metastasis were confirmed in 56 patients in the clinical follow-up after the PET/CT imaging. The sensitivity of PET/CT diagnosis of CRC recurrence and/or metastasis was 94.6%, and the specificity was 83.3%. The positive predictive value (PPV) was 96.4% and the negative predictive value (NPV) was 76.9%. PET/CT imaging detected one or more occult malignant lesions in 8 cases where abdominal/pelvic CT and/or ultrasonography showed negative findings, and also detected more lesions than CT or ultrasonography did in 30.4% (17/56) cases. Recurrence and/or metastasis was detected in 91.7% (22/24) cases with elevated serum CEA levels by (18)F-DG PET/CT imaging. CONCLUSION: (18)F-DG PET/CT could detect the recurrence and/or metastasis of CRC with high sensitivity and specificity.

[Advances in researches on hormonal refractory prostate cancer].

In China, the incidence of prostate cancer has been increasing in recent years. Hormonal therapy has been the mainstay of the therapeutic options for metastatic diseases for many years. But many metastatic tumors progress at a median of two to five years and become hormonal refractory prostate cancer (HRPC). This article summarizes in the advances of diagnostic criteria, molecular biological features, prediction markers, new therapeutic agents and further researches to be undertaken concerning HRPC.

[Role of RASSF1A hypermethylation in prostate cancer].

RASSF1A gene cloned from 3p21.3 region is a novel candidate tumor suppressor gene. The aberrant methylation of CpG lands in the promoter region is the major inactivation mechanism of RASSF1A, and is significantly involved in the genesis and development of multiple solid tumors including prostate cancer. The methylation status examination of RASSF1A could serve as an important technique for the early diagnosis of prostate cancer, while methylation inhibitor is likely to become a novel therapeutic agent.

[Current opinions on the treatment of androgen-independent prostate cancer].

Prostate cancer is a most common malignant neoplasm in males. In recent years, its incidence has been rising dramatically in China. Patients with recurrent prostate cancer may be treated with androgen deprivation strategies, but most cases will eventually develop into androgen-independent prostate cancer (AIPC). Until recently, chemotherapy has been shown to be effective in palliating the symptoms of the disease but not in improving survival. Current strategies for the treatment of AIPC have shown significant palliation, but no definitive increase in survival. Molecular mechanisms underlying the development of androgen-independent prostate cancer (AIPC) are poorly understood. However, there is growing evidence that different molecular profiles may result in the development of AIPC. In this paper, we not only review the molecular mechanism of AIPC, but also present some of the promising management principles and systemic chemotherapy options against AIPC.