Tie Zhou

Could plant lectins become promising anti-tumour drugs for causing autophagic cell death?

Plant lectins, a group of highly diverse carbohydrate‐binding proteins of non‐immune origin, are ubiquitously distributed through a variety of plant species, and have recently drawn rising attention due to their remarkable ability to kill tumour cells using mechanisms implicated in autophagy. In this review, we provide a brief outline of structures of some representative plant lectins such as concanavalin A, Polygonatum cyrtonema lectin and mistletoe lectins. These can target autophagy by modulating BNIP‐3, ROS‐p38‐p53, Ras‐Raf and PI3KCI‐Akt pathways, as well as Beclin‐1, in many types of cancer cells. In addition, we further discuss how plant lectins are able to kill cancer cells by modulating autophagic death, for therapeutic purposes. Together, these findings provide a comprehensive perspective concerning plant lectins as promising new anti‐tumour drugs, with respect to autophagic cell death in future cancer therapeutics.

Retrograde Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shockwave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-Analysis and Systematic Review

BACKGROUND AND PURPOSE The optimal treatment of patients with lower pole renal stones continues to be a dilemma for urologists. Retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), and extracorporeal shockwave lithotripsy (SWL) all constitute viable therapeutic options in selected patients. The aim of this study was to assess the efficacy and safety of RIRS, PCNL, and SWL in management of lower pole renal stones. METHODS A literature search was performed in July 2014 using PubMed, Embase, and Web of Science databases. Literature reviewed included meta-analysis and randomized and nonrandomized controlled studies to identify relevant studies for the meta-analysis. RESULTS Six randomized and eight nonrandomized studies were identified for analysis. PCNL provided a significantly higher stone-free rate (SFR) compared with RIRS and SWL. Furthermore, no statistical significant difference was found when PCNL was compared with RIRS and SWL for complication rate. Compared with the other two treatments, RIRS had a longer operative time and PCNL had a longer hospital stay. SWL was associated with significantly higher re-treatment rate compared with RIRS and PCNL, whereas there were no significant differences in auxiliary procedure rates among the three treatment techniques. CONCLUSION RIRS offers a relative higher SFR while it has a longer operative time. PCNL is associated with the highest SFR at the expense of the longest hospital stay. SWL is performed as an outpatient procedure with a relative shorter operative time; however, it has lower a SFR and higher re-treatment rate. The categories of complications vary while the overall complication rates are comparable among the three treatment techniques.

Testosterone and Androgen Receptor in Human Nephrolithiasis

PURPOSE We investigated the relationship of kidney calculi with plasma free and total testosterone, and androgen receptor up-regulation in the kidneys of men with nephrolithiasis. MATERIALS AND METHODS Male patients with kidney stone and healthy men were included in the study. Blood was collected in a tube containing 2% heparin in the morning. Total and free serum testosterone was measured by enzyme linked immunosorbent assay. All patients underwent percutaneous nephrostolithotomy. At the end of the procedure ultrasound guided puncture biopsy was done to acquire kidney tissue. Normal kidney tissue obtained at autopsy served as the control. Androgen receptor was detected in kidney tissue by immunohistochemistry. Stone composition was analyzed in each patient. RESULTS The study included 37 male patients 22 to 39 years old and 31 healthy men 24 to 37 years old. All calculi were composed of calcium oxalate monohydrate or calcium oxalate dihydrate and a few also contained protein or uric acid. Mean±SD serum total and free testosterone was 13.29±4.79 ng/ml and 63.23±28.58 pg/ml in patients, and 7.30±0.82 ng/ml and 35.59±24.91 pg/ml in healthy men, respectively (each p<0.001). Immunohistochemistry revealed androgen receptor up-regulation in the kidneys of patients with nephrolithiasis. CONCLUSIONS Our data suggest the important role of enhanced androgen signaling in human nephrolithiasis.

Plateau effect of prostate cancer risk-associated SNPs in discriminating prostate biopsy outcomes.

Additional prostate cancer (PCa) risk‐associated single nucleotide polymorphisms (SNPs) continue to be identified. It is unclear whether addition of newly identified SNPs improves the discriminative performance of biopsy outcomes over previously established SNPs.

Effects of Hyperbaric Oxygen Therapy on Tumor Growth in Murine Model of PC-3 Prostate Cancer Cell Line

OBJECTIVES To test the hypothesis that hyperbaric oxygen (HBO) has no effect on tumor growth in a murine model of indolent in vivo prostate cancer. HBO means breathing pure (100%) oxygen under increased atmospheric pressure. METHODS Human prostate PC-3 cells were injected into 40 severe combined-immunodeficient mice. They were randomized to undergo 20 sessions of either HBO or normobaric air in standardized conditions and observed for 4 weeks before histologic assessment of any palpable tumors that had developed. The analysis of the developed PC-3 tumors included tumor volume, microvessel density, apoptosis-associated markers (ie, p53, p27), and the proliferative index (Ki-67). RESULTS The exposure to HBO at 2 atm for 20 treatment sessions, which comprised a daily 90-minute session, 5 d/wk, had no effect on the prostate cancer volume (P > .05). No differences were observed in tumor microvessel density, proliferative index, or apoptosis markers compared with the non-HBO group (P > .05). CONCLUSIONS HBO did not have a tumor stimulatory effect on prostate cancer and could potentially be used safely in conjunction with other therapeutic modalities.

A multicenter, randomized clinical trial comparing the three-weekly docetaxel regimen plus prednisone versus mitoxantone plus prednisone for Chinese patients with metastatic castration refractory prostate cancer.

Purpose To explore the feasibility and efficacy of docetaxel plus prednisone for Chinese population with metastatic castration refractory prostate cancer (mCRPC). Patients and methods A total of 228 patients recruited from 15 centers were randomized to receive 10 cycles of D3P arm (docetaxel: 75 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily) or M3P arm (mitoxantrone: 12 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily). Primary end point was overall survival, and secondary end points were events progression-free survival (PFS), response rate, response duration. Quality of life (QoL) was also assessed in both treatment groups. Results The median overall survival was 21.88 months in D3P arm and 13.67 months in M3P arm (P = 0.0011, hazard ratio = 0.63, 95% confidence interval, 0.46–0.86). Subgroup analysis was consistent with the results of overall analysis. Events progression-free survival (pain, PSA, tumor and disease) were significantly improved in D3P arm compared with M3P arm. PSA response rate was 35.11% for patients treated by D3P arm and 19.39% for M3P arm (P = 0.0155). Pain response rate was higher in D3P arm (61.11%, P = 0.0011) than in M3P (23.08%) arm. No statistical differences were found between D3P arm and M3P arm for QoL, tumor response rate and response duration of PSA and pain. The tolerability and overall safety of D3P arm were generally comparable to that of M3P arm. Conclusions Compared with M3P arm, D3P arm significantly prolonged overall survival for the Chinese patients with mCRPC and improved the response rate for PSA and pain. Trial Registration clinicaltrials.gov NCT00436839

Indirect comparison between abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer: a systematic review

This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate (AA) and enzalutamide (Enz) for metastatic castration-resistant prostate cancer (mCRPC). A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA (active comparator) and Enz (true placebo) randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings (HR: 0.90, 95% CI, 0.73-1.11; HR: 0.85, 95% CI, 0.68-1.07). Compared with AA, Enz may better outperform control arms in treating mCRPC both before and after chemotherapy regarding secondary endpoints based on indirect comparisons: time to prostate-specific antigen (PSA) progression (HR: 0.34, 95% CI, 0.28-0.42; HR: 0.40, 95% CI, 0.30-0.53), radiographic progression-free survival (HR: 0.37, 95% CI, 0.28-0.48; HR: 0.61, 95% CI, 0.50-0.74), and PSA response rate (OR: 18.29, 95% CI, 11.20-29.88; OR: 10.69, 95% CI, 3.92-29.20). With regard to the effectiveness of Enz following AA or AA following Enz, recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy. However, confirmatory head-to-head trials are necessary to determine the optimal sequencing of these agents.

Effect of varicocelectomy on testis volume and semen parameters in adolescents: a meta-analysis

Varicocele repair in adolescent remains controversial. Our aim is to identify and combine clinical trials results published thus far to ascertain the efficacy of varicocelectomy in improving testis volume and semen parameters compared with nontreatment control. A literature search was performed using Medline, Embase and Web of Science, which included results obtained from meta-analysis, randomized and nonrandomized controlled studies. The study population was adolescents with clinically palpable varicocele with or without the testicular asymmetry or abnormal semen parameters. Cases were allocated to treatment and observation groups, and testis volume or semen parameters were adopted as outcome measures. As a result, seven randomized controlled trials (RCTs) and nonrandomized controlled trials studying bilateral testis volume or semen parameters in both treatment and observation groups were identified. Using a random effect model, mean difference of testis volume between the treatment group and the observation group was 2.9 ml (95% confidence interval [CI]: 0.6, 5.2; P< 0.05) for the varicocele side and 1.5 ml (95% CI: 0.3, 2.7; P< 0.05) for the healthy side. The random effect model analysis demonstrated that the mean difference of semen concentration, total semen motility, and normal morphology between the two groups was 13.7 × 10 6 ml−1 (95% CI: −1.4, 28.8; P = 0.075), 2.5% (95% CI: −3.6, 8.6; P= 0.424), and 2.9% (95% CI: −3.0, 8.7; P= 0.336) respectively. In conclusion, although varicocelectomy significantly improved bilateral testis volume in adolescents with varicocele compared with observation cases, semen parameters did not have any statistically significant difference between two groups. Well-planned, properly conducted RCTs are needed in order to confirm the above-mentioned conclusion further and to explore whether varicocele repair in adolescents could improve subsequently spontaneous pregnancy rates.

Radioiodine therapy for castration - resistant prostate cancer following prostate - specific membrane antigen promoter - mediated transfer of the human sodium iodide symporter

Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter (hNIS). Here, we explore the efficacy of a novel form of gene therapy using prostate-specific membrane antigen (PSMA) promoter-mediated hNIS gene transfer followed by radioiodine administration for the treatment of castration-resistant prostate cancer (CRPC). The androgen-dependent C33 LNCaP cell line and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS (Ad.PSMApro-hNIS) or adenovirus.cytomegalovirus–hNIS containing the cytomegalovirus promoter (Ad.CMV-hNIS) or a control virus. The iodide uptake was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the hNIS gene linked to PSMA and the corresponding tumor volume fluctuation were assessed. Iodide accumulation was shown in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after adenovirus.cytomegalovirus (Ad.CMV) infection. At each time point, higher iodide uptake was shown in the C81 cells infected with Ad.PSMApro-hNIS than in the C33 cells (P < 0.05). An in vivo animal model showed a significant difference in 131I radioiodine uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus (P < 0.05) and a maximum reduction of tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specific expression of the hNIS gene delivered by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.

Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

Disordered copper metabolism plays a critical role in the development of various cancers. As a nanomedicine containing copper, cuprous oxide nanoparticles (CONPs) exert ideal antitumor pharmacological effects in vitro and in vivo. Prostate cancer is a frequently diagnosed male malignancy prone to relapse, and castration resistance is the main reason for endocrine therapy failure. However, whether CONPs have the potential to treat castration-resistant prostate cancer is still unknown. Here, using the castration-resistant PC-3 human prostate cancer cell line as a model, we report that CONPs can selectively induce apoptosis and inhibit the proliferation of cancer cells in vitro and in vivo without affecting normal prostate epithelial cells. CONPs can also attenuate the stemness of cancer cells and inhibit the Wnt signaling pathway, both of which highlight the great potential of CONPs as a new clinical castration-resistant prostate cancer therapy.