Improving Image-Guided Surgical and Immunological Tumor Treatment Efficacy by Photothermal and Photodynamic Therapies Based on a Multifunctional NIR AIEgen.

Multimodal therapy is attracting increasing attention to improve tumor treatment efficacy, but generally requires various complicated ingredients combined within one theranostic system to achieve multiple functions. Herein, a multifunctional theranostic nanoplatform based on a single aggregation-induced-emission luminogen (AIEgen), DDTB, is designed to integrate near-infrared (NIR) fluorescence, photothermal, photodynamic, and immunological effects. Intravenously injected AIEgen-based nanoparticles can efficiently accumulate in tumors with NIR fluorescence to provide preoperative diagnosis. Most of the tumors are excised under intraoperative fluorescence navigation, whereafter, some microscopic residual tumors are completely ablated by photodynamic and photothermal therapies for maximally killing the tumor cells and tissues. Up to 90% of the survival rate can be achieved by this synergistic image-guided surgery and photodynamic and photothermal therapies. Importantly, the nanoparticles-mediated photothermal/photodynamic therapy plus programmed death-ligand 1 antibody significantly induce tumor elimination by enhancing the effect of immunotherapy. This theranostic strategy on the basis of a single AIEgen significantly improves the survival of cancer mice with maximized therapeutic outcomes, and holds great promise for clinical cancer treatment.

Statin Use at the Time of Initiation of Androgen Deprivation Therapy and Time to Progression in Patients With Hormone-Sensitive Prostate Cancer.

IMPORTANCE: Statin use has been associated with improved prostate cancer outcomes. Dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone and a substrate for SLCO2B1, an organic anionic transporter. We previously demonstrated that genetic variants of SLCO2B1 correlated with time to progression (TTP) during receipt of androgen deprivation therapy (ADT). Statins also use SLCO2B1 to enter cells, and thus we hypothesized that they may compete with DHEAS uptake by the tumor cells. OBJECTIVE: To evaluate whether statin use prolongs TTP during ADT for hormone-sensitive prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: In vitro studies were performed using prostate cancer cell lines at an academic, comprehensive cancer center. Statin use was retrospectively analyzed in 926 patients who had received ADT for biochemical or metastatic recurrence or de novo metastatic prostate cancer between January 1996 and November 2013. MAIN OUTCOMES AND MEASURES: To determine whether statins interfere with DHEAS uptake, we performed in vitro studies using prostate cancer cell lines. Next, we queried our institutional clinical database to assess for an association between statin use and TTP during ADT using multivariable Cox regression analysis and adjusted for known prognostic factors. RESULTS: In vitro, we demonstrated that statins block DHEAS uptake by competitively binding to SLCO2B1. In our ADT cohort of 926 patients, 283 (31%) were taking a statin at ADT initiation. After a median follow-up of 5.8 years, 644 patients (70%) had experienced disease progression while receiving ADT. Median TTP during ADT was 20.3 months (95% CI, 18-24 months). Men taking statins had a longer median TTP during ADT compared with nonusers (27.5 [95% CI, 21.1-37.7] vs 17.4 [95% CI, 14.9-21.1] months; P < .001). The association remained statistically significant after adjusting for predefined prognostic factors (adjusted hazard ratio, 0.83 [95% CI, 0.69-0.99]; P = .04). The positive statin effect was observed for both patients with and without metastases (adjusted hazard ratio, 0.79 [95% CI, 0.58-1.07] for M0 disease and 0.84 [95% CI, 0.67-1.06] for M1 disease; P for interaction = .72). CONCLUSIONS AND RELEVANCE: Statin use at the time of ADT initiation was associated with a significantly longer TTP during ADT even after adjustment for known prognostic factors. Our in vitro finding that statins competitively reduce DHEAS uptake, thus effectively decreasing the available intratumoral androgen pool, affords a plausible mechanism to support the clinical observation of prolonged TTP in statin users.

Comparation of the predictive value between ultrasonography and urodynamics for the efficacy of transurethral resection of prostate in benign prostatic hyperplasia patients.

BACKGROUND: Transurethral resection of prostate (TURP) has been widely used as a golden standard therapy of benign prostatic hyperplasia for over 40 years. However, not all patients achieved favorable outcome postoperatively. Since the level of bladder outlet obstruction and the dysfunction of detrusor (overactive and underactive) were both found to affect surgical efficacy, urodynamics was recommended as routine preoperative examination in selecting proper surgical candidates by International Continence Society in spite of its invasiveness and high cost. The aim of this research was to compare the predictive value between ultrasonography and urodynamics for TURP efficacy and determine if preoperative urodynamic test could be replaced by ultrasonography. METHODS: Two hundred and seventy-one patients took part in the retrospective analysis. All the subjects had preoperative evaluation of symptoms, life quality, and combined examination of ultrasonography and urodynamics. Surgical efficacy was measured according to the recovery of international prostate symptom score, quality of life score, and maximal flow rate 6 months after TURP. Fisher's linear discriminant analysis was applied to establish the predictive models of surgical efficacy by choosing parameters from ultrasonography or urodynamics as independent factors. Receiver's operating characteristic curve was then plotted to compare the values between the models. RESULTS: Sensitivity, specificity, positive and negative predictive value of models consisting of parameters from both ultrasonography and urodynamics were favorable. Corresponding models of ultrasonography and urodynamics were found to have non-significant difference in area under curve (P > 0.05). CONCLUSIONS: Preoperative ultrasonography has as strong value as urodynamics does in predicting surgical outcome of patients undergone TURP and might take the place of urodynamics in selecting surgical candidates. Further prospective analysis with larger popularity and longer period of follow up should be launched to verify the result of this research.

[Transurethral plasmakinetic enucleation of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To evaluate clinical application of transurethral plasmakinetic enucleation of the prostate (PKEP) to the treatment of benign prostatic hyperplasia (BPH). METHODS: A total of 90 BPH patients, aged 59-83 (mean 71) years and with indication of surgery, underwent transurethral resection of the prostate (the TURP group, n=50) and transurethral plasmakinetic enucleation of the prostate (the PKEP group, n=40), respectively. We recorded and analyzed the preoperative prostate volume, IPSS, QOL and Qmax, operation time, intra- and post-operative bleeding and complications, postoperative continuous bladder irrigation, and IPSS, QOL and Qmax at 2 weeks and 6 months after surgery. RESULTS: The preoperative prostate volume and operation time were 58.9 g and 58.8 min in the TURP group versus 58.3 g and 93.0 min in the PKEP group. Mild transurethral resection syndrome (TURS) appeared in 2 TURP receivers, while no abnormality was found in electrocardiogram monitoring in those undergoing PKEP. Continuous bladder irrigation was necessitated in 3 and urgent incontinence of urine occurred in 4 cases of TURP, as compared with 1 and 4 cases in the PKEP group. None of the 90 patients needed blood transfusion. At 2 weeks before and after surgery and 6 months postoperatively, IPSS averaged 19.7, 11.6 and 5.1, QOL 4.6, 3.3 and 1.1, and Qmax 6.3, 13.0 and 18.1 ml/s in the TURP group versus 18.6, 8.4 and 4.9 (IPSS), 4.5, 2.7 and 1.1 (QOL) and 6.9, 14.2 and 19.0 ml/s (Qmax) in the PKEP group. There were significant differences in operation time, IPSS and QOL at 2 weeks postoperatively between the two groups, as well as in IPSS, QOL and Qmax at 6 months before and after surgery (P < 0.01). But no remarkable differences were found in preoperative prostate volume, IPSS, QOL and Qmax, 6-month postoperative IPSS and QOL, and Qmax at 2 weeks and 6 months after surgery between the two groups (P > 0.01). CONCLUSION: Transurethral PKEP is a safe, effective and thorough surgical method to be chosen for the treatment of BPH.