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Tumor-positive resection margins after surgery can result in tumor recurrence and metastasis. Although adjuvant postoperative radiotherapy and chemotherapy have been adopted in clinical practice, they lack efficacy and result in unavoidable side effects. Herein, a self-intensified in-situ therapy approach using electrospun fibers loaded with a biomimetic nanozyme and doxorubicin (DOX) is developed. The fabricated PEG-coated zeolite imidazole framework-67 (PZIF67) is demonstrated as a versatile nanozyme triggering reactions in cancer cells based on endogenous H

One of the great challenges of postoperative prostate cancer management is tumor recurrence. Although postoperative chemotherapy presents benefits to inhibit unexpected recurrence, it is still limited due to the drug resistance or intolerable complications of some patients. Electrospun nanofiber, as a promising drug carrier, demonstrating sustained drug release behavior, can be implanted into the tumor resection site during surgery and is conductive to tumor inhibition. Herein, we fabricated electrospun nanofibers loaded with doxorubicin (DOX) and ABT199 to synergistically prevent postoperative tumor recurrence. Enzymatic degradation of the biodegradable electrospun nanofibers facilitated the release of the two drugs. The primarily released DOX from the electrospun nanofibers effectively inhibited tumor recurrence. However, the sustained release of DOX led to drug resistance of the tumor cells, yielding unsatisfactory eradication of the residual tumor. Remarkably, the combined administration of DOX and ABT199, simultaneously released from the nanofibers, not only prolonged the chemotherapy by DOX but also overcame the drug resistance via inhibiting the Bcl-2 activation and thereby enhancing the apoptosis of tumor cells by ABT199. This dual-drug-loaded implant system, combining efficient chemotherapy and anti-drug resistance, offers a prospective strategy for the potent inhibition of postoperative tumor recurrence.

Acute antibody-mediated rejection (AAMR) is an important cause of cardiac allograft dysfunction, and more effective strategies need to be explored to improve allograft prognosis. Interleukin (IL)-6/IL-6R signaling plays a key role in the activation of immune cells including B cells, T cells and macrophages, which participate in the progression of AAMR. In this study, we investigated the effect of IL-6/IL-6R signaling blockade on the prevention of AAMR in a mouse model. We established a mouse model of AAMR for cardiac transplantation via presensitization of skin grafts and addition of cyclosporin A, and sequentially analyzed its features. Tocilizumab, anti-IL-6R antibody, and recipient IL-6 knockout were used to block IL-6/IL-6R signaling. We demonstrated that blockade of IL-6/IL-6R signaling significantly attenuated allograft injury and improved survival. Further mechanistic research revealed that signaling blockade decreased B cells in circulation, spleens, and allografts, thus inhibiting donor-specific antibody production and complement activation. Moreover, macrophage, T cell, and pro-inflammatory cytokine infiltration in allografts was also reduced. Collectively, we provided a highly practical mouse model of AAMR and demonstrated that blockade of IL-6/IL-6R signaling markedly alleviated AAMR, which is expected to provide a superior option for the treatment of AAMR in clinic.

Prostate cancer is the second most common malignancy among men worldwide. However, conventional chemotherapy, such as taxane therapy, fails to exhibit efficient treatment for almost half of the patients. In this study, a nano-drug delivery system based on black phosphorus nanosheets (BP NSs) was developed, which was then employed as a multifunctional nanoplatform for targeted combinational chemo-photothermal therapy against prostate cancer. Zinc ion (Zn2+), which has been proven to be able to inhibit prostate cancer cell proliferation, was also introduced into this system. Zn2+ coordination could not only enhance the therapeutic effect of combined chemo-photothermal therapy, but also improve the intrinsic instability of BP NSs through the stabilization of its lone pair electrons. The in vivo study showed the outstanding performance of this system in targeted photothermal/chemotherapy of prostate cancer without side effect to normal organs.

Nanoscopic therapeutic systems that incorporate therapeutic agents, molecular targeting, and imaging capabilities have gained momentum and exhibited significant therapeutic potential. In this study, multifunctional polymeric nanoparticles with controlled drug delivery, cancer-targeted capability, and efficient magnetic resonance imaging (MRI) contrast characteristics were formulated and applied in the treatment of castration-resistant prostate cancer (CRPC). The “core-shell” targeted nanoparticles (NPs) were synthesized by the self-assembly of a prefunctionalized amphiphilic triblock copolymer composed of poly(lactic-co-glycolic-acid) (PLGA), polyethylene glycol (PEG), and the Wy5a aptamer (Apt), which have been screened for targeting the CRPC cell line PC-3 by cell-SELEX technique as described in our previous study. Docetaxel (Dtxl) and a cluster of hydrophobic superparamagnetic iron oxide (SPIO) nanoparticles were simultaneously encapsulated into the targeted nanoparticles. The targeted NPs showed a controlled drug release and an increased contrast-enhanced MRI capability. The presence of Wy5a on the nanoparticle surface resulted in the cancer-targeted delivery to PC-3 cells in vitro and in vivo. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI and increased cytotoxicity of these targeted NPs. In vivo studies revealed that the targeted NPs exhibited a more efficacious antitumor capability without significant systemic toxicity. Our data suggested that these targeted NPs may be a promising drug delivery system for the efficacious treatment of CRPC.

The development of multitargeting drugs is an emerging trend in cancer research. To promote further development and clinical application of multitargeting drugs, this research was performed. MTT assay and flow cytometry of Annexin V/propidium iodide staining were used to confirm the proapoptotic efficacy of a novel combi-targeting molecule, JDF12, against DU145 prostate cancer (PCa) cells. Differentially expressed proteins between control and JDF12-treated cultures were revealed by isobaric tags for relative and absolute quantitation (iTRAQ), and part of them was confirmed by quantitative PCR. Differentially expressed proteins were further analyzed for function, pathway association, and protein−protein interactions using GO, KEGG, and STRING databases. A total of 119 differentially expressed proteins, 70 upregulated and 49 downregulated, were implicated in the anticancer effects of JDF12. Many of these proteins are involved in biosynthesis, response to stress, energy metabolism, and signal transduction. This study provides important information for understanding the anti-PCa mechanisms of JDF12, and well-designed combi-targeting drugs may possess stronger anticancer efficacy than single-targeting drugs and are thus promising candidates for clinical application.

Background: To compare the efficacy and safety of local infiltration anesthesia and mucous surface anesthesia in patients undergoing trans-rectal ultrasound-guided (TRUS guided) prostate biopsy. Methods: Patients with suspected prostate cancer undergoing TRUS guided prostate biopsy were randomly divided into two groups between January 2018 and March 2019. Local infiltration anesthesia was performed in the experimental group with lidocaine; while the control group was treated with mucous surface anesthesia. We collected baseline characteristics. Residual urine volume was measured twice: before biopsy, the first micturition after biopsy. Associated complications, positive rate of biopsy, visual analog pain scale (VAS) and Gleason score were recorded. Results: The study included 78 patients. The pain score of experimental group was significantly lower than the control group. Experimental group had lower rate of urinary retention and catheterization. Both groups had similar positive rate of biopsy, residual urine volume, Gleason score, fever and so on. Conclusion: Comparing with mucous surface anesthesia, local infiltration anesthesia relieved the pain better in patients undergoing TRUS guided prostate biopsy. It was more effective and safer. Trial registration: Chinese Clinical Trial Registry, Trial registration number (TRN): ChiCTR1800016424, Date of registration: 01/06/ 2018.

Prostate Cancer (PCa) is one of the most common cancers and has ranks first among cancers which endanger the health of men and have surpassed lung and colon cancers in the United States [1].

Percutaneous Nephrolithotomy (PCNL) and Retrograde Intrarenal Surgery (RIRS) are widely used in the management of kidney stones. But the safety and efficiency between these two technologies is still a mystery. This meta-analysis was performed to compare the efficacy as well as safety of Minimally Invasive Percutaneous Procedures (MIPPs) including ultra mini-PCNL, mini-PCNL, and micro-PCNL with RIRS. PubMed, Embase and Scopus were searched, and twelve studies included data on 1207 cases (613 for MIPPs and 594 for RIRS) satisfied the inclusion criteria and were included in this research finally. MIPPs were found to be associated with higher stone-free rate but longer hospital stays, and a larger drop in hemoglobin levels. Difference between MIPPs and RIRS in complication rate, operative time, and total cost were not notable. Given no obvious difference in the complication rate and higher efficacy, our findings suggest that mini-PCNL should be recommended over RIRS for stones>2 cm, and that for stones

Recently, several drugs have been introduced for the first-line treatment of chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but few studies have compared treatment outcomes directly. This indirect comparison among 10 clinical trials (n= 4870 patients) retrieved from PubMed, Web of Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T for the initial treatment of mCRPC. No significant differences in primary outcome (overall survival) were found among initial treatments. However, docetaxel had the highest probability (37.53%) of being the most effective, but at the cost of more adverse events, while enzalutamide was associated with the best secondary outcomes (prostate-specific antigen response, progression-free survival, quality of life, and adverse event profile). Thus, docetaxel is recommended as the first agent used for the chemotherapy of mCRPC, while enzalutamide is recommended as the first nonchemotherapy treatment. Additional clinical trials are needed to confirm these findings and establish the optimal order for multidrug treatment of mCRPC.

To compare the effectiveness and safety between retroperitoneal laparoscopic nephrectomy (RLN) and transperitoneal laparoscopic nephrectomy (TLN) for nonfunctional tuberculous kidneys (NTK).From March 2013 to February 2016, 24 patients with NTK underwent laparoscopic nephrectomy in our department. Eleven patients underwent RLN, and 13 underwent TLN. The demographics and perioperative outcomes were compared retrospectively.Characteristics, including gender, age, body mass index, and location, were similar in these two groups. All operations were successfully completed in the RLN group, while 1 case in the TLN group was converted to open surgery due to severe adhesions and excessive bleeding (1 of 13 patients). Time to oral intake after surgery in the TLN and RLN group was 43.85 ± 6.01 hours and 27.45 ± 6.83 hours (P .05). No notable differences were found between two groups in terms of estimated blood loss, operative time, days of drain removal, and postoperative hospital stay. No local or disseminated recurrence was identified during the follow-up period.Taking the same safety and effectiveness into consideration, TLN can be an alternative choice for experienced surgeons to deal with NTK. Also, further studies with a larger sample size should be performed to confirm this finding.

This study aimed to assess the role of pre-designed route on computer tomography urography (CTU) in the ultrasound-guided percutaneous nephrolithotomy (PCNL) for renal calculus. From August 2013 to May 2016, a total of 100 patients diagnosed with complex renal calculus in our hospital were randomly divided into CTU group and control group (without CTU assistance). CTU was used to design a rational route for puncturing in CTU group. Ultrasound was used in both groups to establish a working trace in the operation areas. Patients’ perioperative parameters and postoperative complications were recorded. All operations were successfully performed, without transferring to open surgery. Time of channel establishment in CTU group (6.5 ± 4.3 minutes) was shorter than the control group (10.0 ± 6.7 minutes) (P = .002). In addition, there was shorter operation time, lower rates of blood transfusion, secondary operation, and less establishing channels. The incidence of postoperative complications including residual stones, sepsis, severe hemorrhage, and perirenal hematoma was lower in CTU group than in control group. Pre-designing puncture route on CTU images would improve the puncturing accuracy, lessen establishing channels as well as improve the security in the ultrasound-guided PCNL for complex renal calculus, but at the cost of increased radiation exposure.

Prostate cancer, the most commonly diagnosed male cancer in North America, has a high incidence of bone metastasis. Our previous study showed collapsin response mediator protein 4 (CRMP4) gene inhibited prostate cancer migration and invasion. In this study, we investigated whether overexpression of CRMP4 gene in prostate cancer cells inhibit tumor bone metastasis. The stable prostate cancer cells overexpressing the CRMP4 gene were constructed using lentivirus infection. Prostate cancer bone metastasis nude mouse model was built though orthotopic prostate implantation, intracardiac injection and intratibial injection with CRMP4 overexpress and control cancer cells. Small animal PET/CT scanning results showed no difference of bone metastatic capacity in orthotopic and intracardiac injection models between CRMP4 overexpression and control group, while CRMP4 overexpression inhibited tumor growth in the intratibial injection model. Moreover, our in vitro study showed CRMP4 overexpression downregulates the Neuropilin1 (NRP1) expression and upregulate the Noggin expression. Immunohistochemical staining of the hind limbs of intratibial injection model was confirmed with cytological experiments. Taken together, our research indicated CRMP4 inhibits prostate cancer cells growth in the nude mouse bone microenvironment and this effect may relate with regulation of NRP1 and Noggin expression.

PURPOSE At the preclinical stage, mitozolomide (MTZ) showed exciting preclinical activity but failed later in clinical trial due to toxic side effects. We surmised that by targeting MTZ to epidermal growth factor receptor (EGFR), we may not only alter its toxicity profile, but also enhance its potency in EGFR-overexpressing tumors. To test this hypothesis, we designed JDF12, studied its mechanism of action in human prostate cancer (PCa) cells and determined its potency in vivo. EXPERIMENTAL DESIGN To analyze its mixed EGFR-DNA targeting potential, we performed an enzyme linked immunosorbent assay (ELISA) and western blotting analysis of EGFR phosphorylation in cells stimulated with EGF. DNA damage was analyzed using the comet assay, and apoptosis quantitated by annexin V binding assay. Growth inhibition in vitro was determined by the sulforhodamine B (SRB) assay and in vivo efficacy analyzed in male CD-1 nude mice. RESULTS The results showed that: Under physiological conditions, JDF12 was hydrolyzed to JDF04R and both agents were capable of inhibiting isolated EGFR tyrosine kinase (TK) and EGFR phosphorylation in EGF-stimulated cells. JDF12 significantly damaged DNA, induced apoptosis in DU145 cells and was up to 2–10-fold more potent than equieffective combinations of MTZ and JDF04R or Iressa in a panel that also included LNCaP and its EGFR and ErbB2 transfectants. In vivo, it induced significant antitumor activity in a DU145 xenograft model. CONCLUSIONS The results suggest that the superior cytotoxicity of JDF12 when compared with MTZ and JDF04R may be imputed to its potent EGFR-DNA targeting properties and confirm the ability of this novel strategy to confer EGFR targeting properties to a classical alkylator. Prostate 72:1273–1285, 2012. © 2012 Wiley Periodicals, Inc.

To monitor the subcellular distribution of mixed epidermal growth factor (EGF) receptor (EGFR)–DNA targeting drugs termed combi-molecules, we designed AL237, a fluorescent prototype, to degrade into a green fluorescent DNA damaging species and FD105, a blue fluorescent EGFR inhibitor. Here we showed that AL237 damaged DNA in the 12.5 to 50 μmol/L range. Despite its size, it blocked EGFR phosphorylation in an enzyme assay (IC50 = 0.27 μmol/L) and in MDA-MB468 breast cancer cells in the same concentration range as for DNA damage. This translated into inhibition of extracellular signal-regulated kinase 1/2 or BAD phosphorylation and downregulation of DNA repair proteins (XRCC1, ERCC1). Having shown that AL237 was a balanced EGFR-DNA targeting molecule, it was used as an imaging probe to show that (a) green and blue colors were primarily colocalized in the perinuclear and partially in the nucleus in EGFR- or ErbB2-expressing cells, (b) the blue fluorescence associated with FD105, but not the green, was colocalized with anti-EGFR red-labeled antibody, (c) the green fluorescence of nuclei was significantly more intense in NIH 3T3 cells expressing EGFR or ErbB2 than in their wild-type counterparts (P < 0.05). Similarly, the growth inhibitory potency of AL237 was selectively stronger in the transfectants. In summary, the results suggest that AL237 diffuses into the cells and localizes abundantly in the perinuclear region and partially in the nucleus where it degrades into EGFR and DNA targeting species. This bystander-like effect translates into high levels of DNA damage in the nucleus. Sufficient quinazoline levels are released in the cells to block EGF-induced activation of downstream signaling. Mol Cancer Ther; 9(4); 869–82. ©2010 AACR.

Objective: This study aimed to investigate the biological effects of “combi-targeting” JDF12 and its effect on the DNA repair pathway in hormone-refractory prostate cancer (HRPC). Methods: HRPC cell lines (PC3 cells and VCap cells) were treated with JDF12 at different concentrations, and SRB method was employed to detect the proliferation of HRPC cells; Annexin V-FITC kit was used to detect the apoptosis of PC3 cells; Alkaline comet assay was performed to detect DNA damage; Western blot assay was done to detect the expressions of autophosphorylated EGFR, XRCC1 and ERCC1 (later two are proteins in DNA repair pathway); the anti-tumor effect was evaluated in nude mice inoculated with PC3 cells. Results: JDF12 could inhibit the proliferation of PC3 cells and VCap cells in a concentration dependent manner (IC50: 14.04 ± 1.22 for PC3 and 15.57 ± 1.13 for VCap) and significantly increase the apoptotic cells as compared to those treated with mitozolomide or iressa alone. In PC3 cells, JDF12 induced DNA damage and also inhibited the expressions of phosphorylated EGFR, XRCC1 and ERCC1 in a concentration dependent manner. Moreover, JDF12 markedly inhibited tumor growth in nude mice. Conclusion: The novel “combi-targeting” JDF12 may exert more potent anti-proliferative effect as compared to mitozolomide or iressa alone, and the inhibitory effect on the EGFR signaling pathway and down-regulated XRCC1 and ERCC1 expressions may be ascribed to the JDF12 induced DNA damage.

Xin Gao,1,* Yun Luo,1,* Yuanyuan Wang,1,* Jun Pang,1 Chengde Liao,2 Hanlun Lu,3 Youqiang Fang11Department of Urology, The Third Affiliated Hospital, 2Department of Radiology, The Second Affiliated Hospital, Sun Yat-Sen University, 3Materials Science Institute of Zhongshan University, Guangzhou, China*These authors contributed equally to this workBackground: We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer.Methods: Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-glycolic acid), docetaxel, and hydrophobic superparamagnetic iron oxide nanocrystals (SPIONs), a multilayer shell formed by poly(allylamine hydrochloride) and two different sized poly(ethylene glycol) molecules, and a single-chain prostate stem cell antigen antibody conjugated to the nanoparticle surface for targeted delivery.Results: Drug release profiles indicated that the dual-function nanoparticles had a sustained release pattern over 764 hours, and SPIONs could facilitate the controlled release of the drug in vitro. The nanoparticles showed increased antitumor efficiency and enhanced magnetic resonance imaging in vitro through targeted delivery of docetaxel and SPIONs to PC3M cells. Moreover, in nude mice bearing PC3M xenografts, the nanoparticles provided MRI negative contrast enhancement, as well as halting and even reversing tumor growth during the 76-day study duration, and without significant systemic toxicity. The lifespan of the mice treated with these targeted dual-function nanoparticles was significantly increased (Chi-square = 22.514, P < 0.0001).Conclusion: This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo.Keywords: nanoparticle, prostate cancer, targeting, chemotherapy, imaging

PURPOSE: To compare the curative effects of ureteroscopic lithotripsy and laparoscopic ureterolithotomy for unilateral upper ureteral stones, and to explore optimal surgical indications and skills. METHODS: Fifty cases of unilateral upper ureteral stones were randomly divided into two groups: one group underwent ureteroscopic holmium laser lithotripsy under epidural or lumbar anesthesia (n=25), and another group underwent laparoscopic ureterolithotomy under general anesthesia (n=25). Double-J stent was routinely indwelled in both groups. Operating time, postoperative hospitalization time, stone clearance rate and perioperative complications were compared. RESULTS: Operation was successfully performed in all 50 cases, and no open surgery was converted in any case. In the ureteroscopy and laparoscopy groups, the mean operating time was 49.0±10.7 min and 41.8±8.0 min (t=2.68, P=0.00999), respectively, their hospitalization time was 2.8±1.3 days vs. 2.9±0.8 days (t =-0.40, P=0.69413), and stone clearance rate was 88.0% (22/25) vs. 100% (25/25). Stone moved to the renal pelvis in three cases in the ureteroscopy group, and residual stones were removed by extracorporeal shock-wave lithotripsy (ESWL). All patients were followed up for more than three months, and no serious complications such as ureterostenosis occurred. CONCLUSIONS: Laparoscopic ureterolithotomy has a higher stone clearance rate and shorter operation time compared with ureteroscopic lithotripsy. Laparoscopic ureterolithotomy is one safe and effective treatment on unilateral upper ureteral stones. OBJETIVO: Comparar os efeitos curativos da litotripsia ureteroscópica e a ureterolitotomia laparoscópica para cálculos unilaterais altos e pesquisar as indicações e resultados. MÉTODOS: Cinquenta casos de cálculos unilaterais altos foram distribuídos aleatoriamente em dois grupos: um grupo submetido a litotripsia ureteroscópica com laser holmium sob anestesia epidural ou lombar (n=25) e outro grupo submetido a ureterolitotomia laparoscópica sob anestesia geral (n=25). Duplo-J stent foi rotineiramente instalado em ambos os grupos. Comparou-se o tempo operatório, tempo de hospitalização pós-operatória, nível de desaparecimento dos cálculos e complicações pós-operatórias. RESULTADOS: Atos operatórios nos 50 casos sem ocorrências e nenhum ato convertido. Nos grupos por ureteroscopia e laparoscopia, o tempo operatório médio foi 49,0±10,7 minutos e 41,8±8,0 minutos (t=2,68, P=0,00999) respectivamente, tempo de hospitalização foi 2,8±1,3 dias vs. 2,9±0,8 dias (t=0,40, P=0,69413) e o nível de desaparecimento dos cálculos foi 88.0% (22/25) vs. 100% (25/25). Cálculo deslocado para pelve renal em três casos no grupo ureteroscópico e cálculos residuais foram removidos por litotripsia por onda de choque extracorpóreo (ESWL). Todos pacientes foram seguidos por mais de três meses e não ocorreram complicações sérias como estenoses ureterais. CONCLUSÕES: A ureterolitotomia laparoscópica teve maior nível desaparecimento dos cálculos e tempo operatório menor comparado à litotripsia ureteroscópica A ureterolitotomia laparoscópica é um tratamento seguro e efetivo para cálculos ureterais unilaterais altos.

A superior drug controlled release system capable of achieving efficient osteogenesis is in imperative demand because of limited bone substitute tissue for the treatment of bone defect. In the present study, we investigated the potential of using poly(e-caprolactone)–hydroxyapatite (PCL–HA) composite microspheres as an injectable bone repair vehicle by controlled release of alendronate (AL), a medicine that belongs to the bisphosphonates family. The PCL/HA–AL microspheres were prepared with solid/oil/water emulsion technique, which included two processes: (1) AL was loaded on the hydroxyapatite nanoparticles; (2) the HA–AL complex was built in the PCL matrix. The spherical PCL/HA–AL microspheres were characterized with its significantly improved encapsulation efficiency of hydrophilic AL and better sustained release. Human bone mesenchymal stem cells (hMSCs) were cultured on the surface of these microspheres and exhibited high proliferative profile. Specifically, in osteogenic medium, hMSCs on the surface of PCL/HA–AL microspheres displayed superior osteogenic differentiation which was verified by alkaline phosphatase activity assay. In conclusion, by presenting strong osteogenic commitment of hMSCs in vitro, the PCL/HA–AL microspheres have the potential to be used as an injectable vehicle for local therapy of bone defect.

Current predictive tools and imaging modalities are not accurate enough for preoperative diagnosis of lymph node metastatic prostate cancer (LNM PCa). Proteomic analysis is introduced to screen potential biomarkers for early detection of LNM PCa. In our initial study, protein samples from localized and LNM PCa as well as benign prostatic hyperplasia tissues were analyzed using two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) coupled with MALDI-TOF/TOF MS. We identified 58 proteins that were differentially expressed in the LNM PCa group relative to the localized PCa group. Six of these proteins, e-FABP5, MCCC2, PPA2, Ezrin, SLP2, and SM22, are functionally relevant to cancer metastasis. Expression of these proteins was therefore further validated in tissue samples from the original cohort and also from a larger, independent cohort of patients using real time PCR, Western blotting, and immunohistochemistry staining. In addition, the serum levels of e-FABP5 were also examined by ELISA. Relative to localized PCa tissues, LNM PCa tissues had increased expression of e-FABP5, MCCC2, PPA2, Ezrin, and SLP2 and decreased expression of SM22. Patients with LNM PCa had significantly higher levels of serum e-FABP5. This study presents evidence that increased expression of e-FABP5, MCCC2, PPA2, Ezrin, and SLP2 and decreased expression of SM22 are useful diagnostic markers for the existence of LNM PCa.

Combi-molecules are novel agents designed to be hydrolyzed into two bioactive species: an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor + a DNA alkylating agent. With the purpose of enhancing the tumour concentration of the bioactive species, we synthesized and compared the activities of RB107, a quinazolinotriazene designed to generate the bioactive BJ2000 upon hydrolysis, ZRDM and RB107ZR that require metabolic activation to generate BJ2000. The results showed that RB107 released the highest level of BJ2000 and its degradation product FD105 in vivo and high levels of the DNA alkylating methyl diazonium ion in the brain, kidney, liver and the DU145 tumours as confirmed by (14)C-labeling. The results in toto suggest that RB107 was stable enough to deliver the bioactive species to the tumour site and for optimal tumour distribution of the bioactive species, combi-molecules of the triazene class must be designed to be primarily degraded by hydrolytic cleavage and not by metabolic activation.

Retroperitoneal laparoscopic ureterolithotomy is a new option to treat upper and middle ureter calculi in selected patients. However, migration of the stone and the flow of urine will influence the success.We have developed a new and practical method using a clamp proximally above the stone to fix its position and prevent urine flow. Twenty patients had undergone retroperitoneal laparoscopic ureterolithotomy using this method. A bulldog artery clamp was used as the temporary clamp and was placed at the proximal part of the ureter during the procedures of incision, intubation and suture.The average age of the patients was 42.5 years (range: 26-73) and the average stone size was 13.7 mm (range: 10-28). The average operating time was 38.2 min (range: 30-85). All target stones were successfully extracted without major complications. The average time of post-operation drain removal was 1.5 days. No case of prolonged urine leakage or ureter stricture was recorded.We conclude that using a temporary ureter clamp is a feasible and practical method to fix the stone and minimize the difficulty of retroperitoneal laparoscopic ureterolithotomy.

OBJECTIVE To identify differential protein expression in penile tissue in a rat model of erectile dysfunction (ED) at an early stage after bilateral cavernosal nerve (CN) neurectomy, using proteomic techniques. MATERIALS AND METHODS Twelve male adult Sprague-Dawley rats were randomly divided into two equal groups, one having bilateral CN resection and one a control group. The penises were harvested 7 days after CN resection. Total protein was separated into >1250 protein spots by two-dimensional electrophoresis using pH 3-10 nonlinear immobilized pH gradient strips. Differential expression of proteins was analysed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and database searching. RESULTS Thirty-two proteins were significantly changed in the denervated penis, of which 25 (including nine up-regulated and 16 down-regulated) with cytoskeletal functions, and pathophysiological functions related to energy metabolism and oxidative stress, were identified. Examples include transgelin, creatine kinase B, annexin-1 and galactin-7. CONCLUSIONS The expression of several important proteins participating in pathophysiological processes of penile tissue are changed early after bilateral CN neurectomy. These changes might give new insights into the cellular and molecular mechanisms involved in neurogenic ED development, and indicate potential therapeutic targets.