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Background: Both apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) inhibition and melatonin suppress prostate cancer (PCa) growth., Objective: This study evaluated the therapeutic efficiency of self-assembled and prostate-specific membrane antigen (PSMA)-targeted nanocarrier loading 125 I radioactive particles and encapsulating siRNA targeting APE1 (siAPE1) and melatonin for PCa., Methods: The linear polyarginine R12 polypeptide was prepared using Fmoc-Arg-Pbf-OH. The PSMA-targeted polymer was synthesized by conjugating azide-modified R12 peptide to PSMA monoclonal antibody (mAb). Before experiments, the PSMA-R12 nanocarrier was installed with melatonin and siAPE1, which were subsequently labeled by 125 I radioactive particles. In vitro biocompatibility and cytotoxicity of nanocomposites were examined in LNCaP cells and in vivo biodistribution and pharmacokinetics were determined using PCa tumor-bearing mice., Results: PSMA-R12 nanocarrier was ~120 nm in size and was increased to ~150 nm by melatonin encapsulation. PSMA-R12 nanoparticles had efficient loading capacities of siAPE1, melatonin, and 125 I particles. The co-delivery of melatonin and siAPE1 by PSMA-R12- 125 I showed synergistic effects on suppressing LNCaP cell proliferation and Bcl-2 expression and promoting cell apoptosis and caspase-3 expression. Pharmacokinetics analysis showed that Mel@PSMA-R12- 125 I particles had high uptake activity in the liver, spleen, kidney, intestine, and tumor, and were accumulated in the tumor sites within the first 8 h p.i., but was rapidly cleared from all the tested organs at 24 h p.i. Administration of nanoparticles to PCa tumors in vivo showed that Mel@PSMA-R12- 125 I/siAPE1 had high efficiency in suppressing PCa tumor growth., Conclusion: The PSMA-targeted nanocarrier encapsulating siAPE1 and melatonin is a promising therapeutic strategy for PCa and can provide a theoretical basis for patent applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms., Methods: Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation., Results: A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218μmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients., Conclusion: Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

On March 23, 2022, the U.S. Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan), also known as 177Lu-PSMA-617, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who have highly expressed prostate-specific membrane antigen (PSMA) and have at least one metastatic lesion. It is the first FDA-approved targeted radioligand therapy for eligible men with PSMA-positive mCRPC. Lutetium Lu 177 vipivotide tetraxetan is a radioligand that strongly binds to PSMA, making it ideal for treating cancers of the prostate by targeted radiation, resulting in DNA damage and cell death. PSMA is overexpressed in cancer cells while being lowly expressed in normal tissues, which makes it an ideal theranostic target. As precision medicine advances, this is a thrilling turning point for highly individualized treatments. This review aims to summarize the pharmacology and clinical studies of the novel drug lutetium Lu 177 vipivotide tetraxetan for the treatment of mCRPC, emphasizing its mechanism of action, pharmacokinetics and safety., (Copyright 2023 Clarivate.)

Objective: To compare the safety of transurethral plasma resection of the prostate (TuPkRP) in the treatment of advanced PCa (APC)-related acute urinary retention (AUR) with that in the treatment of BPH-related AUR and investigate the oncologic characteristics of the PCa patient after TuPkRP., Methods: In this retrospective study, we first compared the baseline data between the patients with APC-related AUR (group A, n = 32) and those with BPH-related AUR (group B, n = 45) as well as their surgical parameters, such as the operation time, pre- and post-operative hemoglobin levels, IPSS at 3 months after TuPkRP and length of postoperative hospital stay. Then, we observed possible TuPkRP-induced tumor progression by comparing the oncologic parameters, such as the PSA level and ECT-manifested bone metastasis, between the APC-AUR patients treated by androgen-deprivation therapy (ADT) + TuPkRP and those treated by ADT only (group C, n = 24)., Results: There were no statistically significant differences in the baseline data between the APC-AUR and BPH-AUR patients (P > 0.05). The operation time and postoperative hospital stay were significantly longer in the APC-AUR than in the BPH-AUR group (P < 0.05), but the decreases in the hemoglobin level and IPSS at 3 months after operation showed no significant differences between the two groups of patients (P > 0.05). Besides, no statistically significant differences were observed in the oncologic parameters between the APC-AUR patients treated by ADT + TuPkRP and those by ADT only (P > 0.05)., Conclusion: The safety of TuPkRP was not significantly lower and the rates of postoperative complications and adverse events were not significantly higher in the patients with APC-related AUR than in those with BPH-related AUR. And this surgical strategy did not significantly improve the progression of APC.

Bladder cancer is one of the most common cancers. Approaches that block tumor angiogenesis are a new therapeutic strategy for locally advanced or metastatic BC. VEGF/VEGFR signaling has been obviously and negatively correlated with the progression and invasion of cancer. In this study, we constructed the recombinant adenovirus vAd-VEGFR-3 to investigate its antitumor effector in vitro/vivo . First, we used the recombinant adenovirus vAd-VEGFR-3 to infect bladder cancer cells and then collected the cell culture supernatant to treat human umbilical vein endothelial cells (HUVECs). The proliferation, migration and apoptosis of HUVECs were respectively detected by MTT, transwell and Annexin V-FITC/PI double staining. In addition, mouse bladder mucosa was injured by trypsin, and the orthotopic transplantation model of human bladder cancer was successfully constructed to clarify the anti-tumor effect of Ad-VEGFR in vivo . The results showed that Ad-VEGFR could inhibit the cancer's proliferation and migration, while promoting the apoptosis of HUVECs in vitro . Moreover, Ad-VEGFR could significantly promote the apoptosis of bladder cancer cells and then prevent tumor growth in vivo . In addition, it also down-regulated the expression levels of CD31, an endothelial cell marker which is closely related to the angiogenesis. Taken together, it suggests that the infection of adenovirus-carrying VEGFR in bladder cancer cells may inhibit blood vessel formation and prevent tumor progression., Competing Interests: None., (IJCEP Copyright © 2018.)

Objective: To study the expression of long noncoding RNA (lncRNA) H19 in human prostate cancer tissue and its effect on the glycometabolism and growth of human prostate cancer cells., Methods: Realtime quantitative RTPCR (qRTPCR) was employed to detect the expression of lncRNA H19 in human prostate tissues from 20 patients with prostate cancer (10 cases of highGleason score prostate cancer ［HGPC］ and 10 cases of lowGleason score prostate cancer ［LGPC］) and another 5 with benign prostatic hyperplasia (BPH). After transfection of H19 siRNA into the DU145 and PC3 prostate cancer cells, the growth of the cells and the H19 expression in the cells were determined by MTT and qRTPCR respectively, and the changes in the glycometabolism of the prostate cancer cells were analyzed by measuring the contents of glucose and lactate in the culture medium. Nontransfected and transfected negative vectors were used as blank and negative controls respectively., Results: The relative expression of H19 was significantly increased in both the HGPC and LGPC tissues (0.725±0.385 and 2.086±0.542) as compared with that in the BPH tissue (0.210±0.068) (P< 0.01), even higher in the HGPC than in the LGPC tissue (P< 0.01). After transfection of H19 siRNA, the expressions of H19 were remarkably decreased in the DU145 and PC3 prostate cancer cells in comparison with those in the blank control and negative control groups (P< 0.01), and so were the proliferation of and the glucose and lactate levels in the DU145 and PC3 cells (P< 0.01).