Enzalutamide Sensitizes Castration-Resistant Prostate Cancer to Copper-Mediated Cell Death.

Despite the initial efficacy of enzalutamide in castration-resistant prostate cancer (CRPC), inevitable resistance remains a significant challenge. Here, the synergistic induction of copper-dependent cell death (cuproptosis) in CRPC cells is reported by enzalutamide and copper ionophores (elesclomol/disulfiram). Mechanistically, enzalutamide treatment increases mitochondrial dependence in CRPC cells, rendering them susceptible to cuproptosis, as evidenced by specific reversal with the copper chelator tetrathiomolybdate. This susceptibility is characterized by hallmarks of cuproptosis, including lipoylated protein aggregation and iron-sulfur cluster protein instability. Interestingly, the mitochondrial matrix reductase, FDX1, specifically correlates with elesclomol sensitivity, suggesting a potential mechanistic divergence between the two copper ionophores. Notably, this synergistic effect extends beyond in vitro models, demonstrating efficacy in 22Rv1 xenografts, mouse Pten p53 knockout organoids. Importantly, enzalutamide significantly enhances copper ionophore-mediated cytotoxicity in enzalutamide-resistant cells. Collectively, these findings indicate that enzalutamide and copper ionophores synergistically induce cuproptosis, offering a promising therapeutic avenue for CRPC, potentially including enzalutamide-resistant cases.

Expression and localization of HSD17B13 along mouse urinary tract.

17ß-hydroxysteroid dehydrogenase-13 (HSD17B13), a newly identified lipid droplet-associated protein, plays an important role in the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Emerging evidence demonstrates that NASH is an independent risk factor for chronic kidney disease (CKD), which is frequently accompanied by renal lipid accumulation. In addition, the HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven NAFLD. At present, the role of HSD17B13 in lipid accumulation in the kidney is unclear. ​This study utilized bioinformatic and immunostaining approaches to examine the expression and localization of HSD17B13 along mouse urinary tract. We found that HSD17B13 is constitutively expressed in the kidney, ureter and urinary bladder. Our findings reveal for the first time the precise localization of HSD17B13 in mouse urinary system, providing a basis for further studying the pathogenesis of HSD17B13 in various renal and urological diseases.

A meta-analysis of postoperative wound complications at the surgical site in prostate cancer patients undergoing robotic surgery.

This meta-analysis critically evaluates the role of robotic surgery in reducing postoperative wound complications in prostate cancer patients, comparing it with traditional open and laparoscopic approaches. Our extensive literature search resulted in 9 studies comprising 2063 patients. The results highlighted a significant reduction in the incidence of wound complications, with an 84% heterogeneity index and a standardized mean difference (SMD) of 0.49 (95% Confidence Intervals: 0.42 to 0.58, p < 0.01) in favour of robotic surgery. Additionally, a notable decrease in wound infection rates was observed, marked by a 94% heterogeneity index and a SMD of 0.26 (95% CIs: 0.19 to 0.35, p < 0.01). A considerable reduction in wound dehiscence events was also noted, particularly in a subset of studies, reflecting a 70% heterogeneity index and a SMD of 0.23 (95% CIs: 0.12 to 0.45, p < 0.01). These findings suggest that robotic surgery may offer significant advantages in managing wound-related outcomes in prostate cancer surgeries. However, the variability among the studies warrants cautious interpretation of the results and underscores the need for more targeted research in this area.

14-3-3-η interacts with BCL-2 to protect human endothelial progenitor cells from ox-LDL-triggered damage.

Oxidized low-density lipoprotein (ox-LDL) causes dysfunction of endothelial progenitor cells (EPCs), and we recently reported that 14-3-3-η can attenuate the damage triggered by ox-LDL in EPCs. However, the molecular mechanisms by which 14-3-3-η protects EPCs from the damage caused by ox-LDL are not fully understood. In this study, we observed that the expression of 14-3-3-η and BCL-2 were downregulated in ox-LDL-treated EPCs. Overexpression of 14-3-3-η in ox-LDL-treated EPC significantly increased BCL-2 level, while knockdown of BCL-2 reduced 14-3-3-η expression and mitigated the protective effect of 14-3-3-η on EPCs. In addition, we discovered that 14-3-3-η colocalizes and interacts with BCL-2 in EPCs. Taken together, these data suggest that 14-3-3-η protects EPCs from ox-LDL-induced damage by its interaction with BCL-2.

Value of three-dimensional visualization of preoperative prostatic magnetic resonance imaging based on measurements of anatomical structures in predicting positive surgical margin after radical prostatectomy.

Background: Positive surgical margin (PSM) or apical positive surgical margin (APSM) is an established predictive factor of biochemical recurrence or disease progression in prostate cancer (PCa) patients after radical prostatectomy. Since there are limited usable magnetic resonance imaging (MRI)-based models, we sought to explore the role of three-dimensional (3D) visualization for preoperative MRI in the prediction of PSM or APSM. Methods: From December 2016 to April 2022, 149 consecutive PCa patients who underwent radical prostatectomy were retrospectively selected from the Second Affiliated Hospital of Dalian Medical University. According to the presence of PSM or APSM, patients were divided into a PSM group (n=41) and a without PSM group (n=108) and into an APSM group (n=33) and a without APSM group (n=116). Twenty-one parameters, including prostate apical shape, PCa distance to the membranous urethra, and pubic angle, were measured on 3D visualization of MRI. The development of the nomogram models was built by the findings of multivariate logistic regression analysis for significant factors. Results: To predict the probability of PSM, a longer PCa distance to the membranous urethra (OR=0.136, p=0.019) and the distance from the anterior peritoneum to the anterior border of the coccyx (work space AP, OR=0.240, p=0.030) were independent protective factors, while a type 3 prostate apical shape (OR=8.262, p=0.025) and larger pubic angle 2 (OR=5.303, p=0.029) were identified as independent risk factors. The nomogram model presented an area under the curve (AUC) of the receiver operating characteristic curve (ROC) of PSM of 0.777. In evaluating the incidence of APSM, we found that the distance to the membranous urethra (OR=0.135, p=0.014) was associated with a low risk of APSM, while larger pubic angle 1 (OR=4.666, p=0.043) was connected to a higher risk of APSM. The nomogram model showed that the AUC of APSM was 0.755. Conclusion: As 3D visualization for preoperative MRI showed good performance in predicting PSM or APSM, the tool might be potentially valuable, which also needs to be validated by multicenter, large-scale, prospective studies.

Cervical lymphadenopathy as initial presentation of metastatic prostate cancer: A retrospective study of five cases and literature review.

Cervical lymphadenopathy as the initial presentation of metastatic prostate cancer is particularly uncommon, and easily misdiagnosed. In the current study, we describe five cases of metastatic prostate cancer in our hospital that presented with cervical lymphadenopathy as an initial symptom. The diagnosis was confirmed by needle biopsy of the suspicious lymph nodes and the serum prostate specific antigen (PSA) levels of all patients exceeded 100 ng/ml. The five patients were treated with hormonal therapy; four received traditional hormonal therapy, including bicalutamide and goserelin; one patient received hormonal therapy that included abiraterone and goserelin. Case 1 developed into castration-resistant prostate cancer (CRPC) after 7 months and died after 12 months. Case 2 rejected regular hormonal therapy for personal reasons and died 6 months after the initial diagnosis. Case 3 was still alive at the time of writing. Case 4 was administered with abiraterone, prednisolone and goserelin; the treatment was effective and the patient has remained symptom-free for the last 24 months. Case 5 was treated with hormonal and chemotherapy but died 8 months after diagnosis. In conclusion, any elderly male presenting with cervical lymphadenopathy should be considered the possibility of prostate cancer, especially when the needle biopsy reveals adenocarcinoma. The prognosis for patients presented with cervical lymphadenopathy as the initial presentation is usually poor. Hormone therapy based on abiraterone may yield a better response in such cases.

Immunohistochemical analysis of PD-L1 and tumor-infiltrating immune cells expression in the tumor microenvironment of primary signet ring cell carcinoma of the prostate.

Primary signet ring cell carcinoma (SRCC) of the prostate is a rare neoplasm. However, its potential tumorigenic mechanism, clinicopathological features, and prognostic outcome have not been systematically described. To determine the pathogenic mechanism, we detected distributions of programmed cell death-ligand 1 (PD-L1), programmed death 1 (PD-1), and cellular components in the tumor microenvironment, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (TAMs; CD163 and CD68), and tumor-associated fibroblasts (vimentin and alpha-smooth muscle actin [α-SMA]), in tumor tissues from four patients with primary prostatic SRCC compared with corresponding adjacent tissues and tumor tissues from 30 patients with prostate adenocarcinoma (PCa) by immunohistochemical staining. We found higher expression of PD-L1, CD163, and CD68 in primary SRCC specimens than that in both corresponding adjacent nontumor specimens and PCa specimens with different Gleason scores, indicating that TAMs may participate in the malignant biological behavior of primary SRCC of the prostate. For further analysis, we searched electronic journal databases and Surveillance, Epidemiology, and End Results (SEER) to identify 200 eligible patients including our four cases. According to Kaplan-Meier survival curve analysis, patients <68 years old, with radical prostatectomy (RP), Gleason score of 7-8, and lower clinical stage had longer overall survival (OS). Moreover, Cox multivariate analysis indicated that race (hazard ratio [HR] = 1.422), surgical approach (HR = 1.654), and Gleason score (HR = 2.162) were independent prognostic factors for OS. Therefore, primary SRCC of the prostate represents a distinct and aggressive subtype of prostate cancer associated with a higher distribution of PD-L1 and TAMs, which warrants further clinical investigation.

Upregulation of SDHA inhibited proliferation, migration, and invasion of clear cell renal cell carcinoma cells via inactivation of the Wnt/ß-catenin pathway.

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with high mortality. Recent findings suggest that the succinate dehydrogenase complex subunit A (SDHA) is lowly expressed in many types of cancers and involved in tumorigenesis. However, the potential regulatory roles and molecular mechanisms by which SDHA affects the development and progression of ccRCC remain largely unknown. In this study, our results showed that there was significant downregulation of SDHA in ccRCC tissue relative to corresponding non-cancerous tissue, and low expression of SDHA was associated with Fuhrman pathological grade, tumor size, TNM stage, metastasis, and poor prognosis in ccRCC patients. Moreover, overexpression of SDHA inhibited the proliferation, invasion, and migration capacities of ccRCC cells. Mechanistically, SDHA impeded the proliferation and metastasis of ccRCC cells by inactivation of the Wnt/ß-catenin pathway. In vivo experiments, SDHA suppressed ccRCC growth in a nude mouse model. In conclusion, our study results indicated that SDHA may act as a new molecular marker for judging the occurrence and development of ccRCC and serve as a therapeutic target for the treatment of human ccRCC.

MET inhibition enhances PARP inhibitor efficacy in castration-resistant prostate cancer by suppressing the ATM/ATR and PI3K/AKT pathways.

Up to 30% of patients with metastatic castration-resistant prostate cancer (CRPC) patients carry altered DNA damage response genes, enabling the use of poly adenosine diphosphate-ribose polymerase (PARP) inhibitors in advanced CRPC. The proto-oncogene mesenchymal-epithelial transition (MET) is crucial in the migration, proliferation, and invasion of tumour cells. Aberrant expression of MET and its ligand hepatocyte growth factor is associated with drug resistance in cancer therapy. Here, we found that MET was highly expressed in human CRPC tissues and overexpressed in DU145 and PC3 cells in a drug concentration-dependent manner and is closely related to sensitivity to PARP inhibitors. Combining the PARP inhibitor olaparib with the MET inhibitor crizotinib synergistically inhibited CRPC cell growth both in vivo and in vitro. Further analysis of the underlying molecular mechanism underlying the MET suppression-induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib-induced antitumour effect in DU145 and PC3 cells. In conclusion, we demonstrated that MET inhibition enhances sensitivity of CRPC to PARP inhibitors by suppressing the ATM/ATR and PI3K/AKT pathways and provides a novel, targeted therapy regimen for CRPC.

Targeting c-MET to Enhance the Efficacy of Olaparib in Prostate Cancer.

PURPOSE: Prostate cancer is the second leading cause of cancer death in men worldwide. Olaparib is clinically approved for the treatment prostate cancer, but cytotoxicity and off-target effects including DNA damage limit its clinical applications. In the current study, new strategies to improve the therapeutic efficacy of olaparib for the treatment of prostate cancer were investigated. METHODS: Two prostate cancer cell lines were exposed to the c-MET inhibitor PHA665752 and/or the PARP inhibitor olaparib. Cell counting kit-8, colony formation assays, and transwell assays were conducted to evaluate the cytotoxicity of olaparib alone or in combination with PHA665752 in prostate cancer cell lines. Western blotting, immunofluorescence staining, and the comet assay were used to assess the effects of PHA665752 on olaparib-induced DNA damage. RESULTS: Combined inhibition of c-MET and PARP resulted in effective and synergistic blocking of the growth of prostate cancer cell lines. Invasion and migration were significantly suppressed when the agents were combined. Mechanistically, dual blocking of PARP and c-MET in prostate cancer cell lines was associated with an impaired DNA damage response. Interestingly, immunofluorescence staining analysis of RAD51 protein indicated that the c-MET inhibitor PHA665752 significantly impaired homologous repair via downregulated translocation of RAD51 into the nucleus in prostate cancer cells. CONCLUSION: The combination of the c-MET inhibitor PHA665752 and the PARP inhibitor olaparib may be a promising therapeutic strategy in patients with prostate cancer.

Magnetic Resonance Imaging (MRI)-Targeted Biopsy in Patients with Prostate-Specific Antigen (PSA) Levels <20 ng/mL: A Single-Center Study in Northeastern China.

BACKGROUND We investigated the feasibility of applying magnetic resonance imaging (MRI)-targeted biopsy (TB) in patients with prostate-specific antigen (PSA) levels <20 ng/mL. MATERIAL AND METHODS We retrospectively analyzed 218 patients with PSA levels <20 ng/mL and suspicious lesions according to the Prostate Imaging Recording and Data System version 2.0 (PI-RADS v2). All 218 men underwent transperineal MRI-TB, followed by template-guided 12-core systematic biopsy (SB). Of the 218 patients undergoing TB, 100 received MRI-ultrasound-assisted software fusion biopsy (FB) and 118 received cognitive biopsy (CB). Clinically significant prostate cancer (csPCa) was defined as a Gleason score ≥3+4. RESULTS The overall TB positive rate was similar to that of SB (P=0.156), but with a higher diagnostic rate for csPCa (P=0.034). SB misdiagnosed csPCa in 11.47% of cases; TB misdiagnosed csPCa in 5.50% of cases. SB+TB detected more tumors with a Gleason score of 7 than did SB alone (43 vs 22). Detection rates of csPCa were similar for CB and FB (P=0.217). In total, 47 men had 2 MRI-determined suspicious areas. Of 265 suspicious areas, 143 (53.96%) had a PI-RADS v2 score of 3; 92 (34.71%) had a score of 4; and 30 (11.32%) had a score of 5. The positive detection rates for csPCa in patients with PI-RADS v2 scores of 3, 4, and 5, were 11.19%, 48.91%, and 80.00%, respectively. CONCLUSIONS TB increased the positive biopsy detection rate but missed some cases of csPCa. TB combined with SB may be the most suitable biopsy for patients with PSA <20 ng/mL.

BTF3 confers oncogenic activity in prostate cancer through transcriptional upregulation of Replication Factor C.

High levels of Basic Transcription Factor 3 (BTF3) have been associated with prostate cancer. However, the mechanisms underlying the role of BTF3 as an oncogenic transcription factor in prostate tumorigenesis have not been explored. Herein, we report that BTF3 confers oncogenic activity in prostate cancer cells. Mechanistically, while both BTF3 splicing isoforms (BTF3a and BTF3b) promote cell growth, BTF3b, but not BTF3a, regulates the transcriptional expression of the genes encoding the subunits of Replication Factor C (RFC) family that is involved in DNA replication and damage repair processes. BTF3 knockdown results in decreased expression of RFC genes, and consequently attenuated DNA replication, deficient DNA damage repair, and increased G2/M arrest. Furthermore, knockdown of the RFC3 subunit diminishes the growth advantage and DNA damage repair capability conferred by ectopic overexpression of BTF3b. Importantly, we show that enforced BTF3 overexpression in prostate cancer cells induces substantial accumulation of cisplatin-DNA adducts and render the cells more sensitive to cisplatin treatment both in vitro and in vivo. These findings provide novel insights into the role of BTF3 as an oncogenic transcription factor in prostate cancer and suggest that BTF3 expression levels may serve as a potential biomarker to predict cisplatin treatment response.

The Environmental Pollutant Bromophenols Interfere With Sulfotransferase That Mediates Endocrine Hormones.

Bromophenols (BPs), known as an important environmental contaminant, can cause endocrine disruption and other chronic toxicity. The study aimed to investigate the potential inhibitory capability of BPs on four human sulfotransferase isoforms (SULT1A1, SULT1A3, SULT1B1 and SULT1E1) and interpret how to interfere with endocrine hormone metabolism. P-nitrophenol(PNP) was utilized as a nonselective probe substrate, and recombinant SULT isoforms were utilized as the enzyme resources. PNP and its metabolite PNP-sulfate were analyzed using a UPLC-UV detecting system. SULT1A1 and SULT1B1 were demonstrated to be the most vulnerable SULT isoforms towards BPs' inhibition. To determine the inhibition kinetics, 2,4,6-TBP and SULT1A3 were selected as the representative BPs and SULT isoform respectively. The competitive inhibition of 2,4,6-TBP on SULT1A3. The fitting equation was y=90.065x+1466.7, and the inhibition kinetic parameter (Ki) was 16.28 µM. In vitro-in vivo extrapolation (IVIVE) showed that the threshold concentration of 2,4,6-TBP to induce inhibition of SULT1A3 was 1.628 µM. In silico docking, the method utilized indicated that more hydrogen bonds formation contributed to the stronger inhibition of 3,5-DBP than 3-BP. In conclusion, our study gave the full description of the inhibition of BPs towards four SULT isoforms, which may provide a new perspective on the toxicity mechanism of BPs and further explain the interference of BPs on endocrine hormone metabolism.

[Comparison of clinical efficacy of two different arthroscopic release methods for the treatment of primary frozen shoulder].

OBJECTIVE: To compare clinical effects of inside-out technique and outside-in technique for the treatment of idiopathic frozen shoulder under arthroscopy. METHODS: From April 2015 to July 2019, 65 patients with primary frozen shoulder were divided into observation group and control group according to different treatment methods. In observation group, there were 32 cases, including 14 males and 18 females, aged 48 to 64 (54.82±5.35) years old, 18 cases on the right side and 14 cases on the left side. The course of disease was 4 to 10 (7.76±1.19) months. The patients were treated with outside in technique. In control group, there were 33 cases, 16 males and 17 females, aged 45 to 62 (54.64±4.16) years old, 18 cases on the right side and 15 cases on the left side. The course of disease was 5 to 9 (7.65±1.24) months. The patients were treated with inside out technique. The operation time, hospitalization days and treatment cost were compared between the two groups. Constant-Murley function score before and after the operation andthe shoulder joint range of motion one month after operation were compared to evaluate the clinical efficacy. RESULTS: All 65 patients were followed up for 9 to 17 months with an average follow up time of (11.34±2.24) months. Compared with control group, operation time in observation group was shorter[(55.53± 10.23) min vs (85.58±13.39) min], and functional scores of Constant-Murley after surgery were significantly changed in both groups compared with that before surgery(P<0.05). There was no significant difference in functional scores of Constant-Murley between two groups (P>0.05). There was no significant differences in hospitalization time and treatment cost between two groups (P>0.05), and there was no significant difference in shoulder abduction, extension flexion and rotation activity between two groups (P>0.05), but internal rotation of observation group was improved compared with that of control group (P<0.05). CONCLUSION: The two arthroscopic release schemes have achieved satisfactory results for thetreatment of primary frozen shoulder, and the shoulder joint function and pain degree have been effectively improved. Compared with the inside-out technique, the outside in release technique is more direct, the operation is simpler and the operation time is shorter. It has certain advantages in releasing operation for primary frozen shoulder.

Design and application of α-ketothioesters as 1,2-dicarbonyl-forming reagents.

The 1,2-dicarbonyl motif is vital to biomolecules, especially natural products and pharmaceuticals. Conventionally, 1,2-dicarbonyl compounds are prepared via an α-keto acyl chloride. Based on the methods used in nature, a transition-metal-free approach for the synthesis of an α-ketothioester reagent via the combination of an α-hydroxyl ketone, elemental sulfur and a benzyl halide is reported. Mechanistic studies demonstrate that the trisulfur radical anion and the α-carbon radical of the α-hydroxy ketone are involved in this transformation. The dicarbonylation of a broad range of amines and amino acids, and importantly, cross couplings with aryl borates to construct dicarbonyl-carbon bonds are realized under mild conditions by employing this stable and convenient α-ketothioester as a 1,2-dicarbonyl reagent. The dicarbonyl-containing drug indibulin and the natural product polyandrocarpamide C, which possess multiple heteroatoms and active hydrogen functional groups, can be efficiently prepared using the designed 1,2-dicarbonyl reagent.

[Clinical observation of iron sucrose combined with recombinant human erythropoietin in the treatment of anemia of hip fracture in elderly patients].

OBJECTIVE: To explore the clinical efficacy of iron sucrose combined with recombinant human erythropoietin(EPO) for the treatment of anemia in elderly patients with hip fracture. METHODS: From February 2016 to April 2018, 96 elderly anemia patients who underwent hip fracture surgery were divided into three groups according to the treatment methods. All the three groups received anti-anemia treatment 3 days before operation. Among them, 32 cases in group A were treated with iron sucrose alone, 32 cases in group B were treated with recombinant human erythropoietin alone, and 32 cases in group C were treated with iron sucrose combined with recombinant human erythropoietin. The therapeutic effects of the three groups were observed and compared. RESULTS: The clinical effective rate in group C was significantly higher than that in group A and B (P<0.05). There was no significant difference in perioperative blood loss among the three groups(P>0.05), but the transfusion rate in group C was significantly lower than that in group A and B (P<0.05). There was no significant difference in hemoglobin and erythrocyte counts among the three groups before treatment(P>0.05), but the above indexes in group C were significantly higher than those in group A and B(P<0.05) at 1, 3 and 5 days after operation. There was no significant difference in the incidence of adverse drug reactions among the three groups(P>0.05). CONCLUSIONS: Compared with single drug, the combined use of sucrose and iron and recombinant human erythropoietin in the treatment of elderly hip fracture anemia has a definite effect. It can not only effectively improve the level of hemoglobin, ensure the smooth operation, but also reduce the blood transfusion rate of patients and promote their recovery after operation.

Pseudomyxoma extraperitonei in horseshoe kidney masquerading as renal hilar tumor: a case report.

Pseudomyxoma peritonei, a rare condition consisting of intraperitoneal mucinous tumors and ascites, most commonly arises from mucinous tumors of the appendix. Very rarely, mucinous deposits arise in the retroperitoneum without intraperitoneal involvement. This has been termed pseudomyxoma extraperitonei. It is a rare and poorly understood condition that is heterogeneous in its clinical behavior, and only a few cases presenting as localized disease in the retroperitoneum have been reported. In this paper, we report the first case of pseudomyxoma extraperitonei presenting as a simple renal hilar mass and mimicking a tumor of renal origin in a horseshoe-kidney patient. The patient underwent isthmusectomy and nephrectomy. Immunohistochemical staining suggested appendiceal origin. She remained alive without adjuvant therapy postoperatively, and no evidence of recurrence was present for 25 months.

Primary follicular non-Hodgkin's lymphoma of the ureter: A case report and literature review.

Ureteral cancer is a rare type of neoplasm, with the most prevalent forms including squamous cell carcinoma, transitional cell carcinoma and adenocarcinoma. Ureteral lymphoma is particularly uncommon, and forming a pre-operative diagnosis of the disease is often difficult. The current study describes the case of a 31-year-old man presenting with a space-occupying lesion located in the left lower ureter. Follicular non-Hodgkin's lymphoma was diagnosed via intraoperative frozen section and post-operative pathological analysis. The affected ureteric segment was excised, and the ureter was repaired by end-to-end anastomosis with insertion of a double-J tube for internal drainage. The patient was followed up for 10 months and presented with no signs of recurrence. The current study affirms the importance of pathological examination in the differential diagnosis of ureteral neoplasms and the selection of an appropriate treatment.

[Application of DNA methyltransferase inhibitors for myelodysplastic syndrome].

Epigenetic research plays an important role in the malignant tumor genotyping and tumor clinical treatment recently. Epigenetics is the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence, including DNA methylation and histone modifications. DNA methylation is one of the most important epigenetic modifications often occurring on the cytosine of CpG islands located in gene promoter regions, which is thought to be closely correlated with tumorigenesis. The inducibility and reversibility of DNA methylation provide us an insight into tumor development and treatment. Aberrant DNA hypermethylation is associated with the progress of myelodysplastic syndrome (MDS). The DNA methyltransferase inhibitors (azacytidine and decitabine) have achieved suc-cess in treating high-and intermediate-risk MDS. This will bring new ideas to understand the cause and develop the treat-ment of MDS. This review mainly introduces the latest progress of the action mechanism of those two medicines, the clini-cal effect and new problems during the clinical application on MDS.

Hemagglutinating virus of Japan envelope (HVJ-E) can enhance the immune responses of swine immunized with killed PRRSV vaccine.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically detrimental pig pathogen that causes significant losses for the pig industry. The immunostimulatory effects of hemagglutinating virus of Japan envelope (HVJ-E) in cancer therapy and the adjuvant efficacy of HVJ-E have been previously evaluated. The objective of this study was to investigate the adjuvant effects of HVJ-E on immunization with killed PRRSV vaccine, and to evaluate the protective effects of this immunization strategy against virulent PRRSV infection in piglets. Next, the PRRSV-specific antibody response, lymphocyte proliferation, PRRSV-specific IL-2, IL-10 and IFN-γ production, and the overall protection efficacy were evaluated to assess the immune responses of the piglets. The results showed that the piglets inoculated simultaneously with killed PRRSV vaccine and HVJ-E had a significantly stronger immune response than those inoculated with killed PRRSV vaccine alone. Our results suggest that HVJ-E could be employed as an effective adjuvant to enhance the humoral and cellular responses of piglets to PRRSV.