Evaluation of CD47 in the Suppressive Tumor Microenvironment and Immunotherapy in Prostate Cancer.

Background: CD47 has high levels of expression in malignant cancer cells, which binds to SIRP-α to release the "don't eat me" signal and prevents mononuclear macrophages from phagocytosing the cells. Resistance to drugs and metastases are potential barriers for prostate cancer endocrine therapy. Although immunotherapy for tumors has developed rapidly in the last few decades, its effectiveness in treating prostate cancer is unsatisfactory. Prostate cancer has a high-expression level of CD47. Therefore, a novel approach for potential immunotherapy may be provided by investigating the relationship among CD47 and the infiltration of immune cells in the prostate carcinoma. Methods: The GEPIA database was utilized to compare the abundance of CD47 in malignant tissues with tissues that were normal. Furthermore, the function of CD47 in prostate carcinoma was assessed by CancerSEA. The association among CD47 and the tumor microenvironment was assessed utilizing the TISCH single cell data database. By using TIMER, the connection among CD47 and immunological invasion of prostate cancer was explored. Moreover, macrophages were cocultured with mouse prostate cancer cell RM-1 blocked by CD47 antibody to observe the changes in phagocytosis efficiency in vitro. Results: Expression level of CD47 is upregulated in prostate carcinoma, and it is closely connected with prostate cancer's inadequate immune invasion. CD47 antibody blocking promotes macrophage phagocytosis of RM-1. Conclusion: Our research demonstrates a closely relationship among CD47 and the immunological microenvironment of prostate cancer, and blocking CD47 can promote macrophages to phagocytosis of prostate cancer cells. Therefore, CD47 may provide novel strategies for potential immunotherapy of prostate cancer.

Alkaline phosphatase combines with CT factors for differentiating small (≤ 4 cm) fat-poor angiomyolipoma from renal cell carcinoma: a multiple quantitative tool.

PURPOSE: This study aimed to evaluate the diagnostic value of serum and CT factors to establish a convenient diagnostic method for differentiating small (≤ 4 cm) fat-poor angiomyolipoma (AML) from renal cell carcinoma (RCC). MATERIALS AND METHODS: This study analyzed the preoperative serum laboratory data and CT data of 32 fat-poor AML patients and 133 RCC patients. The CT attenuation value of tumor (AVT), relative enhancement ratio (RER), and heterogeneous degree of tumor were detected using region of interest on precontrast phase (PCP) and the corticomedullary phase. Multivariate regression was performed to filter the main factors. The main factors were selected to establish the prediction models. The area under the curve (AUC) was measured to evaluate the diagnostic efficacy. RESULTS: Fat-poor AML was more common found in younger (47.91 ± 2.09 years vs 53.63 ± 1.17 years, P = 0.02) and female (70.68 vs 28.13%, P < 0.001) patients. Alkaline phosphatase (ALP) was higher in RCC patients (81.80 ± 1.75 vs 63.25 ± 2.95 U/L, P < 0.01). For CT factors, fat-poor AML was higher in PCP_AVT (40.30 ± 1.49 vs 32.98 ± 0.69Hu, P < 0.01) but lower in RER (67.17 ± 3.17 vs 84.64 ± 2.73, P < 0.01). Gender, ALP, PCP_AVT and RER was found valuable for the differentiation. When compared with laboratory-based or CT-based diagnostic models, the combination model integrating gender, ALP, PCP_AVT and RER shows the best diagnostic performance (AUC = 0.922). CONCLUSION: ALP was found higher in RCC patients. Female patients with ALP < 70.50U/L, PCP_AVT > 35.97Hu and RER < 82.66 are more likely to be diagnose as fat-poor AML.

Muscle-derived Stem Cells Combined With Nerve Growth Factor Transplantation in the Treatment of Stress Urinary Incontinence.

OBJECTIVE: To investigate the efficacy of muscle-derived stem cells (MDSCs) combined with nerve growth factor (NGF) in the treatment of stress urinary incontinence (SUI) METHODS: MDSCs were isolated and extracted from 90 SD rats, and the stem cell characteristics of the cells were identified using flow cytometry. NGF overexpression (oe-NGF) plasmid was coated with adenovirus and qRT-PCR was applied to verify adenovirus transfection efficiency. The rat models of SUI were constructed and randomly divided into 5 groups: control group, phosphate buffer (PBS) group, MDSCs + oe-NGF group, MDSCs + vector group, and MDSCs group. After 8 weeks of feeding, the leakage point pressure (LPP) rats, and Masson staining of rat urethral sections were detected. The expression of NGF and vascular endothelial growth factor (VEGF) was detected by western blot and IHC staining. RESULTS: Compared with the control group, the LPP and the ratio of muscle fibers/collagen fibers were significantly increased in the MDSCs treated groups, with the highest increase in the MDSCs + oe-NGF group. Western blot and IHC results showed that the expression of NGF and VEGF in the urethral tissues in the MDSCs treated groups were significantly up-regulated comparing with the control group, with the highest increase in the MDSCs + oe-NGF group. CONCLUSION: MDSCs alone can relieve SUI, while MDSCs combined with NGF is more effective, which may be related to the up-regulating of VEGF.

Comparison of survival in elderly patients treated with uretero-cutaneostomy or ileal conduit after radical cystectomy.

BACKGROUND: In bladder cancer patients with age ≥ 80 years old, there have been controversies in performing uretero-cutaneostomy or ileal conduit as urinary diversion after radical cystectomy. Limited study evaluated overall survival (OS) and cancer-specific survival (CSS) between the two urinary diversions in elderly patients. This study is to compare OS and CSS between uretero-cutaneostomy and ileal conduit after radical cystectomy in bladder cancer patients with age ≥ 80 years old. PATIENTS AND METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Bladder cancer patients diagnosed between 2004 and 2016 with age ≥ 80 years old who underwent radical cystectomy with either UC or IC were selected. After propensity score matching, Cox regression and Kaplan-Meier analysis were used to analyze the survival. We calculated statistical power for survival. RESULTS: Of 1394 patients who met the inclusion criteria, 1093 underwent ileal conduit and 301 underwent uretero-cutaneostomy. After propensity score matching, 285 patients were included in each group. Multivariable Cox analysis showed urinary diversion was not a risk factor of OS and CSS (HR 1.044, [95% CI 0.867-1.257] and 1.012 [0.748-1.368], respectively). Both OS and CSS were not significantly different, with median survival of ileal conduit and uretero-cutaneostomy were 19 [16-24] months and 19 [15-26] months respectively. Additionally, We found OS had the following risk factors: tumor stage (distant vs regional vs localized, 5.332 [3.610-7.875] vs 1.730 [1.375-2.176] vs 1), node density (>0.2 vs ≤0.2 vs none, 1.410 [1.047-1.898] vs 0.941 [0.658-1.344] vs 1) and age (1.067 [1.032-1.103] for each year). While CSS had the following risk factors: tumor stage (distant vs regional vs localized, 4.035 [2.046-7.959] vs 2.476 [1.651-3.713] vs 1), node density (>0.2 vs ≤0.2 vs none, 2.501 [1.645-3.804] vs 1.062 [0.590-1.914] vs 1) and tumor size (greater than 3 cm vs less than 3 cm, 1.596 [1.057-2.412] vs 1). Our analysis obtained 0.707 power for overall survival. CONCLUSION: Urinary diversion by uretero-cutaneostomy or by ileal conduit was not associated with overall and cancer-specific survival. It is reasonable to consider uretero-cutaneostomy as a regular procedure of urinary diversion in elderly bladder cancer patients after radical cystectomy to avoid associate complications.

[Comparison of the effect of three-dimensional versus two-dimensional retroperitoneal laparoscopic ureter lithotomy].

OBJECTIVE: To compare the surgical effect of three-dimensional (3D) versus 2D laparoscopic surgery in ureter lithotomy. METHODS: From January 2014 to 2015 May, 45 patients with ureteral calculi were randomly allocated into 2 groups to undergo ureter lithotomy under 3D laparoscopy (25 cases) and 2D laparoscopy (20 cases). The time used for each surgical process (including the exposure, D-J tube discharge, suture and other surgical procedures) was recorded and compared between the two groups. RESULTS: The operation was completed smoothly in all the 45 patients. In this cohort, the wound drainage tube was removed in a mean of 3.0mnplus;0.8 days after the operation, the catheter was removed after a week, and the double J tube was removed at 1 month. Follow-up intravenous pyelography at 3 months after the operation reveal ureteral stricture in none of the cases. Comparison of the surgical data showed that the time used in each surgical process was significantly shorter in the 3D group than in the 2D group (P<0.05). 3D laparoscopic surgery allowed more precise operation by providing a good sense of depth as in an open surgery to reduce the operation time. CONCLUSIONS: As a minimally invasive surgical technique, 3D laparoscopic surgery facilitates more precise and easier operation compared with 2D laparoscopy in ureter lithotomy.

Inhibition of LDHA suppresses tumor progression in prostate cancer.

A key hallmark of cancer cells is their altered metabolism, known as Warburg effect. Lactate dehydrogenase A (LDHA) executes the final step of aerobic glycolysis and has been reported to be involved in the tumor progression. However, the function of LDHA in prostate cancer has not been studied. In current study, we observed overexpression of LDHA in the clinical prostate cancer samples compared with benign prostate hyperplasia tissues as demonstrated by immunohistochemistry and real-time qPCR. Attenuated expression of LDHA by siRNA or inhibition of LDHA activities by FX11 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of PC-3 and DU145 cells. Mechanistically, decreased Warburg effect as demonstrated by reduced glucose consumption and lactate secretion and reduced expression of MMP-9, PLAU, and cathepsin B were found after LDHA knockdown or FX11 treatment in PC-3 and DU145 cells. Taken together, our study revealed the oncogenic role of LDHA in prostate cancer and suggested that LDHA might be a potential therapeutic target.

[Influences of three surgical approaches to urethral stricture on the erectile function of the patients].

OBJECTIVE: To evaluate the impacts of three different surgical approaches to urethral stricture on the erectile function of the patients. METHODS: This study included 126 male patients with urethral stricture, 35 treated by substitution urethroplasty (group A), 52 by anastomotic urethroplasty (group B), and 39 by internal urethroplasty (group C). We evaluated the pre- and postoperative erectile function of the patients using IIEF-5 scores by telephone calls and interviews. We also monitored their nocturnal penile tumescence (NPT). RESULTS: The IIEF-5 scores in groups A, B and C were 13.5 +/- 4.5, 11.1 +/- 4.8 and 14.5 +/- 4.41 respectively after surgery, all significantly decreased as compared with 17.1 +/- 2.6, 17.1 +/- 3.0 and 17.6 +/- 2.2 preoperatively (P < 0.05). CONCLUSION: All the three surgical approaches can reduce IIEF-5 scores in patients with urethral stricture, but anastomotic urethroplasty may induce a higher incidence of erectile dysfunction than the other two approaches.

Silencing myostatin gene by RNAi in sheep embryos.

Myostatin (MSTN) gene is described as a negative regulator of the skeletal muscle growth. Controlling MSTN gene expression by genetic manipulation could accelerate the muscle growth and meat production of livestock animals. In the present study, several siRNAs targeting sheep MSTN gene were designed and their interfering efficiency was evaluated in vitro. The present study showed that one of the siRNAs, PSL1, could down-regulate the expression of MSTN significantly. PSL1 was ligated into lentivirus vector, GP-Supersilencing, to construct a siRNA expression lentivirus vector. Fibroblast cells were infected by lentivirus particles and positive cells were isolated by flow cytometry. Nucleus of the positive cell was transferred into enucleated oocytes of sheep. The present study showed that 99.4% of the sorted cells displayed green fluorescence. After enucleation of oocytes with microinjection, about 20% of reconstructed embryos can be developed into morulas, and strong green fluorescence could be observed using a fluorescence microscope. This method can be available to produce transgenic cell line for somatic cell nucleus transfer for transgenic animals.

[Sequencing and analysis of the complete genome of encephalomyocarditis virus strain GXLC isolated from swine].

The complete genome of encephalomyocarditis virus (EMCV)strain GXLC isolated from swine was sequenced and analyzed. Five overlapped gene fragments covering the entire open reading frame (ORF) were amplified by RT-PCR, and the 3'-untranslated region (UTR) and 5'-UTR were amplified by the 3'-rapid amplification of cDNA ends (RACE) and 5'-RACE method, respectively. The genome sequences of strain GXLC were obtained by assembling the sequences of RT-PCR-generated cDNA fragments. The length of the complete genome was 7 725 nucleotides (nt). The homology comparison and phylogenetic analysis of the nucleotide and deduced amino acid sequences between strain GXLC and other EMCV strains available in GenBank were performed. The results showed that the complete genome identity between GXLC strain and the strains from China, i.e. GX0601, GX0602, BJC3 and HB1 and the strains from other countries, i.e. CBNU, K3, K11, TEL-2887A, EMCV-R and PV21 was over 99%. The phylogenetic trees based on the complete genome, the structural protein or the non-structural protein gene sequences revealed that the tree topology was similar. All the EMCV strains could be divided into two groups: group I and group II, and group I could be subdivided into subgroup Ia and subgroup Ib. The strains from swine belonged to subgroup Ia or Ib, and the strains from mice belonged to subgroup Ia, while the strains from Sus scro fa belonged to group II. Strain GXLC, together with other EMCV isolates from China, belonged to subgroup Ia.