A new treatment of concealed penis: symmetrical pterygoid flap surgery

ABSTRACT Purpose: Considerable controversy exists regarding the surgery for concealed penis. We describe a new technique for repairing concealed penis by symmetrical pterygoid flap surgery. Methods: From January 2016 to July 2022, we evaluated 181 cases of concealed penis that were surgically treated using the symmetrical pterygoid flap surgery. We measured the penile size preoperative and 2, 4, 12 weeks, and 1 year postoperative to confirm the improvement. A questionnaire was administered to the patients and parents to assess satisfaction regarding penile size, morphology, and hygiene. Result: The perpendicular penile length was1.59±0.32cm preoperative and 3.82±1.02 cm after the procedure (p < 0.05), and 4.21±1.91cm after one year of postoperative (p < 0.05). The overall satisfaction of patients was 97.89%, while the overall satisfaction of older children patients (age>7) was 75.24%. Parents focus more on the penile exposure size, while patients focus more on the penile morphology. Almost every patient had postoperative penile foreskin edema. However, this symptom had spontaneously resolved by 4-6 weeks. The complications such as skin necrosis, tissue contracture, or wound infection were 4.42%. Conclusion: The symmetrical pterygoid flap surgery is an effective surgical technique for the management of concealed penis in children producing predictable results and excellent satisfaction of the parents and patients.

Analysis of factors associated with delayed diagnosis and treatment of testicular torsion in 1005 cases from Chongqing city, China: a cross-sectional study.

This study aimed to investigate the clinical and social factors of delayed treatment for testicular torsion (TT) and to explore the risk factors of testicular excision in China. The clinical data of 1005 patients with TT who were admitted to 48 medical institutions in Chongqing city (China) from January 2012 to December 2021 were retrospectively analyzed. It was revealed that the misdiagnosis rates of non-senior (junior and middle) grade doctors and senior doctors were 25.1% and 9.6%, respectively. The proportion of TT patients who received timely treatment (within 6 h after onset of symptoms) was 23.8%. The results of the multivariable logistic regression analysis indicated that absent cremasteric reflex was a protective factor for delayed surgery of more than 6 h from onset of symptoms to surgery. Misdiagnosis, consultation with a non-urologist as the first consultant doctor, absence blood flow in color Doppler ultrasound, negative high-riding testis findings, the presence of fever, and non-manual detorsion were identified as risk factors associated with delayed surgery (more than 6 h from the onset of symptoms) for TT. Furthermore, misdiagnosis, non-urologist first-consultant doctor, absent blood flow in DUS, non-manual detorsion, fever, degree of cord twisting > 180, and the initial diagnosis in tertiary hospitals were risk factors for orchidectomy. Having TT on the right side, and the presence of nausea and vomiting were identified as protective factors for orchidectomy. Technical training in the diagnosis and treatment of TT should be extended to primary hospitals and doctors to significantly improve their accuracy in managing this condition.

A new treatment of concealed penis: symmetrical pterygoid flap surgery.

PURPOSE: Considerable controversy exists regarding the surgery for concealed penis. We describe a new technique for repairing concealed penis by symmetrical pterygoid flap surgery. METHODS: From January 2016 to July 2022, we evaluated 181 cases of concealed penis that were surgically treated using the symmetrical pterygoid flap surgery. We measured the penile size preoperative and 2, 4, 12 weeks, and 1 year postoperative to confirm the improvement. A questionnaire was administered to the patients and parents to assess satisfaction regarding penile size, morphology, and hygiene. RESULT: The perpendicular penile length was1.59±0.32cm preoperative and 3.82±1.02 cm after the procedure (p < 0.05), and 4.21±1.91cm after one year of postoperative (p < 0.05). The overall satisfaction of patients was 97.89%, while the overall satisfaction of older children patients (age>7) was 75.24%. Parents focus more on the penile exposure size, while patients focus more on the penile morphology. Almost every patient had postoperative penile foreskin edema. However, this symptom had spontaneously resolved by 4-6 weeks. The complications such as skin necrosis, tissue contracture, or wound infection were 4.42%. CONCLUSION: The symmetrical pterygoid flap surgery is an effective surgical technique for the management of concealed penis in children producing predictable results and excellent satisfaction of the parents and patients.

Predictive model for persistent hypertension after surgical intervention of primary aldosteronism.

Primary aldosteronism (PA) is one of the most common causes of secondary hypertension and is potentially curable. However, a large number of patients still undergo persistent hypertension (PHT) after unilateral adrenal surgery. This research retrospectively studied the factors associated with this clinical difficulty and established a prediction model for the postoperative PHT; Methods: 353 patients from 2014 to 2021 with PA undergoing unilateral adrenal surgery were enrolled in this study. Clinical and biochemical characteristics were reviewed and the associating factors were examined using univariate and multivariate analysis. A nomogram-based prediction model was established correspondingly; results: 46.2% (163/190) of patients had post-surgical PHT. Multivariate analysis suggested that BMI ≥ 25, diabetes, duration of hypertension, male gender, and ARR were independent predictors of PHT after surgery. The prediction model based on the nomogram showed good discrimination ability (the C index of the training group and the validation group were 0.783 and 0.769, respectively), and the calibration curves and the Hosmer-Lemeshow test were good as well. Clinical usefulness was quantified using the decision curve analysis; This nomogram is an integration of the clinical and biochemical data of patients before surgery, and is a reliable tool with high accuracy for predicting the postoperative PHT in patients with PA.

Relationship between rumination and post-traumatic growth in mobile cabin hospital nurses: The mediating role of psychological resilience.

Psychological resilience helps individuals to actively respond to various emergencies, but its mediating role between the rumination and post-traumatic growth (PTG) of nurses remains unknown. Our study aimed to explore the extent to which psychological resilience mediates the association between rumination and PTG among nurses working in mobile cabin hospitals. This cross-sectional survey was conducted on 449 medical team members working in mobile cabin hospitals to support the prevention and control of coronavirus disease 2019 in Shanghai, China in 2022. Pearson correlation analysis was applied to assess the correlation between rumination, psychological resilience, and PTG. Structural equation models were used to examine the mediating role of psychological resilience between rumination and PTG. Our study results showed that deliberate rumination directly promoted psychological resilience and PTG and had positive effects on PTG through the mediating effect of psychological resilience. Invasive rumination had no direct effect on PTG. However, it had a negative effect on PTG through the mediating effect of psychological resilience. Together the results of this study indicate that the mediating effect of psychological resilience was significant in the association of rumination and PTG among mobile cabin hospital nurses, with a higher individual psychological resilience level helping nurses to achieve PTG. Therefore, targeted interventions should be implemented to improve nurses' psychological resilience and guide their rapid growth.

lncRNA MAGI2-AS3 suppresses castration-resistant prostate cancer proliferation and migration via the miR-106a-5p/RAB31 axis.

Prostate cancer (PCa) is a common malignant cancer in elderly males in Western countries. Whole-genome sequencing confirmed that long non-coding RNAs (lncRNAs) are frequently altered in castration-resistant prostate cancer (CRPC) and promote drug resistance to cancer therapy. Therefore, elucidating the prospective role of lncRNAs in PCa oncogenesis and progression is of remarkable clinical significance. In this study, gene expression in prostate tissues was determined using RNA-sequencing datasets, and the gene diagnostic and prognostic values of CRPC were analyzed using bioinformatics. Further, the expression levels and clinical significance of MAGI2 Antisense RNA 3 (MAGI2-AS3) in PCa clinical specimens were evaluated. The tumor-suppressive activity of MAGI2-AS3 was functionally explored in PCa cell lines and animal xenograft models. MAGI2-AS3 was found to be aberrantly decreased in CRPC and was negatively correlated with Gleason score and lymph node status. Notably, low MAGI2-AS3 expression positively correlated with poorer survival in patients with PCa. The overexpression of MAGI2-AS3 significantly inhibited the proliferation and migration of PCa in vitro and in vivo. Mechanistically, MAGI2-AS3 could play a tumor suppressor function in CRPC through a novel miR-106a-5p/RAB31 regulatory network and could be a target for future cancer therapy.

Comprehensive analysis of the FOXA1-related ceRNA network and identification of the MAGI2-AS3/DUSP2 axis as a prognostic biomarker in prostate cancer.

Background: Prostate cancer (PCa) is the second most common cause of cancer-related deaths in American men. Even though increasing evidence has disclosed the competitive endogenous RNA (ceRNA) regulatory networks among cancers, the complexity and behavior characteristics of the ceRNA network in PCa remain unclear. Our study aimed to investigate the forkhead box A1 (FOXA1)-related ceRNA regulatory network and ascertain potential prognostic markers associated with PCa. Methods: RNA sequence profiles downloaded from The Cancer Genome Atlas (TCGA) were analyzed to recognize differentially expressed genes (DEGs) derived from tumor and non-tumor adjacent samples as well as FOXA1low and FOXA1high tumor samples. The enrichment analysis was conducted for the dysregulated mRNAs. The network for the differentially expressed long non-coding RNA (lncRNA)-associated ceRNAs was then established. Survival analysis and univariate Cox regression analysis were executed to determine independent prognostic RNAs associated with PCa. The correlation between DUSP2 and immune cell infiltration level was analyzed. Tissue and blood samples were collected to verify our network. Molecular experiments were performed to explore whether DUSP2 is involved in the development of PCa. Results: A ceRNA network related to FOXA1 was constructed and comprised 18 lncRNAs, 5 miRNAs, and 44 mRNAs. The MAGI2-AS3~has-mir-106a/has-mir-204~DUSP2 ceRNA regulatory network relevant to the prognosis of PCa was obtained by analysis. We markedly distinguished the MAGI2-AS3/DUSP2 axis in the ceRNA. It will most likely become a clinical prognostic model and impact the changes in the tumor immune microenvironment of PCa. The abnormal MAGI2-AS3 expression level from the patients' blood manifested that it would be a novel potential diagnostic biomarker for PCa. Moreover, down-expressed DUSP2 suppressed the proliferation and migration of PCa cells. Conclusions: Our findings provide pivotal clues to understanding the role of the FOXA1-concerned ceRNA network in PCa. Simultaneously, this MAGI2-AS3/DUSP2 axis might be a new significant prognostic factor associated with the diagnosis and prognosis of PCa.

Initial Experience of Simultaneous Combined use of Percutaneous Nephrolithotomy and Flexible Ureteroscopy in Complex Renal Calculi: A Novel Surgical Technique of 'Through-Through' Approach.

BACKGROUND: For complex branched renal calculi, the endoscopic combined intrarenal surgery (ECIRS) is worldwide prevalent. This study aimed to present a novel surgical technique of percutaneous nephrolithotomy combined with antegrade flexible ureteroscopy which is named 'Through-through' approach. METHODS: We retrospectively analyzed the data of 68 patients with complex renal calculi who underwent combined PNL and flexible ureteroscopy surgery using 'Through-through' approach at our center between August 2019 and December 2021. The 'Through-through' approach to surgery was indicated in residual calyceal calculi that neither rigid nephroscope nor retrograde flexible ureteroscope could reach. The brief procedure of this technique involved determining the direction of targeted calyces with the nephroscope first, followed by putting flexible ureteroscope into the targeted calyx through the nephroscope instrument channel and basketing or dusting residual calculi through the flexible ureteroscope instrument channel. RESULTS: The mean maximum stone diameter was 4.0 ± 0.4 cm. The mean operative duration was 100.1 ± 18.0 minutes, and mean hemoglobin loss was 21.4 ± 5.1 g/L. In all 68 patients, calculi were cleared in 62 patients, and the stone free rate was 91.2%. Five patients underwent further surgery after 2 weeks because of significant residual calculi. One patient that had a 6 mm residual stone chose observational follow-up. Ten patients emerged with postoperative fever but did not progress to uroseptic shock. There were no Clavien grade ≥ III complications, and none of the patients required blood transfusion. CONCLUSION: The 'Through-through' approach is safe, feasible and effective for complex renal calculi patients. It is a complementary solution to the failed endoscopic combined intrarenal surgery.

[Corrigendum] Combination of phospholipase Cε knockdown with GANT61 sensitizes castration­resistant prostate cancer cells to enzalutamide by suppressing the androgen receptor signaling pathway.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that the same control ß­actin bands had apparently been included in the western blots featured in Fig. 5E and F, even though different experiments were presented in these figure parts. The authors have re­examined their data and realized that Fig. 5G was assembled incorrectly. The results from all the originally performed experiments were presented to the Editorial Office for our perusal. The revised version of Fig. 5, containing the correct ß­actin data for the western blots in Fig. 5F, is shown on the next page. The authors regret the inadvertent error that was made during the preparation of Fig. 5, and confirm that this error did not seriously affect the conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologise to the readership for any inconvenience caused.[Oncology Reports 41: 2689­2702, 2019; DOI: 10.3892/or.2019.7054].

[Corrigendum] PLCε knockdown enhances the radiosensitivity of castration­resistant prostate cancer via the AR/PARP1/DNA­PKcs axis.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that western blots featured in Figs. 4B and 5G (representing the 'AR' experiments in both cases) appeared to be the same, albeit that the bands were flipped vertically in Fig. 5G relative to Fig. 4B. The authors have re­examined their data and realized that Fig. 5 was assembled incorrectly. The results from all the originally performed experiments were presented to the Editorial Office for our perusal. The revised version of Fig. 5, containing the correct data for the 'AR' experiment in Fig. 5G, is shown on the next page. The authors regret the inadvertent error that was made during the preparation of Fig. 5, and confirm that this error did not seriously affect the conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologise to the readership for any inconvenience caused. [Oncology Reports 43: 1397­1412, 2020; DOI: 10.3892/or.2020.7520].

Long non-coding RNA lncHUPC1 induced by FOXA1 promotes tumor progression by inhibiting apoptosis via miR-133b/SDCCAG3 in prostate cancer.

Long non-coding RNAs (lncRNAs) were confirmed to be involved in regulating various malignant behaviors of tumor cells in prostate cancer (PCa). Using The Cancer Genome Atlas (TCGA) prostate adenocarcinoma datasets, several endogenous competing RNA (ceRNA) networks of lncRNA/miRNA/mRNA associated with the progression-free survival (PFS) and Gleason score (GS) were identified using bioinformatics analysis. lncRNA AC004447.2 (lncHUPC1, ENSG00000269131)/miR-133b/serologically defined colon cancer antigen-3 (SDCCAG3) was a newly identified ceRNA network that affected cell growth and apoptosis in PCa. Using q-PCR, lncHUPC1 and SDCCAG3 were found to be up-regulated in PCa cells, while miR-133b was down-regulated. The same results were found in tissue samples from 70 PCa cases. It was confirmed that the knockdown of lncHUPC1 increased the expression of miR-133b and decreased that of SDCCAG3, which further increased apoptosis and inhibited cell growth, while the miR-133b inhibitor partially reversed these effects. After transfection with miR-133b mimic after lncHUPC1-knockdown, the expression of miR-133b increased while that of SDCCAG3 reduced, and the apoptosis of the cells was more obvious and the growth of the cells was slower. Therefore, lncHUPC1 was confirmed to regulate SDCCAG3 by binding to miR-133b. Additionally, we found that the transcription factor Forkhead Box A1 (FOXA1) directly bound to the promoter of lncHUPC1 to activate it. In conclusion, the ceRNA network of lncHUPC1/miR-133b/SDCCAG3 affected the growth and apoptosis of PCa cells, and FOXA1 may be involved in the process as a transcription factor of lncHUPC1.

Lycopene enhances the sensitivity of castration-resistant prostate cancer to enzalutamide through the AKT/EZH2/ androgen receptor signaling pathway.

Enzalutamide is an effective drug for the treatment of castration-resistant prostate cancer (CRPC), but acquired enzalutamide resistance is usually unavoidable within the short term in many patients. Lycopene, a safe and effective phytochemical, has been documented to have anticancer activity in a variety of tumors, especially for prostate cancer (PCa). The aim of this study was to provide data support for the combination of lycopene and enzalutamide in the treatment of CRPC. To this end, tissues from patients with primary prostate cancer (PPC) and CRPC were examined by immunohistochemical analysis and found that p-AKT and p-EZH2 were overexpressed in CRPC. Furthermore, Kaplan-Meier survival analysis showed that the high expression of p-AKT and p-EZH2 may be related to the poor prognosis of patients. In addition, the expression of p-AKT, p-EZH2 and androgen receptor (AR) were significantly down-regulated in 22RV1 and C4-2B cells and the proliferation and invasion of CRPC cells were inhibited after treatment with lycopene, while SC79 (an AKT agonist) markedly rescue this effect. Of note, a combination of lycopene and enzalutamide significantly inhibited the proliferation and invasion of CRPC cells in vitro, as well as tumor growth and bone metastasis in vivo. These results suggest that the enhanced antitumor effects of enzalutamide by lycopene may be related to the reduction of AR protein levels through lycopene-mediated inhibition of AKT/EZH2 pathway, which may provide a new approach to improve the efficacy of enzalutamide in CRPC.

[Corrigendum] HepaCAM inhibits cell proliferation and invasion in prostate cancer by suppressing nuclear translocation of the androgen receptor via its cytoplasmic domain.

Following the publication of the above article, an interested reader drew to the authors' attention that the western blotting data shown in Figs. 2F and 5E were strikingly similar, even though they were intended to show the results from differently performed experiments; furthermore, the migration assay images shown for the 24 h 'Blank' and 'Vector' experiments in Fig. 3C were apparently the same. The authors have consulted their original data, and realized that the errors in the presentation of these figures arose inadvertently as a consequence of selecting the wrong images for the 24 h 'Blank' experiement in Fig. 3C and the western blot for the AR / Nucleus experiment in Fig. 5E. The revised versions of Figs. 3 and 5 are shown on the next two pages. All the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. The authors regret that these errors were included in the paper, and also apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 2115­2124, 2019; DOI: 10.3892/mmr.2019.9841].

Panobinostat reverses HepaCAM gene expression and suppresses proliferation by increasing histone acetylation in prostate cancer.

Increased expression of histone deacetylases (HDACs) affiliated to the epigenetic regulation is common aberration in prostate cancer (PCa). We have confirmed that hepatocyte cell adhesion molecule (hepaCAM), acting as a tumor suppressor gene, is rarely expressed in PCa previously, However, the mechanisms of which is still unknown. The level of histone acetylation reportedly may involve anti-oncogene transcription and expression. In this study, we investigated the effect of panobinostat, the broad-spectrum histone deacetylases inhibitor, on PCa LNCaP and DU145 cell growth, and observed re-expression of hepaCAM when treated with panobinostat. We demonstrated that intranuclear acetylation of lys9 of histone H3 (Ac-H3K9) were increased, while that of both mRNA and protein of HDAC1, HDAC3, and HDAC4 were decreased when the treating concentration of panobinostat increased. We confirmed the relationship between histone acetylation and the expression of hepaCAM and AR in prostate cancer tissues. We also confirmed that panobinostat could overcome the resistance for androgen deprivation therapy (ADT). Further, we combined panobinostat with Ad-hepaCAM, which resulted in significantly increased antitumor activity and significant attenuation of the proliferation-associated genes CCND1 and PCNA compared to each single treatment. In conclusion, panobinostat may enhance the acetylation of lys9 of histone 3 and reverse the hepaCAM expression through its inhibitory effect on HDACs activity in PCa LNCaP and DU145 cells; Ad-hepaCAM combined with panobinostat may synergistically inhibit the growth of LNCaP and DU145 cells, via a potential mechanism associated with the down-regulation of the expression of CCND1 and PCNA. These findings suggest that this therapeutic strategy should be further developed in clinical trials.

Identification of the metabolic signatures of prostate cancer by mass spectrometry-based plasma and urine metabolomics analysis.

OBJECTIVE: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men which is associated with profound metabolic changes. Systematic analysis of the metabolic alterations and identification of new biomarkers may benefit PCa diagnosis and a deep understanding of the pathological mechanism. The purpose of this study was to determine the metabolic features of PCa. METHODS: Plasma and urine metabolites from 89 prostate cancer (PCa) patients, 84 benign prostatic hyperplasia (BPH) patients, and 70 healthy males were analyzed using LC-MS/MS and GC-MS. The Orthogonalised Partial Least Squares Discriminant Analysis (OPLS-DA) was used to find the significantly changed metabolites. The clinical value of the candidate markers was examined by receiver operating characteristic curve analysis and compared with prostate-specific antigen (PSA). RESULTS: Multivariate statistical analyses found a series of altered metabolites, which related to the urea cycle, tricarboxylic acid cycle (TCA), fatty acid metabolism, and the glycine cleavage system. Plasma Glu/Gln showed the highest predictive value (AUC = 0.984) when differentiating PCa patients from healthy controls, with a higher sensitivity than PSA (96.6% vs. 94.4%). Both Glu/Gln and PSA displayed a low specificity when differentiating PCa patients from BPH patients (<53.2%), while the combination of Glu/Gln and PSA can further increase the diagnostic specificity to 66.9%. CONCLUSIONS: The present study showed the metabolic features of PCa, provided strong evidence that the amide nitrogen and the energy metabolic pathways could be a valuable source of markers for PCa. Several candidate markers identified in this study were clinically valuable for further assessment.

MicroRNA-199b-3p suppresses malignant proliferation by targeting Phospholipase Cε and correlated with poor prognosis in prostate cancer.

OBJECTIVES: MicroRNA-199b-3p (miR-199b-3p) plays a crucial role in the malignant development of various cancers, but little known in prostate cancer (PCa). The aim of our study was to demonstrate the function of miR-199b-3p in PCa. METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect miR-199b-3p expression in PCa and benign prostatic hyperplasia (BPH) tissue samples. In addition, we examined the relationship between the poor prognosis in PCa and miR-199b-3p. Western blot was used to analyze the expression of Phospholipase Cε (PLCε). CCK8 and colony-forming assays were applied to detect the proliferation of PCa. EdU assay is used to detect PCa cells uptake of EdU. Luciferase reporter assay was applied to analyze the binding between miR-199b-3p and PLCε. RESULTS: It has been shown that miR-199b-3p in PCa was significantly lower than that in benign prostatic hyperplasia and correlated with poor prognosis. Meanwhile, upregulation of miR-199b-3p can prominently inhibit the proliferation of PCa cells, while its down-regulation triggered opposite result. PLCε was identified as the downstream binding target gene and negatively associated with that of miR-199b-3p. CONCLUSION: miR-199b-3p suppresses malignant proliferation by inhibiting PLCε in prostate cancer in vitro and vivo.

Systematic Evaluation for the Influences of the SOX17/Notch Receptor Family Members on Reversing Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells.

The treatment of castration-resistant prostate cancer (CRPC) remains challenging due to the failure of androgen deprivation therapy (ADT); hence the search for other molecular therapeutic targets besides androgen receptor signaling is ongoing. This study systematically investigated the expression of SOX17 and Notch receptors in CRPC tissues and cells in vitro, showing that consistent clinical CRPC, SOX17/Notch1, and Notch4 were responsible for enzalutamide resistance in CRPC cells. The γ secretase inhibitors, BMS-708163, GSI-IX, PF-3084014, and RO4929097 abrogated the enzalutamide resistance by inhibiting Notch1 or/and Notch4 in vitro, with GSI-IX and RO4929097 being more effective than BMS-708163 and PF-3084014 in reliving bone metastasis in vivo. In conclusion, the Notch1 and Notch4 inhibitors GSI-IX and RO4929097 are promising therapeutic agents for the treatment of CRPC.

Ionizing Radiation Combined with PARP1 Inhibitor Reduces Radioresistance in Prostate Cancer with RB1/TP53 Loss.

Tumor suppressor genes RB1 and TP53 are altered frequently in prostate cancer (PC), whether RB1 and TP53 inactivation promotes radioresistance remains unclear. Herein, we demonstrated that RB1 loss enhanced ionizing radiation (IR)-induced DNA damage to inhibit cell proliferation and promote cellular senescence through a TP53-dependent pathway in LNCaP cells. Furthermore, the stabilization of TP53 was regulated by ATM-mediated phosphorylation of MDM2 at Ser395. However, inactivation of RB1/TP53 reversed DNA damage-induced cellular senescence and promoted radiation survival. Importantly, combined with PARP1 inhibitor restored radiosensitivity. This finding provides a potential approach for the therapy of PC with RB1/TP53 inactivation.

The targeted inhibition of prostate cancer by iron-based nanoparticles based on bioinformatics.

Prostate cancer is an epithelial malignant tumor of the prostate, and it is one of the malignant tumors with a high incidence of urogenital system in men. The local treatment of prostate cancer is mainly radical resection and radical radiotherapy, but they are not applicable to advanced prostate cancer. Systemic therapy mainly includes targeted therapy and immunotherapy which could cause many complications, and will affect the prognosis and quality of life of patients. It is urgent to find new treatments for prostate cancer. Bioinformatics offers hope for us to find reliable therapeutic targets. Bioinformatics can use the tumor informations in database and analyze them to screen out the best differentially expressed genes. Using the selected differentially expressed genes as targets, a gene interference plasmid was designed, and the constructed plasmid was used for targeted gene therapy. There are some problems about gene therapy that need to be solved, such as how to transfer genes to target cells is also an important challenge. Due to their large molecular weight and hydrophilic nature, they cannot enter cells through passive diffusion mechanisms. Here we synthesized a DNA carrier used surface modified iron based nanoparticles, and used it to load plasmid including ShRNA which can inhibit the expression of oncogene SLC4A4 selected by bioinformatics' method. After that we use this iron based nanoparticles/plasmid DNA nanocomposite to treat prostate cancer cells in vitro and in vivo. The target gene SLC4A4 we had selected using bioinformatics had a strong effect on the proliferation of prostate cells; Our nanocomposite could inhibit the expression of SLC4A4 effectively, it had strong inhibitory effects on prostate cancer cells both in vivo and in vitro, and can be used as a potential method for prostate cancer treatment.

Long noncoding RNA HOTAIR regulates the invasion and metastasis of prostate cancer by targeting hepaCAM.

BACKGROUND: The role of HOX transcript antisense RNA (HOTAIR) has been proven to be important in tumorigenesis. However, how this molecule promotes metastasis and invasion in PCa is still unclear. METHODS: The relationship between HOTAIR and hepatocellular adhesion molecule (hepaCAM) in PCa was identified by immunohistochemistry, immunofluorescence, plasmid transfection, quantitative real-time PCR and immunoblotting. The regulatory effects of HOTAIR on hepaCAM and MAPK signalling and their key roles in PCa metastasis were investigated in vitro. RESULTS: The expression of HOTAIR was inversely correlated with hepaCAM in the blood and tissue of PCa patients. Here, hepaCAM was identified as a novel target gene of HOTAIR and was critical for the invasiveness of PCa. HOTAIR recruited PRC2 to the hepaCAM promoter, resulting in high levels of H3K27me3 and the absence of hepaCAM with an abnormally activated MAPK pathway. Both HOTAIR depletion and EZH2 inhibition could induce hepaCAM re-expression with inhibitory MAPK signalling and decrease the invasive and metastatic capabilities of PCa cells. CONCLUSIONS: This study demonstrates that HOTAIR promotes invasion and metastasis of PCa by decreasing the inhibitory effect of hepaCAM on MAPK signalling. Therefore, the HOTAIR/hepaCAM/MAPK axis may provide a new avenue towards therapeutic strategies and prognostic indicators for advanced prostate cancer.