Evaluation of bi-directional causal association between periodontitis and benign prostatic hyperplasia: epidemiological studies and two-sample mendelian randomization analysis.

Background: Periodontitis and benign prostatic hyperplasia (BPH) are all common chronic diseases with higher incidence in middle-aged and old men. Several studies have indicated a potential association between periodontitis and BPH, although the findings remain inconclusive. However, there is no mendelian randomization (MR) studies to assess this association. Methods: The 40 men who had received health check-ups were included in an epidemiological study. Genetic data of BPH (13118 cases and 72799 controls) and periodontitis (3046 cases and 195395 controls) from FinnGen project was used to perform two-sample MR analysis. The inverse-variance weighted (IVW) model was identified as the primary analytical method, with MR Egger, weighted median, simple mode, and weighted mode serving as additional approaches. Results: The epidemiological analysis demonstrated a lack of statistically significant differences in the prevalence of clinical BPH between severe periodontitis group and non-severe periodontitis group. Similarly, no statistically significant differences were found in the prevalence of severe periodontitis among individuals with clinical BPH compared to those without. Additionally, Among the five models utilized in MR analysis, including the IVW model, no evidence of a causal link between periodontitis and BPH was observed. Conclusion: The findings from our epidemiological investigation and MR analysis do not provide support for a causal relationship between periodontitis and BPH.

MMPs-related risk model identification and SAA1 promotes clear cell renal cell carcinoma migration via ERK-AP1-MMPs axis.

Matrix Metalloproteinases (MMPs) have been demonstrated to be essential in facilitating the migration and metastasis of clear cell renal cell carcinoma (ccRCC). However, the ability of the MMP family to predict clinical outcomes and guide optimal therapeutic strategies for ccRCC patients remains incompletely understood. In this investigation, we initially conducted a thorough examination of the MMP family in pan-cancer. Notably, MMPs exhibited distinctive significance in ccRCC. Following this, we undertook an extensive analysis to evaluate the clinical value of MMPs and potential mechanisms by which MMPs contribute to the progression of ccRCC. A novel stratification method and prognostic model were developed based on MMPs in order to enhance the accuracy of prognosis prediction for ccRCC patients and facilitate personalized treatment. By conducting multi-omics analysis and transcriptional regulation analysis, it was hypothesized that SAA1 plays a crucial role in promoting ccRCC migration through MMPs. Subsequently, in vitro experiments confirmed that SAA1 regulates ccRCC cell migration via the ERK-AP1-MMPs axis. In conclusion, our study has explored the potential value of the MMP family as prognostic markers for ccRCC and as guides for medication regimens. Additionally, we have identified SAA1 as a crucial factor in the migration of ccRCC.

Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a potential prognostic biomarker in clear cell renal cell carcinoma that correlates with M2 macrophage infiltration and epithelial-mesenchymal.

BACKGROUND: The six-transmembrane epithelial antigen of the prostate 3 (STEAP3) is a metalloreductase, which is essential for iron uptake. Existing literature has shown that STEAP3 may perform an important role in the onset and progression of tumors. Nonetheless, a complete pan-cancer investigation of the prognostic significance and immune properties of STEAP3 is currently unavailable. AIMS: As part of our investigation into the possible functions of STEAP3 in malignancies, we conducted a comprehensive analysis to examine the prognostic value and immune features of STEAP3 in human pan-cancer. METHODS AND RESULTS: R and Cytoscape programs were applied to analyze and visualize the data. The expression of STEAP3 in both cell lines and tissues was measured utilizing a variety of approaches. Using the shRNA knockdown technique, we tested the viability of the A498 and 786-O cell lines and validated their functions. Both CCK-8 and transwell assays were conducted to estimate cell proliferation and invasion. The expression of STEAP3 was substantially elevated and was shown to be linked to prognosis in the majority of malignancies, notably in clear cell renal cell carcinoma (ccRCC). In addition, the expression of STEAP3 was shown to have a strong correlation with immune infiltrates, which in turn triggered the recruitment and polarization of M2 macrophages in ccRCC. The protein STEAP3 shows promise as a predictor of responses to immune-checkpoint blockade (ICB) therapy. Positive links between STEAP3 and the epithelial-mesenchymal transition (EMT), the p53 pathway, and the immune-associated pathways were also found in the enrichment analysis. Our results illustrated that the STEAP3 expression level was substantially elevated in ccRCC tissues and suggested that it could stimulate EMT in ccRCC by downregulating CDH1. CONCLUSION: In a diverse range of cancers, STEAP3 might serve as a biomarker for determining the prognosis as well as a predictor of immunotherapy responsiveness. STEAP3 is a novel biological marker for determining prognosis, and it also performs a remarkable function in the promotion of tumor growth in ccRCC by enhancing invasion and EMT, as well as by triggering the recruitment and polarization of M2 macrophages.

Benefits of lymphadenectomy for upper tract urothelial carcinoma only located in the lower ureter: a bicentre retrospective cohort study.

Background: Upper tract urothelial carcinoma (UTUC) is a rare and highly malignant urothelial tumor originating from the renal pelvis and ureter associated with poor prognosis. It has been established that 70% of ureteral tumors occur in the lower ureter. Radical nephroureterectomy (RNU) with ipsilateral bladder cuff excision is regarded as the standard treatment for UTUC. Current evidence supports the role of lymph node dissection (LND) in determining tumor staging, but no consensus has been reached on the potential survival benefits. The present study retrospectively analyzed cases of UTUC limited to the lower ureter to evaluate the survival benefits of LND during RNU. Methods: The present study retrospectively analyzed data from patients with UTUC limited to the lower ureter from two medical centers from 2000 to 2016 and assessed the survival outcomes, including recurrence-free survival (RFS) and cancer specific survival (CSS). During subgroup analysis, we stratified by pathological tumor (pT) stages and postoperative adjuvant chemotherapy (AC). Results: The study cohort included 297 patients separated into LND (n=111) and non-LND (n=186) groups. The two groups were comparable except for the pathological N stage. The LND group was associated with superior survival in terms of RFS (27.0% vs. 18.3%, p=0.044) and CSS (53.2 vs. 39.8%, p=0.031) compared to the non-LND group (n=186). In pT2-4 patients, the LND group was associated with better 3-year RFS (50.5% vs. 32.3%, p<0.05), 5-year RFS (29.7% vs. 12.0%, p<0.05), and overall RFS (18.7% vs. 6.0%, p<0.05) than the non-LND group. Besides, the LND group was associated with a significantly better 3-year CSS (68.1% vs. 49.6%, p=0.003), 5-year CSS (51.6% vs. 30.8%, p<0.05) and overall CSS (45.1% vs. 24.1%, p<0.05). In patients that underwent AC, the LND group had better survival benefits in terms of RFS (29.4 vs. 16.7%, p=0.023) and CSS (52.9% vs. 40.5%, p=0.038) compared to the non-LND group. Conclusion: LND has survival benefits in patients with UTUC localized to the lower ureter, especially for≥pT2 stage UTUC and AC cohorts. Overall, the therapeutic effect of LND in UTUC cannot be replaced by AC.

HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer.

Enabled resistance or innate insensitiveness to antiandrogen are lethal for castration-resistant prostate cancer (CRPC). Unfortunately, there seems to be little can be done to overcome the antiandrogen resistance because of the largely unknown mechanisms. In prospective cohort study, we found that HOXB3 protein level was an independent risk factor of PSA progression and death in patients with metastatic CRPC. In vivo, upregulated HOXB3 contributed to CRPC xenografts progression and abiraterone resistance. To uncover the mechanism of HOXB3 driving tumor progression, we performed RNA-sequencing in HOXB3 negative (HOXB3-) and HOXB3 high (HOXB3 + ) staining CRPC tumors and determined that HOXB3 activation was associated with the expression of WNT3A and enriched WNT pathway genes. Furthermore, extra WNT3A and APC deficiency led HOXB3 to be isolated from destruction-complex, translocated to nuclei, and then transcriptionally regulated multiple WNT pathway genes. What's more, we also observed that the suppression of HOXB3 could reduce cell proliferation in APC-downregulated CRPC cells and sensitize APC-deficient CRPC xenografts to abiraterone again. Together, our data indicated that HOXB3 served as a downstream transcription factor of WNT pathway and defined a subgroup of CRPC resistant to antiandrogen which would benefit from HOXB3-targeted therapy.

Primary teratoma of the adrenal gland: a case report.

Background: Teratomas are unusual tumors derived from multiple germ layers but they usually arise from all three germ layers. Knowledge of this disease is still very limited because of its low incidence. Retroperitoneal teratomas are extremely rare neoplasms, especially adrenal teratomas, which frequently found to be large, cystic or cyst-solid lesions. Adrenal teratomas are easily confused with various benign or malignant tumors, such as myelolipomas, adenomas, and hamartomas. Case Description: In this case presentation, we report a rare case in which an adrenal gland mass without apparent discomfort was detected by abdominal computed tomography (CT) for 6 months in a 59-year-old female. Results from the patient's adrenal hormonal evaluation were normal. An abdominal enhanced CT scan revealed a heterogeneous mass in the right adrenal gland. The patient then underwent a laparoscopic right adrenalectomy and the lesion was diagnosed as mature teratoma through histopathological examination. The patient recovered well without any complications. Conclusions: Based on our knowledge, surgical resection is the first-choice intervention for the diagnosis and treatment of mature teratoma. Open surgery is the preferred method for the large tumors, while the laparoscopic adrenalectomy can be a better option in the small one. The patient's prognosis is usually good after complete resection, but close follow-up is also recommended.

Primary Renal Leiomyosarcoma.

To optimise the diagnosis and treatment of primary renal leiomyosarcoma, we present our experience with a similar case and review the literature. A 49-year woman was incidentally found to have a palpable mass in the right kidney. CT scan revealed an enhancing, heterogeneous, 6×7×9 cm right renal mass. On suspicion of renal carcinoma, a right radical nephrectomy was performed.  The pathological diagnosis was primary renal leiomyosarcoma. After 40 months of regular follow-up, local recurrence was found, and she had liver metastases. She died of cachexia due to tumor metastasis, and the survival period was just 44 months. With unobvious clinical manifestations, preoperative imaging and postoperative pathological examination might be helpful for an accurate diagnosis. Radical nephrectomy to completely remove the tumor is recommended, and the combination of neoadjuvant or postoperative therapy should also be considered. Key Words: Renal neoplasms, Leiomyosarcoma, Diagnosis, Therapy.

Progress in studies on pathological changes and future treatment strategies of obesity-associated female stress urinary incontinence: a narrative review.

With the increasing prevalence of obesity worldwide, obesity-related female stress urinary incontinence (FSUI) has become a key health problem. Recent studies indicated that FSUI is primarily caused by obesity-related pathological changes, such as fat droplet deposition, and results in pelvic floor nerve, vascular, and urethral striated muscle injury. Meanwhile, treatments for obesity-associated FSUI (OA-FSUI) have garnered much attention. Although existing OA-FSUI management strategies, including weight loss, pelvic floor muscle exercise, and urethral sling operation, could play a role in symptomatic relief; they cannot reverse the pathological changes in OA-FSUI. The continued exploration of safe and reliable treatments has led to regenerative therapy becoming a particularly promising area of researches. Specifically, micro-energy, such as low-intensity pulsed ultrasound (LIPUS), low-intensity extracorporeal shock wave therapy (Li-ESWT), and pulsed electromagnetic field (PEMF), have been shown to restore the underlying pathological changes of OA-FSUI, which might be related by regulation endogenous stem cells (ESCs) to restore urine control function ultimately in animal experiments. Therefore, ESCs may be a target for repairing pathological changes of OA-FSUI. The aim of this review was to summarize the OA-FSUI-related pathogenesis, current treatments, and to discuss potential therapeutic options. In particular, this review is focused on the effects and related mechanisms of micro-energy therapy for OA-FSUI to provide a reference for future basically and clinical researches.

Aberrant activation of super enhancer and choline metabolism drive antiandrogen therapy resistance in prostate cancer.

Next generation antiandrogens such as enzalutamide (Enz) are effective initially for the treatment of castration-resistant prostate cancer (CRPC). However, the disease often relapses and the underlying mechanisms remain elusive. By performing H3-lysine-27 acetylation (H3K27ac) ChIP-seq in Enz-resistant CRPC cells, we identified a group of super enhancers (SEs) that are abnormally activated in Enz-resistant CRPC cells and associated with enhanced transcription of a subset of tumor promoting genes such as CHPT1, which catalyzes phosphatidylcholine (PtdCho) synthesis and regulates choline metabolism. Increased CHPT1 conferred CRPC resistance to Enz in vitro and in mice. While androgen receptor (AR) primarily binds to a putative CHPT1 enhancer and mediates androgen-dependent expression of CHPT1 gene in Enz-sensitive prostate cancer cells, AR binds to a different enhancer within the CHPT1 SE locus and facilities androgen-independent expression of CHPT1 in Enz-resistant cells. We further identified a long-non coding RNA transcribed at CHPT1 enhancer (also known as enhancer RNA) that binds to the H3K27ac reader BRD4 and participates in regulating CHPT1 SE activity and CHPT1 gene expression. Our findings demonstrate that aberrantly activated SE upregulates CHPT1 expression and confers Enz resistance in CRPC, suggesting that SE-mediated expression of downstream effectors such as CHPT1 can be viable targets to overcome Enz resistance in PCa.

Pseudocapsule of Small Renal Cell Tumors: CT Imaging Spectrum and Correlated Histopathological Features.

PURPOSE: To systematically analyze histopathologic features of pseudocapsule in small renal cell tumor (diameter≤4cm), assess the integrity of pseudocapsules by Computed Tomography (CT), and provide theoretical basis for the safety of nephron sparing surgery. MATERIALS AND METHODS: The pathological data of 116 patients who underwent surgery with clear cell renal cell carcinoma admitted from May 2010 to October 2017 were retrospectively analyzed. All patients underwent a CT scan of the abdomen including an unenhanced and triple-phase (arterial, nephrographic and excretory) post contrast series."All patients underwent a CT scan of the abdomen including an unenhanced and triple-phase (arterial, nephrographic and excretory) post contrast series."All patients underwent a CT scan of the abdomen including an unenhanced and triple-phase (arterial, nephrographic and excretory) post contrast seriesAll patients underwent a CT scan of the abdomen including an unenhanced and three-phase (arterial, nephrographic and excretory) post contrast series. Thorough gross examination and histological sections were used to determine the integrity of the pseudocapsule by two uropathologists. The consistency between pathological findings and CT imaging were evaluated by Kappa consistency test. RESULTS: The mean diameter of tumor was 3.0cm, range (2.6 ± 0.8) cm. On CT the pseudocapsule can present with one of the three following feathers:1) A regular and distinct halo; 2)lobulated clear margins;3) blurred margins. On histopathology, complete psuedocapsule was found in 85 tumors, incomplete psuedocapsule in 25 and no psuedocapsule was found in 6 tumors; CT scan findings demonstrated a regular halo in 82 tumors, lobulated clear margins in 26 and blurred margins in 8 tumors(Kappa=0.833,P=0.000). CONCLUSIONS: Most small renal cell tumors have an obvious psuedocapsule. Preoperative determination of the psuedocapsule's integrity is particularly important. CT scan can reliably evaluate the tumor margins and demonstrate the psuedocapsule when present. The imaging results are well correlated with the pathologic findings.

Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-ß1/EMT pathway.

BACKGROUND: Previous study has reported that loss of epithelial androgen receptor (AR) may promote tumor progression and cause TRAMP mouse model die earlier. The detail mechanisms, however, remain unclear. METHODS: Immunohistochemistry assay, Western blot and real-time PCR were used to detect the expression of epithelial and mesenchymal markers. RNA extraction, RT-PCR, quantitative RT-PCR, BrdU incorporation assays, flow cytometry and other experimental technics were also used in present work. RESULTS: Decreased expression of epithelial markers (Cytokeratin 8, NKX3.1 and E-cadherin) and increased expression of mesenchymal markers (α-SMA, Vimentin, and N-cadherin) in were found in AR knockout TRAMP tumors. Further investigation indicated that AR signal deprivation is associated with cell morphology transition, high cell mobility, high cell invasion rate and resistance to anoikis in TRAMP prostate tumor cells. Together, these findings implied knockout AR in TRAMP prostate tumor may lead to EMT, which may result in earlier metastasis, and then cause TRAMP mice die earlier. TGF-ß1 is responsible for EMT in AR knockout TRAMP tumor cells. CONCLUSIONS: In conclusion, ADT therapy induced hormone refractory prostate cancer may gain the ability of metastasis through cell's EMT which is a phase of poor differentiation. Anti-EMT drugs should be developed to battle the tumor metastasis induced by ADT therapy.

Role and mechanism of micro-energy treatment in regenerative medicine.

With the continuous integration and intersection of life sciences, engineering and physics, the application for micro-energy in the basic and clinical research of regenerative medicine (RM) has made great progress. As a key target in the field of RM, stem cells have been widely used in the studies of regeneration. Recent studies have shown that micro-energy can regulate the biological behavior of stem cells to repair and regenerate injured organs and tissues by mechanical stimulation with appropriate intensity. Integrins-mediated related signaling pathways may play important roles in transducing mechanical force about micro-energy. However, the complete mechanism of mechanical force transduction needs further research. The purpose of this article is to review the biological effect and mechanism of micro-energy treatment on stem cells, to provide reference for further research.

Development and validation of CT imaging-based preoperative nomogram in the prediction of unfavorable high-grade small renal masses.

PURPOSE: In recent years, there has been an increase in the incidence of small renal masses (SRMs) and nephrectomy was the standard management of this disease in the past. Currently, the use of active surveillance has been recommended as an alternative option in the case of some patients with SRMs due to its heterogenicity. However, limited studies focused on the regarding risk stratification. Therefore, in the current study, we developed a nomogram for the purpose of predicting the presence of high-grade SRMs on the basis of the patient information provided (clinical information, hematological indicators, and CT imaging data). PATIENTS AND METHODS: A total of 329 patients (consisting of development and validation cohort) who had undergone nephrectomy for SRMs between January 2013 and May 2016 retrospectively were recruited for the present study. All preoperative information, including clinical predictors, hematological indicators, and CT predictors, were obtained. Lasso regression model was used for data dimension reduction and feature selection. Multivariable logistic regression analysis was applied for the establishment of the predicting model. The performance of the nomogram was assessed with respect to its calibration and discrimination properties and externally validated. RESULTS: The predictors used in the assessment of the nomogram included tumor size, CT tumor contour, CT necrosis, CT tumor exophytic properties, and CT collecting system oppression. Based on these parameters, the nomogram was evaluated to have an effective discrimination and calibration ability, and the C-index was found to be 0.883 after internal validation and 0.887 following external validation. CONCLUSION: Based on the aforementioned findings, it can be concluded that CT imaging-based preoperative nomogram is an effective predictor of SRMs and hence can be used in the preoperative evaluation of SRMs, due to its calibration and discrimination abilities.

Radical cystectomy for pT1 urothelial carcinoma of bladder not amenable to TURBT: Long-term results.

PURPOSE: This study sought to identify factors associated with survival of pT1 urothelial carcinoma of bladder (UCB) after radical cystectomy (RC). METHODS: This study consists of 114 pT1 UCB [primary 83, recurrent 31, none were amenable to transurethral resection (TUR)] treated by radical cystectomy. Survival analysis using Cox regression tests were performed to identify factors associated with survival of pT1 UCB after RC. RESULTS: Pelvic lymph node (LN) status, age and lymphovascular invasion (LVI) are associated with survival of pT1 UCB after RC; recurrent pT1 UCB of high grade origin (HGO) tends to have poorer CSS than primary pT1 UCB or recurrent pT1 UCB of low grade origin (LGO) (5-year and 10-year CSS rates was 75% and 73% for primary cases; 77% and 77% for recurrent pT1 UCB of LGO; and 56% and 37% for recurrent pT1 UCB of HGO, p = 0.078). CONCLUSIONS: LN status, age and LVI were significantly associated with survival of pT1 UCB after RC. Recurrent pT1 UCB of HGO should be managed with radical cystectomy in a timely fashion given that these cases tend to have poorer CSS than primary pT1 UCB after RC, even if they did not progress to muscle-invasive bladder cancer (MIBC).

Restoration of FKBP51 protein promotes the progression of castration resistant prostate cancer.

BACKGROUND: As deregulation of androgen receptor (AR) signaling target genes is associated with tumorigenesis and the development of prostate cancer (PCa), AR signaling is the primary therapeutic target for PCa. Although patients initially responses to first-line androgen deprivation therapies (ADTs), most of them with advanced PCa progress to lethal castration-resistant prostate cancer (CRPC). Recent studies have suggested the molecular mechanisms by which AR elicit the robust up-regulation of the FKBP51 gene. We suggest that restored expression of FKBP51 gene, modulated by androgen receptor splicing variant 7 (AR-V7) which replaces full length androgen receptor (AR-FL) in androgen ablation status, promotes CRPC progression through activating NF-κB signaling. METHODS: Immunohistochemistry assays were used to detect the expression of AR-V7, FKBP51 and NF-κB signaling correlated proteins in CRPC tissues. An androgen ablation resistant PCa cell line model established by Long-term culturing in androgen depleted medium, named androgen-independent LNCaP (LNCaP-AI) cells, were used to dynamically monitor FKBP51 expression during the process of androgen dependent PCa cells transforming into androgen-independent cells, as well as its association with NF-κB signal pathway. LNCaP-AI cell line was determined to express AR-V7 protein continuously. Luciferase reporter assays and DNA pull down were used to determine the association between AR-V7 and FKBP51. RESULTS: Our results suggested that CRPC patients with AR-V7 high expression tend to have higher expression of FKBP51 and enhanced NF-κB signaling compared with AR-V7 negative patients. Knockdown of AR-V7 or FKBP51 in LNCaP-AI cells attenuated the level of p-NF-κB (Ser536) and androgen-resistant cells growth. Luciferase reporter assays and DNA pull down results indicated that FKBP51 was transcriptionally promoted by AR-V7 in absence of androgen, which enhanced NF-κB signaling. CONCLUSIONS: Because of upregulation of AR-V7 in androgen-independent PCa cells, increasing of FKBP51 induced NF-κB signaling, leading to progression of CRPC.

CD4 + T cells promote renal cell carcinoma proliferation via modulating YBX1.

Renal cell carcinoma (RCC) is a common urologic tumor and the third leading cause of death among urological tumors. Recent studies demonstrate that RCC tumors are more heavily infiltrated by lymphocytes than other cancers. However, the exact roles played by CD4 + T cells in RCC proliferation remain unknown. In this study, we cocultured RCC cells with CD4 + T cells. Stable knockdown of YBX1 in RCC cells was constructed. The effects of CD4 + T cells, TGFß1 and YBX1 on RCC cells were investigated using cell viability assays. In situ RCC nude mouse model was used to observe the tumor growth. The potential mechanisms of CD4 + T cells and YBX1 in RCC cells proliferation were explored by qRT-PCR and western blot. Expression of CD4, Foxp3 and TGFß1 in RCC were quantified by immunohistochemical staining. The results indicated that CD4, Foxp3 and TGFß1 were significantly up-regulated in RCC tissues. Human clinical sample and in vitro cell lines studies showed that RCC cells had better capacity than its surrounding normal kidney epithelial cells to recruit the CD4 + T cells. In vivo mouse model studies were consistent with the results by in vitro cell lines studies showing infiltrating T cells enhanced RCC cell proliferation. qRT-PCR and western blot exhibited that CD4 + T cells could enhance RCC cell proliferation via activating YBX1/HIF2α signaling pathway. Furthermore, CD4 + T cells functioned through inducing TGFß1 expression. In a word, infiltrating CD4 + T cells promoted TGFß1 expression in both RCC and T cells and regulated RCC cells proliferation via modulating TGFß1/YBX1/ HIF2α signals.

[Correlation between the expression of Pim-1 and androgen-deprivation therapy for prostate cancer].

OBJECTIVE: To investigate the expression of the Pim-1 gene in the LNCaP cells of the animal model of orthotopically implanted prostate cancer by surgical castration simulating androgen-deprivation therapy. METHODS: We equally allocated 32 male BALBc-nu mice into 4 groups, androgen-dependent prostate cancer (ADPC), androgen-deprivation therapy (ADT) , castration-resistant prostate cancer (CRPC) and blank control, and established the models of orthotopically implanted tumor using human prostate cancer LNCaP cells. We detected and ,compared the expressions of Pim-1, PSA, and androgen receptor (AR) in the tumor tissues of different groups by RT-PCR. qRT-PCR, ELSIA and immunohistochemistry. RESULTS: The relative gray scales in the ADPC and CRPC groups were 0.59 ± 0.01 and 1.14 ± 0.02, with statistically significant differences from 0.62 ± 0.03 in the ADT group (P < 0.05), and the Δ Ct values of Pim-1 were 6.15 ± 0.34 and 4.56 ± 0.23 in the former two groups, also with significant differences from 5.11 ± 0.21 in the latter (P < 0.05). The results of 2-ΔΔ Ct relative quantification analysis showed that the amplification products of Pim-1 in the ADT and CRPC groups increased 2.05 and 3.01 times respectively that of the ADPC group. The concentration of PSA was significantly higher in the ADPC ([480 ± 25] pg/ml) and CRPC ([870 ± 23] pg/ml) than in the ADT ([170 ± 32] pg/ml) and blank control groups (0 µg/L) (P < 0.01). The mean optical densities of Pim-1 and AR proteins were 0.017 ± 0.002 and 0.032 ± 0.009 in the ADPC group and 0.024 ± 0.002 and 0.040 ± 0.011 in the CRPC group, both with significant differences from those in the ADT group (0.018 ± 0.001 and 0.019 ± 0.006) (P < 0.01). CONCLUSION: Pim-1 is highly expressed in nude mice with prostate cancer receiving androgen-deprivation therapy and plays an important role in the progression and metastasis of prostate cancer.

What is the next generation therapeutic strategy for castration-resistant prostate cancer.

Prostate cancer (PCa) is one of the most common cancers in the world. Since androgen receptor (AR) signal plays key roles in the PCa progression, targeting androgens via the current androgen deprivation therapy (ADT) is the main therapeutic strategy for advanced PCa. However, most patients who receive ADT, including the second generation anti-androgens enzalutamide (also known as MDV3100) may finally develop the castration (or anti-androgen) resistance after 12-24 months treatment. In the manuscript by Asangani et al., the authors demonstrated that targeting the amino-terminal bromodomains of BRD4 could preferentially suppress human castration-resistant prostate cancer (CRPC) cell lines. While further studies are required to understand the full impact of their findings, the innovative approach provides a potential novel epigenetic approach for the concerted blockade of oncogenic drivers in CRPC.