Curcumin strengthens a spontaneous self-protective mechanism-SP1/PRDX6 pathway, against di-n-butyl phthalate-induced testicular ferroptosis damage.

As one of the common plasticizers, di-n-butyl phthalate (DBP) has been using in various daily consumer products worldwide. Since it is easily released from products and exists in the environment for a long time, it has a lasting impact on human health, especially male reproductive health. However, the detailed mechanism of testicular damage from DBP and the protection strategy are still not clear enough. In this study, we found that DBP could induce dose-dependent ferroptosis in testicular tissue. Mechanism dissection indicates that DBP can upregulate SP1 expression, which could directly transcriptionally upregulate PRDX6, a negative regulator of ferroptosis. Overexpression of PRDX6 or adding SP1 agonist curcumin could suppress the DBP-induced ferroptosis on testicular cells. In vivo, rats were given 500 mg/kg/day DBP orally for 3 weeks; elevated levels of ferroptosis were detected in testicular tissue. When the above-mentioned doses of DBP and curcumin at a dose of 300 mg/kg/day were administered intragastrically simultaneously, the testicular ferroptosis induced by DBP was alleviated. Immunohistochemistry and quantitative real-time PCR of testis tissue showed that the expression of PRDX6 was upregulated under the action of DBP and curcumin. These findings suggest a spontaneous self-protection mechanism of testicular tissue from DBP damage by upregulating SP1 and PRDX6. However, it is not strong enough to resist the DBP-induced ferroptosis. Curcumin can strengthen this self-protection mechanism and weaken the level of ferroptosis induced by DBP. This study may help us to develop a novel therapeutic option with curcumin to protect the testicular tissue from ferroptosis and function impairment by DBP.

In silico, in vitro and in vivo studies: Dibutyl phthalate promotes prostate cancer cell proliferation by activating Forkhead Box M1 and remission after Natura-α pretreatment.

Dibutyl phthalate (DBP) is widely used in perfumes, cosmetics, shampoos and medical devices. It is ubiquitous in the environment and greatly endangers people's health. Several studies have reported that being exposed to it can promote the development of lung cancer, breast cancer, hepatoma, and multiple myeloma. However, there are still few studies on the specific molecular mechanism and prevention methods of DBP promoting the progression of prostate cancer. This study, in silico, in vitro and in vivo, aims to explore the promoting effect of DBP on prostate cancer cell proliferation. In silico analysis, we obtained a set of DBP interactive genes by utilizing TCGA, CTD and GEO database. These genes are mainly enriched in cell cycle regulatory pathways and they have high degree of homogeneity. We found that these genes shared one transcription factor - Forkhead Box M1 (FOXM1) by performing Chip-X Enrichment Analysis (Version 3.0). FOXM1, once called the 2010 Molecule of the Year, aberrantly expressed in up to 20 kinds of tumors. In vitro experiments, we used DBP at concentrations of 10-8 M and 5 * 10-7 M to treat C4-2 and PC3 cells for 6 days, respectively. Cell viability was promoted significantly. When Natura-α was added in the background of above-mentioned concentration of DBP, this effect was significantly inhibited. In addition, we also found that DBP can interfering with the efficacy of enzalutamide therapy. The introduction of Natura-α can also reverse this phenomenon. In vivo, subcutaneous tumor formation experiments in nude mice, 800 mg/kg/day DBP can promote the growth of prostate cancer. This phenomenon was suppressed when Natura-α (100 mg/kg/day) was added. Based on the results of the above three levels, we confirmed that DBP can target FOXM1 to promote prostate cancer cell proliferation. Natura-α can reverse its cancer-promoting effect. This study provides new insights into the impact of DBP on prostate cancer.

Improving the understanding of PI-RADS in practice: characters of PI-RADS 4 and 5 lesions with negative biopsy.

The Prostate Imaging Reporting and Data System (PI-RADS) has good ability to identify the nature of lesions on prostate magnetic resonance imaging (MRI). However, some lesions are still reported as PI-RADS 4 and 5 but are biopsy-proven benign. Herein, we aimed to summarize the reasons for the negative prostate biopsy of patients who were assessed as PI-RADS 4 and 5 by biparameter MRI. We retrospectively sorted out the prostate MRI, treatment, and follow-up results of patients who underwent a biparameter MRI examination of the prostate in The First Affiliated Hospital of Nanjing Medical University (Nanjing, China) from August 2019 to June 2021 with PI-RADS 4 and 5 but a negative biopsy. We focused on reviewing the MRI characteristics. A total of 467 patients underwent transperineal prostate biopsy. Among them, biopsy pathology of 93 cases were negative. After follow-up, 90 patients were ruled out of prostate cancer. Among the 90 cases, 40 were considered to be overestimated PI-RADS after review. A total of 22 cases were transition zone (TZ) lesions with regular appearance and clear boundaries, and 3 cases were symmetrical lesions. Among 15 cases, the TZ nodules penetrated the peripheral zone (PZ) and were mistaken for the origin of PZ. A total of 17 cases of lesions were difficult to distinguish from prostate cancer. Among them, 5 cases were granulomatous inflammation (1 case of prostate tuberculosis). A total of 33 cases were ambiguous lesions, whose performance was between PI-RADS 3 and 4. In summary, the reasons for "false-positive MRI diagnosis" included PI-RADS overestimation, ambiguous images giving higher PI-RADS, diseases that were really difficult to distinguish, and missed lesion in the initial biopsy; and the first two accounted for the most.

High dose androgen suppresses natural killer cytotoxicity of castration-resistant prostate cancer cells via altering AR/circFKBP5/miRNA-513a-5p/PD-L1 signals.

Most advanced prostate cancer (PCa) patients initially respond well to androgen deprivation therapy, but almost all eventually develop castration-resistant prostate cancer (CRPC). Early studies indicated the bipolar androgen therapy via a cycling of high dose and low dose of androgen to suppress PCa growth might be effective in a select patient population. The detailed mechanisms, however, remain unclear. Here we found the capacity of natural killer (NK) cells to suppress the CRPC cells could be suppressed by a high dose of dihydrotestosterone (DHT). Mechanism dissection indicates that transactivated AR can increase circularRNA-FKBP5 (circFKBP5) expression, which could sponge/inhibit miR-513a-5p that suppresses the PD-L1 expression via direct binding to its 3'UTR to negatively impact immune surveillance from NK cells. Preclinical data from in vitro cell lines and an in vivo mouse model indicate that targeting PD-L1 with sh-RNA or anti-PD-L1 antibody can enhance the high dose DHT effect to better suppress CRPC cell growth. These findings may help us to develop novel therapies via combination of high dose androgen with PD-1/PD-L1 checkpoint inhibitors to better suppress CRPC progression.

A comprehensive prostate biopsy standardization system according to quantitative multiparametric MRI and PSA value: P.R.O.S.T score.

BACKGROUND: Although most studies believe that systematic biopsy (SB) and targeted biopsy (TB) should be performed simultaneously in patients with suspected prostate cancer, we believe that patients with the Prostate Imaging-Reporting and Data System (PI-RADS) score of 4/5 may be able to perform TB only. METHODS: We retrospectively analyzed the pathological results of patients undergoing transperineal prostate biopsy with PI-RADS 4 and 5 in our center. We use the data from 2019 to 2020 as the training set to establish the prediction model and the data from 2021 as the verification set to test the effectiveness. Through stepwise logistics regression analysis, we integrate statistically significant clinical factors and establish a model to further predict whether the target area is tumor. RESULTS: The results showed that age (O), total number of lesions (T), histological region (R), PI-RADS score (S), and PSA density (P) were significantly correlated with the results of TB, and the formula was: p = 1/[1 + e^(- 11.387 + 0.058 × O + (- 0.736 × T) + 0.587 × R + 1.574 × S + 7.338 × P)]. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the prediction model was 0.840 (95% CI 0.802-0.877), with the optimal threshold of 0.762. And the corresponding specificity and sensitivity were 0.765 and 0.752. In the validation set, the AUC of the prediction model was 0.816 (95% CI 0.759-0.874), which means that it has good prediction efficiency. CONCLUSION: The P.R.O.S.T score can effectively screen PI-RADS 4/5 lesions, which may help physicians shunt patients who need prostate biopsy to reduce unnecessary systematic biopsies.

KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma.

BACKGROUND: Studies over the past decade have shown that competitive endogenous RNA (ceRNA) plays an essential role in the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). Meanwhile, immune checkpoint blocker is gradually moving towards the first-line treatment of ccRCC. Hence, it's urgent to develop a new prediction model for the efficiency of immunotherapy. At present, there is no study to reveal the effect of ceRNA network on the efficiency of immunotherapy for ccRCC. METHODS: To systematically analyze the effect of ceRNA hub genes in ccRCCon immune response, we constructed prognosis models based on ceRNAs and immune cells, respectively. We constructed ceRNA network using hypergeometric distribution test and correlation analysis with R script based on The Cancer Genome Atlas (TCGA) database. We then applied the Cibersort algorithm to simulate the infiltration overview of immune cells in kidney renal clear carcinoma (KIRC) samples. Prognosis-related immune cells were screened and a predictive model of these cells was constructed. Prognosis-related immune cells and ceRNA hub genes were performed with co-expression analysis. Finally, qRT-PCR and immunofluorescence assays were performed to validate the results. RESULTS: The construction of ceRNA related prognosis model contained 8 hub genes, including RELT, MYO9B, KCNN4, SIX1, OTOGL, MALAT1, hsa-miR-130b-3p, and hsa-miR-21-5p. The area under the receiver operating characteristic curve (AUC) was 0.77 at 5 years. For the construction of immune cells prognosis model, 3 immune cells (T cells regulatory, Macrophages, Mast cells resting) were adopted, and the AUC was 0.65 at 5 years. We then merged the two models by correlation analysis and co-expression analysis. Finally, we found that KCNN4 positively correlates with T cells regulatory (Tregs) and negatively correlates with mast cells resting significantly. Furthermore, higher expression of KCNN4 may lead to a higher potential for immune evasion and lower efficiency for immune checkpoint inhibitors (ICIs). CONCLUSIONS: Generally, this is the first study to assess the prognostic value of immune related ceRNA hub genes in ccRCC, and KCNN4 was finally demonstrated to be a key regulatory factor with strong correlation with Tregs and mast cells resting.

Diagnosis and Management of Primary Prostatic Signet Ring Cell Carcinoma: Single-Center Experience.

The purpose of the study was to retrospectively summarize the diagnosis and management of 10 primary prostatic signet ring cell carcinoma (PPSRCC) cases in our center. Ten PPSRCC patients diagnosed at the First Affiliated Hospital of Nanjing Medical University from November 2014 to December 2020 were included. Clinical characteristics, image features, therapeutic procedures, histological diagnosis, and outcomes were retrospectively analyzed. All patients received prostate-specific antigen (PSA) examination preoperatively. Nine of them accepted multiparametric magnetic resonance imaging (mpMRI) due to elevated PSA value, and further biopsied. Among them, five patients were diagnosed as prostatic adenocarcinoma and the other four cases were found a mixture of signet ring cell carcinoma (SRCC) and adenocarcinoma. Furthermore, gastrointestinal endoscope and abdominal computed tomography (CT) did not find SRCC originating in gastrointestinal tract. Therefore, these cases were considered to be PPSRCC. Nine patients accepted laparoscopic or robot-assisted RP. Only one patient with normal PSA adopted transurethral resection of the prostate. Postoperative pathological results confirmed SRCC mixed with prostatic adenocarcinoma in nine cases, and only one patient with pure SRCC. After surgery, nine patients received adjuvant hormone therapy, one of which accepted radiotherapy simultaneously. The patient with pure SRCC did not accept any adjuvant therapy postoperatively. During a mean follow-up of 31.9 months, only four patients were alive without disease progression. In summary, PPSRCC is a rare malignant tumor with few specific symptoms, rapid disease progression, and poor prognosis and is frequently accompanied by high-grade prostate adenocarcinoma patterns. There is still no clear and effective strategy to improve the prognosis.

Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1.

Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with tumor stage. Tcam-2 cell line was used to investigate the CLU function in testicular seminoma, and CLU was found to inhibit the proliferation and metastasis abilities. Besides, extracellular matrix protein COL15a1 was demonstrated as the downstream of CLU to affect the epithelial-mesenchymal transition (EMT) process via competitively binding to DDR1 with COL1A1 and inhibiting the phosphorylation of PYK2. MEF2A was found to interact with CLU and bind to the promoter of COL15a1 and so upregulate its expression. This is the first study using testicular xenografts in situ to simulate testicular seminoma metastatic and proliferative capacities. In conclusion, CLU acts as a tumor suppressor to inhibit the metastasis of testicular seminoma by interacting with MEF2A to upregulate COL15a1 and blocking the EMT process.

Identification of autophagy-related long non-coding RNA prognostic and immune signature for clear cell renal cell carcinoma.

BACKGROUND: Studies over the past decade have shown that long non-coding RNAs (lncRNAs) play an essential role in the tumorigenesis and progression of kidney renal clear cell carcinoma (KIRC). Meanwhile, autophagy has been demonstrated to regulate KIRC pathogenesis and targeting therapy resistance. However, the prognostic value of autophagy-related lncRNAs in KIRC patients has not been reported before. METHODS: In this study, we obtained transcriptome data of 611 KIRC cases from the TCGA database and 258 autophagy-related mRNAs from the HADb database to identify autophagy-related lncRNAs by co-expression network. A prognostic model was then established basing on these autophagy-related lncRNAs, dividing patients into high-risk and low-risk groups. Survival analysis, clinical variables dependent receiver operating characteristic (ROC) analyses, univariate/multivariate Cox analyses, and clinical correlation analysis were performed based on risk signature with R language. Gene set enrichment analysis (GSEA) was then performed to investigate the potential mechanism of the risk signature promoting KIRC progression with GSEA software. CIBERSORT algorithm was performed to assess the impact of these lncRNAs on the infiltration of immune cells. RESULTS: A total of 17 lncRNAs were screened out and all these lncRNAs were found significantly related to KIRC patients' overall survival in subsequent survival analyses. Besides, the overall survival time in the high-risk group was much poorer than in the low-risk group. The ROC analysis revealed that the prognostic value of risk signature was better than age, gender, grade, and N stage. Univariate/multivariate analyses suggested that the risk signature was an independent predictive factor for KIRC patients. Immune and autophagy related pathways were dramatically enriched in high-risk and low-risk groups, respectively, and lncRNAs related immune cells were identified by CIBERSORT. CONCLUSIONS: In summary, our identified 17 autophagy-related lncRNAs had prognostic value for KIRC patients which may function in immunomodulation.

TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner.

BACKGROUND: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive. METHODS: RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism. RESULTS: We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-ß1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications. CONCLUSIONS: Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-ß1 signaling in regulating cancerous malignancies.

Acinar with ductal and mucinous adenocarcinoma of prostate cancer complicated with lung metastasis: a case report and literature review.

Acinar adenocarcinoma, ductal adenocarcinoma and mucinous adenocarcinoma are the subtypes of prostate cancer (PCa). Most of the pathological types of PCa are acinar adenocarcinoma, while ductal adenocarcinoma and mucinous adenocarcinoma are uncommon. The case of acinar adenocarcinoma with ductal and mucinous adenocarcinoma has not been reported before. Herein, we report a treatment experience involving a 72-year-old man who presented similarly as most PCa patients, but the pathologic diagnosis was acinar adenocarcinoma with focal ductal and mucinous adenocarcinoma differentiating. Besides, this case is associated with lung metastasis, after radical prostatectomy (RP) and endocrine therapy the pulmonary nodule exerted a shrinking trend and the PSA level of this patient is still maintained at 0 ng/ mL till now. Through literature review, we found that patients who diagnosed as mixed pathological type of PCa had a lower survivor than pure PCa patients. Furthermore, there is no corresponding consensus or guideline for treating such multiple differentiated PCa patients. Surprisingly, this patient showed a high sensitivity to androgen deprivation therapy (ADT). Although the tumor presented aggressiveness, the followup results were satisfactory and we will continue to pay attention to his physical condition. We report this case to provide a treatment strategy for the patients with multi-differentiated PCa complicated with organ metastases.

The clinical application of enhanced recovery after surgery protocol in perioperative period of laparoscopic nephron sparing surgery.

BACKGROUND: The enhanced recovery after surgery (ERAS) program is focused on improving surgical outcomes and enhancing the patient experience before, during and after surgery. We performed this study to evaluate the effect of ERAS in perioperative period of laparoscopic nephron sparing surgery (LNSS). METHODS: A retrospective analysis of 287 consecutive patients with localized renal cell carcinoma (RCC) who underwent LNSS from December 2015 to June 2017 was conducted. Our study design included two cohorts. Patients underwent conventional care in one group (n=136), and ERAS protocol in the other group (n=151). The data of recovery of gastrointestinal function, catheter and drainage tube removal time, length of stay (LOS), hospitalization expenses and incidence of postoperative complications were compared between the two groups. RESULTS: Compared with conventional group, cases in ERAS group presented with shorter time of recovery of gastrointestinal function (P<0.05) and LOS (P<0.05), shorter catheter and drainage tube removal time (P<0.05), lower hospitalization expenses and lower perioperative complications (P<0.05). CONCLUSIONS: Program of ERAS used in perioperative period of LNSS can apparently accelerate the time of postoperative recovery, reduce complications, shorten time stay in hospital and cut down the total cost, finally improve patients' satisfaction.

Experience of diagnosis and management of metanephric adenoma: retrospectively analysis of 10 cases and a literature review.

BACKGROUND: Metanephric adenoma (MA) is a rare benign tumor with only several hundred cases reported worldwide to date. Herein, we retrospectively summarized the experience of diagnosis and management of ten MA cases. METHODS: A total of ten MA patients were included in this study definitely diagnosed by postoperative immunohistochemistry at the First Affiliated Hospital of Nanjing Medical University from January 2010 to January 2019. Clinical characteristics, image features, therapeutic procedures, histological diagnosis and outcomes of them were retrospectively analyzed. RESULTS: Characteristics of the patient population were nine females and one male with age of 36.8±17.5 years. The mean tumor size was 33.6 mm (range from 35.0 to 70.0 mm). Among them, nine cases were asymptomatic and one case showed acute flank pain. All ten cases underwent plain and enhanced computed tomography (CT) scan. Laparoscopic partial nephrectomy (LPN) was performed in seven cases and laparoscopic radical nephrectomy (LRN) was applied in the other three cases. Postoperative routine pathology results confirmed that seven cases were MA. However, two patients were misdiagnosed with papillary renal cell carcinoma (PRCC), and another was misdiagnosed with Wilms' tumor. Further immunohistochemistry eventually confirmed all these ten cases as MA. During a mean follow-up of 58.3 month, all ten patients were alive with no local recurrences nor metastases. CONCLUSIONS: In summary, MA is a rare benign tumor with no distinct clinical symptoms. The definite diagnosis depends on the postoperative pathological findings. Fortunately, due to its non-malignant nature, patients always have a good prognosis.

Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma.

Background: Apolipoprotein C1 (APOC1) has been proved to play a critical role in gastric, breast, lung, and pancreatic cancer. However, the relationship between APOC1 and urinary tumors remains unclear. This study aimed to assess the diagnostic and prognostic value of APOC1 in urinary tumors. Methods: We performed a pan analysis of APOC1 mRNA expression in urinary cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) database. To further investigate the prognostic value of APOC1 expression in urinary cancers, the Kaplan-Meier plotter database was used. Furthermore, we collected the tumor and adjacent normal samples of 32 ccRCC patients to perform qRT-PCR and western blotting assays. A total of 72 cases with ccRCC were analyzed using tissue microarrays (TMAs). Results: Our results based on Kaplan-Meier plotter database indicated that a high expression of APOC1 may lead to poor overall survival (OS, p = 0.0019) in patients with ccRCC. Furthermore, the cancer stages and tumor grade of ccRCC appeared to be strongly linked with APOC1 expression according to UALCAN database. Hence, we reached a preliminary conclusion that APOC1 may play a key role in the tumorigenesis and progression of ccRCC. Furthermore, the Kaplan-Meier survival curve analyses of 72 clinical patients indicated that high expression of APOC1 was associated with poor progression-free survival (PFS, p = 0.007) and OS (p = 0.022). In addition, univariate Cox regression analysis confirmed the significant relationship between APOC1 expression and survival (p = 0.038). The TMAs analysis in combination with the patients' clinicopathological features was also performed. The expression of APOC1 was found to be significantly correlated with the tumor size (p = 0.018) and histological grade (p = 0.016). Conclusions: In conclusion, the findings of our study suggest that APOC1 may serve as a novel diagnostic and prognostic biomarker for ccRCC. Further evidence on the mechanism of APOC1 promoting tumor progression may transform it to a new therapeutic target for the treatment of ccRCC.

The miR-361-3p increases enzalutamide (Enz) sensitivity via targeting the ARv7 and MKNK2 to better suppress the Enz-resistant prostate cancer.

The androgen receptor splicing variant 7 (ARv7) that lacks the ligand-binding domain is increasingly considered as a key player leading to enzalutamide (Enz) resistance in patients with prostate cancer (PCa). However, the detailed mechanisms of how ARv7 expression is regulated and whether it also needs other factors to induce maximal Enz resistance remain unclear. Here, we identified a microRNA, miR-361-3p, whose expression is lower in patients with recurrent PCa, could function via binding to the 3'UTR of ARv7, but not the wild type of AR, to suppress its expression to increase the Enz sensitivity. Importantly, we found that miR-361-3p could also bind to the 3'UTR of MAP kinase-interacting serine/threonine kinase 2 (MKNK2) to suppress its expression to further increase the Enz sensitivity. In turn, the increased Enz can then function via a feedback mechanism through altering the HIF-2α/VEGFA signaling to suppress the expression of miR-361-3p under hypoxia conditions. Preclinical studies using an in vivo mouse model with orthotopically xenografted CWR22Rv1 cells demonstrated that combining the Enz with the small molecule miR-361-3p would result in better suppression of the Enz-resistant PCa tumor progression. Together, these preclinical studies demonstrate that miR-361-3p can function via suppressing the expression of ARv7 and MKNK2 to maximally increase the Enz sensitivity, and targeting these newly identified Enz/miR-361-3p/ARv7 and/or Enz/miR-361-3p/MKNK2 signals with small molecules may help in the development of novel therapies to better suppress the CRPC in patients that already have developed the Enz resistance.

Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis.

BACKGROUND: Published studies present conflicting data regarding the impact of Thrombospondin-1 (TSP-1) expression on prognosis of various cancers. We performed this meta-analysis to illustrate the preliminary predictive value of TSP-1. METHODS: Twenty-four studies with a total of 2379 patients were included. A comprehensive literature search was performed by using PubMed, Cochrane Library, Web of Science, Embase, and hand searches were also conducted of relevant bibliographies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for patient survival and disease recurrence were initially identified to explore relationships between TSP-1 expression and patient prognosis. RESULTS: A total of 24 eligible studies were included in this meta-analysis. Our results showed that high level of TSP-1 was correlated significantly with poor overall survival (OS) (HR = 1.40, 95% CI: 1.17 ~ 1.68; P<0.001). However, high TSP-1 expression predicted no significant impact on progression-free survival (PFS)/ metastasis-free survival (MFS) (HR = 1.35, 95%CI: 0.87-2.10; P = 0.176) and disease-free survival (DFS)/ recurrence-free survival (RFS) (HR = 1.40, 95%CI: 0.77-2.53; P = 0.271). In addition, we performed subgroup analyses which showed that high TSP-1 expression predicted poor prognosis in breast cancer and gynecological cancer. Additionally, the relatively small number of studies on PFS/MFS and DFS/RFS is a limitation. The data extracted through Kaplan-Meier curves may not be accurate. Moreover, only English articles were included in this article, which may lead to deviations in the results. CONCLUSIONS: Our findings indicated high TSP-1 expression may act as a promising biomarker of poor prognosis in cancers, especially in breast cancer and gynecological cancer.

Clinical efficacy of enhanced recovery after surgery (ERAS) program in patients undergoing radical prostatectomy: a systematic review and meta-analysis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol has been identified to be beneficial in the amount of operations such as gastrointestinal surgery. However, the efficacy and safety in robot-assisted laparoscopic prostatectomy/laparoscopic radical prostatectomy (RALP/LRP) still remain controversial. METHOD: We searched randomized controlled trials and retrospective cohort studies comparing ERAS versus conventional care for prostate cancer patients who have undergone RALP/LRP. ERAS-related data were extracted, and quality of included studies was assessed using the Newcastle-Ottawa quality assessment scale and the Jadad scale. RESULT: As a result, seven trials containing 784 prostate cancer patients were included. ERAS was observed to be significantly associated with shorter length of hospital stay (SMD - 2.55, 95%CI - 3.32 to - 1.78, P < 0.05), shorter time to flatus (SMD - 1.55, 95%CI - 2.26 to - 0.84, P < 0.05), shorter time to ambulate (SMD - 6.50, 95%CI - 10.91 to - 2.09, P < 0.05), shorter time to defecate (SMD - 2.80, 95%CI - 4.56 to - 1.04, P < 0.05), and shorter time to remove drainage tube (SMD - 2.72, 95%CI - 5.31 to - 0.12, P < 0.05). Otherwise, no significant difference was reported in other measurements. CONCLUSIONS: In conclusion, ERAS can reduce length of hospital stay, time to flatus, time to defecate, time to ambulate, and time to remove drainage tube in prostate cancer patients who have undergone RALP/LRP compared with conventional care.

Docetaxel suppresses immunotherapy efficacy of natural killer cells toward castration-resistant prostate cancer cells via altering androgen receptor-lectin-like transcript 1 signals.

BACKGROUND: Docetaxel is an effective first-line chemotherapy agent used in the treatment of castration-resistant prostate cancer (CRPC) patients. However, most times chemotherapy with docetaxel eventually fails due to the development of docetaxel resistance. Natural killer (NK) cells are the first line of defense against cancer and infections. NK cell function is determined by a delicate balance between signals received via activating and inhibitory receptors. The aim of this study is to explore whether the potential docetaxel-resistant mechanism is associated with impaired NK cell cytotoxicity toward CRPC cells. METHODS: By performing MTT assay, we explored the role of docetaxel in regulating NK cells' cytotoxicity. Western blot and quantitative real-time polymerase chain reaction analysis were used to measure messenger RNA and protein levels separately. Luciferase reporter assay and chromatin immunoprecipitation assay were performed to analyze the mechanism. RESULTS: We found that docetaxel could suppress the immunotherapy efficacy of NK cells toward CRPC cells via the androgen receptor (AR)-lectin-like transcript 1 (LLT1) signals in vitro. Analysis of the mechanism revealed that docetaxel functioned through increasing AR to upregulate LLT1 expression in CRPC cells. AR transcriptionally activated LLT1 expression by binding to its promoter region. Furthermore, targeting AR with ASC-J9 or blocking LL1 by anti-human LLT1 monoclonal antibody could reverse the suppressive effect of docetaxel on the immunotherapy efficacy of NK cells toward CRPC cells. CONCLUSIONS: We concluded that chemotherapy agent docetaxel could increase AR that transcriptionally regulated the expression of NK inhibitory ligand LLT1 on CRPC cells. An increase of LL1 may further suppress the immunological efficacy of NK cells to kill CRPC cells. Additionally, targeting AR or blocking LL1 could enhance the immunotherapy efficacy of NK cells toward CRPC cells which might be considered as a new therapeutic option for the prevention or treatment of docetaxel resistance.

Solitary fibrous tumor involving urinary bladder: a case report and literature review.

Solitary fibrous tumor (SFT) is a rare fibroblast stroma tumor involving the mediastinum and pleura. We herein describe an SFT of bladder which is extremely rare and review 29 similar cases in the last decades. We present a case of a 52-year-old male patient who suffered from urinary urgency and frequency for 12 months. Non-contrast computed tomography (CT) showed a slightly high density calcified mass with 70 mm × 61 mm in diameter. Contrast-enhanced CT demonstrated the mass was slightly enhanced. Cystoscopy revealed a huge mass with flat surface. Histopathological review of the biopsy specimens could not confirm the diagnosis. Partial cystectomy was then performed and the diagnosis of SFT was confirmed by immunohistochemistry. The patient is doing well at 12 months follow-up without recurrence and metastasis. In conclusion, the diagnosis of SFT involving bladder should combine clinical presentation and imaging features. Complete surgical resection is the primary method and long-term follow-up is necessary.

The management and composition of symptomatic seminal vesicle calculi: aetiological analysis and current research.

OBJECTIVE: To report our experience in the diagnosis, minimally invasive treatment, and composition of seminal vesicle calculi (SVC). PATIENTS AND METHODS: In the present study, we evaluated 20 patients who were admitted to our hospital from January 2013 to January 2018. All the patients were diagnosed with intractable haematospermia and SVC. The diagnosis was further confirmed by seminal vesiculoscopy. SVC were removed by basket extraction; with larger SVC fragmented by holmium laser before extraction. Scanning electron microscopy, X-ray diffraction, and infrared spectroscopy were used to determine the SVC composition. RESULTS: All operations were completed successfully without surgical complications. SVC were mostly composed of hydroxyapatite and protein, suggesting that they were produced by infections. CONCLUSIONS: Seminal vesiculoscopy is a simple, minimally invasive technique that can be used for diagnostic confirmation and treatment of seminal vesiculitis with SVC. This study improves our understanding of SVC and provides a theoretical basis for the prevention of postoperative recurrence of SVC.