Persistence of peripheral CD8 + CD28- T cells indicates a favourable outcome and tumour immunity in first-line HER2-positive metastatic breast cancer.

BACKGROUND: The contradictory role of CD8 + CD28- T cells in tumour immunity has been reported, while their biological and clinical significance in HER2-positive metastatic breast cancer (MBC) is still unknown. METHODS: HER2-positive MBC patients with no prior therapy in the metastatic setting were retrospectively recruited at two medical centres. Peripheral CD8 + CD28- T cells (pTCD8+CD28-) were detected at baseline and following therapeutic intervals. Progression-free survival (PFS) was compared according to pTCD8+CD28- levels. The molecular features of pTCD8+CD28- and its correlation with tumour immunity were also investigated. RESULTS: A total of 252 patients were enrolled, and the median follow-up time was 29.6 months. pTCD8+CD28- high at baseline has prolonged PFS compared to pTCD8+CD28- low (P = 0.001). Patients who maintained pTCD8+CD28- high had a longer PFS than those who kept pTCD8+CD28- low (P < 0.001). The enhanced pTCD8+CD28- level also indicates a longer PFS compared to pTCD8+CD28- low (P = 0.025). Here, pTCD8+CD28- was demonstrated as an antigen-experienced effector T cell. Higher IL-2 level (P = 0.034) and lower TGF-ß level (P = 0.016) in the serum and highly infiltrated CD8 + CD28- T cells (P = 0.037) were also connected to pTCD8+CD28- high. CONCLUSIONS: High pTCD8+CD28- level is associated with a favourable tumour immunity and a better PFS of HER2-targeting therapy in MBC patients.

Dietary bile acid supplementation reveals beneficial effects on intestinal healthy status of tongue sole (Cynoglossus semiliaevis).

The aim of this study was to investigate the effects of dietary bile acids (BAs) on intestinal healthy status of tongue sole in terms of immunity, antioxidant status, digestive ability, mucosal barrier-related genes expression and microbiota. Three experimental diets were prepared with BA levels at 0 mg/kg (CT), 300 mg/kg (BA1) and 900 mg/kg (BA2) in a commercial basal diet. Each diet was fed to three replicates with 120 fish (10.87 ± 0.32 g) in each tank. After an 8-week feeding trial, growth parameters were significantly enhanced in both BAs supplementary groups (P < 0.05), and compared with CT group, survival rate in BA2 group was significantly improved (P < 0.05). Intestinal lysozyme activity and contents of immunoglobulin M and complement 3 were significantly increased in both BAs supplementary groups (P < 0.05), suggesting an enhancement effect on the non-specific immune response. BAs inclusion also significantly improved intestinal antioxidant capabilities by increasing antioxidase activities and decreasing malondialdehyde levels. In addition, compared with CT group, intestinal digestive ability was substantially enhanced as indicated by the significantly increased lipase activity in BA2 group (P < 0.05) and significantly increased amylase activity in BA1 and BA2 groups (P < 0.05). Coincidentally, BAs inclusion significantly upregulated the relative expression of intestinal mucosal barrier-related genes (P < 0.05). Further, dietary BAs distinctly remodeled intestinal microbiota by decreased the abundance of some potential pathogenic bacteria. In conclusion, dietary BAs supplementation is an effective way to improve the intestinal healthy status of tongue sole.

LINC01006 regulates the proliferation, migration and invasion of hepatocellular carcinoma cells through regulating miR-433-3p/CBX3 axis.

INTRODUCTION AND OBJECTIVES: LINC01006 has been verified to be correlated with several cancer types, whereas its biological function in hepatocellular carcinoma (HCC) is still elusive. This study aimed to elucidate the specific regulatory mechanism of LINC01006 in the tumorigenesis of HCC. MATERIALS AND METHODS: The expression of LINC01006, miR-433-3p and CBX3 in HCC tissues and cells was assessed by qRT-PCR or Western blot. MTT, wound-healing, and transwell assays were used to evaluate the effects of LINC01006 on cell viability, migration, and invasion in vitro. A mouse xenograft model was established for in vivo assays. The relations among LINC01006, miR-433-3p, and CBX3 were analyzed by MS2-RNA immunoprecipitation (RIP) and Dual-luciferase reporter (DLR) assays. RESULTS: The expression of LINC01006 was up-regulated in HCC tissues and cells. LINC01006 knockdown inhibited the viability, wound healing rate, and invasive cell number of HeP3B and SK-HeP-1 cells, and decreased the tumor volume and weight in a mouse xenograft model. MiR-433-3p was a target of LINC01006, and LINC01006 overexpression inhibited the viability, wound healing rate, and invasive cell number of HeP3B and SK-HeP-1 cells. In addition, CBX3 was a target of miR-433-3p, which was negatively regulated by miR-433-3p. CBX3 overexpression and miR-433-3p inhibition reversed the inhibiting effects of LINC01006 knockdown on the viability, migration, and invasion of HeP3B cells. CONCLUSIONS: Silencing of LINC01006 inhibited the viability, migration, and invasion of HCC cells through regulating miR-433-3p/CBX3 axis.

Activation of FOXO3 pathway is involved in polyphyllin I-induced apoptosis and cell cycle arrest in human bladder cancer cells.

Polyphyllin I (PPI), an extract from Paris polyphylla, has been demonstrated to possess antitumor activity against multiple cancers. However, whether PPI can inhibit bladder cancer (BCa) and the underlying mechanisms have never been researched. In this study, we initially found that PPI could induce BCa cell apoptosis and cell cycle arrest, as well as inhibit cell proliferation in vitro. Additionally, PPI could effectively suppress the in vivo growth of BCa in the xenograft mice model. Furthermore, we found that forkhead box O3 (FOXO3) and its targets including BIM or NOXA were significantly upregulated in BCa cells following PPI treatment. Interestingly, we observed that FOXO3 knockdown partly reversed the effects of PPI on BCa cells. Taken together, our findings suggested that PPI exerted a cytotoxic effect in vitro and an antitumor activity in vivo against BCa partly by activating FOXO3 signaling pathway. Therefore, PPI may serve as a promising chemotherapy agent for BCa treatment.

Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery.

Urine metabolomics have been used to identify biomarkers for clinical diseases. However, inter-individual variations and effect factors need to be further evaluated. In our study, we explored the urine metabolome in a cohort of 203 health adults, 6 patients with benign bladder lesions, and 53 patients with bladder cancer (BCa) using liquid chromatography coupled with high resolution mass spectrometry. Inter-individual analysis of both healthy controls and BCa patients showed that the urine metabolome was relatively stable. Further analysis indicated that sex and age affect inter-individual variations in urine metabolome. Metabolic pathways such as tryptophan metabolism, the citrate cycle, and pantothenate and CoA biosynthesis were found to be related to sex and age. To eliminate age and sex interference, additional BCa urine metabolomic biomarkers were explored using age and sex-matched urine samples (Test group: 44 health adults vs. 33 patients with BCa). Metabolic profiling of urine could significantly differentiate the cases with cancer from the controls and high-grade from low-grade BCa. A metabolite panel consisting of trans-2-dodecenoylcarnitine, serinyl-valine, feruloyl-2-hydroxyputrescine, and 3-hydroxynonanoyl carnitine were discovered to have good predictive ability for BCa with an area under the curve (AUC) of 0.956 (cross validation: AUC = 0.924). A panel of indolylacryloylglycine, N2 -galacturonyl-L-lysine, and aspartyl-glutamate was used to establish a robust model for high- and low-grade BCa distinction with AUC of 0.937 (cross validation: AUC = 0.891). External sample (26 control vs. 20 BCa) validation verified the acceptable accuracy of these models for BCa detection. Our study showed that urinary metabolomics is a useful strategy for differential analysis and biomarker discovery.

LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway.

BACKGROUND/AIMS: Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression. METHODS: RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance. The underlying mechanisms of TP73-AS1 in ccRCC were analyzed through in vitro functional assays. RESULTS: We found TP73-AS1 was upregulated in 40 ccRCC tissues compared with adjacent normal renal tissues and increased TP73-AS1 was correlated to aggressive clinicopathologic features and unfavorable prognosis. Knockdown of TP73-AS1 suppressed cell proliferation, invasion and induced cell apoptosis. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Knockdown of KISS1 partly reversed TP73-AS1 knockdown-induced inhibition of cell proliferation and promotion of apoptosis. We further determined that TP73-AS1 knockdown activated PI3K/Akt/mTOR signaling pathway, while overexpression of TP73-AS1 induced inhibition of PI3K/Akt/mTOR pathway and these effects could be partly abolished by overexpression of KISS1. CONCLUSION: In conclusion, we identified that TP73-AS1 as an oncogenic lncRNA in the development of ccRCC and a potential target for human renal carcinoma treatment.

INTERLEUKIN-6-PRODUCING PHEOCHROMOCYTOMA AS A NEW REASON FOR FEVER OF UNKNOWN ORIGIN: A RETROSPECTIVE STUDY.

OBJECTIVE: To explore the fever of unknown origin (FUO) in patients with interleukin-6 (IL-6)-producing pheochromocytoma. METHODS: Patients with pheochromocytoma were enrolled from June 2014 to April 2017. Clinical characteristics were recorded including sex, age, 24-h urinary catecholamines (norepinephrine, epinephrine, dopamine), tumor size, axillary temperature (AT), white blood cells (WBC), and serum IL-6 and high-sensitivity C-reactive protein (hsCRP) levels. IL-6 secretion by pheochromocytoma was analyzed by immunohistochemistry (IHC). RESULTS: We identified 29 cases of pheochromocytoma (7 with high AT and 22 with normal AT). Serum IL-6 and hsCRP levels were increased in the high AT group compared with the normal AT group (both P = .001). After pheochromocytoma resection, AT and IL-6 and hsCRP levels decreased significantly ( P<.001, P = .002 and P = .003, respectively). IHC revealed significantly higher IL-6 expression in the high AT group ( P = .002). CONCLUSION: IL-6-producing pheochromocytoma should be included in the differential diagnosis of FUO. ABBREVIATIONS: AT = axillary temperature; CT = computed tomography; FUO = fever of unknown origin; IHC = immunohistochemistry; IL-6 = interleukin-6; hsCRP = high-sensitivity C-reactive protein; WBC = white blood cells.

Clinical characteristics of XP11.2 translocation/TFE3 gene fusion renal cell carcinoma: a systematic review and meta-analysis of observational studies.

BACKGROUND: Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) is a rare subtype of RCC which is firstly described as a distinct entity in 2004 so that clinical characteristics of Xp11.2 RCC in different gender and age are unknown. The purpose of systematic review and meta-analysis is to provide a comprehensive assessment on them. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies which evaluate the clinical characteristics of Xp11.2 RCC. The literature published between July 2004 and May 2014 was searched. RESULTS: A total of 15 studies with 147 participants were included. The meta-analysis demonstrated that number of patients of all age in female was higher than in male with pooled OR of 3.93(95 % CI = 1.66-9.34). However, incidence of distant metastases (OR = 0.34, 95 % CI = 0.12-1.57) and lymphatic metastases (OR = 0.51, 95 % CI = 0.14-1.91), tumor stage (OR = 0.85, 95 % CI = 0.34-2.15) and overall survival (OS) (OR = 0.46, 95 % CI = 0.05-4.34) between male and female were comparable. Incidence in female was higher than in male with pooled OR of 5.13(95 % CI = 1.67-15.72) in adults, while in children no gender-related predominance (OR = 1.19, 95 % CI = 0.38-3.72) was observed. In addition, incidence of distant metastases (OR = 1.00, 95 % CI = 0.13-7.84) and lymphatic metastases (OR = 1.00, 95 % CI = 0.07-13.67) and tumor stage (OR = 1.94, 95 % CI = 0.20-19.03) between children and adults were comparable. Survival curves presented comparable outcomes between male and female (P = 0.707) as well as between children and adults (P = 0.383). CONCLUSIONS: Female patients with Xp11.2 RCC in adults exhibit a high incidence compared to male, but not in children. Comparable clinical characteristics including incidence of distant and lymphatic metastases, tumor stage and prognosis is presented between male and female as well as between children and adults.

[Ultrasound-guided percutaneous radiofrequency ablation treatment for renal clear cell carcinoma].

OBJECTIVE: To investigate clinical outcomes of ultrasound-guided percutaneous radiofrequency ablation (USG-RFA) in patients with renal clear cell carcinoma. METHODS: Medical records of 34 patients who underwent USG-RFA of renal clear cell carcinoma at the Department of Urology of the Affiliated Drum Tower Hospital of Medical School of Nanjing University from May 2009 to January 2014 were retrospectively reviewed, including 28 male and 6 female patients aged between 25 and 85 years (mean age 60.7 years). Of the included cases, 16 had tumors located in the left kidney, 16 in the right, 1 in the solitary kidney, and 1 in the bilateral kidney. There were 35 tumors in this study totally. The maximum diameter of the tumors was 1.8 to 5.0 cm (mean (2.7 ± 0.3) cm), of which 32 cases of renal tumors were ≤ 4.0 cm and 3 cases of renal tumors were > 4.0 cm to 5.0 cm. Pathological diagnosis were acquired by ultrasound-guided percutaneous biopsy after USG-RFA. Contrast-enhanced ultrasound was used to evaluate tumor outcomes at the time of the surgery, and multi-slice spiral CT enhanced scan and contrast-enhanced ultrasound were used to identify residues and recurrences after treatment. RESULTS: Treatments for all the patients were finished with short postoperative hospital stay about 3-5 days. No complications related to USG-RFA were encountered in any of the cases, such as perirenal fluid collection, perirenal hematoma, and peripheral organ damage. All the cases were diagnosed as clear cell carcinoma according to pathological results. The mean follow-up period was 29 ± 6 (range 3-59) months. Of the 35 USG-RFA-treated subjects, 32 tumors ≤ 4 cm reached the standard of complete treatment after one tumor was found with residue after the first month follow-up, and two tumors were noted recurrence at the 4 and 10 months follow-up after USG-RFA. Nonetheless, no residue or recurrence occurred after secondary treatment for these 3 tumors where pathological diagnosis were acquired again. The other 3 cases with tumors > 4.0 cm to 5.0 cm underwent USG-RFA twice or three times before reaching the standard of complete treatment, of which two had twice and one tumor had three times treatments. There was no carcinoma residue or recurrence during follow-up period. CONCLUSIONS: Percutaneous ultrasound-guided radiofrequency ablation for small renal mass (SRM) has satisfied clinical outcomes, with the advantage of less injury, lower complication rates and shorter recovery time for small size of renal clear cell carcinoma. USG-RFA may become the preferred treatment alternative for SRM.

Effect of LY294002 on adriamycin-induced epithelial-mesenchymal transition in human breast carcinoma cells.

OBJECTIVE: To study the effect of LY294002 on the adriamycin- induced epithelial-mesenchymal transition in human breast carcinoma cells. METHODS: Human breast carcinoma cells MCF-7 was cultured in vitro and then exposed to adriamycin with or without LY294002. The protein expression levels of Akt, phosphorylated-Akt (p-Akt), Snail, and E-cadherin was detected by Western blot analysis. The mRNA expressions of Snail and E-cadherin were determined by RT-PCR. RESULTS: Adriamycin significantly increased the protein expression of Snail and depressed the protein expression of E-cadherin (P<0.05). The pre-treatment with LY294002 significantly reversed the changes of activities and levels of the above proteins (P<0.05). CONCLUSION: LY294002 could reverse the adriamycin-induced epithelial-mesenchymal transition in human breast carcinoma cells by regulating the expressions of Snail and E-cadherin through suppressing PI3K/Akt signaling pathway.

GreenLight Laser photoselective vapo-enucleation of the prostate with front-firing emission versus plasmakinetic resection of the prostate for benign prostate hyperplasia.

BACKGROUND: Although the conventional, monopolar transurethral resection of the prostate (TURP) has proven to be an effective and relatively safe treatment for patients with benign prostatic hyperplasia (BPH), many new endoscopic technologies have been introduced to treat BPH. With the development of laser, there are several alternative transurethral procedures embracing laser therapies. Herein, this study sought to explore the efficacy, safety and follow-up of GreenLight laser photoselective vapo-enucleation of the prostate (PVEP) with front-firing emission compared with plasmakinetic resection of the prostate (PKRP) used to surgically manage BPH. METHODS: Data from patients who underwent either GreenLight laser PVEP or PKRP were retrospectively collected from March 2013 to May 2018. Perioperative data from both groups were compared. RESULTS: Totally, 43 and 45 patients were included in the PVEP and PKRP groups, respectively. No significant difference was observed in excision efficiency ratio (resected prostate weight/operation time) between the two groups (P=0.372). The efficiency ratio of the first 20 PVEP procedures (0.36±0.09 g/min) was significantly lower than that of the second 23 PVEP procedures (0.45±0.18 g/min) (P=0.042). The PVEP group experienced a shorter duration of catheterization, postoperative hospital stay and irrigation time than the PKRP group (P<0.001, P=0.001 and P<0.001, respectively). There was no statistically significant difference between the two groups (P=0.937) in terms of overall postoperative complications. Three months after surgery, the international prostate symptoms (IPSS) score, quality of life (QOL) score, postvoid residual (PVR) volume and maximum urinary flow rate (Qmax) were decreased in both groups (P<0.001 for all) and were comparable between both groups (P=0.635, 0.662, 0.671 and 0.924, respectively). CONCLUSIONS: GreenLight laser PVEP with front-firing emission was safe and effective modality in treating patients with BPH with short-term follow-up. PVEP was associated with shorter catheterization and postoperative hospital stay time compared with PKRP.

LC-MS-Based Plasma Metabolomics and Lipidomics Analyses for Differential Diagnosis of Bladder Cancer and Renal Cell Carcinoma.

Bladder cancer (BC) and Renal cell carcinoma(RCC) are the two most frequent genitourinary cancers in China. In this study, a comprehensive liquid chromatography-mass spectrometry (LC-MS) based method, which utilizes both plasma metabolomics and lipidomics platform, has been carried out to discriminate the global plasma profiles of 64 patients with BC, 74 patients with RCC, and 141 healthy controls. Apparent separation was observed between cancer (BC and RCC) plasma samples and controls. The area under the receiving operator characteristic curve (AUC) was 0.985 and 0.993 by plasma metabolomics and lipidomics, respectively (external validation group: AUC was 0.944 and 0.976, respectively). Combined plasma metabolomics and lipidomics showed good predictive ability with an AUC of 1 (external validation group: AUC = 0.99). Then, separation was observed between the BC and RCC samples. The AUC was 0.862, 0.853 and 0.939, respectively, by plasma metabolomics, lipidomics and combined metabolomics and lipidomics (external validation group: AUC was 0.802, 0.898, and 0.942, respectively). Furthermore, we also found eight metabolites that showed good predictive ability for BC, RCC and control discrimination. This study indicated that plasma metabolomics and lipidomics may be effective for BC, RCC and control discrimination, and combined plasma metabolomics and lipidomics showed better predictive performance. This study would provide a reference for BC and RCC biomarker discovery, not only for early detection and screening, but also for differential diagnosis.

Clinical research on stereotactic radiosurgery combined with epithermal growth factor tyrosine kinase inhibitors in the treatment of brain metastasis of non-small cell lung cancer.

PURPOSE: To compare the clinical efficacy and safety of stereotactic radiosurgery (SRS) combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) versus whole-brain radiation therapy (WBRT) combined with EGFR-TKIs in the treatment of brain metastasis of non-small cell Lung cancer (NSCLC). METHODS: The clinical data of patients with brain metastatic NSCLC who had EGFR-sensitive mutation and followed between January 2014 and January 2016 was retrospectively analyzed. Patients were divided into two groups according to their treatment types. Fifty seven patients were treated with SRS combined with EGFR-TKIs, while another 57 patients were treated with WBRT combined with EGFR-TKIs. The clinical efficacy, intracranial progression-free survival (iPFS), systemic progression-free survival (sPFS), overall survival (OS,) and adverse reactions were compared between the two groups. Computed tomography (CT) or magnetic resonance imaging (MRI) were used for imaging evaluation in both groups and all patients underwent symptomatic treatment such as dehydration or hormone therapy according to the patient's condition. The efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) and adverse reactions were assessed based on the criteria for toxic reaction of anti-cancer drugs of WHO. RESULTS: There were no statistically significant differences in general conditions between the two groups of patients. The median iPFS and median sPFS were similar between the two groups (12.2 months vs. 11.5 months and 10.7 months vs. 9.8 months respectively, p>0.05). The median OS of patients treated with SRS + EGFR-TKIs was significantly longer than in those treated with WBRT + EGFR-TKIs (25.1 months vs. 22.0 months, respectively, p=0.042). No statistically significant differences were found in the objective response rate (ORR), disease control rate (DCR), the incidence rates of cytopenia, gastrointestinal reaction and liver dysfunction between the two groups (p>0.05). There were 8 cases with radiotherapy-associated grade 3 or higher brain damage in SRS + EGFR-TKIs group compared to 19 cases in those treated with WBRT + EGFR-TKIs, suggesting that the incidence rate of radiation-induced brain injuries in SRS + EGFR-TKIs group was remarkably lower than those in WBRT + EGFR-TKIs group (p=0.026). CONCLUSION: The clinical efficacy of SRS combined with EGFR-TKIs is comparable to that of WBRT combined with EGFR-TKIs in the treatment of NSCLC patients with ≤3 brain metastases and EGFR-sensitive mutation and the OS of patients is longer, with lower toxic side effect and higher safety, hence SRS combined with EGFR-TKIs should be used as the preferred therapeutic regimen.

Hydrothermal treatment of lincomycin mycelial residues: Antibiotic resistance genes reduction and heavy metals immobilization.

In this study, fate of antibiotic resistance genes (ARGs - lmrA, lmrB, ermB, lnuA, lnuB and vgaC) and species distribution of heavy metals during lincomycin mycelial residues hydrothermal treatment (HT) process were investigated. The results showed that HT could reduce both ARGs and mobile genetic elements effectively by 1.02 to 4.14 logs. Total bacterial biomass reflecting by 16S rRNA decreased from 1.27 × 109 to 4.47 × 105 copies g-1 dry weight. Moreover, half-lives of these targets varied from 2.4 min (ermB) to 8.9 min (lmrB) in the first 30 min of treatment based on a biphasic first-order kinetic model. After the first 30 min, however, half-lives ranged between 15.4 min (lmrA) and 247.6 min (ISCR1). Complexation and precipitation resulted in the transformation of heavy metals from weakly bounded to relatively stable fraction in HT process. Simultaneously, their environmental risk level decreased by at least one grade.

Long non-coding RNA MEG3 suppresses the development of bladder urothelial carcinoma by regulating miR-96 and TPM1.

We aimed at investigating effects of long non-coding RNA maternally expressed 3 (MEG3) on the proliferation, cell cycle and apoptosis of bladder urothelial carcinoma cells and regulatory relationships among lncRNA MEG3, miR-96 and α-tropomyosin 1 (TPM1). Human clinical data from The Cancer Genome Atlas (TCGA) which contains bladder urothelial carcinoma tissues and adjacent tissues were used for analysis. The expression profiles of MEG3, miR-96, TPM1, cell cycle-related genes and apoptosis-related genes were examined by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Regulating relationship among MEG3, miR-96 and TPM1 was confirmed by dual luciferase reporter assay. MTT assay and flow cytometry were performed to observe cell proliferation, cell cycle and apoptosis. The effects of lncRNA MEG3 on bladder urothelial carcinoma were confirmed both in vivo and in vitro. The mRNA expression and protein expression of MEG3, TPM1 were down-regulated in carcinoma tissues, whereas miR-96 expression was up-regulated. MEG3 overexpression resulted in miR-96 downregulation along with TPM1 upregulation, which inhibited cell proliferation and cell cycle but promoted cell apoptosis of bladder urothelial carcinoma cells in vitro, and at the same time inhibited tumor growth in vivo. In this process, expressions of apoptosis-related protein BCL2 associated X (Bax), cleaved-caspase 3 was up-regulated, whereas apoptosis regulator protein (Bcl-2) expression was suppressed when MEG3 was overexpressed, and cell cycle-related protein Cyclin D1 was down-regulated. LncRNA MEG3 low-expression promotes the proliferation and inhibits apoptosis of bladder urothelial carcinoma cells by regulating miR-96 along with TPM1.

Metabolomics of Non-muscle Invasive Bladder Cancer: Biomarkers for Early Detection of Bladder Cancer.

Background: Clinical outcomes of bladder cancer (BC) are tightly associated with the stage and grade of the initial diagnosis of BC because early detection is clearly important for patients with BC. However, the diagnostic capability of current detection methods, such as urinary cytology, cystoscopy, imageology method, and several urine-based tests, is inadequate for early detection of BC. The objective of our study is to discover novel biomarkers for detecting BC at an early stage, called non-muscle invasive (NMI) BC, using liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based metabolomics. Methods: First, morning midstream urine samples were collected from healthy adult and NMIBC patients. The LC-HRMS-based metabolomics were applied to distinguish the NMIBC group without hematuria from the controls (gender- and age-matched volunteers with normal clinically healthy index), low-grade NMIBC from the controls, and high-grade from low-grade NMIBC. Results: A total of 284 subjects were enrolled in our study including 117 healthy adults, 80 NMIBC patients without hematuria, and 87 NMIBC patients with hematuria. The metabolite panel including dopamine 4-sulfate, MG00/1846Z,9Z,12Z,15Z/00, aspartyl-histidine, and tyrosyl-methionine was found in a discovery set, which showed the predictive ability to distinguish the NMIBC group from the control group with an area under the curve (AUC) of 0.838 in an external validation set. The AUC of the panel for low-grade NMIBC samples, which consisted of 3-hydroxy-cis-5-tetradecenoylcarnitine, 6-ketoestriol, beta-cortolone, tetrahydrocorticosterone, and heptylmalonic acid, was 0.899. The sensitivity and specificity were 0.881 and 0.786, respectively. The AUC of the panel for distinction of low-grade NMIBC with and without hematuria against high-grade NMIBC with and without hematuria were 0.827 and 0.755, respectively. In addition, metabolites involved in tryptophan metabolism were upregulated in the urine of high-grade NMIBC patients when compared with low-grade NMIBC patients with the presence or absence of hematuria. Conclusion: The NMIBC urine metabolic profiling was able to assist in the early detection of BC. Panels of metabolites were discovered to have a potential value for high-grade NMIBC and low-grade NMIBC diagnosis as well as for NMIBC grading distinction.

Percutaneous radiofrequency ablation for renal cell carcinoma vs. partial nephrectomy: Comparison of long-term oncologic outcomes in both clear cell and non-clear cell of the most common subtype.

OBJECTIVES: To compare the clinical outcomes of percutaneous radiofrequency ablation (PRFA) and partial nephrectomy (PN) in patients with clear cell renal cell carcinoma (ccRCC) and non-clear cell RCC (nccRCC) of the most common subtypes. MATERIALS AND METHODS: A retrospective study was conducted to review the records of all the patients who underwent PRFA or PN between February 2005 and April 2014 at our institution. Patients with histologic confirmation of ccRCC, papillary RCC, and chromophobe RCC were included. The Mann-Whitney U test was applied to compare PRFA to PN in the ccRCC and nccRCC groups. The Kaplan-Meier method was used to generate the survival curves that were compared to the log-rank test. RESULTS: A total of 264 patients meeting the selection criteria were included in this study. The tumor size ranged from 0.9 to 7.0cm. The median follow-up period was 78 months (range: 8-132 mo). Although PRFA provided comparable 10-year overall survival rates and 10-year disease-free survival (DFS) rates to PN both in ccRCC ≤4cm and nccRCC, the 10-year DFS for patients treated with PRFA was lower than that of PN in ccRCC >4cm. The DFS survival curve between the 2 operations and 2 subtypes was statistically significant in patients with tumor size >4cm. Limitations include retrospective review and selection bias. CONCLUSIONS: Patients with T1b ccRCC treated with PRFA have less favorable outcomes than those with PN whereas PRFA provides comparable oncologic outcomes to PN in patients with T1b nccRCC. It is necessary to take RCC subtypes into consideration when choosing a surgical approach to treat T1b RCC between PFRA and PN.

Pseudocapsule of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion: a clue for tumor enucleation?

OBJECTIVES: To evaluate the feasibility and efficacy of tumor enucleation (TE) for patients with small renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) by analyzing the pseudocapsule characteristics of Xp11.2 RCCs comparing with that of clear cell renal cell carcinoma (ccRCC). METHODS: From June 2007 to February 2014, 22 patients with Xp11.2 RCC who were diagnosed by fluorescence in-situ hybridization polyclonal (FISH) assay and 32 patients with ccRCC treated in our institution were comparatively studied. 12 patients with ccRCC underwent radical nephrectomy (RN) and 20 received TE. Among 22 patients with Xp11.2 RCC, 19 were treated by RN and 3 by TE (1 by radiofrequency ablation assisted TE). Pseudocapsule and other clinicopathological characteristics of the two subtypes of RCC were compared. Survival of patients treated with different surgical methods was evaluated and compared. RESULTS: Pseudocapsule incidence of Xp11.2 RCC (14/22, 63.6%) was lower than that of ccRCC (32/32, 100%, P<0.001). However, pseudocapsule integrity rate of Xp11.2 RCC (10/14, 71.4%) was comparable with that of ccRCC (23/32, 71.9%, P=1.000). The 5-year overall survival of patients with ccRCC treated with RN and TE was 86% and 81%, respectively (P=0.845). Three patients with small Xp11.2 RCC performed well after TE. CONCLUSIONS: Over half Xp11.2 RCC had pseudocapsules, whose integrity rate was comparable to that of ccRCC. Treatment effectives of TE and RN were comparable in ccRCC. A preliminary attempt to treat small Xp11.2 RCC with intact pseudocapsule by using TE produced a favorable treatment outcome.