Prediction of synergistic gemcitabine-based combination treatment through a novel tumor stemness biomarker NANOG in pancreatic cancer.

Gemcitabine remains a first-class chemotherapeutic drug for pancreatic cancer. However, due to the rapid development of gemcitabine resistance in pancreatic cancer, gemcitabine alone or in combination with other anti-cancer drugs only showed limited effect in the clinic. It is extremely challenging to effectively and efficiently determine the optimal drug regimens. Thus, identification of appropriate prediction biomarkers is critical for the rational design of gemcitabine-based therapeutic options. Herein, a pancreatic cancer stem cell (PCSC) model exhibiting chemoresistance to gemcitabine was used to test the activity of clinical cancer drugs in the presence or absence of gemcitabine. As determined by combinatorial treatment, several types of drugs resensitized gemcitabine-resistant PCSCs to gemcitabine, with sorafenib (EGFR inhibitor)/gemcitabine and sunitinib (TBK1 inhibitors)/gemcitabine drug combinations being the most preferred treatments for PCSCs. Following the validation of the PCSC model by an antibody array test of 15-gene expression of stemness biomarkers, NANOG showed markedly different expression in PCSCs compared to the parental cells. From comprehensive analysis of stem cell index versus combination index, a stemness-related correlation model was successfully constructed to demonstrate the correlation between NANOG expression and synergism. Cancer cell stemness was ascertained to be highly relevant to NANOG overexpression that can be abrogated by synergized gemcitabine-drug combinations. Therefore, NANOG works as a therapeutic biomarker for predicating efficient combinatorial treatment of gemcitabine in pancreatic cancer.

Advances in crosslinking chemistry and proximity-enabled strategies: deciphering protein complexes and interactions.

Mass spectrometry, coupled with innovative crosslinking techniques to decode protein conformations and interactions through uninterrupted signal connections, has undergone remarkable progress in recent years. It is crucial to develop selective crosslinking reagents that minimally disrupt protein structure and dynamics, providing insights into protein network regulation and biological functions. Compared to traditional crosslinkers, new bifunctional chemical crosslinkers exhibit high selectivity and specificity in connecting proximal amino acid residues, resulting in stable molecular crosslinked products. The conjugation with specific amino acid residues like lysine, cysteine, arginine and tyrosine expands the XL-MS toolbox, enabling more precise modeling of target substrates and leading to improved data quality and reliability. Another emerging crosslinking method utilizes unnatural amino acids (UAAs) derived from proximity-enabled reactivity with specific amino acids or sulfur-fluoride exchange (SuFEx) reactions with nucleophilic residues. These UAAs are genetically encoded into proteins for the formation of specific covalent bonds. This technique combines the benefits of genetic encoding for live cell compatibility with chemical crosslinking, providing a valuable method for capturing transient and weak protein-protein interactions (PPIs) for mapping PPI coordinates and improving the pharmacological properties of proteins. With continued advancements in technology and applications, crosslinking mass spectrometry is poised to play an increasingly significant role in guiding our understanding of protein dynamics and function in the future.

Robot-assisted Simple Enucleation Versus Standard Robot-assisted Partial Nephrectomy for Low- or Intermediate-complexity, Clinical T1 Renal Tumors: A Randomized Controlled Noninferiority Trial.

BACKGROUND: Although partial nephrectomy has become the gold standard for T1 renal tumors whenever technically feasible, simple enucleation has shown superior results. To the best of our knowledge, no randomized controlled trials comparing these two surgical approaches have been published. OBJECTIVE: To compare the surgical margin status for robot-assisted simple enucleation (RASE) and standard robot-assisted partial nephrectomy (sRAPN) for clinical T1 renal tumors. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, randomized, controlled, noninferiority trial. A total of 380 patients aged 18-80 yr with newly diagnosed, sporadic, unilateral clinical T1 renal tumors (RENAL score <10) were enrolled and randomized to RASE or sRAPN. The primary endpoint was the positive surgical margin (PSM) rate, with a noninferiority margin of 7.5% set. The study was registered on ClinicalTrials.gov (NCT03624673). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We defined noninferiority for RASE versus standard RAPN as an upper 95% confidence interval (CI) bound of <7.5% for the difference in the proportion of patients with a PSM. RESULTS AND LIMITATIONS: A cohort of 380 patients was enrolled and randomly assigned to RASE (n = 190) or sRAPN (n = 190). On intention-to-treat analysis for patients with malignant tumors, 2.3% of patients in the RASE group and 3.0% in the sRAPN group had a PSM. The RASE group showed noninferiority to the sRAPN group within a 7.5% margin (difference -0.7%, 95% CI -4.0% to 2.7%). Per-protocol analysis also demonstrated noninferiority of RASE. The RASE group had a shorter median operative time (145 vs 155 min; p = 0.018) and a lower rate of tumor bed suturing (8.9% vs 43%; p < 0.001) in comparison to the sRAPN group. Estimated blood loss was considerably lower in the sRAPN group than in the RASE group (p = 0.046). The rate of recurrence did not differ between the groups (p > 0.9). CONCLUSIONS: RASE for the management of low- to intermediate-complexity tumors is noninferior to sRAPN in terms of the PSM rate. Long-term follow-up is needed to draw conclusions regarding oncological outcomes. PATIENT SUMMARY: We carried out a trial to compare simple tumor enucleation versus partial nephrectomy for renal tumors. The outcome we assessed was the proportion of patients with a positive surgical margin. Our results show that simple tumor enucleation is not inferior to partial nephrectomy for this outcome. Longer follow-up is needed to assess other cancer control outcomes.

Effect of extensive artery isolation during robotic-assisted partial nephrectomy on blood pressure of patients with poorly controlled hypertension: a preliminary study.

PURPOSE: To investigate whether extensive renal artery isolation during robotic-assisted partial nephrectomy (RAPN) for renal cell carcinoma (RCC) affects blood pressure (BP) of patients with poorly controlled hypertension. METHODS: We included 60 patients diagnosed with poorly controlled hypertension who underwent RAPN by an experienced surgeon. The renal artery of the treated kidney was sufficiently isolated. Systolic BP (SBP), diastolic BP (DBP) and antihypertensive medication information were obtained at baseline and 3- and 6-month follow-up after surgery. Primary endpoints were changes in BP, and medications. Predictors of SBP reduction at 3 months were assessed by multivariable logistic regression. RESULTS: All 60 RAPN procedures were successful, with no major intra- or postoperative complications. Mean SBP and DBP decreased significantly at 3 months after surgery (SBP, -7.8 ± 6.3 mmHg, P < 0.001; DBP, -4.2 ± 6.4 mmHg, P = 0.01). SBP and DBP did not differ between 3- and 6-month follow-up. The mean number of BP medications prescribed was lower at 3 months than baseline (1.7 ± 1.0 vs 2.1 ± 1.0, P = 0.016). The only significant predictor of SBP reduction at 3 months was baseline SBP. CONCLUSIONS: Renal denervation with extensive renal artery isolation during RAPN may improve BP control among patients with poorly controlled hypertension in short term.

Micropeptide MIAC inhibits the tumor progression by interacting with AQP2 and inhibiting EREG/EGFR signaling in renal cell carcinoma.

BACKGROUND: Although, micropeptides encoded by non-coding RNA have been shown to have an important role in a variety of tumors processes, there have been no reports on micropeptide in renal cell carcinoma (RCC). Based on the micropeptide MIAC (micropeptide inhibiting actin cytoskeleton) discovered and named in the previous work, this study screened its tumor spectrum, and explored its mechanism of action and potential diagnosis and treatment value in the occurrence and development of renal carcinoma. METHODS: The clinical significance of MIAC in RCC was explored by bioinformatics analysis through high-throughput RNA-seq data from 530 patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database, and the detection of clinical samples of 70 cases of kidney cancer. In vitro and in vivo experiments to determine the role of MIAC in renal carcinoma cell growth and metastasis; High-throughput transcriptomics, western blotting, immunoprecipitation, molecular docking, affinity experiments, and Streptavidin pulldown experiments identify MIAC direct binding protein and key regulatory pathways. RESULTS: The analysis of 600 renal carcinoma samples from different sources revealed that the expression level of MIAC is significantly decreased, and corelated with the prognosis and clinical stage of tumors in patients with renal carcinoma. Overexpression of MIAC in renal carcinoma cells can significantly inhibit the proliferation and migration ability, promote apoptosis of renal carcinoma cells, and affect the distribution of cells at various stages. After knocking down MIAC, the trend is reversed. In vivo experiments have found that MIAC overexpression inhibit the growth and metastasis of RCC, while the synthetized MIAC peptides can significantly inhibit the occurrence and development of RCC in vitro and in vivo. Further mechanistic studies have demonstrated that MIAC directly bind to AQP2 protein, inhibit EREG/EGFR expression and activate downstream pathways PI3K/AKT and MAPK to achieve anti-tumor effects. CONCLUSIONS: This study revealed for the first time the tumor suppressor potential of the lncRNA-encoded micropeptide MIAC in RCC, which inhibits the activation of the EREG/EGFR signaling pathway by direct binding to AQP2 protein, thereby inhibiting renal carcinoma progression and metastasis. This result emphasizes that the micropeptide MIAC can provide a new strategy for the diagnosis and treatment of RCC.

miR-1/AMPK-Mediated Glucose and Lipid Metabolism under Chronic Hypothermia in the Liver of Freshwater Drum, Aplodinotus grunniens.

Our previous study demonstrated that low temperature could induce hepatic inflammation and suppress the immune and oxidation resistance of freshwater drum. However, the metabolism, especially the glucose and lipid metabolism involved, is poorly studied. To further explore the chronic hypothermia response of freshwater drum, an 8-day hypothermia experiment was conducted at 10 °C to investigate the effect of chronic hypothermia on glucose and lipid metabolism via biochemical and physiological indexes, and metabolic enzyme activities, miRNAs and mRNA-miRNA integrate analysis in the liver. Plasma and hepatic biochemical parameters reveal chronic hypothermia-promoted energy expenditure. Metabolic enzyme levels uncover that glycolysis was enhanced but lipid metabolism was suppressed. Differentially expressed miRNAs induced by hypothermia were mainly involved in glucose and lipid metabolism, programmed cell death, disease, and cancerization. Specifically, KEGG enrichment indicates that AMPK signaling was dysregulated. mRNA-miRNA integrated analysis manifests miR-1 and AMPK, which were actively co-related in the regulatory network. Furthermore, transcriptional expression of key genes demonstrates hypothermia-activated AMPK signaling by miR-1 and subsequently inhibited the downstream glucogenic and glycogenic gene expression and gene expression of fatty acid synthesis. However, glycogenesis was alleviated to the control level while fatty acid synthesis was still suppressed at 8 d. Meanwhile, the gene expressions of glycolysis and fatty acid oxidation were augmented under hypothermia. In conclusion, these results suggest that miR-1/AMPK is an important target for chronic hypothermia control. It provides a theoretical basis for hypothermia resistance on freshwater drum.

Emerging roles of exosome-derived biomarkers in cancer theranostics: messages from novel protein targets.

Effective biomarkers that guide therapeutics with limited adverse effects, have emerged as attractive research topics in cancer diagnosis and treatment. Cancer-derived exosomes, a type of extracellular vesicles representing molecular signatures of cells of origin, could serve as stable reservoirs for potential biomarkers (i.e., proteins, nucleic acids) in non-invasive cancer diagnosis and prognosis. In this review, the physiological and pathological roles of exosomes and their protein components in facilitating tumorigenesis are highlighted. Exosomes carrying proteins can participate in tumor development and progression through multiple signaling pathways, including EMT, invasion and metastasis. Meanwhile, the practical applications of exosomal proteins in detecting and monitoring several solid-tumor cancers (including lung, breast, pancreatic, colorectal and prostate cancers) were also summarized. More clinically relevant, exosomal proteins play pivotal roles in transmitting oncogenic potential or resistance to therapies in recipient cells, which might further support therapeutic strategy determinations.

Trifecta outcomes of modified robot-assisted simple enucleation and standard robot-assisted partial nephrectomy for treating clinical T1b renal cell carcinoma.

BACKGROUND: To compare perioperative outcomes and Trifecta achievement of modified robot-assisted simple enucleation (MRASE) with robot-assisted partial nephrectomy (RAPN) for treating clinical T1b renal tumors. METHODS: We analyzed 203 patients who underwent MRASE or RAPN for clinical T1b renal tumors at our institution from September 2014 to June 2018. The two groups were compared regarding perioperative outcome variables. Trifecta was defined as no perioperative complications, negative surgical margin, and ischemia time ≤25 minutes. RESULTS: In all, 139 patients underwent MRASE and 64 underwent RAPN respectively. Patients in the MRASE group had shorter operative time (197.7 vs. 215.6 min, P=0.039) and warm ischemic time (21.2 vs. 24.1 min, P=0.004) in comparison to the RAPN group. The groups were comparable in estimated blood loss (230.5 vs. 269.8 mL, P=0.259). Tumor bed suturing was performed with a significantly lower frequency in the MRASE group than in the RAPN group (11.5% vs. 90.6%, P<0.01). The incidence of perioperative complications was similar. The rate of positive surgical margins was similar in both groups (2.2% vs. 6.3%, P=0.284). Trifecta was achieved in 61.2% and 42.2% of MRASE and RAPN patients (P=0.012). On multivariable analysis, the type of procedure, RENAL score, estimated blood loss, and operative time were positive factors for the achievement of Trifecta. CONCLUSIONS: In this series MRASE was superior to RAPN with regard to the achievement of Trifecta in treating T1b renal tumors. Besides, MRASE had better outcomes for shorter operative time, shorter warm ischemic time, and less need for tumor bed suturing as compared with RAPN.

Functional and oncologic outcomes of robot-assisted simple enucleation with and without renal arterial cold perfusion in complex renal tumors: a propensity score-matched analysis.

BACKGROUND: To compare robot-assisted simple enucleation with renal arterial cold perfusion (RACP-RASE) and RASE alone in complex renal tumors with regard to perioperative, functional and oncologic outcomes by propensity score-matched analysis. METHODS: Data from 351 patients who underwent RACP-RASE or RASE for complex renal tumors were recorded between September 2014 and December 2017. Propensity score-matched analysis was performed on age, sex, BMI, ECOG score, tumor side and size, preoperative estimated glomerular filtration rate (eGFR), RENAL score and PADUA score. RESULTS: The study included 31 RACP-RASE and 320 RASE procedures. RENAL score and PADUA score were higher and tumor diameter was greater under RACP-RASE than RASE. After matching, the two groups were similar in estimated blood loss (208.3 vs 230.7 ml; p = 0.696) and ischemic time (34.8 vs 32.8 min; p = 0.342). The RACP-RASE group had significantly longer operative time than the RASE group (264.1 ± 55.7 vs 206.9 ± 64.0 min, p = 0.001). There was no difference in the incidence of postoperative complications between the two groups (13.8% vs 24.1%; p = 0.315), as was the overall incidence of positive surgical margins (3.4 vs 0%; p = 1.000). The changes in eGFR significantly differed between the two groups at 3 months (p = 0.018) and 12 months (p = 0.038). More patients in the RASE group were CKD upstaged (p = 0.043). At multivariable analysis, preoperative eGFR and the type of procedure were significant predictive factors for a change of more than 10% in eGFR at 3 months postoperatively. There was no local recurrence or distant metastasis during follow-up. CONCLUSIONS: RACP-RASE is an effective and safe technique for complex renal tumors that can provide appropriate temporary arterial occlusion and renal hypothermic perfusion. Renal arterial cold perfusion may be helpful in protecting renal function in RASE as compared with warm ischemia.

Robot-Assisted versus Conventional Open Kidney Transplantation: A Meta-Analysis.

BACKGROUND: Perioperative and follow-up outcomes for patients that received robot-assisted kidney transplant (RAKT), compared to patients that received conventional open kidney transplant (OKT), remain unknown. We performed a meta-analysis of controlled studies to compare the safety and efficacy of RAKT versus OKT. METHODS: Systematic searching of PubMed, Embase, and Cochrane Library databases was performed to identify relevant randomized or nonrandomized controlled studies. Perioperative, in-hospital, and follow-up outcomes were summarized. A random-effect model incorporating the potential heterogeneity was used to synthesize the results. RESULTS: Six nonrandomized controlled studies including 263 patients with RAKT and 804 patients with OKT were included. Pooled results showed that compared to those that received OKT, patients that received RAKT had significant higher rewarming time (mean difference (MD): 20.8 min, p < 0.001) and total ischemia time (MD: 17.8 min, p = 0.008) but a lower incidence of surgical site infection (SSI, risk ratio (RR): 0.22, p = 0.03). The incidence of delayed graft function was comparable between groups (RR: 1.10, p = 0.82), and the length of hospital stay was similar (MD: -2.03 days, p = 0.21). During a follow-up of 31 months, patients that received RAKT and OKT had similar serum creatinine levels (MD: 10.12 mmol/L, p = 0.42) and similar incidences of graft rejection (RR: 1.16, p = 0.53), graft failure (RR: 0.94, p = 0.79), and all-cause mortality (RR: 1.16, p = 0.77). CONCLUSION: Current evidence from nonrandomized studies suggests that RAKT is associated with a lower risk of SSI and similar midterm functional and clinical efficacy compared to OKT. Randomized studies are needed to validate these findings.

Diagnostic performance of a nomogram incorporating cribriform morphology for the prediction of adverse pathology in prostate cancer at radical prostatectomy.

The aim of the present study was to develop a novel nomogram that incorporated clinical factors, imaging parameters and biopsy pathological factors (including cribriform morphology) to predict adverse pathology in prostate cancer (PCa). A total of 223 patients with PCa, who had undergone preoperative multi-parametric magnetic resonance imaging and had a biopsy of Gleason pattern (GP) 4, absence of GP 5 and pure Grade Group (GG) 3 [Gleason score (GS) 3+4, GS 4+3, GS 4+4], were retrospectively enrolled onto the study. The contribution of GG to the biopsy and Prostate Imaging Reporting and Data System (PI-RADS) score for PCa harboring adverse pathology were analyzed. Univariate and multivariate logistic regression analyses were performed to determine significant pathology predictors of adverse pathology for nomogram development. The nomogram was internally validated using bootstrapping with 1,000 iterations. The diagnostic performance of the nomogram was analyzed by receiver operating characteristics (ROC) analysis and decision curve analysis (DCA). A higher biopsy GG and PI-RADS score were associated with an increased likelihood of adverse pathology. Prostate specific antigen density (PSAD), biopsy GG, cribriform morphology on biopsy and PI-RADS score were significant predictors and were included in the nomogram. The ROC area under the curve of the nomogram was 0.88 (95% confidence interval, 0.84-0.91), with a high specificity (0.91) and moderate sensitivity (0.72). The novel nomogram was shown to have a higher net benefit for the prediction of adverse pathology in PCa, compared with any individual factors determined by DCA. Overall, a novel nomogram incorporating PSAD, PI-RADS score, biopsy GG and cribriform morphology on biopsy was shown to perform well in the prediction of PCa harboring adverse pathology at the time of radical prostatectomy.

Comparisons of the safety and effectiveness of robot-assisted versus laparoscopic partial nephrectomy for large angiomyolipomas: a propensity score-matched analysis.

OBJECTIVE: To compare the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) versus laparoscopic partial nephrectomy (LPN) for large angiomyolipomas (AMLs). MATERIALS AND METHODS: We retrospectively evaluated 150 patients who were treated with either RAPN or LPN for large angiomyolipomas from 2014 to 2018. Propensity score matching was performed on age, gender, BMI, Charlson Comorbidity Index, tumour side and size, preoperative eGFR and RENAL score. RESULTS: In total, 63 and 87 patients underwent RAPNs and LPNs, respectively. There were more large and complex AMLs in the RAPN cohort, with the median tumour maximal diameters and RENAL scores differing between the two groups (8 versus 7 cm and 9 versus 8, P = 0.01). After matching, the median warm ischemic time was significantly shorter in the RAPNs versus the LPNs (17 versus 22 min, P = 0.001). The rate of intraoperative complications in the RAPNs appeared lower than the LPNs (3.2% versus 8.1%). The median postoperative length of stay was significantly shorter in the RAPN cohort than the LPNs (P = 0.001). Twelve months after surgery, RAPNs received a 94.6% renal function prevention; while this was 90.8% in LPNs (P = 0.001). Subgroup analysis indicated that prior selective arterial embolization (SAE) was related to better renal function preservation in the RAPN cohort (P = 0.01). No recurrence occurred in either of the two cohorts. CONCLUSIONS: RAPN is a safe and effective alternative to LPNs for large AMLs with a shorter warm ischemic time and higher renal preservation rate. Recurrence was equivalent in both RAPNs and LPNs.

Comparison of perioperative outcomes in robot-assisted radical cystectomy and laparoscopic radical cystectomy.

OBJECTIVE: To report perioperative outcomes in robot-assisted radical cystectomy and laparoscopic radical cystectomy. PATIENTS AND METHODS: Between January 2010 and July 2019, 298 patients with bladder cancer underwent robotic-assisted radical cystectomy (RARC) (n = 172) and laparoscopic radical cystectomy (LRC) (n = 126) at our institution were enrolled in the retrospective study. The demographic, perioperative, and complication data were collected and analyzed. RESULTS: The RARC group had less operative duration (P < .001), less blood loss (P < .001), lower transfusion rate (P < .05), and shorter hospital stay (P < .001) than the LRC group. The 90-day readmission rate between the RARC and LRC group had no significant differences (P = .401). The 90-day overall complication rates in the RARC group was much lower than the LRC group (P = .009). The 90-day minor complication rates (Clavien-Dindo grade ≤ IIA) between the RARC and LRC groups were similar (P = .274). The 90-day major complication rates (Clavien-Dindo grade ≥ IIIA) in the LRC group was higher than the RARC group (P = .022). CONCLUSIONS: The RARC approach appears to offer some operative and perioperative benefits compared with the LRC approach. Larger, randomized studies are required to confirm these findings.

Investigating the equivalent performance of biparametric compared to multiparametric MRI in detection of clinically significant prostate cancer.

PURPOSE: PIRADS v2 stipulates that dynamic contrast-enhanced (DCE) imaging be used to categorize diffusion-weighted-imaging (DWI) score 3 (DWI 3) peripheral zone (PZ) lesions as PIRADS score 3 (PIRADS 3; DCE -) or PIRADS 4 (DCE +). It's controversial for the value of DCE in improving clinically significant prostate cancer (csPCa) detection. We aimed to figure out whether DCE improves csPCa detection and explore new available measures to improve csPCa detection. PATIENTS AND METHODS: We retrospectively enrolled 375 patients who underwent mp MRI before MRI/ultrasound (US) fusion-targeted biopsy (TB) with transperineal systematic biopsy (SB). All lesions were classified as DWI 3/DCE -, DWI 3/DCE +, DWI 4/PIRADS 4 lesions. Detection rates of csPCa for each lesion group were analyzed. The diagnostic performance of each approach was analyzed by receiver operating characteristics (ROC) analysis and decision curve analysis. RESULTS: Totally, 109 DWI 3 or DWI 4 single lesions in PZ were analyzed (n = 109). The rates of csPCa detection for Group A, Group B, Group C is 10.3%, 13.9%, 55.9%, respectively (A vs. B, p = 0.625; B vs. C, p < 0.001). ROC analysis and decision curve analysis showed the method of combining Age, PSA Density (PSAD) and the mean apparent diffusion coefficient value (ADCmean) outperforms individual approaches for csPCa detection. CONCLUSION: For DWI 3 lesions in PZ, DCE sequence has not additional value for improving detection of csPCa. The integration of clinical characteristics and bpMRI parameter improves the detection of csPCa.

Diagnostic Value of 68Ga-PSMA PET/CT for Detection of Phosphatase and Tensin Homolog Expression in Prostate Cancer: A Pilot Study.

Our purpose was to explore the value of 68Ga-prostate-specific membrane antigen (PSMA) PET/CT for detection of phosphatase and tensin homolog (PTEN)-loss prostate cancer. Methods: We retrospectively enrolled 75 patients who underwent multiparametric MRI and 68Ga-PSMA PET/CT before radical prostatectomy. Lesions were outlined on pathologic images, and regions of interest were drawn on matched multiparametric MRI and PET/CT images. Imaging parameters, including average apparent diffusion coefficient and SUVmax, were derived. Immunohistochemical staining was performed to evaluate the PTEN status. The diagnostic performance of imaging parameters was analyzed by receiver-operating-characteristic analysis. Univariate logistic regression analyses were used to evaluate the association between clinical and imaging variables and PTEN status. Results: In total, 103 lesions from 75 patients were analyzed. Of these lesions, 38 of 103 (36.9%) showed PTEN-loss status. Our study showed a strong association between SUVmax and PTEN-loss tumors both in the per-patient analysis (P < 0.01) and in the per-lesion analysis (P < 0.01), yielding sensitivity and specificity of 0.80 and 0.77, respectively, in the per-patient analysis and 0.83 and 0.74, respectively, in the per-lesion analysis. Meanwhile, higher pathologic PSMA expression was found in the PTEN-deficiency tumors. However, there was no significant difference between PTEN-loss tumors and PTEN-intact tumors using parameters such as average apparent diffusion coefficient (P > 0.05) and score on the Prostate Imaging Reporting and Data System, version 2 (P > 0.05). Surprisingly, SUVmax was a significant predictor for detection of PTEN-loss tumors (odds ratio of 7.56 and 95% confidence interval of 2.18-26.24 on per-patient analysis; odds ratio of 13.66 and 95% confidence interval of 4.32-43.24 on per-lesion analysis). Conclusion:68Ga-PSMA PET/CT could effectively detect aggressive PTEN-loss tumors.

Activatable Photodynamic Therapy for Prostate Cancer by NIR Dye/Photosensitizer Loaded Albumin Nanoparticles.

Prostate cancer is one of the leading causes of death in men worldwide. Photodynamic therapy (PDT) is a new emerging and promising strategy for the treatment of prostate cancer. PDT uses a combination of light and a photosensitizer (PS) to kill cancer cells. However, most photosensitizers (PS) accumulate in normal tissues, in particular the skin and eyes, and can be activated by sunlight, causing severe side effects such as prolonged skin photosensitivity that have limited the clinical application of PDT. Herein, a novel strategy is presented to overcome these limitations using Indocyanine green (ICG) as an activatable PDT agent. We developed a human serum albumin (HSA)-based nanoplatform loaded with Chlorin e6 (Ce6) and ICG. In vitro and in vivo studies showed that ICG effectively turned "OFF" the phototoxicity of Ce6, and the degradation of ICG by laser irradiation at 808 nm turned "ON" the phototoxicity of Ce6. In addition, ICG produced heat upon NIR irradiation to kill cancer cells, which could be used as a photothermal therapy (PTT). Therapeutic efficacy of HSA-ICG-Ce6 NPs in a prostate cancer model showed that tumors were completely damaged in mice treated by combined PTT with activated PDT. Our designed HSA nanoparticles containing ICG and Ce6 could be used as an activatable PDT combined with PTT for the treatment of prostate cancer.

Endoscopic Robot-assisted Simple Enucleation Versus Laparoscopic Simple Enucleation With Single-layer Renorrhaphy in Localized Renal Tumors: A Propensity Score-matched Analysis From a High-volume Centre.

OBJECTIVE: To compare perioperative results and early oncological outcomes of endoscopic robot-assisted simple enucleation (ERASE) and laparoscopic simple enucleation (LSE) by using a propensity score-matched analysis. METHODS: We evaluated 383 patients who underwent transperitoneal ERASE or LSE for renal tumors from November 2012 to October 2016. Propensity score matching was performed on age, gender, body mass index, Eastern Cooperative Oncology Group score, tumor side and size, preoperative estimated GFR and PADUA score. RESULTS: In total, 278 and 105 patients underwent ERASE and LSE, respectively. The PADUA score was ≥10 for 61 (21.9%) and 13 (12.4%), respectively (P = .034). After matching, mean operative time and warm ischemic time were significantly lower with ERASE than LSE (171.9 vs 188.2 minutes; P = 0.016 and 20.9 vs 24.2 minutes; P = .001). The estimated mean blood loss was similar (167.7 vs 183.3 mL; P = .315). The conversion rate to open surgery or radical nephrectomy was similar with ERASE and LSE (1.0% vs 5.0%, P = .214) and the rate of intraoperative complications was lower (2.0% vs 8.9%, P = .030). The overall incidence of positive surgical margins was similar (P = .614). The median follow-up was less for ERASE than LSE patients (22 vs 38 months). Recurrence did not differ between the 2 groups: 2 ERASE cases (2.0%) versus 4 LSE cases (4.0%) (P = .679). CONCLUSION: ERASE is a safe and acceptable alternative to LSE. ERASE appears to confer shorter operative time, shorter warm ischemic time and lower rate of intraoperative complication.

GCN2 is a potential prognostic biomarker for human papillary renal cell carcinoma.

Postoperative recurrence for papillary renal cell carcinoma (PRCC) remains a tough problem in clinic. Previous studies have shown that general control nonderepressible kinase 2 (GCN2) was critically involved in tumour development. However, its function and clinical significance in renal cancer remain unknown. In this study, we investigated the role of GCN2 in PRCC. GCN2 silencing suppressed the viability and proliferation, promoted apoptosis of renal cancer cells. We found that the protein level of GCN2 was increased in PRCC tissues. Immunohistochemistry was performed in 84 patients with PRCC to explore the association of GCN2 level with clinical significance. High GCN2 protein level was observed to be significantly correlated with adverse clinicopathological parameters, such as larger tumor size, higher TNM stage, higher Fuhurman Grade, and lymph node metastasis. We evaluated patient outcomes according to various clinical parameters as well as GCN2 expression by Kaplan-Meier curves. Multivariate analysis revealed that GCN2 overexpression can be a predictive factor correlated with reduced OS and PFS of postoperative PRCC patients. Collectively, GCN2 is potentially to play crucial roles in PRCC progression, and its overexpression may be used to predict poor prognosis and promising therapeutic strategy for PRCC patients.

The miR-486-5p plays a causative role in prostate cancer through negative regulation of multiple tumor suppressor pathways.

MicroRNAs have been broadly implicated in cancer, but their exact function and mechanism in carcinogenesis remain poorly understood. Aberrant miR-486-5p expression is frequently found in human cancers. Here we showed a significant overexpression of miR-486-5p in prostate cancer compared with that in normal tissue and cells, and we proposed that altered expression of miR-486-5p in the prostate contributed to prostate cancer. Firstly, miR-486-5p inhibition expression reduced prostate cancercell proliferation, migration, and colonization in vitro and prostate tumor development in vivo. Moreover, we integrated RNA sequencing and target genes prediction, and systemically identified miR-486-5p candidate target genes. We conducted an experiment verifying that miR-486-5p drives tumorigenesis by directly targeting multiple negative regulators, which were involved in PTEN/PI3K/Akt, FOXO, and TGF-b/Smad2 signaling. Finally, we demonstrated that hypoxia-inducible factor-1a and TCF-12 are located at the miR-486-5p promoter, which stimulates the transcription of miR-486-5p itself. Collectively, our findings unveil miR-486-5p as a powerful prostate cancer driver that coordinates the activation of multiple oncogenic pathways and demonstrates some stimulators, which mediate the miR-486-5p signaling pathway and may be targeted for therapy.