Patients with malignant PCC/PG have diverse clinical courses. Poor survival was independently associated with older age and synchronous metastasis.

Although each scoring system describing the complexity of renal tumors correlates with change in GFR after partial nephrectomy, RENAL and C-index score were significantly predictive of GFR reduction.

Circular RNAs (circRNAs) are generally formed by back splicing and are expressed in various cells. Vascular calcification (VC), a common complication of chronic kidney disease (CKD), is often associated with cardiovascular disease. The relationship between circRNAs and VC has not yet been studied. Inorganic phosphate (Pi) was used to treat rat vascular smooth muscle cells to induce VC. circRNAs were identified by analyzing RNA sequencing (RNA-seq) data, and their expression change during VC was validated. The selected circRNAs, including circSamd4a, circSmoc1-1, circMettl9, and circUxs1, were resistant to RNase R digestion and mostly localized in the cytoplasm. While silencing circSamd4a promoted VC, overexpressing it reduced VC in calcium assay and Alizarin red S (ARS) staining. In addition, microRNA (miRNA) microarray, luciferase reporter assay, and calcium assay suggested that circSamd4a could act as a miRNA suppressor. Our data show that circSamd4a has an anti-calcification role by functioning as a miRNA sponge. Moreover, mRNAs that can interact with miRNAs were predicted from RNA-seq and bioinformatics analysis, and the circSamd4a-miRNA-mRNA axis involved in VC was verified by luciferase reporter assay and calcium assay. Since circSamd4a is conserved in humans, it can serve as a novel therapeutic target in resolving VC.

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PurposeTo evaluate the significance of intravesical prostatic protrusion (IPP) for predicting postoperative outcomes in patients with benign prostatic hyperplasia.Materials and MethodsA total of 177 patients with a possible follow-up of at least 6 months who were treated with transurethral resection of the prostate (TURP) were analyzed. We divided the patients into two groups on the basis of the degree of IPP: the significant IPP group (IPP≥5 mm, n=74) and the no significant IPP group (IPP<5 mm, n=103). We analyzed postoperative changes in parameters, such as the International Prostate Symptom Score (IPSS), IPSS quality-of-life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual urine (PVR). The IPSS was subdivided into voiding (IPSS-v) and storage (IPSS-s) symptoms. Multivariate logistic regression analysis was performed to identify whether IPP could predict surgical outcomes of TURP.ResultsPreoperative parameters were not significantly different between the two groups except for total prostate volume and transitional zone volume. Postoperative changes in IPSS, IPSS-v, IPSS-s, and QoL score were higher in the significant IPP group than in the group with no significant IPP. Changes in Qmax and PVR were not significantly different between the two groups. Multivariate logistic regression analysis (after adjustment for age, prostate-specific antigen level, total prostate volume, and transitional zone volume) revealed that the odds ratios (95% confidence interval) of decreased IPSS and IPSS-s in the significant IPP group were 3.43 (1.03 to 11.44) and 3.51 (1.43 to 8.63), respectively (p=0.045 and 0.006, respectively).ConclusionsSignificant IPP is an independent factor for predicting better postoperative outcomes of IPSS and IPSS-s.

Multivalent presentation of ligands often enhances receptor activation and downstream signaling. DNA origami offers precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we introduce a square-block DNA origami platform to explore the importance of spacing of CpG oligonucleotides, which engage Toll-like receptors and thereby act as danger signals for dendritic cells. Through in vitro cell-culture studies and in vivo tumor-treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3.5 nm. We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T cell activation, Th1-polarized CD4 activation and NK cell activation. The vaccine also synergizes effectively with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induced long-term T cell memories. Our results suggest that DNA origami may serve as an advanced vaccine platform for controlling adjuvant spacing and co-delivering antigens.

The role of adjuvant radiation therapy (RT) in the management of advanced-stage Hodgkin's disease (HD) was analyzed in 222 patients who attained a complete remission (CR) with alternating chemotherapy combinations. Mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) or MOPP/ABV alternating with the lomustine, melphalan, and vindesine combination (MOPP/ABV/CAD) were similarly effective in inducing a CR in 222 of 270 (83%) patients. These patients were scheduled to receive consolidative RT to bulky disease or other critical sites of initial nodal involvement to a total dose of 2,000 cGy, with an optional additional boost of 1,000 cGy. However, only 125 (56%) patients received radiation to all initial nodal sites of disease. In 69 (31%) patients, only selected nodal sites were included in the radiation fields, and 28 (13%) did not receive any RT. Of the 222 CR patients, 42 (19%) relapsed during a median follow-up period of 6.5 years (range, 2 to 15 years). Of these, 26 (62%) patients relapsed exclusively in unirradiated nodal sites, six (14%) within irradiated sites, and 10 (24%) both within and outside irradiated fields. The actuarial 10-year relapse-free survival (RFS) and overall survival (OS) for patients receiving radiation to all initially involved nodal sites were 89% and 94%, respectively, compared with 68% and 71% (P less than .0001) for patients who had only partial or no RT. Cox proportional hazards regression analysis showed that RT to all sites of initial disease was the most significant independent covariate (P less than .005) affecting RFS and OS. These data demonstrate that residual microscopic disease is relatively frequent in patients with apparent CR after alternating combination chemotherapy, and that irradiation of all sites of initial nodal involvement decreases relapse and improves survival in advanced-stage HD.

Vascular calcification, the ectopic deposition of calcium in blood vessels, develops in association with various metabolic diseases and atherosclerosis and is an independent predictor of morbidity and mortality associated with these diseases. Herein, we report that reduction of microRNA-27a-3p ( miR-27a-3p ) causes an increase in activating transcription factor 3 (ATF3), a novel osteogenic transcription factor, in vascular smooth muscle cells. Both microRNA (miRNA) and mRNA microarrays were performed with rat vascular smooth muscle cells, and reciprocally regulated pairs of miRNA and mRNA were selected after bioinformatics analysis. Inorganic phosphate significantly reduced the expression of miR-27a-3p in A10 cells. The transcript level was also reduced in vitamin D 3 -administered mouse aortas. miR-27a-3p mimic reduced calcium deposition, whereas miR-27a-3p inhibitor increased it. The Atf3 mRNA level was upregulated in a cellular vascular calcification model, and miR-27a-3p reduced the Atf3 mRNA and protein levels. Transfection with Atf3 could recover the miR-27a-3p -induced reduction of calcium deposition. Our results suggest that reduction of miR-27a-3p may contribute to the development of vascular calcification by de-repression of ATF3.