Three-dimensional imaging of upper tract urothelial carcinoma improves diagnostic yield and accuracy.

Upper tract urothelial carcinoma (UTUC) is a rare form of urothelial cancer with a high incidence of recurrence and a low survival rate. Almost two-thirds of UTUCs are invasive at the time of diagnosis; therefore, improving diagnostic methods is key to increasing survival rates. Histopathological analysis of UTUC is essential for diagnosis and typically requires endoscopy biopsy, tissue sectioning, and labeling.

GIT1 protects against breast cancer growth through negative regulation of Notch.

Hyperactive Notch signalling is frequently observed in breast cancer and correlates with poor prognosis. However, relatively few mutations in the core Notch signalling pathway have been identified in breast cancer, suggesting that as yet unknown mechanisms increase Notch activity. Here we show that increased expression levels of GIT1 correlate with high relapse-free survival in oestrogen receptor-negative (ER(-)) breast cancer patients and that GIT1 mediates negative regulation of Notch.

Three-dimensional single-cell imaging for the analysis of RNA and protein expression in intact tumour biopsies.

Microscopy analysis of tumour samples is commonly performed on fixed, thinly sectioned and protein-labelled tissues. However, these examinations do not reveal the intricate three-dimensional structures of tumours, nor enable the detection of aberrant transcripts. Here, we report a method, which we name DIIFCO (for diagnosing in situ immunofluorescence-labelled cleared oncosamples), for the multimodal volumetric imaging of RNAs and proteins in intact tumour volumes and organoids.

Single-cell RNA-seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63.

Cancers acquire resistance to systemic treatment with platinum-based chemotherapy (eg, cisplatin [CDDP]) as a result of a dynamic intratumoral heterogeneity (ITH) and clonal repopulation. However, little is known about the influence of chemotherapy on ITH at the single-cell level. Here, mapping the transcriptome of cancers treated with CDDP by scRNA-seq, we uncovered a novel gene, COX7B, associated with platinum-resistance, and surrogate marker, CD63.

BCG-induced cytokine release in bladder cancer cells is regulated by Ca signaling.

Bacillus Calmette-Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG.

Mapping of the three-dimensional lymphatic microvasculature in bladder tumours using light-sheet microscopy.

Background: Cancers are heterogeneous and contain various types of irregular structures that can go undetected when examining them with standard two-dimensional microscopes. Studies of intricate networks of vasculature systems, e.g.

Publisher Correction: Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity.

In this Article originally published, owing to a technical error, author affiliations were incorrectly assigned in the HTML version; the PDF was correct. These errors have now been corrected.

Evolution of cystectomy care over an 11-year period in a high-volume tertiary referral centre.

Objectives: To describe the evolution in radical cystectomy (RC) care over 11 years at a referral centre.

Patients And Methods: The clinical data of patients undergoing either open RC (ORC) or robot-assisted RC (RARC) for cT1-4aN0M0 bladder cancer (BCa) at our centre between January 2006 and December 2016 were retrospectively evaluated. Crude and propensity score-weighted log-binomial regression analyses were conducted to assess the association between pre- and peri-operative variables and the risk of reoperation, intensive care unit (ICU) admission and death <90 days after RC.

Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity.

Intratumoral heterogeneity is a critical factor when diagnosing and treating patients with cancer. Marked differences in the genetic and epigenetic backgrounds of cancer cells have been revealed by advances in genome sequencing, yet little is known about the phenotypic landscape and the spatial distribution of intratumoral heterogeneity within solid tumours. Here, we show that three-dimensional light-sheet microscopy of cleared solid tumours can identify unique patterns of phenotypic heterogeneity, in the epithelial-to-mesenchymal transition and in angiogenesis, at single-cell resolution in whole formalin-fixed paraffin-embedded (FFPE) biopsy samples.

Intracellular calcium release modulates polycystin-2 trafficking.

Background: Polycystin-2 (PC2), encoded by the gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD), functions as a calcium (Ca(2+)) permeable ion channel. Considerable controversy remains regarding the subcellular localization and signaling function of PC2 in kidney cells.

Methods: We investigated the subcellular PC2 localization by immunocytochemistry and confocal microscopy in primary cultures of human and rat proximal tubule cells after stimulating cytosolic Ca(2+) signaling.

[Treatment strategy for elderly patients with prostate cancer].

Because of both the indolent and aggressive nature of prostate cancers, it is not easy to select the best treatment for elderly patients with a high prevalence of comorbidities. Since the growth of prostate cancer is generally slow and all treatments adversely affect the quality of life to some degree, conservative treatment may well be the best option for elderly patients with prostate cancer. In fact, previous studies have indicated that the rate of prostate cancer death was not high in patients with low-intermediate risk of prostate cancer who were treated conservatively.

Nomogram to predict seminal vesicle invasion using the status of cancer at the base of the prostate on systematic biopsy.

Objective: The aim of this study was to predict seminal vesicle invasion (SVI) by developing a new nomogram based on clinical features including the status of cancer at the base of the prostate on systematic biopsy.

Methods: We studied the 466 patients with T1-3N0M0 prostate cancer who were treated with radical prostatectomy at three institutions. Preoperative clinical variables were correlated with the presence or absence of SVI with an area under the curve (AUC) of receiver-operator characteristics analysis.

Development and internal validation of a nomogram predicting extracapsular extension in radical prostatectomy specimens.

Objectives: To present a nomogram predicting the side-specific probability of extracapsular extension (ECE) in radical prostatectomy (RP) specimens.

Methods: Three hundred and fifty-four patients with T1c-T3a prostate cancer undergoing RP were included in the analysis. A receiver operating characteristic (ROC) analysis was carried out to evaluate the predictive values of each clinical and pathological factor, separately and in combination.

Na,K-ATPase signal transduction triggers CREB activation and dendritic growth.

Dendritic growth is pivotal in the neurogenesis of cortical neurons. The sodium pump, or Na,K-ATPase, is an evolutionarily conserved protein that, in addition to its central role in establishing the electrochemical gradient, has recently been reported to function as a receptor and signaling mediator. Although a large body of evidence points toward a dual function for the Na,K-ATPase, few biological implications of this signaling pathway have been described.

Production of erythropoietin and multiple cytokines by metanephric adenoma results in erythrocytosis.

This is the first report of direct evidence that metanephric adenoma cells produce erythropoietin and other types of cytokines, which may be the cause of the high incidence of erythrocytosis in patients with this tumor. The purpose of the study was to establish a metanephric adenoma cell line in vitro from nephrectomized tumor tissue in order to investigate the ability of metanephric adenoma cells to produce erythropoietin and other types of cytokines. The tumor tissue was obtained from a 16-year-old boy who had developed metanephric adenoma with erythrocytosis and was served for cell culture.

Na,K-ATPase generates calcium oscillations in hippocampal astrocytes.

Na,K-ATPase maintains not only ionic homeostasis, but also participates in a multiprotein complex mediating intracellular signalling. We show that ouabain, a specific ligand for Na,K-ATPase, evokes calcium oscillations in hippocampal astrocytes in primary cultures. Coimmunoprecipitation studies suggest that the mechanism underlying these calcium oscillations involves a multiprotein complex consisting of ankyrin-B, the inositol 1,4,5-trisphosphate receptor and Na,K-ATPase.