Incidental seminal vesicle amyloidosis observed in diagnostic prostate biopsies--are routine investigations for systemic amyloidosis warranted？

Seminal vesicle （SV） amyloidosis is a well-documented histological entity, but it is observed infrequently. Its incidence is on the rise, which is probably related to the increasing use of prostate biopsies to investigate patients with elevated serum prostate-specific antigen levels. Here, we report seven cases of incidental SV amyloidosis over a 3-year period and consider their relationship to the previously suggested aetiological factors. Based on our series, we conclude that incidental localized SV amyloidosis observed in diagnostic prostate biopsies does not warrant formal investigations for systemic amyloidosis.

Hzf and hCAS/CSEIL： making the right choice in p53-mediated tumour suppression

Preventing the propagation of damaged cells is a central component of tumour suppression. A key factor in this process is the transcription factor p53 - a fact exemplified by its frequent inactivation in human cancer. Since its discovery, over forty thousand reports have been published investigating p53 function and regulation. It is known that p53 mediates the expression of a diverse set of target genes which are broadly grouped by the biological response they provoke, with the best characterized being the induction of growth arrest, during which cellular damage is repaired, or the induction of apoptosis, which serves to eradicate damaged cells that may otherwise go on to form a tumour .

A variant in IL6ST with a selective IL-11 signaling defect in human and mouse

The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6 st p.R279 Q. We show that human GP130 p.R281 Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice Il6 st p.R279 Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11 RA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.

Modelling synergistic interactions between HER2, Sprouty2 and PTEN in driving prostate carcinogenesis

Prostate cancer remains a major global health issue and a major cause of mor-bidity and mortality in men worldwide. Activation of androgen receptor and inac- tivation of the tumour suppressor gene phosphatase and tensin homologue （PTEN） represent two major events in prostate carcinogenesis. Using a range of clinical resources, in vitro and in vivo models, we explored potential complex interactions among receptor tyrosine kinases （such as HER2/3 and EGFR） and tumour suppressor genes, namely,

THE ROLE OF ONCOGENES AND ONCO-SUPPRESSOR GENES IN CARCINOGENESIS

Carcinogenesis is a multi-stage process.This process may involve both genetic and epi-genetic events. Analyses of the involvement ofgenetic events (mutations in the global sensewhich include point mutations, deletions, trans-locations and rearrangements of genetic mate-rial) in carcinogenesis have implicated twomajor classes of genes, oncogenes and onco-suppressor genes. Oncogenes, a term first usedby Huebner and Todaro, are derived by muta-tion of normal cellular genes, protooncogenes.More than 40 oncogenes have now been isolatedand found to encode proteins with diverse bio-chemical functions.

Tumor invasion and metastasis in Drosophila:A bold past,a bright future

Invasion and metastasis are the most deadly hallmarks of cancer. Once a cancer has acquired the ability to colonize new sites in the body it becomes dramatically more difficult to treat. This has made it a focus of much of cancer research. The humble fruit fly, Drosophila mela- nogaster, has despite its relative simplicity, made significant contributions to the understanding of tumor progression. In this review we outline and highlight those with an emphasis on modeling the genetic and epigenetic changes required for invasion and metastasis. We will revisit the early years of cancer modeling in Drosophila where the first parallels were drawn between Drosophila and vertebrate neoplasms and highlight recent advances using genetic screens and interactions with the epithelial microenvironment and innate immune system. We focus on the power and limitations of current fly models of metastasis.

Developing a coordinate-based strategy to support cognitive targeted prostate biopsies and correlative spatial-histopathological outcome analysis

Lack of investment for magnetic resonance(MR)fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway.We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions.In each patient,the prostate is considered as two separate hemiprostates,and each hemiprostate is divided into 4×4×4 units.Each unit is therefore defined by a three-dimensional coordinate.We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men.Among 45(of 106;42.5%)lesions positive for cancer,27 lesions(60.0%)harbored clinically significant disease.PSA density was significantly higher in patients with proven cancer(median:0.264 ng ml^(-2))when compared to the noncancer group(median:0.145 ng ml-2;P=0.003,Wilcoxon ranksum test).Lesions with Prostate Imaging-Reporting and Data System(PIRADS)score of 5 were found to have a cancer incidence of 65.2%,while PI RADS 4 and 3 lesions have a lower risk of cancer detection,as expected,at 37.3%and 31.3%,respectively.The probability of a lesion being cancerous in our series significantly decreases as we go from the“apex-to-base”dimension(odds ratio[OR]:2.62,95%confidence interval[Cl]:1.55-4.44,P=0.00034).Our analysis also indicates that the probability of cancer decreases as the prostate volume increases(OR:1.03,95%Cl:1.01-1.05,P=0.00327).Based on this feasibility study,the use of coordinates to guide cognitive targeted prostate biopsies warrants future validation study in additional centers.