TRUS-MR Fusion Biopsy of the Prostate: Radiological and Histological Correlation

Objective: Targeted magnetic resonance/ultrasound fusion prostate biopsy has been shown to improve the detection of high-grade prostate cancer and to reduce sampling errors. Our objective is to assess MR-TRUS targeted fusion biopsy versus standard biopsy for the detection of clinically significant tumors. Materials and Methods: Patients were referred for abnormal digital rectal examination (DRE) or risen prostate-specific antigen (PSA). If an MRI-visible lesion was detected, they were included in the study. In total, 102 men underwent MRI followed by MR-TRUS fusion biopsy between November 2014 and January 2016. Tumor grading was done with the clinical relevance in mind; a cutoff was used at Gleason 7 or higher. Standard biopsy results were collected from clinical practice during 2005 at the same institution to provide baseline values. Results: A comparable rate of prostate cancer is found whether sampling is done at random (42.4%) or with the use of fusion biopsy (44.1%). However, these percentages are histologically different: fewer low-grade tumors are detected with MR-TRUS fusion biopsy (–19.1%), while more high-grade tumors are diagnosed (+26%). If there is an ultrasound-visible lesion in the prostate, the gain of combined MRI and fusion biopsy is less impressive. Conclusion: Fusion biopsy can provide more accurate information for optimal patient management, as it detects a higher percentage of high-grade prostate cancers than random sampling. Furthermore, nonrelevant tumors are less commonly detected using fusion biopsy

Evaluation of local tolerance of a plant extract by the slug mucosal irritation (SMI) assay

This article describes the performance of a laboratory exercise, the Slug Mucosal Irritation (SMI) assay, carried out by third year undergraduate students, to investigate the local tolerance of an ethanolic plant extract. The plant extract, Spilanthes acmella, contains various bio-active compounds, such as the N-alkylamide spilanthol. After administration of the plant extract to the slugs, they were observed for possible discomfort and tissue damage. When slugs are exposed to a substance with irritant properties, the mucus production of the slugs will increase. Furthermore, slugs will release proteins, including enzymes, when tissue damage occurs. This laboratory experiment is a practically feasible in vivo test using slugs which are invertebrates that are not protected by the legislation on animal testing. Students were supervised by lab instructors who encouraged students to actively contribute in their groups, to think about the experimental design of the laboratory test, and to facilitate scientific discussions, but the majority of the ideas had to come from the students themselves. Hence, this biomedical in vivo experiment offered a great opportunity for students to learn to work in group, to critically interpret and report their results, to gain knowledge about the subject, and to communicate and discuss with other students as well as with the lab instructors. Furthermore, this experiment teaches students current toxicological methodologies encompassing principles and their application of biochemistry, analytical chemistry, toxicology, animal experimentation and data handling. This way of interdisciplinary teaching is especially important for last year undergraduate students, as this is a good preparation for the Masters dissertation. At the end of the laboratory exercise, students received a questionnaire and most of the students indicated that they gained valuable knowledge and skills. This laboratory exercise can be incorporated into chemical, biological, pharmaceutical, toxicological and medical disciplines

Evaluation of local tolerance of a plant extract by the slug mucosal irritation (SMI) assay

This article describes the performance of a laboratory exercise, the Slug Mucosal Irritation (SMI) assay, carried out by third year undergraduate students, to investigate the local tolerance of an ethanolic plant extract. The plant extract, Spilanthes acmella, contains various bio-active compounds, such as the N-alkylamide spilanthol. After administration of the plant extract to the slugs, they were observed for possible discomfort and tissue damage. When slugs are exposed to a substance with irritant properties, the mucus production of the slugs will increase. Furthermore, slugs will release proteins, including enzymes, when tissue damage occurs. This laboratory experiment is a practically feasible in vivo test using slugs which are invertebrates that are not protected by the legislation on animal testing. Students were supervised by lab instructors who encouraged students to actively contribute in their groups, to think about the experimental design of the laboratory test, and to facilitate scientific discussions, but the majority of the ideas had to come from the students themselves. Hence, this biomedical in vivo experiment offered a great opportunity for students to learn to work in group, to critically interpret and report their results, to gain knowledge about the subject, and to communicate and discuss with other students as well as with the lab instructors. Furthermore, this experiment teaches students current toxicological methodologies encompassing principles and their application of biochemistry, analytical chemistry, toxicology, animal experimentation and data handling. This way of interdisciplinary teaching is especially important for last year undergraduate students, as this is a good preparation for the Masters dissertation. At the end of the laboratory exercise, students received a questionnaire and most of the students indicated that they gained valuable knowledge and skills. This laboratory exercise can be incorporated into chemical, biological, pharmaceutical, toxicological and medical disciplines

Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells

The interplay between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells performs a crucial role in MM pathogenesis by secreting growth factors, cytokines, and extracellular vesicles. Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and they mediate local cell-to-cell communication by transferring mRNAs, miRNAs, and proteins. Although BMSC-induced growth and drug resistance of MM cells has been studied, the role of BMSC-derived exosomes in this action remains unclear. Here we investigate the effect of BMSC-derived exosomes on the viability, proliferation, survival, migration, and drug resistance of MM cells, using the murine 5T33MM model and human MM samples. BMSCs and MM cells could mutually exchange exosomes carrying certain cytokines. Both naive and 5T33 BMSC-derived exosomes increased MM cell growth and induced drug resistance to bortezomib. BMSC-derived exosomes also influenced the activation of several survival relevant pathways, including c-Jun N-terminal kinase, p38, p53, and Akt. Exosomes obtained from normal donor and MM patient BMSCs also induced survival and drug resistance of human MM cells. Taken together, our results demonstrate the involvement of exosome-mediated communication in BMSC-induced proliferation, migration, survival, and drug resistance of MM cells

Retrospective analysis of the Draize test for serious eye damage/eye irritation: importance of understanding the in vivo endpoints under UN GHS/EU CLP for the development and evaluation of in vitro test methods

For more than two decades, scientists have been trying to replace the regulatory in vivo Draize eye test by in vitro methods, but so far only partial replacement has been achieved. In order to better understand the reasons for this, historical in vivo rabbit data were analysed in detail and resampled with the purpose of (1) revealing which of the in vivo endpoints are most important in driving United Nations Globally Harmonized System/European Union Regulation on Classification, Labelling and Packaging (UN GHS/EU CLP) classification for serious eye damage/eye irritation and (2) evaluating the method’s within-test variability for proposing acceptable and justifiable target values of sensitivity and specificity for alternative methods and their combinations in testing strategies. Among the Cat 1 chemicals evaluated, 36–65 % (depending on the database) were classified based only on persistence of effects, with the remaining being classified mostly based on severe corneal effects. Iritis was found to rarely drive the classification (<4 % of both Cat 1 and Cat 2 chemicals). The two most important endpoints driving Cat 2 classification are conjunctiva redness (75–81 %) and corneal opacity (54–75 %). The resampling analyses demonstrated an overall probability of at least 11 % that chemicals classified as Cat 1 by the Draize eye test could be equally identified as Cat 2 and of about 12 % for Cat 2 chemicals to be equally identified as No Cat. On the other hand, the over-classification error for No Cat and Cat 2 was negligible (<1 %), which strongly suggests a high over-predictive power of the Draize eye test. Moreover, our analyses of the classification drivers suggest a critical revision of the UN GHS/EU CLP decision criteria for the classification of chemicals based on Draize eye test data, in particular Cat 1 based only on persistence of conjunctiva effects or corneal opacity scores of 4. In order to successfully replace the regulatory in vivo Draize eye test, it will be important to recognise these uncertainties and to have in vitro tools to address the most important in vivo endpoints identified in this paper.JRC.I.5-Systems Toxicolog

Familial Adenomatous Polyposis-Associated Desmoids Display Significantly More Genetic Changes than Sporadic Desmoids

Desmoid tumours (also called deep or aggressive fibromatoses) are potentially life-threatening fibromatous lesions. Hereditary desmoid tumours arise in individuals affected by either familial adenomatous polyposis (FAP) or hereditary desmoid disease (HDD) carrying germline mutations in APC. Most sporadic desmoids carry somatic mutations in CTNNB1. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumours. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumours, we analysed 17 FAP-associated and 38 sporadic desmoids by array comparative genomic hybridisation and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Recurrent gains at 8q (7%) and 20q (5%) were almost exclusively found in sporadic tumours. Recurrent losses were observed for a 700 kb region at 5q22.2, comprising the APC gene (11%), a 2 Mb region at 6p21.2-p21.1 (15%), and a relatively large region at 6q15-q23.3 (20%). The FAP-associated desmoids displayed a significantly higher frequency of copy number abnormalities (59%) than the sporadic tumours (37%). As predicted by the APC germline mutations among these patients, a high percentage (29%) of FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3%) seen among sporadic tumours. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumour progression

Endovascular Management of Severe Arterial Haemorrhage After Radical Prostatectomy: A Case Series

The aim of this study is to assess the safety, effectiveness and long-term outcome of endovascular management of arterial haemorrhage after radical prostatectomy (RP).status: publishe