Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey‐Holden Prostate Cancer Academy Meeting

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138883/1/pros23424.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138883/2/pros23424_am.pd

SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1

BACKGROUND We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity

Computed tomography for the diagnosis of lumbar spinal pathology in adult patients with low back pain or sciatica: a diagnostic systematic review

Aim: In low back pain if serious pathology is suspected diagnostic imaging could be performed. One of the imaging techniques available for this purpose is computed tomography (

The effect of glucosamine sulphate on osteoarthritis: design of a long-term randomised clinical trial [ISRCTN54513166]

BACKGROUND: Pharmacological treatment for osteoarthritis (OA) can be divided into two groups: symptom-modifying drugs and disease-modifying drugs. Symptom-modifying drugs are currently the prescription of choice for patients with OA, as disease-modifying drugs are not yet available in usual care. However, there has recently been a lot of debate about glucosamine sulphate (GS), a biological agent that is thought to have both symptom-modifying and disease-modifying properties. This assumption has yet to be proved. The objective of this article is to present the design of a blind randomised clinical trial that examines the long-term symptom-modifying and disease-modifying effectiveness of GS in patients with hip OA. This trial is ongoing and will finish in March 2006. METHODS/DESIGN: Patients with hip OA meeting the ACR-criteria are randomly allocated to either 1500 mg of oral GS or placebo for the duration of two years. The primary outcome measures, which are joint space narrowing (JSN), and change in the pain and function score of the Western Ontario McMaster Universities Osteoarthritis index (WOMAC), are determined at baseline and after two years of follow-up during the final assessment. Intermediate measures at three-month intervals throughout the trial are used to study secondary outcome measures. Secondary outcome measures are changes in WOMAC stiffness score, quality of life, medical consumption, side effects and differences in biomarker CTX-II

Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death

Prostate Cancer Foundation, American Cancer Society (RSG-15-067-01-TBG), Prostate Cancer Foundation, National Cancer Institute (R01 CA204749), Howard Hughes Medical Institute, National Institutes of Health (CA193837),(CA092629), (CA155169), (CA008748)

Galectin-3 and Beclin1/Atg6 Genes In Human Cancers: Using cDNA Tissue Panel, qRT-PCR, and Logistic Regression Model to Identify Cancer Cell Biomarkers

Cancer biomarkers are sought to support cancer diagnosis, predict cancer patient response to treatment and survival. Identifying reliable biomarkers for predicting cancer treatment response needs understanding of all aspects of cancer cell death and survival. Galectin-3 and Beclin1 are involved in two coordinated pathways of programmed cell death, apoptosis and autophagy and are linked to necroptosis/necrosis. The aim of the study was to quantify galectin-3 and Beclin1 mRNA in human cancer tissue cDNA panels and determine their utility as biomarkers of cancer cell survival.A panel of 96 cDNAs from eight (8) different normal and cancer tissue types were used for quantitative real-time polymerase chain reaction (qRT-PCR) using ABI7900HT. Miner2.0, a web-based 4- and 3-parameter logistic regression software was used to derive individual well polymerase chain reaction efficiencies (E) and cycle threshold (Ct) values. Miner software derived formula was used to calculate mRNA levels and then fold changes. The ratios of cancer to normal tissue levels of galectin-3 and Beclin1 were calculated (using the mean for each tissue type). Relative mRNA expressions for galectin-3 were higher than for Beclin1 in all tissue (normal and cancer) types. In cancer tissues, breast, kidney, thyroid and prostate had the highest galectin-3 mRNA levels compared to normal tissues. High levels of Beclin1 mRNA levels were in liver and prostate cancers when compared to normal tissues. Breast, kidney and thyroid cancers had high galectin-3 levels and low Beclin1 levels.Galectin-3 expression patterns in normal and cancer tissues support its reported roles in human cancer. Beclin1 expression pattern supports its roles in cancer cell survival and in treatment response. qRT-PCR analysis method used may enable high throughput studies to generate molecular biomarker sets for diagnosis and predicting cancer treatment response

The global naturalized Alien Flora (GloNAF) database

This dataset provides the Global Naturalized Alien Flora (GloNAF) database, ver-sion 1.2. Glo NAF represents a data compendium on th e occurrence and identit y of naturalizedalien vascular plant taxa across geographic regions (e.g. countries, states, provinces, districts,islands) around the globe. The dataset includes 13,939 taxa and covers 1,029 regions (including381 islands). The dataset is based on 210 data sources. For each ta x on-b y-region combination, wepr ovide information on whether the tax on is consider ed to be naturalized in the specific region(i.e. has established self-sustaining popula tions in the wild). Non-native taxa are marked as“alien”, when it is not clear whether they are naturalized. To facilitate alignment with other plantdatabases, we pro v ide f or each taxon the name as given in the original data source and the stan-dardized taxon and family names used by The Plant List Version 1.1 (http://www.theplantlist.org/). We pro vide an ESRI shapefile including polygons f or each region and informa tion on whetherit is an island or a mainland region, the country and the Taxonomic Databases Working Group(TDWG) regions it is part of (TDWG levels 1–4). We also provide several variables that can beused to filter the data according to quality and completeness of alien taxon lists, which varyamong the combinations of regions and da ta sources. A pre vious version of the GloNAF dataset(version 1.1) has already been used in several studies on, for example, historical spatial flows oftaxa between continents and geographical patterns and determinants of naturalization across dif-ferent taxonomic groups. We intend the updated and expanded GloNAF version presented hereto be a global resource useful for studying plant inv asions and changes in biodiversity from regio-nal to global scales. We release these data into the public domain under a Crea ti ve CommonsZer o license waiver (https://creati v ecommons.org/share-y our -work/public-domain/cc0/). Wheny ou use the da ta in your publication, we request that y ou cite this da ta paper. If GloN AF is amajor part of the data analyzed in your study, you should consider inviting the GloNAF coreteam (see Metadata S1: Originators in the Overall project description) as collaborators. If youplan to use the GloNAF dataset, we encourage y ou to contact the GloNAF core team to checkwhether there have been recent updates of the dataset, and whether similar analyses are already ongoing

Demographics of extra-articular calcaneal fractures: Including a review of the literature on treatment and outcome

Introduction: Extra-articular calcaneal fractures represent 25-40% of all calcaneal fractures and an even higher percentage of up to 60% is seen in children. A disproportionately small part of the literature on calcaneal fractures involves the extra-articular type. The aim of this study was to investigate the incidence of extra-articular calcaneal fractures in a Level 1 trauma centre, define the distribution of the various types of fractures and compare patient demographics between extra- and intra-articular calcaneal fractures. In addition the literature was reviewed for the most common types of extra-articular calcaneal fractures with regard to incidence, treatment and clinical outcome. Methods: The radiological records between 2003 and 2005 were reviewed for intra- and extra-articular calcaneal fractures. Patient gender-distribution and age were compared. A literature search was conducted for the treatment of extra-articular calcaneal fractures. Results: In this 3-year study period a total of 49 patients with 50 extra-articular calcaneal fractures and 91 patients with 101 intra-articular fractures were identified. The median age for the first group was 32.7 years, and for the second group 40.3 years; P = 0.04. Male predominance was significantly less pronounced for extra-articular (63%) compared with intra-articular fractures (79%; P = 0.04). Conclusion: One-third of all calcaneal fractures are extra-articular. Significant differences exist between the intra- and extra-articular groups, in terms of lower age and male-female ratio. The literature study shows inconsistencies in treatment options, but most extra-articular fractures are well manageable conservatively

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri