26 research outputs found
Molecular biomarkers in the context of focal therapy for prostate cancer: Recommendations of a delphi consensus from the focal therapy society
BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject
The potential to encode sex, age, and individual identity in the alarm calls of three species of Marmotinae
In addition to encoding referential information and information about the sender’s motivation, mammalian alarm calls may encode information about other attributes of the sender, providing the potential for recognition among kin, mates, and neighbors. Here, we examined 96 speckled ground squirrels (Spermophilus suslicus), 100 yellow ground squirrels (Spermophilus fulvus) and 85 yellow-bellied marmots (Marmota flaviventris) to determine whether their alarm calls differed between species in their ability to encode information about the caller’s sex, age, and identity. Alarm calls were elicited by approaching individually identified animals in live-traps. We assume this experimental design modeled a naturally occurring predatory event, when receivers should acquire information about attributes of a caller from a single bout of alarm calls. In each species, variation that allows identification of the caller’s identity was greater than variation allowing identification of age or sex. We discuss these results in relation to each species’ biology and sociality
Update of the Standard Operating Procedure on the Use of Multiparametric Magnetic Resonance Imaging for the Diagnosis, Staging and Management of Prostate Cancer.
PurposeWe update the prior standard operating procedure for magnetic resonance imaging of the prostate, and summarize the available data about the technique and clinical use for the diagnosis and management of prostate cancer. This update includes practical recommendations on the use of magnetic resonance imaging for screening, diagnosis, staging, treatment and surveillance of prostate cancer.Materials and methodsA panel of clinicians from the American Urological Association and Society of Abdominal Radiology with expertise in the diagnosis and management of prostate cancer evaluated the current published literature on the use and technique of magnetic resonance imaging for this disease. When adequate studies were available for analysis, recommendations were made on the basis of data and when adequate studies were not available, recommendations were made on the basis of expert consensus.ResultsProstate magnetic resonance imaging should be performed according to technical specifications and standards, and interpreted according to standard reporting. Data support its use in men with a previous negative biopsy and ongoing concerns about increased risk of prostate cancer. Sufficient data now exist to support the recommendation of magnetic resonance imaging before prostate biopsy in all men who have no history of biopsy. Currently, the evidence is insufficient to recommend magnetic resonance imaging for screening, staging or surveillance of prostate cancer.ConclusionsUse of prostate magnetic resonance imaging in the risk stratification, diagnosis and treatment pathway of men with prostate cancer is expanding. When quality prostate imaging is obtained, current evidence now supports its use in men at risk of harboring prostate cancer and who have not undergone a previous biopsy, as well as in men with an increasing prostate specific antigen following an initial negative standard prostate biopsy procedure
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AUA Policy Statement on the Use of Multiparametric Magnetic Resonance Imaging in the Diagnosis, Staging and Management of Prostate Cancer
PurposeWe summarize the available data about the clinical and economic effectiveness of magnetic resonance imaging in the diagnosis and management of prostate cancer, and provide practical recommendations for its use in the screening, diagnosis, staging and surveillance of prostate cancer.Materials and methodsA panel of clinicians with expertise in the diagnosis and management of prostate cancer evaluated the current published literature on the use and effectiveness of magnetic resonance imaging for this disease. When adequate studies were available for analysis, recommendations were made on the basis of data and when adequate studies were not available, recommendations were made on the basis of expert consensus.ResultsAt this time the data support the use of magnetic resonance imaging in patients with a previous negative biopsy and ongoing concerns about increased risk of prostate cancer. The data regarding its usefulness for initial biopsy suggest a possible role for magnetic resonance imaging in some circumstances. There is currently insufficient evidence to recommend magnetic resonance imaging for screening, staging or surveillance of prostate cancer.ConclusionsAlthough it adds cost to the management of prostate cancer, magnetic resonance imaging offers superior anatomic detail, and the ability to evaluate cellular density based on water diffusion and blood flow based on contrast enhancement. Imaging targeted biopsy may increase the diagnosis of clinically significant cancers by identifying specific lesions not visible on conventional ultrasound. The clinical indications for the use of magnetic resonance imaging in the management of prostate cancer are rapidly evolving
Novel Pancreatic Endocrine Maturation Pathways Identified by Genomic Profiling and Causal Reasoning
<div><p>We have used a previously unavailable model of pancreatic development, derived <em>in vitro</em> from human embryonic stem cells, to capture a time-course of gene, miRNA and histone modification levels in pancreatic endocrine cells. We investigated whether it is possible to better understand, and hence control, the biological pathways leading to pancreatic endocrine formation by analysing this information and combining it with the available scientific literature to generate models using a casual reasoning approach. We show that the embryonic stem cell differentiation protocol is highly reproducible in producing endocrine precursor cells and generates cells that recapitulate many aspects of human embryonic pancreas development, including maturation into functional endocrine cells when transplanted into recipient animals. The availability of whole genome gene and miRNA expression data from the early stages of human pancreatic development will be of great benefit to those in the fields of developmental biology and diabetes research. Our causal reasoning algorithm suggested the involvement of novel gene networks, such as NEUROG3/E2F1/KDM5B and SOCS3/STAT3/IL-6, in endocrine cell development We experimentally investigated the role of the top-ranked prediction by showing that addition of exogenous IL-6 could affect the expression of the endocrine progenitor genes NEUROG3 and NKX2.2.</p> </div
IL6, the top CRE prediction, has effects on expression of endocrine markers.
<p>(A) Treatment of pancreatic aggregates with IL-6 induces de novo gene expression of the pro-endocrine transcription factors NEUROG3 and NKX2.2, indicating commitment of pancreatic progenitor cells into the endocrine lineage. Noggin induction of these genes resulted in 8-fold increases (data not shown) (B) Gene expression in response to IL-6 was compared between whole aggregates (mixture of pancreatic progenitors and endocrine cells) and cultures of enriched endocrine cells (depleted of pancreatic progenitors). Induction of NKX2.2 expression was only seen in whole aggregates, consistent with the role of IL-6 in converting pancreatic progenitors into new endocrine cells. Enhanced expression of NEUROD1, IAPP, and SOMATOSTATIN seen in response to IL-6 in purified endocrine cells, suggesting IL-6 has additional roles in committed endocrine cells. No significant differences seen in INSULIN or GCG gene expression. Statistical testing using a standard t-test was performed.</p
Top 20 protein causal drivers of early pancreatic endoderm formation between day 8 and day 11.
<p>The number of correctly, incorrectly and ambiguously explained gene expression observations are given for each gene as well as the predicted direction of regulation (up meaning activation/down meaning inhibition). The notes for each gene indicate that in cases where the gene is already associated with beta cell function whether it is generally considered a positive or negative regulator of beta cell differentiation, proliferation (growth) or apoptosis. All hypotheses pass correctness and enrichment p-value thresholds of 10<sup>−5</sup>.</p