Identification of Protein Palmitoylation Inhibitors from a Scaffold Ranking Library.

This report describes a mixture based screening approach to identify inhibitors of Erf2 activity. Erf2 is the Saccharomyces cerevisiae PAT responsible for catalyzing the palmitoylation of Ras2, an ortholog of the human Ras oncogene proteins. A chemical library developed by the Torrey Pines Institute for Molecular Studies consists of more than 30 million compounds designed around 68 molecular scaffolds that are systematically arranged into positional scanning and scaffold ranking formats. We have used this approach to identify and characterize several scaffold backbones and R-groups that reduce or eliminate the activity of Erf2 in vitro. Here, we present the analysis of one of the scaffold backbones, bis-cyclic piperazine. We identified compounds that inhibited Erf2 auto-palmitoylation activity using a fluorescence-based, coupled assay in a high throughput screening (HTS) format and validated the hits utilizing an orthogonal gel-based assay. Finally, we examined the effects of the compounds on cell growth in a yeast cell-based assay. Based on our results, we have identified specific, high affinity palmitoyl transferase inhibitors that will serve as a foundation for future compound design. PMID: 27009891 [PubMed - as supplied by publisher]
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research

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Publication date: Available online 11 December 2019Source: MicronAuthor(s): Benedykt R. Jany, Arkadiusz Janas, Franciszek KrokAbstractAnalysis of microscope images is a tedious work which requires patience and time, usually done manually by the microscopist after data collection. The results obtained in such a way might be biased by the human who performed the analysis. Here we introduce an approach of automatic image analysis, which is based on locally applied Fourier Transform and Machine Learning methods. In this approach, a whole image is scanned by a local moving window with defined size and the 2D Fourier Transform i...
Source: Micron - Category: Biology Source Type: research
A 29-year-old woman with stage IIBX classic Hodgkin's lymphoma presented with a 5.1  × 7.6-cm (mass to mediastinal ratio 0.34) anterior mediastinal mass and additional involvement of the subcarinal, posterior mediastinal, and right infraclavicular lymph nodes (Fig. 1). The patient was otherwise healthy, a lifelong nonsmoker, and European Cooperative Oncology Group performance s tatus 0. She had a National Comprehensive Cancer Network International Prognostic Score of 1. She received 2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), and interim positron emission tomography demonstr...
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Gray Zone Source Type: research
This study was approved by the institutional review board. Sixty patients diagnosed with cervical cancer by pathology were prospectively included. Female pelvic magnetic resonance imaging was performed using a 3 T magnetic resonance scanner; B1 and B2 images were obtained for evaluation. Two radiologists blinded to the scan parameters evaluated the images for signal loss in the background, spatial distortion, image ghosting, confidence in the lesion delineation, and overall image quality using a 5-point scoring system. The scores were compared using a paired Wilcoxon test. SI was measured in the B1 and B2 images for...
Source: European Journal of Radiology - Category: Radiology Source Type: research
ConclusionPretreatment quantities positron emission tomography parameters did not predict survival in head and neck cancer.ResumoIntroduçãoOs parâmetros da tomografia por emissão de pósitrons/tomografia computadorizada com 18F-fluordesoxiglicose, como os máximos valores de captação padronizados, o volume metabólico tumoral padrão e a glicólise total da lesão são importantes biomarcadores prognósticos de câncer.Objetivoinvestigar o valor prognóstico desses parâmetros em pacientes com câncer de cabe&ccedi...
Source: Brazilian Journal of Otorhinolaryngology - Category: ENT & OMF Source Type: research
CONCLUSIONS: These data impose a closer follow-up of smokers and pre-neoplastic cases and the utility of the broadspectrum polymerase chain reaction assay in laryngeal dysplastic and cancer lesions. This study may allow to develop biomarkers for early detection or recurrence surveillance, to identify therapeutic targets, and to begin individualization of treatment based on the biology of these tumours. KEY WORDS: HPV infection, Larynx, Laryngeal chronic hyperplastic inflammation, Squamous cell carcinoma. PMID: 31814599 [PubMed - in process]
Source: Annali Italiani di Chirurgia - Category: Surgery Tags: Ann Ital Chir Source Type: research
Conclusion: Enzalutamide can be used to effectively treat mCRPC patients in daily clinical settings, despite the patients being older and less healthy than those enrolled in the previous randomised, clinical registration studies. PMID: 31815592 [PubMed - in process]
Source: Scandinavian Journal of Urology - Category: Urology & Nephrology Tags: Scand J Urol Source Type: research
ConclusionConsidering the facile preparation and improved biological properties, Al[18F]F-NOTA-PEG3-duramycin seems to be a promising PET tracer candidate for imaging apoptosis in the monitoring of cancer treatment.
Source: Molecular Imaging and Biology - Category: Molecular Biology Source Type: research
As awareness of the habits and risks associated with lung cancer has increased, so has the interest in promoting and improving upon lung cancer screening procedures. Recent research demonstrates the benefits of lung cancer screening; the National Lung Screening Trial (NLST) found as its primary result that preventative screening significantly decreases the death rate for patients battling lung cancer. However, it was also noted that the false positive rate was very high (>94%).In this work, we investigated the ability of various machine learning classifiers to accurately predict lung cancer nodule status while also cons...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: Our data suggest that thyroid hormones influence angiogenic signaling in MSCs via integrin αvβ3 and further substantiate the anti-angiogenic activity of Tetrac in the tumor microenvironment. PMID: 31816265 [PubMed - as supplied by publisher]
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research
CONCLUSIONS: PD-L1 inhibitors lead to immune mediated thyroiditis, the most frequent endocrine IRAE. In most cases, management is supportive without requiring steroids or discontinuation of immunotherapy. Diffusely increased thyroid 18FDG uptake on PET scan may predict the occurrence of thyroiditis, whereas TPO antibodies may help identify its severity. Thyroiditis may be a biomarker for anti-tumor immune response, highlighting the need to further characterize its underlying mechanism. PMID: 31813343 [PubMed - as supplied by publisher]
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research
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