A genome-scale CRISPR screen reveals PRMT1 as a critical regulator of androgen receptor signaling in prostate cancer.

Androgen receptor (AR) signaling is the central driver of prostate cancer across disease states. While androgen deprivation therapy (ADT) is effective in the initial treatment of prostate cancer, resistance to ADT or to next-generation androgen pathway inhibitors invariably arises, most commonly through the re-activation of the AR axis. Thus, orthogonal approaches to inhibit AR signaling in advanced prostate cancer are essential.

Integrative clinical and molecular characterization of translocation renal cell carcinoma.

Translocation renal cell carcinoma (tRCC) is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 patients with tRCC identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.

CDK4/6 inhibition in cancer: the cell cycle splicing connection.

Cyclin-dependent kinase -4 and -6 (CDK4/6) inhibitors are currently being assessed in clinical trials for the treatment of many cancers including melanoma. While investigating the mechanisms of CDK4/6 inhibitor resistance in melanoma, we uncovered a mechanism of action of these inhibitors in regulating the expression of both the mouse double minute 4 (MDM4) oncogene and tumor protein p53 (TP53).

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are an established treatment in estrogen receptor-positive breast cancer and are currently in clinical development in melanoma, a tumor that exhibits high rates of CDK4 activation. We analyzed melanoma cells with acquired resistance to the CDK4/6 inhibitor palbociclib and demonstrate that the activity of PRMT5, a protein arginine methyltransferase and indirect target of CDK4, is essential for CDK4/6 inhibitor sensitivity. By indirectly suppressing PRMT5 activity, palbociclib alters the pre-mRNA splicing of MDM4, a negative regulator of p53, leading to decreased MDM4 protein expression and subsequent p53 activation.

The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells.

Purpose: The androgen receptor (AR) has attracted attention in the treatment of breast cancer. Due to the undesirable side effects of AR agonists, attempts have been undertaken to develop selective AR modulators. One of these compounds is Cl-4AS-1.

Differential expression and androgen regulation of microRNAs and metalloprotease 13 in breast cancer cells.

MicroRNA molecules (miRNAs) play important roles in regulating cell behavior. The expression of certain miRNAs has been shown to be regulated by the androgen receptor (AR), which seems to have a critical role in the tumorigenic process of breast cancer. The differential expression of 84 miRNAs was first examined in three breast cancer cell lines: the luminal MCF-7 and T47D cells and the molecular apocrine MDA-MB-453 cells.

Gene expression alterations in doxorubicin resistant MCF7 breast cancer cell line.

Many molecular mechanisms contribute to the development of doxorubicin resistance and different cancers can express wide and diverse arrays of drug-resistance genes. The aim of this study was to identify the changes in gene expression associated with the development of doxorubicin resistance in MCF7 breast cancer cell line. The doxorubicin resistant MCF7 cell line was developed by stepwise selection of MCF7 cells and was tested using the MTT assay.

Narghile (water pipe) smoking among university students in Jordan: prevalence, pattern and beliefs.

Background And Objectives: Narghile is becoming the favorite form of tobacco use by youth globally. This problem has received more attention in recent years. The aim of this study was to investigate the prevalence and pattern of narghile use among students in three public Jordanian universities; to assess their beliefs about narghile's adverse health consequences; and to evaluate their awareness of oral health and oral hygiene.

Predicting recurrent aphthous ulceration using genetic algorithms-optimized neural networks.

Objective: To construct and optimize a neural network that is capable of predicting the occurrence of recurrent aphthous ulceration (RAU) based on a set of appropriate input data.

Participants And Methods: Artificial neural networks (ANN) software employing genetic algorithms to optimize the architecture neural networks was used. Input and output data of 86 participants (predisposing factors and status of the participants with regards to recurrent aphthous ulceration) were used to construct and train the neural networks.