Primary Paraganglioma of the Prostate: A Systematic Review of the Literature for A Rare Entity.

Background: Paragangliomas of the urinary tract are exceptionally uncommon, and sporadic case reports of primary paraganglioma of the prostate have been reported in the literature.

Methods: Systematic research in PubMed/Medline and Scopus databases concerning primary prostatic paraganglioma was performed by two independent investigators.

Results: This analysis included 25 adult males, with a mean age of 49.

Diagnosis and Management of Intrascrotal Nerve Tumors: A Systematic Review of the Literature.

Scrotal tumors of nerve origin are extremely rare and occur mostly in the extratesticular tissues of scrotum, such as the spermatic cord and epididymis. A systematic search of the literature in PubMed, Medline, and Google Scholar databases concerning intrascrotal nerve tumors was performed by 2 independent investigators. The systematic search retrieved 45 male adults, with a mean age of included patients at 43.

Proximity-Induced Nucleic Acid Degrader (PINAD) Approach to Targeted RNA Degradation Using Small Molecules.

Nature has evolved intricate machinery to target and degrade RNA, and some of these molecular mechanisms can be adapted for therapeutic use. Small interfering RNAs and RNase H-inducing oligonucleotides have yielded therapeutic agents against diseases that cannot be tackled using protein-centered approaches. Because these therapeutic agents are nucleic acid-based, they have several inherent drawbacks which include poor cellular uptake and stability.

Large Cyst of Skene Gland: A Rare Perineum Mass.

 In this report we present a rare case of a large cyst of Skene gland in a female patient with a palpable vaginal mass persisting for at least 2 years.  A 67-year-old female admitted to the department of urology due to the presence of "a vaginal mass" for the past 2 years. A cyst of Skene's duct was suspected based on clinical manifestation and findings of magnetic resonance imaging showing an extensive cyst formation in the upper vaginal area and anterior to the urethra.

Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death.

Resistance to standard and novel therapies remains the main obstacle to cure in acute myeloid leukaemia (AML) and is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), the first enzyme in the mannose metabolism pathway, as a sensitizer to both cytarabine and FLT3 inhibitors across multiple AML models. Mechanistically, we identify a connection between mannose metabolism and fatty acid metabolism, that is mediated via preferential activation of the ATF6 arm of the unfolded protein response (UPR).

METTL1-mediated mG modification of Arg-TCT tRNA drives oncogenic transformation.

The emerging "epitranscriptomics" field is providing insights into the biological and pathological roles of different RNA modifications. The RNA methyltransferase METTL1 catalyzes N7-methylguanosine (mG) modification of tRNAs. Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival.

Identification of SARS-CoV-2-induced pathways reveals drug repurposing strategies.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the rapid development of new therapies against coronavirus disease 2019 (COVID-19) infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2-induced protein network, based on disease signatures defined by COVID-19 multiomics datasets, and cross-examined these pathways against approved drugs.

SETBP1 overexpression acts in the place of class-defining mutations to drive FLT3-ITD-mutant AML.

Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA. These class-defining mutations frequently synergize with internal tandem duplications in FLT3 (FLT3-ITDs) to drive leukemogenesis. However, ∼20% of FLT3-ITD-positive AMLs bare no class-defining mutations, and mechanisms of leukemic transformation in these cases are unknown.

Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia.

N-methyladenosine (mA) is an abundant internal RNA modification that is catalysed predominantly by the METTL3-METTL14 methyltransferase complex. The mA methyltransferase METTL3 has been linked to the initiation and maintenance of acute myeloid leukaemia (AML), but the potential of therapeutic applications targeting this enzyme remains unknown. Here we present the identification and characterization of STM2457, a highly potent and selective first-in-class catalytic inhibitor of METTL3, and a crystal structure of STM2457 in complex with METTL3-METTL14.

The N6-methyladenosine RNA modification in acute myeloid leukemia.

Purpose Of Review: In recent years, the N6-methyladenosine (m6A) modification of RNA has been shown to play an important role in the development of acute myeloid leukemia (AML) and the maintenance of leukemic stem cells (LSCs). In this review we summarise the recent findings in the field of epitranscriptomics related to m6A and its relevance in AML.

Recent Findings: Recent studies have focused on the role of m6A regulators in the development of AML and their potential as translational targets.

Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML.

Leukaemogenic mutations commonly disrupt cellular differentiation and/or enhance proliferation, thus perturbing the regulatory programs that control self-renewal and differentiation of stem and progenitor cells. Translocations involving the Mll1 (Kmt2a) gene generate powerful oncogenic fusion proteins, predominantly affecting infant and paediatric AML and ALL patients. The early stages of leukaemogenic transformation are typically inaccessible from human patients and conventional mouse models.

SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4.

We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonged survival of mice transplanted with MLL-rearranged AML. RNA-seq analysis demonstrates that SRPK1 inhibition leads to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB, BRD4 and MED24.