Durability and efficacy of the ELVeS® Radial® 2ring slim fiber for multiple ablations.

Objectives: To prove that the ELVeS® Radial® 2ring slim fiber (Biolitec AG, Wien, Austria) is safe and effective, with a reliable fiber durability.

Methods: This prospective, non-randomized, registry recruited patients with venous incompetence of the great saphenous vein, with or without concomitant incompetence of the small, anterior accessory and posterior accessory saphenous veins. Anatomic success, clinical success and pain were assessed.

Endovascular treatment of atherosclerotic lesions in the superficial femoral artery and proximal popliteal artery using the sinus-SuperFlex-635 stent: twelve-month results from the HERO Registry.

Background: The aim of this study was to evaluate the safety and performance of the sinus-SuperFlex-635 self-expandable nitinol stent (Optimed GmbH) for the treatment of steno-occlusive lesions in the superficial femoral artery (SFA) and proximal popliteal artery (PPA).

Methods: The prospective, multicenter, observational HERO study recruited 117 eligible patients (83 men; mean age 69.4±9.

De Novo Mutations Affecting the Catalytic Cα Subunit of PP2A, PPP2CA, Cause Syndromic Intellectual Disability Resembling Other PP2A-Related Neurodevelopmental Disorders.

Type 2A protein phosphatases (PP2As) are highly expressed in the brain and regulate neuronal signaling by catalyzing phospho-Ser/Thr dephosphorylations in diverse substrates. PP2A holoenzymes comprise catalytic C-, scaffolding A-, and regulatory B-type subunits, which determine substrate specificity and physiological function. Interestingly, de novo mutations in genes encoding A- and B-type subunits have recently been implicated in intellectual disability (ID) and developmental delay (DD).

PP2A Inactivation Mediated by Haploinsufficiency Promotes Cancer Development.

Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular PP2A inhibitors. Here, we identify a novel genetic mechanism by which PP2A function is recurrently affected in human cancer, involving haploinsufficiency of , a gene encoding the cellular PP2A activator PTPA.

Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras.

Yeast and cancer cells share the unusual characteristic of favoring fermentation of sugar over respiration. We now reveal an evolutionary conserved mechanism linking fermentation to activation of Ras, a major regulator of cell proliferation in yeast and mammalian cells, and prime proto-oncogene product. A yeast mutant (tps1∆) with overactive influx of glucose into glycolysis and hyperaccumulation of Fru1,6bisP, shows hyperactivation of Ras, which causes its glucose growth defect by triggering apoptosis.

Recurrent PPP2R1A Mutations in Uterine Cancer Act through a Dominant-Negative Mechanism to Promote Malignant Cell Growth.

Somatic missense mutations in the Ser/Thr protein phosphatase 2A (PP2A) Aα scaffold subunit gene PPP2R1A are among the few genomic alterations that occur frequently in serous endometrial carcinoma (EC) and carcinosarcoma, two clinically aggressive subtypes of uterine cancer with few therapeutic options. Previous studies reported that cancer-associated Aα mutants exhibit defects in binding to other PP2A subunits and contribute to cancer development by a mechanism of haploinsufficiency. Here we report on the functional significance of the most recurrent PPP2R1A mutations in human EC, which cluster in Aα HEAT repeats 5 and 7.

B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.

Here we report inherited dysregulation of protein phosphatase activity as a cause of intellectual disability (ID). De novo missense mutations in 2 subunits of serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) were identified in 16 individuals with mild to severe ID, long-lasting hypotonia, epileptic susceptibility, frontal bossing, mild hypertelorism, and downslanting palpebral fissures. PP2A comprises catalytic (C), scaffolding (A), and regulatory (B) subunits that determine subcellular anchoring, substrate specificity, and physiological function.

The Basic Biology of PP2A in Hematologic Cells and Malignancies.

Reversible protein phosphorylation plays a crucial role in regulating cell signaling. In normal cells, phosphoregulation is tightly controlled by a network of protein kinases counterbalanced by several protein phosphatases. Deregulation of this delicate balance is widely recognized as a central mechanism by which cells escape external and internal self-limiting signals, eventually resulting in malignant transformation.

Structure, regulation, and pharmacological modulation of PP2A phosphatases.

Protein phosphatases of the type 2A family (PP2A) represent a major fraction of cellular Ser/Thr phosphatase activity in any given human tissue. In this review, we describe how the holoenzymic nature of PP2A and the existence of several distinct PP2A composing subunits allow for the generation of multiple structurally and functionally different PP2A complexes, explaining why PP2A is involved in the regulation of so many diverse cell biological and physiological processes. Moreover, in human disease, most notably in several cancers and Alzheimer's Disease, PP2A expression and/or activity have been found significantly decreased, underscoring its important functions as a major tumor suppressor and tau phosphatase.

The biogenesis of active protein phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity.

Protein phosphatase type 2A (PP2A) enzymes constitute a large family of Ser/Thr phosphatases with multiple functions in cellular signaling and physiology. The composition of heterotrimeric PP2A holoenzymes, resulting from the combinatorial assembly of a catalytic C subunit, a structural A subunit, and regulatory B-type subunit, provides the essential determinants for substrate specificity, subcellular targeting, and fine-tuning of phosphatase activity, largely explaining why PP2A is functionally involved in so many diverse physiological processes, sometimes in seemingly opposing ways. In this review, we highlight how PP2A holoenzyme biogenesis and enzymatic activity are controlled by a sophisticatedly coordinated network of five PP2A modulators, consisting of α4, phosphatase 2A phosphatase activator (PTPA), leucine carboxyl methyl transferase 1 (LCMT1), PP2A methyl esterase 1 (PME-1) and, potentially, target of rapamycin signaling pathway regulator-like 1 (TIPRL1), which serve to prevent promiscuous phosphatase activity until the holoenzyme is completely assembled.

[Natural course of Perthes disease].

The natural history of Perthes' disease can be followed in children with low Catterall rating, absent head-at risk signs and in the age group below 5 years. Thirty-one out of 34 patients who had been followed without active treatment healed with excellent results according to Stulberg's classification. Three unfavorable results were seen in patients who had refused treatment when suggested or who had failed to come in for the follow-up examination for an extensive period of time.