Patients' and physicians' awareness of clinical symptoms and disease severity in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare inherited disease with the potential to affect virtually every organ system. Clinical presentation is age- and partly sex-dependent and varies broadly with respect to disease manifestations including treatment-refractory epilepsy, intellectual disability and TSC-associated neuropsychiatric disorders, chronic kidney disease or progressive lung function decline. Given the complexity of this disease, multidisciplinary care in specialized TSC centres is recommended.

Analyzing the postulated inhibitory effect of Manumycin A on farnesyltransferase.

Manumycin A is postulated to be a specific inhibitor against the farnesyltransferase (FTase) since this effect has been shown in 1993 for yeast FTase. Since then, plenty of studies investigated Manumycin A in human cells as well as in model organisms like Some studies pointed to additional targets and pathways involved in Manumycin A effects like apoptosis. Therefore, these studies created doubt whether the main mechanism of action of Manumycin A is FTase inhibition.

Effect of farnesyltransferase inhibitors on SARS-CoV-2.

Objectives: The emergence of SARS-CoV-2 in 2019 led to a severe pandemic situation. Treatment options are limited, and the efficacy of vaccines decreases due to mutations in SARS-CoV-2 strains. Therefore, new treatment options are urgently needed, and computational compound screenings are used to predict drugs quickly.

Impact of a conserved N-terminal proline-rich region of the α-subunit of CAAX-prenyltransferases on their enzyme properties.

Background: The CAAX-prenyltransferases farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) are heterodimers with a common α- (FTα) and unique β-subunits. Recently, α-subunits of species (e.g.

Promoter Polymorphisms Are Independent Predictors of Survival in Patients with Triple Negative Breast Cancer.

In breast cancer, the promising efficacy of farnesyltransferase inhibitors (FTIs) in preclinical studies is in contrast to only limited effects in clinical Phase II-III trials. The objective of this study was to explore the clinical relevance of farnesyltransferase β-subunit () single nucleotide promoter polymorphisms (-173 6G > 5G (rs3215788), -609 G > C (rs11623866) and -179 T > A (rs192403314)) in early breast cancer. genotyping was performed by pyrosequencing in 797 patients from a prospective multicentre observational PiA trial (NCT01592825).

Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase.

Farnesyltransferase inhibitors (FTIs) are focus for the treatment of several diseases, particularly in the field of cancer therapy. Their potential, however, goes even further, as a number of studies have evaluated FTIs for the treatment of infectious diseases such as malaria, African sleeping sickness, leishmaniosis, and hepatitis D virus infection. Little is known about protein prenylation mechanisms in human pathogens.

Association of caspase 8 polymorphisms -652 6N InsDel and Asp302His with progression-free survival and tumor infiltrating lymphocytes in early breast cancer.

The caspase 8 variants CASP8 -652 6N InsDel and Asp302His have previously been identified to promote survival of T-lymphocytes and to indicate reduced breast cancer susceptibility. Besides some preliminary findings, prognostic relevance of these polymorphisms in patients with existing breast cancer has not been investigated. Considering an immunomodulatory role of these polymorphisms, we genotyped 785 early breast cancer patients and correlated caspase 8 variants with disease-free survival (DFS) and the presence of tumor infiltrating lymphocytes (TILs).

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro.

Background: The number of patients who has a daily intake of antihypertensive drugs is rising, due to an also rising prevalence of lifestyle diseases. Interestingly, knowledge about effects of these drugs in terms of wound healing is low.

Objective: Based on a few differing studies, the idea arose that antihypertensives may have side effects on wound healing.

No Association of CALCA Polymorphisms and Aseptic Loosening after Primary Total Hip Arthroplasty.

Studies of aseptic loosening showed an influence of calcitonin and -CGRP, both encoded from the calcitonin/-CGRP (CALCA) gene by alternative splicing. The aim of this study was to detect a possible association of the CALCA polymorphisms P1(rs1553005), P2(rs35815751), P3(rs5240), and P4(rs2956) with the time to aseptic loosening after THA. 320 patients suffering from aseptic loosening after primary total hip arthroplasty were genotyped for CALCA-P1 polymorphism and 161 patients for CALCA-P2 and CALCA-P3 polymorphisms and 160 patients for CALCA-P4 polymorphism.

A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis.

Particle-induced osteolysis, which by definition is an aseptic inflammatory reaction to implant-derived wear debris eventually leading to local bone destruction, remains the major reason for long-term failure of orthopedic endoprostheses. Fetuin-A, a 66kDa glycoprotein with diverse functions, is found to be enriched in bone. Besides being an important inhibitor of ectopic calcification, it has been described to influence the production of mediators of inflammation.

Impact of BCL2 polymorphisms on survival in transitional cell carcinoma of the bladder.

Purpose: To evaluate the impact of three BCL2 single-nucleotide polymorphisms, i.e., c.

Association of a Common Oxytocin Receptor Gene Polymorphism with Self-Reported 'Empathic Concern' in a Large Population of Healthy Volunteers.

Background: Previous research has linked genomic variations of the oxytocin receptor (OXTR) gene with individual differences in empathy. The impact of these variations on specific cognitive and emotional aspects of empathy, however, remains to be clarified.

Methods: We analysed associations of a common OXTR polymorphism (rs53576) with trait empathy in a sample of 421 blood donors (231 M, 190 F; age 18-74) using the Interpersonal Reactivity Index (IRI) as an established multidimensional self-report measure of empathy.

The FNTB promoter polymorphism rs11623866 as a potential predictive biomarker for lonafarnib treatment of ovarian cancer patients.

Aim: Despite promising preclinical findings regarding clinical utility of farnesyltransferase inhibitors (FTI), such as lonafarnib, success of clinical trials is limited. A multicentre AGO-OVAR-15 phase II trial reported an unfavourable effect of lonafarnib on the outcome of patients with advanced ovarian cancer. This study was performed as a genetic subgroup analysis of the AGO-OVAR-15 trial, and investigated the utility of the promoter polymorphism rs11623866 of the farnesyltransferase ß-subunit gene (FNTB) in predicting the clinical effectiveness of lonafarnib.

Calcitonin gene-related peptide modulates the production of pro-inflammatory cytokines associated with periprosthetic osteolysis by THP-1 macrophage-like cells.

Objective: An anti-resorptive impact of the neuropeptide calcitonin gene-related peptide (CGRP) on periprosthetic osteolysis, the leading cause of early prosthesis loosening, has been shown previously. In this study, the impact of CGRP on pro-inflammatory cytokine production associated with periprosthetic osteolysis was analysed using THP-1 macrophage-like cells.

Methods: Cells were stimulated with ultra-high-molecular-weight polyethylene (UHMWPE) particles (cell-to-particle ratios of 1:100 and 1:500) and lipopolysaccharides (LPS; 1 µg/ml) to establish osteolytic conditions, and simultaneously treated with CGRP (10(-8)M).