J Pain Symptom Manage
December 2024
Due to worldwide increasing resistances, there is a considerable need for antibacterial compounds with modes of action not yet realized in commercial antibiotics. One such promising structure is the acetyl-CoA carboxylase (ACC) inhibitor moiramide B which shows strong antibacterial activity against gram-positive bacteria such as Bacillus subtilis and weaker activities against gram-negative bacteria. However, the narrow structure-activity relationship of the pseudopeptide unit of moiramide B represents a formidable challenge for any optimization strategy.
View Article and Find Full Text PDFRas proteins are implicated in some of the most common life-threatening cancers. Despite intense research during the past three decades, progress towards small-molecule inhibitors of mutant Ras proteins still has been limited. Only recently has significant progress been made, in particular with ligands for binding sites located in the switch II and between the switch I and switch II region of K-Ras4B.
View Article and Find Full Text PDFFront Pain Res (Lausanne)
September 2021
Pain is a common symptom in cancer patients, restricts daily life activities and reduces survival time. Identification of sociodemographic, medical and psychological correlates of pain among cancer patients in Germany could help identify subgroups most in need of pain management. In this multicenter, epidemiologic cross-sectional study, we assessed pain prevalence and severity, quality of life (QoL) and psychological distress in a sample of 3,745 cancer patients across all tumor entities.
View Article and Find Full Text PDFThis review assessed population-based estimate rates of cancer patients with minor and young adult children (≤ 25 years), children and young adults having a parent with cancer as well as the psychosocial situation and well-being of children and young adults affected by parental cancer. Eighteen publications on population-based studies were included. Studies varied in the age ranges of both cancer patients and children.
View Article and Find Full Text PDFPurpose: Distress screening has become mandatory and essential in comprehensive cancer care. We evaluated an electronic psycho-oncological adaptive screening (EPAS) which assesses objective indicators of care needs and subjectively perceived care needs and subsequently provides patient feedback with individualized recommendations about psychosocial care services.
Methods: Patients were assessed within clusters, i.
Aim: To compare prevalence rates of mental disorders in patients with cancer and general population controls.
Method: In two stratified nationally representative surveys, the 12-month prevalence of mental disorders was assessed in 2141 patients with cancer and 4883 general population controls by the standardized Composite International Diagnostic Interview (CIDI). We determined odds ratios (ORs) to compare the odds for mental disorders (combined and subtypes) in cancer patients with age- and gender-matched controls.
AlphaScreen is one of the most widely used assay technologies in drug discovery due to its versatility, dynamic range and sensitivity. However, a presence of false positives and frequent hitters contributes to difficulties with an interpretation of measured HTS data. Although filters do exist to identify frequent hitters for AlphaScreen, they are frequently based on privileged scaffolds.
View Article and Find Full Text PDFObjectives: The Distress Thermometer (DT) is a validated and widely used screening tool to identify clinically relevant distress in cancer patients. It is unclear, to which extend subjectively perceived distress measured by the DT is related to objective burden (mental disorder). We therefore examine the co-occurrence of a mental disorder for different DT thresholds and explore the diagnostic properties of the DT in detecting a mental disorder.
View Article and Find Full Text PDFPurpose: The assessment of patient satisfaction during treatment is essential to provide patient-centered high-quality cancer care. Nevertheless, no German instrument assesses patient satisfaction with comprehensive cancer care, which not only includes oncological treatment, but also interpersonal quality of care as well as psychosocial support services. Based on the French REPERES-60, we developed the German Patient Satisfaction with Comprehensive Cancer Care (SCCC) questionnaire.
View Article and Find Full Text PDFOncogenic Ras proteins are implicated in the most common life-threatening cancers. Despite intense research over the past two decades, the progress towards small-molecule inhibitors has been limited. One reason for this failure is that Ras proteins interact with their effectors only via protein-protein interactions, which are notoriously difficult to address with small organic molecules.
View Article and Find Full Text PDFIntroduction: At the end of life, patients with advanced cancer and their informal caregivers may confront multiple existential concerns. Despite the strong potential to alleviate existential distress through psychosocial interventions, existential distress and its impact on healthcare outcomes have not yet been studied systematically. We aim to investigate the frequency, longitudinal trajectory and predictive impact of existential distress on end-of-life outcomes.
View Article and Find Full Text PDFAltered expression of mitochondrial DNA (mtDNA) occurs in ageing and a range of human pathologies (for example, inborn errors of metabolism, neurodegeneration and cancer). Here we describe first-in-class specific inhibitors of mitochondrial transcription (IMTs) that target the human mitochondrial RNA polymerase (POLRMT), which is essential for biogenesis of the oxidative phosphorylation (OXPHOS) system. The IMTs efficiently impair mtDNA transcription in a reconstituted recombinant system and cause a dose-dependent inhibition of mtDNA expression and OXPHOS in cell lines.
View Article and Find Full Text PDFObjective: In order to optimize psycho-oncological care, studies that quantify the extent of distress and identify certain risk groups are needed. Among patients with prostate cancer (PCa), findings on depression and anxiety are limited.
Methods: We analyzed data of PCa patients selected from a German multi-center study.
We aimed to analyze preferred and perceived levels of patients' involvement in treatment decision-making in a representative sample of cancer patients. We conducted a multicenter, epidemiological cross-sectional study with a stratified random sample based on the incidence of cancer diagnoses in Germany. Data were collected between January 2008 and December 2010.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
March 2020
The prenyl-protein chaperone PDEδ modulates the localization of lipidated proteins in the cell, but current knowledge about its biological function is limited. Small-molecule inhibitors that target the PDEδ prenyl-binding site have proven invaluable in the analysis of biological processes mediated by PDEδ, like KRas cellular trafficking. However, allosteric inhibitor release from PDEδ by the Arl2/3 GTPases limits their application.
View Article and Find Full Text PDFObjective: In order to optimize psycho-oncologic care for patients with severe stressor-related symptomatology, we aimed to provide (a) valid and generalizable prevalence rates of posttraumatic stress disorder (PTSD) in oncological patients and (b) the percentage of PTSD cases elicited by cancer-related events.
Methods: This multi-center study was based on a representative sample of patients across cancer types. A diagnostic interview (CIDI-O) was used to assess PTSD according to DSM-IV.
Despite the availability of hundreds of antibiotic drugs, infectious diseases continue to remain one of the most notorious health issues. In addition, the disparity between the spread of multidrug-resistant pathogens and the development of novel classes of antibiotics exemplify an important unmet medical need that can only be addressed by identifying novel targets. Herein we demonstrate, by the development of the first in vivo active DegS inhibitors based on a pyrazolo[1,5-a]-1,3,5-triazine scaffold, that the serine protease DegS and the cell envelope stress-response pathway σE represent a target for generating antibiotics with a novel mode of action.
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