A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis.

Purpose: Cisplatin resistance is the major obstacle in the clinical treatment of ovarian cancer patients. Molecular mechanisms of cisplatin resistance are multifaceted. Gold(I)-compounds, i.

Characterization of the nuclear import of the human CHD4-NuRD complex.

Chromatin remodeling enzymes form large multiprotein complexes that play central roles in regulating access to the genome. Here, we characterize the nuclear import of the human CHD4 protein. We show that CHD4 enters the nucleus by means of several importin-α proteins (1, 5, 6 and 7), but independently of importin β1.

Generation of colon cancer-derived tumor-infiltrating T cells (TILs) for adoptive cell therapy.

Adoptive cell therapy (ACT) using specific immune cells and stem cells has emerged as a promising treatment option that could complement traditional cancer therapies in the future. In particular, tumor-infiltrating lymphocytes (TILs) have been shown to be effective against solid tumors in various clinical trials. Despite the enormous disease burden and large number of premature deaths caused by colorectal cancer (CRC), studies on TILs isolated from tumor tissue of patients with CRC are still rare.

Tumor-infiltrating lymphocytes mediate complete and durable remission in a patient with NY-ESO-1 expressing prostate cancer.

Adoptive transfer of autologous tumor-specific lymphocytes represents a viable treatment method for patients with advanced malignancies. Here, we report a patient's case with metastatic hormone-refractory New York esophageal squamous cell carcinoma 1 (NY-ESO-1) expressing prostate cancer treated with in vitro expanded tumor-infiltrating lymphocytes (TILs) in conjunction with IL-2 and immune-checkpoint blockade. Complete and durable tumor remission was observed after three TIL infusions consisting of 1.

Metallodrug Profiling against SARS-CoV-2 Target Proteins Identifies Highly Potent Inhibitors of the S/ACE2 interaction and the Papain-like Protease PL.

The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has called for an urgent need for dedicated antiviral therapeutics. Metal complexes are commonly underrepresented in compound libraries that are used for screening in drug discovery campaigns, however, there is growing evidence for their role in medicinal chemistry. Based on previous results, we have selected more than 100 structurally diverse metal complexes for profiling as inhibitors of two relevant SARS-CoV-2 replication mechanisms, namely the interaction of the spike (S) protein with the ACE2 receptor and the papain-like protease PL .

[(C C)Au(N N)] Complexes as a New Family of Anticancer Candidates: Synthesis, Characterization and Exploration of the Antiproliferative Properties.

A library of eleven cationic gold(III) complexes of the general formula [(C C)Au(N N)] when C C is either biphenyl or 4,4'-ditertbutyldiphenyl and N N is a bipyridine, phenanthroline or dipyridylamine derivative have been synthesized and characterized. Contrasting effects on the viability of the triple negative breast cancer cells MDA-MB-231 was observed from a preliminary screening. The antiproliferative activity of the seven most active complexes were further assayed on a larger panel of human cancer cells as well as on non-cancerous cells for comparison.

Sequence and functional differences in the ATPase domains of CHD3 and SNF2H promise potential for selective regulability and drugability.

Chromatin remodelers use the energy of ATP hydrolysis to regulate chromatin dynamics. Their impact for development and disease requires strict enzymatic control. Here, we address the differential regulability of the ATPase domain of hSNF2H and hCHD3, exhibiting similar substrate affinities and enzymatic activities.

Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike-ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics*.

Gold complexes have a long tradition in medicine and for many examples antirheumatic, anticancer or anti-infective effects have been confirmed. Herein, we evaluated the lead compound Auranofin and five selected gold organometallics as inhibitors of two relevant drug targets of severe acute respiratory syndrome coronaviruses (SARS-CoV). The gold metallodrugs were effective inhibitors of the interaction of the SARS-CoV-2 spike protein with the angiotensin converting enzyme 2 (ACE2) host receptor and might thus interfere with the viral entry process.

A Multitarget Gold(I) Complex Induces Cytotoxicity Related to Aneuploidy in HCT-116 Colorectal Carcinoma Cells.

A novel alkynyl phosphane gold(I) complex (trimethylphosphane)(3-(1,3-dimethylxanthine-7-yl)prop-1-yn-1-yl)gold(I) 1 displayed mutiple biological activites including selective proliferation inhibitory, anti-metastatic, and anti-angiogenic effects. The complex also induced effects related to aneuploidy in HCT-116 colon carcinoma cells, which might be mainly ascribed to the dysfunction of mitochondrial bioenergetics and downregulation of glycolysis. Induction of aneuploidy beyond a critical level can provide an effective strategy to target cancer, in particular colorectal tumours with a low tolerance of aneuploidy, and could be of relevance for 1 and other metallodrugs.

Procedural Success Rates and Mortality in Elderly Patients With Percutaneous Coronary Intervention for Cardiogenic Shock.

Objectives: The aim of this study was to determine the impact of age on procedural and clinical outcomes in patients with cardiogenic shock (CS).

Background: The use of early revascularization therapy with percutaneous coronary intervention (PCI) has been shown to improve outcome in patients with acute myocardial infarction (AMI) complicated by CS.

Methods: Data from consecutive patients with AMI and CS treated with PCI enrolled into the prospective ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte) PCI registry were centrally collected and analyzed.

Mass Production of Highly Active NK Cells for Cancer Immunotherapy in a GMP Conform Perfusion Bioreactor.

NK cells have emerged as promising candidates for cancer immunotherapy, especially due to their ability to fight circulating tumor cells thereby preventing metastases formation. Hence several studies have been performed to generate and expand highly cytotoxic NK cells , e.g.

Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI) : Joint Consensus Document of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V. (ALKK) and cooperating Cardiac Surgery Departments.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement).

Elucidation of the functional roles of the Q and I motifs in the human chromatin-remodeling enzyme BRG1.

The Snf2 proteins, comprising 53 different enzymes in humans, belong to the SF2 family. Many Snf2 enzymes possess chromatin-remodeling activity, requiring a functional ATPase domain consisting of conserved motifs named Q and I-VII. These motifs form two recA-like domains, creating an ATP-binding pocket.

Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR): consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC.

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible aetiology. Currently, there are no randomised, controlled studies on eCPR. Thus, prospective validated predictors of benefit and outcome are lacking.

[Certification in cardiology : Contra: The concept should be improved].

Increasing complexity and new highly differentiated therapeutic procedures in cardiology result in a need for additional training beyond cardiology board certification. The German Cardiac Society therefore developed a variety of certifications of educational curricula and definition of specialized centers. Standardization and structuring in education and patient treatment, as defined by certifications may be helpful; however, introduction of certification can have serious consequences for hospital structure, the side effects of which may impair quality of treatment for individual patients.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC].

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC].

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking.

Tumour-associated missense mutations in the dMi-2 ATPase alters nucleosome remodelling properties in a mutation-specific manner.

ATP-dependent chromatin remodellers are mutated in more than 20% of human cancers. The consequences of these mutations on enzyme function are poorly understood. Here, we characterise the effects of CHD4 mutations identified in endometrial carcinoma on the remodelling properties of dMi-2, the highly conserved Drosophila homologue of CHD4.

[Hemorrhage under direct oral anticoagulants : Occurrence and treatment in intensive care patients].

The use of anticoagulants is associated with an increased risk of bleeding and nevertheless bleeding complications can be lifethreatening. The focus is on bleeding under direct oral anticoagulants (DOAC) because antidotes and specific measures are lacking for some DOACs. Furthermore, routinely carried out clotting tests cannot be used to determine the degree of anticoagulation under DOACs.

CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality.

CHD3 and CHD4 (Chromodomain Helicase DNA binding protein), two highly similar representatives of the Mi-2 subfamily of SF2 helicases, are coexpressed in many cell lines and tissues and have been reported to act as the motor subunit of the NuRD complex (nucleosome remodeling and deacetylase activities). Besides CHD proteins, NuRD contains several repressors like HDAC1/2, MTA2/3 and MBD2/3, arguing for a role as a transcriptional repressor. However, the subunit composition varies among cell- and tissue types and physiological conditions.

Sex Differences in Percutaneous Coronary Intervention-Insights From the Coronary Angiography and PCI Registry of the German Society of Cardiology.

Background: Several studies have suggested sex-related differences in diagnostic and invasive therapeutic coronary procedures.

Methods And Results: Data from consecutive patients who were enrolled in the Coronary Angiography and PCI Registry of the German Society of Cardiology were analyzed. We aimed to compare sex-related differences in in-hospital outcomes of patients undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease, non-ST elevation acute coronary syndromes, ST elevation myocardial infarction, and cardiogenic shock.

[Management of NOAK administration during invasive or surgical interventions : When and how to pause and when to restart?].

Many patients under oral anticoagulation therapy need percutaneous or surgical interventions/operations. For vitamin K antagonists (VKA), there are recommendations regarding preoperative or postoperative administration. Management of the new oral anticoagulants (NOAC) was supposed to be easier - but some aspects must be considered.

Effect of GPIIb/IIIa inhibition with eptifibatide or tirofiban on the expression of cellular adhesion molecules on monocytes.

Aim: The aim of the present study was to investigate the effect of GPIIb/IIIa inhibition with eptifibatide and tirofiban on the expression of cellular adhesion molecules on monocytes at different temperatures.

Materials And Methods: Circulation of blood from six volunteers was performed in an extracorporal circulation model at 36°C and 18°C for 30 min. The blood of each donor was prepared either with addition of eptifibatide or tirofiban, or was left untreated as control.

Expression of CD11b (MAC-1) and CD162 (PSGL-1) on monocytes is decreased under conditions of deep hypothermic circulatory arrest.

Deep hypothermic circulatory arrest (DHCA) is a common technique used to protect vital organs during surgical interventions on the thoracic aorta or during surgery for complex congenital heart disease. Activated leukocytes are key mediators of inflammatory responses during ischemia. Intercellular crosstalk between leukocytes, platelets and endothelial cells is mediated by cell adhesion molecules.