Epidemiologische Auswertung der Krebsregisterdaten des Zervixkarzinoms

Das Zervixkarzinom ist weltweit eines der häufigsten Malignome der Frau. Weltweit variiert die Inzidenz des Zervixkarzinoms stark. In Deutschland ist diese Tumorentität in den letzten Jahrzehnten u.a. durch die Früherkennung zu einer weniger häufigen Tumorart geworden. Dieser Rückgang der Zervixkarzinome wird unter anderem durch die Früherkennungsuntersuchungen mittels zytologischem Abstrich seit 1971 erklärt, durch die Vor- und Frühstadien der Krebserkrankung rechtzeitig erkannt und erfolgreich behandelt werden können. Die Inzidenz höherer Tumorstadien (≥ FIGO-Stadium IIB) sowie die Zahl der Todesfälle sind seit 1980 zurückgegangen, stagnieren aber in den letzten 10 Jahren. Die Altersverteilung zeigt einen Gipfel zwischen 40 und 59 Jahren. Das mittlere Alter bei der Erstdiagnose des Zervixkarzinoms mit derzeit 55 Jahren hat sich in den letzten 25 Jahren um 15 Jahre verringert. Mit 80% ist das Plattenepithelkarzinom der häufigste histologische Subtyp. Allerdings steigt der Anteil des Adenokarzinoms von 10% auf ca. 20% in den letzten 25 Jahren. Ziel des Forschungsvorhabens:Darstellung der Entwicklung der Inzidenz (Inzidenz; altersstandardisierte Inzidenzraten, ASIR; average annual percentage changes, AAPC) des invasiven Zervixkarzinoms (ICD-10-GM C53) und relatives 5-Jahres-Überleben des invasiven Zervixkarzinoms (ICD-10-GM C53), Stratifizierungsmerkmale: Zeit (Datum der Diagnose), Alter bei Erstdiagnose (jüngere und ältere Frauen) Tumorstadium (TNM), histologischer Subtyp (Plattenepithelkarzinom, Adenokarzinom, Neuroendokrines-Ca.), histopathologisches Grading, ggfs. regional (Bundesland)

8 authors, including:

Mature dendritic cells (DC) are the most potent antigen-presenting cells within the entire immune system. Interference with the function of these cells therefore constitutes a very powerful mechanism for viruses to escape immune responses. Several members of the Herpesviridae family have provided examples of such escape strategies, including interference with antigen presentation and production of homologous cytokines. In this study we investigated the infection of mature DC with herpes simplex virus type 1 (HSV-1) and the way in which infection alters the phenotype and function of mature DC. Interestingly, the T-cell-stimulatory capacity of these DC was strongly impaired. Furthermore, we demonstrated that HSV-1 leads to the specific degradation of CD83, a cell surface molecule which is specifically upregulated during DC maturation. These data indicate that HSV-1 has developed yet another novel mechanism to escape immune responses. Herpes simplex virus type 1 (HSV-1) belongs to the Herpes-viridae, a large and diverse family of vertebrate pathogens including several human pathogens such as HSV-1 and HSV-2 (23). Members of the Herpesviridae characteristically have a large double-stranded DNA genome, and virions consist of an icosahedral nucleocapsid surrounded by a lipid layer envelope

Supplementary Material for: Rationale, Design, and Baseline Characteristics of ARTS-DN: A Randomized Study to Assess the Safety and Efficacy of Finerenone in Patients with Type 2 Diabetes Mellitus and a Clinical Diagnosis of Diabetic Nephropathy

Background/Aims: Finerenone decreases albuminuria in patients having heart failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic kidney disease. The MinerAlocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN; NCT01874431) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b study. ARTS-DN investigated whether the mineralocorticoid receptor antagonist finerenone reduces albuminuria without causing major alterations in serum potassium levels in patients with type 2 diabetes mellitus and a clinical diagnosis of DN who were receiving a renin-angiotensin-system (RAS) inhibitor. Methods: Patients were randomized to oral finerenone 1.25-20 mg or placebo once daily. The primary objectives were to assess the ratio of the urinary albumin-to-creatinine ratio at day 90 to that at baseline in patients receiving finerenone, and to compare it with that in the placebo group. Additional exploratory analyses included evaluating changes from baseline in serum potassium levels, efficacy and safety biomarkers, and health-related quality of life. Results: Of 1,501 patients screened, 821 (the sample population) received at least one dose of finerenone/placebo. Baseline characteristics included: male, 77.8%; white, 84.2%; very high albuminuria (formerly macroalbuminuria), 38.4%; high albuminuria (formerly microalbuminuria), 60.3%; median (range) estimated glomerular filtration rate, 66.3 (24.5-130.7) ml/min/1.73 m2; and systolic blood pressure (mean ± standard deviation), 138.1 ± 14.4 mm Hg. There was a history of cardiovascular disease in 39.6%, diabetic neuropathy in 20.0%, and diabetic retinopathy in 19.9% of patients. Conclusion: ARTS-DN is the first phase 2b trial of finerenone in combination with a RAS inhibitor in patients with type 2 diabetes mellitus and a clinical diagnosis of DN

Tristetraprolin-driven regulatory circuit controls quality and timing of mRNA decay in inflammation

For a successful yet controlled immune response, cells need to specifically destabilize inflammatory mRNAs but prevent premature removal of those still used. The regulatory circuits controlling quality and timing in the global inflammatory mRNA decay are not understood. Here, we show that the mRNA-destabilizing function of the AU-rich element-binding protein tristetraprolin (TTP) is inversely regulated by the p38 MAPK activity profile such that after inflammatory stimulus the TTP-dependent decay is initially limited to few mRNAs. With time, the TTP-dependent decay gradually spreads resulting in cumulative elimination of one third of inflammation-induced unstable mRNAs in macrophages in vitro. We confirmed this sequential decay model in vivo since LPS-treated mice with myeloid TTP ablation exhibited similar cytokine dysregulation profile as macrophages. The mice were hypersensitive to LPS but otherwise healthy with no signs of hyperinflammation seen in conventional TTP knockout mice demonstrating the requirement for myeloid TTP in re-installment but not maintenance of immune homeostasis. These findings reveal a TTP- and p38 MAPK-dominated regulatory mechanism that is vital for balancing acute inflammation by a temporally and qualitatively controlled mRNA decay