University of Marburg

About: University of Marburg is a education organization based out in Marburg, Germany. It is known for research contribution in the topics: Population & Virus. The organization has 23195 authors who have published 42907 publications receiving 1506069 citations. The organization is also known as: Philipps University of Marburg & Philipps-Universität.

The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers

Abstract: The use of agonistic analogues of luteinizing hormone releasing hormone (LHRH) is an established therapy for hormone-dependent metastatic pre-menopausal breast cancer. Their mechanism of action in this disease is the suppression of ovarian oestrogen production (medical castration). In the treatment of post-menopausal metastatic breast cancer, LHRH agonists also have some effect, although minor, probably through a suppression of ovarian androgen production. Convincing evidence has been accumulated that LHRH analogues can directly inhibit the proliferation of breast cancer cells in vitro. The clinical impact of these findings, however, is still controversial. Experimental data and several pilot clinical trials suggest that in epithelial ovarian cancer and sex-cord-stromal tumours of the ovary, LHRH agonists might have antitumour activity through the suppression of gonadotrophin secretion (selective medical hypophysectomy). Phase III clinical trials, evaluating this hypothesis, are in progress. Direct antiproliferative effects of LHRH analogues on epithelial ovarian cancer cells have been demonstrated in vitro. In endometrial cancer, experimental and early clinical results support the concept of a direct antiproliferative activity of LHRH analogues. Recently, potent antagonistic analogues of LHRH, devoid of relevant side-effects have become available for clinical testing. These new antagonists might be superior to agonistic LHRH analogues with respect to the rapidity and efficacy of selective medical hypophysectomy and medical castration. Modern LHRH antagonists might also permit a better exploitation of direct antitumour effects. A further therapeutic improvement in gynaecological oncology might result from a combination of LHRH agonists or antagonists with other peptide hormone analogues such as agonists of somatostatin or antagonists of bombesin/gastrin releasing peptide which have antitumour activity. Since 50% of breast cancers and 80% of epithelial ovarian cancers and endometrial cancers have high affinity binding sites for LHRH, cytotoxic LHRH analogues might provide a targeted chemotherapy, which would be more efficacious and less toxic than conventional regimens.

Exacerbations of COPD

Abstract: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. While COPD is a mainly chronic disease, a substantial number of patients suffer from exacerbations. Severe exacerbations are related to a significantly worse survival outcome. This review summarises the current knowledge on the different aspects of COPD exacerbations. The impact of risk factors and triggers such as smoking, severe airflow limitation, bronchiectasis, bacterial and viral infections and comorbidities is discussed. More severe exacerbations should be treated with β-agonists and anticholinergics as well as systemic corticosteroids. Antibiotic therapy should only be given to patients with presumed bacterial infection. Noninvasive ventilation is indicated in patients with respiratory failure. Smoking cessation is key to prevent further COPD exacerbations. Other aspects include choice of pharmacotherapy, including bronchodilators, inhaled corticosteroids, phosphodiesterase-4 inhibitors, long-term antibiotics and mucolytics. Better education and self-management as well as increased physical activity are important. Influenza and pneumococcal vaccination is recommended. Treatment of hypoxaemia and hypercapnia reduce the rate of COPD exacerbations, while most interventional bronchoscopic therapies increase exacerbation risk within the first months after the procedure.

Origin and consequences of the compensation (Meyer-Neldel) law.

Abstract: We have recently demonstrated that the Meyer-Neldel (MN) rule (compensation law) may be understood as arising naturally when the activation energy for a process is significantly larger than both the typical excitations available and kT. This conclusion was supported by the results of two microscopic models, related to special cases. In the present paper we present arguments, based on general results from statistical physics, which lead to the same conclusion. We show that this simple explanation also leads to the solution of a number of puzzles which have been associated with Meyer-Neldel behavior. We show that phenomena in groups of similar materials yield similar MN slopes. Finally, we show that the values of the slope for semiconductors with gaps in the 1--2-eV range are consistent with the suggestion that optical phonons are the source of the excitation energy in such processes.

MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity.

Abstract: Instability of the nuclear genome is a hallmark of cancer and aging. MMS19 protein has been linked to maintenance of genomic integrity, but the molecular basis of this connection is unknown. Here, we identify MMS19 as a member of the cytosolic iron-sulfur protein assembly (CIA) machinery. MMS19 functions as part of the CIA targeting complex that specifically interacts with and facilitates iron-sulfur cluster insertion into apoproteins involved in methionine biosynthesis, DNA replication, DNA repair, and telomere maintenance. MMS19 thus serves as an adapter between early-acting CIA components and a subset of cellular iron-sulfur proteins. The function of MMS19 in the maturation of crucial components of DNA metabolism may explain the sensitivity of MMS19 mutants to DNA damage and the presence of extended telomeres.