The paper discusses the decisions on the reform of the CAP from June 2003. The decisions focus on the decoupling of the direct payments to farmers from production. This will reduce production ...incentives and thereby improve the allocation of resources. However, payments to farmers will hardly be reduced in total but rather partly be redirected towards rural development policies, environmental policies and animal health measures. Since a consistent rationale for permanent payments to farmers is missing, payments should be stopped completely. The increase of financial support for rural development is the wrong way, since most measures, again, are interventions in favour of farmers. The latest WTO-Agreement on the continuation of the Doha-Round will put additional reform pressure on the EU. Reprinted by permission of Lucius and Lucius Verlagsgesellschaft
This paper discusses the decisions on the reform of the CAP from June 2003. The decisions focus on the decoupling of the direct payments to farmers from production. This will reduce production ...incentives and thereby improve the allocation of resources. However, payments to farmers will hardly be reduced in total but rather partly be redirected towards rural development policies, environmental policies and animal health measures. Since a consistent rationale for permanent payments to farmers is missing, payments should be stopped completely. The increase of financial support for rural development is the wrong way, since most measures, again, are interventions in favour of farmers. The latest WTO-Agreement on the continuation of the Doha-Round will put additional reform pressure on the EU.
Neuroendocrine tumors (NET) diagnosed during pregnancy are extremely rare. This case report describes diagnosis and treatment of a metastasized pancreas NET that became symptomatic in the second ...trimester.
A 33-year-old patient presented to the emergency department in the 19
week of pregnancy (WOP) with persistent diarrhea. Laboratory tests showed a pronounced hypercalcemia (3.53 mmol/l). Imaging revealed a mass in the pancreatic corpus/tail with extensive liver metastasis. Histologically, a NET (G2, SSTR-positive) with paraneoplastic parathormone-related-peptide secretion was found to be the cause of hypercalcemia. Under a treatment with octreotide, calcium values normalized and diarrhea stopped. After delivery of a healthy child (32.WOP via cesarean section) tumor progress was found. The pancreatic mass was resected completely, the liver metastases as far as possible. Postoperatively, in a CT scan, residual suspicious liver lesions could be found, and a palliative therapy with lanreotide was initiated. With this treatment, the patient has been asymptomatic for one year, and serum calcium remained normal. The child developed normally.
This unusual case shows that even in extensively metastasized symptomatic NETs during pregnancy, there may be sufficient diagnostic and therapeutic options that allow for a continuation of pregnancy in close interdisciplinary cooperation under careful risk-benefit assessment for mother and child.
This guideline was created for the first time and is intended as a practical aid for the diagnosis and therapy of neuroendocrine tumors. The aim is to represent the current state of science, promote ...the recognition of the disease and improve the treatment of patients. The guideline was created under the leadership of the DGVS and with participation of neighbouring scientific societies.
Patients with advanced stages of hepatocellular carcinoma (HCC) face a poor prognosis. Although encouraging clinical results have been obtained with multikinase inhibitor sorafenib, the development ...of improved therapeutic strategies for HCC remains an urgent goal. Aurora kinases are key regulators of the cell cycle, and their uncontrolled expression promotes aneuploidy and tumor development. In tissue microarray analyses, we detected aurora-A kinase expression in all of the examined 93 human HCC samples, whereas aurora-B kinase expression levels significantly correlated with the proliferation index of HCCs. In addition, two human HCC cell lines (Huh-7 and HepG2) were tested positive for aurora-A and -B and revealed Ser10 phosphorylation of histone H3, indicating an increased aurora-B kinase activity. The antiproliferative features of a novel aurora kinase inhibitor, PHA-739358, currently under investigation in phase 2 clinical trials for other solid tumors, were examined
in vitro
and
in vivo
. At concentrations exceeding 50nM, PHA-739358 completely suppressed tumor cell proliferation in cell culture experiments and strongly decreased histone H3 phosphorylation. Cell cycle inhibition and endoreduplication were observed at 50 nM, whereas higher concentrations led to a complete G
2
/M-phase arrest.
In vivo
, administration of PHA-739358 resulted in significant tumor growth inhibition at a well-tolerated dose. In combination with sorafenib, additive effects were observed. Remarkably, when tumors restarted to grow under sorafenib monotherapy, subsequent treatment with PHA-739358 induced tumor shrinkage by up to 81%. Thus, targeting aurora kinases with PHA-739358 is a promising therapeutic strategy administered alone or in combination with sorafenib for patients with advanced stages of HCC.
Background & Aims HMG-CoA-reductase-inhibitors (statins) have been shown to interfere with HCV replication in vitro. We investigated the mechanism, requirements and contribution of heme ...oxygenase-1(HO-1)-induction by statins to interference with HCV replication. Methods HO-1-induction by fluva-, simva-, rosuva-, atorva- or pravastatin was correlated to HCV replication, using non-infectious replicon systems as well as the infectious cell culture system. The mechanism of HO-1-induction by statins as well as its relevance for interference with HCV replication was investigated using transient or permanent knockdown cell lines. Polyacrylamide(PAA) gels of different density degrees or the Rho-kinase-inhibitor Hydroxyfasudil were used in order to mimic matrix conditions corresponding to normal versus fibrotic liver tissue. Results All statins used, except pravastatin, decreased HCV replication and induced HO-1 expression, as well as interferon response in vitro. HO-1-induction was mediated by reduction of Bach1 expression and induction of the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) cofactor Krueppel-like factor 2 (KLF2). Knockdown of KLF2 or HO-1 abrogated effects of statins on HCV replication. HO-1-induction and anti-viral effects of statins were more pronounced under cell culture conditions mimicking advanced stages of liver disease. Conclusions Statin-mediated effects on HCV replication seem to require HO-1-induction, which is more pronounced in a microenvironment resembling fibrotic liver tissue. This implicates that certain statins might be especially useful to support HCV therapy of patients at advanced stages of liver disease.
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