Increased cytotoxicity of cisplatin in SK-MEL 28 melanoma cells upon down-regulation of melanoma inhibitor of apoptosis protein

BACKGROUND: Malignant melanoma is a highly metastatic cutaneous cancer and typically refractory to chemotherapy. Deregulated apoptosis has been identified as a major cause of cancer drug resistance, and upregulated expression of the inhibitor of apoptosis protein melanom, an inhibitor of apoptosis (ML-IAP) is frequent in melanoma. METHODS: Based on the conclusion that ML-IAP expression contributes to a malignant phenotype, we down-regulated the ML-IAP mRNA using sequence optimized antisense oligonucleotides. RESULTS: As measured by real-time PCR, oligonucleotides M706 and M711 inhibited ML-IAP mRNA expression by 47% and 52%, respectively in the highly metastatic and drug resistant SK-MEL28 cell line. Oligonucleotide M706, which was previously evaluated in G361 cells as the most efficient inhibitor of ML-IAP expression, was chosen to compare cell viability and drug sensitivity of these two melanoma cell lines with different p53 functionality. Protein expression was reduced by oligonucleotide M706 to 49% of the normal level and resulted in a dose-dependent specific reduction of cell viability with a maximum of 39% at 600 nM. Typical morphological changes showed that loss of viability was mainly due to cell death. In combination experiments, the use of oligonucleotide M706 resulted in a two-fold increase of cisplatin cytotoxicity at different concentrations of oligonucleotide and cisplatin (P<0.05). This is in line with our previous findings in G361 melanoma cell line, in which oligonucleotide M706 caused a 3-fold increase in cisplatin cytotoxicity. CONCLUSION: Our data suggest the use of ML-IAP antisense oligonucleotides to overcome drug resistance in metastatic melanoma, in spite of its p53 status.

Eine neue Chronologie des 3. Jahrtausends v. Chr. Ergebnisse der ARCANE Final Conference

Das Projekt ARCANE zeigt der Archäologie der Alten Welt einen neuen methodischen Weg auf und revolutionierte zugleich die Chronologie des 3. Jts. v. Chr. Sechs Jahre lang hatten mehrere Arbeitsgruppen unter Hinzuziehung einer streng materialbezogenen Methodik an der Erstellung von Regionalchronologien gearbeitet, aus denen anschließend durch interregionale Verknüpfungen eine neue Chronologie für ein Gebiet entstand, das von der Ägäis im Westen bis zum Iran im Osten sowie vom Kaukasus im Norden bis zum Sinai im Süden reichte.

Excavation at Bakr Awa 2010 and 2011

The site of Bakr Awa is situated in north-eastern Iraq, in the Plain of Shahrizor. Excavations were undertaken in 1960/61by the Iraqi Department of Antiquities and 2010/11 by the University of Heidelberg/Germany. Occupation layers from the beginning of the Early Bronze Age tothe Ottoman period were uncoveredin the lower city and on the citadel. Archaeological evidence from the secondmillennium B.C. shows the most intensive settlement activities and apparent prosperity at Bakr Awa. Several forms of pottery, small finds and architecture reflect dynamic processes of cultural and political transformation at this site located in an area of transition between northern and southern Mesopotamia and western Iran.

Procerenone: a Fatty Acid Triterpenoid from the Fruit Pericarp of Omphalocarpum procerum (Sapotaceae)

Phytochemical investigation of a dichloromethane-methanol (1:1) extract of the fruit pericarp of Omphalocarpum procerum which exhibited antiplasmodial activity during preliminary screening led to the isolation of the new fatty ester triterpenoid 3β-hexadecanoyloxy-28-hydroxyolean-12-en-11-one (1), together with five known compounds 2-6. The structure of the new compound as well as those of the known compounds was established by means of spectroscopic methods and by comparison with previously reported data. Compounds 1- 4 were evaluated in-vitro for their cytotoxicity against L6 cell lines and antiprotozoal activities against Plasmodium falciparum, Leishmania donovani, Trypanosoma brucei rhodesiense and Trypanosoma cruzi (species responsible for human malaria, visceral leishmaniasis, African trypanosomiasis and Chagas disease, respectively). The tested compounds showed weak to moderate antiprotozoal activity and, no significant effect was detected regarding their cytotoxic potency.

Genetic diversity of bovine Neospora caninum determined by microsatellite markers

Neospora caninum is one of the most significant parasitic organisms causing bovine abortion worldwide. Despite the economic impact of this infection, relatively little is known about the genetic diversity of this parasite. In this study, using Nc5 and ITS1 nested PCR, N. caninum has been detected in 12 brain samples of aborted fetuses from 298 seropositive dairy cattle collected from four different regions in Tehran, Iran. These specimen (Nc-Iran) were genotyped in multilocus using 9 different microsatellite markers previously described (MS4, MS5, MS6A, MS6B, MS7, MS8, MS10, MS12 and MS21). Microsatellite amplification was completely feasible in 2 samples, semi-completely in 8 samples, and failed in 2 samples. Within the two completely performed allelic profiles of Nc-Iran strains, unique multilocus profiles were obtained for both and novel allelic patterns were found in the MS8 and MS10 microsatellite markers. The Jaccard's similarity index showed significant difference between these two strains and from other standard isolates derived from GenBank such as Nc-Liv, Nc-SweB1, Nc-GER1, KBA1, and KBA2. All samples originating from the same area showed identical allelic numbers and a correlation between the number of repeats and geographic districts was observed.

Anke von Kügelgen on Contemporary Islamic Thought

Anke von Kügelgen joins Peter to discuss developments over the last century or so, including attitudes towards past thinkers like Avicenna, Averroes and Ibn Taymiyya. This interview is based on research conducted to write a forthcoming book on Philosophy in the Islamic world in the 19th and 20th centuries, to be co-edited by Prof von Kügelgen together Professor Ulrich Rudolph, and Michael Frey as redactor. It will be the fourth volume of a German Overview of the whole history of philosophy in the Islamic world (Grundriss der Geschichte der Philosophie in der islamischen Welt, published by Schwabe Verlag in Basel). Prof von Kügelgen would like to recognize the contribution of her collaborators: her main partner for the philosophy in the Arab speaking countries is Sarhan Dhouib, originally from Tunesia, now at the University of Kassel. For Muslim Southasia, she is working with Jan Peter Hartung from the SOAS in London, and for Iran, Reza Hajatpour, Katajun Amirpur and Roman Seidel who are all at present at German Universities. The part on Philosophy in the Ottoman Empire is written by Sait Özervarlı from the Yildiz Teknik Universitesi in Istanbul and for Turkey by Christoph Herzog from the University of Bamberg.