HCC: miRNA profiles of the tumor-surrounding tissue

The presence of hepatocellular carcinoma (HCC) is a significant complication of cirrhosis because it changes the prognosis and the treatment of the patients. By now, contrast-enhanced CT and MR scans are the most reliable tools for the diagnosis of HCC; however, in some cases, a biopsy of the tumor is necessary for the final diagnosis. The aim of the study was to develop a diagnostic tool using the microRNA (miRNA) profiles of the tissue surrounding the HCC tumor combined with clinical parameters in statistical models. At a transplantation setting, 32 patients with HCC and cirrhosis (B) were compared to 22 patients suffering from cirrhosis only (A). The diagnosis and exclusion of HCC was confirmed following the histopathological examination of the explanted liver. The HCC patients were significantly older than the patients with cirrhosis only (B: 60.6 and A: 49.9, p<0.001) and showed higher levels of ALT (A: 0.76μkat/l, B: 1.02μkat/, p=0.006) and AFP (A: 5.8ng/ml, B: 70.3ng/ml, p<0.001), whereas the bilirubin levels were higher in the cirrhosis only group (p=0.002). Using age (cut-off 50.23years) and AFP (cut-off 4.2ng/ml) thresholds, the levels of expression of miR-1285-3p and miR-943 differentiated between the patients with HCC and cirrhosis from those with cirrhosis only with an accuracy of 96.3%. This is the first report about the use of stepwise penalized logistic regression and decision tree analyses of miRNA expressions in the tumor-surrounding tissue combined with clinical parameters for the diagnosis of HCC.

Authors are Mehmet Haluk Morgul, Sergej Klunk, Zografia Anastasiadou, Ulrich Gauger, Corinna Dietel, Anja Reutzel-Selke, Philipp Felgendref, Hans-Michael Hau, Hans-Michael Tautenhahn, Rosa Bianca Schmuck, Nathanael Raschzok, Igor Maximillian Sauer, and Michael Bartels.
Exp Mol Pathol. 2016 Aug 20;101(2):165-171. doi: 10.1016/j.yexmp.2016.07.014. [Epub ahead of print]

Dr. rer. medic. Dipl.-Ing. Annekatrin Leder

Dr. Leder
Today, Anne Leder successfully defended her thesis "summa cum laude"!

Her work entitled "Entwicklung und Evaluierung eines mikroskaligen, Oligonukleotid-gekoppelten Eisenoxidpartikels zur Stimulation kultivierter humaner Hepatozyten" deals with particle-based delivery systems for therapeutic manipulation and tracking of transplanted cells by magnetic resonance imaging (MRI) based on multifunctional, silica based micron-sized iron oxide-containing particles (sMPIO) that combine fluorescence imaging, MRI tracking, and on-the-spot targeting of specific microRNAs on a particle surface for therapeutic manipulation by RNA interference.


Bile: miRNA Pattern post OLT

BIOMARKERS accepted our latest paper on "Bile: miRNA Pattern and Protein Based Biomarkers May Predict Acute Cellular Rejection after Liver Transplantation" for publication. Authors are Rosa Bianca Schmuck, Anja Reutzel-Selke, Nathanael Raschzok, Mehmet Haluk Morgul, Benjamin Struecker, Steffen Lippert, Cynthia de Carvalho Fischer, Moritz Schmelzle, Sabine Boas-Knoop, Marcus Bahra, Andreas Pascher, Johann Pratschke, and Igor M. Sauer.

Bile rather than blood depicts the local inflammation in the liver and may improve prediction and diagnosis of acute cellular rejection (ACR) after liver transplantation (OLT). Secretome and miRNAs were analyzed during the first two weeks and on clinical suspicion of ACR in the bile of 45 OLT recipients. Levels of CD44, CXCL9, miR-122, miR-133a, miR-148a and miR-194 were significantly higher in bile of patients who developed ACR within the first 6 months after OLT and during ACR. Analysis of secretome and miRNA in bile could further our understanding of the local inflammatory process during rejection.

Biomarkers. 2016 Aug 5:1-9. [Epub ahead of print]

LTx – microRNA signatures in peripheral blood ?

BIOMARKERS accepted our latest paper on „microRNA signatures in peripheral blood fail to detect acute cellular rejection after liver transplantation“ for publication. Authors are N. Raschzok, A. Reutzel-Selke, R. Schmuck, L. Tannus, M. Morgul, C. Dietel, A. Leder, B. Struecker, S. Lippert, H. Sallmon, M. Schmelzle, M. Bartels, S. Jonas, J. Pratschke, and I.M. Sauer.

We investigated whether microRNA signatures in whole blood samples are associated with acute cellular rejection (ACR) after liver transplantation. Blood samples were collected using Paxgene technology and analyzed by microarrays and qRT-PCR.
microRNA signatures failed to distinguish between 19 patients with ACR and 16 controls. Let-7b-5p and let-7c were up-regulated in a subgroup of patients with ACR during the 6th and 7th postoperative day but failed in an independent validation of 20 patients.
microRNA signatures in whole blood processed by Paxgene technology are not suited for detection of ACR after liver transplantation.

microRNAs in liver tissue engineering

Our paper "microRNAs in liver tissue engineering - New promises for failing organs" was accepted for publication in Advanced Drug Delivery Reviews (IF: 15.038). Authors are Nathanael Raschzok, Hannes Sallmon, Johann Pratschke and Igor M. Sauer.

miRNA-based technologies provide attractive tools for several liver tissue engineering approaches. Herein, we review the current state of miRNA applications in liver tissue engineering. Several miRNAs have been implicated in hepatic disease and proper hepatocyte function. However, the clinical translation of these findings into tissue engineering has just begun. miRNAs have been successfully used to induce proliferation of mature hepatocytes and improve the differentiation of hepatic precursor cells. Nonetheless, miRNA-based approaches beyond cell generation have not yet entered preclinical or clinical investigations. Moreover, miRNA-based concepts for the biliary tree have yet to be developed. Further research on miRNA based modifications, however, holds the promise of enabling significant improvements to liver tissue engineering approaches due to their ability to regulate and fine-tune all biological processes relevant to hepatic tissue engineering, such as proliferation, differentiation, growth, and cell function.

Presentations at DTG 2014

Nathanael Raschzok presented his poster „Protein biomarkers for diagnosis and prediction of acute cellular rejection after liver transplantation“, Benjamin Strücker his work entitled „Oszillierende Druckschwankung verbessern signifikant die Ratten- und Schweineleber Dezellularisierung“ and Rosa Schmuck her posters „Risk of postoperative infections after LTX rises with MELD score“ and „Protein biomarkers in bile as a diagnostic tool after liver transplantation“.

Sham Laparotomy and microRNA Expression in Rats

Ohne Titel
BMC Research Notes accepted our latest paper on „Independent Effects of Sham Laparotomy and Anesthesia on Hepatic microRNA Expression in Rats“ for publication.

Studies on liver regeneration following partial hepatectomy (PH) have identified several microRNAs (miRNAs) that show a regulated expression pattern. These studies involve major surgery to access the liver, which is known to have intrinsic effects on hepatic gene expression and may also affect miRNA screening results. We performed two-third PH or sham laparotomy (SL) in Wistar rats to investigate the effect of both procedures on miRNA expression in liver tissue and corresponding plasma samples by microarray and qRT-PCR analyses. As control groups, non-treated rats and rats undergoing anesthesia only were used. We found that 49 out of 323 miRNAs (15%) were significantly deregulated after PH in liver tissue 12 to 48 hours postoperatively (>20% change), while 45 miRNAs (14%) were deregulated following SL. Out of these miRNAs, 10 miRNAs were similarly deregulated after PH and SL, while one miRNA showed opposite regulation. In plasma, miRNA upregulation was observed for miR-133a and miR-133b following PH and SL, whereas miR-100 and miR-466c were similarly down-regulated following anesthesia and surgery. We show that miRNAs are indeed regulated by sham laparotomy and anesthesia in rats. These findings illustrate the critical need for finding appropriate control groups in experimental surgery.

Authors are W. Werner, H. Sallmon, A. Leder, S. Lippert, A. Reutzel-Selke, M.H. Morgül, S. Jonas, S. Dame, P. Neuhaus, J. Iacomini, S.G. Tullius, I.M. Sauer and N. Raschzok.

Profiles of microRNA after rat partial hepatectomy

The website of the  24th International Congress of The Transplantation Society is online! Please go to www.transplantation2012.org for more information.
Following the exceptionally successful meetings in Boston, Sydney and Vancouver, we would like to welcome you to a city which twenty years after reunification has evolved into one of the most important capitals of Europe. Once the capital of Prussia and leading cultural centre of the 1920s, today the new capital of Germany is characterized by its dazzling modernity and breathtaking architecture. Berlin is young, dynamic and bursting with joie de vivre. Few cities has been shaped to such an extent by history and undergone as much major transformation as Berlin. “Berlin is always in the process of becoming”, remarked historian Karl Scheffler. Even in the 21st century transplantation still is in a process  of becoming, too.  Therefore, the 24th International Congress of The Transplantation Society will promote the dialogue of experts from around the world. An attractive scientific program will be developed together with the Deutsche Transplantationsgesellschaft (DTG).
The 24th Congress is designed for physicians, surgeons, scientists and organ procurement personnel, who are interested in clinical and research aspects of solid organ, cell and tissue transplantation. The program is developed to encourage the exchange of new scientific and clinical information, and and support an interchange of opinions regarding care and management issues, as well as socioeconomic, ethical and regulatory issues relevant to transplantation.
In addition to the classical types of scientific sessions including plenary sessions, symposia, workshops and poster presentations, we will also offer new types of scientific sessions within the
Forum Futurum focusing on Tailored Pharmacotherapy, Imaging and Regenerative Medicine. All of this is designed to develop a highly interactive forum to discuss cutting-edge science in our field.
We therefore cordially invite you and your colleagues together with your friends and family to come to Berlin. Your active participation in the scientific program will be the fundament for a successful event in 2012.