https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Tumors are cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like features (CSCs). Epithelial to mesenchymal transitions (EMT) are transdifferentiation programs that are required for tissue morphogenesis during embryonic development. The EMT process can be regulated by a diverse array of cytokines and growth factors, such as transforming growth factor (TGF)-β, whose activities are dysregulated during malignant tumor progression. Thus, EMT induction in cancer cells results in the acquisition of invasive and metastatic properties. Recent reports indicate that the emergence of CSCs occurs in part as a result of EMT, for example, through cues from tumor stromal components. Recent evidence now indicates that EMT of tumor cells not only causes increased metastasis, but also contributes to drug resistance. In this review, we will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs. We will also highlight recent studies implicating the function of TGF-β-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal. Finally we will discuss how EMT and CSCs may contribute to drug resistance, as well as therapeutic strategies to overcome this clinically.

/pdf/emt-cancer-stem-cells-and-drug-resistance-an-emerging-axis-3ztp4dopjd.pdf

EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Nach Organtransplantation sind die Empfanger ein Leben lang auf die Einnahme von immunsuppressiven Medikamenten angewiesen, um eine Abstosungsreaktion und somit einen Verlust des Transplantates zu verhindern. Der vorliegende Beitrag zeigt aktuelle Standards auf und diskutiert neue Erkenntnisse der letzten Jahre. Gerade der Bereich der Immunsuppression steht im standigen Wandel. Ziele der intensiven klinischen Forschungsbemuhungen sind nicht nur die Wahl der richtigen Kombination verschiedener Wirkstoffe, sondern ebenso die Findung eines adaquaten therapeutischen Wirkspiegels, um eine Uberimmunsuppression, welche mit einer erheblichen Steigerung des Auftretens von Nebenwirkungen einhergeht, zu vermeiden.

Immunsuppression bei Pankreasorgan-, Insel(zell)- und Nierentransplantation

Die 90° axial rotierte mesenteriko-antimesenteriale End-zu-End Anastomose – eine innovative Anastomosentechnik auf dem Prüfstand

There is a high medical need to identify new treatments for patients with pancreatic cancer, since in many cases only palliative treatment is possible. The standard 1st line chemotherapy in inoperable, locally advanced (stage II and III) and metastatic (stage IV) adenocarcinoma of the pancreas is Gemcitabine as a single agent with a median survival of about 6 month. In addition, Gemcitabine is indicated as adjuvant chemotherapy after surgery. Although the anti-metabolite 5-Flourouracil (5-FU) and the EGF-R inhibitor Tarceva (Erlotinib) have been approved for 2nd line treatment, new and more efficient drugs are urgently needed. In the present study, more than 60 samples of pancreatic carcinomas were transplanted subcutaneously (s.c.) into NMRI nude mice directly after tumor resection. In most cases, tumor material from chemonaive patients with defined histology and staging was used for implantation. Up to now, 17 tumor models were passaged in nude mice and characterized comprehensively. In general, the histology of the primary tumor was comparable to that of the established xenograft. Chemosensitivity in vivo was evaluated by treatment of tumor bearing nude mice with 5-FU (100 or 75mg/kg, q7dx3, i.p.), Gemcitabine (240mg/kg, q7dx3, i.v.) and Erlotinib (25 and 50mg/kg, qdx21, p.o.). In general, tumor growth was not inhibited with best T/C values >50% highlighting the general chemoresistance of pancreatic cancer. Only for two models (PAXF 1872 and PAXF 1998), a high sensitivity towards Gemcitabine was evident with best T/C values of 8% and 3.8%, respectively. There was no correlation to the transcriptional levels of proteins involved in transportation and metabolism of Gemcitabine. Concerning Erlotinib, best T/C values were ranging from 89.6% (PAXF 1876) to 38.5% (PAXF 1982) with no correlation to EGFR expression status. A more broad chemosensitivity profile was established with the ex-vivo clonogenic assay. Interestingly, several tumors responded strongly to treatment with Rapamycin (IC50 ≤ 10nM). Based on this data, in vivo treatment experiments with RAD001 (Everolimus) were done and data are presented. Mutational analysis of p53 (exons 4 to 10) revealed only 4 out of 13 models as p53 wild-type. Nevertheless, the p53 pathway is dysregulated in all tumor models and for selected tumors, an aneuploid cell population was identified by ex vivo cell cycle analysis. In summary, a unique collection of patient-derived pancreatic xenograft models of high clinical relevance has been established. These models are available for translational research studies including in-vivo efficacy testing of new investigational drugs. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4168.

Ulrich T. Hopt

Papers

Immunsuppression bei Pankreasorgan-, Insel(zell)- und Nierentransplantation

Die 90° axial rotierte mesenteriko-antimesenteriale End-zu-End Anastomose – eine innovative Anastomosentechnik auf dem Prüfstand

Abstract 4168: Comprehensive characterisation of a newly established patient-derived pancreatic adenocarcinoma xenograft collection

Prophylactic splenectomy for asymptomatic splenic vein thrombosis during resection for chronic pancreatitis

Minimal invasive Gastrektomie mit D2 Lymphadenektomie (Videobeitrag)