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

The migration of indium-III-labeled specifically sensitized lymphocytes (SSLs) and unsensitized spleen lymphocytes (ULs) into sponge matrix allografts was studied in irradiated mice Intravenously injected SSLs were preferentially recruited to the graft bearing the sensitizing alloantigen High numbers of these SSLs, however, were attracted regardless of their immunological specificity to a third-party graft, when cells sensitized against the third-party antigen were given simultaneously When SSLs were injected locally into a specific and third-party graft, iv injected ULs also homed preferentially to the specific graft Prior treatment of SSLs with anti-theta serum and complement abrogated their cell recruiting capacity The percentage of injected lymphocytes recruited to the specific allograft during the first 36 hr increased with the number of SSLs injected The duration of augmented lymphocyte recruitment, however, was inversely related to the number of SSLs injected into the graft Furthermore, there is some evidence that SSLs which have been recruited to an allograft migrate to a second site of antigen challenge and initiate there a high lymphocyte recruitment These results suggest that increased lymphocyte recruitment to an allograft is initiated by an immunologically specific interaction between SSLs and alloantigen The cells, however, which are preferentially recruited to an allograft, comprise small unsensitized lymphocytes and SSLs regardless of their immunological specificity Lymphocytes with cell recruiting activity are T cells and appear to be very mobile in vivo The mechanism described might have an important amplifying effect on allograft rejection

Migration and cell recruiting activity of specifically sensitized lymphocytes in sponge matrix allografts.

Timing of surgical therapy in patients with synchronous colorectal liver metastases is becoming more complex. The standard therapy for most of the patients remains resection of the colorectal cancer first followed 6 weeks later by liver resection. Simultaneous colon and liver resection is safe and advisable in cases of minor liver resections and right-sided colon tumours. Major liver resections in combination with resection of the colorectal cancer carry the risk of increased postoperative morbidity and mortality. They should be considered for selected patients only. A pre-requisite is, in addition, special expertise of the operating surgeon in colorectal as well as in hepatobiliary surgery. If the synchronous liver metastases are near to essential anatomic structures, the liver resection should be performed before the bowel resection. The same holds if the metastases are technically resectable, but the future liver remnant seems to be too small. Using well known techniques, the future liver remnant should be increased and the liver metastases resected before treatment of the colonic primary tumour. The risk for local complications is very low when leaving the colorectal tumour in situ during treatment of liver metastases. When synchronous liver metastases are technically not resectable or carry a high risk of an R1 resection, patients should be treated first with systemic neo-adjuvant chemotherapy. If sufficient down-sizing of the metastases can be achieved, liver resection should be performed before bowel resection. A close cooperation between the oncologist and the hepatobiliary surgeon is most important, since the window for curative surgery is rather limited in these patients. In patients with resectable synchronous liver metastases, the advantage of a neoadjuvant chemotherapy has not been proven yet.

Timing of resection in patients with colorectal carcinoma and synchronous liver metastases

Kupffer cells, ED2+ macrophages of the liver, play an important role in liver damage and regeneration. It is proposed that Kupffer cells are stationary and regenerate after acute liver trauma by local

Kupffer cells infiltrate liver tissue early after ischemia-reperfusion and partial hepatectomy.

Lungenembolien in der fruhen postoperativen Phase sind immer noch mit hoher Morbiditat und Letalitat verbunden. Eine systemische Lyse ist in dieser Phase aufgrund der zu befurchtenden Blutungskomplikationen kontraindiziert, die operative Thromembolektomie ist mit einer hohen Letalitat verbunden. Wir berichten uber den Fall einer erfolgreichen lokalen Thrombolyse in Kombination mit Katheterfragmentation einer am 4. postoperativen Tag diagnostizierten massiven beidseitigen Lungenembolie nach pyloruserhaltender partieller Duodenopankreatektomie mit Lymphadenektomie bei distalem Choledochuskarzinom. Die Thrombolyse erfolgte in 3 Sitzungen durch Kombination der kathetergestutzten interventionellen Thrombusfragmentation mit lokaler rt-PA-Lysetherapie. Im Verlauf zeigten sich keine Blutungskomplikationen, ebenfalls kam es zu keiner Storung der Anastomosenheilung. Der Patient konnte am 23. postoperativen Tag nach Umstellung auf einen Vitamin-K-Antagonisten aus der stationaren Behandlung entlassen werden. Der vorliegende Fall zeigt die Moglichkeit der lokalen Lyse in Kombination mit interventionellen Methoden zur Therapie der massiven Lungenembolie in der fruhen postoperativen Phase als Alternative zu operativen Strategien auf.

Ulrich T. Hopt

Papers

Migration and cell recruiting activity of specifically sensitized lymphocytes in sponge matrix allografts.

Timing of resection in patients with colorectal carcinoma and synchronous liver metastases

Kupffer cells infiltrate liver tissue early after ischemia-reperfusion and partial hepatectomy.

Erfolgreiche lokale Katheterfragmentation und Thrombolyse bei akuter Lungenembolie in der frühen postoperativen Phase nach Pankreaskopfresektion

Hybrid laparoscopic versus open Pylorus-Preserving Pancreatoduodenectomy: retrospective matched case comparison in 80 patients