Die Transformation des ostdeutschen Schiffbaus: Restruktierung, Privatisierung, Arbeitsmarktfolgen 1990 - 92

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel C 191602 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Arbeits- und Lebenssituation in laendlichen Raeumen des Landes Brandenburg

IAB-96-100-32 AX 684 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Endothelin-1 induced Mxi-2/Ago2 complex formation resulting in 5P536 downregulation promoting breast cancer development

Increased endothelin-1 decreases PKC alpha (PKCα), resulting in high miRNA 15a levels in kidney tumors. Breast cancer cells treated with ET-1, β-estrogen, Tamoxifen, Tamoxifen + β-estrogen and Tamoxifen + ET-1 were analysed regarding miRNA 15a expression. Significantly increased miRNA 15a levels were found after ET-1, becoming further increased in Tamoxifen + ET-1 treated cells. Our group already showed that miRNA 15a induces MAPK p38 splicing resulting in a truncated product called Mxi-2, whose function has yet to be defined in tumors. We described for the first time in ET-1 induced tumor cells that Mxi-2 builds a complex with Ago2, a miRNA binding protein, which is important for the localization of miRNAs to the 3′UTR of target genes. Furthermore, we show that Mxi-2/Ago2 is important for the interaction with the miRNA 1285 which binds to the 3′end of the tumor suppressor gene p53, being responsible for the downregulation of p53. Tissue arrays from breast cancer patients were performed, analysing Mxi-2, p53 and PKCα. Since the Mxi-2 levels increase in Tamoxifen + ET-1 treated cells, we claim that increasing ET-1 levels in Tamoxifen treated breast cancer patients are responsible for decreasing p53 levels. In summary, ET-1 decreases nuclear PKCα levels, while increasing the amount of miRNA 15a. This causes high levels of Mxi-2, necessary for complex formation with Ago2. The newly identified Mxi-2/Ago2 complex interacting with miRNA 1285 leads to increased 3′UTR p53 interaction, resulting in decreased p53 levels and subsequent tumor progression. This newly identified mechanism is a possible explanation for the development of ET-1 induced tumors

First reported case of a collision tumor composed of pancreatic adenocarcinoma and retroperitoneal liposarcoma: a case report

BackgroundCollision tumors are rare cases with two different tumor entities growing synchronously. While adenocarcinoma of the pancreas is the most common pancreatic tumor with an incidence of 10 per 100.000, retroperitoneal liposarcoma remains very rare. This is the first report of a collision tumor between these two tumor entities.Case presentationDemographic details:The tumor was diagnosed in a 64 male Caucasian patient. Besides atrial fibrillation, arterial hypertension and a hypothyroidism there is no relevant medical history especially no history of cancer.Clinical details:During a routine check-up an unclassified tumor of the pancreatic tail was diagnosed. The lab showed no pathologies. Tumor markers were negative for carbohydrate antigen 19-9 and 72-4 (CA 19-9, CA 72-4) and carcinoembryonic antigen (CEA). Alpha-fetoprotein (AFP) and neuron specific enolase (NSE) were both elevated (AFP 97kU/l, (<5,8kU/l) and NSE 30,0g/l (16,4g/l)). A computed tomography-guided core needle biopsy was performed which revealed a low-grade liposarcoma (G1). A CT scan showed no metastases. A surgical resection was recommended by the interdisciplinary tumor board.Interventions: A systematic left sided retroperitoneal compartment resection including en-bloc-left sided pancreatectomy, splenectomy, nephrectomy, hemicolectomy, adrenalectomy, partial gastrectomy and partial resection of the diaphragm was performed. Pathology revealed a collision tumor consisting of pancreatic adenocarcinoma that was classified pT3, pN2 (11/33 ece+) L1V0 Pn0, R0; G2 [UICC Stage III] and a liposarcoma pT2, pN0 (0/33) L0V0 Pn0, G1 [UICC Stage Ib].The postoperative tumor board recommended an adjuvant chemotherapy with gemcitabine and capecitabine for the locally advanced pancreatic adenocarcinoma.Outcome: At the latest follow-up (1year after surgery) the patient was in good clinical condition and without evidence of tumor recurrence.ConclusionCollision tumors are rare and difficult to diagnose. This is the first description of a collision tumor composed of pancreatic adenocarcinoma and retroperitoneal liposarcoma.The reported case demonstrates that inconsistent diagnostic results (e.g. imaging and pathology) should raise suspicion concerning the diagnosis. Awareness of these rare cases might protect us from underdiagnosing patients and therefore leading to better patient care.There is evolving evidence that will lead to more personalized treatment options for somatic BRCA mutated pancreatic cancer

ET-1 Induced Downregulation of MRP2 via miRNA 133a-A Marker for Tubular Nephrotoxicity?

Background: Multiple drug resistance (MDR), known from treating malignant tumors with chemotherapy, increases the efflux of reabsorbed reagents in tumor cells. This mechanism has been reported in the renal proximal tubule and may prevent therapeutic tubular protection in proteinuria. Since endothelin-1 (ET-1), a major component in the urine of proteinuric patients, stimulates proximal tubules, its influence on MDR was analyzed with emphasis on the multidrug resistance-associated protein 2 (MRP2), a prominent transporter in the human proximal tubule and microRNA (miRNA) 133a. Methods: ET-1 stimulated, cultured human renal proximal tubule cells (RPTECs), were analyzed via Western blot for the expression of MRP2 and via qRT-PCR for miRNA 133a. For direct interaction between the miRNA 133a and the 3'UTR of MRP2, an immunoprecipitation was performed using FITC-labelled miRNA 133a as capture, followed by MRP2 PCR analysis and Sanger sequencing. Murine Adriamycin nephropathic model and human proteinuric samples showed high levels of miRNA 133a but low levels of MRP2. The increasing miRNA 133a levels were detectable in urine samples of humans and animals. Results: ET-1 activates the miRNA 133a, which can bind to the 3'UTR of MRP2 and is therefore responsible for the detectable decrease of MRP2. Conclusion: This is the first report to analyze the correlation between ET-1-induced miRNA 133a overexpression in proteinuria resulting in MRP2 downregulation, which is a contributing factor for renal cytotoxicity. The detection of the miRNA 133a in urine samples can be possibly used as a monitor for cytotoxicity. (C) 2015 S. Karger AG, Base

Young male patient with unusual space-occupying lesion of the lower eyelid

Background. A space-occupying lesion of the eyelid in young adults is often a sign of an inflammation, a trauma or a benign neoplasm. The aim of this case report is to demonstrate a rare basal cell carcinoma, which presumably already arose in adolescence without further high-risk factors. Methods. A 28-year-old male patient presented for a second opinion on a painless swelling of the right lower eyelid. According to the patient's history the swelling had been present since the age of 16 years and originally resembled a molluscum contagiosum. An ophthalmologist in private practice made the diagnosis of a suspected trichoepithelioma. The extended patient history revealed a blood coagulation disorder. The clinical ophthalmological examination revealed a nodular space-occupying lesion with a border wall and telangiectasia. The further ophthalmological examination was bilaterally inconspicuous. Due to the suspicion of a malignant process, an operation was promptly carried out using local anesthesia with complete tumor excision and pedicled flap plasty as well as a histopathological investigation to confirm the diagnosis. Results. The histopathological investigation revealed underlying infiltrates of a basaloid tumor with bale-shaped trabecular growth, sometimes with peripheral palisading of the cells. The cells were predominantly monomorphic with isolated pleomorphic nuclei and sometimes enclosed mitoses. Immunohistochemically the cells were strongly positive for BerEP4 and negative for epithelial membrane antigen (EMA). The diagnosis of a nodular basal cell carcinoma of the right lower eyelid was made. All incision margins were free of tumor cells (R0 resection). In the dermatological screening no further manifestations were detected. Conclusion. Despite the occurrence of a space-occupying lesion of the eyelid in a young adult patient and also with no further risk factors, in addition to an inflammatory event and a benign tumor, a malignant disease, such as a basal cell carcinoma should also be taken into consideration. A tissue biopsy or complete excision with subsequent histological examination including an immunohistochemical analysis are essential for differentiation from other tumor entities

Die Wirksamkeit arbeitsmarktpolitischer Instrumente zur Reintegration von Arbeitslosen in den ersten Arbeitsmarkt im Bundesland Mecklenburg-Vorpommern

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel C 188844 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Copy-number variation and protein expression of DOT1L in pancreatic adenocarcinoma as a potential drug target

Adenocarcinoma of the pancreas has a poor prognosis. At present, no relevant personalized targets have been identified. Sequencing studies have implicated gene alterations of disruptor of telomeric silencing 1 like histone lysine methyltransferase (DOT1L) in pancreatic adenocarcinoma. DOT1L is part of the histone modification system and catalyzes methylation of H3K79, which is crucial in cell signaling and DNA damage repair. DOT1L is considered to be a target of therapy in mixed lineage leukemia gene-deficient leukemia cases and a potential target in breast carcinoma. The frequencies and importance of DOT1L copy-number variations and their specific correlation with protein expression in adenocarcinoma of the pancreas have yet to be investigated. In the present study, tissue microarrays of 230 resected pancreatic adenocarcinoma cases were constructed. The tumor tissue was analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry. In total, 10/225 carcinoma cases (4.4%) analyzed by immunohistochemistry demonstrated intense nuclear protein expression of DOT1L and in 9/224 tumors analyzed using FISH (4.0%), copy-number variations (CNV) were detectable. No DOT1L amplification was detected in the carcinoma cohort. To the best of our knowledge, the present study describes for the first time the frequency of CNV of DOT1L using the gold standard fluorescence in situ hybridization (FISH) and their specific correlation to the protein expression in adenocarcinomas of the pancreas. Although the positive cases by immunohistochemistry and copy-number variations by FISH were not congruent with each other, the data suggest a potential role for DOT1L in a small subset of pancreatic cancer cases. The significance of the two analysis methods concerning their druggability in pancreatic adenocarcinoma requires further studies