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BACKGROUND: Liposarcoma constitute about 13% of all soft tissue sarcoma and are associated with a high risk of metastases. As the preoperative differentiation between benign and malign lipomatous tumors is restricted to magnetic resonance imaging, computed tomography and biopsy, we performed a miRNA array to distinguish dedifferentiated liposarcoma patients from healthy controls and lipoma patients. METHODS: Blood samples of patients with dedifferentiated liposarcoma, healthy controls and lipoma patients were collected. Whole blood RNA was extracted and samples of patients with dedifferentiated liposarcoma ( n = 6) and of healthy donors ( n = 4) were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm the most differentially expressed miRNA; being further analyzed in an independent cohort of healthy controls as well as in lipoma patients. RESULTS: As shown by the microarray, two miRNAs (miR-3613-3p, miR-4668-5p) were shown to be significantly upregulated (fold change: > 2.5; p < 0.05) in patients with dedifferentiated liposarcoma ( n = 6) as compared to healthy controls ( n = 4). miR-3613-3p was further validated by qRT-PCR to be significantly upregulated in dedifferentiated liposarcoma patients compared to an independent cohort of healthy controls ( n = 3) and lipoma patients ( n = 5). CONCLUSION: We identified a specific whole blood miRNA (miR-3613-3p) that may serve to distinguish between dedifferentiated liposarcoma patients and healthy controls, thus potentially serving as a specific biomarker for dedifferentiated liposarcoma. [ABSTRACT FROM AUTHOR]

The cysteine protease cathepsin B (CTSB) is frequently overexpressed in human breast cancer and correlated with a poor prognosis. Genetic deficiency or pharmacological inhibition of CTSB attenuates tumor growth, invasion and metastasis in mouse models of human cancers. CTSB is expressed in both cancer cells and cells of the tumor stroma, in particular in tumor-associated macrophages (TAM). In order to evaluate the impact of tumor- or stromal cell-derived CTSB on Polyoma Middle T (PyMT)-induced breast cancer progression, we used in vivo and in vitro approaches to induce human CTSB overexpression in PyMT cancer cells or stromal cells alone or in combination. Orthotopic transplantation experiments revealed that CTSB overexpression in cancer cells rather than in the stroma affects PyMT tumor progression. In 3D cultures, primary PyMT tumor cells showed higher extracellular matrix proteolysis and enhanced collective cell invasion when CTSB was overexpressed and proteolytically active. Coculture of PyMT cells with bone marrow-derived macrophages induced a TAM-like macrophage phenotype in vitro, and the presence of such M2-polarized macrophages in 3D cultures enhanced sprouting of tumor spheroids. We employed a doxycycline (DOX)-inducible CTSB expression system to selectively overexpress human CTSB either in cancer cells or in macrophages in 3D cocultures. Tumor spheroid invasiveness was only enhanced when CTSB was overexpressed in cancer cells, whereas CTSB expression in macrophages alone did not further promote invasiveness of tumor spheroids. We conclude that CTSB overexpression in the PyMT mouse model promotes tumor progression not by a stromal effect, but by a direct, cancer cell-inherent mode of action: CTSB overexpression renders the PyMT cancers more invasive by increasing proteolytic extracellular matrix protein degradation fostering collective cell invasion into adjacent tissue. [ABSTRACT FROM AUTHOR]

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A letter to the editor is presented related to the B-cell chronic lymphocytic leukemia (B-CLL).

The role of peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) in the pathogenesis of colon cancer remains highly controversial. This study specifically silenced the PPAR-β expression in three colon cancer cell lines with different metastatic potentials. Although PPAR-β knockdown resulted in more malignant morphological changes, bigger colony sizes and lower carcinoembryonic antigen (CEA) secretion, and enhanced the cell–fibronectin adhesion, cell invasion and migration were unaffected. These effects were stronger in poorly metastatic cell lines compared with highly metastatic ones. Simultaneously, PPAR-β knockdown decreased the mRNAs encoding adipocyte differentiation-related protein and liver fatty acid binding protein, and increased the mRNA of ILK, whereas the mRNAs encoding integrin-β1 and angiopoietin-like 4 were unchanged. Using immunohistochemistry, we determined that the intensity of PPAR-β expression was stronger in rectal cancers with better differentiation than in those with poor differentiation, and was stronger in early-stage tumors than in advanced ones. Together, these findings consistently indicate that PPAR-β may facilitate differentiation and inhibit the cell–fibronectin adhesion of colon cancer, having a role as an inhibitor in the carcinogenesis and progression of colorectal cancer. Interestingly, PPAR-β seems to have a more important role in poorly metastatic cells than in highly metastatic ones. [ABSTRACT FROM AUTHOR]

Ligands specifically binding to leukemia cells may be used for drug targeting, resulting in more effective treatment with less side effects. Little is known about receptors specifically expressed on acute myeloid leukemia (AML) cells or ligands thereof. We selected random phage display peptide libraries on Kasumi-1 AML cells. A peptide with the sequence CPLDIDFYC was enriched. Phage displaying this peptide strongly bound to Kasumi-1 and SKNO-1 cells and binding could be inhibited by the cognate peptide. Both, Kasumi-1 and SKNO-1 cells carry the chromosomal translocation t(8;21), leading to aberrant expression of the fusion protein AML1/ETO. CPLDIDFYC also strongly and specifically bound primary AML1/ETO-positive AML blasts as well as U-937 cells with forced AML1/ETO expression, suggesting that the CPLDIDFYC receptor may be upregulated upon AML1/ETO expression. Gene expression profiling comparing a panel of CPLDIDFYC-binding and CPLDIDFYC-nonbinding cell lines identified a set of potential receptors for the CPLDIDFYC peptide. Further analysis suggested that α4β1 integrin (VLA-4) is the CPLDIDFYC receptor. Finally, we showed that the CPLDIDFYC-phage is internalized upon receptor binding, suggesting that the CPLDIDFYC-receptor–ligand interaction may be exploitable for targeting drugs or gene therapy vectors to leukemia cells carrying the suitable receptor.Leukemia (2007) 21, 411–420. doi:10.1038/sj.leu.2404548; published online 25 January 2007 [ABSTRACT FROM AUTHOR]

We employ a simple stochastic model for the Syracuse problem (also known as the 3x + 1 problem) to get estimates for the average behavior of the trajectories of the original deterministic dynamical system. The use of the model is supported not only by certain similarities between the governing rules in the systems, but also by a qualitative estimate of the rate of approximation. From the model, we derive explicit formulae for the asymptotic densities of some sets of interest for the original sequence. We also approximate the asymptotic distributions for the stopping times (times until absorption in the only known cycle {1, 2}) of the original system and give numerical illustrations of our results. [ABSTRACT FROM AUTHOR]

We present a unified and self-contained approach to Poisson approximation problems for independent Bernoulli summands with respect to several metrics by a general semigroup technique, expanding and completing earlier work on this subject by the first two authors [4], [5], [6]. [ABSTRACT FROM AUTHOR]

We present a simple joint strong approximation for the logarithms of record and inter-record times from an exchangeable sequence, including an exact estimation for the rate of convergence in terms of upper and lower class functions of a Wiener process. The approach chosen here allows for simple proofs of exact and asymptotic (joint) results for record and inter-record times, such as the Law of Large Numbers (LLN), Central Limit Theorem (CLT) and Law of the Iterated Logarithm (LIL), and others. [ABSTRACT FROM AUTHOR]

Motivated by a simple probabilistic model for the radioactive decay, we show that Serfling's [1978] approach to Poisson approximation using coupling techniques can in a natural way also be applied to Poisson process approximation. This provides at the same time uniform estimations for the deviation of a Markov-Bernoulli process from the approximating Poisson process with respect to the total variation distance. An application to quasirandom input queuing models is also given. [ABSTRACT FROM AUTHOR]

Asymptotic expansions for the mean and variance of the logarithms of record and inter-record times from i.i.d. random variables are given, refining rough estimations from Rényi's and Neuts' Central Limit Theorem for these record statistics. [ABSTRACT FROM AUTHOR]

The characterization of three YAC/P1 contigs from adjacent segments of the central region of mouse Chromosome (Chr) 11 is described. These contigs are based upon 63 YACs and 40 P1 recombinants. From these clones, 185 end sequences were obtained, of which 147 sequences could be converted into sequencetagged sites and mapped within the three contigs. Deletions were detected in 16 out of 63 YACs; 19 of 63 YACs were found to be chimeric. No such aberrations were found in P1 recombinants. A total of 22 public and 34 newly developed microsatellite markers were unambiguously localized to and ordered in the contigs. In the cryb1/Nf1 interval of the central contig, several new genes have been identified by exon trapping and precisely localized with respect to known STS markers. [ABSTRACT FROM AUTHOR]

Measurements of the beta-gamma directional correlation in the decay of Tm were performed as a function of the time delay inserted in the fast coincidence circuit. Various chemical compounds of Thulium were used to study the influences of the crystal fields and the chemical bonds on the directional correlation. Attenuations up to 40% were observed. The largest anisotropy was found with a liquid source of a Ga-Tm alloy. Also the intensity and directional correlation of the internal brems-strahlung was measured. Since there is a pronounced angular dependence of the internal bremsstrahlung relative to the direction of the emitted beta-particle, the directional correlation measurement can be disturbed seriously even if the intensity of the internal bremsstrahlung is weak. [ABSTRACT FROM AUTHOR]

The sticky platelet syndrome (SPS) is a congenital disorder characterized by platelet hyperaggregability to epinephrine and/or adenosine diphosphate; this predisposes affected individuals to acute myocardial infarction, ischemic optic neuropathy, recurrent venous thromboembolism, and transient ischemic cerebral attacks and strokes. Here, we describe an unusual case with recurrent cerebrovascular accidents due to SPS, in the presence of a patent foramen ovale (PFO). We report an unusual case of a 56-year-old female patient with a PFO, who suffered from recurrent strokes despite long-term medication with clopidogrel for SPS. The patient underwent successful transcatheter closure of the PFO, and, in addition, she has been placed on low-dose acetylsalicylic acid. After 18-month follow-up, she demonstrated an intact atrial septum without any vegetations on the percutaneous device until today. She has had no further thromboembolic events. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the identification of second c-kit mutant model for t(8;21) acute myeloid leukemia (AML).

We present simple conditions under which Markov time changes are obtained, and give formulae for the resulting transition probabilities. [ABSTRACT FROM PUBLISHER]

The article presents an abstract of research paper on early-onset of inflammatory bowel disease submitted at the 5th European Workshop on Immune-Mediated Inflammatory Diseases held at Barcelona, Spain, on December 1-3, 2010.