Clonal evolution in myelodysplastic syndromes.

Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years).

[Bickerstaff brainstem encephalitis after upper respiratory infection].

Bickerstaff brainstem encephalitis (BE) is a very rare neurological condition with subacute onset of ophthalmoplegia, ataxia and altered sensorium, often postinfectious. The condition is associated with the anti-GQ1b antibody syndrome and is part of the spectrum of diseases including Miller Fisher syndrome and Guillain-Barré syndrome. In this case, we report the history, workup, treatment and follow-up of a 48-year-old woman with probable BE without anti-GQ1b antibodies in relation to the international diagnostic criteria.

Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial.

We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.

Toxicological aspects of injectable gold-hyaluronan combination as a treatment for neuroinflammation.

Secondary inflammatory reactions to stroke or trauma contribute to irreplaceable loss of brain tissue of the affected patients. Likewise, neuroinflammatory processes are the main pathophysiological feature in Multiple Sclerosis (MS), a common neurodegenerative disease among young adults. In the search for safe and efficient ways to reduce inflammation within nervous tissue older immunosuppressive remedies have been re-investigated.

The Interlaboratory RObustness of Next-generation sequencing (IRON) study: a deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories.

Massively parallel pyrosequencing allows sensitive deep sequencing to detect molecular aberrations. Thus far, data are limited on the technical performance in a clinical diagnostic setting. Here, we investigated as an international consortium the robustness, precision and reproducibility of amplicon next-generation deep sequencing across 10 laboratories in eight countries.

Uptake of silver from metallic silver surfaces induces cell death and a pro-inflammatory response in cultured J774 macrophages.

In clinical medicine metallic silver is used as anti-bacterial coating on various catheters, bandages and prostheses. By means of dissolucytosis, i.e.

Metallic silver fragments cause massive tissue loss in the mouse brain.

Silver is a metal with well-known antibacterial effects. This makes silver an attractive coating material for medical devices for use inside the body, e.g.

In vivo liberation of silver ions from metallic silver surfaces.

In vivo liberation of electrically charged silver atoms/silver ions from metallic silver pellets, silver grids and silver threads placed in the brain, skin and abdominal cavity was proved by way of the histochemical technique autometallography (AMG). A bio-film or "dissolution membrane" inserted between the metallic surface and macrophages was recognized on the surface of the implanted silver after a short period of time. Bio-released silver ions bound in silver-sulphur nanocrystals were traced within the first 24 h in the "dissolution membrane" and the "dissolucytotic" macrophages.

Cultured macrophages cause dissolucytosis of metallic silver.

The present study proves that cultured macrophages can liberate silver ions from metallic silver surfaces by a process called dissolucytosis. Macrophages (J774) were grown on a silver plate for different periods of time and after fixation in glutaraldehyde, they were subjected to autometallograhy in order to amplify possible cellular silver-sulphur nanocrystals. Light and electron microscopic analysis of the cells revealed that silver ions released from the plate had been taken up by the macrophages and accumulated in lysosome-like structures.

Autometallographic tracing of quantum dots.

A short clarifying view of how semiconductor quantum dots (QDs) can be made visible in tissue sections by autometallographic (AMG) silver enhancement and how the introduction of AMG enhanceable gold nanoparticles into isolated cells can be used to follow the fate of these marked cells in organisms and cell cultures. As the AMG approach for visualizing quantum dots is extremely sensitive, QDs less than one nanometer can be made visible at both LM and EM levels.

Expression of C-IAP1, C-IAP2 and SURVIVIN discriminates different types of lymphoid malignancies.

(De-)regulation of apoptosis plays an important role in normal and malignant lymphopoiesis. Apoptosis-regulating genes of the BCL-2 family and the recently identified inhibitors of apoptosis (IAP) family have been implicated in different types of non-Hodgkin lymphoma (NHL). To investigate whether expression of specific apoptosis-regulating genes correlated with different types of lymphoid malignancies, we measured the expression of five BCL-2 family genes, four IAP family genes and SMAC by real-time quantitative polymerase chain reaction in patient samples.

Transcriptional repression of the Neurofibromatosis-1 tumor suppressor by the t(8;21) fusion protein.

Von Recklinghausen's disease is a relatively common familial genetic disorder characterized by inactivating mutations of the Neurofibromatosis-1 (NF1) gene that predisposes these patients to malignancies, including an increased risk for juvenile myelomonocytic leukemia. However, NF1 mutations are not common in acute myeloid leukemia (AML). Given that the RUNX1 transcription factor is the most common target for chromosomal translocations in acute leukemia, we asked if NF1 might be regulated by RUNX1.

Epigenetic regulation of tumor suppressors in t(8:21)-containing AML.

The t(8;21) is perhaps the most frequent chromosomal translocation associated with acute myeloid leukemia. The translocation creates a fusion protein that consists of the DNA binding domain of the RUNX1 transcription factor fused to the MTG8 transcriptional co-repressor to create a potent transcriptional repressor. Here, we discuss the possibility that the t(8;21) fusion protein represses tumor suppressors that regulate the RAS signaling pathway and the p53 oncogenic checkpoint.

Intratumoral administration of recombinant human interleukin 12 in head and neck squamous cell carcinoma patients elicits a T-helper 1 profile in the locoregional lymph nodes.

The objective of this Phase II study was to evaluate the pharmacodynamic and immune effects of intratumorally administered recombinant human interleukin-12 (IL-12) on regional lymph nodes, primary tumor, and peripheral blood. Ten previously untreated patients with head and neck squamous cell carcinoma were injected in the primary tumor two to three times, once/week, at two dose levels of 100 or 300 ng/kg, before surgery. We compared these patients with 20 control (non-IL-12-treated) patients.

Epigenetic regulation of tumor suppressors in t(8:21)-containing AML.

The t(8;21) is perhaps the most frequent chromosomal translocation associated with acute myeloid leukemia. The translocation creates a fusion protein that consists of the DNA binding domain of the RUNX1 transcription factor fused to the MTG8 transcriptional co-repressor to create a potent transcriptional repressor. Here, we discuss the possibility that the t(8;21) fusion protein represses tumor suppressors that regulate the RAS signaling pathway and the p53 oncogenic checkpoint.

In vivo cellular uptake of bismuth ions from shotgun pellets.

Shotgun pellets containing bismuth (Bi) are widely used and may cause a rather intense exposure of some wild animals to Bi. A Bi shotgun pellet was implanted intramuscularly in the triceps surae muscle of 18 adult male Wistar rats. Another group of 9 animals had a Bi shotgun pellet implanted intracranially in the neocortex.

Biodistribution and retention time of retrovirally labeled T lymphocytes in mice is strongly influenced by the culture period before infusion.

T lymphocytes used for adoptive immunotherapy are often cultured before transfer to generate sufficient amounts of effector cells with desired specificity. Modification of lymphocytes induced by in vitro activation and expansion may influence their potential effector capacity by altering the survival and trafficking patterns after transfer. In this report, the authors show that the culture period of T cells after ConA/IL-2 stimulation strongly influences the retention and tissue distribution of these cells after infusion into syngeneic C57BL/6 mice.

Abnormal WT1 expression in the CD34-negative compartment in myelodysplastic bone marrow.

In normal bone marrow, WT1 expression is restricted to CD34+ cells. We assessed WT1 mRNA expression levels with quantitative, real-time reverse transcription polymerase chain reaction in normal, myelodysplastic (MDS) and secondary acute myeloid leukaemia (sAML) bone marrow subfractions, based on differentiation status. The highest WT1 expression was observed in the primitive CD34+ rhodamine-123 (rho) dull cells, both in healthy donors and MDS or sAML patients.

The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia.

The t(8;21) is one of the most frequent chromosomal translocations associated with acute leukemia. This translocation creates a fusion protein consisting of the acute myeloid leukemia-1 transcription factor and the eight-twenty-one corepressor (AML1 ETO), which represses transcription through AML1 (RUNX1) DNA binding sites and immortalizes hematopoietic progenitor cells. We have identified the p14(ARF) tumor suppressor, a mediator of the p53 oncogene checkpoint, as a direct transcriptional target of AML1 ETO.

Bismuth tracing in organotypic cultures of rat hippocampus.

Bismuth is known to have neurotoxic side effects in humans and animals. In the 1970s France experienced about a thousand cases of patients suffering from bismuth-induced encephalopathy. Studies suggest that bismuth may provoke a selective degeneration of CA1 pyramidal cells in the organotypic cultures of rat hippocampus.

Degradable dU-based DNA template as a standard in real-time PCR quantitation.

Development of real-time quantitative PCR assays requires suitable positive controls. For assays with clinical applications, these controls may be difficult to obtain because some molecular aberrations are rare and patient material may be available in limited amounts. Because of the risk of introducing contaminations in the laboratory, cloned DNA is not a desirable alternative.