ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression.

Gliomas in general and the more advanced glioblastomas (GBM) in particular are the most usual tumors of the central nervous system with poor prognosis. GBM patients develop resistance to distinct therapies, in part due to the existence of tumor cell subpopulations with stem-like properties that participate in trans-differentiation events. Within the complex tumor microenvironment, the involvement of extracellular proteases remains poorly understood.

PIM kinases mediate resistance of glioblastoma cells to TRAIL by a p62/SQSTM1-dependent mechanism.

Glioblastoma (GBM) is the most common and aggressive brain tumor and is associated with poor prognosis. GBM cells are frequently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and finding new combinatorial therapies to sensitize glioma cells to TRAIL remains an important challenge. PIM kinases are serine/threonine kinases that promote cell survival and proliferation and are highly expressed in different tumors.

Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics.

NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas.

Anti-cancer cytotoxic effects of multiwalled carbon nanotubes.

Recent research has opened new alternatives to traditional chemotherapy treatments using nanomaterials as cytotoxic agents. Anti-cancer nanomedicines do not require specific target sites on key proteins or genes to kill cancer cells and have radically different mechanisms to interact with the living matter. Among 1D nanomaterials, multiwalled carbon nanotubes (MWCNTs) have the intrinsic ability to bind tubulin and interfere with microtubule dynamics, mimicking the effect of traditional cytotoxic microtubule-binding agents such as paclitaxel (taxol®).

Expression and function of toll-like receptors in peripheral blood mononuclear cells of patients with polymyalgia rheumatica and giant cell arteritis.

Objective: To investigate the expression and function of the Toll-like receptor (TLR) family in peripheral blood mononuclear cells (PBMCs) of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA).

Methods: The authors analysed 70 patients with PMR, 20 with GCA, and 24 healthy controls (HC). TLR expression was assessed by flow cytometry.

[Prevalence of the A1555G MTDNA mutation in sporadic hearing-impaired patients without known history of aminoglycoside treatment].

Introduction: The A1555G mitochondrial DNA (mtDNA) mutation is responsible for maternally inherited non-syndromic hearing loss that is increased by aminoglycoside exposure. The objective of this study was to ascertain the frequency of the A1555G mutation among patients without family history of hearing loss or known exposition to aminoglycosides.

Methods: We screened for the mtDNA A1555G mutation in Spanish patients with sporadic sensorineural hearing impairment without a known family history of hearing loss or aminoglycoside exposition seen at the ENT Department in Sierrallana Hospital (Torrelavega, Cantabria, Spain) over a four-year period.

Elevated levels of IL-1beta in Fanconi anaemia group A patients due to a constitutively active phosphoinositide 3-kinase-Akt pathway are capable of promoting tumour cell proliferation.

FA (Fanconi anaemia) is a hereditary disease characterized by congenital malformations, progressive bone marrow failure and an extraordinary elevated predisposition to develop cancer. In the present manuscript we describe an anomalous high level of the proinflammatory cytokine IL-1beta (interleukin-1beta) present in the serum of FA patients. The elevated levels of IL-1beta were completely reverted by transduction of a wild-type copy of the FancA cDNA into FA-A (FA group A) lymphocytes.

Deficiency of CARD8 is associated with increased Alzheimer's disease risk in women.

NF-kappaB, a major transcription factor controlling inflammation, is activated in Alzheimer's disease (AD) brains. CARD8 protein has been implicated in the suppression of NF-kappaB activity, but a truncating polymorphism (p.C10X, rs2043211) renders a non-functional CARD8 protein that gives rise to a more active NF-kappaB and an amplification of the inflammatory process.

Plexin B1 is downregulated in renal cell carcinomas and modulates cell growth.

Plexins are a family of transmembrane receptors that interact with the repulsive axon guidance molecules (Semaphorins) in neural tissues. In extraneural tissues, plexins are involved in other cellular functions often altered in neoplastic cells, such as adhesion, migration, and apoptosis. Plexin B1 has been implicated in the regulation of Akt, which is an activated pathway in renal cell neoplasms, and only 1 report has emphasized its role as an oncogenic factor.

Cannabinoid receptors as novel targets for the treatment of melanoma.

Melanoma causes the greatest number of skin cancer-related deaths worldwide. Despite intensive research, prevention and early detection are the only effective measures against melanoma, so new therapeutic strategies are necessary for the management of this devastating disease. Here, we evaluated the efficacy of cannabinoid receptor agonists, a new family of potential antitumoral compounds, at skin melanoma.

Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes.

Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.

Breast cancer cells can evade apoptosis-mediated selective killing by a novel small molecule inhibitor of Bcl-2.

Proteins of the Bcl-2 family are key regulators of caspase activation and apoptosis. Some members of this family, notably Bcl-2 and Bcl-x(L), are overexpressed in cancer cells, which have been associated with chemoresistance. We have designed and synthesized a small molecule inhibitor of Bcl-2, named YC137, and studied its role in cancer cells.

Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis.

Purpose And Experimental Design: The stem cell factor/KIT receptor loop may represent a novel target for molecular-based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines.

Results: KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.

Jun N-terminal kinase activity and early growth-response factor-1 gene expression are down-regulated in Fanconi anemia group A lymphoblasts.

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome characterized by cellular sensitivity to genotoxic agents. In recent years, FA proteins have been associated with different molecules involved in signal transduction, which has raised the interest in FA-dependent signaling pathways. Here, we report that the c-Jun N-terminal kinase (JNK) fails to phosphorylate in response to UV radiation and treatment with mitomycin C in FA lymphoblast cells derived from type A patients (FA-A).

Fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via DREAM inhibition in human leukemia cells.

Background And Objectives: The apoptotic Bcl-2 family member Hrk is transcriptionally silenced via DREAM in hematopoietic progenitor cell lines, and is specifically induced after growth factor withdrawal. Given that expression of Hrk is sufficient to induce apoptosis, we studied the expression of this apoptotic protein and its regulatory mechanism in human leukemia cells.

Design And Methods: K562 chronic myeloid leukemia cells were treated with STI571, a Bcr-Abl kinase inhibitor, and the Jurkat T-cell leukemia cell line was incubated with agonistic anti-Fas antibodies.