Endovesical instillation of Cidofovir in the treatment of BK polyomavirus hemorrhagic cystitis after allogeneic hematopoietic cell transplantation.

Background: Hemorrhagic cystitis (HC) with BK polyomavirus (BKPyV) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT) that may lead to severe discomfort for the patient and significant morbidity (urinary obstruction, increased transfusion requirements and prolonged hospitalization). So far, there is no clear consensus on how to manage this complication.

Patients And Methods: Here, we report a single-center case series of 9 patients (4 children and 5 adults) treated with cidofovir endovesical (EV) instillation(s) for BKPyV-HC after alloHCT.

Development and validation of a liquid chromatographic method for the stability study of a pharmaceutical formulation containing voriconazole using cellulose tris(4-chloro-3-methylphenylcarbamate) as chiral selector and polar organic mobile phases.

The ophthalmic solution of voriconazole, i.e. (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, made from an injection formulation which also contains sulfobutylether-β-cyclodextrin sodium salt as an excipient (Vfend), is used for the treatment of fungal keratitis.

Clustering methods applied in the detection of Ki67 hot-spots in whole tumor slide images: an efficient way to characterize heterogeneous tissue-based biomarkers.

Whole-slide scanners allow the digitization of an entire histological slide at very high resolution. This new acquisition technique opens a wide range of possibilities for addressing challenging image analysis problems, including the identification of tissue-based biomarkers. In this study, we use whole-slide scanner technology for imaging the proliferating activity patterns in tumor slides based on Ki67 immunohistochemistry.

In vitro and in vivo evaluation of a dry powder endotracheal insufflator device for use in dose-dependent preclinical studies in mice.

The aim of this study was to evaluate the ability of the Penn-Century Dry Powder Insufflator for mice (DP-4M) to reproducibly, uniformly, and deeply deliver dry powders for inhalation in the mouse lung. Itraconazole-based dry powder formulations produced by spray-drying were different in terms of composition (different ratios of drug and mannitol, with or without phospholipids), but relatively similar in terms of particle size and mass median aerodynamic diameter. The ability of the dry powder insufflator to disaggregate each formulation was the same, indicated by the absence of a statistically significant difference between the particle size distribution parameters, as measured by laser scattering.

TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas.

Based on the molecular profiling of astrocytomas, we previously identified a series of genes involved in astrocytoma invasion. Of these, tissue inhibitor of metalloproteinase-4 (TIMP-4) was found to be overexpressed in pilocytic astrocytomas relative to diffuse astrocytomas of any histological grade. Although some data suggest that TIMP-4 may be an anti-tumoral actor in astrocytomas, recent findings challenge this concept.

In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy.

The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolise the suspension.

Requirements for the valid quantification of immunostains on tissue microarray materials using image analysis.

Antibody-based proteomics applied to tissue microarray (TMA) technology provides a very efficient means of visualizing and locating antigen expression in large collections of normal and pathological tissue samples. To characterize antigen expression on TMAs, the use of image analysis methods avoids the effects of human subjectivity evidenced in manual microscopical analysis. Thus, these methods have the potential to significantly enhance both precision and reproducibility.

Galectin 1 proangiogenic and promigratory effects in the Hs683 oligodendroglioma model are partly mediated through the control of BEX2 expression.

We have previously reported that galectin 1 (Gal-1) plays important biological roles in astroglial as well as in oligodendroglial cancer cells. As an oligodendroglioma model, we make use of the Hs683 cell line that has been previously extensively characterized at cell biology, molecular biology, and genetic levels. Galectin 1 has been shown to be involved in Hs683 oligodendroglioma chemoresistance, neoangiogenesis, and migration.

Targeting the alpha 1 subunit of the sodium pump to combat glioblastoma cells.

Objective: Ion transporters play pivotal roles in cancer cell migration in general and in glioblastomas (GBMs) in particular. However, the specific role of Na/K-ATPase (the sodium pump) and, in particular, its alpha1 subunit, has remained unexplored in GBMs.

Materials And Methods: The expression of Na+/K+ -ATPase alpha1 in GBM clinical samples, normal brain tissue, and a human GBM cell line has been investigated.

The Amaryllidaceae isocarbostyril narciclasine induces apoptosis by activation of the death receptor and/or mitochondrial pathways in cancer cells but not in normal fibroblasts.

Our study has shown that the Amaryllidaceae isocarbostyril narciclasine induces marked apoptosis-mediated cytotoxic effects in human cancer cells but not in normal fibroblasts by triggering the activation of the initiator caspases of the death receptor pathway (caspase-8 and caspase-10) at least in human MCF-7 breast and PC-3 prostate carcinoma cells. The formation of the Fas and death receptor 4 (DR4) death-inducing signaling complex was clearly evidenced in MCF-7 and PC-3 cancer cells. Caspase-8 was found to interact with Fas and DR4 receptors on narciclasine treatment.

New approach for the preparation of efficient DNA cleaving agents: ditopic copper-platinum complexes based on 3-Clip-Phen and cisplatin.

The design and synthesis of new heterodinuclear DNA-targeting agents are described. The abilities of cisplatin and Cu(3-Clip-Phen) [Cu(1-(1,10-phenanthrolin-3-yloxy)-3-(1,10-phenanthrolin-8-yloxy)propan-2-amine)Cl2], an artificial DNA-cleaving agent, have been combined through their "covalent coupling". This strategy has led to bifunctional complexes that are able to cleave the DNA in a double-stranded fashion in contrast to Cu(3-Clip-Phen) alone and have promising cytotoxicities compared to cisplatin in several cell lines.

Galectin-1 knockdown increases sensitivity to temozolomide in a B16F10 mouse metastatic melanoma model.

The rapid increase in the incidence of malignant melanomas has not been associated with improved therapeutic options over the years. Indeed melanomas have proven resistant to apoptosis (type I programmed cell death (PCD)) and consequently to most chemotherapy and immunotherapy. It is believed that this resistance can be partly overcome by proautophagic drugs inducing type II (autophagy) PCD.

Disabled-2 is an epithelial surface positioning gene.

The formation of the primitive endoderm layer on the surface of the inner cell mass is one of the earliest epithelial morphogenesis in mammalian embryos. In mouse embryos deficient of Disabled-2 (Dab2), the primitive endoderm cells lose the ability to position on the surface, resulting in defective morphogenesis. Embryonic stem cells lacking Dab2 are also unable to position on the surface of cell aggregates and fail to form a primitive endoderm outer layer in the embryoid bodies.

Loss of TNF-alpha-regulated COX-2 expression in ovarian cancer cells.

Cyclooxygenase 2 (COX-2) is often found overexpressed in cancer and is thought to have a role in carcinogenic promotion, and thus is a target for therapeutic intervention. Here, we investigated the regulation of COX-2 expression in normal and cancer ovarian surface epithelial cells. Tumor necrosis factor alpha (TNF-alpha) is a potent inducer of COX-2 expression in the ovarian surface epithelium and this regulation is a critical step in ovulation.

Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration.

The purpose of this research was to investigate the effects of processing conditions on the characteristics of solid lipid microparticles (SLM) with a potential application as carriers for pulmonary administration. Compritol (5.0% wt/wt) SLM dispersions were prepared by rotor-stator homogenization, at different surfactant concentrations and emulsification times.

Modulation of the arachidonic cascade with omega3 fatty acids or analogues: potential therapeutic benefits.

Increasing interest in the role of omega3 fatty acids has arisen in these latest years since evidence of their implication in the cardioprotective fish based diet of the Inuit has been demonstrated. Furthermore, several in vitro, in vivo and epidemiological studies support the benefit of this fatty acids intake in various pathological states such as in the cardiovascular, cancer, inflammation, psychiatric, paediatric, pulmonary, dermatological and ophthalmologic fields. This review will focus on metabolism and pharmacological implication of omega3 fatty acids intake as well as its interest in the prevention or treatment of the above-mentioned pathologies.

Loss of surface and cyst epithelial basement membranes and preneoplastic morphologic changes in prophylactic oophorectomies.

Background: The authors suggested that the loss of collagen IV and laminin-containing basement membrane and the loss of Disabled-2 (Dab2) expression were two critical events associated with morphologic dysplastic changes of the ovarian surface epithelium as a step in tumorigenicity. Both the basement membrane and Dab2, a candidate tumor suppressor of ovarian carcinoma, were involved in epithelial cell surface positioning and organization. The authors speculated that the purging of the basement membrane may be similar to the proteolysis during gonadotropin-stimulated ovulation, a cyclooxygenase 2 (Cox-2)-mediated process.

Anomalous expression of epithelial differentiation-determining GATA factors in ovarian tumorigenesis.

Tumor cells often appear in a deviant differentiated stage, and dedifferentiation is a hallmark of malignancy; however, the causative mechanism of the global changes in dedifferentiation is not understood. The GATA transcription factors function in cell lineage specification during embryonic development and organ formation. The transcriptional targets of the GATA factors in early embryonic development include Disabled-2 and collagen IV, markers for epithelial lineages.

Disabled-2 is essential for endodermal cell positioning and structure formation during mouse embryogenesis.

The signal transduction adapter protein Disabled-2 (Dab2) is one of the two mammalian orthologs of the Drosophila Disabled. The brain-specific Disabled-1 (Dab1) functions in positional organization of brain cells during development. Dab2 is widely distributed and is highly expressed in many epithelial cell types.

Dynamic alterations of the extracellular environment of ovarian surface epithelial cells in premalignant transformation, tumorigenicity, and metastasis.

Background: Ovarian surface epithelial cells are positionally organized as a single cell layer by a sheet of basement membrane. It is believed that the contact of the ovarian surface epithelial cells with the basement membrane regulates cell growth and ensures the organization of the epithelium. Disabled-2 (Dab2), a signal transduction protein and a candidate tumor suppressor of ovarian carcinoma, functions in positional organization of ovarian surface epithelial cells.