PhAc-ALGP-Dox, a Novel Anticancer Prodrug with Targeted Activation and Improved Therapeutic Index.

Clinical use of doxorubicin (Dox) is limited by cumulative myelo- and cardiotoxicity. This research focuses on the detailed characterization of PhAc-ALGP-Dox, a targeted tetrapeptide prodrug with a unique dual-step activation mechanism, designed to circumvent Dox-related toxicities and is ready for upcoming clinical investigation. Coupling Dox to a phosphonoacetyl (PhAc)-capped tetrapeptide forms the cell-impermeable, inactive compound, PhAc-ALGP-Dox.

Robot-assisted retinal vein cannulation in an in vivo porcine retinal vein occlusion model.

Purpose: To evaluate the feasibility of robot-assisted retinal vein cannulation for retinal vein occlusion.

Methods: Prospective experimental study performed in in vivo porcine eyes. A standard three port pars plana vitrectomy was followed by laser-induced branch retinal vein occlusion.

Release of experimental retinal vein occlusions by direct intraluminal injection of ocriplasmin.

Purpose: Retinal vein occlusions (RVO) are a major cause of vision loss in people aged 50 years and older. Current therapeutic options limit the consequences of RVO but do not eliminate the cause. Cannulation of the involved vessel and removal of the clot may provide a more permanent solution with a less demanding follow-up.

Robotic Assisted Cannulation of Occluded Retinal Veins.

Purpose: To develop a methodology for cannulating porcine retinal venules using a robotic assistive arm after inducing a retinal vein occlusion using the photosensitizer rose bengal.

Methodology: Retinal vein occlusions proximal to the first vascular branch point were induced following intravenous injection of rose bengal by exposure to 532nm laser light delivered by slit-lamp or endolaser probe. Retinal veins were cannulated by positioning a glass catheter tip using a robotically controlled micromanipulator above venules with an outer diameter of 80μm or more and performing a preset piercing maneuver, controlled robotically.

CD248 facilitates tumor growth via its cytoplasmic domain.

Background: Stromal fibroblasts participate in the development of a permissive environment for tumor growth, yet molecular pathways to therapeutically target fibroblasts are poorly defined. CD248, also known as endosialin or tumor endothelial marker 1 (TEM1), is a transmembrane glycoprotein expressed on activated fibroblasts. We recently showed that the cytoplasmic domain of CD248 is important in facilitating an inflammatory response in a mouse model of arthritis.

CD248 and its cytoplasmic domain: a therapeutic target for arthritis.

Objective: CD248 is a transmembrane glycoprotein expressed on the surface of activated perivascular and fibroblast-like cells. This study was undertaken to explore the function of CD248 and its cytoplasmic domain in arthritis.

Methods: Synovial tissue biopsy samples from healthy controls, from patients with psoriatic arthritis (PsA), and from patients with rheumatoid arthritis (RA) were stained for CD248.

Interlaboratory diagnostic validation of conformation-sensitive capillary electrophoresis for mutation scanning.

Background: Indirect alternatives to sequencing as a method for mutation scanning are of interest to diagnostic laboratories because they have the potential for considerable savings in both time and costs. Ideally, such methods should be simple, rapid, and highly sensitive, and they should be validated formally to a very high standard. Currently, most reported methods lack one or more of these characteristics.

Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin.

Background: Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated.

Results: To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ) and the subgranular zone (SGZ).

Diagnostic guidelines for high-resolution melting curve (HRM) analysis: an interlaboratory validation of BRCA1 mutation scanning using the 96-well LightScanner.

Genetic analysis of BRCA1 by sequencing is often preceded by a scanning method like denaturing gradient gel electrophoresis (DGGE), protein truncation test (PTT) or DHPLC. High-resolution melting curve (HRM) analysis is a promising and economical method for high-throughput mutation scanning. The EuroGentest network (www.