Contemporary Updates on Clinical Trials of Antiangiogenic Agents in the Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) has the highest rate of vascular proliferation among solid tumors. Angiogenesis is the central feature of rapid tumor growth in GBM and therefore remains an appealing therapeutic target in the treatment of these highly malignant tumors. Antiangiogenic therapy is emerging as an important adjuvant treatment. Multiple antiangiogenic agents targeting various sites in vascular endothelial growth factor (VEGF) and integrin pathways have been tested in clinical trials of newly diagnosed and recurrent GBMs. These include bevacizumab, enzastaurin, aflibercept, cediranib, and cilengitide. In this review, we discuss the current status and challenges facing clinical application of antiangiogenic treatment including anti-VEGF therapy and integrin pathway agents' therapy in glioblastoma. Here, we highlight a strong biologic rationale for this strategy, also focusing on integrin pathways. PubMed-indexed clinical trials published in English on antiangiogenic treatment of glioblastomas in the past 5 years were reviewed. The results of the current clinical trials of these agents are presented.

Johann Friedrich Horner and the Repeated Discovery of Oculosympathoparesis: Whose Syndrome Is It?

Disruption of cranial sympathetic tone leads to the symptom complex of miosis, ptosis, and hemifacial anhidrosis. It is widely believed that this phenomenon was discovered in 1869 by the Swiss ophthalmologist Johann Friedrich Horner, and as a result, the term Horner syndrome has become synonymous with the clinical presentation. However, the syndrome that would become Horner syndrome had actually been described several times before his report. François Pourfour du Petit documented the ocular effects of sympathetic trunk lesions in animal studies in 1727. Claude Bernard identified the full clinical triad in animal studies in 1852, and as a result, the condition is sometimes called Bernard syndrome. There were also 2 previous reports of ptosis and miosis resulting from sympathetic nerve damage in humans: 1 by Edward Selleck Hare in 1838 associated with brachial plexus tumor, and the other by Silas Weir Mitchell in 1864 associated with a gunshot wound to the neck. Although Horner was the first to objectively characterize the co-occurrence of vasomotor and ocular changes in a human patient, he did not identify the etiology of the condition, discuss its relationship to the sympathetic nervous system, or reference any of the previous studies in animals or humans. It is possible that a lack of familiarity with previous investigations delayed the full appreciation of the mechanism underlying this disorder.

Validating continuous digital light processing (cDLP) additive manufacturing accuracy and tissue engineering utility of a dye-initiator package.

This study tested the accuracy of tissue engineering scaffold rendering via the continuous digital light processing (cDLP) light-based additive manufacturing technology. High accuracy (i.e., <50 µm) allows the designed performance of features relevant to three scale spaces: cell-scaffold, scaffold-tissue, and tissue-organ interactions. The biodegradable polymer poly (propylene fumarate) was used to render highly accurate scaffolds through the use of a dye-initiator package, TiO2 and bis (2,4,6-trimethylbenzoyl)phenylphosphine oxide. This dye-initiator package facilitates high accuracy in the Z dimension. Linear, round, and right-angle features were measured to gauge accuracy. Most features showed accuracies between 5.4-15% of the design. However, one feature, an 800 µm diameter circular pore, exhibited a 35.7% average reduction of patency. Light scattered in the x, y directions by the dye may have reduced this feature's accuracy. Our new fine-grained understanding of accuracy could be used to make further improvements by including corrections in the scaffold design software. Successful cell attachment occurred with both canine and human mesenchymal stem cells (MSCs). Highly accurate cDLP scaffold rendering is critical to the design of scaffolds that both guide bone regeneration and that fully resorb. Scaffold resorption must occur for regenerated bone to be remodeled and, thereby, achieve optimal strength.

Therapeutic potential of autologous stem cell transplantation for cerebral palsy.

Background. Cerebral palsy (CP) is a severe disabling disease with worldwide incidence being 2 to 3 per 1000 live births. CP was considered as a noncurable, nonreparative disorder, but stem cell therapy offers a potential treatment for CP. Objective. The present study evaluates the safety and efficacy of autologous bone-marrow-derived mononuclear cell (BMMNCs) transplantation in CP patient. Material and Methods. In the present study, five infusions of autologous stem cells were injected intrathecally. Changes in neurological deficits and improvements in function were assessed using Gross Motor Function Classification System (GMFCS-E&R) scale. Results. Significant motor, sensory, cognitive, and speech improvements were observed. Bowel and bladder control has been achieved. On the GMFCS-E&R level, the patient was promoted from grade III to I. Conclusion. In this study, we report that intrathecal infusion of autologous BMMNCs seems to be feasible, effective, and safe with encouraging functional outcome improvements in CP patient.