Current Pharmaceutical Design - Volume 18, Issue 25, 2012

The blood-brain barrier (BBB) has been considered as an important regulator of brain homeostasis, and its disturbance has been implicated in the onset and/or evolution of many pathological manifestations of neurodegenerative and inflammatory diseases [1, 2]. In particular, BBB breakdown has been closely associated with the primary insult, as well as the secondary cell death of stroke. Here, we review the pioneering contrib Read More

The blood-brain barrier (BBB) is a critical regulator of brain homeostasis. Additionally, the BBB is the most significant obstacle to effective CNS drug delivery. It possesses specific charcteristics (i.e., tight junction protein complexes, influx and efflux transporters) that control permeation of circulating solutes including therapeutic agents. In order to form this “barrier,” brain microvascular endothelial cells require support of a Read More

Blood-brain barrier (BBB) leakage and brain edema is a critical part of stroke pathophysiology. In this mini-review, we briefly survey the potential role of matrix metalloproteinases (MMPs) in BBB dysfunction. A large body of data in both experimental models as well as clinical patient populations suggests that MMPs may disrupt BBB permeability and interfere with cell-cell signaling in the neurovascular unit. Hence, ong Read More

Recent evidence indicates that circulating endothelial progenitor cells can play an important role, not only in endothelium homeostasis of the pre-stroke brain, but also in angiogenesis of the post-stroke brain. Circulating endothelial progenitor cells are considered to repair endothelial cells by incorporating them into newly formed vessels, or by releasing pro-angiogenic factors. The number or function of circulating endothelial Read More

Central nervous system pericytes have critical and complex inductive, structural, and regulatory roles interacting with other cell types of the neurovascular unit, especially endothelial cells and astrocytes. Pericyte-endothelial interactions are particularly prominent for blood-brain barrier (BBB) maintenance, with profound effects on basement membrane and endothelial tight junction structure and function. Under experim Read More

Stroke remains a major cause of death in the US and around the world. Despite major scientific advances in our understanding of stroke pathology, the only FDA-approved drug for ischemic stroke is tissue plasminogen activator (tPA). Moreover, the therapeutic window for tPA is confined to the acute phase of stroke, thereby greatly limiting its benefits to less than 3% of ischemic stroke patients. Many treatment strategies for str Read More

Cell therapy has been shown as a potential treatment for stroke and other neurological disorders. Human umbilical cord blood (HUCB) may be a promising source of stem cells for cell therapy. The most desired outcomes occur when stem cells cross the blood brain barrier (BBB) and eventually reach the injured brain site. We propose, from our previous studies, that mannitol is capable of disrupting the BBB, allowing t Read More

Thrombolytic therapy with tissue plasminogen activator (tPA) remains the most effective treatment for acute ischemic stroke, but can cause vascular damage leading to edema formation and hemorrhagic transformation (HT). In this review, we discuss how tPA contributes to the pathogenesis of vascular damage and highlight evidence to support combination therapy of tPA with pharmacological agents that are va Read More

Stem cell transplantation has emerged as a promising treatment strategy for stroke. The development of effective ways to monitor transplanted stem cells is essential to understand how stem cell transplantation enhances stroke recovery and ultimately will be an indispensable tool for advancing stem cell therapy to the clinic. In this review, we describe existing methods of tracking transplanted stem cells in vivo, includi Read More

Stroke is the 4th leading cause of death and disability in adults in the USA. However, in the majority of patients, the detrimental effects of an ischemic insult go untreated because of the lack of efficacious neuroprotective compounds. Using naturally occurring compounds as a building block to create efficacious neuroprotective compounds that cross the blood brain barrier may eventually benefit the stroke patients. Ho Read More

Stroke is a devastating disease with few therapeutic options. Despite our growing understanding of the critical mechanistic events in post-stroke brain injury, the clinical translation of these findings has been less effective. A monumental hurdle to the field has been the inability of many systemically applied therapies to efficiently cross the blood brain barrier (BBB) and enter brain cells. Over the last two decades, however Read More

Stroke pathology involves multifactorial pro-death responses, including inflammation, oxidative stress, vascular dysfunction, and activation of necrotic and apoptotic pathways. The interruption of a single specific pathway in defined stroke model systems has not been sufficient to address the multifactorial nature of stroke-induced injuries in the human population. CD36 is a class B scavenger receptor that functions in regul Read More

Endothelial progenitor cells (EPCs) correspond to a population of cells with novel properties capable of angiogenesis and vasculogenesis, thus they are likely to display unique role in the reconstitution of the blood brain barrier (BBB) after stroke. Laboratory evidence supports safety and efficacy of cell therapy for stroke, with limited clinical trials recently initiated. This lab-to-clinic ascent of cellbased therapeutics has been aided b Read More

Ovarian cancer is the most lethal gynecological cancer in women in the western world with a 5-year survival of 49.7%. Advanced stage ovarian cancer is treated both surgically and with chemotherapy, but despite initial high response rates of 60- 75%, many women experience disease recurrence with a dismal prognosis, 5 year overall survival for FIGO stage IIIc and IV disease being only 32 and 18%. In an attempt to im Read More

Trabectedin (ET-743, Yondelis®) is a novel marine antineoplastic alkaloid with a unique mechanism of action. The active substance trabectedin, a tetrahydroisoquinoline alkaloid, is a natural product originally isolated from the Caribbean sea squirt, Ecteinascidia turbinata and is currently manufactured by total synthesis. Trabectedin is licensed by the Spanish pharmaceutical drug company, PharmaMar and co-developed b Read More

Homologous recombination (HR), a key mechanism of DNA double strand break (DSB) repair, is commonly defective in high grade serous carcinomas (HGSC) of the ovary. BRCA1/2 mutations, as well as many other molecular and genetic defects, can lead to impaired HR. Treatment of HR-defective tumours with poly-ADP ribose polymerase (PARP) inhibitors, which block the key mechanism of single strand DNA breaks (S Read More

Background: There is a strong rationale for usage of anti-angiogenic agents in epithelial ovarian cancer. Bevacizumab is the most widely investigated anti-VEGF agent and has shown promising results in recent clinical trials. Objective: To review the rationale and usage of bevacizumab in advanced epithelial ovarian cancer; as mono-therapy, in combination with chemotherapy both as first line and for recurrent ovarian c Read More

Objective: Insight into the expression of multiple vascular endothelial growth factor (VEGF) family members can support the implementation of anti-angiogenic therapy. This study aimed to assess VEGF family member expression in ovarian cancers and related omental metastases. Methods: Tissue microarrays encompassing 270 primary cancers and 112 paired metastases were immunostained for VEGF-A, VEGF-B, VEGF-C a Read More