Role of Chemokine Network in the Development and Progression of Ovarian Cancer: A Potential Novel Pharmacological Target

Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development

Spinal Cord Injury Repair by Intrathecal Infusion of Stromal Cell-Derived Factor-1/CXC Chemokine Receptor 4 in a Rat Model

Background: Stromal cell-derived factor-1 (SDF-1)/CXC Chemokine receptor 4 (CXCR4) is an important cytokine, with multiple functions, which plays a crucial role in the recruitment of multiple stem cell types in the defect sites of central nervous system (CNS). Various strategies have been managed to improve functional recovery after spinal cord injury (SCI). One of these strategies is the use of factors to limit damage and increase recovery. Objectives: In this study we investigated the effect of SDF-1 in spinal cord injury repair in a rat model. Materials andMethods: Adult male Wistar rats were randomly divided to four groups (n = 5) as follows: Sham, SCI, SDF-1 and Vehicle. Spinal cord injury model was created by contusion of T8-T9 by clips and SDF-1 infusion pump implanted in the neck region. One week after injury, 5-Bromo-20-Deoxyuridine (BrdU) was injected to trace the proliferative cells. Basso-Beattie-Bresnahan (BBB) test was performed to evaluate locomotor activity following SCI. Immunohistochemistry test was performed to determine proliferating cells, and real time polymerase chain reaction (PCR) was performed to detect the CXCR4 cells in tissue. Results: Significant improvements in locomotor function were detected in the SDF-1 group compared with the SCI and vehicle groups (P < 0.05). The results showed that SDF-1 treatment increased proliferative cells at the spinal cord injury site. Real time PCR revealed that these proliferative cells are CXCR4 positive that intake Bromodeoxyuridine (Brdu). Conclusions: These results showed that the administration of SDF-1a increases the number of proliferating cells in the injured area in the spinal cord and improves functional recovery