ABSTRACT
We have previously demonstrated that the stromal cellderived factor (SDF1)/CXCR4 system is involved in the metastasis of head and neck cancer. Additionally, it has been revealed that the blockade of CXCR4 by subcutaneous daily injection with AMD3100, a CXCR4 antagonist, may be effective in preventing metastasis in CXCR4related head and neck cancer. Recent investigations have suggested that AMD070, a novel orally bioavailable inhibitor of CXCR4, may be minimally invasive compared with AMD3100. In the present study, we examined the effect of AMD070 on metastasis induced by the SDF1/CXCR4 axis in B88SDF1 oral cancer cells, which express high levels of SDF1 and CXCR4. Although treatment with AMD070 did not affect the anchoragedependent growth of B88SDF1 cells, it significantly suppressed the anchorageindependent growth. Moreover, the SDF1/CXCR4dependent migration and invasion of B88SDF1 cells was significantly inhibited following treatment with AMD070. Subsequently, we performed an experimental therapy using AMD070 to prevent the distant metastasis of B88SDF1 cells in vivo. Daily oral administration of AMD070 significantly inhibited the lung metastasis of B88SDF1 cells in nude mice. These results indicated that AMD070 could be useful as a novel orally bioavailable inhibitor of oral cancer metastasis.
Subject(s)
Heterocyclic Compounds, 1-Ring/administration & dosage , Lung Neoplasms/drug therapy , Mouth Neoplasms/drug therapy , Receptors, CXCR4/genetics , Administration, Oral , Aminoquinolines , Animals , Benzimidazoles , Biological Availability , Butylamines , Cell Line, Tumor , Heterocyclic Compounds, 1-Ring/adverse effects , Humans , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Mice , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Neoplasm Metastasis , Receptors, CXCR4/antagonists & inhibitors , Xenograft Model Antitumor AssaysABSTRACT
A 75-year-old Japanese woman with acute mitral valve prolapse and regurgitation, that developed one month previously, suffered from intractably progressive congestive heart failure (CHF). However, the emergent surgery was declined, and pharmacological treatment was discontinued due to hypotension and malignant arrhythmia. She was treated with 5-8 cmH2O of continuous positive airway pressure (CPAP) to manage CHF and Cheyne-Stokes respiration during the preoperative period of five weeks, after which plastic surgery of the mitral valve was successfully performed. CPAP can be an effective non-pharmacological treatment for CHF, unloading the left ventricle hydrostatically in order to reduce mitral regurgitation and improve oxygenation.
