Morphine promotes migration and lung metastasis of mouse melanoma cells

Abstract Background Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. Methods Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 μM) or in combination with a TLR4 inhibitor (morphine10 μM +CLI-095 1μM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg−1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. Results Morphine (0.1, 1, and 10 μM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 μM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). Conclusion Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.

Image analysis in In Vivo Stem Cell Tracking.

Regenerative medicine has begun to define a new perspective of future clinical practice. The lack of basic data regarding to basic stem cell biology-survival, migration, differentiation, integration in a real time manner when transplanted into damaged tissue remains a major challenge for design stem cell therapies. So, visualization of injected stem cells provides additional insight into the future therapeutic benefits. Although current imaging modalities including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, bioluminescence imaging, and fluorescence imaging offer some morphological as well as functional information, they lack the ability to assess and track in vivo biological phenomenon, a pivotal link for greater mechanistic understanding following cell-based intervention. This review will therefore discuss currently available in vivo imaging modalities and image processing techniques which may potentiate this field of research.

Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats

INTRODUCTION: Cardiovascular disease is one of the main causes of mortality and morbidity in diabetic patients. This study evaluated the effects of diabetes on myocardial capillary density and several serum angiogenic factors including nitric oxide, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptors. METHODS: Twelve male rats were divided into two groups: control and diabetic (n = 6 each). Diabetes was induced with a single dose of streptozotocin (50 mg/kg). After 21 days, capillary density in the myocardial tissue was evaluated using immunohistochemical staining and is reported as capillaries per mm². Blood samples were collected before and after the induction of diabetes. RESULTS: In the diabetic group, serum nitric oxide and soluble vascular endothelial growth factor receptor 2 concentrations were lower than the levels in the control group, while the level of soluble vascular endothelial growth factor receptor 1 was significantly higher. There was no significant change in the serum vascular endothelial growth factor concentration between the diabetic and control groups; however, the ratio of vascular endothelial growth factor to vascular endothelial growth factor receptor 1 was significantly lower in the diabetic animals. The myocardial capillary density was also lower in the diabetic group compared with the control group (1549 ± 161 vs. 2156 ± 202/mm², respectively). CONCLUSION: Reduced serum nitric oxide and vascular endothelial growth factor receptor 2 levels, increased serum vascular endothelial growth factor receptor 1 levels and a lower vascular endothelial growth factor to vascular endothelial growth factor receptor 1 ratio may be responsible for the decreased myocardial capillary density in diabetic rats.