Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, and uPAR Expression of Prostate Cancer Cells

Background: Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors. Methods and Findings: In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis. Conclusions: These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of it

THE VIBRATIONAL FREQUENCIES OF HALOSIL YLENES HSiX (X = F, Cl, Br)

Author Institution: Department of Chemistry, The University of KentuckyThere are a number of ambiguities and curiosities found in the published Si-H stretching vibrational frequencies of the ground states, $\tilde{X}^{1}A^{\prime}$, and first excited singlet states, $\tilde{A}^{1}A$, of the halosilylenes HSiF, HSiCl, and HSiBr. Here we have investigated these molecules using self-consistent field. SCF, configuration interaction including all single and double excitations, CISD, and triple excitations, CISDT, and complete active space, CAS-SCF, quantum mechanical methods. For the ground and first excited triplet states, all these methods give similar results, but for the excited singlet states, only the CASSCF results are believable

A plain language summary of how lefamulin alone can be used to treat pneumonia caught outside of the hospital due to common bacterial causes, including drug-resistant bacteria

What is this summary about?Bacterial pneumonia is an infection of the lung caused by bacteria that is potentially deadly, costly, and affects millions of people worldwide every year. Treatment is becoming more challenging-many current treatments no longer work well because some strains of bacteria that cause pneumonia have become resistant to current antibiotics. Many of the antibiotics that do still work have undesirable side effects. Therefore, new antibiotics that work differently are needed to treat bacterial pneumonia. Lefamulin (brand name, Xenleta®) is an antibiotic that was approved to treat bacterial pneumonia caught outside a hospital (also called community-acquired bacterial pneumonia, or CABP) based on results of two clinical studies. In both studies, participants started treatment with lefamulin before the type of bacteria causing the infection was known. Lefamulin was well tolerated and worked well in 5 to 7 days to kill the bacteria causing the infection and to improve symptoms in almost all participants with CABP.What were the results?After the studies were completed, the researchers looked back at what kinds of bacteria were identified from the study participants. Lefamulin worked well to kill bacteria and to improve CABP symptoms for most kinds of infecting bacteria, including bacteria resistant to many current antibiotics.What do the results mean?These results suggest that lefamulin, by itself, provides a much-needed treatment option for CABP that covers most of the key bacteria causing this infection

DBP-maf inhibits tumor cell migration.

<p>LNCaP (<b>A</b>), LNCaPLN3 (<b>B</b>), PC3M (<b>C</b>) or PC3MLN4 (<b>D</b>) cells were added (150,000/well) to the top chamber of a modified Boyden chamber (+/− DBP-maf) with 10% FBS in the bottom chamber. After 6 hours cells were removed that had not migrated and remaining cells were quantitated using an acid phosphatase assay. Results were normalized to control. Experiments were performed a minimum of three times and error is shown as +/− SD. Compared to cell growth without DBP-maf, adding DBP-maf had a statistically significant overall reduction of cell migration at 30% (P = 0.0003) for the combined four tumor cell types. Individual significant reduction rates were found with each of these tumor cell types. Compared to control, significant reduction was seen with DBP-maf at (<b>A</b>) 20% P = 0.0022 (<b>B</b>) 20% P = 0.0029 (<b>C</b>) 10% P = .0045 (<b>D</b>) 30% P = .0094. n = 3.</p

FACS analysis of apoptosis or necrosis.

<p>Cells were treated with or without 1 µg/mL DBP-maf for 48 hours, propidium iodide and annexin V were added and cells were analyzed using flow cytometry. Results are representative of three experiments.</p

DBP-maf inhibits expression of uPAR in PC3M cells.

<p>PC3M, and PC3MLN4 cells were treated with DBP or DBP-maf (0.001 and 1 µg/mL) and incubated for 24 hours then harvested. RT products (cDNA), identified as uPAR1, 2, and 3, were amplified by real-time quantitative PCR. p<0.05.</p

A DBP-maf peptide inhibits tumor cell migration.

<p>LNCaP (<b>A</b>), LNCaPLN3 (<b>B</b>), PC3M (<b>C</b>) or PC3MLN4 (<b>D</b>) cells were added (150,000/well) to the top chamber of a modified Boyden chamber (+/− DBP-maf) with 10% FBS in the bottom chamber. After 6 hours cells were removed that had not migrated and remaining cells were quantitated using an acid phosphatase assay. Results were normalized to control. Experiments were performed a minimum of three times and error is shown as +/− SD. Compared to migration without DBP-maf, adding DBP-maf had a statistically significant reduction of migration at 40% (P<0.0001) for the combination of all four tumor cell types. Individual significant reduction rates were found with each of these tumor cell types. Compared to control, significant reduction was seen with DBP-maf at (<b>A</b>) 30% P = 0.0038 (<b>B</b>) 40% P = 0.0016 (<b>C</b>) 20% P = .0038 (<b>D</b>) 40% P = .0005. n = 3.</p