1.Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension.
Gabriel L1, Delavenne X, Bedouch P, Khouatra C, Bouvaist H, Cordier JF, Mornex JF, Pison C, Cottin V, Bertoletti L. Respiration. 2016 Apr 16. [Epub ahead of print]
BACKGROUND: Patients treated for pulmonary arterial hypertension (PAH) frequently receive vitamin K antagonists (VKAs) for PAH or validated indications (such as atrial fibrillation or venous thromboembolism). In these latter indications, VKAs are challenged by direct oral anticoagulants (DOAs). Decreased dosage of DOAs has been proposed in patients at risk of bioaccumulation.
2.Whole-body Distribution and Radiation Dosimetry of 11C-Elacridar and 11C-Tariquidar in Humans.
Bauer M1, Blaickner M2, Philippe C1, Wadsak W1, Hacker M1, Zeitlinger M1, Langer O1. J Nucl Med. 2016 Apr 14. pii: jnumed.116.175182. [Epub ahead of print]
11C-elacridar and11C-tariquidar are two new PET tracers to assess the transport activities of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). This study investigates the whole-body distribution and radiation dosimetry of both radiotracers in humans.
3.A novel EGR-1 dependent mechanism for YB-1 modulation of paclitaxel response in a triple negative breast cancer cell line.
Lasham A1,2, Mehta SY1,2, Fitzgerald SJ1, Woolley AG3, Hearn JI1, Hurley DG2,4,5,6, Ruza I3, Algie M3, Shelling AN7, Braithwaite AW2,3, Print CG1,2,4. Int J Cancer. 2016 Apr 12. doi: 10.1002/ijc.30137. [Epub ahead of print]
Chemotherapy with taxanes such as paclitaxel (PTX) is a key component of triple negative breast cancer (TNBC) treatment. PTX is used in combination with other drugs in both the adjuvant setting and in advanced breast cancer. Since a proportion of patients respond poorly to PTX or relapse after its use, a greater understanding of the mechanisms conferring resistance to PTX is required. One protein shown to be involved in drug resistance is Y-box binding protein 1 (YB-1). High levels of YB-1 have previously been associated with resistance to PTX in TNBCs. In this study, we aimed to determine mechanisms by which YB-1 confers PTX resistance. We generated isogenic TNBC cell lines that differed by YB-1 levels and treated these with PTX. Using microarray analysis, we identified EGR1 as a potential target of YB-1. We found that low EGR1 mRNA levels are associated with poor breast cancer patient prognosis, and that EGR1 and YBX1 mRNA expression was inversely correlated in a TNBC line and in a proportion of TNBC tumours.
4.Nedaplatin sensitization of cisplatin-resistant human non-small cell lung cancer cells.
Wang H1, Zhu X1, Huang J1, Chen P2, Han S1, Yan X1. Oncol Lett. 2016 Apr;11(4):2566-2572. Epub 2016 Feb 24.
Cisplatin (DDP) has been one of the most widely used chemotherapy drugs for advanced non-small cell lung cancer. However, the increase in the number of DDP-resistant cancer cells has become a major impediment in the clinical management of cancer. In the present study, for the first time, the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay was used to demonstrate that nedaplatin (NDP) could have a stronger inhibitory effect than DDP alone in DDP-resistant A549 (A549DDP) cells and that it could attenuate the resistance of these cells. Additionally, flow cytometry analysis showed that the apoptosis rate of these resistant cells when exposed to NDP was markedly increased and the number of cells in the G2 stage of the cell cycle was significantly increased. Furthermore, western blot analysis indicated that NDP decreased the protein expression of P-glycoprotein, tumor protein p53 and B-cell lymphoma 2, and increased the expression of Bcl-2-associated X protein, all of which could possibly improve the NDP intracellular drug concentration and promote cell apoptosis.
