Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas.

BACKGROUND: Lymphomas are among the most common human cancers and represent the cause of death for still too many patients. The B-cell receptor with its downstream signaling pathways represents an important therapeutic target for B-cell lymphomas. Here, we evaluated the activity of the MEK1/2 inhibitor pimasertib as single agent and in combination with other targeted drugs in lymphoma preclinical models. MATERIALS AND METHODS: Cell lines derived mature B-cell lymphomas were exposed to increasing doses of pimasertib alone. Immunoblotting and gene expression profiling were performed. Combination of pimasertib with idelalisib or ibrutinib was assessed. RESULTS: Pimasertib as single agent exerted a dose-dependent antitumor activity across a panel of 23 lymphoma cell lines, although at concentrations higher than reported for solid tumors. Strong synergism was observed with pimasertib combined with the PI3K inhibitor idelalisib and the BTK inhibitor ibrutinib in cell lines derived from diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. The data were confirmed in an in vivo experiment treating DLBCL xenografts with pimasertib and ibrutinib. CONCLUSION: The data presented here provide the basis for further investigation of regimens including pimasertib in relapsed and refractory lymphomas.

[Use of ropivacaine in axillary brachial plexus block]. / Impiego della ropivacaina nel blocco del plesso brachiale per via ascellare.

The aim of the study was to evaluate the efficiency and safety of ropivacaine, in comparison with bupivacaine, in axillary brachial plexus block. 24 patients, undergoing upper limb surgery, was divided into 2 homogeneous groups and the local anaesthetics was administered: A (ropivacaine 0.75%, 25 ml; total dose 187.5 mg) and B (bupivacaine 0.5%, 25 ml; total dose 125 mg). The axillary plexus block was executed with the help of an electrostimulator. The results show that using ropivacaine the onset-time is lower and the duration of sensory and motor block is higher than using bupivacaine. In conclusion we can affirm that ropivacaine is a new step in local anaesthetic field.

[Peridural analgesic therapy in orthopedic surgery: comparison of ropivacaine and bupivacaine]. / Terapia antalgica peridurale in chirurgia ortopedica: confronto tra ropivacaina e bupivacaina.

The aim of our study was to compare the efficiency of ropivacaine and bupivacaine, in epidural administration, in postoperative analgesia. 20 patients, undergone knee surgery, in epidural anaesthesia (bupivacaine 0.5%-2 mg/Kg-1 administered in level L3L4), was divided into 2 groups (10 each one) and the local anaesthetics in study was administered by epidural catheter with an elastomeric pump: A (ropivacaine 0.15%) and B (bupivacaine 0.15%). The results demonstrate that ropivacaine is better than bupivacaine to keep a check on analgesia in postoperative pain.

[Use of mivacurium in orthopedic surgery: comparison of 2 different-dose inductions]. / Impiego del mivacurium in chirurgia ortopedica: confronto tra due diversi dosaggi-induzione.

The aim of our study was to evaluate the efficiency and safety of mivacurium, comparing two dose-induction in patients undergone a minor orthopaedic surgery. 30 patients were divided into two groups and mivacurium were administered at the dose of 0.15 mg Kg-1 and 0.20 mg Kg-1 respectively. The results confirmed its efficiency in short surgery. Mioresolution was excellent only in the second group (0.20 mg Kg-1) despite an histamine-related blood pressure reduction.