Enhanced pro-apoptotic activity of rituximab through IBTK silencing in non-Hodgkin lymphoma B-cells.

Rituximab is a commonly used chemotherapeutic drug for patients with aggressive lymphomas, such as non-Hodgkin's lymphoma (NHL). Currently, the combination of Rituximab and chemotherapy (R-CHOP) stands as the most prevalent first-line therapy for NHL. Nevertheless, the development of new therapeutic approaches remains imperative. An increasing body of evidence highlights a novel role for IBTK in tumorigenesis and cancer growth. In this study, we aim to broaden our understanding of IBTK's function in B-lymphoma, with a particular focus on its impact on the expression of the oncogene MYC. Here, we assessed the effects of combining Rituximab with IBTK silencing on cell viability through cell cycle analysis and Annexin V assays in vitro. Furthermore, we leveraged the transplantability of Eµ-myc lymphomas to investigate whether the inhibition of IBTK could elicit anti-tumor effects in the treatment of lymphomas in vivo. Our data suggests that IBTK silencing may serve as an effective anti-tumor agent for aggressive B-Lymphomas, underscoring its role in promoting apoptosis when used in combination with Rituximab, both in in vitro and in vivo settings.

Very low doses of ethanol induce behavioral changes involving dopamine D2 receptors.

In male rats, pretreatment for 20 days with very low (0.5, 1%, v/v) but not with high (5, 10%, v/v) oral doses of ethanol delayed the initiation and reduced the duration of narcosis induced by an acute high intraperitoneal (i.p.) dose of the drug (3 g/kg in 25% saline solution). Furthermore, the treatment improved the acquisition of shuttle-box active avoidance response but did not affect the emission of ultrasonic calls, an index of emotional state of animals. These effects were inhibited by peripheral administration of the dopamine D2 receptor antagonist, sulpiride (1 mg/kg). A higher dose of sulpiride (10 mg/kg) prolonged the duration of narcosis in rats pretreated with high-dose ethanol and reduced the number of conditioned avoidance responses in the shuttle-box paradigm. The pretreatment with the dopamine D2 receptor agonist, (+/-)-2-(N-phenethyl-N-propylamino)-5-hydroxytetralin (PPHT, 0.1 mg/kg), enhanced the effects of ethanol very low doses in delaying the initiation and reducing the duration of narcosis induced by an acute i.p. dose of the drug. A pharmacokinetic study in ethanol-pretreated animals revealed that administration of 0.5% or 1% ethanol for 20 days did not modify significantly the bioavailability of acute ethanol administered i.p. in a dose of 3 g/kg in 25% saline solution. Thus, repeated administration of ethanol very low doses may have affected the sensitivity of presynaptic dopamine D2 receptors. The influence on dopamine release through an action on presynaptic receptors may be involved in these effects of small doses of ethanol.