Leukemia encompasses several hematological malignancies with shared phenotypes that include rapid proliferation, abnormal leukocyte self-renewal, and subsequent disruption of normal hematopoiesis. While communication between leukemia cells and the surrounding stroma supports tumor survival and expansion, the mechanisms underlying direct leukemia cell-cell communication and its contribution to tumor growth are undefined. Gap junctions are specialized intercellular connections composed of connexin proteins that allow free diffusion of small molecules and ions directly between the cytoplasm of adjacent cells. To characterize homotypic leukemia cell communication, we employed in vitro models for both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and measured gap junction function through dye transfer assays. Additionally, clinically relevant gap junction inhibitors, carbenoxolone (CBX) and 1-octanol, were utilized to uncouple the communicative capability of leukemia cells. Furthermore, a qRT-PCR screen revealed several connexins with higher expression in leukemia cells compared with normal hematopoietic stem cells. Cx25 was identified as a promising adjuvant therapeutic target, and Cx25 but not Cx43 reduction via RNA interference reduced intercellular communication and sensitized cells to chemotherapy. Taken together, our data demonstrate the presence of homotypic communication in leukemia through a Cx25-dependent gap junction mechanism that can be exploited for the development of anti-leukemia therapies.

Objectives/AimsTo evaluate the antimicrobial activity of a newly developed foam mouthwash containing a modified lactoperoxidase system in vitro.Materials and methodsBiofilms of five bacterial species were developed on hydrophobic and hydrophilic surfaces whilst salivary-based biofilm was grown on tooth enamel. Each surface was exposed to the foam mouthwash or saline in vitro. Optical density and scanning electron microscopy (SEM) was used to determine retention of the biofilm following 5 or 30 s exposure time.ResultsThe foam mouthwash was active against biofilms formed by S. aureus, K. rhizophila, M. thailandicus, E. coli, and C. violaceum and eliminated significant amount of biofilm from each surface; immature 4 h biofilm was less resistant than 24 h biofilm. A 30 s rinse showed best performance, with removal of up to 66% of biofilm from the hydrophilic surface. SEM imaging confirmed oral biofilm removal from the enamel surface after a 5 s rinse with the foam mouthwash.DiscussionFoam mouthwash demonstrated a significant impact on growing biofilm when compared against saline solution. Growing biofilms were more susceptible to the action of the foam mouthwash, which justifies after-meal use of the mouthwash when traditional dentifrices may not be accessible.ConclusionsFoam mouthwash can be a convenient on-the-go format of oral care products that can be used after meals or when needed to reduce the risk of biofilm-associated oral conditions.

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