Organotypic 3D Cell Culture of the Embryonic Lacrimal Gland.

Ectodermal organ development, including lacrimal gland, is characterized by an interaction between an epithelium and a mesenchyme. Murine lacrimal gland is a good model to study non-stereotypical branching morphogenesis. In vitro cultures allow the study of morphogenesis events with easy access to high-resolution imaging.

Differentiation of Fibroblasts to Adipocytes in 3D for a Co-culture with Mammary Organoids and Immunohistological Analysis.

Mammary epithelial ducts, the main functional compartment of the mammary gland, are embedded in an adipocyte-rich stroma, which is essential for proper mammary gland development, function, and tissue homeostasis. Moreover, the adipocyte compartment has an important role in cancer progression. To better understand cell-to-cell interactions and the role of the adipocytes in the mammary gland, development of proper in vitro models which realistically mimic in vivo conditions has been essential.

Smooth Complete Coverage Trajectory Planning Algorithm for a Nonholonomic Robot.

The complete coverage path planning is a process of finding a path which ensures that a mobile robot completely covers the entire environment while following the planned path. In this paper, we propose a complete coverage path planning algorithm that generates smooth complete coverage paths based on clothoids that allow a nonholonomic mobile robot to move in optimal time while following the path. This algorithm greatly reduces coverage time, the path length, and overlap area, and increases the coverage rate compared to the state-of-the-art complete coverage algorithms, which is verified by simulation.

Morphological and Molecular Evaluation of the Tissue Repair following Nasal Septum Biopsy in a Sheep Model.

Objective: Nasal septal pathologies requiring surgical intervention are common in the population. Additionally, nasal chondrocytes are becoming an important cell source in cartilage tissue engineering strategies for the repair of articular cartilage lesions. These procedures damage the nasal septal cartilage whose healing potential is limited due to its avascular, aneural, and alymphatic nature.

Lentivirus- or AAV-mediated gene therapy interventions in ischemic stroke: A systematic review of preclinical studies.

Due to the limited therapeutic options after ischemic stroke, gene therapy has emerged as a promising choice, especially with recent advances in viral vector delivery systems. Therefore, we aimed to provide the current state of the art of lentivirus (LV) and adeno-associated virus (AAV) mediated gene interventions in preclinical ischemic stroke models. A systematic analysis including qualitative and quantitative syntheses of studies published until December 2020 was performed.

An interdisciplinary team-training protocol for robotic gynecologic surgery improves operating time and costs: analysis of a 4-year experience in a university hospital setting.

Main aim of this study is to assess the effect of a structured, interdisciplinary, surgical, team-training protocol in robotic gynecologic surgery, with the gradual integration of an advanced nurse practitioner. Data from all robotic surgical procedures were prospectively acquired. The surgical team consisted of one experienced surgeon and two surgical fellows and the scrub nurse team from three advance nurse practitioners, specialized in robotic surgery.

CDC25 inhibitors as anticancer agents are moving forward.

The identification of a CDC25 inhibitor to arrest the cell cycle closely followed the discovery of CDC25 by Russell and Nurse in 1986. Recent advances at the preclinical and clinical stages reinforce the rationale to consider CDC25 as a relevant target for a cancer treatment. Here, in order to exemplify recent drug discovery efforts, we present our own experience with various chemical series of CDC25 inhibitors.

IRC-083864, a novel bis quinone inhibitor of CDC25 phosphatases active against human cancer cells.

CDC25 phosphatases are key actors in cyclin-dependent kinases activation whose role is essential at various stages of the cell cycle. CDC25 expression is upregulated in a number of human cancers. CDC25 phosphatases are therefore thought to represent promising novel targets in cancer therapy.

Pharmacologic inhibition of CDC25 phosphatases impairs interphase microtubule dynamics and mitotic spindle assembly.

The CDC25 cell cycle regulators are promising targets for new pharmacologic approaches in cancer therapy. Inhibitory compounds such as BN82685 have proven to be effective in specifically targeting CDC25 in cultured cells and in inhibiting tumor cell growth. Here, we report that BN82685 impairs microtubule dynamic instability and alters microtubule organization and assembly at the centrosome in interphase cells.

Anticancer activity of BIM-46174, a new inhibitor of the heterotrimeric Galpha/Gbetagamma protein complex.

A large number of hormones and local agonists activating guanine-binding protein-coupled receptors (GPCR) play a major role in cancer progression. Here, we characterize the new imidazo-pyrazine derivative BIM-46174, which acts as a selective inhibitor of heterotrimeric G-protein complex. BIM-46174 prevents the heterotrimeric G-protein signaling linked to several GPCRs mediating (a) cyclic AMP generation (Galphas), (b) calcium release (Galphaq), and (c) cancer cell invasion by Wnt-2 frizzled receptors and high-affinity neurotensin receptors (Galphao/i and Galphaq).

Genotoxic-activated G2-M checkpoint exit is dependent on CDC25B phosphatase expression.

Cell cycle arrest at the G2-M checkpoint is an essential feature of the mechanisms that preserve genomic integrity. CDC25 phosphatases control cell cycle progression by dephosphorylating and activating cyclin-dependent kinase/cyclin complexes. Their activities are, therefore, tightly regulated to modulate cell cycle arrest in response to DNA damage exposure.

Synthesis and biological evaluation of novel heterocyclic quinones as inhibitors of the dual specificity protein phosphatase CDC25C.

A focused set of heterocyclic quinones based on the benzothiazole, benzoxazole, benzimidazole, indazole and isoindole was prepared and screened with respect to the inhibition of the phosphatase activity of CDC25C. Benzoxazole- and benzothiazole-diones were at least 50 times more potent in inhibiting CDC25C than their benzimidazole-indazole- or isoindole-dione counterparts. These in vitro activities were in good correlation with the anti-proliferative effects observed with Mia PaCa-2 and DU-145 human tumor cell cultures.

Inhibition of human tumor cell growth in vivo by an orally bioavailable inhibitor of CDC25 phosphatases.

Cell cycle regulators, such as the CDC25 phosphatases, are potential targets for the development of new anticancer drugs. Here we report the identification and the characterization of BN82685, a quinone-based CDC25 inhibitor that is active in vitro and in vivo. BN82685 inhibits recombinant CDC25A, B, and C phosphatases in vitro.

Synthesis of small molecule CDC25 phosphatases inhibitors.

A targeted library of small molecules has been prepared to optimize the biological activity of BN82002, our initial lead compound, recently described as an original inhibitor of CDC25 phosphatases. Some of these compounds inhibit CDC25 in the micromolar range and therefore reinforce the interest of CDC25 as an anticancer target.

A novel synthetic inhibitor of CDC25 phosphatases: BN82002.

CDC25 dual-specificity phosphatases are essential regulators that dephosphorylate and activate cyclin-dependent kinase/cyclin complexes at key transitions of the cell cycle. CDC25 activity is currently considered to be an interesting target for the development of new antiproliferative agents. Here we report the identification of a new CDC25 inhibitor and the characterization of its effects at the molecular and cellular levels, and in animal models.

A fission yeast strain expressing human CDC25A phosphatase: a tool for selectivity studies of pharmacological inhibitors of CDC25.

Fission yeast is a simple eukaryotic model organism in which many aspects of cell cycle control can be explored. We examined by homologous recombination whether the human CDC25A phosphatase could substitute for the function of the fission yeast Cdc25. We first show: (a).

Inhibitors of the CDC25 phosphatases.

As essential cell cycle regulators, the CDC25 phosphatases are currently considered as potential targets for the development of novel therapeutic approaches. Here, we review the function and regulation of CDC25 phosphatases, their involvement in cancer and Alzheimer's disease, and the properties of several recently identified inhibitors.

Apoptosis and TRAF-1 cleavage in Epstein-Barr virus-positive nasopharyngeal carcinoma cells treated with doxorubicin combined with a farnesyl-transferase inhibitor.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinomas (NPC) are much more sensitive to chemotherapy than other head and neck carcinomas. Spectacular regressions are frequently observed after induction chemotherapy. However, these favorable responses are difficult to predict and often of short duration.

Inhibition of human tumor cell growth in vivo by an orally bioavailable inhibitor of human farnesyltransferase, BIM-46228.

Oncogenic mutations of the ras gene leading to constitutive activation of downstream effectors have been detected in a wide spectrum of human cancers (pancreas, thyroid, colon, non-small-cell lung cancer). Membrane anchorage of Ras, required for functional activity in signal transduction, is facilitated by post-translational modifications resulting in covalent attachment of a farnesyl group to the cysteine in the C-terminal CAAX motif. This attachment is mediated by farnesyltransferase (FTase).

Inhibition of human tumor cell growth in vitro and in vivo by a specific inhibitor of human farnesyltransferase: BIM-46068.

Oncogenic mutations of the ras gene leading to constitutive activation of downstream effectors have been detected in a large spectrum of human cancers (pancreas, thyroid, colon and NSCLC). Membrane anchorage of Ras required for functional activity in signal transduction is facilitated by post-translational modifications resulting in covalent attachment of a farnesyl group to the cysteine in the C-terminal CAAX motif. This attachment is mediated by farnesyltransferase (FTase).