Six Sigma Approach for a First Evaluation of a Pharmacological Therapy in Tongue Cancer

Tongue cancers are among the most frequent malignancies in the population and their influence can be affected by many risk factors. Patients undergoing tongue surgery face different complications and can experience a long length of hospital stay (LOS). The aim of this paper is to compare two pharmacological therapies in order to understand which one decreases the LOS. At the University hospital of Naples “Federico II” two antibiotics were employed: Cefazolin plus Clindamycin and Ceftriaxone. Six Sigma methodology was employed to analyse two group of patients treated with these two different antibiotics: 55 patients treated with the antibiotic Cefazolin plus Clindamycin and 66 patients with the antibiotic Ceftriaxone. This is the first time that this methodology is used in order to compare two antibiotics in the oncology field. The results obtained show clearly and with a statistical evidence that patients treated with Ceftriaxone experienced a lower LOS (−28.6% in terms of percentage between medians). Reducing the LOS for patients means limiting the number of complications and, therefore, reducing the hospitalization costs. It would be valuable for both hospital and patients: the former would save money that they could invest in other important care activities; the latter would experience a higher quality of care with fewer complications

Engagement of nuclear coactivator 7 by 3-hydroxyanthranilic acid enhances activation of aryl hydrocarbon receptor in immunoregulatory dendritic cells

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first step in the kynurenine pathway of tryptophan (Trp) degradation that produces several biologically active Trp metabolites. L-kynurenine (Kyn), the first byproduct by IDO1, promotes immunoregulatory effects via activation of the Aryl hydrocarbon Receptor (AhR) in dendritic cells (DCs) and T lymphocytes. We here identified the nuclear coactivator 7 (NCOA7) as a molecular target of 3-hydroxyanthranilic acid (3-HAA), a Trp metabolite produced downstream of Kyn along the kynurenine pathway. In cells overexpressing NCOA7 and AhR, the presence of 3-HAA increased the association of the two molecules and enhanced Kyn-driven, AhR-dependent gene transcription. Physiologically, conventional (cDCs) but not plasmacytoid DCs or other immune cells expressed high levels of NCOA7. In cocultures of CD4+ T cells with cDCs, the co-addition of Kyn and 3-HAA significantly increased the induction of Foxp3+ regulatory T cells and the production of immunosuppressive transforming growth factor β in an NCOA7-dependent fashion. Thus, the co-presence of NCOA7 and the Trp metabolite 3-HAA can selectively enhance the activation of ubiquitary AhR in cDCs and consequent immunoregulatory effects. Because NCOA7 is often overexpressed and/or mutated in tumor microenvironments, our current data may provide evidence for a new immune check-point mechanism based on Trp metabolism and AhR

Interferon-γ Regulates the Proliferation and Differentiation of Mesenchymal Stem Cells via Activation of Indoleamine 2,3 Dioxygenase (IDO)

The kynurenine pathway (KP) of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs) express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO) and IDO2, that it is highly regulated by type I (IFN-β) and II interferons (IFN-γ), and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation

Microfluidics assisted biosensors for label-free optical monitoring of molecular interactions

Porous silicon biosensors are by far used in optical monitoring of molecular interactions. These photonic devices could greatly benefit of integration with specific microfluidic circuits that allow small volume, and thus low consumption of reagents, fast time of incubation, and highly controlled reaction conditions. In this paper, we summarize the experience of our research group in fabrication and characterization of optical biochip, and also present new, original results on biosensing. In particular, a porous silicon based microarray of one-dimensional photonic crystals has been integrated with innovative microfluidic circuit for parallel feeding of chemical solutions. The device has been used for the label free optical monitoring of ssDNA–cDNA interactio