Ajeet Kumar Gandhi

BACKGROUND AND PURPOSE: Apremilast is an orally administered phosphodiesterase-4 inhibitor, currently in phase 2 clinical studies of psoriasis and other chronic inflammatory diseases. The inhibitory effects of apremilast on pro-inflammatory responses of human primary peripheral blood mononuclear cells (PBMC), polymorphonuclear cells, natural killer (NK) cells and epidermal keratinocytes were explored in vitro, and in a preclinical model of psoriasis. EXPERIMENTAL APPROACH: Apremilast was tested in vitro against endotoxin- and superantigen-stimulated PBMC, bacterial peptide and zymosan-stimulated polymorphonuclear cells, immunonoglobulin and cytokine-stimulated NK cells, and ultraviolet B light-activated keratinocytes. Apremilast was orally administered to beige-severe combined immunodeficient mice, xenotransplanted with normal human skin and triggered with human psoriatic NK cells. Epidermal skin thickness, proliferation index and inflammation markers were analysed. KEY RESULTS: Apremilast inhibited PBMC production of the chemokines CXCL9 and CXCL10, cytokines interferon-gamma and tumour necrosis factor (TNF)-alpha, and interleukins (IL)-2, IL-12 and IL-23. Production of TNF-alpha by NK cells and keratinocytes was also inhibited. In vivo, apremilast significantly reduced epidermal thickness and proliferation, decreased the general histopathological appearance of psoriasiform features and reduced expression of TNF-alpha, human leukocyte antigen-DR and intercellular adhesion molecule-1 in the lesioned skin. CONCLUSIONS AND IMPLICATIONS: Apremilast displayed a broad pattern of anti-inflammatory activity in a variety of cell types and decreased the incidence and severity of a psoriasiform response in vivo. Inhibition of TNF-alpha, IL-12 and IL-23 production, as well as NK and keratinocyte responses by this phosphodiesterase-4 inhibitor suggests a novel approach to the treatment of psoriasis.

AIM: Head and neck cancers (HNCa) are the most common cancers among males in India and 70-80% present in advanced stage. The study aims to assess symptom burden and quality of life (QOL) in advanced incurable HNCa patients at presentation. MATERIALS AND METHODS: One hundred patients were asked to fill EORTC QLQ-C15-PAL questionnaire, which consisted of Global QOL, physical functioning (PF), emotional functioning (EF), fatigue (FA), nausea-vomiting (NV), pain (PA), dyspnea (DY), sleep (SL), appetite (AP), and constipation (CO). Additional questions pertaining to swallowing (SW), hoarseness (HO), cough (CG), weight loss (WL), using pain killers (PK), taste (TA), bleeding (BL), hearing (HE), pain in neck lump (PALMP), opening mouth (OM), and oral secretions (OS) were asked based on a modified EORTC-HN35 questionnaire. Scoring was according to EORTC scoring manual. Mean, median and range were calculated for each item for the entire cohort. RESULTS: The female:male ratio was 17:83.42% of them were ≥60 years of age. Sixty-six patients had T4, 25 had T3, 36 had N2, and 33 had N3 disease. Median QOL was 50 (range 0-83.33) and PF was 77.78 (0-100). Median score for EF and FA was 50. Median score for PA, PK, and SL was 66.67 while that for AP was 33.33. Median value for SW, HO, WL, BL, PALMP, OM, and OS was 33.33 (100-0) while TA, CG, NV, DY, and HE had a median score of 0.00. CONCLUSION: Advanced HNCa has a significant burden of symptoms. These results would help in giving patients better symptom directed therapies and improve their QOL.

© 2014. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

India has a rapidly growing population inflicted with cancer diagnosis. From an estimated incidence of 1.45 million cases in 2016, the cancer incidence is expected to reach 1.75 million cases in 2020. With the limitation of facilities for cancer treatment, the only effective way to tackle the rising and humongous cancer burden is focusing on preventable cancer cases. Approximately, 70% of the Indian cancers (40% tobacco related, 20% infection related and 10% others) are caused by potentially modifiable and preventable risk factors. We review these factors with special emphasis on the Indian scenario. The results may help in designing preventive strategies for a wider application.