O6-methylguanine-DNA methyltransferase depletion and DNA damage in patients with melanoma treated with temozolomide alone or with lomeguatrib

We evaluated the pharmacodynamic effects of the O6-methylguanine-DNA methyltransferase (MGMT) inactivator lomeguatrib (LM) on patients with melanoma in two clinical trials. Patients received temozolomide (TMZ) for 5 days either alone or with LM for 5, 10 or 14 days. Peripheral blood mononuclear cells (PBMCs) were isolated before treatment and during cycle 1. Where available, tumour biopsies were obtained after the last drug dose in cycle 1. Samples were assayed for MGMT activity, total MGMT protein, and O6-methylguanine (O6-meG) and N7-methylguanine levels in DNA. MGMT was completely inactivated in PBMC from patients receiving LM, but detectable in those on TMZ alone. Tumours biopsied on the last day of treatment showed complete inactivation of MGMT but there was recovery of activity in tumours sampled later. Significantly more O6-meG was present in the PBMC DNA of LM/TMZ patients than those on TMZ alone. LM/TMZ leads to greater MGMT inactivation, and higher levels of O6-meG than TMZ alone. Early recovery of MGMT activity in tumours suggested that more protracted dosing with LM is required. Extended dosing of LM completely inactivated PBMC MGMT, and resulted in persistent levels of O6-meG in PBMC DNA during treatment

Microalgal pigments: A source of natural food colors

Naturally sourced colorants and dyes are currently gaining demand over synthetic alternatives due to an increase in consumer awareness brought forward by health and environmental issues. Microalgae are unicellular organisms which are microscopic in size and represent major photosynthesizers with the ability to efficiently convert available solar energy to chemical energy. Due to their distinct advantages over terrestrial plants such as faster growth rates, ability to grow on non-arable land, and diversity in the production of various natural bioactive compounds (e.g., lipids, proteins, carbohydrate, and pigments), microalgae are currently gaining promise as a sustainable source for the production of natural food-grade colorants. The versatility of microalgae to produce various pigments (e.g., chlorophylls, carotenoids, xanthophylls, and phycobiliproteins) that can be commercially exploited as a source of natural colorant is there to be explored. Various growth factors such as temperature, pH, salinity, and light in terms of both quality and quantity have been shown to significantly impact pigment production. In this chapter, we comprehensively review the characteristics of microalgal pigments and factors that affect pigment production in microalgae while evaluating the overall feasibility of exploiting them as a natural source of food colorants