Thermal sensitisation by lonidamine of human melanoma cells grown at low extracellular pH

Purpose: This study tested the ability of lonidamine (LND), a clinically applicable inhibitor of monocarboxylate transporters (MCT), to thermally sensitise human melanoma cells cultured at a tumour-like extracellular pH (pH_e) 6.7.

Materials and methods: Human melanoma DB-1 cells cultured at pH_e 6.7 and pH_e 7.3 were exposed to 150?µM LND for 3?h, beginning 1?h prior to heating at 42?°C (2?h). Intracellular pH (pH_i) was determined using 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) and whole spectrum analysis. Levels of heat shock proteins (HSPs) were determined by immunoblot analysis. Cell survival was determined by colony formation.

Results: Treatment with LND at pH_e 6.7 reduced pH_i to 6.30?±?0.21, reduced thermal induction of HSPs, and sensitised cells growing at pH_e 6.7 to 42?°C. When LND was combined with an acute acidification from pH_e 6.7 to pH_e 6.5, pH_i was reduced to 6.09?±?0.26, and additional sensitisation was observed. LND had negligible effects on cells cultured at pH 7.3.

Conclusions: The results show that LND can reduce pH_i in human melanoma cells cultured at a tumour-like low pH_e so that the 42?°C induction of HSPs are abrogated and the cells are sensitised to thermal therapy. Cells cultured at a normal tissue-like pH_e 7.3 were not sensitised to 42?°C by LND. These findings support the strategy that human melanoma cells growing in an acidic environment can be sensitised to thermal therapy in vivo by exposure to an MCT inhibitor such as LND.     

Newspaper Coverage of Mental Illness: Is It Changing?

Abstract

Because the public gets much of its knowledge of mental illness from the news media, it is important to understand what those media report about mental illnesses. It is also useful to know whether or not news coverage of mental illness is changing. The current study looked at 300 newspaper articles containing the key phrase “mental illness” from 6 different newspapers for 1989 and for 1999. Each article was read and rated with respect to a variety of elements, including what specific disorders were named, what the main themes of each article were, and what was the overall tone of the article. Results indicated that there was more coverage of issues of stigma and mental health insurance parity, fewer themes of dangerousness, and fewer articles with negative tone in 1999 than in 1989. However, dangerousness was still the most common theme of 1999 articles and negative articles were still twice as likely to occur as positive ones. Articles in 1999, as in 1989, tended not to name specific psychiatric disorders, tended not to describe the symptoms of those disorders named, and rarely included the perspectives of mental health consumers.