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.     

Preparation of Nanoparticles by Solvent Displacement Using a Novel Recirculation System

Submicron colloidal suspensions of poly(ε-caprolactone) (PCL) were prepared by the solvent displacement method, using either the conventional form or a new recirculation device. In the latter case, a process that allows the recirculation of the aqueous phase into a device, providing a continuous flow, is proposed. The influence of the organic solution injection rate and polymer concentration on mean particle size and process yield were studied for both methods. The recirculation rate was also analyzed for the recirculation system. Nanoparticles (NPs) showed mean sizes that ranged from 156 to 381. The smallest particles were obtained when recirculation rate, injection rate and polymer concentration were maximized but at the expense of the yield. The only acceptable yields (83–96%) were obtained at the lowest PCL concentration (2.5% w/v). ANOVA tests (α = 0.05) showed that the variables implicated in the recirculation system significantly affected the mean particle size and the process yield. The entrapment efficiencies of NPs prepared by the conventional method were not significantly different (α = 0.05) from those obtained by the recirculation system.     

Carboplatin delays mammary cancer 4T1 growth in mice

Carboplatin is commonly used to treat a variety of tumors. We investigated the effects of carboplatin (100 mg/kg) in the development and metastatic dissemination of the 4T1 mice mammary carcinoma. Carboplatin was able to reduce tumor volume and the number of lung metastases in 50% compared to the control animals. Mitotic and apoptotic indices were also decreased by the treatment. Assessment of the vascularization of the tumors revealed a significant decrease in blood vessel formation by carboplatin. A decrease in nuclear positivity of CDC47 and cyclin D1 was observed in the group treated with carboplatin when compared to the control group. Positivity for p53 was observed in the control group (2/28; 5%) and the treated group (5/71; 4%). Carboplatin has been demonstrated to be an efficient regulator of 4T1MMT growth and dissemination. The action of this chemotherapeutic agent seems to be related to the induction of apoptosis and inhibition of angiogenesis and cell proliferation.     

Surgical treatment of pleural empyema in Coronavirus disease 19 patients: the Southern Switzerland experience

We report the first surgical series of patients developing pleural empyema after severe bilateral interstitial lung disease in confirmed severe acute respiratory syndrome coronavirus 2 infection. The empyema results in a complex medical challenge that requires combination of medical therapies, mechanical ventilation and surgery. The chest drainage approach was not successful to relieve the symptomatology and to drain the excess fluid. After multidisciplinary discussion, a surgical approach was recommended. Even though decortication and pleurectomy are high-risk procedures, they must be considered as an option for pleural effusion in Coronavirus disease-positive patients. This is a life-treating condition, which can worsen the coronavirus disease manifestation and should be treated immediately to improve patient’s status and chance of recovery.     

Malaria control in Malawi: Current status and directions for the future

The last decade has seen an increase in investment and concerted efforts by the Malawi Ministry of Health and partners to control malaria disease. This report summarizes what is known about the burden of malaria and the strategies being implemented to control it in Malawi. Over the past 5 years, roll out of treatment and prevention efforts have been successful in the country, as demonstrated by increased use of insecticide treated nets, improved access to prompt and effective treatment and the initiation of pilot studies of indoor residual spraying. However, unlike other countries in the region, the recent data have not suggested a decrease in the burden of disease. We describe the environment in which the activities of Malawi's International Center for Excellence in Malaria Research (ICEMR) will be carried out and provide the rationale for the clinical, entomological and molecular studies. Our approach is to establish consistent, stainable data collection systems that are embedded within the public health sector. Through standardized and long-term studies of hosts, parasites and vectors, we hope to contribute to assessment of malaria disease burden, the appropriate application of interventions and policies and provide both the data collection and the health care infrastructure to ultimately eliminate the disease.