A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours.

Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers.

Blastomycosis in Children: A Study of 14 Cases.

We retrospectively reviewed 14 children with active blastomycosis. Pulmonary disease occurred in 86% of the cohort and extrapulmonary dissemination was noted in 46%. Urine blastomycosis or histoplasmosis antigens were positive in all tested patients. Acute kidney injury was common in patients who were treated with amphotericin. Mortality tended to be associated with a delay in diagnosis.

2,3-Dichloro-benzene-1,4-diol.

The achiral title compound, C(6)H(4)Cl(2)O(2), crystallizes with O-H⋯O hydrogen bonding linking mol-ecules into layers. Between layers there are chains of Cl⋯Cl⋯Cl inter-actions with alternating distances of 3.274 (2) and 3.742 (2) Å. Augmenting this arrangement there are also C-H⋯Cl (2.97 and 3.17 Å) and Cl⋯π (shortest distances 3.40 and 3.54 Å) inter-actions.

1,4-Dichloro-naphthalene-2,3-diol.

The achiral planar (maximum deviation 0.014 Å) title compound, C(10)H(6)Cl(2)O(2), crystallizes in the chiral space group P2(1)2(1)2(1) in an arrangement incorporating conventional O-H⋯O hydrogen bonding leading to a supra-molecular chain.