Glioblastoma is one of the most aggressive, lethal and incurable primary brain tumors with a dismal prognosis in humans. Mango ginger (<em>Curcuma amada</em>) and hops <em>(Humulus lupulus</em>) are two botanicals containing phytochemicals with potential anticancer effects. We have investigated the anticancer and antimetastatic properties of supercritical CO<sub>2</sub> extract of mango ginger (CA) and ethanol extract of hops (HL) in the U-87MG human glioblastoma cell line. Both CA and HL individually demonstrate strong cytotoxicity against glioblastoma cells. CompuSyn analysis of cytotoxicity data confirms that CA and HL are synergistic for cytotoxicity with combination index (CI) values of <1.0. Additionally, CA and HL individually as well as the combination significantly inhibit MMP-2 and MMP-9 activity, tumor cell migration (transendothelial cell migration assay) and AKT phosphorylation in U-87MG cells. CA and HL inhibit glycolysis in U-87MG cells as indicated by the inhibition of ATP and lactate synthesis with the CA+HL combination demonstrating strong inhibition of glycolysis via the reduction of ATP and lactate synthesis compared to cells treated by each extract alone. CA and HL treatment down regulates the expression of proteins associated with metastasis, MMP-2 and MMP-9 and up regulates the expression of TIMP1. Proteins associated with apoptosis, inflammation and energy metabolism were also modulated by CA and HL treatment of glioblastoma cells. These results suggest that CA and HL can be combined for the therapeutic management of glioblastomas.
Allergic contact dermatitis (ACD) affects 20% of patients and combined with irritant contact dermatitis (ICD) account for more than 90% of occupational skin diseases. Patch testing is the gold standard for diagnosis of ACD but result interpretation may be patient and physician dependent. The purpose of this study is to examine whether noninvasive tape stripping can be used to differentiate ACD, ICD, and normal skin. We examined 39 immune and barrier genes expressed in various skin layers. Patients referred to the Massachusetts General Hospital Contact Dermatitis Clinic with confirmed diagnosis of ACD through patch testing were recruited. 100% petrolatum vehicle served as control and 2% and/or 4% sodium lauryl sulphate was used to induce ICD. 20 consecutive tape strips were collected on sites of ACD, ICD, and vehicle-control skin. Tape strip samples were extracted to isolate total RNA and profiled by quantitative real-time PCR to analyze molecular biomarkers. A total of 9 patients, 7 females and 2 males; mean age, 38.6 years (range, 24-72 years), had at least one ACD reaction on patch testing. 13 ACD, 10 ICD, and 9 vehicle-control samples were obtained from 9 patients. All 39 biomarkers were detected amongst the samples with 4/39 markers significantly different between ACD and vehicle-control samples. Our analysis revealed that CD1A (Langerhans cell marker) was significantly increased, whereas loricrin (skin barrier component), KRT1 (suprabasal epidermal keratin), and KRT14 (basal epidermal keratin) were significantly decreased in ACD relative to vehicle-control samples (p<.05). In comparison of ACD and ICD samples, loricrin and KRT1 demonstrated significant differences (p<.05). These findings illustrate divergent epidermal molecular differences associated with ACD, ICD, and normal skin. We propose skin tape stripping as a novel strategy that potentially enables noninvasive and molecular marker-based diagnosis of ACD.
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