Green Tea Epigallocatechin Gallate Exhibits Anticancer Effect in Human Pancreatic Carcinoma Cells via the Inhibition of Both Focal Adhesion Kinase and Insulin-Like Growth Factor-I Receptor

The exact molecular mechanism by which epigallocatechin gallate (EGCG) suppresses human pancreatic cancer cell proliferation is unclear. We show here that EGCG-treated pancreatic cancer cells AsPC-1 and BxPC-3 decrease cell adhesion ability on micro-pattern dots, accompanied by dephosphorylations of both focal adhesion kinase (FAK) and insulin-like growth factor-1 receptor (IGF-1R) whereas retained the activations of mitogen-activated protein kinase and mammalian target of rapamycin. The growth of AsPC-1 and BxPC-3 cells can be significantly suppressed by EGCG treatment alone in a dose-dependent manner. At a dose of 100 μM which completely abolishes activations of FAK and IGF-1R, EGCG suppresses more than 50% of cell proliferation without evidence of apoptosis analyzed by PARP cleavage. Finally, the MEK1/2 inhibitor U0126 enhances growth-suppressive effect of EGCG. Our data suggests that blocking FAK and IGF-1R by EGCG could prove valuable for targeted therapy, which can be used in combination with other therapies, for pancreatic cancer

Abnormal localized [¹⁸F]FDG accumulation in a Hoffman 3D brain phantom caused by Pseudomonas aeruginosa and Stenotrophomonas maltophilia

The version of record of this article, first published in European Journal of Nuclear Medicine and Molecular Imaging, is available online at Publisher’s website: https://doi.org/10.1007/s00259-024-06816-5.Hoffman 3D brain phantom was scanned to standardize the image quality in a clinical trial. Dynamic [¹⁸F]fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG PET), which started 15 min after being filled with [¹⁸F]FDG (25 MBq), revealed an abnormally increasing accumulation of [¹⁸F]FDG in the left occipital cortex region at one hour. This abnormal accumulation showed an increasing trend (Fig. 1A, B). The presence of bacteria was suggested by the culture of scrabbed samples taken from the corresponding region in the phantom, later confirmed to be Pseudomonas aeruginosa and Stenotrophomonas maltophilia (Fig. 1C). Pseudomonas aeruginosa is an aerobic Gram-negative rod with a single flagellum at one end. It is a facultative anaerobic bacterium that generates ATP (adenosine triphosphate) necessary for growth by aerobic respiration and grows by oxidative degradation of glucose in the presence of oxygen [1]. Stenotrophomonas maltophilia is a non-fermentative Gram-negative bacterium that consumes proteins and peptides rather than sugars and carbohydrates as carbon and nutrient sources [2]. There have been several reports on the uptakes of [¹⁸F]FDG [3, 4]. We concluded that the abnormal accumulation was caused by FDG-avid bacterium, Pseudomonas aeruginosa and Stenotrophomonas maltophilia.It is preferable to use degassed tap water rather than purified or distilled water to prevent the growth of bacteria. Hoffman 3D brain phantom should be disassembled and completely dried after the scan, especially for multicenter clinical trials

Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases

The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment