Summary
Resistance to platinum compounds is a major determinant of patient survival in high-grade serous ovarian cancer (HGSOC). To understand mechanisms of platinum resistance and identify potential therapeutic targets in resistant HGSOC, we generated a data resource composed of dynamic (±carboplatin) protein, post-translational modification, and RNA sequencing (RNA-seq) profiles from intra-patient cell line pairs derived from 3 HGSOC patients before and after acquiring platinum resistance. These profiles reveal extensive responses to carboplatin that differ between sensitive and resistant cells. Higher fatty acid oxidation (FAO) pathway expression is associated with platinum resistance, and both pharmacologic inhibition and CRISPR knockout of
carnitine palmitoyltransferase 1A
(
CPT1A
), which represents a rate limiting step of FAO, sensitize HGSOC cells to platinum. The results are further validated in patient-derived xenograft models, indicating that CPT1A is a candidate therapeutic target to overcome platinum resistance. All multiomic data can be queried via an intuitive gene-query user interface (
https://sites.google.com/view/ptrc-cell-line
).
Background: Cadmium is an environmental pollutant which can induce the overproduction of free radicals while suppressing the antioxidant defense system. Curcumin is considered a free-radical scavenger and a potent antioxidant. This study was conducted to investigate the effect of curcumin on serum antioxidant enzymes and histopathological changes in mice treated with cadmium. Methods: In this experimental study, adult mice were divided into four groups, namely, control, cadmium chloride (5 mg kg−1), curcumin (100 mg kg−1), and curcumin+cadmium chloride. The animals received curcumin 24 h prior to cadmium chloride injection. After 24 h, blood samples were collected and used to assess the levels of malondialdehyde (MDA), antioxidant enzymes activity (catalase, superoxide dismutase, and glutathione peroxidase), total glutathione, total thiol, and hydrogen peroxide. Histopathological evaluation was also performed for testicular tissue. Results: Mice treated with cadmium showed a significant ( p < 0.001) decrease in the activity of antioxidant enzymes, serum amounts of total glutathione and total thiol, and the diameter of seminiferous tubules compared to the control group. This pollutant also significantly ( p < 0.001) increased serum levels of MDA and hydrogen peroxide and the lumen diameter of seminiferous tubules compared to the control group. In the curcumin+cadmium group, curcumin significantly ( p < 0.001) reversed the adverse effects of cadmium, compared to the cadmium group. In addition, curcumin alone significantly ( p < 0.001) increased serum glutathione peroxidase activity and thiol content compared to the control group. Conclusion: Curcumin, as a potent antioxidant, could compensate the adverse effects of cadmium on lipid and protein peroxidation, potentiated serum antioxidant defense system, and ameliorated some morphometrical parameters in the testis of cadmium-treated mice.
Gold nanorods (GNRs) can be used in various biomedical applications; however, very little is known about their in vivo tissue distribution by radiolabeling. Here, we have developed a rapid and simple method with high yield and without disturbing their optical properties for radiolabeling of gold rods with iodine-131 in order to track in vivo tissue uptake of GNRs after systemic administration by biodistribution analysis and γ-imaging. Following intravenous injection into rat, PEGylated GNRs have much longer blood circulation times.
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