ABSTRACT
AIMS AND OBJECTIVES: To investigate and examine the reversal effects of canertinib on the activity of EGFR and tamoxifen resistance in drug-resistant human breast carcinoma cells (MCF-7/TamR). MATERIALS AND METHODS: The antiproliferative activity of canertinib alone or in combination with a conventional EGFR-targeting chemotherapies cytotoxic drugs differing in the mechanism(s) of action, such as paclitaxel, carboplatin, etoposide, vinorelbine, and daunorubicin as well as resistance mechanisms of EGFR targeting, have been investigated. RESULTS: With an elevated dosage of canertinib, a significant decrease in proliferation and increase in apoptosis was observed. The treatment with higher doses of canertinib resulted in a 2-3-fold increase in apoptosis. In the combined treatment, it had been noticed a significant developed apoptotic cell death rather induced by single agent treatment. A significant downregulation of the antiapoptotic protein bcl-2 was exposed by immunocytochemistry investigation. Sensitivity to paclitaxel was also measured and was found to inversely correlate to bcl-2 status. CONCLUSION: Proliferation inhibition and apoptosis in MCF-7/TAM-R cells increase with increasing dosage of canertinib. This suggests that canertinib can reverse tamoxifen resistance in breast cancer cells. The antitumor effect of this EGFR-irreversible tyrosine kinase inhibitor provides a rationale for its clinical evaluation in combination with other cytotoxic drugs.
ABSTRACT
OBJECTIVE: To investigate histopathological and biochemical effects of green tea and/or licorice aqueous extracts in thyroid functions in male albino rats intoxicated with Dimethylnitrosamine. METHODS: 40 Male albino rats were divided into two main groups, 20 normal rats and 20 DMN intoxicated rats. Normal rats were subgrouped into 4 equal groups, group A without treatment (controls), group B treated with green tea, group C treated with licorice, group D treated with green tea and licorice. DMN intoxicated rats were subgrouped into 4 equal groups, group E treated with DMN, group F treated with DMN and green tea, group G treated with DMN and licorice, group H treated with DMN, green tea and licorice. The rats were permitted for free access to solubilized extracts of green tea and or licorice for 4 weeks. All rats in groups E, F, G, H were treated by intraperitoneal DMN (4 mg dissolved in 2.5 ml distilled water/kg body weight) seven times every 2 days in the first two weeks. Plasma total triiodothyronine and tetraiodothyronine were determined by radioimmunoassay. Thyroxine 5-monodeiodinase activity of liver was determined by spectrophotometeric method. Plasma thyroid stimulating hormone was determined by chemiluminometric technique. Histopathological examination was conducted. RESULTS: Histopathologically thyroid gland of DMN intoxicated rats showed degeneration (DG)and desquamation (DS) of the lining epithelium and atrophy of many acini with hyperemia (H) in the stromal capillaries and In comparison with control, the administration of DMN alone induced decrease in plasma levels of T3 and T4 while it induced increase in plasma levels of TSH and hepatic activity of Thyroxine 5-monodeiodinase. Coadminstration of DMN and green tea attenuated the lowering effect of DMN on plasma levels of T3 and T4 and induced increase in these levels but values are still below normal ones while Co administration of DMN with licorice or mixture did not affect these levels. Co administration of green tea and/or licorice with DMN attenuated the rising effect of DMN on hepatic activity of Thyroxine 5--DI while augmented the rising effect of DMN on plasma level of TSH. CONCLUSION: Aqueous extract of green tea may be effective in amelioration of biochemical effects and histopathological lesions induced by DMN.
