Druggable Molecular Targets for the Treatment of Triple Negative Breast Cancer / 한국유방암학회지

Breast cancer (BC) is still the most common cancer among women worldwide. Amongst the subtypes of BC, triple negative breast cancer (TNBC) is characterized by deficient expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. These patients are therefore not given the option of targeted therapy and have worse prognosis as a result. Consequently, much research has been devoted to identifying specific molecular targets that can be utilized for targeted cancer therapy, thereby limiting the progression and metastasis of this invasive tumor, and improving patient outcomes. In this review, we have focused on the molecular targets in TNBC, categorizing these into targets within the immune system such as immune checkpoint modulators, intra-nuclear targets, intracellular targets, and cell surface targets. The aim of this review is to introduce and summarize the known targets and drugs under investigation in phase II or III clinical trials, while introducing additional possible targets for future drug development. This review brings a tangible benefit to cancer researchers who seek a comprehensive comparison of TNBC treatment options.

Intracellular GSH alterations and its relationship to level of resistance following exposure to cisplatin in cancer cells

One of the major complications in cancer chemotherapy with cisplatin as one of the important medicines in treatment regimens of different cancers is the development of resistance. One of the most described cellular defense mechanisms involved in resistance is glutathione [GSH], thus in this study, the effects of cisplatin on the total intracellular GSH level [GSHi] in some sensitive and resistant variants of human cell lines [hepatocarcinoma HepG2, sking A375, cisplatin sensitive glioblastoma U373MG and cisplatin resistant glioblastoma U373MGCP, cisplatin sensitive ovary A2780S and cisplatin resistant A2780CP cells] were studied. MTT assay was performed to measure cytotoxicity of cisplatin [33.3 microM for 1 hour]. Following cisplatin exposure, GSHi [per million cells] was evaluated using a photometrical assay up to 90 minutes. Our results indicate that there are significant differences between GSHi content of A2780CP and U373MGCP cells compared to other cell lines. Moreover, IC[50] of cisplatin in different cells seems to have a relation with mean of GSH level in 90 minutes [GSH [mean][90]]. As a conclusion, it seems that resistance to cisplatin in different cell lines is more related with the diverse patterns of GSHi variations following cisplatin exposure than its original level, and/or its cellular increase or decrease. It is also suggested that GSH [mean][90] may be used as a factor for the prediction of cellular resistance to cisplatin

FTIR-microspectroscopy detection of metronidazole teratogenic effects on mice fetus

Metronidazole is used to treat trichomoniasis, bacterial vaginosis, and other diseases. There are controversy aspects about its teratogenicity. A teratogenic agent can alter morphology or subsequent function of the fetus. The aim of this study was to examine an alternative method for the recognition of the mechanism or the bimolecular potential changes in mice fetus caused by Metronidazole using FTIR micro spectroscopy. The mice were injected with metronidazole [60 mg/Kg] on gestation day 9. Fetuses were dissected on day 15 of gestation and morphological and histological studies on the fetus were carried out. Serial sectioning [10 micro m] of normal and metronidazole-treated brains and livers were used for FTIR measurement in the wave number region of 600- 3600 cm[-1].The results showed that there were some variations between the fetus of normal and treated brain and liver. The band intensities in fetus brain and liver of test animals were reduced and shifted at 707 cm[-1], 1155 cm[-1], 1054 cm[-1], 1256 cm[-1] and 1219 cm[-1], 1453 cm[-1] and 1525 cm[-1], 1622 cm[-1], 1645 cm[-1] and 2944 cm[-1],while the band intensities were increased and shifted at 879 cm[-1], 810 cm[-1], 1223 cm[-1], 1256 cm[-1] 1360 cm[-1], 1723 cm[-1]. It was concluded that most of variations in brain and liver of Metronidazole treated fetuses are in amid bands, nucleic acid and carbohydrate related bands. Based on these findings FTIR spectroscopy can be a useful tool for bio diagnostic

Cytotoxicity of selected novel chalcone derivatives on human breast, lung and hepatic carcinoma cell lines

Cancer is considered as a challenging deathly disease and discovering or synthesis of new cytotoxic agents is a worldwide attempt. In this study, a group of recently synthesized chalcones, with the structure of 1,3-diarylprop-2-en-1-one having differesnt COX-1 and/or COX-2 selectivities, have been examined on human hepatocarcinoma [HepG2], lung carcinoma [A549], and breast adenocarcinoma [MCF-7] cell line, using Sulforhodamine B [SRB] assay. Briefly, cells were treated with 1-100 microM of each compound for 72, 96 and 168 hours. In each case, a control row was set with the exposure of cells to compounds-free solvents. Median lethal concentration [LC50] values [compared to controls] were calculated using regression fitness analysis on GraphPad Prism® software. Our results show that the subgroup possessing p-azido COX-2 pharmacophore seems to be more cytotoxic, while the cells seem to show more acquired resistance to them and the subgroup possessing a p-MeSO2NH COX-2 pharmacophore is less cytotoxic, while the cells also acquire less resistance to them. In conclusion, considering the diversity in COX-1 or COX-2 inhibition among these compounds in each group, and also revealing no correlation between COX inhibition selectivity and cell death, it seems that selective inhibition of each isoenzyme doesn't cause substantial effect on toxicity potency. Further studies to determine the main mechanism[s] for these compounds induced cell death are encouraged