TRIP-Brs, a group of transcription factors (TFs) that modulate several mechanisms in higher organisms. However, the novel paradigm to target TRIP-Brs in specific cancer remains to be deciphered. In particular, comprehensive analysis of TRIP-Brs in clinicopathological and patients’ prognosis, especially in breast cancer (BRCA), is being greatly ignored. Therefore, we explored the key roles of TRIP-Br expression, modulatory effects, mutations, immune infiltration, and prognosis in BRCA using multidimensional approaches. We found elevated levels of TRIP-Brs in numerous cancer tissues than normal. Higher expression of TRIP-Br-2/4/5 was shown to be positively associated with lower survival, tumor grade, and malignancy of patients with BRCA. Additionally, higher TRIP-Br-3/4 were also significantly linked with worse/short survival of BRCA patients. TRIP-Br-1/4/5 were significantly overexpressed and enhanced tumorigenesis in large-scale BRCA datasets. The mRNA levels of TRIP-Brs have been also correlated with tumor immune infiltrate in BRCA patients. In addition, TRIP-Brs synergistically play a pivotal role in central carbon metabolism, cancer-associated pathways, cell cycle, and thyroid hormone signaling, which evoke that TRIP-Brs may be a potential target for the therapy of BRCA. Thus, this investigation may lay a foundation for further research on TRIP-Br-mediated management of BRCA.

Simultaneous induction of other types of programmed cell death, alongside apoptosis, in cancer cells may be considered an attractive strategy for the development of more effective anticancer therapies. The present study aimed to investigate the role of AMP-activated protein kinase (AMPK) in nutrient/serum starvation-induced necroptosis, which is a programmed form of necrosis, in the presence or absence of p53. The present study detected higher cell proliferation and lower cell death rates in the HCT116 human colon cancer cell line containing a p53 null mutation (HCT116 p53 -/-) compared with in HCT116 cells harboring wild-type p53 (HCT116 p53 +/+ ), as determined using a cell viability assay. Notably, western blot analysis revealed a relatively lower level of necroptosis in HCT116 p53 -/cells compared with in HCT116 p53 +/+ cells. Investigating the mechanism, it was revealed that necroptosis may be induced in HCT116 p53 +/+ cells by significantly increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), whereas little alterations were detected in HCT116 p53 -/cells. Unexpectedly, a much lower level of ATP was detected in HCT116 p53 -/cells compared with in HCT116 p53 +/+ cells. Accordingly, AMPK phosphorylation on the Thr172 residue was markedly increased in HCT116 p53 -/cells. Furthermore, western blot analysis and ROS measurements indicated that AMPK inhibition, using dorsomorphin dihydrochloride, accelerated necroptosis by increasing ROS generation in HCT116 p53 -/cells. However, AMPK activation by AICAR did not suppress necroptosis in HCT116 p53 +/+ cells. In conclusion, these data strongly suggested that AMPK activation may be enhanced in HCT116 p53 -/cells under serum-depleted conditions via a drop in cellular ATP levels. In addition, activated AMPK may be at least partially responsible for the inhibition of necroptosis in HCT116 p53 -/cells, but not in HCT116 p53 +/+ cells.

In attempting to identify effective anticancer drugs from natural products that are harmless to humans, we found that the gomisin J from Schisandra chinensis fruit has anticancer activity. Schisandra chinensis fruits are used in traditional herbal medicine and gomisin J is one of their chemical constituents. In the present study, we examined the anticancer activity of gomisin J in MCF7 and MDA-MB-231 breast cancer cell lines and in MCF10A normal cell line, in a time-and concentration-dependent manner. Our data revealed that gomisin J exerted a much stronger cytotoxic effect on MCF7 and MDA-MB-231 cancer cells than on MCF10A normal cells. Gomisin J suppressed the proliferation and decreased the viability of MCF7 and MDA-MB-231 cells at relatively low (<10 µg/ml) and high (>30 µg/ml) concentrations, respectively. Our data also revealed that gomisin J induced necroptosis, a programmed form of necrosis, as well as apoptosis. Notably, gomisin J predominantly induced necroptosis in MCF7 cells that are known to have high resistance to many pro-apoptotic anticancer drugs, while MDA-MB-231 exhibited a much lower level of necroptosis but instead a higher level of apoptosis. This data indicated the possibility that it may be used as a more effective anticancer drug, especially in apoptosis-resistant malignant cancer cells. In an extended study, gomisin J exhibited a strong cytotoxic effect on all tested various types of 13 cancer cell lines, indicating its potential to be used against a wide range of different types of cancer cells.

Angelica amurensis has traditionally been used to treat various medical problems. In this report, we introduce cis-khellactone as a new anti-cancer agent, which was isolated from the chloroform soluble fraction of the rhizomes of Angelica amurensis. Its anti-cancerous effect was at first tested in MCF7 and MDA-MB-231 breast cell lines, in which MCF7 is well known to be resistant to many anti-cancer drugs; MCF10A normal breast cell line was used as a control. In vitro experiments showed that cis-khellactone suppressed cell growth and proliferation at a relatively low concentrations (<5 μg/ml) and decreased cell viability at high concentrations (>10 μg/ml) in both cancer cell lines in a time- and concentration-dependent manner. This anti-cancerous effect was also checked in additional 16 different types of normal and cancer cell lines. Cis-khellactone treatment significantly suppressed cell proliferation and enhanced cell death in all tested cancer cell lines. Furthermore, Western blot analysis showed that cis-khellactone induced three types of programmed cell death (PCD): apoptosis, autophagy-mediated cell death, and necrosis/necroptosis. Cis-khellactone concentration-dependently decreased cell viability by increasing the level of reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), which are related to all three types of PCD. Mitochondrial fractionation data revealed that cis-khellactone induced the translocation of BAX and BAK into mitochondria as well as the overexpression of VDAC1, which probably accelerates MMP disruption and finally cell death. Importantly, our extended in vivo studies with xenograft model further confirmed these findings of anti-cancerous effects and showed no harmful effects in normal tissues, suggesting that there would be no side effects in humans.

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Playing a vital role in assuring reliability of language performance assessment, rater training has been a topic of interest in research on large-scale testing. Similarly, in the context of VSTEP, the effectiveness of the rater training program has been of great concern. Thus, this research was conducted to investigate the impact of the VSTEP speaking rating scale training session in the rater training program provided by University of Languages and International Studies - Vietnam National University, Hanoi. Data were collected from 37 rater trainees of the program. Their ratings before and after the training session on the VSTEP.3-5 speaking rating scales were then compared. Particularly, dimensions of score reliability, criterion difficulty, rater severity, rater fit, rater bias, and score band separation were analyzed. Positive results were detected when the post-training ratings were shown to be more reliable, consistent, and distinguishable. Improvements were more noticeable for the score band separation and slighter in other aspects. Meaningful implications in terms of both future practices of rater training and rater training research methodology could be drawn from the study.

Chemotherapy has been widely used as a clinical treatment for cancer over the years. However, its effectiveness is limited because of resistance of cancer cells to programmed cell death (PCD) after treatment with anticancer drugs. To elucidate the resistance mechanism, we initially focused on cancer cell-specific mitophagy, an autophagic degradation of damaged mitochondria. This is because mitophagy has been reported to provide cancer cells with high resistance to anticancer drugs. Our data showed that TRIP-Br1 oncoprotein level was greatly increased in the mitochondria of breast cancer cells after treatment with various anticancer drugs including staurosporine (STS), the main focus of this study. STS treatment increased cellular ROS generation in cancer cells, which triggered mitochondrial translocation of TRIP-Br1 from the cytosol via dephosphorylation of TRIP-Br1 by protein phosphatase 2A (PP2A). Up-regulated mitochondrial TRIP-Br1 suppressed cellular ROS levels. In addition, TRIP-Br1 rapidly removed STS-mediated damaged mitochondria by activating mitophagy. It eventually suppressed STS-mediated PCD via degradation of VDACI, TOMM20, and TIMM23 mitochondrial membrane proteins. TRIP-Br1 enhanced mitophagy by increasing expression levels of two crucial lysosomal proteases, cathepsins B and D. In conclusion, TRIP-Br1 can suppress the sensitivity of breast cancer cells to anticancer drugs by activating autophagy/mitophagy, eventually promoting cancer cell survival.

Abstract:In the context of rapid regional and international integration, particularly the official establishment of the ASEAN Economic Community in 2015, English capacity has become essential for Vietnamese people to create their competitiveness in employment, education and other opportunities. In the reform of English education and assessment in response to this demand, VSTEP tests were developed and introduced by the Ministry of Education and Training as national English assessment instruments. VSTEP tests are meant to be alternative to the existing expensive international standardised English tests (e.g. IELTS, TOEFL). But this requires VSTEP developers to take action to assure test validity. They also need to accumulate and disseminate evidence of validity of the tests to gain international recognition. By doing so, they have taken meaningful action to contribute to the nation's international and regional integration. The paper highlights the commitment of ULIS-VNU as a VSTEP developing institution in this mission. It reports a recent VSTEP validation study as an example of this commitment 1 .