Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA.

The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.

Arabinoxylan rice bran (MGN-3) enhances the effects of interventional therapies for the treatment of hepatocellular carcinoma: a three-year randomized clinical trial.

BACKGROUND AND AIMS: This study examined the efficacy of arabinoxylan rice bran (MGN-3) in conjunction with an interventional therapy (IT) for the treatment of hepatocellular carcinoma patients. PATIENTS AND METHODS: A total of sixty-eight patients with hepatocellular carcinoma (stages I and II) participated in the study. Patients were randomized to receive IT (30 patients, control group) or IT+MGN-3 (38 patients), and randomly divided into two groups using a computer-generated randomization list. Patients and investigators were blinded. IT included transarterial oily chemoembolization (TOCE) or a combination of TOCE and percutaneous ethanol injection treatment (PEIT). RESULTS: Patients in the IT+MGN-3 group showed: (i) lower recurrence of the disease, 31.6% (12/38), as compared to 46.7% (14/30) for the control; (ii) higher survival after the second year, 35%, as compared to 6.7% for the control; (iii) significantly lower alpha-fetoprotein level, a 38% decrease (p = 0.0001), as compared to baseline value, while the control showed no significant change; and (iv) a significant decrease in tumor volume, in contrast to the control, which showed no significant change. When the results were analyzed according to each IT modality, MGN-3+IT sub-groups displayed a greater response to treatment, in every aspect examined, than the IT sub-groups alone. However, the patients in the MGN-3+TOCE+PEIT sub-group demonstrated greater reduction in AFP levels and longer survival time than the MGN-3+TOCE sub-group. CONCLUSION: MGN-3 in conjunction with IT may be useful for the treatment of hepatocellular carcinoma and warrants further investigation in multiple clinical trials.

MRN-100, an Iron-based Compound, Possesses Anti-HIV Activity In Vitro.

We examined the in vitro anti-human immunodeficiency virus (HIV) activity of MRN-100, an iron-based compound derived from bivalent and tervalent ferrates. MRN-100 action against HIV-1 (SF strain) was tested in primary cultures of peripheral blood mononuclear cells (MNC) by analyzing p24 antigen production and percent survival of MNC infected with HIV. MRN-100 at a concentration of 10% (v/v) inhibited HIV-1 replication in 11 out of 14 samples (79%). The percentage of suppression of p24 antigen was -12.3 to 100% at 10 days post-treatment. MRN-100 also exhibited a significant protective effect in the survival of HIV-1-infected MNC. MNC survival post-treatment was dose dependent, 70.4% ± 8.4, 83.6% ± 10.7 and 90% ± 11.4, at concentrations 2.5, 5 and 10% (v/v), respectively, as compared with 53% ± 4 for HIV-1-infected MNC without treatment. The effect was detected as early as 4 days and continued up to 11 days. Treatment with MRN-100 caused no significant change in proliferative response of MNC alone or cocultured with different mitogens: PHA and Con-A (activators of T cell function) and PWM (activator of CD4(+) T cell-dependent B cells). We concluded that MRN-100 possesses anti-HIV activity in vitro and without an increase in lymphocyte proliferation, MRN-100 may be a useful agent for treating patients with acquired immunodeficiency syndrome.