Targeting Glutamine Metabolism with a Novel Na+/K+-ATPase Inhibitor RX108 in Hepatocellular Carcinoma.

The poor prognosis and limited therapeutic options for human hepatocellular carcinoma (HCC), the most common form of liver cancer, highlight the urgent need to identify novel therapeutic modalities. Here, we describe the antitumor activity and underlying molecular mechanisms of a novel Na+/K+-ATPase inhibitor RX108 in human HCC cells and its xenograft model. RX108 dose-dependently inhibited HCC cell proliferation in vitro and tumor growth in a xenograft mouse model, and that the inhibition was associated with induction of apoptosis. Mechanistically, RX108 significantly downregulated alanine serine cysteine transporter 2 (ASCT2) protein expression and reduced glutamine and glutamate concentration in HCC cells and tumors. In addition, RX108 exposure led to a significant decrease in cell energy metabolism in Huh7 and Hep3B cells, including decreased levels of glutathione, NADH, NADPH, and mitochondrial respiration oxygen consumption rate. Furthermore, HCC cells exhibited evidence of glutamine addiction; the antiproliferative effect of RX108 was dependent on glutamine transport. Clinically, elevated ASCT2 mRNA expression in HCCs was associated with unfavorable survival. Taken together, these findings reveal a novel approach to target glutamine metabolism through inhibiting Na+/K+-ATPase and provide a rationale for using RX108 to treat HCC in patients whose tumors express ASCT2 at high levels. RX108 is currently under clinical development.

Gutuo Jiejiu decoction improves survival of patients with severe alcoholic hepatitis: A retrospective cohort study.

AIM: To verify the value of Gutuo Jiejiu decoction in improving the survival of patients with severe alcoholic hepatitis (SAH). METHODS: We performed a retrospective cohort study in consecutive patients diagnosed with SAH at the Teaching Hospital of Chengdu University of Traditional Chinese Medicine and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. The traditional Chinese medicine formula Gutuo Jiejiu decoction was employed as an exposure factor. Patients from the Teaching Hospital of Chengdu University of Traditional Chinese Medicine who had been treated with Gutuo Jiejiu decoction + prednisone were assigned to an observation group, and patients from Shuguang Hospital, Shanghai University of Traditional Chinese Medicine who had been treated with prednisone alone were selected as a control group. A retrospective analysis was performed by comparing age, alcohol intake, and clinical parameters of liver injury before and after treatment. Additionally, the 3- and 12-mo survival rates and the occurrence of complications were analyzed. RESULTS: One hundred and twenty-eight eligible patients were selected from 175 cases with SAH, of which 68 were assigned to the observation group and the other 60 to the control group. No significant difference was found in the patients' baseline characteristics (P > 0.05). However, significant improvements of 90-d survival rate [56/68 (82.4%) vs 27/60 (45.0%), P = 0.0000] and 365-d survival rate [48/68 (70.6%) vs 13/60 (21.7%), P = 00000] were observed in the observation group after treatment. After the first 3 mo of treatment, more improvements in the clinical parameters and scoring systems related to liver injury occurred in the observation group than in the control group (P < 0.05). After treatment for 12 mo, the differences in the clinical parameters and scoring systems related to liver injury between the two groups were more significant (P < 0.05). No significant differences in complications and adverse effects were found between the two groups. CONCLUSION: Gutuo Jiejiu decoction could improve the survival rates and clinical parameters of liver injury in patients with SAH, and may represent a new option for treating SAH.

Moxibustion for Primary Dysmenorrhea at Different Interventional Times: A Systematic Review and Meta-Analysis.

Primary dysmenorrhea (PD) is one of the most common diseases in gynecology at present. Some clinical trials have reported the effects of moxibustion and confirmed temporal factors are the important elements influencing the efficacy of moxibustion. However, no systematic review has yet been conducted. In this study, we assessed the effects of moxibustion in patients with PD enrolled in randomized controlled trials (RCTs) and the difference among different intervention times to start moxibustion. We extracted data for studies searched from 10 electronic databases and evaluated the methodological quality of the included studies. We discussed three outcomes: effective rate, pain remission, and the level of PGF2α in serum. Current clinical researches showed that, compared with nonmoxibustion treatments for PD, moxibustion leads to higher effective rate and lower level of PGF2α in serum. However, there was no difference in using moxibustion to treat PD at different intervention times. Based on the theory of Chinese medicine and the results of this study, choosing 5 ± 2 days before menstruation to start moxibustion can achieve good efficacy for PD patients. However, more high-quality RCTs are needed to confirm the conclusions.

[Synergism and attenuation effects of taurine on cyclophosphamide].

BACKGROUND AND OBJECTIVE: Cyclophosphamide (CTX) is a commonly used clinical antitumor drug with severe side effects. Therefore, it is important to find ancillary drugs which have synergism and attenuation effects on CTX. This study was to investigate the synergism and attenuation effects of taurine (Tau) on CTX via different administration methods. METHODS: S180-bearing mice were given Tau combined with CTX via either intravenous injection or intragastric administration. The tumor inhibition rate, the count of bone marrow nucleate cells and white blood cells, the spleen index, the thymus index, lymphocyte proliferation and the phagocytic activity of peritoneal macrophage were calculated. RESULTS: The tumor inhibition rates of intravenous administration of 40 mg * kg(-1), 80 mg * kg(-1),160 mg * kg(-1) Tau combined with CTX (20 mg * kg(-1)) were 66.4%, 74.5% and 84.6%, while those of intragastric administration of 160 mg * kg(-1), 320 mg * kg(-1), 640 mg * kg(-1) Tau with CTX (20 mg * kg(-1)) were 60.1%, 69.7% and 81.2%, all of which were higher than that of CTX administration (20 mg * kg(-1)) alone (55.8%). Compared to the CTX group, the count of bone marrow nucleate cells and the white blood cells, the spleen index, the thymus index, lymphocyte proliferation and the phagocytic activity of peritoneal macrophage were elevated in all Tau and CTX combination groups. CONCLUSION: Tau has synergism and attenuation effects on CTX via both intravenous and intragastric administration.