Context: Hepatocellular carcinoma (HCC) is a common cancer around the world, with high mortality rate. Currently, there is no effective drug for the therapy of HCC. Ursolic acid (UA) is a natural product which exists in various medicinal herbs and fruits, exhibiting multiple biological effects such as its outstanding anticancer and hepatoprotective activity, which has drawn many pharmacists' attention.Objective: This paper summarizes the current status of the hepatoprotective activity of UA analogues and explains the related mechanism, providing a clear direction for the development of novel anti-HCC drugs.Methods: All of the data resources were derived from PubMed. By comparing the IC50 values and analyzing the structure–activity relationships, we listed compounds with good pharmacological activity from the relevant literature, and summarized their anti-HCC mechanism.Results: From the database, 58 new UA derivatives possessing wonderful anticancer and hepatoprotective effects were listed, and the relevant anti-HCC mechanism were discussed.Conclusion: UA's anti-HCC effect is the result of combined action of many mechanisms. These 58 new UA derivatives, particularly compounds 45 and 53, can be used as potential drugs for the treatment of liver cancer.
5543 Background: High grade serous ovarian cancers (HGSC) with BRCA mutation are biologically unique, with distinct molecular and clinical behaviour from sporadic cases. It is unclear if these biological differences translate to favorable outcomes at the time of primary cytoreductive surgery (PCS). The aim of this study is to compare the amount of residual disease following PCS in BRCA-mutated (BRCAm) and wildtype (BRCAwt) HGSC, and to assess whether BRCA status is an independent predictor of residual disease. Methods: We conducted a retrospective analysis of patients with HGSC with known germline and somatic BRCA mutation status, treated with PCS from 2000 to 2017. We compared the cytoreduction outcomes between the BRCAm and the BRCAwt cohorts and built a predictive model to assess whether BRCA status was associated with amount of residual disease at the time of PCS. Results: Of 355 women, 144 harbored germline or somatic BRCA mutations (41%) and 211 were BRCAwt (59%). BRCAm women tended to be younger (54 vs. 59; p < 0.001), but there were no differences between the two groups in stage, disease burden at presentation, surgical complexity score, length of surgery, or perioperative complications. The BRCAm group had a higher rate of complete cytoreduction to no residual disease (0mm) [75% vs. 54%], and a lower rate of optimal cytoreduction (1-9mm) [16% vs. 34%] or suboptimal cytoreduction (≥10mm) [9% vs. 12%] (p < 0.001). In our predictive model, after accounting for length of surgery, CA-125 level, stage, disease scores and surgical complexity scores, BRCAm status was predictive of complete cytoreduction to 0mm residual disease (OR 4.78; 95% CI 2.32-9.85; p < 0.001). Conclusions: BRCA status is predictive of complete cytoreduction at time of PCS in HGSC. Timely availability of BRCA testing is paramount as it may aid in the therapeutic decision making between PCS or neoadjuvant chemotherapy in women with newly diagnosed HGSC.
To study the effect of Zhibai Dihuang Pill (ZBDHP) on urokinase-type plasminogen activator (uPA) and sperm quality in ureaplasma urealyticum (Uu) infection infertile patients.Recruited were 80 infertility patients with Uu infection at Andriatrics Clinics and Department of Reproduction, including 130 cases of positive Uu semen and 50 cases of negative Uu semen. Patients with positive Uu semen were randomly assigned to the observation group (72 cases) and the control group (58 cases) according to the visit sequence. All patients took antibiotics for 2 weeks. Patients in the observation group additionally took ZBDHP, 6 g each time, twice daily. Those in the control group additionally took Vit E (100 mg each time, twice per day) and ATP (40 mg each time, twice per day). The therapeutic course for all was 90 days. Semen parameters and uPA contents of the sperm membrane were detected and comparatively analyzed.The sperm membrane uPA content, the sperm motility, the sperm viability, and the percentage of normal morphology sperm in Uu positive infected patients were lower than those in Uu negative infected patients with statistical difference (P < 0.05), but with no significant difference in the sperm density between the two groups (P > 0.05). There was no statistical difference in pre-treatment sperm membrane uPA contents and sperm parameters between the two groups (P > 0.05). Compared with before treatment in the same group, the sperm membrane uPA content, the sperm motility, the sperm viability, and the percentage of normal morphology sperm obviously increased in the two groups with statistical difference (P < 0.05). After treatment, the sperm membrane uPA content increased more obviously in the observation group, with statistical difference when compared with the control group (P < 0.05).Infection with Uu leads to decreased uPA content of sperm membrance and the sperm motility. ZBDHP could effectively treat Uu infected infertility possibly through fighting against Uu damaged sperm membrane and make the sperm membrane uPA content return to normal, and elevate the fertilizability of sperms.
<p>Detailed protocol of the HYDRA-1 (NCT03081702) Trial. TITLE: A phase I/II trial investigating the tolerability, toxicity and efficacy of hydroxychloroquine and itraconazole in patients with advanced platinum-resistant epithelial ovarian cancer (EOC) (HYDRA-1 study).</p>
<p>Detailed protocol of the HYDRA-1 (NCT03081702) Trial. TITLE: A phase I/II trial investigating the tolerability, toxicity and efficacy of hydroxychloroquine and itraconazole in patients with advanced platinum-resistant epithelial ovarian cancer (EOC) (HYDRA-1 study).</p>
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