1.
Surufatinib in Chinese Patients with Locally Advanced or Metastatic Differentiated Thyroid Cancer and Medullary Thyroid Cancer: A Multicenter, Open-Label, Phase II Trial.
Chen, J, Ji, Q, Bai, C, Zheng, X, Zhang, Y, Shi, F, Li, X, Tang, P, Xu, Z, Huang, R, et al
Thyroid : official journal of the American Thyroid Association. 2020;(9):1245-1253
Abstract
Background: Thyroid cancer is the most common endocrine tumor with an increasing incidence. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Surufatinib targets multiple kinases (vascular endothelial growth factor receptors, fibroblast growth factor receptor-1, and colony-stimulating factor-1 receptor) involved in tumor angiogenesis and tumor immune evasion. Surufatinib has demonstrated promising antitumor activity in various advanced solid tumors. This study aimed to determine the objective response rate (ORR) of surufatinib in patients with locally advanced or distant metastatic differentiated thyroid cancer (DTC) or medullary thyroid cancer (MTC). Methods: This Phase II open-label study by Simon's two-stage design was conducted at 10 sites across China. Patients with radioiodine (RAI)-refractory DTC with locally advanced disease or distant metastasis (DTC1 group); patients who received limited initial surgery and then developed locally advanced unresectable recurrences and were not considered candidates for RAI therapy due to residual normal thyroid tissue (DTC2 group); or patients with MTC with locally advanced disease or distant metastasis (MTC group) were enrolled. A total of 59 patients were enrolled (26 in DTC1, 6 in DTC2, and 27 in MTC) and received 300 mg surufatinib daily in 28-day cycles. The primary endpoint was ORR as determined by the investigators. Results: Overall ORR was 23.2% [95% confidence interval, CI 12.98-36.42]: 21.7% in the DTC1 cohort, 33.3% in the DTC2 cohort, and 22.2% in the MTC cohort. Forty-nine patients achieved disease control (87.5% [CI 75.93-94.82]): 87.0% in the DTC1 cohort, 83.3% in the DTC2 cohort, and 88.9% in the MTC cohort. Median time to response was 59.0 days, and 59.0, 85.5, and 59.0 days in the DTC1, DTC2, and MTC cohorts. Overall median progression-free survival was 11.1 months [CI 5.98-16.69]; 11.1 months in DTC1 and MTC cohorts, while the DTC2 cohort had not reached the median at the data cutoff. The most common treatment-emergent adverse events grade ≥3 were hypertension (20.3%), proteinuria (11.9%), and then elevated blood pressure, hypertriglyceridemia, and pulmonary inflammation (5.1% each). Conclusions: Surufatinib demonstrated promising efficacy with a tolerable and manageable safety profile for patients with locally advanced or metastatic MTC, RAI-refractory DTC, or locally advanced unresectable recurrences unable to receive RAI.
2.
The RADAR study: week 48 safety and efficacy of RAltegravir combined with boosted DARunavir compared to tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Impact on bone health.
Bedimo, RJ, Drechsler, H, Jain, M, Cutrell, J, Zhang, S, Li, X, Farukhi, I, Castanon, R, Tebas, P, Maalouf, NM
PloS one. 2014;(8):e106221
Abstract
BACKGROUND NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression. METHODS In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48. RESULTS Using an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48 (p = 0.045; chi-square test). The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4+ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (-0.25 vs. -0.71 mg/dL (p = 0.270), and eGFR (-4.4 vs. -7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. -7 g/cm2 with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = -0.394, p = 0.003 for CTX; and R = -0.477, p<0.001 for P1NP). CONCLUSION The NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health. TRIAL REGISTRATION ClinicalTrials.gov NCT 00677300.
3.
[Impact on the carotid intima-medial thickness and safety of rosuvastatin in Chinese patients with carotid atherosclerosis: a meta-analysis].
Feng, X, Zhang, J, Liu, M, Li, X
Zhonghua xin xue guan bing za zhi. 2014;(3):247-53
Abstract
OBJECTIVE To evaluate the efficacy and safety of rosuvastatin in Chinese patients with carotid atherosclerosis. METHOD A systematic search of Pubmed, EMBase, CENTRAL, CBMdisc, CNKI and WANFANG databases up to January 2013 was performed to identify studies comparing rosuvastatin with a placebo or other statins on carotid intima-medial thickness (IMT) with a minimum follow-up of 6 months in Chinese patients. Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included studies independently by two reviewers. RESULTS Twenty-eight studies involving 1 392 individuals were included in this review. The pooled weighted mean difference (WMD) between rosuvastatin and placebo or control on IMT was 0.28 mm (95%CI 0.14-0.42, P < 0.01), with 0.31 mm (95%CI 0.14-0.49, P < 0.01) on 6-8 months and 0.16 mm (95%CI 0.05-0.27, P = 0.005) on 12 months, respectively. Analysis on studies in core journals showed the WMD between rosuvastatin and placebo or control on IMT was 0.18 mm (95%CI 0.09-0.27, P < 0.01). The WMD between rosuvastatin and other statins on IMT was 0.06 mm (95%CI 0.04-0.08, P < 0.01). The WMD between rosuvastatin and placebo or control on plaque score was 0.89 (95%CI 0.78-0.99, P < 0.01). The WMD between rosuvastatin and placebo or control on plaque area was 1.46 (95%CI 0.67-2.25, P < 0.01).Reports of adverse effect were elevated liver enzyme (2.30%, 19/825), elevated muscle enzyme (0.73%, 6/825), muscle aches (0.61%, 5/825). CONCLUSIONS Rosuvastatin therapy is effective and safe to decrease IMT in Chinese patients with carotid atherosclerosis.
4.
Liver X receptor agonist alleviated high glucose-induced endothelial progenitor cell dysfunction via inhibition of reactive oxygen species and activation of AMP-activated protein kinase.
Li, X, Song, Y, Han, Y, Wang, D, Zhu, Y
Microcirculation (New York, N.Y. : 1994). 2012;(6):547-53
Abstract
OBJECTIVE Liver X receptors (LXRs) are key regulators of cholesterol homeostasis. Synthetic LXR agonists are anti-atherogenic and anti-inflammatory. However, the effect of LXR agonists on endothelial progenitor cell (EPC) function is largely unknown. Here, we explored the effect of the LXR agonist TO901317 (TO) on EPC biology and the underlying mechanisms. METHODS Endothelial progenitor cells were cultured in mannitol or 30 mm glucose (high glucose) for 24 hours. For TO treatments, cells were pretreated with TO (10 μm) for 12 hours, then mannitol or high glucose was added for an additional 24 hours. EPCs function, reactive oxygen species (ROS) release, and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) were analyzed. RESULTS TO could restore the high glucose-impaired adhesion and migration capacity of EPCs. High glucose impaired EPC-mediated angiogenesis, and TO reversed the impairment. TO also alleviated ROS release induced by high glucose. Western blot analysis revealed that high glucose downregulated the phosphorylation of AMPK and endothelial nitric oxide synthase, which could be reversed with TO treatment. Furthermore, inhibiting AMPK activation by compound C could abolish the protective effects of TO on EPCs. CONCLUSIONS TO had a protective effect on EPCs under high glucose by inhibiting ROS release and activating AMPK.