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Anlotinib for the Treatment of Patients with Locally Advanced or Metastatic Medullary Thyroid Cancer.
Sun, Y, Du, F, Gao, M, Ji, Q, Li, Z, Zhang, Y, Guo, Z, Wang, J, Chen, X, Wang, J, et al
Thyroid : official journal of the American Thyroid Association. 2018;(11):1455-1461
Abstract
BACKGROUND The prognosis of advanced or metastatic medullary thyroid carcinoma (MTC) is poor, and there are few therapeutic options. Anlotinib has previously shown promising antitumor activity on MTC in preclinical models and a Phase I study. This Phase II clinical trial was devised to confirm the antitumor activity of anlotinib in patients with advanced or metastatic MTC. METHODS Patients with unresectable locally advanced or metastatic MTC received once daily oral anlotinib 12 mg, two weeks on/one week off, until disease progression, death, unacceptable toxicity, or withdrawal of consent for any reason. The dose was adjusted on the basis of observed toxicity. The primary endpoint was progression-free survival (PFS). RESULTS Fifty-eight patients received anlotinib treatment. The primary endpoint PFS has not yet been reached at the time of analysis. On the basis of investigator assessments, 56.9% of patients experienced a partial response. PFS rate at 48 weeks was 85.5%. Forty-five patients had a ≥50% decrease in serum calcitonin concentration from baseline. The most common adverse events were hand-foot syndrome, hypertriglyceridemia, cholesterol elevation, fatigue, and proteinuria. CONCLUSIONS Anlotinib demonstrated a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic MTC.
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Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake.
Chen, X, Zhang, J, Yuan, L, Lay, Y, Wong, YK, Lim, TK, Ong, CS, Lin, Q, Wang, J, Hua, Z
Molecules (Basel, Switzerland). 2017;(9)
Abstract
Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR's anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling.
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Activation of microbubbles by low-intensity pulsed ultrasound enhances the cytotoxicity of curcumin involving apoptosis induction and cell motility inhibition in human breast cancer MDA-MB-231 cells.
Li, Y, Wang, P, Chen, X, Hu, J, Liu, Y, Wang, X, Liu, Q
Ultrasonics sonochemistry. 2016;:26-36
Abstract
Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy.
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The clinical research of the endoscopic sequential treatment for patients with intermediate-advanced esophageal cancer: a randomized clinical trial.
Wen, L, Quan, H, Li, L, Huang, C, Chen, X, Yang, Y, Wang, L, He, X, Zhang, X
Medical oncology (Northwood, London, England). 2014;(12):284
Abstract
We tried to find an ideal therapeutic regimen for patients with advanced esophageal cancer. Totally 240 patients with advanced esophageal cancer were randomly divided into experimental group (endoscopic sequential treatment, 126 cases) and control group (traditional treatment, 114 cases) with a 2-year follow-up period. The experimental group was randomly divided into three subgroups: group A: local chemotherapeutic drug injection with ordinary metal stent implantation; group B: local chemotherapeutic drug injection with iodine-125 particle implantation; and group C: radiofrequency (RF) therapy with ordinary metal stent group. The control group was also randomly divided into three subgroups: group D: local chemotherapeutic drug injection group; group E: RF therapy group; and group F: common metal stent implantation group. The survival rate, survival quality, adverse reactions, and complications were compared among these groups. A significant improvement of curative effect was found in the experimental group. Group A and B had higher survival rate and survival quality, and lower esophagotracheal fistula incidence and metastasis rate, compared with group C. There was no significant difference in survival rate between group A and group B, while the quality of life was higher in group B than in group A. While patients in group B had lower esophagotracheal fistula incidence and metastasis rate comparing with group A. Local chemotherapeutic drug injection combined with iodine-125 particle stent might be an effective sequential treatment to improve the life quality of advanced esophageal cancer patients.
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Statil suppresses cancer cell growth and proliferation by the inhibition of tumor marker AKR1B10.
Cao, Z, Zhou, B, Chen, X, Huang, D, Zhang, X, Wang, Z, Huang, H, Wang, Y, Cao, D
Anti-cancer drugs. 2014;(8):930-7
Abstract
Aldo-keto reductase 1B10 (AKR1B10) is an oncogenic carbonyl reductase that eliminates α,β-unsaturated carbonyl compounds/lipid peroxides and mediates retinoic acid signaling. Targeted inhibition of AKR1B10 activity is a newly emerging strategy for cancer therapy. This study evaluated the inhibitory activity of a small chemical statil towards AKR1B10 and tested its antiproliferative activity in breast (BT-20) and lung (NCI-H460) cancer cells that express AKR1B10. Experimental results showed that statil inhibited AKR1B10 enzyme activity efficiently, with an IC50 at 0.21±0.06 µmol/l. Exposing BT-20 and NCI-H460 cells to statil and diclofenac, a selective AKR1B10 inhibitor, led to dose-dependent inhibition of cell growth and proliferation and plating efficiency. At higher doses (50 µmol/l or higher), statil induced cell death with apoptotic characteristics, such as DNA fragmentation and Annexin-V staining. Furthermore, statil enhanced the susceptibility of cells to acrolein, an active substrate of AKR1B10. Taken together, these data suggest that statil possesses potent antiproliferative activity by inhibiting AKR1B10 activity.
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Rigid nanoparticle-based delivery of anti-cancer siRNA: challenges and opportunities.
Wang, Z, Liu, G, Zheng, H, Chen, X
Biotechnology advances. 2014;(4):831-43
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Abstract
Gene therapy is a promising strategy to treat various genetic and acquired diseases. Small interfering RNA (siRNA) is a revolutionary tool for gene therapy and the analysis of gene function. However, the development of a safe, efficient, and targetable non-viral siRNA delivery system remains a major challenge in gene therapy. An ideal delivery system should be able to encapsulate and protect the siRNA cargo from serum proteins, exhibit target tissue and cell specificity, penetrate the cell membrane, and release its cargo in the desired intracellular compartment. Nanomedicine has the potential to deal with these challenges faced by siRNA delivery. The unique characteristics of rigid nanoparticles mostly inorganic nanoparticles and allotropes of carbon nanomaterials, including high surface area, facile surface modification, controllable size, and excellent magnetic/optical/electrical properties, make them promising candidates for targeted siRNA delivery. In this review, recent progresses on rigid nanoparticle-based siRNA delivery systems will be summarized.
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VEGF pathway-targeted therapy for advanced renal cell carcinoma: a meta-analysis of randomized controlled trials.
Liu, F, Chen, X, Peng, E, Guan, W, Li, Y, Hu, Z, Ye, Z, Zhuang, Q
Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. 2011;(6):799-806
Abstract
Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma (mRCC). Anti-angiogenesis-targeted therapy has recently been identified as a promising therapeutic strategy for mRCC. This study was aimed to evaluate the effectiveness of vascular endothelial growth factor (VEGF) pathway-targeted therapy for mRCC by comparing its effectiveness with that of immunotherapy. The electronic databases were searched. Randomized controlled trials (RCTs) on comparison of VEGF inhibiting drugs (sorafenib, sunitinib and bevacizumab) with interferon (IFN) or placebo for mRCC treatment were included. Data were pooled to meta-analyze. A total of 7 RCTs with 3451 patients were involved. The results showed that anti-VEGF agents improved progression-free survival (PFS) and offered substantial clinical benefits to patients with mRCC. Among them, sunitinib had a higher overall response rate (ORR) than IFN (47% versus 12%, P<0.000001). Bevacizumab plus IFN produced a superior PFS [risk ratio (RR): 0.86, 95% confidence interval (CI): 0.76-0.97; P=0.01] and ORR (RR: 2.19; 95% CI: 1.72-2.78; P<0.00001) in patients with mRCC over IFN, but it yielded an increase by 31% in the risk of serious toxic effects (RR: 1.31; 95% CI: 1.20-1.43; P<0.00001) as compared with IFN. The overall survival (OS) was extended by sorafenib (17.8 months) and sunitinib (26.4 months) as compared with IFN (13 months). It was concluded that compared with IFN therapy, VEGF pathway-targeted therapies improved PFS and achieved significant therapeutic benefits in mRCC. However, the risk to benefit ratio of these agents needs to be further evaluated.