1.The mechanism research of STIM1 in breast cancer cells
Bing WU ; Tianji LIN ; Shijuan RUAN ; Bin WANG ; Fei ZOU
The Journal of Practical Medicine 2017;33(9):1373-1376
Objectives To explore the calcium signaling mechanism of STIM1 in breast cancer cells. Meth-ods After SiRNA interruption, Western blot and Transwell were used to measure protein expression of STIM1 and cell migration in MDA-MB-231 cells respectively. The relationship between STIM1 and SOCE calcium signaling were analysed by Laser confocal microscopy. Western blots were used to measure protein expression of FAK after si-lence STIM1. Results The numbers of cells without STIM1 were significantly lower than those cells with STIM1 by Transwell assay. STIM1 mediated SOCE in MDA-MB-231. Blocking SOCE might inhibite cells migration. Si-lence STIM1 did not affect the expression or activation of FAK in MDA-MB-231 cells. Conclusion STIM1 influ-ences cell migration through SOCE pathway in breast cancer cells, which is independent on the expression or activa-tion of FAK.
2.Oral JS-38, a metabolite from Xenorhabdus sp., has both anti-tumor activity and the ability to elevate peripheral neutrophils.
Min-Yu LIU ; Lin XIAO ; Geng-Hui CHEN ; Yong-Xiang WANG ; Wei-Xia XIONG ; Fei LI ; Ying LIU ; Xiao-Ling HUANG ; Yi-Fang DENG ; Zhen ZHANG ; Hai-Yan SUN ; Quan-Hai LIU ; Ming YIN
Chinese Journal of Natural Medicines (English Ed.) 2014;12(10):768-776
AIM:
JS-38 (mitothiolore), a synthetic version of a metabolite isolated from Xenorhabdus sp., was evaluated for its anti-tumor and white blood cell (WBC) elevating activities.
METHOD:
These anti-proliferative activities were assessed in vitro using a panel of ten cell lines. The anti-tumor activities were tested in vivo using B16 allograft mouse models and xenograft models of A549 human lung carcinoma and QGY human hepatoma in nude mice. The anti-tumor interactions of JS-38 and cyclophosphamide (CTX) or 5-fluorouracil (5-Fu) were studied in a S180 sarcoma model in ICR mice. Specific stimulatory effects were determined on peripheral neutrophils in normal and CTX- and 5-Fu-induced neutropenic mice.
RESULTS:
The IC50 values ranged from 0.1 to 2.0 μmol·L(-1). JS-38 (1 μmol·L(-1)) caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38 (15, 30, and 60 mg·kg(-1)·d(-1)) inhibited in vivo tumor progression without a significant effect on body weight. JS-38 additively enhanced the in vivo anti-tumor effects of CTX or 5-Fu. JS-38 increased peripheral neutrophil counts and neutrophil rates in normal BALB/c mice almost as effectively as granulocyte colony-stimulating factor (G-CSF). In mice with neutropenia induced by CTX or 5-Fu, JS-38 rapidly restored neutrophil counts.
CONCLUSION
These results suggest that JS-38 has anti-tumor activity, and also has the ability to increase peripheral blood neutrophils.
Animals
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Antineoplastic Agents
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administration & dosage
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metabolism
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Cell Count
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Female
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Humans
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Hydrocarbons, Fluorinated
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administration & dosage
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metabolism
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Lung Neoplasms
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drug therapy
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physiopathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred ICR
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Neutrophils
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cytology
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drug effects
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Xenorhabdus
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chemistry
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metabolism
3.A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis.
Lin CAI ; Gen-Hui CHEN ; Qian-Jin LU ; Min ZHENG ; Yu-Zhen LI ; Jin CHEN ; Jie ZHENG ; Fu-Ren ZHANG ; Jian-Bin YU ; Sen YANG ; Fu-Qiu LI ; Sheng-Xiang XIAO ; Qiu-Ning SUN ; Jin-Hua XU ; Xing-Hua GAO ; Hong FANG ; Tian-Wen GAO ; Fei HAO ; Quan-Zhong LIU ; Ya-Ting TU ; Ruo-Yu LI ; Bao-Xi WANG ; Dan-Qi DENG ; Qing-Shan ZHENG ; Hong-Xia LIU ; Jian-Zhong ZHANG
Chinese Medical Journal 2020;133(24):2905-2909
BACKGROUND:
Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis.
METHODS:
We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12.
RESULTS:
The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported.
CONCLUSION:
During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method
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Follow-Up Studies
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Humans
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Ointments
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Psoriasis/drug therapy*
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Resorcinols
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Severity of Illness Index
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Stilbenes
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Treatment Outcome