1.Study on anti-tumor mechanism of Chinese medicine Fuzhengyiliufufang by molecular docking method
Chunsong ZHENG ; Liwu CHEN ; Jian DU ; Hongzhi YE
Chinese Journal of Clinical Pharmacology and Therapeutics 2004;0(08):-
AIM:To investigate the anti-tumor effects of Chinese medicine Fuzhengyiliufufang(FZYLFF) and its mechanism.METHODS:Molecular docking was apllied to simulate the interactions between Chinese medicine small molecules and TNF-?,IL-2 receptors respectively,with the aid of ligand-fit module in the software package Cerius2 4.10 of Accelrys company,to predict the effects of FZYLFF on anti-tumor.RESULTS:According to the dockscore of original ligand and the receptor as threshold value,thirty-seven molecules were predicted to have good interactions with TNF-? and ten molecules with IL-2.CONCLUSION:FZYLFF is a promising Chinese medicine for tumor therapy.Its mechanism is possibly attributed to indirect inhibition by interfering inflammatory cell factors and enhancing immunoregulation.
2.Percutaneous intratumoral injection of ricin-loaded thermosensitive hydrogel in treatment of hepatic carcinoma xenograft
Zhikui CHEN ; Liwu LIN ; Faduan YANG ; Xiaodong LIN ; Ensheng XUE ; Bin ZHENG ; Yan WANG ; Yimi HE ; Shangda GAO
Chinese Journal of Ultrasonography 2008;17(7):631-633
Objective To evaluate the effectiveness and feasibility of riein-loaded thermosenaitive hydrogel in percutaneous intratumoral injection for treatment of hepatic carcinoma. Methods BALB/c-nu mice were inoculated subcutaneously in the right flank with human liver cancer cell line HepG2. A total of 32 male mice bearing subcutaneous hepatic carcinoma (7-10mm in diameter) were randomized into 4 groups. Each group of mice were administered percutaneous intratumoral injection of different agents as follows: salin, thermosensitive hydrogel,ricin, ricin-loaded thermosensitive hydrogel. The tumor volume was totally measured 3 times by high frequency ultrasound once a week. One mouse of each group was sacrificed to perform tumor histopathological examination on 7th day, 14th day, respectively, and survival time of the remaining mice was recorded. Results After intratumoral therapy,tumor volume in ricin group was smaller than that of saline group on 7th day, 14th day and 21st day( P<0.01 ),and mice got a life-prolonging rate of 36.8%. In ricin-loaded thermosensitive hydrogel group,obvious necrosis occurred in tumors treated since 5th day, and the tumor almost regressed on 21st day. Histopathological assay showed serious necrosis with a large number of leucocyte infiltration in tumor. All the remaining mice treated with riein-loaded thermosensitive hydrogel survived at the end of experiment sans tumor recurrence. Conclusions Percutaneous intratutnoral injection of ricin-loaded thermosensitive hydrogel could completely ablate hepatic carcinoma,which may provide an effective and feasible method for tumor ablation therapy.
3.Clinical outcomes of the vulnerable plaque sealing with drug-eluting stents for the treatment of intermedi-ate coronary stenosis
Hanhua ZHU ; Weide YANG ; Ping ZHENG ; Xiaoming HUANG ; Guilin BU ; Ying MIAO ; Xiaoyan MA ; Xiufeng LUO ; Feng CHEN ; Liwu TAN
The Journal of Practical Medicine 2017;33(17):2877-2880
Objective To evaluate the one-year clinical outcomes in patients with the vulnerable plaque sealing with drug-eluting stents for the treatment of intermediate coronary stenosis. Methods 327 patients with an-giographically intermediate lesions(diameter stenosis 50%~70%)with the vulnerable plaque which were detected by 64 slice coronary CT were prospectively enrolled. Patients were divided into medical therapy group (n = 160) and sirolimus-eluting stent group group(n=160). The incidences of one-year major adverse cardiovascular events (MACE)was evaluated(cardiac death,myocardial infarction ,revascularization). Results The MACE tended to be lower in the sirolimus-eluting stent group than medical therapy group(3.13%vs. 10%,log-rankχ2=6.62,P=0.01). The incident of cardiac death and myocardial infarction were lower in the sirolimus-eluting stent group than medical therapy group(1.25%vs. 5.63%,log-rankχ2=4.61,P=0.03). Conclusion The treatment of the siroli-mus-eluting stent can reduce MACE for the paitents with the vulnerable plaque of intermediate coronary stenosis than medical therapy only.
4.Clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder
Shuping ZHOU ; Shimin LI ; Yingguang SHI ; Liwu ZHENG ; Chaonan CHANG ; Junjie CHEN ; Huanpeng WANG ; Ke SUN ; Xiuhuan WANG ; Linbo LIU
Chinese Journal of Burns 2024;40(7):665-672
Objective:To explore the clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder.Methods:The study was a retrospective observational study. From April 2016 to December 2022, 4 cases with circular hot crush injuries in limbs with blood supply disorder were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 3 males and 1 female, aged from 24 to 48 years. Among them, 2 cases were injured in the calf and 2 cases were injured in the forearm. After emergency debridement, the area of skin and soft tissue defects was from 20 cm×20 cm to 44 cm×20 cm. The patients had defects in tibialis anterior and posterior tibial arteries with a length of 13 to 18 cm, and in ulnar and radial arteries with a length of 9 to 12 cm. Flaps were designed and cut, including a flow-through anterolateral thigh perforator flap with area of 20 cm×9 cm to 24 cm×21 cm carrying the descending branch of the lateral circumflex femoral artery and the accompanying veins of 8 to 18 cm in length; and a flow-through posterior tibial artery perforator flap with area of 21 cm×13 cm and 20 cm×14 cm carrying the posterior tibial artery, the accompanying veins with a length of 14 and 17 cm respectively, and the great saphenous vein with a length of 22 and 21 cm. The circular hot crush injury wounds in the calf with blood supply disorder were repaired by a parallel combination of flow-through posterior tibial artery perforator flap and flow-through anterolateral thigh perforator flap, and the circular hot crush injury wounds in the forearm with blood supply disorder were repaired by a parallel combination of bilateral flow-through anterolateral thigh perforator flap, and the injured main vessels were reconstructed. The donor site wounds of flap were closed directly or treated with split-thickness skin grafts from abdomen. After surgery, the blood supply and survival of the flap and distal affected limb, the healing of wounds in the donor and recipient sites, the survival of the skin graft in the flap donor site were observed. During follow-up, the condition of flaps, the appearance, blood supply, and function of affected limbs were observed. At the last follow-up, the foot and ankle functions were evaluated according to the scoring standards of American Orthopedic Foot and Ankle Association, and the wrist and hand function was evaluated according to the trial standard of replantation of amputated upper limb function assessment of the Hand Surgery of Chinese Medical Association. Results:The flaps and distal affected limbs of 4 patients had good blood circulation and successfully survived after surgery. The wounds of 3 cases successfully healed, while one patient with circular hot crush injury in the forearm experienced exudation in the recipient site in the later stage, and the wound healed after re-expansion and suturing. The donor site wounds healed smoothly, and the skin grafts successfully survived. During follow-up of 12 to 24 months after surgery, the flaps were slightly swollen, the limbs had good appearance, normal blood circulation, and fine functional recovery. At the last follow-up, the foot and ankle function of 2 patients with circular hot crush injuries in the calf was evaluated as good in 1 case and commonly in 1 case; the wrist and hand function of 2 patients with circular hot crush injuries in the forearm was evaluated as excellent in 1 case and good in 1 case.Conclusions:The parallel combined flow-through perforator flap can reconstruct the damaged main blood vessels and repair the wound at the same time. It can not only effectively save the limb, but also restore part of the function of the affected limb. It is one of the effective methods to treat the circular hot crush injuries in limbs with blood supply disorder.
5.Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells and o.
Fanpu ZENG ; Fang WANG ; Zongheng ZHENG ; Zhen CHEN ; Kenneth Kin WAH TO ; Hong ZHANG ; Qian HAN ; Liwu FU
Acta Pharmaceutica Sinica B 2020;10(5):799-811
Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.