ABSTRACT
Monoclonal antibody-based therapy has achieved great success and is now one of the most crucial therapeutic modalities for cancer therapy. The first monoclonal antibody authorized for treating human epidermal growth receptor 2 (HER2)-positive breast cancer is trastuzumab. However, resistance to trastuzumab therapy is frequently encountered and thus significantly restricts the therapeutic outcomes. To address this issue, tumor microenvironment (TME) pH-responsive nanoparticles (NPs) were herein developed for systemic mRNA delivery to reverse the trastuzumab resistance of breast cancer (BCa). This nanoplatform is comprised of a methoxyl-poly (ethylene glycol)-b-poly (lactic-co-glycolic acid) copolymer with a TME pH-liable linker (Meo-PEG-Dlink m -PLGA) and an amphiphilic cationic lipid that can complex PTEN mRNA via electrostatic interaction. When the long-circulating mRNA-loaded NPs build up in the tumor after being delivered intravenously, they could be efficiently internalized by tumor cells due to the TME pH-triggered PEG detachment from the NP surface. With the intracellular mRNA release to up-regulate PTEN expression, the constantly activated PI3K/Akt signaling pathway could be blocked in the trastuzumab-resistant BCa cells, thereby resulting in the reversal of trastuzumab resistance and effectively suppress the development of BCa.
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AIM: To detect the effect of conjunction matrigel with mammary fad pat(MFP)implantation on the tumorigenesis, proliferation, apoptosis and metastasis of Her2 positive and negative breast cancer model. METHODS: The Her2 positive BT 474 and Her2 negative MDA-MB 231 breast cancer cells were injected into MFP of nude mice with or without matrigel to establish breast cancer model. The tumor volume was measured every 3 d. Followed up for 30 d after implantation, the nude mice were killed and the tumors and associated organs were dissected for pathological sectioning and staining with hematoxylin and eosin. The time of tumor formation and the tumorigenesis were determined after implantation. The tumor volume and metastasis rate were calculated and compared with each other. The proliferation and apoptosis of Her2 positive and negative tumors were also determined. RESULTS: Matrigel and MFP implantation technology shortened the time of tumorigenesis significantly(P<0.01). The tumorigenesis rate of BT 474 and MDA-MB 231 breast cancer cells did not show any different(P>0.05). The metastasis rate of MDA-MB 231 breast cancer cells were improved from 25.0% to 37.5%(P<0.05). CONCLUSION: Matrigel and MFP implantation can be combined to shorten the time of tumor formation by two kinds of breast cancer cells, and improve the metastasis of Her2 negative MDA-MB 231 cells. Using matrigel does not show any effect of proliferation and apoptosis on Her2 positive and negative breast cancer cells.
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objective To evaluate the therapeutic efficacy of endovenous radiofrequency ablation in combination with TriVex for the treatment of chronic venous insufficiency (CVI)of the lower extremity.Methods One hundred and fifty CVI cases(150 limbs)were randomly assigned to Group A(75 limbs)and Group B(75 limbs).Patients in Group A were treated with greater saphenous vein radiofrequency ablation procedures in combination with TriVex.Patients in Grpup B were treated with greater saphenous vein traditional stripping operation in combination with TriVex.The short-term results in hospital and patient self-assessment for the operation at postoperative 4 week were compared with each other:The changes of CEAP classification and venous clinical severity score(VCSS)were compared. Results Operation time was(67±11)min in Group A versus(69-4-9)min in Group B(P＞0.05).Postoperative pain,average hospital stay in Group A were significantly less and shorter than in Group B(P ＜0.05).The scores of selfassessment for the operation were(11.21±2.00)in Group A versus(10.52±2.08)in Group B(P＜0.05).The change of CEAP classification and VCSS were statistically significant after operation in both groups(P＜0.01).The VCSS decreased 4.6 ±2.5 in Group A versus 4.3±2.7 in Grpup B(P＞0.05).Conclusions Endovenous radiofrequency ablation in combination with TriVex for treatment of CVI are effective,less traumatic,of fast recovery.CEAP classification and VCSS are useful tools for assessing outcomes after the operation.
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ObjectiveTo evaluate the feasibility of angioscopically external valve suture repair. MethodAngioscope was introduced through the terminal great sapherous to the first venous valve of superficial femoral vein. With general femoral vein, deep femoral vein, superficial femoral vein blocked, heparin-contained NS was used to establish water column, and video-guided angioscopy demonstrates the valve′s shape and its degree of defect and deformation. Twelve patients with primary deep venous insufficiency underwent video-valvuloplasty.ResultsPostoperative phlebography showed disappearance of reflux in 9 cases, and significantly reduced reflux in 3 cases. There was no morbidity postoperatively. Conclusion Angioscopic external suture valve repair is safe and effective in the treatment of femoral superficial venous insufficiency.
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AIM: To investigate the effect of norcantharidin(NCTD)on proliferation and invasion of human breast cancer cell line SKBR3 in vitro and its anticancer mechanisms.METHODS: MTT assay was used to determine SKBR3 cell proliferation. Light and FACScan were used to detect apoptosis and cell cycle. The invasiveness of SKBR3 was evaluated by the adhesion test,Matrigel experiment and the crossing-river test.RESULTS: NCTD had inhibitive effects on growth of SKBR3 cells in a dose and time-dependent manner, with the IC50 value of 12.5 mg/L at 24 h.The cells treated with 10 mg/L NCTD for 24 h and 48 h showed typical apoptotic morphology and hypodiploid peak before G1 phase. The cell cycle was arrested at G2/M phase. The apoptosis percentage was up to 3.44% and 6.17%, and the G2/M percentage was up to 35.82% and 38.70%. NCTD also could inhibit obviously the adhesion, movement and invasive capability simulating human basement membrane of SKBR3. Its effect was also in a dose-dependent manner. In the NCTD-treated group, crossing-river time was prolonged significantly and passing-membrane cells markedly decreased. CONCLUSION: NCTD in vitro inhibits not only the proliferation and growth of human breast cancer cells but also invasion and metastasis of the cells at relatively low concentration. NCTD shows prominent anti-tumor effects.