ABSTRACT
Objective Pathologic complete response (pCR) has been suggested as a surrogate prognostic indicator in breast cancer patients treated with neoadjuvant chemotherapy.We assessed whether the likelihood of pCR and survival is associated with the immunohistochemistry-based molecular subtypes.Methods We retrospectively analyzed the records of l01 patients with breast cancer who received neoadjuvant chemotherapy between January 2007 and January 2010.Patients were dassified into four molecular subtypes based on the immunohistochemistry prnfiles of estrogen receptor,progesterone receptor,and HER2.Logistic regression was used to analyze variables associated with pCR.Results The pCR was achieved in 19 patients (18.8％).The triple negative subtype was an independent predictive factor for pCR (odds ratio,3.35,95％ confidence interval,1.25-9.79,P =0.012),and the Her-2 subtype showed a trend for higher pCR rates (odds ratio,3.11;95％ confidence interval,1.09-10.89,P =0.021) compared with the luminal A subtype.The pCR was significantly associated with prolonged disease-free survival (P =0.002).The triple negative subgroup had shorter disease-free survival (P =0.0006) and overall survival (P =0.008) than the other subgroups.Conclusions We demonstrated that the triple negative and Her-2 subtypes are more likely to obtain pCR when neoadjuvant chemotherapy is given,compared to the luminal A subtype.Despite the high pCR rate,the triple negative subtype showed worse survival outcomes,paradoxically,primarily due to patients who had residual disease.
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Aim To investigate the treatment effect of Tongxinluo(TXL)combined peripheral blood derived mesenchymal stem cells(PB-MSCs)transplantation on angiogenesis of HIF-1 /VEGF pathway and miR-21 0 in diabetic foot(DF)rats.Methods Seventy male Spra-gue-Dawley rats were fed with high-fat diet and given combined streptozotocin injection to build diabetic rat model.The femoral artery and vein of right lower ex-tremity of modeled rats were ligatured to induce DF model.The normal rats in the same batch copied is-chemia model served as control group.The modeled rats were divided into 6 groups :model group ,TXL group,Cilostazol group,PB-MSCs group,TXL com-bined PB-MSCs(T-MSCs)group and Cilostazol com-bined PB-MSCs(C-MSCs)group.After the treatment for 28 days,animal gastrocnemius muscle and serum were taken for detection,in which serum was used to detect VEGF-A and HIF-1 α by ELISA,and muscle was used to detect VEGF-A and VEGF-R2 by Western blot,and VEGF-A by RT-PCR.Results Compared with the control group,the expressions of VEGF-A, HIF-1 α,VEGF-R2 and miR-21 0 in the model group were significantly reduced(P R2 and miR-21 0 in each treatment group were signifi-cantly increased(P <0.01 ),where the expressions of VEGF-A,HIF-1 α,VEGF-R2 and miR-21 0 in the T-MSCs were higher than these in the TXL,cilostazol and PB-MSCs group(P <0.05,P <0.01 ).Conclusion TXL combined with PB-MSCs transplantation may be regulated by HIF-1 /VEGF pathway and miR-21 0,pro-moting endothelial cell proliferation,differentiation, and promoting the formation of new blood vessels.
ABSTRACT
Ob jectiev Oxidized low-density lipoprotein ( ox-LDL) induces vascular endothelial cell injury , which is one of the factors initiating atherosclerosis .This study aimed to investigate the protective effect of Tongxinluo ( TXL ) on vascular endothelial cells with ox-LDL-induced injury . Methods Human umbilical vein endothelial cells ( HUVEC ) were cultured in vitro and divided into five groups:normal control, oxidative stress injury (OSI) model, and high, medium and low dose TXL.The HUVECs were incubated with ox-LDL at the concentration of 30 mg/L for 24 hours to induce oxidative stress injury and then treated with TXL at 50, 100 and 150 mg/L for 4 hours, followed by 24 hour incubation with 30 mg/L ox-LDL added to the culture medium .The viability of the cells was detected by MTS assay, the nitric oxide (NO) content, superoxide dismutase (SOD) activity and mitochondrial membrane poten-tial ( MMP) in the cell culture supernatant were measured with respective kits , and the expressions of iNOS , MMP9, and NF-κBp65 proteins were determined by Western blot . Results The HUVECs of the OSI model group showed a significant decrease in cell via-bility compared with the normal control , ([73 .89 ±0.67] vs [100.00 ±2.23]%, P<0.01) but a remarkably increase after treated with medium and high dose TXL ([92.15 ±0.76]%and [ 97.19 ±1.45]%, P<0.01).The MMP, NO content, and SOD activity were markedly reduced in the model group (P<0.01) but elevated in the low, medium, and high dose TXL groups (P<0 .01).The expressions of the iNOS, MMP9, and NF-κBp65proteins were significantly up -regulated in the model group (P<0.01) but down reg-ulated in the low, medium, and high dose TXL groups (P<0.05).C on clusion TXL has the effects of anti-oxidation and anti-in-flammation and can protect vascular endothelial cells against ox-LDL-induced injury .