Clinical Observation of Rh-endostatin in the Treatment of Keloid / 中国药房

OBJECTIVE:To investigate effectiveness and safety of rh-endostatin in the treatment of keloid.METHODS:Sixty-four keloid patients in Nanchong Central Hospital during Jan.2015-Jan:2016 were divided into observation group and control group by random number table,with 32 cases in each group.Both group received fractional CO2 laser treatment.After surgery,control group was given antioxidant drug and antibiotics routinely.Observation group was additionally given Rh-endostatin injection 0.1-0.2 mg/cm2 via keloid body,once a month,for twice,on the basis of control group.Clinical efficacy,symptom score after laser treatment and 2 months after laser treatment,wound healing time,wound pigmentation area and keloid area before and after treatment,the occurrence of ADR were compared between 2 groups.RESULTS:There was no statistical significance in total re sponse rate (93.75％ vs.87.50％) and the incidence of ADR (15.63％ vs.12.50％) between observation group and control group (P＞0.05).There was no statistical significance in symptom score of control group between after laser treatment and after 2 months of treatment (P＞0.05).The erythema,edema and pigmentation scores of observation group were significantly lower than before treatment and control group,with statistical significance (P＜0.05);there was no statistical significance in skin itching and burning sensation score between 2 groups (P＞0.05).The wound incrustation time,decrustation time and wound healing time of observation group were significantly shorter than those of control group,with statistical significance (P＜0.05).Pigmentation area and keloid area of 2 groups were significantly smaller than before,and the observation group was significantly smaller than the control group,with statistical significance (P＜0.05).CONCLUSIONS:Rh-endostatin can alleviate erythema,edema,pigmenta tion and other symptoms effectively,shorten healing time,and inhibit pigmentation and keloid regeneration effectively with good safety.

A Study for the Mechanism of Abnormal Proliferation in Vascular Endothelial Cells using Inhibitors to the Signal Transduction Pathway

Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, take a significant role in signal transduction pathway of angiogenesis. The authors utilized the inhibitors, targeting the formation of three co-enzyme in signal transduction pathway in order to quantify the suppression of abnormal vascular endothelial cell proliferation induced by DMH, to compare the level suppression in each up-regulated growth factors, CTGF, CYR61, ITGbeta1, FHL2, and to identify the relationship between abnormal cell proliferation and signal transduction pathway. Five groups were established; Control group, Group of DMH, Group of DMH-mixed Herbimycin, inhibitor of protein tyrosine kinase, Group of DMH-mixed Calphostin C, inhibitor of protein kinase C, Group Of Dmh-Mixed 10U Catalase, Inhibitor Of oxidase. The rise of vascular endothelial cell was compared by MTT assay, and four growth factors were analysed with RT-PCR method, at pre-administration, 4, 8, 12, and 24 hours after administration. In comparison of abnormal proliferation of vascular endothelial cell induced by DMH, suppression was noticed in Herbimycin and Calphostin C group, and Calphostin C group revealed higher suppression effect. Nevertheless, Catalase group did not have any suppression. In manifestation of four growth factors, Herbimycin and Calphostin C group presented similar manifestation with control group, except in ITGbeta. Catalse group had similar manifestation with DMH group in all four growth factors. Abnormal proliferation of vascular endothelial cell induced by DMH have a direct relationship with PTK and PKC, more specifically to PKC. Oxidase was confirmed not to have any relevance.

Activation of Protein Tyrosine Kinase Pathway after Cat BRVO

To examine the effect of retinal branch vein occlusion (BRVO) on protein tyrosine phosphorylation, production of angiogenic growth factors, and activation of signal proteins in the tyrosine kinase pathways in the retina, BRVO was induced in cat retina by coagulation of retinal veins with diathermy. At 2 days, 1, 3, and 6 weeks after induction of BRVO, the retina was divided into 3 parts; a part within the distribution of the occluded vein [BRVO(IN)] or a part outside the distribution of the occluded vein [BRVO(OUT)], an prepared for western blot analysis. Overall, tyrosine-phosphorylated proteins were increased after BRVO, especially in BRVO(IN) at 2 days and 1 week. The vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were also increased in BRVO(IN) at 1 week and 2 days, respectively. The phospholipase Cgamma(PLCgamma) and mitogen-activated protein kinase (MAPK) were activated at these points. In this study, we concluded that the BRVO increased overall protein tyrosine phosphorylation in the cat retina in association with the increase of angiogenic growth factors (VEGF, bFGF) and activation of 2 signal proteins (PLCgamma and MAPK)in the tyrosine kinase pathways. These results suggest that the protein tyrosine phosphorylation may in part play an important role in mitogenesis of vascular endothelial cells and other retinal responses after BRVO.

Activation of Protein Tyrosine Kinase Pathway in Diabetic Rats

One mechanism of vascular damage in diabetic retinopathy is thought to result from the effect of hyperglycemia on the neural retina and microvasculature eventually causing the signs of capillary closure and clinical retinopathy. We reasoned that protein tyrosine kinase (PTK) pathways are abnormally activated in the retina prior to the onset of clinical changes. In this study, twelve Zucker diabetic fatty rats were compared with twelve male lean litter mates as control. The rats were examined for changes in the relative retinal levels of angiogenic growth factors, phosphotyrosine, PCNA, and tyrosine kinase pathway intermediates by western blot analysis. We found that the Zucker diabetic fatty rats have increased levels of the angiogenic growth factors, VEGF and PDGF. The levels of phosphotyrosine and PCNA, and phosphorylated intermediates, MAPK and PI3-K were also increased as compared with the lean control rats. These data indicate that the microvascular changes known to occur in this model are associated with elevation of VEGF and PDGF prior to the development of clinical apparent retinopathy. The elevations of VEGF and PDGF may explain in part the activation of the tyrosine kinase pathways, especially pathways that include MAPK and PI3K.