Objective To investigate the therapeutic effects of retinal angiomatosis in different clinical stages. To discuss the indication of vitrectomy for retinal hemangioblastoma. Methods The clinical data of 22 cases (33 eyes) were retrospectively analyzed. The retinal hemangiomas were divided into 5 stages according to their degrees of development from simple angioma without vessel dilation to feeder vessel dilation and intra-retinal exudates, local retinal detachment, massive retinal detachment and co mplication occurrence in proper order. The methods of treatment were laser photo coagulation, trans－scleral cryotherapy and vitrectomy. 13 eyes were treated with laser photocoagulation, 5 eyes with cryotherapy combined with laser and 11 eye s with vitrectomy. Tumor resection and silicone oil tamponade was performed in 3 eyes during vitrectomy. The patients were followed up for 46 months on average. Visual acuity (VA), the condition of the hemangioma and retina was compared pre- and post-operation respectively. Results In all 13 eyes treated with laser photocoagulation the hemangiomas regressed and the retina remained attached. VA improved in 2 eyes, and remained unchanged in 11 eyes. Cryother apy combined with laser photocoagulation was performed on 5 eyes. In this group, 4 eyesprime; hemangiomas regressed and no new hemangiomas occurred, proliferative vitreous retinopathy and vitreous hemorrhage was observed in 1 eye which vitrecto my was performed later. VA improved in 2 eyes, unchanged in 2 eyes and decreased in 1 eye. In the 11 eyes treated with vitreoretinal surgery, new hemangiomas wa s found in 1 eye, exudative retinal detachment was caused by hemangiomas in 2 eyes, proliferative vitreous retinopathy was observed in 2 eyes, and the retina re mained attached in 8 eyes. VA improved in 3 eyes, unimproved in 3 eyes, and decreased in 5 eyes. In the 3 eyes with surgical resection of retinal hemangioma during vitrectomy, 2 eyesprime; retina remained attached, 1 eye had exu dative retinal detachment and no new hemangiomas occurred. VA improved in 2 eyes and decreased in 1 eye. Conclusions Laser photocoagulation or combined with cryotherapy is effective in treating the hemangiomas in early stage. Vitrectomy is advisable for late stage of retinal angiomatosis, especially with vitreous hemorrhage, epiretinal membrane, proliferation and large scale of r etinal detachment. Surgical resection of isolated large retinal hemangioblastoma may be useful for selected patients. (Chin J Ocul Fundus Dis,2008,24:107-110)
ObjectiveTo investigate regulation mechanism of glypican-3 (GPC3) on Hippo signaling pathway and its effects on biological behavior of hepatocellular carcinoma Huh7 cells. MethodsShort hairpin RNAs (shRNA) targeting GPC3 and Yes-associated protein 1 (YAP1) genes were constructed. All of the shRNAs were transfected into Huh7 cells by liposome transfection in order to screen out the stable expression cell lines. The expressions of GPC3 and YAP1 in Huh7 cells were detected by PCR and Western blot in order to screen out the effective shRNAs. The proliferation, invasion, and apoptosis of Huh7 cells were detected by Edu cell proliferation assay, transwell, and flow cytometry. GPC3 shRNA transfection experiments were divided into 6 groups:non-transfection group, empty vector group, GPC3-714-shRNA group, GPC3-647-shRNA group, GPC3-1718-shRNA group, and GPC3-2134-shRNA group. YAP1 shRNA transfection experiments were divided into 6 groups:non-transfection group, empty vector group, YAP1-906-shRNA group, YAP1-1363-shRNA group, YAP1-1666-shRNA group, and YAP1-2895-shRNA group. GPC3 regulation experiments were divided into 5 groups:non-transfection group, empty vector group, GPC3-1718-shRNA group, GPC3-1718-shRNA+ rhYAP1 group, and YAP1-1666-shRNA group. Results① GPC3-1718-shRNA and YAP1-1666-shRNA plasmids were successfully constructed to silence the expressions of GPC3 and YAP1. ② The expressions of GPC3 mRNA and protein in each transfection group were significantly lower than those in the non-transfection group (P<0.05) and the empty vector group (P<0.05), while which in the GPC3-1718-shRNA group was significantly lower than those in all the other transfection groups (P<0.05). The expressions of YAP1 mRNA and protein in each transfection group were significantly lower than those in the non-transfection group and empty vector group (P<0.05), while which in the YAP1-1666-shRNA group was significantly lower than those in all the other transfection groups (P<0.05). ③ The expressions of YAP1 mRNA and protein in the GPC3-1718-shRNA group and the YAP1-1666-shRNA group were significantly lower than those in the non-transfection group (P<0.05) and the empty vector group (P<0.05), while which in the GPC3-1718-shRNA+rhYAP1 group were significantly higher than those in the GPC3-1718-shRNA group (P<0.05) and the YAP1-1666-shRNA group (P<0.05). ④ Compared with the non-transfection group and the empty vector group, the abilities of cell proliferation and invasion in the GPC3-1718-shRNA group and the YAP1-1666-shRNA group were significantly decreased, and the cell apoptosis was significantly increased (P<0.05); The cell proliferation, invasion, and apoptosis in the GPC3-1718-shRNA+rhYAP1 group were significantly improved (P<0.05). ConclusionGPC3 is likely to affect biological behavior of hepatocellular carcinoma Huh7 cells through regulation of YAP1 in Hippo signaling pathway.
The classical Hippo pathway leads to the phosphorylation of downstream effector molecules Hippo-Yes-associated protein (Yap) and transcriptional coactivator PDZ-binding motif (Taz) serine sites through a kinase response, thereby promoting cell proliferation, controlling cell polarity, changing cytoskeleton, it plays an important regulatory role in various pathophysiological processes such as epithelial-mesenchymal transition and inhibition of cell contact. Studies have shown that Yap/Taz can affect the progression of vitreoretinal diseases, opening up new prospects for the pathogenesis and clinical treatment of diabetic retinopathy, proliferative vitreoretinopathy, and retinal ischemia-reperfusion injury. Exploring the molecular mechanism of Yap/Taz provides a possible therapeutic target for future research in the treatment of retinal fibrosis diseases such as diabetic retinopathy and proliferative vitreoretinopathy. At the same time, regulating the activity of local Yap/Taz in the retina will also become an effective therapeutic target for damage-repair in retinal ischemia-reperfusion injury. However, Yap inhibitors have potential retinal toxicity and are still in the preclinical development stage. Further research on the mechanism of action and clinical safety of Yap inhibitors will provide new methods for the treatment of retinal diseases.
ObjectiveTo summarize the research progress of Hippo signaling pathway in triple negative breast cancer (TNBC). MethodLiteratures about studies the role of Hippo signaling pathway in cancer stem cells, epithelial-mesenchymal transformation, tumorigenesis and development, distant metastasis, treatment resistance, and treatment strategies were retrieved. ResultsIn TNBC, overexpression of Yes-associated protein and PDZ-binding motif could promote the development of tumor stem cells, induce epithelial-mesenchymal transformation of TNBC cells, and promote tumor development, distant metastasis, and chemotherapy resistance. ConclusionHippo/Yes-associated protein axis plays an important role in carcinogenesis and progression of TNBC, and targeting Hippo signaling pathway might be a potential therapeutic target for TNBC.
Pulmonary hypertension is a kind of progressive pulmonary vascular diseases in which there is excessive vasoconstriction and abnormal pulmonary vascular remodeling, and then a gradual increase in pulmonary arterial pressure, and it eventually leads to right ventricular failure and even death. The pathogenesis of pulmonary hypertension is still uncertain, but some studies suggest that Hippo pathway or some components of the Hippo pathway may be involved in the progress of pulmonary hypertension. In this review, we describe the mechanism of the Hippo pathway or some components of the Hippo pathway in the progress of pulmonary hypertension.
Objective To explore the expression of yes-associated protein 1 (YAP1), as a key protein of Hippo signal pathway, in rats with brain injury. Methods A total of 18 Sprague Dawley rats were randomly divided into three groups: normal group, sham operation group and brain injury group. The expression of YAP1 in rats with brain injury was detected by immunochemistry, quantitative polymerase chainreaction and Western blotting. Result Seventy-two hours after the brain injury, the expression level of YAP1 in protein and gene increased significantly in brain injury group, compared with those in the normal and sham operation group (P<0.05). Conclusion The expression of YAP1 increases in rats with brain injury, which maybe a new target for therapy.
Objective To investigate the expression of SAPCD2 in the lung adenocarcinoma cells, and to study the effect of SAPCD2 regulating Hippo signaling pathway on the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cells and its mechanism. Methods Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression levels of SAPCD2 mRNA and protein in four types of lung cancer cells (HCC827, H1650, SK-MES-1, A549) and human normal lung epithelial cells (BESA-2B), respectively. Then, lung cancer cells with relatively high levels of SAPCD2 expression were selected for subsequent experiments. The experiment cells were divided into a normal control group (NC group), a si-SAPCD2 group, and a pathway inhibitor group (si-SAPCD2+XMU-MP-1 group). Firstly, SAPCD2 mRNA was silenced using small interfering RNA (siRNA) technology, and then qRT-PCR was used to detect the expression of SAPCD2 in transfected lung cancer cells; using clone plate assay to detect the proliferation of lung cancer cells after silencing; using flow cytometry to detect the apoptosis of lung cancer cells after silencing; observe the number of lung cancer cells at different stages through cell cycle experiments; then Transwell experiment was used to analyze the effect of silencing SAPCD2 on the migration and invasion of lung cancer cell migration. Finally, Western blot was used to detect the expression of ki-67, Bcl-2, Caspase-3, NF2, P-MST1, P-LATS1, P-YAP, YAP, and TAZ proteins.Results SAPCD2 had the highest expression level in lung adenocarcinoma A549 cells (P<0.01). Silencing SAPCD2 significantly decreased the proliferation ability of A549 cells (P<0.01), inhibited their migration (P<0.05) and invasion (P<0.01), and promoted A549 cell apoptosis (P<0.01); more than half of the cells remained in the G0/G1 phase. Compared with the NC group, A549 cells showed a significant increase in G0/G1 phase cells (P<0.01), a significant decrease in G2/M and S phase cells (P<0.01), and a significant increase in the proportion of early apoptotic cells (P<0.01). Western blot results showed that silencing SAPCD2 down-regulated the expression of ki-67, Bcl-2, YAP, and TAZ proteins compared to the NC group (P<0.01), and up-regulated the expression of Caspase-3, NF2, P-MST1, P-LATS1, and P-YAP proteins (P<0.01). Conclusions The expression of SAPCD2 in lung adenocarcinoma A549 cells is significantly higher than that in normal lung epithelial cells (BESA-2B), which promotes the proliferation, migration and invasion of A549 cells and inhibits apoptosis. The mechanism may be related to the inhibition of Hippo signaling pathway.
Objective To evaluate the clinical valueof the revision of total hip replacement(THR), to analyse the reason of the rev isions, and to discuss the main difficulties and measures to manage it.Methods From June 1998 to January 2002, 15 cases (15 hips) were revised on totalhip replacement. The reasons for revision in the cases were as follows:failure of primary operative techenique, loosening and sinking of the components, displacement of the prosthesis, erosion of the acetabulum, as well as fracture of the femoral stem. The main difficulties of the revision were:poor health condition of the patients; the remove of the prosthesis of the primary THR,especially the broken femoral stem and the cements; the loss of localbone. The measures to remove the broken femoral stem were described.ResultsAll cases were followed up 2.4 years on average: 2 patients died from heart disease and cerebrovascular disease respectively, while the good results were achieved in the others.No infection, dislocation, loosening, and other complications occurred. The good effects were related with following factors:mild degree of illness; no severe bone defect; most of the first femoral head replacement.Conclusion The revision of THRis a more difficult operation, so that the special instrument and equipment andoperative experience are required.
Objective To evaluate the therapeutic outcome of artificial total hip arthroplasty (THA) with collum femoris preserving for hip joint desease in young and middle-aged patients. Methods From March 2002 to March 2005, 26 cases (31 hips) of hip joint disease were treated with artificial THA with collum femoris preserving, including 19 males (23 hips)and 7 females (8 hips) and aged 32-48 years with an average of 37 years. In 31 hips, 17 left hips and 14 right hips were involved. There were 9 cases of osteoarthritis of the hip joint caused by avascular necrosis of the femoral head (ANFH), 7 cases of ANFH, 3 cases of femoral head necrosis caused by dysplasia of acetabular, 1 case of osteoarthritis of the hip joint caused by ankylosing spondyl itis, and 2 cases of rheumatoid arthritis; the course of disease was 2-11 years (5.6 years on average). Two cases of femoral neck fracture (Garden IV), and 2 cases of non-union femoral neck fractures (1 for Garden III and 1 for Garden IV), the course of disease was 5 days, 24 months, and 26 months. The prime symptoms were pain, difficult walk and l imp. All patients were taken X-ray to exclude osteoporosis. Results The right distal femur prosthesis of a bilateral patient cracked owing to excessive amputation of collum femoris, and fracture healed after symptomatic treatment. All the incisions healed by first intention and no compl ications occurred. All patients were followed up for 4-7 years, with an average of 5.6 years. One case had poor hip function because he did not follow rehabil itation procedure, and the others achieved good outcome with normal gait. One case complained of persistent pain 6 months after operation, and was rel ieved by administration of some non-steroidal antiinflammatory drugs and anti-osteoporosis drugs 6 months later. The X-ray films after operation and at last follow up showed good location of prosthesis and no bone resorption. Harris score at last follow-up was 91.31 ± 0.77, and it was significantly higher than that before operation (50.88 ± 0.90), (P lt; 0.05). The excellent and good rate was 93.5% (excellent in 11 hips, good in 18 hips, and fair in 2 hips). Conclusion Artificial THA with collum femoris preserving can retain more bone, be easier for revision, and has an excellent outcome.