Insulin-like growth factor binding protein related protein 1 knockdown attenuates hepatic ?brosis via the regulation of MMPs/TIMPs in mice

Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.

Interaction between insulin-like growth factor binding protein-related protein 1 and transforming growth factor beta 1 in primary hepatic stellate cells

BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.

Increased serum levels of soluble CD146 and vascular endothelial growth factor receptor 2 in patients with exudative age-related macular degeneration

AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.

Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

AIM： To investigate the serum levels of vascular endothelial growth factor receptor-2（VEGFR-2） and adropin in age-related macular degeneration（AMD）patients.·METHODS： Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group.Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups.· RESULTS： AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness（P =0.01, 0.047, 0.025 and 〈0.001, respectively）. Serum VEGFR-2level revealed a significant decrease in AMD patients compared to controls（26.48 ±6.44 vs 30.42 ±7.92 ng/m L,P 〈0.001）. There was an insignificant increase in serum adropin level in AMD patients（6.17±3.19 vs 5.79±2.71 ng/m L,P =0.4）. Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness（r =-0.226, P =0.025） and a significant positive correlation with subfoveal choroidal thickness（r=0.2, P=0.048）.·CONCLUSION： The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD.

Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration in a Turkish population

AIM:To assess the association between age-related macular degeneration(AMD) and three single nucleotide polymorphisms(SNPS) related to the vascular endothelial growth factor(VEGF) gene.METHODS:The patients who were diagnosed with AMD were included in this prospective study. Three SNPs(rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls.RESULTS:The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group(P =0.072 and P =0.058).However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD(P =0.005 and P =0.010,respectively). One of the SNPs(rs1413711) was also found to be associated with the severity of AMD(P =0.001)with significant genotype distribution between early,intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD.CONCLUSION:VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

Factors Affecting the Relation of Fracture Toughness V_(GC) with Critical Void Growth Ratio R_C/R_O

The relationship between fracture toughness VGC and critical void growth RC/RO was studied for ten kinds of Steel. The macroscopic fracture toughness VGC was determined by using notched tensile specimens. and the microscopic parameters of critical void growth ratio RC/RO were quantitatively measured under SEM. Then, the coefhcient C in the relation VGC = C In(RC/RO) proposed in author's past work was specifically explored. The correlation of C with tensile proderty parameter φ=σyδ/(Eφn) was presented for the Steel investigated, and the effects of low temperature on C were also discussed. Results show that the coefficient C is linearly related to the parameter and insensitive to low temperature.

Phosphatase and tensin homology deleted in chromosome 10,hypoxia-inducible factor-1 alpha gene expression in colorectal adenoma and adenocarcinoma and their relation to vascular endothelial growth factor protein expression

To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.

Basic fibroblast growth factor attenuates the degeneration of injured spinal cord motor endplates

The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Allen＇s method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also well recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additionally, anterior tibial muscle fibers slowly, but progressively, atrophied. Immu- nohistochemical staining showed that the absorbance values of calcitonin gene related peptide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic fi- broblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related peptide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through gene related peptide and acetylcholinesterase cord. attenuating the decreased expression of calcitonin n anterior horn motor neurons of the injured spinal

Temporal pattern of resolution/recurrence of choroidal neovascularization during bevacizumab therapy for wet age-related macular degeneration

AIMTo characterize temporal pattern of resolution and recurrence of naive choroidal neovascularization (CNV) secondary to wet age-related macular degeneration (AMD) treated with intravitreal bevacizumab on as needed regimen, and to analyze baseline risk factors for CNV resolution or recurrence.

Bilateral same-session intravitreal injections of antivascular endothelial growth factors

AIMTo document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.

Spontaneous or secondary to intravitreal injections of anti-angiogenic agents retinal pigment epithelial tears in age-related macular degeneration

·AIM:Toevaluatethevisualfunctionevolutionofretinal pigment epithelial(RPE) tears in patients with age-related macular degeneration(AMD) according to type of occurrence [spontaneous or secondary to anti-vascular endothelial growth factor(anti-VEGF) injection] and the topographic location of the tear after a two-year followup period.·METHODS: A total of 15 eyes of 14 patients with RPE tears in exudative AMD were analyzed retrospectively at the University Eye Clinic of Trieste. Inclusion criteria were: patient age of 50 or older with AMD and RPE tears both spontaneous occurring or post anti-VEGF treatment. Screening included: careful medical history,complete ophthalmological examination, fluorescein angiography(FA), indocyanine green angiography(ICG),autofluorescence and infrared imaging and optical coherence tomography(OCT). Patients were evaluated every month for visual acuity(VA), fundus examination and OCT. Other data reported were: presence of PED,number of injections before the tear, location of the lesion.·RESULTS:Meanfollow-up was24wk(SD±4wk). Atotal of 15 eyes were studied for RPE tear. In 6 cases(40%),the RPE tears occurred within two years of anti-VEGF injections the others occurred spontaneously. In 13cases(86.6%), the RPE tear was associated with pigment epithelial detachment(PED). In 7 cases(46.6%), the RPE tear occurred in the central area of the retina and involved the fovea. Two lesions were found in the parafoveal region, six in the extra-macular area. In all cases visual acuity decreased at the end of the follow-up period(P <0.01) independently of the type or the topographical location of the lesion.·CONCLUSION: RPE tear occurs in exudative AMD as a spontaneous complication or in relation to anti-VEGF injections. Visual acuity decreased significantly and gradually in the follow-up period in all cases. No correlation was found between visual loss and the type of onset or the topographic location of the tears.

Association of IGF1R polymorphisms(rs1546713) with susceptibility to age-related cataract in a Han Chinese population

AIM:To explore the susceptible association between the insulin-like growth factor-1 receptor(IGF1 R)single nucleotide polymorphism(SNP)and age-related cataract(ARC),and investigate the underlying mechanisms in human lens epithelium(HLE)cells.METHODS:Totally 1190 unrelated participants,comprising 690 ARC patients and 500 healthy individuals in Han Chinese population were recruited and genotyped for target SNP.Theχ2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender.Meanwhile,different biological experimental methods,such as cell counting kit 8(CCK-8)assay,flow cytometry,quantitative real time polymerase chain reaction(Q-PCR)and Western blot,were used to detect cell viability,cell cycle progression and apoptosis in HLE cells or IGF1 R knockdown HLE cells.RESULTS:The rs1546713 in IGF1 R gene was identified(P=0.046,OR:1.606,95%CI:1.245-2.071),which shown a significant relevance with ARC risk under the dominant model.The results demonstrated that IGF1 R knockdown inhibited cell proliferation by inducing cell cycle arrested at S phase and promoting apoptosis.Mechanistically,the cell cycle blocked at S phase was linked with the alterations of cyclin A,cyclin B,cyclin E and P21.The pro-apoptosis function of IGF1 R may related with stimulating the activation of Caspase-3 and altering the expression levels of apoptotic proteins,including Bcl-2,Bax and Caspase-3.CONCLUSION:This study first report that IGF1 R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provide new clues to understand the pathogenic mechanism of ARCs.Notably,IGF1 R is likely a potential target for ARC prevention and treatment.

Fixed bimonthly aflibercept in nave and switched neovascular age-related macular degeneration patients:one year outcomes

AIM: To determine real life clinical outcomes in poorly responsive and treatment-nave neovascular age-related macular degeneration(nv AMD) patients using bimonthly fixed dosing aflibercept regimen.METHODS: This was a retrospective study of 165 eyes with nv AMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata(PRN) ranibizumab/bevacizumab due to poor response(107 eyes), or treatment- nave( 58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity(BCVA) and central retinal thickness(CRT)from baseline were assessed using the Wilcoxon signedrank test. The proportion of patients maintaining BCVA(<15 letters loss) at 12 mo was also evaluated.RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and nave aflibercept groups respectively(P <0.01). BCVA was maintained in 95.3% of switched and 96.6% of nave patients. CRT at month 12 showed a decrease of -6.16 μm in the switched group and -35.36 μm in the nave group(P <0.01).Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6 mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections(nave group), 7.5 injections(switched group) and 4 clinic visits per year.CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-nave and poorly responsive nv AMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.

Activation of Rac1-PI3K/Akt is required for epidermal growth factorinduced PAK1 activation and cell migration in MDA-MB-231 breast cancer cells

Epidermal growth factor （EGF） may increase cell motility, an event implicated in cancer cell invasion and metastasis. However, the underlying mechanisms for EGF-induced cell motility remain elusive. In this study, we found that EGF treatment could activate Ras-related C3 botulinum toxin substrate 1 （Racl）, PI3K/Akt and p21- actived kinase （PAK1） along with cell migration. Ectopic expression of PAK1 K299R, a dominant negative PAK1 mutant, could largely abolish EGF-induced cell migration. Blocking PI3K/Akt signalling with LY294002 or Akt siRNA remarkably inhibited both EGF-induced PAK1 activation and cell migration. Furthermore, expression of dominant-negative Racl （T17N） could largely block EGF-induced PI3K/Akt-PAK1 activation and cell migration. Interestingly, EGF could induce a significant production of ROS, and N-acetyl-L-cysteine, a scavenger of ROS which abolished the EGF-induced ROS generation, cell migration, as well as activation of PI3K/Akt and PAK, but not Racl. Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Racl, generation of ROS and subsequent activation of PI3K/Akt and PAK1.

Real-life experience of ranibizumab therapy for neovascular age-related macular degeneration from Turkey

AIM： To report the real-life experience and clinical results of intravitreal ranibizumab injections to neovascular agerelated macular degeneration（nAMD） in a single institution in Turkey.METHODS： A total of 101 eyes of 89 patients with nAMD treated with intravitreal ranibizumab injection, followed up for at least 24 mo between 2009 and June 2014, which were evaluated retrospectively. A pro re nata（PRN） treatment protocol was performed after the patients had received three, monthly loading injections. Best corrected visual acuity（BCVA） and central macular thickness measurements were evaluated at baseline and 3, 6, 12, 18, and 24 mo. Number of injections and visits were also recorded.RESULTS： Of the 89 patients, 34（38.2%） were male and 55（61.8%） were female and the mean age was 74.0±9.5（52-91）y. The mean follow-up period was 24.82±4.4（24-29）mo. Mean number of visits was 8.4±1.12（7-12） in the first year and 6.6±1.33（4-12） in the second year. The mean number of injections was 5.8±1.6（3-10） and 4.2±2.2（0-9） in the first and second year, respectively. The mean BCVA was 59±15.8 letters at baseline by the Early Treatment Diabetic Retinopathy Study（ETDRS） chart. The mean BCVA at 3, 12, and 24 mo was 70.3±15.9, 67.9±14.3 and 67.3±16.9 letters, respectively. Improvement in visual acuity for each of the visits from baseline was found to be statistically significant（P〈0.01）. Visual acuity in 9 eyes at month 3, 7 eyes at month 12, and 13 eyes at month 24 did not change. The mean central macular thickness（CMT） was 437.99±164.78 μm at baseline. The mean CMT was 348.05±138.47 μm, 349.27±139.79 μm, and 344.13±146.30 μm at months 3, 12, and 24, respectively. The decrease in CMT for each of the visits from baseline was found to be statistically significant（P〈0.01）.CONCLUSION： Anatomical and functional achievement are obtained in our study, but the mean number of injections and visits are found to be lower than the findings reported in randomized controlled clinical trials in the literature. However, the mean number of injections and visits in our study are compatible with the findings reported in real-life experience studies in the literature.

Age-related macular degeneration treatment in the era of molecular medicine

Age-related macular degeneration(AMD) is the leading cause of irreversible blindness in the developed world. The quality of life of both patients and families is impacted by this prevalent disease. Previously, macular degeneration had no known effective treatment. Today, vitamins for non-exudative AMD and intravitreal injection of medications for its exudative form are primary forms of current treatment. Modern advances in molecular science give rise to new possibilities of disease management. In the year 2003 the sequencing of the entire human genome was completed. Since that time, genes such as complement factor H, high-temperature requirement factor A1, and age-relateed maculopathy susceptibility 2 have been discovered and associated with a higher risk of AMD. A patient's genetic make-up may dictate the effectiveness of current or future therapeutic options. In addition, utilizing genetic data and incorporating it into new treatments(such as viral vectors) may lead to longer-lasting(or permanent) VEGF blockade and specific targeting of complement related genes. There have also been considerable advances in stem cell directed treatment of AMD. Retinal pigment epithelial(RPE) cells can be derived from human embryonic stem cells, induced pluripotent stem cells, or adult human RPE stem cells. Utilizing animal models of RPE and retinal degeneration, stem cell-derived RPE cells have been successfully implanted into the subretinal space. They have been injected as a cell mass or as a pre-prepared monolayer on a thin membrane. Visual recovery has been demonstrated in a retinal dystrophic rat model. Preliminary data on 2 human subjects also demonstrates possible early visual benefit from transplantation of stem cell-derived RPE. As more data is published, and as differentiation and implantation techniques are optimized, the stabilization and possible improvement of vision in individuals with non-exudative macular becomes a real possibility. We conclude that the technologic advances that continue to unfold in both genetic and stem cell research offer optimism in the future treatment of AMD.

Infant guinea pig retina model of glutamate toxicity and intervention of basic fibroblast growth factor

Impaired vision with oligemic ophthalmopathy is a result of excitotoxicity caused by excitatory amino acids, resulting in pathological changes, such as loss of retinal neurons and in particular retinal ganglionic cells. The present study utilized infant guinea pigs, aged 45-50 days, to establish injury models via intraperitoneal injection of fixed sodium glutamate doses. Results from hematoxylin- eosin staining revealed significantly reduced retinal ganglionic cell numbers and retinal damage at 10 days after 7 consecutive days of 3 g/kg sodium glutamate treatment; these animals served as the injury model group. In addition, models of moderate injury （glutamate 3 g/kg daily, for 7 consecutive days） were intraperitoneally pretreated with basic fibroblast growth factor （800 U/kg daily）. Immunohistochemistry results confirmed reduced anti-apoptotic gene bcl-2 expression in the ganglion cell layer of glutamate-injured guinea pigs. Expression of the pro-apoptotic gene caspase-3 was increased in the ganglion cell layer and inner plexiform layer. Somatostatin expression was primarily distributed in the ganglion cell layer and inner nuclear layer. Expression of the presynaptic element synaptophysin was weak. However, following basic fibroblast growth factor injection, expressions of the above-described bioactive molecules were reversed, which suggested that basic fibroblast growth factor exerted protective effects on sodium glutamate-induced retinal injury in infant guinea pigs by regulating expression of synaptophysin, somatostatin, Bcl-2, and caspase-3.

Basic fibroblast growth factor gene transfection in repair of internal carotid artery aneurysm wall

Surgery or interventional therapy has some risks in the treatment of cerebral aneurysm. We established an internal carotid artery aneurysm model by dripping elastase in the crotch of the right internal and external carotid arteries of New Zealand rabbits. Following model induction, lentivirus carrying basic fibroblast growth factor was injected through the ear vein. We found that the longer the action time of the lentivirus, the smaller the aneurysm volume. Moreover, platelet-derived growth factor expression in the aneurysm increased, but smooth muscle 22 alpha and hypertension-related gene 1 mRNA expression decreased. At 1,2, 3, and 4 weeks following model establishment, following 1 week of injection of lentivirus carrying basic fibroblast growth factor, the later the intervention time, the more severe the blood vessel damage, and the bigger the aneurysm volume, the lower the smooth muscle 22 aJpha and hypertension-related gene ~ mRNA expression. Simultaneously, platelet-derived growth factor expression decreased. These data suggest that recombinant lentivirus carrying basic fibroblast growth factor can repair damaged cells in the aneurysmal wall and inhibit aneurysm dynamic growth, and that the effect is dependent on therapeutic duration.

生存素、人类表皮生长因子受体2、巨囊性病液体蛋白15、Yes相关蛋白表达对乳腺癌患者术后复发转移的预测价值

目的:研究生存素(Survivin)、人类表皮生长因子受体2(HER-2)、巨囊性病液体蛋白15(GCDFP15)、Yes相关蛋白(YAP)表达对乳腺癌患者术后复发转移的预测价值。方法:收集156例经乳腺癌改良根治术治疗的乳腺癌患者乳腺癌病理组织及癌旁正常组织,比较乳腺癌患者癌组织和癌旁正常组织Survivin、HER-2、GCDFP15、YAP蛋白表达情况;所有患者术后均随访2年,根据患者术后随访期间复发转移情况将其分为Ⅰ组(51例)和Ⅱ组(105例),统计两组一般资料,比较两组癌组织Survivin、HER-2、GCDFP15、YAP蛋白表达情况,分析乳腺癌患者术后2年内复发转移的影响因素及癌组织Survivin、HER-2、GCDFP15、YAP蛋白单一及联合检测对乳腺癌患者术后2年复发转移的预测价值。结果:癌组织Survivin、HER-2、GCDFP15阳性表达率高于正常组织,YAP阳性表达率低于正常组织(均P<0.05)。Ⅰ组低分化、临床分期Ⅲ期患者占比高于Ⅱ组(均P<0.05)。Ⅰ组癌组织Survivin、HER-2、GCDFP15阳性表达率高于Ⅱ组,YAP阳性表达率低于Ⅱ组(均P<0.05)。分化程度为低分化、临床分期Ⅲ期及Survivin、HER-2、GCDFP15蛋白阳性表达均为乳腺癌患者术后2年内复发转移的独立危险因素(OR=2.092、1.992、2.059、1.815、1.857,均P<0.05);YAP蛋白阳性表达为乳腺癌患者术后2年内复发转移的保护因素(OR=0.489,P<0.05)。癌组织Survivin、HER-2、GCDFP15、YAP蛋白联合预测乳腺癌患者术后2年复发转移的曲线下面积(AUC)值高于四者单独检测(均P<0.05)。结论:乳腺癌的发生与Survivin、HER-2、GCDFP15、YAP蛋白表达情况有关,且患者术后2年复发转移的发生与其分化程度、临床分期及Survivin、HER-2、GCDFP15、YAP蛋白表达情况有关,同时Survivin、HER-2、GCDFP15、YAP蛋白联合可有效提高对乳腺癌患者术后2年复发转移的预测价值。

Twist 1 correlates with poor differentiation and progression in gastric adenocarcinoma via elevation of FGFR2 expression

AIM: To explore the correlation between Twist-related protein (Twist)1, fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma differentiation and progression.