乳腺癌抗血管化治疗的动物实验研究进展

血管生成在乳腺癌的生长、浸润和转移过程中起着重要的作用。针对肿瘤血管生成的抗血管化治疗为治疗乳腺癌提供一个新的策略。在动物实验研究中。

^(99)Tc^m标记的肿瘤血管化特异性多肽的实验研究

本文旨在寻找一种的99Tcm标记的抗肿瘤血管化的显像剂。将具抗肿瘤血管化的多肽适当修饰后,用99Tcm标记,并在肿瘤荷鼠体内筛选比较。选择在肿瘤部位放射性浓聚明显的多肽,进行肿瘤荷鼠的体内分布和竞争试验。GPRPAA(D)A(D)-HYNIC-99Tcm标记率高、产物稳定,放化纯度>98%,室温下6h后>93%。能在荷鼠肿瘤组织较快浓聚,0.5h时肿瘤%ID/g为13.5973±1.3642,清除较慢,6h肿瘤%ID/g仍有4.0399±0.5876;血及其它血供丰富的组织清除较快,1h时血ID/g为1.7035±0.2742,心%ID/g为3.2578±1.3121,肿瘤在2h显像清晰。GPRPAA(D)A(D)-HYNIC-99mTc有希望成为一种肿瘤血管化显像剂。

血管内皮生长因子与乳腺癌的临床研究进展

血管内皮生长因子 (VEGF)是一种重要的血管生成刺激因子 ,可以作为乳腺癌患者的独立预后判断因素 ,以VEGF为靶点的抗血管化治疗成为治疗乳腺癌的新方法。

负载姜黄素支架体内构建组织工程软骨的可行性研究

目的探索以负载姜黄素材料为支架,在动物皮下构建组织工程软骨的可行性。方法通过细胞划痕试验明确既可抑制血管但又不影响干细胞生物活性的姜黄素的最佳浓度范围。负载姜黄素的支架材料与单纯明胶支架材料分别植入裸鼠皮下,术后3、6周取材,比较局部皮下血管抑制程度。软骨细胞-负载姜黄素支架复合物与软骨细胞-明胶支架复合物分别植入裸鼠皮下,术后3、6周取材进行组织学检测,比较软骨形成情况。结果姜黄素对h UVEC的有效抑制浓度为30μmol/L,而对BMSC的有效抑制浓度为40μmol/L。负载姜黄素支架在裸鼠皮下具有明显的血管抑制作用。软骨细胞-负载姜黄素支架复合物在裸鼠皮下可形成成熟软骨。结论负载姜黄素支架具有血管抑制作用且不影响软骨再生,有望成为软骨再生的理想支架。

明胶/姜黄素纳米纤维电纺膜皮下环境构建组织工程软骨的可行性研究

目的探讨以明胶/姜黄素电纺材料为支架,在动物皮下构建组织工程化软骨的可行性。方法取兔耳软骨获取软骨细胞作为种子细胞,体外培养扩增,并以明胶电纺膜(对照组)和明胶/姜黄素电纺膜(实验组)为支架构建软骨。将支架材料植入BALB/c裸鼠背部皮下后行大体观察;对支架材料及细胞-支架复合物行电镜观察;对细胞-支架复合物进行细胞增殖率检测;另将体外培养1周的细胞-支架复合物植入BALB/c裸鼠背部皮下,3周、12周后行组织学检测,比较不同时间点的软骨形成情况。结果大体观察显示,相比对照组,实验组材料周围组织血管化受到明显抑制;SEM结果显示,两组材料中细胞均黏附良好;细胞增殖率检测结果显示,姜黄素对细胞增殖无显著影响;组织学观察显示,3周、12周时,两组细胞-支架复合物均有软骨陷窝形成;但相比对照组,实验组材料可见明显吸收,软骨基质形成较厚,均质性更佳。结论明胶/姜黄素材料可作为支架在裸鼠皮下构建组织工程化软骨,具有潜在的应用前景。

Relationship between Vascular Elasticity and Spontaneous Rupture of Hepatocellular Carcinoma

Objective Spontaneous rupture of hepatocellular carcinoma (HCC) is common in Asia and Africa with unclear mechanism. In our previous study, we found that the deposition of immune complex on vascular wall and vascular injury were related to the HCC rupture. In this study, the structure of elastin around the small artery was deeply investigated to confirm our previous study. Methods Immunohistochemical technique and transmission electron microscopy were used to study 23 specimens from ruptured HCC and 30 cases of nonruptured HCC. Results The layer of elastin around the vascular wall was significant thicker in patients with ruptured HCC than that in nonruptured HCC. The proliferation of elastin, abnormal distribution of neutrophil elastase and degradation of collagen fibril were predominantly present in the specimens from ruptured HCC. The phenomenon of electron—dense deposit in the elastic lamina that represented the deposition of immune complex, and the signs of infiltrated neutrophils from bloodstream into the vascular wall that caused the vascular injury, also can be found in ruptured HCC. Since the damaged vessels could become stiff and weak, which would more prone to be splitting and results in hemorrhage and the rupture of HCC, we postulated that the preexisting of immune complex deposition and vascular injury may be relate to the ruptured HCC. Conclusion The vascular injury caused by immune complex deposition might relate to ruptured HCC. Key words hepatocellular carcinoma - rupture - elastin - elastase

Autoimmune liver serology:Current diagnostic and clinical challenges

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseas-es(AiLD),namely autoimmune hepatitis types 1 and 2(AIH-1 and 2),primary biliary cirrhosis(PBC),and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody(ANA) and smooth muscle antibody(SMA).AIH-2 is specified by antibody to liver kidney microsomal antigen type-1(anti-LKM1) and anti-liver cytosol type 1(anti-LC1).SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies(AMA) react-ing with enzymes of the 2-oxo-acid dehydrogenase complexes(chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly react-ing with nuclear pore gp210 and nuclear body sp100.Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis(PSC) mostly affecting adult men wherein the only(and non-specific) reactivity is an atypical perinuclear antineutro-phil cytoplasmic antibody(p-ANCA),also termed peri-nuclear anti-neutrophil nuclear antibodies(p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis(ASC) with serological features resembling those of type 1 AIH.Liver diagnostic serol-ogy is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automatedtechnologies such as ELISAs and bead assays,become available to complement(or even compete with) tradi-tional immunofluorescence procedures.We survey for the first time global trends in quality assurance impact-ing as it does on(1) manufacturers/purveyors of kits and reagents,(2) diagnostic service laboratories that fulfill clinicians' requirements,and(3) the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.

Fumagillin treatment of hepatocellular carcinoma in rats: An in vivo study of antiangiogenesis

AIM: To investigate the effect and possible mechanisms of antiangiogenesis therapy for HCC in rats.METHODS: Adult male LEW/SsN rats were divided into 3groups, 25 animals each. Group A was the control group.Groups B and C were given diethylnitrosamine, 5 mg/kg/d.In addition, group C rats received an intraperitoneal injection of fumagillin, 30 mg/(kg.d). Five animals in each group were killed at 6th, 12th, 18th, 20th and 24th wk to evaluate the development of HCC and metastasis. Weight of the rats, liver tumors, and number of organs involved by HCC were measured at each stage. We compared methionine aminopeptidase-2 (MetAP-2) mRNA, Bcl-2mRNA, telomerase mRNA, and telomerase activity at 24th wk in the liver tissue of group A rats and tumor tissue of HCC from group B and C rats.RESULTS: No HCC developed in group A, but tumors were present in group B and C rats by the 18th wk. At wk 20 and 24, the median liver weight in group B was 0.64 g (range:0.58-0.70 g) and 0.79 g (range: 0.70-0.90 g) (P = 0.04),and that in group C was 0.37 g (range: 0.35-0.42 g) and 0.39 g (range: 0.35-0.47 g) (P = 0.67). The liver weight in group C rats was significantly lower than that in group B rats (P = 0.009). At the same time, the median metastasis score (number of organ systems involved) was 3 (range2-3)in group B, and 1 (range 1-2) in group C, a significant difference between the groups (P = 0.007, 0.004). The levels of MetAP-2 mRNA were significantly higher in groups B and C than in group A (P = 0.025), and significantly higher in group C than in group B (P = 0.047). The level of Bcl-2 mRNA was significantly higher in group B than in group A (P = 0.024), but lower in group C than in group B, although not significantly (P = 0.072). Telomerase mRNA was significantly higher in group B than in group A (P = 0.025), but significantly lower in group C than in group B (P = 0.016). The same inter-group relationship was also true for telomerase activity (P = 0.025 and 0.046).CONCLUSION: Fumagillin effectively inhibits both liver tumor growth and metastasis in rats in vivo. A possible mechanism is fumagillin-induced inhibition of MetAP-2,which plays an essential role in endothelial cell proliferation.Inhibition of MetAP-2 also results in inhibition of Bcl-2and telomerase activity.

Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C

AIM： To evaluate the effect of combination treatment with the interferon （IFN） and angiotensin-converting enzyme inhibitor （ACE-Ⅰ） on several fibrotic indices in patients with refractory chronic hepatitis C （CHC）. METHODS： Perindopril （an ACE-Ⅰ; 4 mg/d） and/or natural IFN （3 MU/L; 3 times a week） were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed. RESULTS： ACE-Ⅰ decreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-β was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. CONCLUSION： The combination therapy of an ACE-Ⅰand IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect.

Oxidative stress and damage induced by abnormal free radical reactions and IgA nephropathy

Objective: To estimate the oxidative stress and oxidative damage induced by abnormal free radical reactions in IgA nephropathy (IgAN) patients' bodies. Methods: Seventy-two IgA N patients (IgANP) and 72 healthy adult volunteers (HAV) were enrolled in a random control study design, in which the levels of nitric oxide (NO) in plasma, lipoperoxide (LPO) in plasma and in erythrocytes, and vitamin C (VC), vitamin E (VE) and β-carotene (β-CAR) in plasma as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric mothods. Results: Compared with the HAV group, the averages of NO in plasma, and LPO in plasma and in erythrocytes in the IgANP group were significantly increased (P＜0.0001), while those ofVC, VE and β-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the IgANP group were significantly decreased (P＜0.0001). Linear correlation analysis showed that with the increase of the values of NO, and LPO in plasma and in erythrocytes, and with the decrease of those ofVC, VE, β-CAR,SOD, CAT and GPX in the IgAN patients, the degree of histological damage of tubulointerstitial regions was increased gradually (P＜0.0001); and that with the prolongation of the duration of disease the values of NO, and LPO in plasma and erythrocytes were increased gradually, while those of VC, VE, β-CAR, SOD, CAT and GPX were decreased gradually (P＜0.005). The discriminatory correct rates of the above biochemical parameters reflecting oxidative damage of the IgAN patients were 73.8%-92.5%, and the correct rates for the HAV were 70.0%-91.3% when independent discriminant analysis was used; and the correct rate for the IgAN patients was increased to 98.8%, the correct rate for the HAV was increased to 100% when stepwise discriminant analysis was used. The above biochemical parameters' reliability coefficient (alpha) were used to estimate the oxidative damage of the IgAN patients as 0.8145, the standardized item alpha=0.9730, F=53273.5681, P＜0.0001. Conclusions: A series of free radical chain reactions caused serious pathological aggravation in the IgANP' bodies, thus resulting in oxidative damage in their bodies. In treating IgANP, therefore, it is necessary that suitable dose antioxidants should be supplemented to them so as to alleviate the oxidative damage in their bodies.

Physiological characteristics and commercial application of edible mushroom dietary fiber

Edible mushrooms are considered as healthy food because they are low in calories and fat but rich in proteins minerals and dietary fiber(DF). Edible mushrooms are recognized as new potential resource of DF since the components of edible mushroom dietary fiber(EMDF) have shown special physiological and pharmacological effects on human and animals. In this article,the soluble and insoluble fractions of DF in different edible mushroom species have been evaluated. Biological effects of EMDF are related to promoting desired responses,for example,reducing blood cholesterol,protecting cells from free radicals attack by antioxidative effects,attenuating levels and fluctuations of blood glucose and selectively supporting the growth of beneficial gut bacteria. The EMDF plays an important role in reducing risk of cardiovascular diseases,diabetes mellitus and intestinal diseases. The non-starch polysaccharides(NSP),a kind of EMDF,is the best known and most potent mushroom-derived substances with antitumor and immunomodulatory properties. EMDF has also been reported to take part in the control of body weight,lipid homeostasis and insulin sensitivity due to its effect on specific chemical structures and physical properties. Many pharmaceutical substances with potent and unique health- enhancing properties were isolated recently from edible mushrooms and distributed worldwide. Mushroom-based dietary supplements(DSs) with potential therapeutic effects are produced from the mycelia or the fruiting bodies of mushrooms,and are consumed in the forms of capsules,tablets,or extracts. The EMDF, based on its special physiological functions on human health,shows a wide range of potential application prospects.

Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

Effect of acupuncture on antioxidant capacities and protection of vascular endothelium in hyperlipidemia mice

Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, a model group （40 mice）, an acupuncture group （20 mice）, and a drug group （20 mice）. The hyperlipidemia model was prepared in the latter 3 groups by feeding with high fat diet. After the successful modeling, bilateral ＂Fenglong＂ （丰隆 ST 40）, ＂Quchi＂ （曲池 LI 11）, and ＂Sanyinjiao＂ （三阴交 SP 6） were selected in the acupuncture group and Han＇s Acupuncture Stimulator was connected to intervent for 10 rain, once daily, for 10 successive days. Mice in the drug group were orally given Simvastatin, once daily, for 10 successive days. No intervention was given to the normal group and the model group. Serum contents of total cholesterol （TC）, triglyeeride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, malondialdehyde （MDA）, nitric oxide （NO）, endothelin （ET）, and the activity of superoxide dismutase （SOD） were detected. Results The serum contents of TG, TC and LDL-C in the model group detected on the 15th day were all higher than those of the normal group [（1.31±0.32） mmol/L vs （0.70±0.21） retool/L, （5.72±0.85） mmol/L vs （3.08±0.74） retool/L, （2.68±0.55） mmol/L vs （1.83±0.36） retool/L, respectively]. The serum content of HDL-C in the model group was lower than that in the normal group [（0.60±0.26） mmol/L vs （0.94±0.30） mmol/L], showing successful modeling. On the lOth day of successful modeling, the serum contents of MDA and ET in the acupuncture group were lower than those in the model group [（21.58±3.54） p, mol/mL vs （29.94±2.79） p, mol/mL, （44.51±5.23） pg/mL vs （67.07±11.98） pg/mL]. The serum SOD activities and NO content in the acupuncture group were higher than those in the model gropu [（264.57±14.46） U/mL vs （222.66±25.48） U/mL, （85.02±10.06） μmol/L vs （63.83±9.19） μmol/L]. Conclusion Acupuncture could lower serum contents of MDA and ET, improve SOD activities and NO content, showing acupuncture could fight against lipid peroxidation, clear free radicals, regulate as well as ameliorate the metabolic balance of free radicals, and protect the vascular endothelium in hyperlipidemia mice.

Effects of acupuncture on blood-lipids, anti-oxidizing ability and vascular endothelial protective function in hyperlipemia mice

Objective To observe therapeutic effects of acupuncture on the mouse of hyperlipemia and to explore the mechanisms. Methods One hundred and twenty Kunming mice, male, sanitary degree, were randomly divided into normal group （n=40）, a model group （n=40）, an acupuncture group （n=20） and a medicine group （n=20）. Except the normal group, the mice were fed with high fat forage to prepare mouse hyperlipemia model. On the 15th day of modeling, serum total cholesterol （TC）, triglyceride （TG）, low density lipoprotein-cholesterol （LDL-C）, high density lipoprotein-cholesterol （HDL-C） levels were detected in 20 normal mice and 20 model mice; electroacupuncture was given at bilateral ＂Fēnglóng＂ （丰隆 ST 40）, ＂Qūchí＂ （曲池 LI 11）, ＂Sānyīnjiāo＂ （三阴交 SP 6） in the acupuncture group, once a day, for 10 consecutive days; in the medicine group, the mice were intragastrically administrated with Simvastatin, once daily , for 10 consecutive days. After the end of treatment, serum TC, TG, LDL-C, HDL-C, malondialdehyde （MDA）, nitric oxide （NO） and endothelin （ET） contents and superoxide dismutase （SOD） activities were detected in the groups. Results On the 15th day of modeling, in the model group serum TG, TC, LDL-C contents were significantly higher （all P〈0.05） and HDL-C content was significantly lower （P〈0.01） than those in the normal group. After treatment for 10 days, in the acupuncture group and the medicine group serum TG, TC, LDL-C, MDA and ET contents were significantly lower and serum HDL-C and NO contents and SOD activities were significantly higher than those in the model group （P〈0.05, P〈0.01）, and the improving action in the acupuncture group was better than that in the medicine group （P〈0.05, P〈0.01）. Conclusion Acupuncture can regulate fat metabolism, resist lipid peroxidation and protect vascular endothelial function in the mouse of hyperlipemia.

Inhibitory activity of gold and silica nanospheres to vascular endothelial growth factor （VEGF）-mediated angiogenesis is determined by their sizes

Nanoparticles can be involved in biological activities such as apoptosis, angiogenesis, and oxidative stress by themselves. In particular, inorganic nanoparticles such as gold and silica nanoparticles are known to inhibit vascular endothelial growth factor （VEGF）-mediated pathological angiogenesis. In this study, we show that anti-angiogenic effect of inorganic nanospheres is determined by their sizes. We demonstrate that 20 nm size gold and silica nanospheres suppress VEGF-induced activation of VEGF receptor-2, in vitro angiogenesis, and in vivo pathological angiogenesis more efficiently than their 100 nm size counterparts. Our results suggest that modulation of the size of gold and silica nanospheres determines their inhibitory activity to VEGF-mediated angiogenesis.