血管内皮生长因子与乳腺癌临床病理因素及预后的关系

目的：探讨血管内皮生长因子在乳腺癌中的表达情况及其与预后的关系。方法：采用免疫组化法对1985年至1986年手术治疗的109例乳腺癌的原发灶进行血管内皮生长因子（VEGF）和微血管密度（MVD）检测，并与临床病理资料进行比较分析。结果：VEGF强表达组淋巴结转移率（52．2％）和病理分级明显高于弱表达且（23．5％，P＜0．05）；随VEGF表达强度的增加，生存率（5年、10年、15年）呈下降趋势，但无明显差异；VEGF与肿瘤大小、绝经状况、雌孕激素受体之间未见相关性。结论：VEGF表达与乳腺癌淋巴结转移和病理分级呈正相关，与预后呈负相关趋势，是估计恶性程度的有用指标，对判断预后有参考价值。     

Chronic treatment with scopolamine and physostigmine changes nerve growth factor (NGF) receptor density and NGF content in rat brain

Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (K_d= 0.045nM) and low (K_d= 21nM) affinity¹²⁵I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50–90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity.     

重组人血小板源性生长因子增加细胞外信号调节激酶磷酸化促进糖尿病大鼠全层皮肤缺损创面愈合

目的 在体观察重组人血小板源性生长因子（recombinant human platelet—derived growth factor，rhPDGF）促进糖尿病大鼠全层皮肤缺损创面修复可能涉及的细胞和分子机制，研究其可能涉及的信号通路。方法 26只糖尿病大鼠，每只动物背部制备4个全层皮肤缺损创面，选取其中52个创面，随机分成3组，即对照组，创面自然愈合；rhPDGF治疗组，创面rhPDGF用量为7．0μg／cm^2；赋形剂组，创面用等量赋形剂凝胶。观察治疗后3、7和14d创面肉芽形成、胶原沉积、再上皮化速率以及炎性细胞浸润情况，并采用免疫荧光和免疫组织化学技术观察创面周围和创面修复细胞内细胞外信号调节激酶1／2（extracellular signal—regulated kinase1／2，ERK1／2）磷酸化和增殖细胞核抗原（proliferative cell nuclear antigen，PCNA）的表达。结果 组织学观察，rhPDGF治疗组创面可见大量炎性细胞浸润，毛细血管胚芽及成纤维细胞明显多于另两组（P〈0．05）；胶原沉积明显，肉芽组织生长活跃，创面收缩显著，与对照组比较差异有统计学意义（P〈0．05）。免疫学研究显示，应用rhPDGF7～14d后，rhPDGF治疗组ERK1／2明显强于对照组和赋形剂组（P〈0．05）；且损伤后3～7d rhPDGF治疗组修复细胞PCNA的表达明显高于对照组和赋形剂组（P〈0．05）。结论 rhPDGF促糖尿病大鼠刨面愈合的作用部分是通过ERK1／2信号通路的磷酸化来完成的。     

表皮生长因子受体抑制剂AG1478对乳腺癌裸鼠移植瘤的生长影响

目的 观察表皮生长因子受体抑制剂AG1478和内分泌治疗联合应用对乳腺癌荷瘤裸鼠移植瘤生长的影响.方法 应用MCF-7乳腺癌细胞建立裸鼠动物模型,当肿瘤体积在100～200 mm3时,按肿瘤体积大小将裸鼠随机分成溶剂对照组、AG1478组、三苯氧胺(TAM)组、AG1478+TAM组,分别给予空白溶剂、AG1478腹腔注射、TAM灌胃、AG1478腹腔注射和TAM灌胃.同时给药6周,动态观察移植瘤生长,用药结束后2d处死裸鼠,取肿瘤称重、计算肿瘤体积(V=长径×短径2×π/6)、抑瘤率([(V对照组-V实验组)/V对照组]×100%).结果 各组裸鼠体重和肿瘤体积在治疗前具有均衡性.用药期间,溶剂对照组肿瘤生长最快,AGl478组次之,TAM组肿瘤生长较缓慢,而AGl478+TAM组肿瘤有缩小趋势.用药结束后,各组的抑瘤率分别为AG1478组30.4%,TAM组62%,AG1478+TAM组84.8%,与对照组比较差异有统计学意义(P<0.05).结论 AG1478对乳腺癌裸鼠移植瘤具有抑制作用,也可以加强三苯氧胺的抑瘤效果,两者有明显协同作用.     

Vascular endothelial growth factor in psoriasis: an indicator of disease severity and control

Background  Psoriasis is a chronic disease characterized by abnormal epidermal proliferation, inflammation and angiogenesis. It has been reported that vascular endothelial growth factor (VEGF) is overexpressed in lesional psoriatic skin and its serum levels are significantly elevated in patients with moderate to severe disease.
Objective  This study aims to evaluate the possible role of VEGF in the pathogenesis of psoriasis, and its significance as an indicator of disease severity and control.
Methods  Thirty patients with moderate to severe psoriasis and 10 healthy controls were subjected to baseline evaluation of VEGF. Patients were divided into three groups according to the received treatment: psoralen plus ultraviolet A (PUVA) thrice weekly (group 1), acitretin 50 mg daily (group 2), and combined PUVA twice weekly and acitretin 25 mg daily (group 3).Treatment continued for 16 weeks or up to clinical cure. Every patient was subjected to severity evaluation by Psoriasis Area and Severity Index (PASI) and measurement of serum VEGF before and after treatment.
Results  Mean serum levels of VEGF were significantly elevated in patients (327 ± 66.2 pg/mL) than control subjects (178 ± 83.4 pg/mL). A highly significant correlation was found between VEGF and PASI score, but not with other variables. The best clinical response, the least side-effects and the highest reduction of VEGF serum levels were achieved by the combined therapy.
Conclusion  The present study supported the proposed role of VEGF in the pathogenesis of psoriasis, and suggested that it could serve as a good indicator of disease severity and control.     

Angiolipoma of the buccal mucosa: a possible role of mast cell-derived VEGF in its enhanced vascularity

A case of angiolipoma occurring in the buccal mucosa of a 69-year-old male is described. The patient had noticed a painless mass in his buccal mucosa for 2 years. The surgically removed tumor, measuring 9 mm in diameter, was mainly located in the submucosal layer with focal expansion into the muscle layer. Histologically, the tumor was well-demarcated and composed of proliferations of mature fat cells and fibrous connective tissue containing many small blood vessels, which were evenly distributed. There was diffuse infiltration of a large number of mast cells, which were immunopositive for vascular endothelial growth factor (VEGF) especially around blood vessels, suggesting that VEGF produced by mast cells in angiolipomas plays an important role in the vascular proliferation in this particular tumor.     

Stimulation of Alpha-Adrenoceptors Facilitates the Release of Growth Hormone-Releasing Hormone from Rat Hypothalamus in vitro

While extensive evidence suggests that adrenoceptors play an important role in the control of growth hormone in the rat, there are few studies involving the direct measurement of growth hormone-releasing hormone (GHRH). We have therefore developed a radioimmunoassay for rat GHRH, and used it to investigate the modulation of GHRH release by noradrenaline from incubated rat hypothalamus in vitro. The GHRH radioimmunoassay had no significant cross-reactivity with other hypothalamic or GHRH-related peptides, and was sensitive to 4 pg/tube; intra- and interassay coefficients of variation were 6% and 12% respectively. Single incubated rat hypothalami produced a stable and readily measurable output of GHRH in successive 20 min incubations after an initial 60 min preincubation; the release of GHRH was increased in the presence of 56 mM KCI, but did not respond to KCI-depolarization when calcium was excluded from the medium. Stimulated GHRH release was identical to synthetic rat GHRH(1–43) on high-performance liquid chromatography and Sephadex G-75 chromatography.
Noradrenaline stimulated GHRH secretion in a dose-dependent manner in the concentration range 10⁻¹⁰— 10⁻⁶M, with a plateau in response at 10⁻⁷M. Stimulation with noradrenaline 10⁻⁷M was blocked by idazoxan 10⁻⁵M and attenuated by thymoxamine 10⁻⁵M, but was unaffected by timolol 10⁻⁵M. Both the α₂-adrenoceptor agonist guanfacine, and the α₁-adrenoceptor agonist methoxamine, specifically stimulated GHRH secretion.
It is concluded that noradrenaline stimulates the release of GHRH at both α₁ and α₂-adrenoceptors.     

老年与青壮年脑挫裂伤组织NGF的表达差异及意义

目的 研究衰老对脑挫裂伤组织神经生长因子（NGF）基因表达的影响,进一步探讨老年颅脑损伤病人神经功能缺失程度较重的分子生物学机制.方法 收集重型颅脑损伤开颅手术中的脑挫裂伤组织,应用免疫组化和医学数码图像分析技术,观察老年组（≥60岁）和青壮年组（19～59岁）病人脑损伤后3～9 h脑挫裂伤组织NGF蛋白的表达差异.结果 脑损伤后NGF在老年和青壮年脑挫裂伤组织中的表达均明显增强;老年组脑挫裂伤组织中的NGF蛋白表达显著性低于青壮年组（P＜0.05）.结论 老年人脑挫裂伤后NGF表达水平下降明显,提示其受损神经元的修复和生存能力降低,这可能是老年颅脑损伤病人恢复不良的重要原因之一.     

表皮生长因子对大鼠脑梗死后神经功能恢复的影响

目的 观察表皮生长因子（EGF）对大鼠脑梗死后神经功能恢复的影响。方法 采用肾血管性高血压大鼠制作一侧大脑中动脉皮层支闭塞（MCAO）模型。MCAO术后24 h，32只大鼠侧脑室注入10μl EGF（100μg/L），连续2d，共2μg（EGF组）；32只大鼠只注入不含EGF的等量溶液（对照组）。MCAO术后1、2、3和4w，行Bederson神经功能评分后，免疫印迹检测双侧大脑半球生长相关蛋白（GAP43）、突触囊泡蛋白（SYN）和胶质原纤维酸性蛋白（GFAP）的表达。结果 与同期对照组相比，EGF组大鼠在MCAO术后1、2w神经运动功能恢复更好，脑梗死灶同侧半球GAP43、SYN和GFAP有更早期和更高表达（P<0.05）。结论 GAP43、SYN和GFAP等蛋白的早期高峰表达可能与EGF引起的早期神经可塑性改善有关。