头颈部肿瘤组织中纤溶酶原激活性的测定

采用纤维蛋白板测定头颈瘤组织中纤溶酶原激活物，结果表明：（１）头颈恶性性肿瘤原发灶／颈淋巴结转移癌ＰＡ活性增高，比活性均值高于相应癌灶领近正常组织和头颈良性肿瘤组织（Ｐ＜０．０１）；（２）在原发灶中ＰＡ比活性均值随肿瘤分期的进展而递增。提示ＰＡ可能是参与头颈恶性瘤生长、浸润及转移的机制之一，ＰＡ使头颈癌细胞激活纤溶系统解癌周组织而浸润、转移。     

头颈部鳞状细胞癌与纤维蛋白溶解因子的关系

用免疫组化方法检查３１例头颈部鳞癌患者癌组织内ｔ－ＰＡ、１１－ＰＡ、ＰＡＩ－－１、ＰＩ及ＴＧＦ－ｐ的定位，并对上述因子的定位与局部癌浸润、原发肿瘤的范围和颈淋巴转移的相关性进行研究。以酶抗体技术对头颈鳞状细胞癌中；①尿激酶型ＰＡ（１１－ＰＡ），属蛋白酶，也是蛋白酶激活物；②组织型ＰＡ（ｔ－ＰＡ），较Ｕ－ＰＡ更具血栓特异性；③ＰＡＬＩ；④纤溶酶抑制因子（ＰＩ）；⑤ＴＧＦ－ｐ进行定位，并探讨它们与肿瘤浸润、大小（即ＵＩＣＣ标准中ＴＮＭ分期中的Ｔ，原发癌的侵犯范围）以及淋巴结转移的关系。共检查了３１例…     

头颈恶性肿瘤浸润转移的凝血纤溶因素

涉及头颈恶性肿瘤浸润转移过程的凝血纤溶因素主要有：血小板和纤溶酶原激活物，通常表现为血小板数量增多、血小板聚集机能亢进及纤溶酶原激活物活性增高，这种变化随恶性肿瘤病程进展而趋普遍和显著，反映了高凝、高纤溶状态有可能促进头颈恶性肿瘤的局部浸润及全身转移。     

纤溶酶原激活物与肿瘤的关系

纤溶酶原激活物（ＰＡ）的肿瘤学意义自７０年代始受到关注，国外深入研究认为：恶性肿瘤组织中ＰＡ升高，其直接参与肿瘤的转化、发生、浸润及转移；肿瘤细胞ＰＡ的合成和分泌可被许多生物活性物质调节；测定ＰＡ在肿瘤组织和体液中的含量有助于诊断、病情观察和预后判断。本对此方面的研究进行综述。     

免疫抑制酸性蛋白在头颈部恶性肿瘤中的分布及其意义

本文以抗免疫抑制酸性蛋白（ＩＡＰ）单克隆抗体、ＡＢＣ免疫酶标组化技术，对５５例头颈部恶性肿瘤和２４例头颈部良性病变组织中ＩＡＰ进行了定位研究。结果表明，良性病变的ＩＡＰ表达均为阴性，恶性肿瘤的阳性表达率为９１．６％，其中高分化癌（Ⅰ、Ⅱ级）、低分化癌（Ⅲ级）、未分化癌（Ⅳ级）的阳性率分别为６６．７％、９０．０％、１００．０％和１００．０％。ＩＡＰ表达阳性率的高低及表达程度的强弱与头颈癌的分化程度有密切关系。ＩＡＰ可望成为一种有用的肿瘤标记物。     

尿激酶型纤溶酶原激活剂系统在肿瘤浸润转移过程中的作用

尿激酶型纤溶酶原激活剂（ｕ－ＰＡ）系统是纤溶系统的组成部分,主要包括：ｕ－ＰＡ、ｕ－ＰＡ受体、ｕ－ＰＡ抑制剂等,ｕ－ＰＡ是一种丝氨酸蛋白水解酶,它能激活纤溶酶原成为纤溶酶从而解胞外基质（ＥＣＭ）介导肿瘤细胞的侵袭和转移。本文就ｕ－ＰＡ系统化学性能及在肿瘤侵袭转移中的作用加以简要介绍。     

P^16抑癌基因与喉癌颈淋巴结转移和恶性度关系的探讨

目的：为了探讨Ｐ＾１６蛋白表达与喉癌颈淋巴结转移及瑟癌组织恶性度的关系。方法：用免疫组化ＳＰ法对８２例声门上型喉癌的原发灶、癌旁组织及颈淋巴进行了Ｐ＾１６蛋白表达的检测。结果：喉癌原发灶中Ｐ＾１６蛋白表达阳性率５４．９％；其中无颈淋巴结转移组阳性率为６８．３％；有颈淋巴结转移组的阳性率４１．５％，差异有显著性意义（Ｐ〈０．０５）。低度恶性组原发灶中Ｐ＾１６蛋白表达阳性率６２．２％；高度恶性组原发灶     

FDG—PET在头颈鳞状细胞癌患者诊断中的应用

正电子发射断层（ＰＥＴ）在头颈鳞癌患者的诊断中较ＣＴ和ＭＲＩ具有较明显的优势，尤其是对原发灶不明肿瘤的诊断、肿瘤放射、化学治疗的评价、复发肿瘤的监测以及颈淋巴结转移灶的诊断等方面都具有一定的临床价值。     

头颈鳞状细胞癌干细胞研究进展

头颈鳞状细胞癌容易发生局部复发、颈淋巴结转移以及远处转移,预后差。肿瘤干细胞在肿瘤转移中具有重要意义,而肿瘤干细胞标记物是分离鉴定肿瘤干细胞的重要物质基础。循环肿瘤细胞是肿瘤细胞从原发灶脱落入外周血中继而形成转移灶的一类细胞,其中部分具有干细胞特性,其与肿瘤的转移、临床特征、预后密切相关。本文就与头颈鳞状细胞癌相关的肿瘤干细胞研究进展做一综述。     

头颈鳞癌的颈淋巴结转移与nm23—H1基因的相关性研究

目的：研究转移抑制基因nm23-H1的表达产物NDPK（二磷酸核苷激酶）在人头颈鳞癌原发灶中的表达及其意义。方法：应用S－P染色方法检测106例头颈鳞癌原发灶组织中nm23-H1/NDPK的表达,结果:nm23-H1/NDPK表达在未发生颈淋巴结转移的头颈鳞癌原发灶中的表达阳性率为75．41％（46／61）,在已发生颈淋巴结转移的头颈鳞癌原发灶中的表达阳性率为35．56％（16／45）,两者差异有显著性（P＜0．05）,结论：nm23-H1/NDPK表达与头颈鳞癌的颈淋巴结转移与否呈显著负相关,可能在头颈鳞癌的颈淋巴结转移过程中起负性调控作用,可用于预估颈淋巴结转移出现的风险。     

Fibrin binding,fibrinolytic and fibrinogenolytic activity of plasminogen activator derived from the paranasal mucous membrane of humans

It is known that large amounts of plasminogen activator (PA) are contained in tissue extracts of the human paranasal mucous membrane (PMM) with chronic sinusitis. The present study was undertaken to isolate and purify the PA in tissue extracts of PMM. Furthermore, the purified PA was identified as to whether it was of the tissue type or urokinase (UK) type, and some of its fibrinolytic characteristics were determined in comparison with those of urokinase. As starting material, extracts of acetone powder of PMM with chronic sinusitis were used, and Zn-imminodiacetate affinity chromatography, lysine-Sepharose affinity chromatography, and ultrafiltration were carried out to separate and purify the PA from the PMM. The PA was purified to a 107-fold increase in specific activity. The molecular weight of the PA was estimated to be 65, 000 to 70, 000 d by gel filtration using Sephacryl S-200. The purified PA was stable in the range of pH 8.0. to 9.0. Using S-2288, a synthetic substrate, the Michaelis constant (Km) of the purified PA was estimated to be 0.11 mmol. The binding of the purified PA to fibrin was stronger than that of UK, while the fibrinogenolytic activity of the purified PA was not stronger than that of UK. Based on these results, the purified PA was identified as a tissue-type plasminogen activator (t-PA). From the kinetic data, it was identified as being of the two-chain variety. It is considered that, as a thrombolytic agent, t-PA derived from the PMM could be more useful than UK.     

Identification of a plasminogen activator derived from nasopharyngeal carcinoma

Summary The activity of plasminogen activator (PA) in tissue extracts from nasopharyngeal carcinoma (NPC) was determined by means of the fibrin plate method. Development of PA activity was observed in 16 out of 25 cases investigated. Furthermore, using tissue extract of NPC with PA activity, characterization and identification of the activator were carried out by means of electrophoretic analysis, fibrin zymography and immunological analysis. The molecular weight of this PA was found to be 38,000 daltons. Additionally, a urokinase type of plasminogen activator was contained in the tissue extracts.     

Plasminogen activators in tissue extract of aural cholesteatoma

Using a biochemical technique, the authors characterized and identified the plasminogen activator (PA) derived from tissue extracts of six aural cholesteatomas. The results of fibrin zymography indicated that the tissue extracts of two cholesteatomas demonstrated two lytic zones on fibrin-agarose plates. One of the lytic zones was at about 72 kd, while the other zone was at about 64 kd. Using various goat immunoglobulin G (IgG)-containing antibodies (anti-human uterine tissue type PA (t-PA), anti-human low-molecular-weight (LMW) urokinase, and nonspecific goat IgG) and plasminogen-free fibrin-agarose plates, we confirmed that the cholesteatoma tissue extracts contained 72 kd t-PA and 64 kd urokinase type PA (u-PA). Furthermore, we measured the t-PA and u-PA activities in the tissue extracts selectively by parabolic rate assay. In order to estimate the PA activity, we developed optimal conditions for this assay. The specific t-PA activity ranged from 0.03 to 0.43 mIU/μg-protein and the specific u-PA activity ranged from 0 to 0.35 mIU/μg-protein. The highest percentage of u-PA with respect to the total PA activity was 44.9%. However, in four of the six cases, we failed to detect u-PA activity. In the present study, we thus clarified the presence of PAs in tissue extracts of aural cholesteatomas. Furthermore, we confirmed that measurable u-PA occurred in some tissue extracts. We anticipate that the u-PA in inflammatory tissues plays an important role in the degradation of the extracellular matrix via the formation of plasmin and collagenases.     

Studies on proactivator from the paranasal mucous membrane in chronic sinusitis

We succeeded in differentiating the proactivator (PA) in tissue extract of paranasal mucous membrane with chronic sinusitis by the gel filtration technique. Furthermore, the results demonstrated that PA in the tissue extracts of the paranasal mucous membrane with chronic sinusitis and antrochoanal polyp was unrelated to the antigenicity of plasminogen. In particular, it was clarified that the tissue extract of antrochoanal polyp as a source of PA was not related to the antigenicity of plasminogen.     

Fibrinolytic activity in medium from tissue culture of paranasal mucous membrane

It is known that a remarkable fibrinolytic activity of plasminogen activator (PA) can be seen in extracts of wet tissue and acetone powder preparation of paranasal mucous membrane evidencing chronic sinusitis. However, the origin of the PA in extract of paranasal mucous membrane has not yet been clarified up to the present time. In this experiment, using a tissue culture of paranasal mucous membrane, it was observed that two species of cells, epithelial cells and fibrocytes, proliferated in the implanted tissue. PA was isolated from the conditioned medium on the fifth day after culture. From these results, it appears that the PA may be released from epithelial cells and/or fibroblasts.     

The role of fibrinolytic enzymes in inflammation and paranasal mucous membrane

The distribution and role of tissue plasminogen activator (TA) and proactivator (PA) in various diseases of the nasal and paranasal cavity were investigated. The stronger the inflammatory and proliferative response of the paranasal mucous membrane, the weaker was the fibrinolytic activity of TA. The fibrinolytic activity of PA tended to be stronger than TA activity. It is considered that PA may play an important role in inflammatory enlargement and proliferation of the paranasal mucous membrane, but does not play an important role in carcinogenic enlargement and proliferation of the nasal and paranasal mucous membrane.     

Some chemical properties of tissue plasminogen activator purified from paranasal mucous membrane

Plasminogen activator (PA) was purified from an acetone powder preparation of paranasal mucous membrane with chronic sinusitis, and some chemical properties of the purified PA were investigated in this paper. Zn-imminodiacetate affinity chromatography, lysine sepharose affinity chromatography and ultrafiltration for concentrating a PA fraction were consecutively performed to purify the PA from the acetone powder preparation. Finally, gel filtration was performed using Sephacryl S-200 in order to estimate the molecular weight of the purified PA. The purified PA in this experiment showed a stronger affinity to fibrin than urokinase did. The molecular weight of the purified PA was estimated to be 65,000 to 70,000 daltons as determined by Sephacryl S-200 gel filtration. The Km of the purified PA was 0.11 mM. From these results, it is apparent that the PA purified from an acetone powder preparation of paranasal mucous membrane belongs to the class of tissue type plasminogen activators (t-PA).     

Plasminogen activators in human xenografted oro-pharyngeal squamous cell carcinomas

Specimens of squamous cell carcinomas of the head and neck established as xenografted tumour lines on nude mice were examined by the fibrin slide method for the presence of plasminogen activator(s). The fibrinolytic activity was partly quenched by antibodies against the vessel-related tissue plasminogen activator and partly by antibodies against urokinase. The results indicate that inactive pre-urokinase in tumour tissue is to some degree activated when the tumour tissue is transplanted to the nude mice. In organ culture of the tumours, urokinase of both low and high molecular form was secreted into the medium, but only traces of tissue plasminogen activator. Inhibition of urokinase activity might be an approach to hinder tumour growth.     

Presence of urokinase-type plasminogen activator (u-PA) in tissue extracts of antrochoanal polyp.

Using a biochemical technique, the authors characterized and identified a plasminogen activator (PA) derived from tissue extracts of antrochoanal polyp (AP) and paranasal mucous membrane (PMM) with chronic sinusitis. The results of fibrin zymography indicated that the tissue extracts of AP revealed two lytic zones and that those of PMM revealed a single lytic zone on fibrin-agarose plates. One of the AP zones exhibited the same relative mobility as the PMM zone (molecular weight: 65 kd), while the other AP zone had a smaller molecular weight (about 54 kd). Goat immunoglobulin G (IgG) fraction of antihuman uterine tissue-type plasminogen activator (t-PA) inhibited the 65-kd lytic zones of AP and PMM. Antihuman low-molecular-weight urokinase inhibited only the 54-kd lytic zone of AP, and nonspecific goat IgG failed to inhibit any of the lytic zones. On the other hand, 10(-2) mol trans 4-(aminomethyl)cyclohexane-carboxylic acid (t-AMCHA) inhibited all of the lytic zones. No lytic zones could be observed on plasminogen-free fibrin-agarose plates. These findings confirmed that the tissue extracts of PMM contained t-PA, and that those of AP contained both t-PA and urokinase-type plasminogen activator (u-PA). In addition, it appeared that u-PA in inflammatory tissue was related to proliferative changes of the mucous membrane.     

Expression pattern of the plasminogen activator-plasmin system in human cholesteatoma

The plasminogen activator-plasmin system plays a pivotal role in the delicately regulated process of extracellular matrix remodeling. Recent studies have shown that an imbalance of proteolytic enzymes over specific inhibitors in this system may lead to an aggressive, expanding, and infiltrating cellular phenotype. As cholesteatoma resembles a tumor in many ways, we investigated the pattern of expression for members of the plasminogen activator-plasmin system in 12 human cholesteatomas, using immunohistochemistry. As controls, 3 tympanic membranes and 4 ear canal skin specimens were used. In contrast to the tympanic membranes, all cholesteatoma specimens showed a strong expression of plasminogen at the basal epithelial cell layers. In ear canal skin, only the basal surface of the most basal epithelia stained discretely positive. The urokinase-type plasminogen activator (uPA) could be detected in the basal stratum of the cholesteatoma matrix and in the surrounding granulation tissue, while tissue-type plasminogen activator (tPA) was not detectable at all. Plasminogen activator inhibitor-1 (PAI-1) was expressed in both the granulation tissue and the granular cell layer of the matrix, but not in the basal epithelial cells; PAI-2 showed a pericellular expression pattern in the subbasal and granular cell layers. Neither uPA, tPA, nor the PAIs could be detected in tympanic membrane controls; ear canal skin showed the same staining pattern as cholesteatoma only for PAI-2. Our data demonstrate that there is a clear imbalance in favor of proteolytic activity in the basal epithelial layers of the cholesteatoma matrix, which might at least partly account for the aggressive behavior of this tumorlike lesion. Further, the pattern of expression resembles the pattern described for several epithelial malignancies.