转化生长因子—α,表皮生长因子受体与胃癌发生的关系及其与增 …

研究在胃癌发生的不同阶段转化生成因子－α，表皮生长因子受体的表达情况及与增殖细胞核抗原表达的关系。     

转化生长因子β1 mRNA在实验性肝癌间质差异形成中的 …

目的：应用原位分子杂交技术观察了ＴＧＦ－β１ｍＲＮＡ在实验性大鼠胆管细胞性肝癌（ＣＣ）和肝细胞性肝癌（ＨＣＣ）中的表达,探讨肝癌间质差异形成的可能机制。方法：大鼠肝癌组织经ＨＥ和Ａｌｃｉａｎ Ｂｌｕｅ染色确认ＣＣ或ＨＣＣ,用ＴＧＦ－β１反应ＲＮＡ探针检测ＴＧＦ－β１ｍＲＮＡ的表达,同时以ＴＧＦ－β１正链,β－ｍＲＮＡ呈弱到中等强度的表达,少数ＣＣ的间质细胞也有ＴＧＦ－β１ｍＲＮＡ表达。结论：由于Ｔ     

表皮生长因子、转化生长因子-α及其受体在人垂体腺瘤组织中的表达

目的探讨表皮生长因子 (EGF)、转化生长因子 α(TGF α)和表皮生长因子受体 (EGFR)在垂体腺瘤发生、发展过程中的作用。方法应用放射性原位分子杂交法 ,观察上述3种分子的表达。结果在检测的22例垂体腺瘤组织中 ,分别有17例 (77 % )、12例(55 %)和20例(91 %)显示有EGF ,TGF α和EGFRmRNA的过度表达 ,它们在正常垂体组织中的阳性率分别为42 % ,25 %和42 %。不同的垂体腺瘤组织中3种mRNA的表达强度有差异。结论垂体腺瘤中存在着EGF/EGFR或/和TGF α/EGFR自分泌系统 ,该系统在垂体腺瘤的分化及增殖过程中可能起着重要的作用。     

转化生长因子、碱性纤维细胞生长因子、在胃肠道癌组织的表达

一、材料和方法１促血管内皮细胞生长因子的抗体：兔抗转化生长因子（ＴＧＦβ３）和碱性纤维细胞生长因子（ＢＦＧＦ）均由美国ＳａｎｔａＣｒｕｚ公司供应。２组织来源：１３例胃癌，１６例肠癌和１９例肝癌组织均为手术切除标本，正常胃（５例），肠（３例）及...     

肝病患者血清表皮生长因子、转化生长因子—α含量变化的探讨

目的探讨肝病患者血清表皮生长因子(EGF)、转化生长因子-α(TGF-α)含量变化的意义.方法应用放射免疫分析法检测212例各类肝病患者和88例正常对照组的血清EGF和TGF-a的含量.结果与对照组相比,原发性肝癌组、肝硬化组的EGF、TGF-α水平显著升高(p<0.01).急性肝炎组和慢性重型肝炎组的血清TGF-α也明显增高,而慢性轻型肝炎组的血清中EGF、TGF-α含量与对照组比较差异无显著性意义(p>0.05).急、慢性肝炎组的血清中TGF-α含量与血清中总胆红素和谷丙转氨酶的含量变化呈正相关.肝硬化组中TGF和EGF均与A/G比值相关.结论提示EGF和TGF-α的活性与肝脏疾病中的炎症损伤、修复再生、纤维化和肿瘤增殖的形成起重要作用.     

转化生长因子α

转化生长因子α(TGFα)是一种主要由肿瘤细胞产生的小肽分子,其前体为160个氨基酸,成熟体为50个aa残基,各种形式的TGFα均具有生物活性。TGFα为分泌性蛋白,它与细胞表面的表皮生长因子受体结合,以自分泌和旁分泌的形式参与对细胞增殖和分化的调节,TGFα与肿瘤密切相关,大多数肿瘤中已发现有TGFα高表达,TGFα具有肿瘤诊断、预后以及治疗临床外伤等多方面的应用价值。     

碱性成纤维细胞生长因子在乙型肝炎肝组织中的表达

目的：研究肝组织中碱性成纤维细胞生长因子（bFGF)及bFGF mRNA的表达及其与慢性乙型肝炎（CHB）肝血管增生、改建及肝血管纤维化的关系。方法：对120例CHB及50只CC14诱导肝损伤大鼠肝标本进行bFGF免疫组织化学染色及bFGF mRNA原位杂交，并检测了CHB肝组织中α－SMA、FN、LN、CoⅣ表达与bFGF的关系。结果：随着CHB肝细胞变性坏死及肝血管病变加重，bFGF在肝血管及肝窦壁表达强阳性率逐渐上升（P＜0．01），部分固缩性肝细胞也未强阳性显示。原位杂交显示，bFGF mRNA主要分布于血管纤维化区域肝窦壁及部分肝细胞。同时bFGF在肝组织的表达与α－SMA、FN、LN及CoⅣ呈同步关系。结论：bFGF通过激活血管及肝窦内皮细胞，引发肝血管增生及内皮细胞凋亡，在细胞外基质等参与下，最终导致肝血管纤维化、肝窦毛细血管化及假小叶纤维间隔形成。     

CAS基因在原发性肝癌组织中的表达及其与HBV感染的关系

目的 探讨细胞凋亡易感基因(CAS)可否作为肝癌的病理诊断标志物,以及肝细胞癌中CAS蛋白的表达与HBV感染之间的关系.方法 应用免疫组化法检测肝癌、癌旁组织及未发生肿瘤的肝硬化、肝炎组织中CAS蛋白的表达情况,同时应用免疫组化法、核酸原位杂交法检测HBV感染的肝细胞癌组织、癌旁组织中HBsAg、HBcAg以及HBV DNA的表达情况,分析肝细胞癌中CAS蛋白的表达与HBV感染之间的关系.结果 CAS蛋白在肝癌组织中的表达较癌旁组织明显升高(P＜0.01),而癌旁组织中CAS蛋白表达较未发生肿瘤的肝硬化、肝炎组织显著增强(P＜0.01).低分化型肿瘤细胞的CAS蛋白表达明显高于中分化型和高分化型(P＜0.01).CAS蛋白在HBV感染的肝细胞癌组织中的表达明显高于非HBV感染的癌组织(P＜0.01),其中HBV DNA阳性的肝细胞癌组织中CAS蛋白表达水平显著高于HBV DNA阴性的肝细胞癌组织(P＜0.05).结论 CAS蛋白在肝细胞癌组织中呈高表达,肝细胞癌分化愈低其表达愈强,表明CAS蛋白可作为肝细胞癌的病理诊断与分化程度的评价标志物.并推测HBV DNA可能通过上调CAS的表达,在HBV感染相关性肝癌的发生发展过程中发挥重要的作用.     

Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas

Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-α) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-α was detected with a monoclonal mouse antibody and EGF with polyclonal rabbit antiserum. Thirty-five of the tumours were positive for TGF-α and 26 of the tumours for EGF. None of the poorly differentiated tumours was positive for EGF, but they all were for TGF-α. In sections including normal differentiated oral mucosa, the cells above the basal cell layer were positive for both TGF-α and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells, thus paralleling the situation observed in the normal differentiated oral mucosa. In four cases, material was available from both a primary tumour and a metastasis. Three of these were positive for TGF-α and EGF with the same staining pattern as that of the primary tumours. This investigation together with our previous results confirms the existence of TGF-α, EGF, and EGF-receptors in the majority of oral squamous cell carcinomas and their metastases.     

Immunohistochemical localization of transforming growth factor alpha in chemically induced rat hepatocellular carcinomas with reference to differentiation and proliferation

Hepatocellular carcinomas (HCCs) were induced in male Fischer 344 rats with dietary 3'-methyl-4-(dimethylamino)-azobenzene treatment and were classified into solid, glandular (well- or poorly differentiated), and trabecular types. Investigation of cell proliferation kinetics and immunohistochemical localization of transforming growth factor alpha (TGF-alpha) demonstrated all solid (n = 24) and poorly differentiated glandular type (n = 6) HCCs to have TGF-alpha-positive nuclei. Nuclear staining of TGF-alpha was also observed in 13 of 28 (46%) trabecular-type HCCs, whereas 12 (43%) exhibited cytoplasmic staining, and 3 (11%) were negative. As for well-differentiated glandular HCCs, 7 of 20 (35%) were positively stained in their nucleus, another 7 (35%) demonstrated antibody binding in the cytoplasm, and 6 (30%) were negative. The order for growth rate evaluated by bromodeoxyuridine (BrdU) labeling was solid (38.22%), poorly differentiated glandular (26.82%), trabecular (7.98%), and well-differentiated glandular (2.57%) types. For trabecular HCCs with nuclear, cytoplasmic, or negative TGF reactions, values were 13.39% (n = 13), 3.61% (n = 12), and 2.01% (n = 3), respectively. Likewise, BrdU-labeling indices for the counterpart groups of well-differentiated glandular type HCCs were 4.53, 1.91, and 1.29%, respectively. The results indicate that TGF-alpha expression might be linked to histopathological differentiation and cell proliferation in rat HCCs.     

肺泡Ⅱ型TGFβ1和PDGF基因表达及其肺纤维化中的意义

目的：研究转化生长因子β1（TGFβ1）和血小板源性生长因子（PDGF）在肺泡Ⅱ型细胞中的表达及其在肺纤维化过程中的意义。方法：分离培养正常成年大鼠肺泡Ⅱ型细胞,建立大鼠矽肺模型,用原位杂交和免疫组化技术检测体外培养的和矽肺病变中的肺泡Ⅱ型细胞TGFβ1和PDGF-B mRNA和蛋白的表达。结果：（1）体外培养的肺泡Ⅱ型细胞免疫组化染色TGFβ1强阳性,PDGF-B弱阳性;原位杂交TGFβ1和PDGF-B mRNA均为阳性。（2）大鼠矽肺实验组增生的肺泡Ⅱ型细胞明显表达TGFβ1和PDGF-B mRNA和蛋白;对照组仅有部分正常肺泡Ⅱ型细胞TGFβ1 mRNA呈弱阳性。结论：增生的肺泡Ⅱ型细胞有TGFβ1和PDGF-B基因表达,其在矽肺纤维化病变中可能起重要作用。     

Expression of transforming growth factor beta1 and its receptors in normal human urothelium and human transitional cell carcinomas

Previous studies indicated that transforming growth factor beta1 (TGFbeta1) is expressed by normal urothelial cells and exerts regulatory autocrine functions in urothelial maintenance and wound healing. However, little is known about the expression patterns of TGFbeta1 and its receptors in bladder tumors. Therefore, we studied the protein and mRNA localization of TGFbeta1 and TGFbeta receptor types I and II (TGFbetaRI and TGFbetaRII) in normal human urothelium and transitional cell carcinomas (TCCs) of different grades and stages. Expression of TGFbeta1 and its receptors was examined by immunocytochemistry and mRNA in situ hybridization in normal urothelium and TCCs using a semiquantitative method. By immunocytochemistry, the expression of TGFbeta1 and TGFbetaRII was higher in superficial and basal cell layers of normal urothelium than in the intermediate layer. A similar localization was seen in superficial TCCs. TGFbetaRI was mainly present in basal and intermediate cell layers of normal urothelium and superficial TCCs. In contrast, in muscle invasive TCCs, all tumor cells stained intensely for all three proteins. No correlation was found between immunostaining and TCC grade. In situ hybridization pointed out that all cell layers in normal urothelium exhibit similar TGFbeta1 mRNA levels. Elevated TGFbeta1 mRNA levels were noted in TCCs irrespective of grade or stage. In conclusion, these data indicate that in normal urothelium TGFbeta1, TGFbetaRI, and TGFbetaRII expression depend on maturation and differentiation. This pattern is particularly lost in muscle invasive TCCs, in which the expression of the three proteins is enhanced. These data suggest autocrine TGFbeta1 mechanisms in human TCC cells that may be more pronounced in muscle invasive TCC cells.     

转化生长因子β1及其受体在横纹肌肉瘤中的表达

目的 :探讨横纹肌肉瘤 (RMS)中转化生长因子 β1(TGFβ1)及其Ⅰ、Ⅱ型受体 (TGFβRⅠ ,TGFβRⅡ )表达及其意义。 方法 :应用免疫组化技术 (S P法 )检测 4 9例经电镜或 (和 )免疫组化证实的横纹肌肉瘤及 2 0例正常横纹肌组织中的TGFβ1、TGFβRⅠ和TGFβRⅡ表达水平 ,并结合临床病理资料进行分析。 结果 :TGFβ1在RMS中的高表达率高于正常横纹肌组织 (P<0 0 1) ;TGFβRⅠ、TGFβRⅡ在 98% (48/ 4 9)的RMS及所有正常横纹肌组织中均有表达 ,两组无差异。TGFβ1表达与肌球蛋白重链呈负相关 (r=- 0 6 6 1,P <0 0 1)。TGFβ1在低分化组高表达率为 79% ,高分化组为 38%。 结论 :横纹肌肉瘤中存在TGFβ1自分泌和旁分泌现象 ,且肿瘤细胞表达相关受体。TGFβ1的表达与肌源性分化程度有关。TGFβ1信号传导途径可能参与了横纹肌肉瘤的发展与演进     

Greater expression of transforming growth factor alpha and proliferating cell nuclear antigen staining in mouse hepatoblastomas than hepatocellular carcinomas induced by a diethylnitrosamine-sodium phenobarbital regimen

Transforming growth factor alpha (TGF-alpha) is a potent stimulator of normal hepatocyte proliferation, considered to have relationship to the liver regeneration or carcinogenesis. In this study, we investigated immunohistochemically the association between expression of TGF-alpha and cell proliferation activity in mouse hepatoblastomas (HBs) and hepatocellular carcinomas (HCCs) induced in B6C3F1 mice by diethylnitrosamine and sodium phenobarbital. The TGF-alpha-positive rate in HBs (29.2%) was significantly higher than that in HCCs (12.7%). Likewise, the proliferating cell nuclear antigen-positive rate (22.2%) was higher than the HCC value (14.5%). On the individual data for both TGF-alpha and PCNA, most of the HBs showed higher positive rates than HCCs. In HBs, TGF-alpha was localized only in the nuclei, whereas some HCC cells stained positive both in their nuclei and cytoplasm (0.6%). These results suggest expression of TGF-alpha and its localization might be linked to cell proliferation and play a role in malignant progression of mouse HBs.     

TGF-α与IGF-Ⅱ在血液透析中的检测及其临床意义

目的；研究多肽生长因子ＴＧＦ－α与ＩＧＦ－Ⅱ在长期血透（ＨＤ）患者血清及体液中的表达特征。方法；采用放射免疫分析法，检测４５例维持性ＨＤ患者血清１２ｈ尿液中ＴＧＦ－α与ＩＧＦ－Ⅱ的水平。结果：ＴＧＦ－α水平明显低于正常组，ＩＧＦ－Ⅱ则明显高于正常组。ＨＤ后血清中两项指标水平均明显高于ＨＤ前，测定１２ｈ尿液ＴＧＦ－α和ＩＧＦ－Ⅱ含量较正常对照组增高明显。     

Expression of transforming growth factor alpha in human tissues: Immunohistochemical study and Northern blot analysis

Summary The expression of transforming growth factor alpha (TGF-) was examined in various human tissues and the fetus, using immunohistochemistry and Northern blot analysis. TGF- immunoreactivity was detected mainly in the epithelial cells of the digestive tract, liver, pancreas, kidney, thyroid, adrenal, skin, mammary gland and genital organs. In the digestive tract, epithelial cells with regenerative change or hyperplastic change showed strong immunoreactivity to TGF-. Peripheral nerve, vessels, megakaryocytes and macrophages in the lung and spleen were also positive for TGF-. By Northern blot analysis the expression of TGF- mRNA was confirmed in the digestive tract, salivary gland, thyroid, kidney and mammary gland. In the human fetus, the nerve tissues, liver, adrenal and kidney were positive for TGF-. Strong immunoreactivity to TGF- was observed in the hepatocytes of the fetus. These findings indicate that TGF- is produced by a variety of nonneoplastic cells in both adult and fetal tissues.