外用重组人表皮生长因子凝胶治疗浅Ⅱ度烧伤创面的临床观察

目的观察重组人表皮生长因子在促进浅Ⅱ度烧伤创面愈合中的疗效。方法将32例四肢浅Ⅱ度烧伤患者64个烧伤部位随机分成两组,对照组32个部位应用凡士林油纱换药方法治疗,治疗组32个部位在凡士林油纱的基础上加用重组人表皮生长因子治疗,观察比较创面的愈合时间。结果治疗组较对照组创面愈合时间缩短：治疗组（8.4±1.2）d,对照组（11.6±1.8）d,两组差异有统计学意义（P〈0.01）。结论局部外用重组人表皮生长因子治疗浅Ⅱ度烧伤能加速创面愈合。     

重组人表皮生长因子及碱性成纤维细胞生长因子联合应用促进内镜鼻窦手术后术腔创面上皮化的疗效观察

目的观察rhEGF凝胶及bFGF滴眼液联合应用对鼻内窥镜鼻窦相关手术后的术腔创面黏膜上皮化的效果。方法对30例（60侧）经鼻内镜全鼻窦开放术患者进行同体对照观察，左侧为观察组，鼻窦术后每周在鼻内镜下作一次详尽术腔清理，于术腔置放rhEGF凝胶及bFGF滴眼液，混合抗生素和地塞米松的明胶海绵；右侧为对照组鼻窦每天使用鼻腔冲洗器自行冲洗鼻腔，鼻内使用局部类固醇激素，每周作鼻内镜下的术腔清理1次。连续内镜随访12周，观察双侧术腔上皮化过程。结果观察组治愈（28例）93．33％，好转（2例）6．67％，平均上皮化时间4周；对照组治愈（24例）80％，好转（6例）20％，平均上皮化时间9周，平均上皮化时间差异有统计学意义（P〈0．01）。结论鼻内窥镜鼻窦手术后联合应用rhEGF及bFGF可以促进术腔上皮化，显著缩短上皮化时间，治疗效果好。     

Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer.

Overexpression of the epidermal growth factor receptor (EGFR) has been reported as an important molecular abnormality in human pancreatic cancer. There is in vitro evidence that simultaneous overproduction of one of its ligands, transforming growth factor alpha (TGF-alpha), might result in an autocrine loop with an increased proliferation signal. We analysed by immunocytochemical staining a retrospective series of human pancreatic cancers, chronic pancreatitis, and normal fetal and adult pancreatic tissues for the presence of TGF-alpha and epidermal growth factor (EGF). Ductal epithelial cells showed TGF-alpha immunoreactivity in both normal tissue and chronic pancreatitis, and 95 per cent of tumours showed strong immunoreactivity. In contrast, EGF immunoreactivity was not found in normal pancreas, but was expressed in 12 per cent of pancreatic carcinomas. Well-defined areas of EGF immunoreactivity in exocrine ducts showing reactive changes in pancreatitis might represent a benign response to tissue damage similar to that previously described in the gastric mucosa.     

Efficacy of intralesional recombinant human epidermal growth factor in chronic diabetic foot ulcers

Abstract

Objective: The aim of this study was to explore the clinical effects of intralesional administration of an epidermal growth factor (EGF) up to complete wound closure. Methods: Seventeen diabetic patients with full-thickness lower extremity ulcers of more than 4 weeks of evolution were enrolled in the study. Mean ulcer size was 15.5 +/? 7.5?cm². Intralesional injections of 75?µg of Heberprot-P three times per week for 5–8 weeks were given up to complete wound healing. Results: Full granulation response was achieved in all patients in 32.4 +/? 6.6 days. Complete wound closure was obtained in 16 (94.1%) cases in 53.1 +/? 4.7 days. The most frequent adverse events were burning sensation, tremors, chills and pain at the site of administration. After 1-year follow-up, only one patient relapsed. Conclusions: Intralesional EGF administration up to complete closure can be safe, effective and suitable to improve healing of chronic diabetic foot ulcer (DFU).     

抗重组人表皮生长因子单克隆抗体的制备及生物学特性鉴定

目的　制备出高效价的抗重组人表皮生长因子 (EGF)单克隆抗体。方法　以重组人表皮生长因子作为抗原 ,免疫Balb/c小鼠 ,以未免疫的Balb/c小鼠脾细胞为饲养细胞 ,运用细胞杂交瘤技术制备 ,间接ELISA法筛选产生针对人表皮生长因子的单克隆抗体细胞株 ;以体内诱生法产生腹水 ,并采用ProteinA Sepharose柱对其纯化 ,快速定性试纸鉴定McAb的Ig亚类 ,采用间接ELISA法相加实验鉴定抗原识别表位。结果　获得 3株产生针对人表皮生长因子的单克隆抗体细胞株EGF B2 、EGF C7、EGF A8,Ig亚分别为IgG1κ型 ,IgG1λ型 ,IgG3 κ型 ,亲和力常数分别为 2 .76× 10 10 、3.2× 10 9、1.4 5× 10 9。结论　成功制备 3株稳定分泌抗rhEGF的杂交瘤细胞株 ,产生的McAb特异性好 ,亲和力高 ,为探讨EGF的作用机制及临床应用奠定了基础 ,为肿瘤的诊断与治疗提供具有实用价值的研究工具 ,此外 ,为EGF的纯化提供实验材料     

Histomorphologic observations for cynomolgus monkeys after subchronic subcutaneous injection of recombinant human interleukin-4.

Recombinant human interleukin-4 (rhuIL-4) is a candidate for the treatment of refractory cancer based on its potential to enhance the function of the immune system. Total daily dosages of 0 (placebo control), 1, 5, or 25 micrograms/kg of rhuIL-4 were given as divided (b.i.d.) subcutaneous dosages to male and female cynomolgus monkeys (5/sex/group) for 1 month followed by a 2-week recovery. Histomorphologic evaluation of 3/sex/group at 1 month revealed vascular lesions, granulocytic hyperplasia, and seminiferous tubular atrophy attributed to treatment with rhuIL-4. Dosage-dependent proliferative and inflammatory vascular lesions with eosinophil infiltration affected principally the arterial tree. After 2 weeks of recovery, these lesions, including chronic endarteritis and chronic and/or obliterative arteritis, occurred with an overall lower incidence, and were not observed for monkeys from the 1.0 micrograms/kg/day group. Granulocytic hyperplasia in bone marrow observed for monkeys from all groups given rhuIL-4 at 1 month was not present after 2 weeks of recovery. Seminiferous tubular atrophy was observed for monkeys from the 5 and 25 micrograms/kg/day groups at 1 month and after 2 weeks of recovery.     

Gene expression and immunolocalization of heparin-binding epidermal growth factor-like growth factor and human epidermal growth factor receptors in human corpus luteum

BACKGROUND: The objective of this study was to elucidate gene expression and immunolocalization of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and human epidermal growth factor receptor (HER) family in the human ovary during luteal growth and regression. METHODS: Ovaries obtained from pre-menopausal women were used for immunohistochemistry and semiquantitative RT-PCR analysis. RESULTS: Immunoreactive HB-EGF was not detected in follicles or oocyte, while HB-EGF became apparent in granulosa luteal cells in the early luteal phase, and most abundant in the mid-luteal phase, but less abundant in the late luteal phase. Immunostaining for HER1 was very weak in granulosa luteal cells in the early and mid-luteal phases, and was not detected in the late luteal phase. Immunoreactive HER4 was abundant in the early luteal phase and became less abundant in the mid-luteal phase, whereas it was negative in the late luteal phase. Semiquantitative RT-PCR analysis revealed that HB-EGF and HER1 mRNA levels were high in the mid-luteal phase, whereas HER4 mRNA expression was high in the early luteal phase. CONCLUSIONS: HB-EGF may play a vital role in regulating luteal growth in a juxtacrine manner and through activating HER4 signalling.     

Renal changes associated with naproxen sodium administration in cynomolgus monkeys.

Naproxen sodium was administered to cynomolgus monkeys (Macaca fascicularis) by oral gavage at daily doses of 44, 88, or 176 mg/kg for 2 wk (2 monkeys/gender) or of 44 mg/kg for 13 wk (4 monkeys/gender). Body weight loss occurred in at least one monkey in all naproxen sodium-dosed groups in the 2-wk (up to 16% loss) and 13-wk (up to 22% loss) studies. Increases in plasma naproxen concentrations were dose proportional between 44 and 88 mg/kg but were less than dose proportional between 88 and 176 mg/kg. Up to 2-fold increases in creatinine and/or serum urea nitrogen values as well as higher renal weights occurred in monkeys receiving 176 mg/kg for 2 wk or 44 mg/kg for 13 wk. Microscopically, renal changes were observed in all naproxen sodium-dosed groups. Renal findings after 2 wk of exposure included increased interstitial ground substance, tubular dilatation, and tubulointerstitial nephritis; in the 13-wk study, cortical tubular atrophy and interstitial fibrosis were also observed. These studies identify the kidney as the target organ of naproxen sodium in cynomolgus monkeys.     

The epidermal growth factor receptor in human pancreatic cancer.

The epidermal growth factor receptor (EGFR) and its ligands are thought to be important in the control of proliferation of many epithelial systems, including the exocrine pancreas. Abnormalities in expression of two of the known ligands of the EGFR, transforming growth factor alpha and epidermal growth factor, occur frequently in ductal adenocarcinoma of the human pancreas. We have examined an archival series of cases of pancreatic pathology for expression of the EGFR using the anti-EGFR antiserum 12E and found that there is almost ubiquitous overexpression of EGFR in pancreatic cancer and in chronic pancreatitis. Southern blot analysis showed no evidence of amplification or rearrangement of the EGFR gene. We conclude that an autocrine loop involving the EGFR system may be involved in the genesis of both neoplasia and reactive hyperplasia of pancreatic ductal epithelium.     

Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation

Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.     

Expression of epidermal growth factor in human tissues

Summary The expression of epidermal growth factor (EGF) was examined on various human tissues by radioimmunoassay, immunohistochemistry and Northern blot analysis. Immunoreactive EGF was found in most of the human tissues by radioimmunoassay at various levels. Large quantities of EGF were detected in the kidney and thyroid gland. Immunohistochemically, EGF immunoreactivity was detected mainly in the epithelial cells of the lung, stomach, duodenum, pancreas, kidney, pituitary gland, thyroid gland, mammary gland, ovary, uterus and placenta. Weakly EGF-positive cells were also found in the adrenal gland. The results of EGF-immunostaining were not always consistent with the data from radioimmunoassay. We consider that the amount of EGF measured by radioimmunoassay reflects the density of EGF-positive cells in the tissues and the concentration of EGF in individual EGF-positive cells. Furthermore, EGF mRNA was expressed in the salivary gland, thyroid gland, mammary gland and kidney. It is thus evident that EGF is produced by a variety of human tissues. The kidney expressed exceptionally high levels of EGF mRNA which was about one-tenth of the expression in mouse submandibular gland, suggesting that most of EGF in the urine is produced and secreted by the epithelial cells of renal tubules.     

Expression of epidermal growth factors and epidermal growth factor receptor in normal cycling human ovaries

Immunolocalization of transforming growth factor- (TGF), epidermalgrowth factor (EGF), cripto-1, amphireg-ulin and epidermal growthfactor receptor (EGFR ) was studied in 51 premenopausal humanovaries at various phases of the menstrual cycle. Localizationof mRNA for TGF and EGF was also studied by in-situ hybridization.Immunoreactive TGF was observed predominantly in theca cellsin 12 of 33 antral follicles in the follicular phase (6/14 dominantfollicles, and 6/19 non-dominant) but not in any of the 18 folliclesin the luteal phase or in primordial and pre-antral follicles.TGF immunoreactivity was present predominantly in the luteinizedgranulosa cells in 13 of 15 corpora lutea in the luteal phase,which are considered to be active in steroidogenesis, but notin any of the regressed corpora lutea. Accumulation of TGF mRNAhybridization signal was observed only in the theca cells inthe follicles and luteinized theca cells in the ovaries thatwere immunohistochemically positive for TGF. EGFR immunoreactivitywas detected in 24 of 33 antral follicles in the follicularphase and in two of 18 follicles in the luteal phase but notin any of the corpora lutea. Immunoreactive EGF, cripto-1 andamphiregulin or EGF mRNA was not detected in any follicles,corpora lutea, or the stroma cells examined. These results indicatethat, of the epidermal growth factors examined in this study,TGF is locally synthesized in normal cycling human ovaries andTGF may be synthesized in theca cells and act on the granulosacells in a paracrine fashion through the EGFR in ovarian follicles. EGF family/human/immunohistochemistry/in-situ hybridization/ovary     

重组人表皮细胞生长因子对人皮肤细胞增殖作用的研究

目的：观察重组人表皮生长因子（recombinant human epidermal growth factor,rhEGF）对人表皮细胞增殖的变化。方法：运用包皮环切术后收集培养角质细胞,不同浓度的重组人表皮细胞生长因子处理细胞,MTT法测细胞生长率;流式细胞仪检测细胞周期以及蛋白的表达。结果：5～10ng·ml^-1重组人表皮细胞生长因子可促进人表皮细胞细胞生长。流式细胞仪检测10ng·ml^-1重组人表皮细胞生长因子处理后细胞增殖明显,S和G2／M期细胞数明显增加。结论：重组人表皮细胞生长因子可促进细胞生长以及切口愈合。     

重组人表皮生长因子凝胶联合纳米银敷料对烧伤后瘢痕的影响

背景：研究已证实重组人表皮生长因子具有促进肉牙组织形成、加快烧伤创面愈合的作用,但重组人表皮生长因子的抗菌作用有限。 目的：观察重组人表皮生长因子凝胶联合纳米银敷料治疗烧伤的效果及对瘢痕的作用。 方法：纳入浅Ⅱ度及深Ⅱ度烧伤患者76例,随机均分为两组,研究组将重组人表皮生长因子涂于创面表面,并以纳米银敷料覆盖;对照组将重组人表皮生长因子涂于创面表面,并以普通无菌纱布覆盖。比较两组创面愈合时间、细菌阳性率、瘢痕情况及不良反应。 结果与结论：研究组创面愈合时间、创面愈合后增生瘢痕率均低于对照组(P < 0.01),创面愈合后扁平瘢痕率高于对照组(P < 0.01),治疗后7,14,21 d创面细菌阳性率显著低于对照组(P < 0.05)。两组过敏反应及局部烧灼感发生率比较差异无显著性意义(P > 0.05)。表明重组人表皮生长因子凝胶联合纳米银敷料治疗烧伤具有较好的疗效,可加速创面愈合,减少瘢痕增生,提高美观度。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

肺腺癌表皮生长因子受体基因突变与CT征象的相关性

目的 探讨肺腺癌CT征象对表皮生长因子受体（EGFR）基因突变的预测价值.方法 回顾性分析200例经手术切除的肺腺癌患者的CT资料,统计其术后病理标本的EGFR基因检测结果,分析两者之间的相关性.结果 单因素分析显示非吸烟、女性患者、CT征象中的含气支气管征及较小肿瘤直径与肺腺癌EGFR基因突变存在明显相关性,突变组与野生组的差异均有统计学意义（P＜0.05）,EGFR基因突变组肺腺癌磨玻璃密度（GGO）发生率高于野生组,但差异无统计学意义（P＞0.05）,其他临床及CT征象如年龄、分叶征、毛刺征、钙化、空洞、胸膜凹陷征均与EGFR基因突变无关,突变组与野生组的差异均无统计学意义（P＞0.05）.Logistics回归分析显示非吸烟及含气支气管征与EGFR基因突变明显相关,突变组与野生组的差异均有统计学意义（P＜0.05）,而性别及肿物大小与EGFR基因突变与否无明显相关性,突变组与野生组的差异均无统计学意义（P＞0.05）.结论 非吸烟、含气支气管征可作为肺腺癌EGFR基因突变的预测因素.     

Expression of epidermal growth factor receptor in human meningiomas and meningeal tissue.

The aim of this study was to examine meningeal tissue under normal, reactive, and neoplastic conditions for expression of epidermal growth factor receptor (EGFR) using an improved histochemical method, namely biotinylated epidermal growth factor. EGFR was found in all the examined meningiomas (12 benign and three anaplastic) and in neonatal rat meninges, whereas normal and injured adult human and rat meninges did not exhibit detectable EGFR. These observations indicate that EGFR is involved in the development of meningeal tissue. Further, EGFR is abnormally expressed in meningeal tumours, indicating a role of EGFR in the neoplastic process of these tumours. The regular expression of EGFR in human meningiomas suggests EGFR as a tumour marker for this tumour type.     

Effects of platelet-derived growth factor and epidermal growth factor on antigen-induced proliferation of human T-cell lines.

When the serum content of tissue culture medium is reduced from 10% to 1%, the capacity of T cells to proliferate in response to antigen within that medium is dramatically reduced. Physiological concentrations of platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) are able to partially replace the requirement for serum, in that they are able to increase antigen-driven T-cell proliferation at a serum concentration of 1%. Neither growth factor is mitogenic for T cells in the absence of antigen, and neither is able to act synergistically with T-cell growth factor (TCGF) or IL-2) in the absence of antigen. Antigen-presenting cells (APC) pulsed with antigen in the presence of PDGF or EGF are able to stimulate antigen-specific T-cell proliferation to a greater extent than antigen-presenting cells pulsed in the absence of exogenous PDGF or EGF. Both growth factors increase the expression of MHC Class II antigens on antigen-presenting cells.     

Differentiation-related expression of epidermal growth factor receptors in human lung carcinoma demonstrated histochemically by biotinylated epidermal growth factor

Biotin-labeled epidermal growth factor (EGF) was applied to routinely processed sections of 64 cases of human lung carcinoma as a histochemical tool for demonstrating EGF-specific receptors. Formalin-fixed, paraffin-embedded tissue sections were deparaffinized and incubated with the labeled EGF (10 micrograms/ml) for 60 min at room temperature. The specific binding of the growth factor to its receptor was visualized by the avidin-biotin complex (ABC) technique. Positive binding capacities were obtained for the following cases: 15/16 epidermoid carcinoma; 13/15 adenocarcinoma; 2/11 large cell anaplastic carcinoma; 12/20 small cell anaplastic carcinoma; 0/11 normal lung tissue; 0/6 main bronchi; 0/1 hamartoma; 0/1 primary fibrosarcoma of lung. In addition, a strong positive reaction was seen for neutrophilic granulocytes present within the tumorous tissue. Data indicate that EGF receptors are frequently expressed in more differentiated carcinoma in comparison with anaplastic carcinoma of lung.     

Early Australian clinical studies with pegylated recombinant human megakaryocyte growth and development factor

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF, an Mpl ligand) is a truncated form of native thrombopoietin currently undergoing clinical development. A series of studies in Australia have examined the safety and biological activities of PEG-rHuMGDF. Administration of PEG-rHuMGDF causes a dose-dependent increase in platelet count but has no effect on white cell count or hematocrit. These platelets are morphologically and functionally normal. When administered following moderately myelosuppressive chemotherapy, PEG-rHuMGDF significantly enhances platelet recovery, although scheduling in relation to chemotherapy may be important in optimizing the full effects. PEG-rHuMGDF mobilizes progenitor cells of multiple hematopoietic lineages, and alters the kinetics of peripheral blood progenitor cell mobilization after chemotherapy and filgrastim. PEG-rHuMGDF is well tolerated and does not cause toxicity similar to that observed with other thrombopoietic cytokines. Numerous studies are underway to help determine the precise role of PEG-rHuMGDF in clinical practice.