Effect of the epidermal growth factor on 1,2-dimethylhydrazine-induced carcinogenesis in the rat intestinal mucosa

The radioimmunological and radioreceptor methods have been used to show that sialadenectomy leads to the stable decrease of the epidermal growth factor (EGF) concentration in saliva and blood serum. The mean number of colon tumours per rat was significantly lower among the rats which had been sialadenectomized before injections of the carcinogen, than in the control. But a sharp stimulation of carcinogenesis in the duodenal mucosa was observed after sialadenectomy. The production of the alpha-transforming growth factor with the EGF-competing activity for the EGF-receptors was found in the chemically-induced rat colon tumours.     

Organ-specific intestinal antigens contained in tumors of the human gastrointestinal tract

Two organospecific antigens were found in extracts of human fetal intestinal mucosa. One of them is destroyed by boiling and its electrophoretic mobility corresponds to that of beta 1-globulins. On the contrary, the other antigen is thermostable and its electrophoretic mobility corresponds to alpha 2 globulins. Other properties of these antigens are similar. The comparison of the test systems to these antigens in double immunodiffusion showed that they reacted with each other making a "spure", but these antigens immunologically differ from CEA. Both of organospecific antigens were determined in all extracts of nonmalignant specimens of definite intestinal and colon mucosa and in most extracts of colon tumours. These antigens are usually absent in extracts of other normal and tumour tissues. These antigens are suggested to be of use as tumour markers in immunodiagnosis, immunoclassification and immunolocalization of gastrointestinal cancer.     

The production of epidermal growth factor and polypeptides similar to it in the intestinal mucosa of rats in 1,2-dimethylhydrazine-induced carcinogenesis and compensatory regeneration

The production of EGF and EGF-like polypeptides in the normal intestinal mucosa and during 1,2-dimethylhydrazine (DMH)-induced carcinogenesis and postresection regeneration was studied in albino rats using chromatographic separation of acid-ethanol extracts. Fractions after gel filtration on Biogel P-60 with subsequent reverse-phase high performance liquid chromatography in acetonitrile gradient were tested in radioreceptor assay for competition with EGF. It has been established that intestinal tumours induced by DMH and regenerating intestinal mucosa have amplified production of EGF--alpha-TGF and related proteins of high molecular weight (approx. 30; 45-55; 120 kD) with the EGF-competitive activity. It is supposed that the high molecular weight EGF-competitive material represents nonprocessed forms of EGF and/or alpha-TGF which are accumulated in rapidly proliferating low-differentiated cells due to the intensified expression of their genes.     

Changes in the epidermal growth factor receptors in the liver cells of rats in N-nitrosodiethylamine-induced hepatic carcinogenesis

A sharp decrease in the number of epidermal growth factor receptors (EGF-R) in the rat liver plasma membranes had been found at different stages of diethylnitrosamine-induced carcinogenesis. The complete loss of high-affinity binding sites for EGF did not prevent EGF-dependent autophosphorylation of EGF-R. Hepatocytes from the rat liver tumors in the primary culture had two classes of EGF-R: high and low affinity ones, though their number had been twice less than in the normal hepatocytes. The dynamics of internalization and down-regulation of EGF-R was very similar in the primary culture of transformed and normal hepatocytes. It testifies that there are some factors of microenvironment in the liver during carcinogenesis which cause the loss of EGF-R (down-regulation) and a decrease of their affinity (activation of protein kinase C). A possible autocrine or paracrine nature of these factors is discussed.     

1,2-dimethylhydrazine induction of epithelial tumors of the kidneys in CBA strain mice

The results of experiments on the 1,2-dimethylhydrazine (DMH) induction of epithelial renal tumours in CBA male mice are presented. The dose-response study shows a sharp increase (from 5 to 75%) of the epithelial renal tumour incidence in the range of 2, 4 and 8 injections of DMH. Higher doses induce a decrease of the tumour incidence due to the early death caused by other tumours. DMH is shown to be the most powerful renal carcinogen in mice. Serial sacrifice of mice after 5 injections of DMH is a convenient model for the study of renal carcinogenesis in mice. Main histological types of epithelial renal tumours are illustrated.     

Proliferative activity of the uterine epithelium and mesenchymal elements in CBA-strain mice administered 1,2-dimethylhydrazine and estradiol dipropionate

Difference have been demonstrated in proliferative responses of epithelial and mesenchymal cells in the uterus of CBA mice under administration of 20 weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH) and estradiol dipropionate (EP) separately and in combination (DMH+EP). The proliferative pool (Pc) of uterine glands epithelium increases under the effect of EP and decreases under the effect of both DMH and DMH+EP. The proliferative pool of mesenchymal cells increases under the effect of DMH, EP, and DMH+EP 5 to 10 weeks after the beginning of their administration, then it decreases. But percentage of DNA synthesizing cells in the regions of hyperplasia and the tumour formation enhances significantly by the 15th to 20th weeks after the beginning of DMH+EP administration.     

Increase in the level of polypeptide growth factors and their receptors in induced carcinogenesis and regeneration of the intestinal mucosa in rats

It has been established for the first time that in extracts of the regenerating and preneoplastic (4 months after the beginning of carcinogen introduction) intestine as well as in the peritumor tissue the content of EPR-similar polypeptides and insulin raises, whereas in tumours it remains not high. Proteins with molecular weight greater than 120 kD able to compete with 125I-EPR for the binding with the receptors of EPR and being, evidently, the precursors of EPP are found in case of carcinogenesis. Besides, the content of insulin receptors rises, this process being most typical of the large intestine.     

Effects of cortiphen and cyclophosphamide in uterine sarcoma induced primarily by 1,2-dimethylhydrazine and estradiol dipropionate in CBA mice

Cortiphen and cyclophosphamide were studied for their effect on the mixed uterus sarcoma induced primarily by 1,2-dimethylhydrazine and oestradiol-dipropionate in CBA mice and its transplants. Their inhibitory action on the growth of these tumours is established.     

Modifying effect of ascorbic acid and sodium ascorbate on uterine carcomogenesis induced by 1,2-dimethylhydrazine in CBA mice

Administration of ascorbic acid (0.3% in drinking water) inhibited the promoting effect of estradiol dipropionate on the 1,2-dimethylhydrazine-induced uterine sarcomogenesis in CBA mice. However administration of sodium ascorbate intensified the promoting effect of estradiol on the uterine sarcomogenesis, as evidenced by the shortening of the periods of tumour incidence.     

Changes in the contents of epidermal growth factor and EGF-like polypeptides in the liver tissue of rats in N-nitrosodiethylamine-induced hepatocarcinogenesis

It has been determined that concentration of EGF-like substances in the liver of rats with N-diethylnitrosamine-induced hepatocarcinogenesis increases and reaches its maximum in tumours (50-150 ng/mg protein). In the regenerating liver the amount of these peptides does not exceed 10 ng/mg protein. High pressure gel-filtration of appropriate extracts has revealed EGF-competing substances with m. w. about 20-30 kD in the liver carcinomas. The presented data confirm that registered EGF-like substances belong to TGF-alpha peptides.     

Effect of 1,2-dimethylhydrazine on the estrous cycle in different strains of mice

CBA, C3HA, C57Bl, Balb/c and DBA female mice received 20 subcutaneous weekly injections of 1,2-dimethylhydrazine in the dose of 8 mg/kg body weight. Estrous cycles were studied in vaginal smears taken 5, 10, 15 and 20 weeks after the 1st DMH injection. In CBA strain susceptible to DMH induction of uterine sarcomas a persistent estrus was observed in 50% of mice after 5 to 10 DMH injections. In C3HA, C57B1, Balb/c and DBA strains resistant to the DNH induction of uterine sarcomas persistent estrus was not observed; the majority of these mice retained a normal estrus cycle. Persistent diestrus which was absent in susceptible CBA mice was found in these resistant strains. No CBA females with a normal estrous cycle were observed after the beginning of DMH treatment. The differences in the estrous cycle found in the mouse strains treated with DMH may partly explain the observed strain differences in the susceptibility to the DMH induction of uterine sarcomas.     

Rapid isolation of highly purified epidermal growth factor by reverse-phase liquid chromatography

The first step in the isolation of murine epidermal growth factor (EGF) from submaxillary glands was the trace enrichment of the acid-ethanol extract on Sep-pak C18 cartridges using the step elution with ethanol. The fraction eluted by 60% ethanol contained above 75% of EGF. The final purification of EGF was achieved by reverse-phase liquid chromatography on Novapak C18 column in the gradient of acetonitrile. A comparison of the effectiveness of gel filtration (on Bio-gel P-60 column) and trace enrichment (on Sep-pak C18 cartridges) of the appropriate fractions were analyzed by the reverse-phase high-pressure liquid chromatography, which had demonstrated that hydrophobic separation of EGF had a number of advantages. The homogeneous character of EGF was confirmed by the silver staining of gels after disc-electrophoresis and isoelectric focusing (pI 4.8). The pronounced mitogenic effect of EGF on the primary culture of the rat hepatocytes is described.     

Epithelial-stromal interrelations in mammary gland tumors induced by 7,12-dimethylbenzanthracene in rats

DMBA-induced mammary tumours in rats are mixed adenocarcinomas with various growth rate (rapid, slow and stabilized). The electron-microscopic study has shown that ultrastructure of tumours and their growth rate depend on a degree of the parenchyma cell differentiation and on the maturity of connective tissue being the result of their specific interaction.     

Inhibiting effect of thymogen on the development of tumors of the esophagus and forestomach induced by N-nitrososarcosine ethyl ester in rats

Immunostimulating synthetic peptide thymogen being an analog of the thymus polypeptide drug thymalin was studied for its effect on carcinogenesis of the esophagus and forestomach in male rats. Rats received N-nitrososarcosine ethyl ester (NSEE) per os in the daily dose of 100 mg/kg of body weight during 8 weeks. After cessation of the carcinogen administration rats were treated with thymogen (the daily dose of 10 micrograms per rat) or immune-inactive polypeptide drug pulmolin from the alveolar tissue of lung (the daily dose of 0.5 mg per rat) during the following 32 weeks. Animals were killed 40 weeks after the experiment beginning. NSEE induced the esophagus and forestomach tumours, mainly papillomas and rarely carcinomas, practically in all rats, more than 5 tumours per rat, on the average. Thymogen decreased the tumour incidence by 12% and made tumour multiplicity 1.7 times as low. Pulmolin did not influence development of these tumours.     

肺癌中EGFR蛋白表达和基因扩增相关性研究

目的对肺癌EGFR蛋白表达和基因扩增进行比较分析：方法对2004年至2006年期间本院病理科常规病理诊断中确诊为啼腺癌和BAC的病例按照2004年WHO最新肺肿瘤分类标准重新分类，应用组织芯片、免疫组织化学和FISH技术对总计89例肺癌进行EGFR蛋白表达和基因扩增的检测.结果经典型肺腺癌EGFR蛋白的阳性表达率为56．52％，基因扩增率为45．45％；混合亚型肺腺癌EGFR蛋白的阳性表达率为20．51％，基因扩增率为22．58％；BAC病例中的EGFR蛋白的表达率为3．85％，扩增率为14．81％。经典型肺腺癌EGFR的蛋白表达阳性病例和基因扩增病例均明显多于BAC和混合亚型肺腺癌，（P〈0．05）。EGFR蛋白表达和基因扩增之间存在正相关（P〈0．005）：结论EGFR基因的扩增及蛋白的表达在肺腺癌病例中均高于BAC，EGFR基因扩增与蛋白表达之间存在相关关系。     

Analysis and development of locomotion devices for the gastrointestinal tract

The authors are developing devices for semi-autonomous or autonomous locomotion in the gastrointestinal (GI) tract. In this paper, they illustrate the systematic approach to the problem of "effective" locomotion in the GI tract and the critical analysis of "inchworm" locomotion devices, based on extensor and clamper mechanisms. The fundamentals of locomotion and the practical problems encountered during the development and the testing (in vitro and in vivo) of these devices are discussed. A mini device capable of propelling itself in the colon and suitable to perform, at least, rectum-sigmoidoscopy (the tract where approximately 60% of all colon cancers are found) is presented. This paper introduces preliminary, but useful, concepts for understanding, modeling and improving the performance of virtually any existing and novel devices for endoscopy of the GI tract.     

地塞米松与血管内皮生长因子共同促进骨髓间充质干细胞形成毛细血管样结构的研究

目的：观察骨髓间充质干细胞（bone mesenchymal stem cells,BMSCs）在地塞米松（dexamethasone,DEX）和血管内皮生长因子（vascular endothelial growth factor,VEGF）组成的培养液中是否能形成毛细血管样结构。方法：将BMSCs在加入DEX（10^-8mol／L）和VEGF（10m）形成的微环境中培养12天,采用光镜和透射电镜观察血管样结构的形成情况;将BMSCs培养12天后与海藻酸钠凝胶混合后移植入Wistar大鼠体内让其继续生长,10天后取材,采用组织切片HE染色观察血管的生成情况。结果：透射电镜可观察到数个细胞通过紧密连接围成一个环状、类似于血管样结构;组织切片HE染色显示生成了原始血管腔。结论：DEX和VEGF形成的微环境可以使BMSCs分化后形成毛细血管样结构,并在活体动物体内进一步形成原始血管腔。为骨组织工程化血管形成提供了一条新的途径。     

Changes in the larynx of rats induced by chemical carcinogens

Carcinogenesis of the larynx induced by local application of 0.5% DMBA acetone solution or 1% methylnitrosourea acetone solution twice a week for 5-6 months was studied in 40 rats. The rats were killed by means of ether inhalation 7-12 months later. The carcinogens have induced epithelial hyperplasia, squamous cell metaplasia, acanthosis, dyskeratosis and hyperkeratosis, Epithelial downgrowths and papillomas have developed in 60-80% of animals. DMBA proved to be a stronger carcinogenic agent.     

Effect of 1,2-dimethylhydrazine on the level of specific binding and ligand affinity to the estradiol receptor in the cytosol of uterine tissue in CBA mice

1,2-dimethylhydrazine (DMH) inducing uterine sarcomas in CBA mice was studied for its prolonged effect on the level of specific binding and affinity to the estradiol receptors in cytosol fraction of CBA mice uterine tissue. It is shown that the dissociation constant 3H-estradiol-17 beta with a receptor protein in the cytosol of uterine tissue of DMH treated mice was slightly higher than in control mice. The theoretical number of the ligand binding sites with receptor protein and the level of free binding sites of estrogen receptors were higher in DMH-treated animals than in control mice during the whole period of observation.     

Decreased isoproterenol sensitivity of the salivary epithelium in mice with transplanted tumors

The proliferative response of secretory cells of parotid glands to isoproterenol could not be observed in tumour-bearing mice, while in normal mice a ten-fold increase was usually observed. Mice with subcutaneous allografts of normal tissue (tail fragments) demonstrated sensitivity similar to normal mice. Apparently, a lack of sensitivity in tumour-bearing mice is characteristic of the tumour-host interaction. According to electron microscopic cytochemical data the adenylate cyclase activity is not changed in the mentioned cells of the tumour-bearing mice. It is supposed that lack of sensitivity is due to an alteration of certain properties of some other components of the beta-adrenergic system.