Changes in the content of pepsinogen messenger RNA in the gastric mucosa of rats during N-methyl-N'-nitro-N-nitrosoguanidine-induced carcinogenesis

Pepsinogen mRNA is shown to be the major fraction of rat poly (A)+RNA. It codes polypeptide with molecular weight of about 45 kD. Changes in the pepsinogen mRNA content at the early stage of carcinogenesis are nonspecific and are due to the toxic effect of MNNG. Steady shifts in the quantity of pepsinogen mRNA are found between the 1st and 3d months. Pepsinogen mRNA content decreases down to the half of the normal one between the 3d and 6th months. A quantity of RNA capable to be a template for pepsinogen synthesis is reduced by more than 90% in the MNNG induced tumour. The pepsinogen production defect in gastric mucosa neoplasia is mainly due to pepsinogen mRNA synthesis damage.     

Markers of malignant transformation in mouse cell lines

The expression of three phenotypic markers of transformation in vitro, i.e. serum dependence, contact inhibition and anchorage dependence of growth has been investigated using the lines of mouse cells obtained from spontaneously in vitro transformed embryonal fibroblasts (three stages of a continuous passage in vitro being considered) and from induced tumours. The results obtained indicate that in the cell lines arising spontaneously in the continuous passage in vitro the origin of the transformation features can be observed. Anchorage independence demonstrates not high (r = 0.69) but much better correlation with tumourigenicity than other studied markers.     

Suppression of the proliferative activity in in vivo tissue culture of esophageal and stomach tumor cells during preoperative irradiation

Pathomorphological changes and indices of proliferative ability of tumour tissue in the esophagus and in the cardia are studied in 14 patients after and without the preoperative irradiation following its cultivation in diffuse chambers. The tissue was implanted into the abdominal cavity of 84 rats. Inhibition of the mitotic activity and synthesis of DNA in cell nuclei as well as the impairment of the formation processes typical of the unirradiated blastomas of the same histological structure in the tissue culture in vivo evidence for a pronounced effect of irradiation.     

水通道蛋白4在脂多糖致大鼠感染性脑水肿模型中的表达变化

目的:观察脂多糖(LPS)致大鼠感染性脑水肿后水通道蛋白4的表达情况.探讨其在脑水肿形成发展中的作用.方法:84只雄性SD大鼠,随机分为3组:空白对照组(C组,n=12):生理盐水对照组(S组,n=12):水肿组(L组,n=60).水肿组又按注射脂多精后6h、12h、24h、48h、72h分为5个亚组(n=12).向颈...     

不同浓度酒精对小鼠胃肠道粘膜的影响

众所周知 ,酒精可导致脂肪肝、肝硬变、损害心脏及中枢神经系统 ,甚至导致后代畸形等病理性变化。为揭示酒精对胃肠道粘膜结构的影响 ,本实验以幼龄小鼠为实验材料 ,让其自由饮用自来水以及 5 %、1 0 %和 1 5 %三种不同浓度酒精水溶液 ,然后用扫描电子显微镜观察胃、十二指肠和空肠粘膜表面结构的变化 ,为揭示酒精对胃肠道的影响提供一些形态学依据。材料和方法本实验选用 2 1日龄昆明种雄性小白鼠 1 0 5只 ,随机分成对照组 (30只 )、5 %酒精实验组 (2 5只 )、1 0 %酒精实验组 (2 5只 )、1 5 %酒精实验组 (2 5只 )。从 2 2日龄幼鼠开始同时…     

Distribution of one of the ascitic fluid antigens of ovarian cancer patients in malignant tumors of the stomach and intestines

The indirect immunofluorescent technique was used to study the distribution of the ascitic fluid antigen (AgD) on histological sections from surgical specimens of gastric and colon tumours from proximal to distal lines of resection. AgD was found in gastric tumours exceptionally in the tumour area and in colon cancer--both in the tumour stroma and in surrounding histologically normal mucosa.     

Malignant cell transformation in rats in vitro as affected by the variolovaccine virus

The capacity of the variolovaccine virus with low cytopathogenic activity to cause morphologic and malignant transformation of normal rat cells in vitro is detected. The transformed cells induced tumours in gamma-irradiated rats.     

The role of protein kinase C in tumor growth

A review of recent papers dealing with the role of protein kinase C (PK C) in regulation of normal and tumour cell proliferation contains the data on the interaction of PK C with the tumour promoters and oncoproteins as well as the data which characterize changes of the PK C activity in tumour cells and during carcinogenesis. Probable mechanisms of the PK C influence on the functioning of the growth factors receptors are discussed. It is proposed that one of the PK C functions which is substantial for induction of the mitogenic signal is the polyamine synthesis stimulation. Participation of PK C in the tumour promotion may play a key role in multistep processes of the carcinogenesis.     

Changes in the total proteolytic activity and inhibitory potential of tumor and lung tissue in mice during growth and metastatic spread of malignant neoplasms

In tumour tissue and in lungs of mice with carcinoma 3LL, melanoma B-16, adenocarcinoma 755 different changes of proteolytic and antitryptic activities have been revealed. An excessive level of the protease activity and/or a decrease of the inhibitory potential activity are the factors of decompensation of the body's protease-inhibitory system and stimulate development of metastatic process.     

Antiproliferative activity of difluoromethylornithine and the factors decreasing its effectiveness in malignant growth

The inhibitory effect of difluoromethylornithine (DFMO) synthesized by the authors on the activity of the ornithine decarboxylase (ODC) and proliferation of microbial and mammalian cells in vitro was studied. The in vivo growth of ascite plasmocytoma of solid melanoma B-16 cells in mice was also effectively inhibited by DFMO. But the antiproliferative activity of DFMO in solid tumours was substantially lower. Such a decrease in the antitumour activity may be associated with polyamines released from necrotic areas of solid tumours. As the tumour cells "catch" the vitally important metabolites, their effect inside solid tumours is turned against the tumour cells themselves. The second reason of the decrease in the DFMO activity is adsorption of polyamines on the erythrocyte surface.     

The ultrastructure and histochemical characteristics of the cells of malignant fibrous histiocytoma in rats

Samples of tissue from malignant fibrous histiocytoma of rats induced by subcutaneous injection of paraffin pill-enclosed DMBA were studied for localization of acid phosphatase and non-specific esterases (15 samples) and cell ultrastructure (10). Tumours showed cellular heterogeneity consisting of 5 types of cells: histiocyte-like, fibroblast-like, giant multinuclear xanthomatous and undifferentiated. Acid phosphatase and non-specific esterases were found both in histiocyte-like and fibroblast-like cells which means that those enzymes are not the specific markers of tumors arising from monocytic-macrophagal system. Histochemical and ultrastructural features of experimental malignant fibrous histiocytoma were similar to those of its human analogue.     

Enhancement of 5-hydroxytryptamine3A receptor function by phorbol 12-myristate, 13-acetate is mediated by protein kinase C and tyrosine kinase activity

The effects of phorbol 12-myristate, 13-acetate (PMA) on 5-hydroxytryptamine (5-HT)-evoked ion currents in the mouse 5-HT3A receptor were examined. Perfusion with PMA caused a concentration dependent potentiation of 5-HT mediated currents and increased both potency and efficacy of 5-HT at the 5-HT3A receptor expressed in Xenopus oocytes. Enhancement of receptor function was partially blocked by injection of oocytes with PKCI, the peptide inhibitor of protein kinase C (PKC). Mutation of all 12 intracellular serine and threonine residues to alanine was without effect on PMA-induced potentiation of 5-HT elicited currents. Mutation of tyrosine 458 in the 5-HT3A receptor lacking intracellular serines and threonines reduced the PMA-induced potentiation of 5-HT evoked currents by approximately 55%. In contrast, mutation of tyrosine 458 in the wild-type receptor did not alter PMA-induced enhancement. The tyrosine kinase inhibitor, lavendustin A, reduced the enhancement of 5-HT3A receptor mediated currents by PMA in the mutant 5-HTA3A receptor containing no intracellular serine or threonine residues, but not in the wild-type receptor. Thus, the role of intracellular serines and threonines is redundant with that of tyrosine, suggesting that these two components act through a similar pathway in response to PMA treatment.     

Changes in the supramolecular structure of chromatin and pepsinogen synthesis in the gastric mucosa of rats undergoing N-methyl-N'-nitro-N-nitrosoguanidine-induced carcinogenesis

A model of gastric tumour induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in rats made it possible to detect essential alterations of chromatin-DNA-protein complexes, that is a weakening of the DNA-protein linkage. The changes appear at early stages of carcinogenesis and persist in induced adenocarcinomas of the stomach. Simultaneously an inhibition was established in pepsinogen synthesis during MNNG carcinogenesis, which reflects a damage in expression of functionally important genetic information. This fact shows a molecular-genetic connection between the process of the gastric mucosa malignization and a disturbance of physiologically important tissue-specific gene functions.     

Effect of ethanol on N-nitrososarcosine ethyl ester-induced carcinogenesis in the esophageal and forestomach mucosa of mongrel rats

Administration of N-nitrososarcosine ethyl ether (50 mg/kg, per os, every day during 4 months) to rats induced after 8 months multiple tumours (most often papillomas) of oesophagus and forestomach. Total incidence of tumour-bearing animals was 42.4% in oesophagus and 21.2% in forestomach, distribution of tumours being 85.6 and 14.4%, respectively. The combined administration of carcinogen with 40% water solution of ethanol (0.5 ml, per os, every day during 8 months) did not change general incidence and multiplicity of all tumours, but decreased the relative incidence of oesophagus tumours and increased that of forestomach tumours. Possible mechanisms of organotropism shifts are discussed.     

热盐水致大鼠萎缩性胃炎胃粘膜扫描电镜观察

目的：研究热盐水灌胃导致大鼠萎缩性胃炎(CAG)胃粘膜组织细胞超微结构的变化，探讨长期热成饮食与慢性萎缩性胃炎间的关系。方法：用热盐水灌胃(55℃，150g／mL，2．5ml／d)建立大鼠萎缩性胃炎动物模型，选取大鼠腺胃胃窦组织进行病理组织学检查，以扫描电镜观察胃粘膜上皮细胞超微结构的变化、结果：光镜下热盐水灌胃后第12周，大鼠胃粘膜出现腺体明显缩小，粘膜肌层的平滑肌呈柬状增生插入粘膜固有层中一腺体上1／3至2／3腺上皮萎缩，腺管腔增宽，胃小凹颈部粘膜宽度变窄。扫描电镜见正常组大鼠胃粘膜被纵横交错的小沟分隔成许多胃小区，呈网状，胃小凹(胃腺开口)壁衬有圆形或椭圆形上皮细胞，体积基本一致，有短而稀的微绒毛。上皮细胞排列规则，被覆一薄层连续的粘液。热盐水组大鼠在12周时见胃粘膜细胞表面粗糙，粘膜表面糜烂、扁平；在32周时见胃粘膜细胞萎缩、腺腔直径增大、细胞表面破溃，并见纤维性渗出。结论：热盐水灌胃可引起胃粘膜上皮细胞损害，长期过成及过热刺激可能会诱发萎缩性胃炎。     

诱导血红素氧合酶-1及雷帕霉素对PDGF诱导的大鼠平滑肌细胞表型转化的抑制作用

目的观察血红素氧合酶-1(HO-1)与雷帕霉素对血小板源性生长因子-BB(PDGF-BB)诱导的大鼠血管平滑肌细胞(VSMCs)表型转化的作用。方法原代大鼠VSMCs给予PDGF-BB诱导表型转化。同时给予不同剂量的血红素氧合酶诱导剂氯血红素诱导HO-1的表达,和雷帕霉素共培养24h。结果PDGF-BB20nmol/ml作用原代VSMCs24h后,SM-α-actin与PCNA表达减弱,PCNA表达增强。氯血红素诱导HO-1后可以抑制PDGF-BB诱导的VSMCs表型改变,并且随剂量的增加,抑制强度增加。较低剂量的雷帕霉素可以抑制PDGF诱导的VSMCs表型转化。结论PDGF-BB亚型可以促进原代培养的大鼠VSMCs由收缩表型向合成表型转化,给予氯血红素诱导HO-1表达可以对抗PDGF-BB诱导的大鼠VSMCs表型转化,并呈剂量相关。     

Functional activity of the thymus gland and pituitary-adrenal system in patients with malignant skin melanoma

Essential changes in the thymus functional condition and hypophyseal-adrenal system were revealed in patients with skin melanoma. The secretory activity of the thymus loosens, and there is a reduction of thymic hormone titer in blood. The increased levels of ACTH and hydrocortisone in blood indicate an enhanced activity of the hypophyseal-adrenal system under this pathology.     

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.     

Effect of vinblastine during high activity of the anticoagulating system on the growth of sarcoma 45 in rats and several blood indicators in animals with tumors

The strong depressive effect of vinblastine on the rat sarcoma 45 growth and intensification of this effect by the combination of vinblastine treatment with the activation of the blood anticoagulating system (BAS) were found. Vinblastine had no negative effect on the BAS activation process and induced no persistent changes in the qualitative content of leucocytes in the peripheral blood.