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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine hamster lung tumors, induced by exposure to 60% hyperoxia and subcutaneous administration of the tobacco-specific nitrosamine 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) for 12 weeks, were placed in cell culture. By subsequent selective transfer of epithelial cells and maintenance in an atmosphere of 8% CO2, cell lines with characteristics of neuroendocrine cells were established. The neuroendocrine markers expressed by these cell lines included electron dense neuroendocrine secretion granules as well as secretion of calcitonin and mammalian bombesin. In keeping with data previously reported for a human neuroendocrine lung tumor cell line, nicotine, acetylcholine, and mammalian bombesin (MB) acted as strong growth factors in these neuroendocrine hamster tumor lines. The mitogenic effect of nicotine and acetylcholine was abolished by nicotinic receptor inhibition while the effects of mammalian bombesin were inhibited by an antagonist of MB receptors. Our data suggest that a receptor-mediated mitogenic effect of nicotine on neuroendocrine lung cells may be instrumental in the induction of smoking-associated small cell lung cancer.
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PMID:Nicotine, acetylcholine and bombesin are trophic growth factors in neuroendocrine cell lines derived from experimental hamster lung tumors. 169 39

Oxygen and ozone both have been found to enhance or to inhibit the development of tumors in mouse lung. As a general rule, preexposure to the oxidant, before administration of a carcinogen, or exposure to high levels for a comparatively short time immediately following carcinogen administration favors development of tumors. On the other hand, prolonged exposure begun after a certain time following carcinogen exposure inhibits tumor development. The paradoxical effects of the two oxidants depend on experimental design; results can be tentatively explained in terms of oxidant-induced cell proliferation or by oxidant-mediated cytotoxicity. Besides being capable of modifying chemically induced lung tumorigenesis, ozone and oxygen also appear to induce tumors in mouse lung on their own. The conclusions drawn from the study of mouse lung tumors have recently been reinforced in experiments with hamsters, where hyperoxia has clear tumor-modulating effects.
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PMID:Effects of oxygen and ozone on mouse lung tumorigenesis. 205 44

The chemotherapeutic effect of B859-35, the (-)-enantiomer of dihydropyrine 3-methyl-5-3-(4,4-diphenyl-1-piperidinyl)-propyl-1,4-dihydro-2,6-dimethy l-4- (3-nitrophenyl)-pyridine-3,5-dicarboxylate-hydrochloride (niguldipine), was tested on tumors induced in Syrian golden hamsters by N-nitrosodiethylamine (DEN). Peripheral pulmonary adenomas/adenocarcinomas were induced in hamsters maintained under ambient air conditions by multiple s.c. injections of DEN for 20 weeks. We have reproducibly shown that within this time interval lung adenomas develop in a significant number of the animals. The carcinogen treatment was discontinued at this point and one group of these hamsters was given B859-35 intragastrically 5 days/week for 20 weeks while the second group of such tumor-bearing hamsters were kept for an identical time interval without further treatment. Neuroendocrine lung tumors were induced in hamsters maintained in an atmosphere of 60% O2 by multiple s.c. injections of DEN for 8 weeks. We have reproducibly shown that within this short time interval neuroendocrine lung tumors develop in a significant number of the animals. The carcinogen treatment was discontinued at this point and the animals were returned to ambient air conditions. One group of these tumor-bearing hamsters was then given B859-35 intragastrically 5 days/week for 20 weeks while a second group of these hamsters was kept untreated for an identical time interval. A control group was given s.c. injections of saline for 20 weeks under ambient air conditions. A dramatic and selective anticarcinogenic effect of B859-35 was observed on the neuroendocrine lung tumors and nasal cavity tumors induced by DEN/hyperoxia while tumors of larynx/trachea were not affected. B859-35 had no effect on peripheral adenomas/adenocarcinomas, nasal cavity tumors, papillary polyps of larynx/trachea, or liver tumors induced by DEN under ambient air conditions.
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PMID:Successful chemotherapy of experimental neuroendocrine lung tumors in hamsters with an antagonist of Ca2+/calmodulin. 230 20

Neuroendocrine lung cancer is among the most common types of lung cancers in smokers. We have recently shown that exposure of hamsters to N-nitrosodiethylamine and hyperoxia causes a high incidence of this tumor type. In this study, we show that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone also causes neuroendocrine lung tumors in hyperoxic hamsters. Animals maintained in ambient air while being treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone developed pulmonary adenomas composed of Clara cells and alveolar type II cells. Pathogenesis experiments provide evidence for the tumors caused by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in ambient air being derived from Clara cells. In the hyperoxic hamsters, the neuroendocrine carcinogenesis appears to involve two stages: (a) transformation of focal alveolar type II cells into neuroendocrine cells and (b) development of neuroendocrine lung tumors from such foci.
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PMID:Pathobiology of lung tumors induced in hamsters by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and the modulating effect of hyperoxia. 230 45

Recent evidence supports the concept that Adriamycin cytotoxicity may be mediated by drug semiquinone free radical and oxyradical generation. We tested this hypothesis further by exposing drug-sensitive (WT) and 500-fold Adriamycin-resistant MCF-7 human breast tumor cells (ADRR) to exogenous superoxide- and hydrogen peroxide-generating systems and subsequently monitored cell proliferation as a measure of cytotoxicity. The ADRR tumor cells tolerated a 4-fold greater exposure than sensitive cells to superoxide generated by the xanthine/xanthine oxidase system. Likewise, exposure to hydrogen peroxide produced by the action of glucose oxidase on glucose revealed a 4-fold diminished susceptibility of the drug-resistant cells to this reduced form of oxygen. Similar results were obtained by the direct application of hydrogen peroxide to cells. For both cell lines, cytotoxicity was dependent upon the magnitude and the duration of reactive oxygen exposure. When WT and ADRR cells were cultured under hyperoxia (95% O2:5% CO2), in order to stimulate the intracellular production of oxyradicals, proliferation was inhibited to a greater extent in the drug-sensitive cell line. Additionally, hyperoxia potentiated the cytotoxicity of Adriamycin to both sensitive and drug-resistant cells, but the effect depended upon the concentration of the drug. Under hyperoxic conditions, Adriamycin caused oxygen radical-dependent cytotoxicity to the WT tumor cells at clinically relevant drug concentrations as low as 2 to 3 nM. With ADRR tumor cells, hyperoxia increased the cytotoxicity of Adriamycin at concentrations above 5 microM. Paradoxically, both the WT and the ADRR tumor cells were equally susceptible to the cytotoxic effects of gamma irradiation. It is known that the Adriamycin-resistant MCF-7 cells greatly overexpress glutathione peroxidase and glutathione transferase activities; however, other biochemical defenses against reactive drug intermediates and oxygen radicals have been reported to be similar in the two cell lines. We have reexamined those observations in this report. The resistance of ADRR breast tumor cells to Adriamycin appears to be associated with a developed tolerance to superoxide, most likely because of a twofold increase in superoxide dismutase activity, and a decreased susceptibility to hydrogen peroxide, most likely because of 12-fold augmented selenium-dependent glutathione peroxidase activity. Acting in concert, these two enzymes would decrease the formation of hydroxyl radical from reduced molecular oxygen intermediates.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential oxygen radical susceptibility of adriamycin-sensitive and -resistant MCF-7 human breast tumor cells. 253 95

The in vivo effects of hyperoxia were studied in lung colonies formed by B16-F10 melanoma cells in C57BL/6 mice. Several antioxidant defenses were found to change with in vivo exposure: glutathione reductase and glucose-6-phosphate dehydrogenase activities decreased as compared with levels in the cultured cells, glutathione peroxidase activity dramatically increased, and Mn-superoxide dismutase activity and levels of total glutathione were similar in vivo and in vitro. Exposure of tumor-bearing animals to 70%, O2 for 3 weeks did not alter the antioxidant defenses measured in the tumors. One hundred percent O2 exposure did not affect either initial arrest or subsequent retention of radiolabeled B16-F10 cells in the lung. Likewise, hyperoxia did not appear to alter cell division in B16-F10 cells growing in the lung. These results are consistent with our previous studies indicating that the B16-F10 cell line is resistant to levels of O2 in vivo that adversely affect other tumor cell lines.
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PMID:Effects of hyperoxia on B16-F10 cells in vivo. 318 29

Mice were given i.v. injections of various tumor cell lines and, beginning 24 h later exposed for 3 weeks to 70% oxygen. Hyperoxia reduced the number of lung colonies derived from MT-7 cells (originally a mammary carcinoma) and of the lung-tumor derived cell lines 498 and Line-1 early passage. Lung colonies derived from Line-1 late passage, lines M109, B16-F10 and Lewis lung carcinoma were oxygen resistant. Lung metastases following i.m. injection of MT-7 cells were oxygen-sensitive and metastases derived from B16-F10 cells or Lewis lung carcinoma were oxygen resistant. Pre-exposure of mice for 48 h to 100% oxygen enhanced colony formation for all cell lines examined whereas exposure to 100% oxygen after i.v. injection only curtailed the growth of the cell lines previously shown to be sensitive to 70% oxygen. There was no correlation between oxygen sensitivity or resistance and the levels of total glutathione or activities of superoxide dismutase (SOD), glutathione reductase or peroxidase or glucose 6-phosphate dehydrogenase in the cell lines. However, upon injection in mice a resistant cell line increased its anti-oxidant defense mechanisms while growing in vivo whereas a sensitive cell line failed to show such adaptation.
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PMID:Effects of hyperoxia on growth of experimental lung metastasis. 334 81

In an experimental model of lung metastasis we have observed that more metastatic tumors are located on the pleura of the lung than in the parenchyma. To study possible reasons for this differential pattern we have now related the initial distribution of injected tumor cells to the later location and growth rate of metastases in different regions of the lung in C57bl/6 mice. It was found that labeled murine fibrosarcoma cells were evenly distributed throughout the lungs 24 h after intravenous injection into controls and animals previously treated with bleomycin or by exposure to hyperoxia. These treatments, known to induce pulmonary endothelial injury, were associated with increased tumor cell localization in the lung. In all cases, using morphometric methods, we found that after 2 weeks, approximately 75 per cent of metastatic tumors were located at the pleura. By [3H]thymidine labeling in autoradiographs, pleural tumors in all experimental groups had a growth rate 14 times the growth rate of tumors located in the internal regions of the lung. In vitro, the fibrosarcoma cells proliferated more rapidly on connective tissue matrices prepared from normal pleuras than they did on matrices from the remainder of the lung. Protease digestion of these matrices indicated differences in composition with more insoluble collagen, probably type I collagen, present at the pleura. These data suggest that, in spite of the initial random distribution and localization of tumor cells in the lung, there is preferential growth of metastatic tumors at the pleura which may be related to regional differences in the composition of the extracellular matrix.
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PMID:Preferential growth of metastatic tumors at the pleural surface of mouse lung. 334 65

Suspensions of an oxygen-sensitive (MT-7) and of an oxygen-insensitive(M109) tumor cell line were injected i.v. into BALB/c mice. Exposure to 100% O2 after injection of the cells did not modify the initial arrest of either cell line in the lung. Exposure of animals given injections of MT-7 cells for 60 h to 100% oxygen decreased the number of lung colonies formed even when onset of oxygen exposure was delayed up to 10 days after injection of the cell suspension. Cell cycle time and growth fraction in lung colonies growing in vivo were estimated from an analysis of the percentage of mitoses labeled. In lung colonies formed by MT-7 cells, hyperoxia produced a mitotic delay and a 30 to 40% reduction in the growth fraction. In M109-derived colonies, oxygen did not change cell cycle times or reduce growth fraction. In earlier experiments done in vitro and reported by others it had been found that, in tumor cell lines other than the ones used in the present study, a prolongation of the early prophase was the most oxygen-sensitive event. The present data show that in vivo oxygen inhibits lung colony formation in MT-7 cells by a similar mechanism.
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PMID:Effects of hyperoxia on growth characteristics of metastatic murine tumors in the lung. 335 40

Pulmonary metastasis is a common event. The studies described here were done to test the hypothesis that there is a relationship between endothelial injury and the localization and metastasis of circulating tumor cells. Mice were exposed for periods of up to 4 days to an atmosphere of 90% oxygen; some were allowed to recover in room air for 3 or 14 days. Air-exposed animals served as controls. Endothelial injury, demonstrated morphologically and quantitated by measuring protein levels in bronchoalveolar lavage fluid, increased from 2 to 4 days exposure when injury was maximal. Metastatic events increased in frequency concurrently. When radiolabeled syngeneic fibrosarcoma cells were injected, a 5-fold increase in localization at 24 hours was seen in the 3-day exposed group and a 36-fold increase was found in the 4-day group. Tumor cells were found by electron microscopy at sites of denuded endothelial basement membrane, often associated with small platelet-fibrin thrombi and sometimes, after 4-day exposure, with sequestered neutrophils. The subsequent development of metastatic nodules in the lung and the percentage of lung occupied by tumor were also maximal in the 4-day group. Increased metastasis and endothelial injury were also seen in mice returned to air for 3 days, but by 14 days the endothelium was normal and metastases were at control levels. The results demonstrate a relationship between the degree of pulmonary endothelial damage produced by hyperoxia and the extent of metastatic tumor growth.
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PMID:Tumor metastasis after hyperoxic injury and repair of the pulmonary endothelium. 359 13


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