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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycolysis is not of importance for the process of carcinogenesis. It is very likely, however, that certain molecular-biological and genetic changes are produced which enable the malignant cell to develop an intensive glycolysis, for instance, to form specialized glycolytic isoenzymes already during oncogenesis, and may possible become effective in the primary tumour. As soon as the capacity of the cancer cell to intensive aerobic and anaerobic glycolysis has become manifest, this process is an irreversible one. The extent of glycolysis of a malignoma is greatly dependent on the degree of its dedifferentiation and vascularization (glucose supply), although a direct correlation between growth and the amount of lactic acid formed does not seem to exist. However, a certain utilization of glucose is essential for cell proliferation (supply of basic substances). In many cases there is a correlation between the extent of glycolysis measurable under optimal conditions in vitro (glycolytic power) in a malignant tumour and its growth rate recognizable in vivo. The formation of a strong capacity for glucose degradation via the Embden-Meyerhof pathway that cannot be fully utilized by the whole tumour in vivo is first of all designed to ensure survival and proliferation of cells even at extremely low levels of glucose supply. This process can be regarded as an adaptation of cancer cells to a situation of unsufficient supply. This circumstance endows the cancer cell with an essential advantage over the normal cell which enables or even promotes its invasive and destructive growth and metastatic dissemination. In this respect they differ, for instance, from benignant neoplasms. The possibility is discussed to control neoplastic growth by adjusting an optimal pH difference between normal and tumour tissue by combined administration of detoxicated drugs which are converted to their toxic forms only in the tumour by means of strongly pH-dependent exogenous enzymes.
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PMID:[Origination and importance of glycolysis for malignomas and utilization of this property in the chemotherapy of cancer (author's transl)]. 0 18

The effects and site(s) of action of progesterone on DMBA mammary carcinogenesis in the rat, when a small dose of the carcinogen was applied directly to the inguinal mammary gland, were investigated. No reduction in tumour yield was apparent when progesterone was administered s.c. for 18 days before dusting DMBA. This finding contrasts with a previously reported inhibitory effect on carcinogenesis when hormone treatment was followed by intragastric administration of DMBA. When progesterone injections were begun either 2 days before or 2 days after direct application of DMBA, and were continued until the end of the experiment (135 or 195 days) an enhancement in carcinogenesis was observed similar to that previously demonstrated after gastric intubation of DMBA. These findings, together with previously reported observations, suggest that progesterone may exert its inhibitory effect on carcinogenesis by acting at a site outside the breast, perhaps on the liver. However, it is likely that the hormone acts directly on the mammary tissue to exert its enhancing effect on tumorigenesis.
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PMID:Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae. 11 24

The results of experiments carried out to test some of the consequences of the earlier general theory of oncogenesis, according to which the malignant tumor cell can arise as a result of somatic hybridization of cells of different organ- and tissue-specificity, are described. In the first series a tumor induced by cellophane film, was grafted into syngeneic and allogeneic mice, and antilymphocytic serum (ALS) was then injected. Metastases occurred only in allogeneic recipients receiving ALS. It was thus shown that the ability of cells of this particular tumor to metastasize is not a property inherent in its cells but is acquired by them as a result of interaction with the recipient organism. In the second series it was shown by two immunological methods that the cells of metastases arising under these conditions contain tissue compatibility antigens of donor and recipient origin, i. e., that they are somatic hybridsmin the third series skin from individuals of another strain was grafted on to mice and ALS was injected; hepatomas developed in 74% of these mice. The theory is used to explain several phenomena of carcinogenesis not explicable by other theories: the phenotypic nature of cell transformation, the causes and nature of the duration of the latent period of tumor development, the mechanism responsible for the ability of tumors to overcome the system of immunological defense, the mechanism of activation of endogeneous oncogenic viruses, etc. Finally an answer is given to the question: what is a tumor?
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PMID:Somatic hybridization and oncogenesis; (Mechanism of formation of malignant tumors and metastases by the action of antilymphocytic serum). 16 99

The etiology of cancer resembles that of many other diseases in that multiple factors may be required. Because of this, the role or viruses in the etiology of human cancers is especially difficult to assess. When animal tumor systems were used as models, the roles of various predisposing characteristics in virus oncogenesis were elucidated. Extrapolation of these findings to the human diseases suggests the importance of genetics, age, hormones, immune competence, and stress in determining susceptibility to tumor development in individuals infected with an oncogenic virus. The importance of cofactors in induction of those human tumors most strongly associated with virus infection, including Burkitt's lymphoma, nasopharyngeal carcinoma, cerviccal carcinoma, acute myelogenous leukemia, and breast cancer, is reviewed. Understanding of the role of these cofactors in virus carcinogenesis may lead to disease prevention through elimination of one or more of the cofactors.
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PMID:The viral etiology of cancer: a realistic approach. 19 10

All known tumor types have been reported in the neonate. A numerical listing and discussion are beyond the scope of this review. Wells and Fraumeni give some insight into common congenital malignant neoplasms. Table 2 lists the percentage of neonatal deaths caused by type-specific cancers. Retinoblastoma is probably the most common malignant tumor in the neonate. About seven per cent of these tumors have been apparent at birth. This tumor is not discussed in either article because it is not lethal until muypes in neonatal and pediatric patients. Some congenital malformations in the in the neonate are recognized as being frankly benign (cysts), potentially malignant (teratomas), and frankly malignant (neuroblastoma). A high percentage of teratomas are benign in the newborn period. Leukemia in the newborn appears to be more aggressive yet neuroblastoma has a better prognosis. More studies are needed to help us define why the neonate does better with some tumors and worse with others. Surface cell markers on neonatal leukemia, B and T cell function studies, and other immunologic surveillance studies are needed. Study of neonatal oncology may add to our knowledge of carcinogenesis and oncogenesis in the future.
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PMID:Neonatal oncology. 19 75

The temporal acquisition of in vitro phenotypes associated with neoplasia were examined after exposure of Syrian hamster embryo cells to a chemical carcinogen. Quantitative assays measuring morphological changes, enhanced fibrinolytic activity, and anchorage independent growth were used to detect the development of transformed cells within a population of normal hamster embryo cells. Morphological transformation and enhanced fibrinolytic activity were early changes observed after treatment with benzo[alpha]-pyrene, whereas the ability to grow in semisolid agar was delayed 32-75 population doublings after carcinogen exposure. This delay was not due to selection of a small number of cells that were present early after treatment but at a level below detection, because a large percentage of the cells isolated at early passage (10(3)-fold above the level of detection) developed the potential for anchorage independent growth at later passages. This development of the anchorage independent growth phenotype was induced by the carcinogen treatment, because spontaneous transformation was rare. These observation suggest that multiple cellular changes are required for the acquisition of the capacity for anchorage independent growth and that neoplastic transformation in vitro is a progressive process through qualitatively different stages. Thus, an analogy can be drawn to the progressive nature of in vivo carcinogenesis. These results strongly justify the study of oncogenesis in cell culture as a model for neoplastic transformation in vivo.
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PMID:Evidence for the progressive nature of neoplastic transformation in vitro. 27 86

An integrative theory is proposed in which environmental carcinogenesis is viewed as a process by which the genetic control of cell division and differentiation is altered by carcinogens. In this theory, carcinogens include physical, chemical, and viral "mutagens," as well as chemical and viral gene modulators. Existing explanations of carcinogenesis can be considered either as somatic mutation theories or as epigenetic theories. Evidence seems to support the hypothesis that both mutations and epigenetic processes are components of carcinogenesis. The mutational basis of cancer is supported by the clonal nature of tumors, the mutagenicity of most carcinogens, high mutation frequencies in cells of cancer-prone human fibroblasts lacking DNA repair enzymes, the correlation of in vitro DNA damage and in vitro mutation and transformation frequencies with in vivo tumorigenesis, age-related incidences of various hereditary tumors, and the correlation between photoreactivation of DNA damage and the biological amelioration of UV-induced neoplasms. Since both mutagens and gene modulators can be carcinogenic it may be that carcinogens affect genes which control cell division. An integration of the mutation and epigenetic theories of cancer with the "two-stage" theory and Comings's general theory of carcinogenesis is proposed. This integrative theory postulates that carcinogens can affect regulatory genes which control a series of "transforming genes." A general hypothesis is advanced that involves a common mechanism of somatic mutagenesis via error-prone repair of DNA damage which links carcinogenesis, teratogenesis, atherosclerosis and aging. Various concepts are presented to provide a framework for evaluating the scientific, medical, and social implications of cancer.
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PMID:Environmental carcinogenesis: an integrative model. 36 70

Carcinogen-induced hyperplastic alveolar nodules failed to form tumors after transplantation into isologous female rats; instead they developed ductal or ductal-alveolar outgrowths. Mammary glands from mid-pregnant female rats showed similar outgrowths following transplantation to the isologous hosts. In vitro and in vivo studies failed to demonstrate that subcarcinogenic doses of 7,12-dimethylbenz(a)anthracene can induce mammary tumorigenesis in the hyperplastic alveolar nodules. Our observations suggest that carcinogen-induced hyperplastic alveolar nodules are not 'preneoplastic' lesions in mammary carcinogenesis in the rat.
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PMID:Hyperplastic alveolar nodules of the rat mammary gland: tumor-producing capability in vivo and in vitro. 40 7

A maximum tolerated dose (15 mug/g) of the carcinogen 4-nitroquinoline 1-oxide (4NQO) induced neither fetal deaths nor malformations when given to pregnant ICR/Jcl mice at the sensitive stages (Days 9 to 11) for the induction of malformations, although these embryotoxicities were detected with urethan and X-ray. This may not be due to the lack of teratogenic actions of 4NQO, but to the difficulty this compound has in reaching the embryo, because direct injection of 4NQO into the amniotic cavity of the Day-11 embryo, so that exposure was more direct, induced a high incidence of malformations. Similarity of the mechanism of chemical carcinogen-initiated teratogenesis and carcinogenesis was also suggested by the following findings. Urethan-initiated teratogenesis was almost completely inhibited by posttreatment with caffeine during the period of 0 to 24 and 24 to 48 hr after urethan treatment, whereas it was not inhibited during the 48- to 72-hr post-urethan and the 6- to 30-hr pre-urethan period. The results are similar to those of 4NQO-initiated transformation in cultured mouse embryo cells and 4NQO- and urethan-initiated lung tumorigenesis in mice. Cells carrying preteratogenic or pretumorigenic damage produced by some chemical carcinogens may be extremely sensitive to caffeine treatment during and/or after the postcarcinogen DNA replication period, thus resulting in decrease of malformations and tumors. The process may be related to error-prone DNA repair, because caffeine is known to inhibit the postreplication repair in cultured mouse cells.
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PMID:Similarity of the mechanism of chemical carcinogen-initiated teratogenesis and carcinogenesis in mice. 40 2

The previously observed alterations in the energy transducing system of rat liver mitochondria during 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) carcinogenesis were investigated using aliphatic dicarbonyl compounds as molecular probes and the effect of temperature on the membrane-linked NADH-indophenol reductase. The vicinal diketone, diacetyl, uncouples oxidative phosphorylation in normal rat liver mitochondria while the higher diketones, acetylacetone and acetonylacetone, are increasingly less effective in that order; diacetyl totally abolishes respiratory control with substrates the oxidation of which involves the NADH leads to CoQ segment, but only partially with succinate which bypasses this segment. Diacetyl, likewise, uncouples oxidative phosphorylation in liver mitochondria from rats fed 3'-Me-DAB, but the mitochondria are most resistant to this uncoupling (in terms of the P/O ratio) at the time period when the respiratory control index (determined in the absence of diacetyl) is at the dye-induced minmum. This time period is at 3 to 4 weeks of dye administration, representing the cumulative dose for tumorigenesis threshold. At this threshold period of feeding 3'-Me-DAB, discontinuities in the Arrhenius plot of the mitochondrial membrane-localized NADH-indophenol reductase appear, with a return toward the control state (no break) at 8 weeks, only to reappear in the plot of the enzyme from tumor mitochondria, suggesting sequential membrane phase transitions in the mitochondria during azo dye carcinogenesis.
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PMID:Mitochondrial membrane-linked reactions in carcinogenesis: change in steroselective uncoupling of oxidative phosphorylation by aliphatic dicarbonyls and in the Arrhenius plot of NADH-indophenol reductase. 40 68


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