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

Some parallels and differences are considered between the nutritional circumstances that favor carcinogenesis and those that favor tumor growth and host cachexia. From evidence on deletion of physiological feeding controls and changes in feeding behavior during tumor growth and from evidence on differences in sets of available feeding controls and in feeding behavior among normal individuals, it is suggested that acquisition of possibly carcinogenic dietary habits may originate, in part, from innate deficits in physiological feeding controls.
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PMID:Origins of nutritional imbalance in cancer. 105 3

We studied the mouse NC tumour, a subcutaneously transplanted adenocarcinoma originally of mammary origin. Measurements per g tissue were made of 17 fatty acids (FAs), the combined amounts of n-3, n-6, saturated, unsaturated, and total FAs, and of various FA ratios in the tumour, mammary tissue, spleen, liver and plasma. Compared with mammary tissue from normal mice, tumours of vehicle-treated controls had less of seven of the FAs and more of two FAs. Mice bearing the NC tumour often had changed (usually decreased) amounts of FAs in the 'normal' spleen, liver and plasma, but not in mammary tissue. Treatment with methotrexate (MTX) was studied alone and with indomethacin which can potentiate MTX cytotoxicity. Indomethacin 1.25 mg kg-1 (INDO) increased the amounts of 3/17 tumours FAs and the unsaturated FAs, but reduced 9/17 FAs, the saturated and the unsaturated FAs in 'normal' mammary tissue, and usually had no effect on the FAs of other tissues. MTX 2 or 4 mg kg-1 (MTX 2 or 4 mg) +/- INDO in general partly restored (increased) the amounts of tumour FAs, and reduced the saturated/unsaturated FA ratio. In the 'normal' spleen and plasma also, but not in the liver, MTX 2 mg generally somewhat restored the FA composition. However, as in the liver, the spleen 20:4 and 22:6 (which form prostaglandins and lipid peroxides) did not increase in the presence of INDO. With MTX 4 mg, some of the plasma and liver FAs decreased, in contrast to the tumour. There was generally no evidence of MTX potentiation by INDO. These results are discussed in relation to carcinogenesis, cachexia, and the response to treatment.
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PMID:Changes in tissue fatty acid composition in murine malignancy and following anticancer therapy. 173 11

Post-traumatic stress-induced disorders are still the focus of interest and most recently discussions are under way whether stress-induced cortisol excess leads to atrophy of the brain. In investigation on carcinogenesis the first reports were published on the use of antisense-oligonucleotides during inhibition of the development of tumours by a humoral mechanism and on the gene-based neuroendocrine differentiation of the lungs, perhaps associated with the basis for the development of small cell carcinoma. The oncogenic action of superoxides has also humoral mediators. Interest in nitrogen oxide is focused on two areas: inflammations and hypertension. Intraluminal NO concentrations increase in asthma 2-10x, in cystitis 30-100x, in Crohn's disease 20-200x. Humoral mechanisms in asthma offer new drugs--inhibitors of the development or action of leucotrienes. The basal NO production is reduced in "essential" hypertension but it is not known whether it is the cause or consequence. IGF-I increases the formation of NO in the vascular wall and thus perhaps reduces vascular contractility. As far as IGF is concerned, it is obvious that if recombinant preparations will be available, they will be tested in amyotrophic lateral sclerosis, myotonic dystrophy, multiple sclerosis, catabolic conditions, osteoporosis, in renal failure and to promote wound healing. STH may also prove useful in cardiac failure, in particular in cardiac cachexia. That TRH has receptors in the gut is not surprising, it acts, however, even there via TSH. Thrombopoietin is being tested in clinical trials. Neocytolysis is a new phenomenon: when erythropoietin secretion declines new erythrocytes disappear and only old ones remain in the blood stream. Alpha-adducin is a renal tubular protein, regulating the sodium balance.
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PMID:[Endocrinology 1996-1997]. 965 Mar 40

The accumulated evidence indicates that tumor stroma with its cells and cell products plays a much more active and important role than previously believed. Growth factors and cytokines produced by macrophages and other cells are crucial for stroma formation and angiogenesis. Lytic enzymes provided by stromal cells may be essential for invasion. TNF and other inflammatory mediators may be operative in the systemic effects of tumors, e.g. cachexia. All these effects may come about through the action of soluble substances produced by tumor cells or by more intimate interactions. There is no evidence that stromal cells are directly involved in carcinogenesis--i.e. the cellular transformation to produce the malignant cell. On the other hand, stromal cells and other components of the interstitia are instrumental in tumorigenesis--i.e. the development of a real malignant tumor from its start on the cellular or subcellular level. In one way of looking at it, the stromal cells, e.g. macrophages may be considered as "slaves", kept to carry out certain functions, synthesize essential substances e.g. growth factors that the tumor cells do not have the capacity or the degree of finely tuned machinery to produce. The objective of immunomodulation should then be to create a "slave uprising", to make the macrophages and other cells turn against their masters, stop producing growth factors and start producing harmful factors that would lead to the elimination of the malignant growth. The first target of immunomodulation in tumor disease should probably be local malignancies where no effective treatment exists today- and selected cases of metastatic prevention (181, 182).
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PMID:Tumor stroma. 1069 94

In this Chapter we evaluate complementarity and contradictoriness regarding theories and data of carcinogenesis described in this issue. Most theories and data are compatible with a multimutation model of carcinogenesis. There are a few authors having severe criticism regarding this mainstream. From a view of philosophy of science such criticism is valuable and this type of papers deserves careful evaluation. Zajicek has the most serious criticism. He argues that cachexia, due to the absence of essential molecules, induces the tumor which tries to produce these missing essential molecules. So, in his view, cachexia causes cancer instead of cancer cachexia. The implication is that cachexia should be treated. Duesberg argues that cancer is due to an imbalance of chromosomes rather than to cancer specific mutations. A few points and implications seem important: (a) Duesberg does not really object to a multimutation model; (b) he wants to defend the view that cancer can also be due to chromosomal imbalance, and (c) cancer due to chromosomal imbalance cannot be inherited, in contrast to cancer based on a mutation.
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PMID:Evaluation: complementarity and contradictoriness of cancer theories. A genetic perspective. 1069 4

A great deal of evidence has accumulated in recent years for an important but complex role for proteases in tumor development. However, attempts to treat cancer in humans with anti-proteases have been disappointing, and it has been suggested that more basic groundwork is needed before anti-proteases can be effectively applied. Considerable basic information comes from the recognition that earlier results on transformation of chicken embryo fibroblasts (CEF) by the Bryan strain of Rous sarcoma virus (B-RSV) can be explained in terms of proteases and their inhibitors. In particular, the full but reversible normalization of discrete transformed foci by appropriate concentrations of fetal bovine or of calf serum implies a causal role for multiple proteases in transformation, and the efficacy of treatment with a physiological balance of their natural inhibitors. Addition of certain proteases to contact-inhibited normal cultures was then found to stimulate their proliferation. The toxicity of medium produced by CEF heavily transformed with B-RSV suggests that cachexia and other systemic effects of human cancer may result from vascular dissemination of peptides from pericellular proteolysis within tumors. Comprehensive studies revealed significant increases of plasminogen activator and matrix metalloproteinases (MMPs) after infection of CEF with other strains of RSV, and correlation of the proteases with aspects of transformation. A similar role for proteases is indicated in the transformation of mammalian cells by chemical and physical agents. The information gained from functional experiments on cell transformation in culture is complementary to that obtained from the molecular identification of proteases and their inhibitors in all stages of tumor development. The speed, quantification and easy manipulation of the RSV-CEF transformation assay can be combined with current methods of characterizing proteases and anti-proteases to further enrich our basic knowledge of neoplastic development in cells, and facilitate its application to the treatment of cancer.
Carcinogenesis 2003 May
PMID:Complementary approaches to understanding the role of proteases and their natural inhibitors in neoplastic development: retrospect and prospect. 1277 Oct 23

Leukaemia Inhibitory Factor (LIF) is a polyfunctional cytokine, that belongs to the family of haemopoietic growth factors. LIF plays a role in growth-promotion and differentiation, regulates calcium and bone metabolism, induces acute phase proteins and causes cachexia in organisms with neoplastic disorders. LIF is also to be found in normal skin, where it may be involved in the differentiation process of keratinocytes. In addition, recent data in medical literature indicates that LIF is engaged in the pathogenesis of some skin disorders as well. It has been clearly demonstrated that LIF may act as a proinflammatory cytokine. In allergic contact dermatitis, the expression of LIF mRNA is augmented to a significant degree, indicating that LIF may play a role in the early phase of allergic contact dermatitis. LIF also plays an important role in psoriatic lesions. As the mechanism is not yet fully understood, however, it is hypothesized that the LIF function in psoriatic processes is solely connected with IL-8, as it is known that LIF is able to induce the release of IL-8. Also, some reports have suggested that LIF may also play a role in the carcinogenesis of the skin.
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PMID:The multifunctional role of leukaemia inhibitory factor in cutaneous biology. 1581 47

Mitochondrial dysfunction has crucial importance in carcinogenesis. Due to several reasons, it may lead to insufficiency in the electron transport chain, which activates a series of cytosolic proteins. These proteins are transported to the nucleus and promote the activation of genes leading to intracellular diverse metabolic, regulatory, signalization and stress-related pathways. Retrograde regulation is the general term for mitochondrial signaling, and is broadly defined as cellular responses to alterations in functional state of mitochondria. This signaling pathway is triggered by mitochondrial dysfunction. The retrograde response is not a simple On-Off switch, but rather it responds in a continuous manner to the changing metabolic needs of the cell. Communication between mitochondria and the nucleus is important for a variety of cellular processes such as carbohydrate and nitrogen metabolism, cell cycle and proliferation, and cell growth and morphogenesis. As a result of retrograde regulation, the cell, actually a component of the multicellular organism, transforms to a unicellular lifestyle and initiates a developing course, independent of the systemic structure. This transformed cell runs metabolic regulations effectively in order to utilize all energy depots, mainly the adipose tissue of the multicellular organism. The most important one is the active utilization of glyoxylate cycle, through which the malign cells supply glucose from fats. Continuously acting glycolysis and gluconeogenesis, fatty acid oxidation and de novo lipogenesis constitute futile cycles. This in turn causes cachexia by maintaining the organism in constant negative energy balance. Mitochondria-to-nucleus stress signaling activates some of the genes implicated in tumor progression and tumor cell metastasis. Retrograde regulation also renders the cell more resistant to apoptosis. It is becoming clearer which genes control the retrograde response in human cells. Most probably, MYC is one of the transcription factors necessary for this response.
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PMID:Retrograde regulation due to mitochondrial dysfunction may be an important mechanism for carcinogenesis. 1590 43

Epidemiological studies have indicated that a high intake of saturated fat and/or animal fat increases the risk of colon and breast cancer. Laboratory and clinical investigations have shown a reduced risk of colon carcinogenesis after alimentation with omega-3 fatty acids, as found in fish oil. Mechanisms accounting for these anti-tumor effects are reduced levels of PGE(2) and inducible NO synthase as well as an increased lipid peroxidation, or translation inhibition with subsequent cell cycle arrest. Further, omega-3 eicosapentaenoic acid is capable of down-regulating the production and effect of a number of mediators of cachexia, such as IL-1, IL-6, TNF-alpha and proteolysis-inducing factor. In patients with advanced cancer, it is possible to increase energy and protein intake via an enteral or parenteral route, but this seems to have little impact on progressive weight loss. Fish oil administration improved patients' conditions in cancer cachexia and during radio- and chemotherapy. In patients undergoing tumor resection surgery we observed improvement of liver and pancreas biochemical indices when omega-3 fatty acids were administered. This paper is a review of recent developments in the field of nutrition in cancer patients with emphasis on the acute phase response following cancer surgery and the beneficial aspects of fish oil administration.
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PMID:Omega-3 fatty acid effects on biochemical indices following cancer surgery. 1679 97

There is a proven association between carcinoma of the pancreas and both the sporadic and hereditary forms of chronic pancreatitis. In chronic pancreatitis the standardised incidence ratio for development of pancreatic cancer is 14-18 and is further increased by cigarette smoking. Underlying mechanisms are unclear but current theories point to the progressive accumulation of genetic mutations as a consequence of repeated DNA damage and cell regeneration in an environment favouring proliferation and neovascularisation. In patients who develop pancreatic cancer, there is interest in the role of the inflammatory response in the development of cancer cachexia and in determining prognosis. Furthermore, markers of a systemic inflammatory response have prognostic significance in both advanced, inoperable pancreatic cancer and in patients undergoing resection. Further understanding of the details of the relationship between inflammation, carcinogenesis and cancer prognosis may lead to new therapeutic possibilities as part of multi-modality management of this difficult disease.
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PMID:Chronic inflammation and pancreatic cancer. 1820 13


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