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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty-nine breast cancer patients were studied for the end result of therapy. During surgery, the anaesthesia administered was either halothane (61 cases) or ether (28 cases) mixture with nitrogen and oxygen. The holstead method for mastectomy was used for all cases. The results showed that the type of anaesthesia influenced the end results of therapy of breast cancer patients. The survival rates of patients receiving halothane were much higher than those of ether anaesthetized cases. The differences were most pronounced among cases who received both preoperative radiotherapy and postoperative chemotherapy, and in cases with metastasis into regional lymph node. A comparison of groups of patients on the basis of such parameters as the anaesthetic used, age and degree of tumor progression (according to TNM classification and post-operative histological assays) showed them to well matched. These results may be explained by the effects of the anaesthesia on the role of immunity in controlling tumor cell implantation and growth of metastasis.
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PMID:Survival rates of breast carcinoma patients after surgery and anaesthetic. 45 20

The multistage model of mouse skin tumorigenesis has been extremely useful for studying various factors that modify the carcinogenic process. Using this model system one can specifically study the effects of potential modifiers on both the initiation and the promotion stages independently. Studies have been performed on many exogenous compounds that have the capacity to inhibit (and in some cases enhance) the initiation phase by either: (i) alteration of the metabolism of the carcinogen (decreased activation and/or increased detoxification); (ii) scavenging of active molecular species of carcinogens to prevent their reaching critical target sites in the cells; (iii) competitive inhibition; or (iv) modulation of epidermal DNA synthesis. In addition, there have been a number of studies on compounds that either inhibit (or again in some cases enhance) promotion of skin carcinogenesis by (i) altering the state of differentiation; (ii) inhibiting the promoter-induced cellular proliferation; (iii) preventing gene activation by promoters; or (iv) scavenging free radicals and reactive oxygen species. Recent studies have also begun to unravel the nature of the tumor progression process of skin carcinogenesis. Many factors can modulate tumor progression including: (i) subsequent exposure to genotoxic agents; (ii) dose, duration and frequency of promoter treatment, (iii) chemical nature of the promoting agent. The multistage model of skin tumorigenesis has also begun to provide insight into the role of specific dietary, immunologic, and genetic factors involved in chemical carcinogenesis. It is believed that further study of all of these factors will greatly enhance our understanding of the process of chemical carcinogenesis in epithelial tissues in general as well as the process of skin carcinogenesis specifically. Finally, a greater understanding of those factors modifying skin tumorigenesis in mice will provide valuable information on the further development of early detection and prevention strategies for chemical carcinogenesis in humans.
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PMID:Modification of multistage skin carcinogenesis in mice. 190 60

The role of free radicals and active states of oxygen in human cancer is as yet unresolved. Various lines of evidence provide strong but inferential evidence that free radical reactions can be of crucial importance in certain carcinogenic mechanisms. A central point in considering free radical reactions in carcinogenesis is that human cancer is really a group of highly diverse diseases for which the initial causation and the progression to clinical disease occur through a wide variety of mechanisms. Furthermore, for many human cancers it appears that there are alternate pathways capable of tumor initiation and tumor progression. While for certain of these pathways free radical reactions appear necessary, it is unlikely that there are human cancers for which free radicals, or any other mechanism, are sufficient for the entire process beginning with the genetic alteration leading to a somatic mutation and eventually resulting in clinically overt disease. It is crucial that we view free radical reactions as among a panoply of mechanisms leading to human cancer, and consider research about the role of free radicals in cancer as opportunities to prevent the initiation or progression of human cancer.
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PMID:Free radicals and carcinogenesis. 207 48

We tested clinical significance of hemocirculatory and metabolic values and ratios as determined by positron emission tomography (PET) in twenty-three patients with cerebral gliomas. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rates of oxygen (rCMRO2) and glucose (rCMRGl) were measured prior to treatment using PET with 15O2, C15O, 15O2, and 18F-fluorodeoxyglucose tracers. For the quantitative analysis, regions of interest were delineated on tumor regions including peak activity, the contralateral gray and white matter. The regional values and the ratios of tumor/gray matter and tumor/white matter were compared to performance status (PS) according to the five functional grades system which are defined by the Japan Society for Cancer Therapy, tumor progression-free time (PFT), survival time (ST) from the time of the PET study, regardless of type of therapy. As with rCMRGl, the tumor values and the ratios of tumor/gray matter and tumor/white matter correlated significantly with PS (tumor/gray: p less than 0.05, tumor/white: p less than 0.01). Both the gray rCBF and the tumor/gray rCBF ratio had close relation with PS and/or PFT (p less than 0.05). The gray matter rCMRO2 and the tumor/gray matter rCMRO2 ratio related significantly (gray matter: p less than 0.01, tumor/gray: p less than 0.05) to each clinical parameter of PS, PFT, and ST. These indicate that values and ratios as determined by PET can be useful in predicting the prognosis of glioma patients.
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PMID:[Prognostic significance of regional blood flow, blood volume, oxygen extraction fraction, and metabolic rates of oxygen and glucose as measured by positron emission tomography in patients with gliomas]. 261 91

The two-step initiation-promotion protocol for the induction of skin tumors in mice is a convenient model to elucidate what molecular events are involved in the multistage process of carcinogenesis and how they can be modulated. The current theories concerning the mechanisms of skin tumor initiation, stages 1 and 2 of tumor promotion, and tumor progression are reviewed. Because chemical carcinogens and tumor promoters may, directly or indirectly, generate reactive oxygen species (ROS) and because various antioxidants inhibit effectively some of the biochemical and biological events linked to tumor initiation, promotion and/or progression, it is conceivable that different sequences and levels of free radical-induced macromolecule damage may contribute to the evolution of the epidermal target cells from the preneoplastic stage to the malignant stage.
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PMID:Antioxidants and multistage carcinogenesis in mouse skin. 269 40

We investigated the effects of host inflammatory cells on the progression of QR (C57BL/6 mouse) and ER (SHR rat) regressor tumor cells which spontaneously regress in normal syngeneic hosts. We noted an enhanced tumorigenicity of regressor tumor cells after s.c. implantation with attachment to plastic plate, a situation which induces inflammation in normal hosts accompanied by the development of tumors as compared to normal mice injected with regressor tumor cells in suspension in PBS- which spontaneously regressed. We also observed enhanced tumorigenicity of regressor tumor cells injected into the site of the plastic plate which had been previously implanted into the normal host. Regarding these phenomena, we suggest that tumor progression may be induced by host induced inflammatory cells or their products. We also found enhanced tumor progression of QR regressor tumor cells after co-inoculation with inflammatory cells produced by the implantation of hemostatic spongel into the peritoneal cavity of mice. The mechanisms involved in the progression of regressor tumor cells by co-existence with inflammatory cells are thought to be associated with the production of oxygen radicals, tumor cell chemotactic factors, soft agar colony promoting factors and PGE2.
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PMID:[Experimental approach to the investigation of tumor progression]. 273 20

Cultured cells subjected to oxygen deprivation have been shown to undergo anomalous DNA synthesis, which can result in DNA overreplication and the generation of cellular variants [Rice, G. C., Hoy, C. & Schimke, R. T. (1986) Proc. Natl. Acad. Sci. USA 83, 5978-5982]. In the present study, murine tumor cells were exposed to severe hypoxia and then tested for their ability to form experimental metastases. Upon reoxygenation, cells transiently, yet dramatically, increased their metastatic potential. Flow cytometric analysis confirmed that hypoxia and reoxygenation induced cell cycle perturbations and DNA overreplication in these tumor cell lines. Fibrosarcoma cells with overreplicated DNA isolated by fluorescence-activated cell sorting proved to be highly metastatic, although cells with 2-4 times the haploid DNA content in populations treated with hypoxia were also markedly more metastatic than oxic populations. These results support the hypothesis that hypoxic conditions existing in regions of solid tumors promote cellular heterogeneity and tumor progression.
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PMID:Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. 320 Aug 38

Progressive weight loss and anorexia are frequent phenomena in cancer patients. Although cachexia is an expected occurrence in the terminal stages of nearly all malignancies, it may be a presenting sign when the tumor burden is quite small. Lipid depletion occurs out of proportion to the protein loss and accounts for most of the weight loss in cancer. Lipids, more specifically fatty acids, are the major source of fuel in mammals and may also be used in the synthesis of new cell products. Lipolysis and lipogenesis are under the influence of several important enzymes and peptide hormones that may be modulated by a variety of exogenous factors. There is evidence that cancer patients have lost the normal homeostatic responses to decreased energy intake or starvation that allow a decrease in oxygen consumption and protein sparing. An increase in Cori cycle activity or futile recycling of metabolic products occurs with a net energy expenditure rather than energy production. Clinical studies have shown that the body lipid depletion accompanying tumor progression is not solely secondary to decreased food intake and may be reproduced by the transplantation of certain noninvasive tumors to normal hosts. Elevated basal lipolysis has occasionally been seen early in tumor growth. Such findings suggest the presence of a tumor-associated factor responsible for this increase in lipid mobilization. Some of the potential mechanisms for the altered lipid metabolism seen in cancer have been discussed. Metabolic substrates may be remodeled and directed away from fuel-efficient into energy-requiring pathways. An increased energy expenditure may occur as a result of the energy costs of tumor synthesis, an uncoupling of oxidative phosphorylation, or energy-requiring futile cycling. An overall depletion of lipid may be the final outcome of the inhibition of lipid deposition. TNF/cachectin has recently been found to suppress the activity and synthesis of several key lipogenic enzymes, including lipoprotein lipase. Abnormalities in insulin secretion or sensitivity may be involved in the decrease of fat storage in malignancy. Insulin also exerts a significant antilipolytic effect by its antagonism of hormone-sensitive lipase. Mediators of lipolysis and abnormal lipid metabolism may occur in a number of clinical conditions and include ectopic hormone production, growth factors, and tumor-associated lipolytic factors (lipid mobilizing factor, toxohormone).
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PMID:Fat metabolism and cancer. 353 75

The emergence of diversified tumor cell subpopulations in malignant neoplasms accounts for their heterogeneous cellular phenotypes and virtually ensures that some tumor cells will ultimately evolve with the most favorable properties for their enhanced abilities to survive, grow, invade and metastasize (tumor progression). The rates of cellular phenotypic diversification appear to vary greatly among different tumors and within the same tumor, and they are probably controlled, at least in part, by cellular instability due to chromosomal defects and random somatic mutational events, the rates of which are known to be higher in more malignant cells, and by epigenetic events, which may vary widely depending on the nature of the tumor cells and their microenvironments. As tumor progression proceeds, the most malignant cell subpopulations appear to lose their responsiveness to changes in tumor microenvironment while maintaining their high rates of phenotypic diversification. Tumor and normal cell-cell and cell-extracellular matrix interactions, as well as tumor cell nutrients, oxygen, hormones, growth factors, inducers and other regulatory molecules provide individual malignant cells with microenvironmental signals that could act through epigenetic cellular modifications, such as DNA methylation, and transcriptional, posttranscriptional, translational and posttranslational controls, or combinations of these. In addition, integration of viral gene sequences or viral modification of host DNA in critical regions could affect phenotypic stability. Finally, manipulation of tumor cells by antitumor therapy can also have profound effects on the rates of phenotypic diversification of the surviving tumor cells. A model for generating cellular phenotypic diversity based on the proposed mechanism for rapid generation of immunoglobulin molecular diversity in B cells may be applicable to malignant cells and to cells in general. In this model the expression and activity of gene products from multigene families are affected by a variety of genetic and epigenetic controlling mechanisms, and alterations in regulatory genes caused by recombination, methylation, mutation, or other changes could lead to differences in gene expression, resulting in widespread quantitative (and perhaps some qualitative) changes in particular gene products or their activities. As they proceed down different pathways of gene expression, each cell would be exposed to continual host selection pressures creating diverse, ever-changing malignant cell-populations.
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PMID:Generation of phenotypic diversity and progression in metastatic tumor cells. 637 Apr 18

Studies over the past 20 years have established that the development of new capillaries from an existing vascular network (a process called angiogenesis) is an essential component of tumor growth. Malignant tumors do not grow beyond 2-3 mm3 in size unless they stimulate the formation of new blood vessels and thus provide a route for the increased inflow of nutrients and oxygen and outflow of waste products. Tumor angiogenesis also provides an essential exit route for metastasizing tumor cells from the tumor to the bloodstream. Indeed, extensive neovascularization is a poor prognostic factor in several forms of human cancer. Angiogenesis is a complex, multistep process driven by many local signals within the tumor. This involves the degradation of the extracellular matrix around a local venule after the release of collagenases and proteases, the proliferation and migration of capillary endothelial cells, and their differentiation into functioning capillaries. Cytokines produced by various cell types present within the microenvironment of solid tumors form a complex, dynamic network in which they have multiple effects on tumor progression. Herein we review our work on the presence, and possible regulatory influence on tumor angiogenesis, of a number of these cytokines within invasive breast carcinomas. We have combined immunocytochemistry with a single cell cytokine release assay called the reverse hemolytic plaque assay to investigate the cellular sources of the key angiogenic cytokines, vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor-alpha. Tumor-associated macrophages in the stromal compartment of these tumors and/or malignant epithelial cells were seen to be a major producer cell for these cytokines, whereas tumor necrosis factor-alpha receptors were expressed by leukocytes, malignant cells, and endothelial cells in tumor blood vessels.
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PMID:Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. 753 28


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