Search results for "Tumor Hypoxia"
showing 10 items of 56 documents
Pathophysiology of Solid Tumors
2009
It is generally accepted that tumor blood flow, microcirculation, oxygen and nutrient supply, tissue pH distribution, lactate levels, and the bioenergetic status— factors that are usually closely linked and that define the so-called pathophysiological microenvironment (“tumor pathophysiome”)—can markedly influence the therapeutic response of malignant tumors to conventional irradiation, chemotherapy, other non-surgical treatment modalities, malignant progression, and the cell proliferation activity within tumors. Currently available information on the parameters defining the pathophysiological micromilieu in human tumors is presented in this chapter. According to these data, significant var…
Can Tumor Oxygenation be Improved by Reducing Cellular Oxygen Consumption?
1999
Tumor hypoxia, which can be found in many experimental and human tumors is an important factor influencing the therapeutic efficacy of standard radiotherapy, O2-dependent chemotherapy and photodynamic therapy (Hall, 1994) and might be responsible for the development of aggressive tumor cell subpopulations (Graeber et al., 1996). Since this oxygen deficiency results from a disparity between O2 supply to the tumor tissue and the oxygen demand of the cells, several attempts have been undertaken to improve tumor oxygenation primarily by increasing the arterial oxygen supply. The O2 supply to the tumor cells can be improved by (a) increasing the arterial O2 content (by breathing hyperoxic gases …
Lack of Association Between Tumor Oxygenation and Cell Cycle Distribution or Proliferation Kinetics in Experimental Sarcomas
2003
In tumor cells, pronounced hypoxia induces an arrest of cell cycle in the late G1phase1−3. Since hypoxia is a common phenomenon in experimental and human tumors the hypoxia-induced disturbance of the cell cycle may play a role in the reduced efficacy of non-surgical treatment modalities resulting in a reduced long-term prognosis and a higher rate of local recurrences in hypoxic tumors4,5. It has been shown that a cell cycle arrest reduces the efficacy of standard radiotherapy6,7 and may alter the cytotoxic effects of various chemotherapeutic agents such as cisplatin, alkylating agents, doxorubicin or taxols8−12 and of cytokines13. If tumor hypoxia plays a relevant role in affecting the cell…
Blood Flow and Oxygenation Status of Head and Neck Carcinomas
1997
Solid tumors contain a significant fraction of microregions which are chronically or transiently hypoxic. Experimental evidence is growing, showing that hypoxia may have a profound impact on malignant progression and on responsiveness to therapy [1–4].The clinical relevance of tumor oxygenation in human solid malignancies is under investigation (for a recent review see [5]). In this presentation, relevant clinical findings available to date on blood and oxygen supply of human head and neck carcinomas will be reviewed and emphasis will be given to the relevance of these factors in clinical oncology.
HIF-1α induces MXI1 by alternate promoter usage in human neuroblastoma cells
2009
Adaptation to low oxygen conditions is essential for maintaining homeostasis and viability in oxygen-consuming multi-cellular tissues, including solid tumors. Central in these processes are the hypoxia-inducible transcription factors, HIF-1 and HIF-2, controlling genes involved in e.g. glucose metabolism and neovascularization. Tumor hypoxia and HIF expression have also been associated with a dedifferentiated phenotype and increased aggressiveness. In this report we show that the MAX interactor-1 (MXI1) gene is directly regulated by HIF proteins in neuroblastoma and breast cancer cells. HIF-binding and transactivation were detected within MXI1 gene regulatory sequences in the vicinity of th…
Impact of oxygenation status and patient age on DNA content in cancers of the uterine cervix.
2003
Abstract Purpose In carcinomas of the uterine cervix, the tumor oxygenation status has been shown to be a prognostic indicator that is independent of treatment modality. In vitro studies suggest gene amplification and polyploidization to be among the major consequences of hypoxia (with or without consecutive reoxygenation) and to be associated with treatment resistance and tumor progression. This study analyzed whether hypoxia alters net DNA content in uterine cervix cancer cells to the extent that it is identifiable by DNA image cytometry. Methods and materials In 64 patients with primary cervical cancer, tumor oxygenation was assessed polarographically and correlated with cell DNA content…
Hypoxia and anemia: effects on tumor biology and treatment resistance
2004
In locally advanced solid tumors, oxygen (O2) delivery is frequently reduced or even abolished. This is due to abnormalities of the tumor microvasculature, adverse diffusion geometries, and tumor-associated and/or therapy-induced anemia. Up to 50-60% of locally advanced solid tumors may exhibit hypoxic and/or anoxic tissue areas that are heterogeneously distributed within the tumor mass. In approximately 30% of pretreatment patients, a decreased O2 transport capacity of the blood as a result of tumor-associated anemia can greatly contribute to the development of tumor hypoxia. While normal tissues can compensate for this O2 deficiency status by a rise in blood flow rate, locally advanced tu…
Tumor Hypoxia and Malignant Progression
2004
Publisher Summary This chapter discusses tumor hypoxia and malignant progression. Hypoxic (or anoxic) areas arise as a result of an imbalance between the supply and the consumption of oxygen. Whereas in normal tissues or organs the O2 supply matches the metabolic requirements, in locally advanced solid tumors the O2 consumption rate of neoplastic as well as stromal cells may outweigh an insufficient oxygen supply and result in the development of tissue areas with very low O2 levels. Major pathogenetic mechanisms involved in the emergence of hypoxia in solid tumors are (a) severe structural and functional abnormalities of the tumor microvessels (b) a deterioration of the diffusion geometry, …
Biological consequences of tumor hypoxia
2001
Growing evidence from experimental and clinical studies points to the fundamental, pathophysiologic role of hypoxia in solid tumors. Intratumoral hypoxia is a consequence of a structurally and functionally disturbed microcirculation, with deterioration of the diffusion geometry and of tumor-associated anemia. Hypoxia-induced changes of the proteome in the neoplastic and stroma cells may lead to neoplastic growth impairment through molecular mechanisms, resulting in cellular quiescence, differentiation, and apoptosis. Alternatively, hypoxia-induced proteome changes activating nonspecific stress response, anaerobic metabolism, angiogenesis, tissue remodeling, and change of cell contacts may p…
Pathophysiological aspects of hyperthermia
1992
Blood flow in many rapidly growing tumors is sluggish leading to an impairment of convective heat dissipation which facilitates tumor heating compared to normal tissues. In addition, the compromised microcirculation causes a hostile metabolic micromilieu which can modulate the therapeutic effect of heat. After clinically relevant heat doses, a shut-down of tumor microcirculation is often observed creating a “heat-reservoir” and aggravating tumor hypoxia, acidosis, and substrate and energy depletion, factors which are known to greatly enhance tumor cell killing by heat. Since the mechanisms described are mostly derived from experimental results on fast-growing animal tumors, the clinical rel…