Tumour Hypoxia: Impact on Biology, Prognosis and Treatment of Solid Malignant Tumours

Klinik für Radioonkologie, Universität Tübingen, Germany.
Onkologie (Impact Factor: 0.86). 03/2004; 27(1):83-90. DOI: 10.1159/000075611
Source: PubMed


Tumour hypoxia is a major constraint for radiotherapy and many types of chemotherapy. A variety of different pathogenetic mechanisms contribute to the development of hypoxia in solid tumours. Hypoxia is associated with unfavourable prognosis, regardless of the treatment modality applied. Two different effects have been considered to explain the deleterious effects of hypoxia on the outcome of tumour patients. The first aspect encompasses the direct interference of hypoxia with antineoplastic treatment modalities. The efficacy of ionizing radiation, but also of a variety of cytotoxic drugs and cytokines rely directly on adequate oxygen tensions. The second aspect concerns the effects of hypoxia on the biology of tumour and stromal cells. Hypoxia is related to malignant progression, increased invasion, angiogenesis and an increased risk of metastasis formation. Possibly, hypoxia is furthermore a stressor which selects cells with increased resistance to apoptosis and thereby indirectly contributes to treatment resistance. This article reviews in brief the specific pathophysiology of tumour oxygenation and its implications for prognosis, tumour treatment and biology.

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    • "Several reports have described a close relationship between genetic stability of the tumor and the selective pressure of the tumor microenvironment [6]. Many biomarkers predicting the response to chemotherapy are suggested to be linked to pathways of cell survival that are activated as adaptive response mechanisms in stressing microenvironments such as poor nutrient supply or low oxygen levels [7]. One candidate that is suggested to play an important role in cancer cell survival is class III β-tubulin (TUBB3) "
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    ABSTRACT: Introduction/Background: βIII-tubulin expression correlates with poor outcome in various malignancies. Materials and methods: βIII-tubulin expression was analyzed by immunohistochemistry on a tissue microarray containing 1800 colorectal cancers. Results were compared to clinic-pathological and molecular parameters. Results: βIII-tubulin expression was detectable in 79.2% of 1619 interpretable colorectal cancers. Whole tumor slide analysis showed that βIII-tubulin is homogenously expressed in CRC. High βIII-tubulin expression was associated with left-sided tumor localization (p=0.0303) and nuclear β-catenin expression (p=0.003). High βIII-tubulin expression was not linked to the gender of the patient (p=0.5842).When all tumors were analyzed the prognostic role of βIII-tubulin expression was not independent of pT stage, pN stage, tumor grade or tumor localization (p=0.0517). Conclusion: βIII-tubulin expression is not an independent prognostic parameter in colorectal cancer. The significant association with left-sided tumor localization and a key genomic alteration of colorectal cancer such as β-catenin suggest interaction with important pathways involved in colorectal cancer.
    Full-text · Article · Dec 2015 · Cancer Treatment Communications
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    • "In addition, some solid tumours are found to have necrotic (dead) cores, a direct effect of long-standing tissue hypoxia [8] [9]. Tumour hypoxia has been demonstrated to reduce the efficacy of many standard cytotoxic drugs used in the treatment of cancer [10]. This is due to ineffective penetration of the drug into the hypoxic mass of the tumour, due to poor vascularisation . "
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    ABSTRACT: Despite substantial investment in prevention, treatment and aftercare, cancer remains a leading cause of death worldwide. More effective and accessible therapies are required. A potential solution is the use of endospore forming Clostridium species, either on their own, or as a tumour delivery vehicle for anti-cancer drugs. This is because intravenously injected spores of these obligate anaerobes can exclusively germinate in the hypoxic/necrotic regions present in solid tumours and nowhere else in the body. Research aimed at exploiting this unique phenomenon in anti-tumour strategies has been ongoing since the early part of the 20th century. Only in the last decade, however, has there been significant progress in the development and refinement of strategies based on spore-mediated tumour colonisation using a range of clostridial species. Much of this progress has been due to advances in genomics and our ability to modify strains using more sophisticated gene tools.
    Full-text · Article · Jan 2015 · Research in Microbiology
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    • "With few exceptions, solid tumors have regions with little or no oxygen [1] [2] [3]. This is due to poor vascularization and is called hypoxia (low oxygen tension) or anoxia (no oxygen). "
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    ABSTRACT: The sections in this article areIntroductionThe Role of Oxygen in Photodynamic Therapy: 1O2 GenerationDependence of the Photosensitizing Effect on O2 ConcentrationThe Oxygenation Status in Tumors and Normal TissuesPDT-Induced Reduction of Tumor OxygenationO2 Consumption (Primary Reduction)Vascular Damage (Secondary Reactions)Photosensitizer Photobleaching (Secondary Reactions)Methods to Reduce Tumor Deoxygenation During PDTLow Fluence RatesFractionated Light ExposureOther Methods Changes of Quantum Yields Related to Photosensitizer RelocalizationChanges of Optical Penetration Caused by Changes in O2 ConcentrationConclusion Keywords:photodynamic therapy;oxygen;photosensitization;oxygenation;tumor deoxygenation;cancer
    Full-text · Chapter · Jan 2013
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