![]() ![]() 10 This phenomenon occurred primarily for oxygen tensions 20 mm Hg. 10 In the presence of oxygen, free radical attack enhances radiation-induced DNA damage such that tumor cells lacking oxygen were found to be 2.5–3 times more resistant to radiation than their normoxic counterparts. 9 Radiation causes DNA damage in cells, most importantly double strand breaks, by both direct and indirect effects. 8 In the 1970s, Adams demonstrated that oxygen had to be present during or within submilliseconds after radiation damage in order to observe the “oxygen effect”. 7 The same radiation-enhancing effect of oxygen was soon observed in mammalian cells, with the use of the clonogenic cell survival assay developed by Puck and Marcus. Initially, evidence of the impact of oxygen on radiation sensitivity was discovered in 1956, utilizing experiments that exposed Escherichia coli to radiation while in hypoxic conditions. Modified with permission from Thomlinson and Gray. 6 These findings implied that tumor cells near the limit of oxygen diffusion would survive at lower than normal oxygen tensions, rendering them resistant to radiation therapy.įixed section of a human squamous cell carcinoma of the bronchus stained by hematoxylin and eosin. 3– 5 The landmark publication of Thomlinson and Gray, which evaluated histological structures of human lung cancers ( Figure 1), concluded that, “there must exist a falling gradient in oxygen tension between the periphery and the centre of each tumour cord”. 2 In the 1950s, Hal Gray’s research team explored the potential impact of oxygen in radiotherapy in vitro and in vivo. 1 However, it was not until the 1920 and 30s that the absence of oxygen was found to be the culprit behind the lack of radiation-induced damage. Interestingly, it was reported by Schwarz that clamping the skin to reduce blood flow to the arm decreased the skin irritation effects of ionizing radiation. Unfortunately, the frequent exposure to radiation resulted in many of these individuals developing leukemia. The telltale burn would indicate the instrument was at the proper setting. To test the status of the radiotherapy machine, radiologists would expose the skin of their arms to the instrument. Following the discovery in 1896 by German physicist Wilhelm Conrad Roentgen, X-rays were used for diagnosis, and within 3 years radiation was used to treat cancer. Radiation therapy has been used since the end of the 19th century as a means to control tumor burden, both with curative and palliative intent. This review discusses the physiological basis of hypoxia, methods of detection, and strategies to overcome the resulting therapy resistance. Tumor cells existing in such hypoxic environments have long been known to be resistant to anticancer therapy, display an aggressive phenotype, and promote tumor progression and dissemination. A critical consequence of the inadequate vascular networks in solid tumors is the development of regions of hypoxia. Functionally, the ability of the tumor vasculature to deliver nutrients and remove waste products is severely diminished. A disorganized labyrinth of vessels that are immature, tortuous and hyperpermeable typifies tumor vasculature. In tumors, the aggressive growth of the neoplastic cell population and associated overexpression of pro-angiogenic factors lead to the development of disorganized blood vessel networks that are structurally and functionally different from normal vasculature. The disease predominantly affects aged populations and is one of the leading causes of death in most western countries. ![]() Specialist ensembles, including Concerto Köln, Les Arts Florissants and Les Talens Lyriques, bring apt nuance and colour to these sumptuous productions showcasing worthy masterworks of the Baroque.In 2012, cancer affected 14.1 million people worldwide and was responsible for 8.2 million deaths. Sally Matthews is ‘captivating’ as Deidamia (New York Times), Anna Bonitatibus is an uncompromisingly intense Didone, and Luca Pisaroni’s Hercules is by turns heroic and melodious. The 18th-century Baroque theatre machinery at Drottningholm lends authenticity to Rameau’s Zoroastre, as does the period Pergolesi Theatre at Jesi to the performance of Adriano in Siria. By contrast, prior to its revival in the very Baroque gem of a theatre that hosted its premiere, the courtly farce Dove è amore è gelosia was virtually unknown, as was the hitherto neglected Deidamia, Handel’s final Italian opera. La Didone is one of the earliest operas in existence, and Ercole amante, at the time of its premiere, was the grandest show ever performed in Europe. ![]()
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