Cancer lethality fractions

In estimating the total detriment due to stochastic responses in any organ as described above, the probability coefficient for fatal cancers (F) or severe hereditary responses is based on data in humans and animals described in Section 3.2.2.2, and the lethality fraction (k) and relative length of life lost per fatal response (.II) are based on data on responses from all causes in various national populations. The values of F, k, and t/l for different organs, as well as the probability coefficient for severe hereditary responses, assumed by ICRP (1991) and the resulting estimates of total detriment, F((/T)(2 - k ), are summarized in Table 3.2. The two entries for Total in the last row represent the probability coefficient for... 

Organ Fatal Cancers (FT Severe Hereditary Effects 1 Lethality Fraction (kY Relative Length of Life Lost m) Total Detriment F(til 2 - kf... 

From the expression for the total detriment given above and the data in Table 3.2, the following observations can be made. For cancers that are nearly always fatal (e.g., leukemia from irradiation of bone marrow), the total detriment is determined essentially by the probability of a fatal cancer, absent consideration of the relative length of life lost (fJl), and the contribution from weighted nonfatal cancers is insignificant. For cancers that are rarely fatal (e.g., skin or thyroid cancers), the total detriment exceeds the probability of a fatal cancer by no more than a factor of two, based on the assumption that nonfatal cancers should be weighted by the lethality fraction (k). In general, if the lethality fraction is less than about 0.1, the total detriment essentially is twice the probability of a fatal cancer, independent of the lethality fraction. 

Until 2002 our search for compounds with potential anticancer activity was restricted to those that were brine shrimp lethal and to serendipity. All of our new compounds are sent to the National Cancer Institute for screening against their battery of human cancer cell lines. Brine shrimp lethality is a reasonable indicator of cytotoxicity, so many cytotoxic compounds exhibit some degree of activity against certain human cancer cell lines. Compounds occasionally exhibit activity against a particular cancer cell line even if they are not cytotoxic. This is not at all unreasonable as anticancer activity can be a function of many different metabolic phenomena. We still routinely test all of our crude extracts, column fractions and pure compounds for brine shrimp lethality. Several studies have shown that most cancer chemotherapeutic agents exhibit brine shrimp... 

Approximately 40% of cancer patients receive radiotherapy as some part of their treatment (http //www.cancerhelp.org.uk/help) and radiosensitization may represent the most significant anticancer therapeutic utility of PARP inhibitors. Radioresistance is a major clinical problem and there is good evidence that it is due to a radiation-resistant, growth-arrested cell fraction within a tumour that can reenter the cell proliferation cycle and thereby repopulate the tumour after radiotherapy.In some in vitro radiopotentiation smdies attempts have been made to mimic the clinical situation by measuring recovery from potentially lethal damage (PLD). In in vitro models of PLD recovery, the increased survival of growth-arrested cells is assessed after a recovery period, in comparison with the survival of cells without the recovery period. In other smdies with exponentially growing cells irradiation dose-response curves in the presence and absence of PARP inhibitor have been compared. Alternatively, recovery from... 

Petersen C, Zips D, Krause M, et al (2005) Recovery from sub-lethal damage during fractionated irradiation of human FaDu see. Radiother Oncol 74 331-336 Raabe A, Eickholter S, Zieron J, et al (2000) Influence of dose per fraction and overall treatment time on the response of pulmonary micrometastases of the RlH-tumour to fractionated irradiation. Radiother Oncol 56 259-264 Sanguineti G, Richetti A, Bignardi M, et al (2005) Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer results of a multicenter phase III study. Int J Radial Oncol Biol Phys 61 762-771... 

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