Info

10"7

sd

sd

sd

sd

sd

sd

10"5

sd

sd

sd

sd

sd

sd

1er4

dd

sd

sd

sd

sd

sd

10"a

dd

dd

dd

dd

sd

sd

10~2

dd

dd

dd

dd

dd

dd

The parameter p2 is the rate of inactivation of the second allele of the APC gene. In Table 5.1, it is varied between 10-7 per cell division (the basic point mutation rate, [Albertini et al. (1990)]) and 10"2. The elevated values of p2 may be related to the phenomenon of chromosomal instability, which is commonly observed in colon cancers [Lengauer et al. (1998)]. There is evidence that chromosomal instability arises very early in colorectal cancers [Shih et al. (2001b)], and the in vitro estimates of the corresponding elevated rate of LOH give the value as high as p2 = 10~2 per cell division [Lengauer et al. (1997)]. We can see that without chromosomal instability (low values of mutation rate), the pathway sd is more likely. For elevated rates of APC inactivation, it is more likely that both hits will occur in the migrating compartment.

There are several examples in the literature which support the notion that cancer cells might arise in partially differentiated cells. One such example is leukemia, [Grisolano et al. (1997)]. Acute myeloid leukemia (AML) is assumed to reflect transformation of a primitive stem cell compartment. On the other hand, it is thought that acute promyelocytic leukemia (APL) arises in committed myeloid progenitors. The evidence in support of the partially-differentiated-cell origin of APL has been re ported in [Turhan et al. (1995)], where clonality of leukemia was studied. Furthermore, many mouse models of APL have been designed [Brown et al. (1997); Grisolano et al. (1997); He et al. (1997); Westervelt et al. (2003); Westervelt and Ley (1999)], which suggest that genetic changes occurring in committed cells may lead to cancer initiation. For some solid tumors, it has also been proposed that the first change may occur in differentiated cells; this includes skin cancers [Perez-Losada and Balmain (2003)], and stomach cancers [Kirchner et al. (2001)]. However, for most other cancers, including colorectal cancers, no experiments have so far been performed to clearly establish whether a partially differentiated cell can be a target for cancer initiation.

Chapter 6

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment