Cell abnormalities Jamil Momand 1/31/12

Koch's postulates are: 1) The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms. 2) The microorganism must be isolated from a diseased organism and grown in pure culture.culture 3) The cultured microorganism should cause disease when introduced into a healthy organism. 4) The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

Definitions of cell states Neoplasia-1) the state of cancerous growth; 2) Benign or malignant tumor composed of cells having an abnormal appearance and abnormal proliferation pattern. Displasia-a pre-malignant tissue composed of abnormally appearing cells forming a tissue architecture that deviates from normal. Hyperplasia-accumulation of excessive numbers of normal-appearing cells with a tissue. Weinberg, The Biology of Cancer, 2007.

Figure 1. Targeting endogenous KRAS G12D expression to the mouse pancreasA: Simplified schematic diagram of the program of transcription factor expression in the developing mouse pancreas. PDX-1 expression (blue) is apparent by embryonic day 8.5 (E8.5), while P48 expression (red) begins on approximately E9.5. The resultant PDX-1 and P48 double-positive cells give rise to all of the cells of the mature organ.B: Conditional LSL-KRAS G12D allele and generation of expressed KRAS G12D allele after Cre-mediated excision-recombination. Arrows indicate relative position of PCR primers used to detect alleles. PCR distinguishes presence of recombined allele from WT allele by addition of 40 bp (34 bp for LoxP site plus 6 bp added SalI restriction site). A separate reaction is used to detect the presence of the unrecombined conditional allele (not shown).C: PCR of tail (T) and pancreatic (P) DNA from 2- and 5-month-old control, PDX-1-Cre; LSL-KRAS G12D and P48 +/Cre ; LSL-KRAS G12D mice. The recombined allele is present in the pancreata but not the tails of compound mutant mice.D: Pancreata from young (2 months, top panels) and older (5 months, bottom panels) PDX-1-Cre;LSL-KRAS G12D and P48 +/Cre ;LSL- KRAS G12D animals are larger than those of the respective control animals. Arrows indicate pancreatic nodules.E: Kras G12D, Ras-GTP, and total Ras levels in whole pancreatic lysates of 2- month-old PDX-1-Cre;LSL-KRAS G12D, P48 +/Cre ;LSL-KRAS G12D, and control animals. Detectable levels of Kras G12D and Ras-GTP are seen in compound mutant animals but not in controls. Hingorani et al., Cancer Cell, 2003