Magoo Settembre 6,
However, the methods of specimen acquisition, preparation, and evaluation of the Pap smear have changed little since its introduction in the s. One-half of the false negatives are due to inadequate sampling, and the other half are attributed to a failure to identify the abnormal cells or to interpret them accurately 62, 64, Manual screening of Pap smears is very labor intensive and demands that the cytotechnologist be capable of high levels of concentration for extended periods.
In addition, cytotechnologists may feel pressure to examine as many slides as they can legally despite recent regulatory changes attributable to the Clinical Laboratory Improvement Act of CLIA ' A slide may have only a few abnormal cells, which could be easily overlooked by a fatigued technologist at the end of a busy workday.
Recent reports suggest that some of the false negative results are caused by these screening errors. An automated screening machine, such as our AnuCyte system, would not be subject to fatigue and, therefore, could reduce this type of error 64, Failure to Bis 220 wk2 reflection summary abnormal cells is another possible source of error.
A few states have instituted proficiency testing programs in an effort to minimize this type of error. A hypothetical ideal automated screening machine could be programmed so that it would recognize all types of potentially abnormal cells.
Of course, no machine performs ideally in practice. Several companies are developing automated screening machines in an attempt to reduce the false negative rate of Pap smears without having an unreasonably high rate of false positives. The systems currently under development generally automate the 50year old Pap smear technology without incorporating the advanced fluorescent probe technologies of the s.
A couple of firms include the additional feature of automating the preparation of conventional Pap smear slides.
In the fall ofthe Food and Drug Administration FDA approved two automated instruments for re-screening smears evaluated as negative on the initial screen. Data from the trials suggest that the new instruments could reduce the rate of false-negative smears. However, neither the efficacy in routine practice nor the cost-benefit of these devices has been determined.
None of the supposed 'advances' in screening technology use chromosomal imbalance as the sole or primary means of detecting cancer. Aneuploidy is the most common chromosomal abnormality observed in cervical and ovarian cancers 46, According to a number of authorities on cancer of the cervix, "[Aneu]ploidy appears to be a good predictor of biologic behavior and may have better predictive value than histopathologic characteristics judged by the eye.
After 30 years of research and billions upon billions of dollars spent, these cancer theories have yielded precisely zero results.
In fact, except for the rare cancers produced in the laboratory 10diploidy does not seem to occur in human solid tumors After a decade of searching we are not aware of any example of any type of cancer with balanced chromosomes. As most if not all suspected oncogenes are perfectly heritable, cancer should be a disease of youth if tumor progression required the gradual accumulation of mutations.
The mounting evidence against the mutation theory of cancer explains why specific cancer genes have not resulted in clinical diagnostic markers of cancer and targets of therapeutic intervention.
We, on the other hand, have chosen a different strategy of cancer diagnosis. We have considered a hundred years of scientific and medical observation, looking for the most characteristic differences between cancer cells and normal tissues. InTheodor Boveri proposed that cancer was caused by chromosomal imbalance aneuploidy However, over the last 25 years the gene mutation hypothesis has become so dominant that aneuploidy, still considered a viable candidate for cancer etiology by the editors of the Journal of the National Cancer Institute in 16is today not even listed in the indexes of the most important molecular biology textsand this is in spite of the fact that numeric chromosome imbalance is the most prominent genetic change in essentially all of over 20, solid tumors that have been examined to date 11, While none of the "oncogenes" is a general diagnostic for cancer not even a specific type of canceraneuploidy is always present in solid cancers28, 30, 31, The mass of data accumulating on cancer "demonstrates the more general principle that some increase in chromosome number most often to a mode centered in the triploid or hypotetraploid range is associated with poorer prognosis, atypia, and other measures of tumor progression.
Peter Duesberg et al. The results show that transforming normal cells into robust cancer requires a 2-fold increase in the expression of thousands of normal genes. The massive change in gene dose produces abnormal changes in the physiology and metabolism of cells and tissues.
Aneuploidy explains virtually all of the gross biochemical abnormalities of cancer cells including increased cellular size, the appearance of numerous membrane-bound tumor-associated antigens and the high levels of secreted proteins that are responsible for invasiveness as the natural consequence of aneuploidy.
The well known genetic instability of cancer cells is due to the perpetual regrouping of the genome following the disruption of nuclear symmetry by aneuploidy. Aneuploid cells are less robust than normal cells.
This result may be the basis for the age dependence of most cancers and the spontaneous remission of some.
Finally, the results show that mutated genes are neither necessary nor sufficient to produce the cancer phenotype in wild-type organisms. Table III compares the explanatory powers of the gene mutation and aneuploidy theories of cancer. Jones and Bartlett Publishers, ; Bishop, J.
The molecular genetics of cancer, Science. Cold Spring Harbor Lab. Press, ; Varmus, H.None of virgin queens observed in four observation hives ever attacked another virgin queen nor did any of 88 virgin queens introduced into queenright colonies ever attack the resident queen.
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