As the brain is encased within the skull, the space available for a tumor to grow is severely limited before it reaches a size fatal to the patient. Thus, quantitation of the proliferative potentials of individual tumors is extremely important in predicting precise prognosis as well as in designing treatment modalities for individual patients with brain tumors. In the past rate of tumor growth has been estimated by the histopathology of individual tumors and is thus equivocally expressed. Even though the pathology of brain tumors is reasonably well defined, magnitudes of differences in survival or prognosis from such microscopic studies have been observed. The development of monoclonal antibodies (MAb) against bromodeoxyuridine (BUdR or BrdUrd), thymidine analogues, was a breakthrough for cell kinetic studies on human tumors in situ, as BUdR is not radioactive and can be rapidly detected in the labeled nuclei by immunocytochemical techniques. From our past four years of study, the BUdR labeling index (Ll) obtained from tumors that were exposed to a pulse of BUdR at the time of craniotomy have revealed that: 1) S phase fraction (or BUdR Ll) of individual brain tumors measured by BUdR labeling reflect proliferative activity or biological malignancy as a whole; 2) histologically similar tumors may have different proliferative potentials, demonstrated by differences in Lls; and, 3) a higher Ll indicates a higher rate as well as a shorter interval of tumor recurrence (especially in low grade astrocytomas, ependymomas and meningiomas). The current diagnostic BUdR study appears to predict more precisely the proliferative potential of each brain tumor than does histopathological diagnosis and may even correlate better with survival than histology. Thus, it has been yielding very beneficial prognostic information in individual patients with various brain tumors. This method, however, does not predict actual rate of tumor growth or other important cell kinetic parameters, such as duration of S phase, cell cycle time, potential doubling time, etc. Recently, another monoclonal antibody, which can identify only BUdR, was developed. This contrast to current anti-BUdR MAb, which is reactive to both BUdR and another thymidine analogue, iododeoxyuridine (lUdR or ldUrd). Therefore taking advantage of these two antibodies, double labeling studies using BUdR and lUdR are now feasible, and selecting appropriate timing and mode of BUdR and lUdR administration one can acquire far more information about proliferative characteristics of individual tumors from single biopsied materials within a few days after biopsy. The results earned can be taken into consideration in routine clinical practice. This new approach promises not only elucidation of cell kinetic characteristics of individual brain tumors, but will also benefit brain tumor patients in predicting more precise prognosis, appropriate time of follow-up, evaluation of tumor responses to any treatment modalities, as well as in designing treatments based on a more scientific rationale.
The specific aims are: 1) to estimate various cell kinetic parameters of brain tumors in situ; 2) to correlate the parameters obtained with the pathological diagnosis, growth of individual tumors, the patient's survival and response to treatment protocols; and, 4) to determine which of these parameters are most reliable in predicting prognosis and developing tailored treatment protocols.
Showing the most recent 10 out of 27 publications
