Proliferation kinetics of NK/Ly tumor cells after single and fractionated irradiation with fast electrons]

With single irradiation, the inhibition of tumor cell division and DNA synthesis was more pronounced than with fractionation irradiation. In fractionated schedules, the dose increase per fraction, and the interval prolongation between fractions, with decrease of the number of fractions (within the same time of irradiation), enhanced the effect of radiation. Yield of pahologic mitoses and extent of morphologic injury of cells was less expressed with fractionated irradiation and did not depend on the schedule of fractionation of the total dose.     

Proliferative capability of nuclested rat bone marrow cells following freeze--thawing]

A study was made of the proliferative capacity of myelokariocytes of the rat bone marrow after freezing and thawing under protection of the oxyetyl derivative of the tetratomic alcohol; experiments were conducted on mouse-rat radiation chimerae. The rat bone marrow cells proved to retain their proliferative capacity.     

Increased monoamine oxidase activity following repeated electroshock seizures

W e H ave recently reported that chronic electroconvulsive seizures (ECS) lead to a long-lasting increase (up to 6 weeks) in the activity of monoamine oxidase (MAO) in the brain of rats (P ryor and O tis , 1970). Other investigators have shown increased levels of norepinephrine (NE) and 5-HT, more rapid clearance of intracisternally-injected [³H]HNE (K ety , J avoy , T hierry , J ulou and G lowinski , 1967), and increased tyrosine hydroxylase activity (M usacchio , J ulou , K ety and G lowinski , 1969) at 24 h after a series of two ECS daily for 7 days. Together, these data suggest a sustained activation of the 5-HT and/or NE systems following chronic ECS. We now report the results of a series of experiments in which some of the potential variables that may be involved in the MAO response were investigated and that indicate some biochemical specificity of the response. In these experiments, succinate dehydrogenase (SDH) activity was also assayed to assess possible nonspecific effects of repeated seizures on mitochondrial metabolism and catechol O -methyltransferase (COMT) activity was determined to see if this extracellular degradative enzyme for NE was affected in the same way as MAO located intracellularly in the mitochondria.     

Conditioned reflex activity and several vegetative reactions in dogs during the recovery period following repeated reanimation]

Conditioned activity and vegetative reactions were studied in dogs which repeatedly underwent clinical death from electrical trauma and were reanimated by donor artificial blood circulation. (The first clinical death was provoked 15 to 18 months prior to the repeated death and was caused by drowning and blood loss). On the first few days after reanimation the functions of the higher parts of the CNS and the vegetative nervous system were considerably disturbed. This was manifested in diminished effector reactions to conditioned stimuli, in narcotic and ultraparadoxal phases in conditioned activity, in tachycardia and a higher respiratory rate. The disturbances gradually diminished and by the 5th to 13th day following reanimation completely disappeared. The nature and depth of the disturbances correlated with the basic properties of the animals' type of higher nervous activity. The conditioned reactions were restored despite the retained pronounced dystrophic and destructive changes in the cerebral cortex. This is significant proof of important compensatory capacity for conditioned activity in dogs.     

Progressive polyploidy in mouse liver following repeated hepatectomy]

Mouse liver regeneration after partial hepatectomy results in sharp changes of ploidy classes towards the increase of high ploidy cells and the decrease low ploidy ones. These changes retain during three months. Each following partial hepatectomy (till 3 times) intensifies the hepatocyte polyploidy with appearance of cells with 32--64 ploidy nuclei. The cell polyploidization stimulated by repeated regenerations is similar to that observed in normal postnatal liver growth.     

Proliferative activity of pigmented nevus cells and malignant melanoma of human skin]

The findings in the study of special features of proliferative activity in 58 pigmented neoplasms of skin have revealed a pronounced heterogeneity of tumor cell populations, malignant melanomas based on the values of the mitotic index (MI) and label index (LI). It is shown that while evaluating tumor anaplasia, these parameters provide more information as compared to the morphological characteristics.     

Noise amplification in human tumor suppression following gamma irradiation

The influence of noise on oscillatory motion is a subject of permanent interest, both for fundamental and practical reasons. Cells respond properly to external stimuli by using noisy systems. We have clarified the effect of intrinsic noise on the dynamics in the human cancer cells following gamma irradiation. It is shown that the large amplification and increasing mutual information with delay are due to coherence resonance. Furthermore, frequency domain analysis is used to study the mechanisms.     

A mathematical model of tumor growth and its response to single irradiation

Background

Mathematical modeling of biological processes is widely used to enhance quantitative understanding of bio-medical phenomena. This quantitative knowledge can be applied in both clinical and experimental settings. Recently, many investigators began studying mathematical models of tumor response to radiation therapy. We developed a simple mathematical model to simulate the growth of tumor volume and its response to a single fraction of high dose irradiation. The modelling study may provide clinicians important insights on radiation therapy strategies through identification of biological factors significantly influencing the treatment effectiveness.

Methods

We made several key assumptions of the model. Tumor volume is composed of proliferating (or dividing) cancer cells and non-dividing (or dead) cells. Tumor growth rate (or tumor volume doubling time) is proportional to the ratio of the volumes of tumor vasculature and the tumor. The vascular volume grows slower than the tumor by introducing the vascular growth retardation factor, θ. Upon irradiation, the proliferating cells gradually die over a fixed time period after irradiation. Dead cells are cleared away with cell clearance time. The model was applied to simulate pre-treatment growth and post-treatment radiation response of rat rhabdomyosarcoma tumors and metastatic brain tumors of five patients who were treated with Gamma Knife stereotactic radiosurgery (GKSRS).

Results

By selecting appropriate model parameters, we showed the temporal variation of the tumors for both the rat experiment and the clinical GKSRS cases could be easily replicated by the simple model. Additionally, the application of our model to the GKSRS cases showed that the α-value, which is an indicator of radiation sensitivity in the LQ model, and the value of θ could be predictors of the post-treatment volume change.

Conclusions

The proposed model was successful in representing both the animal experimental data and the clinically observed tumor volume changes. We showed that the model can be used to find the potential biological parameters, which may be able to predict the treatment outcome. However, there is a large statistical uncertainty of the result due to the small sample size. Therefore, a future clinical study with a larger number of patients is needed to confirm the finding.

     

Proliferative processes in the epithelium of mouse skin allotransplants following cortisone administration]

Proliferative processes were studied in the epithelium of skin grafts from mice of strain CC57 Brown and that of the skin surrounding the grafts in mice of CBA strain. The chart (Fig 1) illustrates cortisone action on normalization of DNA synthesis in the epithelial cells of the allotransplant. Throughout the experiment in operated animals which received no cortisone (Fig. 2, a and 3, a) a high proliferative activity was observed in the recipient's skin epithelium while it was sharply decreased in the epithelium of the allograft. Repeated cortisone injections gave a reverse picture: inhibition of proliferative processes in the recipient's epithelium and their intensification in the epithelium of the allotransplant.