Weikang Wang

Dynamics between cancer cell subpopulations reveals a model coordinating with both hierarchical and stochastic concepts.

Tumors are often heterogeneous in which tumor cells of different phenotypes have distinct properties. For scientific and clinical interests, it is of fundamental importance to understand their properties and the dynamic variations among different phenotypes, specifically under radio- and/or chemo-therapy. Currently there are two controversial models describing tumor heterogeneity, the cancer stem cell (CSC) model and the stochastic model. To clarify the controversy, we measured probabilities of different division types and transitions of cells via in situ immunofluorescence. Based on the experiment data, we constructed a model that combines the CSC with the stochastic concepts, showing the existence of both distinctive CSC subpopulations and the stochastic transitions from NSCCs to CSCs. The results showed that the dynamic variations between CSCs and non-stem cancer cells (NSCCs) can be simulated with the model. Further studies also showed that the model can be used to describe the dynamics of the two subpopulations after radiation treatment. More importantly, analysis demonstrated that the experimental detectable equilibrium CSC proportion can be achieved only when the stochastic transitions from NSCCs to CSCs occur, indicating that tumor heterogeneity may exist in a model coordinating with both the CSC and the stochastic concepts. The mathematic model based on experimental parameters may contribute to a better understanding of the tumor heterogeneity, and provide references on the dynamics of CSC subpopulation during radiotherapy.

Impact of cell dissociation on identification of breast cancer stem cells

BACKGROUND Fluorescence-activated cell sorting was commonly used for identification of cancer stem cells (CSCs), which relied on specific cell surface markers. And this approach makes it possible for us to study characteristics of CSCs in vitro. However, the pattern of membrane protein including surface makers might be vitally influenced during the dissociation of the adherent cells, thus it might heavily impact the quantity and quality of CSCs identified by flow cytometry. METHODS To address this question, in present study, three commonly used digestive reagents and two different temperatures were performed in MCF-7 cells to assay CD44(+)CD24(-) CSCs subpopulation. The potential of sorted CD44(+)CD24(-) cells from different digestion to form mammosphere in culture was also compared. RESULTS The results showed that trypsin, a commonly used reagent in CSCs studies, most aggressively reduced antigenicity for surface markers and make part of CD44(+)CD24(-) CSCs subpopulation cleaved into CD44(+)CD24(-) non-stem cancer cells (NSCCs). And it also increased the mammosphere formation efficiency of CD44(-)CD24(-) subpopulation. This cleavage effect is especially serious when cells are digested at 37°C. While accutase, a purified collagenase/neutral protease cocktail, provides the best balance of dissociation efficiency and antigen retention. CONCLUSION Taken together; these results indicate that enzymatic digestion process plays an important role in identification of CSCs with surface marker via flow cytometer, suggesting that researchers need to reconsider this process seriously.

Quantitative EEG effects of topiramate.

Objective: The study is to invesigate the effect of topiramate (TPM) on EEG by means of quantitative pharmacoelectroencephalography (QPEEG). Methods: One dose of TPM was administrated to epileptics and healthy adults. The EEG samples were obtained prior to and at regular intervals within the 24 hours following the administration of TPM. The EEG activity was processed with power spectral analysis. Results: The power of slow wave, alpha 1 bands and total power increased after the administration of TPM, the power or slow wave in both occipital areas, and the total power of all scalp areas also increased. The percent of power increased at the theta band and alpha 1 band (healthy adults) or delta band, theta band (patients). Conclusion: TPM can change the EEG background activity. These changes are different from other antiepileptic drugs.

Exploring the inhibitory effect of membrane tension on cell polarization

Cell polarization toward an attractant is influenced by both physical and chemical factors. Most existing mathematical models are based on reaction-diffusion systems and only focus on the chemical process occurring during cell polarization. However, membrane tension has been shown to act as a long-range inhibitor of cell polarization. Here, we present a cell polarization model incorporating the interplay between Rac GTPase, filamentous actin (F-actin), and cell membrane tension. We further test the predictions of this model by performing single cell measurements of the spontaneous polarization of cancer stem cells (CSCs) and non-stem cancer cells (NSCCs), as the former have lower cell membrane tension. Based on both our model and the experimental results, cell polarization is more sensitive to stimuli under low membrane tension, and high membrane tension improves the robustness and stability of cell polarization such that polarization persists under random perturbations. Furthermore, our simulations are the first to recapitulate the experimental results described by Houk et al., revealing that aspiration (elevation of tension) and release (reduction of tension) result in a decrease in and recovery of the activity of Rac-GTP, respectively, and that the relaxation of tension induces new polarity of the cell body when a cell with the pseudopod-neck-body morphology is severed.

Structure of the spontaneous all night sleep in epileptics with polysomnography.

Twenty epileptics and 11 healthy controls were investigated with polysomnography. Epileptics with interictal discharges had significantly longer total recording time and longer REM latency than the controls (P<0.05). Epileptics had a more fragmentized sleep than controls. Sleep efficiency of patients with interictal discharges was lower than that of patients without them (P<0.05). Among the patients with interictal discharges, those with partial seizures had a significantly higher arousal number than those with generalized seizures (P<0.05). The number of NREM stage shifts in patients with partial seizures tended to be higher than in those with generalized seizures.

Latency of P3 in semantic categorization of Chinese characters: preliminary report

ERPs to target stimulation with tone and semantic categorization of Chinese characters were studied in 100 healthy subjects. Age ranged from 40-50 years old (80 subjects) and 50-68 years old (20 subjects). Two hundred Chinese characters were divided into four groups in accordance with the meaning of characters. The probability of each group was 25%. Each group could be used as target stimulus. The latencies of the exogenous components on these two different tasks were the same. The endogenous components on the semantic categorization of Chinese characters were longer than with tone stimulation. In the 40-50 years age group the mean latencies of positive waves at Fz, Cz, C3, and Pz were 546.1034 msec, 547.8621 msec, 548.0345 msec and 547.3103 msec, respectively; latencies in the 50-68 years group were 542.9412 msec, 545.2941 msec, 543.8824 msec and 553.0588 msec respectively. A positive wave, which we called P550 and divided into P550a and P550b, could be recognized in 27.5% of them.

A computational model for low-dose radiation induced cellular transformation by different radiation quantity

In this study, a new mechanism model is constructed to fit the experimental data from different radiation quantities. The aim of the study was to construct a comprehensive model that contained all the essential biological mechanisms, such as direct irradiation effects or bystander effects, induced DNA damage, Double-Strand Break (DSB) error-free or error-prone repair and genomic instability, which can influence dose responses at low doses of ionising radiation. Results demonstrate that this new model is reasonably predictive of observed in in vitro experimental data obtained with alpha particles or X-rays, producing the correct shape of complex curves and satisfactory numerical agreement, respectively. On the other hand, the comparison of calculated repair rates with different quantities of irradiation suggests that X-ray induced DSB error-free repair rate is faster than alpha particles. In addition, both the highand low-LET irradiation induced dose-response curves could be fitted with the present model.