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Biomedical subjects

Wei R Chen

Publications and source records attributed to Wei R Chen.

8 recordsLinked to original sources

Synergistic effect of sequential administration of mitoguazone (MGBG) and gemcitabine in treating tissue cultured human breast cancer cells and mammary rat tumors.

Modulation of cancer chemotherapeutic drugs has been attempted to increase efficacy and overcome resistance to the chemotherapeutic agent. Studies have shown schedule-dependent interactions in combined use of chemotherapeutic drugs. Mitoguazone (MGBG), an old drug with possible modulating activity, was used in combination with gemcitabine, a relatively new cancer drug, in treating tissue cultured human breast cancer cells and mammary rat tumors. Tissue cultured BOT-2 cancer cells were first treated with varying concentrations of gemcitabine and MGBG, independently. Combinations of the two drugs were then used with different scheduled administrations. Marked synergistic activity was found between gemcitabine and MGBG when the MGBG was given first, followed by gemcitabine 24 hours later. A non-toxic dose of MGBG enhanced the toxicity of gemcitabine by eight orders of magnitude using MTT assays in the tissue cultured human breast cancer cell study. The sequential administration of MGBG and gemcitabine also increased the survival rate of rats bearing mammary tumors in our pilot animal study.

Animals↗

Effect of different components of laser immunotherapy in treatment of metastatic tumors in rats.

Induction of a long-term tumor-specific immunity is the ultimate cure of metastatic cancers. Laser immunotherapy is a novel approach that aims at the tumor-directed stimulation of the immune system of the host. It involves an intratumor administration of a laser-absorbing dye and an immunoadjuvant, followed by noninvasive laser irradiation. Previous studies using glycated chitosan (GC) as immunoadjuvant and indocyanine green (ICG) as laser-absorbing dye have shown positive effects of the treatment on metastatic breast tumors in rats. In vivo experiments showed promising results such as: (a) eradication of treated primary tumors; (b) regression of untreated metastases; (c) induced antitumor immune response; and (d) long-term resistance to tumor rechallenge. In this study, rats bearing metastatic breast tumors and metastatic prostate tumors were treated with various combinations of the three components of laser immunotherapy. The rat survival rates and profiles of primary and metastatic tumors, after treatment by individual components and various combinations of the components, were analyzed. In the treatment of breast tumors, all of the experimental groups without immunoadjuvant showed little or no positive effect. The use of GC, either by itself or in combination with other components, had a noticeable impact on the survival rate of tumor-bearing rats. However, it was the combination of all of the three components that resulted in the highest cure rate. Three different concentrations of GC, 0.5, 1, and 2%, were also used to treat the metastatic breast tumors. The results showed that 1% GC was most effective in laser immunotherapy. In the treatment of metastatic prostate tumors, both the laser-ICG and laser-ICG-GC treatments significantly reduced the growth of primary tumors and lung metastases. Long-term survival of the rats bearing the prostate tumors was also observed after the laser immunotherapy treatment in our preliminary studies. These results revealed the important function of the immunoadjuvant in laser immunotherapy.

Adjuvants, Immunologic↗

Characterization of a CCD-based digital x-ray imaging system for small-animal studies: properties of spatial resolution.

A digital x-ray imaging system was designed for small-animal studies. This system is a fiber-optics taper-coupled imaging system with two CCD arrays uniquely jointed. The x-ray source of the system has a small focal spot of 20 microm. This digital imaging system contains specially designed shelves to provide magnification levels, ranging from 1.5x to 5x. The system is characterized in terms of its properties of spatial resolution. An observer-based spatial resolution measurement was conducted with a line-pair target and a sector test pattern. The modulation transfer function of the system, with different magnifications, was studied by use of a 10-microm lead slit. The average resolutions at 50% and 5% modulations at 1x magnification were measured as 3.9 and 8.4 lp/mm, respectively, where lp indicates line pairs. With 5x magnification, the 50% and the 5% modulations provided 13.2- and 29.9-lp/mm, respectively, average spatial resolutions. The measurements showed consistency between the two individual CCD arrays; the difference in resolution between the two CCDs is less than 1%, even at high magnifications.

Animals↗

Dynamic gating of spike propagation in the mitral cell lateral dendrites.

A unique feature of the olfactory bulb circuit is the long projection of the mitral cell lateral dendrites. Through dendrodendritic reciprocal synapses, these dendrites connect one olfactory glomerular module to hundreds of others; but the functional principles governing these extensive lateral interactions remain largely unknown. Here we report that the spatial extent of action potential propagation in these dendrites is dynamically regulated by inhibitory synapses distributed along the dendrites. The extent of propagation determines the spatial pattern of Ca(2+) influx and thus the range and number of dendrodendritic synapses to be activated. Accordingly, network control of spike traffic in the mitral cell lateral dendrites can mediate dynamic interaction with different combinations of glomerular modules in response to different odorants.

Action Potentials↗

Techniques to improve the accuracy and to reduce the variance in noise power spectrum measurement.

Several techniques to increase the accuracy and to reduce the variance of the noise power spectrum (NPS) measurement for digital X-ray imaging systems are investigated. These techniques include: 1) averaging the outputs from subblocks of the entire image; 2) averaging the two-dimensional NPS data along a circular route centered on the origin of spectral domain; and 3) masking a window function on each subblock before Fourier transforms. Techniques 1) and 2) are used mainly to reduce the variance of the NPS measurement. Technique 3) serves to improve the accuracy of the final result. Experiments with two different charge-coupled device-based X-ray imaging systems demonstrated that the precision and accuracy of the NPS measurement could be significantly improved using these techniques. The impact of the image partition for averaging is discussed and the corresponding NPS estimations are presented for the number of subblocks ranging from 4 to 64. The effect of masking on the NPS is also studied using four different window functions.

Models, Statistical↗

Comparison of analog and digital Fourier transforms in medical image analysis.

The effectiveness and limitations of medical image processing using analog and digital methods are studied. Several types of errors introduced during the image processing are analyzed. For the analog optical Fourier transform, errors are introduced by the vignetting effect and lens aberration. For the digital Fourier transform, errors are introduced by the aliasing effect and the band limit. To compare the results obtained by the two techniques, a set of x-ray images was processed both optically and digitally. The former was achieved by an optical system containing a large Fourier telephoto lens and the latter by a personal computer using a Fourier transform algorithm. The veracity of both the optical and digital Fourier spectra is analyzed. Our results indicate that the optical method has high speed due to parallel processing. High veracity can be achieved in high frequency regions by using an optimal optical system. In comparison, the digital method has the advantages of high processing precision and programmability, but has low processing speed. The comparison of the two different techniques presented in this article can provide a basis for selection of the processing method in different clinical settings. Even with today's fast computers, the optical method is still suitable for many clinical applications. The best choice lies in an analog-digital combination.

Algorithms↗

Multiple modes of action potential initiation and propagation in mitral cell primary dendrite.

The mitral cell primary dendrite plays an important role in transmitting distal olfactory nerve input from olfactory glomerulus to the soma-axon initial segment. To understand how dendritic active properties are involved in this transmission, we have combined dual soma and dendritic patch recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated in the distal primary dendrite but failed to propagate to the soma. As the inhibition became weaker, a "double-spike" was often observed at the dendritic recording site, corresponding to a single action potential at the soma. Simulation demonstrated that, in the course of forward propagation of the first dendritic spike, the action potential suddenly jumps from the middle of the dendrite to the axonal spike-initiation site, leaving the proximal part of primary dendrite unexcited by this initial dendritic spike. As Na(+) conductances in the proximal dendrite are not activated, they become available to support the back-propagation of the evoked somatic action potential to produce the second dendritic spike. In summary, the balance of spatially distributed excitatory and inhibitory inputs can dynamically switch the mitral cell firing among four different modes: axo-somatic initiation with back-propagation, dendritic initiation either with no forward propagation, forward propagation alone, or forward propagation followed by back-propagation.

Action Potentials↗