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Biomedical subjects

E S Wallen

Publications and source records attributed to E S Wallen.

8 recordsLinked to original sources
PubMed1998

Effects of combined treatment of chemotherapeutics and hyperthermia on survival and the regulation of heat shock proteins in Dunning R3327 prostate carcinoma cells.

BACKGROUND: Hyperthermia can enhance the clinical response of chemotherapeutic agents in prostate cancer, but optimal sequencing of this combination therapy needs to be developed. Given the role of heat shock proteins (HSPs) in the development of resistance (thermotolerance) to subsequent hyperthermic stresses as well as to certain chemotherapeutics, the study of HSP regulation is important in the establishment of effective schedules in multimodal treatment strategies. METHODS: In this study we evaluated the effects of the chemotherapeutic agents cisplatin, 5-fluorouracil, and adriamycin in combination with hyperthermia. (43 degrees C, 1 h) on clonogenic survival and inducible HSP70 regulation in Dunning rat adenocarcinoma of the prostate. HSP70 was analyzed by Western blot and by measuring beta-galactosidase produced by cells stably transfected with a gene construct containing the E. coli beta-galactosidase gene driven by the Drosophila HSP70 promoter. RESULTS: Colony formation assays revealed a sensitizing effect of hyperthermia when simultaneously combined with each chemotherapeutic agent, resulting in a potentiated cytotoxicity compared to subsequenced treatments. Thermotolerant cells showed a significantly better survival when treated with adriamycin alone, but also when each chemotherapeutic agent was combined with hyperthermia. This enhanced survival was correlated with inducible HSP70 accumulation. The chemotherapeutics modified the HSP70 promoter activation induced by hyperthermia, suggesting changes in the development of cellular thermotolerance. CONCLUSIONS: Our data reveal synergistic cytotoxic effects of the synchronous application of chemotherapeutic agents and hyperthermia on this model of prostate cancer. Furthermore, they demonstrate that the induction of HSPs in thermotolerant cells, as measured by HSP70 induction, results in a modulation the chemotherapeutic-mediated cytotoxicity. Therefore, HSP70 is a useful marker of cellular resistance in multimodal approaches combining hyperthermia and chemotherapeutic agents in the treatment of locally advanced prostate carcinoma.

Animals↗
PubMed1997

Beta-galactosidase as a marker of HSP70 promoter induction in Dunning R3327 prostate carcinoma cells.

Hyperthermia is known to improve the response of tumors to radiation or chemotherapeutic treatment when combined in multimodal strategies. The cellular response to hyperthermia is associated with the synthesis of heat shock proteins (HSP). To study the stress response in prostate cancer we have developed a clone of Dunning R3327 rat prostate carcinoma cells stably transfected with a gene construct containing the E. coli beta-galactosidase gene driven by the Drosophila HSP70 promoter. The measurement of beta-galactosidase serves as a rapid and semiquantitative assay of HSP70 gene activation. The Dunning cell clone showed evidence of incorporation of the HSP70/beta-galactosidase construct within the genomic DNA by Southern blot analysis. When compared to mock-transfected control cells, the clone showed minimal baseline beta-galactosidase activity, which significantly increased following a hyperthermic stress. The time course of beta-galactosidase elevation following heat stress paralleled the time course of cellular HSP70 elevation by Western blot analysis. These stably transfected Dunning R3327 cells may provide a useful tool to study the effects of hyperthermia, radiation, and chemotherapeutic agents on the cellular stress response and in the establishment of HSP70 as a marker of cellular resistance in the multimodal treatment of prostate cancer.

Adenocarcinoma↗
PubMed1997

A computer program to aid in visual concept development in dentistry.

Beginning dental students normally receive their first exposure to the study of tooth forms (morphology) through a dental anatomy laboratory course in which they are required to reproduce tooth morphology, usually with wax. The fabrication of a tooth in wax requires proper visual recognition skills and fine eye-hand coordination. Many students struggle with one or both of these. A computer program, designed to teach recognition concepts, was delivered to three groups of beginning freshman dental students in conjunction with their dental anatomy laboratory course while a group of their classmates served as the controls. This study investigated (1) instructional design and interface improvement and (2) the best method to implement the computer program. Experimental and control groups all received normal daily critiques of their course project work. After completion of the computer program, all groups were tested with a recognition-based examination as well as with a practical examination, requiring the reproduction of a tooth in wax. All experimental groups scored better than the control group on both examinations. Results indicated that computer-based instruction may be a useful means to foster visual concept development. An expanded program, using better graphics, animation and movies is currently under development.

Anatomy↗
PubMed1997

Effect of heat stress on LPS-induced fever and tumor necrosis factor.

Exposure to heat stress leads to both short-term and long-term effects on morbidity. Male rats were exposed to a high ambient temperature of 40 degrees C, which resulted in biotelemetered core body temperature rising to approximately 42 degrees C. This treatment led to a marked enhancement in lipopolysaccharide (LPS)-induced fever at 24 h after exposure to heat stress. The increase in fever was accompanied by a significant suppression in the circulating concentration of tumor necrosis factor. Heat-shock protein-70 measured in liver was elevated by the heat exposure (but not further elevated by the injection of LPS). An enhanced fever to LPS and other inflammatory stimuli found in heat-stressed human subjects could explain the apparent increase in susceptibility to disease.

Animals↗
PubMed1994

Thermal stress induces epithelial permeability.

The mechanisms by which heat injury results in multiorgan system failure are unknown, but the presence of endotoxemia and intestinal hemorrhage suggests that changes in gut epithelial permeability may be crucial to this process. To determine whether alterations in epithelial permeability occur at physiologically relevant temperatures, heat-induced changes on epithelial barrier integrity were studied using a high-resistance clone of Madin-Darby canine kidney epithelial cells. Transepithelial electrical conductance increased when monolayers were heated above 38.3 degrees C. Early changes in conductance were completely reversible with cooling. Increased conductance was due to increased paracellular permeability because heat also induced increased mannitol permeability across the monolayers. A conditioning heat stress (42 degrees C for 90 min) altered heat-induced permeability. When cell monolayers were exposed to this conditioning stress 48 h before measurement of conductance with increasing temperatures, the conductance increase did not occur until they were heated to 39.4 degrees C compared with 38.8 degrees C in naive control cells. This conditioning treatment also conferred thermotolerance as measured by cell survival after a lethal 45.0 degrees C heat stress. There was no difference in the temperature at which conductance increased between preheated and control cells 96 h after a preconditioning heat stress. The conditioning heat stress resulted in accumulation of heat-shock protein (HSP) 70 in cells at 48 h, but HSP 70 returned to control levels at 96 h. These studies demonstrate that small temperature elevations increase epithelial permeability and that prior heat stress which induces HSP 70 shifts the threshold temperature required to disrupt the epithelium.

Adaptation, Physiological↗
PubMed1993

Heat stress regulates the human 70-kDa heat-shock gene through the 3'-untranslated region.

Cells respond to a variety of stresses by synthesizing a family of proteins termed heat-shock proteins (HSP). Recently, the 3'-untranslated regions (UTRs) of some mRNAs have been shown to be important in the posttranscriptional regulation of protein production. Therefore, we hypothesized that heat could regulate HSP70 production through the HSP70 3'-UTR, in addition to its known effects on transcription. To test this hypothesis, cells were transfected with either a plasmid containing sequences encoding the human HSP70 or beta-globin 3'-untranslated region placed downstream of a chloramphenicol acetyltransferase (CAT) reporter gene. In both plasmids, the CAT gene was driven by an SV40 promoter. Following heat stress, cells transfected with the CAT construct containing the HSP70 3'-UTR showed increased CAT activity relative to the beta-globin 3'-UTR construct. This effect paralleled increases in HSP70 mRNA and levels of the inducible HSP70 protein by Western blot. These studies identify a heat-induced mechanism of posttranscriptional control of HSP70 synthesis utilizing the HSP70 3'-UTR, which may be important in the cells ability to regulate the heat-shock response.

Base Sequence↗
PubMedDate not supplied

Oxidants differentially regulate the heat shock response.

Cells, animals, and humans respond to hyperthermia through the synthesis of a family of proteins termed heat shock proteins (HSPs). Because hyperthermic stress may also result in mitochondrial uncoupling and the generation of reactive oxygen species, we wondered whether oxidant stress was sufficient to increase cellular levels of HSP70. HSP70 was detected in cells heated or treated with menadione but not in those treated with hydrogen peroxide or xanthine/xanthine oxidase. We speculate that oxidant stress from menadione exposure is qualitatively different from exposure from hydrogen peroxide or xanthine/xanthine oxidase.

Animals↗