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Biomedical subjects

Daniel P Theele

Publications and source records attributed to Daniel P Theele.

3 recordsLinked to original sources

A potential synergistic anticancer effect of paclitaxel and amifostine on endometrial cancer.

Although paclitaxel is one of the most effective chemotherapeutic agents, its usefulness is still limited in advanced and recurrent endometrial cancer. Amifostine protection of normal tissues against the side effects of chemotherapeutic agents has been clinically proven in cancer patients; however, its application in endometrial cancer has not been fully evaluated. We have investigated the use of paclitaxel and amifostine in controlling the growth of poorly differentiated endometrial cancer cells, Hec50co, in vitro and in vivo. Our studies show that amifostine had direct anticancer effects on endometrial cancer cells in vitro by arresting the cell cycle at the G1 phase and inducing apoptosis. Amifostine also inhibited s.c. tumor growth in athymic mice. Paclitaxel IC50 value was reduced from 14 to 2 nmol/L with pretreatment of a single dose of 178 micromol/L of amifostine for 72 hours. Amifostine also synergized with paclitaxel in the arrest of the cell cycle at the G2-M phase and in the induction of apoptosis. This two-drug regimen inhibited s.c. tumor growth as well as improved mouse survival significantly more than paclitaxel alone. Amifostine also significantly improved paclitaxel-induced cytotoxic effects on peripheral blood profiles. Our studies show that amifostine has direct anticancer effects on endometrial cancer. Our data have also shown a potential anticancer synergy between amifostine and paclitaxel in vitro and in vivo, whereas amifostine maintained a protective role in peripheral blood profiles. The dual specificity of amifostine action should be further investigated.

Amifostine↗

Age-related differences in amplification of covalently closed circular DNA at early times after duck hepatitis B virus infection of ducks.

Inoculation of 3-day-old (3D) or 3-week-old (3W) ducklings with duck hepatitis B virus results in chronic or transient infection, respectively. We previously showed that rapid production of neutralizing antibody following inoculation of 3W ducklings prevents virus from spreading in the liver and leads to a transient infection (Y.-Y. Zhang and J. Summers, J. Virol. 78:1195-1201, 2004). In this study we further investigated early events of viral infection in both 3D and 3W ducks. We present evidence that a lower level of virus replication in the hepatocytes of 3W birds is an additional factor that probably favors transient infection. We suggest that lower virus replication is due to a less rapid covalently closed circular DNA amplification, leading to lower viremias and a slower spread of infection in the liver, and that the slower spread of infection in 3W ducks makes the infection more sensitive to interruption by the host immune responses.

Age Factors↗

Selecting an external light source for fetal biophysical testing.

OBJECTIVE: To select the most intense light source that penetrates tissues and is safe for fetal biophysical testing STUDY DESIGN: A 3-step series of experiments was undertaken using a digital light meter (Extech Light Probe Meter, Extech Instruments, Waltham, Massachusetts). First, the density of light through a light filter was compared between the sun and 4 commercially available light sources. Second, penetration of light through the abdominal subcutaneous tissue (3-4 cm thick) of 6 pigs was compared between these light sources. Last, the skin reaction to the preferred light source and the distance in penetrating the uterine cavity were assessed in 50 pregnant women. RESULTS: Light emitted from a halogen bulb was significantly more intense than from a photographic flash, krypton bulb or penlight. Maximal intensity was gained with the light source placed against the skin. The halogen bulb penetrated a pig's abdominal wall more than the photographic flash or krypton bulb. The thickness of a pig's abdominal wall is similar to the distance in pregnant humans near term from the skin to the uterine cavity. No thermal injury or discomfort to the skin was observed for exposures <10 seconds. CONCLUSION: The halogen bulb was safe, penetrated tissues most effectively and was the best light source for fetal biophysical testing.

Abdomen↗