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Biomedical subjects

D Li

Publications and source records attributed to D Li.

962 records · Page 54Linked to original sources

Dietary supplementation of selenomethionine reduces metastasis of melanoma cells in mice.

The present study investigated the effect of dietary supplementation of selenomethionine on pulmonary metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Mice were assigned to four groups of 15 each. They were fed a basal AIN93G diet and the basal diet supplemented with 2.5 ppm or 5 ppm selenium as selenomethionine or with 2.5 ppm selenium as selenite for two weeks before and after the intravenous injection of 0.5 x 10(5) tumor cells. At necropsy, the number and size of tumors that developed in the lungs were determined. The number of mice that had > or = 11 tumors was 13, 8, 8, and 6 (p < 0.02 compared with the control), and the median number of lung tumors was 64, 14, 12 (p < 0.05 compared with the control), and 8 (p < 0.01 compared with the control) in the control group and the groups with 2.5 ppm and 5 ppm selenium as selenomethionine and 2.5 ppm selenium as selenite. Dietary supplementation of selenomethionine decreased tumor cross-sectional area and tumor volume compared with the controls. At the same dietary level, selenite had a greater inhibitory effect on tumor size than selenomethionine. These results demonstrate that dietary supplementation of selenomethionine reduced experimental metastasis of melanoma cells in mice and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that selenomethionine is an active form of selenium that reduces experimental metastasis.

Animals↗

MEQ and V-IL8: cellular genes in disguise?

One of the hallmarks of oncogenic viruses is their ability to subvert the growth regulation and evade immune response of the host. There are a number of tricks devised by various virus families. Oncogenic herpesviruses often accomplish this by encoding homologs of cellular genes involved in these functions. These viral homologs sometimes are hyperactive forms of their cellular counterparts, which function to overtake the cellular pathways, other times serve as decoys to mask the cellular functions. Marek's disease virus (MDV) carries at least two genes in that category. We have previously described Meq protein (MEQ gene product), a transcriptional factor with homology to proto-oncogenes Jun and Fos in the bZIP domain. Meq dimerizes with Jun or Fos and the Meq/Jun heterodimer is able to transactivate promoters with AP-1 site. We show here that Meq and Jun colocalize in living cells, adding to the physiological significance of the dimer formation. In addition, we present data to show that Meq and Jun can functionally complement each other in cis and in trans, using transformation and transactivation assays. Finally we describe the discovery of an IL8 chemokine homolog, designated as v-IL8 (viral IL8) in the MDV genome and discuss its possible function in MDV infection.

Amino Acid Sequence↗

Molecular epidemiology of pancreatic cancer.

Pancreatic cancer is a leading cause of cancer-related death in this country. There are no early screening tests and no effective treatment options for this deadly disease. Prevention of pancreatic cancer is difficult because little is known about the etiology. Main risk factors for pancreatic cancer include cigarette smoking, dietary factors, and maybe occupational exposure to certain carcinogens. A few molecular epidemiologic studies of pancreatic cancer have been conducted so far. Although these studies have had a very limited sample size, they have provided some clues to the etiology. DNA adducts derived from exposure to polycyclic aromatic hydrocarbon and aromatic amines have been detected in pancreatic tissues in relation to the cancer risk. Oxidative DNA damage and lipid peroxidation-induced DNA adducts are also shown to be present in the pancreas. The level of aromatic DNA adducts has been correlated with the spectrum of K-ras mutation in the tumor. The mutation profiles of p53 and K-ras genes in pancreatic cancer resemble that in bladder cancer rather than that in lung cancer. The high proportion of G to A transition in pancreatic cancer suggests the involvement of nitrosamines or alkylating agents in pancreatic carcinogenesis. This notion was supported bythe observation that individuals with deficient repair of the DNA alkylation products seemed to have an increased risk for pancreatic cancer. K-ras mutation in pancreatic cancer has also been associated with alcohol consumption, organochlorines, and dietary habits. The associations between these environmental factors and K-ras mutations suggest that the mortality of pancreatic cancer can be decreased by changing of behavior and reducing exposure to environmental carcinogens.

Biomarkers, Tumor↗

Soft tissue anatomy of proximal femoral focal deficiency.

The soft tissue anatomy of Aitken types A, B, C, and D proximal femoral focal deficiency (PFFD) was examined by magnetic resonance imaging (MRI). A characteristic pattern of soft tissue abnormalities is described. All muscles were present, but most were smaller than their normal counterparts. The exception was the obturator externus muscle, which was elongated and remained muscular almost up to its insertion. In type A PFFD, it is straight; in types B, C, and D PFFD, it is L-shaped. The sartorius is hypertrophied.

Adolescent↗

MRI of coronary arteries: 2D breath-hold vs 3D respiratory-gated acquisition.

OBJECTIVE: Respiratory motion degrades MR images of the coronary arteries. The purpose of this study was to assess and compare two methods of reducing the effects of respiration in coronary artery MRI. Single-slice 2D imaging with breath-holding and a respiratory-gated 3D technique were used. MATERIALS AND METHODS: A comparison was made in 10 normal subjects between a 2D multiple breath-holding approach and a 3D technique with and without retrospective respiratory gating in imaging the coronary arteries. RESULTS: Respiratory gating improved the image quality in 76% of the 3D images. Both the 2D and the 3D approaches were capable of visualizing the proximal parts of the coronary arteries, with comparable vessel length and diameter. The image quality was somewhat better for images obtained by breath-holding in 83% of the vessels, probably due to less blurring by remnant respiratory motion and higher inflow contrast. CONCLUSION: The 2D breath-holding approach reveals a better image quality. However, the 3D respiratory-gated acquisition is less operator dependent, faster, and less strenuous for patients.

Adult↗

IL-2 gene therapy of advanced lung cancer patients.

We report here Phase I clinical-trial studies of retroviral-mediated interleukin-2 (IL-2) gene transfer to tumor-infiltrating lymphocytes that are re-infused to advanced lung cancer patients with pleural effusions. Ten lung cancer patients with malignant pleural effusions for whom all conventional therapy had failed were included in this Phase I protocol. Tumor infiltrating lymphocytes (TIL) from the patients were exposed to the retroviral plasmid pL(IL-2)SN containing the human IL-2 gene. Approximately 1-6 x 10(10) TIL cells transfected with IL-2 were re-infused into the chest cavity of each patient. The toxicity of this treatment with TIL/IL-2 gene therapy in these patients was minimal with transient slight fever of approximately 37.5. Pleural effusions did not re-accumulate for at least 4 weeks in six of ten patients. One patient was observed to have not only the resolution of the pleural effusions, but in addition the size of the original tumor decreased as seen by CT. The clinical results indicate this method of cancer gene therapy is safe and possibly efficacious against pleural effusions due to advanced lung cancer.

Adenocarcinoma↗

Retroviral insertional mutagenesis of a herpesvirus: a Marek's disease virus mutant attenuated for oncogenicity but not for immunosuppression or in vivo replication.

Our earlier studies have shown that retrovirus insertion into herpesvirus is an efficient process that engenders recombinant herpesviruses with altered biological properties. The RM1 clone is derived from the JM strain of Marek's disease virus (MDV) through retrovirus insertional mutagenesis and contains sequences of reticuloendotheliosis virus inserted at the junction of the internal repeat and unique short regions of the genome. In previous studies, the RM1 clone appeared attenuated for oncogenicity but caused marked atrophy of the thymic lobes. The present studies represent a detailed analysis of the biological characteristics of the RM1 clone in order to better understand mechanisms of oncogenicity and gene function of MDV. RM1 was almost fully attenuated for oncogenicity but retained other in vivo properties of virulent viruses such as thymic and bursal atrophy, early immunosuppression, early cytolytic infection followed by efficient replication, and contact spread--all normally absent in attenuated strains. This suggests that, for serotype 1 MDV, oncogenicity is not tightly linked with immunodepression or viral replication and that these properties may be controlled by different genes or mechanisms. The mutation was stable through serial passage of the virus in chickens as determined by molecular analysis. None of the mutant viruses demonstrated expansion of the 132-bp repeat region of the genome, indicating that such expansion is not required for attenuation. Chickens vaccinated with RM1 clones were protected against challenge with virulent MDV, and levels of protection exceeded those of other attenuated serotype 1 vaccine viruses. Thus, attenuation by selective mutation may be an advantageous strategy for development of serotype 1 Marek's disease vaccines.

Animals↗

Functional MR imaging of the porcine kidney: physiologic changes of prolonged pneumoperitoneum.

BACKGROUND: Increased intraabdominal pressure (IPA) during laparoscopy has been associated with decreased urine output. The purpose of this study was to use a noninvasive MRI technique to measure renal vessel flow velocity and change in differential renal medulla and cortex perfusion during pneumoperitoneum. STUDY DESIGN: Six female farm pigs underwent general endotracheal anesthesia and dynamic imaging following left ventricular (LV) injection of Gd-DTPA, utilizing a dual echo gradient echo sequence. MRI was repeated after three hours of continuous 15 mm Hg pneumoperitoneum in three study pigs and after three hours of monitored general anesthesia without pneumoperitoneum in three control pigs. Renal artery and renal vein flow velocities were calculated using cine phase-contrast technique. Renal perfusion was independently measured by LV injection of radiolabelled microspheres. RESULTS: There was a decrease in mean renal vein flow velocity in the pneumoperitoneum group as compared to the control group. During pneumoperitoneum there was a similar percentage reduction in the perfusion of the cortex (-28%) and medulla (-31%); this corresponded with a decreased urine output. In addition, radiolabelled microspheres corroborated the similar decrease in both cortical and medullary perfusion rates during pneumoperitoneum. CONCLUSIONS: Prolonged IAP is associated with a decrease in renal vein flow velocity and urine output. There is a similar decrease in the renal medulla and cortex perfusion rates during pneumoperitoneum of 15 mm Hg.

Animals↗