Development of a Conditional Replication Competent Adenovirus, Controlled by the Human Telomerase Promoter (hTERT) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study has been planned to generate a replication-competent adenovirus which replicates in a cancer cell-specific manner, thus minimizing the side effects and toxicity of cancer gene therapy. MATERIALS AND METHODS: we have generated an E1B 19 kD attenuated recombinant adenoviruses, Ad-TERT-delta19 and Ad-mTERT-delta19, which encode E1A gene driven by the wild type hTERT and modified m-hTERT promoter containing additional c-myc and Sp1 binding sites in the backbone of Ad-deltaE1B19. The in vitro efficacy and specificity of the hTERT and m-hTERT promoter have been evaluated by the comparison of viral replication and cytopathic effect in cancer cells and normal cell lines. To assess anti-tumor effect and safety of hTERT or m-hTERT promoter driven replication competent adenoviruses, tumor regression after subcutaneous injection in subcutaneous C33A xenografts and lacZ expression after systemic injection in organs were examined. RESULTS: The activation of hTERT or m-hTERT promoter was significantly up-regulated only in hTERT-positive cells, but not in hTERT-negative cells. Moreover, the activity of m-hTERT promoter was substantially increased in hTERT-positive cancer cells, but not in hTERT-negative cells. While Ad-TERT-delta19 replicated in and induced cytopathic effect in cancer and in some normal cell lines, Ad-mTERT-delta19 enhanced viral replication and cytopathic effect in cancer cells only. Furthermore, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intratumoral injection of Ad-mTERT-delta19. CONCLUSIONS: The use of m-hTERT promoter is not only useful in the regulation of therapeutic gene expression but also that replication-competent oncolytic adenovirus under the control of m-hTERT promoter may be a new promising tool for the treatment of human malignancies.

A Case of Extrapontine Myelinolysis with both Frontal Lobe Dysfunction and Decreased Perfusion in SPECT

A thirty-nine year old woman was consulted because of personality change, agitation and memory disturbance. She received chemotherapy and oral steroids because of carcinoma within the bronchus. She had a high serum osmolarity caused by hyperglycemia and hypernatremia, and it was corrected rapidly. Her brain MRI showed EPM (extrapontine myelinolysis). Brain SPECT showed hypoperfusion in the bilateral orbitofrontal regions. We report a patient with EPM with typical frontal lobe dysfunction as an initial manifestation and bilateral orbitofrontal hypoperfusion.

Analysis of Role of Peripheral Vestibular Receptors on Orthostatic Tolerance using Heart Rate Variability in Rats

BACKGROUND: There is substantial evidence that the vestibular system is involved in the regulation of blood pressure. Heart rate variability (HRV) is useful to investigate the role of the peripheral vestibular receptors and the baroreceptors in the orthostatic tolerance. METHODS: EKG was recorded during postural changes with the head up either after sinoaortic denervation or after bilateral labyrinthectomies in Sprague-Dawley rats. HRV, including mean, standard deviation, coefficient of variation (CV), and power spectrum, were analyzed from R-R intervals of EKG. RESULTS: Phenylephrine increased low frequency region and sodium nitroprusside increased high frequency region in the power spectral analysis of HRV in anesthetized rats. Postural changes decreased blood pressure transiently and then increased blood pressure gradually in control rats, but the depression of blood pressure induced by postural change was greater in rats with both sinoaortic denervation and bilateral labyrinthectomies. The increase of CV of HRV just after sinoaortic denervation or bilateral labyrinthectomies represents an unstable heart rate in resting position, however, CV of HRV was increased markedly by postural change 7 days after bilateral labyrinthectomies. Postural change with sinoaortic denervation increased low-frequency region representing sympathetic activity, whereas bilateral labyrinthectomies increased highfrequency region representing parasympathetic activity in power spectral analysis. CONCLUSIONS: These results suggest that both the peripheral vestibular receptors and the baroreceptors have subsidiary action in orthostatic tolerance and the peripheral vestibular receptors regulate blood pressure during postural change through the sympathetic nervous system.

A Case of Secondary Erythromelalgia with Regional Arterial Blood Pressure Change between Symptomatic and Asymptomatic Period

No abstract available.