Heterotransplantation of human adenocarcinomas of the colon and rectum to the mouse mutant Nude. A study of nine consecutive transplantations.
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Biomedical subjects
Publications and source records attributed to J Rygaard.
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Glycoprotein D (gD-1) is an essential virion envelope component of herpes simplex virus type 1 (HSV-1) normally transported to the plasma membrane of the infected cells. In the present study, the intracellular transport of gD-1 was inhibited in cultured HSV-1 infected human fibroblasts by Brefeldin A (BFA) 1 microgram/ml medium added for 12 h after virus adsorption. Immunofluorescence light- and confocal microscopy revealed abolished transport of gD-1 to the plasma membrane, juxtanuclear accumulation of gD-1, and a disorderly arrangement of the tubulin fibres. Withdrawal of BFA influence for more than 60 min resulted in incomplete transport but increasing accumulation of gD-1 in the plasma membrane and in Golgi-like areas close to the nuclei. The tubulin pattern was almost normalized 6 h after removal of BFA. The egress of infectious HSV-1 particles released 9 h post-BFA treatment was not fully reestablished. The results indicate that BFA effects were not completely reversible and caused a sort of cytotoxic influence involving the structure of tubulin.
Short-term therapy effects on heterotransplanted tumours are important to know in order to study the action of anticancer treatment. They are, however, difficult to assess due to interference from such factors as edema, vascular swelling and necrosis. Non-invasive methods such as NMR can be of some use, but the applicability is limited since background noise from the host animal organism may confound measurements. We studied a series of Cisplatine-treated bladder carcinomas heterotransplanted to nude mice and their untreated controls in order to illustrate short-term chemotherapy effect. We applied simple unbiased morphometric methods on formalin-fixed and paraffin-embedded material in order to obtain an unbiased estimate of the volume of the whole tumour and the volume of vital tumour tissue on day 1 and day 3 after treatment, at which time no gross changes in tumour size were evident. Furthermore, we estimated the number of tumour cells in the tumours. The estimate was based on measurement of the mean nuclear volume and the nuclear volume fraction in combination with the measured volume of vital tissue in the tumour. The pronounced therapy effects seen in this experimental system may be of potential interest in monitoring effects at the clinic.
In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic phosphate and phosphomonoesters and a decrease of phosphocreatine. Fast growing tumours and early stage of regrowth after treatment presented a higher phosphocreatine/beta NTP ratio. Following CDDP treatment, 31P metabolite ratios and pH were significantly altered compared with age-matched controls, as early as 6 hours after treatment. Although necrotic area was clearly visible in MRI, no treatment effect could be detected on the images of treated tumours.