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Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.

Animals↗

Application of thermal dilution measurements for thermal treatment planning.

The use of thermal dilution measurements is demonstrated in quantifying effective thermal conductivity distributions through tumours. For focused acoustic sources these data are applied in the solution of the heat diffusion equation to estimate steady-state temperature distributions. The advantages and disadvantages of this approach are presented. The effective conductivity measurements are found to be useful in predicting the circumstances under which this simple model can be applied and in aiding the selection of the most appropriate heating modality.

Animals↗

Retroperitoneal sarcomas obstructing delivery: two case reports.

Two patients with abnormal fetal lies underwent elective Caesarean section. Both abnormal lies were found to be due to retroperitoneal sarcomas overlying the bifurcation of the iliac vessels. One proved to be an inoperable and radioresistant fibrosarcoma. At seven and a half years after Caesarean section and following chemotherapy this patient is alive and well and has had two more children. The other tumour was a large myxoid liposarcoma which was completely removed at the time of Caesarean section. This patient is alive and well 18 months after operation.

Adult↗

Time-gated fluorescence imaging for the diagnosis of tumors in a murine model.

A system for time-gated fluorescence imaging was used to perform measurements on tumor-bearing mice treated with hematoporphyrin derivative (HpD). The aim of the study was to define the potential of this technique in the diagnosis of tumors by taking advantage of the long fluorescence lifetime of the exogenous dye with respect to the decay times of the natural fluorescence. After the administration of three different drug doses (5, 10 and 25 mg/kg body weight), fluorescence images were acquired at various uptake times (from 2 h to 10 d), to determine the best instrumental conditions and experimental procedure for the detection of tumors in the murine model considered. The optimal fluorescence contrast between the tumor area and the surrounding healthy tissue was found at 12 h after the administration of either 5 or 10 mg/kg HpD and was anticipated at 8 h for the highest drug dose. In this optimum condition, the tumor region could be identified even after the injection of 5 mg/kg HpD. A better fluorescence contrast was always obtained in 15 ns-delayed images with respect to synchronous ones.

Animals↗

Regression of a murine fibrosarcoma after intralesional injection of a synthetic C39 glycolipid related to cord factor.

Intratumoral injection of ultrasonically prepared emulsions of the synthetic glycolipid methly 6-O-(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha-D-glucopyranoside (designated C39) induced complete regression of transplants of a syngeneic murine fibrosarcoma in most of the treated animals as did 6,6'-di-O(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha,alpha,-trehalose (designated C76) in a previous study. The C76 compound, about twice the molecular weight of C39, was more effective therapeutically than the smaller molecule. Ultrasonically prepared emulsions of C39 and C76 were not toxic when given intravenously. Intravenously administered emulsions of C39 prepared by mechanical grinding were more toxic, but less granulomagenic, than those containing C76. Squalane and squalene, but not peanut oil, were effective substitutes for mineral oil as carriers of C39 in the treatment of the tumor.

Animals↗

Unstable expression and amplification of a transfected oncogene in confluent and subconfluent cells.

NIH 3T3 cells were transfected with a plasmid containing the transforming gene, v-src, from Rous sarcoma virus. One of the transformed cell lines isolated reverted to a flat, nontransformed morphology after cloning through soft agar. This cell line did not express the src gene and could no longer grow in soft agar. When these cells were held at confluence, spontaneous foci appeared which eventually covered the dish. The appearance of foci correlated with an increase in v-src gene expression, ability to grow in soft agar, and tumorigenicity in mice. When these transformed cells were trypsinized and held at subconfluence, both v-src expression and the transformed phenotype were progressively lost. Whereas rearrangement of the transfected gene was not detected, the gene copy number in the transformed cells was markedly increased (greater than 50-fold). Confluence-dependent gene amplification and deamplification have been retained after several cycles of growth alternately at high and low density, in cells recloned through soft agar, and after cells had been maintained continuously at high or low density. The results suggest that, in this cell line, reversible gene amplification plays a central role in expression of the transfected gene.

Animals↗

The role of cell surface proteins in the induction of histogenetic differentiative responses by some human breast tumours and hamster tumors implanted into chick embryos.

Cells of human breast tumours and fibrocystic hyperplasia grown in culture, and three hamster tumours were implanted between the cell layers of 18-hour-old chick blastoderm. Their ability to induce histogenetic responses in the ectodermal and endodermal embryonic tissues was investigated. The surface proteins of these tumour cells were labelled by lactoperoxidase-catalysed radioiodination. It is shown that the ability to induce the histogenetic effects may be related to the expression of 265K (K = 10(3) daltons) and 233K proteins on the surface of human tumour cells and of 115K proteins on the hamster tumour cells. The antiproteinase, aprotinin, inhibits the induction of the histogenetic responses by and apparently also prevents the deletion of 115K proteins from the hamster tumour cells. It is therefore suggested that cell surface proteins are involved in the complex processes of interaction between embryonic and tumour cells and in the recognition by the embryonic cells of the tumour cells implanted into their midst.

Animals↗

The increase of a normally occurring K cell population during progressive tumor growth in mice.

K cell activity of the spleen cells from normal and tumor-bearing mice was compared using an antibody-dependent cellular cytotoxicity assay. The K cell activity increased with progressive tumor growth (syngeneic) compared to the K cell activity of normal mice. The increase in K cell activity most likely reflected an increase in the numbers of K cells normally present in nontumor-bearing mice rather than the emergence of a distinct population of K cells induced by the growing tumor.

Animals↗

Immunohistochemical characterization of hemangiopericytomas and other spindle cell tumors in the dog.

The immunohistochemical expression of muscle actin has been studied in 45 canine hemangiopericytomas (CHP) using a monoclonal antibody (HHF35) and formalin-fixed, paraffin-embedded specimens. The distribution of vimentin, desmin, cytokeratins, lysozyme, factor VIII-related antigen, S-100 protein, and glial fibrillary acidic protein was studied both in CHP and in some canine soft-tissue neoplasms (seven fibrosarcomas, seven benign schwannomas, seven benign fibrous histiocytomas, and six leiomyosarcomas) used as controls for differential diagnosis. All CHP and control tumors expressed vimentin. Twenty-three CHP expressed muscle actin, whereas all control tumors analyzed were muscle actin-negative, with the exception of leiomyosarcomas. Among muscle actin- and vimentin-positive CHP, one case could be reclassified as leiomyosarcoma because it was desmin-positive, two cases expressed lysozyme, and nine cases expressed S-100 protein. Among muscle actin-negative and vimentin-positive CHP, seven expressed S-100 protein. In addition, S-100 protein was detected in five schwannomas. All CHP and control tumors analyzed were negative for cytokeratins, factor VIII-related antigen, and glial fibrillary acidic protein. Our results support the hypothesis of a pericytic origin of CHP, and suggest that muscle actin, desmin, vimentin, and lysozyme could be useful for the differential diagnosis of canine spindle cell tumors, but not all these neoplasms can be identified with these tumor tissue markers.

Actins↗

Response of selected tumour cell populations separated from a fibrosarcoma following irradiation in situ with fast neutrons.

We have characterized selected populations of fibrosarcoma cells separated on density gradients of Renografin with respect to distribution in the cell cycle, clonogenic ability, and response to radiation. The latter two parameters have been observed to be related to the density of the cells, the denser populations being less clonogenic but more resistant to both low and high LET radiation. We have determined that these cells effectively repair potentially lethal damage if allowed to remain in situ following exposure to low LET radiation. This repair ability is not observed, however, following neutron irradiation. In addition, cells left in situ are relatively more sensitive to low doses of either low or high LET radiation. This difference in response is believed to be due to differences in the expression of damage by cells left in situ as compared to those assayed immediately. These data reflect the usefulness of cell separation methods in the study of solid tumour systems. Specifically, these methods reduce the heterogeneity found in the solid tumour by allowing for the isolation of subpopulations which then can be studied either individually or in relation to the entire tumour.

Animals↗