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Biomedical subjects

C R Jerusalem

Publications and source records attributed to C R Jerusalem.

34 records · Page 2Linked to original sources
PubMed1983

Growth pattern of tumor xenografts in Wistar rats after treatment with cyclophosphamide, total lymphoid irradiation and/or cyclosporin A.

Wistar rats treated with cyclophosphamide, total lymphoid irradiation (TLI), and/or cyclosporin A (CSA) develop a state of immune suppression permitting the growth of tumor xenografts. Experiments were carried out on this newly developed model to investigate the growth patterns of a mouse osteosarcoma and a human colon adenocarcinoma. The combination of cyclophosphamide and CSA permitted a limited period of growth of the mouse osteosarcoma with a tumor take rate of 66%. No takes were observed with the human adenocarcinoma. The combination of cyclophosphamide and TLI resulted in a period of immunosuppression followed by recovery of the immune status. During the period of immunosuppression, tumor xenografts showed a 100% take rate. The most efficient immunosuppression was achieved by a combination of cyclophosphamide, TLI and CSA administered on alternate days. Wistar rats subjected to this treatment showed prolonged tolerance to mouse osteosarcoma and human adenocarcinoma xenografts. There was no alteration in the tumor doubling time or histological morphology of the xenografts in the adapted host as compared with those in the donor tumors. The tumor growth curve showed a pattern of initial growth, a period of stagnation, followed by a steady but slower growth phase. The significance of the results and the advantages of the rat model described in this paper for human tumor xenotransplantation are discussed.

Adenocarcinoma↗
PubMed1982

Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation.

Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

Animals↗
PubMed1978

Hemodynamic parameters and blood gas analyses in the normal and the cirrhotic rat.

Thioacetamide-fed rats developed cirrhosis with portal hypertension (P portal=23.0 +/- 5.2 cm H2O, controls: 14.4 +/- 1.0 cm H2O). The PO2 of liver tissue was markedly reduced in cirrhosis (PO2=7.6 +/- 3.4 torr, controls 22.3 +/- 5.8 torr), and the aortal pH was significantly lower as well. No correlation was found between portal hypertension, development of large--nodular cirrhosis, and ascites.

Animals↗
PubMed1975

Studies on the oxygen supply of heterotopic auxiliary liver grafts in rats.

Heterotopic auxiliary liver transplantations were performed in rats using the method of Hess et. al. [6]. Oxygen pressure of liver tissue was measured with a Pt-surface electrode of Kessler and Lübbers [10]. After ligation of the hepatic artery, liver tissue PO2 decreased and remained low during further preparation. Only two of the seven lobes of the rat liver (= 30% of the parenchyma) were used as a graft. After revascularization and application of a gelatine plasma substitute, tissue PO2 of the graft increased to values of normal rat liver, although the graft was supplied with portal blood only. We suggest that one reason for this is the increase of portal perfusion rate, for the whole amount of portal blood perfuses only 30% of liver parenchyma. In the first month after transplantation PO2 of the graft parenchyma was low, but increased continually in the following months, reaching PO2 values of normal rat livers after 1 year.

Animals↗
PubMed1975

[Enzyme levels and morphological picture of normal and cirrhotic rat livers following portal vein ligation and subcutaneous transposition of the spleen].

The effect of portal vein ligation after subcutaneous transposition of the spleen is investigated on enzyme-activities. and morphological pattern of the normal and cirrhotic rat-liver. The increase of glycolytic enzyme-activities and the decrease of enzyme-activities of oxidative metabolic pathways can be explained by adaptation on throttled blood supply of the liver. Significant decrease of arginase-activity (urea-cycle) can not be explained by reduced protein content of food (pair-fed-animals). Diminished substrate (ammonia)-level (NH3/t/hepatocytes) may be an explanation. Histological pattern of normal and cirrhotic rat liver is nearly unchanged after portal vein ligation.

Animals↗
PubMedDate not supplied

Oxygen tensions in two human tumor cell lines grown and irradiated as multicellular spheroids.

Cells from two human cell lines were irradiated both as multicellular tumor spheroids (MTS) and in monolayer culture. Radiation response of MTS was quantified in terms of specific growth delay and proportion cured, and as clonogenic cell survival for monolayer cells. Radiation was applied either as a single or as a split dose with time intervals of 1, 2, and 4 h to determine the rate of sublethal damage repair. Using as endpoint the fraction of MTS cured at an iso-effect level, in MTS of NB-100 neuroblastoma cells repair of sublethal damage was complete within 1 h, whereas in MTS of HN-1 squamous cell carcinoma cells there was still some unrepaired damage left. At a larger dose for NB-100 MTS the repair curve showed a similar shape as for HN-1 spheroids. Using as endpoint specific growth delay, no difference in repair between the various time intervals was observed. In monolayer cells from both cell lines sublethal damage was not fully repaired in the time intervals used. Polarographic microelectrode measurements of oxygen tension inside MTS showed a marked difference in steepness of oxygen tension profiles between MTS from both cell lines. In HN-1 squamous cell carcinoma MTS with diameters up to 500 microns the central pO2 amounted to about 100 Torr, whereas in NB-100 neuroblastoma MTS with the same diameters central pO2-values lower than 30 Torr were observed. NB-100 MTS were irradiated with doses of 5 and 10 Gy gamma rays and subsequently the oxygen tension was measured 1 and 5 h after irradiation. A reoxygenation effect could not be observed, either after single dose or after split dose irradiation. If spheroids may be regarded as a suitable model for tumor responses in vivo, the results from these experiments indicate that reoxygenation is a process eluding polarographic measurements, or that no dramatic changes in oxygen tension are to be expected shortly after high single doses or early in a fractionation scheme.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Multicellular aggregates from human tumor cell lines for radiation studies.

Aggregates of human tumor cells are widely used in experimental studies on tumor responses to treatment. Only a limited number of human tumor cell lines are capable of forming spheroids. In this study cellular characteristics of 7 lung cancer and 4 bladder cancer cell lines are described with respect to their spheroid forming capacity. Comparisons were made with four reference lines known for their propensity to form growing aggregates. In the absence of vimentin expression no spherical aggregates were formed. Spherical aggregates were formed by one bladder and one lung cancer cell line, of which only the latter exhibited growth. Cellular factors influencing the ability of spheroids to increase in volume after spherical aggregation are not yet defined. Viability and clonogenicity of cells in aggregates are not the determinant of growth capacity. The growth rate of cell lines that exhibited growth is determined by tissue culture conditions and additives. Type of medium, percentage of foetal bovine serum and glucose concentration influenced the growth rate of spheroids. Since the response to radiation may be influenced by the growth rate of the tumors, manipulation of tissue culture medium composition offers the possibility of testing the influence of growth rate on the radiation response of one type of spheroids.

Carcinoma, Small Cell↗
PubMedDate not supplied

Development and applications of an animal model for human tumor xenografts.

Wistar rats treated with cyclophosphamide (4x 10 mg/kg), total lymphoid irradiation (9.0 Gy; dose rate 0.60 Gy/min) and cyclosporin A (15 mg/kg, daily, orally) developed a state of immune suppression permitting the growth of human tumor xenografts. Immunosuppression was monitored by lymphocyte counts, serum IgG determination. PHA and Con A lymphocyte-responses, proportion of B cells and histopathological studies of the lymphoid organs. The lymphocyte counts, IgG levels, PHA and Con A stimulation values remained severely depressed, during the period of cyclosporin A administration. Repopulation of the paracortical areas of the lymph nodes and the peri-arteriolar sheaths of the spleen did not occur, neither the reconstruction of the germinal centers in these organs. The thymus underwent severe atrophy. Seven of eight different types of human tumors were successfully xenografted in the immunomodified rat. The xenografted tumors maintained their original morphologic features and the mitotic rate did not change during subsequent transplantations.

Animals↗