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Biomedical subjects

C W Song

Publications and source records attributed to C W Song.

At least 109 records · Page 6Linked to original sources
PubMed1990

Radiosensitization of murine tumors by Fluosol-DA 20%.

The effect of perfluorochemicals in combination with carbogen breathing on the response of SCK tumors of mice to fractionated irradiation was investigated. The SCK tumors of A/J mice were irradiated twice a day at 3 Gy per fraction (6 Gy per day), with a total dose of 18 Gy over 3 days. When the host animals were treated with an intravenous (iv) injection of 12 ml/kg of Fluosol-DA 20% before the first daily tumor irradiation and carbogen breathing during every X irradiation with Fluosol-DA 20% injection without carbogen breathing. The hypoxic cell fraction, as determined by an in vivo-in vitro cloning assay, decreased significantly, and the intratumor pO2, as determined with microelectrodes, was markedly increased by Fluosol-DA 20% injection and carbogen breathing. It was concluded that oxygenation of hypoxic cells in SCK tumors during the course of fractionated irradiation was improved by the iv injection of Fluosol-DA 20% and carbogen breathing.

Adenocarcinoma↗
PubMed1990

Effects of hydralazine on the blood flow in RIF-1 tumors and normal tissues of mice.

Hydralazine is a peripheral vasodilator used as an antihypertensive agent. Hydralazine has been reported to potentiate tumor damage by hyperthermia as well as by hypoxic-cell-specific drugs through the reduction of tumor blood flow and pO2. In the present study, we investigated the changes in blood perfusion caused by hydralazine in S.C. RIF-1 tumors and normal tissues in C3H mice using the 86Rb uptake technique and laser Doppler flowmetry. The tumor blood flow was decreased significantly by an intravenous administration of 0.5-10.0 mg/kg hydralazine, as determined by both uptake of 86Rb and laser Doppler flowmetry. The tumor pO2 was also decreased significantly by the injection of hydralazine. On the other hand, the uptake of 86Rb was increased significantly in the skin and muscle by hydralazine. The changes seen in the skin and muscle after injection of hydralazine as assessed by laser Doppler flowmetry were similar to those assessed by uptake of 86Rb, indicating a significant increase in blood circulation in these tissues. Uptake of 86Rb remained unchanged in the kidney and decreased in the liver and spleen in the presence of hydralazine in a dose-dependent manner at 0.5-10.0 mg/kg. The decline in uptake of 86Rb in normal tissues strongly suggests that hydralazine decreases the blood flow in these normal tissues. Thus the recent proposal to use hydralazine to increase the antitumor activity of heat or certain drugs needs to be reexamined.

Animals↗
PubMed1990

Effects of a second heating on blood flow in tumors.

The blood flow in RIF-1 tumors of C3H mice, as measured with the 86Rb uptake method, declined markedly after a single heating at 43.5 degrees C or 44.5 degrees C for 1 h. However, preheating at 42.5 degrees C for 1 h significantly lessened the decrease in tumor blood flow caused by subsequent heating at 43.5 degrees C or 44.5 degrees C for 1 h. Such an influence of preheating on the effect of reheating in decreasing the tumor blood flow was significant as early as 6 h after the preheating, peaked at 36 h, and then decayed the following 2-3 days. In fact, a reheating at 43.5 degrees C for 1 h applied 36 h after a preheating at 42.5 degrees C for 1 h resulted in an increase rather than a decrease in blood flow. The cause of such a profound impact of preheating on the effect of reheating on the blood flow is unclear. However, circumstantial evidence including the histopathological appearance of tumors suggests that thermotolerance is induced in the blood vessels of the tumor as a result of preheating.

Animals↗
PubMed1989

The influence of Fluosol-DA and carbogen breathing on the antitumor effects of cyclophosphamide in vivo.

The effects of Fluosol-DA, an oxygen-carrying perfluorochemical emulsion, and carbogen breathing alone or in combination on the antitumor activity of cyclophosphamide (CTX) in vivo were investigated. The addition of 12 ml/kg Fluosol-DA immediately prior to CTX treatment exerted no effect on the antitumor effect of CTX on the RIF-1 tumor in C3H mice. On the other hand, carbogen breathing alone for 8 h significantly enhanced the antitumor effect of CTX, with a dose-modification factor of 1.29 +/- 0.07. The combination of Fluosol-DA and carbogen breathing further increased the effect of CTX, with a dose-modification factor of 1.63 +/- 0.05. There was no significant difference in animal lethality within the treatment groups. It was concluded that Fluosol-DA in combination with carbogen breathing may be useful for the enhancement of CTX chemotherapy of human neoplasms.

Administration, Inhalation↗
PubMed1989

The kinetics of vascular thermotolerance in SCK tumors of A/J mice.

Development of thermotolerance has been observed in diverse biological systems. Despite the important role of blood circulation in heat-induced tissue damage, little is known about vascular thermotolerance. The kinetics of vascular thermotolerance in SCK tumors of A/J mice was investigated in this study. A single heating at 43.5 degrees C or 44.5 degrees C for 1 hr caused marked damage in tumor vasculature, as demonstrated by a marked decrease in Rb-86 uptake (% of injected dose/g of dried tissue). The tumor vasculature became resistant or tolerant to subsequent heatings at those temperatures when the tumors were preheated at 42.5 degrees C for 1 hr. Vascular thermotolerance became significant at 5 hr and reached its maximum at 18 hr after preheating at 42.5 degrees C. When the vascular thermotolerance was at its peak, heating at temperatures as high as 44.5 degrees C for 1 hr could not reduce the tumor blood flow. The vascular thermotolerance decayed considerably but not completely at 72 hr after the preheating. The vascular thermotolerance may exert a profound implication on the response of tissues, including tumors, to multiple heatings.

Adaptation, Physiological↗
PubMed1989

Radiobiological features of human pluripotent bone marrow progenitor cells (CFU-GEMM).

The purpose of this study was to evaluate the radiobiologic features of human pluripotent bone marrow progenitor cells (CFU-GEMM; colony forming unit-granulocyte-erythroid-macrophage/monocyte-megakaryocyte). Experiments were performed using fresh bone marrow cells as well as bone marrow cells stimulated with recombinant granulocyte-macrophage-colony stimulating factor (rGM-CSF) to increase the CFU-GEMM pool. The D0 values for CFU-GEMM in normal bone marrow samples (n = 9) ranged from 30.9 cGy to 85.7 cGy (mean +/- SE = 54.4 cGy +/- 6.2 cGy) and the D0 value of the composite radiation survival curve was 56.9 cGy, indicating that CFU-GEMM were acutely sensitive to the lethal effects of ionizing radiation. There was no distinct shoulder on the single dose radiation survival curves with Dq values ranging from -29.6 cGy to 4.4 cGy, and no increase in CFU-GEMM survival was observed when the radiation was fractionated. Hence, CFU-GEMM were unable to repair sublethal radiation damage. These findings confirm and extend previous studies on the radiobiologic features of human hematopoietic progenitor cell populations.

Cell Survival↗
PubMed1989

Effects of temperature on blood circulation measured with the laser Doppler method.

The effects of local heating or cooling on skin microcirculation in volar aspect of human forearms was studied using laser Doppler flowmetry. When the skin was heated to 40 degrees C from a normal temperature of 32 degrees C, red cell flow (laser Doppler flow, blood flow) momentarily increased several fold and then temporarily decreased. The flow subsequently resumed a gradual increase reaching 10-15 times that of control in 30-40 min. When the skin temperature was returned to 32 degrees C after 60 min of heating, the blood flow momentarily declined but soon increased for several minutes before it began its major descent. When cooled from 32 degrees C to 5 degrees C, the flow momentarily decreased, but soon increased, surpassing the pre-cooling level. The flow began to decline when the cooling was prolonged for more than 15-20 min. The changes in flow corresponded well with the changes in number (volume) and speed of red cells. Laser Doppler flowmetry was found to be very useful for continuously monitoring microcirculatory blood flow in human skin.

Adult↗
PubMed1989

Effects of recombinant growth factors on radiation survival of human bone marrow progenitor cells.

The purpose of this study was to evaluate the individual radioprotective effects of 4 distinct purified recombinant human hematopoietic growth factors, namely recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF), recombinant human granulocyte colony stimulating factor (rG-CSF), recombinant human interleukin 1 (rIL-1), and recombinant human interleukin 2 (rIL-2) on human myeloid (CFU-GM) and erythroid (BFU-E) bone marrow progenitor cells. We demonstrate that (a) preconditioning with rGM-CSF, rG-CSF, or rIL-1 enables CFU-GM to repair sublethal radiation damage and renders CFU-GM less radiosensitive, (b) preconditioning with rGM-CSF or rIL-1 enables BFU-E to repair sublethal radiation damage, and (c) preconditioning with rIL-2 does not increase the radiation survival of CFU-GM or BFU-E. The effects of recombinant growth factors, in particular rGM-CSF, on the radiation damage repair, radiosensitivity, and proliferative activity of bone marrow progenitor cells resulted in a substantial increase in the mean numbers of progenitor cell-derived hematopoietic colonies in irradiated marrow samples. The effects of rGM-CSF on the radiation response of CFU-GM and BFU-E, and the effects of rG-CSF as well as rIL-1 on the radiation response of CFU-GM did not appear to require the presence of T-cells/T-cell precursors, NK-cells, B-cells/B-cell precursors, monocytes, macrophages, MY8 antigen positive non-CFU-GM myeloblasts, promyelocytes, myelocytes, metamyelocytes, granulocytes, or glycophorin A positive erythroid cells since virtually identical results were obtained with unsorted marrow samples or highly purified fluorescence activated cell sorter (FACS) isolated progenitor cell suspensions. To our knowledge, this report represents the first study on recombinant human growth factor-induced modulation of the radiation responses of normal human bone marrow progenitor cells.

Cell Survival↗
PubMed1989

Leukemic B-cell precursors express functional receptors for human interleukin-3.

The purpose of this study was to analyze the expression of functional interleukin-3 (IL-3) receptors on leukemic B-cell precursors (BCPs) from 12 BCP acute lymphoblastic leukemia (ALL) patients and five BCP ALL cell lines. The specific binding of biosynthetically labeled 35S-recombinant (r) IL-3 to freshly obtained leukemic marrow blasts was initially investigated. In five of 12 BCP ALL cases, the binding of 35S-rIL-3 was markedly blocked by excess cold rIL-3, and the percentage of inhibitable binding ranged from 53% to 78% (mean +/- SE = 65% +/- 4%). In these cases, the cell-bound radioactivity ranged from 146 cpm/10(7) cells to 1,433 cpm/10(7) cells (mean +/- SE = 627 +/- 250 cpm/10(7) cells), indicating that 1 to 14 femtomole (mean +/- SE = 6 +/- 2 fms) of [35S]rIL-3/10(7) cells were specifically bound (= 60 to 840 molecules per cell). rIL-3 stimulated the proliferative activity of leukemic BCPs in a dose-dependent fashion without inducing differentiation, and the half-maximal stimulatory activity was observed at a concentration of 17 to 34 pmol/L. Fluorescence-activated cell sorter (FACS)-isolated virtually pure populations of CD10+CD19+ leukemic BCPs from two BCP ALL patients, as well as from two of five BCP ALL cell lines, showed a marked proliferative response to highly purified rIL-3, providing formal evidence that the observed IL-3 responses were not mediated by accessory cells. There was a high correlation between [35S]rIL-3 binding and proliferative response in colony assays, indicating that functional IL-3 receptors were detected in ligand binding assays. Scatchard plot analysis of the specific equilibrium binding data for IL-3-responsive leukemic BCPs from one BCP ALL patient and two BCP ALL cell lines yielded a straight linear regression line, indicating the existence of a single class of 60 to 210 high-affinity IL-3 binding sites/cell. The calculated apparent affinity constant (Ka) values ranged from 3.6 x 10(9) to 5.9 x 10(9) mol/L-1. Hence, the concentration of IL-3 required to produce 50% maximal receptor occupancy (Kd) was in the range of 168 to 280 pmol/L. These concentrations are approximately tenfold higher than those required to induce 50% maximal proliferative response from leukemic BCPs in colony assays, indicating that low receptor occupancy is sufficient for growth stimulation of leukemic BCPs by rIL-3. In comparison, less than 10 to 20 IL-3 molecules/cell were bound to IL-3 unresponsive leukemic BCPs even when the concentration of free-[35S]rIL-3 was as high as 2 nmol/L.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Clinical experience with thermotron RF-8 capacitive heating for bulky tumors: University of Minnesota experience.

We conducted a phase I clinical trial of the feasibility of using the Thermotron RF-8, a capacitative heating device utilizing 8-MHz RF, for the treatment of deep-seated and bulky human tumors. Preclinical studies with agar phantoms demonstrated that deep heating can be achieved with this device when the electrode diameters are sufficiently large relative to the thickness of the heated object. In the clinical application of capacitive heating with radiofrequency, excessive heating of subcutaneous tissue has often been a problem. However, this could be minimized by continuous cooling of the subcutaneous fat with a 10 degrees C saline bolus, beginning more than 20 minutes prior to the start of heating. It was often possible to raise the temperature of deep-seated tumors even in obese patients by applying this pre-cooling method. The mean achieved temperature during 30 to 40 minutes of heating was higher than 42 degrees C and 40 degrees C to 42 degrees C in 26% and 50% of 58 tumors treated, respectively. A combination of hyperthermia (four to ten sessions, twice a week) with full-course or a limited dose of radiotherapy resulted in complete tumor remission in 7% of patients, and partial tumor remission in 50% of patients. In the full-course radiotherapy group, 69% of the tumors were judged to show complete or partial regression, and in the low-dose group, 43% of the tumors regressed completely or partially. Histologic examination of many of the tumors that did not regress showed massive necrosis, indicating that tumor size after hyperthermia is not an accurate criterion of the treatment result. Side effects were minimal, and vital sign changes during heating were insignificant. Our data, together with those reported by Japanese investigators, clearly demonstrated that hyperthermia with the Thermotron RF-8 in combination with radiotherapy is useful in treating deep-seated and bulky tumors that fail to respond to conventional treatment modalities.

Adult↗
PubMed1988

Radiobiological features of fresh leukemic bone marrow progenitor cells in acute lymphoblastic leukemia.

The radiobiological features of leukemic progenitor cells (LPC) freshly obtained from 14 T-lineage acute lymphoblastic leukemia (ALL) and 11 B-lineage ALL patients were evaluated using LPC colony assays. No significant radiobiological differences were observed between T-lineage versus B-lineage ALL LPC. Notably, the D0 values displayed a significant interpatient variation in both groups, indicating a pronounced heterogeneity in the radiation sensitivity of LPC. LPC from some patients were very radioresistant, and in additional experiments using cryopreserved bone marrow blasts, up to 32% of LPC could survive 1600 cGy delivered at 100 cGy/min. In six of 11 T-lineage ALL cases and five of ten B-lineage ALL cases, a distinct initial shoulder was present on the single dose radiation survival curves, providing circumstantial evidence that LPC are able to repair sublethal radiation damage. A greater proportion of LPC survived 400 cGy when the dose was delivered in two fractions instead of a single dose, providing direct evidence that LPC in ALL possess a substantial capacity to repair sublethal radiation damage. The interpatient differences in Dq and recovery factor values indicated a marked heterogeneity in the ability of LPC to repair sublethal radiation damage. Analysis of the dose rate effects on the radiation survival of LPC in four ALL cases suggested that the radiation sensitivity of LPC is dose rate dependent. Normal bone marrow progenitor cells (colony-forming unit, granulocyte-macrophage, and burst-forming unit, erythroid) were more radiosensitive and unable to repair sublethal radiation damage. To our knowledge, this report represents (a) the first detailed comparative analysis of the radiobiological features of freshly obtained LPC in T-lineage and B-lineage ALL patients, and (b) the first elucidation of radiobiological differences between leukemic ALL versus normal bone marrow progenitor cells.

B-Lymphocytes↗
PubMed1988

Antigen-independent regulation of cytoplasmic calcium in B cells with a 12-kDa B-cell growth factor and anti-CD19.

Increases in cytoplasmic free calcium ([Ca2+]i) can be induced in resting B cells either by a low molecular weight (12-kDa) B-cell growth factor (LMW-BCGF) or by crosslinking the B-cell antigen CD19 with monoclonal antibody (mAb). LMW-BCGF causes a slow [Ca2+]i increase in peripheral blood and tonsillar B cells but has no effect on [Ca2+]i in resting T cells. B-cell [Ca2+]i responses mediated by anti-surface immunoglobulin (sIg) or anti-CD19 are potentiated by LMW-BCGF, but anti-sIg and anti-CD19 do not show additive [Ca2+]i responses. LMW-BCGF- and anti-CD19-induced [Ca2+]i signals are similar to the sIgM or sIgD-mediated signals in that they are inhibited by prior treatment with phorbol 12-myristate 13-acetate. However, LMW-BCGF- and CD19-mediated signals do not depend on the expression of sIg, since they were also observed on sIg-B-cell precursor acute lymphoblastic leukemia (ALL) cells. Both anti-CD19 and LMW-BCGF stimulated in vitro colony formation by ALL cells and showed additive effects when used together. [Ca2+]i responses to LMW-BCGF or CD19 cross-linking were also evident on certain pre-B-cell and lymphoma B-cell lines.

Antibodies, Monoclonal↗
PubMed1988

Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immunotoxins.

Extensive immunologic surface marker analyses and binding competition assays demonstrated that B43 monoclonal antibody (MoAb) is a new member of the CD19 cluster that recognizes the same surface epitope as several other anti-CD19 MoAbs. We used B43 MoAb to test for CD19 expression on neoplastic cells from 340 leukemia and 151 malignant lymphoma patients and on nonneoplastic cells in normal lymphohematopoietic and nonlymphohematopoietic tissues. Our study more than doubles the total number of cases with classified hematologic malignancies that have been examined for CD19 antigen expression. The data presented confirm that CD19 is the most reliable B lineage surface marker and support our view that this B lineage-restricted surface determinant may be an important functional receptor. Our findings provide unique and direct evidence that (a) CD19 is expressed on leukemic B lineage lymphoid progenitor cells freshly obtained from B lineage acute lymphoblastic leukemia patients but not on normal myeloid, erythroid, megakaryocytic, or multilineage bone marrow progenitor cells; (b) ligation of CD19 with B43 MoAb induces sustained increases in [Ca2+]i when crosslinked and inhibits high-molecular weight B cell growth factor (HMW-BCGF)-induced proliferation of activated B cells without affecting their low-molecular weight B cell growth factor (LMW-BCGF) response; therefore CD19 may be a unique signal receptor; (c) HMW-BCGF and LMW-BCGF augment expression of CD19, which suggests that CD19 and BCGF receptors may be under coordinate regulatory control; (d) approximately two million B43 MoAb molecules per cell can be bound to target B lineage lymphoma cells with a Ka of 1.9 x 10(8)/mol/L; (e) CD19 can undergo B43 MoAb-induced internalization; and (f) the opportunity is thus provided for using anti-CD19 MoAb to deliver toxins to B lineage neoplastic cells for more effective treatment of high-risk leukemia/lymphoma patients.

Antibodies, Monoclonal↗
PubMed1987

Difference in the thermotolerance of mouse mammary carcinoma cells in vivo and in vitro.

The kinetics of thermotolerance development were compared for cells in the SCK mammary carcinoma of A/J mice, and the same cells cultured in vitro. Tumors in the legs of mice or cells in culture flasks were conditioned with heat in a water bath at 43 degrees C for 30 min and the cells were left in the tumors or the culture flasks for various lengths of time after heat conditioning. The magnitude of thermotolerance was determined by preparing single cells and subjecting them to a test heating in a controlled environment in vitro at 43 degrees C, and the survival of the cells was determined by measuring the colony-forming ability in vitro. Thermotolerance in tumors reached its maximum 12 h after heat conditioning, at which time the survival response was characterized by Do (the duration of heating required for exponential cell inactivation to 1/e) of 116 min. This changed to a Do of 170 min when the cells in tumors were incubated in culture medium of neutral pH during the development of thermotolerance. In contrast, the thermotolerance of cells cultured in vitro was fully developed within 8 h, at which time the Do was 306 min. The kinetics of thermotolerance development, therefore, varied significantly between the cells of the same origin but grown in vivo or in vitro. Killing of tumor cells in vivo caused by the heat-conditioning dose was about three times greater than that for tumor cells in vitro, but the greater damage did not result in a greater development of thermotolerance. The above results indicate that the development of thermotolerance in tumors is suppressed by the influence of intratumor environment.

Animals↗
PubMed1987

Increase in pO2 and radiosensitivity of tumors by Fluosol-DA (20%) and carbogen.

The potential usefulness of i.v. injection of perfluorochemicals and breathing carbogen (95% O2 and 5% CO2) to improve the radiation-induced control of tumors was investigated. When C3H mice, bearing RIF-1 tumors in the legs, were given i.v. injections of Fluosol-DA (20%) at 12 ml/kg, and allowed to breathe carbogen for 1 h before and during a single dose of X-irradiation, the curability of tumors increased by a dose modification factor of 1.47 +/- 0.03 (SE). Such a treatment also increased the radiation-induced skin damage by a factor of 1.15 +/- 0.12, resulting in a therapeutic gain of 1.28 +/- 0.04. Measurement of intratumor pO2 by oxygen microelectrodes demonstrated small increases in pO2 when the animals breathed carbogen, and marked increases in pO2 when Fluosol-DA (20%) was injected into the animals and the animals breathed carbogen. It was concluded that i.v. injection of Fluosol-DA (20%) followed by carbogen breathing significantly improved the oxygen supply to hypoxic cells in the RIF-1 tumors and thus increased the control of tumors by radiation.

Animals↗
PubMed1987

Increase in tumor pO2 by perfluorochemicals and carbogen.

The effects of perfluorochemicals (Fluosol-DA) in combination with carbogen (95% O2 and 5% CO2) breathing on the tumor pO2 was investigated. The pO2 in RIF-1 tumors grown in the leg of C3H mice was determined by polarographic method using oxygen microelectrodes with diameters of 50-60 micron. The average and median pO2 in the control RIF-1 tumors was about 13 mm Hg and 6 mm Hg, respectively. Carbogen breathing alone could cause a significant increase in pO2 in some tumors and Fluosol-DA injection (i.v.) alone caused a slight change in tumor pO2. When the animals were treated with both Fluosol-DA injection and carbogen breathing, the pO2 markedly increased in most of the tumors resulting in an average and median tumor pO2 of 80 mm Hg and 60 mm Hg, respectively. Such an increase in tumor pO2 may account for the previous observations by us and others that the response of experimental tumors to radiation could be markedly increased by treating the tumor-bearing animals with carbogen and Fluosol-DA.

Animals↗