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Biomedical subjects

C W Song

Publications and source records attributed to C W Song.

At least 127 records · Page 7Linked to original sources
PubMed1987

Heterogeneity of cultured leukemic lymphoid progenitor cells from B cell precursor acute lymphoblastic leukemia (ALL) patients.

Colony assays were performed for 50 patients with B cell precursor acute lymphoblastic leukemia (ALL). Blast colony formation was observed for 33 patients, and the plating efficiency (PE) showed a marked interpatient variation, which indicates a pronounced biological heterogeneity at the level of leukemic progenitor cells. Notably, the mean PE of leukemic B cell precursors from patients with a pseudodiploid or near-diploid karyotype with structural chromosomal abnormalities (SCA) was significantly higher than the mean PE of normal diploid or hyperdiploid cases. All patients who had SCA involving 7p13, 11q23-24, or 12p11-13, and patients with a Philadelphia chromosome had high PE values. The S phase percentage, expression of CD19 antigen, and relapse status were also correlated with PE. Significantly, colony blasts had slightly different surface marker profiles in each case and were common ALL antigen negative in 33% of cases, which indicates the existence of a marked immunological heterogeneity at the level of leukemic progenitor cells.

Adolescent↗
PubMed1987

Effects of Fluosol DA 20% and carbogen on the radioresponse of SCK tumors and skin of A/J mice.

The effect of Fluosol DA 20%, an emulsion of perfluorochemicals, in combination with carbogen (95% O2 and 5% CO2) breathing on the response of mouse tumors to radiation was studied. When A/J mice bearing SCK tumors in the right hind limb were injected iv with Fluosol DA 20% at 12 ml/kg and exposed to carbogen for 1 h before and during the irradiation of tumors, the response of tumors to a single dose of X irradiation was significantly enhanced. The dose modification factors for growth delay and cure of SCK tumors were 2.10 +/- 0.01 (SE) and 1.86 +/- 0.18 (SE), respectively. Such a treatment slightly increased the radiation-induced skin damage by a factor of 1.17 +/- 0.02 (SE), resulting in a therapeutic gain of 1.79 +/- 0.01 (SE) for the growth delay and 1.59 +/- 0.09 (SE) for the curability. Carbogen breathing alone also increased the response of tumor and skin to radiation, but it was far less effective than the combination of Fluosol DA 20% and carbogen breathing. It was concluded that iv injection of Fluosol DA 20% in conjunction with carbogen breathing significantly increased the O2 transport to hypoxic areas in the SCK tumors and thus significantly enhanced the tumoricidal effect of radiation on SCK tumors.

Administration, Inhalation↗
PubMed1987

B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells.

The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS-sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL.

Acute Disease↗
PubMed1986

Effects of temperature on blood flow in facial tissues.

This study evaluated the effect of temperature on blood flow by using rubidium 86 to determine the fraction of cardiac output going to specific facial tissues of rats. Seventy-seven male Holtzman rats were divided into two groups and various subgroups. The intraoral subgroups were categorized according to the temperature of the water irrigating the oral cavity (11 degrees, 39 degrees, 41 degrees, 43 degrees, or 45 degrees C). The extraoral subgroups were categorized according to whether heat or ice was applied to the cheek of the rats and the duration of application (10 or 20 minutes). Rats were killed within 60 seconds after injection of 86Rb, and tissue samples were taken from the buccal mucosa, facial skin, masseter muscle, mandible, tongue, and maxilla. The fraction of isotope uptake in each gram of these tissues (FU/g) was then calculated. For the intraoral group, the bath temperature of 39 degrees C increased the FU/g in all tissues except masseter muscle and tongue. Higher bath temperature did not further alter the FU/g. Lowering the temperature to 11 degrees C changed the FU/g significantly only in the tongue. For the extraoral group, 20-minute application of ice was required to reduce FU/g significantly in all tissues but masseter muscle and skin. Extraoral heat application for 10 minutes increased FU/g significantly in skin and tongue, but no further change was seen after 20 minutes of application.

Animals↗
PubMed1986

Capacitive heating of phantom and human tumors with an 8 MHz radiofrequency applicator (Thermotron RF-8).

The thermal profile was investigated in agar phantoms and in human tumors heated capacitively with 8 MHz RF. Deep and homogeneous heating could be achieved in a large homogeneous phantom of 25 cm diameter and 24 cm thick when heated with a pair of 25 cm diameter electrodes, coupled to both bases of the phantom. When the size of the two electrodes was not the same, the region near the smaller electrode was preferentially heated. It was, therefore, possible to control the depth of heating by choosing properly sized electrodes. Therapeutic temperature (greater than 42 degrees C) could be obtained in 7 out of 9 small, as well as, bulky superficial human tumors as large as 8 X 8 X 10 cm. Indications are that heating of some deep-seated human tumors might be achieved by the capacitive method, provided that subcutaneous fat layer is cooled by temperature controlled bolus and large electrodes are used. The effect of the anatomical structure on the power deposition in the human body during capacitive heating should be further investigated.

Adenocarcinoma↗
PubMed1986

The clonogenic response of bovine aortic endothelial cells in culture to radiation.

The effect of ionizing radiation on the survival of bovine aortic endothelial (BAE) cells was determined by the in vitro colony formation method. The BAE cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% calf serum, antibiotics, and growth factors obtained from the culture of mouse S-180 cells. The cultured BAE cells were positive to the staining of antibodies against human factor VIII and formed clones in plastic culture flasks with a plating efficiency of about 11%. The survival curve of the BAE cells following an exposure to a single dose of X rays was characterized by D0 = 101 rad, Dq = 65 rad, and an extrapolation number (n) of 1.9. These parameters were not modified by the absence of growth factors at the time of irradiation. The response of BAE cells to radiation was dose-rate dependent. The split-dose studies demonstrated that the BAE cells were able to repair sublethal radiation damage within 1 h after irradiation.

Animals↗
PubMed1985

Change in fibrinogen turnover in tumors by hyperthermia.

The effect of hyperthermia on the turnover of fibrinogen and albumin in the SCK tumor of A/J mice was studied. Immediately after heating at 43.5 degrees C for 30 min, the content of 131I-labeled fibrinogen in the tumors was about 2.7-fold that in the control tumor and remained elevated for 24 hr. On the other hand, the content of 125I-labeled serum albumin in the tumor immediately after heating was only 1.7-fold that in the control tumor and started to decrease soon after heating. The greater increase in the accumulation and the longer retention of the labeled fibrinogen as compared with the labeled albumin in the heated tumors appeared to be related to the heat-induced vascular damage accompanied by vascular occlusion, fibrination and subsequent thrombus formation.

Animals↗
PubMed1985

Increased radiosensitivity of tumors by perfluorochemicals and carbogen.

The efficacy of an emulsion of perfluorochemicals (Fluosol-DA) to sensitize RIF-1 tumors of C3H mice to radiation was studied. An i.v. injection of 12 ml/kg of Fluosol-DA (20%) to tumor-bearing animals and keeping the animals in an atmosphere of a mixture of O2 (95%) and CO2 (5%) (carbogen) for 1 hr before and during irradiation of s.c. tumors in the thigh significantly enhanced the tumoricidal effect of radiation as measured with growth delay of the treated tumors. A lesser but significant enhancement of radiation damage in the tumors was also observed when the animals were kept in carbogen for 1 hr without injection of Fluosol-DA. It was concluded that Fluosol-DA increased the delivery of oxygen to hypoxic areas in the tumors and enhanced the response of hypoxic cells to radiation.

Animals↗
PubMed1985

Effect of fractionation and rate of radiation dose on human leukemic cells, HL-60.

The capacity of HL-60 cells, human acute promyelocytic leukemic cells established in culture, to repair sublethal radiation damage was estimated from the response of the cells to fractionated irradiation or to a single irradiation at different dose rates. The HL-60 cells grown as a suspension culture in RPMI 1640 medium supplemented with 10% calf serum and antibiotics showed a cloning efficiency of about 0.46 in an agar culture bed. After exposure of cells to a single dose of X rays at a dose rate of 78 rad/min, the survival curve was characterized by n = 2.5, Dq = 80 rad, and D0 = 83.2 rad. Split-dose studies demonstrated that the cells were able to repair a substantial portion of sublethal radiation damage in 2 hr. The response of the cells to irradiation at different dose rates decreased with a decrease in the dose rates, which could be attributed to repair of sublethal radiation damage. The radiation response of leukemic cells is only one of the many factors which affect the clinical outcome of total-body irradiation (TBI) followed by bone marrow transplantation. Nevertheless, the possibility that some of the malignant hemopoietic cells, if not all, may possess a substantial capacity to repair sublethal radiation damage should not be underestimated in planning total-body irradiation followed by bone marrow transplantation.

Cell Line↗
PubMed1985

A correlation between conditioning and engraftment in recipients of MHC-mismatched T cell-depleted murine bone marrow transplants.

We studied engraftment in a murine model of allogeneic bone marrow (BM) transplantation. Recipient C57BL/6 (H-2b) mice were conditioned with single-dose (9 or 7.5 Gy) total body irradiation (TBI), fractionated (4 X 3.3 Gy) TBI, hyperfractionated (8 X 1.65 Gy) TBI, 2 X 120 mg/kg cyclophosphamide (CY) followed by 7.5 Gy TBI, or 300 mg/kg CY followed by 9 Gy total lymphoid irradiation (TLI). Conditioned mice were transplanted with BALB/c (H-2d) BM supplemented with splenocytes (BMS) to facilitate graft-vs-host disease (GVHD). Ex vivo T cell depletion of the BMS with anti-Thy-1.2 antibody and complement protected recipients from lethal GVHD. Engraftment was measured in transplanted animals by serotyping peripheral blood mononuclear cells with anti-H-2-specific antibodies and complement. Mice that were given a T cell-depleted BMS transplant after conditioning with 9 Gy TBI, fractionated TBI, or CY plus TBI showed a 99 to 100% incidence of engraftment. However, if the T cell-depleted graft was given to mice conditioned with hyperfractionated TBI, 7.5 Gy TBI, or CY plus TLI, only 3 to 32% of the animals engrafted. BM which was not T cell-depleted engrafted in 63 to 100% of the mice regardless of the conditioning used. Nonengrafted mice tested with anti-host type antibody demonstrated autologous recovery. We conclude that engraftment or failure/rejection of BM in transplanted mice is determined in part by a dynamic equilibrium between T cells present in the donor graft and the surviving hemopoietic cells in the conditioned recipient. More intensive conditioning of the recipient allows engraftment of T cell-depleted, mismatched BMS. Such conditioning is not limited to a single modality, but can be achieved with single-dose TBI, fractionated TBI, or with TBI combined with CY. These findings have timely and important implications for the current understanding of engraftment in human allogeneic BM transplantation following T cell depletion.

Animals↗
PubMed1984

The role of luminal contents in radiation enteritis.

A guinea pig model was used to evaluate luminal content as a factor in the development of acute radiation enteritis. Surgical bypass of one half of the small bowel created an isolated segment free of luminal contents. Radiation effects on this empty intestine were compared with effects on bowel in continuity, on intestine containing bile only, and on intestine containing pancreatic enzymes plus food. The animals were subjected to a single dose of 1600 rad via an abdominal port and killed 4 days later. Surviving crypts per circumference provided one index of the severity of the injury. Intestinal damage was further evaluated by histologic grading. Surviving crypts were significantly fewer for irradiated segments of bowel containing any of the components of the intestinal stream compared to either nonirradiated controls or irradiated but empty bowel. Histologic scoring revealed a gradation of injury, with progressively more severe damage in empty irradiated bowel, and in intestine containing only pancreatic secretion, bile, and all components of the luminal stream. We conclude that both bile and pancreatic secretions in the lumen enhance acute radiation-induced small-bowel injury.

Animals↗
PubMed1984

Physiological mechanisms in hyperthermia: a review.

In experimental animal systems, hyperthermia at therapeutic temperature (43-45 degrees C) causes a profound increase in blood flow in normal tissues while it induces only meager and temporal increases in blood flow in tumors. A severe vascular occlusion and hemorrhage usually follows the increase in blood flow in the tumors at the above temperatures. Another pronounced physiological change in tumors by heat is a prompt decrease in intratumor pH. The decrease in intratumor pH would accentuate the thermokilling of tumor cells and also possibly inhibit repair of thermodamage and development of thermotolerance in tumors. The temperature in tumors may rise higher than that in normal tissues during heating because of inefficient heat dissipation from the tumor as a result of decrease blood flow or vascular occlusion. Thus, the differential effects of heat on vascular function and pH in tumors and normal tissues may result in a greater damage in tumors than in surrounding normal tissues. Further investigation is urgently needed to find out whether similar physiological changes occur in human tumors and normal tissues by hyperthermia.

Animals↗
PubMed1984

Changes in acidity of mouse tumor by hyperthermia.

The intratissue pH of SCK tumor and leg muscle of unanesthetized mice were determined before, during and after hyperthermia with the use of bulb type pH microelectrodes having pH-sensitive hemisphere 20-40 micron in outer radius. Intratumor pH was heterogeneous throughout tumor (range, 6.60-7.38; average, 6.96), and was more acidic than the intramuscle pH of mouse leg (average, 7.46). Hyperthermia at 43.5 degrees C for 30 min induced a further increase in acidity (decrease in pH of about 0.2 units) in tumor but not in muscle. The heat-induced acidity in tumor lasted for 12 hr following hyperthermia and then recovered to almost control pH value 24 hr after heating. The cause of the increase in acidity in the heated tumors is not clear, but it appears to result from an increase in the contents of acidic metabolites and a sluggish drainage of them due to induced vascular damage. The increased acidity in the heated tumors may inhibit the repair of thermal damage and sensitizes the tumor cells to subsequent heating.

Acid-Base Equilibrium↗
PubMed1984

Effect of local hyperthermia on blood flow and microenvironment: a review.

The blood flow in tumors varies considerably among different tumor types. Even in the same tumor, the distribution of vasculature and blood flow is quite heterogeneous. The tumor blood flow generally decreases as the tumors grow larger, owing partially to progressive deterioration of vascular beds and to the rapid growth of tumor cell population relative to vascular beds. Contrary to the general notion that blood flow is less in tumors than in normal tissues, blood flow in many tumors, particularly in small tumors, is actually greater than that in surrounding normal tissues at normothermic conditions. Compared to the normal tissue blood flow, however, the capacity of tumor blood flow to increase upon heating appears to be rather limited. Consequently, the heat dissipation by blood flow in tumors is slower than that in normal tissues, and thus the temperature of tumor rises higher than that in normal tissue during heating. Preferential heating of tumors, however, may not be achieved all the time because the relative blood perfusion in some tumors remains greater than that in the surrounding normal tissues despite the profound increase in normal tissue blood flow during heating. The vasculature in tumor can be significantly damaged at temperatures which may alter but do not damage the vasculature of normal tissue. Upon heating, the intratumor environment becomes acidic, hypoxic, and nutritionally deprived due probably to vascular damage. Such a suboptimal environment in the heated tumors potentiates the response of tumor cells to hyperthermia, inhibits the repair of thermal damage, and also interferes with the development of thermal tolerance. The acidic environment also appears to potentiate the response of tumor cells to certain drugs at elevated temperatures. The changes in oxygenation of tumors and normal tissues caused by the changes in blood flow may have significant implications in the effectiveness of different sequences of hyperthermia and radiotherapy in the combined use of these two modalities. Changes in the distribution of drugs in tumors and normal tissues due to changes in blood flow will also determine the optimal use of hyperthermia in conjunction with chemotherapy.

Animals↗
PubMed1983

Blood flow and intravascular volume of mammary adenocarcinoma 13726A and normal tissues of rat during and following hyperthermia.

The effects of hyperthermia on blood flow and intravascular volume were studied in mammary adenocarcinoma 13762A growing subcutaneously in the leg of Fischer F344 rats. The blood flow was determined using microspheres labelled with 125I, and the blood volume was determined using red blood cells labelled with 51Cr. At the end of heating with water bath at 43.5 degrees C for 1 hour, there was a marked elevation of 51Cr in tumor. The 125I content in tumor also was mildly elevated. Histologically there was a greater number of patent blood vessels per unit area, and they were dilated and hyperemic. In addition, widespread and diffuse hemorrhage could be seen. It appeared, therefore, that the increased 51Cr and 125I label in the tumors immediately after heating was, at least in part, a result of leakage of the labels to extravascular space in addition to possible vasodilation and increased blood flow. At 1 and 5 hours after heating, tumor blood flow was considerably reduced, and at 16 hours both tumor blood flow and blood volume were considerably reduced. Histological examination demonstrated that the tumor blood vessels remained dilated and hyperemic after heating. The effect of heat on blood flow and blood volume in the skin and muscle adjacent to the tumors was also investigated. Blood flow and blood volume in the surrounding normal tissues were significantly elevated at the end of heating. Blood flow was relatively unchanged at 1, 5, and 16 hours after heating, but blood volume was reduced to about one half. These findings indicate that hyperthermia may induce greater damage to vasculature of tumors than normal tissues, and that vascular damage in tumors may take some time to express itself following moderate hyperthermia.

Adenocarcinoma↗
PubMed1983

Skin radioprotection by 5-thio-D-glucose.

The radioprotective effect of 5-thio-D-glucose on mouse skin was studied. Intraperitoneal injection of A/J mice with 1.5 g/kg of 5-thio-D-glucose 2 hr prior to X irradiation of the foot reduced early foot skin damage through Day 40 postirradiation by a dose modification factor of 1.3 +/- 0.1. Similarly, late foot deformity during Days 60-90 postirradiation was reduced by a factor of 1.2 +/- 0.1. The radioprotective effect of 5-thio-D-glucose was also compared with that of WR-2721, an aminothiol radioprotector, in CDF1 mice. An intraperitoneal injection of 1.5 g/kg of 5-thio-D-glucose reduced early radiation-induced skin damage by a dose modification factor of 1.2 +/- 0.1 as compared to that of 1.5 +/- 0.2 by 0.65 g/kg of WR-2721 in this strain of mice. 5-Thio-D-glucose is also known to specifically kill and radiosensitize hypoxic tumor cells. Consequently, this drug may be a useful radiotherapy adjuvant, reducing normal tissue damage and enhancing tumor control by minimizing hypoxic protection.

Amifostine↗