• Radiation Oncology Journal
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• v.16 no.2
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• pp.107-114
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• 1998

Purpose : Ginkgo biloba extract(GBE) is known to increase the peripheral blood circulation. This study was designed to evaluate the effect of GBE on the acute normal tissue radiation reaction. Materials and Methods : mice were divided into two groups, radiation alone and two doses GBE plus radiation, for both acute skin reaction and jejunal crypt assay. GBE was given i.p. one hour before irradiation with priming dose given one day earlier. Thirty to Fifty Gy for acute skin reaction and 11 to 14 Gy for jejunal crypt were irradiated to right hind leg and whole body, respectively. Results : Radiation doses($RD_{50}$) for Peak skin score of 2.0 were 44.2Gy (40.6-48.2Gy) for radiation alone and 44.4Gy(41.6-47.4Gy) for two doses GBE plus radiation, showing no effect of GBE on acute radiation skin damage. The numbers of regenerating jejunal crypts per circumference were also almost the same for each radiation dose level(p=0.57-0.94), and the mean lethal doses($D_o$) were 1.800y(1.57-2.09Gy) for radiation alone and 1.88Gy(1.65-2.18Gy) for two doses GBE plus radiation, indicating no effect of GBE on jejunal crypt cell survival after radiation. Conclusion : GBE doesn't increase acute normal tissue radiation reaction in this model system. As GBE was verified to enhance radiation effect on tumor, high therapeutic gain is expected when GBE is combined with radiation therapy.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.13 no.3
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• pp.265-277
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• 1991

In this study, the healing changes of the implanted bone and its surrounding tissues were examined on the histopathologic basis following implantation of the freeze - dried and radiation - sterilized allogeneic bone in Rectus abdominicus of the rat. This study was performed to see the tissue recations after implantation of the freeze - dried and radiation - sterilized allogeneic bone and whether osteogenesis or osteo - induction or osteo - conduction is happened. And the results were as follows : 1. The shape of the implanted allogeneic bone of the 1, 2 - week group specimen was similar to that of normal bone in light - microscopic finding and the atrophy of cellular organells was found in trans - mission electron - microscopic finding. 2. The implanted allogeneic bone was surrounded with the dense fibroconnective tissues, and infiltration of the chronic inflammatory cells gradually became increased. 3. Hyaline degeneration was observed in the surrounding tissue at the 3, 4, 6 - week group specimen. 4. Light - microscopically the resorption of implanted bone became prominent after 4 - week group and the necrosis of allogeneic bone implant became severe with loss of cell components in lacuna. 5. Electron - microscopically, the osteoclast - like cells ere fond after, 2 - week group. It is summarized that the osteo - conduction potential of the bone is remained just after implanting the freeze - dried and radiation - sterilized allogeneic bone on Rectus abdominicus of the rat, but gradually it disappeared with the gradual increse of chronic inflammatory reaction and osteoclastic activity. So it is suggested that the antigenicity of the freeze - dried and radiation - sterilized bone is remained and it has little osteo - conductive activity when it is implanted in the muscle.

• Applied Microscopy
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• v.33 no.2
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• pp.117-130
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• 2003

This research investigates the fine structural as well as the morphological changes of the mouse ovarian tissue after irradiation of various dose rates of 6 MeV LINAC radiation. The normal structure of the ovarian tissue is consisted of various stages of follicles including primordial and growing follicles, and ovarian stromal connectives. When we observed the ovarian tissues irradiated with a dose rate of 200 cGy/min using light and electron microscopes, granular cells in growing follicles are in irregular shape unlike normal follicles. Small segments of cells scattered in follicular antrum among granular cells. We could observe neutrophils and macrophages around the segments, which means the cells already got in the process of decease owing to the effects radiation. With coincident to the increase of the dose rate of x-ray irradiation as 400 or 600 cGy/min, the mature follicles appeared as an irregular form and the granular cells surrounding oocyte also deformed comparing to their normal counterparts. The granulosa cells within mature follicle are already occurred necrotic change and apoptosis. The nuclei in some cells got so fragmented that the segments formed the shape of a horseshoe or scattered in small and condensed pieces. All the cells at a granular layer irradiated with a dose rate of 600 cGy/min show typical characteristics of apoptosis. The neutrophils involved in inflammatory reaction appear evidently in follicular antrum of growing follicles, and macrophage scattered with residual and apoptotic bodies.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3715-3721
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• 2015

Leukemia is a clonal disorder with blocked normal differentiation and cell death of hematopoietic progenitor cells. Traditional modalities with most used radiation and chemotherapy are nonspecific and toxic which cause adverse effects on normal cells. Differentiation inducing therapy forcing malignant cells to undergo terminal differentiation has been proven to be a promising strategy. However, there is still scarce of potent differentiation inducing agents. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), has potential differentiation inducing activity in human chronic erythro-megakaryoblastic leukemia K562 cells. MTT assays and flow cytometric analysis demonstrated that ASP inhibited K562 cell proliferation and arrested the cell cycle at the G0/G1 phase. ASP also triggered K562 cells to undergo erythroid differentiaton as revealed by morphological changes, intensive benzidine staining and hemoglobin colorimetric reaction, as well as increased expression of glycophorin A (GPA) protein. ASP induced redistribution of STAT5 protein from the cytoplasm to the nucleus. Western blotting analysis further identified that ASP markedly sensitized K562 cells to exogenous erythropoietin (EPO) by activating EPO-induced JAK2/STAT5 tyrosine phosphorylation, thus augmenting the EPO-mediated JAK2/STAT5 signaling pathway. On the basis of these findings, we propose that ASP might be developed as a potential candidate for chronic myelogenous leukemia inducing differentiation treatment.

• Radiation Oncology Journal
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• v.4 no.2
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• pp.115-128
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• 1986

Hyperthermia can enhance the radiation effect as a synergistic reaction in combined X-ray irradiation and hyperthermia; hyperthermia sensitize radioresistant S-phase cells and inhibit cellular recovery from sublethal damage. We fabricated 100 watts, 2450 MHz microwave applicator for hyperthermia and planned the method and condition of heating and measured the temperature by using Agar phantom as a preliminary test. For biological examination, 102 rats were divided into 4 groups as hyperthermia, X-ray irradiation (6Gy-15Gy), combined X-ray and hyperthermia, and normal control groups. Microscopic examination of the rectum and bladder was done and the results were as followings: 1. The microwave generator with 100 watts, 2450MHz magnetron could be heating up to $40^{\circ}{\sim}50^{\circ}C$ for one hour in living tissue. 2. The thermal distribution in tissue equivalent phantom with microwave can be maintained at $40^{\circ}{\sim}44^{\circ}C$ in area of 3cm in depth and 2-10cm in diameter. 3. In Hyperthermia alone group, there was submucosal edema of the rectum but no histologic change in the urinary bladder was seen. 4. The minimal necrosis of the mucosa was appeared in the rectum and bladder after 15 days of 6 Gy and 8 Gy irradiation respectively. The minimal necrosis of the muscle layer of rectum and bladder was appeared after 15 days of 8Gy and 60days of 10Gy irradiation respectively. 5. In combined group of radiation and hyperthermia, thermal enhancement ratio (calculated at necrosis of mucosa and muscle layer) of rectum and bladder was 1.0, and it suggest that there is no change of tolerance dose of normal rectum and bladder.

• Journal of Radiation Protection and Research
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• v.32 no.4
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• pp.140-156
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• 2007

This research was performed to investigate the morphological changes of folliculus ovary according to the radiation dose. The whole body radiation of 200 cGy, 400 cGy, and 600 cGy was given to the each groups of 5 months-aged female mouse. Various staining methods used in this research are: Hematosylin-Eosin method, and immunohistochemistrical methods using BrdU, TUNEL, p53, p21, PCNA and inhibin. The minute structural changes of folliculus ovary were observed through an electron microscope with high magnification. The morphological changes of growing folliculus ovary became distinct as the dose of X-rays increased. Especially, the nuclei of granular cells showed manifest condensation and the changes of the transparent zone were distinct. As a result of histochemical reaction according to Masson's trichrome method and reticular fiber method, the changed granular cells, the deformed basilar membrane of folliculus ovary and the abnormal arrangement of the reticular fiber were observed. In the reaction of BrdU, the granular cells of normal folliculus ovary with positive reaction rapidly decreased according to the increase of the dose of X-rays. In TUNEL study, granular cells showing positive reaction in retarded folliculus ovary were expanded to growing folliculus ovary and primordial folliculus ovary according to the increase of the dose of X-rays. In case of 600 cGy of X-rays, oocyte underwent apoptosis. In p53 immunohistochemistry, p53 manifested to be stronger as the dose of X-rays increased. p53 reactivity was manifested distinctively in all cells comprising folliculus ovary following irradiation of 600 cGy. p21 was manifested in granular cells of folliculus ovary and showed very positive reaction around follicular antrum according to the increase of the dose of X-rays. In PCNA, positive reaction was manifested in growing folliculus ovary, mature folliculus ovary and primordial folliculus ovary, but the extent of the reaction decreased as the dose of the X-rays decreased. The finding that the reaction of granular cells around folliculus ovary was stronger than that near follicular membrane indicates that what was damaged first by X-ray was the cells near folliculus ovary and follicular antrum. The reactivity of $inhibin-{\alpha}$ showed difference according to the growing stage of folliculus ovary: $inhibin-{\alpha}$ showed the most strong reaction in mature folliculus ovary with follicular antrum. There was strong reaction in granular cells around follicular membrane but $inhibin-{\alpha}$ did not occur at all in theca cells comprising follicular membrane. $Inhibin-{\alpha}$ in ovary tissue exposed to 400 cGy of X-rays was manifested more strongly than in ovary tissue exposed to 600 cGy of X-rays, which was related to the phenomenon that granular cells of mature folliculus ovary underwent necrosis or apoptosis increasingly due to X-rays. In an electron microscope with high magnification, nuclei and protoplasm of granular cells in growing folliculus ovary abruptly underwent minute structural changes according to the increase of dose of X-rays. Cell residue, by-product of cell decease, neutrophil and macrophage around follicular antrum were observed. The minute structural changes in granular cells showed typical characteristics of apoptosis: the increase of electronic density due to nuclear condensation, fragmentation of nuclei and atrophy of protoplasm. Necrosis of cells was identified but it was not so remarkable. Macrophage with apoptotic bodies was scattered. Proportional to the radiation dose, we found that the generation of heterogeneous substance of normal ovary texture's follicular fluid, the emergence of dyeing characteristic in the basilar membrane of folicle, the generation of apoptosis, and the transformation of macrophages, etc. From this results, we can infer the possible radiation hazard on the ovary of cervix cancer patient with radiation therapy.

• Radiation Oncology Journal
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• v.6 no.2
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• pp.155-161
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• 1988

The usefulness of hypertermia for cancer therapy have well been established. The purpose of the present investigation was to ascess the effect of step-up $(42^{\circ}{\rightarrow}44^{\circ}C$ sequence) and step-down $(44^{\circ}{\rightarrow}42^{\circ}C$ sequence) heating on the skin of the hind foot of the mouse. Hyperthermic treatments were given by immersion the hind foot of the mouse in circulating water baths. Skin response was studied by the leg reaction, which was scored according to a numerical scoring system proposed by Urano et al (1980). The results were as follows 1. The skin damage of $44^{\circ}C$ control group was more severe than $42^{\circ}C$ control group (P<0.05), except for 15 min. heating group. 2. The Skin damage of step-down group was more severe than step-up group (P<0.05). 3. The skin damage of $44^{\circ}C$ control group was more severe than step-up group when there is no difference in $44^{\circ}C$ heating time of step-up group from $44^{\circ}C$ control group (P<0.05). 4. In step-down group, the skin damage was more severe than $44^{\circ}C$ control group after preheating 45 min at $44^{\circ}C$ (P<0.05). Therefore, the above findings suggest the normal tissue damage by step-up heating was correlated with heating time of post step-up. The dropping of heating temperature in late phase had more severe damage of the skin than that in early phase during hyperthermia, and so contineous control of satisfactory temperature should be considered as the one of the most important factor for prognosis, complications of clinical hyperthermia

• The Journal of the Korean bone and joint tumor society
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• v.9 no.2
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• pp.190-199
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• 2003

Purpose: The aim of this study was to find out a clinically appliable method to insert a biodegradable solid material containing holmium-166-chitosan complex into the surgical field, and to evaluate the histological changes in the normal tissues after ${\beta}$ -ray irradiation from holmium-166 according to the dose, period and type of tissues. Materials and Methods: 3.0 mCi, 50 ${\mu}l$ of the liquid state $^{166}$Ho-chitosan complex was attached to the absorbable gelatin sponge. The radiation activity measured by dose caliberator was 1.5 mCi. These $^{166}$Ho-chitosan complex containing absorbable gelatin sponges were inserted into the thigh muscles and over the femur bones of the Wistar rats. The cases were evaluated at 2 weeks after insertion, and 4, 6 weeks with respect to the histological changes of the soft tissues and bone, the depth of the tissue necrosis, and the changes of the $^{166}$Ho-chitosan complex containing absorbable gelatin sponges. Results: At 2 weeks, the muscles showed coagulation necrosis, degenerating myocytes, regenerating myocytes, intermuscular edema, and inflammatory cells. The necrosis depth was 3.3 mm. In the bones, there was no osteocyte in the lacuna of cortex (empty lacuna), marrow fibrosis, inflammation. The necrosis depth was 2.9 mm. At 4 weeks, in the muscle, calcification and increased fibrosis with necrosis depth by 3.3 mm were the additional findings. In the bone, marrow fibrosis with necrosis depth by 3.3 mm were detected. At 6 weeks, soft tissue shrinkage, increased fibrosis and granulation tissue formation, and nearly resolving inflammatory reaction were the findings. Conclusion: The local application of the $^{166}$Ho-chitosan complex attached to biodegradable gelatin material with surgery in the laboratory animals resulted in no mortality and morbidity, and satisfactory tissue necrosis. Holmium-166 can be applied to the treatment of the malignant tumor patients.