• Title/Summary/Keyword: Radiation necrosis

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Expression of Jun and p53 Genes from the Brain of Rats Irradiated with $^{60}Co{\gamma}$-ray (감마선 조사에 의한 뇌조직의 Jun 및 p53유전자 발현)

  • Kim Yong Seok;Woo Chong Kyu;Lee Yong Sung;Koh Jai Kyung;Chun Ha Chung;Lee Myung Za
    • Radiation Oncology Journal
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    • v.14 no.4
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    • pp.265-279
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    • 1996
  • Damage produced by radiation elicits a complex response in mammalian cells, including growth rate changes and the induction of a variety of genes associated with growth control and apoptosis. At doses of 10,000 cGy or greater, the exposed individual was killed in a matter of minutes to a couple of days, with symptoms consistent with pathology of the central nervous system(CNS) including degenerative changes. The nature of the damage in irradiated cells underlies the unique hazards of ionizing radiation. Radiation injury to CNS is a rare event in clinical medicine, but it is catastrophic for the patient in whom it occurs. The incidence of cerebral necrosis has been reported as high as 16% for doses greater than 6,000 cGy. In this study, the effect of radiation on brain tissue was studied in vivo. Jun and p53 genes in the rat brain were induced by whole body irradiation of rat with 600Co in doses between 1 Gy and 100 Gy and analyzed for expression of jun and p53 genes at the postirradiation time up to 6 hours. Northern analyses were done using 1.8 Kb & 0.8 Kb-pGEM-2-JUN/Eco RI/Pst I fragments, 2.0 Kb-php53B/Bam HI fragment and ,1.1 Kb-pBluescript SK--ACTIN/Eco RI fragment as the digoxigenin or [${\alpha}^{32}P$] dCTPlabeled probes for Jun, p53 and ${\beta}$-actin genes, respectively. Jun gene seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 1 hour after irradiation of $^{60}$Co in dose of 30 Gy. Jun was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in doses of 1 Gy and 10 Gy. After irradiation of $^{60}$Co in dose between 20 Gr and 100 Gy, the expression of Jun was however increased to peak in 2 hours and decreased thereafter. p53 gene in this study also seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 6 hours after irradiation of $^{60}$Co in dose of 1 Gy, p53 was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in dose between 1 Gy and 40 Gy. After irradiation of $^{60}$Co in doses of 50 Gy and 100 Gy, the expression of p53 was however increased to peak in 2 hours and decreased thereafter. The expression of Jun and p53 genes was not correlative in the brain tissue from rats. It seemed to be very important for the establishment of the optimum conditions for the animal studies relevant to the responses of genes inducible on DNA damage to ionizing radiation in mammalian cells. But there are many limitations to the animal studies such as the ununiform patterns of gene expression from the tissue because of its complex compositions. It is necessary to overcome the limitations for development of in situ Northern analysis.

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Therapeutic Effect of Combined Radiotherapy and Hyperthermia in Primary Hepatocellular Carcinoma (원발성 간암의 방사선치료및 온열요법의 병용치료 효과)

  • Kang Ki Mun;Choi Ihl Bohng;Kay Chul Seung;Choi Byung Ok;Chung Su Mi;Kim In Ah;Han Sung Tae;Sun Hee Sik;Chung Kyu Won;Shinn Keyong Sub
    • Radiation Oncology Journal
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    • v.12 no.2
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    • pp.191-199
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    • 1994
  • Purpose : This study was undertaken to show the clinical results of combined radiotherapy and hyperthermia in primary hepatoma Materials and Methods : Between December 1989 and March 1993, 50 patients with hepatomas were treated by combined radiotherapy and hyperthermia. Among them, we analyzed retrospectively 33 patients who received the complete course of treatment. The ages of the patients ranged from 36 to 75(mean age: 55.5 years). Twenty-six patients ($78.8\%$) were men, and 7 ($21.2\%$ were women. According to Child's classification, nine patients ($27.3{\%}$) were A group, 9 ($27.3\%$) were B group, 15 ($45.4\%$) were C group. Radiation therapy was done by a 6 MV and 15 MV linear accelerator. Patients were treated with daily fractions of 150-180 cCy to doses of 2550 cGy -4950 cGy (median : 3000 cGy). Local hyperthermia was done by 8 MHZ RF capacitive heating device (Cancermia. Green Cross Co., Korea), 50-60 min/session, 1-2 sessions/wk, and 8.5 sessions (median number)/patient. We analyzed the prognostic factors including age, sex, tumor type, Child's classification, $\alpha$-fetoprotein, liver cirrhosis, ascites, portal vein invasion, esophageal varix, number of hyperthermia, chemotherapy, total bilirubin level, Karnofsky perfomance status. Results : The overall 1-year survival was $24.2\%$, with a mean survival of 10months. Of 33 patients, tumor regression (PR+MR) was seen in $30.4\%$, no response was seen in $52.2\%,\;17.4\%$ patient was progressed. In patients who had tumor regression, the overall 1-year survival was $42.1\%$ with a mean survival of 14 months. Factors influencing the survival were sex (p=0.05), tumor type (p=0.0248), Child's classification (p=0.0001), liver cirrhosis (p=0.0108), ascites (p=0.0009), and Karnofsky perfomance status (p=0.0028). Complications developed in 28 patients, including 18 hot pain,5 fat necrosis, 3 transient fever, 2 nausea and vomiting. Conclusion : In this study, the results suggests that combined radiotherauy and hyperthermia may improve the survival rate of hepatoma.

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Appropriate Timing of Surgery after Neoadjuvant Chemo-Radiation Therapy for Locally Advanced Rectal Cancer

  • Garrer, Waheed Yousry;Hossieny, Hisham Abd El Kader El;Gad, Zeiad Samir;Namour, Alfred Elias;Amer, Sameh Mohammed Ahmed Abo
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4381-4389
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    • 2016
  • Background: Surgery is the corner stone for the management of rectal cancer. The purpose of this study was to demonstrate the optimal time of surgical resection after the completion of neoadjuvant chemo-radiotherapy (CRT) in treatment of locally advanced rectal cancer. Materials and Methods: This study compared 2 groups of patients with locally advanced rectal cancer, treated with neoadjuvant CRT followed by surgical resection either 6-8 weeks or 9-14 weeks after the completion of chemo-radiotherapy. The impact of delaying surgery was tested in comparison to early surgical resection after completion of chemo-radiotherapy. Results: The total significant response rate that could result in functional preservation was estimated to be 3.85% in group I and 15.4% in group II. Some 9.62% of our patients had residual malignant cells at one cm surgical margin. All those patients with positive margins at one cm were in group I (19.23%). There was less operative time in group II, but the difference between both groups was statistically insignificant (P=0.845). The difference between both groups regarding operative blood loss and intra operative blood transfusion was significantly less in group II (P=0.044). There was no statistically significant difference between both groups regarding the intra operative complications (P=0.609). The current study showed significantly less post-operative hospital stay period, and less post-operative wound infection in group II (P=0.012 and 0.017). The current study showed more tumor regression and necrosis in group II with a highly significant main effect of time F=61.7 (P<0.001). Pathological TN stage indicated better pathological tumor response in group II (P=0.04). The current study showed recurrence free survival for all cases at 18 months of 84.2%. In group I, survival rate at the same duration was 73.8%, however none of group II cases had local recurrence (censored) (P=0.031). Disease free survival (DFS) during the same duration (18 months) was 69.4 % for patients in group I and 82.3% for group II (P=0.429). Conclusions: Surgical resection delay up to 9-14 weeks after chemo-radiation was associated with better outcome and better recurrence free survival.

Protective Effects of Chemical Drugs on the Course of Uranium-induced Acute Renal Failure (우라늄오염에 의한 신부전증에 미치는 제염제의 방호효과)

  • Kim, Tae-Hwan;Chung, In-Yong;Kim, Sung-Ho;Kim, Kyeng-Jung;Bang, Hyo-Chang;Yoo, Seong-Yul;Chin, Soo-Yil
    • Journal of Radiation Protection and Research
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    • v.15 no.2
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    • pp.27-39
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    • 1990
  • Appreciable radiation exposures certainly were occurred in the reactor burn-up, the nuelear fall-out and the surroundings of nuclear installations with radioactive effluents. Therefore, radioactive nuclides is not only potentially hazardous to workers of nuclear power plants and related industrials, but also the wokers who handle radioactive nuclides in biochemical research and nuclear medicine diagnostics. And in the case of occurring the nuclear accidents, the early medical treatment of radiation injury should be necessary but little is established medical procedures to decontaminate the victims of internal contamination of radioactive nuclides in korea. Accordingly, to achieve the basic data for protective roles and medical treatment of radiation injury, the present studies were carrid out to evaluate the decontamination of uranium by the chemical drugs. The results observed were summarized as follows: 1. The combined treatmet group of sodium bicarbonate and saline with uranyl nitrate injection simultaneously and the dithiothreitol group that was administered 30 minutes after uranyl nitrate injection were increased significantly in the change of body weight than uranyl nitrate-only group (P<0.005). 2. All the experimental groups were increased the fluid intake and urine volume on the uranyl nitrate-induced acute renal failure. but the combined treatment group of sodium bicarbonate and saline with uranyl nitrate injection simultaneously and the dithiothreitol group that was administered 30 minutes after uranyl nitrate injection have the higher increment of fluid intake and urine volume (P<0.05). 3. When sodium bicarbonate and saline was treated with uranyl nitrate injection simultaneously. and dithiothreitol was administered 30 minutes after uranyl nitrate injection. there was significantly reduced in BUN concentration (P<0.01). 4. When dithiothreitol was administered 30 minutes after uranyl nitrate injection. there was reduced more significantly on the increment of serum creatinine concentration than that observed in uranyl nitrate-only group(P<0.01). but when the combined treatment of sodium bicarbonate and saline with uranyl nitrate simultaneously, there was still. albeit much less marked. decrease in serum creatinine concentration. 5. The sodium bicarbonate and saline was treated with uranyl nitrate simultaneously and dithiothreitol was administered at 30 minutes after uranyl nitrate were excreted markedly higher urine creatinine concentration than the uranyl nitrate-only group. 6. Uranyl nitrate has been used in experimental animals to produce hydropic degeneration and swelling of proximal tubules, disappearance of microvilli and brush border or necrosis in the kidney and centrilobular necrosis, congestion, and telangiectasia of the liver. When the sodium bicarbonate and saline was treated with uranyl nitrate simultaneously, and dithiothreitol was administered. 30 minutes after uranyl nitrate, there was more marked the protective effect than uranyl nitrate-only group. Finally, if the sodium bicarbonate and saline may administered as quickly as possible each time that some risk for internal contamination, with uranium, and dithiothreitol is administered 30 minutes after uranium contamination, there ameliorates the course of uranyl nitrate-induced acute renal failure.and this effect is assocciated with prevention of uranium (heavy metal)-induced alterations in BUN, serum creatinine, urine creatinine, fluid intake, urine volume and body weight.

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Effect of lonizing Radiation on the Host Resistance Against Listeria Monocytogenes Infection and the Cytokine Production in Mice (방사선조사후 마우스에서의 Cytokine 생산능 및 Listeria monecytogenes에 대한 저항성의 변화)

  • Oh, Yoon-Kyeong;Chang, Mee-Young;Kang, In-Chol;Oh, Jong-Suk;Lee, Hyun-Chul
    • Radiation Oncology Journal
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    • v.15 no.3
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    • pp.175-186
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    • 1997
  • Purpose : To evaluate the qualitative immunologic changes by ionizing radiation. we studied the altered capacities of the macrophages and lymphocytes to produce cytokines in conjunction with resistance to Listeria monocytegenes (LM) infection in mice Materials and Methods : BALB/c mice and Listeria monocytogenes were used. The mice were infected intraperitoneally with $10^5LM$ at 1 day after irradiation (300cGy) and sacrificed at 1, 3, 5 days after infection, and then the numbers of viable LM per spleen in the irradiated and control group were counted. Tumor necrosis factor-alpha ($TNF-\alpha$), interferon-gamma ($IFN-\gamma$). interleukin-2 (IL-2), and nitric oxide (NO) were assessed after irradiation. Results : Under gamma-ray irradiation with a dose range of 100-850cGy, the number of total splenocytes decreased markedly in a dose-dependent manner, while peritoneal macrophages did so slightly Cultured peritoneal macrophages produced more $TNF-\alpha$ in the presence of lipopolysaccharide (LPS) during the 24 hours after in vitro irradiation, but their capacity of $TNF-\alpha$ Production showed a decreased tendency at 5 days after in vivo total body irradiation. With 100cGy and 300cGy irradiation, cultured peritoneal macrophages produced more NO in the presence of LPS during the 24 hours after in vitro irradiation than without irradiation. Activated splenocytes from irradiated mice (300cGy) exhibited a decreased capacity to Produce IL-2 and $IFN-\gamma$ with Concavalin-A stimulation at 3 days after irradiation. When BALB/c mice were irradiated to the total body with a dose of 300cGy, they showed enhanced resistance during early innate phase, but a significant inhibition of resistance to LM was found in the late innate and acquired T-cell dependent phases. Conclusion : These results su99es1 that increased early innate and decreased late innate and acquired immunity to LM infection by ionizing radiation (300cGy) may be related to the biphasic altered capacity of the macrophages to produce $TNF-\alpha$ and the decreased capacities of the lymphocytes to produce IL-2 and $IFN-\gamma$ in addition to a marked decrease in the total number of cells.

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Effect of irradiation on cell cycle, cell death and expression of its related proteins in normal human oral keratinocytes (방사선조사가 사람 정상 구강각화 세포의 세포주기, 세포사 및 수종 단백질의 발현에 미치는 영향)

  • Kang Mi-Ae;Heo Min-Suk;Lee Sam-Sun;Oh Sung-Ock;Lee Sul-Mi;Jeon In-Seong;Choi Soon-Chul;Park Tae-Won
    • Imaging Science in Dentistry
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    • v.33 no.3
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    • pp.143-149
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    • 2003
  • Purpose: To investigate the radiosensitivity of the normal human oral keratinocytes (NHOK), and the effect of irradiation on cell cycle and protein expression. Materials and Methods: To evaluate the radiosensitivity of NHOK, the number of colonies and cells were counted after irradiation and the SF2 (survival fraction at 2Gy) value, and the cell survival curve fitted on a linear-quadratic model were obtained. LDH analysis was carried out to evaluate the necrosis of NHOK at 1, 2, 3, and 4 days after 2, 10, and 20 Gy irradiation. Cell cycle arrest and the induction of apoptosis were analyzed using flow cytometry at 1, 2, 3, and 4 days after 2, 10, and 200y irradiation. Finally, proteins related cell cycle arrest and apoptosis were analysed by Western blot. Results: The number of survived cell was significantly decreased in a dose-dependent manner. The cell survival curve showed SF2, α, and β values to be 0.568, 0.209, and 0.020 respectively. At 200y irradiated cells showed higher optical density than the control group. After irradiation, apoptosis was not observed but G2 arrest was observed in the NHOK cells. 1 day after 10 Gy irradiation, the expression of p53 remained unchanged, the p2l/sup WAF1/Cipl/ increased and the mdm2 decreased. The expression of bax, bcl-2, cyclin B1, and cyclin D remained unchanged. Conclusion: These results indicate that NHOK responds to irradiation by G2 arrest, which is possibly mediated by the expression of p21/sup WAFl/Cipl/, and that cell necrosis occurs by high dose irradiation.

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Induction of Apoptosis in Human Osteosarcoma Cell Lines(Saos-2) by Single Fraction High Dose Irradiation (고용량 방사선 조사 후 골육종 세포주(Saos-2)의 아포프토시스 발생)

  • Kim, Jae-Do;Chung, So-Hak;Hong, Young-Gi;Choi, Jang-Seok
    • The Journal of the Korean bone and joint tumor society
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    • v.5 no.1
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    • pp.1-8
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    • 1999
  • A single fraction of 50 Gy extracorporeal irradiation, as a modality of limb-sparing operation, has been used to achieve tumor necrosis in osteosarcoma. Although this modality of radiation therapy preserving the mobility of a joint is commonly practiced, the precise knowledge on the radiobiological response of osteosarcoma cell has remained to be elucidated. We therefore observed whether a single high dose irradiation caused apoptosis in osteosarcoma cells and whether the commitment to apoptosis was associated with cell kinetics. We also investigated radiation dose response along the time course for development of apoptosis following single high dose irradiation. The morphologic change in apoptosis was observed by fluorescence with Hoechst 33258 and the degree and the fraction of cells by flow cytometry. Irradiation of osteosarcoma cells with 10, 30 and 50 Gy resulted in chromatin condensation and apoptotic body formation. The degree of apoptosis in osteosarcoma cells was $29.5{\pm}3.56%$, $39.9{\pm}4.83%$ at 24 and 48 hours after 10 Gy irradiation ; $41.1{\pm}3.93%$, $66.9{\pm}5.21%$ at 24 and 48 hours after 30 Gy irradiation ; and $48.0{\pm}3.69%$, $75.6{\pm}4.65%$ at 24 and 48 hours after 50 Gy irradiation. The fraction of cells in cell-cycle kinetic was $39.2{\pm}4.3%$ in G2/M, $22.1{\pm}4.65%$ in G1 at 24 hours after 10 Gy irradiation ; $51.0{\pm}4.3%$ in G2/M, $20.4{\pm}4.7%$ in G1 at 48 hours after 10 Gy irradiation ; $40.3{\pm}3.9%$ in G2/M, $26.1{\pm}4.7%$ in G1 at 24 hours after 30 Gy irradiation ; $59.2{\pm}3.9%$ in G2/M, $5.9{\pm}5.1%$ in G1 at 48 hours after 30 Gy irradiation ; and $44.3{\pm}4.2%$ in G2/M, $21.1{\pm}3.5%$ in G1 at 24 hours after 50 Gy irradiation. The fraction of cells at 48 hours after 50 Gy irradiation could not be observed because of irradiation induced cell death of most of cells. All values for irradiated cells showed accumulation in G2/M phase and reduction in G1 phase, irrespective of irradiation dose. The results suggest that a single fraction of high dose irradiation with 50 Gy results in accumulation of cells at G2/M phase, leading to apoptosis.

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Biochemical Effect on Potato Tubers Irradiated by Gamma-Ray at Sprout-Inhibition Dose (방사선 조사에 의한 감자 발아 억제시 생화학적 효과)

  • Jeon, J.H.;Byun, S.M.;Chang, Y.S.P.;Chung, K.H.;Cho, H.O.
    • Applied Biological Chemistry
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    • v.28 no.1
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    • pp.28-35
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    • 1985
  • Potato tubers treated at $4^{\circ}C$ for 4 weeks were irradiated with a dose of 0.12 kGy from $^{60}Co$ source and stored at $20^{\circ}C,\;70{\sim}90%$ humidity for 5 weeks. Changes of ${\alpha}-amylase$, peroxidase, indole acetic acid oxidase, indole acetic acid synthesizing enzyme activities were determined. In addition, treatment of gibberellin or indole acetic acid to tubers irradiated were carried out to examine reversal of sprout-inhibition of tubers irradiated. Results are as follows; 1. Irradiation by ${\gamma}-ray$ at 0. 12 kGy dose inactivated easily the enzyme activities in vitro. $D_{37}$ values obtained were 0.94, 0.36 kGy for ${\alpha}-amylase$ and peroxidase, respectively 2. Complete inhibition of the toter sprouting was resulted by the irradiation of tubers with a dose of 0.12 kGy. 3. The indole acetic acid oxidase activity increased 2 times immediately after irradiation. Meanwhile, indole acetic acid synthesizing activity decreased about $50{\sim}75%$ for 5-week storage in irradiated potatoes, whereas the activity increased about 3.5 times along with sprouting in non-irradiated tubers. 4. In morphological aspects, deformed buds with necrosis in the meristmatic tissue were developed in irradiated tubers. Treatment of gibberellin or indole acetic acid at the concentration of 100 or 20 ppm to the irradiated tubers reversed the sprout-inhibition partially. Nevertheless, the deformed buds remained without change.

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Immunomodulatory Activity of Crude Polysaccharide Separated from Cudrania tricuspidata Leaf (꾸지뽕(Cudrania tricuspidata) 잎으로부터 분리된 다당류 추출물의 면역 활성)

  • Byun, Eui-Baek;Jang, Beom-Su;Sung, Nak-Yun;Byun, Eui-Hong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.8
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    • pp.1099-1106
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    • 2016
  • The objective of this study was to evaluate the immunomodulatory activity of crude polysaccharide separated from Cudrania tricuspidata leaf. C. tricuspidata polysaccharide (CTP) was extracted by ethanol precipitation. Immunomodulation activity was tested in macrophage cells (RAW 264.7 and bone-marrow derived macrophage) and splenocytes. CTP treatment significantly increased cell proliferation up to $250{\mu}g/mL$ in both RAW 264.7 and bone-marrow derived macrophages. In this concentration range (below $250{\mu}g/mL$), nitric oxide and cytokine [tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6] production also significantly increased. Similarly, splenocyte proliferation dosedependently increased except for the $1,000{\mu}g/mL$ treated group. Regarding cytokine production activity in splenocytes, CTP treatment significantly increased production of Th 1 type cytokines [interferon $(IFN)-{\gamma}$] production but not Th 2 type cytokines (IL-4). Therefore, the results indicate that CTP may have a potential effect on immunomodulatory activity in various immune cells, and this is useful for development of immune enhancing adjuvant materials as a natural ingredient.

A study of the [$Ca^{2+}$] and the Apoptosis of the KB Cell Lines after 10Gy Irradiation (방사선조사 후 유표피암종세포내 칼슘농도의 변화와 apoptosis 발현에 관한 연구)

  • Moon Je-Woon;Lee Sam-Sun;Heo Min-Suk;Choi Soon-Chul;Park Tae-Won;You Dong-Soo
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.29 no.1
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    • pp.105-117
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    • 1999
  • Purpose: Ionizing radiations have been reported as an apoptosis initiating stimulus in various cells and it has established that sustained elevations in [Ca/sup 2+/] can lead to DNA fragmentation by Ca/sup 2+/-dependent endonucleases, ultimately resulting in apoptotic cell death. The previous experiments have been reported by using primarily thymocytes and lymphocytes and the change of [Ca/sup 2+/] was measured only by minutes or hours respectively. We need to evaluate [Ca/sup 2+/] in both several minutes and hours after irradiation of radiation of radiation therapy and verify the apoptotic cells. Materials and Methods: We have measured [Ca/sup 2+/] in human gingival epitheloid cancer cell with 10Gy irradiation, at minutely intervals and hourly intervals using digitized video-intensified fluorescence microscopy and the fluorescent Ca/sup 2+/ indicator dye, fura-2. In order to find out that the transient rise in [Ca/sup 2+/] could induced apoptosis, cells were incubated for 1 hour at 37℃ with TdT enzyme, rinsed and resuspended containing fluorescence and observed under a confocal fluorescence microscope. MTT assay was done to determine cell activity and LDH assay was done to determine the amount of necrotic cells. Results: After irradiation, the transient and temporal increasing of [Ca/sup 2+/] in the KB cells was founded. Though, there was no change in the intracellular [Ca/sup 2+/] at 30 minutes and 2 hours after irradiation. We could detect of DNA fragmented cells at 4 hours after 10Gy irradiated cells. There were no significant differences between 4 hour, 1 day, 3 day cells. There were no significant differences in MTT and LDH assay between the irradiated group and the control group after 4 hours and 1 day. Though after 3 days there were differences in MTT and LDH assay between the irradiated group was significantly decreased than the control group, in LDH assay the number of necrotic cell death of the irradiated was higher than the control group. Conclusion: In KB cells there were incipient and temporal increasing of the [Ca/sup 2+/] with 10Gy irradiation and the apoptosis was founded from 4 hours later which was earlier than seeing of the change of the amount of the cellular ability and necrosis.

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