• Title/Summary/Keyword: Gamma Model

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Potentiation of Antitumor Effect of Radiotherapy by Recombinant Tumor Necrosis Factor-$\alpha$ (방사선의 항암작용에 대한 재조합 TNF-$\alpha$의 효과)

  • Seong Jinsil;Shin Hang Chul;Kim Gwi Eon;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.225-231
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    • 1998
  • Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

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Effects of Fermented Red Ginseng Supplementation on Blood Glucose and Insulin Resistance in Type 2 Diabetic Patients (발효홍삼이 제2형 당뇨병 환자의 혈당 및 인슐린저항성에 미치는 영향)

  • Kim, Hey-Ok;Park, Min-Jung;Han, Ji-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.5
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    • pp.696-703
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    • 2011
  • We performed a randomized placebo-controlled trial to determine whether or not fermented red ginseng supplementation modulates blood glucose and insulin resistance in type 2 diabetic patients. A total of 38 patients were randomized to either a fermented red ginseng group or placebo group. The patients in the experimental or placebo group consumed 780 mg of fermented red ginseng or cellulose supplement per day for 12 weeks, respectively. Lifestyle factors and dietary intakes of the patients were not altered during the 12-weeks period. In the fermented red ginseng group after 12 weeks, the fasting blood glucose levels were significantly decreased ($136.29{\pm}16.45$ mg/dL to $127.71{\pm}17.74$ mg/dL) and $HbA_1c$ was also decreased. Especially, high HbA1c (HbA1c $\geq$8%, $8.45{\pm}0.56%$ to $7.82{\pm}0.53%$) was significantly decreased compared to low HbA1c (HbA1c <8%, $6.71{\pm}0.85%$ to $6.44{\pm}0.49%$) in the fermented red ginseng group. Serum low-density lipoprotein was slightly decreased in the fermented red ginseng group compared to the placebo group. Homeostasis model assessment-insulin resistance was significantly reduced in the fermented red ginseng group compared to the placebo group. These results suggest that fermented red ginseng supplementation could be helpful to reduce blood glucose by improving insulin resistance in type 2 diabetic patients.

Differences in Thrombolytic Effects in Accordance with Dosing-regimens of Tissue-type Plasminogen Activator in Experimental Pulmonary Embolism (실험적 폐색전증에서 조직형플라스미노겐활성체의 투여방법에 따른 혈전용해효과의 차이)

  • Chung, Hee-Soon;Kim, Ho-Jung;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.2
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    • pp.123-134
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    • 1993
  • Background: Tissue-type plasminogen activator is a physiologic activator, which has high affinity for fibrin and is activated by fibrin. Because of these properties, t-PA has the potential to induce effective thrombolysis without producing a systemic lytic state. In practice, however, therapeutically efficacious doses of t-PA has been associated with the development of a systemic lytic state. As experience with t-PA has accumulated, it has suggested that the fibrin selectivity is influenced by the dose and duration of t-PA infusion, and many studies have performed in an attempt to optimize the duration of t-PA regimen. Methods: This study was designed to assess the thrombolytic efficacy of t-PA and the differences of two dosing regimens of t-PA (infusion of 1 mg/kg t-PA over 15 or 180 minutes) in a canine model of pulmonary embolism, induced by injection of radioactive autologous blood clots. By continuously counting over both lung fields with a external gamma counter, we correlated rate and extent of pulmonary thrombolysis with corresponding pulmonary hemodynamics in addition to the gas analyses of arterial and mixed venous blood. Results: 1) While total clot lysis was similar ($36.2{\pm}3.3%$ and $39.6{\pm}2.3%$ respectively, p>0.05) when t-PA was infused over 15 or 180 minutes, the rate of lysis during infusion was markedly increased with the shorter infusion ($81.4{\pm}16.8%/hr$ vs $37.3{\pm}2.4%/hr$, p<0.05). 2) The duration of thrombolysis was $63.3{\pm}22.2$ minutes although t-PA was administered over 15 minutes, and it was only $148.5{\pm}14.0$ minutes in case of the infusion over 180 minutes (p<0.05). 3) The increased rate of thrombolysis with the shorter infusion was accompanied by a faster amelioration of cardiopulmonary impairment from pulmonary embolism (p<0.05). Conclusion: It is concluded that the shorter (15 minutes) infusion of t-PA is superior to the longer (180 minutes) infusion when the dose is equal, in consideration of the faster improvement in cardiopulmonary impairment from pulmonary embolism.

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Evaluation on the radiation exposure from activated wedge filter (10MV 이상 고에너지 사용시 wedge filler의 방사화가 작업환경에 미치는 영향평가)

  • Lee HwaJung;Kim DaeYoung;Kim WonTaek;Lee KangHyeok
    • The Journal of Korean Society for Radiation Therapy
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    • v.16 no.2
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    • pp.69-79
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    • 2004
  • In the process of photon treatments, linear accelerators with energies higher than 10 MV produce neutrons through the (${\gamma}$, n) interactions with the composite materials of the linac head md these materials further produce the induced radiations. We investigate the possible risks from these induced radiations especially in the wedge filters to the radiation workers. Wedge filters are used to modify the isodose profiles in the radiation treatment using the linear accelerator and always be handled by the radiation workers. For the background radiation, we measured the radiation in both the waiting room and the outside of the building for two hospitals, S and H. The results of S hospital were $0.11\;{\mu}Sv/hr$ and $0.10\;{\mu}Sv/hr$ for waiting room and outside respectively, and in the case of H hospital, they were $0.12\;{\mu}Sv/hr$ and $0.11\;{\mu}Sv/hr$. Using a survey meter, we measured the radiation from wedge filters inserted in 10 MV and 15 MV Siemens linear accelerators. The time series measurements were done in ${\sim}1$ minutes after exposure of 5 Gy of monitor units for the field size of $25{\times}25cm^2$. The starting value of 10 MV machine was about $3.26\;{\mu}Sv/hr$, which was three times higher than that of 10 MV. The measured radiation was from $^{28}Al$ and $^{53}Fe$ with a half life of 3.5 min. If the treatment patients are $20{\sim}50$ per day and the number of process of wedge filter change per patient is one or two, the annual dose equivalent is $0.08{\sim}0.4\;mSv$ for 10 MV, and $0.27{\sim}1.36\;mSv$ for 15 MV, which are in the range of dose equivalent limits of radiation workers.

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Effects of polygalacin D extracted from Platycodon grandiflorum on myoblast differentiation and muscle atrophy (길경에서 추출한 polygalacin D가 근원세포 분화 및 근위축에 미치는 영향)

  • Eun-Ju Song;Ji-Won Heo;Jee Hee Jang;Eonmi Kim;Yun Hee Jeong;Min Jung Kim;Sung-Eun Kim
    • Journal of Nutrition and Health
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    • v.56 no.6
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    • pp.602-614
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    • 2023
  • Purpose: The balance between synthesis and degradation of proteins plays a critical role in the maintenance of skeletal muscle mass. Mitochondrial dysfunction has been closely associated with skeletal muscle atrophy caused by aging, cancer, and chemotherapy. Polygalacin D is a saponin derivative isolated from Platycodon grandiflorum (Jacq.) A. DC. This study aimed to investigate the effects of polygalacin D on myoblast differentiation and muscle atrophy in association with mitochondrial function in in vitro and in zebrafish models in vivo. Methods: C2C12 myoblasts were cultured in differentiation media containing different concentrations of polygalacin D, followed by the immunostaining of the myotubes with myosin heavy chain (MHC). The mRNA expression of markers related to myogenesis, muscle atrophy, and mitochondrial function was determined by real-time quantitative reverse transcription polymerase chain reaction. Wild type AB* zebrafish (Danio rerio) embryos were treated with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without polygalacin D, and immunostained to detect slow and fast types of muscle fibers. The Tg(Xla.Eef1a1:mitoEGFP) zebrafish expressing mitochondria-targeted green fluorescent protein was used to monitor mitochondrial morphology. Results: The exposure of C2C12 myotubes to 0.1 ng/mL of polygalacin D increased the formation of MHC-positive multinucleated myotubes (≥ 8 nuclei) compared with the control. Polygalacin D significantly increased the expression of MHC isoforms (Myh1, Myh2, Myh4, and Myh7) involved in myoblast differentiation while it decreased the expression of atrophic markers including muscle RING-finger protein-1 (MuRF1), mothers against decapentaplegic homolog (Smad)2, and Smad3. In addition, polygalacin D promoted peroxisome proliferator-activated receptor-gamma coactivator (Pgc1α) expression and reduced the level of mitochondrial fission regulators such as dynamin-1-like protein (Drp1) and mitochondrial fission 1 (Fis1). In a zebrafish model of FOLFIRI-induced muscle atrophy, polygalacin D improved not only mitochondrial dysfunction but also slow and fast muscle fiber atrophy. Conclusion: These results demonstrated that polygalacin D promotes myogenesis and alleviates chemotherapy-induced muscle atrophy by improving mitochondrial function. Thus, polygalacin D could be useful as nutrition support to prevent and ameliorate muscle wasting and weakness.