• Title/Summary/Keyword: Cancer

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Mouse model system based on apoptosis induction to crypt cells after exposure to ionizing radiation (방사선에 전신 조사된 마우스 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구)

  • Kim, Tae-Hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.571-578
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    • 2001
  • To evaluate if the apoptotic fragment assay could be used to estimate the dose prediction after radiation exposure, we examined apoptotic mouse crypt cells per 1,000 cells after whole body $^{60}Co$ $\gamma$-rays and 50MeV ($p{\rightarrow}Be^+$) cyclotron fast neutron irradiation in the range of 0.25 to 1 Gy, respectively. The incidence of apoptotic cell death rose steeply at very low doses up to 1 Gy, and radiation at all doses tigger rapid changes in crypt cells in stem cell region. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for the data of apoptotic fragments was obtained by the linear-quadratic model $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$) after $\gamma$-rays irradiation, while $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$) after neutrons in mice. The dose-response curves were linear-quadratic, and a significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic crypt cells with increasing dose. Both the time course and the radiation dose-response curve for high and low linear energy transfer (LET) radiation modalities were similar. The relative biological effectiveness (RBE) value for crypt cells was 2.072. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morpholoigcal findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis in crypt cells could be a useful in vivo model for studying radio-protective drug sensitivity or screening test, microdosimetric indicator and radiation-induced target organ injury. Since the apoptotic fragment assay is simple, rapid and reproducible in the range of 0.25 to 1 Gy, it will also be a good tool for evaluating the dose response of radiation-induced organ damage in vivo and provide a potentially valuable biodosimetry for the early dose prediction after accidental exposure.

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Immuno-stimulating and Antitumor Effects of Crude Polysaccharides Extracted from Fruiting Body of Grifola frondosa (잎새버섯(Grifola frondosa)의 자실체에서 추출한 조다당류의 면역증강 및 항암효과)

  • Kim, Jeong-Hwa;Cha, Youn-Jeong;Shim, Mi-Ja;Lee, Min-Woong;Lee, Tae-Soo
    • The Korean Journal of Mycology
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    • v.39 no.1
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    • pp.68-77
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    • 2011
  • 80% methanol and 0.9% neutral saline soluble and hot water substances (hereinafter referred to Fr. NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from fruiting bodies of Grifola frondosa. In vitro cytotoxicity tests, crude polysaccharides were not cytotoxic against cancer cell lines such as Sarcoma 180 and RAW 264.7 at the concentration of 10~2000 ${\mu}g/ml$, but crude polysaccharides from Fr. NaCl was slightly toxic to HT-29 and NIH3T3 at the concentration of 2000 ${\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited life prolongation effect of 25.0~52.9% in mice previously inoculated with Sarcoma 180. Fr. HW increased the numbers of spleen cells by 1.3 fold at the concentration of 200 ${\mu}g/ml$ compared with control. Fr. NaCl improved the immuno-stimulating activity of B lymphocyte by increasing the alkaline phosphatase activity by 1.5 fold compared with control at the concentration of 200 ${\mu}g/ml$. 10~14 ${\mu}M$ of nitric acid were generated when Fr. NaCl was added to RAW 264.7 at the concentration of 50~500 ${\mu}g/ml$, while the control group produced 4.3 ${\mu}M$ of nitric oxide. The Fr. NaCl, Fr. HW and Fr. MeOH increased the production of TNF-${\alpha}$, IL-$1{\beta}$, Il-2 and IL-6 by more than 1.4 times compared with the control group. The Fr. of MeOH increased the numbers of peritoneal exudate cells and circulating leukocytes by 3.0 and 2.0 folds compared with the control at the concentration of 50 ${\mu}g/ml$, respectively. Therefore, the crude polysaccharides extracted from fruiting bodies of Grifola frondosa could improve antitumor activity of mice.

Cooperative Induction of HL-60 Cell Differentiation by Combined Treatment with Eugenol and 1α,25-Dihydroxyvitamin D3 (Eugenol과 1α,25-dihydroxyvitamin D3의 병합처리에 의한 HL-60 세포의 분화 유도)

  • Oh, Mi-Kyung;Park, Seon-Joo;Kim, Nam-Hoon;Cho, Jin-Kyung;Jin, Jong-Youl;Kim, In-Sook
    • Journal of Life Science
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    • v.17 no.9 s.89
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    • pp.1191-1196
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    • 2007
  • Eugenol (4-allyl-2-methoxyphenol) is a main component of essential oils obtained from various spices. Recent reports have shown that eugenol induces growth inhibition and apoptosis of malignant tumor cells. In this study, the stimulatory effect of eugenol on cell differentiation was investigated in HL-60 promyelocytic leukemia cells. When HL-60 cells were treated in combination with 150 ${\mu}M$ of eugenol and 3 nM of $1{\alpha},25-dihydroxyvitamin$ $D_{3}$, cell growth was slower than that of cells treated with eugenol or $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ alone. Eugenol enhanced low dose of $1{\alpha,25-dihydroxyvitamin }$ $D_{3}-induced$ a $G_{0}/G_{1}$ phase arrest in cell cycle. Consistent with this, combined treatment of eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ cooperatively increased p27 level and decreased cyclin A, cdk 2 and cdk 4 levels, which are cell cycle regulators related to $G_{0}/G_{1}$ arrest. According to flow cytometric analysis, the expression of CD14 (monocytic differentiation marker) was more increased in the cells co-treated with eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$. These results indicate that eugenol potentiates cell differentiation mediated by $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ of suboptimal concentration. The differentiation-inducing property of eugenol maybe contributes to chemopreventive activity of cancer.

Improving Diagnostic Accuracy for Malignant Nodes and N Staging in Non-Small Cell Lung Cancer Using CT-Corrected FDG-PET (비소세포폐암에서 CT-보정 양전자단층촬영술을 이용한 악성 림프절 평가 및 N 병기 결정 성적 향상)

  • Lee, Eun-Jeong;Choi, Joon-Young;Lee, Kyung-Soo;Chung, Hyun-Woo;Lee, Su-Jin;Cho, Young-Seok;Choi, Yong;Choe, Yearn-Seong;Lee, Kyung-Han;Kwon, O-Jung;Shim, Young-Mog;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.4
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    • pp.231-238
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    • 2005
  • Purpose: We investigated prospectively whether the interpretation considering the patterns of FDG uptake and the findings of unenhanced CT for attenuation correction can improve the diagnostic accuracy for assessing malignant lymph node (LN) and N stage in non-small cell lung cancor (NSCLC) using CT-corrected FDG-PET (PET/CT). Materials & Methods: Subjects were 91 NSCLC patients (M/F 62/29, age: $60{\pm}9$ yr) who underwent PET/CT before in dissection. We evaluated the maximum SUV (maxSUV), patterns of FDG uptake, short axis diameter, and calcification of LN showing abnormally increased FDG uptake. Then we investigated criteria improving the diagnostic accuracy and correlated results with postoperative pathology. In step 1, in was classified as benign or malignant based on maxSUV only. In step 2, LN was regarded as benign if it had lower maxSUV than the cut-off value of step 1 or it had calcification irrespective of its maxSUV. In step 3, LN regarded as malignant in step 2 was classified as benign if they had indiscrete margin of FDG uptake. Results: Among 432 LN groups surgically resected (28 malignant, 404 benign), 71 showed abnormally increased FDG uptake. We determined the cut-off as maxSUV=3.5 using ROC curve analysis. The sensitivity, specificity, and accuracy for assessing malignant LN were 64.3%, 86.9%, 85.4% in step 1, 64.3%, 95.0%, 93.1% in step 2, and 57.1%, 98.0%, 95.4% in step3, respectively. The accuracy for assessing N stage was 64.8% in step 1, 80.2% in step 2, and 85.7% in step 3. Conclusion: interpreting PET/CT, consideration of calcification and shape of the FDG uptake margin along with maxSUV can improve the diagnostic accuracy for assessing malignant involvement and N stage of hilar and mediastinal LNs in NSCLC.

Studies on the Standardization of Chinese Cabbage Kimchi (배추김치의 표준화 연구)

  • Cho, Eun-Ju;Lee, Seon-Mi;Rhee, Sook-Hee;Park, Kun-Young
    • Korean Journal of Food Science and Technology
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    • v.30 no.2
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    • pp.324-332
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    • 1998
  • In order to standardize the chinese cabbage kimchi, the preparation method, kinds of ingredients and levels of the ingredients were determined by the statistical survey of literatures obtained from cooking books, scientific papers and kimchi manufacturing factory. The standardized ingredient kinds and ratio of chinese cabbage kimchi were $13.0{\pm}7.0$ of radish, $2.0{\pm}0.5$ of green onion, $3.5{\pm}0.8\;or\;2.5{\m}0.3$ of red pepper powder, $1.4{\pm}0.4$ of garlic, $0.6{\pm}0.3$ of ginger, $2.2{\pm}1.6$ of anchovy juice, and $1.0{\pm}0.3$ of sugar in the proportion of 100 salted chinese cabbage, and the final salt concentration was adjusted to 2.7% using salt. Red pepper powder level was quite different from the literature sources, so sensory evaluation, chemical properties and antimutagenic effect and growth inhibitory effect on human cancer cells of the kimchi samples were studied to decide the proper ratio of the red pepper powder as an ingredient. Red pepper powder 3.5% (average level for kimchi manufacturing factory) added kimchi was better in quality than red pepper powder 2.5% (average level for cooking books and scientific papers) added kimchi in sensory evaluation and chemical properties. The juice of red pepper powder 3.5% added kimchi showed not only the stronger antimutagenicity against aflatoxin $B_1$ in Salmonella typhimurium TA100 but also the higher inhibitory effect on the growth of AGS human gastric adenocarcinoma cells in SRB assay than that of red pepper powder 2.5% added kimchi. In conclusion, the standardized ratio of the ingredients was 13.0 radish, 2.0 green onion, 3.5 red pepper powder, 1.4 garlic, 0.6 ginger, 2.2 anchovy juice, 1.0 sugar, and 2.7 final salt concentration in the proportion of 100 salted chinese cabbage.

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Anti-Cell Adhesion Effect of Animal Cell with Regional Special Natural Products of Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus (지역 특산 천연산물 전호, 파고지, 희첨 및 산수유의 동물세포간의 부착 억제효과)

  • Shin, Jin-Hyuk;Cha, Gu-Yong;Kim, Hui-Jin;Hwang, Jae-Ho;Han, Kyeong-Ho;Seo, Hyo-Jin;Kim, Min-Yong;Oh, Suk-Jung;Kim, Jong-Deog
    • KSBB Journal
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    • v.24 no.6
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    • pp.541-548
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    • 2009
  • For investigation of anti-angiogenesis mechanism of Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus, anti-cell adhesion experiment was performed. The adhesion of U937 cells to IL-$1\beta$-stimulated HUVECs was completely suppressed by 276% at 0.2 mg/L of Anthrisci radix, 220% at 5 mg/L of Psoraleae semen, 158% at 10 mg/L of Siegesbeckiae herba and 132% at 20 mg/L of Corni fructus, respectively. And the adhesion of PMA-chemical stimulated U937 cells to HUVECs, it was inhibited 139% at 0.2 mg/L of Anthrisci radix, 442% at 5 mg/L of Psoraleae semen, 720% at 10 mg/L of Siegesbeckiae herba and 664% at 20 mg/L of Corni fructus. Also, the adhesion of chemical stimulated U937 cells to IL-$1\beta$/chemical stimullated HUVECs, it was inhibited by 286% at 0.2 mg/L of Anthrisci radix, 146% at 5 mg/L of Psoraleae semen, 436% at 10 mg/L of Siegesbeckiae herba and 297% at 20 mg/L of Corni fructus, respectively. It would be a useful substance for anti-cell adhesion based on anti-angiogenesis for anti-obesity and anti-cancer.

Dose Verification Study of Brachytherapy Plans Using Monte Carlo Methods and CT Images (CT 영상 및 몬테칼로 계산에 기반한 근접 방사선치료계획의 선량분포 평가 방법 연구)

  • Cheong, Kwang-Ho;Lee, Me-Yeon;Kang, Sei-Kwon;Bae, Hoon-Sik;Park, So-Ah;Kim, Kyoung-Joo;Hwang, Tae-Jin;Oh, Do-Hoon
    • Progress in Medical Physics
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    • v.21 no.3
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    • pp.253-260
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    • 2010
  • Most brachytherapy treatment planning systems employ a dosimetry formalism based on the AAPM TG-43 report which does not appropriately consider tissue heterogeneity. In this study we aimed to set up a simple Monte Carlo-based intracavitary high-dose-rate brachytherapy (IC-HDRB) plan verification platform, focusing particularly on the robustness of the direct Monte Carlo dose calculation using material and density information derived from CT images. CT images of slab phantoms and a uterine cervical cancer patient were used for brachytherapy plans based on the Plato (Nucletron, Netherlands) brachytherapy planning system. Monte Carlo simulations were implemented using the parameters from the Plato system and compared with the EBT film dosimetry and conventional dose computations. EGSnrc based DOSXYZnrc code was used for Monte Carlo simulations. Each $^{192}Ir$ source of the afterloader was approximately modeled as a parallel-piped shape inside the converted CT data set whose voxel size was $2{\times}2{\times}2\;mm^3$. Bracytherapy dose calculations based on the TG-43 showed good agreement with the Monte Carlo results in a homogeneous media whose density was close to water, but there were significant errors in high-density materials. For a patient case, A and B point dose differences were less than 3%, while the mean dose discrepancy was as much as 5%. Conventional dose computation methods might underdose the targets by not accounting for the effects of high-density materials. The proposed platform was shown to be feasible and to have good dose calculation accuracy. One should be careful when confirming the plan using a conventional brachytherapy dose computation method, and moreover, an independent dose verification system as developed in this study might be helpful.

Retention Characteristics of Tc-99m-Pullulan-Derivatives in CT26 Tumor of Mice (마우스 CT26 종양에서 Tc-99m 표지 플루란유도체의 저류 특성)

  • Heo, Young-Jun;Song, Ho-Chun;Bom, Hee-Seung;Na, Kun;Kim, Seong-Min
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.6
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    • pp.393-401
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    • 2003
  • Objective: Pullulan derivatives (PD) can be used to make self-assembled hydrogel nanoparticles which are responsive to ionic strength. The aim of this study is to evaluate the potential of PD as a retaining carrier of radioisotope inside tumors. Materials and Methods: Four types of PD were evaluated which included pullulan acetate (PA), succinylated PA (SPA), PA-DTPA and SPA-DTPA conjugates. They were radiolabeled with Tc-99m. Labelling efficiencies were determined at 30 min, 1, 2, 4 and 12 hours after radiolabeling. CT-25 colon cancer cells were subcutaneously injected into Balb/c mice. After 2 weeks of subcutaneous injection, Tc-99m-labelled PD (Tc-99m-PD) were injected into the tumors. Whole body images of mice were obtained at 30 min, 1, 2, and 12 hr after intratumoral injection. All twenty mice were grouped into four groups by largest diameter; control A (largest diameter = 5 mm, n = 5), control B (largest diameter = 10 mm, n = 5), pullulan A (largest diameter = 5 mm, n = 5), pllulan B (largest diameter = 10 mm, n = 5). Dynamic images were obtained for 1 hour after intratumoral injection. Static images were obtained at 1 hr, 2 hr, 3 hr and 4 hr after intratumoral injection with Tc-99m pertechnetate and Tc-99m-PA. Target-to-background ratios and retention rates were calculated. Results: Labeling efficiencies of PA, SPA, PA-DTPA and SPA-DTPA were $94.5{\pm}5.9%,\;97.8{\pm}3.5%\;94.2{\pm}3.8%,\;and\;92.5{\pm}6.2%$, respectively (p>0.05). Percent retention rates (%RR) of PA and PA-DTPA were significantly higher than those of control, however, those of SP-DTPA and SPA became similar to control at 4 and 12 hr, respectively. %RR of pullulan A and pullulan B at 1, 4 and 8 hr is significantly higher than that of control (p < 0.05). However, %RR between pullulan A and pullulan B were similar. Conclusion: The lonic strength dependent PD-nanoparticles are retained in the tumor. No difference of %RR according to tumor size was noted. Therapeutic application of PD labelled with beta- or alpha- emitting radionuclides can be expected.

Aideo-Assisted Thoracic Surgery in Pleural Adhesion (늑막유착을 동반한 질환에서의 비디오 흉부수술)

  • Seong, Suk-Hwan;Kim, Hyeon-Jo;Lee, Chang-Ha;Kim, Ju-Hyeon
    • Journal of Chest Surgery
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    • v.29 no.8
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    • pp.916-922
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    • 1996
  • In patients with pleural adhesion, video-assisted thoracic surgery (VATS) has been regarded as a contra- indication. When such adhesions were found during a thoracoscopic trial, the thoracotomy proceeded with for fear of parenchymal Injury and bleeding. We had a question whether or not thoracoscopic surgery should be done in such pleural adhesions. Of the 226 consecutive thoracoscopic surgeries from Jul. 1992 through Sep. 1995, pleural adhesions were detected intraoperatively in 50 cases (22.1%): a detailed breakdown is as follows: pneumothorax (16 cases), pleural disease (15), benign pulmonary nodule(7), mediastinal mass(5), hyperhidrosis (2), diffuse parenchymal or interstitial lung disease (2), bronchiectasis(2), and primary lung cancer(1). We classified pleural adhesions according to their extent and severity. Extent is categorized as the involved area of the lung: degree 1, II, or III; severity is given one of four grades: mild, moderate, severe, or ve y severe. In cases of very severe severity requiring decortication, the possibility of VATS was excluded. Of the 50 cases, mild adhesions were detected in 15 cases(30.0%), moderate in 29 (58.0%), and severe in 6 (12.0%). As for the extent of the adhesions, 8 cases (16.0%) were categorized as degree 1, 32 cases (64. 0%) as degree II, and 10 cases (20.0%) as degree III. For patients with pleural adhesions, the operation time, the chest tube indwelling time, and the postoperative hospital stay were all longer than for patients in the non-adhesion group. Postoperative complications, namely prolonged air-leakage and pleural drain- age, were more common (18.0% and 6.0%, respectively) than in the non-adhesion group (5.1% and 1.7%, respectively). Only two bronchiectatic patients (4%) were converted to an open thoracotomy because of in- ability to control bleeding. Although complications were encountered more frequently in the group with adhesions, patients were still able to enjoy the benefi s of thoracoscopic surgery. It is advisable to proceed with thoracoscopic surgery even in cases of unpredicted pleural adhesions.

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Inhibitory Mechanisms of Cell Cycle Regulation Induced by Indole-3-carbinol in Hepatocellular Carci-noma HepG2 Cells. (간암 세포주에서의 Indole-3-Carbinol에 의해 유도되는 세포주기 억제 기전)

  • 김동우;이광수;김민경;조율희;이철훈
    • Microbiology and Biotechnology Letters
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    • v.29 no.3
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    • pp.181-185
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    • 2001
  • The naturally occurring chemical indole-3-carbinol (13C), found in vegetables of the Brassica genus, is a promising anticancer agent that was shown previ- ously to induce a Gl cell cycle arrest of human breast cancer cell lines, independent of estrogen receptor signaling. The anticancer activity of 13C and the possible mechanisms of its action were explored in a human hepatocellular carcinoma cell line, HepG2. Treatment of HepG2 cells with 13C suppressed the growth of the cells. The growth sup- pression caused by 13C ($IC_{50}$/: 444$\mu$M) was found to be partially due to its ability to stop the cell cycle in HepG2 cells. Western blot analysis for the Gl phase artiest demonstrated that the expression-levels of cyclin-dependent kinase (Cdk4, Cdk6) and cyclic D were reduced strongly after treatment of Hep72 cells with 13C (4007M) for 24- 72 hrs. Furthermore, I3C selectively abolished the expression of Cdk6 in a dose- and time-dependent manner, and accordingly, inhibited the phosphorylation of retinoblastoma. Interestingly, after the HepG2 cells reached their max- imal growth arrest, the level of the p21, a well-known Cdk inhibitor, increased significantly. Therefore, it could be considered that the Gl arrest of HepG2 cells treated with 13C was due to the indirect inhibition of Cdk4/6 activities by p21 Western blot analysis for G2/M phase arrest of demonstrated the levels of Cdc2 and cyclin Bl werer reduced dramatically after the treatment of HepG2 cells with 13C ($40\mu$M) for 24-72 hrs. flow cytometry of propidium iodide-stained HepG2 cells revealed that 13C induces a Gl (53%,72hr incubation) and G2 (25%,24hr incubation) cell cycle arrest. Thus, our observations have uncovered a previously undefined antiproliferative pathway for r3C that implicates Cdk4/6 and Cdc2 as a target for cell cycle control in human HepG2 cells. However, the 13C-medi- ated cell cycle arrest and repression of Cdk4/6 production did not affect the apoptotic induction of HepG2 cell.

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