• Title/Summary/Keyword: Radiation Necrosis

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Downregulation of $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation in human keratinocytes by melanogenic inhibitors

  • Ahn, Kwang-Seok;Lee, Jinseon;Kim, Yeong-Shik
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.780-803
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    • 2003
  • Exposure of skin cells, particularly keratinocytes to various nuclear factor-kappaB ($\textrm{NF}_{-{\kappa}}\textrm{B}$) activators [e.g. tumor necrosis factor-$\alpha$, interleukin-1, lipopolysaccharides, and ultraviolet light] leads to phosphorylation and degradation of the inhibitory protein, $\textrm{I}_{{\kappa}}\textrm{B}$. Liberated $\textrm{NF}_{-{\kappa}}\textrm{B}$ is translocated into the nucleus where it can change or alter expression of target genes, resulting in the secretion of extracellular signaling molecules including melanotrophic factors affecting melanocyte. In order to demonstrate the possible role of $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation on the synthesis of melanotrophic factors from the keratinocytes, the activities of $\textrm{NF}_{-{\kappa}}\textrm{B}$ induced by melanogenic inhibitors (MIs) were determined in human HaCaT keratinocytes transfected with $\textrm{pNF}_{-{\kappa}}\textrm{B}$-SEAP-NPT plasmid. Transfectant cells released the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the $\textrm{NF}_{-{\kappa}}\textrm{B}$ activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selection marker for geneticin resistance. MIs such as niacinamide, kojic acid, hydroquinone, resorcinol, arbutin, and glycolic acid were preincubated with transfectant HaCaT cells for 3 h and then ultraviolet B (UVB) was irradiated. $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation was measured with the SEAP reporter gene assay using a fluorescence detection method. Of the Mis tested, kojic acid ($IC_{50}$/ = 60 $\mu$M) was found to be the most potent inhibitor of UVB-upregulating $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation in transfectant HaCaT cells, which is followed by niacinamide ($IC_{50}$/= 540 $\mu$M). Pretreatment of the transfectant HaCaT cells with the Mis, especially kojic acid and niacinamide, effectively lowered $\textrm{NF}_{-{\kappa}}\textrm{B}$ binding measured by electrophoretic mobility shift assay. Furthermore, these two inhibitors remarkably reduced the secretion level of IL-6, one of melanotrophic factors, triggered by UV-radiation of the HaCaT cells. These observations suggest that Mis working at the in vivo level might act partially through the modulation of the synthesis of melanotrophic factors in keratinocyte.

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Central, Extraventricular and Atypical Neurocytomas: a Clinicopathologic Study of 35 Cases from Pakistan Plus a Detailed Review of the Published Literature

  • Ahmad, Zubair;Din, Nasir Ud;Memon, Aisha;Tariq, Mohammad Usman;Idrees, Romana;Hasan, Sheema
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1565-1570
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    • 2016
  • Background: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas. Aim: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors. Materials and Methods: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015. Results: Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer-Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.

Salvage of Infected Breast Implants

  • Song, Joon Ho;Kim, Young Seok;Jung, Bok Ki;Lee, Dong Won;Song, Seung Yong;Roh, Tai Suk;Lew, Dae Hyun
    • Archives of Plastic Surgery
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    • v.44 no.6
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    • pp.516-522
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    • 2017
  • Background Implant-based breast reconstruction is being performed more frequently, and implants are associated with an increased risk of infection. We reviewed the clinical features of cases of implant infection and investigated the risk factors for breast device salvage failure. Methods We retrospectively analyzed 771 patients who underwent implant-based breast reconstruction between January 2010 and December 2016. Age, body mass index, chemotherapy history, radiation exposure, and smoking history were assessed as potential risk factors for postoperative infection. We also evaluated the presence and onset of infection symptoms, wound culture pathogens, and other complications, including seroma, hematoma, and mastectomy skin necrosis. Additionally, we examined the mastectomy type, the use of acellular dermal matrix, the presence of an underlying disease such as hypertension or diabetes, and axillary node dissection. Results The total infection rate was 4.99% (58 of 1,163 cases) and the total salvage rate was 58.6% (34 of 58). The postoperative duration to closed suction drain removal was significantly different between the cellulitis and implant removal groups. Staphylococcus aureus infection was most frequently found, with methicillin resistance in 37.5% of the cases of explantation. Explantation after infection was performed more often in patients who had undergone 2-stage expander/implant reconstruction than in those who had undergone direct-to-implant reconstruction. Conclusions Preventing infection is essential in implant-based breast reconstruction. The high salvage rate argues against early implant removal. However, when infection is due to methicillin-resistant S. aureus and the patient's clinical symptoms do not improve, surgeons should consider implant removal.

Effect of retinoic acid on the radiosensitivity of normal human oral keratinocyte (Retinoic acid가 사람 정상 구강각화세포의 방사선감수성에 미치는 영향에 관한 연구)

  • Lee Jean;Heo Min-Suk;Lee Sam-Sun;Oh Sung-Ook;Lee Sul-Mi;Choi Hang-Moon;Choi Soon-Chul;Park Tae-Won
    • Imaging Science in Dentistry
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    • v.33 no.2
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    • pp.97-105
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    • 2003
  • Purpose : To evaluate the effect of all-trans-retinoic acid (ATRA) on the radiosensitivity of normal human oral keratinocyte (NHOK). Materials and methods: Relative cell survival fraction including SF2 (survival fraction at 2 Gy) was calculated on the basis of colony formation assay. Data were fitted to the linear-quadratic model to establish the survival curve and calculate α and β values. Using flow cytometry at 1, 2, 3, 4, and 5 days after exposure to 2 and 10 Gy irradiation, cell cycle arrest and apoptosis were analysed. To understand the molecular mechanism of the radiosensitization of ATRA on NHOK, proteins related with apoptosis and cell cycle arrest were investigated by Western blot analysis. Results: Treatment with ATRA resulted in a significant decrease of SF2 value for NHOK from 0.63 to 0.27, and increased α and β value, indicating that ATRA increased radiosensitivity of NHOK. ATRA increased LDH significantly, but increasing irradiation dose decreased LDH, suggesting that the radiosensitizing effect of ATRA is not directly related with increasing cell necrosis by ATRA. ATRA did not induce appotosis but increased G2 arrest after 10 Gy irradiation, implying that the increased radiosensitivity of NHOK may be due to a decrease in mitosis casued by increasing G2 arrest. ATRA inhibited the reduction of p53 at 3 days after l0Gy irradiation and increased p21 at 1 day after 10 Gy irradiation. Further study is required to determine the precise relationship between this effect and the radiosensitizing effect of A TRA. Conclusion: These results suggested that ATRA increase radiosensitivity by inhibiting mitosis caused by increasing G2 arrest.

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Fine Structure on the Pigment Epithelial Cell and the Bruch's Membrane of the Rat Retina after X-Irradiation (X-선 조사를 받은 흰쥐 망막의 색소상피세포와 기저복합층의 미세구조)

  • Ko, Jeong-Sik;Shin, Ki-Ho;Ahn, E.Tay;Yang, Nam-Gil;Park, Kyung-Ho;Kim, Jin-Gook
    • Applied Microscopy
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    • v.23 no.2
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    • pp.11-26
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    • 1993
  • This experiment was performed to study the morphological responses of the pigment epithelial cell and the Bruch's membrane of the retina of rat following X-ray irradiation. Male rats were divided into normal and experimental groups. The heads of the rats, under sodium thiopental anesthesia, were exposed to 3,000 rads or 6,000 rads of radiation in a single dose, respectively. The source was a Mitsubishi Linear Accelerator ML-4MV. The target to skin distance was 80cm, and the. dose rate was 200 rads/min. The experimental groups were sacrificed on the 6th hour, 2nd and 6th day after X-ray irradiation. Under anesthesia, 1% glutaraldehyde-1% paraformaldehyde solution(0.1M Millonig's phosphate buffer, pH 7.3) was perfused through the left ventricle and ascending aorta. Pieces of the tissue taken from the posterior region of the retina were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde(0.1M Millonig's phosphate buffer, pH 7.3) and 1% osmium tetroxide(0.1M Millonig's phosphate buffer, pH7.3), and embedded in araldite mixture. The ultrathin sections contrasted with uranyl acetate and lead citrate were observed with JEM 100 CX-II electron microscope. The results were as follow; 1. The morphological changes of the pigment epithelial cells were not pronounced after exposure to 3,000 rads of X-ray. But on the 6th hour after exposure to 6,000 rads of X-ray, bulging nuclear membrane protruding into the cytoplasm and nuclear chromatin clumped into numerous masses along the nuclear membrane were observed. At the 2nd and 6th day post-irradiation, partial cytolysis or necrosis were seen. 2. The thickness of the Bruch's membrane of the experimental groups were increased in the time and dose range covered by this study, and splitting or diffusing basal laminae of the choriocapillary layer were observed frequently in the experimental group. Above results suggest that large amount(6,000 rads) of head irradiation induce direct hazardous effects on the pigment epitherial cells and Bruch's membrane of the retina of the rat, but pigment epithelial cells are more radioresistant than Bruch's membrane.

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Effects of 166Holmium and 166Holmium-chitosan Complex(166Ho-CHICO) on Normal Brain of Rats (홀뮴 및 홀뮴-키토산 복합체가 정상 백서 뇌에 미치는 효과에 대한 연구)

  • Sun, Jing He;Joh, Chul W;Ahn, Young Hwan;Park, Chan Hee;Shim, Chull;Park, Kyung Bae;Cho, Kyung Gi
    • Journal of Korean Neurosurgical Society
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    • v.29 no.10
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    • pp.1309-1315
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    • 2000
  • Objectives : We performed an in vivo experiment to investigate the effect of $^{166}Holmium$ and $^{166}Holmium$-chitosan complex($^{166}Ho$-CHICO) on the normal brain of rats and to determine the sublethal dose of $^{166}Ho$-CHICO. Materials and Methods : $^{166}Ho$ is a beta and gamma ray emitter. $^{166}Ho$-CHICO is a novel radio-pharmaceutical complex with chitosan to facilitate the transport of $^{166}Ho$ obtained from Korea Atomic Energy Research Center(Taejon, Korea). It is in acidic form and becomes gel state at alkaline pH. One hundred and seventy consecutive rats were divided into four groups : $^{166}Ho$ treated(n=50), $^{166}Ho$-CHICO treated(n=57), saline treated(n=5) and chitosan treated(n=5) groups. $^{166}Ho$ and $^{166}Ho$-CHICO were injected into the rat brain stereotactically with various doses of 0.1mCi/$20{\mu}l$, 0.2mCi/$20{\mu}l$, 0.3mCi/$20{\mu}l$, and 0.4mCi/$20{\mu}l$ using an automated microinjector. Nuclear imaging, histopathological and hematological studies were performed in 10 rats in each group at 1 day, 3days, 7 days, 1 month and 3 months after the injections. Results : An infiltration of inflammatory cells and necrotic changes were noted in $^{166}Ho$ treated group at 1 week after the injection. A wedge-shaped tissue defect due to necrosis, lined with infiltrated glial cells in $^{166}Ho$ treated group and a cystic defect lined with reactive astroglial cells in $^{166}Holmium$-CHICO treated group at 3 months after the injection were observed. $^{166}Ho$ alone without chitosan leaked out and caused necrotic lesion on the cerebral surface but $^{166}Holmium$-CHICO treated group did not show this feature. As the dose of $^{166}Ho$ increased, the mortality rates were also increased. The mortality rate of the $^{166}Holmium$-CHICO group was higher than the $^{166}Ho$ treated group at a dose of 0.4mCi/$20{\mu}l$/300g. There was no detectable radioactivity due to the leakage or extravasation from the injected site of the brain on the scintigraphy performed at 1 hour, 24 hours and 48 hours after the injection. There was also no detectable activity of $^{166}Holmium$-CHICO in other organs including spleen, liver and kidney. Conclusions : $^{166}Ho$-CHICO did not leak out to the critical cortical surface of the brain from the injection site and induced radiation changes of the parenchyma around the injection site without cortical damage. The sublethal dose of $^{166}Ho$-CHICO for the normal brain in rats was determined to be 0.2mCi/$20{\mu}l$/300g.

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The Effects of Vitamin C on the Activity of Liver Enzymes and Hepatic Damage in Rats Treated with Radiation and Aflatoxin $B_1$ (Vitamin C가 방사선과 Aflatoxin $B_1$을 투여한 흰쥐의 간 기능 효소 활성 및 간 손상에 미치는 효과)

  • Kang, Jin-Soon
    • The Korean Journal of Food And Nutrition
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    • v.23 no.1
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    • pp.30-38
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    • 2010
  • This study was conducted to determine the effects of vitamin C on the activity of liver function enzymes and electromicrographic changes in white rats treated with aflatoxin $B_1(AFB_1)$ or X-ray and $AFB_1$. Six week-old male Sprague-Dawley rats were randomly divided into five groups: a control group, $AFB_1$ treated group, $AFB_1$ treated group with vitamin C, X-ray and $AFB_1$ co-treated group, X-ray and $AFB_1$ co-treated group with vitamin C. On the first day of the experiment, only one dose of X-rays was exposed to the entire liver at 1,500 cGy. Next, vitamin C was injected at 10 mg/kg body weight by intraperitoneal injection, followed 1 hr later by the administration of 0.4 mg/kg of $AFB_1$ by intraperitoneal injection. These treatments were then administered every three days over a period of 15 days. On the 16th day of treatments, the animals were sacrificed. Analysis of the activity of the liver function enzymes, GOT, ALK phatase and LDH, in the sera of rats revealed that they were somewhat increased by $AFB_1$ treatment, X-ray and $AFB_1$ co-treatment when compared to the control group. Furthermore, the activity of these enzymes decreased in response to administration of vitamin C. Especially, the levels of GOT were remarkably decreased in the $AFB_1$ treated group treated with vitamin C when compared to the group treated with $AFB_1$ alone(p<0.001). Electromicrographic analysis revealed cloudy swelling, necrosis, vesicular degeneration and fat accumulation of hepatocytes in response to treatment with $AFB_1$ or co-treatment with X-ray and $AFB_1$. However, the destruction of hepatic cells was considerably lower in the vitamin C-treated group. These results indicate that vitamin C had ameliorating effects on the hepatic cell damage.

Direct Intratumoral Injection of Ethanol in the Patients with Obstruction of Major Bronchus (주기관지 폐색환자에서 종양내 ETHANOL 주입치료 효과)

  • Lee, Bong-Chun;Yum, Ho-Kee;Choi, Soo-Jeon;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.5
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    • pp.495-500
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    • 1993
  • Background: For the relief of the occlusion of major bronchi, laser therapy, radiation therapy or combined therapy is generally used. But the effect of radiation therapy is very slow and not consistent and laser therapy requires expensive equipments and technical expertise with occasional serious side effects. Direct ethanol injection has been widely used for the control of bleeding in gastrointestinal lesion, esophageal varices or renal cell carcinoma with good results. So we tried direct injection of ethanol into the tumor to relieve the obstruction of major bronchus in 11 patients. Method: All procedures were done under the fiberoptic bronchoscopy with continuous oxygen supplement and aliquoted 0.5-1.0 ml of absolute ethanol directly into the tumor through the endobronchial aspiration needle. The tumor was endoscopically removed with a biopsy forceps immediately after ethanol injection. The whole procedure was repeated 3-4 days interval until the lumen opens. Usually after 2-3 trials of ethanol injection, the lumen opened up. Results: The immediate effect of ethanol injection was whitening of the mucosa and prompt cessation of bleeding. The late effect was necrosis of the tumor. The final results of this procedure were improvement of symptoms and reexpnasion of the lung in all patients. $FEV_{1.0}$ and FVC were improved and $PaO_2$ was increased from $68.1{\pm}9.2$ mmHg to $83.9{\pm}8.1$ mmHg, $SaO_2$: from $94{\pm}8.5%$ to $96.6{\pm}1.1%$, and $AaDO_2$ was reduced from $26.5{\pm}8.5$ mmHg to $10.9{\pm}9.1$ mmHg. Conclusion: Direct ethanol injection into the tumor tissue is a rapid, cheap and relatively safe method of relieving the complete occlusion of major bronchus.

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Preoperative Evaluation of Brain Lesion with $^{201}Tl$ Brain SPECT: Is It Useful to Differentiate Benign and Malignant Lesions? (수술 전 뇌 병변의 $^{201}Tl$ 뇌 SPECT: 양성과 악성 병변을 감별하는데 유용한가?)

  • Sohn, Hyung-Sun;Kim, Euy-Neyng;Kim, Sung-Hoon;Chung, Yong-An;Chung, Soo-Kyo;Bong, Yong-Gil;Lee, Youn-Soo
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.5
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    • pp.371-380
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    • 2000
  • Purpose: Thallim-201 ($^{201}Tl$) brain SPECT, which can represent cellular activity of brain lesions, may provide more useful information in differentiating between benign and malignant brain lesions more so than CT of MRI, that merely represents anatomic changes or breakdown of blood brain barrier. We used $^{201}Tl$ brain SPECT prospectively to evaluate the utility of $^{201}Tl$-indices as an indicator of benign or malig nant lesions. Materials and Methods: We studied 28 patients. There were 13 cases of benign lesions (3: nonspecific benign lesion, 3: meningioma, 2: low grade glioma, 1: tuberculoma, central neurocytoma, hemangioblastoma, radiation necrosis, and choroid plexus papilloma) and 15 cases of malignant lesions (6: glioblastoma multiforme, 5: anaplastic glioma, 2: medulloblastoma, 1: metastasis and lymphoma). In all patients, CT and/or MRI were obtained and then $^{201}Tl$ brain SPECT was obtained with measuring mean $^{201}Tl$ index and peak $^{201}Tl$ index. An unpaired t-test was performed to compare the $^{201}Tl$-indices and pathologic diagnoses to evaluate the utility of $^{201}Tl$-indices as all indicator of benign or malignant lesions. Results: There were no statistically significant difference in $^{201}Tl$-indices between benign and malignant brain lesion (p>0.05). Conclusion: These results demonstrated that we could not use $^{201}Tl$ indices on brain SPECT alone as an indicator of benign or malignant brain lesions.

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