• Molecules and Cells
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• v.39 no.12
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• pp.877-887
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• 2016

Tazarotene-induced gene 1 (TIG1) is a retinoic acid-inducible protein that is considered a putative tumor suppressor. The expression of TIG1 is decreased in malignant prostate carcinoma or poorly differentiated colorectal adenocarcinoma, but TIG1 is present in benign or well-differentiated tumors. Ectopic TIG1 expression led to suppression of growth in cancer cells. However, the function of TIG1 in cell differentiation is still unknown. Using a yeast two-hybrid system, we found that transmembrane protein 192 (TMEM192) interacted with TIG1. We also found that both TIG1A and TIG1B isoforms interacted and co-localized with TMEM192 in HtTA cervical cancer cells. The expression of TIG1 induced the expression of autophagy-related proteins, including Beclin-1 and LC-3B. The silencing of TMEM192 reduced the TIG1-mediated upregulation of autophagic activity. Furthermore, silencing of either TIG1 or TMEM192 led to alleviation of the upregulation of autophagy induced by all-trans retinoic acid. Our results demonstrate that the expression of TIG1 leads to cell autophagy through TMEM192. Our study also suggests that TIG1 and TMEM192 play an important role in the all-trans retinoic acid-mediated upregulation of autophagic activity.

• Molecules and Cells
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• v.41 no.6
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• pp.562-574
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• 2018

The tazarotene-induced gene 1 (TIG1) protein is a retinoidinducible growth regulator and is considered a tumor suppressor. Here, we show that DnaJ heat shock protein family member C8 (DNAJC8) is a TIG1 target that regulates glycolysis. Ectopic DNAJC8 expression induced the translocation of pyruvate kinase M2 (PKM2) into the nucleus, subsequently inducing glucose transporter 1 (GLUT1) expression to promote glucose uptake. Silencing either DNAJC8 or PKM2 alleviated the upregulation of GLUT1 expression and glucose uptake induced by ectopic DNAJC8 expression. TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. In conclusion, TIG1 acts as a pivotal repressor of DNAJC8 to enhance glucose uptake by partially regulating PKM2 translocation.

• Korean Journal of Medicinal Crop Science
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• v.27 no.2
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• pp.143-150
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• 2019

Background: Skin is an organ that protects the human body from various environmental stimuli that can induce immune system activation. Skin aging can be largely divided into two categories: physiological aging, which is caused by the a decreased physiological function of the skin and structural changes with aging, and photoaging, which is caused by the chemical stress induced by external stimuli such as ultraviolet (UV) radiation. Methods and Results: The objective of this study was to investigate the anti-wrinkle and UV protective effect of catechin-rich green tea extract (CGTE) in activated keratinocyte (HaCaT cells) and UV-induced skin damage in hairless mice. The results showed that CGTE inhibits the tumor necrosis factor-alpha interferon-gamma ($TNF-{\alpha}+IFN-{\gamma}$)-induced expression of matrix metalloproteinase (MMP)-1 in HaCaT cells. In addition, the CGTE treatment significantly reduced wrinkle formation, epidermal thickness, collagen deposition, and transepidermal water loss in dorsal skin irradiated with UVB. However, the ${\beta}$-glucosidase activity was significantly increased. The CGTE treatment inhibits mRNA expression and enzyme activity of MMP-2 and MMP-9 in the dorsal skin irradiated with UVB. Conclusions: It is expected that CGTE can be effectively used as a functional food and cosmetic ingredient to improve skin moisture retention and reduce wrinkle formation.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.303-310
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• 1991

Nineteen patients with previously untreated invasive squamous cell carcinoma of the uterine cervix were treated by irradiation alone at the Keimyung University Hospital from January, 1990 to July, 1991. The serial samplings of the tissue taken before and during radiation of the uterine cervix were studied by light and electron microscopic examination. Radiation-induced cellular changes, particularly nuclear degeneration was pronounced. The tumor invasion pattern remained unchanged but the number of mitosis and tumor cells decreased, The number of infiltrating inflammatory cells, multinucleated giant cells and karyolytic cells were increased with radiation. Fibrosis was also increased. Electron microscopically, the amount of tonofilament in the tissue samplings was increased in the postirradiated state, but the desmosomes were decreased in numbers. Fibroblasts began to appear after an irradiation dose of 2700 cGy. After an irradiation dose of 3000 cGy or more, tumor cells were nearly completely degenerated and displaced with mature fibrotic tissue. There was an increase of activated fibroblasts and collagen fibers but a decrease of inflammatory cells in the interstitial tissue. Swelling of the mitochondria and endoplasmic reticulum, loss of intercellular bridges and an increased number of secondary lysosomes were also found with radiation.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.1-10
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• 2000

Purpose : Although using the high energy Photon beam with conventional Parallel-opposed beams radiotherapy for nasopharyngeal carcinoma, radiation-induced xerostomia is a troublesome problem for patients. We conducted this study to explore a new parotid gland sparing technique in 3-D conformal radiotherapy (3-D CRT) in an effort to prevent the radiation-induced xerostomia. Materials and Methods : We peformed three different planning for four clinically node-negative nasopharyngeal cancer patients with different location of tumor(intracranial extension, nasal cavity extension, oropharyngeal extension, parapharyngeal extension), and intercompared the plans. Total prescription dose was 70.2 Gy to the isocenter. For plan-A, 2-D parallel opposing fields, a conventional radiotherapy technique, were employed. For plan-B, 2-D parallel opposing fields were used up until 54 Gy and afterwards 3-D non-coplanar beams were used. For plan-C, the new technique, 54 Gy was delivered by 3-D conformal 3-port beams (AP and both lateral ports with wedge compensator; shielding both superficial lobes of parotid glands at the AP beam using BEV) from the beginning of the treatment and early spinal cord block (at 36 Gy) was peformed. And bilateral posterior necks were treated with electron after 36 Gy. After 54 Gy, non-coplanar beams were used for cone-down plan. We intercompared dose statistics (Dmax, Dmin, Dmean, D95, DO5, V95, VOS, Volume receiving 46 Gy) and dose volume histograms (DVH) of tumor and normal tissues and NTCP values of parotid glands for the above three plans. Results : For all patients, the new technique (plan-C) was comparable or superior to the other plans in target volume isodose distribution and dose statistics and it has more homogenous target volume coverage. The new technique was most superior to the other plans in parotid glands sparing (volume receiving 46 Gy: 100, 98, 69$\%$ for each plan-A, B and C). And it showed the lowest NTCP value of parotid glands in all patients (range of NTCP; 96$\~$100$\%$, 79$\~$99$\%$, 51$\~$72$\%$ for each plan-A, B and C). Conclusion : We conclude that the new technique employing 3-D conformal radiotherapy at the beginning of radiotherapy and cone down using non-coplanar beams with early spinal cord block is highly recommended to spare parotid glands for node-negative nasopharygeal cancer patients.

• Journal of Korean Neurosurgical Society
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• v.42 no.3
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• pp.200-204
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• 2007

Objective : Radiation therapy is an important treatment for brain tumor. However, serious complications such as radiation necrosis can occur and it may be secondary to the expression of acute phase genes, like cytokines. In particular, inflammatory cytokines (IL-$1{\beta}$, TNF-${\alpha}$) and other immunomodulatory cytokines (TNF-${\alpha}$, TGF-${\beta}1$) might be changed after irradiation (high single dose irradiation). Although it has been reported that IL-1 level is remarkably elevated within 8 week after the irradiation to the rat brain. the change of cytokines levels at acute phase (within 24 hours) has not been reported. In the present study, we examined TNF-${\alpha}$, TGF-${\beta}1$, and IL-$1{\beta}$ levels in acute phase to clarify the early effect of cytokines on the radiation-induced brain damage. Methods : Fifty Sprague-Dawley rats were used and these were divided into irradiation group and control group. After a burr-hole trephination on the right parietal area using a drill, a single 10Gy was irradiated at the trephined site. Their forebrains were extirpated at 30 min, 2 hr, 8 hr, 12 hr and 24 hr, respectively and examined for the expression of TNF-${\alpha}$, TGF-${\beta}1$, and IL-$1{\beta}$. Results : The expression of TNF-${\alpha}$ and TGF-${\beta}1$ were decreased until 12 hr after irradiation but elevated thereafter. The expression of IL-1 was peak at 8 hr and then decreased until 12 hr but elevated after this time window. The present study indicated that expression of cytokines (TNF-${\alpha}$, TGF-${\beta}1$ and IL-$1{\beta}$) were increased at 24 hr after the irradiation to the rat brain. IL-$1{\beta}$ level, on the other hand. reached peak at 8 hr after radiation injury. Conclusion : These findings indicate that IL-1, among various cytokines, may have a more important role in the inflammatory reaction by radiation injury at acute phase and provide some clues for better understanding of the pathogenesis of radiation injury.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.41-52
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• 2002

Purpose : 3D conformal radiotherapy, the optimum dose delivered to the tumor and provided the risk of normal tissue unless marginal miss, was restricted by organ motion. For tumors in the thorax and abdomen, the planning target volume (PTV) is decided including the margin for movement of tumor volumes during treatment due to patients breathing. We designed the respiratory gating radiotherapy device (RGRD) for using during CT simulation, dose planning and beam delivery at identical breathing period conditions. Using RGRD, reducing the treatment margin for organ (thorax or abdomen) motion due to breathing and improve dose distribution for 3D conformal radiotherapy. Materials and Methods : The internal organ motion data for lung cancer patients were obtained by examining the diaphragm in the supine position to find the position dependency. We made a respiratory gating radiotherapy device (RGRD) that is composed of a strip band, drug sensor, micro switch, and a connected on-off switch in a LINAC control box. During same breathing period by RGRD, spiral CT scan, virtual simulation, and 3D dose planing for lung cancer patients were peformed, without an extended PTV margin for free breathing, and then the dose was delivered at the same positions. We calculated effective volumes and normal tissue complication probabilities (NTCP) using dose volume histograms for normal lung, and analyzed changes in doses associated with selected NTCP levels and tumor control probabilities (TCP) at these new dose levels. The effects of 3D conformal radiotherapy by RGRD were evaluated with DVH (Dose Volume Histogram), TCP, NTCP and dose statistics. Results : The average movement of a diaphragm was 1.5 cm in the supine position when patients breathed freely. Depending on the location of the tumor, the magnitude of the PTV margin needs to be extended from 1 cm to 3 cm, which can greatly increase normal tissue irradiation, and hence, results in increase of the normal tissue complications probabiliy. Simple and precise RGRD is very easy to setup on patients and is sensitive to length variation (+2 mm), it also delivers on-off information to patients and the LINAC machine. We evaluated the treatment plans of patients who had received conformal partial organ lung irradiation for the treatment of thorax malignancies. Using RGRD, the PTV margin by free breathing can be reduced about 2 cm for moving organs by breathing. TCP values are almost the same values $(4\~5\%\;increased)$ for lung cancer regardless of increasing the PTV margin to 2.0 cm but NTCP values are rapidly increased $(50\~70\%\;increased)$ for upon extending PTV margins by 2.0 cm. Conclusion : Internal organ motion due to breathing can be reduced effectively using our simple RGRD. This method can be used in clinical treatments to reduce organ motion induced margin, thereby reducing normal tissue irradiation. Using treatment planning software, the dose to normal tissues was analyzed by comparing dose statistics with and without RGRD. Potential benefits of radiotherapy derived from reduction or elimination of planning target volume (PTV) margins associated with patient breathing through the evaluation of the lung cancer patients treated with 3D conformal radiotherapy.

• Journal of Radiation Protection and Research
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• v.3 no.1
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• pp.6-22
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• 1978

High energy electron beams took effect for tumor radio-therapy, however, had a lot of problems in clinical application because of various conversion factors and complication of physical reactions. Therefor, we had experimentally studied the important properties of high energy electron beams from the linear accelerator, LMR-13, installed in Yonsei Cancer Center. The results of experimental studies on the problems in the 8, 10, 12 Mev electron beam therapy were reported as following. 1. On the measurements of the outputs and absorbed doses, the ionization type dosimeters that had calibrated by $^{90}Sr$ standard source were suitable as under 3% errors for high energy electrons to measure, but measuring doses in small field sizes and the regions of rapid fall off dose with ionization chambers were difficult. 2. The electron energy were measured precisely with energy spectrometer consisted of magnet analyzer and tele-control detector and the practical electron energy was calculated under 5% errors by maximum range of high energy electron beam in the water. 3. The correcting factors of perturbated dose distributions owing to radiation field, energy and material of the treatment cone were checked and described systematically and variation of dose distributions due to inhomogeneous tissues and sloping skin surfaces were completely compensated. 4. The electron beams, using the scatterers; ie., gold, tin, copper, lead, aluminium foils, were adequately diffused and minimizing the bremsstrahlung X-ray induced by the electron energy, irradiation field size and material of scatterers, respectively. 5. Inproving of the dose distribution from the methods of pendulum, slit, grid and focusing irradiations, the therapeutic capacity with limited electron energy could be extended.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6279-6284
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• 2015

Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) is an important cancer in the Great Mekong region, particularly in Thailand. Limitations of treatment options and the lack of an effective diagnostic tool for early detection of CCA are major concerns for the control of this type of cancer. The aim of the study was to investigate anti-CCA activity of the ethanolic extract of Atractylodes lancea (Thunb.) DC., and the applicability of positron emission tomography-computed tomography (PET-CT) as a tool for detection and monitoring the progression of CCA in Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN)-induced CCA hamsters. Male Syrian hamsters were used for toxicity tests and anti-CCA activity evaluation. Development of CCA was induced by initial feeding of 50 metacercariae of OV, followed by drinking water containing 12.5 ppm of DMN in hamsters. The ethanolic extract of A. lancea (Thunb.) DC. was administered orally for 30 days. PET-CT was performed every 4 weeks after initiation of CCA using 18F-fluorodeoxyglucose ($^{18}F-FDG$). Results from the present study suggest that the ethanolic extract of A. lancea (Thunb.) DC. rhizome exhibited promising anti-CCA activity and safety profile in the OV/DMN-induced hamster model. To successfully apply PET-CT as a tool for early detection of tumor development and progression, modification of radiolabeling approach is required to improve its specificity for CCA cells.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.40-54
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• 2004

Purpose : Captopril (angiotension converting enzyme inhibitor) is known to have a radioproptective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotectlve efiect and mechanism of captopril on the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. Materials and Methods : The histopathological changes and immunohistochemical stains ($TNF{\alpha}$, $TGF{\beta}1$, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. Results : In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial $TNF-{\alpha}$ and $TGF-{\beta}1$ in the radiation alone group continuously increased. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of $TNF-{\alpha}$ in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). Conclusion : This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.