• Title/Summary/Keyword: Tumor metabolism

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Expression of Endothelial Nitric Oxide Synthase in Benign Nodular Hyperplasia and Papillary Carcinoma of Human Thyroid Gland (인간의 갑상선 결절성 과증식증과 유두상 암종에서의 Endothelial Nitric Oxide의 발현)

  • Kim Young-Mo;Cho Jung-Il;Kim Yong-Jai;Yang Tae-Yong;Kim Dae-Hyung;Park Chang-Sin;Han Chang-Jun
    • Korean Journal of Head & Neck Oncology
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    • v.17 no.2
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    • pp.155-161
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    • 2001
  • Background and Objectives: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. This reaction is catalyzed by nitric oxide synthase (NOS). NO is an important bioactive agent and a signalling molecule that mediates a variety of biologic actions such as vasodilation, neurotransmission, host defense, and iron metabolism but increased NO production may also contribute to the pathogenesis of a various of disorders, including cancer. Before now, the role of NO in thyroid gland is still investigated and it was supposed that NO mediate the angiogenesis in tumor growth. Others journal and works identified the expression of iNOS that involve by neutrophil and eNOS that involve in part in the vascular remodeling and to understand the role of NO in human thyroid gland. But authors revealed only eNOS in thyroid neoplasm. iNOS was identifed by inflammation in fault. Materials and Methods: Western blot analysis was performed, using a polyclonal antibody against eNOS (Rabbit polyclonal IgG). Using the same antibody, the distribution of eNOS was examined in 15 formalin-fixed paraffin embedded samples by immunohistochemistry. By NADPH consumption rate, NOS activity was estimated at nodular hyperplasia. Results: Western blot analysis exhibited that eNOS was significantly elevated in thyroid papillary carcinoma, compared to that in nodular hyperplasia and normal tissue. Immunohistochemistry showed that the immunoreacitivity was present more significantly in thyroid follicular epithelial cell layer than vascular endothelial cell. NOS activity increased in nodular hyperplasia. Conclusions: Thyroid papillary cancer without neutrophil invasion expressed only eNOS. The endothelial localization of eNOS may play an important role in pathogenensis of human thyroid nodular hyperplasia and the follicular localization of thyroid papillary carcinomas.

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Study for Metabolism of Resistant Production in Anticancer drug Resistant Stomach Cancer Cell SNU-1 (항암제 내성 위암 세포주 SNU-1의 내성생성기전에 관한 연구)

  • Kim, Jung-Hye;Kang, Mi-Wha;Kim, Jae-Ryong
    • Journal of Yeungnam Medical Science
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    • v.6 no.2
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    • pp.195-205
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    • 1989
  • Development of drug resistance in tumors during treatment is a major factor limiting the clinical use of anticancer agents. When tumor cells acquire resistance to anticancer drug, they show cross-resistance to other antitumor agents. In the present study, SNU-1 cell was induced adriamycin $10^{-7}M$ drug resistance, SNU-1/ADR, in vitro culture system. We got the doubling time and number for viability test during 96 hours by MTT assay. To investigate the cross resistance of various anticancer drugs in human stomach cancer cell SNU-1 and SNU-1/ADR. We compared $IC_{50}$ (drug concentration of 50% reduction) and the relative resistance(RR). SNU-1/ADR was expressed multidrug resistant with vinblastine(RR ; 31.62), vincristine(RR ; 29.50), dactinomycin(RR ; 21.37), epirubicin(RR ; 17.78), daunorubicin(RR ; 14.12), adriamycin(RR ; 7.76), and etoposide(RR ; 4.46), and other drugs, 5-fluorouracil, cisplatin, cyclophosphamide, methotrexate, and aclarubicin, have not cross resistant with adriamycin. There was double minute chromosome in SNU-1/ADR by karyotyping although this change was not seen in SNU-1.

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A Case Report : TMJ Osteoarthritis in a Patient with Renal Osteodystrophy (턱관절의 골관절염을 동반한 신성골이영양증 환자 증례보고)

  • Lee, Gi-Ho
    • Journal of Oral Medicine and Pain
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    • v.38 no.3
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    • pp.247-253
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    • 2013
  • Renal osteodystrophy(RO) is characterized by skeletal changes in patients with renal disease and developed as a result of alterations in the metabolism of calcium, phosphate and secondary hyperparathyroidism. Bony changes in the craniofacial region include decreased bone density, radiolucent lesions(brown tumors), depletion of cortical bone and loss of lamina dura, but such changes rarely occur in the temporomandibular joint(TMJ). We report an uncommon case of bony changes and pain of both TMJs in a patient with RO. A 41-year-old man with RO came to our clinic due to TMJ pain and sounds. Occlusal change was also reported. Radiographs revealed degenerative changes of the both condyles. The patient had medical history of renal cancer therapy and hemodialysis. The patient was diagnosed with TMJ arthritis of RO and referred for systemic management through medication of calcium and vitamin D and parathyroidectomy. At 15-month follow-up, most of TMD symptoms disappeared and second radiographs revealed that bone density and cortical thickness of the mandible increased and the skeletal outline of the both condyles became relatively clear. As bony changes may begin in the early stage of the renal disease, dentists should be alert to detect the sign of the disease. In addition, it is important to differentiate TMJ arthritis of systemic cause because the treatment protocol is quite different.

Changes in mRNA Expression of Obesity-related Genes by GyeongshinhaeGihwan 1 (GGT1) in hGHTg (human growth hormone transgenic) obese Female Rats (암컷 hGHTg 비만 쥐에서 경신해지환(輕身解脂丸) (GGT1)에 의한 비만관련 유전자 mRNA 발현의 변화)

  • Yoon, Ki-Hyeon;Yoon, Mi-Chung;Kim, Hoon;Shin, Soon-Shik
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.2
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    • pp.383-387
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    • 2006
  • To investigate the effect of GyeongshinhaeGihwan 1(GGT1) frequently used as an anti-obesity herbal medicine in oriental medicine on the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese female rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), $PPAR{\gamma}$ (peroxisome proliferator activated receptor-gamma), $PPAR{\delta}$ (peroxisome proliferator activated receptor-delta), leptin, $TNF{\alpha}$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3-phosphate dehydrogenase) were analyzed by RT-PCR. Compared with control group, $PPAR{\gamma}$ mRNA levels of liver and kidney were decreased in both RD and GGT1 groups, and the effects were more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of lipid storage by decreasing the $PPAR{\gamma}$ expression. $PPAR{\delta}$ mRNA levels of adipose tissue were increased by RD and GGT1 compared with DW, and the magnitude of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating $PPAR{\delta}$ expression. GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite, than control and RD groups. However, The mRNA levels of leptin, LPL, and $TNF{\alpha}$ were not changed by GGT1. These results indicate that GGT1 can prevent obesity in hGHTg obese female rats by down-regulating and up-regulating the mRNA expression of $PPAR{\gamma}$ and $PPAR{\delta}$, respectively, and that this anti-obesity effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to inhibit obesity by increasing the circulating leptin levels.

Hypoallergenic and Physicochemical Properties of the A2 β-Casein Fractionof Goat Milk

  • Jung, Tae-Hwan;Hwang, Hyo-Jeong;Yun, Sung-Seob;Lee, Won-Jae;Kim, Jin-Wook;Ahn, Ji-Yun;Jeon, Woo-Min;Han, Kyoung-Sik
    • Food Science of Animal Resources
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    • v.37 no.6
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    • pp.940-947
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    • 2017
  • Goat milk has a protein composition similar to that of breast milk and contains abundant nutrients, but its use in functional foods is rather limited in comparison to milk from other sources. The aim of this study was to prepare a goat A2 ${\beta}$-casein fraction with improved digestibility and hypoallergenic properties. We investigated the optimal conditions for the separation of A2 ${\beta}$-casein fraction from goat milk by pH adjustment to pH 4.4 and treating the casein suspension with calcium chloride (0.05 M for 1 h at $25^{\circ}C$). Selective reduction of ${\beta}$- lactoglobulin and ${\alpha}_s$-casein was confirmed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and reverse-phase high-performance liquid chromatography. The hypoallergenic property of A2 ${\beta}$-casein fraction was examined by measuring the release of histamine and tumor necrosis factor alpha from HMC-1 human mast cells exposed to different proteins, including A2 ${\beta}$-casein fraction. There was no significant difference in levels of both indicators between A2 ${\beta}$-casein treatment and the control (no protein treatment). The A2 ${\beta}$-casein fraction is abundant in essential amino acids, especially, branched-chain amino acids (leucine, valine, and isoleucine). The physicochemical properties of A2 ${\beta}$-casein fraction, including protein solubility and viscosity, are similar to those of bovine whole casein which is widely used as a protein source in various foods. Therefore, the goat A2 ${\beta}$-casein fraction may be useful as a food material with good digestibility and hypoallergenic properties for infants, the elderly, and people with metabolic disorders.

Rutin Improves Bone Histomorphometric Values by Reduction of Osteoclastic Activity in Osteoporosis Mouse Model Induced by Bilateral Ovariectomy

  • Lee, Hye-Hwa;Jang, Jae-Won;Lee, Jung-Kil;Park, Choon-Keun
    • Journal of Korean Neurosurgical Society
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    • v.63 no.4
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    • pp.433-443
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    • 2020
  • Objective : Osteoporosis is a disease of unbalanced bone metabolism that results in low bone mineral density with increased bone fragility and propensity for fractures. The increased rate of bone fracture due to osteoporosis places a significant burden on public health care expenditures. Therefore, numerous studies have been designed and performed to identify the drugs or health foods that can improve the bone quality or quantity. This study was designed to evaluate and analyze the therapeutic effects of rutin on histomorphometric values of the spine and femur in an osteoporotic mouse model induced by bilateral ovariectomy. Methods : Thirty female ICR mice (8 weeks old) underwent either a sham operation (only abdominal incision, sham group, n=10) or bilateral ovariectomy (n=20). The ovariectomized (OVX) animals were randomly divided into two groups : untreated OVX group (OVX-C, n=10), or rutin-administered group (OVX-R, n=10). The OVX-C group received weight-adjusted doses of saline vehicle and the OVX-R group received 50 mg/kg of rutin intraperitoneally, starting 1 day after surgery. At 4 and 8 weeks after surgery, serum estrogen, osteocalcin, alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX-1) were analyzed. Interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α were also analyzed. Bone histomorphometric parameters of the 4th lumbar vertebra and femur were determined by micro-computed tomography. Results : In OVX-C group, ALP, osteocalcin, CTX-1, IL-1β, IL-6, and TNF-α levels were significantly increased at 4 and 8 weeks compared to sham operation group. Rutin administration after OVX statistically significantly reduced ALP, CTX-1, IL-1β, IL-6, and TNF-α levels at 4 and 8 weeks. Rutin administration also improves bone histomorphometric parameters including trabecular bone volume fraction, trabecular thickness, and trabecular number. Trabecular separation was also decreased in OVX-R group compared to OVX-C group. Conclusion : The present study demonstrated that rutin has therapeutic effects on improving bone histomorphometric values in an OVX mouse model. The improvement in histomorphometric values may be associated with the reduction of osteoclastic activity via inhibition of IL-1β, IL-6, and TNF-α. In future studies, the mechanism for the effect of rutin on osteoporosis should be demonstrated more clearly to use rutin in human osteoporosis.

A Study of Diabetic Control for Diabetic Patient in $^{18}F$-FDG PET ($^{18}F$-FDG PET 검사를 위한 당뇨 환자의 혈당 조절에 관한 연구)

  • Cha, Min-Kyeong;Nam, Ki-Pyo;Lee, Young-Hee;Choi, Jae-Min;Cho, Shee-Man
    • The Korean Journal of Nuclear Medicine Technology
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    • v.12 no.1
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    • pp.57-61
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    • 2008
  • Purpose: $^{18}F$-FDG PET is to evaluate the tumor using glucose metabolism. Blood Glucose Level (BGL) is important factor that affects on a result of examination. But it often appears the distort result on diabetic patient due to a failure of BGL control. The aim of this study is to make a effective guideline for diabetic patient prescribed $^{18}F$-FDG PET and improve accuracy and reliability of examination. Materials and methods: A subject of study is 69 diabetic patients and divided them into 3 groups; 1) BGL is less than 120 mg/dl & performed PET, 2) BGL is over than 120 mg/dl & performed PET, 3) BGL is over than 120 mg/dl & not performed PET. And we investigated the type of diabetic medications and the time of dosage, whether they have meal or not. And we analyzed SUV of liver and mediastinum to recognize the effect of BGL on PET images. Results: As a methods to diabetic control, Amalyl showed high percentage of 27.5% in oral medication and Humulin R showed 14.5% in insulin. Their peak time was 2-3 hrs, 2-4 hrs and duration time was 24 hrs, 5-7 hrs. The number of that had a breakfast was 16, 7 mens (43.8%) couldn't perform PET as over 120 mg/dl and 5 mens (31.3%) performed PET as less than 120 mg/dl after they took a medication. When we set the SUV of normal for 1.5-2.0, 1.0-1.5 on liver and mediastinum, the percentage out of the range was 31.8%, 52.9%, 62.5% in 120-139 mg/dl, 140-159 mg/dl, 160-200 mg/dl respectively. Conclusions: We completed standardized guideline for diabetic patients. As a result of this study, improved customer satisfaction and increased economic benefits. It is expect to be a effective model in other PET centers.

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Effects of GyeongshinhaeGihwan 1(GGT1) on the Expression of Obesity-related Genes in Obese Male hGHTg Rats (경신해지환(輕身解脂丸) (GGT1)이 형질전환 비만모델 hGHTg 수컷 쥐의 비만관련 유전자 발현에 미치는 영향)

  • Jung Yang-Sam;Yoon Mi-Chung;Kim Gyeong-Cheol;Shin Soon-Shik
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.93-97
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    • 2006
  • To investigate whether GyeongshinhaeGihwan 1(GGT1), an anti-obesity herbal medicine widely used in oriental medicine, regulates the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese male rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), PPAR $\gamma$ (peroxisome proliferator activated receptor-gamma), PPAR$\delta$ (peroxisome proliferator activated receptor-delta), leptin, TNF$\alpha$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3- phosphate dehydrogenase) were analyzed by RT-PCR. PPAR$\gamma$ mRNA levels of liver and kidney were decreased in drug-treated groups compared with control group and the decrease of PPAR$\gamma$ expression was more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of adipogenesis and lipid storage by decreasing the PPAR$\gamma$ expression. In contrast, PPAR$\delta$ mRNA levels of adipose tissue and kidney were increased by RD and GGT1 , and the magnitudes of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating PPAR$\delta$ expression, Compared with control and RD groups, GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite. However, The mRNA levels of leptin, LPL, and TNF$\alpha$ were not changed by GGT1 and RD, compared with DW. These results demonstrate that GGT1 not only decreases PPAR$\gamma$ expression of liver and kidney, but also increases PPAR$\delta$ expression of adipose tissue and kidney, leading to the regulation of obesity and that these effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to prevent obesity by increasing the serum leptin levels.

Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products (천연물 항암제제 임상시험 평가지표 개발연구)

  • Namgung, Mi-Ae;Chang, Yoo-Sung;Jeong, Seung-Gi;Kim, Jin-Seung;Yoon, Sung-Woo;Jang, Ki-Young;Yoo, Hwa-Seung;Jung, Myeon-Woo;Lee, Sung-Ho;Kim, Sung-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1678-1727
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    • 2006
  • This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.

Synergic Effect on Adipocytic Differentiation by a Combination of Thyroxine andGlucocorticoid in A549 Cells (A549 폐암세포주의 지방세포 분화에 미치는 티록신 및 당질 코르티코이드 호르몬의 상승 효과)

  • Hyeon-Ji Kim;Sun-Ha Moon;Sung-Ho Lee;Byeong-Gyun Jeon
    • Journal of Life Science
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    • v.33 no.9
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    • pp.693-702
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    • 2023
  • The present study examined the rate of cell growth and differentiation potential into adipocytes in A549 lung adenocarcinoma cells exposed to each adipogenic medium containing glucose metabolism hormones, such as thyroxine (T4) thyroid hormone and glucocorticoid (GC) adrenal steroid hormone, as well as pioglitazone (PGZ), a PPARγ agonist. Following each adipogenic treatment for 2 weeks, the rate of cell growth was significantly (p<0.05) inhibited, and the level of telomerase activity was significantly (p<0.05) decreased in the PGZ-based adipogenic medium containing both T4 and GC hormone compared with those containing each T4 or GC hormone. Moreover, the adiposome-like vesicles were highly reacted with Oil-Red O staining solution, and the levels of transcripts expressed in the differentiating adipocytes for adipogenesis, including adinopectin, leptin, and resistin, were significantly (p<0.05) increased in the PGZ-based adipogenic medium containing both T4 and GC hormone compared with those of the adipogenic medium containing each T4 or GC hormone, implying that adipocytic differentiation has fully occurred in the A549 cancer cells. Based on present observations, the PGZ-based adipogenic medium containing both T4 and GC efficiently induces inhibition of cell growth and cellular differentiation into adipocytes in A549 cancer cells rather than in the adipogenic medium containing only T4 or GC hormone. Adipogenic treatment could provide potential probability in cancer chemotherapy.