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Young Il Kim  (Kim YI) 10 Articles
Thyroid
Combined Effects of Baicalein and Docetaxel on Apoptosis in 8505c Anaplastic Thyroid Cancer Cells via Downregulation of the ERK and Akt/mTOR Pathways
Chan Ho Park, Se Eun Han, Il Seong Nam-Goong, Young Il Kim, Eun Sook Kim
Endocrinol Metab. 2018;33(1):121-132.   Published online March 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.1.121
  • 5,057 View
  • 64 Download
  • 41 Web of Science
  • 35 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells.

Methods

The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis.

Results

The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt.

Conclusion

The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.

Citations

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Close layer
Thyroid
Curcumin Enhances Docetaxel-Induced Apoptosis of 8505C Anaplastic Thyroid Carcinoma Cells
Jung Min Hong, Chan Sung Park, Il Seong Nam-Goong, Yon Seon Kim, Jong Cheol Lee, Myung Weol Han, Jung Il Choi, Young Il Kim, Eun Sook Kim
Endocrinol Metab. 2014;29(1):54-61.   Published online March 14, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.1.54
  • 3,911 View
  • 33 Download
  • 26 Web of Science
  • 27 Crossref
AbstractAbstract PDFPubReader   
Background

Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its progression is poorly controlled by existing therapeutic methods. Curcumin has been shown to suppress inflammation and angiogenesis. In this study, we evaluated whether curcumin could augment docetaxel-induced apoptosis of ATC cells. We also analyzed changes in nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) expression levels to delineate possible mechanisms of their combined action.

Methods

ATC cells were cultured and treated with curcumin and docetaxel alone or in combination. The effects on cell viability were determined by MTS assay. Apoptosis was assessed by annexin V staining and confirmed by flow cytometric analysis. Caspase, COX-2, NF-κB levels were assayed by Western blotting.

Results

Curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of ATC cells. Additionally, curcumin inhibited docetaxel-induced p65 activation and COX-2 expression.

Conclusion

We conclude that curcumin may enhance docetaxel's antitumor activity in ATC cells by interfering with NF-κB and COX-2. Our results suggest that curcumin may emerge as an attractive therapeutic candidate to enhance the antitumor activity of taxanes in ATC treatment.

Citations

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Close layer
A Case of Parathyroid Carcinoma Underwent Radiation Therapy on the Metastatic Bone Lesions.
Jun Ho Lee, Young Min Kim, Dae Seong Hwang, Young Tae Hwang, Jun Bum Eum, Jung Min Seo, Dae Hwa Choi, Byeong Seong Kang, Young Ju Noh, Il Seong Nam-Goong, Young Il Kim, Eun Sook Kim
J Korean Endocr Soc. 2007;22(5):344-352.   Published online October 1, 2007
DOI: https://doi.org/10.3803/jkes.2007.22.5.344
  • 2,017 View
  • 24 Download
  • 2 Crossref
AbstractAbstract PDF
Parathyroid carcinoma is a rare malignancy that is responsible for only 0.5 to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative treatment. We report a case of a 46-year-old woman referred for a severe osteoporosis with frequent bone fracture associated with hypercalcemia. Initially, though she had multiple osteolytic lesions, we thought that the lesions were brown tumors resulting from hyperparathyroidism. The patient underwent surgery and was diagnosed with parathyroid carcinoma. After surgery, her intact PTH level normalized for brief period of time, but it was again elevated at 6 weeks after surgery. We suggest that the multiple osteolytic lesions were metastases because there was no evidence of local recurrence of parathyroid carcinoma, and the lesions looked like metastases on CT and PET-CT. The patient was treated with radiation therapy on the lumbar vertebra, one a site of the metastatic lesions. After radiotherapy, her serum intact PTH was decreased.

Citations

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  • Successful Localization of Distant Metastasis in Parathyroid Carcinoma Using Intraoperative Parathyroid Hormone Assay
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Suppression of Pathogenic Autoreactive CD4+ T Cells by CD137-mediated Expansion of CD4+CD25+ Regulatory T Cells in Graves' Disease.
Eun Sook Kim, Hyo Won Jung, Jung Il Choi, Il Seung Nam-Goong, Soon Hyung Hong, Young Il Kim
J Korean Endocr Soc. 2007;22(5):332-338.   Published online October 1, 2007
DOI: https://doi.org/10.3803/jkes.2007.22.5.332
  • 1,796 View
  • 21 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Graves' disease (GD) is an organ-specific autoimmune disease that is characterized by lymphocyte infiltration of the thyroid, which finally leads to follicular destruction. The CD4+CD25+ regulatory T cells are important for maintaining peripheral tolerance to self-antigens and impaired activity can cause autoimmune diseases. CD137 (4-1BB), a member of the tumor necrosis factor receptor superfamily and expressed on activated T cells, is a candidate molecule for a co-stimulatory role in autoimmune thyroid disease. In this study, we aimed to assay the frequency of CD4+CD25+ T cells in GD patients and to investigate the role of CD137-mediated costimulation in CD4+CD25+ T cells. METHODS: The frequencies of the CD4+CD25+ T cells in the peripheral blood (PB) of GD patients were determined by flow cytometric analysis. After the CD4+CD25+ T cells were isolated from PB mononuclear cells (PBMC) of the GD patients using immunomagnetic beads, the functional activity of the CD4+CD25+ T cells was characterized by use of a proliferation assay. mRNA expression of Foxp 3 in the CD4+CD25+ T cells of the GD patients was observed by real-time RT-PCR. RESULTS: In this study, we found that GD patients had a low proportion of CD4+CD25+ T cells (mean +/- SD; 1.47 +/- 0.31%) in PBMC as compared with normal subjects. CD137-mediated costimulation increased the expression of CD25 and Foxp 3 in CD4+ T cells in GD patients as compared with normal subjects. Moreover, the CD137-mediated costimulation also induced the proliferation of CD4+CD25+ T cells in GD patients, and the expanded CD4+CD25+ T cells could suppress other CD4+CD25- T cells in a co-culture. CONCLUSION: These results suggest that the peripheral expansion of CD4+CD25+ T cells by CD137-mediated co-stimulation can suppress effector T cells and may be a potent therapy for Graves' disease.

Citations

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  • Effects of Gastrodia elata Blume on Apoptotic Cell Death of Liver Cancer Cells by Expression of Bcl-2, Bax, and AMPKα
    Jae Hyun Park, Min Ho Kang, Ji Woo Hong, So Hee Kim, Yoon Seon Hwang, Jae Hoon Park, Jin Woo Kim
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Expression of 4-1BB and 4-1BBL in Graves'Disease.
Eun Sook Kim, Hyo Won Jung, Il Sung Nam-Goong, Soon Joo Woo, Jung Il Choi, Young Il Kim
J Korean Endocr Soc. 2006;21(2):116-124.   Published online April 1, 2006
DOI: https://doi.org/10.3803/jkes.2006.21.2.116
  • 1,835 View
  • 22 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
4-1BB mediated costimulatory signal is a recently identified immunotherapeutic strategy for treating autoimmune diseases without depressing the immune response. In this study, we investigated the expression of 4-1BB and 4-1BBL on the peripheral blood mononuclear cells (PBMC) and we assessed whether the serum levels of soluble (s) 4-1BB and s4-1BBL in the patients with Graves' disease (GD) and compared them with normal subjects. METHODS: Expression of 4-1BB and 4-1BBL on PBMC of GD patients was determined by flow cytometry. The concentrations of s4-1BB and s4-1BBL were assessed in the sera of GD patients by performing ELISA. RESULTS: 4-1BB was constitutively expressed on naive CD4+ and CD8+ T cells of the GD patients and this was increased by stimulation. 4-1BBL was also expressed on the antigen-presenting cells such as CD19+ B cells, monocytes and dendritic cells in GD patients. The serum levels of s4-1BB and s4-1BBL were significantly higher in GD patients than those in controls, and these levels were significantly correlated with the serum levels of thyroid-binding inhibitory immunoglobulin and free T4. CONCLUSION: These results indicate that effector T cells of GD patients can be activated through the 4-1BB-mediated costimulatory signal. Elevated s4-1BB and s4-1BBL levels in the sera of GD patients may affect modulation of the clinical course in GD patients.

Citations

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  • Suppression of Pathogenic Autoreactive CD4+ T Cells by CD137-mediated Expansion of CD4+CD25+ Regulatory T Cells in Graves' Disease
    Eun Sook Kim, Hyo Won Jung, Jung Il Choi, Il Seung Nam-Goong, Soon Hyung Hong, Young IL Kim
    Journal of Korean Endocrine Society.2007; 22(5): 332.     CrossRef
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Regulation of Prolactin Gene Expression by Hypothalamic Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in the Female Rat Pituitary Gland.
Young Il Kim, Tae Young Ha, Eun Sook Kim, Il Seong Nam-Goong, M S O'Dorisio, Min Kyu Hur, Sang Kyu Park
J Korean Endocr Soc. 2004;19(2):152-164.   Published online April 1, 2004
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BACKGROUND
Pituitary adenylate cyclase-activating polypeptide (PACAP) plays the role of a hypophysiotropic factor, which regulates the synthesis and secretion of pituitary hormones through the hypothalamo-hypophysial portal system. No clear evidence has yet been reported regarding the regulation of prolactin (PRL) by PACAP. In the present study, we tested a hypothesis that PACAP regulates the synthetic machinery of PRL during the estrus cycle and pubertal process using intracerebroventricular (i.c.v.) injection of an antisense oligodeoxynucleotide (ODN) against type I PACAP receptor (PAC1). METHODS: An RNase protection assay (RPA) was used to determine the pattern of hypothalamic PACAP and PAC1 mRNA expressions during the estrus cycle. Antisense PAC1 ODN was administered via i.c.v. injection to the female rats in normal estrus cycle of pubertal process. Northern blot analysis was used to determine the mRNA ievel of PRL in the pituitary gland. RESULTS: 1) PACAP mRNA in the medial basal hypothalamus was significantly increased at the diestrus I, while PAC1 mRNA showed no significant change. 2) PRL mRNA level of pituitary was increased by an injection of antisense PAC1 ODN at the proestrus and estrus stages. 3) PRL mRNA level of pituitary was significantly decreased by antisense PAC1 ODN injection at stage of prepuberty and initiate puberty, while its level was increased at stage of puberty. CONCLUSION: These data suggest that PACAP suppresses PRL mRNA synthesis through the PAC1 signaling pathway in the certain estrus cycle environments. It may be also involved in the regulation of pituitary PRL gene expression during the pubertal process
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A Case of Ventricular Fibrillation Aassociated with Hyperthysoidism.
Il Min Ahn, Young Il Kim, Eun Joo Lee, Mi Heon Lee, Young Ki Song, Yoo Ho Kim
J Korean Endocr Soc. 1998;13(3):459-465.   Published online January 1, 2001
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The cardiovascular manifestations in hyperthyroidism are sinus tachycardia, paroxysmal supraventricular tachycardia, atrial flutter, atrial fibrillation, atrioventricular block, bundle branch block(especially right bundle branch block), angina pectoris, heart failure and cardiomyopathy. Of these, angina pectoris is commonly seen in hyperthyroidism with coronary artery disease and the potential mechanisms have been attributed to the increased metabolic demand and consequently increased cardiac work which result in the more demand of coronary blood flow than that can be delivered via a fixed atherosclerotic coronary artery stenosis. Hyperthyroidism associated anginas without underlying coronary artery stenosis have also been reported where the mechanism of these was suspected to be the coronary vasospasm. Ventricular fibrillation may occur in the thyrotoxic patients due to myocardial ischemia such as variant angina, but it is very rare in the condition without previous heart disease. A 30-year-old male was admitted to the hospital because of palpitation, weight loss and proptosis for the previous 3 months. There was no history of effort related chest pain, syncope, drug abuse or medical illnesses such as diabetes mellitus, hypertension. The laboratory results were, TSH: 0.38uU/mL(0.4~5,0 uU/mL), free T4: 8.9ng/dL(0.8~1.9ng/dL), TSH receptor antibody: 43.6%(-15~15%), antiTPO antibody: 5000 IU/mL(0~100 IU/mL). The initial EKG showed normal sinus rhythm. He was diagnosed as Graves disease with ophthalmopathy, class 3a and was put on propylthiouracil 200 mg po tid, propanolol 40 mg po tid and started solumedrol pulse therapy for the exophthalmos on the first day of admission. He was found to have generalized tonic seizure with apnea attack on second hospital day and twice thereafter. Ventricular fibrillation was documented at that time. DC cardioversion was performed with successful response. After the attack, he was treated as accelerated hyperthyroidism namely with increased dosage of propylthiouracil, dexamethasone and Lugols solution, The echocardiogram, treadmill test, ergonovine echocardiography, coronary angiography and electrophysiologic study disclosed no abnormalities. Further episodes of ventricular fibrillation didnt occur after being euthyroid state. In conclusion, we report a case of ventricular fibrillation associated with hyperthyroidism itself without underlying coronary artery disease with brief review of literatures.
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Prevalence of Gsa, ras, p53 Mutations and ret/PTC Rearrangement in Differentiated Thyroid Tumors of Korean Population.
Il Min Ahn, Young Il Kim, Hyun Soo Park, Ki Young Park, Seok Jun Hong, Eun Joo Lee, Kyung Yub Gong
J Korean Endocr Soc. 1998;13(2):189-197.   Published online January 1, 2001
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BACKGROUND
In thyroid tumor, ras, Gsa, p53 mutation and ret/FfC rearrangement have been reported with variable prevalences in different geographic regions. We studied the prevalences of these mutations and reammgement in thyroid tumors of Korean population. METHODS: Eleven cases of adenamatous goiter, 8 cases of follicular adenoma, 5 cases of foliicular carcinoma, 37 cases of papillary carcinoma were included in this study. To find mutations and rearrangement, RT-PCR, SSCP, and/or direct sequencing, after subcloning if necessary, were used. RESULTS: We could not find any rearrangment for ret/PTC-l, -2, -3 and mutations of Gsa. For ras oncogene, K and H-ras mutations were not found, but N-ras mutations, point mutation of CAA to CGA in codon 61, were detected in 1 follicular adenoma(12.5%, 1/8) and 1 follicular carcinoma(33%, 1/3). And p53 mutations were detected only in 1 case of papillary carcinoma (3%, 1/31: exon 8, codon 266 GGA-GAA). CONCLUSION: ret/PTC rearrangement, Gsa, ras and p53 mutations are relatively rare in differentiated thyroid neoplasms of Korean population, which may reflect the genetic and environmental differences from those countries with high prevalence.
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Expression of Human Sodium Iodide Symporter mRNA in Papillary Thyroid Carcinoma.
Hong Kyu Kim, Il Min Ahn, Young Il Kim, Eun Sook Kim, Hyun Soo Park, Ki Young Park, Seok Jun Hong
J Korean Endocr Soc. 1998;13(2):181-188.   Published online January 1, 2001
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BACKGROUND
The sodium iodide symporter(NIS) is a plasma membrane protein which is respoasibIe for iodide transport into thyroid cell. The cDNA sequence of NIS has recently been cloned from rat and human. Intrinsic ability and its differences in iodide accumulation have been exploited as a useful tool for diagnosis and therapy of thyroid diseases. It is also known that some differentiated thyroid cancers do not take up radioactive iodine at therapeutic dose. METHODS: To understand the expression and regulation of NIS in thyroid tumars, we measured the expressons of human NIS(hNIS), TSH-receptor(R), and thyroglohulin(Tg) mRNAs from papillary thyroid carcinoma(PTC) tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNase protection assay(RPA). RESULT: By RT-PCR analysis, 87% of PTC expressed hNIS mRNA, but the degree of expression were variable. Interestingly, 32% of PTC showed significant level of hNIS expression even though pre-operative technetium thyroid scan of all thyroid tumors were cold but the level was lower than normal control tissues. All of PTC showed the expressions of Tg and TSH-R mRNAs and there was a correlation between hNIS mRNA and TSH-R mRNA(Rsq 0.35, p=0.01). By RPA, the expression of hNIS and TSH-R in normal control tissue were detected with 20microgram and 40microgram of total RNA respectively, but the higher concentrations(> or =60microgram for hNIS and > or =40microgram for TSH-R) were required to detect in PTC, showing that tbe expression of hNIS in FTC was lower than TSH-R expression. CONCLUSION: PTC tends to lose hNIS mRNA expression earlier than TSH-R mRNA and the measurement of hNIS mRNA in PTC may be useful as an indicator of the therapeutic response to radioactive iodine.
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A Case with Isolated ACTH Deficiency.
Myoung Sik Kim, Byung Doo Lee, Sang Min Shin, Young Il Kim, Byung Oh Jeong, Hong Jib Choi, Phil Ho Kim, Kyung Soo Ko, Jae Hong Park
J Korean Endocr Soc. 1996;11(4):538-543.   Published online November 7, 2019
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Isolated ACTH deficiency is a rare cause of secondary adrenocortical insufficiency. Adrenal crisis in isolated ACTH deficiency is less common compared to primary adrenal insufficiency, but isolated ACTH deficiency is an important cause of hypoglycemia. Recently we experienced a 41-year-old man admitted because of mental confusion. On admission, plasma glucose and sodium concentration were 1.7, 132 mmol/L, respectively. Basal plasma ACTH and cortisol levels were low and other pituitary hormone showed normal response to combined pituitary stimulation test except growth hormone. Plasma ACTH concentration remained low even after intravenous injection of ovine corticotropin releasing factor. It suggest that the defect of ACTH secretion was apparently due to intrinsic pituitary rather than hypothalamic disease. The sellar CT showed the fossa to be filled by cerebrospinal fluid. After treatment with glucocorticoid, he had no further evidence of hypoglycemia and hyponatremia. In conclusion, we report a case of isolated ACTH deficiency with empty sella.
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