176. 갑상선암의 임상적 고찰

최길돈,전갑승,박인근,장일성,손기섭 대한외과학회 1988 대한외과학회 학술대회 초록집 Vol.1988 No.11

갑상선암의 발생빈도와 수술적 방법에 대한 임상적 고찰

최길돈(Gil Don Choi),장일성(Eil Sung Chang) 대한외과학회 1989 Annals of Surgical Treatment and Research Vol.37 No.6

Contribution of a Low-Barrier Hydrogen Bond to Catalysis Is Not Significant in Ketosteroid Isomerase

장도수,최길돈,차형진,신세정,홍비학,이희천,이형주,최관용 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.5

Low-barrier hydrogen bonds (LBHBs) have been proposed to have important influences on the enormous reaction rate increases achieved by many enzymes. Δ5-3-ketosteroid isomerase (KSI) catalyzes the allylic isomerization of Δ5-3- ketosteroid to its conjugated Δ4-isomers at a rate that approaches the diffusion limit. Tyr14, a catalytic residue of KSI, has been hypothesized to form an LBHB with the oxyanion of a dienolate steroid intermediate generated during the catalysis. The unusual chemical shift of a proton at 16.8 ppm in the nuclear magnetic resonance spectrum has been attributed to an LBHB between Tyr14 Oη and C3-O of equilenin, an intermediate analogue, in the active site of D38N KSI. This shift in the spectrum was not observed in Y30F/Y55F/D38N and Y30F/Y55F/Y115F/D38N mutant KSIs when each mutant was complexed with equilenin, suggesting that Tyr14 could not form LBHB with the intermediate analogue in these mutant KSIs. The crystal structure of Y30F/Y55F/Y115F/D38N-equilenin complex revealed that the distance between Tyr14 Oη and C3-O of the bound steroid was within a direct hydrogen bond. The conversion of LBHB to an ordinary hydrogen bond in the mutant KSI reduced the binding affinity for the steroid inhibitors by a factor of 8.1-11. In addition, the absence of LBHB reduced the catalytic activity by only a factor of 1.7-2. These results suggest that the amount of stabilization energy of the reaction intermediate provided by LBHB is small compared with that provided by an ordinary hydrogen bond in KSI.

외과 질환에서 예방적 및 치료적으로 시용한 Sagacin^(�)(KW-1062)의 임상적 효과

배진선,최길돈 최신의학사 1988 最新醫學 Vol.31 No.3

갑상선 항진증에 관한 외과적 치료의 임상적 연구

장일성,최길돈,하기정 충남대학교 의과대학 지역사회의학연구소 1987 충남의대잡지 Vol.14 No.2

A clinical study of hyperthyroidism was performed for 20 patient who received operation at the department of surgery of C. N. U. H. from March, 1973 to July, 1987. The results were as follows: 1) In clinical classification, 14 cases (80%) were diffuse toxic goiter and 6 cases (20%) were nodular toxic goiter. 2) Male to female ratio was 1 : 19 and the highest incidence in the 3rd decade. 3) Main symptoms and signs were, in the order of decreasing frequency, neck mass (95%), palpitation (85%), fatigability (80%), heat intolerance (75%), weight loss (65%), tremor (60%) headache (50%). 4) Pulse rate changed from 130 per minute preoperatively to 60 postoperatively. 5) Thyroid function test revealed high level above the normal in 16 (80%) and the mean value of T_3RI_4 4.06mg/ml, T_3RI_4 10.48mg/ml, free T_4 4.65/ug/dl, postoperatively all cases showed teuthyroid function. 6) Electro-cardiographic findings were sinus tachycardia 9 cases (45%), normal 6 cases (30%). sinus bradycardia 5 cases (25%). 7) In preoperative preparation, Lugol solution was more frequently used 8 cases (40%) and others prophylthiouracil plus lugol solution 4 cases (20%), Inderal plus lugol solution 4 cases (20%) Methimazole plus lugol solution 2 cases (10%), prophylthiouracil plus Inderal plus comthyroid plus lugol solution 2 cases (10%). Average mean duration of preoperative preparation was 12.8 days. 8) The types of operation were in the order of decreasing frequency near total thyroidectomy 9 cases (45%), subtotal thyroidectomy 6 cases (30%), Lobectomy 4 cases (20%) and total thyroide ctomy 1 case (5%), 9) Early postoperative complication were transient tremor 3 cases (15%) transient hoarseness 1 case (5%), hypothyroidism 1 case (5%), recurrent hyperthyrodism 1 case (53%), hypoparathyroidism l. case (53%) but there was no case of operative motality.

갑상선암의 임상적 고찰

장일성,노승무,최길돈 충남대학교 의과대학 지역사회의학연구소 1988 충남의대잡지 Vol.15 No.2

The thyroid cancer are more frequntly detected in anually due to improvement of diagnostic method and interesting knowledge of the cancer among the general population. This paper represent a clinical study of 80 cases of carcinoma of the thyroid gland which were histol ogically diagnosed and treated surgically at Chungnam National University Hospital from January 1981 to September 1988 with special emphasis on the surgical management of the thyroid cancer. The results were summerized as follows: 1) The incidence of the thyroid cancer was 22.22% among the 360 cases of the surgical thyroid disease and incidence of the thyroid cancer was increased anually. 2) The thyroid cancer was prevalent in third fourth decades of life (51.25% of all) and in female (5.67 to 1). 3) The average duration of the thyroid cancer was 2.9 years. 4) In histopathological classification of the thyroid cancer, papillary adenocarcinoma was 78.75% of all casses of thyroid cancer. 5) In the location of the thyroid cancer nodule,' 40/% of the thyroid cancer nodules were located in right lobe, 25% at the left lobe and the most prevalent location was right upper lobe(18.9O% of all). 6) In thyroid scanning of the thyroid cancer, the prevalent nodules were cold nodules, The most prevalent nodules were single cold nodules(62.50% of all). 7) In thyroid function test of the thyroid cancer, all most revealed normal function(88.75% of all). 8) Cervical lymphnode metastasis were present 29 casses (36.25%) and most common in papillary adenocarcinoma 26 cases(25%). Distant metastasis was present one case (1.25%), anaplastic cell carcinoma and the site was left breast. 9) The surgical procedure performed in thyroid cancer were followed unilateral lobectomy (28 cases), near total thyroidectomy (26 cases) and total thyroidectomy with neck dissection (1lcases) 10) The most common postoperative complication was transient hoarser ness in 14 casee (17.5O%). 11) After operation, the thyroid cancer recurrence rate was 8 cases (10% of all).

Inhibition of c-Kit signaling by diosmetin isolated from Chrysanthemum morifolium

이성진,정태훈,김호정,정대영,최길돈,박우규,공재양,진무현,조희영 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.2

The interaction of stem cell factor (SCF) withits cognate receptor c-Kit is closely associated with thesurvival and maturation of melanocytes. To investigatenovel depigmentation agents, we screened 2,000 plantextracts for c-Kit inhibitors to identify active small moleculesby using time-resolved fluorescence enzyme assays. For the active extracts identified as inhibitors of c-Kitenzyme, we evaluated the effects of the active extracts andisolated flavonoids on c-Kit phosphorylation in MO7e/melanocytes. Anti-melanogenic activity was also examinedin melanocytes and melanoderm model. The flavonoidssuch as diosmetin, apigenin, acacetin and luteolin isolatedfrom Chrysanthemum morifolium were found to be activein inhibiting c-Kit both at enzyme and cellular levels. Inaddition, these flavonoids attenuated SCF-induced proliferationof human primary melanocytes without toxicity andsuppressed ultraviolet (UV) B irradiation-mediated melaninsynthesis significantly. Among the active flavonoids,diosmetin was found to inhibit SCF-induced melanogenesisin a human melanoderm model. These results stronglysuggest that C. morifolium extract and diosmetin have potential to suppress SCF-/UVB-induced melanogenesis,and could be developed as anti-pigmentation agents.

일반외과계의 Ceftriaxone 투여 환자에 대한 임상적 관찰

손기섭,김완식,박혜덕,목우균,최길돈 최신의학사 1987 最新醫學 Vol.30 No.3

Synthesis and biological evaluation of (2‐aminosulfonylpyridin‐6‐yl)pyrazolopyrimidinone derivatives as Wee1 inhibitors for cancer treatment

김연주,정명은,이주영,이윤한,최길돈,Jeon Moon‐Kook 대한화학회 2024 Bulletin of the Korean Chemical Society Vol.45 No.1

For an analog‐based design of novel Wee1 inhibitors, we profiled in vitro ADMET and in vivo PK properties of adavosertib. Based on the properties of adavosertib, we aimed to improve its metabolic stability by designing a novel target compound 1a with an aminosulfonyl group instead of the 2‐hydroxypropan‐2‐yl moiety in adavosertib. Derivatives of target compound 1a were synthesized and evaluated for Wee1 enzyme inhibition and liver microsomal phase I stability. We identified compound 1a as a sub‐nanomolar Wee1 inhibitor and 10 additional compounds with one‐digit nanomolar Wee1 inhibitory activity, among which seven compounds including 1a exhibited improved metabolic stabilities compared with adavosertib. However, MDA‐MB‐231 cell growth inhibitory activities of all synthesized compounds and Wee1 substrate phosphorylation inhibitory activities of selected compounds were inferior to adavosertib overall. Moreover, the representative compound 1a exhibited low permeability, which may be the reason for the low cellular activities of compound 1a . For an analog-based design of novel Wee1 inhibitors, we profiled in vitro ADMET and in vivo PK properties of adavosertib. Based on the properties of adavosertib, we aimed to improve its metabolic stability by designing a novel target compound 1a with an aminosulfonyl group instead of the 2-hydroxypropan-2-yl moiety in adavosertib. Derivatives of target compound 1a were synthesized and evaluated for Wee1 enzyme inhibition and liver microsomal phase I stability. We identified compound 1a as a sub-nanomolar Wee1 inhibitor and 10 additional compounds with one-digit nanomolar Wee1 inhibitory activity, among which seven compounds including 1a exhibited improved metabolic stabilities compared with adavosertib. However, MDA-MB- 231 cell growth inhibitory activities of all synthesized compounds and Wee1 substrate phosphorylation inhibitory activities of selected compounds were inferior to adavosertib overall. Moreover, the representative compound 1a exhibited low permeability, which may be the reason for the low cellular activities of compound 1a.

Structure–Activity Relationship Study of 2,4-Dianilinopyrimidine Containing Methanesulfonamide (TRE-069) as Potent and Selective Epidermal Growth Factor Receptor T790M/C797S Mutant Inhibitor for Anticancer Treatment

최현정,전병욱,정명은,전문국,신인지,조병철,최길돈,채종학,LEEKWANGHO 대한화학회 2017 Bulletin of the Korean Chemical Society Vol.38 No.11