종설 : Nitric Oxide와 종양

임창열 ( Chang Yeol Yim ) 대한내과학회 2010 대한내과학회지 Vol.78 No.4

Nitric oxide (NO) is emerging as a potential anti-cancer agent to overcome tumor cell resistance to conventional therapeutic agents. NO is a short-life molecule produced from L-arginine by the nitric oxide synthase (NOS). There are three isoforms of the enzyme: neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3). Each of these isoforms may be expressed in a variety of cell types. The actions of NO are highly variable in oncology revealing both sides of the spectrum as an anti-neoplastic versus a pro-neoplastic agent. The final activity of NO is dependent on its working microenvironment, including the type of cell exposed to NO, the redox state of the reaction, as well as the final intracellular concentration and the duration of exposure to NO. NO donors mimic continuous production of NO in a wide range of time intervals (seconds to days). Thus, multiple biological and (pro-versus anti-) neoplastic responses are elicited from NO donors depending on the half-life and the type of cell exposed to the compound. This paper is a review of the current knowledge of various roles of NO in cancer. (Korean J Med 78:430-436, 2010)

Cascade 기형위 , 위하수 , 과민성 장 증후군을 동반한 만성위염 환자에서 공복시 혈청 gastrin 치의 변동

임창열(Chang Yeol Yim),홍보희(Bok Hee Hong),이용구(Yong Koo Lee),권철(Cheol Kwon),안득수(Keuk Soo Ahn) 대한소화기학회 1983 대한소화기학회지 Vol.15 No.1

N/A Chronic gastritis associated with nonspecific gastrointestinal symptoms is cne of the most. Common diseases, especially in Korea. But the etiology, clinicopathologic correlations, course and prognosis of the disease remain obscure. we observed the age and sex distribution, associated disease, symptomatology and fasting serum gastrin level in 77 patients composed of 28 cases of chronic gastritis without any othor anatomic and functional abnormality, 24 cases of chronic gastritis with cascade stomach, 20 cases of chronic gastritis with gastric ptosis and 5 cases of chronic gastritis with irritable bowel syndrome, who were treated from March 1982 to September 1982 at Jeonbug Naticnal University Hospital. The results were as follosws: 1. The ratios of male to female were 13 to 15 in chronic gastritis without any other abnormality, 17 to 7 in chronic gastritis with cascade stomach, 3 to 17 in chronic gastritis with gastric ptosis and 2 to 3 in chronic gastritis with irritable bowel syndrome. In all 7 patient, the ratio was 35 to 42. 2. The mean age of all 77 patients was 41.55+-1.22(mean+-S.E.) years and the most prevalent age group was fifth decade of life in all four groups of patients. 3, Sixteen(20.8%) of the 77 patients had associated diseases which were pulmonary tuberculosis(4 cases), clonorchiasis(3 cases), arthritis(3 cases), allergic skin diseases,(3 cases), toxic goiter (1 case), cirrhosis of the liver (1 case) and hypertension(1 case). In 2 cases, the nonspecific gastrointestinal syrnptoms developed after adrninistration of herbs. In sympatology, the most common symptom was postprandial epigastric distress which was complained in 60 of the 77 patients. The next common symptonis in descending order were postprandial epigastric fullness, epigasrtic hunger pain, dry mouth, belching, bitter taste, nausea, meteorism, lower abdominal pain, constipation and diarrhea. The fasting serum gatrin levels of the patients with chronic gastritis without ariy other abnorma!.ty, chron!c gastrit!s rvith cascade stornach and chrcnic gastritis with irritable tcwel syndro me were significantly lover than that of normal controls. But the fasting eerim gastrin levels of the patients with chronic gastritis with gastric ptosis revealed no sipnificant diffcrence compared with that of normal controls

Sarcoma-bearing Mice에서 Cadmium-109과 Gallium-67의 체내 분포의 비교

손명희,장숙경,정경호,한영민,김종수,최기철,임창열,강신화,Sohn, Myung-Hee,Chang, Sook-Kyeong,Chung, Kyung-Ho,Han, Young-Min,Kim, Chong-Soo,Choi, Ki-Chul,Yim, Chang-Yeol,Kang, Shin-Hwa 대한핵의학회 1994 핵의학 분자영상 Vol.28 No.1

Metallothionein (MT)는 세포내에 존재하는 cystein이 풍부한 적은 단백질로서 핵의학적 영상이나 치료에 이응이 가능할 여러 금속성 방사성 동위원소와 결합한다. 본 연구는 sarcoma를 주사한 Balb/C mice에서 MT와 결합하는 방사성동위원소인 cadmium이 종양에 축적되는가를 확인하고, 그것이 핵의학적인 영상과 치료에 이용될 수 있는지와 Ga-67을 대신할 수 있는지를 보기 위해 종양과 정상조직에서 Cd-109과 Ga-67의 섭취율을 비교하고 종양과 정상조직의 비를 비교하였다. Balb/3T3 세포를 Molony murine sarcoma virus (MMSV)로 변형시킨 세포를 Balb/C mice의 왼쪽 서혜부에 피하로 주사한 후 종양이 $0.6{\sim}l.0cm^2$로 자랐을 때 $25{\mu}Ci$ Cd-109 chloride와 $40{\mu}Ci$ Ga-67 citrate을 피하주사 한 후 18 또는 72시간에 쥐를 희생하여 종양과 여러 정상조직을 제거하여 무게를 잰 후 방사능을 측정하였다. Cd-109의 종양섭취는 Ga-67과 비슷하나 대부분의 정상조직에 비해 (MT가 풍부한 간과 신장을 제외) Ga-67보다 높았다. 종양대 정상조직의 섭취비는 Cd-109이 Ga-67에 비해 배후방사능에 중요한 영향을 미치는 장기인 뼈, 장, 지방조직, 근육, 혈액에서 월등히 높아서 (P<0.001) 같은 종양에서 Ga-67보다 좋은 영상을 얻을 수 있으리라고 생각되며, MT에 결합하는 cadmium은 암의 종양영상과 치료에 이용될 수 있을 것으로 생각된다. The search for tumor-avid agents for use in nuclear medicine imaging or therapy is a field of ongoing importance. Metallothionein (MT) is an intracellular protein that binds many metals with isotopes having imaging or radiotherapeutic potential. The purpose of the study was to determine whether uptake of radioisotopes that bind to MT is increased in tumor. We measured the uptake of Cd-109 and Ga-67 in tumor and normal tissues of sarcoma-bearing mice. Tumors were grown subcutaneously in female Balb/C mice from cultured Balb/3T3 cells transformed by the Moloney murine sarcoma virus (MMSV). When the tumors reached about 1 cm in diameter, mice were injected subcutaneously with Cd-109 and Ga-67. Eighteen and seventy-two hours later, the mice were sacrified. Organs and tissues were removed, weighed, and activity per mg tissue determined by gamma well-counting. Uptake of Cd-109 by MMSV tumors exceeded that by normal tissues examined, with the exception of liver and kidney (the organs known to be richest in MT). The tumor-to-tissue ratios of uptake for Cd-109 were far greater than those for Ga-67 for many normal tissues of great importance in terms of background activity (bone, intestine, fat, muscle, and blood). We concluded that metals that bind to MT may be useful for oncologic imaging or rediotherapy of cancer.

표적세포의 Nitric oxide 합성이 LAK 세포의 세포독성에 대한 예민도에 미치는 영향

박성일,박주형,이치국,김신재,최보금,곽재용,임창열,Park, Sung Il,Park, Ju Hyung,Lee, Chi Kug,Kim, Shin Chae,Choi, Bo Geum,Kwak, Jae Yong,Yim, Chang Yeol 대한면역학회 2001 Immune Network Vol.1 No.2

Background: Nitric oxide (NO), a cytotoxic molecule is produced in various tissues including tumor cells during interleukin-2 (IL-2) therapy . Lymphokine-activated killer (LAK) cells are induced during IL-2 therapy, and have cytotoxic activity against tumor cells. The current study investigated the effects of NO synthesized in target cells or exposure of target cells to NO on the sensitivity of target cells to LAK cell cytotoxicity. Methods: Cytotoxicity was measured using 4 h chromium release assays. LAK cells which were induced by a 4 day incubation of BALB/c mouse splenocytes with IL-2 (6,000 IU/mL) were employed as effector cells. RD-995 skin tumor cells originated from a C3H/HeN mouse were employed as target cells. NO synthesis in target cells was induced by a 24 h incubation of RD-995 cells with $IFN{\gamma}$ (25 U/mL), TNF (50 U/mL) and IL-1 (20 U/mL). S-nitrosyl acetylpenicillamine (SNAP), an NO donor, was used to expose target cells to NO. $N^G$-monomethyl-L-arginine (MLA) and carboxy-PTIO were added during cytotoxicity assays to inhibit NO synthesis, and to scavenge NO produced by target cells, respectively. Results: Sensitivity of NO-producing RD-995 cells to LAK cell cytotoxicity was decreased by addition of MLA and carboxy-PTIO during cytotoxicity assays. However, the two reagents had no effect on the sensitivity of non-NO-producing RD-995 cells. Pretreatment of RD-995 target cells with SNAP increased the sensitivity in comparison with untreated cells. Conclusions: Sensitivity of target cells to LAK cell cytotoxicity is increased by target cell NO synthesis or exposure to NO. Further studies are needed to evaluate whether these in vitro results have relevance to in vivo phenomena.

A Case of Renal Infartion in von Willebrand`s Disease

김원 ( Won Kim ),박재성 ( Jae Sung Park ),곽재영 ( Jae Yong Kwak ),임창열 ( Chang Yeol Yim ),박성광 ( Sung Kwang Park ),강성귀 ( Sung Kyew Kang ) 대한내과학회 1999 대한내과학회 추계학술대회 Vol.57 No.-

생쥐 종양모델에서 57Co-Vitamin B12의 종양 친화성에 관한 연구

손명희(Myung Hee Sohn),정경호(Gyung Ho Chung),임창열(Chang Yeol Yim),박순아(Soon A Park),김수현(Su Hyun Kim) 대한핵의학회 1998 핵의학 분자영상 Vol.32 No.1

N/A The search for tumor-avid agents for use in nuclear medicine imaging is an ongoing field of importance. The purpose of this study was to determine the affinity for radiolabeled vitamin B12 by a wide histologic variety of tumor types in mice. Seventeen different types of tumor were grown subcutaneously in female Balb/C or Balb nu/nu(nude) mice. When the tumors reached about 1 cm in diameter, mice were injected intraperitoneally with 57Co-vitamin B12. Twenty-foul hours later, the mice were sacrificed. Organs and tissues were removed, weighed, and activity per mg determined by gamma counter. Values represented cpm/mg tissue that was normalized to 20 grams body weight for each mouse. A wide variety of tumor types showed significant uptake and concentration of 57Co-vitamin B12, as evidenced by tumor:tissue activity ratios. For many tissues of great importance in terms of background(bone, muscle, blood), the tumor:tissue activity ratios of uptake were high. These data strongly suggest that further efforts to evaluate the utility of radiolabeled adducts of vitamin B12 for clinical use in oncologic imaging are warranted.

특발성혈소판감소증에서 위나선균 제균요법의 효과: 세 가지 증례 보고

송은기 ( Eun Kee Song ),이나리 ( Na Ri Lee ),곽재용 ( Jae Yong Kwak ),임창열 ( Chang Yeol Yim ) 대한내과학회 2008 대한내과학회지 Vol.74 No.3

위 나선균 감염이 특발성혈소판감소증을 일으키고 위 나선균 제균요법을 통해 혈소판 수치의 상승을 시킬 수 있다는 몇몇 보고들이 있다. 하지만 위 나선균의 발병율이 특발성혈소판감소증 환자들과 일반인들 사이에 차이를 보이지 않고, 제균요법 이후 혈소판 회복 정도가 보고에 따라 큰 차이를 보이고 있다. 저자들은 최근 세 가지의 다양한 임상상황에서 위 나선균 제균요법을 통해 성공적인 말초혈액 및 혈소판 수치의 회복 효과를 경험하였기에 보고하는 바이다. 첫번째 증례는 기존의 치료에 불응성 환자였고, 두번째 증례는 재발성 환자였고, 마지막 증례는 초치료로 제균요법을 시행한 경우였다. 저자들은 한국인들 중 일부 환자의 경우에서는 위 나선균 제균요법 만으로도 특발성혈소판감소증을 치료 할 수 있으며, 향후 많은 수의 환자를 대상으로하는 전향적 연구를 통해 위 나선균 감염과 특발성혈소판감소증 사이의 연관성을 밝힐 수 있는 연구들이 필요하리라 생각한다. There are several reports suggesting Helicobacter pylori can initiate and perpetuate idiopathic thrombocytopenic purpura (ITP) and eradication of H. pylori can increase the platelet counts, however, the prevalence of H. pylori infection in patients with ITP is similar to that found in the general population and a recovery of thrombocytopenia after H. pylori eradication therapy has not been identified reliably. We report three different cases of H. pylori infected patients with ITP who recovered completely after eradication of H. pylori. The first case was refractory, the second was recurred after conventional treatment for ITP, and the third was treated with H. pylori eradication on first line treatment. We believe that the eradication of H. pylori is useful in some patients with ITP in Korea and well controlled randomized study is necessary for further identification of such population. (Korean J Med 74:330-335, 2008)

골 신티그래피상 두개골에 열소로 나타난 대뇌겸과 경수뇌막에 다발성석회화 (흥미영상)

손명희 ( Myung Hee Sohn ),정환정 ( Hwan Jeong Jeong ),임석태 ( Seok Tae Lim ),임창열 ( Chang Yeol Yim ) 대한핵의학회 2007 핵의학 분자영상 Vol.41 No.1

흥미영상 : Kasabach-Merritt 증후군을 동반한 거대 간 혈관종: Tc-99m 적혈구 간 및 전신 혈액풀 신티그래피와 SPECT소견

손명희 ( Myung Hee Sohn ),정환정 ( Hwan Jeong Jeong ),임석태 ( Seok Tae Lim ),김동욱 ( Dong Wook Kim ),임창열 ( Chang Yeol Yim ) 대한핵의학회 2009 핵의학 분자영상 Vol.43 No.1

Sarcoma-bearing Bice 에서 Cadmium-109 과 Gallium-67 의 체내 분포의 비교

손명희(Myung Hee Sohn),김종수(Chong Soo Kim),최기철(Ki Chul Choi),한영민(Young Min Han),임창열(Chang Yeol Yim),장숙경(Sook Kyeong Chang),정경호(Kyung Ho Chung),강신화(Shin Hwa Kang) 대한핵의학회 1994 핵의학 분자영상 Vol.28 No.1

N/A The search for tumor-avid agents for use in nuclear medicine imaging or therapy is a field of ongoing importance. Metallothionein (MT) is an intracellular protein that binds many metals with isotopes having imaging or radiotherapeutic potential. The purpose of the study was to determine whether uptake of radioisotopes that bind to MT is increased in tumor. We measured the uptake of Cd-109 and Ga-67 in tumor and normal tissues of sarcoma-bearing mice. Tumors were grown subcutaneously in female Balb/C mice from cultured Balb/3T3 cells transfor- med by the Moloney murine sarcoma virus (MMSV). When the tumors reached about 1 cm in diameter, mice were injected subcutaneously with Cd-109 and Ga-67. Eighteen and seventy-two hours later, the mice were sacrified. Organs and tissues were removed, weighed, and activity per mg tissue determined by gamma well-counting. Uptake of Cd-109 by MMSV tumors exceeded that by normal tissues examined, with the exception of liver and kidney (the organs known to be richest in MT). The tumor-to-tissue ratios of uptake for Cd-109 were far greater than those for Ga-67 for many normal tissues of great importance in terms of background activity (bone, intestine, fat, muscle, and blood). We concluded that metals that bind to MT may be useful for oncologic imaging or radiotherapy of cancer.