• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4627-4634
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• 2013

Chemoprotection refers to the use of specific natural or synthetic chemical agents to suppress or prevent the progression to cancer. The purpose of this study is to assess the protective effect of aspirin, vitamin C or zinc in a dimethyl hydrazine (DMH) colon carcinoma model in rats and to investigate the effect of these supplements on changes associated with colonic zinc status. Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) and group 3 (zinc), each being subdivided into two groups and given subcutaneous injection of DMH (30 mg/kg body wt) twice a week for 3 months and sacrificed at 4 months (A-precancer model) and 6 months (B-cancer model). Groups 1, 2, 3 were simultaneously given aspirin, vitamin C, or zinc supplement respectively from the beginning till the end of the study. It was observed that 87.5% of rats co-treated with aspirin or vitamin C showed normal colonic histology, along with a significant decrease in colonic tissue zinc at both time points. Rats co-treated with zinc showed 100% reduction in tumor incidence with no significant change in colonic tissue zinc. Plasma zinc, colonic CuZnSOD (copper-zinc superoxide dismutase) and alkaline phosphatase activity showed no significant changes in all 3 cotreated groups. These results suggest that aspirin, vitamin C or zinc given separately, exert a chemoprotective effect against chemically induced DMH colonic preneoplastic progression and colonic carcinogenesis in rats. The inhibitory effects are associated with maintaining the colonic tissue zinc levels and zinc enzymes at near normal without significant changes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3279-3283
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• 2015

Background: Colorectal cancer (CRC) is the most common gastrointestinal cancer and the incidence is increasing. CRC is more common with increasing age, but a proportion occurs in young adults, termed young CRC. This study assessed the incidence and the demographic of young CRC in Brunei Darussalam. Materials and Methods: All histologically proven CRC between 1986 and 2014 registered with the Department of Pathology cancer registry were reviewed and data extracted for analyses. Young CRC was defined as cancer in patients aged less than 45 years. The various population groups were categorized into locals (Malays, Chinese and Indigenous) and expatriates. Results: Over the study period, there were 1,126 histologically proven CRC (mean age $59.1{\pm}14.7$ years, Male 58.0%, Locals 91.8% and 8.2% expatriates). Young CRC accounted for 15.1% with the proportion declining over the years, from 29% (1986-1990) to 13.2% (2011-2014). The proportion of young CRC was highest among the indigenous (30.8%), followed by the expatriates (29.3%), Malays (14.3%) and lowest among the Chinese (10.8%). The mean age of young CRC was $35.9{\pm}6.2$; lowest among the indigenous ($33.5{\pm}6.7$), expatriate ($34.9{\pm}6.0$) groupd and the Malays ($35.6{\pm}6.5$) compared to the Chinese ($38.6{\pm}4.6$), a similar trend being observed in the non-young CRC groups. There were no difference between the genders and tumor locations (rectum or colon) between the young and the non-young CRC cases. Female young CRC was significantly younger than male (p<0.05) without any significant variation between the various population groups (p>0.05). Conclusions: Our study showed that the young CRC accounted for 15.1% of all CRC with declining trend observed over recent years. Young CRC was more common among indigenous, expatriates and Malays and least common among the Chinese. There were no differences in the gender and tumor locations.

• Preventive Nutrition and Food Science
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• 제16권4호
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• pp.283-290
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• 2011

The recent increase of colon, breast, and prostate cancer incidence in Korea has been attributed to a diet pattern change to a more Western style, in which the foods eaten are higher in protein and fat. Whether high protein intake itself stimulates tumor cell growth and exacerbates disease status has been investigated, however, many epidemiological studies have inconsistent results between meat intake and the risk of certain cancers. These inconsistent results are partly because of the difficulty of studying the effects of just the meat intake. Other factors, such as overall meal context, could not be completely excluded in the study. To address the question of whether high protein itself is independently associated with carcinogenesis, we initiated ICR mice with 200 nmol ($50{\mu}g$) 7,12-dimethylbenz[a]anthracene (DMBA) and fed animals either a normal diet (ND, 14% casein) or a high protein diet (HPD, 50% casein) for 15 weeks with 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in two-stage skin carcinogenesis protocol. There was no significant difference between ND and HPD group in food intake and body weight throughout the experiment. However, tumor multiplicity of the HPD group was decreased by 75.5% compared to that of the ND group. In addition, HPD inhibited skin hyperplasia and epidermal cell proliferation. Western analyses with whole skin lysates showed that HPD inhibited TPA-induced Akt (S473), S6K (T389), 4E-BP1 (Thr 37/46) and Erk1/2 (Thr202/Tyr204) phosphorylation as well as COX-2 expression. Taken together, these data suggest that a high protein diet has an anticarcinogenic effect by inhibiting the TPA-induced Akt signaling pathway.

• Journal of Chest Surgery
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• 제41권2호
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• pp.253-259
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• 2008

배경: 경부식도암은 흉부식도암에 비해 발생 빈도가 상대적으로 낮고 방사선치료나 항암 약물치료의 역할이 흉부식도암에서보다 상대적으로 높다. 따라서 경부식도암에 대한 수술적 치료의 역할이 흉부식도암에 비해 상대적으로 제한적이다. 저자들은 경부식도암에 대한 수술적 치료의 결과를 알아보기 위해 본 연구를 시행하였다. 대상 및 방법: 1989년 1월부터 2002년 12월까지 경부식도암(경흉부식도 암 포함 )으로 수술을 시행 받은 환자 43명의 결과를 후향적으로 분석하였다. 모든 환자에서 추적이 가능하였으며, 최종 추적일은 2004년 2월 28일이었다. 결과: 대상 환자의 평균 나이는 60세$(43{\sim}77)$였고, 남녀 비는 40:3이었다. 조직학적으로 편평상피세포암이 42명, 악성 흑색종이 1명이었다. 식도 재건 방법은 gastric pull-up 32명, 유리 공장 이식 7명, colon interposition 4명이었다. 전체 43명 중 31명(72%)의 환자에서 합병증이 발생하였고, 수술 사망자는 7명(16%)이었다. 수술 후 최종 병기는 I 3명, IIa 14 명, IIb 1명, III 19명, IVa 6명이었다. 수술 사망자를 제외한 36 명 중 16명(44%)에서 종양이 재발하였고, 수술 후 3년, 5년 생존율은 29.3% 와 20.9%이었다. 결론: 경부식도암에 대한 수술은 수술 사망률, 합병증 발생률, 재발률이 높고, 장기 생존율이 낮지만, 방사선치료나 항암약물치료 만으로는 연하곤란의 완전한 해소 및 종양의 완치가 어려우므로 수술이 포함되는 다방법 병합치료가 필요하다고 생각한다.

• 대한의생명과학회지
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• 제12권3호
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• pp.153-160
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• 2006

Human colon cancer is the second most fatal disease among a variety of cancers to cause cancer death in U.S.A. and its incidence rate is currently increased in Korea. Recently, many studies have been being progressed on the efficacy of diverse combination treatments. But results of these studies in vitro were not similar those in vivo. This study compared the anticancer reactions between each use of arsenic trioxide and taxol against human colon cancer HT-29 cell line and combined use of two drugs. And these results compared with the results of HT-29 spheroid cells having similar characteristics to the solid tumor in vivo. The spheroid of HT-29 cells was formed by using a multicellular spheroid system and the result was observed through electron microscopy. In vitro cytotoxicity of each use of arsenic trioxide and taxol was evaluated in HT-29 monolayer cells. The $IC_{50}$ value for arsenic trioxide was to be $33{\mu}M$ and taxol was to be 18nM. The result treated with the combination of taxol and arsenic trioxide decreased the cytotoxicity on the HT-29 monolayer cells. The spheroid cells represented higher resistance against drugs than the monolayer cells. I demonstrated DNA fragmentation after incubation with concentrations more than $10{\mu}M$ arsenic trioxide and 100nM taxol for 48h, on the monolayer cells. But the results of HT-29 cell line treated with the combination of taxol and arsenic trioxide was the same as the outcome of control samples that were not treated with any drug. And I don't demonstrated DNA fragmentation on the spheroid cells. These results suggest that apoptosis was not induced in the use of the combination can be thought as that arsenic trioxide might work as an antagonist to inhibit a taxol mechanism to induce apoptosis. And the spheroid cells represented higher resistance against drugs than the monolayer cells.

• Journal of Chest Surgery
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• 제16권2호
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• pp.231-242
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• 1983

A clinical study was performed on 75 cases of the esophageal cancer and benign esophageal diseases experienced at Department of thoracic & cardiovascular surgery, School of Medicine, Keimyung University during 3 year period from 1978 to 1982. Of 75 cases of the surgical esophageal diseases, there were 35 patients of the esophageal cancer. 17 patients of benign esophageal stenosis, 10 patients of esophageal perforation, 4 patients of diverticulum. 3 patients of achalasia, 2 patients of congenital T-E fistula, one of upper esophageal web, one of esophageal foreign body, one of leiomyoma and patient of hemangioma. First, esophageal carcinoma was more frequent in men than in women by a ratio of five to one, and the peak incidence occurred in the 5th to 6th decade. Dysphagia was the most common symptom in 88.6 percent of our cases. The tumor was located mostly in the middle & the lower one third [91.4%]. The histological diagnosis was made in 35 cases. The squamous cell carcinoma was the most common [82.9%] and the rest was the adenocarcinoma in the lower one third [17.1%]. Thirty-five cases were operated and resection was feasible in the twenty-five patients [71.4%] with 2 cases of hospital mortality [5.7%]. All but two of the esophageal stenosis were caused by corrosive esophagitis and ages ranged from 7 to 70 years with average age of 32 years. Corrective operations were performed on 17 patients of esophageal stenosis of whom 12 patients had esophagocologastrostomy, 3 patients esophagogastrostomy and in non-corrosive esophageal stenosis one case and esophagoplasty and another case had release of external compression. There was one complication of stenosis of the esophageal perforation were traumatic in five cases, empyema in three cases, caustics in one case and postemetic in one case. 10 patients of the esophageal perforation underwent operation: primary closure in 5 cases, two staged colon interposition in 2, esophagogastrostomy in 1 and closed thoracotomy in 2 cases There were 2 complications of leakage of anastomosis sites in postoperative period. 4 patients of traction type of diverticulum underwent diverticulectomy & 3 patients of achalasia underwent modified Heller`s operation. 2 patients of congenital esophageal atresia had distal tracheoesophageal fistula & underwent one staged operation with the results of one death caused by pneumonia. Upper esophageal web had divulsion through the esophagoscope and foreign body in upper esophagus was removed through cervical esophagotomy. One case of leiomyoma in esophagus had esophagectomy and reconstruction with right colon. And one case of hemangioma in esophagus had esophagectomy & esophagogastrostomy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5239-5243
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• 2014

Background: The prognosis of young colorectal cancer (CRC) patients has been addressed by several studies but with contradictory results. The aim of the present study was to evaluate the clinico-pathological features of young Saudi patients with CRC in addition to displaying their survival outcome. Materials and Methods: In this retrospective study, young CRC patients (${\leq}40$ years) diagnosed between 2007 and 2011 from 4 centres in western Saudi Arabia, were included. Clinico-pathological features, tumor markers, dates of disease relapse and death were collected. Survival parameters were compared with those of older Saudi patients, reported in previous studies. Results: One hundred and sixteen young patients with CRC were identified (32.2% rectal, 67.8% colon). Some 44% were metastatic while 32.7% had stage III at diagnosis. Patients with grade 3 tumors made up 29.4% of the total while 49.5% had positive lymphovascular invasion (LVI), 56% had a lymph node (LN) ratio ${\geq}0.2$ and 40.2% were K-ras mutant. Median disease-free survival (DFS) and overall survival (OS) in non-metastatic cases were 22.8 and 49.6 months respectively with better median DFS in K-ras wild compared to mutant patients (28.5 vs 20.9 months, p=0.005). In metastatic cases, median OS was 19.5 months. These survival outcomes are inferior compared to those of older Saudi patients reported in prior studies. Conclusions: Young CRC patients present more commonly with advanced stage and a high incidence of adverse prognostic factors such as LVI and high LN ratio. Young CRC patients seem to have worse survival compared to older Saudi patients.

• Journal of Gastric Cancer
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• 제2권2호
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• pp.73-80
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• 2002

In spite the fact that H. pylori infection might be the causative organisms of acute and chronic gastritis, peptic ulcer diseases and the definition as the class I carcinogen by WHO IARC, still debates exist about the relationship between H. pylori and gastric carcinogenesis. Epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H, pylori, but the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remain obscure. In order to declare the clear association, definate evidences like that decrement in the incidence of gastric cancer after the eradication of H. pylori in designated area compared to noneradicated region or the blockade of specific mechanism acting on the carcinogenesis by H. pylori infection. The other way is to identify the upregulating oncogenes or downregulating tumor suppressor genes specifically invovled in H. pylori-associated carcinogenesis. For that, we established the animal models using C57BL/6 mice strain. Already gastric carcinogenesis was developed in Mongolian gerbils infected with H. pylori, but there has been no development of gastric cancer in mice model infected with H. pylori after long-term evaluation. Significant changes such as atrophic gastritis were observed in mice model. However, we could observe the development of mucosal carcinoma in the stomach of transgenic mice featuring the loss of TGF-beta sig naling by the expressions of dominant negative forms of type II receptor specifically in the stomach. Moreover, the incidence of gastric adenocarcinoma was significantly increased in group administered with both MNU and H. pylori infection than MNU alone, signifying that H. pylori promoted the gastric carcinogenesis and there might be host susceptibility genes in H. pylori-associated gastric carcinogenesis. Based on the assumption that chronic, uncontrolled inflammation might predispose to carcinogenesis, there have been several evidences showing chronic atrophic gastritis predisposed to gastric carcinogenesis in H. pylori infection. Although definite outcome of chemoprevention was not drawn after the longterm administration of anti-inflammatory drug in H. pylori infection, the actual incidence of atrophic gastritis and molecular evidence of chemoprevention could be obtained. Selective COX-2 inhibitor was effective in decreasing the development of gastric carcinogenesis provoked by H. pylori infection and carcinogen like in chemoprevention of colon carcinogenesis.

• Radiation Oncology Journal
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• 제13권4호
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• pp.359-368
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• 1995

목적 : 자궁경부암환자에서 근치적 목적으로 방사선치료를 외부조사와 강내조사를 시행한 환자의 실패양상과 생존율을 관찰하고 예후인자를 분석하기 위하여 본 연구를 시도하였다. 방법 : 1982년 3월 부터 1990년 5월 까지 8년간 자궁경부암으로 진단받고 이대부속병원 치료방사선과에서 방사선치료를 시행한 환자 280예 중 근치목적의 방사선치료로서 외부조사와 강내조사를 완료한 환자 114예를 대상으로 후향적 분석을 하였다. 연령분포는 30세에서 77세 까지로 중앙값은 53세이었다. FIGO에 의한 병기분포는 IB 19예($16.7{\%}$), IIA 23예($20.2{\%}$), IIB 42예($36.8{\%}$), IIIA 12예($10.5{\%}$), IIIB 18예($15.8{\%}$)이었다. 병리조직학적소견은 112예가 편평상피암이었고 2예는 선암이었다. 방사선치료방법으로 외부조사는 6MV 선형가속기(6MV,NEC 1000X)를 사용하여 전 골반강에 40-54 Gy를 조사하였으며, 강내조사는 Cs-137 밀봉선원으로 Fletcher-Suit applicator를 사용하여 1회 내지 2회 시행하여 point A에 40-42 Gy를 조사하여 point A의 총 방사선 선량은 병기 IB-IIA는 80-90 Gy(중앙값: 8580 cGy)로, IIB이상은 85-100 Gy(중앙값: 8850 cGy)로 하였다. 추적기간은 1개월에서 85개월로서 중앙값은 30개월이었다. 결과 : 국소실패만 보인 경우는 20예로 전체환자의 $17.5{\%}$이었으며 원격전이와 동반한 국소실패를 보인 경우는 7예($6.1{\%}$)로 전체 국소실패율은 $23.7{\%}$(27/114)이었다. 병기에 따른 국소실패율은 IB에서 $10.5{\%}$, IIA에서 $8.7{\%}$, IIB에서 $23.8{\%}$, IIIA에서 $50.5{\%}$, IIIB에서 $38.9{\%}$이었다. 국소실패부위는 자궁경부가 가장 많아서 전체 국소실패의 $37.5{\%}$(12/32)를 차지하였으며 다음은 자궁막조직으로 $34.3{\%}$(11/32)이었다. 원격전이만 있는 보인 경우는 6예로 전체환자의 $5.3{\%}$를 차지하였다. 원격전이된 부위는 골에 가장 많았으며(4/14), 다음으로 쇄골상관절종(3/14), 간(2/14)의 순으로 나타났다. 재발시기는 치료완료후 3개월에서 50개월이며 중앙값은 15개월이었다. 합병증으로 직장손상이 5예, 방광손상이 9예로서 총 14예($12.3{\%}$)이었다. 전체환자의 5년 생존율은 $70.5{\%}$이었고 병기 IB는 $100{\%}$, IIA는 $76.9{\%}$, IIB는 $77.6{\%}$, IIIA는 $87.5{\%}$, IIIB는 $69.1{\%}$이었다. 5년 무병생존율은 전체환자에서 $53.6{\%}$이었으며, 병기 IB는 $81.3{\%}$, IIA는 $67.9{\%}$, IIB는 $46.8{\%}$, IIIA는 $45.4{\%}$, IIIB는 $34.4{\%}$를 보였다. 무병생존율에 관계되는 예후인자는 다변수 분석에 의하면 performance status(P=0.0063)와 치료반응율(P=0.0026)은 유의성이 있었으나 병기,나이 및 point A의 방사선 선량은 유의성이 없었다. 결론: 자궁경부암환자에서 방사선치료 단독요법에 의한 치료성적은 병기 IB와 IIA는 양호하였으나 IIB이상에서 Point A의 방사선 선량을 90 Gy이상 증가시켜도 국소실패율이 높고 생존율의 향상을 얻을 수 없기 때문에 항암제 혹은 방사선감작제와 병용함으로써 국소제어율을 높이고 원격전이를 감소시키는 방법이 앞으로 연구되어져야 할 과제라고 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제48권1호
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• pp.24-32
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• 2000

연구배경: MMR 유전자의 불활성화에 의해 야기되는 유전적 불안정성은 발암기전의 한 부류로 인정되고 있다. 저자들은 비소세포폐암의 발암과정에서의 MSI의 역할을 규명하기 위해 비소세포폐암에서 MSI의 빈도 및 MSI 유무에 따른 임상상의 차이를 조사하였다. 대상 및 방법: 근치적 절제술을 받은 비소세포폐암 20예를 대상으로 하였다. 동결된 폐암조직과 환자의 림프구에서 DNA를 추출한 후 3p와 9p의 15개의 marker들을 대상으로 PCR을 시행하고 7% polyacrylamide gel에서 전기영동한 후 silver 염색을 시행하였다. 암조직과 림프구 DNA의 PCR product의 band를 비교하여 MSI와 LOH를 판정하였다. 결 과: 1) 대상환자들은 남자 19예, 여자 1예였으며 모두 흡연자였고 평균 흡연력은 47 갑년이었다. 폐암의 조직형은 편평상피암 15예, 선암 4예, 대세포암 1예였고, 술후병리학적병기는 I기 6예, II기 5예, IIIA기 7예, IIIB 기 2예였다. 2) 20예 가운데 8예(40%)에서 MSI가 관찰되었으며 3예는 한 개의 marker에서, 5예는 2개 이상의 marker에서 MSI가 관찰되었다. 3) LOH는 10예(50%) 에서 있었으며, LOH 유무에 따른 병기 및 흡연력의 차이가 없었다. 4) 분석한 marker의 10% 이상에서 MSI가 관찰된 MSI-L 종양은 5 예였으며, 대부분의 marker에서 MSI 양성인 MSI-H 종양은 없었다. MSS 종양과 MSI-L 종양은 흡연력, 병기, 폐암 조직형 및 LOH 빈도의 유의한 차이가 없었다. 결 론: 비소세포폐암에서 MSI는 비교적 흔히 관찰되지만 MMR 유전자의 불활성화에 의한 MMP pathway는 비소세포폐암의 주요 발생기전은 아닐 것으로 생각된다. 향 후 비소세포폐암의 발암과정에 있어서 MMP pathway의 역할을 규명하기 위해서는 보다 많은 예를 대상으로 한 연구가 필요할 것으로 생각되며, MSI 발생기전에 관한 추가적인 연구가 필요할 것으로 생각된다.