• Title/Summary/Keyword: Colon Cancer

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Regulation of Wnt/β-catenin Signal Transduction in HT-29 Colon Cancer Cells by a Rhododendron brachycarpum Fraction (홍만병초 분획물에 의한 HT-29대장암 세포의 Wnt/β-catenin 신호전달 조절)

  • Sim, Bo Ram;Nam, Young Sun;Lee, Ja Bok
    • Journal of Life Science
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    • v.29 no.8
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    • pp.871-878
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    • 2019
  • The aim of this study was to determine the anticancer activities of an 80% methanol extract and various fractions of Rhododendron brachycarpum (RB). The n-hexane fraction of RB showed the highest inhibitory activity (Inhibit concentration $50%=20.2{\pm}1.2{\mu}g/ml$) in HT-29 cells. Colony- and sphereforming abilities were significantly correlated with a decrease in the cell count and size. A TOP/FOP flash reporter assay revealed that the inhibitory activity of the n-hexane fraction of RB ($0.22{\pm}0.02$ fold change) was lower than that of the 80% methanol extract and that of other fractions. The n-hexane and ethyl acetate fractions of RB were predominantly dependent on the expression levels of intracellular ${\beta}-catenin$. Western blotting using $p-GSK3{\beta}$ with only the n-hexane fraction of RB was conducted to examine whether these secondary metabolites reduced ${\beta}-catenin$ degradation. Intracellular ${\beta}-catenin$ regulation resulted in quantitative changes in the nucleus. In summary, these results demonstrate the potential of the n-hexane fraction of RB as a natural anticancer agent.

Clinical Outcomes of Corrective Surgical Treatment for Esophageal Cancer (식도암의 외과적 근치 절제술에 대한 임상적 고찰)

  • Ryu Se Min;Jo Won Min;Mok Young Jae;Kim Hyun Koo;Cho Yang Hyun;Sohn Young-sang;Kim Hark Jei;Choi Young Ho
    • Journal of Chest Surgery
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    • v.38 no.2 s.247
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    • pp.157-163
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    • 2005
  • Background: Clinical outcomes of esophageal cancer have not been satisfactory in spite of the development of surgical skills and protocols of adjuvant therapy. We analyzed the results of corrective surgical patients for esophageal cancer from January 1992 to July 2002. Material and Method: Among 129 patients with esophageal cancer, this study was performed in 68 patients who received corrective surgery. The ratio of sex was 59 : 9 (male : female) and mean age was $61.07\pm7.36$ years old. Chief complaints of this patients were dysphagia, epigastric pain and weight loss, etc. The locations of esophageal cancer were 4 in upper esophagus, 36 in middle, 20 in lower, 8 in esophagogastric junction. 60 patients had squamous cell cancer and 7 had adenocarcinoma, and 1 had malignant melanoma. Five patients had neoadjuvant chemotherapy. Result: The postoperative stage I, IIA, IIB, III, IV patients were 7, 25, 12, 17 and 7, respectively. The conduit for replacement of esophagus were stomach (62 patients) and colon (6 patients). The neck anastomosis was performed in 28 patients and intrathoracic anastomosis in 40 patients. The technique of anastomosis were hand sewing method (44 patients) and stapling method (24 patients). One of the early complications was anastomosis leakage (3 patients) which had only radiologic leakage that recovered spontaneously. The anastomosis technique had no correlation with postoperative leakage, which stapling method (2 patients) and hand sewing method (1 patient). There were 3 respiratory failures, 6 pneumonia, 1 fulminant hepatitis, 1 bleeding and 1 sepsis. The 2 early postoperative deaths were fulminant hepatitis and sepsis. Among 68 patients, 23 patients had postoperative adjuvant therapy and 55 paitents were followed up. The follow up period was $23.73\pm22.18$ months ($1\~76$ month). There were 5 patients in stage I, 21 in stage 2A, 9 in stage IIB, 15 in stage III and 5 in stage IV. The 1, 3, 5 year survival rates of the patients who could be followed up completely was $58.43\pm6.5\%,\;35.48\pm7.5\%\;and\;18.81\pm7.7\%$, respectively. Statistical analysis showed that long-term survival difference was associated with a stage, T stage, and N stage (p<0.05) but not associated with histology, sex, anastomosis location, tumor location, and pre and postoperative adjuvant therapy. Conclusion: The early diagnosis, aggressive operative resection, and adequate postoperative treatment may have contributed to the observed increase in survival for esophageal cancer patients.

Limb Salvage Surgery with Tumor Prosthesis for the Malignant Bone Tumors Involving the Proximal Femur (대퇴골 근위부 악성 골종양 환자에서 종양 대치물을 이용한 사지 구제술)

  • Chun, Young Soo;Baek, Jong Hun;Lee, Seung Hyuk;Lee, Chung Hwan;Han, Chung Soo
    • The Journal of the Korean bone and joint tumor society
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    • v.20 no.1
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    • pp.7-13
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    • 2014
  • Purpose: As well as patient survival, the restoration of postoperative function such as ambulation is important in limb salvage operations for treatment of malignant bone tumors involving the proximal femur. The authors analyzed clinical outcomes of limb salvage operations using tumor prostheses for metastatic or primary malignant bone tumors in the proximal femur. Materials and Methods: From February 2005 to January 2014, 20 cases (19 patients) with malignant bone tumor involving the proximal femur with pain or complicated pathologic fracture were treated with segmental resection and limb salvage operations with tumor prostheses. Mean age was 63.1 years (range 35-86). Fourteen patients were male and six ones were female. The mean follow-up period was 20 months (1-94 months). There were 15 cases of metastatic bone tumor, 4 cases of osteosarcoma, and 1 case of multiple myeloma. The primary tumors of the metastatic bone tumors included 4 lung cancers, 3 hepatocellular carcinomas, and 3 renal cell carcinomas. Other primary tumors were breast cancer, thyroid cancer, colon cancer, prostate cancer, and malignant spindle cell tumor, each in 1 case. Modular tumor prostheses were used in all cases; (Kotz's$^{(R)}$ Modular Tumor prosthesis (Howmedica, Rutherford, New Jersey) in 3 cases, MUTARS$^{(R)}$ proximal femur system (Implantcast, Munster, Germany) in 17 cases). Perioperative pain was assessed with Visual Analogue Scales (VAS). Postoperative functional outcome was assessed with Musculoskeletal Tumor Society (MSTS) grading system. Results: Out of 20 cases (19 patients), 11 cases (10 patients) survived at the last follow-up. Average postoperative survival of the 9 deceased patients was 10.1 months (1-38 months). VAS score improved from pre-operative average of 8.40 (5-10) to 1.35 (0-3) after operation. Average postoperative MSTS function score was 19.65 (65.50%, 7-28). The associated complications were 2 local recurrences, 3 hematomas, 3 infections, 2 scrotal swellings, and 1 dislocation. There was no case of periprosthetic fracture or loosening. Conclusion: Limb salvage operation with tumor prosthesis is an appropriate treatment for early pain reduction and functional restoration in malignant bone tumors in the proximal femur with pain an/or complicated pathologic fractures.

Increases in Doxorubicin Sensitivity and Radioiodide Uptake by Transfecting shMDR and Sodium/Iodide Symporter Gene in Cancer Cells Expressing Multidrug Resistance (다약제내성 암세포에서 shMDR과 Sodium/Iodide Symporter 유전자의 이입에 의한 Doxorubicin 감수성과 방사성옥소 섭취의 증가)

  • Ahn, Sohn-Joo;Lee, Yong-Jin;Lee, You-La;Choi, Chang-Ik;Lee, Sang-Woo;Yoo, Jeong-Soo;Ahn, Byeong-Cheol;Lee, In-Kyu;Lee, Jae-Tae
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.3
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    • pp.209-217
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    • 2007
  • Purpose: Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. Material and Methods: At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. Results: In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Conclusion: Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and radioiodine after cotransfection shMDR and NIS gene can be used to overcome MDR.

Urokinase Plasminogen Activator Receptor Gene Expression and Clinico-Pathologic Feature in Gastric Cancer Patients (위암 환자의 Urokinase Plasminogen Activator Receptor 유전자의 발현양상)

  • Kim Yong Gil;Lee Kyung Hee;Kim Min Kyung;Lee Jae Lyun;Hyun Myung Sue;Kim Sang Hun;Kim Hee Sun
    • Journal of Gastric Cancer
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    • v.4 no.4
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    • pp.207-212
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    • 2004
  • Purpose: Invasion and metastasis in solid tumors require the action of tumor-associated proteases. The serine protease urokinase-type plasminogen (uPA) and receptor (uPAR) appear to have a major function in these processes. Expression of the uPAR is elevated in breast and colon carcinomas, and this is often associated with invasiveness and poor prognosis. The purpose of this study was to determine whether the expression of the uPAR gene correlates with clinico-pathological parameters in human gastric carcinomas. Materials and Methods: We examined the expression of uPAR mRNA by using northern blot analysis and RT-PCR in 35 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumor findings and survival rates were obtained from the patient records and from endoscopic, surgical, and pathological reports. Results: The expression of uPAR and was higher in most neoplasms than in the corresponding normal mucosal tissue. uPAR mRNA expression in tumors correlated well with lymph-node metastasis (P<0.02) and tumor stage (P<0.01). The survival rate of patients with tumors displaying high uPAR expression levels was significantly lower (P<0.04) than that of patients without uPAR expression, but IL-8 showed only the tendency of survival difference. Conclusion: These results suggest that uPAR may be an important prognostic factor in human gastric carcinomas.

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Growth Inhibitory Effect of Kimchi Prepared with Four Year-Old Solar Salt and Topan Solar Salt on Cancer Cells (토판염 및 4년 숙성 천일염으로 제조한 김치의 암세포 성장 억제 효과)

  • Yoon, Hae-Hoon;Chang, Hae-Choon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.7
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    • pp.935-941
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    • 2011
  • The growth inhibitory effects of kimchi prepared with solar salt were investigated. Chinese cabbages were brined with purified salt, four year-old solar salt, and Topan solar salt, and then mixed with other ingredients. The final salt concentration was adjusted to 2.2~2.4% (w/v) for each salt, and the kimchi was fermented at $7^{\circ}C$. When the acidity reached around 0.5~0.6%, the kimchi was used as a sample for further experimentation. MTT assay was used to measure the growth inhibitory effect of kimchi extracts (water, methanol) on BJ human foreskin normal cells, AGS human gastric adenocarcinoma cells, and HT-29 human colon carcinoma cells. Water extracts of all the kimchi samples showed growth inhibitory effects on cancer cells; however, there was no significant difference among the used salts. Methanol extracts of all the kimchi samples showed higher growth inhibitory effects compared to the water extracts. The methanol extracts of four year-old solar salt kimchi (AGS: 73%, HT-29: 48%) and Topan solar salt kimchi (AGS: 62%, HT-29: 46%) showed higher growth inhibitory effects than that of purified salt kimchi (AGS: 52%, HT-29: 39%). In addition, morphological changes of cancer cells (AGS, HT-29) and decreased cell numbers were observed when methanol extract of four year-old solar salt kimchi was treated to AGS and HT-29 cells. However, none of the kimchi extracts showed any growth inhibitory effect on BJ normal cells.

Comparative Studies of the Cytotoxic Effect of Four Different Sea Bream Species (Pagrus major, Acanthopagus schlegeli, Oplegnathus fasciatus, and Girella punctata) (4종 돔 추출물의 세포독성 효과 비교)

  • Hwang, Seong Yeon;Lim, Sun-Young
    • Journal of Life Science
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    • v.27 no.9
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    • pp.1064-1069
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    • 2017
  • This study compared the cytotoxic effect of extracts from four different sea bream species (Pagrus major, Acanthopagus schlegeli, Oplegnathus fasciatus, and Girella punctata) in human cancer cell lines. Cytotoxic activity against the growth of human gastric adenocarcinoma (AGS) and HT-29 human colon cancer cell lines was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Treatment with acetone/methylene chloride (A+M) and methanol (MeOH) extracts from the four sea bream species dose-dependently increased cytotoxicity against the growth of AGS and HT-29 cancer cells (p < 0.05). As shown by a cell viability assay, treatment with A+M and MeOH extracts from red sea bream (P. major) had the highest cytotoxic effect (p < 0.05) among the sea bream species. The IC50 values of an 85% aqueous methanol (85% aq. MeOH) fraction from red sea bream (P. major) against AGS and HT-29 cancer cells was 0.33 and 1.58 mg/ml, respectively, suggesting that the 85% aq. MeOH fraction had the highest cytotoxic effect among the fractions (p < 0.05). Our results demonstrate that four different sea bream species exhibited cytotoxic activity, as well as high-quality amino acids and fatty acids. Among the sea bream species, red sea bream (P. major) showed the greatest cytotoxic effect. The results could be used to improve nutrition information available to consumers.

CHEMOPREVENTION OF COLON CANCER BY THE KOREAN FOOD STUFFS COMPONENTS

  • Kim, Dae-Joong;Shin, Dong-Hwan;Ahn, Byeong-Woo;Jang, Dong-Deuk;Hiroyuki Tsuda;Shoji Fukushima
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05b
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    • pp.106.2-132
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    • 2002
  • 형질전환 (유전자 결핍; Knockout) Min 마우스를 이용하여 대장암 발생에서 배추, 양배추 주성분인 indole-3-carbinol (I3C)의 대장암 예방효과를 규명하고자 하였다. 실험동물로는 C57BL/6J-Apc$^{min/+}$(Min 마우스)계의 5내지 6주령의 수컷 이형접합체 형질전환 마우스 70마리와 C57BL/6J계의 동일 산자, 동일 주령의 수컷 wildtype 비형질전환 마우스 10kfl를 The Jackson Laboratory 사 (Bar harber, ME, USA)로부터 직접 구입하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 (Min)마우스 70마리를 각 군 20내지 25마리씩 세군으로 나누었다. Group 1에는 20마리, Group 2에는 25마리, Group 3에는 25마리를 배치하고, I3C 투여 실험군 (Group 1과 2)에는 실험시작시에 AIN-76A 분말사료에 I3C가 각각 100 및 300ppm이 함유되도록 조제하여 공급하였다. 그리고 실험군(Group 3)에는 실험시작부터 종료시까지 AIN-76A 정제고형사료(Teklad사, WI, USA)를 자유로이 급이하였다. 각군간의 체중, 사료 및 음수소비량을 매 2주마다 측정하였고, 10주간 (16주령)의 실험종료시에는 최종체중과 간장, 신장, 비장 등의 장기무게를 측정하여 상대장기 무게비를 산출하였다. 대조군으로서 C57BL/6J계의 동일 산자, 동일 주령의 수컷 wildtype 비형질전환 마우스 10마리는 같은 조건의 사육실에서 AIN-76A 정제고형사료를 33주간 자유로이 급이하였다. 실험동물은 부검전에 하룻밤 동안 절식하고 이산화탄소 흡입 마취하에서 흉대동맥을 절단하여 방혈하고 각 장기(심장, 폐, 위)를 적출하여 생리심염수에 넣어 장기무게를 측정하고 포르말린에 고정하였다. 소장과 대장의 검사를 위하여 위의 식도부위와 직장을 실로 결찰하여 적출하고 생리심염수를 주입하여 팽창시켜, 십이지장, 공장, 및 회장, 그리고 대장으로 나누어 여과지에 펼친 후 포르말린에 고정하였다. 소장과 대장은 육안 및 자동 영상분석길ㄹ 이용한 분석이 끝난 후에 각 부위별로 4-6개의 절편을 작제하여 포르말린에 재고정하고, 통상적인 조직처리과정, 파리핀 포매 및 3-4$\mu$m 두께의 조직절편을 제작하여 H&E 염색을 실시하여 현미경으로 검경하였다. 약 1주일간의 포르말린 고정이 끝난 소장 및 대장을 부위별, 별 종양개수 및 분포를 자동영상분석기(Kontron Co. Ltd., Germany)로 분석하였다. 체의 변화, 장기무게, 사료소비량 및 마리당 종양의 개수에 대한 통계학적 유의성 검증을 위하여 Duncan's t-test로 통계처리 하였고, 종양 발생빈도에 대하여는 Likelihood ration Chi-square test로 유의성을 검증하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군의 대장선종의 발생률은 84%(Group 3; 21/25례)로써 I3C 100ppm 및 300ppm을 투여한 경우에 있어서는 각군 모두 60%(Group 1; 12/20 례, Group 2; 15/25 례)로 감소하는 경향을 나타내었다. 대장선종의 마리당 발생개수에 있어서는 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군은 1.40$\pm$0.24(100%)에 비하여 I3C 저농도 투여 실험군(Group 1; 0.85$\pm$0.23; 61%, P<0.01), 그리고 I3C 고농도 투여 실험군(Group 2 ; 1.32$\pm$0.29 ; 94%)의 순으로 감소하였다. 선종의 크기별 종양의 발생개수의 분포에 있어서 I3C 저농도 투여 실험군에 있어서는 선종의 크기가 3mm이하의 수가 현저하게 감소하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군의 부위별 소장선종의 발생수는 십이지장부위를 제외하고 각 군에서 유의한 변화는 관찰되지 않았다. 십이지장 종양의 발생개수에서만 I3C 저농도 투여 실험군(Group 1 ; 3.11$\pm$0.85)이 대조군 (Group 3: 1.48$\pm$0.35) 및 I3C 고농도 투여 실험군(Group 2: 1.56$\pm$0.47)에 비하여 유의성 있게 증가하였다. (P<0.05). 따라서 I3C은 소장에서는 암예방 효과가 뚜렷하지 않으나, 대장에 대한 암에방 효과가 있을 것으로 생각된다. 소장 및 대장을 제외한 간장, 신장, 비장, 심장, 폐 그리고 위 등의 기타 장기에서의 조직병리학적 변화는 관찰되지 않았다. 소장 및 대장의 종양은 선종(polyps)으로 관찰되었다. 지난 10여년간 형질전환 및 유전자 결핍 실험동물의 종류가 기하 급수적으로 증가하여 이용되고 있다. 가족성 대장 선종성 용종증(FAP)의 대표적인 모델로 이용되고 있는 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스를 사용하여 배추나 양배추의 주요성분인 Indole-3-carbinol(I3C)의 대장암 예방효과가 있는지를 검색하여 본 결과 AIN-76A정제사료만을 투여한 대조군의 대장선종의 발생률 84%에 비하여 I3C 100 및 300ppm을 투여한 실험군에 있어서 각군 모두 60%로서 감소하는 경향을 나타내었으며, 대장선종의 마리당 발생개수에 있어서는 대조군의 1.40$\pm$1.041를 100%로 환산하였을 경우 I3C 저농도 및 고농도 투여 실험군에서는 각각 약 61%와 94%를 나타내여 감소하였다. 특히 대장선종의 크기별 분포에 있어서 선종의 크기가 3mm이하의 수가 현저하게 감소하였다. 따라서 저농도 I3C의 투여는 실험적 유전성 가족성 대장 선종성 용종증 모델에 있어서 어느정도 암 예방효과가 있는 것으로 생각된다. 그러나 소장 선종의 발생에는 별 영향이 없는 것으로 생각된다. 그러나 본 실험에 사용된 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스는 실험개시 시점이 7내지 8주령이 경과하여 이미 태생기부터 소장 및 대장의 선종 발생이 진행되어 온 것을 감안하고 특히 비스테로이드계 항염증 소염제(NSAIDS)와 같은 강력한 COX-2억제제가 아님을 고려하면, 상당한 선종의 발생을 억제할 수 있는 가능성이 매우 높다고 생각한다. 또한 이제까지 배추나 양배추 성분의 복합성분들에 대한 실험적 대장암 모델에서의 촉진효과 등에 대한 보고들이 있어 온 점을 고려할 때 위암(Kim 등, 1994) 간암(Kim 등, 1994), 유방암(Grubbs, 등, 1995; Bradlow 등, 1995)에 대한 예방효과가 있을 것으로 생각된다. 앞으로 이러한 종양조직내에서의 COX-2 및 iNOS mRNA와 단백질의 발현정도를 분자병리학적으로 연구중에 있으며, 향후 십자화과식물 성분인 indole-3-carbinol이 마우스뿐 만 아니라 랫드의 화학발암물질에 의한 대장종양에 대한 억제효과 있는지 연구 필요가 있다. Min 마우스와 같은 형질 전환(유전자결핍;knockout) 실험동물을 이용한 새로운 중기 발암성 시험범의 확립을 통한 각종 환경 유해물질의 발암성 유무 및 COX-2 억제작용이 있는 식품인자의 암예방 후보물질을 체계적으로 검색하는데 유용하게 활용될 수 있을 것으로 생각한다.

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Preliminary Results of Concurrent Chemotherapy and Radiation Therapy using High-dose-rate Brachytherapy for Cervical Cancer (자궁경부암에 항암화학요법과 동시 병용요법으로 외부 방사선조사와 고선량률 강내조사의 예비적 치료 결과)

  • Lee, Kyung-Ja;Lee, Ji-Hye;Lee, Re-Na;Suh, Hyun-Suk
    • Radiation Oncology Journal
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    • v.24 no.3
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    • pp.171-178
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    • 2006
  • [ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.

Sodium Salicylate(NaSaL) Induces Apoptosis of NCI-H1299 Lung Carcinoma Cells via Activation Caspase-3 Protease (NCI-H1299 폐암 세포주에서 Caspase-3 Protease 활성을 통한 Sodium Salicylate(NaSaL)의 세포고사)

  • Shim, Hyeok;Yang, Sei-Hoon;Bak, Sang-Myeon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.5
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    • pp.485-496
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    • 2002
  • Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and/or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. Methods : A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and unclear staining(DAPI). The talytic activity of the caspase family was measured by the fluirigenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the death substrates(PARP and ICAD). Results : NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the $subG_0/G_1$ population and unclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. Conclusion : NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.