• 한국약용작물학회지
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• 제10권5호
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• pp.403-408
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• 2002

마가목 잎, 수피, 열매 추출물의 Spore-rec assay와 Ames test에 의한 항돌연변이 활성탐색 결과, 추출물 모두 돌연변이원성을 나타내지 않았으며 열매와 수피의 에탄올 추출물에서 MNNC에 대하여 높은 항돌연변이원성을 나타내었다. 인간 암세포주를 이용한 항암효과 실험은 먼저 정상간세포인 WRL68에 대한 세포독성효과를 검토한 결과, 0.75mg/ml 이하의 농도에서 수피의 물 추출물을 제외하고는 모두 20% 이하의 낮은 세포독성을 나타내어 추출물 자체의 세포 독성은 낮은 것으로 확인되었다. 인간 폐암세포(A549), 유방암세포(MCF7), 간암세포(HepG2)에 대한 세포독성 결과, 수피의 에탄올 추출물이 폐암세포주인 A549에 대하여 1.0 mg/ml의 농도에서 94%의 가장 높은 암세포 생육억제능을 나타내었으며, 0.75mg/ml 이상의 농도에서 65%이상의 생육억제 활성을 나타내었다. 유방암세포주인 MCF7에 대하여서는 0.75mg/ml 이상의 농토에서 58%이상의 생육억제능을 나타내었으며, 열매의 에탄올 추출물이 1.0mg/ml의 농도에서 91%의 생육을 억제하였다. 간암세포주인 HepG2에 대하여서는 수피와 열매의 추출물들이 0.75mg/ml 이상의 농도에서 56%이상의 생육억제활성을 나타내었다. 이와 같은 결과로부터 마가목 잎, 열매, 수피 추출물들은 시료자체의 독성은 낮은 반면 항돌연변이원성 및 암 세포주에 대한 생육억제활성이 높아 앞으로 이들 추출물을 이용한 기능성 식품소재로의 이용 가능성이 높을 것으로 사료된다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권1호
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• pp.41-51
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• 2008

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which compromises about 6$\sim$8% of all tumors followed by the adenoid cystic carcinoma (ACC) and adenocarcinoma. Most deaths from salivary carcinomas are caused by recurrent or metastatic lesions that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the vascular metastasis is important for the design of more effective therapy of salivary carcinomas. Neoangiogenesis is essential for tumor growth, which is postulated to be fundamentally dependent on the induction of stromal neovascularization. However, how neovascularization takes place in live tissue has not been fully established, especially in recruitment and differentiation of endothelial cells in the salivary gland tumors. Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide growth factor known to exert its mitogenic activity specifically on endothelial cells. VEGF has been shown th be directly involved in angiogenesis, which in essential for the pathogenesis of many solid tumors. von Willebrand factor (vWF) is a large multimeric protein synthesized by megakaryocytes and endothelial cells that enable platelets to adhere to exposed subendothelium and, as well, to respond to changes in the blood flow. Recent studies suggest that increased levels of vWF correlate with progression of disease, metastasis, or survival time and thus may have a prognostic significance. vWF is explained as an acute phase proteins which is increased in cancer or as a result of increased endothelial cell synthesis associated with tumor-induced angiogenesis. Due to adhesive properties of vWF, its increased concentrations may also contribute metastasis of tumor. In this study, we determined the mRNA expression of VEGF and vWF in salivary ACC, MEC and pleomorphic adenoma by in situ hybridization. As a result, stronger expression of VEGF and vWF was seen in salivary ACC and MEC which has more invasive nature than the salivary benign tumor.

• Journal of Radiation Protection and Research
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• 제28권3호
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• pp.233-237
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• 2003

It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorectal cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. The clonogenic cell survival in vitro indicated that RKO-ATM cells were markdely radioresistant than RKO.C cells. Treatment with 3 mM of caffeine significantly increased the radiosensitivity of cells, particulary the RKO-ATM cells, so that the radiosensitivity of RKO.C cells and RKO-ATM cells were almost similar. The radiation induced G2/M arrest in RKO-ATM cells was noticeably longer than that in RKO.C cells and caffeine treatment significantly reduced the length of the radiation induced G2/M arrest in both RKO.C and RKO-ATM cells. Pentoxifylline and wortmannin were also less effective than caffeine to radiosensitize RKO.C or RKO-ATM cells. However, wortmannin was more effective than caffeine against human lung adenocarcinoma A549 cells indicating the efficacy of ATM inhibitor to increase radiosensitivity is cell line dependent. For in vivo study, RKO.C cells were injected s.c. into the hind-leg of BALB/C-nuslc nude mice, and allowed to grow to 130mm3 tumor. The mice were i.p. injected with caffeine solution or saline and the tumors irradiated with 10 Gy of X-rays. The radiation induced growth delay was markedly increased by 1-2 mg/g of caffeine. It was concluded that caffeine increases radiosensitivity of tumor cells by inhibiting ATM kinase function, thereby inhibiting DNA repair, that occurs during the G2/M arrest after radiation.

• 대한두경부종양학회지
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• 제22권2호
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• pp.130-136
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• 2006

Introduction : The sensitivity of tumor cells to radiotherapy is a critical determinant of local control and potential cure in advanced head and neck squamous cell carcinoma(HNSCC). The emergence of radioresistant tumor cells is an obstacle to cancer therapy. Most radioresistant cells have a higher proportion of cells in the Sphase of the cell cycle and a lower apoptotic fraction than radiosensitive cells. HSV replication is increased in cells that have higher S-phase fractions. NV1066 is an oncolytic herpes simplex virus type-1 mutant. We hypothesized that NV1066 replication and cytotoxicity are increased in radioresistant cells. The purpose of this study is to evaluate the antitumor efficacy of NV1066 to treat radioresistant HNSCC. Methods : Radioresistant cells were selected by treating five HNSCC cell lines with repeated conventional fractionated doses of radiation(2Gy/day), using a Cs-137 irradiator, up to a cumulative dose of 70Gy. Clonogenic cell survival and S-phase fractions were compared between radioresistant and parental radiosensitive cells. The two cell populations were then treated with NV1066 to examine viral replication, by the viral plaque assay and viral cytotoxicity. Results : Fractionated irradiation resulted in the selection of radioresistant cells. Radioresistant cells had a higher S-phase fraction(42.9%) compared to parental cells(26.2%). NV1066 replication in radioresistant cells was 7.4 times higher than in parental cells(p<0.01). Treatment with NV1066 resulted in increased cytotoxicity of 24.5% in radioresistant cells compared to parental cells(p<0.05). Conclusion : NV1066 showed increased viral replication and cytotoxicity in radioresistant HNSCC cell lines. These findings suggest a potential clinical application for this oncolytic viral therapy as treatment for radioresistant head and neck cancers.

• 한국미생물·생명공학회지
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• 제34권2호
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• pp.136-142
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• 2006

Haematococcus pluvialis는 astaxanthin을 많이 생산하는 미세조류로써 astaxanthin은 항산화제로 면역반응을 강화시켜주며 항암효과 등을 가지고 있다. 그런데 야생종의 낮은 생장속도와 astaxanthin의 생산에는 한계가 있기 때문에 이를 극복하기위해 돌연변이 방법을 사용하였다. 돌연변이 방법으로는 자외선 조사와 EMS와 colchicines 처리를 사용하여 야생종보다 colony가 크고 더 붉은 것은 선택하였다. 선별된 돌연변이들은 carotenoid 생합성과정을 억제하는 nicotine 과 diphenylamine을 이용하여 다시 선별하였다. 그때 생존율은 40-50%이었고 여기서 선별된 균주들을 다시 규모를 키워 배양한 결과 자외선 처리한 돌연변이인 U15-5가 야생종보다 세포당 total carotenold 생산량이 1.68배 증가하였고, colchicine 처리한 DS와 M4-3은 생장속도가 $20\sim30%$ 증가하였다.

• Clinical and Experimental Pediatrics
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• 제45권3호
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• pp.354-361
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• 2002

목 적: 본 연구에서는 in vitro 및 in vivo에서 HSV-TK 유전자 치료의 bystander 효과 및 기전을 관찰하고, 싸이토카인 유전자의 병합 치료가 bystander 효과를 증폭시킬 수 있는지 조사하여 그 결과를 향후 신경모세포종 치료에 적용하고자 본 연구를 시행하였다. 방 법: A/J 마우스 신경모세포종 모델에서, neuro-2a/TK 세포와 unmodified neuro-2a세포를 여러 비율로 혼합하여 접종한 후 GCV를 투여하여 종양의 크기 변화 및 생존 유무를 관찰하였다. 마우스 신경모 세포종에서 bystander 효과의 기전을 알아보기 위해 neuro-2a/TK 세포를 주입한 마우스의 조직을 절개하여 connexin 43, CD4+ 및 CD8+ 세포 침윤을 관찰 하였다. 10% 및 25% HSV-TK 투여 군에서 neuro-2a/IL-2 세포의 투여가 bystander 효과를 증폭시키는 지 조사하였다. 결 과 : 1) in vitro 및 in vivo에서 bystander 효과는 뚜렷하게 관찰되었다. 2) 마우스 신경모세포종의 면역 조직 화학 염색 검사에서 connexin 43 발현은 관찰되지 않았으나 많은 수의 CD4+ 및 CD8+ T 세포의 침윤이 관찰되었다. 3) 10% 및 25% HSV-TK 투여군의 마우스에서 neuro-2a/IL-2 세포의 투여는 대조군과 비교하여 종양의 성장을 더 억제 시켰다. 결 론: In vitro 및 in vivo에서 HSV-TK/GCV 유전자 치료의 bystander 효과는 뚜렷하였으며, 그 기전으로 면역 세포가 중요한 역할을 할 것으로 추측된다. 그리고 bystander 효과는 IL-2 투여에 의해 증폭됨을 확인하였다. 이는 향후 신경모세포종의 수술 후 잔존암 치료에 HSV-TK/GCV 유전자 치료가 이용 가능할 것으로 생각된다.

• Journal of Chest Surgery
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• 제29권3호
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• pp.315-321
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• 1996

폐암 환자에서 기관지성형술은 전폐절제술을 받기에 폐기능이 충분치 않은 환자에서 사용되었으나 최근에는 일부 환자에서 전폐절제술을대신할만큼 발달되었다 1992년 1월부터 1995년 7월까지 15례의 폐암 환자에서 기관지성형술을 시행하였다. 연령 분포는 46세에서 70세까지였으며 60대가 8례로 가장 많았다. 남자 13례 여자 2례 였다. 소매우상엽절제술이 7례로 가장 많았고 소매우하엽절제술 2례, 소매좌 상엽절제술 5례, 소매전폐절제술이 1례였다. 수술 병기는제 1병기 3례, 제 2병기 8례,제 3병기가 1례였고 T4N2MO가 1례 였다. 술후 합병증을 보면 국소적 재발이 3례로 가장 많았고 그외 문합부위 육아조직 형성이 1례, 창상감염이 1례였다. 패혈증에 의한 수술사망이 1례 있었으며 만기사망이 2례 발생하여 전 체 환자의 3년 생존율이 80%였다. 술전 폐기능검사를 이용하여 술후 예상 FEVI을 구하여 술후 실측 FE'Vl과 비교해 본 결과 상관계수 0.71로 상관관계가 있는 것으로 나타나 문합부위 이하의 폐기능이 잘 보존 된 것으로 사료되 었다. 결론적으로 폐암 환자의 일부에서 수술이 원만히 이루어지고 술후 적절한 환자관리가 된다면 기관지 성형술이 幌瓚卉┝杏릿\ulcorner향상된 폐기능을 유지하면서 높은 생존율을 보일 것으로 사료된다.

• Radiation Oncology Journal
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• 제35권2호
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• pp.112-120
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• 2017

Purpose: To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. Materials and Methods: Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). Results: The age range was 26-87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. Conclusion: Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2004년도 학술대회지
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• pp.1-20
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• 2004

Polychlorinated biphenyls (PCBs), one a group of persistent and widespread environmental pollutants, have been considered to be involved in immunotoxicity, carcinogenesis, and apoptosis. However, the toxic effects and physical properties of a PCB congener are dependent on the structure. In the present study, we investigate the toxic effects and action mechanisms of PCBs In cells. Among the various congeners tested, 2,2',4,6,6'-PeCB-pentachlorobiphenyl (PeCB), a highly ortho-substituted congener having negligible binding affinity for aryl hydrocarbon receptor (AhR), caused the most potent toxicity and specific effects in several cell types. 2,2',4,6,6'-PeCB induced apoptotic cell death of human monocytic cells, suggesting that PCB-induced apoptosis may be linked to immunotoxicity. In addition, 2,2',4,6,6'-PeCB induced mitotic arrest by interfering with mitotic spindle assembly in NIH3T3 fibroblasts, followed by genetic instability which triggers p53 activation. Which suggests that 2,2',4,6,6'-PeCB may be involved in cancer development by causing genetic instability through mitotic spindle damage. On the other hand, 2,2',4,6,6'-PeCB increased cyclooxygenase-2 (COX-2) involved in cell survival through ERK1/2 MAPK and p53 in Rat-1 fibroblasts and mouse embryonic fibroblasts, triggering compensatory mechanism for abating its toxicity. Taken together, these results demonstrate that PCB congeners of different structure have distinct mechanism of action and 2,2',4,6,6'-PeCB causes several toxicity as well as compensatory mechanism in cells.

• 대한바이러스학회지
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• 제28권1호
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• pp.71-78
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• 1998

Vaccinia virus is the prototype orthopoxvirus that has been used as a vaccine strain for small pox. This virus has been used to express a variety of cellular and viral genes in mammalian cells at high levels. Interleukin-4 (IL-4) has been found to stimulate the proliferation of T cells and enhance the cytolytic activity of cytotoxic T lymphocytes. To test the immunotherapeutic potential of IL-4 delivered in vivo by poxvirus, a recombinant vaccinia virus expressing the murine IL-4 gene (RVVmIL-4) was constructed. A high level of IL-4 production was confirmed by infecting HeLa cells and measuring IL-4 in cell culture supernatant by ELISA. As a tumor model, two cell lines were used; the murine T leukemic line P388 and the murine breast cancer line TS/A. CDF1 mice were intraperitoneally inoculated with $1\;{\times}\;10^5$ cells of P388. Mice were injected at the same site with $5\;{\times}\;10^5\;PFU$ of recombinant vaccinia virus; first, 3 days after the injection of tumor cells and thereafter once every week for 3 weeks. Intraperitoneal injections of RVVmIL-4 significantly prolonged the survival time of mice inoculated with tumor cells. All mice injected with RVVmIL-4 remained alive for 30 days after the postinoculation of tumor cells, while 100% and 70% of the animals injected with saline or wild type vaccinia virus died, respectively. In another tumor model using TS/A, tumor was established by subcutaneously inoculating $2{\times}10^5$ tumor cells to BALB/c mice. After tumor formation was confirmed on day 4 in all mice, $5\;{\times}\;10^6\;PFU$ of RVVmIL-4 was inoculated subcutaneously three times, once every week for 3 weeks. The TS/A tumor was eradicated in two of the nine mice. Seven of the nine mice treated with RVVmIL-4 developed a tumor, but tumor growth was significantly delayed compared to those treated with saline or wild type vaccinia virus. These results indicate that recombinant vaccinia viruses may be used as a convenient tool for delivering immunomodulator genes to a variety of tumors.