• 대한방사성의약품학회지
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• 제1권1호
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• pp.38-45
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• 2015

Most tumors are believed to overexpress several receptors, and small peptides targeting these receptors were developed for diagnosis and tumor therapy during past decade. Here we report that fibroadenoma can be visualized by bladder cancer specific peptide. A 9-mer bladder cancer specific peptide, which was discovered from the phage display method, was synthesized by peptide synthesizer, and additional tyrosine was conjugated at the N-terminal for radioiodination (Y-BP). Y-BP was radiolabeled with $^{131/124}I$ using Iodogen tube. The rat treated with N-butyl-N-(4-hydroxybutyl)nitrosamine for 8 weeks was allowed to grow until large size tumor was developed under axilla. The tumor model was microPET imaged sequentially using [$^{18}F$]FDG and radioiodinated $^{124}I-Y-BP$. The tumor was excised and examined by immunostaining studies. Radioiodinated $^{124}I-Y-BP$ was purified using fast protein liquid chromatography (FPLC) in > 90% radiochemical purity. The whole tumor was well visualized by [$^{18}F$]FDG with several intense focal uptake within tumor. The tumor was also clearly seen with $^{124}I-Y-BP$ at 4 h post-injection, and to our surprise the tumor uptake of $^{124}I-Y-BP$ lasted up to three days. The tumor was diagnosed histologically as a fibroadenoma derived from mammary gland. In conclusion, the bladder cancer specific peptide showed the good potential as a new radiotracer for the detection of breast fibroadenoma.

• 대한두경부종양학회지
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• 제30권2호
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• pp.90-94
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• 2014

Salivary duct carcinoma(SDC) is rare malignancy, accounting for approximately 1-3% of all malignant salivary gland tumors. Systemic chemotherapy has been used for stage IV SDC, but there is no consensus on the standard treatment. SDC is histologically similar to ductal carcinoma of breast and often overexpress HER2/neu, hence HER2/neu targeted therapy could be one of treatment options. A 75-year-old Arabian man was diagnosed as SDC of right parotid gland with extensive metastases. He received oral 5-FU as palliative chemotherapy, but he was intolerable to oral chemotherapy due to severe oral mucositis. Considering immunohistochemical stain of tumor tissue showing strong positive for HER2/neu, we decided to administer an anti-HER2/neu antibody, trastuzumab. Follow-up CT scans before the third dose of trastuzumab demonstrated remarkable regression of multiple metastases as well as primary tumor. This case suggests that HER2/neu targeted therapy may be a potential therapeutic option for the SDC patient with overexpression of HER2/neu.

• Archives of Pharmacal Research
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• 제21권5호
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• pp.581-590
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• 1998

We developed a novel water-soluble camptothecin analobue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respecitively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to imduce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/$ED-{58}$) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in <5% tumor bearing mouse. this schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.

• 대한임상검사과학회지
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• 제41권4호
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• pp.167-172
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• 2009

Methotrexate (MTX) in one of the antineoplastic drug and it is known to effective to management of acute lymphoblastic leukemia in children, management of choriocarcinoma and related trophoblastic tumors in women, management of carcinomas of the breast, tongue, pharynx, and tests, maintenance of remission in leukemia and treatment of serve, debilitating psoriasis. Intermediate to high-dose methotrexate administration followed by leucovorin rescue is effective in treatment of carcinoma of the lung and osteogenic sarcoma. Intrathecal administration is effective in treating meningeal leukemia or lymphoma. There are FPIA (Fluorescence polarization immunoassay) and EMIT (Enzyme multiplied immunotechique) methods that measure for MTX. We evaluated the FPIA and EMIT methods. MTX were measured by Hitachi-7600 P-module using EMIT and FPIA using TDX in the sera 60 patients. The performance characteristics evaluated were, light influence, linearity, comparison with FPIA. Also, precision evaluated were three level controls through put following CLSI evaluation protocols (EP10-A). When the MTX value of $4.16{\pm}5.78{\mu}{\mu}mol/L$ (mean, SD) by the Hitachi-7600 P-module was compared with that of $4.05{\pm}5.47{\mu}{\mu}mol/L$ by FPIA, coefficients of correlation of 0.988 was obtained. The regression equation was Y (Hitachi-7600 P-module) = 0.9408 x (FPIA) + 0.1316 (r=0.9885, n=60). CVs of MTX measured by Hitachi 7600 P-module was 6.78% at $0.33{\mu}{\mu}mol/L$, 0.96% at $1.16{\mu}{\mu}mol/L$, and 0.96% at $8.04{\mu}{\mu}mol/L$. The precision was excellent in each group. The linearity was acceptable. We evaluated that MTX is light-sensitive on prolonged exposure to direct sunlight. Comparing with the FPIA using TDX, the Hitachi-7600 P-module using EMIT showed good coefficient of correlation and precision. Therefore the Hitachi-7600 P-module can replace the FPIA for quantitative analysis of MTX.

• 대한골관절종양학회지
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• 제11권1호
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• pp.46-53
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• 2005

목적: Bisphosphonate(BPs)는 endogenous pyrophosphates의 유사체로 Paget's disease, 골다공증, 종양 유발성 골용해와 같은 골격계 질환의 치료에 쓰이고 있으며, 유방암의 골파괴성 전이에 대한 치료제로 사용되어 지고 있다. 골전이의 양상이 골흡수성 및 골생성이 혼합되어 나타나는 전립선암의 전이에서도 치료제의 하나로 이용되고 있다. BPs는 파골세포성 골흡수가 과하게 일어난 질환에 대해서는 비교적 널리 알려져 있지만, 골종양 세포에 대한 직접적인 효과에 대해서는 아직 밝혀져 있지 않다. 가장 강력한 질소 함유(nitrogen-containing) BPs인 Zoledronic acid(ZOL)로서 골육종이 발현된 nude mouse model을 이용하여 ZOL의 종양 억제능을 생체내 실험으로 확인하고자 하였다. 대상 및 방법: 인간 골육종 세포주로는 MG-63과 HOS 골육종 세포주를 이용하였고, 종양의 크기 변화를 육안으로 확인하기 위하여 GFP 유전자가 형질 전환된 MG-63-GFP, HOSGFP 세포를 6주령된 수컷 마우스 10마리에 각각 피하주사하여 종양의 조각이 $3{\times}3{\times}3$ mm이 될 때까지 사육한 후, ZOL을 120 ug/kg의 농도로 일주일에 2번 피하에 주사하였다. 종양의 크기를 일주일에 두 번씩 측정하고, 형광조명을 이용하여 촬영하였다. 결과: HOS 골육종 세포주를 이용한 생체실험에서 대조군의 종양의 평균 크기는 2,520 $mm^3$이며 ZOL 투여군은 131 $mm^3$로서 94%의 감소를 보이며, MG-63 골육종 세포주를 이용한 생체실험에서는 대조군의 종양의 평균 크기는 2,866 $mm^3$이며 실험군은 209 $mm^3$로서 72%의 감소를 보였다(P<0.05). 결론: Nude mouse를 이용한 생체실험에서 ZOL은 골육종의 세포사멸에 직접적인 영향을 미치며 이것은 앞으로 골육종 치료의 약제중 하나로 선택되어 질수 있다고 판단되며, 종양세포주에 따라 ZOL의 영향이 다를 수 있으므로 ZOL에 감수성 있는 종양세포를 찾아 적용하는 것이 좋을 것으로 사료된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권5호
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• pp.373-384
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• 2001

Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

• Radiation Oncology Journal
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• 제18권4호
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• pp.251-256
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• 2000

목적 : 1990년대 이후 개발된 정위 체부 고정틀을 이용한 체부 정위방사선수술의 치료효과, 치료의 정확성과 후유증에 대해 후향적으로 알아보고자 하였다. 대상 및 방법 : 1997년 12월부터 1999년 6월까지 간암 3명, 동정맥기형 1명, 폐전이 6명와 간전이 1명 등 모두 11명에서 정위 체부 고정틀을 이용하여 체부 방사선수술을 시행했다. 환자의 고정은 정위 체부 고정틀에 vacuum pillow를 이용하여 수행하였고 chest marker와 leg marker를 이용하여 흉골부위 또는 등부위와 경골부위의 피부에 환자 위치 표시를 하였다. 이후 모의치료실로 이동하여 X선 투시기를 통해 횡경막의 움직임을 측정한 후 Diaphragm control을 사용하여 1 cm 이하로 횡경막의 움직임을 최소화하였다. CT-simulator를 이용하여 치료부위의 단층촬영을 시행한 후 치료계획을 세웠다. 매회 치료전 CT-simulator를 이용하여 단층촬영을 반복하여 최초의 단층촬영의 영상과 수동적으로 비교하여 치료의 정확성을 확인하고 오차가 5 mm 이내인 경우 치료를 시행하였다. 방사선 치료는 90$\%$ 등선량곡선에 10 Gy씩 1일 내지 2일 간격으로 3회 시행하여 총30 Gy를 조사하였다. 결과 : 중앙 추적관찰기간은 12개월이었다. 11명의 환자 중 1명(9$\%$)의 환자에서 국소적 완전관해를 보였고 4명(36$\%$)에서 부분관해를 보였다. 계획용표적체적은 3$\~$111 cc 였고 평균값은 18.4 cc 였다. 치료 오차를 측정한 결과 X, Y, Z 축으로 오차범위는 모두 5 mm 이내를 보였다. 치료 중 또는 치료 직후에 올 수 있는 고열, 통증 등의 급성후유증은 관찰되지 않았다. 결론 : 정위 체부 고정틀을 이용한 체부 방사선수술은 뛰어난 치료의 재현성을 보여주었고 간 혹은 펴종양에서 유용한 치료 방법으로 이용될 수 있을 것으로 기대된다.

• 대한골관절종양학회지
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• 제1권1호
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• pp.38-44
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• 1995

1988년부터 1993년까지 최근 6년간 고신의료원에서 전이성 골종양으로 진단받고 치료받았던 환자중 조직학적으로 확진되었던 417명의 환자를 대상으로 후향적 조사를 통하여 연령별, 성별, 골전이 부위별 분포와 원발성 암에 따른 전이의 양상을 분석하여 다음과 같은 결과를 얻었다. 1. 골전이를 가장 잘 일으키는 원발성 암은 폐암(29.5%), 위암(15.3%), 유방암(11.3%), 자궁경부암(5.3%), 간암(4.8%)등의 순이었으며, 원발 부위 미상의 전이성 골종양은 7.7%였다. 2. 연령 분포는 40대 이후에서 발생한 경우가 85.3%로 대부분을 차지하였으며, 평균 연령은 54.8세였다. 남자의 경우 50대(39.4%), 60대(27.5%), 40대(14.3%)의 순이었으며, 여자의 경우는 50대(31.9%), 40대(21.7%), 60대(20.5%)의 순으로 발생하였다. 3. 골전이 부위별 분포는 척추(25.2%), 골반골(16.0%), 늑골(15.3%), 대퇴골(14.5%), 두개골(8.3%), 상완골(5.5%), 견갑골(5.1%)등의 순이었으며, 골전이의 분포 양상은 체간골이 75.8%로 가장 많았고, 그 다음으로 근위부의 장관골이 19.8%, 슬관절과 주관절 이하의 원위 골격계가 4.4%의 순으로 나타났다. 척추 중에서는 흉추(42.1%), 요추(39.1%), 경추(13.2%), 천추(5.6%)의 순으로 나타났다. 4. 골전이 부위별 분포는 원발성 암의 종류에 관계없이 다발성 전이(73.1%)가 단발성 전이(26.9%) 보다 많았다. 5. 원발성 종양에 따른 분포 양상은 폐암의 경우 연령 분포는 50대, 60대, 40대의 순이었고, 남녀비는 2.3 : 1이었으며, 골전이는 척추, 골반, 대퇴골의 순으로 발생하였다. 위암의 경우 연령 분포는 50대, 60대, 40대의 순이었고, 골전이 부위는 척추, 대퇴골, 골반의 순이었다. 유방암의 경우 연령 분포는 40대, 50대, 30대의 순이었고, 골전이 부위는 척추, 늑골, 골반의 순이었다. 6. 원발 부위 미상의 전이성 골종양의 경우는 60대가 가장 많았으며, 30대부터 70대까지 분포되어 있었다. 골전이 부위는 척추, 대퇴골, 골반골, 늑골, 견갑골의 순이었으며, 조직학적으로는 선암, 편평세포암이 많았다.

• Clinical and Experimental Pediatrics
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• 제51권1호
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• pp.73-77
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• 2008

목 적 : p16 유전자는 염색체 9p21에 위치하는데 종양억제 유전자 중 하나로 cyclin-dependent kinase의 억제제로 작용하며 Rb 인산화를 억제한다. 다양한 종류의 종양에서 p16 유전자의 결실 또는 과메틸화가 발견되고 있는데 이는 급성림프구성백혈병에서도 흔히 발견되는 이상 소견으로 높은 빈도로 나타나고 있지만 급성림프구성백혈병의 예후와 p16 유전자의 연관성에 대해서는 아직 논란의 여지가 있다. 본 연구에서는 면역조직화학염색으로 확인한 p16 단백질의 소실과 급성림프구성백혈병 환아들의 임상 경과와의 연관성에 대하여 조사하고자 하였다. 방 법 : 1998년 1월부터 2006년 12월까지 급성림프구성백혈병으로 진단된 74명의 진단 시 골수 슬라이드에서 p16 단백질 면역조직화학염색을 하였다. 환아들의 임상 양상, 검사실 소견, 치료 후 경과에 대해서 후향적으로 조사하였다. 결 과 : 74명 중 12명에서 p16 단백질이 면역화학염색 결과 음성이었다. 이들 중 남아가 7명 여아가 5명이었으며 진단 시 연령의 중앙값은 5.8(1.3-18.8)세였다. 백혈구 수의 중앙값은 17,225 $(500-403,300)/{\mu}L$ 이었으며 면역표현형은 early pre-B CALLA (+)형이 7명, T 세포형은 5명이었다. 진단 시 예후 중간군이었던 두 명의 환아들에서 골수 재발 하였으며 3명의 환아들이 유방암의 가족력이 있었다. 4명이 사망하여 8년 생존율은 $53.5{\pm}18.7%$였다. 결 론 : p16 단백질의 소실은 소아 급성림프구성백혈병에서 불량한 예후와 연관된 인자로 추정되며 임상에서 진단 시 p16에 대한 유전자 검사뿐만 아니라 단백질에 대해서도 검사가 필요할 것으로 생각된다. 하지만 좀더 많은 환자들에 대한 분석이 더 정확한 연관성을 밝히는데 도움이 될 것으로 사료된다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권2호
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.