• Radiation Oncology Journal
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• 제16권4호
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• pp.409-423
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• 1998

목적 : 비소세포성 폐암 환자에서 근치적 방사선 치료 단독 또는 항암화학요법과 병용으로 치료했을 때, 환자의 임상적 양상, 실패 양상, 생존율, 생존에 영향을 미치는 인자 및 방사선치료와 연관된 부작용에 대하여 알아보기 위하여 본 연구를 시행하였다. 대상 및 방법 : 1982년 3월부터 1996년 4월까지 비소세포성 폐암으로 이화대학병원 치료방사선과에서 근치적 목적의 방사선치료를 시행받은 70명의 환자에 대한 치료 결과를 후향적으로 분석하였다. 환자의 병기는 1기 2례, 2기 6례, 3-A기 30례, 3-B기 29례, 4기가 3례였다. 방사선치료는 6MV X-선을 이용하여 일일선량 1.8y-2.0Gy씩 주 5회 조사하였고, 총방사선량은 50.4-72.0Gy(중앙값 59.4Gy)였다. 전체 환자 중 34례(47$\%$)에서 유도 또는 동시 화학요법이 시행되었고 대부분 etoposide와 cisplatin이 포함된 복합화학요법이었다. 관찰조사가 사망 또는 연구시점까지 가능했던 경우가 43례(61$\%$)였고 생존율은 Kapian-Meier 방법으로 분석하였다. 결과 : 전체 환자의 생존율은 1년 63$\%$, 2년 29$\%$, 3년 26$\%$였고, 중앙생존기간은 17개월이였으며, 무병생존율은 1년 23$\%$, 2년 16$\%$였다. 각 병기별 전체 1년 생존율은 1기 100$\%$, 2기 80$\%$, 3기 61$\%$, 4기 50$\%$였고, 3기 환자만의 생존율은 1년 61$\%$, 2년 23$\%$, 3년 20$\%$였고, 중앙생존기간은 15개월이었다. 방사선치료 후 완전관해가 11례(16$\%$), 부분관해가 35례(50$\%$)인 반면, 국소제어된 경우는 30례(43$\%$)로서, 이 중 24례(80$\%$)에서 치료실패에 대한 추적관찰이 가능하였으며, 추적된 24례에서 치료실패를 보인 14례(58$\%$)중 6례(43$\%$)는 국소재발, 6례(43$\%$)는 원격전이, 2례(14$\%$)는 국소재발과 원격전이가 동반된 경우로서 전체 환자 중 16례(23$\%$)에서 국소치유를 관찰할 수 있었다. 원격전이에 대한 추적관찰이 가능한 50례 중 23례(46$\%$)에서 원격전이를 보였다. 근치적 방사선 치료만 시행한 군의 1년 생존율은 59$\%$, 유도 또는 동시 화학요법이 복합된 군은 68$\%$로서 두 군간의 생존율 차이는 다변량분석에서 통계학적 의의가 있었고(p=0.0049), 3기 환자만의 경우 방사선치료 단독군의 1년 생존율은 51$\%$, 유도 또는 동시 화학요법 병행군은 68$\%$로서 통계학적으로 유의한 생존율 차이가 있었다(p=0.0015). 단변수 변량분석에서 전체환자는 병기(p=0.015) 및 국소제어유무(p=0.0001)가, 3기 환자군은 유도 또는 동시 화학요법 병행 유무(p=0.0488), 시기에 무관한 화학요법 시행 유무(P=0.001) 및 국소제어 유무(p=0.0001)가 통계적 유의성이 있었으며, 다변수 변량분석에서 전체 환자 또는 3기 환자만을 대상으로 할 때 병기(p=0.0001), 치료전 전신수행능력(p=0.001), 유도 또는 동시 화학요법 병행유무(p=0.0015), 총방사선량(p=0.0049), 국소제어 유무(P=0.0001)가 통계적 의의가 있었다. 방사선치료와 관련된 합병증은 식도염, 방사선폐렴, 혈액학적 부작용, 피부염이었으며, 2례의 치명적인 방사선폐렴이 관찰되었다. 결론 : 비소세포성 폐암 환자에서 고식적인 방사선 치료만으로는 만족할만한 생존율을 얻기 어려우므로 원격전이 제어에 필요한 적절한 복합화학요법의 추가가 필요하고, 국소제어율을 높이기 위해서는 수술을 병용하는 다원적 치료나 충분한 방사선량을 조사하기 위한 다분할조사방법의 활용 등 적극적인 치료가 필요하다.

• 대한한의학원전학회지
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• 제20권4호
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• pp.211-250
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• 2007

1. The 'Kao Zheng Pai(考證派) comes from the 'Zhe Zhong Pai' and is a school that is influenced by the confucianism of the Qing dynasty. In Japan Inoue Kinga(井上金娥), Yoshida Koton(吉田篁墩) became central members, and the rise of the methodology of historical research(考證學) influenced the members of the 'Zhe Zhong Pai', and the trend of historical research changed from confucianism to medicine, making a school of medicine based on the study of texts and proving that the classics were right. 2. Based on the function of 'Nei Qu Li '(內驅力) the 'Kao Zheng Pai', in the spirit of 'use confucianism as the base', researched letters, meanings and historical origins. Because they were influenced by the methodology of historical research(考證學) of the Qing era, they valued the evidential research of classic texts, and there was even one branch that did only historical research, the 'Rue Xue Kao Zheng Pai'(儒學考證派). Also, the 'Yi Xue Kao Zheng Pai'(醫學考證派) appeared by the influence of Yoshida Kouton and Kariya Ekisai(狩谷掖齋). 3. In the 'Kao Zheng Pai(考證派)'s theories and views the 'Yi Xue Kao Zheng Pai' did not look at medical scriptures like the "Huang Di Nei Jing"("黃帝內經") and did not do research on 'medical' related areas like acupuncture, the meridian and medicinal herbs. Since they were doctors that used medicine, they naturally were based on 'formulas'(方劑) and since their thoughts were based on the historical ideologies, they valued the "Shang Han Ja Bing Lun" which was revered as the 'ancestor of all formulas'(衆方之祖). 4. The lives of the important doctors of the 'Kao Zheng Pai' Meguro Dotaku(目黑道琢) Yamada Seichin(山田正珍), Yamada Kyoko(山田業廣), Mori Ritsi(森立之) Kitamura Naohara(喜多村直寬) are as follows. 1) Meguro Dotaku(目黑道琢 1739${\sim}$1798) was born of lowly descent but, using his intelligence and knowledge, became a professor as a Shi Jing Yi(市井醫) and as a professor for 34 years at Ji Shou Guan mastered the "Huang Di Nei Jing" after giving over 300 lectures. Since his pupil, Isawara Ken taught the Lan Men Wu Zhe(蘭門五哲) and Shibue Chusai, Mori Ritsi(森立之), Okanishi Gentei(岡西玄亭), Kiyokawa Gendoh(淸川玄道) and Yamada Kyoko(山田業廣), Meguro Dotaku is considered the founder of the 'Yi Xue Kao Zheng Pai'. 2) The family of Yamada Seichin(山田正珍 1749${\sim}$1787) had been medical officials in the Makufu(幕府) and the many books that his ancestors had left were the base of his art. Seichin learned from Shan Ben Bei Shan(山本北山), a 'Zhe Zhong Pai' scholar, and put his efforts into learning, teaching and researching the "Shang Han Lun"("傷寒論"). Living in a time between 'Gu Fang Pai'(古方派) member Nakanishi Goretada(中西惟忠) and 'Kao Zheng Pai' member Taki Motohiro(多紀元簡), he wrote 11 books, 2 of which express his thoughts and research clearly, the "Shang Han Lun Ji Cheng"("傷寒論集成") and "Shang Han Kao"("傷寒考"). His comparison of the 'six meridians'(3 yin, 3 yang) between the "Shang Han Lun" and the "Su Wen Re Lun"("素問 熱論) and his acknowledgement of the need and rationality of the concept of Yin-Yang and Deficient-Replete distinguishes him from the other 'Gu Fang Pai'. Also, his dissertation of the need for the concept doesn't use the theories of latter schools but uses the theory of the "Shang Han Lun" itself. He even researched the historical parts, such as terms like 'Shen Nong Chang Bai Cao'(神農嘗百草) and 'Cheng Qi Tang'(承氣湯) 3) The ancestor of Yamada Kyoko(山田業廣) was a court physician, and learned confucianism from Kao Zheng Pai 's Ashikawa Genan(朝川善庵) and medicine from Isawa Ranken and Taki Motokata(多紀元堅), and the secret to smallpox from Ikeda Keisui(池田京水). He later became a lecturer at the Edo Yi Xue Guan(醫學館) and was invited as the director to the Ji Zhong(濟衆) hospital. He also became the first owner of the Wen Zhi She(溫知社), whose main purpose was the revival of kampo, and launched the monthly magazine Wen Zi Yi Tan(溫知醫談). He also diagnosed and prescribed for the prince Ming Gong(明宮). His works include the "Jing Fang Bian"("經方辨"), "Shang Han Lun Si Ci"("傷寒論釋司"), "Huang Zhao Zhu Jia Zhi Yan Ji Yao"("皇朝諸家治驗集要") and "Shang Han Ja Bing Lun Lei Juan"("傷寒雜病論類纂"). of these, the "Jing Fang Bian"("經方辨") states that the Shi Gao(石膏) used in the "Shang Han Lun" had three meanings-Fa Biao(發表), Qing Re(淸熱), Zi Yin(滋陰)-which were from 'symptoms', and first deducted the effects and then told of the reason. Another book, the "Jiu Zhe Tang Du Shu Ji"("九折堂讀書記") researched and translated the difficult parts of the "Shang Han Lun", "Jin Qui Yao Lue", "Qian Jin Fang"("千金方"), and "Wai Tai Mi Yao"("外臺秘要"). He usually analyzed the 'symptoms' of diseases but the composition, measurement, processing and application of medicine were all in the spectrum of 'analystic research' and 'researching analysis'. 4) The ancestors of Mori Rits(森立之 1807${\sim}$ 1885) were warriors but he became a doctor by the will of his mother, and he learned from Shibue Chosai(澁江抽齋) and Isawaran Ken and later became a pupil of Shou Gu Yi Zhai, a historical research scholar. He then became a lecturer of medical herbs at the Yi Xue Guan, and later participated in the proofreading of "Yi Xin Fang"("醫心方") and with Chosai compiled the "Jing Ji Fang Gu Zhi"("神農本草經"). He visited the Chinese scholar Yang Shou Jing(楊守敬) in 1881 and exchanged books and ideas. Of his works, there are the collections(輯複本) of "Shen Nong Ben Cao Jing"(神農本草經) and "You Xiang Yi Hwa"("遊相醫話") and the records, notes, poems, and diaries such as "Zhi Yuan Man Lu"("枳園漫錄") and "Zhi Yuan Sui Bi"("枳園隨筆") that were not published. His thoughts were that in restoring the "Shen Nong Ben Cao Jing", "the herb to the doctor is like the "Shuo Wen Jie Zi"("說文解字") to the scholar", and he tried to restore the ancient herbal text using knowledge of medicine and investigation(考據). Also with Chosai he compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志") using knowledge of ancient text. Ritzi left works on pure investigation, paid much attention to social problems, and through 12 years of poverty treated all people and animals in all branches of medicine, so he is called a 'half confucianist half doctor'(半儒半醫). 5) Kitamurana Ohira(喜多村直寬 1804${\sim}$1876) learned scriptures and ancient texts from confucian scholar Asaka Gonsai, and learned medicine from his father Huai Yaun(槐園). He became a teacher in the Yi Xue Guan in his middle ages, and to repay his country, he printed 266 volumes of "Yi Fang Lei Ju("醫方類聚") and 1000 volumes of "Tai Ping Yu Lan"("太平禦覽") and devoted it to his country to be spread. His works are about 40 volumes including "Jin Qui Yao Lue Shu Yi" and "Lao Yi Zhi Yan" but most of them are researches on the "Shang Han Za Bing Lun". In his "Shang Han Lun Shu Yi"("傷寒論疏義") he shows the concept of the six meridians through the Yin-Yang, Superficial or internal, cold or hot, deficient or replete state of diseases, but did not match the names with the six meridians of the meridian theory, and this has something in common with the research based on the confucianism of Song(宋儒). In clinical treatment he was positive toward old and new methods and also the experience of civilians, but was negative toward western medicine. 6) The ancestor of the Taki family Tanbano Yasuyori(丹波康賴 912-955) became a Yi Bo Shi(醫博士) by his medical skills and compiled the "Yi Xin Fang"("醫心方"). His first son Tanbano Shigeaki(丹波重明) inherited the Shi Yao Yuan(施藥院) and the third son Tanbano Masatada(丹波雅忠) inherited the Dian You Tou(典藥頭). Masatada's descendents succeeded him for 25 generations until the family name was changed to Jin Bao(金保) and five generations later it was changed again to Duo Ji(多紀). The research scholar Taki Motohiro was in the third generation after the last name was changed to Taki, and his family kept an important part in the line of medical officers in Japan. Taki Motohiro(多紀元簡 1755-1810) was a teacher in the Yi Xue Guan where his father was residing, and became the physician for the general Jia Qi(家齊). He had a short temper and was not good at getting on in the world, and went against the will of the king and was banished from Ao Yi Shi(奧醫師). His most famous works, the "Shang Han Lun Ji Yi" and "Jin Qui Yao Lue Ji Yi" are the work of 20 years of collecting the theories of many schools and discussing, and is one of the most famous books on the "Shang Han Lun" in Japan. "Yi Sheng" is a collection of essays on research. Also there are the "Su Wen Shi"("素問識"), "Ling Shu Shi"("靈樞識"), and the "Guan lu Fang Yao Bu"("觀聚方要補"). Taki Motohiro(多紀元簡)'s position was succeeded by his third son Yuan Yin(元胤 1789-1827), and his works include works of research such as "Nan Jing Shu Jeng"("難經疏證"), "Ti Ya"("體雅"), "Yao Ya"("藥雅"), "Ji Ya"("疾雅"), "Ming Yi Gong An"("名醫公案"), and "Yi Ji Kao"("醫籍考"). The "Yi Ji Kao" is 80 volumes in length and lists about 3000 books on medicine in China before the Qing Dao Guang(道光), and under each title are the origin, number of volumes, state of existence, and, if possible, the preface, Ba Yu(跋語) and biography of the author. The younger sibling of Yuan Yin(元胤 1789-1827), Yuan Jian(元堅 1795-1857) expounded ancient writings at the Yi Xue Guan only after he reached middle age, was chosen for the Ao Yi Shi(奧醫師) and later became a Fa Yan(法眼), Fa Yin(法印) and Yu Chi(樂匙). He left about 15 texts, including "Su Wen Shao Shi"("素間紹識"), "Yi Xin Fang"("醫心方"), published in school, "Za Bing Guang Yao"("雜病廣要"), "Shang Han Guang Yao"(傷寒廣要), and "Zhen Fu Yao Jue"("該腹要訣"). On the Taki family's founding and working of the Yi Xue Guan Yasuka Doumei(失數道明) said they were "the people who took the initiative in Edo era kampo medicine" and evaluated their deeds in the fields of 'research of ancient text', 'the founding of Ji Shou Guan and medical education', 'publication business', 'writing of medical text'. 5. The doctors of the 'Kao Zheng Pai ' based their operations on the Edo Yi Xue Guan, and made groups with people with similar ideas to them, making a relationship 'net'. For example the three families of Duo Ji(多紀), Tang Chuan(湯川) and Xi Duo Cun(喜多村) married and adopted with and from each other and made prefaces and epitaphs for each other. Thus, the Taki family, the state science of the Makufu, the tendency of thinking, one's own interests and glory, one's own knowledge, the need of the society all played a role in the development of kampo medicine in the 18th and 19th century.

• 동국한의학연구소논문집
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• 제10권
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• pp.1-40
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• 2008

1.The 'Kao Zheng Pai'(考證派) comes from the 'Zhe Zhong Pai(折衷派)' and is a school that is influenced by the confucianism of the Qing dynasty. In Japan Inoue Kinga(井上金峨), Yoshida Koton(古田篁墩 $1745{\sim}1798$) became central members, and the rise of the methodology of historical research(考證學) influenced the members of the 'Zhe Zhong Pai', and the trend of historical research changed from confucianism to medicine, making a school of medicine based on the study of texts and proving that the classics were right. 2. Based on the function of 'Nei Qu Li'(內驅力) the 'Kao Zheng Pai', in the spirit of 'use confucianism as the base', researched letters, meanings and historical origins. Because they were influenced by the methodology of historical research(考證學) of the Qing era, they valued the evidential research of classic texts, and there was even one branch that did only historical research, the 'Rue Xue Kao Zheng Pai'(儒學考證派). Also, the 'Yi Xue Kao Zheng Pai'(醫學考證派) appeared by the influence of Yoshida Kouton and Kariya Ekisai(狩谷掖齋). 3. In the 'Kao Zheng Pai(考證派)'s theories and views the 'Yi Xue Kao Zheng Pai' did not look at medical scriptures like the "Huang Di Nei Jing"("黃帝內經") and did not do research on 'medical' related areas like acupuncture, the meridian and medicinal herbs. Since they were doctors that used medicine, they naturally were based on 'formulas'(方劑) and since their thoughts were based on the historical ideologies, they valued the "Shang Han Ja Bing Lun" which was revered as the 'ancestor of all formulas'(衆方之祖). 4. The lives of the important doctors of the 'Kao Zheng Pai' Meguro Dotaku(目黑道琢) Yamada Seichin(山田正珍), Yamada Kyoko(山田業廣), Mori Ritsi(森立之) Kitamura Naohara(喜多村直寬) are as follows. 1) Meguro Dotaku(目黑道琢 $1739{\sim}1798$) was born of lowly descent but, using his intelligence and knowledge, became a professor as a Shi Jing Yi(市井醫) and as a professor for 34 years at Ji Shou Guan(躋壽館) mastered the "Huang Di Nei Jing" after giving over 300 lectures. Since his pupil, Isawara Ken(伊澤蘭軒) taught the Lan Men Wu Zhe(蘭門五哲) and Shibue Chusai(澀江抽齋), Mori Ritsi(森立之), Okanishi Gentei(岡西玄亭), Kiyokawa Gendoh(淸川玄道) and Yamada Kyoko(山田業廣), Meguro Dotaku is considered the founder of the 'Yi Xue Kao Zheng Pai'. 2) The family of Yamada Seichin(山田正珍 $1749{\sim}1787$) had been medical officials in the Makufu(幕府) and the many books that his ancestors had left were the base of his art. Seichin learned from Shan Ben Bei Shan(山本北山), a 'Zhe Zhong Pai' scholar, and put his efforts into learning, teaching and researching the "Shang Han Lun"("傷寒論"). Living in a time between 'Gu Fang Pai'(古方派) member Nakanishi Goretada(中西惟忠) and 'Kao Zheng Pai' member Taki Motohiro(多紀元簡), he wrote 11 books, 2 of which express his thoughts and research clearly, the "Shang Han Lun Ji Cheng"("傷寒論集成") and "Shang Han Kao"("傷寒考"). His comparison of the 'six meridians'(3 yin, 3 yang) between the "Shang Han Lun" and the "Su Wen Re Lun"("素問 熱論") and his acknowledgement of the need and rationality of the concept of Yin-Yang and Deficient-Replete distinguishes him from the other 'Gu Fang Pai'. Also, his dissertation of the need for the concept doesn't use the theories of latter schools but uses the theory of the "Shang Han Lun" itself. He even researched the historical parts, such as terms like 'Shen Nong Chang Bai Cao'(神農嘗百草) and 'Cheng Qi Tang'(承氣湯). 3) The ancestor of Yamada Kyoko(山田業廣) was a court physician, and learned confucianism from Kao Zheng Pai's Ashikawa Genan(朝川善庵) and medicine from Isawa Ranken(伊澤蘭軒) and Taki Motokata(多紀元堅), and the secret to smallpox from Ikeda Keisui(池田京水). He later became a lecturer at the Edo Yi Xue Guan(醫學館) and was invited as the director to the Ji Zhong(濟衆) hospital. He also became the first owner of the Wen Zhi She(溫知社), whose main purpose was the revival of kampo, and launched the monthly magazine Wen Zi Yi Tan(溫知醫談). He also diagnosed and prescribed for the prince Ming Gong(明宮). His works include the "Jing Fang Bian"("經方辨"), "Shang Han Lun Si Ci"("傷寒論釋詞"), "Huang Zhao Zhu Jia Zhi Yan Ji Yao"("皇朝諸家治驗集要") and "Shang Han Ja Bing Lun Lei Juan"("傷寒雜病論類纂"). of these, the "Jing Fang Bian"("經方辨") states that the Shi Gao(石膏) used in the "Shang Han Lun" had three meanings-Fa Biao(發表), Qing Re(淸熱), Zi Yin(滋陰)-which were from 'symptoms', and first deducted the effects and then told of the reason. Another book, the "Jiu Zhe Tang Du Shu Ji"("九折堂讀書記") researched and translated the difficult parts of the "Shang Han Lun", "Jin Qui Yao Lue"("金匱要略"), "Qian Jin Fang"("千金方"), and "Wai Tai Mi Yao"("外臺秘要"). He usually analyzed the 'symptoms' of diseases but the composition, measurement, processing and application of medicine were all in the spectrum of 'analystic research' and 'researching analysis'. 4) The ancestors of Mori Ritsi(森立之 $1807{\sim}1885$) were warriors but he became a doctor by the will of his mother, and he learned from Shibue Chosai(澁江抽齋) and Isawaran Ken(伊澤蘭軒) and later became a pupil of Shou Gu Yi Zhai(狩谷掖齋), a historical research scholar. He then became a lecturer of medical herbs at the Yi Xue Guan, and later participated in the proofreading of "Yi Xin Fang"("醫心方") and with Chosai compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志"). He visited the Chinese scholar Yang Shou Jing(楊守敬) in 1881 and exchanged books and ideas. Of his works, there are the collections(輯複本) of "Shen Nong Ben Cao Jing"("神農本草經") and "You Xiang Yi Hwa"("遊相醫話") and the records, notes, poems, and diaries such as "Zhi Yuan Man Lu"("枳園漫錄") and "Zhi Yuan Sui Bi"(枳園隨筆) that were not published. His thoughts were that in restoring the "Shen Nong Ben Cao Jing", "the herb to the doctor is like the "Shuo Wen Jie Zi"(說文解字) to the scholar", and he tried to restore the ancient herbal text using knowledge of medicine and investigation(考據), Also with Chosai he compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志") using knowledge of ancient text. Ritzi left works on pure investigation, paid much attention to social problems, and through 12 years of poverty treated all people and animals in all branches of medicine, so he is called a 'half confucianist half doctor'(半儒半醫). 5) Kitamurana Ohira(喜多村直寬, $1804{\sim}1876$) learned scriptures and ancient texts from confucian scholar Asaka Gonsai(安積艮齋), and learned medicine from his father Huai Yaun(槐園), He became a teacher in the Yi Xue Guan in his middle ages, and to repay his country, he printed 266 volumes of "Yi Fang Lei Ju"("醫方類聚") and 1000 volumes of "Tai Ping Yu Lan"("太平禦覽") and devoted it to his country to be spread. His works are about 40 volumes including "Jin Qui Yao Lue Shu Yi"("金匱要略疏義") and "Lao Yi Zhi Yan"(老醫巵言) but most of them are researches on the "Shang Han Za Bing Lun". In his "Shang Han Lun Shu Yi"("傷寒論疏義") he shows the concept of the six meridians through the Yin-Yang, Superficial or internal, cold or hot, deficient or replete state of diseases, but did not match the names with the six meridians of the meridian theory, and this has something in common with the research based on the confucianism of Song(宋儒). In clinical treatment he was positive toward old and new methods and also the experience of civilians, but was negative toward western medicine. 6) The ancestor of the Taki family Tanbano Yasuyori(丹波康賴 $912{\sim}955$) became a Yi Bo Shi(醫博士) by his medical skills and compiled the "Yi Xin Fang"("醫心方"). His first son Tanbano Shigeaki(丹波重明) inherited the Shi Yao Yuan(施藥院) and the third son Tanbano Masatada(丹波雅忠) inherited the Dian You Tou(典藥頭). Masatada's descendents succeeded him for 25 generations until the family name was changed to Jin Bao(金保) and five generations later it was changed again to Duo Ji(多紀). The research scholar Taki Motohiro was in the third generation after the last name was changed to Taki, and his family kept an important part in the line of medical officers in Japan. Taki Motohiro(多紀元簡 $1755{\sim}1810$) was a teacher in the Yi Xue Guan where his father was residing, and became the physician for the general Jia Qi(家齊). He had a short temper and was not good at getting on in the world, and went against the will of the king and was banished from Ao Yi Shi(奧醫師). His most famous works, the "Shang Han Lun Ji Yi"("傷寒論輯義") and "Jin Qui Yao Lue Ji Yi"("金匱要略輯義") are the work of 20 years of collecting the theories of many schools and discussing, and is one of the most famous books on the "Shang Han Lun" in Japan. "Yi Sheng"("醫勝") is a collection of essays on research. Also there are the "Su Wen Shi"(素問識), "Ling Shu Shi"("靈樞識"), and the "Guan Ju Fang Yao Bu"("觀聚方要補"). Taki Motohiro(多紀元簡)'s position was succeeded by his third son Yuan Yin(元胤 $1789{\sim}1827$), and his works include works of research such as "Nan Jing Shu Jeng"(難經疏證), "Ti Ya"("體雅"), "Yao Ya"("藥雅"), "Ji Ya"(疾雅), "Ming Yi Gong An"(名醫公案), and "Yi Ji Kao"(醫籍考). The "Yi Ji Kao" is 80 volumes in length and lists about 3000 books on medicine in China before the Qing Dao Guang(道光), and under each title are the origin, number of volumes, state of existence, and, if possible, the preface, Ba Yu(跋語) and biography of the author. The younger sibling of Yuan Yin(元胤 $1789{\sim}1827$), Yuan Jian(元堅 $1795{\sim}1857$) expounded ancient writings at the Yi Xue Guan only after he reached middle age, was chosen for the Ao Yi Shi(奧醫師) and later became a Fa Yan(法眼), Fa Yin(法印) and Yu Chi(禦匙). He left about 15 texts, including "Su Wen Shao Shi"("素問紹識"), "Yi Xin Fang"("醫心方"), published in school, "Za Bing Guang Yao"("雜病廣要"), "Shang Han Guang Yao"("傷寒廣要"), and "Zhen Fu Yao Jue"("診腹要訣"). On the Taki family's founding and working of the Yi Xue Guan Yasuka Doumei(矢數道明) said they were "the people who took the initiative in Edo era kampo medicine" and evaluated their deeds in the fields of 'research of ancient text', the founding of Ji Shou Guan(躋壽館) and medical education', 'publication business', 'writing of medical text'. 5. The doctors of the 'Kao Zheng Pai' based their operations on the Edo Yi Xue Guan, and made groups with people with similar ideas to them, making a relationship 'net'. For example the three families of Duo Ji(多紀), Tang Chuan(湯川) and Xi Duo Cun(喜多村) married and adopted with and from each other and made prefaces and epitaphs for each other. Thus, the Taki family, the state science of the Makufu, the tendency of thinking, one's own interests and glory, one's own knowledge, the need of the society all played a role in the development of kampo medicine in the 18th and 19th century.

• 대한한방종양학회지
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• 제4권1호
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• pp.37-53
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• 1998

과학기술(科學技術)의 발전(發展)에 따른 생활(生活) 및 의료(醫療) 수준의 향상(向上)에도 불구하고 산업발전(産業發展)에 따른 환경오염(環境汚染), 스트레스 증가(增加) 등 그 역기능(逆機能) 때문에 발암물질(發癌物質) 또는 자극(刺戟)에의 노출(露出) 등으로 인해서 전세계적(全世界的)으로 암(癌)으로 인(因)한 사망율(死亡率)이 증가(增加)되고 있다. 암(癌)은 현재(現在) 인류(人類)의 건강(健康)을 위협하는 주요(主要)한 질환(疾患)의 하나로, 오늘날 우리 나라에서 질환(疾患)으로 인(因)한 사망원인중(死亡原因中) 수위(首位)를 차지하고 있다. 이러한 암(癌)의 발생(發生)은 80%-90%가 환경적(環境的) 인자(因子)에 기인(起因)한다고 보고(報告)되고 있는데 앞으로 환경성(環境性) 발암물질(發癌物質)이 점차 증가(增加)됨에 따라 암환자(癌患者)의 발생(發生)도 더욱 증가(增加)될 것으로 예상(豫想)된다. 암(癌)의 서의학적(西醫學的) 치료(治療)는 주로 수술요법(手術療法), 방사선요법(放射線療法), 화학요법(化學療法) 및 면역요법(免疫療法) 등이 활용(活用)되고 있다. 이중 수술요법(手術療法)과 방사선요법(放射線療法)은 암(癌)이 전신(全身)에 전이(轉移) 증식(增殖)되기 전에 실시(實施)함으로써 효과(效果)를 거둘 수는 있으나, 암(癌)이 원발병소(原發病巢) 이외(以外)에까지 전이(轉移) 증식(增殖)되었을 경우에는 이 두가지 방법(方法)의 국소요법(局所療法)만으로서는 좋은 치료효과(治療效果)를 거두기 어렵다. 따라서 최근 항암제(抗癌劑)에 의한 화학요법(化學療法)이 다른 방법(方法)보다 유효(有效)하다고 인정(認定)이 되어 가장 많이 활용(活用)되고 있으나, 암종(癌種)에 대한 감수성차이(感受性差異), 치료후(治療後)의 부작용(副作用), 재발(再發) 및 합병증(合倂症) 등의 문제점(問題點)때문에 부작용(副作用)을 감소(減少)시키면서 항암효과(抗癌效果)를 높이는 치료법(治療法)이 계속 연구(硏究)되고 있다. 이에 1972년(年) 미국(美國) 국립암연구소(國立癌硏究所)에서 실시(實施)한 항암제(抗癌劑) 개발연구(開發硏究)에 있어서 항종양성(抗腫瘍性) Screening test에 이용(利用)된 물질중(物質中) 약 47%가 천연물질(天然物質)이었다는 사실은 주목(注目)할만 하다. 한의학적(韓醫學的) 치료법(治療法)은 최근(最近)에 변증시치(辨證施治)를 근간(根幹)으로 하여 건비익기(健脾益氣)를 위주(爲主)로한 부정거사법(扶正祛邪法)과 부정배본법(扶正培本法)이 많이 활용(活用)되고 있으며 부정법(扶正法)으로는 익기건비(益氣健脾), 자음보혈(滋陰補血), 온보비신(溫補裨腎) 등이, 거사법(祛邪法)으로는 활혈거어법(活血祛瘀法), 청열해독법(淸熱解毒法), 연견화담법(軟堅化痰法) 등이 활용(活用)되고 있는데, 이를 근거(根據)로 하여 한약(韓藥)의 복방(複方).단미(單味).단미추출물(單味抽出物) 등의 투여(投與)와 침(鍼) 구(灸) 수침(水鍼) 전침(電鍼) laser침(鍼)등의 치료방법(治療方法)을 수술(手術) 후(後) 혹(或)은 화학요법(化學療法)이나 방사선요법(放射線療法)와 병행(幷行)하여 치료효과(治療效果)가 향상(向上)되었다고 보고(報告)하고 있다. 항암제(抗癌劑)의 항암효과(抗癌效果) 정도(程度)를 검사(檢査)하는 방법(方法)은 크게 5가지로 분류(分類)되는데, 하나는 세포(細胞)를 약제(藥劑)에 노출(露出)시킨 후 현미경(顯微鏡)을 통하여 나타난 형태학적(形態學的) 변화(變化)를 가지고 약제(藥劑)의 효과정도(效果程度)를 결정(決定)하는 방법(方法)이고, 둘째는 Dye exclusion assay방법(方法)으로 살아있는 세포(細胞)가 trypan blue, eosin, nigrosin과 같은 염색액(染色液)에 염색(染色)되지 않는 점을 이용(利用)한 것이며, 세번째는 항암제(抗癌劑)의 항암효과(抗癌效果)를 알아보는 지표(指標)로 사용(使用)되는 Crrelease assay가 있으나, 세가지 방법(方法) 모두 현재(現在) 사용(使用)되고 있지 않다. 넷째로는 세포(細胞) 대사(代謝)의 방해정도(妨害程度)를 측정(測定)하거나 세포내(細胞內) 방사성(放射性) 동위원소(同位元素)의 유입방해(流入妨害) 정도(程度)를 측정(測定)하는 방법(方法)이 있고, 다섯째로는 본(本) 실험(實驗)에서 사용(使用)한 방법(方法)으로 stem cell assay라고도 하는 clonogenetic assay가 있는데, 이는 세포(細胞)를 약제(藥劑)에 노출(露出) 시킨 후 soft agar에 single cell suspension으로 배양(培養)하여 그 세포(細胞)의 분열(分裂).증식능력(增殖能力)을 측정(測定)하는 방법(方法)이다. 이 방법(方法)은 특히 성장(成長) 특성(特性)이 다른 종양세포(腫瘍細胞)의 경우 개개(個個) 세포(細胞)에 대한 약제효과(藥劑效果)를 반영(反映)할 수 있어서 종양세포(腫瘍細胞)의 이질성(異質性)에 따른 차이점(差異點)을 보정(補整)할 수 있는 방법(方法)이며, 1971년(年) Park 등이 마우스 골수종(骨髓腫) 세포(細胞)에 대한 stem cell assay를 시행(施行)해 본 결과(結果) in vivo에서의 결과(結果)와 잘 일치(一致)하여 그 이후로는 종양세포(腫瘍細胞)에 대한 항암제(抗癌劑)의 약제(藥劑) 감수성검사(感受性檢査)에 많이 사용(使用)되고 있다. 진령탕가감방은 담습응결(痰濕凝結)을 치료(治療)하는 효능(效能)을 가진 처방(處方)으로 거담작용(祛痰作用)을 가진 반하(半夏), 패모(貝母), 거습작용(祛濕作用)을 가진 의이인(薏苡仁), 백복령, 이기(理氣) 하기작용(下氣作用)을 가진 진피(陳皮), 대자석, 정향(丁香), 비파엽(枇杷葉), 항암작용(抗癌作用)을 가진 용규(龍葵), 반지련(半枝蓮), 모려(牡蠣), 하고초(夏枯草), 저령 등(等)의 약물(藥物)로 구성되어 있다. 근래(近來) 단일약물(單一藥物)의 항암효과(抗癌效果)에 대한 실험적(實驗的) 연구(硏究)로는 금(金) 등에 의한 인삼(人蔘), 녹용(鹿茸)의 항체생산(抗體生産) 억제(抑制) 완화효과(緩和效果) 및 임(任)에 의한 어성초(魚腥草), 녹혈(鹿血), 저령, 천산갑(穿山甲) 등이 정상(正常) 면역세포(免役細胞)에는 거의 독작용(毒作用)을 일으키지 않으면서 강력(强力)한 항암효과(抗癌效果)가 있다는 보고(報告), 금(金) 등에 의한 자완, 동풍채(東風菜), 영지(靈芝), 선학초(仙鶴草), 파두(巴豆) 등이 항암작용(抗癌作用) 및 면역반응(免疫反應)에 효과(效果)를 미친다는 보고(報告) 등이 있고, 복합제제(複合製劑) 약물(藥物)의 항암효과(抗癌效果)에 대한 연구(硏究)로는 강(姜) 등에 의한 식분환(息賁丸), 비기환(肥氣丸) 및 비기환이 백혈병(白血病)과 임파종환자(淋巴腫患者)에서 추출(抽出)한 암세포(癌細胞)에 항암효과(抗癌效果)가 있다는 보고(報告) 및 금(金) 등에 의한 복량환(伏梁丸), 비기환 및 소적정원산(消積正元散)이 각종(各種) 암세포주(癌細胞柱)이 성장저애(成長沮碍) 효과(效果), 윤(尹) 등에 의한 육군자탕(六君子湯), 소시호탕(小柴胡湯), 사묘탕(四妙湯), 대시호탕(大柴胡湯), 방독탕(防毒湯), 반하백출천마탕(半夏白朮天麻湯), 파두(巴豆)를 가미(加味)한 사군자탕(四君子湯) 및 사물탕(四物湯) 등이 항암작용(抗癌作用) 및 면역반응(免疫反應)에 효과(效果)를 보인다는 보고(報告) 등이 있었으나, 아직까지 진령탕가감방의 항암효과(抗癌效果)에 대한 실험연구(實驗硏究)는 없었다. 이에 저자(著者)는 항암효과(抗癌效果)가 있을 것으로 추정(推定)되는 진령탕가감방의 항종양효과(抗種瘍效果)를 알아보기 위하여, 수용성(水溶性) 추출액(抽出液)을 얻은 후 현대(現代) 병리학적(病理學的)으로 다용(多用)하는 colony형성억제실험(形成抑制實驗), SRB assay에 의한 항종양효과(抗種瘍效果), 생명연장율(生命延長率), 화학적(化學的)인 방법(方法)과 암종세포(癌腫細胞) 이식(移植)에 의한 종양(腫瘍) 유발(誘發)을 통하여 암(癌) 발생(發生) 및 그 경과(經過)에 미치는 영향(影響) 및 NK세포활성(細胞活性)에 미치는 영향(影響) 등을 관찰(觀察)하였다. 본(本) 실험(實驗)에서는 진령탕가감방의 종양세포(腫瘍細胞)에 대한 증식억제작용(增殖抑制作用)을 관찰(觀察)하고자 in vitro test인 colony형성억제실험(形成抑制實驗)과 SRB assay를 이용(利用)하였는데, 진령탕가감방의 추출액(抽出液)이 종양세포(腫瘍細胞)의 성장(成長)을 억제(抑制)하는 효과(效果)가 농도의존적(濃度依存的)으로 증가(增加)하는 결과(結果)를 보여 항종양(抗腫瘍)의 효과(效果)가 있음을 나타냈고(Table 3, 4), in vivo assay로서 sarcoma 180 복수암세포를 이식(移植)한 마우스의 평균생존일수(平均生存日數)를 관찰(觀察)하여 NCI protocol에 의하여 검정(檢定)한 결과(結果), 진령탕가감방 추출액(抽出液)을 투여(投與)한 마우스의 평균생존기간(平均生存期間) 및 생명연장율(生命延長率)이 뚜렷하게 증가(增加)되었다(Table 5). 또한 진령탕가감방 추출액(抽出液)을 마우스에 투여(投與)하면 MCA로 유도(誘導)한 종양(腫瘍) 및 3LL 세포(細胞) 이식(移植)에 의한 종양(腫瘍)의 발생율(發生率) 및 발생(發生)된 종양(腫瘍)의 크기가 현저히 감소(減少)되었다(Table 6, 7). 이러한 효과(效果)는 진령탕가감방이 감수성(感受性) 암종세포(癌腫細胞)에 직접적으로 영향(影響)을 미쳐 그 증식(增殖)이 억제(抑制)되었을 가능성(可能性)을 생각할 수 있다. 그렇지만 본(本) 연구(硏究)에서는 암종특이성(癌腫特異性)에 관한 결론(結論)을 내릴 수는 없으므로 암종특이성(癌腫特異性)에 관한 연구(硏究)는 진행(進行)해야 할 것으로 생각된다. 또 다른 가능(可能)한 진령탕가감방 추출액(抽出液)의 항종양(抗腫瘍) 작용기전(作用機轉)은 진령탕가감방 추출액(抽出液)이 NK세포(細胞)의 활성(活性)을 항진(亢進)시킨 실험결과(實驗結果)로 유추(類推)하여, 진령탕가감방 추출액(抽出液)이 종양(腫瘍)마우스에 비특이적(非特異的)인 면역활성(免疫活性)을 촉진(促進)시킴으로써 진령탕가감방 추출액(抽出液)의 항종양작용(抗腫瘍作用)이 발현될 가능성(可能性)도 생각할 수 있다. 따라서 앞으로 여러 암종세포(癌腫細胞)에 대한 진령탕가감방 추출액(抽出液)의 항종양작용(抗腫瘍作用)과 종양동물(腫瘍動物)에서의 진령탕가감방 추출액(抽出液) 투여(投與)에 의한 생체생리현상(生體生理現象)의 변화(變化), 생리활성물질(生理活性物質)의 본능(本能) 등을 밝히기 위한 보다 구체적(具體的)이고 광범위(廣範圍)한 연구(硏究)가 수행(隨行)되어져야 되리라고 사료(思料)된다. 세포성(細胞性) 면역반응중(免疫反應中) 중요(重要)한 역할(役割)을 하는 작동세포중 NK세포(細胞)는 여러 종양(腫瘍)에 대해 자연살해능(自然殺害能)을 보여 소위 T비의존성(非依存性) 면역감시기전(免疫監視機轉)에 관하여는 바이러스 및 세균(細菌)에 감염(感染)된 세포(細胞)를 파괴(破壞)하는 활성(活性)을 가지며, IL-2 및 Interferon 등에 의하여 활성(活性)이 증가(增加)된다. NK세포(細胞)가 표적세포를 파괴(破壞)하는 기전(機轉)에 관해서는 아직 확실히 알려져 있지 않으나, 첫째로 표적세포를 인식(認識)하는 시기(時期), 둘째로 융해기전(融解機轉)을 활성화(活性化)시키는 시기(時期), 셋째로 NK lymphotoxin이 유리(遊離)되는 시기(時期), 넷째로 표적세포의 사멸기(死滅期)로 나눌 수 있다. 본(本) 실험(實驗)에서 진령탕가감방 추출액(抽出液)으로 전처리(前處理)시 NK세포(細胞)의 표적세포와의 결합능(結合能)은 물론 결합(結合)된 표적세포의 융해능(融解能)이 촉진(促進)된 결과(結果)를 보이는데(Table 8), 이와 같은 결과(結果)는 진령탕가감방 추출액(抽出液)이 NK세포(細胞)의 표적세포 파괴 4단계 전체를 항진(亢進)시킨 결과(結果)로 인정(認定)된다. 이상에서 다음과 같은 결론을 얻었다. 1. 진령탕가감방 추출액(抽出液)을 폐암세포주인 A549와 간암세포주인 hep3B 및 신장암 유래의 종양세포주인 Caki-1 cell에 투여(投與)한 결과, in vitro test인 colony형성억제실험(形成抑制實驗)과 SRB assay에서 모두 농도의존적(濃度依存的)으로 암세포주 성장(成長)을 억제(抑制)하였다. 2. Strcoma 180세포(細胞)를 마우스에 이식(移植)하여 평균생존기간(平均生存期間) 및 생명연장율(生命延長率)을 측정(測定)하는 in vivo test에서는 진령탕가감방 추출액(抽出液)이 마우스의 평균생존기간(平均生存期間) 및 생명연장율(生命延長率)을 증가(增加)시키는 결과(結果)를 보였다. 3. 진령탕가감방 추출액(抽出液)은 MCA로 유도(誘導)한 종양(腫瘍)의 발생율(發生率) 및 발생종양(發生腫瘍)의 크기를 현저히 감소(減少)시켰으며, 3LL세포(細胞) 이식(移植)에 의한 종양발생(腫瘍發生) 또한 현저히 감소(減少)시켰다. 4. 진령탕가감방 추출액(抽出液)은 NK세포(細胞)의 활성도(活性度)를 증가(增加)시켰다. 특히 $10{\mu}g/ml$ 농도 에서 NK세포(細胞) 활성도(活性度)가 가장 현저히 증가(增加)되었다. 이상(以上)의 결과(結果)로 보아 진령탕가감방은 암종세포(癌腫細胞)에 대한 직접적(直接的)인 성장억제(成長抑制) 및 세포(細胞)의 활성(活性)을 통한 면역증진(免疫增進)에 의해 다양(多樣)한 항종양효과(抗腫瘍效果)를 보인 것으로 사료(思料)된다.