• Food preservation and processing industry
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• v.8 no.2
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• pp.6-12
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• 2009

면역반응은 외부 감염원으로부터 신체를 보호하고 외부감염원을 제거하고자 하는 주요항상성 유지기전의 하나이다. 이들 반응은 골수에서 생성되고 비장, 흉선 및 임파절 등에서 성숙되는 면역세포들에 의해 매개된다. 보통 태어나면서부터 얻어진 선천성 면역반응을 매개하는 대식세포, 수지상 세포 등과, 오랜기간 동안 감염된 다양한 면역원에 대한 경험을 토대로 얻어진 획득성 면역을 담당하는 T 임파구 등이 대표적인 면역세포로 알려져 있다. 다양한 면역질환이 최근 주요 사망률의 원인이 되고 있다. 최근, 암, 당뇨 및 뇌혈관질환 등이 생체에서 발생되는 급 만성염증에 의해 발생된다고 보고됨에 따라 면역세포 매개성 염증질환에 대한 치료제 개발을 서두르고 있다. 또한 암환자의 급격한 증가는 암발생의 주요 방어기전인 면역력 증강에 대한 요구들을 가중시키고 있다. 예로부터 사용되어 오던 고려인삼과 홍삼은 기를 보호하고 원기를 회복하는 명약으로 알려진 대표적인 우리나라 천연생약이다. 특별히, 홍삼은 단백질과 핵산의 합성을 촉진시키고, 조혈작용, 간기능 회복, 혈당강하, 운동수행 능력증대, 기억력 개선, 항피로작용 및 면역력 증대에 매우 효과가 좋은 것으로 보고되고 있다. 홍삼에 관한 많은 연구에 비해, 현재까지 홍삼이 면역력 증강에 미치는 효과에 대한 분자적 수준에서의 연구는 매우 미미한 것으로 확인되어져 있다. 홍삼의 투여는 NK 세포나 대식세포의 활성이 증가하고 항암제의 암세포 사멸을 증가시키는 것으로 확인되어졌다. 현재까지 알려진 주요 면역증강 성분은 산성다당류로 보고되었다. 또 한편으로 일부 진세노사이드류에서 항염증 효능이 확인되어졌으며, 이를 통해 피부염증 반응과 관절염에 대한 치료 효과가 있는 것으로 추측되고 있다 [본 연구는 KT&G 연구출연금 (2009-2010) 지원을 받아 이루어졌기에 이에 감사드린다]. 면역반응은 외부 감염물질의 침입으로 유도된 질병환경을 제거하고 수복하는 중요한 생체적 방어작용의 하나이다. 이들 과정은 체내로 유입된 미생물이나 미세화학물질들과 같은 독성물질을 소거하거나 파괴하는 것을 주요 역할로 한다. 외부로 부터 인체에 들어온 이물질에 대한 방어기전은 현재 두 가지 종류의 면역반응으로 구분해서 설명한다. 즉, 선천성 면역 반응 (innate immunity)과 후천성 면역 반응 (adaptive immunity)이 그것이다. 선천성 면역반응은 1) 피부나 점막의 표면과 같은 해부학적인 보호벽 구조와 2) 체온과 낮은 pH 및 chemical mediator (리소자임, collectin류) 등과 같은 생리적 방어구조, 3) phagocyte류 (대식세포, 수지상세포 및 호중구 등)에 의한 phagocytic/endocytic 방어, 그리고 4) 마지막으로 염증반응을 통한 감염에 저항하는 면역반응 등으로 구분된다. 후천성 면역반응은 획득성면역이라고도 불리고 특이성, 다양성, 기억 및 자기/비자기의 인식이라는 네 가지의 특징을 가지고 있으며, 외부 유입물질을 제거하는 반응에 따라 체액성 면역 반응 (humoral immune response)과 세포성 면역반응 (cell-mediated immune response)으로 구분된다. 체액성 면역은 침입한 항원의 구조 특이적으로 생성된 B cell 유래 항체와의 반응과 간이나 대식세포 등에서 합성되어 분비된 혈청내 보체 등에 의해 매개되는 반응으로 구성되어 있다. 세포성 면역반응은 T helper cell (CD4+), cytotoxic T cell (CD8+), B cell 및antigen presenting cell 중개를 통한 세포간 상호 작용에 의해 발생되는 면역반응이다. 선천성 면역반응의 하나인 염증은 우리 몸에서 가장 빈번히 발생되고 있는 방어작용의 하나이다. 예를 들면 감기에 걸렸을 경우, 환자의 편도선내 대식세포나 수지상세포류는 감염된 바이러스 단독 혹은 동시에 감염된 박테리아를 상대로 다양한 염증성 반응을 유도하게 된다. 또한, 상처가 생겼을 경우에도 감염원을 통해 유입된 병원성 세균과 주위조직내 선천성 면역담당 세포들 간의 면역학적 전투가 발생되게 된다. 이들 과정을 통해, 주위 세포나 조직이 손상되면, 즉각적으로 이들 면역세포들 (주로 phagocytes류)은 신속하게 손상을 극소화하고 더 나가서 손상된 부위를 원상으로 회복시키려는 일련의 염증반응을 유도하게 된다. 이들 반응은 우리가 흔히 알고 있는 발적 (redness), 부종 (swelling), 발열 (heat), 통증 (pain) 등의 증상으로 나타나게 된다. 즉, 손상된 부위 주변에 존재하는 모세혈관에 흐르는 혈류의 양이 증가하면서 혈관의 직경이 늘어나게 되고, 이로 인한 조직의 홍반과, 부어 오른 혈관에 의해 발열과 부종이 초래되는 것이다. 확장된 모세혈관의 투과성 증가는 체액과 세포들이 혈관에서 조직으로 이동하게 하는 원동력이 되고, 이를 통해 축적된 삼출물들은 단백질의 농도를 높여, 최종적으로 혈관에 존재하는 체액들이 조직으로 더 많이 이동되도록 유도하여 부종을 형성시킨다. 마지막으로 혈관 내 존재하는 면역세포들은 혈판 내벽에 점착되고 (margination), 혈관벽의 간극을 넓히는 역할을 하는 히스타민 (histamine)이나 일산화질소(nitric oxide : NO), 프로스타그린딘 (prostagladins : PGE2) 및 류코트리엔 (leukotriens) 등과 같은 chemical mediator의 도움으로 인해 혈관벽 사이로 삼출하게 되어 (extravasation), 손상된 부위로 이동하여 직접적인 외부 침입 물질의 파괴나 다른 면역세포들을 모으기 위한 cytokine (tumor necrosis factor [TNF]-$\alpha$, interleukin [IL]-1, IL-6 등) 혹은 chemokine (MIP-l, IL-8, MCP-l등)의 분비 등을 수행함으로써 염증반응을 매개하게 된다. 염증과정시 발생되는 여러 mediator 중 PGE2나 NO 및 TNF-$\alpha$ 등은 실험적 평가가 용이하여 이들 mediator 자체나 생성관련효소 (cyclooxygenase [COX] 및 nitric oxide synthase [NOS] 등)들은 현재항염증 치료제의 개발 연구시 주요 표적으로 연구되고 있다. 염증 반응은 지속기간에 따라 크게 급성염증과 만성염증으로 나뉘며, 삼출물의 종류에 따라서는 장액성, 섬유소성, 화농성 및 출혈성 염증 등으로 구분된다. 급성 염증 (acute inflammation)반응은 수일 내지 수주간 지속되는 일반적인 염증반응이라고 볼 수 있다. 국소반응은 기본징후인 발열과 발적, 부종, 통증 및 기능 상실이 특징적이며, 현미경적 소견으로는 혈관성 변화와 삼출물 형성이 주 작용이므로 일명 삼출성 염증이라고 한다. 만성 염증 (chronic inflammation)은, 급성 염증으로부터 이행되거나 만성으로 시작된다. 염증지속 기간은 보통 4주 이상 장기화 된다. 보통 염증의 경우에는 염증 생성 cytokine인 Th1 cytokine (IL-2, interferone [IFN]-$\gamma$ 및 TNF-$\alpha$ 등)의 생성 후, 거의 즉각적으로 항 염증성 cytokine인 Th2 cytokine(IL-4, IL-6, IL-10 및 transforming growth factor [TGF]-$\beta$ 등)이 생성되어 정상반응으로 회복된다. 그러나, 어떤 원인에서든 면역세포에 의한 염증원 제거 반응이 문제가 되면, 만성염증으로 진행된다. 이 반응에 주로 작용을 하는 염증세포로는 단핵구와 대식세포, 림프구, 형질세포 등이 있다. 암은 전세계적으로 사망률 1위의 원인이 되는 면역질환의 하나이다. 산화적 스트레스나 자외선 조사 혹은 암유발 물질들에 의해 염색체내 protooncogene, tumor-suppressor gene 혹은 DNA repairing gene의 일부 DNA의 돌연변이 혹은 결손 등이 발행되면 정상세포는 암화과정을 시작하게 된다. 양성세포 수준에서 약 5에서 10여년 후 악성수준의 암세포가 생성되게 되면 이들 세포는 새로운 환경을 찾아 전이하게 되는데 이를 통해 암환자들은 다양한 장기에 동인 오리진의 암세포들이 생성한 종양들을 가지게 된다. 이들 종양세포는 정상 장기의 기능을 손상시켜며 결국 생명을 잃게 만든다. 이들 염색체 수준에서의 돌연변이 유래 암세포는 거의 대부분이 체내 면역시스템에 의해 사멸되는 것으로 알려져 있다. 그러나 계속되는 스트레스나 암유발 물질의 노출은 체내 면역체계를 파괴하면서 최후의 방어선을 무너뜨리면서 암발생에 무방비 상태를 만들게 된다. 이런 이유로 체내 면역시스템의 정상적 가동 및 증강을 유도하게 하는 전략이 암예방시 매우 중요한 표적으로 인식되면서 다양한 형태의 면역증강 물질 개발을 시도하고 있다. 인삼은 두릅나무과의 여러해살이 풀로써, 오랜동안 한방 및 민간에서 원기를 회복시키고, 각종 질병을 치료할 수단으로 사용되고 있는 대표적인 전통생약이다. 예로부터 불로(不老), 장생(長生), 익기(益氣), 경신(經身)의 명약으로 구전되어졌는데, 이는 약 2천년 전 중국의 신농본초경(神農本草經)에서 "인삼은 오장(五腸)을 보하고, 정신을 안정시키고, 혼백을 고정하며 경계를 멈추게 하고, 외부로부터 침입하는 병사를 제거하여주며, 눈을 밝게 하고 마음을 열어 더욱 지혜롭게 하고 오랫동안 복용하면 몸이 가벼워지고 장수한다" 라고 기술되어있는 데에서 유래한 것이다. 다양한 연구를 통해 우리나라에서 생산되는 고려인삼 (Panax ginseng)이 효능 면에서 가장 탁월한 것으로 알려져 있으며 특별이 고려인삼으로부터 제조된 고려홍삼은 전세계적으로도 그 효능이 우수한 것으로 보고되어 있다. 대부분의 홍삼 약효는 dammarane계열의 triterpenoid인 ginsenosides라고 불리는 인삼 saponin에 의해 기인된 것으로 알려져 있다. 이들 화합물군의 기본 골격에 따라, protopanaxadiol (PD)계 (22종) 및 protopanaxatriol (PT)계 (10종)으로 구분되고 있다 (표 1). 실험적 접근을 통해 인삼의 약리작용 이해를 위한 다양한 노력들이 경주되고 있으나, 여전히 많은 부분에서 충분히 이해되고 있지 않다. 그러나, 현재까지 연구된 인삼의 약리작용 관련 연구들은 심혈관, 당뇨, 항암 및 항스트레스 등과 같은 분야에서 인삼효능이 우수한 것으로 보고하고 있다. 그러나 면역조절 및 염증현상과 관련된 최근 연구결과들은 많지 않으나, 향후 다양하게 연구될 효능부분으로 인식되고 있다.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.155-163
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• 2004

Purpose : To confirm the reproducibility of in vivo transmission dosimetry system and the accuracy of the a1gorithms for the estimation of transmission dose in head and neck radiation therapy patients. Materials and Methods : From September 5 to 18, 2001, transmission dose measurements were peformed when radiotherapy was given to brain or head and neck cancer patients. The data of 35 patients who were treated more than three times and whose central axis of the beam was not blocked were analyzed in this study. To confirm the reproducibility of this system, transmission dose was measured before dally treatment and then repetitively every hour during the treatment time, with a field size of 10$\times$10 cm$^{2}$ and a delivery of 100 MU. The accuracy of the transmission dose calculation algorithms was confirmed by comparing estimated dose with measured dose. To accurately estimate transmission dose, tissue inhomogeneity correction was done. Results : The measurement variations during a day were within $\pm$0.5$\%$ and the dally variations in the checked period were within $\pm$ 1.0$\%$, which were acceptable for system reproducibility. The mean errors between estimated and measured doses were within $\pm$5.0$\%$ in Patients treated to the brain, $\pm$2.5$\%$ in head, and $\pm$ 5.0%$\%$in neck. Conclusion : The results of this study confirmed the reproducibility of our system and its usefulness and accuracy for dally treatment. We also found that tissue inhomogeneity correction was necessary for the accurate estimation of transmission dose in patients treated to the head and neck.

• Journal of Life Science
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• v.31 no.11
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• pp.1028-1036
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• 2021

Firefly luciferase (FLuc) can function as an efficient marker in the gene and viral therapies. Nonetheless, its clinical translation has been unaccomplished with the concerns on its exogenous nature and the similarity with human fatty acyl-CoA synthetase. In this study, we aimed to show safety of FLuc by conducting a set of preclinical experiments and a human use. Initially, FLuc permeability across the plasma membrane was investigated by delivering the FLuc-carrying viral vector, OTS-412, or the FLuc recombinant protein. After in vitro infection of OTS-412 into different cancer cell lines, FLuc activity was detected only in the cell lysates, but not in culture media. In addition, recombinant FLuc protein further showed the impermeability against the plasma membrane. Similar result was also observed in the in vivo experiment. After being injected into the VX2 tumor-bearing rabbit, the FLuc exclusively resided within the tumor tissue without being detected in the blood plasma or other organs. Human cancer cell lines originated from various organs were lysed and treated to the FLuc, and none of the human substrates was reactive against the FLuc. As a final step, FLuc recombinant protein was intravenously injected into a human. The luciferase was degraded with the half-life of 20 to 30 minutes in blood, and was untraceable from 1.5 hr after the injection. In addition, the blood plasma was nonresponsive against the fatty acids. Hematological analysis was also comparable between the pre- and post-injection. Altogether, our study collectively demonstrates the safety of the firefly luciferase.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.133-139
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• 2009

Purpose: This study was designed to analyze the outcome and toxicity of thoracic radiation therapy (TRT) and chemotherapy for patients who suffer with limited-stage small-cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively studied 35 patients with LS-SCLC. TRT was administered once daily (1.8 to 2 Gy per fraction) and it was directed to the primary tumor for a total 50 to 66 Gy in 6 to 7 weeks. The patients received four cycles of etoposide plus cisplatin. TRT was begun on day 1 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. Results: The median progression-free survival time was 16.5 months (95% confidence interval [CI], 9.0 to 24.1 months) for the sequential arm, and 26.3 months (95% CI, 16.6 to 35.9 months) for the concurrent arm. The 2-year progression-free survival rate was 16.0 percent for the sequential arm and 50.0 percent for the concurrent arm (p=0.0950 by log-rank test). Leukopenia was more severe and more frequent in the concurrent arm than in the sequential arm. However, severe esophagitis was infrequent in both arms. The radiotherapy was interrupted more frequently in the concurrent arm than in the sequential arm due to hematologic toxicities (p=0.001). Conclusion: This study suggests that concurrent TRT with etoposide plus cisplatin is more effective for the treatment of LS-SCLC than sequential TRT. However, there is a significant increase in the risk of toxicities, and radiotherapy was frequently interrupted in the concurrent arm due to hematologic toxicities.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.227-232
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• 2007

Purpose: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosisrelated genes of human laryngeal and lung cancer cells. Materials and Methods: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. Results: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin 01 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. Conclusion: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according to the individual cell line and it did not affect Akt activation of both cell lines.

• Journal of Hospice and Palliative Care
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• v.10 no.2
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• pp.74-77
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• 2007

Purpose: We evaluated how many patients received radiotherapy and how many those of them could not complete radiation therapy in Hospice Ward. Methods: We retrospectively reviewed the general characteristics in 33 patients who began to receive palliative radiation therapy, and radiation dose and reasons of not-completing radiation therapy in Hospice Ward of St. Vincent's Hospital. Results: Thirty three (8.2%) among 404 patients who had been admitted from November 2003 and October 2005 received palliative radiation therapy. The main indications of radiation therapy included brain metastasis, painful bone metastasis, painful tumor mass, and obstructive shortness of breath. Forty five percent of these patients could not complete. And 20% could receive less than 1/3 of planned radiation dose. They failed to complete the treatment often due to poor general rendition. Conclusion: Although palliative radiation therapy had been used frequently for patients with advanced cancer in Hospice Ward of St. Vincent's Hospital, but it was often not completed. With appropriate selection criteria of patients and shorter modification of radiation treatment period, more patients would be benefited with palliative radiation therapy in Hospice Ward.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.293-299
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• 2000

Purpose :We conducted a prospective non-randomized clinical study to evaluate the efficacy and toxic of the preoperative concurrent chemoradiotherapy for locally advanced unresectable rectal cancer. Materials and Methods: Between January 1995 and June 1998, 37 conecutive patients with locally unresectable advanced rectal cancer were entered into the study. With 3- or 4- fields technique, a total of 45 Gy radiation was delivered on whole pelvis, followed by 5.4 Gy boost to the primary tumor in some cases. Chemotherapy was done at the first and fifth week of radiation with bolus i.v. 5-Fluorouracil (FU) 370$\~$450 mg/m$^{2}$, days 1$\~$5, plus Leucovorin 20 mg/m$^{2}$, days 1$\~$5. OF 37 patients, 6 patients did not receive all planned treatment course (refusal in 4, disease progression in 1, metastasis to lung in 1). Surgical resection was undergone 4$\~$6 weeks after preoperative concurrent chemoradiotherapy. Results :Complete resection rate with negative margins was 94$\%$ (29/31). Complete response was seen in 7 patients (23$\%$) clinically and 2 patients (6$\%$) pathologically. Down staging of tumor occured in 21 patients (68$\%$). Treatment related toxicity was minimal except grade III & IV leukopenia in 2 patients, respectively. Conclusion : Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer was effective in inducing down staging and complete resection rate. Treatment related toxicity was minimal. Further follow up is on-going to determine long term survival following this treatment.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.244-250
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• 2000

Purpose : To see the relationship between the response to chemotherapy and the final outcome of neoadiuvant chemotherapy and radiotherapy in patients with mocanry advanced hypopharyngeal cancer. Methods and Materials :A retrospective analysis was done for thirty-two patients with locally advanced hypopharyngeal cancer treated in the Seoul National University Hospital with neoadiuvant chemotherapy and radiotherapy from August 1979 to July 1997. The patients were treated with Co-60 teletherapy unit or 4MV or 6MV photon beam produced by linear accelerator. Daily fractionation was 1.75 to 2 Gy, delivered five times a week. Total dose ranged from 60.8 Gy to 73.8 Gy. Twenty-nine patients received continuous infusion of cisplatin and 5-FU. Other patients were treated with cisplatin combined with bleomycin or vinblastin. Twenty-four (75$\%$) patients received all three prescribed cycles of chemotherapy delivered three weeks apart. Six patients received two cycles, and two patients received only one cycle. Results :The overall 2-year and 5-year survival rates are 65.6$\%$ and 43.0$\%$, respectively. 5-year local control rate is 34$\%$. Organ preservation for more than five years is achieved in 12 patients (38$\%$). After neoadjuvant chemotherapy, 24 patients achieved more than partial remission (PR): the response rate was 75$\%$ (24/32). Five patients had complete remission (CR), 19 patients PR, and 8 patients no response (NR). Among the 19 patients who had PR to chemotherapy, 8 patients achieved CR after radiotherapy. Among the 8 non-responders to chemotherapy, 2 patients achieved CR, and 6 patients achieved PR after radiotherapy. There was no non-responder after radiotherapy. The overall survival rates were 60$\%$ for CR to chemotherapy group, 35.1$\%$ for PR to chemotherapy group, and 50$\%$ for NR to chemotherapy group, respectively (p=0.93). There were significant difference in five-year overall survival rates between the patients with CR and PR after neoadjuvant chemotherapy and radiotherapy (73.3$\%$ vs. 14.7$\%$, p<0.01). The prognostic factor affecting overall survival was the response to overall treatment (CR vs. PR, p<0.01). Conclusion :In this study, there were only five patients who achieved CR after neoadiuvant chemotherapy. Therefore the difference of overall survival rates between CR and PR to chemotherapy group was not statistically significant. Only the response to chemo-radiotherapy was the most important prognostic factor. There needs to be more effort to improve CR rate of neoadjuvant chemotherapy and consideration for future use of concurrent chemoradiotherapy.

• The Journal of Internal Korean Medicine
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• v.45 no.3
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• pp.335-341
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• 2024

Objectives: Patients with cancer eventually fail to respond to therapy when malignant cells develop effective ways to evade immunosurveillance. Conventional cancer treatments, such as radiation therapy and chemotherapy, aim to cure the disease or prolong the patient's life. However, the toxicity and side effects of conventional treatments limit their efficacy. Herbal medicine is a typical complementary and integrative form of medicine for cancer treatment in Asia. This protocol evaluates the effectiveness of herbal medicines in improving the immune function of patients with cancer. Methods: The following electronic databases will be searched: MEDLINE via PubMed, EMBASE via Elsevier, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), and Korean databases including Regional Information Sharing Systems (RISS), National Digital Science Library (NDSL), and Oriental Medicine Advanced Searching Integrated System (OASIS). Additionally, prospective randomized controlled trials that evaluate the effectiveness of herbal medicines on immune function in patients with cancer will be included in this review. All outcomes related to the immune function of patients with cancer (e.g., CD3, CD4, CD8, CD4/CD8 ratio, CD19 (B cells), dendritic cells (CD11), CD56 (NK cells), and macrophages) will be included in this review. Results: This review is expected to provide data on the effectiveness of herbal medicines on improving immune functions in patients with cancers. Conclusion: This systematic review will help patients and clinicians establish new management options for cancer treatment.