• Journal of Life Science
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• v.22 no.9
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• pp.1224-1230
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• 2012

Cancer chemotherapy drugs command a large share of the market, and the development of new therapeutics with high efficacy and specificity is an active area of study. Recently, the development of cancer therapeutics from natural products targeting angiogenesis has drawn attention due to conventional chemotherapeutics showing serious side effects and resistance in cancer cells. In this study, we investigated the pharmacological efficacy of Gomisin A, an active ingredient of Schizandra chinensis baillon, on tumor growth and metastasis. Administration of Gomisin A at 10 and 100 ${\mu}g/ml$ reduced tumor growth in vivo by $80.5{\pm}8.1%$ and $96.2{\pm}2%$, respectively, compared with positive tumor controls. Treatment of Gomisin A in normal and various tumor cell lines did not exert significant toxicity. Mice treated with Gomisin A at a concentration of 10 and 100 ${\mu}g$/head showed a significant reduction in tumor-induced angiogenesis of $151{\pm}16.9%$ and $98.5{\pm}29.5%$, respectively. Furthermore, tumor metastasis analysis revealed that the administration of Gomisin A at a concentration of 10 and 100 ${\mu}g$/head inhibited tumor metastasis by $13.5{\pm}8.56%$ and $58.3{\pm}9.12%$, respectively. In addition, Gomisin A significantly decreased cell adhesion of the B16BL6 cells to the extracellular matrix. These results demonstrate that Gomisin A inhibits tumor growth via suppression of angiogenesis and tumor metastasis inhibition, without cellular toxicity. The pharmacological efficacy of Gomisin A suggests that it may be a potential candidate for the development of cancer drugs.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.178-185
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• 2005

Purpose : The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia(JMML) treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods : Eleven JMML patients aged 8-39 months underwent allo-HSCT. The sources of grafts were unrelated donors(n=7), HLA-matched siblings(n=3) and an HLA 1-antigen mismatched familial donor. All patients had received chemotherapy ${\pm}13$-cis-retinoic acid(CRA) before transplant, and CRA was used, posttransplant, in six patients. Results : Only three patients were in complete remission(CR) at the time of transplantation. Initial chimeric status revealed complete donor chimerism(CC) in five patients, mixed chimerism(MC) in five and autologous recovery(AR) in one. One patient with MC having persistent splenomegaly eventually turned to CC and CR after rapid tapering of cyclosporine, combined with daily use of CRA. An AR case relapsed shortly after transplant but was rescued with second, unrelated cord blood transplantation. Ultimately, six patients are alive, event-free, with a median follow-up of 15.5 months posttransplant. All three deaths occurred in patients who failed to achieve CC, leading to disease progression. Conclusion : We suggest that graft-versus-leukemia effect play an important role and CRA a possible role in posttransplant leukemic involution in JMML. In patients whose leukemic burden is still high with MC after transplant, early tapering of immunosuppressants and introduction of CRA might provide a chance of a cure for some patients.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.314-320
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• 2006

Background : The overall response (20-30%) to chemotherapy in non-small cell lung cancer (NSCLC) is quite poor. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation. There is increasing evidence suggesting that the induction of HO-1 might have an important protective effect against oxidative stress including cisplatin containing chemotherapy. This study retrospectively investigated the relationship between HO-1 expression and the response to chemotherapy containing cisplatinin advanced NSCLC patients. Material and Methods : The medical records including the responses to chemotherapy of fifty nine cases were evaluated retrospectively, and the tissue samples of these patients were immunohistochemically stained for HO-1. Results : Forty three of the fifty nine patients(72.8%) showed positive staining for HO-1 in their cancer tissues. There was no significant difference according to the cell type, stage and tumor size. In addition, there was no correlation between HO-1 expression and the responses to chemotherapy. Conclusion : HO-1 expression in tumor tissue dose not predict the response to cisplatin containing chemotherapy in advanced NSCLC. Further prospective studies with a larger number of patients will be needed to confirm these results.

• Journal of the Korean Applied Science and Technology
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• v.38 no.6
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• pp.1543-1552
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• 2021

Atractylodes japonica has been widely used in a traditional Korean herbal medicine exerting various pharmacological activities such as diauretic action, asriction, anti-allergy, neuroprotective activity, anti-cancer, immunomodulation and gastrointestinal protective effect. This study was to investigate the antioxidant, nitric oxide and inflammatory cytokines production of A. japonica extract by water and 70% ethanol. DPPH and ABTS free radical scavenging activity were increased in a dose-dependent manners with both extracts and there was no difference with extract solvents. 70% ethanol extract of A. japonica showed a very strong inhibitory effect on NO production. Both extracts of A. japonica significantly reduce the expression of iNOS and COX-2 proteins involved in NO prodction. A. japonica extract by water and 70% ethanol inhibited LPS-induced proinflammatory cytokines such as IL-6 and IL-1b. In this study, 70% ethanol extract of A. japonica significantly suppresses LPS-induced NO and inflammatory cytokine production. Therefore it can be widely used to treat and improve inflammatory diseases.

• Journal of Life Science
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• v.34 no.10
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• pp.744-754
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• 2024

Cancer cells exhibit a unique metabolic process for uncontrolled cell division, providing bioenergy and intermediates, which are significantly different from normal cells. Here an aerobic glycolysis converts most of the pyruvate produced from glucose into lactate and inefficiently produced ATP. Cancer cells counter their lack of energy through glutamine metabolism, together with glucose. Glutamine is the most abundant amino acid in the blood and is used for the synthesis of amino acids, nucleotides, and lipids, as well as bioenergy through glutaminolysis. Cancer cells rely on glutamine rather than normal cells, showing more than half of the tricarboxylic acid cycle metabolites derived from glutamine, called glutamine addiction. Oncogenes c-Myc also regulates the expression of various genes involved in glutamine metabolism and promotes the absorption of glutamine. Whether glutaminase (GLS) causes or inhibits tumors is controversial. However, GLS1 is a promising treatment target due to its higher carcinogenic incidence, whereas GLS2 is known to act as a tumor suppressor. The 4th-generation metabolic anti-cancer therapy, which has been actively investigated since the mid-2010s, is based on a complex and sophisticated network of cancer metabolites. These drugs directly regulate the energy metabolism of cancer cells to maximize anti-cancer effects without side effects. GLS is a crucial enzyme for cancer metabolism and tumor progression that catalyzes the first stage in the process of glutaminolysis. The development of anti-cancer drugs targeting GLS enzymes has emerged as a promising strategy.

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.167-173
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• 2007

Purpose: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. Materials and Methods: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum $Q^{(R)}$ was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-$1{\beta}$, IL-2, IL-6, IFN-$\gamma$, TNF-$\alpha$) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. Results: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. Conclusion: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

• Proceedings of the Korean Journal of Food and Nutrition Conference
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• 1997.06b
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• pp.8-10
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• 1997

종양은 아직 그 발생 원인과 기작이 정확히 밝혀져 있지 않으므로 정확한 정의를 내리는 것은 어려우나 일반적으로 종양이란 정상 세포가 갖고 있는 세포 분열의 특이성을 상실하여 일어나는 조직의 자율적인 과잉 성장을 말한다. 이와 같은 세포의 비정상적인 증식에 의한 종양을 임상 및 병리 형태학적으로 양서 종양과 악성종양으로 분류한다. 양성 종양을 일으키는 종양 세포는 정상 세포와 비슷할 뿐 아니라 그 주변 세포들과 확실한 경계를 이루고 있으며 증식도 느리며 다른 부위로의 전이가 없다. 이에 반해 악성종양은 일반적으로 증식도 빠르고 이형의 세포로서 주변의 조직으로 확산, 전이될 뿐만 아니라 최종적으로 숙주인 개체를 사망시킨다. 악성종양은 다시 상피 조직에서 유례한 암, 비상피 조직에서 유래된 육종, 백혈구에서 유래된 백혈병 등으로 구별하지만 그의 본질은 거의 같으며 모든 악성종양은 통속적으로 암이라고 불리운다. 종양의 발생원인으로 크게 3가지로 나눌 수 있는데 화학물질, 바이러스 및 유전적 요인에 의한 것으로 알려졌다. 최초의 발암물질로 알려진 benzopyrene에 의한 발암 등 연구에 의해 화학적 발암원들은 직접 발암 물질로 작용하는 것이 아니라, 일단 체내에서 대사된 후 이들 대사 산물일 DNA 등에 작용함으로써 발암이 유도 되는 것으로 밝혀졌다. 이와 같이 화학적 변화를 거친 후에야 DNA에 영향을 미치는 것외에 다른 화학물질들은 또 다른 기작을 통해 암을 유발하는데 쥐의 피부에 benzopyrene을 한 번 처리하면 암을 유발하지 않으나 여기에 phorbol ester를 처리하면 높은 빈도로 암이 형성된다. 여기서 benzopyrene과 같이 세포의 DNA에 돌연변이를 일으키는 작용을 하는 발암물질을 발암개시제라 하고 phorbol ester처럼 그 자체로는 발암능이 없으나 발암개시제에 노출된 세포에 영향을 미쳐 발암능을 크게 강화시켜 주는 것을 발암촉진제라고 한다. 암은 세포증식 제어계에 DNA가 이상을 일으킨 현상을 말하는 데 이와 같은 DNA의 변형된 유전정보에 의해 암과 관련된 단백질을 합성하므로 이 DNA를 암유전자라 부르며 바이러스에서 유래된 것을 V-one 그리고 세포에서 유래된 것을 c-one이라 한다. 암유전자는 본래 암을 형성하기 위한 것이 아니라 증식제어 유전자로서 변이나 비정상으로 활성화 됨으로써 암을 유발시키므로 proto-oncogene이라 부른다. 또한 고등동물의 유전자 중에는 세포성장을 억제하는 유전자들이 있으며 이들은 세포의 성장 생존 분화를 조절하는 것으로 생각되고 있다. 따라서 이들 유전자는 세포의 암변형을 억제하는 기능을 가지고 있다. 이들 유전자의 이상으로 세포성장 억제기능이 상실되면 세포의 과잉 성장이 초래되면 결과적으로 암으로 유발하는 것으로 추측되고 있다. 최근의 연구에 의하면 암세포에서 암억제 유전자의 이상과 암유전자의 활성화가 함께 발견 되면서 정상세포가 암으로 변형되는 과정에는 암억제 유전자의 이상과 암유전자의 활성화가 동시에 관여한 가능성이 높은 것으로 알려져 있다. 정상 세포가 암을 유발하기 위해서는 발암의 다단계설에서와 같이 여러 단계의 변과가 필요한데 여러 가지 요인에 의해 정상세포의 염색체가 변화되어 정상세포들이 가지고 있는 세포분열의 특이성을 상실하고 증식이 빠르고 저항력이 강한 세포가 선택 되어지고 비정상 서ㅔ포으 과잉 분여러에 의해 종양이 형성되며 이어서 혈관의 신생을 촉진하는 맥관형성, 전이 등이 과정을 거쳐 신체의 다른 부위로 전이된다. 20세기 초까지는 암은 노화와 함께 자연발생적으로 일어나는 피할 수 없는 질병으로 여겨졌으며 그 치료도 조기에 발견된 암환자에게 외과적인 치료를 하는 것이 최선의 방법 이었다. 그러나 현재에는 암환자의 80% 이상이 환경적 요인에 의해 암이 발생 된다고 믿어지고 있다. 과거 치료에 중점을 둔 것에서 점차 예방의 가능성과 그 방법의 모색에 관심을 갖게 되었으며 치료적인 면에서도 외과적 수술 이외에 방사선 치료, 항암제의 투여 등 약물요법, 면역요법의 이용 이외에 더 나아가 gene theraph 및 tumor vaccines 개발에 대한 관심도 증가되고 있다. 국제암연구협회에서는 인간에게 발암이 가능한 물질의 종류를 정기적으로 발표하고 있는데 지금까지 발암 가능성이 높다고 널리 알려진 위험요인을 크게 나누어 보면 다음과 같다. 흡연, 음주, 식이요인, 호르몬 및 기타 요인으로 약물, 자외선 등을 들 수 있는데 현재까지 이들 요인에 의한 발암 기작이 완전히 규명된 것은 아니지만 이들에 의한 발암의 확률이 높다는 것은 사실이므로 이 위험요인에 노출되는 것을 방지함으로써 암발생을 예방할 수 있을 것이다. 암발생의 예방법으로는 암발생 자체를 예방하는 것과 이미 발생한 암환자를 조기 발견하고 치료하는 방법이 있을 수 있다. 현재까지의 여러 연구 결과들을 보면 유전적인 요인을 제외한 대부분의 발암 위험인자들은 개개인의 생활습관과 밀접히 관련되어 있음을 알 수 있다. 이를 바탕으로 1992년 대한 암협회에서는 '암 예방 14개 권장 사항'을 발표하여 국민 홍보활동을 하고 있는데 그 내용의 반 이상이 식생활 습관과 관련되어 있을 정도이므로 암예방에 있어서의 식품의 역할이 매우 크다 할 수 있다. 따라서 건전한 생활습관과 더불어 적절한 식품의 섭취는 암예방을 위한 기본이 될 것이다.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.209-217
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• 1994

Between July 1987 and December 1992, we treated 22 patients with chronic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation(TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6fractions/3days (6 patients) or 1320 cGy/8 fractions/4days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were $58.5\%$ and $41.2\%$, respectively, and the relapse rate was $36\%$ among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase ($76\%\;vs\;33\%$, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation ($50\%\;vs\;0\%$, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patients remains in the chronic phase.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.317-329
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• 2002

Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.62-72
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• 1992

Background: T-cell mediated cellular immunity has been suggested as an important mechanism in mycobacterial infection and imbalance between helper/inducer and suppressor/cytotoxic T-cell has been suggested as an important immunological abnormality in the pathogenesis of tuberculosis in human. Method: To determine whether there is any difference in T-cell mediated immunity in the pathogenesis of pulmonary and extra pulmonary tuberculosis, total numbers of WBC&lymphocytes were counted and helper/inducer and suppressor/cytotoxic cells were calculated by flow cytometry. Blastogenesis after stimulation with Concanavalin-A, Phytohemagglutinin and PPD were measured by $^3H$-thymidine uptake. PPD skin test was performed as an in vivo test. Results: 1)There was no significant difference in the size of PPD skin test between pulmonary and extrapulmonary tuberculosis groups. 2)Number of total lymphocytes significantly decreased in tuberculosis patients compared with healthy control group. But there was no significant difference between pulmonary and extrapulmonary tuberculosis groups. 3) Number of HLA-DR and Interleukin-2 receptor (+) cells were significantly increased in tuberculosis patients. But there was no significant difference between pulmonary and extra pulmonary tuberculosis groups. 4) There was no significant difference in the numbers of WBC, $T_3$, $T_4$ and $T_8$ lymphocytes and $T_4/T_8$ ratio between tuberculosis patients and healthy controls. 5) There was no significant difference in the blastogenesis after stimulation with specific and non-specific blastogens between tuberculosis patients and healthy controls. 6) The percentage and absolute number of $T_4$ lymphocyte were significantly correlated with the size of PPD skin test. (r=0.689 and 0.598). Conclusion: From these results, it is concluded that there was no difference in T-cell mediated immunity between pulmonary and extra pulmonary tuberculosis group. But, because it is suspected that there might be some difference in the role of T-cell mediated immunity in the pathogenesis of pulmonary and extra pulmonary tuberculosis or even among the extrapulmonary tuberculosis patients, further studies would be required.