• Journal of Digestive Cancer Research
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• v.5 no.2
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• pp.97-104
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• 2017

Background: Cachexia is a multi-factorial syndrome presenting with chronic illness, decreases in body weight, and loss of adipose tissue and skeletal muscle, mostly in patients with advanced cancer and chronic wasting disease. Even after years of intensive researches, there remains no convincing therapy to prevent cancer cachexia. Methods: In this in vivo study, we have established C26 adenocarcinoma-induced cancer cachexia model in mice to explore the underlying core changes in cytokine, signal transduction, and muscle wasting. The ultimate aim of establishing animal model is to find optimal therapeutics to mitigate cancer cachexia. Results: We have administered C26 adenocarcinoma cells onto BALB/c mice and observed 4 weeks to assess the progression of cancer cachexia. Significant loss of weight accompanied with loss of appetite was noted. As C26 adenocarcinoma xenograft progressed, mortality was started from 3 weeks, accompanied with significant sarcopenia and decreased mice movement. Surges in TNF-α and IL-6 were noted with the commencement of cancer cachexia. Conclusion: Using C26 adenocarcinoma cancer cachexia model, we can screen the optimal therapeutics to mitigate cancer cachexia, in which agents to modulate IL-6, TNF-α, and NF-κB were essential.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.112-117
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• 1993

Background Radioiodine ($^{131}I$), a major component of nuclear fallout and a valuable therapeutic agent for thyrotoxicosis and thyroid cancer, has been regarded as a mutagen or a carcinogen without any convincing evidence. To evaluate the genotoxicity of radioiodine ($^{131}I$) we performed a micronuclei test in mice bone marrow. Materials and methods : Mice (ICR strain, $25{\sim}30 g$) were divided to 4 groups: control, group 1 (0.17 mCi/kg, usual therapeutic dose for thyrotoxicosis), group 2 (1.67 mCi/kg, usual therapeutic dose for thyroid cancer), and group 3 (16.67 mCi/kg, usual accumulated dose causing bone marrow suppression). $^{131}I$ was administered intraperitoneally. Ten mice of each group were sacrificed at days 1 and 3. Bone marrow were smeared and stained with May-Grunwald Giemsa method. One thou-sand polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were counted under the light microscope, and the number of micronucleated PCEs were recorded. Results : The frequency of micronuclei in PCE (and NCE in parenthesis) in the control group was $0.25{\pm}0.07$ ($0.23{\pm}0.07$)% in day 1 and $0.24{\pm}0.07$ ($0.21{\pm}0.07$)% in day 3. Those in group 1 was $0.27{\pm}0.1$ ($0.23{\pm}0.09$)% in day 1 and $0.28{\pm}0.07$ ($0.25{\pm}0.06$)% in day 3. Micronuclei was noted in $0.29{\pm}0.08$ ($0.26{\pm}0.09$)% in day 1 and $0.31{\pm}0.05$ ($0.29{\pm}0.06$)% in day 3 in group 2, and in $0.32{\pm}0.06$ ($0.25{\pm}0.09$)% in day 1 and $0.33{\pm}0.08$ ($0.3{\pm}0.06$)% in day 3 in group 3. There was no difference in the frequency of micronuclei between each groups (p> 0.05). Conclusion : Radioiodine ($^{131}I$) did not cause any genotoxicity in mice bone marrow even at the large dose (16.67 mCi/kg).

• Radiation Oncology Journal
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• v.12 no.2
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• pp.175-184
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• 1994

From March 1983 through January 1990, two hundred sixty six patients with non-small cell lung cancer were treated with external radiation therapy at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. A retrospective analysis was performed on eligible 116 patients who had been treated with radiation dose over 40 Gy and had been able to be followed up. There were 104 men and 12 women. The age ranged from 33 years to 80 years (median ; 53 years). Median follow up period was 18.8 months ranging from 2 months to 78 months. According to AJC staging system, there were 18($15.5\%$) patients in stage II, 79($68.1\%$) patients in stage III and 19($16.4\%$) patients in stage IV. The Pathologic classification showed 72($62.8\%$) squamous cell carcinomas, 16($13.8\%$) adenocarcinomas, 7($6\%$) large cell carcinomas, 5($4\%$) undifferentiated carcinomas, and 16($13.8\%$) un-known histology. In Karnofsky performance status, six ($5.2\%$) patients were in range below 50, 12($10.4\%$) patients between 50 and 60, 46($39.6\%$) patients between 60 and 70, 50($44.0\%$) patients between 70 and 80 and only one ($0.8\%$) patient was in the range over 80. Sixty ($51.7\%$) patients were treated with radiation therapy (RT) alone. Thirty three ($28.4\%$) patients were treated in combination RT and chemotherapy, twenty three ($19.8\%$) patients were treated with surgery followed by postoperative adjuvant RT and of 23 Patients above, five ($4.3\%$) patients, were treated with postoperative RT and chemotherapy. Overall response according to follow-up chest X-ray and chest CT scans was noted in $92.5\%$ at post RT 3 months. We observed that overall survival rates at 1 year were $38.9\%$ in stage II, $27.8\%$ in stage III, and $11.5\%$ in stage IV, and 2 year overall survival rates were $11.1\%$ in stage II, $20.8\%$ in stage III and $10.5\%$ in stage IV, respectively. We evaluated the performance status, radiation dose, age, type of histology, and the combination of chemotherapy and/or surgery to see the influence on the results fellowing radiation therapy as prognostic factors. Of these factors, only performance status and response after radiation therapy showed statistical significance (P<0.05)

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.347-355
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• 1999

Background: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate($PIP_2$) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate($IP_3$) and diacylglycerol. PLC-${\gamma}1$, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-yl have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by $IP_3$, phosphatidic acid, etc. Very recently, another PLC-${\gamma}1$ activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-${\gamma}1$ activator, AHNAK, in lung cancer specimens and their paired normal. Methods: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract Immunohistochemical stain was performed with primary antibody against AHNAK protein. Results: Twenty-two among twenty-eight lung cancer tissues showed overexpression of AHNAK protein (eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomas). The resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot Conclusion: The overexpression of PLC-${\gamma}1$ activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-${\gamma}1$ act in concerted manner in carcinogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.6
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• pp.474-481
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• 2004

Squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its low survival rate, high malignancy, mortality with facial defects, and poor prognosis. Exact cause and pathogenesis of the squamous cell carcinoma is still unknown. Various routes including smoking, radiation, and viral infections predispose its genesis, and recent studies revealed that genetic defects which fail to prevent cancer proliferation play a role. Generally, a cancer develops from the decreased rate of apoptosis which is an active and voluntary cell death, and from the altered cell cycles. Anticancer effect can be obtained by recovering the apoptotic process, and by suppressing the cell cycles. Among the apoptosis related factors, bcl-2, caspase-9, and VDAC (voltage-dependent anion channel)are produced in mitochondria of the cell. Cyclosporin-A is known to induce apoptosis through its activation with VDAC. This study was to reveal the anticancer effect of Cyclosporin A to the oral squamous cell carcinoma. The inverted microscope was used to find alterations in the tissue, and sensitivity test to the anticancer cells was performed with MTT (Tetrazolium-based colorimetric) assay. Following cell line culture of primary and metastastic oral squamous cell carcinoma, electrophoresis was performed with extracted total RNA. Finally, semi-quantitative study was carried out through RT-PCR (Reverse Transcription-Polymerase Chain Reaction). The results of this study are as follows: 1. The inverted microscopic observation revealed a poorly defined cytoplasm at $2000ng{\sim}3000ng/ml$, indistinct nucleus, and apoptosis. 2. The Growth of cancer cells was decreased at 1000ng/ml of cyclosporin-A. No cancer cell growth was observed at over 2000ng/ml concentration of cyclosporin-A, and at one week, growth of cancer cells was ceased. 3. The MTT assays were decreased as cyclosporin-A concentration was increased. This means that the activation of succinyl dehydrogenase in mitochondria was decreased following administration of cyclosporin A. 4. A result of RT-PCR showed that amount of mRNA of VDAC-2 was decreased half times at a cyclosporine-A concentration of 2000ng/ml. In bcl-2, amount of mRNA was significantly decreased 1/5 times at 2000ng/ml. caspase-9, however, showed slight increase compared to the control group. From the results obtained in this study, administration of cyclosporin-A to the cell lines of oral squamous cell carcinoma induced alterations in morphology and growth of the cells as its concentration increased. Since apoptosis related factors such as VDAS-2, bcl-2, and caspase-9 also showed distinct alterations on their mRNAs, further research on cyclosporin A as an anti-cancer agent will be feasible.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.37-46
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• 2006

Objectives : The purpose of this study was to investigate the effect of Dangguibohyultang (DB) and its combination (DB-I; Astragali membraneus BUNGE : Angelica gigas NAKAI=5:1, DB-II; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:1, DB-III; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:5,) on apoptosis in human colorectal adenocarcinoma HCT116 cells. Methods : To study the cytotoxic effect of methanol extract of DB-I, DB-II and DB-III on HCT116 cells, the cell viability was determined by XTT reduction method and ttypan blue exclusion assay. To confirm the induction of apoptosis, the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, DB-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome C from mitochondria to cytosol, the level of Bcl-2 and Bax, and the expressions of Raf/MEK/ERK were examined by western blot analysis. Results : DB-I and DB-II reduced proliferation of HCT116 cells in a dose-dependent manner. DB-I and DB-II decreased procaspase-3, -8, -9 levels in a dose-dependent manner and induced the clevage of PARP. DB-I and DB-II also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol, decreasing of anti-apoptotic Bcl-2, and increasing of pro-apoptotic Bax. DB-I and DB-II decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. Conclusion : These results suggest that DB-I and DB-II induce apoptosis via mitochondrial pathway in HCT116 cells. Furthermore, Raf/MEK/ERK cascade is involved in DB-induced apoptosis. These results suggest that DB is potentially useful as a chemotherapeutic agent in human liver cancer.

• Herbal Formula Science
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• v.14 no.2
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• pp.21-32
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• 2006

The purpose of this study was to investigate the effect of Imyosan on apoptosis in human colorectal cancer HCT116 cells. Phellodendron amurense Rupr. and Atratylodes lancea D.C. compose Imyosan. First of all, to study the cytotoxic effect of methanol extract of Imyosan (IMS-MeOH) on HCT116 cells, the cells were treated with various concentrations of IMS-MeOH and then cell viability was determined by XTT reduction method. IMS-MeOH reduced viability of HCT116 cells in a dose and time-dependent manner. To confirm the induction of apoptosis, the c1eavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of caspase-3, procaspase-8 and procaspase-9 were examined by western blot analysis. IMS-MeOH decreased procaspase-3, procaspase-8 and procaspase-9 levels in a dose-dependent manner and induced the clevage of PARP. IMS-MeOH triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome c from mitochondria to cytosol. Furthermore, IMS-MeOH also downregulated the anti-apoptotic Bcl-2 and upregulated the pro-apoptotic-Bax. Therefore, these results suggest that IMS-MeOH induced HCT1l6 cell death through the mitochondrial pathway. To explore whether the activities of caspases was required for induction of apoptosis by IMS-MeOH, caspase-3, -8, -9 activity measured by using substrates, respectively. IMS-MeOH increased caspase-3, -8, -9 activity. Co-treatment with inhibitors of caspase-3, -8, -9 and IMS-MeOH significantly blocked IMS-MeOH-triggered apoptosis in HCT1l6 cells. These results suggest that IMS-MeOH induces caspases-mediated apoptosis.

• Journal of Radiation Protection and Research
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• v.25 no.4
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• pp.183-190
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• 2000

Medicinal plants with synergistic effects on growth inhibition of canter cells under oxidative stress were screened in this study. Methanol extracts from 51 natural medicinal plants which were reported to have anticancer effort on hepatoma stomach cancer or colon cancers which are frequently found in Korean, were prepared and screened for their synergistic activity on growth inhibition of cancer cells under chemically-induced oxidative stress by using MTT assay. Twenty seven samples showed synergistic activity on the growth inhibition in various extent under chemically-induced oxidative stress. Among those samples, eleven samples such as Melia azedarach, Agastache rugosa, Catalpa ovata, Prunus persica, Sinomenium acutum Pulsatilla koreana, Oldenlandia diffusa, Anthriscus sylvestris, Schizandra chinensis, Gieditsia sinensis, Cridium officinale, showed decrease in $IC_{50}$ values more than 50%, other 16 samples showed decrease in $IC_{50}$ values between 50-25%, compared with the value acquired when medicinal plant sample was used alone. Among those 11 samples, extract of Catalpa ovata showed the highest activity. $IC_{50}$ values were decrease to 61% and 28% when carcinoma cells were treated with Catalpa ovata extract in combination of 75 and 100 uM of hydrogen peroxide, respectively.

• Horticultural Science & Technology
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• v.28 no.5
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• pp.857-863
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• 2010

This study was conducted to evaluate the antioxidant activity, Angiotensin I Converting Enzyme (ACE) inhibitory activity, ${\alpha}$-glucosidase inhibitory activity, nitrate synthesis inhibitory activity, and antiproliferation inhibitory effect on ethanol extract and its solvent fractions of $Coreopsis$ $tinctoria$ Nutt. Ethyl acetate fraction was the strongest at 1,1-diphenyl-2-picryl hydrazyl (DPPH) ($IC_{50}=0.100mg{\cdot}mL^{-1}$) and 2,2'-Azino-bis-(3-ethylbenozothiazoline-6-sulfonic acid) (ABTS) (15.785 mg AA $eq{\cdot}10mg^{-1}$) radical scavenging activity, ACE (40.96% at $1mg{\cdot}mL^{-1}$), and ${\alpha}$-glucosidase ($IC_{50}=0.125mg{\cdot}mL^{-1}$) inhibitory effect among the solvent fractions. Nitrate synthesis inhibitory activity of ethanol extract, chloroform fraction, and ethyl acetate fraction effectively inhibited NO formation in a dose-dependent manner without the cytotoxic effect. Ethanol extract and its solvent fractions inhibited growth of HCT-116 colon cancer cells in a dose-dependent manner. n-Hexane fraction showed the highest antiproliferation inhibitory effect of $0.041mg{\cdot}mL^{-1}$ among fractions.

• Proceedings of the Korean Society for Food Science of Animal Resources Conference
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• 2004.05a
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• pp.357-361
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• 2004

반복적인 실험을 통해 부추 김치에서 분리된 대부분의 유산균은 항유전독성 효과를 갖는 것으로 보인다. 이는 전에 시행되었던 각종 김치의 유산균을 이용한 항유전독성 효과 조사에서도 다른 김치유산균에 비해서 부추김치의 유산균이 항유전독성효과가 높다는 것을 통해서도 증명되었다. 유산균 섭취시에 균주가 장내의 혐기성 상태에서 존재하게 되는데 아직까지는 혐기성 상태에서 배양된 균주의 항유전독성효과가 그다지 높지 않은 것으로 보여진다. 따라서 혐기성 상태에서 배양된 항유전독성효과가 높은 균주를 찾는 것이 시급하다고 본다. 그러나 호기성 상태에서 배양된 항유전독성이 높은 균주들이 혐기성 상태에서도 배양되는 것을 확인하였고 이 균주들의 장내 생존 가능성을 예측할 수 있다. 물론 이를 뒷받침하기 위해서 이 유산균들이 위와 장내의 조건에서 생존가능하는지에 대해 pH 생존 조사를 해야 할 것이다. 또한 혐기성 상태에서 배양되었을 때에도 이 균주들이 항유전독성 효과가 있는지도 앞으로 실시되어야 할 과제일 것이다. 항유전독성 효과와 달리 항암효과에 대해서는 높은 효과를 보이지 않았지만 본래 CT-26 세포가 대장암 세포이기에 이 세포 자체의 DNA에 손상 복구율을 부여했다는 것에 의미를 둘 수 있겠다. 항유전독성효과와 항암효과가 있는 유산균의 분리를 통해 우리가 다음으로 해야 될 일은 첫째로 이 균주들에 대해 여러 가지 특성을 찾아 동정하고 둘째로 지금까지 밝혀진 결과를 in vivo상에서 검증하는 것이다. 지금까지 밝혀진 유산균은 대부분 발효 유제품에서 자라는 유산균인데 한국인이 주로 섭취하는 각종 김치나 부추김치 등에서 분리한 균주에서도 이 기능이 있음을 밝힌다면 이들의 소비에 도움이 될 것이고 또한 이 균주들을 이용해 향유전독성, 항암성 등이 있는 기능성 제품을 만들어 낼 수 있을 것이다.첨가한 햄보다 적었다.분산시키는 것으로 나타났다. 또한 고기를 단계별 복합처리로 저 allergy 처리는 단계별로 점차적으로 allergy가 감소되었다. 즉 단계별로 억제가 안되는 것부터 억제되는 처리를 복합적으로 처리한 것으로 그 단계는 천연효소처리에 인산염 처리, 여기에 초음파 처리, 마지막 단계로 3분 끓이면 억제율이 68%까지 억제되었다. 이는 단일처리시 전혀 억제를 못하는 처리를 단계별로 한 단계씩 더해가면 allergy 억제효과가 나타난다고 할 수 있겠다. 초음파 처리도 역시 저 allergy 처리 공정에 이용될 수 있는데 이것은 그 처리로 인해 새로운 알러젠이 생성될 수도 있다. 또한 복합처리로 allergy를 감소시키면 연속적이고 동시적으로 하기 때문에 원가를 절감할 수 있다.환경현안에 대한 정치경제적 접근을 외면하지 말고 교과서 저작의 소재로 삼을 수 있어야 하며, 이는 '환경관리주의'와 '녹색소비'에 머물러 있는 '환경 지식교육'과 실천을 한단계 진전시키는 작업으로 이어질 것이다. 이후 10년의 환경교육은 바로 '생태적 합리성'과 '환경정의'라는 두 '화두'에 터하여 세워져야 한다.배액에서 약해를 보였으나, 25% 야자지방산의 경우 50 ${\sim}$ 100배액 어디에서도 액해를 보이지 않았다. 별도로 적용한 시험에서, 토마토의 경우에도 25% 야자지방산 비누 50 ${\sim}$ 100배액 모두 약해를 발생하지 않았으나, 오이에서는 25% 야자지방산 비누 100배액에도 약해를 나타내었다. 12. 이상의 결과, 천연지방산을 이용하여 유기농업에 허용되는 각종의 살충비누를 제조할 수 있었으며, 방제가 조사결과 진딧물, 응애 등 껍질이 연약한 곤충의 방제에 효과적인 것으로 나타났다. 따라서 제조된 살충비누를 활용하면 환경친화적인 해