• Radiation Oncology Journal
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• v.26 no.3
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• pp.160-165
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• 2008

Purpose: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy(CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine ($1,200\;mg/m^2$, $1^{st}$ and 8th day) and cisplatin ($60\;mg/m^2$) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range $3{\sim}39$ months) and the median survival time was 16 months (95% CI; $2.4{\sim}39.2$ months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.948-957
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• 2016

We previously developed an herbal composition (HemoHIM) based on the water extracts of Angelica gigas radix, Cnidium officinale rhizoma, and Paeonia japonica radix to protect and recover hematopoietic and intestinal tissues against radiation injuries. In this study, to develop a composition with improved activities based on enhanced fat-soluble polyphenol contents, we prepared a new herbal composition, MH-30, from the above three herbs by 30% ethanol extraction and hot water extraction. HPLC analysis of the ethanol fractions of MH-30 and HemoHIM revealed that MH-30 had higher contents of many fat-soluble polyphenol compounds than HemoHIM (8.7-fold increase for decursin), whereas contents of water-soluble polyphenol compounds showed little differences between the two compositions. Then, we evaluated MH-30 and HemoHIM for their in vitro antioxidant and immune cell-stimulating activities as well as in vivo protective effects against radiation injuries in hematopoietic and self-renewal tissues. In antioxidant activity assays, MH-30 showed higher hydroxyl radical scavenging activity than HemoHIM (1.4- to 1.9-fold for compositions and 2.3- to 4.5-fold for ethanol fractions). On the other hand, MH-30 and HemoHIM exhibited similar immune cell-stimulating activities as measured by in vitro lymphocyte proliferation. MH-30 increased endogenous spleen colony formation, decreased bone marrow cell apoptosis, and enhanced survival of intestinal crypts in irradiated mice, demonstrating effective protection of MH-30 against radiation-induced injuries in hematopoietic and self-renewal tissues. The 30-day survival rate of lethally irradiated mice, a comprehensive index for radioprotective efficacy, was also elevated by MH-30. Noticeably, MH-30 showed higher protective effects than HemoHIM in all mouse experiments. These results demonstrate that MH-30 can protect hematopoietic and self-renewal tissues against radiation injuries more effectively than HemoHIM. Therefore, MH-30 can be a good candidate to reduce radiation injuries in hematopoietic and self-renewal tissues incurred by radiation accidents or cancer radiation therapy.

• Korean Journal of Food Science and Technology
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• v.39 no.6
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• pp.681-687
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• 2007

This study was designed to examine the suitable characteristics of potential probiotic bacteria. Possible probiotic bacteria, including Lactobacillus acidophilus DDS-1, Lb. acidophilus B-3208, Bifidobacterium bifidum KCTC 3357, Lb. plantarum, Leuconostoc mesenteroides ssp. mesenteroides ATCC 8293, and Lactococcus lactis ssp. lactis ATCC 7962 were selected. We then measured their acid and bile tolerances, adhesion properties in the gastrointestinal tract, antimicrobial activity against pathogenic bacteria, and immunomodulation activity. The acid tolerances of Lb. acidophilus DDS-1, Lb. acidophilus B-3208, Lb. plantarum, and Leu. mesenteroides ssp. mesenteroides ATCC 8293, in PBS (pH 2.5) for 2 hr, were high enough that 50% of the inocula survived. The bile tolerances of all bacteria, except Lc. lactis ssp. lactis ATCC 7962, were also observed at a 3% oxgall concentration in MRS broth. The results of the adhesion property assay showed that the total binding affinities of Lb. acidophilus DDS-1, Lb. acidophilus B-3208, and B. bifidum were about three times higher than those of the other bacteria. In testing their antimicrobial activities against pathogens, Lb. acidophilus B-3208, B. bifidum KCTC 3357, and Lb. plantarum inhibited the growth of pathogenic bacteria. For their immunomodulation activity, the cell wall fractions from Lb. acidophilus DDS-1 and Lb. acidophilus B-3208 showed the highest bone marrow cell proliferation activities. However, the cell wall fractions of Lb. acidophilus DDS-1 and B. bifidum, and the cytosol fraction of Lc. lactis ssp. lactis ATCC 7962 showed higher macrophage stimulation activities than those of the other bacteria. Since Lb. acidophilus DDS-1 and Lb. acidophilus B-3208 satisfy the requirements for probiotics, they can be considered suitable probiotic bacteria.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.4
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• pp.646-652
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• 2004

With the aim of using a cosmetic material, chondroitin sulfates extracted from midduck tunics (Styela clava) and munggae tunics (Halocynthia roretzi) were examined in vitro with two cell lines for cell toxicity, collagen synthesis, cell growth and recovery ability after U.V. irradiation. Cell toxicity test with A 431 and CCD 1108Sk was able to observe high activity between 400 and 600 $\mu\textrm{g}$/m while standard chondroitin sulfate (CS) purchased from Sigma was showed at 80 $\mu\textrm{g}$/mL. Even fraction 1 and 2 collected from chondroitin sulfates originated from midduck appeared having the highest activity between 600 and 1000 $\mu\textrm{g}$/mL, but slightly lower compared to crude chondroitin sulfates from both mideduck and munggae. In cell growth examination, it was not able to find significant differences between chondroitin sulfates used. Both crude chondroitin sulfates were exhibited the highest activity for two cell lines except that of mideduck which was showed activity for CCD 1108Sk. CS, fraction 1 and 2 from midduck were not able to demonstrate a significant activity in collagen synthesis. On the contrary, crude chondroitin sulfates from both munggae and midduck were showed the highest activity at 100 and 50 $\mu\textrm{g}$/mL with only CCD 1108Sk. The recovery ability after U.V. irradiation with crude chondroitin sulfates from both munggae and midduck were showed high activity at 400 $\mu\textrm{g}$/mL with CCD 1108Sk and A 431. But there were no activity observed in fractions examined, As a consequence, the crude chondroitin sulfates from both munggae and midduck might not only be available as a cosmetic material but also useful for increasing some activity by blending properly.

• 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.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.407-417
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• 1999

Objective: Mammalian follicle cells are the most important somatic cells which help oocytes grow, mature and ovulate and thus are believed to provide oocytes with various functional and structural components. In the present study we have examined whether cumulus or granulosa cells might playa role in establishing the plasma membrane structure of mouse oocytes during meiotic maturation. Design: In particular the differential resistances of mouse oocytes against chymotrypsin treatment were examined following culture with or without cumulus or granulosa cells, or in these cell-conditioned media. Results: When mouse denuded oocytes, freed from their surrounding cumulus cells, were cultured in vitro for $17{\sim}18hr$ and then treated with 1% chymotrypsin, half of the oocytes underwent degeneration within 37.5 min ($t_{50}=37.5{\pm}7.5min$) after the treatment. In contrast cumulus-enclosed oocytes showed $t_{50}=207.0$. Similarly, when oocytes were co-cultured with cumulus cells which were not associated with the oocytes but present in the same medium, the $t_{50}$ of co-cultured oocytes was $177.5{\pm}13.1min$. Furthermore, when oocytes were cultured in the cumulus cell-conditioned medium, $t_{50}$ of these oocytes was $190.0{\pm}10.8min$ whereas $t_{50}$ of the oocytes cultured in M16 alone was $25.5{\pm}2.9min$. Granulosa cell-conditioned medium also increased the resistance of oocytes against chymotrypsin treatment such that $t_{50}$ of oocytes cultured in granulosa cell-conditioned medium was $152.5{\pm}19.0min$ while that of oocytes cultured in M16 alone was $70.0{\pm}8.2min$. To see what molecular components of follicle cell-conditioned medium are involved in the above effects, the granulosa cell-conditioned medium was separated into two fractions by using Microcon-10 membrane filter having a 10 kDa cut-off range. When denuded oocytes were cultured in medium containing the retentate, $t_{50}$ of the oocytes was $70.0{\pm}10.5min$. In contrast, $t_{50}$ of the denuded oocytes cultured in medium containing the filtrate was $142.0{\pm}26.5min$. $T_{50}$ of denuded oocytes cultured in medium containing both retentate and filtrate was $188.0{\pm}13.6min$. However, $t_{50}$ of denuded oocytes cultured in M16 alone was $70.0{\pm}11.0min$ and that of oocytes cultured in whole granulosa cell-conditioned medium was $156.0{\pm}27.9min$. When surface membrane proteins of oocytes were electrophoretically analyzed, no difference was found between the protein profiles of oocytes cultured in M16 alone and of those cultured in the filtrate. Conclusions: Based upon these results, it is concluded that mouse follicle cells secrete a factor(s) which enhance the resistance of mouse oocytes against a proteolytic enzyme treatment. The factor appears to be a small molecules having a molecular weight less than 10 kDa.

• Radiation Oncology Journal
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• v.33 no.4
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• pp.284-293
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• 2015

Purpose: To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. Materials and Methods: Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was $50mg/m^2$ weekly paclitaxel combined with $20mg/m^2$ cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. Results: The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. Conclusion: Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.3
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• pp.364-370
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• 2008

Chemical analysis and in vitro studies were conducted to investigate the nutritive value for ruminants of cell mass from lysine production (CMLP) which is a by-product of the lysine manufacturing process. Proximate analysis, protein fractionation, and in vitro protein degradation using protease from Streptomyces griseus and strained ruminal fluid were carried out to estimate ruminal protein degradability of CMLP with two reference feedstuffs-soybean meal (SBM) and fish meal (FM). Amino acid composition and pepsin-HCl degradability were also determined to evaluate postruminal availability. CMLP contained 67.8% crude protein with a major portion being soluble form (45.4% CP) which was composed of mainly ammonium nitrogen (81.8% soluble CP). The amount of nucleic acids was low (1.15% DM). The total amount of amino acids contained in CMLP was 40.60% DM, which was lower than SBM (47.69% DM) or FM (54.08% DM). CMLP was composed of mainly fraction A and fraction B2, while the protein fraction in SBM was mostly B2 and FM contained high proportions of B2 and B3 fractions. The proportion of B3 fraction, slowly degradable protein, in CP was the highest in fish meal (23.34%), followed by CMLP (7.68%) and SBM (1.46%). CMLP was degraded up to 51.40% at 18 h of incubation with Streptomyces protease, which was low compared to FM (55.23%) and SBM (83.01%). This may be due to the insoluble portion of CMLP protein being hardly degradable by the protease. The in vitro fermentation by strained ruminal fluid showed that the amount of soluble fraction was larger in CMLP (40.6%) than in SBM (17.8%). However, because the degradation rate constant of the potentially degradable fraction of CMLP (2.0%/h) was lower than that of SBM (5.8%/h), the effective ruminal protein degradability of CMLP (46.95%) was slightly lower than SBM (53.77%). Unavailable fraction in the rumen was higher in CMLP (34.0%) compared to SBM (8.8%). In vitro CP degradability of CMLP by pepsin was 80.37%, which was lower than SBM (94.42%) and FM (89.04%). The evaluation of protein degradability using different approaches indicated that soluble protein in CMLP may supply a large amount of ammonia in the rumen while insoluble protein can be by-passed from microbial attacks due to its low degradability. The results from this study suggest that CMLP can be used as a protein supplement to ruminants for supplying both non-protein nitrogen to rumen microbes and rumen undegradable protein to the host animal.

• Korean Journal of Environmental Agriculture
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• v.24 no.4
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• pp.379-385
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• 2005

This study was conducted to find out a useful bioremediation technology for heavy metal contaminated soil and water. We isolated strain CPB from heavy metal contaminated soil and evaluated the tolerance level and adsorption capacity of strain CPB to heavy metals (Strain is not determined yet). Strain CPB showed variable tolerance limit to different kinds heavy metal or concentrations of heavy metals. The growth of strain CPB was significantly inhibited by mixed heavy metals (Cd+Cu+Pb+Zn) than that of by single heavy metal. Strain CPB showed high binding capacity with Pb (Pb>Cd>Cu>Zn). In general, strain CPB showed high uptake of heavy metals such as Pb, Cd and Cu. It was observed that the capacity of heavy metal uptake from mixture of heavy metals was reduced in comparison with single heavy metal treatment. But total contents of heavy metal bound with cell in mixed heavy metal showed higher than in single heavy metal treatment. Heavy metal adsorption in cells was affected by several external factors, such as temperature and pH etc.. The optimum temperature and pH of the adsorption of heavy metal into cells were ca. $25{\sim}35^{\circ}C$ and pH ca. $5{\sim}7$, respectively. A large number of the electron dense particles were found mainly on the cell wall and cell membrane fractions, which was determined by transmission electron microscope. Energy dispersive X-ray spectroscopy revealed that the electron dense particles were the heavy metal complexes the substances binding with heavy metals.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.89-97
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• 2015

Purpose: To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods: From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results: The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion: The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication.