• Title/Summary/Keyword: Team efficacy

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Enriching CCL3 in the Tumor Microenvironment Facilitates T cell Responses and Improves the Efficacy of Anti-PD-1 Therapy

  • Tae Gun Kang;Hyo Jin Park;Jihyun Moon;June Hyung Lee;Sang-Jun Ha
    • IMMUNE NETWORK
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    • v.21 no.3
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    • pp.23.1-23.16
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    • 2021
  • Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for pre-clinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote anti-tumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy.

In vivo Antifungal Activity of Pyrrolnitrin Isolated from Burkholderia capacia EB215 with Antagonistic Activity Towards Colletotrichum Species (탄저병균에 대하여 길항작용을 보이는 Burkholderia cepacia EB215로부터 분리한 Pyrrolnitrin의 항균활성)

  • Park, Ji-Hyun;Choi, Gyung-Ja;Lee, Seon-Woo;Jang, Kyoung-Soo;Choi, Yong-Ho;Chung, Young-Ryun;Cho, Kwang-Yun;Kim, Jin-Cheol
    • The Korean Journal of Mycology
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    • v.32 no.1
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    • pp.31-38
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    • 2004
  • An endophytic bacterial strain EB215 that was isolated from cucumber (Cucumis sativus) roots displayed a potent in vivo antifungal activity against Colletotrichum species. The strain was identified as Burkholderia cepacia based on its physiological and biochemical characteristics, and 16S rDNA gene sequence. Optimal medium and incubation period for the production of antifungal substances by B. cepacia EB215 were nutrient broth (NB) and 3 days, respectively. An antifungal substance was isolated from the NB cultures of B. cepacia EB215 strain by centrifugation, n-hexane partitioning, silica gel column chromatography, preparative TLC, and in vitro bioassay. Its chemical structure was determined to be pyrrolnitrin by mass and NMR spectral analyses. Pyrrolnitrin showed potent disease control efficacy of more than 90% against pepper anthracnose (Colletotrichum coccodes), cucumber anthracnose (Colletotrichum orbiculare), rice blast (Magnaporthe grisea) and rice sheath blight (Corticium sasaki) even at a low concentration of $11.1\;{\mu}g/ml$. In addition, it effectively controlled the development of tomato gray mold (Botrytis cinerea) and wheat leaf rust (Puccinia recondita) at concentrations over $33.3\;{\mu}g/ml$. However, it had no antifungal activity against Phytophthora infestans on tomato plants. Further studies on the development of microbial fungicide using B. cepacia EB215 are in progress.

Growth Survival of Listeria monocytogenes in Enoki Mushroom (Flammulina velutipes) at Different Temperatures and Antilisterial Effect of Organic Acids (팽이버섯에서 Listeria monocytogenes의 온도별 생존과 유기산에 의한 저감화)

  • Kim, Se-Ri;Kim, Won-Il;Yoon, Jae-Hyun;Jeong, Do-Yong;Choi, Song-Yi;Hwang, Injun;Rajalingam, Nagendran
    • Journal of Food Hygiene and Safety
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    • v.35 no.6
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    • pp.630-636
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    • 2020
  • Listeria monocytogenes (L. monocytogenes) was responsible for several recall cases owing to its incidence in mushrooms exported from the Republic of Korea. In this study, we investigated the survival of L. monocytogenes in enoki mushroom (Flammulina velutipes) at different temperatures and the antilisterial effect of its organic acids. Enoki mushrooms were innoculated with L. monocytogenes (initial concentration 4.5 log CFU/g) and stored at 1-35℃, No growth of L. monocytogenes in enoki mushrooms was observed at 1℃ for 30 days. 3.0 log CFU/g growth of L. monocytogenes was also achieved after 36 h and 24 h at 30℃ and 35℃, respectively. To evaluate the antilisterial effect of the organic acids (acetic acid, lactic acid, malic acid), enoki mushrooms were treated with 1-3% of each acid for 10-30 min. The efficacy of malic acid and lactic acid was significantly higher than that of acetic acid. Over 3.0 log reductions were observed when L. monocytogenes in enoki mushrooms was immersed in 3% lactic acid and malic acid over 10 minutes or more. Therefore, it is necessary to keep enoki mushrooms at 1℃ during the export process and treat them with 3% lactic acid and malic acid for 10 min prior to consumption.

Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products (천연물 항암제제 임상시험 평가지표 개발연구)

  • Namgung, Mi-Ae;Chang, Yoo-Sung;Jeong, Seung-Gi;Kim, Jin-Seung;Yoon, Sung-Woo;Jang, Ki-Young;Yoo, Hwa-Seung;Jung, Myeon-Woo;Lee, Sung-Ho;Kim, Sung-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1678-1727
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    • 2006
  • This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.

Anti-inflammatory effects of the Rubus occidentalis seed extracts on UV-B induced inflammation in HaCat cells (각질형성세포에서 UV-B와 사이토카인에 의하여 유도되는 염증 반응에 대한 복분자 씨앗 추출물의 항염증 효과)

  • Kim, Dong-Hee;Park, Tae-Soon;Son, Jun-Ho
    • Journal of Applied Biological Chemistry
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    • v.59 no.3
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    • pp.247-253
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    • 2016
  • It confirmed the applicability as an anti-inflammatory material from Rubus occidentalis seed (RSE) extract. In HaCaT cells to evaluate the anti-inflammatory potential as a material RSE extract on the activity of the inflammatory factors caused by UVB and $IFN-{\gamma}/TNF-{\alpha}$. We measured the activity of ROS, interleukin-$1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6) and interleukin-8 (IL-8) by ROS-Glo $H_2O_2$ assay and ELISA kit. Our results showed that the RSE extracts inhibit the UVB and $IFN-{\gamma}/TNF-{\alpha}$-induced ROS activities and expression of $IL-1{\beta}$, IL-6 and IL-8 in a dose-dependent manner. Also it was found that inflammatory mediators of the expression of cyclooxygenase-2 (COX-2) inhibition were also brought, the expression of which is increased $PGE_2$ by COX-2 also inhibited. Finally RSE extracts measure the seed expression of filaggrin in the skin barrier, the main factor of the extract could be confirmed to increase the expression of the filaggrin damaged as a result of this concentration-dependent manner. Through this, it was able to confirm that the efficacy RSE extract to protect the inflammation by restoring the damaged layers of the epidermis. Results from more than RSE extract was able to confirm that the extract that has anti-inflammatory effects by improving the inflammation being produced from UVB.

Genetic Polymorphisms of UGT1A and their Association with Clinical Factors in Healthy Koreans

  • Kim, Jeong-Oh;Shin, Jeong-Young;Lee, Myung-Ah;Chae, Hyun-Suk;Lee, Chul-Ho;Roh, Jae-Sook;Jin, Sun-Kyung;Kang, Tae-Sun;Choi, Jung-Ran;Kang, Jin-Hyoung
    • Genomics & Informatics
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    • v.5 no.4
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    • pp.161-167
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    • 2007
  • Glucuronidation by the uridine diphosphateglucuronosy-ltransferase 1A enzymes (UGT1As) is a major pathway for elimination of particular drugs and endogenous substances, such as bilirubin. We examined the relation of eight single nucleotide polymorphisms (SNPs) and haplotypes of the UGT1A gene with their clinical factors. For association analysis, we genotyped the variants by direct sequencing analysis and polymerase chain reaction (PCR) in 218 healthy Koreans. The frequency of UGT1A1 polymorphisms, -3279T>G, -3156G>A, -53 $(TA)_{6>7}$, 211G>A, and 686C>A, was 0.26, 0.12, 0.08, 0.15, and 0.01, respectively. The frequency of -118 $(T)_{9>10}$ of UGT1A9 was 0.62, which was significantly higher than that in Caucasians (0.39). Neither the -2152C>T nor the -275T>A polymorphism was observed in Koreans or other Asians in comparison with Caucasians. The -3156G>A and -53 $(TA)_{6>7}$ polymorphisms of UGT1A were significantly associated with platelet count and total bilirubin level (p=0.01, p=0.01, respectively). Additionally, total bilirubin level was positively correlated with occurrence of the UGT1A9-118 $(T)_{9>10}$ rare variant. Common haplotypes encompassing six UGT1A polymorphisms were significantly associated with total bilirubin level (p=0.01). Taken together, we suggest that determination of the UGT1A1 and UGT1A9 genotypes is clinically useful for predicting the efficacy and serious toxicities of particular drugs requiring glucuronidation.

Implementation of Student Teams Achievement Divisions (STAD) in a Robotic Technology Class for Pre-service High School Teachers (예비기술교사를 위한 로봇기술수업에서 성취과제분담 협동학습(STAD)의 실현)

  • Kim, Seong Jin;Kwon, Hyuksoo;Jeong, Jeongyoon
    • 대한공업교육학회지
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    • v.40 no.1
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    • pp.180-200
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    • 2015
  • The problems current robotic technology education class has are the students with different basic background knowledge levels and the class based on the instructional teaching method. This study shows the implementation of the student teams achievement divisions (STAD) learning model into an introductory robotic technology education class to resolve the problems in the current robotic technology class. The STAD learning model focuses on the ability of each team member with different knowledge levels and make team members help each other through class activities such as assignments and a project. All members get rewarded by their performance output as a team in a course grade. The outputs of STAD learning models were measured by paired sample t-test as pre-test and post-test in terms of students's transition on basic knowledge for robotic technology, students' attitudinal transition on teaching robotic technology class, and students' competencies and self-efficacy on related subject areas. The study participants were 22 pre-service technology teachers at a university. The results show that all four measured areas were improved significantly, compared to pre-test with respect to the means scores of each measurement area. The STAD learning model could be an alternate for the current robotic technology class to deliver the better class outcomes for students under the specific circumstances.

Anti-wrinkle effects of extracts and solvent fractions from Nymphoides peltata on CCD-986sk (CCD-986sk 세포내에서의 노랑어리연꽃 추출물 및 분획물의 주름개선 효과)

  • Kim, You Ah;Kim, Dong Hee;Yu, Jae Myo;Park, Chae Bin;Park, Tae soon;Park, Byoung Jun
    • Journal of Applied Biological Chemistry
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    • v.60 no.4
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    • pp.357-362
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    • 2017
  • The purpose of this study was to investigate the antiaging effect in the fibroblasts by using the extracts and fractions of Nymphoides peltata for the development of new functional cosmetic materials. The anti-aging effects of the extracts and fractions of N. peltata were measured using CCD-986sk cells. Ethyl aceate (EA) fraction inhibited UVB-induced reactive oxygen species expression by more than 50%, and n-butyl alcohol (BuOH) fraction increased expression of pro-collagen mRNA by more than 50% at $25{\mu}g/mL$. In addition, EA and BuOH fractions inhibited MMP-1 protein and mRNA expression in a concentration-dependent manner, BuOH fraction inhibited MMP-1 mRNA expression by more than 40% at $10{\mu}g/mL$. Especially, the high efficacy of EA and BuOH of the N. peltata was confirmed. Therefore, the EA and BuOH of N. peltata are expected to be useful as anti-aging materials in cosmetics field.

Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data

  • Kim, Jaewon;Rhee, Hwanseok;Kim, Jhingook;Lee, Sanghyuk
    • Genomics & Informatics
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    • v.18 no.1
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    • pp.3.1-3.8
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    • 2020
  • Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.

Reducing Fungicidal Spray Frequency for Major Apple Diseases by Increasing the Spray Interval from 15 to 25 days

  • Lee, Dong-Hyuck;Shin, Ho-Cheol;Cho, Rae-Hong;Uhm, Jae-Youl
    • The Plant Pathology Journal
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    • v.25 no.3
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    • pp.270-279
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    • 2009
  • During the course of a study to develop a spraying program at 15-day spray intervals, two important findings were identified allowing for further reduction of spray frequency by increasing the spray interval. In evaluating the contribution of fungicides from a 15-day spray interval program, control of white rot, which is of prime importance in Korea, was not affected, in spite of the extended spray interval caused by omitting the fungicides during the season. In another experiment assessing the duration of the protective activities of several key fungicides used in the 15-day spray interval program, infection control was maintained for almost 30 days for some fungicide. Based on these two findings, a basic spraying program with a 25-day spray interval was developed. This program was modified for four successive years to improve the control efficacy against bitter rot and Marssonina blotch, which sometimes causes as much damage as white rot.