• 제목/요약/키워드: induction therapy

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Efficient Induction of Th1-type Immune Responses to Hepatitis B Virus Antigens by DNA Prime-Adenovirus Boost

  • Lee, Chang-Geun;Yang, Se-Hwan;Park, Su-Hyung;Song, Man-Ki;Choi, So-Young;Sung, Young-Chul
    • IMMUNE NETWORK
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    • v.5 no.1
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    • pp.1-10
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    • 2005
  • Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

Transforming Growth Factor-$\alpha$ Increases the Yield of Functional Dopaminergic Neurons from in vitro Differentiated Human Embryonic Stem Cells Induced by Basic Fibroblast Growth Factor

  • Lee, Keum-Sil;Shin, Hyun-Ah;Cho, Hwang-Yoon;Kim, Eun-Young;Lee, Young-Jae;Wang, Kyu-Chang;Kim, Yong-Sik;Lee, Hoon-Taek;Chung, Kil-Saeng
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.102-102
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    • 2003
  • Embryonic stem (ES) cells proliferate extensively in the undifferentiated state and have the potential to differentiate into a variety of cell types in response to various environmental cues. The generation of functional dopaminergic neurons from ES cells is promising for cell replacement therapy to treat Parkinson's disease. We compared the in vitro differentiation potential of pluripotent human embryonic stem (hES, MB03) cells induced with basic fibroblast growth factor (bFGF) or retinoic acid (RA). Both types of treatment resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with brain derived neurotrophic factor (BDNF) or transforming growth factor (TGF)- $\alpha$ during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression, compared to control (P<0.05). In contrast, no effect was observed on the rate of mature or glutamic acid decarboxylase-positive neurons. Immunostaining and HPLC analyses revealed the higher levels of TH (20.3%) and dopamine in bFGF and TGF-$\alpha$ treated hES cells than in RA or BDNF treated hES cells. The results indicate that TGF-$\alpha$ may be successfully used in the bFGF induction protocol to yield higher numbers of functional dopaminergic neurons from hES cells.

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Apoptotic Effect of Co-treatment with Curcumin and Cisplatin on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line

  • Sohn, Hyeon-Jin;Kim, In-Ryoung;Kim, Yong-Ho;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.39 no.3
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    • pp.159-167
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    • 2014
  • Curcumin is a widely used flavoring agent in food, and it has been reported to inhibit cell growth, to induce apoptosis, and to have antitumor activity in many cancers. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatment with curcumin and cisplatin on human tongue SCC25 cells. To investigate whether the co-treatment efficiently reduced the viability of the SCC25 cells compared with the two treatments separately, an MTT assay was conducted. The induction and the augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining, and an analysis of DNA hypoploidy. Western blot, MMP and immunofluorescence tests were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following the co-treatment. In this study, following the co-treatment with curcumin and cisplatin, the SCC25 cells showed several forms of apoptotic manifestation, such as nuclear condensation, DNA fragmentation, reduction of MMP, increased levels of Bax, decreased levels of Bcl-2, and decreased DNA content. In addition, they showed a release of cytochrome c into the cytosol, translocation of AIF and DFF40 (CAD) to the nuclei, and activation of caspase-7, caspase-3, PARP, and DFF45 (ICAD). In contrast, separate treatments of $5{\mu}M$ of curcumin or $4{\mu}g/ml$ of cisplatin, for 24 hours, did not induce apoptosis. Therefore, our data suggest that combination therapy with curcumin and cisplatin could be considered as a novel therapeutic strategy for human oral squamous cell carcinoma.

Inhibition of Proliferation of Human Fibroblast by δ-Aminolevulinic Acid (ALA) Derivatives through the Induction of Mitochondria Membrane Depolarization (δ-Aminolevulinic acid (ALA) 유도체들의 미토콘드리아 탈분극 유도에 의한 인간 섬유아세포의 세포분열 억제)

  • Jun, Yong-woo;Han, Du-Gyeong;Lee, Jin-A;Jo, Su-Yeon;Jang, Deok-Jin
    • KSBB Journal
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    • v.30 no.6
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    • pp.313-318
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    • 2015
  • ${\delta}$-Aminolevulinic acid (ALA) is an endogenous metabolite formed in the mitochondria from succinyl-CoA and glycine, and plays a key role in the living body as an intermediate of the compound in the porphyrin biosynthesis pathway. ALA has been commonly used in photodynamic therapy for several years, because ALA is of interest as a biodegradable mediator, a growth regulator, and an effective agent used in dermatology. Here, we determined which ALA derivatives were the most effective for the inhibition of the cell proliferation and growth of human fibroblast. As a result, we found that the treatment of ALA derivatives including ALA, ALAP (ALA phosphate salt), MAL (Methyl 5-aminolevulinate hydrochloride salt), PBGL (phophobilinogen lactam) and PBGH (phophobilinogen-HCl) could attenuate cell proliferation of human fibroblast cells. Among them, PBGH was the most effective derivative. In addition, PBGH treatment could induce mitochondrial membrane depolarization, leading to cell death of human fibroblast. These results suggest that mitochondrial membrane depolarization induced by ALA and PBGH treatment might be responsible for inhibition of cell proliferation and death. Taken together, our results propose the possibility that PBGH can be used as one of the effective drugs in human skin disease, psoriasis.

Neutropenia & Nutritional status during Chemotherapeutic cycle in Acute Myeloid Leukemia (급성골수성백혈병환자의 항암화학요법 주기내의 호중구감소증과 영양상태)

  • Kim, Myung-Hee;Kang, In-Soon;Jo, Ho-Yoon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.10 no.2
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    • pp.438-446
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    • 2009
  • This study aims to investigate chemotherapy-induced neutropenia, nutritional status and both relation of patients with acute myeloid leukemia during 1st consolidation chemotherapy and the therapy-related cytopenic phase in order to determine more effective nutritional support. We review medical records of total 54 cases received first consolidation chemotherapy on P hospital in Busan. The duration of neutropenia(Absolute Neutrophil Count<$1000/{\mu}{\ell}$) is mean 14.78 days, neutropenia occur on mean 10th(9.54) day of chemotherapy(D10). The nutritional parameters of total protein, body weight, BMI showed no significant interval change during chemotherapeutic cycle except albumin, cholesterol. The neutropenia wasn't dependent on general factor of gender, age, comorbidities, Body Surface Area(BSA). The correlation wasn't revealed between neutropenia and nutritional status. In conclusion, although nutritional status didn't affect neutropenia, this study provides detailed information on the neutropenic response of acute myeloid leukemia patients during induction chemotherapy.

Apoptotic Potential and Chemical Composition of Jordanian Propolis Extract against Different Cancer Cell Lines

  • Abutaha, Nael
    • Journal of Microbiology and Biotechnology
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    • v.30 no.6
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    • pp.893-902
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    • 2020
  • Propolis is a resinous substance that is collected by Apis mellifera from plant sources and is used in traditional medicine. To study the phytochemical constituents and apoptotic potential of Jordanian propolis extract against different cancer cell lines, propolis was extracted using methanol, hexane, and ethyl acetate and was fractionated using chromatographic methods. Cytotoxicity was assessed using MTT and LDH assays. The apoptotic potential was investigated using florescence microscopy, multicaspase assay, Annexin-V and dead cell assay, and cell cycle assay. The phytochemical constituents were analyzed using GC-MS. The methanol extract of propolis exhibited cytotoxic potential against all cell lines tested. The IC50 values of the methanol extract were 47.4, 77.8, 91.2, and 145.0 ㎍/ml for HepG2, LoVo, MDAMB231, and MCF7 cell lines, respectively. The IC50 values of the F1 fraction were 31.6 (MDAMB231), 38.9 (HepG2), 36.7 (LoVo) and 75.5 (MCF7) ㎍/ml. On further purification using thin-layer chromatography, the IC50 values of the F1-3 fraction were found to be 84.31(HepG2), 79.2 (MCF7), 70.4 (LoVo), and 68.9 (MDAMB231) ㎍/ml, respectively. The anticancer potential of the F1 fraction was confirmed through the induction of apoptosis and cell cycle arrest at the G0/G1 phase. The GC-MS analysis of the F1 fraction revealed the presence of 3-methyl-4-isopropylphenol (29.44%) as a major constituent. These findings indicate the potential of propolis extract as a cancer therapy. However, further investigation is required to assess the acute and subacute toxicity of the most active fraction.

Comparison of Ondansetron with Ondansetron and Dexamethasone in Preventing of PONV in Major Gynecologic Surgery (부인과 수술 후 Ondansetron과 병용한 Dexamethasone의 오심, 구토 예방과 제통 효과의 비교)

  • Lee, Kee-Heung;Shin, Hyo-Sang;Jeon, Young-Hoon;Kim, Si-Oh;Hong, Jung-Gil
    • The Korean Journal of Pain
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    • v.14 no.1
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    • pp.76-82
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    • 2001
  • Background: Postoperative nausea and vomiting (PONV) are common after general anesthesia and patient controlled analgesia (PCA) using opioids. This study was designed to compare the effectiveness of ondansetron plus dexamethasone versus ondansetron alone in the prevention of PONV in a patient undergoing a PCA. Methods: We studied 166 ASA I, and II in-patients undergoing general anaesthesia for major gynecological surgery. After induction of anesthesia, Group 1 (n = 64) received intravenous (IV) dexamethasone 10 mg and Group 2 (n = 102) received IV saline 2 ml before the surgical incision. Each patient received IV meperidine 50 mg as a loading dose. Meperidine 5 mg/kg, ketorolac 3.6 mg/kg and ondansetron 8 mg diluted in 40 ml solutions were connected to PCA pump for postoperative pain control. Mean arterial blood pressure, heart rate, pain score and symptom-therapy score were checked at 1, 4, 8, 16, 24, and 36 hours after the PCA connection. Results: For Group 1 and Group 2, respectively, the overall incidence of PONV was 12.5% and 23.5%. The pain scores were lower in patients receiving a combination of ondansetron and dexamethasone than those on ondansetron alone at 4 hr (P < 0.05), 8 hr (P < 0.05) and 16 hr (P < 0.05). Conclusions: This study suggests that the combination of ondansetron and dexamethasone is not more effective than ondansetron alone in the prevention of postoperative nausea and vomiting in women having PCA following major gynecological surgery but is more effective for pain control.

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Effect of Parthenogenetic Mouse Embryonic Stem Cell (PmES) in the Mouse Model of Huntington′s Disease

  • 이창현;김용식;이영재;김은영;길광수;정길생;박세필;임진호
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.80-80
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    • 2003
  • Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by marked cell death in the striatum and cortex. Stereotaxic injection of quinolinic acid (QA) into striatum results in a degeneration of GABAergic neurons and exhibits abnormal motor behaviors typical of the illness. The objective of this study was carried out to obtain basic information about whether parthenogenetic mouse embryonic stem (PmES) cells are suitable for cell replacement therapy of HD. To establish PmES cell lines, hybrid F1 (C57BL/6xCBA/N) mouse oocytes were treated with 7% ethanol for 5 min and cytochalasin-B for 4 hr to initiate spontaneous cleavage. Thus established PmES cells were induced to differentiate using bFGF (20ng/ml) followed by selection of neuronal precursor cells for 8 days in N2 medium. After selection, cells were expanded at the presence of bFGF (20 ng/ml) for another 6 days, then a final differentiation step in N2 medium for 7 days. To establish recipient animal models of HD, young adult mice (7 weeks age ICR mice) were lesioned unilaterally with a stereotaxic injection of QA (60 nM) into the striatum and the rotational behavior of the animals was tested using apomorphine (0.1mg/kg, IP) 7 days after the induction of lesion. Animals rotating more than 120 turns per hour were selected and the differentiated PmES cells (1$\times$10$^4$cells/ul) were implanted into striatum. Four weeks after the graft, immunohistochemical studies revealed the presence of cells reactive to anti-NeuN antibody. However, only a slight improvement of motor behavior was observed. By Nissl staining, cell mass resembling tumor was found at the graft site and near cortex which may explain the slight behavioral improvement. Detailed experiment on cell viability, differentiation and migration explanted in vivo is currently being studied.

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Histological Changes of the Acupoint by Acupuncture Stimulation (침자(鍼刺)한 경혈(經穴) 부위(部位)의 조직학적 변화(組織學的 變化))

  • Kim, Jeong-Sang;Park, Min-Hee;Cho, Kwang-Phil;Jung, Hae-Man
    • Applied Microscopy
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    • v.30 no.1
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    • pp.81-87
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    • 2000
  • This study has been carried out to understand histochemical and ultrastructural changes by acupuncture stimulation at the acupoint of the Zusanli (St. 36) in the rat. A lot of mast cells are observed in the peripheral of the hole with a sparrow-pecking and twistin -needle manipulation to the acupoint Zusanli for induction of 'Qi'. These cells contained a lot of granules with varied electron density and exocytosis granules were observed near the mast cell. H-bands of the muscle fiber that situated near the hole were shortened. It is assumed that these muscles are contracted by acupuncture stimulation. These results imply that functional relationship between mast cells in the dermis and Qi-sensation induced by acupuncture plays an important role on the specific receptor response to the mechanical stimulation.

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The Effect of a Cooperative System of Oriental and Western Medicine in the Treatment of Allergic Rhinitis

  • Jeong, Su-Hyeon;Kim, Sung-Wan;Jeong, Soo-Jin;Lee, Won-Chul
    • The Journal of Korean Medicine
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    • v.24 no.4
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    • pp.64-70
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    • 2003
  • Background and Purpose : Allergic rhinitis is a well-known, relatively controllable chronic disease. Although a number of methods for treating allergic rhinitis have been tried, many patients have not been satisfied with their treatment. Therefore, this study tried to evaluate the effect of a cooperative system of Oriental and Western medicine and to develop a new diagnosis protocol for treatment of allergic rhinitis. Methods : We measured improvement rate and acoustic rhinometry after the allergeninduction test and performed a filter paper test as a nonspecific hypersensitivity test with 60 patients who are allergic to house dust mite. Patients were divided into two groups, one treated with Western medicine only and one treated with both Western and Oriental herbal medicine. For the group with Western medicine only, antihistamine for one week and local steroid medicine for two weeks were prescribed. For the group with combined medicine, Oriental herbal medicine was prescribed according to the patient s constitution, along with Western medicine. After all treatments, the above tests were re-performed and the improvement rate was compared. Results and Conclusion : We observed better results in the group treated with both Western and Oriental herbal medicines, comparing improvement rate and the alteration of total nasal volume through acoustic rhinometry after the allergen induction test. In the filter paper test, there was no significant difference between the two groups. In conclusion, we showed the additive effect of Oriental herbal medicine without any severe side effects compared with treatment with Western medicine only. In this study, we set only two patient groups, but further study is required to create various experimental groups and compare among them. We suggest that it might enhance understanding of the improved effect of Oriental herbal medicine in the therapy of allergic rhinitis.

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