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Jin, Juyoun,Joo, Kyeung Min,Lee, Se Jeong,Jo, Mi-Young,Kim, Yonghyun,Jin, Younggeon,Kim, Joong Kyu,Ahn, Ji Mi,Yoon, Mi-Jung,Lim, Jaeseung,Nam, Do-Hyun National Hellenic Research Foundation 2011 ONCOLOGY REPORTS Vol.25 No.1
<P>The presence of active immunity within the brain supports the possibility of effective immunotherapy for glioblastoma (GBM). To provide a clinically-relevant adoptive immunotherapy for GBM using ex vivo expanded cytokine-induced killer (CIK) cells, the treatment capability of CIK cells, either alone or in combination with temozolomide (TMZ) were evaluated. Human CIK (hCIK) cells were cultured from PBMC using activating anti-CD3 antibody and IL-2, which were 99% CD3+, 91% CD3+CD8+ and 29% CD3+CD56+. In vitro, hCIK cells showed tumor-specific cytotoxicity against U-87MG human GBM cells. When hCIK cells were injected into tail veins of immune-compromised mice bearing U-87MG tumors in their brains, numerous CIK cells infiltrated into the brain tumors. CIK treatments (1x10(5), 1x10(6) or 1x10(7), once a week for four weeks) inhibited the tumor growth significantly in a dose-dependent manner; 44, 54 and 72% tumor volume reduction, respectively, compared with the control group (P<0.05). Moreover, hCIK cells (1x10(7), once a week for four weeks) and TMZ (2.5 mg/kg, daily for 5 days) combination treatment further increased tumor cell apoptosis and decreased tumor cell proliferation and vessel density (P<0.05), creating a more potent therapeutic effect (95% reduction in tumor volume) compared with either hCIK cells or TMZ single therapy (72% for both, P<0.05). Taken together, CIK cell-immunotherapy and TMZ chemotherapy have synergistic therapeutic effects and could be combined for a successful treatment of GBM.</P>
Lee, Se Jeong,Kim, Yonghyun,Jo, Mi-Young,Kim, Hyeong-Seok,Jin, Younggeon,Kim, Seung U,Jin, Juyoun,Joo, Kyeung Min,Nam, Do-Hyun National Hellenic Research Foundation 2011 Oncology reports Vol.25 No.1
<P>Previous studies showed promise of coupling genetically engineered neural stem cells (NSCs) with blood-brain barrier permeable prodrugs as an effective anti-brain tumor therapy. Here, we further advance those findings by testing the suicide gene therapeutic system in syngenic glioblastoma immunocompetent mice. After intracranial injection of HB1.F3.CD, an immortalized human NSC cell line engineered to constitutively produce cytosine deaminase (CD), the prodrug 5-fluorocytosine (5-FC) was administered for five days, q.d., via intraperitoneal injection. The HB1. F3.CD hNSCs migrated specifically to the brain tumor site via the corpus callosum and significantly reduced the tumor volume (67%) by converting 5-FC into the cytotoxic 5-fluorouracil. A corresponding increase in F4/80-positive population was observed in the treatment group, although CD3-positive population remained unchanged compared to control. No toxic effects or morphological changes were observed in the spleen and the lymph nodes. The data suggest that the NSC-enzyme/prodrug treatment is an effective anti-tumor therapeutic strategy that specifically targets only the tumor site with little or no systemic side effects. In addition, the treatment modeled here successfully elicited a macrophagic immune response which seemed to have a synergistic role in reducing tumor volume, thus showing promise for treatment-mediated enhancement of inherent immune responses against brain tumors.</P>
Functional characterization of $P_{2X}/P_{2Y}$ receptor in isolated swine renal artery
Kim, Joo-heon,Jeon, Je-cheol,Lee, Sang-kil,Lee, Su-jin,Lee, Younggeon,Won, Jinyoung,Kang, Jae seon,Hong, Yonggeun The Korean Society of Veterinary Science 2007 大韓獸醫學會誌 Vol.47 No.4
To understand the role of $PM_{2X}/P_{2Y}$ receptor in cortex region of kidney and renal artery, molecular and functional analysis of $PM_{2X}/P_{2Y}$ receptor by pharmacophysiological skill in conventional swine tissues were performed. In functional analysis of $P_{2Y}$ receptor for vascular relaxation, 2-methylthio adenosine triphosphate, a strong agonist of $P_{2Y}$ receptor, induced relaxation of noradrenaline (NA)-precontracted renal artery in a dose-dependent manner. Strikingly, relaxative effect of ATP, 2-msATP, agonists of $P_{2Y}$ receptor, abolished by treatment of reactive blue 2, a putative $P_{2Y}$ receptor antagonist. In contrast, no significant differences of gene encoding $PM_{2X}/P_{2Y}$ and protein expression in immortalized suprachiasmatic nucleus from brain, primary isolated vascular smooth muscle cells from renal artery of pigs and HEK293 from human embryonic kidney under with/without adenosine triphosphate were observed. Taken together, the relationship between molecular and functional characteristic of $PM_{2X}/P_{2Y}$ receptors in conventional pig should be considered that they are another important factor which regulate the kidney function in swine. Based on this study, we propose the purinergic receptor as well as adrenergic and cholinergic receptors is an essential component of the renal homeostasis.
TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR, blocks tumor angiogenesis
Lee, Weon Sup,Pyun, Bo-Jeong,Kim, Sung-Woo,Shim, Sang Ryeol,Nam, Ju Ryoung,Yoo, Ji Young,Jin, Younggeon,Jin, Juyoun,Kwon, Young-Guen,Yun, Chae-Ok,Nam, Do-Hyun,Oh, Keunhee,Lee, Dong-Sup,Lee, Sang Hoon Taylor Francis 2015 mAbs Vol.7 No.5