• IMMUNE NETWORK
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• 제22권1호
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• pp.2.1-2.22
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• 2022

Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.

• 대한소아치과학회지
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• 제42권1호
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• pp.10-21
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• 2015

본 연구의 목적은 Streptococcus mutans의 Ag I/II와 glucosyltransferase에 대해 개발된 단일클론항체를 사용한 타액 내 Streptococcus mutans 검출의 효용성을 평가하기 위함이다. 세 군(성인, 미성년자, 그리고 교정치료중인 미성년자)을 대상으로 DMFT, $Dentocult^{(R)}$-SM strip mutans를 이용한 타액내의 colony density (CFU/mL), polymerase chain reaction을 이용한 Sreptococcus mutans와 Sreptococcus sobrinus의 존재여부, 그리고 4가지 단일클론항체를 사용한 타액 내 Streptococcus mutans 검출 실험을 시행하였다. 그 결과 Streptococcus mutans가 Streptococcus sobrinus보다 치아우식 형성에 더 주요하게 작용한다는 것을 입증하였으며, glucosyltransferases (gtf B, gtf C, gtf D)와 Ag I/II에 대한 단일클론항체들의 Streptococcus mutans를 검출해 내는 능력이 $Dentocult^{(R)}$-SM strip mutans나 polymerase chain reaction을 사용한 검출법보다 뛰어남을 보였다.

• 생명과학회지
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• 제15권4호
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• pp.600-606
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• 2005

신경미세섬유(neurofilament, NF) 단백질은 신경세포의 주된 중간세사로서, NF-L (61 kDa), NF-M (90 kDa) 및 NF-H (115 kDa) 단백질의 공동중합체로 구성된다. 신경세사섬유는 신경세포의 성장, 구성, 형태 및 가소성에 중요한 역할을 하지만 발생학적 표현에 대하여는 아직 잘 알려지지 않았다. 본 연구에서는 NF-M에 특이한 항체를 제조하여 배양한 대뇌신경세포에서 NF-M의 표현을 조사하였다. 배양 12 및 24시간 세포에서 NF-M은 축삭과 그 성장추 그리고 축삭에 가까운 세포체에 강하게 표현하였다. 배양 4 및 14일 신경세포를 NF-M과 PSD95 항체로 이중염색한 결과 NF-M은 축삭과 가지돌기에 공히 강하게 표현되었으며, PSD95와 같이 위치할 경우에는 점박이로 나타났다. .면역염색에서도 NF-M이 PSD 분획에서 검출되었는데, 따라서 이 점박이는 가지돌기가시임을 시사한다. 본 연구의 결과는 NF-M이 신경세포의 초기 형태발달과정에서 축삭으로 강하게 몰려가며, 성숙한 신경세포에서는 가지돌기 및 가지돌기가시에도 위치하여 특정기능을 수행함을 시사한다.

• 한국방사선학회논문지
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• 제8권3호
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• pp.123-136
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• 2014

본 논문에서는 분자영상을 분류하고 적용 분야와 미래를 예측해 보고자 하였다. 분자영상은 생체 내에서 분자수준과 세포수준에서 일어나는 변화를 영상화하는 것으로써 분자세포생물학과 첨단영상기술이 발전하여 접목된 새로운 분야이다. 분자영상은 형광, 생물발광, SPECT, PET, MRI, Ultrasound 등의 영상 기법들을 이용하여 유전자 치료 모니터링, 세포추적, 세포 치료 모니터링, 항체영상, 약제 개발, 분자 상호작용 영상, 근적외선 형광 물질을 이용한 암 형광 영상, Bacteria 를 이용한 종양 표적 영상, 치료효과 조기 평가, 치료 효과 예측 등에 적용되고 있다. 분자 영상의 미래는 분자세포 생물학, 유전학, 화학, 약학, 물리학, 전산학, 의공학, 핵의학, 영상의학, 임상의학 등 여러 학문 분야가 융합되어 상호협조와 공동연구를 통하여 발전해 나갈 것이다. 분자영상의 태동으로 미래의 의료의 모습은 질병의 조기진단과 개인 맞춤형 치료가 가능하게 될 것이다.

• The Plant Pathology Journal
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• 제34권5호
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• pp.426-434
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• 2018

During the spring season of 2014, a total of 148 melon and watermelon leaf samples were collected from symptomatic and asymptomatic plants in the western and southwestern regions of Saudi Arabia and were tested for the presence of Watermelon chlorotic stunt virus (WmCSV) and other suspected cucurbit viruses by double antibody sandwich enzyme-linked immunosorbent assays. Ninety-eight samples were found to be positive for the presence of WmCSV, nine samples were positive for the presence of Cucurbit yellow stunting disorder virus (CYSDV), and 22 showed a mixed infection with both WmCSV and CYSDV. No other cucurbit viruses were detected in any of the samples. Host range experiments revealed that eight out of fourteen tested plant species were susceptible to WmCSV. PCR products of approximately 1.2 kb were obtained after amplification using primers specifically targeting the coat protein region of WmCSV. Positive PCR results were confirmed by dot blot hybridization. Coat protein gene sequences from eleven WmCSV isolates indicated that the highest identity was between the 104WMA-SA isolate from the Wadi Baish location and a previously reported isolate from the AL-Lith location in Saudi Arabia. The lowest identity was observed between the 42WMA-SA isolate and an isolate from Palestine.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7441-7447
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• 2015

Objective: This study evaluated the safety and objective response of combining $^{131}I$-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). Results: The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were $3.19{\pm}1.01Gy$ and $0.55{\pm}0.22Gy$, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved ($6.82{\pm}1.28$ vs. $4.7{\pm}1.14months$, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). Conclusions: Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.

• BMB Reports
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• 제44권11호
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• pp.758-763
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• 2011

Immunostimulatory CpG-DNA targeting TLR9 is one of the most extensively evaluated vaccine adjuvants. Previously, we found that a particular form of natural phosphodiester bond CpG-DNA (PO-ODN) encapsulated in a phosphatidyl-${\beta}$-oleoyl-${\gamma}$-palmitoyl ethanolamine (DOPE) : cholesterol hemisuccinate (CHEMS) (1 : 1 ratio) complex (Lipoplex(O)) is a potent adjuvant. Complexes containing peptide and Lipoplex(O) are extremely useful for B cell epitope screening and antibody production without carriers. Here, we showed that IL-12 production was increased in bone marrow derived dendritic cells in a CpG sequence-dependent manner when PO-ODN was encapsulated in Lipoplex(O), DOTAP or lipofectamine. However, the effects of Lipoplex(O) surpassed those of PO-ODN encapsulated in DOTAP or lipofectamine and also other various forms of liposome-encapsulated CpG-DNA in terms of potency for protein antigen-specific IgG production and Th1- associated IgG2a production. Therefore, Lipoplex(O) may have a unique potent immunoadjuvant activity which can be useful for various applications involving protein antigens as well as peptides.

• Journal of Microbiology and Biotechnology
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• 제29권3호
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• pp.489-499
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• 2019

Subunit vaccines are safer and more stable than live vaccines although they have the disadvantage of eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanospheres (OCNs) were used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease. TB is among the deadliest infectious diseases worldwide and an effective vaccine is urgently needed. The ability of OCNs to deliver recombinant Mycobacterium tuberculosis (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) was investigated. For immunization, OCNs were mixed with the two TB antigens as well as the adjuvant monophosphoryl lipid A (MPL). The protective efficacy was analyzed in vaccinated mice by aerosol Mtb challenge with a virulent strain of Mtb and the bacterial burdens were measured. The results showed that OCNs are highly effective in delivering Mtb proteins into the cytosol of BMDMs and BMDCs. Upon immunization, this vaccine formula induced robust Th1 immune response characterized by cytokine profiles from restimulated splenocytes and specific antibody titer. More importantly, enhanced cytotoxic $CD8^+$ T cell activation was observed. However, it did not reduce the bacteria burden in the lung and spleen from the aerosol Mtb challenge. Taken together, OCNs are highly effective in delivering subunit protein vaccine and induce robust Th1 and $CD8^+$ T cell response. This vaccine delivery system is suitable for application in settings where cell-mediated immune response is needed.

• The Plant Pathology Journal
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• 제35권3호
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• pp.243-256
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• 2019

Field surveys for Plum pox virus (PPV) infection were conducted in stone fruit orchards all over Bulgaria. In total, 1168 out of 3020 leaf samples from cultivated Prunus spp. and wildly growing P. cerasifera trees reacted positive for PPV in DASI-ELISA with the universal monoclonal antibody (MAb) 5B. Further ELISA analyses showed that 987 and 127 isolates belonged to PPV-M and PPV-D serotypes, respectively. The plum and P. cerasifera showed 82.0% and 50.5% levels of infection, respectively followed by the peach (40.0%) and the apricot (32.0%). Five hundred fifty one PPV isolates were further typed by IC-RT-PCR with PPV-Rec, -M and -D-specific primers, targeting (Cter)NIb-(Nter) CP genome region, as 125 isolates were sequenced. The results revealed the presence of PPV-Rec, PPV-M and PPV-D and mixed infections of these strains. PPV-Rec was the most prevalent strain (49.0%), followed by PPV-M (40.1%), while PPV-D was the less spread strain (8.2%). PPV-Rec was the most common strain in plums, including the eight "old-aged" trees from the region of the first Sharka discovery. PPV-M was the most prevalent strain in peach and apricot. Phylogenetic analyses on (Cter)NIb-(Nter)CP of the isolates were performed. PPV-Rec isolates formed a homogeneous group, while PPV-M isolates split into PPV-Ma and PPV-Mb subgroups. Five separated clades were formed by the analyzed PPV-D isolates. Nucleotide sequences of the partial CP coding region of the analyzed isolates revealed a slightly higher intra-strain genetic variability in PPV-Rec and PPV-M isolates, while that of PPV-D strain isolates was higher from the reported for these strains.

• 생체재료학회지
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• 제22권4호
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• pp.303-310
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• 2018

Background: Photodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens and induces tumour regressions. Several photodynamic treatments have been extensively studied and the photosensitizers (PS) are key to their biological efficacy, while laser and oxygen allow to appropriate and flexible delivery for treatment of diseases. Introduction: In presence of oxygen and the specific light triggering, PS is activated from its ground state into an excited singlet state, generates reactive oxygen species (ROS) and induces apoptosis of cancer tissues. Those PS can be divided by its specific efficiency of ROS generation, absorption wavelength and chemical structure. Main body: Up to dates, several PS were approved for clinical applications or under clinical trials. $Photofrin^{(R)}$ is the first clinically approved photosensitizer for the treatment of cancer. The second generation of PS, Porfimer sodium ($Photofrin^{(R)}$), Temoporfin ($Foscan^{(R)}$), Motexafin lutetium, Palladium bacteriopheophorbide, $Purlytin^{(R)}$, Verteporfin ($Visudyne{(R)}$), Talaporfin ($Laserphyrin^{(R)}$) are clinically approved or under-clinical trials. Now, third generation of PS, which can dramatically improve cancer-targeting efficiency by chemical modification, nano-delivery system or antibody conjugation, are extensively studied for clinical development. Conclusion: Here, we discuss up-to-date information on FDA-approved photodynamic agents, the clinical benefits of these agents. However, PDT is still dearth for the treatment of diseases in specifically deep tissue cancer. Next generation PS will be addressed in the future for PDT. We also provide clinical unmet need for the design of new photosensitizers.