• IMMUNE NETWORK
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• v.9 no.5
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• pp.158-168
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• 2009

Tumor therapy using cytokines has been developed for last two decades. Several recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer have been in clinical trials, but several side effects hamper routine clinical applications. Many cytokines are originally expressed as membrane-bound form and then processed to secretory form exerting paracrine effects. Though functional differences of these two types of cytokines are elusive yet, the membrane-bound form of cytokine may exert its effects on restricted target cells as a juxtacrine, which are in physical contacts. With the efforts to improve antitumor activities of cytokines in cancer patients, developing new strategies to alleviate life-threatening side effects became an inevitable goal of tumor immunologists. Among these, tumor cell vaccines expressing cytokines as membrane-bound form on tumor cell surface have been developed by genetic engineering techniques with the hope of selective stimulation of the target cells that are in cell-to-cell contacts. In this review, recent progress of tumor cell vaccines expressing membrane-bound form of cytokines will be discussed.

• Nuclear Engineering and Technology
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• v.38 no.4
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• pp.327-342
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• 2006

Radiation therapy is an important part of cancer treatment in which cancer patients are treated using high-energy radiation such as x-rays, gamma rays, electrons, protons, and neutrons. Currently, about half of all cancer patients receive radiation treatment during their whole cancer care process. The goal of radiation therapy is to deliver the necessary radiation dose to cancer cells while minimizing dose to surrounding normal tissues. Success of radiation therapy highly relies on how accurately 1) identifies the target and 2) aim radiation beam to the target. Both tasks are strongly dependent of imaging technology and many imaging modalities have been applied for radiation therapy such as CT (Computed Tomography), MRI (Magnetic Resonant Image), and PET (Positron Emission Tomogaphy). Recently, many researchers have given significant amount of effort to develop and improve imaging techniques for radiation therapy to enhance the overall quality of patient care. For example, advances in medical imaging technology have initiated the development of the state of the art radiation therapy techniques such as intensity modulated radiation therapy (IMRT), gated radiation therapy, tomotherapy, and image guided radiation therapy (IGRT). Capability of determining the local tumor volume and location of the tumor has been significantly improved by applying single or multi-modality imaging fur static or dynamic target. The use of multi-modality imaging provides a more reliable tumor volume, eventually leading to a better definitive local control. Image registration technique is essential to fuse two different image modalities and has been In significant improvement. Imaging equipments and their common applications that are in active use and/or under development in radiation therapy are reviewed.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.61-64
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• 2002

As intensity modulated radiation therapy compared with conventional radiation therapy, tumor target dose increased and normal tissues and critical organs dose reduced. In brain tumor, treatment planning of intensity modulated radiation therapy was practiced in 4MV, 6MV, 15MV X-ray energy. In these X-ray energy, was considered the dose distribution and dose volume histogram. As 4MV X-ray compared with 6MV and 15MV, maximum dose of right optic-nerve increased 10.1 %, 8.4%. Right eye increased 5.2%, 2.7%. And left optic-nerve, left eye, optic chiasm and brainstem incrased 1.7% - 5.2%. Even though maximum dose of PTV and these critical organs show different from 1.7% - 10.1% according to X-ray energies, these are a piont dose. Therefore in brain tumor, treatment planning of intensity modulated radiation therapy in 9 treatment field showed no relation with energy dependency.

• The Journal of Korean Society for Radiation Therapy
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• v.17 no.2
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• pp.95-103
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• 2005

Purpose : In the radiosurgery, to obtain CT image to find more accurate tumor position during respiration, and using them, to increase the accuracy of radiation treatment by applying image guided. Materials and Methods : Using the self-made vacuum cushion for the body SRS, CT images were obtained three for each patient during respiration (shallow, inhalation, exhalation). They were transformed to the RTP computer and then were fused. Global GTVs were delineated on the fused images and more appropriated treatment planning was established. Results : We can find the tumor position is moving toward cranio-caudal with max 10 mm margin and volume is transformed. As a result from the comparision of DVH (pre & post radio surgery), we observed about 100% dose to tumor. Conclusion : BSRS was skeptical due to the tumor movement during respiration. More accurate by the combination of the development of immobilization devices and BSRS based on Image Guide, it will be applied to more cases for BSRS.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.1
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• pp.8-17
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• 2009

Purpose: We determined the therapeutic effect of an epidermal growth factor receptor (EGFR)-specific monoclonal antibody (mAb), cetuximab (Erbitux) on the growth of oral squamous cell carcinoma (OSCC) xenografted in athymic nude mice. Experimental Design: We induced subcutaneous tumors by inoculating human tumor cell suspension into the right flank of nude mice. Nude mice with subcutaneous tumors were randomized to receive cetuximab alone, paclitaxel alone, cetuximab plus paclitaxel, or a placebo (control). Antitumor mechanisms of cetuximab were determined by immunohistochemical and apoptosis assays. Results: Cetuximab, paclitaxel, and cetuximab/paclitaxel combined therapy resulted in 50%, 52%, 67% in vivo inhibition of tumor proliferation, respectively. Tumors of mice treated with cetuximab plus paclitaxel demonstrated decreased PCNA-positive tumor cells and increased apoptotic tumor cells, which slowed growth of the murine tumors. Conclusion: These data show that EGFR can be a molecular target for the treatment of OSCC. And combination therapy with cetuximab and paclitaxel warrants further clinical study.

• Progress in Medical Physics
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• v.28 no.4
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• pp.164-170
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• 2017

One of the methods to consider the effect of respiratory motion of a tumor target in radiotherapy is to establish a treatment plan with the internal target volume (ITV) created based on an accurate analysis of the target motion displacement. When this method is applied to intensity modulated radiotherapy (IMRT), it is expected to yield a different treatment dose distribution under the motion condition according to the IMRT method. In this study, we prepared ITV-based IMRT plans with conventional IMRT using fixed gantry angle beams, RapidArc using volumetric modulated arc therapy, and tomotherapy using helical therapy. Then, the variation in dose distribution caused by the target motion was analyzed by the dose measurement in the actual motion condition. A delivery quality assurance plan was prepared for the established IMRT plan and the dose distribution in the actual motion condition was measured and analyzed using a two-dimensional diode detector placed on a moving phantom capable of simulating breathing movements. The dose measurement was performed considering only a uniform target shape and motion in the superior-inferior (SI) direction. In this condition, it was confirmed that the error of the dose distribution due to the target motion is minimum in tomotherapy. This is thought to be due to the characteristic of tomotherapy that treats the target sequentially by dividing it into several slices. When the target shape is uniform and the main target motion direction is SI, it is considered that tomotherapy for the ITV-based IMRT method has a characteristic which can reduce the dose difference compared with the plan dose under the target motion condition.

• Journal of Radiation Industry
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• v.9 no.4
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• pp.193-198
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• 2015

Most of targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells to produce its cytotoxic effect. Either small molecule drugs or monoclonal antibodies are mostly used in targeted therapies. Unfortunately, targeted therapy has a certain degree of unwanted side effect like other cytotoxicity inducing chemotherapies. To overcome and to reduce unwanted side effects during a cancer therapy, recently radiopeptide therapies has got the worlds' attraction for the tumor targeting modalities due to its beneficial effect on less side effect compared to cytotoxic chemotherapies. Among radiopeptide therapies, $^{177}Lu$-DOTATATE is a major modality as an effective one invented so far in treating neuroendocrine tumor (NET) and it has been in clinical trials at least one decade. Although it does have rather effective therapeutic effect on NET, it has less effective in rather large solid tumor. There are many ways to improve or increase therapeutic effect of radiopeptide are a finding the potent small molecules to target the tumor site selectively, or a labeling with radioisotope of emitting high energy, or an improving its biological half-life by introducing different moieties to increase lipophilicity. Present study was focus to increase a biological half-life of radio somatostatin which will target the somatostatin receptor by altering the bifunctional chelator (BFCA) by introducing lipophilic moiety to the somatostatin, which would make the labeled peptide stay longer in the tumor site and thus it can intensify the therapeutic effect on tumor cell itself and around tissues.

• BMB Reports
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• v.52 no.7
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• pp.415-423
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• 2019

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2173-2179
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• 2013

Ubiquitin carboxyl-terminal hydrolase 37 (UCH37, also called UCHL5), a member of the deubiquitinating enzymes, can suppress protein degradation through disassembling polyubiquitin from the distal subunit of the chain. It has been proved that UCH37 can be activated by proteasome ubiqutin chain receptor Rpn13 and incorporation into the 19S complex. UCH37, which has been reported to assist in the mental development of mice, may play an important role in oncogenesis, tumor invasion and migration. Further studies will allow a better understanding of roles in cell physiology and pathology, embryonic development and tumor formation, hopefully providing support for the idea that UCH37 may constitute a new interesting target for the development of anticancer drugs.

• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.493-509
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• 2015

Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris$^{(R)}$(anti-CD30-drug conjugate) and Kadcyla$^{(R)}$(anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.