• IMMUNE NETWORK
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• 제9권5호
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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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• 제38권4호
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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.

• 한국의학물리학회:학술대회논문집
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• 한국의학물리학회 2002년도 Proceedings
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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.

• 대한방사선치료학회지
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• 제17권2호
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• pp.95-103
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• 2005

목 적 : 정위적 방사선수술 시 환자의 set up을 정확히 하며 정확한 종양의 위치를 찾아내어 확인하고 평가하는 것은 치료성적을 좌우하는데 매우 중요한 일이다. 특히 체부에 종양이 있는 환자의 경우 호흡 등에 의한 종양의 움직임으로 인하여 정확한 종양위치에 치료를 시행하는데는 많은 어려움이 따르는데 이러한 문제점들을 보완하기 위하여 본원에서 자체 제작한 고정용구를 이용하여 환자의 움직임을 최소화시키고 또한 환자의 호흡에 따른 CT 영상을 획득하였으며 이를 통하여 Image Guided Radiosurgery를 시행함으로써 방사선수술의 정확성을 높이고자 한다. 대상 및 방법 : 본원에서 자체 개발한 Body SRS용 Vacuum cushion (BSRS Vacuum cushion)을 이용하여 환자의 호흡에 따른 CT영상을 세 번에 걸쳐 획득한 후 (shallow, inhalation, exhalation) RTP computer상에서 이들을 fusion하며 Global GTV (PTVsim target)를 찾아내어 가장 적합한 수술계획을 수립한다. 수술 전 위와 같은 방법으로 Global GTV (PTVtx target)를 찾아내어 Posterior Pb ball을 기준으로 처음 수립된 수술계획의 PTVsim target에 PTVtx target을 조합시켜 비교함으로써 환자의 New PTVcenter를 찾아내고 수술을 시행한 후 EPID 영상을 획득하며 환자의 움직임 여부와 정확한 방사선수술이 시행되었는지 확인한다. 결 과 : 환자의 호흡에 따른 target volume의 위치는 Inhalation에서 cranio-caudal 방향으로 최대 10 mm까지 변화되었으며 체적은 Shallow respiration 일 때 $0.93cm^3$로 가장 크게 변화되는 것을 확인할 수 있었다. 수술 전후의 CT 영상을 통하여 New PTVcenter target volume의 위치에 따른 치료 정확성을 DVH로 분석한 결과 100% 전후의 치료 선량이 조사되는 것을 확인할 수 있었다. 결 론 : 체부의 SRS는 환자의 호흡에 따른 종양의 움직임 때문에 환자의 적용에는 회의적인 입장이었으나 고정기구 개발과 IGRT를 접목함으로써 보다 정확한 방사선수술을 시행할 수 있었고 이를 통하여 많은 BSRS에 적용할 수 있을 것으로 사료된다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제31권1호
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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.

• 한국의학물리학회지:의학물리
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• 제28권4호
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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.

• 방사선산업학회지
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• 제9권4호
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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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• 제52권7호
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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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• 제14권4호
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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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• 제23권6호
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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.