• The Korean Journal of Nuclear Medicine
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• v.22 no.1
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• pp.83-92
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• 1988

The cocktails of two $^{131}I$ labeled Monoclonal antibody (MCAB) (Anti CA 19-9 F$(ab')_2$ + Anti CEA $F(ab')_2$ fragment), which react specially, with human gastrointestinal cancers, were administered to 10 patients with colorectal (7), stomach(2) and pancreas(1) cancer for scintigraphic detection. All patients were known or postoperatively recurrent cases, and serum tumor markers, CA 19-9 and CEA, were measured with immunoradiometric assay, just before immunoscintigraphy (ISG). The tumor marker's level in serum is not correlated with positive tumor uptake in ISG. The sensitivity and specificity of ISG in detection of 21 tumor sites, based on surgery, CT, ultrasonography and pathology, were 90.5% and 100% One case of colon cancer showed gall bladder metastasis, which was neglected on CT study. Tumor/non tumor uptake ratio of radiolabelled antibody were progressively increased from day 3 to day 7 during study. We summerized as follows 1) The use of cocktails of CEA and CA 19-9 MCAB $F(at')_2$ increased sensitivity and specificity in ISG. 2) Delayed imaging (later than 5 days) increases sensitivitv and specificity due to exclusion of nonspecific iodine accumulation in stomach and lung. 3) Second tracer technique is essential for anatomical landmark by use of a double isotope scan, but subtraction technique, a possible source of artifacts, is no longer necessory when delayed imaging is performed. 4) It may be possible to use two MCAB cocktails of CA 19-9 and CEA in Radioimmunodetection of stomach and pancreas cancer. In conclusion, ISG using MCAB cocktails, $F(ab')_2$ fragment of anti CA 19-9 and Anti CEA, provide additional opportunity for tumor localization and detection of colorectal and other G-I cancer, such as stomach and pancreas.

• Genomics & Informatics
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• v.3 no.4
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• pp.172-174
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• 2005

Recent anti-cancer approaches have been based to target tumor-specifically associated and/or causative molecules such as RNAs or proteins. As this specifically targeted anti-cancer modulator, we have previously described a novel human cancer gene therapeutic agent that is Tetrahymena group I intron-based trans-splicing ribozyme which can reprogram and replace human telomerase reverse transcriptase (hTERT) RNA to selectively induce tumor-specific cytotoxicity in cancer cells expressing the target RNA. Moreover, the specific ribozyme has been shown to efficiently retard tumor tissues in xenograft mice which had been inoculated with hTERT-expressing human cancer cells. In this study, we assessed specificity of trans-splicing reaction in cells to evaluate the therapeutic feasibility of the specific ribozyme. In order to analyze the trans-spliced products by the specific ribozyme in hTERT-positive cells, RT, 5'-end RACE-PCR, and sequencing reactions of the spliced RNAs were employed. Then, whole analyzed products resulted from reactions only with the hTERT RNA. This study suggested that the developed ribozyme perform highly specific RNA replacement of the target RNA in cells, hence trans-splicing ribozyme will be one of specific agents for genetic approach to revert cancer.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.4
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• pp.243-247
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• 2012

Recent studies suggest that immunization with autologous dendritic cells (DCs) results in protective immunity and rejection of established tumors in various human malignancies. The purpose of this study is to determine whether DCs are generated from peripheral blood mononuclear cells (PBMNs) by using cytokines such as F1t-3 ligand (FL), granulocyte macrophage-colony stimulating factor (GM-CSF), IL-4, and TNF-${\alpha}$, and whether cytotoxic T cells activated against the thyroid cancer tissues by the DCs. Peripheral blood was obtained from 2 patients with thyroid cancer. DCs were established from PBMNs by culturing in the presence of FL, GM-CSF, IL-4, and TNF-${\alpha}$ for 14 days. At day 14, the differentiated DCs was analyzed morphologically. The immunophenotypic features of DCs such as CDla, CD83, and CD86 were analyzed by immunofluorelescence microscopy. At day 18, DCs and T cells were incubated with thyroid cancer tissues or normal thyroid tissues for additional 4 days, respectively. DCs generated from the PBMNs showed the typical morphology of DCs. Activated cytotoxic T lymphocytes (CTLs) were observed also. DCs and the CTLs were attached to the cancer tissues on scanning electron microscope. The DCs activated the CTLs, which able to specifically attack the thyroid cancer. This study provides morphologic evidence that the coculture of T cells/cancer tissues activated the T cells and differentiated CTLs. The CTLs tightly adhered to cancer tissues and lysed cancer tissues vigorously. Therefore DCs could be used as potential vaccines in the immunotherapy.

• The Korean Journal of Nuclear Medicine
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• v.36 no.1
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• pp.64-73
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• 2002

FDG-PET has potential as an effective, non-invasive tool to measure tumor response to anticancer therapy. The changes in tumor FDG uptake may provide an early, sensitive guide to the clinical and subclinical response of tumors to cancer treatment, as well as functional assessment of residual viable tumor. This may allow the evaluation of subclinical response to anticancer drugs in early clinical trials and improvements in patients management. However, monitoring tumor responses with FDG-PET is still in its infancy. The methods of measurement of FDG uptake are currently diverse and timing with respect to anti cancer therapy variable. Therefore, there is a need for larger-scale trials along with standardized methodology and a collection of reproducibility data. The recent guideline from the European group seems to be the most comprehensive. In future, the combination of morphological and metabolic images may improve the quantitative nature of these measurements by relating tumor viability to total tumor mass. More data on sensitivity and specificity of FDG-PET technique are needed along with continued advancement of PET methodology.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.424-431
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• 2024

Among the therapeutic strategies in cancer immunotherapy-such as immune-modulating antibodies, cancer vaccines, or adoptive T cell transfer-T cells have been an attractive target due to their cytotoxicity toward tumor cells and the tumor antigen-specific binding of their receptors. Leveraging the unique properties of T cells, chimeric antigen receptor-T cells and T cell receptor (TCR)-T cells were developed through genetic modification of their receptors, enhancing the specificity and effectiveness of T cell therapy. Adoptive cell transfer of chimeric antigen receptor-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen, which is called TCR-T therapy. This review discusses anti-tumor T cell therapies, with a focus on engineered TCR-T cell therapy. We outline the characteristics of TCR-T cell therapy and its clinical application to non-hematological malignancies.

• Genomics & Informatics
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• v.6 no.2
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• pp.84-86
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• 2008

The Tetrahymena group I intron has been shown to employ a trans-splicing reaction and has been modified to specifically target and replace human telomerase reverse transcriptase (hTERT) RNA with a suicide gene transcript, resulting in the induction of selective cytotoxicity in cancer cells that express the target RNA, in animal models as well as in cell cultures. In this study, we evaluated the target RNA specificity of trans-splicing phenomena by the group I intron in mice that were intraperitoneally inoculated with hTERT-expressing human cancer cells to validate the anti-cancer therapeutic applicability of the group I intron. To this end, an adenoviral vector that encoded for the hTERT-targeting group I intron was constructed and systemically injected into the animal. 5'-end RACE-PCR and sequencing analyses of the trans-spliced cDNA clones revealed that all of the analyzed products in the tumor tissue of the virus-infected mice resulted from reactions that were generated only with the targeted hTERT RNA. This study implies the in vivo target specificity of the trans-splicing group I intron and hence suggests that RNA replacement via a trans-splicing reaction by the group I intron is a potent anti-cancer genetic approach.

• Journal of Food Hygiene and Safety
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• v.28 no.3
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• pp.202-206
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• 2013

High-grade mucoepidermoid carcinomas (MECs) have difficulty in cure and 5-year survival rate is quiet low. Therefore, we need new therapeutic agents and molecular targets. Betulinic acid (BA) is one of the materials which is easily found in the world and shows tumor-suppress effects in various tumor types. In addition, many kinds of normal tissues have a resistance to BA treatment. In this study, we investigated the anti-proliferative activity of BA and its molecular targets in MC-3 human MEC cells using western blot analysis and DAPI staining. BA inhibited cell viability and induced apoptosis in MC-3 cells. It affected Specificity protein 1 (Sp1) and its downstream molecule, survivin whereas it did not affect myeloid cell leukemia-1 (Mcl-1). Therefore, we suggest that BA can be a potential anti-cancer drug candidate regulating Sp 1 and survivin to exert apoptotic cell death.

• BMB Reports
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• v.48 no.8
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• pp.454-460
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• 2015

Naturally occurring reoviruses are live replication-proficient viruses that specifically infect human cancer cells while sparing their normal counterpart. Since the discovery of reoviruses in 1950s, they have shown various degrees of safety and efficacy in pre-clinical or clinical applications for human anti-cancer therapeutics. I have recently discovered that cellular tumor suppressor genes are also important in determining reoviral tropism. Carcinogenesis is a multi-step process involving the accumulation of both oncogene and tumor suppressor gene abnormalities. Reoviruses can exploit abnormal cellular tumor suppressor signaling for their oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ataxia telangiectasia mutated (ATM), and retinoblastoma associated (RB) are known to play important roles in genomic fidelity/maintenance. Thus, a tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to the accumulation of genetic defects which in turn could result in oncolytic reovirus susceptibility. This review outlines the discovery of oncolytic reovirus strains, recent progresses in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and reoviral oncotropism, and their clinical implications. Future directions in the utility of reovirus virotherapy is also proposed in this review. [BMB Reports 2015; 48(8): 454-460]

• IMMUNE NETWORK
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• v.4 no.3
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• pp.184-189
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• 2004

Background: Hu syndrome, a neurological disorder, is characterized by the remote effect of small cell lung cancer on the neural degeneration. The suspicious effectors for this disease are anti-Hu autoantibodies or Hu-related CD8+ T lymphocytes. Interestingly, the same effectors have been suggested to act against tumor growth and this phenomenon may represent natural tumor immunity. For these diagnostic and therapeutic reasons, the demand for antibodies against Hu protein is rapidly growing. Methods: Polyclonal and monoclonal antibodies were generated using recombinant HuR protein. Western blot analyses were performed to check the specificity of generated antibodies using various recombinant proteins and cell lysates. Extracellular stimuli for HuR expression had been searched and HuR-associated proteins were isolated from polysome lysates and then separated in a 2-dimensional gel. Results: Polyclonal and monoclonal antibodies against HuR protein were generated and these antibodies showed HuR specificity. Antibodies were also useful to detect and immunoprecipitate endogenous HuR protein in Jurkat and BJAB. This report also revealed that TNF-${\alpha}$ treatment in BJAB up-regulated HuR expression. Lastly, protein profile in HuR-associated mRNAprotein complexes was mapped by 2-dimensional gel electrophoresis. Conclusion: This study reported that new antibodies against HuR protein were successfully generated. Currently, project to develop a diagnostic kit is in process. Also, this report showed that TNF-${\alpha}$ up-regulated HuR expression in BJAB and protein profile associated with HuR protein was mapped.