• 대한방사성의약품학회지
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• 제6권1호
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• pp.53-58
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• 2020

Pretargeting is a two-component strategy often used for tumor targeting to enhance the tumor-to-background ratio in cancer diagnosis as well as therapy. In the multistep strategy, the highly specific unlabeled monoclonal antibodies (mAbs) with the reactive site is allowed to get localized at tumor site first, and then small and fastclearing radiolabeled chelator with counter reactive site is administered which covalently attaches to mAbs via inverse electron demand Diels-Alder reaction (IEDDA). The catalyst-free IEDDA cycloaddition reaction between 1,2,4,5-tetrazines and strained alkene dienophiles aid with properties like selective bioconjugation, swift and high yielding bioorthogonal reactions are emergent in the development of radiopharmaceutical. Due to its fast pharmacokinetics, the in vivo formed radioimmunoconjugates can be imaged at earlier time points by short-lived radionuclides like ¹⁸F and ⁶⁸Ga; it can also reduce radiation damage to the normal cells. Ultimately, this review elucidates the updated status of pretargeting based on antibodies and IEDDA for tumor diagnosis (PET and SPECT) and therapy.

• Molecules and Cells
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• 제38권3호
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• pp.202-209
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• 2015

Hepatocellular carcinoma (HCC), a highly malignant disease and the third leading cause of all cancer mortalities worldwide, often responses poorly to current treatments and results in dismal outcomes due to frequent chemoresistance and tumor relapse. The heterogeneity of HCC is an important attribute of the disease. It is the outcome of many factors, including the cross-talk between tumor cells within the tumor microenvironment and the acquisition and accumulation of genetic and epigenetic alterations in tumor cells. In addition, there is accumulating evidence in recent years to show that the malignancy of HCC can be attributed partly to the presence of cancer stem cell (CSC). CSCs are capable to self-renew, differentiate and initiate tumor formation. The regulation of the stem cell-like properties by several important signaling pathways have been found to endow the tumor cells with an increased level of tumorigenicity, chemoresistance, and metastatic ability. In this review, we will discuss the recent findings on hepatic CSCs, with special emphasis on their putative origins, relationship with hepatitis viruses, regulatory signaling networks, tumor microenvironment, and how these factors control the stemness of hepatic CSCs. We will also discuss some novel therapeutic strategies targeted at hepatic CSCs for combating HCC and perspectives of future investigation.

• Journal of Breast Cancer
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• 제21권4호
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• pp.354-362
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• 2018

Cellular stress severely disrupts endoplasmic reticulum (ER) function, leading to the abnormal accumulation of unfolded or misfolded proteins in the ER and subsequent development of endoplasmic reticulum stress (ERS). To accommodate the occurrence of ERS, cells have evolved a highly conserved, selfprotecting signal transduction pathway called the unfolded protein response. Notably, ERS signaling is involved in the development of a variety of diseases and is closely related to tumor development, particularly in breast cancer. This review discusses recent research regarding associations between ERS and tumor metastasis. The information presented here will help researchers elucidate the precise mechanisms underlying ERS-mediated tumor metastasis and provide new directions for tumor therapies.

• 한국정보통신학회논문지
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• 제20권12호
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• pp.2395-2400
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• 2016

암 환자들을 대상으로 하는 항암치료법은 나노입자, 폴리머 중합체, 지질, 리포솜 등을 치료 전달체로 이용하여 항암치료를 진행하는 방법들이 주로 활발하게 사용되고 있다. 이러한 전달체는 항암 치료제를 직접 암세포로 정확하게 표적 운반하는 정확성, 정확하게 운반한 후 선택적으로 항암치료제를 방출해야하는 유출제어, 다른 일반 세포들을 약물로부터 보호하는 기능 등을 동시에 가지고 있어야 하지만, 대부분 항암약물의 독성에 기인한 부작용이 발생하고 있다. 겸형적혈구는 암세포주변 혈관세포와 멤브레인 표면에 존재하는 리셉터 사이에의 점착성이 존재하며 추가적 생화학처리 없이 암세포 주변에 표적화가 가능함을 보인다. 또한, 암세포 주변의 혈관의 구조적 변화특성은 겸형적혈구의 중합화 반응을 증가시킨다. 따라서 본 논문에서는 겸형적혈구를 이용한 새로운 항암치료법의 효과를 정량적 혈관분석 방법을 통해 제시하고자 한다.

• Macromolecular Research
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• 제16권1호
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• pp.15-20
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• 2008

The enhanced permeability and retention (EPR) effect is used extensively for the passive targeting of many macromolecular drugs for tumors. Indeed, the EPR concept has been a gold standard in polymeric anticancer drug delivery systems. This study investigated the tumoral distribution of self-assembled nanoparticles based on the EPR effect using fluorescein and radio-labeled nanoparticles. Self-assembled nanoparticles were prepared from amphiphilic chitosan derivatives, and their tissue distribution was examined in tumor-bearing mice. The size of the nanoparticles was controlled to be 330 run, which is a size suited for opening between the defective endothelial cells in tumors. The long-circulating polymer nanoparticles were allowed to gradually accumulate in the tumors for 11 days. The amount of nanoparticles accumulated in the tumors was remarkably augmented from 3.4%ID/g tissue at 1 day to 25.9%ID/g tissue at 11 days after i.v. administration. The self-assembled nanoparticles were sustained at a high level throughout the 14 day experimental period, indicating their long systemic retention in the blood circulation. The ${\gamma}$-images provided clear evidence of selective tumor localization of the $^{131}I$-labeled nanoparticles. Confocal microscopy revealed the fluorescein-labeled nanoparticles to be preferentially localized in the perivascular regions, suggesting their extravasation to the tumors through the hyperpermeable angiogenic tumor vasculature. This highly selective tumoral accumulation of nanoparticles was attributed to the leakiness of the blood vessels in the tumors and their long residence time in the blood circulation.

• Molecular Medicine Reports
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• 제20권5호
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• pp.4111-4118
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• 2019

The administration of D-galactose triggers brain aging by poorly understood mechanisms. It is generally recognized that D-galactose induces oxidative stress or affects protein modifications via receptors for advanced glycated end products in a variety of species. In the present study, we aimed to investigate the involvement of astrocytes in D-galactose-induced brain aging in vitro. We found that D-galactose treatment significantly suppressed cell viability and induced cellular senescence. In addition, as of the accumulation of senescent cells, we proposed that the senescence-associated secretory phenotype (SASP) can stimulate age-related pathologies and chemoresistance in brain. Consistently, senescent astrocytic CRT cells induced by D-galactose exhibited increases in the levels of IL-6 and IL-8 via NF-κB activation, which are major SASP components and inflammatory cytokines. Conditioned medium prepared from senescent astrocytic CRT cells significantly promoted the viability of brain tumor cells (U373-MG and N2a). Importantly, conditioned medium greatly suppressed the cytotoxicity of U373-MG cells induced by temozolomide, and reduced the protein expression levels of neuron marker neuron-specific class III β-tubulin, but markedly increased the levels of c-Myc in N2a cells. Thus, our findings demonstrated that D-galactose treatment might mimic brain aging, and that D-galactose could contribute to brain inflammation and tumor progression through inducing the accumulation of senescent-secretory astrocytes.

• Nuclear Medicine and Molecular Imaging
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• 제40권5호
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• pp.271-274
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• 2006

We report the case of a 64-year-old man with superior vena cava (SVC) syndrome due to tumor thrombus from recurrent hepatocellular carcinoma (HCC). He presented with new onset of facial swelling for 10 days. HCC was detected ten years ago. He has undergone repeated transcatheter arterial embolization (TAE) and chemotherapy. Chest computed tomography (CT) demonstrated tumor thrombus in the SVC extending to right atrium. He underwent whole body F-18 fluorodeoxyglucose(FDG) positron emission tomography/computed tomography (PET/CT) scanning for assessing the effect of TAE in HCC. F-18 FDG PET/CT showed increased uptake in the residual liver mass indicating viable tumor. There was another intense F-18 FDG accumulation in SUV extending to right atrium to suggest tumor thrombus. This case illustrates that F-18 FDG PET/CT is useful to identification of distant metastases as well as assessment of response to therapy in long-term survival HCC patients.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.189-195
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• 2021

Fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, exhibits various other mechanisms of action in numerous cell types and has been shown to induce cell death in cancer cells, paving the way for its potential use in cancer therapy. The aim of this study was to determine the off-target effects of the anti-depressant drug FLX, on the human ovarian granulosa tumor COV434 cells stimulated by forskolin (FSK), by measuring the real-time kinetics of intracellular cyclic AMP (cAMP), ATP level, cytoplasmic calcium ([Ca2+]cyt) and survival of COV434 cells. We show that incubating COV434 cells with FLX (between 0.6 and 10 μM) induces a decrease in intracellular cAMP response to FSK, a drop in ATP content and stimulates cytoplasmic Ca2+ accumulation in COV434 cells. Only the highest concentrations of FLX (5-10 μM) diminished cell viability. The present report is the first to identify an action mechanism of FLX in human tumor ovarian cells COV434 cells and thus opening the way to potential use of fluoxetine as a complementary tool, in granulosa tumor treatments.

• 한국환경성돌연변이발암원학회지
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• 제22권2호
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• pp.65-69
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• 2002

To elucidate the effect of microsphere coinjection on the administration of oligodeoxynucleotides (ODN), we have investigated biodistribution of ［S-35］-labeled antisense ODN targeted to cAMP-dependent protein kinase (PKA) RI-$\alpha$ subunit in nude mice xenografted with WiDr (human colon cancer, ATCC CCL218). The strategy of using microsphere has been proposed for cancer treatment as a carrier of therapeutic ODN so that it could offer an advantage with respect to maintaining constant ODN levels in blood and obtaining higher therapeutic ODN concentration at tumor sites. Comparative biodistribution studies were performed in nude mice (female, 20 g of body weight, n = 4-6) xenografted with WiDr cancer cells, when 0.1 $\mu$Ci (specific activity, 2.94 mCi/$\mu$mole) of ［S-35］-labeled RI-$\alpha$ antisense ODN was injected alone or with microsphere (PLG-18, polylactic copolymer with cationic surfactant DDAB18). Peak tumor uptake of ［S-35］-labeled ODN was significantly increased from 17.7% (at 6 h) of injected dose per gram of tissue (ID/g) to 42.5% (at 24 h) ID/g when microsphere was coinjected with ODN. The different biodistribution in the kidney accumulation (e.g., 100.2% ID/g for ODN alone and 54.9%/ID/g for microshpere coinjection) may contribute to higher blood concentration (e.g., 21.5%ID/$m\ell$ for ODN alone and 37.5%ID/$m\ell$ for microsphere coinjection) of radiolabeled ODN. Of importance is the fact that the whole body retention of radioactivity increased with microsphere coinjection from 50.8%ID/g to 68.0%ID/g after 24-h of injection. This decreased kidney accumulation and increased whole body retention of ［S-35］-labeled ODN resulted in a significant improvement of ODN targeting to the tumor site. In conclusion, the coinjection of microsphere appears to be an important carrier system in vehiculation of antisense oligonucleotide to the tumor tissue in vivo.

• BMB Reports
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• 제46권5호
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• pp.252-257
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• 2013

Fibroblast activation protein (FAP) is a specific serine protease expressed in tumor stroma proven to be a stimulatory factor in the progression of some cancers. The purpose of this study was to investigate the effects of FAP knockdown on tumor growth and the tumor microenvironment. Mice bearing 4T1 subcutaneous tumors were treated with liposome-shRNA complexes targeting FAP. Tumor volumes and weights were monitored, and FAP, collagen, microvessel density (MVD), and apoptosis were measured. Our studies showed that shRNA targeting of FAP in murine breast cancer reduces FAP expression, inhibits tumor growth, promotes collagen accumulation (38%), and suppresses angiogenesis (71.7%), as well as promoting apoptosis (by threefold). We suggest that FAP plays a role in tumor growth and in altering the tumor microenvironment. Targeting FAP may therefore represent a supplementary therapy for breast cancer.