• Journal of Korean Neurosurgical Society
• /
• 제61권4호
• /
• pp.434-440
• /
• 2018

Objective : The purpose of this study was to find an optimal delivery route for clinical trials of intrathecal cell therapy for spinal cord injury in preclinical stage. Methods : We compared in vivo distribution of Cy5.5 fluorescent dye in the spinal cord region at various time points utilizing in vivo optical imaging techniques, which was injected into the lateral ventricle (LV) or cisterna magna (CM) of rats. Results : Although CM locates nearer to the spinal cord than the LV, significantly higher signal of Cy5.5 was detected in the thoracic and lumbar spinal cord region at all time points tested when Cy5.5 was injected into the LV. In the LV injection Cy5.5 signal in the thoracic and lumbar spinal cord was observed within 12 hours after injection, which was maintained until 72 hours after injection. In contrast, Cy5.5 signal was concentrated at the injection site in the CM injection at all time points. Conclusion : These data suggested that the LV might be suitable for preclinical injection route of therapeutics targeting the spinal cord to test their treatment efficacy and biosafety for spinal cord diseases in small animal models.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권22호
• /
• pp.9939-9943
• /
• 2014

Lobaplatin, one of the third - generation platinum compounds, has shown encouraging anticancer activity in a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemically evaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in - vitro and in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects of lobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovarian cancer cell lines. In addition, in - vitro antitumor activities were evaluated with cisplatin - sensitive and cisplatin - resistant human ovarian cancer xenografts in nude mice. The cytotoxicity of lobaplatin was similar to or higher than that of cisplatin and carboplatin, with $IC_{50}$ values from 0.9 to $13.8{\mu}mol/L$ in a variety of ovarian cancer cells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, in platinum - sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatin and carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activity in platinum - resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or in combination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Further clinical development of lobaplatin is clearly warranted.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권22호
• /
• pp.9693-9698
• /
• 2014

Background: Associations between the 8473T>C polymorphism (rs5275) in the cyclooxygenase-2 (COX-2) gene and breast cancer (BC) risk are still inconclusive and ambiguous. The aim of this meta-analysis was to comprehensively estimate the genetic risk of 8473T>C polymorphism in the COX-2 gene for BC. Materials and Methods: We searched PubMed, Web of Science, Medline, Chinese biomedical (CBM), Weipu, China national knowledge infrastructure (CNKI), and Wanfang databases, covering all publications (last search was updated on Aug 17, 2014). Statistical analyses were performed using Revman 5.3 and STATA 10.0 software. Results: A total of 6,720 cases and 9,794 controls in 12 studies were included in this study. The results indicated no significant associations between the 8473T>C polymorphism of the COX-2 gene and BC risk for the CC+TC vs TT model (pooled odds ratio (OR)=0.97, 95% confidence interval (CI)=0.90-1.03, and p=0.29). On subgroup analysis, we also found that subdivision on ethnicity among Caucasians, Asians and others also revealed no relationship with BC susceptibility. With the study design (CC+TC vs TT), no significant associations were found in either population-based case-control studies (PCC), or hospital-based case-control studies (HCC). Conclusions: This present meta-analysis suggests that the 8473T>C polymorphism in the COX-2 gene is not a conspicuous low-penetrant risk factor for developing BC.

• 한국방사선학회논문지
• /
• 제16권5호
• /
• pp.559-565
• /
• 2022

대체적으로는 전임상 평가로써 소·대동물을 통한 의료기기 개발 평가를 이루고 있으며 본 연구에서는 소화기계 위 날문부 협착 치료 평가모델 개발을 위해 스텐트 삽입 후 발생하는 조직 과증식 형성 모델을 개발하고자 한다. 파일럿실험으로 백서 3마리에서 날문부에 조영제를 주입하고 정상의 날문부 사이즈를 확인하였으며, 그에 맞는 사이즈의 스텐트를 삽입하였다. 1주일 내에 모든 백서에서 스텐트의 이동이 확인되었으며 본 실험에서는 스텐트를 투시 가이드 하에 gastrostomy 후 스텐트 삽입 시 날문부를 suture 하여 고정하여 조직 과증식이 형성이 가능하도록 하였다. 20마리의 백서를 Healthy Group / Gastrostomy Group으로 나누었다. Stent Group 백서를 마취 후 복부 절개 후 투시 가이드하에 gastrostomy를 실시하여 위 날문부에 스텐트를 삽입하였다. 또한, 연동운동에 의한 스텐트의 이동을 방지하기 위하여 위의 스텐트와 스텐트가 삽입된 위의 날문부를 suture 하여 고정하였다. 수술 후 행동 및 체중 변화를 매주 모니터링 하였다. 수술 후 4주 뒤 위장조영술을 시행 후 희생하였다. 위의 날문부 과증식 정도 평가를 위해 희생 후 적출한 위의 날문부 병리학적 분석을 실시하였다. 조직병리 및 면역 염색 평가에서 Gastrostomy Group이 통계적으로 유의하게 더 높았다(all p<.001). 결론적으로 Gastrostomy를 통한 위 날문부 수술 모델은 위 날문부 스텐트 삽입술 전임상 평가를 위한 조직 과증식의 형성 정도가 연구평가 툴로써 적정한 것으로 사료된다.

• IMMUNE NETWORK
• /
• 제21권6호
• /
• pp.45.1-45.13
• /
• 2021

Many mouse models of rheumatoid arthritis have been identified, but only a limited number are present for axial spondyloarthritis (AxSpA). Collagen Ab-induced arthritis (CAIA) is one of the most widely used mouse models of arthritis, and it is complement-dependent. We found that mice developing CAIA also developed spinal lesions similar to those found in AxSpA. To induce CAIA, mice were injected intraperitoneally at day 0 with anti-collagen Abs, followed by LPS injection at day 3. CAIA mice demonstrated a significant kyphosis through the spine, as well as hypertrophic cartilage and osseous damage of the intravertebral joints. Immunohistochemical staining of the kyphotic area revealed increased complement C3 deposition and macrophage infiltration, with localization to the intravertebral joint margins. Near Infrared (NIR) in vivo imaging showed that anti-collagen Abs conjugated with IRDye^® 800CW not only localized to cartilage surface in the joints but also to the spine in arthritic mice. We report here a novel preclinical mouse model in which, associated with the induction of CAIA, mice also exhibited salient features of AxSpA; this new experimental model of AxSpA may allow investigators to shed light on the local causal mechanisms of AxSpA bone and soft tissue changes as well as treatment.

• Journal of Gastric Cancer
• /
• 제14권2호
• /
• pp.67-86
• /
• 2014

Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field.

• Bulletin of the Korean Chemical Society
• /
• 제31권11호
• /
• pp.3318-3326
• /
• 2010

Five new series of 3,4-ethylenedioxythiophene derivatives carrying important pharamacophores, viz., amide, ester, ether and active secondary aryl moieties have been designed and synthesized through multistep reactions starting from thiodiglycolic ester and diethyl oxalate. They have been characterized by elemental and spectral data. All the target compounds have been screened for their anticonvulsant activity at three different models viz. maximal electroshock (MES), subcutaneous metrazole (scMET), and 6 Hz screen and evaluated for their neurotoxicity in rotorod model. Compound 6a emerged as lead with no neurotoxicity. All the five series of compounds are safe in the toxicity studies at the maximum dose of 300 mg/kg of body weight. Amongst the tested compounds, the ester pharmacophore with thioamide fragment has showed better activity than the other analogs.

• BMB Reports
• /
• 제54권7호
• /
• pp.344-355
• /
• 2021

Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling transduction, and tissue homeostasis. Abnormality of mucus expression and structure contributes to biological properties related to human cancer progression. Tumor growth sites induce inhospitable conditions. Many kinds of research suggest that mucins provide a microenvironment to avoid hypoxia, acidic, and other biological conditions that promote cancer progression. Given that the mucus layer captures growth factors or cytokines, we propose that mucin helps to ameliorate inhospitable conditions in tumor-growing sites. Additionally, the composition and structure of mucins enable them to mimic the surface of normal epithelial cells, allowing tumor cells to escape from immune surveillance. Indeed, human cancers such as mucinous carcinoma, show a higher incidence of invasion to adjacent organs and lymph node metastasis than do non-mucinous carcinoma. In this mini-review, we discuss how mucin provides a tumor-friendly environment and contributes to increased cancer malignancy in mucinous carcinoma.

• Laboraroty Animal Research
• /
• 제34권4호
• /
• pp.160-165
• /
• 2018

Breast cancer remains the second leading cause of cancer death among woman, worldwide, despite advances in identifying novel targeted therapies and the development of treating strategies. Classification of clinical subtypes (ER+, PR+, HER2+, and TNBC (Triple-negative)) increases the complexity of breast cancers, which thus necessitates further investigation. Mouse models used in breast cancer research provide an essential approach to examine the mechanisms and genetic pathway in cancer progression and metastasis and to develop and evaluate clinical therapeutics. In this review, we summarize tumor transplantation models and genetically engineered mouse models (GEMMs) of breast cancer and their applications in the field of human breast cancer research and anti-cancer drug development. These models may help to improve the knowledge of underlying mechanisms and genetic pathways, as well as creating approaches for modeling clinical tumor subtypes, and developing innovative cancer therapy.

• Journal of the Korean Physical Society
• /
• 제73권11호
• /
• pp.1764-1773
• /
• 2018

A-PET is a quad-head PET scanner developed for use in small-animal imaging. The dimensions of its volumetric field of view (FOV) are $46.1{\times}46.1{\times}46.1mm^3$ and the gap between the detector modules has been minimized in order to provide a highly sensitive system. However, such a small FOV together with the quad-head geometry causes image quality degradation. The main factor related to image degradation for the quad-head PET is the mispositioning of events caused by the penetration effect in the detector. In this paper, we propose a precise method for modelling the system at the high spatial resolution of the A-PET using a LOR (line of response) based ML-EM (maximum likelihood expectation maximization) that allows for penetration effects. The proposed system model provides the detection probability of every possible ray-path via crystal sampling methods. For the ray-path sampling, the sub-LORs are defined by connecting the sampling points of the crystal pair. We incorporate the detection probability of each sub-LOR into the model by calculating the penetration effect. For comparison, we used a standard LOR-based model and a Monte Carlo-based modeling approach, and evaluated the reconstructed images using both the National Electrical Manufacturers Association NU 4-2008 standards and the Geant4 Application for Tomographic Emission simulation toolkit (GATE). An average full width at half maximum (FWHM) at different locations of 1.77 mm and 1.79 mm are obtained using the proposed system model and standard LOR system model, which does not include penetration effects, respectively. The standard deviation of the uniform region in the NEMA image quality phantom is 2.14% for the proposed method and 14.3% for the LOR system model, indicating that the proposed model out-performs the standard LOR-based model.