• Title/Summary/Keyword: preclinical study

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In Vivo Spinal Distribution of Cy5.5 Fluorescent Dye after Injection via the Lateral Ventricle and Cisterna Magna in Rat Model

  • Lee, Kee-Hang;Nam, Hyun;Won, Jeong-Seob;Hwang, Ji-Yoon;Jang, Hye Won;Lee, Sun-Ho;Joo, Kyeung Min
    • Journal of Korean Neurosurgical Society
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    • v.61 no.4
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    • pp.434-440
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    • 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.

Preclinical Activity of Lobaplatin as a Single Agent and in Combination with Taxanes for Ovarian Carcinoma Cells

  • Sun, Xu;Lou, Li-Guang;Sui, Dong-Hu;Wu, Xiao-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9939-9943
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    • 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.

Association of the Glutathione S-transferase T1 Null Genotype with Risk of Gastric Cancer: a Meta-analysis in Asian Populations

  • Zeng, Yan;Bai, Jian;Deng, Li-Cong;Xie, Yu-Ping;Zhao, Fen;Huang, Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1141-1148
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    • 2016
  • Background: A large number of studies have been published to investigate the association between the null genotype of glutathione S-transferase T1 (GSTT1) with gastric cancer. However, the results were inconsistent and conflicting. The aim of this study was to estimate the relationship between this polymorphism in the GSTT1 gene and gastric cancer risk in Asian populations by meta-analysis. Materials and Methods: A literature search was performed in PubMed, Embase, Chinese Biomedical database (CBM), Weipu database, Wanfang database, and China National Knowledge Infrastructure database (CNKI). Statistical analysis was conducted by using Review Manager 5.3. Results: Thirty-nine studies with a total of 7,737 gastric cancer cases and 10,823 controls were included in this meta-analysis. The meta-analysis of total studies showed that the null genotype in GSTT1 was associated with increased risk of gastric cancer in Asians (OR=1.19, 95% CI=1.08-1.31, p=0.0002). Subgroup analysis showed a significant relationship between GSTT1 null genotype and gastric cancer in East-Asians, as well as in subgroup analysis of hospital-based design. On subgroup analysis by smoking status, alcohol status, Helicobacter pylori infection status, and histology type, no significant association of this polymorphism with susceptibility to gastric cancer was found. Conclusions: In conclusion, the results showed that the null genotype of GSTT1 is significantly associated with an increased risk in gastric cancer in Asian populations.

Effect of Tea Polyphenols on the Adhesion of Highly Metastatic Human Lung Carcinoma Cell Lines to Endothelial Cells in Vitro

  • Zheng, Feng-Jin;Shi, Lin;Yang, Jun;Deng, Xiao-Hui;Wu, Yu-Quan;Yan, Xi-Qing;Huang, Ning
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3751-3755
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    • 2012
  • Aim: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis. For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted to investigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelial cells (EC cells) and adhesion molecule expression in vitro. Methods: The expression of CD44 or CD54 in the PG cells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopy double fluorescence staining. Results: The results showed that tea polyphenols: (1) inhibited the expression of CD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantly blocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influenced CD44 and CD54 expression during the adhesion process of PG cells to EC cells. Conclusions: The data indicated that the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54. The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibiting adhesion molecule expression to block cancer cell adhesion.

Application of Optimized Gompertz Algorithm for Estimation of Controlled Drug Release (Gompertz modeling을 이용한 약물유출 예측시스템의 최적화)

  • Choe, Se-Woon;Woo, Young Woon
    • Journal of the Korea Society of Computer and Information
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    • v.19 no.12
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    • pp.219-225
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    • 2014
  • A Gompertz modeling, sigmoid in shape, is a widely used application for social science, natural science, engineering, and medical research to allow confident approximation and accurate analysis and has been applied to estimate an elderly population on aging of population. Due to the high toxicity of currently available drug delivery vehicles, various efforts have been made to reduce side-effects in clinical fields, but its application to preclinical and clinical studies is limited and there are some difficulties to optimize the parameters of Gompertz modeling applicable to preclinical studies. Therefore, in this study, we demonstrated the ability of sickle red blood cells loaded by hypotonic dialysis then photosensitized and light-activated ex vivo for controlled release and simultaneously optimized Gompertz function to evaluate controlled drug release properties of photosensitized sickle red blood cells to reduce pain-related treatments in cancer patients.

The Concurrent Use of Rhus verniciflua Stokes as Complementary Therapy with Second or More Line Regimens on Advanced Non-small-cell Lung Cancer: Case Series

  • Lee, Sang-Hun;Kim, Kyung-Suk;Choi, Won-Cheol;Yoon, Seong-Woo
    • The Journal of Korean Medicine
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    • v.30 no.6
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    • pp.112-117
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    • 2009
  • Objective: Rhus verniciflua Stokes (RVS) has anticancer effect confirmed by preclinical studies and historical records. We thus tried to evaluate retrospectively the effect of RVS as a complementary medicine for patients with advanced non-small-cell lung cancer (NSCLC) showing refractory to conventional chemotherapy. Patients and Methods: From June 1, 2006 to June 30, 2007, patients with advanced NSCLC who received both the standardized RVS extract and a standard course of second or more line therapy such as pemetrexed ($Alimta^{(R)}$), erlotinib ($Tarceva^{(R)}$), and gefitinib ($Iressa^{(R)}$) were checked. A total of 13 patients were eligible for the final analysis after fulfilling inclusion/exclusion criteria. Time to progression (TTP) of these patients treated with the standardized RVS extract was checked in the aftercare period. Results: Patients received RVS treatment for a median period of 296 (range 84-698) days. The median TTP was 220.5 (range 36-489) days, and three patients (23.1%) had TTP values of 15 more months. No significant side effects from RVS treatment have been observed. Conclusion: The standardized RVS extract might have synergetic effects by assisting apoptosis in advanced NSCLC with concurrent standard therapy agents, since it prolonged TTP without significant adverse effects. This study suggests that the standardized RVS extract is beneficial to patients with chemotherapy-refractory NSCLC. Further clinical trials and preclinical studies are necessary to determine the efficacy and safety of the standardized RVS extract in NSCLC.

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Incidental Finding of Abnormal Cervical Pathology in Hysterectomy Specimens after Normal Preoperative Papanicolaou Smears in Thammasat University Hospital

  • Chundarat, Pong-Anan;Suwannarurk, Komsun;Bhamarapravatana, Kornkarn;Pattaraarchachai, Junya;Thaweekul, Yuthadej;Mairaing, Karicha;Poomtavorn, Yenrudee
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5811-5814
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    • 2014
  • Background: To investigate abnormal cervical histopathology (ACH) from hysterectomy specimens with normal preoperative Papanicolaou (Pap) smears. Materials and Methods: Medical records from May 2009 to April 2012 were retrospectively reviewed of subjects from whom hysterectomy specimens were taken in Thammasat University Hospital. All had normal preoperative Pap smears. ACH was the primary outcome. A p-value less than 0.05 was considered significant. A total of 483 subjects with an average age of 50.5 years were recruited. Benign cases of enlarged uterus and pelvic mass were present in 94% (430/483). Endometrial and ovarian cancer were found at 6.2 and 4.7%, respectively. In hysterectomy specimens there were 19 (4%) cases of ACH. Silent ACH with benign disease, endometrial and ovarian cancers were 1.2% (5/430), 33.3% (10/30) and 17.4% (4/23), respectively. The negative predictive value (NPV) and false negative rate of Pap smears were 96 and 4%, respectively. ACH in malignant cases were 27.9% (12/43) and 20% (2/10) in adequate (APS) and inadequate (IPS) Pap collection groups, respectively. ACH in benign condition were 0.68% (2/292) and 2.2% (3/138) in APS and IPS, respectively. ACH was more often found in hysterectomy specimens with indication of malignancy than benign conditions with statistical significance. One third of preoperative stage I endometrial cancer cases had cervical involvement. Conclusions: Silent ACH in normal preoperative Pap smear was 4 %. Inadequate Pap smear collection is still the major problem in this study. Reducing inadequate Pap smear collection could reduce the false negative rate.

Combination of BEZ235 and Metformin Has Synergistic Effect on Cell Viability in Colorectal Cancer Cells

  • Kim, Taewan;Kim, Taehyung;Choi, Soonyoung;Ko, Hyeran;Park, Deokbae;Lee, Youngki
    • Development and Reproduction
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    • v.22 no.2
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    • pp.133-142
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    • 2018
  • Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.

Generation of Neural Progenitor Cells from Pig Embryonic Germ Cells

  • Choi, Kwang-Hwan;Lee, Dong-Kyung;Oh, Jong-Nam;Kim, Seung-Hun;Lee, Mingyun;Jeong, Jinsol;Choe, Gyung Cheol;Lee, Chang-Kyu
    • Journal of Animal Reproduction and Biotechnology
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    • v.35 no.1
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    • pp.42-49
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    • 2020
  • As a preclinical study, many researchers have been attempted to convert the porcine PSCs into several differentiated cells with transplantation of the differentiated cells into the pigs. Here, we attempted to derive neuronal progenitor cells from pig embryonic germ cells (EGCs). As a result, neuronal progenitor cells could be derived directly from pig embryonic germ cells through the serum-free floating culture of EB-like aggregates (SFEB) method. Treating retinoic acid was more efficient for inducing neuronal lineages from EGCs rather than inhibiting SMAD signaling. The differentiated cells expressed neuronal markers such as PAX6, NESTIN, and SOX1 as determined by qRT-PCR and immunostaining. These data indicated that pig EGCs could provide valid models for human therapy. Finally, it is suggested that developing transgenic pig for disease models as well as differentiation methods will provide basic preclinical data for human regenerative medicine and lead to the success of stem cell therapy.

Trends of Studies in Journal of Korean Medicine Rehabilitation: Focused on Diseases and Treatment for Recent 10 years (한방재활의학과학회지의 연구동향: 최근 10년간의 연구들을 질환과 치료법 중심으로)

  • Ji-Hong Jeong;Hong-Ryoul Yoon;Soon-Joong Kim
    • Journal of Korean Medicine Rehabilitation
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    • v.33 no.1
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    • pp.61-75
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    • 2023
  • Objectives The purpose of this study is to find out what diseases or treatments the Korean Medicine Rehabilitation department is dealing with. Methods For data collection, papers published from 2012 to 2021 were searched and collected on the website of the Korean Society of Rehabilitation Medicine (https://www.ormkorea.org/). After that, reconfirmed data at the Oriental Medicine Advanced Searching Integrated System (OASIS) Traditional Medicine Portal (https://oasis.kiom.re.kr/). The searched papers were classified by year and classified according to format based on thesis and abstract. In addition, the papers were classified by subject, focusing on diseases and treatments. Results Total 557 studies were classified. The format of a total of 557 papers was distributed in 129 preclinical studies (23.2%), 136 literature studies (24.4%), 153 clinical studies (27.5%), 112 case reports (20.1%), and 27 other studies (4.8%). While preclinical studies and clinical studies are gradually decreasing over the years, case reports and literature studies are gradually increasing. Conclusions The number of papers in Journal of Korean Medicine Rehabilitation is gradually decreasing. Papers on more diverse topics is needed for the qualitative growth of journals and Department of Korean Medicine Rehabilitation.