• Genomics & Informatics
• /
• v.16 no.2
• /
• pp.30-35
• /
• 2018

Patient-derived xenograft (PDX) models are useful tools for tumor biology research and testing the efficacy of candidate anticancer drugs targeting the druggable mutations identified in tumor tissue. However, it is still unknown how much of the genetic alterations identified in primary tumors are consistently detected in tumor tissues in the PDX model. In this study, we analyzed the genetic alterations of three primary colorectal cancers (CRCs) and matched xenograft tissues in PDX models using a next-generation sequencing cancer panel. Of the 17 somatic mutations identified from the three CRCs, 14 (82.4%) were consistently identified in both primary and xenograft tumors. The other three mutations identified in the primary tumor were not detected in the xenograft tumor tissue. There was no newly identified mutation in the xenograft tumor tissues. In addition to the somatic mutations, the copy number alteration profiles were also largely consistent between the primary tumor and xenograft tissue. All of these data suggest that the PDX tumor model preserves the majority of the key mutations detected in the primary tumor site. This study provides evidence that the PDX model is useful for testing targeted therapies in the clinical field and research on precision medicine.

• Toxicological Research
• /
• v.30 no.1
• /
• pp.1-5
• /
• 2014

Xenograft models of human cancer play an important role in the screening and evaluation of candidates for new anticancer agents. The models, which are derived from human tumor cell lines and are classified according to the transplant site, such as ectopic xenograft and orthotopic xenograft, are still utilized to evaluate therapeutic efficacy and toxicity. The metastasis model is modified for the evaluation and prediction of cancer progression. Recently, animal models are made from patient-derived tumor tissue. The patient-derived tumor xenograft models with physiological characters similar to those of patients have been established for personalized medicine. In the discovery of anticancer drugs, standard animal models save time and money and provide evidence to support clinical trials. The current strategy for using xenograft models as an informative tool is introduced.

• The Journal of the Korean bone and joint tumor society
• /
• v.1 no.2
• /
• pp.189-193
• /
• 1995

The authors reviewed 49 cases(48 patients) of benign bone tumor who had surgical treatment with xenograft at department of orthopedic surgery, Seoul National University Hospital from May, 1980 to May, 1994. Materials consist of 21 males and 27 females. The mean age at operation was 20.1 years(range : 4 -55 years) and the mean follow up period was 25.4 months(range : 7 - 85 months). We did xenograft only in 34 cases and xenograft mixed with autograft in 15 cases(14 cases, from ilium, 1 case from femur). The used materials for xenograft were $Lubboc^{(R)}$ in 29 cases, $Surgibone^{(R)}$ in 17 cases and $Pyrost^{(R)}$ in 3 cases. The average durations when bony union was achieved in radiograph were 13.8 weeks in whole cases, 12.5 weeks(range : 8 - 24 weeks) in $Lubboc^{(R)}$ graft cases and 15.7 weeks(range : 6 - 24 weeks) in $Surgibone^{(R)}$ graft cases. The tumor recurred in 4 cases, 1 case was recurred giant cell tumor at distal femur treated with mixed auto and $Lubboc^{(R)}$ graft and 2 cases were large cystic lesions at the proximal humerus diagnosed as simple bone cyst and at distal tibia diagnosed as fibrous dysplasia treated with $Surgibone^{(R)}$ graft and 1 case was aneurysmal bone cyst of the proximal tibia treated with $Lubboc^{(R)}$ graft. Wound infection occurred in 1 case. More transfusion was done in the cases that the lesion was larger than 5cm, the lesions were in the ilium or femur and the cases that were treated with mixed with autograft. This study implies that benign bone tumor is successfully treqated with curettage and xenograft or xenograft mixed with autograft. And also this method will reduce morbidity of donor site, intraoperative bleeding and post-transfusion complications.

• The Korea Journal of Herbology
• /
• v.35 no.6
• /
• pp.35-41
• /
• 2020

Objectives : The object of this study was to observe anticancer and immunomodulatory effects of Formosa plum aqueous extracts (PLe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Method : Three different dosages of PLe, 50, 100 and 200 mg/kg were orally administered once a day for 28 days from 11 days after tumor cell inoculation. Five groups, each of seven mice per group were used in the present study as follows. Tumor volume and weights, serum interferon (IFN)-γ levels, serum IL-6 were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. Result : Although no meaningful changes on the tumor weights and volumes were observed after treatment of all three different dosages of PLe, decreases of tumor cell volumes in tumor masses were dose-dependently decreased mediated by increases of apoptosis among tumor cells by treatment of PLe 100 and 200 mg/kg as compared with tumor-bearing control. In addition, decreases on the body weight and gains were also demonstrated in tumor-bearing control with increases of serum IL-6 levels. Conclusion : The results obtained in this study suggest that over 50 mg/kg of PLe showed favorable immunomodulatory and anticachexic effects with anticancer effects in 100 and 200 mg/kg of PLe treated groups on the NCI-H520 cell xenograft. However, detail mechanism studies should be conducted in future with the screening of the biological active compounds in this herb.

• Journal of Korean Neurosurgical Society
• /
• v.55 no.3
• /
• pp.131-135
• /
• 2014

Objective : With the growing interests of bacteria as a targeting vector for cancer treatment, diverse genetically engineered Salmonella has been reported to be capable of targeting primary or metastatic tumor regions after intravenous injection into mouse tumor models. The purpose of this study was to investigate the capability of the genetically engineered Salmonella typhimurium (S. typhimurium) to access the glioma xenograft, which was monitored in mouse brain tumor models using optical bioluminescence imaging technique. Methods : U87 malignant glioma cells (U87-MG) stably transfected with firefly luciferase (Fluc) were implanted into BALB/cAnN nude mice by stereotactic injection into the striatum. After tumor formation, attenuated S. typhimurium expressing bacterial luciferase (Lux) was injected into the tail vein. Bioluminescence signals from transfected cells or bacteria were monitored using a cooled charge-coupled device camera to identify the tumor location or to trace the bacterial migration. Immunofluorescence staining was also performed in frozen sections of mouse glioma xenograft. Results : The injected S. typhimurium exclusively localized in the glioma xenograft region of U87-MG-bearing mouse. Immunofluorescence staining also demonstrated the accumulation of S. typhimurium in the brain tumors. Conclusion : The present study demonstrated that S. typhimurium can target glioma xenograft, and may provide a potentially therapeutic probe for glioma.

• Genomics & Informatics
• /
• v.18 no.1
• /
• pp.3.1-3.8
• /
• 2020

Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.2
• /
• pp.1067-1072
• /
• 2013

Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of $SSC^{lo}\;Alde^{br}$ cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell $SSC^{lo}\;Alde^{br}$ cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers.

• Journal of Korean Traditional Oncology
• /
• v.20 no.2
• /
• pp.23-36
• /
• 2015

Purpose : The object of this study was to observe anti-cachexic effects of Kwibi-tang extracts (KBTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of KBTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, each of 8 mice per group were used in the present study. Changes on the body weight, the epididymal fat weight and serum IL-6 levels were detected with the thicknesses of deposited cervical brown adipose tissue and their mean diameters to monitor the tumor-related anticachexic effects. Results : Deceases on the body weight and gains were also demonstrated in tumor-bearing control with increases of serum IL-6 levels, decreases of epididymal fat pad weight, atrophic changes of cervical brown adipose tissues. These are means that tumor-related cachexia are induced by tumor cell inoculations in the present study. However, these tumor-related cachexia were markedly inhibited by all three different dosages of KBTe treatment as compared with tumor-bearing control. 5-FU showed somewhat deteriorated the tumor-related cachexia in the present study. Conclusion : The results obtained in this study suggest that over 50 mg/kg of KBTe showed favorable anticachexic effects on the NCI-H520 cell xenograft. However, detail mechanism studies should be conducted in future with the screening of the biological active compounds in this herb.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1077-1082
• /
• 2015

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823. RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then, we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal. After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.

• YAKHAK HOEJI
• /
• v.59 no.4
• /
• pp.164-169
• /
• 2015

In the present study, we determined the effect of $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) in the mice model bearing xenografts of HT-29 human colon cancer cell line. Data from the cytotoxicity assay displayed that $18{\beta}$-GA induced cell death in HT-29. The cytotoxicity was enhanced as the $18{\beta}$-GA treatment was prolonged. In case of 72 hrs treatment, $LD_{50}$ of $18{\beta}$-GA was approximately $90{\mu}M$, and the efficacy at $100{\mu}M$ of $18{\beta}$-GA appeared to be equivalent to that of doxorubicin at $1{\mu}M$. Based on the in vitro data, we tested the anti-tumor effect of $18{\beta}$-GA in thymic mice (Balb/c strain). Xenograft tumors were generated by subcutaneous injection of HT-29 ($3{\times}10^6cells/mouse$) to mice and the mice were treated intraperitoneally with $18{\beta}$-GA ($50{\mu}g/time/mouse$) every other day for 4 times. The tumor volumes were measured for a period of 14 days. Data displayed that the $18{\beta}$-GA treatment reduced the tumor volumes (P < 0.05) as compared to control mice. However, this activity was demolished when athymic mice (Balb/c nu/nu) were used instead of thymic mice. This observation appeared that T lymphocyte played an important role in the anti-tumor activity. In conclusion, our results indicate that $18{\beta}$-GA has anti-tumor activity in HT-29 tumor-bearing mice, which may be associated with T cells.