• Maxillofacial Plastic and Reconstructive Surgery
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• v.40
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• pp.4.1-4.4
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• 2018

Background: Along with the advances in technology of three-dimensional (3D) printer, it became a possible to make more precise patient-specific 3D model in the various fields including oral and maxillofacial surgery. When creating 3D models of the mandible and maxilla, it is easier to make a single unit with a fused temporomandibular joint, though this results in poor operability of the model. However, while models created with a separate mandible and maxilla have operability, it can be difficult to fully restore the position of the condylar after simulation. The purpose of this study is to introduce and asses the novel condylar repositioning method in 3D model preoperational simulation. Methods: Our novel condylar repositioning method is simple to apply two irregularities in 3D models. Three oral surgeons measured and evaluated one linear distance and two angles in 3D models. Results: This study included two patients who underwent sagittal split ramus osteotomy (SSRO) and two benign tumor patients who underwent segmental mandibulectomy and immediate reconstruction. For each SSRO case, the mandibular condyles were designed to be convex and the glenoid cavities were designed to be concave. For the benign tumor cases, the margins on the resection side, including the joint portions, were designed to be convex, and the resection margin was designed to be concave. The distance from the mandibular ramus to the tip of the maxillary canine, the angle created by joining the inferior edge of the orbit to the tip of the maxillary canine and the ramus, the angle created by the lines from the base of the mentum to the endpoint of the condyle, and the angle between the most lateral point of the condyle and the most medial point of the condyle were measured before and after simulations. Near-complete matches were observed for all items measured before and after model simulations of surgery in all jaw deformity and reconstruction cases. Conclusions: We demonstrated that 3D models manufactured using our method can be applied to simulations and fully restore the position of the condyle without the need for special devices.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.2
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• pp.81-93
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• 2007

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1771-1777
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• 2012

The impact of anatomic resection (AR) as compared to non-anatomic resection (NAR) for hepatocellular carcinoma (HCC) as a factor for preventing intra-hepatic and local recurrence after the initial surgical procedure remains controversial. A systematic review and meta-analysis of nonrandomized trials comparing anatomic resection with non-anatomic resection for HCC published from 1990 to 2010 in PubMed and Medline, Cochrane Library, Embase, and Science Citation Index were therefore performed. Intra-hepatic recurrence, including early and late, and local recurrence were considered as primary outcomes. As secondary outcomes, 5 year survival and 5 year disease-free survival were considered. Pooled effects were calculated utilizing either fixed effects or random effects models. Eleven non-randomized studies including 1,576 patients were identified and analyzed, with 810 patients in the AR group and 766 in the NAR group. Patients in the AR group were characterized by lower prevalence of cirrhosis, more favorable hepatic function, and larger tumor size and higher prevalence of macrovascular invasion compared with patients in the NAR group. Anatomic resection significantly reduced the risks of local recurrence and achieved a better 5 years disease-free survival. Also, anatomic resection was marginally effective for decreasing the early intra-hepatic recurrence. However, it was not advantageous in preventing late intra-hepatic recurrence compared with non-anatomic resection. No differences were found between AR and NAR with respect to postoperative morbidity, mortality, and hospitalization. Anatomic resection can be recommended as superior to non-anatomic resection in terms of reducing the risks of local recurrence, early intra-hepatic recurrence and achieving a better 5 year disease-free survival in HCC patients.

• Journal of the Korean Physical Society
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• v.73 no.10
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• pp.1577-1583
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• 2018

Tumor-treating fields therapy involves placing pads onto the patient's skin to create a low- intensity (1 - 3 V/cm), intermediate frequency (100 - 300 kHz), alternating electric field to treat cancerous tumors. This new treatment modality has been approved by the Food and Drug Administration in the USA to treat patients with both newly diagnosed and recurrent glioblastoma. To deliver the prescribed electric field intensity to the tumor while minimizing exposure of organs at risk, we developed an optimization method for the electric field distribution in the body and compared the electric field distribution in the body before and after application of this optimization algorithm. To determine the electric field distribution in the body before optimization, we applied the same electric potential to all pairs of electric pads located on opposite sides of models. We subsequently adjusted the intensity of the electric field to each pair of pads to optimize the electric field distribution in the body, resulting in the prescribed electric field intensity to the tumor while minimizing electric fields at organs at risk. A comparison of the electric field distribution within the body before and after optimization showed that application of the optimization algorithm delivered a therapeutically effective electric field to the tumor while minimizing the average and the maximum field strength applied to organs at risk. Use of this optimization algorithm when planning tumor-treating fields therapy should maintain or increase the intensity of the electric field applied to the tumor while minimizing the intensity of the electric field applied to organs at risk. This would enhance the effectiveness of tumor-treating fields therapy while reducing dangerous side effects.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.185-191
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• 2006

Background: Based on outstanding progresses in animal experiments, vaccines for some human tumors have been developed. However, clinical effects of these vaccines have been far below than expected. This discrepancy might come from differences between animal models and human patients with respect to immunocompetency. The immune status of mice after tumor inoculation has not been well studied, which make us cautious in interpreting and applying the results from mice to human. We evaluated cell-mediated immune responses in mice after tumor cell inoculation. Methods: Mice were inoculated with TA3Ha, CT26, or 4T1. Delayed-type hypersensitivity (DTH) responses were induced 2-4 weeks after inoculation using 2,4-dinitro-1-fluorobenzene as an antigen. The relationships between the severity of DTH responses and the duration of tumor inoculation or the size of tumor mass were analyzed. Results: In T A3Ha groups, DTH response was elevated 2 weeks after inoculation, but depressed after 4 weeks, compared to the control group. When analyzed based on the sizes of tumor masses elicited, DTH responses were inversely related to the mass size, especially in those greater than 10 mm in diameter. In CT26 groups, while the duration after inoculation did not affect the severity of DTH responses, those with large mass showed depressed responses regardless the duration of inoculation. 4T1 cells grew so slowly that the size of tumor mass was small even 4 weeks after inoculation, and this group showed much higher DTH responses compared to that of tumor-free group. Conclusion: At least in an experimental setting where tumor model was induced by inoculating tumor cell lines into immunologically competent mice, the host immune response was elevated in early stage, and then depressed in late stage when the mass grew over a critical size.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.501-508
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• 2019

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and $NF-{\kappa}B$ p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of $CD4^+/CD8^+$ and the secretion of interleukin (IL)-2 and interferon-${\gamma}$, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1241-1245
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• 2015

Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4263-4266
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• 2012

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP-labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.6
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• pp.529-539
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• 2008

Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.60-71
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• 2020

Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([¹⁸F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [¹⁸F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [¹⁸F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [¹⁸F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.